FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hirota, M Watanabe, K Hamada, S Sun, YP Strizzi, L Mancino, M Nagaoka, T Gonzales, M Seno, M Bianco, C Salomon, DS AF Hirota, Morihisa Watanabe, Kazuhide Hamada, Shin Sun, Youping Strizzi, Luigi Mancino, Mario Nagaoka, Tadahiro Gonzales, Monica Seno, Masaharu Bianco, Caterina Salomon, David S. TI Smad2 functions as a co-activator of canonical Wnt/beta-catenin signaling pathway independent of Smad4 through histone acetyltransferase activity of p300 SO CELLULAR SIGNALLING LA English DT Article DE activin; beta-catenin; smads; Tcf/Lef; TGF-beta; Wnt ID TUMOR-SUPPRESSOR SMAD4/DPC4; GROWTH-FACTOR-BETA; TGF-BETA; BREAST-CANCER; WNT PATHWAY; TRANSCRIPTIONAL ACTIVATION; INTESTINAL TUMORIGENESIS; COLORECTAL-CANCER; CELLULAR INVASION; IN-VIVO AB Both canonical Wnt/beta-catenin and TGF beta/Smad signaling pathways coordinately regulate pattern formation during embryogenesis as well as tumor progression. Evidence of cross-talk between these two pathways has been reported. Here we demonstrated that the Activin-like kinase 4 (Alk4)/Smad2 pathway facilitates the transcriptional activity of the oncogenic Wnt/beta-catenin/Tcf4 pathway through a novel Smad4-independent mechanism. Upon activation, Smad2 physically interacted with Tcf4, beta-catenin and the co-activator p300 to enhance transcriptional activity of beta-catenin/Tcf4 through the histone acetyltransferase activity of p300. Transactivation by Smad2 was independent of a Smad-binding element (SBE) and Smad4. Indeed, the enhancement of beta-catenin/Tcf4 transcriptional activity by activated Smad2 was negatively regulated by the presence of Smad4. Moreover, a tumor-derived missense mutant of Smad2, lacking the ability to bind to Smad4 was still able to enhance the Tcf4 transcriptional reporter in the presence of p-catenin and Tcf4. Our findings suggest that Smad2 may function as an activator of canonical Wnt/beta-catenin/Tcf4 signaling through a SBE/Smad4-independent pathway. Published by Elsevier Inc. C1 [Hirota, Morihisa; Watanabe, Kazuhide; Hamada, Shin; Sun, Youping; Strizzi, Luigi; Mancino, Mario; Nagaoka, Tadahiro; Gonzales, Monica; Bianco, Caterina; Salomon, David S.] NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Canc Res Ctr,Natl Inst Hlth, Bethesda, MD 20892 USA. [Hirota, Morihisa; Watanabe, Kazuhide] Tohoku Univ, Div Gastroenterol, Sendai, Miyagi 9810933, Japan. [Strizzi, Luigi] Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA. [Seno, Masaharu] Okayama Univ, Lab Nanobiotechnol, Dept Med & Bioengn Sci, Okayama, Japan. [Sun, Youping] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Mancino, Mario] Oncol Res Ctr, Mercogliano, AV, Italy. RP Watanabe, K (reprint author), Bldg 37,Rm 1112,37 Convent Dr, Bethesda, MD 20892 USA. EM watanabek@mail.nih.gov RI SENO, Masaharu /B-2092-2011; OI SENO, Masaharu /0000-0001-8547-6259; Nagaoka, Tadahiro/0000-0002-9391-0243 FU Intramural NIH HHS [Z01 BC009003-25] NR 54 TC 28 Z9 29 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD SEP PY 2008 VL 20 IS 9 BP 1632 EP 1641 DI 10.1016/j.cellsig.2008.05.003 PG 10 WC Cell Biology SC Cell Biology GA 336MQ UT WOS:000258368400006 PM 18595660 ER PT J AU Botello-Harbaum, M Nansel, T Haynie, DL Iannotti, RJ Simons-Morton, B AF Botello-Harbaum, M. Nansel, T. Haynie, D. L. Iannotti, R. J. Simons-Morton, B. TI Responsive parenting is associated with improved type 1 diabetes-related quality of life SO CHILD CARE HEALTH AND DEVELOPMENT LA English DT Review DE parenting style; quality of life; responsiveness; type 1 diabetes ID METABOLIC-CONTROL; SELF-CARE; ADOLESCENTS; STYLES; CHILDREN; INVOLVEMENT; ADHERENCE; COMPETENCE; ADJUSTMENT; MANAGEMENT AB Background Improved quality of life is an important treatment goal for children and adolescents with type 1 diabetes. While previous research supports a relationship between family environment and quality of life, little research has addressed the relationship of parenting style constructs to quality of life in children with chronic disease. The present investigation assesses the relationship of parent responsiveness and demandingness with diabetes-related quality of life among children and adolescents with type 1 diabetes. Methods Baseline and 12-month follow-up self-report assessments were collected on a sample of 81 children with type 1 diabetes participating in an efficacy trial of a behavioural intervention to enhance adherence. The sample had a mean age of 13.3 years (SD = 1.7) and duration of diabetes of 7.7 years (SD = 3.7). Multiple regression analyses were conducted to determine the relationship of parent responsiveness and demandingness to diabetes-related quality of life at each time point. Results After adjusting for demographic and diabetes characteristics, as well as diabetes-specific parent-child behaviours, parent responsiveness was significantly associated with baseline diabetes-related quality of life (beta = 0.23; P = 0.04). This relationship was sustained at 12-month follow-up (beta = 0.22; P = 0.04) after adjusting for baseline quality of life and treatment group assignment, suggesting that parent responsiveness is associated with improved quality of life. Conclusions Findings indicate the importance of a supportive and emotionally warm parenting style in promoting improved quality of life for children with type 1 diabetes. Appropriate parenting skills should be an element of diabetes family management health care. C1 [Botello-Harbaum, M.; Nansel, T.; Haynie, D. L.; Iannotti, R. J.; Simons-Morton, B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol & Stat, Prevent Res Branch, Bethesda, MD USA. RP Nansel, T (reprint author), NICHD, Prevent Res Branch, DESPR, NIH, MSC 7510,6100 Execut Blvd, Bethesda, MD 20852 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, Z99 HD999999] NR 43 TC 17 Z9 18 U1 3 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0305-1862 J9 CHILD CARE HLTH DEV JI Child Care Health Dev. PD SEP PY 2008 VL 34 IS 5 BP 675 EP 681 DI 10.1111/j.1365-2214.2008.00855.x PG 7 WC Psychology, Developmental; Pediatrics SC Psychology; Pediatrics GA 335GS UT WOS:000258279400018 PM 18796059 ER PT J AU Wainer, IW AF Wainer, Irving W. TI Investigation of molecular recognition in biological systems using cellular membrane affinity chromatography SO CHIMICA OGGI-CHEMISTRY TODAY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; CATION TRANSPORTER HOCT1; CHIRAL STATIONARY-PHASE; NONCOMPETITIVE INHIBITORS; IDENTIFICATION; DOCKING; BINDING; COLUMN AB Cellular membrane affinity chromatography (CMAC) columns have been created through the immobilization of cellular membrane fragments on liquid chromatographic supports. A CMAC column containing the human organic cation transporter, CMAC(hOCT1) column, has been used to study the stereoselective binding of competitive inhibitors. The chromatographic data obtained using the CMAC( hOCT1) column was to develop a pharmacophore model that described the stereoselectivity. The results indicate that a dynamic chiral recognition model based upon conformational adjustments between the inhibitors and hOCT1 is responsible for the observed steroeselectivity. C1 NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Wainer, IW (reprint author), NIA, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. FU National Institute on Aging Intramural Research Program FX This work was supported by funding from the National Institute on Aging Intramural Research Program. NR 22 TC 2 Z9 2 U1 0 U2 1 PU TEKNOSCIENZE PUBL PI MILANO PA VIALE BRIANZA 22, 20127 MILANO, ITALY SN 1973-8250 J9 CHIM OGGI JI Chim. Oggi-Chem. Today PD SEP-OCT PY 2008 VL 26 IS 5 SU 1 BP 19 EP 22 PG 3 WC Biotechnology & Applied Microbiology; Chemistry, Multidisciplinary SC Biotechnology & Applied Microbiology; Chemistry GA 356XS UT WOS:000259811500007 PM 19430544 ER PT J AU Marraccini, P Brass, DM Hollingsworth, JW Maruoka, S Garantziotis, S Schwartz, DA AF Marraccini, P. Brass, D. M. Hollingsworth, J. W. Maruoka, S. Garantziotis, S. Schwartz, D. A. TI Bakery flour dust exposure causes non-allergic inflammation and enhances allergic airway inflammation in mice SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE allergic asthma; baker's asthma; endotoxin; flour dust; LPS; occupational airways disease; toll-like receptor 4 ID WHEAT-FLOUR; ASTHMA; SENSITIZATION; WORKERS; PREVENTION; SYMPTOMS; DISEASE AB Background Baker's asthma is one of the most commonly reported occupational lung diseases in countries where fresh bread is baked daily in large quantities, and is characterized by rhinitis, bronchial hyperresponsiveness, and reversible airflow obstruction. Epidemiological studies have identified pre-existing atopy as an important risk factor for developing baker's asthma, yet the aetiology and pathogenesis of baker's asthma remain poorly understood. Objective We sought to develop a mouse model of baker's asthma that could be used to characterize the development and progression of baker's asthma. Methods We were unable to sensitize mice to bakery flour dust or flour dust extract. We assessed total inflammatory cells, cellular differential, total serum IgE and the pro-inflammatory cytokine response to oropharyngeally instilled bakery flour dust or flour dust extract by itself or in the context of ovalbumin (OVA) sensitization and challenge. Results Both bakery flour dust and flour dust extract consistently elicited a neutrophilic inflammation in a Toll-like receptor 4-independent manner; suggesting that endotoxin is not playing a role in the inflammatory response to flour dust. Moreover, bakery flour dust and dust extract significantly enhance the inflammatory response in OVA-sensitized and challenged mice. Conclusions Bakery flour dust and flour dust extract are strongly pro-inflammatory and can cause non-allergic airway inflammation and can enhance allergen-mediated airway inflammation. C1 [Brass, D. M.; Maruoka, S.] Duke Univ, Med Ctr, Neonatal & Perinatal Res Inst, Dept Pediat,Neonatol Div, Durham, NC 27710 USA. [Marraccini, P.] Fdn Maggiore Policlin Hosp Mangiagalli & Regina E, Prevent & Occupat Med Dept, Unit Environm & Occupat, Milan, Italy. [Hollingsworth, J. W.] Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. [Schwartz, D. A.] Natl Inst Environm Hlth Sci, NHLBI, Lab Environm Lung Dis, Res Triangle Pk, NC USA. RP Brass, DM (reprint author), Duke Univ, Med Ctr, Neonatal & Perinatal Res Inst, Dept Pediat,Neonatol Div, Box 3373, Durham, NC 27710 USA. EM david.brass@duke.edu RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU National Heart, Lung and Blood Institute [HL91335]; National Institute of Environmental Health Sciences [ES11961]; National Institute of Allergy and Infectious Diseases [AI058161] FX Funding Support: This research was supported, in part, by the Intramural Research Program of the National Heart, Lung and Blood Institute; the National Institute of Environmental Health Sciences and by grants from the National Institute of Environmental Health Sciences (ES11961); the National Heart, Lung, and Blood Institute (HL91335) and the National Institute of Allergy and Infectious Diseases (AI058161). NR 29 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD SEP PY 2008 VL 38 IS 9 BP 1526 EP 1535 DI 10.1111/j.1365-2222.2008.03038.x PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 341PS UT WOS:000258727400015 PM 18564331 ER PT J AU Keller, JE AF Keller, James E. TI Characterization of new formalin-detoxified botulinum neurotoxin toxoids SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID CLOSTRIDIUM-BOTULINUM; INTERNATIONAL STANDARDS; IMMUNOLOGICAL RESPONSE; IMMUNE GLOBULIN; SEROTYPE-A; B TOXINS; VACCINE; FORMALDEHYDE; ANTITOXINS; TOXICITY AB Antigenicities of several formalin-detoxified botulinum neurotoxin preparations were measured by inhibition and sandwich enzyme-linked immunosorbent assay (ELISA), and immunogenicity was studied in mice. The toxoids were derived primarily from the serotype A 150-kDa neurotoxin protein, while one toxoid was derived from the naturally occurring 900-kDa toxin-hemagglutinin complex. Antigenicity was severely compromised in two commercially available toxoids. A variety of new toxoids were synthesized in-house by optimizing formaldehyde reaction conditions. Three of the resulting toxoids were found to be antigenically identical to the native toxin, as measured by inhibition ELISA, in spite of showing a reduction of toxicity by more than 100,000-fold. Sandwich ELISAs indicated that the in-house toxoids were two-to threefold less antigenic than the neurotoxin compared to commercial toxoids, which were about 100-fold less antigenic. Mice were immunized twice, on day 0 and day 14. By day 28, relatively high toxin-specific immunoglobulin G (IgG) titers were detected in animals that had received any of the in-house toxoids, with greater than 99% being IgG1 and the remainder being IgG2. These immunized mice remained asymptomatic after being challenged with 50 to 1,000,000 50% lethal dose (LD50) units of the 900-kDa neurotoxin. In contrast, animals immunized with several different batches of commercially available toxoids did not develop measurable toxin-specific antibody titers. However, these mice survived neurotoxin challenges with 2 LD50 units but died when challenged with 6 LD50 units. Neutralizing titers measured from pools of sera generated with the in-house toxoid preparations ranged from 2.5 to 5 U/ml. In terms of predicting immunogenicity, inhibition ELISAs comparing each formalin toxoid to the parent toxin provided good insight for screening the new toxoids as well as for estimating their relative in vivo potencies. Inhibition ELISA data indicate that those toxoids that most closely resemble the native toxin are highly immunogenic and protective. The superior quality of these new toxoids makes them useful tools for continued use in ELISA development and for antitoxin production. C1 US FDA, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Keller, JE (reprint author), US FDA, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, HFM-434,Bldg 29,Room 122,29 Lincoln Dr,NIH Campus, Bethesda, MD 20892 USA. EM james.keller@fda.hhs.gov FU FDA/CBER; FDA/CBER-NIAID/NIH [Y1-AI-6153-01, 224-06-1322] FX Much of the ELISA analysis was performed by Pravina Mattoo (FDA/CBER) and Adaku Iwueze. Dan Li (FDA/CBER) assisted with determining mouse neutralization titers. Christine Anderson (FDA/CBER) provided the standard equine antitoxin, and Juan Arciniega (FDA/CBER) provided valuable discussion and advice during the writing of this paper. D. Sesardic (NIBSC, United Kingdom) and R. Jones (NIBSC, United Kingdom) provided valued assistance to confirm some of the neutralizing titer data. Michael Goodnough and Carl Malizio (Metabiologics, Inc.) provided very helpful information on the preparation of the commercial toxoid and subsequently performed confirmatory testing by immunizing mice with botulinum toxoids and challenging with botulinum toxin.; This work was supported by intramural FDA/CBER funding and by FDA/CBER-NIAID/NIH interagency agreement no. Y1-AI-6153-01/no.224-06-1322.; The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any agency determination or policy. NR 36 TC 17 Z9 17 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD SEP PY 2008 VL 15 IS 9 BP 1374 EP 1379 DI 10.1128/CVI.00117-08 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 344UF UT WOS:000258952100010 PM 18667637 ER PT J AU Chinnaiyan, P Cerna, D Burgan, WE Beam, K Williams, ES Camphausen, K Tofilon, PJ AF Chinnaiyan, Prakash Cerna, David Burgan, William E. Beam, Katie Williams, Eli S. Camphausen, Kevin Tofilon, Philip J. TI Postradiation sensitization of the histone deacetylase inhibitor valproic acid SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN GLIOBLASTOMA CELLS; DNA-DAMAGE REPAIR; GAMMA-H2AX FOCI; IONIZING-RADIATION; CHROMATIN DYNAMICS; PROTEIN 53BP1; RADIOSENSITIZATION; CANCER; HDAC; P53 AB Purpose: Preclinical studies evaluating histone deacetylase (HDAC) inhibitor-induced radiosensitization have largely focused on the preirradiation setting based on the assumption that enhanced radiosensitivity was mediated by changes in gene expression. Our previous investigations identified maximal radiosensitization when cells were exposed to HDAC inhibitors in both the preradiation and postradiation setting. We now expand on these studies to determine whether postirradiation exposure alone affects radiosensitivity. Experimental Design: The effects of the HDAC inhibitor valproic acid (VA) on postirradiation sensitivity in human glioma cell lines were evaluated using a clonogenic assay, exposing cells to VA up to 24 h after irradiation. DNA damage repair was evaluated using gamma H2AX and 53BP1 foci and cell cycle phase distribution was analyzed by flow cytometry. Western blot of acetylated gamma H2AX was done following histone extraction on AUT gels. Results: VA enhanced radiosensitivity when delivered up to 24 h after irradiation. Cells accumulated in G(2)-M following irradiation, although they returned to baseline at 24 h, mitigating the role of cell cycle redistribution in postirradiation sensitization by VA. At 12 h after irradiation, significant gamma H2AX and 53BP1 foci dispersal was shown in the control, although cells exposed to VA after irradiation maintained foci expression. VA alone had no effect on the acetylation or phosphorylation of H2AX, although it did acetylate radiation-induced gamma H2AX. Conclusions: These results indicate that VA enhances radiosensitivity at times up to 24 h after irradiation, which has direct clinical application. C1 [Chinnaiyan, Prakash] H Lee Moffitt Canc Ctr & Res Inst, Div Radiat Oncol Neurooncol Expt Therapeut, Tampa, FL 33612 USA. [Williams, Eli S.; Tofilon, Philip J.] H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Program, Tampa, FL 33612 USA. [Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Cerna, David; Burgan, William E.; Beam, Katie] NCI, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. [Burgan, William E.; Beam, Katie] NCI, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. RP Chinnaiyan, P (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Div Radiat Oncol Neurooncol Expt Therapeut, SRB3,12902 Magnolia Dr, Tampa, FL 33612 USA. EM prakash.chinnaiyan@moffitt.org FU Intramural NIH HHS [ZIA SC010373-10] NR 31 TC 57 Z9 58 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2008 VL 14 IS 17 BP 5410 EP 5415 DI 10.1158/1078-0432.CCR-08-0643 PG 6 WC Oncology SC Oncology GA 347UG UT WOS:000259166000013 PM 18765532 ER PT J AU Bilke, S Chen, QR Wei, JS Khan, J AF Bilke, Sven Chen, Qing-Rong Wei, Jun S. Khan, Javed TI Whole chromosome alterations predict survival in high-risk neuroblastoma without MYCN amplification SO CLINICAL CANCER RESEARCH LA English DT Article ID PEDIATRIC-ONCOLOGY-GROUP; GENE-EXPRESSION; GENOMIC ALTERATIONS; ARRAY-CGH; STRATIFICATION; PROGNOSIS; PROFILES; PATTERNS; TUMORS; STAGE AB Purpose: Patients with stage IV neuroblastoma over the age of 500 days without MYCN amplification have a survival rate of < 30% and there are currently no reliable means of predicting which of these patients will survive or succumb to the disease. The goal of this study is to develop a DNA copy number-based prognostic profile for these patients. Experimental Design: We have used comparative genomic hybridization to identify genome copy number changes that can predict outcome in patients with stage IV neuroblastoma without MYCN amplification. Results: A strong correlation of patient survival with the presence of whole chromosome changes (WCC >= 2) was observed, even in the group of patients older than 500 days at time of diagnosis. This novel prognostic marker showed a significant dependence on the date of diagnosis; patients with WCC >= 2 diagnosed after 1998 had a significantly higher probability of survival compared with those diagnosed earlier. At the same time, no such time dependence was found among the samples with WCC < 2, suggesting that medical progress patients in recent years has particularly benefited those patients with a stage IV non - MYCN-amplified disease if WCC >= 2 were present. Conclusions: In this pilot study, we present a novel prognostic marker for survival of high-risk neuroblastoma patients over the age of 500 days without MYCN amplification and diagnosed after 1998. Further validation study is required to establish this risk stratification for these patients. C1 [Bilke, Sven; Khan, Javed] NCI, Canc Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Bilke, Sven; Chen, Qing-Rong; Wei, Jun S.; Khan, Javed] NCI, Oncogenom Sect, Pediat Oncol Branch, Adv Technol Ctr, Gaithersburg, MD USA. [Chen, Qing-Rong] NCI, Adv Biomed Comp Ctr, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. RP Khan, J (reprint author), NCI, Canc Genet Branch, Ctr Canc Res, 8717 Grovemont Circle,Room 134E, Bethesda, MD 20892 USA. EM khanjav@mail.nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 FU Intramural NIH HHS [Z01 BC010592-03, Z99 CA999999]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 27 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2008 VL 14 IS 17 BP 5540 EP 5547 DI 10.1158/1078-0432.CCR-07-4461 PG 8 WC Oncology SC Oncology GA 347UG UT WOS:000259166000027 PM 18765546 ER PT J AU Smith, FO Downey, SG Klapper, JA Yang, JC Sherry, RM Royal, RE Kammula, US Hughes, MS Restifo, NP Levy, CL White, DE Steinberg, SM Rosenberg, SA AF Smith, Franz O. Downey, Stephanie G. Klapper, Jacob A. Yang, James C. Sherry, Richard M. Royal, Richard E. Kammula, Uclai S. Hughes, Marybeth S. Restifo, Nicholas P. Levy, Catherine L. White, Donald E. Steinberg, Seth M. Rosenberg, Steven A. TI Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines SO CLINICAL CANCER RESEARCH LA English DT Article ID HIGH-DOSE INTERLEUKIN-2; RENAL-CELL-CANCER; GP100 MELANOMA; RECOMBINANT INTERLEUKIN-2; BOLUS INTERLEUKIN-2; INTERFERON-ALPHA; T-LYMPHOCYTES; ANTIGEN; IDENTIFICATION; GUIDELINES AB Purpose: To identify prognostic factors associated with survival beyond 4 years and overall response in patients with metastatic melanoma treated with high-dose bolus i.v. interleukin-2 (IL-2) given either alone or in combination with a variety of melanoma vaccines. Study Design: 684 consecutive patients with metastatic melanoma received high-dose bolus i.v. IL-2 either alone or in conjunction with a variety of melanoma vaccines. Treatments occurred between August 1, 1985 and January 1, 2006. Results: The overall objective response rate was 13% for patients receiving IL-2 alone and 16% for patients who received IL-2 with vaccine. In patients treated with IL-2 alone (n = 305) and IL-2 with vaccine (n = 379), having an objective response was associated with survival beyond 4 years (P < 0.0001). No pretreatment factors could be identified that were strongly associated with increased rate of objective response or long-term survival in patients receiving IL-2 alone. In patients receiving IL-2 with vaccines, there were increased response rates in patients with s.c. or cutaneous disease only and lower response rates with visceral disease only. Patients who received the gp100: 209-217 (210 M) peptide plus IL-2 showed a strong trend to increased objective responses compared with IL-2 alone (22% versus 12.8%; P = 0.01) and also compared with patients who received a variety of vaccines that did not include this immunogenic peptide (13.8%; P = 0.009). Conclusion: IL-2 can produce a modest response rate in patients with metastatic melanoma including patients with durable complete responses. S.c. or cutaneous disease only and vaccination with gp100:209-217(210M) peptide was associated with significant increase in response rates. C1 [Smith, Franz O.; Downey, Stephanie G.; Klapper, Jacob A.; Yang, James C.; Sherry, Richard M.; Royal, Richard E.; Kammula, Uclai S.; Hughes, Marybeth S.; Restifo, Nicholas P.; Levy, Catherine L.; White, Donald E.; Rosenberg, Steven A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Dept Biostat, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Room 3-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM franz_smith@nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 SC003811-33] NR 28 TC 114 Z9 120 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2008 VL 14 IS 17 BP 5610 EP 5618 DI 10.1158/1078-0432.CCR-08-0116 PG 9 WC Oncology SC Oncology GA 347UG UT WOS:000259166000036 PM 18765555 ER PT J AU Kurkjian, C Murgo, AJ Kummar, S AF Kurkjian, Carla Murgo, Anthony J. Kummar, Shivaani TI Treatment of recurrent metastatic colon cancer in the age of modern adjuvant therapy SO CLINICAL COLORECTAL CANCER LA English DT Article DE metastasis; oxaliplatin; platinum resistance; recurrence ID ADVANCED COLORECTAL-CANCER; PHASE-III TRIAL; STAGE-II; OVARIAN-CANCER; OXALIPLATIN RESISTANCE; CHEMOTHERAPY; FLUOROURACIL; LEUCOVORIN; CISPLATIN; IRINOTECAN AB The treatment of patients with metastatic colon cancer has evolved tremendously over the past 10 years, with improved overall survival (OS) rates as a result of the advent of several important agents. Following the results of important adjuvant trials, the incorporation of oxaliplatin into the adjuvant setting has significantly increased the disease-free survival and OS rates in patients who undergo curative resection. However, still a significant number of patients will present with recurrent disease after being treated with oxaliplatin-containing chemotherapy regimens. Herein, we present approaches to the chemotherapeutic management of such patients with a review of the literature. C1 [Murgo, Anthony J.; Kummar, Shivaani] NCI, Med Oncol Branch, Clin Res Ctr, Bethesda, MD 20892 USA. [Kurkjian, Carla; Murgo, Anthony J.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Kummar, S (reprint author), NCI, Med Oncol Branch, Clin Res Ctr, 10 Ctr Dr,10-12N226, Bethesda, MD 20892 USA. EM kummars@mail.nih.gov NR 31 TC 4 Z9 4 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD SEP PY 2008 VL 7 IS 5 BP 321 EP 324 DI 10.3816/CCC.2008.n.042 PG 4 WC Oncology SC Oncology GA 348UJ UT WOS:000259235300005 PM 18794064 ER PT J AU Tadjine, M Lampron, A Ouadi, L Horvath, A Stratakis, CA Bourdeau, I AF Tadjine, Mimi Lampron, Antoine Ouadi, Lydia Horvath, Anelia Stratakis, Constantine A. Bourdeau, Isabelle TI Detection of somatic beta-catenin mutations in primary pigmented nodular adrenocortical disease (PPNAD) SO CLINICAL ENDOCRINOLOGY LA English DT Article ID MACRONODULAR ADRENAL-HYPERPLASIA; WNT SIGNALING PATHWAY; CARNEY COMPLEX; GENE; FREQUENT; CANCER; HETEROGENEITY; ADENOMAS; PDE11A; TUMORS AB Background Primary pigmented nodular adrenocortical disease (PPNAD) leads to Cushing syndrome (CS) and is often associated with Carney complex (CNC). Genetic alterations of the type 1-alpha regulatory subunit of cAMP-dependent protein kinase A (PRKAR1A) and phosphodiesterase 11A4 (PDE11A) genes have been found in PPNAD. Recent studies have demonstrated that beta-catenin mutations are frequent in adrenocortical adenomas and carcinomas and that the Wnt-signalling pathway is involved in PPNAD tumorigenesis. We hypothesized that adrenocortical adenomas that form in the context of PPNAD may harbour beta-catenin mutations. Methods We studied 18 patients with CS secondary to PPNAD who were screened for germline PRKAR1A and PDE11A mutations. Tumor DNA was extracted from pigmented adrenocortical adenoma and nodular adrenal hyperplasia. Mutation analysis of exons 3 and 5 of beta-catenin was performed using polymerase chain reaction and direct sequencing. Sections from formalin-fixed, paraffin-embedded tumour samples were studied by immunohistochemistry with an antibody against beta-catenin. Results Nine patients were carrying germline PRKAR1A mutations and one patient had a PDE11A mutation. We found somatic beta-catenin mutations in 2 of 18 patients (11%). In both cases, the mutations occurred in relatively large adenomas that had formed in the background of PPNAD. Tumor DNA analysis revealed a heterozygous ACC-to-GCC missense mutation in codon 41 (T41A) and a TCT-to-CCT missense mutation in codon 45 (S45P) of exon 3 of the beta-catenin gene that was confirmed at the cDNA level. There were no alterations in the DNA of PPNAD-adjacent tissues and lymphocytes from the patients, indicating somatic events. Immunohistochemistry showed nuclear accumulation of beta-catenin in more than 90% of cells in adenomatous tissue whereas no nuclear immunoreactivity was detected in adjacent PPNAD nodular cells. Nuclear translocation of beta-catenin protein in the PPNAD adenoma suggests activation of the Wnt-beta-catenin pathway in PPNAD. Conclusions We report, for the first time, beta-catenin mutations in adenomas associated with PPNAD, further implicating Wnt-beta-catenin signalling in tumorigenesis linked to bilateral adrenal hyperplasias. C1 [Tadjine, Mimi; Lampron, Antoine; Ouadi, Lydia; Bourdeau, Isabelle] CHUM Hotel Dieu, Div Endocrinol, Dept Med, Res Ctr, Montreal, PQ H2W 1T7, Canada. [Horvath, Anelia; Stratakis, Constantine A.] NICHD, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD USA. RP Bourdeau, I (reprint author), CHUM Hotel Dieu, Div Endocrinol, Dept Med, Res Ctr, 3850 St Urbain St, Montreal, PQ H2W 1T7, Canada. EM isabelle.bourdeau@umontreal.ca RI Levesque, Isabelle/A-1899-2012 FU Fonds de la Recherche en Sante du Quebec [FRSQ-6519/5360]; Cancer Research Society; National Institute of Child Health of Human Development (NICHD) FX We are grateful to Dr Andre Lacroix, Centre hospitalier de l'Universite de Montreal (CHUM), Montreal, Quebec, Canada, for providing adrenocortical samples. We thank Dr Anne-Marie Mess-Masson and members of her laboratory for their assistance in the immunohistochemical studies as well as the MacDonald Stewart Foundation for photographic support. The editing of our manuscript by Mr Ovid Da Silva, Research Support Office, Research Centre, CHUM, is acknowledged. This study was supported by Grant FRSQ-6519/5360 from Fonds de la Recherche en Sante du Quebec (PI: Dr I. B.) and The Cancer Research Society ( PI: Dr I. B.), and, in part, by the National Institute of Child Health of Human Development (NICHD) intramural program (to Dr C. A. S.). NR 25 TC 54 Z9 55 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD SEP PY 2008 VL 69 IS 3 BP 367 EP 373 DI 10.1111/j.1365-2265.2008.03273.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337MW UT WOS:000258441200003 PM 18419788 ER PT J AU Malik, M Webb, J Catherino, WH AF Malik, Minnie Webb, Joy Catherino, William H. TI Retinoic acid treatment of human leiomyoma cells transformed the cell phenotype to one strongly resembling myometrial cells SO CLINICAL ENDOCRINOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR-BETA; UTERINE LEIOMYOMAS; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; TGF-BETA; PROMYELOCYTIC LEUKEMIA; TUMOR; PROLIFERATION; TGF-BETA-3 AB Background Uterine leiomyomas are clinically significant tumours that may develop due to an altered differentiation pathway. We have previously identified a dysregulated retinoic acid (RA) pathway that reduced retinoic exposure in human leiomyoma surgical specimens, and have shown that the leiomyoma phenotype was characterized by excessive and disorganized extracellular matrix (ECM). Objective The goal of this study was to determine the impact of RA exposure on the disrupted ECM phenotype of leiomyomas. Design and methods Study of immortalized and molecularly confirmed cells generated from surgical specimens of spontaneous uterine leiomyoma and matched myometrium. Results Immortalized leiomyoma and myometrial cells retained the molecular characteristics of their progenitor tissue. Proliferation of leiomyoma cells was inhibited by all-trans retinoic acid (ATRA). Furthermore, there was a dose-dependent decrease in soluble extracellular collagen protein in ATRA-treated leiomyoma cells. Exposure of leiomyoma cells to ATRA resulted in a dose-dependent inhibition of templates for specific ECM protein production including collagen 1, collagen 4, fibronectin and versican. Notably, expression levels in treated leiomyoma cells approached those found in myometrial cells. These mRNA alterations translated into altered protein. Down-regulation was also observed among the RA pathway genes such as CYP26A1 with exposure to ATRA. Finally, ATRA down-regulated TGF-beta 3 mRNA expression and the TGF-beta regulated genes in leiomyoma cells. Conclusion Exposure of leiomyomas to ATRA down-regulated cell proliferation, ECM formation, RA metabolism and TGF-beta regulation, suggesting that RA exposure can alter the leiomyoma phenotype to one that more closely approximates normal myometrium. C1 [Malik, Minnie; Webb, Joy; Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Catherino, William H.] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A, Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM wcatherino@usuhs.mil OI Malik, Minnie/0000-0003-1129-6575 FU Intramural NIH HHS NR 45 TC 35 Z9 36 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD SEP PY 2008 VL 69 IS 3 BP 462 EP 470 DI 10.1111/j.1365-2265.2008.03207.x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337MW UT WOS:000258441200017 PM 18248652 ER PT J AU Takahashi, M Furihata, M Akimitsu, N Watanabe, M Kaul, S Yumoto, N Okada, T AF Takahashi, Munehisa Furihata, Mutsuo Akimitsu, Nobuyoshi Watanabe, Morihiro Kaul, Sunil Yumoto, Noboru Okada, Tomoko TI A highly bone marrow metastatic murine breast cancer model established through in vivo selection exhibits enhanced anchorage-independent growth and cell migration mediated by ICAM-1 SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE breast cancer; metastasis; bone marrow; anchorage-independent growth; migration; ICAM-1 ID COMPLEX CLASS-II; TUMOR-CELLS; EXPRESSION; IMMUNOTHERAPY; INVASIVENESS; INHIBITION; INVASION; VITRO; CD43; SUBPOPULATIONS AB To understand the mechanisms underlying bone marrow metastasis precisely, we established the highly metastatic 4T1E/M3 murine breast cancer cell line. 4T1 murine breast cancer cells were transfected with the neomycin resistance gene, selected in G418, intravenously injected into mice, and harvested from bone marrow. By repeating this protocol three times, we established the 4T1E/M3 cells. The clonality of 4T1E/M3 cells was markedly high confirmed by genomic southern analysis using neo-gene probe. When tissues harvested from mice after intravenous injection of 4T1E/M3 cells were examined histologically, markedly enhanced bone marrow metastasis was observed; 77% of spines from 4T1E/M3-injected mouse showed metastasis as compared to 14% metastasis seen with the parent cells. In vitro, 4T1E/M3 cells attached more strongly to the plastic plate and to bone marrow-derived endothelial cells. DNA micro arrays, real time RT-PCR and FACS analyses revealed that the expression of ICAM-1 and beta 2 integrin was upregulated in 4T1E/M3 cells at both the mRNA and cell surface protein levels. 4T1E/M3 cells also showed greater anchorage-independent proliferation in soft agar, and migrated markedly faster than the parent cells in wound healing assays. Anti-ICAM-1 antibodies strongly inhibited both the colony formation and the migration activity of 4T1E/M3 suggesting the importance of the role of ICAM-1. Our newly established highly metastatic 4T1E/M3 cells may provide a potentially powerful tool to study the molecular mechanisms of bone marrow metastasis and to identify new molecular targets for therapeutic interventions. C1 [Takahashi, Munehisa; Akimitsu, Nobuyoshi; Okada, Tomoko] Natl Inst Adv Ind Sci & Technol, Inst Biol Resources & Funct, Tsukuba, Ibaraki 3058566, Japan. [Furihata, Mutsuo] Kochi Med Sch, Dept Pathol, Nanko Ku, Kochi 7838505, Japan. [Watanabe, Morihiro] NCI, Expt Immunol Lab, Ft Detrick, MD 21702 USA. [Kaul, Sunil] Natl Inst Adv Ind Sci & Technol, Res Inst Cell Engn, Tsukuba, Ibaraki 3058562, Japan. [Yumoto, Noboru] Natl Inst Adv Ind Sci & Technol, Tsukuba, Ibaraki 3058568, Japan. RP Okada, T (reprint author), Natl Inst Adv Ind Sci & Technol, Inst Biol Resources & Funct, 1-1-1 Higashi, Tsukuba, Ibaraki 3058566, Japan. EM t.okada@aist.go.jp NR 45 TC 30 Z9 30 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD SEP PY 2008 VL 25 IS 5 BP 517 EP 529 DI 10.1007/s10585-008-9163-5 PG 13 WC Oncology SC Oncology GA 327HE UT WOS:000257719400003 PM 18340424 ER PT J AU Fleisher, TA Notarangelo, LD AF Fleisher, Thomas A. Notarangelo, Luigi D. TI What does it take to call it a pathogenic mutation? SO CLINICAL IMMUNOLOGY LA English DT Editorial Material ID X-LINKED AGAMMAGLOBULINEMIA; IDENTIFICATION; PHENOTYPE; BTK C1 [Fleisher, Thomas A.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. [Notarangelo, Luigi D.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA. RP Fleisher, TA (reprint author), NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. EM tfleishe@mail.nih.gov RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 12 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD SEP PY 2008 VL 128 IS 3 BP 285 EP 286 DI 10.1016/j.clim.2008.04.013 PG 2 WC Immunology SC Immunology GA 341SB UT WOS:000258734100001 PM 18617443 ER PT J AU Segal, BH Herbrecht, R Stevens, DA Ostrosky-Zeichner, L Sobel, J Viscoli, C Walsh, TJ Maertens, J Patterson, TF Perfect, JR Dupont, B Wingard, JR Calandra, T Kauffman, CA Graybill, JR Baden, LR Pappas, PG Bennett, JE Kontoyiannis, DP Cordonnier, C Viviani, MA Bille, J Almyroudis, NG Wheat, LJ Graninger, W Bow, EJ Holland, SM Kullberg, BJ Dismukes, WE De Pauw, BE AF Segal, Brahm H. Herbrecht, Raoul Stevens, David A. Ostrosky-Zeichner, Luis Sobel, Jack Viscoli, Claudio Walsh, Thomas J. Maertens, Johan Patterson, Thomas F. Perfect, John R. Dupont, Bertrand Wingard, John R. Calandra, Thierry Kauffman, Carol A. Graybill, John R. Baden, Lindsey R. Pappas, Peter G. Bennett, John E. Kontoyiannis, Dimitrios P. Cordonnier, Catherine Viviani, Maria Anna Bille, Jacques Almyroudis, Nikolaos G. Wheat, L. Joseph Graninger, Wolfgang Bow, Eric J. Holland, Steven M. Kullberg, Bart-Jan Dismukes, William E. De Pauw, Ben E. TI Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses study group and European Organization for Research and Treatment of Cancer consensus criteria SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID RECONSTITUTION INFLAMMATORY SYNDROME; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CELL TRANSPLANT RECIPIENTS; BETA-D-GLUCAN; AMPHOTERICIN-B; PULMONARY ASPERGILLOSIS; BACTERIAL-MENINGITIS; ANTIFUNGAL THERAPY; DISSEMINATED HISTOPLASMOSIS; CRYPTOCOCCAL MENINGITIS AB Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge. C1 [Segal, Brahm H.; Almyroudis, Nikolaos G.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Perfect, John R.] Duke Univ, Med Ctr, Durham, NC USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, San Antonio, TX USA. [Ostrosky-Zeichner, Luis] Univ Texas Hlth Sci Ctr Houston, San Antonio, TX USA. [Patterson, Thomas F.; Graybill, John R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Kauffman, Carol A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Sobel, Jack] Wayne State Univ, Sch Med, Detroit, MI USA. [Wingard, John R.] Univ Florida, Coll Med, Gainesville, FL USA. [Stevens, David A.] Santa Clara Valley Med Ctr, San Jose, CA 95128 USA. [Herbrecht, Raoul] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Pappas, Peter G.; Dismukes, William E.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Walsh, Thomas J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Bennett, John E.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Wheat, L. Joseph] MiraVista Diagnost MiraBella Technol, Indianapolis, IN USA. [Baden, Lindsey R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Div Infect Dis, Cambridge, MA 02138 USA. [Bow, Eric J.] Univ Manitoba, Winnipeg, MB, Canada. [De Pauw, Ben E.] Univ Med Ctr St Raboud, Nijmegen, Netherlands. [Kullberg, Bart-Jan] Univ Nijmegen, Med Ctr, Dept Med, Nijmegen, Netherlands. [Kullberg, Bart-Jan] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Bille, Jacques] Univ Lausanne Hosp, Inst Microbiol, Lausanne, Switzerland. [Calandra, Thierry] CHU Vaudois, Dept Med, Infect Dis Serv, CH-1011 Lausanne, Switzerland. [Calandra, Thierry] Univ Lausanne, Lausanne, Switzerland. [Herbrecht, Raoul] Hosp Hautepierre, Dept Hematol & Oncol, Strasbourg, France. [Dupont, Bertrand] Hop Necker Enfants Malad, Paris, France. [Cordonnier, Catherine] Hop Henri Mondor, APHP, F-94010 Creteil, France. [Cordonnier, Catherine] Univ Paris 12, Creteil, France. [Graninger, Wolfgang] Med Univ Vienna, Vienna, Austria. [Graninger, Wolfgang] Univ Hosp Vienna, Div Infect Dis, Vienna, Austria. [Viviani, Maria Anna] Univ Milan, Dept Publ Hlth Microbiol & Virol, Sect Publ Hlth, Milan, Italy. [Viscoli, Claudio] Univ Genoa, Genoa, Italy. [Viscoli, Claudio] San Martino Univ Hosp, Div Infect Dis, Genoa, Italy. [Maertens, Johan] Univ Hosp Gasthuisberg, Dept Hematol, Acute Leukemia & Hematopoiet Stem Cell Transplant, B-3000 Louvain, Belgium. RP Segal, BH (reprint author), Roswell Pk Canc Inst, Dept Med, Elm & Carlton Sts, Buffalo, NY 14263 USA. EM brahm.segal@roswellpark.org RI Herbrecht, Raoul/D-3471-2013; Kullberg, Bart Jan/C-8520-2013; Calandra, Thierry/D-9017-2015; OI Calandra, Thierry/0000-0003-3051-1285; Herbrecht, Raoul/0000-0002-9381-4876 FU Intramural NIH HHS [Z01 AI000654-16] NR 78 TC 172 Z9 185 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2008 VL 47 IS 5 BP 674 EP 683 DI 10.1086/590566 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 333VN UT WOS:000258181000013 PM 18637757 ER PT J AU Xie, DW Joffe, MM Brunelli, SM Beck, G Chertow, GM Fink, JC Greene, T Hsu, CY Kusek, JW Landis, R Lash, J Levey, AS O'Conner, A Ojo, A Rahman, M Townsend, RR Wang, H Feldman, HI AF Xie, Dawei Joffe, Marshall M. Brunelli, Steven M. Beck, Gerald Chertow, Glenn M. Fink, Jeffrey C. Greene, Tom Hsu, Chi-yuan Kusek, John W. Landis, Richard Lash, James Levey, Andrew S. O'Conner, Andrew Ojo, Akinlolu Rahman, Mahboob Townsend, Raymond R. Wang, Hao Feldman, Harold I. TI A comparison of change in measured and estimated glomerular filtration rate in patients with nondiabetic kidney disease SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID DIETARY-PROTEIN RESTRICTION; TYPE-2 DIABETIC-PATIENTS; RENAL-FUNCTION DECLINE; SERUM CYSTATIN-C; PREDICTION EQUATIONS; AFRICAN-AMERICAN; CREATININE; GFR; NEPHROPATHY; PROGRESSION AB Background and objectives: All glomerular filtration rate (GFR) estimating equations have been developed from cross-sectional data. The aims of this study were to examine the concordance between use of measured GFR (mGFR) and estimated GFR (eGFR) in tracking changes in kidney function over time among patients with moderately severe chronic kidney disease. Design, setting, participants, & measurements: A retrospective cohort study of subjects who had been enrolled in the MDRD Study A and who had two or more contemporaneous assessments of mGFR and eGFR (n = 542; mGFR range, 25 to 55 ml/min per 1.73 m(2)) during the chronic phase (month 4 and afterwards). mGFR was based on urinary iothalamate clearance; eGFR was based on the 4-variable MDRD Study equation. Temporal changes in GFR were assessed by within-subject linear regression of time on GFR. Results: Median follow-up time for all subjects was 2.6 yr; median number of GFR measurements was six. The eGFR slope tended to underestimate measured decrements in GFR. The absolute value of the difference in mGFR and eGFR slopes was <= 2 ml/min per 1.73 m(2) per yr among 58.3% of subjects; the remainder of subjects had larger absolute differences. Among the 22 variables studied, none predicted a systematic difference between mGFR slope and eGFR slope. Conclusions: Although eGFR and mGFR exhibited similar relationships to 22 baseline variables, the overall bias seen in the full cohort suggests that clinicians and researchers should exercise caution when interpreting eGFR slope as a marker of progression of kidney disease. C1 [Xie, Dawei; Joffe, Marshall M.; Brunelli, Steven M.; Landis, Richard; Wang, Hao; Feldman, Harold I.] Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, Philadelphia, PA 19104 USA. [Brunelli, Steven M.; Townsend, Raymond R.; Feldman, Harold I.] Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19104 USA. [Beck, Gerald] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [Fink, Jeffrey C.] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. [Greene, Tom] Univ Utah, Sch Med, Div Clin Epidemiol, Salt Lake City, UT USA. [Hsu, Chi-yuan] Univ Calif San Francisco, Sch Med, Div Nephrol, San Francisco, CA USA. [Kusek, John W.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA. [Lash, James] Univ Illinois, Sch Med, Div Nephrol, Chicago, IL USA. [Levey, Andrew S.] Tufts Univ, Sch Med, Div Nephrol, Boston, MA 02111 USA. [O'Conner, Andrew] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Emergency Med, New Brunswick, NJ USA. [Ojo, Akinlolu] Univ Michigan, Sch Med, Div Nephrol, Ann Arbor, MI USA. [Rahman, Mahboob] Case Western Reserve Univ, Sch Med, Div Nephrol & Hypertens, Cleveland, OH USA. RP Feldman, HI (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, 923 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM hfeldman@mail.med.upenn.edu RI Landis, J. Richard/A-9330-2010; OI Fink, Jeffrey/0000-0002-5622-5052 FU NIDDK NIH HHS [R01 DK072231] NR 24 TC 40 Z9 40 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2008 VL 3 IS 5 BP 1332 EP 1338 DI 10.2215/CJN.05631207 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 342AR UT WOS:000258757500020 PM 18667734 ER PT J AU Xu, S Kruecker, J Turkbey, B Glossop, N Singh, AK Choyke, P Pinto, P Wood, BJ AF Xu, Sheng Kruecker, Jochen Turkbey, Baris Glossop, Neil Singh, Anurag K. Choyke, Peter Pinto, Peter Wood, Bradford J. TI Real-time MRI-TRUS fusion for guidance of targeted prostate biopsies SO COMPUTER AIDED SURGERY LA English DT Article; Proceedings Paper CT 10th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2007) CY OCT 29-NOV 02, 2007 CL Brisbane, AUSTRALIA DE Motion compensation; prostate biopsy; tracking; image registration ID ELASTIC REGISTRATION; ULTRASONOGRAPHY; IMAGES; SYSTEM AB Targeted prostate biopsy is challenging because no currently established imaging modality is both accurate for prostate cancer diagnosis and cost-effective for real-time procedure guidance. A system that fuses real-time transrectal ultrasound images with previously acquired endorectal coil MRI images for prostate biopsy guidance is presented here. The system uses electromagnetic tracking and intraoperative image registration to superimpose the MRI data on the ultrasound image. Prostate motion is tracked and compensated for without the need for fiducial markers. The accuracy of the system in phantom studies was shown to be 2.4 +/- 1.2 mm. The fusion system has been used in more than 20 patients to guide biopsies with almost no modification of the conventional protocol. Retrospective clinical evaluation suggests that clinically acceptable spatial accuracy can be achieved. C1 [Xu, Sheng; Kruecker, Jochen] Philips Res N Amer, Briarcliff Manor, NY USA. [Glossop, Neil] Traxtal Inc, Toronto, ON, Canada. RP Xu, S (reprint author), Philips Res N Amer, NIH, Clin Sites Res Program, Ctr Clin, Bldg 10,Room 1C-504X,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sheng.xu@philips.com FU Intramural NIH HHS [Z99 CL999999] NR 17 TC 142 Z9 148 U1 4 U2 18 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1092-9088 J9 COMPUT AIDED SURG JI Comput. Aided Surg. PD SEP PY 2008 VL 13 IS 5 SI SI BP 255 EP 264 DI 10.1080/10929080802364645 PG 10 GA 372RD UT WOS:000260918200003 PM 18821344 ER PT J AU Richesson, RL Fung, KW Krischer, JP AF Richesson, Rachel L. Fung, Kin Wah Krischer, Jeffrey P. TI Heterogeneous but "standard" coding systems for adverse events: Issues in achieving interoperability between apples and oranges SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE biomedical research; adverse effects; informatics; forms and records control; terminology; Systematized Nomenclature of Medicine ID CLINICAL-RESEARCH; MEDDRA AB Monitoring adverse events (AEs) is an important part of clinical research and a crucial target for data standards. The representation of adverse events themselves requires the use of controlled vocabularies with thousands of needed clinical concepts. Several data standards for adverse events currently exist, each with a strong user base. The structure and features of these current adverse event data standards (including terminologies and classifications) are different, so comparisons and evaluations are not straightforward, nor are strategies for their harmonization. Three different data standards - the Medical Dictionary for Regulatory Activities (MedDRA) and the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) terminologies, and Common Terminology Criteria for Adverse Events (CTCAE) classification - are explored as candidate representations for AEs. This paper describes the structural features of each coding system, their content and relationship to the Unified Medical Language System (UMLS), and unsettled issues for future interoperability of these standards. (C) 2008 Elsevier Inc. All rights reserved. C1 [Richesson, Rachel L.; Krischer, Jeffrey P.] Univ S Florida, Coll Med, Dept Pediat, Tampa, FL 33612 USA. [Fung, Kin Wah] Natl Lib Med, Bethesda, MD USA. RP Richesson, RL (reprint author), Univ S Florida, Coll Med, Dept Pediat, 3650 Spectrum Blvd,Suite 100, Tampa, FL 33612 USA. EM richesrl@epi.usf.edu FU NCRR NIH HHS [U54 RR019259-02, U54 RR019259, RR019259] NR 30 TC 8 Z9 8 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2008 VL 29 IS 5 BP 635 EP 645 DI 10.1016/j.cct.2008.02.004 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 351KY UT WOS:000259424400002 PM 18406213 ER PT J AU Beigel, JH AF Beigel, John H. TI Influenza SO CRITICAL CARE MEDICINE LA English DT Article DE influenza; avian flu; pandemic; pneumonia; complications; treatment ID COMMUNITY-ACQUIRED PNEUMONIA; A VIRUS-INFECTION; NEURAMINIDASE INHIBITOR OSELTAMIVIR; RESISTANT STAPHYLOCOCCUS-AUREUS; RANDOMIZED CONTROLLED-TRIAL; ACUTE RESPIRATORY SYNDROME; UNITED-STATES; ORAL OSELTAMIVIR; IMMUNOCOMPROMISED PATIENTS; REQUIRING HOSPITALIZATION AB Objective: Influenza is a major concern for intensivists in all communities in the U.S. While there is considerable concern whether or not the country will be ready for a pandemic influenza, even seasonal influenza poses a major challenge to hospitals. The objective of this review is to summarize current knowledge of influenza with emphasis on the issues that intensivist will encounter. Setting: Intensive care unit in a 450-bed, tertiary care, teaching hospital. Methods: Source data were obtained from a PubMed search of the medical literature. PubMed "related articles" search strategies were likewise employed frequently. Summary and Conclusions: Seasonal influenza causes more than 200,000 hospitalizations and 41,000 deaths in the U.S. every year, and is the seventh leading cause of death in the U.S. Despite this impact there is a shortcoming in knowledge of influenza among many health care workers, and a paucity of clinical data and studies to guide therapy. Intensivists need to recognize the importance of seasonal influenza as a cause of severe morbidity and mortality. This review summarizes current knowledge of the diagnosis, complications, therapy, and infection control measures associated with influenza. C1 NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Beigel, JH (reprint author), NIAID, Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jbeigel@niaid.nih.gov RI Chiang, Vincent, Ming-Hsien/D-4312-2016 OI Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863 FU Intramural Program of the NIH; National Allergy and Infectious Diseases Institute and Critical Care Medicine Department, Clinical Center; National Institutes of Health FX This research was supported, in part, by the Intramural Program of the NIH, National Allergy and Infectious Diseases Institute and Critical Care Medicine Department, Clinical Center, National Institutes of Health. NR 88 TC 42 Z9 46 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2008 VL 36 IS 9 BP 2660 EP 2666 DI 10.1097/CCM.0b013e318180b039 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 345TV UT WOS:000259020800024 PM 18679129 ER PT J AU Carson, JL Reynolds, RC Klein, HG AF Carson, Jeffrey L. Reynolds, Richard C. Klein, Harvey G. TI Bad bad blood? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE blood transfusion ID TRANSFUSION; OUTCOMES; TRIAL C1 [Carson, Jeffrey L.; Reynolds, Richard C.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Gen Internal Med, New Brunswick, NJ USA. [Klein, Harvey G.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. RP Carson, JL (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Gen Internal Med, New Brunswick, NJ USA. NR 6 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2008 VL 36 IS 9 BP 2707 EP 2708 DI 10.1097/CCM.0b013e3181843ee7 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 345TV UT WOS:000259020800045 PM 18728495 ER PT J AU Shurin, SB AF Shurin, Susan B. TI The Genome-wide Association Studies Data Sharing Policy SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Editorial Material C1 NHLBI, Bethesda, MD 20892 USA. RP Shurin, SB (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD SEP PY 2008 VL 1 IS 2 BP 91 EP 91 DI 10.1111/j.1752-8062.2008.00044.x PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 532RT UT WOS:000272767900007 PM 20443825 ER PT J AU Korman, BD Kastner, DL Gregersen, PK Remmers, EF AF Korman, Benjamin D. Kastner, Daniel L. Gregersen, Peter K. Remmers, Elaine F. TI STAT4: Genetics, mechanisms, and implications for autoimmunity SO CURRENT ALLERGY AND ASTHMA REPORTS LA English DT Review ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TYROSINE-PHOSPHATASE PTPN22; GENOME-WIDE ASSOCIATION; RHEUMATOID-ARTHRITIS; RISK LOCUS; VARIANTS; ASTHMA; RESPONSES; DISEASES; POLYMORPHISMS AB Recent advances in genetics and technology have led to breakthroughs in understanding the genes that predispose individuals to autoimmune diseases. A common haplotype of the signal transducer and activator of transcription 4 (STAT4) gene has been shown to be associated with susceptibility to rheumatoid arthritis, systemic lupus erythematosus, and primary Sjogren's syndrome. STAT4 is a transcription factor that transduces interleukin-12, interleukin-23, and type I interferon cytokine signals in T cells and monocytes, leading to T-helper type I and T-helper type 17 differentiation, monocyte activation, and interferon-gamma production. Although the evidence for this association is very strong and well replicated, the exact mechanism by which polymorphisms in this gene lead to disease remains unknown. In concert with the identification of other disease-associated loci, elucidating how the variant form of STAT4 modulates immune function should lead to an improved understanding of the pathophysiology of autoimmunity. C1 [Remmers, Elaine F.] NIAMSD, Bethesda, MD 20892 USA. RP Remmers, EF (reprint author), NIAMSD, 9 Mem Dr,NIH Bldg,Room 1W108, Bethesda, MD 20892 USA. EM remmerse@mail.nih.gov FU National institutes of Health (NIH) [NO1-AR-2-2263, RO1 AR44422]; National Institute of Arthritis, Musculoskeletal, and Skin Diseases; NIH Clinical Research Program FX This work was supported by the National institutes of Health (NIH) NO1-AR-2-2263 and RO1 AR44422 awards to Dr. Gregersen and by the Intramural Program of the National Institute of Arthritis, Musculoskeletal, and Skin Diseases. Dr. Korman was supported by the NIH Clinical Research Program, a public private partnership between the Foundation for the NIH and Pfizer. NR 43 TC 81 Z9 84 U1 2 U2 18 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1529-7322 J9 CURR ALLERGY ASTHM R JI Curr. Allergy Asthma Rep. PD SEP PY 2008 VL 8 IS 5 BP 398 EP 403 DI 10.1007/s11882-008-0077-8 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 338ZI UT WOS:000258547500005 PM 18682104 ER PT J AU Kakizaki, S Yamazaki, Y Takizawa, D Negishi, M AF Kakizaki, Satoru Yamazaki, Yuichi Takizawa, Daichi Negishi, Masahiko TI New insights on the xenobiotic-sensing nuclear receptors in liver diseases - CAR and PXR- SO CURRENT DRUG METABOLISM LA English DT Review DE nuclear receptor; constitutive androstane receptor; pregnane X receptor; liver disease ID PREGNANE-X-RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; THYROID-HORMONE METABOLISM; RESISTANCE-ASSOCIATED PROTEIN-3; INFLAMMATORY-BOWEL-DISEASE; PRIMARY BILIARY-CIRRHOSIS; DRUG-INDUCED OSTEOMALACIA; NF-KAPPA-B; CROSS-TALK; RAT-LIVER AB The xenobiotic receptors CAR and PXR constitute two important members of the NRII nuclear receptor family. They function as sensors of toxic byproducts derived from the endogenous metabolism and of exogenous chemicals, in order to enhance their elimination. They regulate numerous genes which are involved in drug and xenobiotic metabolism, including Phase I (cytochrome P450), Phase II (conjugation catalyzed by sulfotransferases, glucuronosyltransferases and glutathione S-transferases), and transporters ( multidrug resistance proteins, multidrug resistance-associated proteins, and organic anion-transporting polypeptides). Although CAR and PXR were initially characterized as xenosensors, it is now evident that CAR and PXR also trigger pleiotropic effects on physiological or pathological functions. Recent studies have shown that the activation of CAR and PXR alters lipid metabolism, glucose homeostasis, and inflammation. Therefore, in addition to regulating drug elimination pathways, they also play important roles in regulating metabolic pathways. As a result, these receptors may be closely associated with the pathogenesis of many diseases. However, the pathophysiological roles of CAR and PXR are not fully understood. The purpose of this review is to discuss the physiological and pathological roles of CAR and PXR in liver diseases. C1 [Kakizaki, Satoru; Yamazaki, Yuichi; Takizawa, Daichi] Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, Gunma 3718511, Japan. [Negishi, Masahiko] Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Kakizaki, S (reprint author), Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, 3-39-15 Showa Machi, Gunma 3718511, Japan. EM kakizaki@showa.gunma-u.ac.jp NR 119 TC 60 Z9 62 U1 1 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2002 J9 CURR DRUG METAB JI Curr. Drug Metab. PD SEP PY 2008 VL 9 IS 7 BP 614 EP 621 DI 10.2174/138920008785821666 PG 8 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 351TA UT WOS:000259447600005 PM 18781913 ER PT J AU Foster, PS Rosenberg, HF Asquith, KL Kumar, RK AF Foster, Paul S. Rosenberg, Helene F. Asquith, Kelly L. Kumar, Rakesh K. TI Targeting eosinophils in asthma SO CURRENT MOLECULAR MEDICINE LA English DT Review DE asthma; eosinophils; antiviral defense; interleukin-5 receptor; beta-common subunit ID BONE-MARROW EOSINOPHILOPOIESIS; ALLERGIC AIRWAY INFLAMMATION; RESPIRATORY SYNCYTIAL VIRUS; COLONY-STIMULATING FACTOR; PERSISTENT ASTHMA; EPITHELIAL-CELLS; MOUSE MODEL; IN-VITRO; MONOCLONAL-ANTIBODY; HUMAN INTERLEUKIN-5 AB Recruitment of eosinophils has long been recognized as a hallmark of the inflammatory response in asthma. However, the functions of this population of cells in host defense remain poorly understood. Eosinophils play an important part in the inflammatory response and have key regulatory roles in the afferent arm of the immune response. More recently, eosinophils have been demonstrated to participate in host defense against respiratory viruses. The specific contributions of eosinophils to the pathophysiology of asthma remain controversial. However, the balance of evidence indicates that they have a significant role in the disease, suggesting that they may be appropriate targets for therapy. Towards this end, a novel intervention of considerable potential interest is the use of an antibody directed against the common chain of the receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor. However, eliminating eosinophils may not be a risk-free therapeutic strategy, as there is potentially an increased likelihood of respiratory viral infections. This may predispose to the development of acute exacerbations of asthma, an outcome that would have significant clinical implications. C1 [Foster, Paul S.] Univ Newcastle, Ctr Asthma & Resp Dis, Fac Hlth, Discipline Immunol & Microbiol, Newcastle, NSW 2300, Australia. [Foster, Paul S.] Australian Natl Univ, John Curtin Sch Med Res, Div Mol Biosci, Canberra, ACT 2601, Australia. [Rosenberg, Helene F.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Kumar, Rakesh K.] Univ New S Wales, Sch Med Sci, Dept Pathol, Sydney, NSW, Australia. RP Foster, PS (reprint author), Univ Newcastle, Ctr Asthma & Resp Dis, Fac Hlth, Discipline Immunol & Microbiol, 5th Floor David Maddison Clin Sci Bldg,Cnr Watt &, Newcastle, NSW 2300, Australia. EM Paul.Foster@newcastle.edu.au RI Kumar, Rakesh/J-6124-2012; Foster, Paul/G-5057-2013 OI Kumar, Rakesh/0000-0002-9531-8411; FU Intramural NIH HHS [Z99 AI999999, ZIA AI000941-08, ZIA AI000943-08] NR 90 TC 18 Z9 19 U1 2 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD SEP PY 2008 VL 8 IS 6 BP 585 EP 590 DI 10.2174/156652408785748013 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 351SQ UT WOS:000259446600014 PM 18781965 ER PT J AU Kurkjian, C Kummar, S Murgo, AJ AF Kurkjian, Carlo Kummar, Shivaani Murgo, Anthony J. TI DNA Methylation: Its Role in Cancer Development and Therapy SO CURRENT PROBLEMS IN CANCER LA English DT Review ID ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; CPG ISLAND METHYLATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; ABERRANT PROMOTER METHYLATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMOR-SUPPRESSOR GENES; RENAL-CELL CARCINOMA; HELICOBACTER-PYLORI ERADICATION; LOW-DOSE 5-AZA-2'-DEOXYCYTIDINE C1 [Kurkjian, Carlo] NCI, Div Canc Treatment & Diagnosis, Adv Dev Therapeut Training Program, Bethesda, MD USA. [Kummar, Shivaani] Yale Univ, Ctr Canc, New Haven, CT USA. [Kummar, Shivaani] NCI, Med Oncol Branch, Ctr Clin Res, Bethesda, MD USA. [Kummar, Shivaani] Yale Univ, Dept Pharmacol, New Haven, CT 06520 USA. [Murgo, Anthony J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. [Murgo, Anthony J.] W Virginia Univ, Sch Med, Morgantown, WV 26506 USA. [Murgo, Anthony J.] W Virginia Univ, Hematol Oncol Sect, Morgantown, WV 26506 USA. [Murgo, Anthony J.] US FDA, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Kurkjian, C (reprint author), NCI, Div Canc Treatment & Diagnosis, Adv Dev Therapeut Training Program, Bethesda, MD USA. NR 256 TC 28 Z9 35 U1 0 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-0272 EI 1535-6345 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD SEP-OCT PY 2008 VL 32 IS 5 BP 185 EP 235 DI 10.1016/j.currproblcancer.2008.08.002 PG 51 WC Oncology SC Oncology GA 360ZL UT WOS:000260097200002 PM 18926281 ER PT J AU Longmire, M Choyke, PL Kobayashi, H AF Longmire, Michelle Choyke, Peter L. Kobayashi, Hisataka TI Dendrimer-based contrast agents for molecular imaging SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE dendrimer; contrast agent; molecular imaging; nanomedicine; magnetic resonance imaging; optical imaging; radionuclide imaging; multiple modalities ID MAGNETIC-RESONANCE; IN-VIVO; MRI; CORES; MICE; GENERATION; CHEMISTRY; DELIVERY AB The extensive adaptability of dendrimer-based contrast agents is ideal for the molecular imaging of organs and other target-specific locations. The ability of literally atom-by-atom modification on cores, interiors, and surface groups, permits the rational manipulation of dendrimer-based agents in order to optimize their physical characteristics, biodistribution, receptor-mediated targeting, and controlled release of the payload. Such modifications enable agents to localize preferentially to areas or organs of interest for facilitating target-specific imaging as well as assume excretion pathways that do not interfere with desired applications. Recent innovations in dendrimer research have increased agent directibility and new synthetic chemistry approaches have increased efficiency of production as well as led to the creation of novel dendrimer-based contrast agents. In addition, by taking advantage of the numerous attachment sites available on the surface of a single dendrimer molecule, new synthetic chemistry techniques have led to the development of multi-modality magnetic resonance, radionuclide, and fluorescence imaging agents for molecular imaging. Herein we discuss advances in dendrimer-based contrast agents for molecular imaging focusing mainly on the chemical design as applied to optical, magnetic resonance, computer tomography, radionuclide, and multi-modality imaging. C1 [Longmire, Michelle; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, NIH, Bldg 10,Room 1B40,MSC 1088, 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 27 TC 59 Z9 62 U1 0 U2 20 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD SEP PY 2008 VL 8 IS 14 BP 1180 EP 1186 DI 10.2174/156802608785849021 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 352MN UT WOS:000259501400004 PM 18855704 ER PT J AU Trinchieri, G AF Trinchieri, Giorgio TI Role of pro-inflammatory cytokines in carcinogenesis SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 231 EP 231 DI 10.1016/j.cyto.2008.07.020 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900003 ER PT J AU Thomas, E Hu, ZY Dong, S Feld, JJ Liang, TJ AF Thomas, Emmanuel Hu, Zongyi Dong, Stephen Feld, Jordan J. Liang, T. Jake TI A novel innate immune antiviral mechanism of action of ribavirin in mammalian cells contributes to efficacy of combination therapy for hepatitis C SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Thomas, Emmanuel; Hu, Zongyi; Dong, Stephen; Feld, Jordan J.; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 237 EP 237 DI 10.1016/j.cyto.2008.07.042 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900021 ER PT J AU Tsuno, T Mejido, J Zhao, TM Morrow, A Zoon, KC AF Tsuno, Takaya Mejido, Josef Zhao, Tongmao Morrow, Angel Zoon, Kathryn C. TI Roles of JAK-STAT pathway factors in antiproliferative activities of human IFN-alpha and IFN-gamma: A comprehensive assessment in human ovarian adenocarcinoma OVCAR3 cells SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Tsuno, Takaya; Mejido, Josef; Zhao, Tongmao; Morrow, Angel; Zoon, Kathryn C.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 237 EP 237 DI 10.1016/j.cyto.2008.07.043 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900022 ER PT J AU Bekisz, J Mejido, J Veenstra, T Zoon, K AF Bekisz, Joseph Mejido, Josef Veenstra, Timothy Zoon, Kathryn TI Gene and protein expression observed after treatment of Daudi cells with IFN-alpha 2c and IFN-alpha 21 beta SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Bekisz, Joseph; Mejido, Josef; Zoon, Kathryn] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Veenstra, Timothy] SAIC Frederick Inc, Natl Canc Inst, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 240 EP 240 DI 10.1016/j.cyto.2008.07.055 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900034 ER PT J AU Morrow, AN Schmeisser, H Tsuno, T Zoon, KC AF Morrow, Anzel N. Schmeisser, Hana Tsuno, Takaya Zoon, Kathryn C. TI Induction of ISGF3 in response to interferon gamma in human cells SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Morrow, Anzel N.; Schmeisser, Hana; Tsuno, Takaya; Zoon, Kathryn C.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 240 EP 241 DI 10.1016/j.cyto.2008.07.058 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900037 ER PT J AU Schmeisser, H Mejido, J Zoon, KC AF Schmeisser, Hana Mejido, Josef Zoon, Kathryn C. TI Identification of IFN-alpha-induced genes and proteins that are associated with antiviral activity in Daudi cells SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Schmeisser, Hana; Mejido, Josef; Zoon, Kathryn C.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 240 EP 240 DI 10.1016/j.cyto.2008.07.057 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900036 ER PT J AU Masters, SL Aksentijevich, I Ferguson, PJ Booty, MG Laurence, A Pham, H Stone, DL Cowen, EW Plass, N Bing, XY Clarke, GI Ohson, K Ei-Shanti, HI van Royen, A Frenk, J AF Masters, Seth L. Aksentijevich, Ivona Ferguson, Polly J. Booty, Matthew G. Laurence, Arian Pham, Hang Stone, Deborah L. Cowen, Edward W. Plass, Nicole Bing, Xinyu Clarke, Gillian I. Ohson, Kamal Ei-Shanti, Hatem I. van Royen, Annet Frenk, Joost TI Mutations in the interleulkin-1 receptor antagonist cause a new autoinflammatory disease SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Masters, Seth L.; Aksentijevich, Ivona; Booty, Matthew G.] Genet & Genom Branch, Bethesda, MD USA. [Pham, Hang; Stone, Deborah L.; Plass, Nicole] Off Clin Director, Bethesda, MD USA. [Laurence, Arian] NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. [Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ferguson, Polly J.; Bing, Xinyu; Ei-Shanti, Hatem I.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Ei-Shanti, Hatem I.] Shafallah Med Genet Ctr, Doha, Qatar. [van Royen, Annet] Univ Med Ctr, Div Pediat, Dept Gen Pediat, Utrecht, Netherlands. [Ohson, Kamal] Mem Univ Newfoundland, Dept Med, St John, NF A1C 5S7, Canada. [Clarke, Gillian I.] Div Dermatol, St John, NF, Canada. RI Laurence, Arian/A-8770-2009 OI Laurence, Arian/0000-0003-0942-8292 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 244 EP 245 DI 10.1016/j.cyto.2008.07.075 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900053 ER PT J AU Siegel, RM Kahle, E Acharya, K Fuss, I Wang, E Meylan, F AF Siegel, Richard M. Kahle, Erin Acharya, Krishika Fuss, Ivan Wang, Eddie Meylan, Francoise TI TL1A-DR3 interactions drive immunopathology mediated by multiple T-cell SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Siegel, Richard M.; Kahle, Erin; Acharya, Krishika; Meylan, Francoise] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy. [Fuss, Ivan] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Wang, Eddie] Cardiff Univ, Sch Med, Cardiff, Wales. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 246 EP 246 DI 10.1016/j.cyto.2008.07.082 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900060 ER PT J AU Schwartz, B Anton, K Koltchev, D Skawinski, M Clark, W Lavoie, T Izotova, LS Lembo, D Day, P Pang, S Schiller, JT Pestka, S AF Schwartz, Barbara Anton, Kevin Koltchev, Dolly Skawinski, Michael Clark, William Lavoie, Thomas Izotova, Lara S. Lembo, David Day, Patricia Pang, Susana Schiller, John T. Pestka, Sidney TI Ultra human interferons exhibit higher activity than the standard interferons in prevention of human papillomavirus infection in cells SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Schwartz, Barbara; Anton, Kevin; Pestka, Sidney] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet Microbiol & Immunol, Piscataway, NJ 08854 USA. [Koltchev, Dolly; Skawinski, Michael; Clark, William; Lavoie, Thomas; Izotova, Lara S.; Pestka, Sidney] PBL Biotechnol Labs, Piscataway, NJ 08854 USA. [Lembo, David] Univ Turin, Dept Publ Hlth & Microbiol, I-10126 Turin, Italy. [Day, Patricia; Pang, Susana; Schiller, John T.] NCI, NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 261 EP 261 DI 10.1016/j.cyto.2008.07.150 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900128 ER PT J AU Sato, N Waldmann, TA Tagaya, Y AF Sato, Noriko Waldmann, Thomas A. Tagaya, Yutaka TI Cytokine responses of naive T-cells requires special permission by accessory cells SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Sato, Noriko; Waldmann, Thomas A.; Tagaya, Yutaka] NCI, NIH, Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 267 EP 267 DI 10.1016/j.cyto.2008.07.173 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900150 ER PT J AU Borrego, F Narayanan, S Tang, XB Alvarez, Y Coligan, JE AF Borrego, Francisco Narayanan, Sriram Tang, Xiaobin Alvarez, Yelina Coligan, John E. TI The immunomodulatory CD300A receptor is differentially expressed on human TH1 and TH17 cells SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Borrego, Francisco; Narayanan, Sriram; Tang, Xiaobin; Alvarez, Yelina; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 272 EP 272 DI 10.1016/j.cyto.2008.07.198 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900174 ER PT J AU Boirivant, M Amendola, A Butera, A Sanchez, M Xu, LL Marinaro, M Kitani, A Di Giacinto, C Strober, W Fuss, IJ AF Boirivant, Monica Amendola, Antonello Butera, Alessia Sanchez, Massimo Xu, Lili Marinaro, Mariarosaria Kitani, Atsushi Di Giacinto, Claudia Strober, Warren Fuss, Ivan J. TI A transient breach in the epithelial barrier leads to regulatory T-cell generation and resistance to TNBS-colitis induction SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Boirivant, Monica; Amendola, Antonello; Butera, Alessia; Marinaro, Mariarosaria; Di Giacinto, Claudia] Ist Super Sanita, Dept Infect Parasit & Immunemed Dis, Immunemed Dis Sect, I-00161 Rome, Italy. [Sanchez, Massimo] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. [Xu, Lili; Kitani, Atsushi; Strober, Warren; Fuss, Ivan J.] NIAID, Mucosal Immun Sect, Host Def Lab, Bethesda, MD 20892 USA. RI BOIRIVANT, MONICA/B-9977-2016; AMENDOLA, ANTONELLO/B-9979-2016 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 273 EP 273 DI 10.1016/j.cyto.2008.07.203 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900179 ER PT J AU Pandiyan, P Lenardo, M AF Pandiyan, Pushpa Lenardo, Michael TI cytokines control CD4+CD25+Foxp3+regulatory T-cell survival and their mechanism of suppression SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Pandiyan, Pushpa; Lenardo, Michael] NIAID, Immunol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 273 EP 273 DI 10.1016/j.cyto.2008.07.201 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900177 ER PT J AU Ozato, K Tailor, P Ramakrishna, L Chang, TH Kubota, T Matsuoka, M Morse, CH AF Ozato, Keiko Tailor, Prafullakumar Ramakrishna, Lakshimi Chang, Tsung Hsien Kubota, Toru Matsuoka, Mayumi Morse, C. Herbert, III TI The mechanism of interferon gene transcription in dendritic cells SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Ozato, Keiko; Tailor, Prafullakumar; Ramakrishna, Lakshimi; Chang, Tsung Hsien; Kubota, Toru; Matsuoka, Mayumi] NICHD, Program Genom Differentiat, Bethesda, MD USA. [Kubota, Toru; Matsuoka, Mayumi] Natl Inst Infect Dis, Tokyo, Japan. [Morse, C. Herbert, III] NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 277 EP 277 DI 10.1016/j.cyto.2008.07.219 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900194 ER PT J AU Savan, R Yalamanchili, R Hakim, S Young, HA AF Savan, Ram Yalamanchili, Rajesh Hakim, Shakeeb Young, Howard A. TI The Role of miRNAs in the regulation of interferon-gamma gene expression SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Savan, Ram; Yalamanchili, Rajesh; Hakim, Shakeeb; Young, Howard A.] NCI, Canc & Inflammat Program, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 278 EP 278 DI 10.1016/j.cyto.2008.07.224 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900198 ER PT J AU O'Shea, J AF O'Shea, Jahn TI Cytokine signaling and T-cell differentiation SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [O'Shea, Jahn] NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 279 EP 279 DI 10.1016/j.cyto.2008.07.230 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900203 ER PT J AU Kennedy, MA Nechaev, S Gilchrist, DA Muse, GW Chinenov, Y Adelman, K Rogatsky, I AF Kennedy, Megan A. Nechaev, Sergei Gilchrist, Daniel A. Muse, Ginger W. Chinenov, Yurii Adelman, Karen Rogatsky, Inez TI Regulation of TNF alpha gene transcription at the post-initiation step SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Kennedy, Megan A.; Chinenov, Yurii; Rogatsky, Inez] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. [Kennedy, Megan A.; Chinenov, Yurii; Rogatsky, Inez] Cornell Univ, Hosp Special Surg, Weill Med Coll, New York, NY 10021 USA. [Nechaev, Sergei; Gilchrist, Daniel A.; Muse, Ginger W.; Adelman, Karen] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 280 EP 280 DI 10.1016/j.cyto.2008.07.234 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900206 ER PT J AU Klaschik, S Tross, D Klinman, DM AF Klaschik, Sven Tross, Debra Klinman, Dennis M. TI Inductive and suppressive networks regulate TLR19-dependent gene expression in vivo SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Klaschik, Sven; Tross, Debra; Klinman, Dennis M.] NCI, Expt Immunol Lab, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 283 EP 283 DI 10.1016/j.cyto.2008.07.248 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900220 ER PT J AU Petrenko, L Klaschik, S Shirota, H Klinman, DM AF Petrenko, Lev Klaschik, Sven Shirota, Hidekazu Klinman, Dennis M. TI Synergistic up-regulation of cytokine encoding genes by CpG oligonucleotides plus poly (I:C) SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Petrenko, Lev; Klaschik, Sven; Shirota, Hidekazu; Klinman, Dennis M.] NCI, Expt Immunol Lab, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 284 EP 284 DI 10.1016/j.cyto.2008.07.250 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900222 ER PT J AU Gamero, AM Scarzello, AJ Young, MR Mentor-Marcel, R Babe, G Wise, J Colburn, NH AF Gamero, Ana M. Scarzello, Anthony J. Young, Matthew R. Mentor-Marcel, Roycelynn Babe, Gerd Wise, Jennifer Colburn, Nancy H. TI STAT2 Contributes to inflammation-induced colorectal cancer SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Gamero, Ana M.] Temple Univ, Sch Med, Dept Biochem, Philadelphia, PA 19140 USA. [Scarzello, Anthony J.] NCI, Expt Immunol Lab, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA. [Young, Matthew R.; Mentor-Marcel, Roycelynn; Babe, Gerd; Wise, Jennifer; Colburn, Nancy H.] NCI, Lab Canc Prevent, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 290 EP 290 DI 10.1016/j.cyto.2008.07.279 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900250 ER PT J AU Snyder, GA Jiang, JS Xiao, T AF Snyder, Greg A. Jiang, Jiansheng Xiao, Tsan TI Mechanism of TOLL/IL-1 receptor domain dimerization and signaling revealed by a crystal structure of the MYD88 SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Snyder, Greg A.; Jiang, Jiansheng; Xiao, Tsan] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RI Xiao, Tsan/A-8590-2010 NR 0 TC 0 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 291 EP 291 DI 10.1016/j.cyto.2008.07.282 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900252 ER PT J AU Dufour, F Sasseville, AMJ Chabaud, S Siegel, RM Massie, B Largelier, Y AF Dufour, Florent Sasseville, A. Marie-Josee Chabaud, Stephane Siegel, Richard M. Massie, Bernard Largelier, Yves TI The R1 subunit of Herpes simplex virus type 2 ribonucleotide reductase protects cells against TNF-alpha and double-stranded-RNA-induced apoptosis by direct interaction with procaspase-8 SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Dufour, Florent; Sasseville, A. Marie-Josee; Chabaud, Stephane; Largelier, Yves] CHU Montreal, Ctr Rech, Montreal, PQ, Canada. [Dufour, Florent; Sasseville, A. Marie-Josee; Chabaud, Stephane; Largelier, Yves] Hop Notre Dame De Bon Secours, Inst Canc Montreal, Montreal, PQ, Canada. [Massie, Bernard; Largelier, Yves] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada. [Massie, Bernard] Inst Rech Biotechnol, Montreal, PQ, Canada. [Siegel, Richard M.] NIAMS, Immunoregulat Unit, Autoimmun Branch, NIH, Bethesda, MA USA. [Massie, Bernard] Univ Quebec, Inst Armand Frappier, INRS, Laval, PQ, Canada. [Largelier, Yves] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 300 EP 300 DI 10.1016/j.cyto.2008.07.322 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900291 ER PT J AU Feldmann, H AF Feldmann, Heinz TI Ebola and Marburg viruses: Immunopathology and immunoprotection SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Feldmann, Heinz] NIAID, Rocky Mt Labs, Virol Lab, NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 302 EP 302 DI 10.1016/j.cyto.2008.07.330 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900298 ER PT J AU Leonard, W AF Leonard, Warren TI Signaling and gene regulation by gamma c-dependent cytokines SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Leonard, Warren] NHLBI, Lab Mol Immunol, Div Intramural Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 304 EP 304 DI 10.1016/j.cyto.2008.07.335 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900302 ER PT J AU Shevach, EM Huter, E Tran, D Andersson, J AF Shevach, Ethan M. Huter, Eva Tran, Dar Andersson, John TI Control of immune responses by natural and adaptive regulatory T cells SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Shevach, Ethan M.; Huter, Eva; Tran, Dar; Andersson, John] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 305 EP 305 DI 10.1016/j.cyto.2008.07.339 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900306 ER PT J AU Li, WQ Guszczynski, T Hixon, J Durum, SK AF Li, Wenqing Guszczynski, Tad Hixon, Julie Durum, Scott K. TI Development and maintenance of T-cell requires post-translational regulation of anti-apoptotic MCL-1 and pro-apoptotic BIM by IL-7 SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Li, Wenqing; Hixon, Julie; Durum, Scott K.] NCI, Lab Mol Immunoregulat Canc & Inflammat Program, CCR, NIH, Frederick, MD 21701 USA. [Guszczynski, Tad] NCI, Lab Cell & Dev Signaling, CCR, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 306 EP 306 DI 10.1016/j.cyto.2008.07.344 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900310 ER PT J AU Hodge, DL Berthet, C Subleski, J Bere, W Chen, X Coppola, V Buschman, M Wolfe, T Shuggi, I Young, HA AF Hodge, Deborah L. Berthet, Cyril Subleski, Jeff Bere, William Chen, Xin Coppola, Vincenzo Buschman, Matthew Wolfe, Thomas Shuggi, Isabelle Young, Howard A. TI IFN-gamma 3 ' untranslated region AU-RICH element-deleted mice have altered immune structure and function SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Hodge, Deborah L.; Subleski, Jeff; Bere, William; Buschman, Matthew; Wolfe, Thomas; Shuggi, Isabelle; Young, Howard A.] NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21702 USA. [Berthet, Cyril; Coppola, Vincenzo] NCI, Mouse Canc Genet Program, Canc Res Ctr, Frederick, MD 21702 USA. [Chen, Xin] NCI, Mol Immunoregulat Lab, Canc Res Ctr, Frederick, MD 21702 USA. RI Coppola, Vincenzo/E-2917-2011; Chen, Xin/I-6601-2015 OI Coppola, Vincenzo/0000-0001-6163-1779; Chen, Xin/0000-0002-2628-4027 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 313 EP 313 DI 10.1016/j.cyto.2008.07.376 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900341 ER PT J AU Mielke, LA Elkins, K Starr, R Hilton, DJ Tsichlis, P O'Shea, JJ Watford, WT AF Mielke, Lisa A. Elkins, Karen Starr, Robyn Hilton, Douglas J. Tsichlis, Philip O'Shea, John J. Watford, Wendy T. TI Receptor and cell-specific function of MAP3K8/TPL2 in innate immune signaling and cytokine production SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Mielke, Lisa A.; O'Shea, John J.; Watford, Wendy T.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Mielke, Lisa A.; Hilton, Douglas J.] Walter & Eliza Hall Inst Med Res, Div Mol Med, Parkville, Vic, Australia. [Mielke, Lisa A.] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia. [Elkins, Karen] US FDA, CEBR, Div Bacterial Parasit & Allergen Prod, Rockville, MD 20857 USA. [Starr, Robyn] St Vincents Inst, Signal Transduct Lab, Melbourne, Vic, Australia. [Tsichlis, Philip] Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA USA. RI Hilton, Douglas/C-7250-2013 OI Hilton, Douglas/0000-0002-7698-2392 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 314 EP 314 DI 10.1016/j.cyto.2008.07.381 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900346 ER PT J AU Brann, TW Yang, J Huang, DW Frank, A Lempicki, RA Baseler, MW Kottilili, S Lane, HC Imamichi, T AF Brann, Terrence W. Yang, Jun Huang, Da-Wei Frank, Astrid Lempicki, Richard A. Baseler, Michael W. Kottilili, Shaym Lane, H. Clifford Imamichi, Tom TI IL-27 is a novel anti-viral cytokine that inhibits replication of HIV-1 and HCV SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Brann, Terrence W.; Imamichi, Tom] NCI, Lab Human Retrovirol, SAIC Frederick Inc, Frederick, MD 21701 USA. [Yang, Jun; Huang, Da-Wei; Lempicki, Richard A.] NCI, Lab Immunopathogenesis & Bioinformat, SAIC Frederick Inc, Frederick, MD 21701 USA. [Frank, Astrid; Kottilili, Shaym; Lane, H. Clifford] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Baseler, Michael W.] NCI, AIDS Monitoring Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 320 EP 321 DI 10.1016/j.cyto.2008.07.408 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900372 ER PT J AU Baron, S Poast, J Suzuki, F Kobayashi, M Clouse, K Bacot, S Tiffany, L Lankford, C Boekhoudt, G Morrow, A Fey, S Schmeisser, H Bekisz, J Zoon, K AF Baron, Samuel Poast, Joyce Suzuki, Fujio Kobayashi, Makiko Clouse, Kathleen Bacot, Sylvia Tiffany, Linda Lankford, Carla Boekhoudt, Gunther Morrow, Angel Fey, Samuel Schmeisser, Hana Bekisz, Joseph Zoon, Kathryn TI Innate immunity: Preclinical study of eradication of tumor cells by IFN-activated monocytes in vitro and in vivo SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Baron, Samuel; Poast, Joyce] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX USA. [Baron, Samuel; Suzuki, Fujio; Kobayashi, Makiko] Univ Texas Med Branch, Dept Internal Med, Galveston, TX USA. [Clouse, Kathleen; Bacot, Sylvia; Tiffany, Linda; Lankford, Carla; Boekhoudt, Gunther] US FDA, Bethesda, MD 20014 USA. [Baron, Samuel; Morrow, Angel; Fey, Samuel; Schmeisser, Hana; Bekisz, Joseph; Zoon, Kathryn] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 322 EP 322 DI 10.1016/j.cyto.2008.07.415 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900379 ER PT J AU Wilhelm, C Di Mascio, M Hu, ZH Srinivasula, S Thaker, V Adelsberger, J Rupert, A Baseler, M Tagaya, Y Roby, G Rehm, C Follmann, D Lane, C Catalfarno, M AF Wilhelm, Christopher Di Mascio, Michele Hu, Zonghui Srinivasula, Sharat Thaker, Vishakha Adelsberger, Joseph Rupert, Adam Baseler, Michael Tagaya, Yutaka Roby, Gregg Rehm, Catherine Follmann, Dean Lane, Clifford Catalfarno, Marta TI HIV Infection leads to increased proliferation of T-cells by two distinct pathways that differentially affect CD4 and CD8 T-cells SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Wilhelm, Christopher; Thaker, Vishakha; Roby, Gregg; Rehm, Catherine; Lane, Clifford; Catalfarno, Marta] NIAID, CMRS, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Di Mascio, Michele; Hu, Zonghui; Follmann, Dean] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Srinivasula, Sharat] NCI, Biostat Res Branch, SAIC Frederick Inc, Frederick, MD 21701 USA. [Adelsberger, Joseph; Rupert, Adam; Baseler, Michael] NCI, AIDS Monitoring Labs, SAIC Frederick Inc, Frederick, MD 21701 USA. [Tagaya, Yutaka] NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 322 EP 322 DI 10.1016/j.cyto.2008.07.416 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900380 ER PT J AU Hendee, WR Cleary, K Ehman, RL Fullerton, GD Grundfest, WS Haller, J Kelley, CA Meyer, AE Murphy, RF Phillips, W Torchilin, VP AF Hendee, William R. Cleary, Kevin Ehman, Richard L. Fullerton, Gary D. Grundfest, Warren S. Haller, John Kelley, Christine A. Meyer, Anne E. Murphy, Robert F. Phillips, William Torchilin, Vladimir P. TI Bioengineering and Imaging Research Opportunities Workshop V: A summary on imaging and characterizing structure and function in native and engineered tissues SO CYTOMETRY PART A LA English DT Editorial Material DE tissue engineering; functional; molecular and structural imaging; imaging of engineered tissues; targeted cell, gene, and drug delivery; single-cell measurements; emerging imaging technologies ID MAGNETIC-RESONANCE ELASTOGRAPHY; CANCER-THERAPY; WHITE PAPER; MICROSCOPY; RECOMMENDATIONS; VISUALIZATION; SYSTEMS AB The Fifth Bioengineering and Imaging Research Opportunities Workshop (BIROW V) was held on January 18-19, 2008. As with previous BIROW meetings, the purpose of BIROW V was to identify and characterize research and engineering opportunities in biomedical engineering and imaging. The topic of this BIROW meeting was Imaging and Characterizing Structure and Function in Native and Engineered Tissues. Under this topic, four areas were explored in depth: 1) Heterogeneous single-cell measurements and their integration into tissue and organism models; 2) Functional, molecular, and structural imaging of engineered tissue in vitro and in vivo; 3) New technologies for characterizing cells and tissues in situ; 4) Imaging for targeted cell, gene, and drug delivery. (C) 2008 international Society for Advancement of Cytometry. C1 [Hendee, William R.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. [Cleary, Kevin] Georgetown Univ, Dept Radiol, Imaging Sci & Informat Syst Ctr, Washington, DC USA. [Ehman, Richard L.] Mayo Clin, Dept Radiol, Rochester, MI USA. [Fullerton, Gary D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Grundfest, Warren S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Haller, John] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Kelley, Christine A.] Natl Inst Biomed Imaging & Bioengn, Div Discovery Sci & Technol, NIH, Bethesda, MD USA. [Meyer, Anne E.] SUNY Buffalo, Biomat Grad Program, Buffalo, NY USA. [Murphy, Robert F.] Carnegie Mellon Univ, Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. [Phillips, William] Univ Texas Med Ctr, Dept Radiol, San Antonio, TX USA. [Torchilin, Vladimir P.] Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. [Torchilin, Vladimir P.] Northeastern Univ, Ctr Pharmaceut Biotechnol & Nanomed, Boston, MA 02115 USA. RP Hendee, WR (reprint author), Med Coll Wisconsin, Dept Radiol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM whendee@mcw.edu NR 26 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD SEP PY 2008 VL 73A IS 9 BP 779 EP 784 DI 10.1002/cyto.a.20568 PG 6 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 343XV UT WOS:000258890500002 PM 18677767 ER PT J AU Roederer, M Moody, MA AF Roederer, Mario Moody, M. Anthony TI PolyChromatic plots: Graphical display of multidimensional data SO CYTOMETRY PART A LA English DT Article ID SYSTEMS; POINTS; SPACE AB Limitations of graphical displays as well as human perception make the presentation and analysis of multidimensional data challenging. Graphical display of information on paper or by current projectors is perforce limited to two dimensions; the encoding of information from other dimensions must be overloaded into the two physical dimensions. A number of alternative means of encoding this information have been implemented, such as offsetting data points at an angle (e.g., three-dimensional projections onto a two-dimensional surface) or generating derived parameters that are combinations of other variables (e.g., principal components). Here, we explore the use of color to encode additional dimensions of data. PolyChromatic Plots are standard dot plots, where the color of each event is defined by the values of one, two, or three of the measurements for that event. The measurements for these parameters are mapped onto an intensity value for each primary color (red, green, or blue) based on different functions. In addition, differential weighting of the priority with which overlapping events are displayed can be defined by these same measurements. PolyChromatic Plots can encode up to five independent dimensions of data in a single display. By altering the color mapping function and the priority function, very different displays that highlight or de-emphasize populations of events can be generated. As for standard black-and-white dot plots, frequency information can be significantly biased by this display; care must be taken to ensure appropriate interpretation of the displays. PolyChromatic Plots are a powerful display type that enables rapid data exploration. By virtue of encoding as many as five dimensions of data independently, an enormous amount of information can be gleaned from the displays. In many ways, the display performs somewhat like an unsupervised cluster algorithm, by highlighting events of similar distributions in multivariate space. Published 2008 Wiley-Liss, Inc. C1 [Roederer, Mario] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Moody, M. Anthony] Duke Univ, Dept Pediat, Sch Med, Durham, NC 27706 USA. RP Roederer, M (reprint author), NIH, Vaccine Res Ctr, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA. EM Roederer@nih.gov OI Moody, Tony/0000-0002-3890-5855 FU Intramural NIH HHS [Z01 AI005020-06] NR 11 TC 10 Z9 11 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD SEP PY 2008 VL 73A IS 9 BP 868 EP 874 DI 10.1002/cyto.a.20610 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 343XV UT WOS:000258890500012 PM 18629844 ER PT J AU El-Bizri, N Guignabert, C Wang, L Cheng, A Stankunas, K Chang, CP Mishina, Y Rabinovitch, M AF El-Bizri, Nesrine Guignabert, Christophe Wang, Lingli Cheng, Alexander Stankunas, Kryn Chang, Ching-Pin Mishina, Yuji Rabinovitch, Marlene TI SM22 alpha-targeted deletion of bone morphogenetic protein receptor 1A in mice impairs cardiac and vascular development, and influences organogenesis SO DEVELOPMENT LA English DT Article DE Bmpr1a (Alk3); vasculogenesis; heart development; craniofacial development; matrix metalloproteinase (metallopeptidase); MMP2; MMP9; smooth muscle cell proliferation; pericyte apoptosis; SM22 alpha (transgelin, Tagln); mouse ID PRIMARY PULMONARY-HYPERTENSION; MATRIX METALLOPROTEINASE-2 EXPRESSION; ABDOMINAL AORTIC-ANEURYSMS; MUSCLE-CELL MIGRATION; RAT CAROTID-ARTERY; SMOOTH-MUSCLE; ENDOCARDIAL CUSHION; KNOCKOUT MICE; MOUSE EMBRYOS; TGF-BETA AB Expression of bone morphogenetic protein receptor 1A (BMPR1A) is attenuated in the lung vessels of patients with pulmonary arterial hypertension, but the functional impact of this abnormality is unknown. We ablated Bmpr1a in cardiomyocytes and vascular smooth muscle cells (VSMCs) by breeding mice possessing a loxP allele of Bmpr1a (Bmpr1a(flox)) expressing R26R with SM22 alpha-Cre mice. SM22 alpha-Cre;R26R;Bmpr1a(flox/flox) mice died soon after embryonic day 11 (E11) with massive vascular and pericardial hemorrhage and impaired brain development. At E10.5, SM22 alpha-Cre;R26R;Bmpr1a(flox/flox) embryos showed thinning of the myocardium associated with reduced cell proliferation. These embryos also had severe dilatation of the aorta and large vessels with impaired investment of SMCs that was also related to reduced proliferation. SM22 alpha-Cre;R26R;Bmpr1a(flox/flox) mice showed collapsed telencephalon in association with impaired clearing of brain microvessels in areas where reduced apoptosis was observed. Transcript and protein levels of matrix metalloproteinase (MMP) 2 and 9 were reduced in E9.5 and E10.5 SM22 alpha-Cre; R26R;Bmpr1a(flox/flox) embryos, respectively. Knock-down of BMPR1A by RNA interference in human pulmonary artery SMCs reduced MMP2 and MMP9 activity, attenuated serum-induced proliferation, and impaired PDGF-BB-directed migration. RNA interference of MMP2 or MMP9 recapitulated these abnormalities, supporting a functional interaction between BMP signaling and MMP expression. In human brain microvascular pericytes, knock-down of BMPR1A reduced MMP2 activity and knock-down of either BMPR1A or MMP2 caused resistance to apoptosis. Thus, loss of Bmpr1a, by decreasing MMP2 and/or MMP9 activity, can account for vascular dilatation and persistence of brain microvessels, leading to the impaired organogenesis documented in the brain. C1 [El-Bizri, Nesrine; Guignabert, Christophe; Wang, Lingli; Cheng, Alexander; Rabinovitch, Marlene] Stanford Univ, Sch Med, Cardiopulmonary Res Program, Vera Moulton Wall Ctr Pulm Vasc Dis, Stanford, CA 94305 USA. [El-Bizri, Nesrine; Guignabert, Christophe; Wang, Lingli; Cheng, Alexander; Rabinovitch, Marlene] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. [Stankunas, Kryn; Chang, Ching-Pin] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Mishina, Yuji] Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Mol Dev Biol Grp, Res Triangle Pk, NC USA. RP Rabinovitch, M (reprint author), Stanford Univ, Sch Med, Cardiopulmonary Res Program, Vera Moulton Wall Ctr Pulm Vasc Dis, Stanford, CA 94305 USA. EM marlener@stanford.edu FU Intramural NIH HHS; NHLBI NIH HHS [HL085345, R01 HL074186, R01 HL074186-01A1, R01 HL074186-02, R01 HL074186-03, R01 HL074186-04, R01 HL074186-05, R01 HL085345, R01 HL087118, R01 HL087118-01A1] NR 61 TC 27 Z9 27 U1 1 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP 1 PY 2008 VL 135 IS 17 BP 2981 EP 2991 DI 10.1242/dev.017863 PG 11 WC Developmental Biology SC Developmental Biology GA 336WL UT WOS:000258395500016 PM 18667463 ER PT J AU Crowe, SL Blair, RJR AF Crowe, S. L. Blair, R. J. R. TI The development of antisocial behavior: What can we learn from functional neuroimaging studies? SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; INTERMITTENT EXPLOSIVE DISORDER; POSITRON-EMISSION TOMOGRAPHY; CALLOUS-UNEMOTIONAL TRAITS; CEREBRAL-BLOOD-FLOW; VENTROMEDIAL PREFRONTAL CORTEX; PEDIATRIC BIPOLAR DISORDER; VOXEL-BASED MORPHOMETRY; CHILDHOOD SEXUAL-ABUSE; TEMPORAL-LOBE EPILEPSY AB The recent development of low-risk imaging technologies. such as functional magnetic resonance imaging (fMRI), have had a significant impact on the investigation of psychopathologies in children and adolescents. This review considers what we can infer from fMRI work regarding the development of conduct disorder (CD) and oppositional defiant disorder (ODD). We make two central assumptions that are grounded in the empirical literature. First the diagnoses of CD and ODD identify individuals with heterogeneous pathologies: that is, different developmental pathologies can receive a and ODD identify individuals with heterogeneous pathologies: that is, different developmental pathologies can receive a CDD or ODD diagnosis. This is indicated by the comorbidities associated with CD/ODD. some of which appear to be mutually exclusive at the biological level (e.g., posttraumatic stress disorder [PTSD] and psychopathic tendencies). Second, two populations of antisocial individuals can be identified: those that show an increased risk for only reactive aggression and those that show an increased risk for both reactive and instrumental aggression. We review the fMRI data indicating that particular comorbidities of CD/ODD (i.e., mood and anxiety conditions such as childhood bipolar disorder and PTSD) are associated with either increased responsiveness of neural regions implicated in the basic response to threat (e.g., the amygdala) or decreased responsiveness in regions of frontal cortex (e.g., ventromedial frontal cortex) that are implicated in the regulation of the basic threat response. We suggest why such pathology would increase the risk for reactive aggression and, in turn, lead to the association with a CD/ODD diagnosis. We also review the literature on psychopathic tendencies, a condition where the individual is at significantly elevated risk for both reactive and instrumental aggression. We show that in individuals with psychopathic tendencies, the functioning of the amygdala in stimulus-reinforcement learning and of the ventromedial frontal cortex in the representation of reinforcement expectancies is impaired. We suggest why such pathology would increase the risk for reactive and instrumental aggression and thus also lead to the association with a CD/ODD diagnosis. C1 [Blair, R. J. R.] NIMH, Mood & Anxiety Program, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Program, Natl Inst Hlth, 15 K N Dr, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov FU Intramural NIH HHS NR 142 TC 57 Z9 59 U1 9 U2 30 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD FAL PY 2008 VL 20 IS 4 BP 1145 EP 1159 DI 10.1017/S0954579408000540 PG 15 WC Psychology, Developmental SC Psychology GA 373SU UT WOS:000260993800007 PM 18838035 ER PT J AU Lenroot, RK Giedd, JN AF Lenroot, Rhoshel K. Giedd, Jay N. TI The changing impact of genes and environment on brain development during childhood and adolescence: Initial findings from a neuroimaging study of pediatric twins SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID STRESSFUL LIFE EVENTS; MONOZYGOTIC TWINS; CORTICAL THICKNESS; MALTREATED CHILDREN; UNAFFECTED SIBLINGS; ONSET SCHIZOPHRENIA; MAJOR DEPRESSION; DIZYGOTIC TWINS; EEG COHERENCE; CHORION TYPE AB Human brain development is created through continuing complex interactions of genetic and environmental influences. The challenge of linking specific genetic or environmental risk factors to typical or atypical behaviors has led to interest in using brain structural features as an intermediate phenotype. Twin studies in adults have found that many aspects of brain anatomy are highly heritable. demonstrating that genetic factors provide a significant contribution to variation in brain structures. Less is known about the relative impact of genes and environment while the brain is actively developing. We summarize results from the ongoing National Institute of Mental Health child and adolescent twin study that suggest that heritability of different brain areas changes over the course of development in a regionally specific fashion. Areas associated with more complex reasoning abilities become increasingly heritable with maturation. The potential mechanisms by which gene-environment interactions may affect heritability values during development is discussed. C1 [Giedd, Jay N.] NIMH, Child Psychiat Branch, Brain Imaging Unit, Bethesda, MD 20892 USA. RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, Brain Imaging Unit, 10 Ctr Dr,MSC 1600,Bldg 10,Room 4C110, Bethesda, MD 20892 USA. EM jg@nih.gov RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU Intramural NIH HHS [ZIA MH002794-08] NR 113 TC 44 Z9 44 U1 6 U2 17 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD FAL PY 2008 VL 20 IS 4 BP 1161 EP 1175 DI 10.1017/S0954579408000552 PG 15 WC Psychology, Developmental SC Psychology GA 373SU UT WOS:000260993800008 PM 18838036 ER PT J AU Maheu, FS Mazzone, L Merke, DP Keil, M Stratakis, CA Pine, DS Ernst, M AF Maheu, Francoise S. Mazzone, Luigi Merke, Deborah P. Keil, Margaret Stratakis, Constantine A. Pine, Daniel S. Ernst, Monique TI Altered amygdala and hippocampus function in adolescents with hypercortisolemia: A functional magnetic resonance imaging study of Cushing syndrome SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; MEMORY CONSOLIDATION; CORTISOL SECRETION; COGNITIVE DECLINE; ANIMAL-MODELS; STRESS; CHILDREN; BRAIN; FMRI; EXPERIENCE AB Chronic elevations of endogenous cortisol levels have been shown to alter medial temporal cortical structures and to be accompanied by declarative memory impairments and depressive symptons in human adults. These effects of elevated endogenous levels of cortisol have not been directly Studied in adolescents. Because adolescents with Cushing syndrome show endogenous elevations in cortisol, they, represent a unique natural model to study the effects of prolonged hypercortisolemia on brain fuction. and memory and affective processes during this developmental stage. Using functional magnetic resonance imaging (fMRI), we compared 12 adolescents with Cushing syndrome with 22 healthy control adolescents on amygdala and anterior hippocampus activation during an emotional faces encoding task. None of these adolescents manifested depressive symptoms. Encoding Success was assessed using a memory recognition test performed after the scan. The fMRI analyses followed all event-related design and were conducted using the SPM99 platform. Compared to healthy adolescents, patients with Cushing syndrome showed greater left amygdala and right anterior hippocampus activation during Successful face encoding. Memory performance for faces recognition did riot differ between groups. This first study of cerebral function in adolescents with chronic endogeneous hypercortisolemia due to Cushing syndrome demonstrates the presence of functional alterations in amygdala and hippocampus, which are not associated with affective or memory impairments. Such findings need to be followed by work examining the role of age and related brain maturational stage on these effects, as well as the identification of possible protective factors conferring resilience to affective and cognitive consequences in this disease and/or during this stage of cerebral development. C1 [Ernst, Monique] NIMH, Mon Ernst Emot Dev & Affec Neurosci Branch, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, Mon Ernst Emot Dev & Affec Neurosci Branch, Mood & Anxiety Disorders Program, 15K N Dr,Room 118, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov FU Intramural NIH HHS [ZIA HD000642-13] NR 58 TC 26 Z9 26 U1 2 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD FAL PY 2008 VL 20 IS 4 BP 1177 EP 1189 DI 10.1017/S0954579408000564 PG 13 WC Psychology, Developmental SC Psychology GA 373SU UT WOS:000260993800009 PM 18838037 ER PT J AU Sperber, SM Dawid, IB AF Sperber, Steven M. Dawid, Igor B. TI barx1 is necessary for ectomesenchyme proliferation and osteochondroprogenitor condensation in the zebrafish pharyngeal arches SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Barx1; pharyngogenesis; viscerocranium; zebrafish; pharyngeal arches; neural crest; chondrogenesis; cartilage; BMP; FGF ID CRANIOFACIAL DEVELOPMENT; HOMEOBOX GENE; CARTILAGE MORPHOGENESIS; VASCULAR DEVELOPMENT; SKELETAL DEVELOPMENT; LIMB DEVELOPMENT; BRANCHIAL ARCH; EXPRESSION; FGF; CHONDROGENESIS AB Barx1 modulates cellular adhesion molecule expression and participates in specification of tooth-types, but little is understood of its role in patterning the pharyngeal arches. We examined barx1 expression during zebrafish craniofacial development and performed a functional analysis using antisense morpholino Oligonucleotides. Barx1 is expressed in the rhombencephalic neural crest, the pharyngeal arches, the pectoral fill buds and the gut in contrast to its paralogue barx2, which is most prominently expressed ill the arch epithelium. Additionally, barx1 transient expression was observed in the posterior lateral line ganglia and developing trunk/tail. We show that Barx1 is necessary for proliferation of the arch osteochondrogenic progenitors, and that morphants exhibit diminished and dysmorphic arch cartilage elements due to reductions in chondrocyte differentiation and condensation. Attenuation of Barx1 results in lost arch expression of osteochondrogenic markers col2al, runx2a and chondromodulin, as well as odontogenic marker dlx2b. Further, loss of barx1 positively influenced gdf5 and chordin, markets of jaw joint patterning. FGF signaling is required for maintaining barx1 expression, and that ectopic BMP4 induces expression of barx1 ill the intermediate region of the second pharyngeal arch. Together, these results indicate ail essential role for barx1 at early stages of chondrogenesis within the developing zebrafish viscerocranium. Published by Elsevier Inc. C1 [Sperber, Steven M.; Dawid, Igor B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, Bethesda, MD 20892 USA. RP Sperber, SM (reprint author), Natl Inst Child Hlth, Mol Genet Lab, Bldg 6B,Room 422,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sperbers@mail.nih.gov FU NICHD; NIH FX We thank Pfizer Inc. for the generous gift of the SU5402, Dr. Chisa Shukunami for chondromodulin, Dr. Matthias Hammerschmidt for the lia embryos: Drs. Tom Sargent and Ting Luo for the inca probe. Dr. Marc Ekker for the dlx2b probe, our laboratory colleagues for their helpful discussions, Dr. G.H. Sperber and the NIH Fellows Editorial Board for their comments oil the manuscript, and Mark Rath and John Gonzales for their assistance with zebrafish husbandry. This research has been supported by the Intramural Program of the NICHD, NIH. NR 71 TC 35 Z9 36 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 1 PY 2008 VL 321 IS 1 BP 101 EP 110 DI 10.1016/j.ydbio.2008.06.004 PG 10 WC Developmental Biology SC Developmental Biology GA 341JP UT WOS:000258710800009 PM 18590717 ER PT J AU Moore, AF Jablonski, KA McAteer, JB Saxena, R Pollin, TI Franks, PW Hanson, RL Shuldiner, AR Knowler, WC Altshuler, D Florez, JC AF Moore, Allan F. Jablonski, Kathleen A. McAteer, Jarred B. Saxena, Richa Pollin, Toni I. Franks, Paul W. Hanson, Robert L. Shuldiner, Alan R. Knowler, William C. Altshuler, David Florez, Jose C. CA Diabetes Prevent Program Res Grp TI Extension of type 2 diabetes genome-wide association scan results in the Diabetes Prevention Program SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; INSULIN-RESISTANCE; GLUCOSE-TOLERANCE; VARIANTS; SUSCEPTIBILITY; LOCI; POLYMORPHISMS; SECRETION; CDKAL1; GENES AB OBJECTIVE-Genome-wide association scans (GWASs) have identified novel diabetes-associated genes. We evaluated how these variants impact diabetes incidence, quantitative glycemic traits, and response to preventive interventions in 3,548 Subjects at high risk of type 2 diabetes enrolled in the Diabetes Prevention Program (DPP), which examined the effects of lifestyle intervention, metformin, and troglitazone versus placebo. RESEARCH DESIGN AND METHODS-We genotyped selected single nucleotide polymorphisms (SNPs) in or near diabetes-associated loci, including EXT2, CDKAL1, CDKN2A/B, IGF2BP2, HHEX, LOC387761, and SLC30A8 in DPP participants and performed Cox regression analyses using genotype, intervention, and their interactions as predictors of diabetes incidence. We evaluated their effect on insulin resistance and secretion at 1 year. RESULTS-None of the selected SNPs were associated with increased diabetes incidence in this population. After adjustments for ethnicity, baseline insulin secretion was lower in subjects with the risk genotype at HHEX rs1111875 (P = 0.01); there were no significant differences in baseline insulin sensitivity. Both at baseline and at 1 year, subjects with the risk genotype at, LOC387761 had paradoxically increased insulin secretion; adjustment for self-reported effinicity abolished these differences. In ethnicity-adjusted analyses, we noted a nominal differential improvement in P-cell function for carriers of the protective genotype at CDKN2A/B after 1 year of troglitazone treatment (P = 0.01) and possibly lifestyle modification (P = 0.05). CONCLUSIONS-We were unable to replicate the GWAS findings regarding diabetes risk in the DPP. We did observe genotype associations with differences in baseline insulin secretion at the HHEX locus and a possible pharmacogenetic interaction at CDKNA2/B. C1 [Moore, Allan F.; McAteer, Jarred B.; Saxena, Richa; Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Med, Boston, MA 02114 USA. [Moore, Allan F.; Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Diabet, Dept Med, Boston, MA 02114 USA. [Moore, Allan F.; Altshuler, David; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Moore, Allan F.; McAteer, Jarred B.; Saxena, Richa; Altshuler, David; Florez, Jose C.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Moore, Allan F.; McAteer, Jarred B.; Saxena, Richa; Altshuler, David; Florez, Jose C.] MIT, Cambridge, MA 02139 USA. [Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Pollin, Toni I.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Franks, Paul W.] Umea Univ Hosp, Genet Epidemiol & Clin Res Grp, Dept Publ Hlth & Clin Med, Div Med, S-90185 Umea, Sweden. [Hanson, Robert L.; Knowler, William C.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Med, Boston, MA 02114 USA. EM dppmail@biostat.bsc.gwuj.edu RI Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009; Hanson, Robert/O-3238-2015; Uwaifo, Gabriel/M-2361-2016 OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858; Hanson, Robert/0000-0002-4252-7068; Uwaifo, Gabriel/0000-0002-6962-9304 FU National Institutes of Health [R01-DK-072041]; Doris Duke Charitable Foundation Distinguished Scientist Clinical Award; NIH Research Career Award [K23-DK-65978-04]; The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIDDK; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association; McKesson BioServices; Matthews Media Group; Henry M. Jackson Foundation FX K.A.J. has received National Institutes of Health (NIH) Grant R01-DK-072041. T.I.P. has received NIH Grant R01-DK-072041. A.R.S. has received NIH Grant R01-DK-072041. D.A. has received NIH Grant R01-DK-072041 and a Doris Duke Charitable Foundation Distinguished Scientist Clinical Award. J.C.F. has received NIH Grant R01-DK-072041 and NIH Research Career Award K23-DK-65978-04. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH provided funding to the clinical centers and the coordinating center for the design and conduct of the study, collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported in part by the intramural research program of the NIDDK. LifeScan, Health O Meter, Hoechst Marion Roussel, Merck-Medco Managed Care, Merck, Nike Sports Marketing, Slim Fast Foods, and Quaker Oats donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices, Matthews Media Group, and the Henry M. Jackson Foundation provided support services under subcontract with the coordinating center. The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian Health Service or other funding agencies. A complete list of centers, investigators, and staff can be found in the online appendix. We gratefully acknowledge the commitment and dedication of all participants in the DPP, without whom this work would not have been possible. NR 26 TC 60 Z9 61 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2008 VL 57 IS 9 BP 2503 EP 2510 DI 10.2337/db08-0284 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 343QP UT WOS:000258869000029 PM 18544707 ER PT J AU Bainbridge, KE Cowie, CC Rust, KF Fradkin, JE AF Bainbridge, Kathleen E. Cowie, Catherine C. Rust, Keith F. Fradkin, Judith E. TI Mitigating case mix factors by choice of glycemic control performance measure threshold SO DIABETES CARE LA English DT Article; Proceedings Paper CT Joint Statistical Meetings of the American-Statistical-Association CY JUL 29-AUG 02, 2007 CL Salt Lake City, UT SP Amer Stat Assoc ID QUALITY-OF-CARE; ETHNIC-DIFFERENCES; DIABETES CARE; US ADULTS; RACE; TARGETS; A1C AB OBJECTIVE - Performance measures are tools for assessing quality of care but may be influenced by patient factors. We investigated how currently endorsed performance measures for glycemic control in diabetes may be influenced by case Mix composition. We assessed differences in A1C performance measure threshold attainment by case mix factors for A1C >9% and examined how lowering the threshold to A1C >8% or >7% changed these differences. RESEARCH DESIGN AND METHODS - Using data from the 1.999-2002 National Health and Nutrition Examination Survey for 843 adults self-reporting diabetes, we computed the mean difference in A1C threshold attainment of >9, >8, and >7% by various case mix factors. The mean difference is the average percentage point difference in threshold attainment for population groups compared with that for the overall population. RESULTS - Diabetes medication was the only factor for which the difference in threshold attainment increased at lower thresholds, with mean differences of 5.7 percentage points at A1C >9% (reference), 10.1 percentage points at A1C >8% (P < 0.05), and 14.1 percentage points at A1C >7% (P < 0.001). CONCLUSIONS - As 87% of U.S. adults have A1C <9%, a performance measure threshold of >9% will not drive major improvements in glycemic control. Lower thresholds do not exacerbate differences in threshold attainment for most factors. Reporting by diabetes medication use may compensate for heterogeneous case mix when a performance measure threshold of A1C >8% or lower is used. C1 [Bainbridge, Kathleen E.] Social & Sci Syst, Silver Spring, MD USA. [Cowie, Catherine C.; Fradkin, Judith E.] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. [Rust, Keith F.] Westat Corp, Rockville, MD USA. RP Bainbridge, KE (reprint author), Social & Sci Syst, Silver Spring, MD USA. EM kbainbridge@s-3.com FU NIAAA NIH HHS [HHSN267200700001C]; NIDDK NIH HHS [N001-DK-1-2478]; NLM NIH HHS [HHSN267200700001G]; PHS HHS [HHSN267200700001G] NR 28 TC 13 Z9 13 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2008 VL 31 IS 9 BP 1754 EP 1760 DI 10.2337/dc07-2010 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 343QN UT WOS:000258868800010 PM 18509211 ER PT J AU Strotmeyer, ES De Rekeneire, N Schwartz, AV Faulkner, KA Resnick, HE Goodpaster, BH Shorr, RI Vinik, AI Harris, TB Newman, AB AF Strotmeyer, Elsa S. De Rekeneire, Nathalie Schwartz, Ann V. Faulkner, Kimberly A. Resnick, Helaine E. Goodpaster, Bret H. Shorr, Ronald I. Vinik, Aaron I. Harris, Tamara B. Newman, Anne B. CA Health ABC Study TI The relationship of reduced peripheral nerve function and diabetes with physical performance in older white and black adults - The Health, Aging, and Body Composition (Health ABC) Study SO DIABETES CARE LA English DT Article ID WOMENS HEALTH; AGE; DISABILITY; NEUROPATHY; FOOT; ASSOCIATION; IMPAIRMENTS; DYSFUNCTION; MUSCLES; DISEASE AB OBJECTIVE - Poor peripheral nerve function is prevalent in diabetes and older populations, and it has great potential to contribute to poor physical performance. RESEARCH DESIGN AND METHODS - Cross-sectional analyses were done for the Health, Aging, and Body Composition (Health ABC) Study participants (n = 2,364; 48% men; 38% black; aged 73-82 years). Sensory and motor peripheral nerve function in legs/feet was assessed by 10- and 1.4-g monofilament perception, vibration detection, and peroneal motor nerve conduction amplitude and velocity. The Health ABC lower-extremity performance battery was a supplemented version of the Established Populations for the Epidemiologic Studies of the Elderly battery (chair stands, standing balance, and 6-m walk), adding increased stand duration, single foot stand, and narrow walk. RESULTS - Diabetic participants had fewer chair stands (0.34 vs. 0.36 stands/s), shorter standing balance time (0.69 vs. 0.75 ratio), slower usual walking speed (1.11 vs. 1.14 m/s), slower narrow walking speed (0.80 vs. 0.90 m/s), and lower performance battery score (6.43 vs. 6.93) (all P < 0.05). Peripheral nerve function was associated with each physical performance measure independently. After addition of peripheral nerve function in fully adjusted models, diabetes remained significantly related to a lower performance battery score and slower narrow walking speed but not to chair stands, standing balance, or usual walking speed. CONCLUSIONS - Poor peripheral nerve function accounts for a portion of worse physical performance in diabetes and may be directly associated with physical performance in older diabetic and nondiabetic adults. The impact of peripheral nerve function on incident disability should be evaluated in older adults. C1 [Strotmeyer, Elsa S.; Faulkner, Kimberly A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [De Rekeneire, Nathalie] Epictr, Paris, France. [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Resnick, Helaine E.] Amer Assoc Homes & Serv Aging, Washington, DC USA. [Goodpaster, Bret H.] Univ Pittsburgh, Sch Med, Div Endocrinol & Metab, Pittsburgh, PA USA. [Shorr, Ronald I.] Univ Florida, Geriatr Res Educ & Clin Ctr, N Florida S Georgia Vet Hlth Syst, Gainesville, FL USA. [Shorr, Ronald I.] Univ Florida, Dept Aging & Geriatr, Gainesville, FL USA. [Vinik, Aaron I.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Div Geriatr Med, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Strotmeyer, ES (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. EM strotmeyere@edc.pitt.edu RI Strotmeyer, Elsa/F-3015-2014; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, 1-R01-AG 028050]; Intramural Research Program of the National Institutes of Health; National Institute on Aging; University of Pittsburgh Claude D. Pepper Older Americans Independence Center [P30-AG024827]; American Diabetes Association [1-04-JF-46] FX This work was funded by the National Institute on Aging (contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106) and 1-R01-AG 028050 (to E.S.S.) and supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, the University of Pittsburgh Claude D. Pepper Older Americans Independence Center (P30-AG024827) Pilot Grant (to E.S.S.), and the American Diabetes Association (1-04-JF-46 to E.S.S.). NR 24 TC 53 Z9 53 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2008 VL 31 IS 9 BP 1767 EP 1772 DI 10.2337/dc08-0433 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 343QN UT WOS:000258868800012 PM 18535192 ER PT J AU Nettleton, JA Steffen, LM Ni, H Liu, K Jacobs, DR AF Nettleton, Jennifer A. Steffen, Lyn M. Ni, Hanyu Liu, Kiang Jacobs, David R., Jr. TI Dietary patterns and risk of incident type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA) SO DIABETES CARE LA English DT Article ID SWEETENED BEVERAGES; INSULIN-RESISTANCE; METABOLIC SYNDROME; FOOD-CONSUMPTION; WOMEN; MEN; MELLITUS; COHORT AB OBJECTIVE - We characterized dietary patterns and their relation to incident type 2 diabetes in 5,011 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). RESEARCH DESIGN AND METHODS - White, black, Hispanic, and Chinese adults, aged 45-84 years and free of cardiovascular disease and diabetes, completed food frequency questionnaires at baseline (2000-2002). Incident type 2 diabetes was defined at three follow-up exams (2002-2003, 2004-2005, and 2005-2007) as fasting glucose > 126 mg/dl, self-reported type 2 diabetes, or use of diabetes medication. Two types of dietary patterns were studied: four empirically derived (principal components analysis) and one author-defined (low-risk food pattern) as the weighted sum of whole grains, vegetables, nuts/seeds, low-fat dairy, coffee (positively weighted), red meat, processed meat, high-fat dairy, and soda (negatively weighted). RESULTS - The empirically derived dietary pattern characterized by high intake of tomatoes, beans, refined grains, high-fat dairy, and red meat was associated with an 18% greater risk (hazard ratio per 1-score SD 1.18 [95% CI 1.06-1.321; P-trend = 0.004), whereas the empirically derived dietary pattern characterized by high intake of whole grains, fruit, nuts/seeds, green leafy vegetables, and low-fat dairy was associated with a 15% lower diabetes risk (0.85 [0.76-0.95] P-trend = 0.005). The low-risk food pattern was also inversely associated with diabetes risk (0.87 [0.81-0.99]; P-trend = 0.04). Individual component food groups were not independently associated with diabetes risk. Associations were not modified by sex or race/ethnicity. CONCLUSIONS - Multiple food groups collectively influence type 2 diabetes risk beyond that of the individual food groups themselves. C1 [Nettleton, Jennifer A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol & Dis Control, Houston, TX USA. [Ni, Hanyu] NHLBI, NIH, Minneapolis, MN USA. [Liu, Kiang] Northwestern Univ, Sch Med, Chicago, IL USA. [Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, Oslo, Norway. RP Nettleton, JA (reprint author), Univ Texas Hlth Sci Ctr Houston, Div Epidemiol & Dis Control, Houston, TX USA. EM jennifer.a.nettleton@uth.tmc.edu FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95165, N01-HC-95169] FX This research was supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute.; The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions (a full list of participating Multi-Ethnic Study of Atherosclerosis investigators and institutions can be found at http://www.mesa-nhlbi.org). NR 26 TC 93 Z9 98 U1 1 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2008 VL 31 IS 9 BP 1777 EP 1782 DI 10.2337/dc08-0760 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 343QN UT WOS:000258868800014 PM 18544792 ER PT J AU Burbelo, PD Hirai, H Leahy, H Lernmark, A Ivarsson, SA Iadarola, MJ Notkins, AL AF Burbelo, Peter D. Hirai, Hiroki Leahy, Hannah Lernmark, Ake Ivarsson, Sten A. Iadarola, Michael J. Notkins, Abner Louis TI A new luminescence assay for autoantibodies to mammalian cell-prepared insulinoma-associated protein 2 SO DIABETES CARE LA English DT Article ID IA-2 AB OBJECTIVE - Insulinoma-associated protein 2 (IA-2) is a major autoantigen in type I diabetes, and IA-2 autoantibodies are routinely detected by a liquid-phase radioimmunoprecipitation assay. The present experiments were initiated to develop a new assay that does not require the use of radioisotopes or autoantigens prepared in bacteria or by in vitro transcription/translation. RESEARCH DESIGN AND METHODS - IA-2 luciferase fusion protein was expressed in mammalian cells and assayed for autoantibodies by liquid-phase luciferase immunoprecipitation. RESULTS - Our study showed that there was no significant difference between the luciferase immunoprecipitation and the radioimmunoprecipitation assays in sensitivity and specificity, and comparison of the two assays revealed a high correlation coefficient (R-2 = 0.805). CONCLUSIONS - The luciferase system offers a robust, inexpensive, nonradioactive method for the detection of autoantibodies to mammalian cell-prepared IA-2 and could be of practical value at the clinical level. C1 [Burbelo, Peter D.; Leahy, Hannah; Iadarola, Michael J.] Natl Inst Dent & Craniolacial Res, Sensory Biol Branch, Natl Inst Hlth, Bethesda, MD USA. [Hirai, Hiroki; Notkins, Abner Louis] Natl Inst Dental & Craniofacial Res, Oral Infect & Immun Branch, Natl Inst Hlth, Bethesda, MD USA. [Lernmark, Ake] Univ Washington, Dept Clin Sci, RH Williams Lab, Seattle, WA 98195 USA. [Ivarsson, Sten A.] Lund Univ, Univ Hosp MAS, Dept Clin Sci, Malmo, Sweden. RP Iadarola, MJ (reprint author), Natl Inst Dent & Craniolacial Res, Sensory Biol Branch, Natl Inst Hlth, Bethesda, MD USA. EM miadarol@mail.nih.gov; anotkins@mail.nih.gov FU Intramural Research Program of the National Institute of Dental and Craniofacial Research; National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health. NR 7 TC 20 Z9 21 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2008 VL 31 IS 9 BP 1824 EP 1826 DI 10.2337/dc08-0286 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 343QN UT WOS:000258868800022 PM 18535195 ER PT J AU O'Sullivan, EP McDermott, JH Murphy, MS Sen, S Walsh, CH AF O'Sullivan, E. P. McDermott, J. H. Murphy, M. S. Sen, S. Walsh, C. H. TI Declining prevalence of diabetes mellitus in hereditary haemochromatosis - The result of earlier diagnosis SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE prevalence; diabetes; hereditary haemochromatosis ID INSULIN; MUTATIONS; GLUCOSE; POPULATION; SECONDARY; GENE AB Aims: The aims of this study were to describe the prevalence and clinical features of diabetes in hereditary haemochromatosis (HH), with particular emphasis to how this has changed since the introduction of genetic testing in 1996. Subjects and methods: Two hundred and thirty-seven patients were diagnosed with HH (based on elevated iron indices and liver biopsy or genetic testing) by a single physician, and all biochemical and clinical data recorded from diagnosis to the end of the study. Results: The prevalence of diabetes (21.9%) was lower than most previously published studies. There was a significantly greater prevalence of diabetes and cirrhosis in those diagnosed before the introduction of genetic testing, p < 0.001. The type of genetic mutation for HH, degree of ferritin elevation at diagnosis, or the presence of cirrhosis was not predictive for the development of diabetes. Iron depletion did not result in an improvement in glycaemic control or reduction in insulin requirements in the majority of patients. Conclusions: This is one of the largest published series of diabetes in HH. Because the occurrence of diabetes in patients with HH reduces life expectancy, our finding of a lower prevalence of diabetes is expected to translate into a greater survival rate in these patients. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [O'Sullivan, E. P.; Walsh, C. H.] Univ Hosp, S Infirm Victoria, Dept Endocrinol & Diabet, Cork, Ireland. [McDermott, J. H.] Connolly Hosp, Dublin, Ireland. [Murphy, M. S.] Univ Coll Hosp, Galway, Ireland. [Sen, S.] NIDDK, NIH, Bethesda, MD USA. RP O'Sullivan, EP (reprint author), Beaumont Hosp, Diabet Day Ctr, Dept Diabet, Dublin 9, Ireland. EM eoinosullivan@beaumont.ie NR 21 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD SEP PY 2008 VL 81 IS 3 BP 316 EP 320 DI 10.1016/j.diabres.2008.05.001 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 350XY UT WOS:000259388300008 PM 18565609 ER PT J AU Montori-Grau, M Minor, R Lerin, C Allard, J Garcia-Martinez, C de Cabo, R Gomez-Foix, AM AF Montori-Grau, M. Minor, R. Lerin, C. Allard, J. Garcia-Martinez, C. de Cabo, R. Gomez-Foix, A. M. TI Effects of aging and calorie restriction on rat skeletal muscle glycogen synthase and glycogen phosphorylase SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Montori-Grau, M.; Garcia-Martinez, C.; Gomez-Foix, A. M.] Univ Barcelona, E-08007 Barcelona, Spain. [Lerin, C.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Minor, R.; Allard, J.; de Cabo, R.] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 646 BP S261 EP S261 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660200645 ER PT J AU Perry, JRB Melzer, D Maggio, M Hernandez, D Singleton, A Ferrucci, L Palmer, C Bennett, A Ruokonen, A Panicker, V Jarvelin, MR Hattersley, A McCarthy, M Frayling, T AF Perry, J. R. B. Melzer, D. Maggio, M. Hernandez, D. Singleton, A. Ferrucci, L. Palmer, C. Bennett, A. Ruokonen, A. Panicker, V. Jarvelin, M. -R. Hattersley, A. McCarthy, M. Frayling, T. TI A Mendelian randomisation study provides initial evidence that sex hormone binding globulin (SHBG) levels alter type 2 diabetes risk SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Perry, J. R. B.; Melzer, D.; Hattersley, A.; Frayling, T.] Peninsula Med Sch, Exeter, Devon, England. [Maggio, M.] NIA, NIH, Baltimore, MD 21224 USA. [Hernandez, D.; Singleton, A.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Ferrucci, L.] NIA, Longitudinal Studies Sect, Bethesda, MD 20892 USA. [Palmer, C.] Univ Dundee, Biomed Res Ctr, Dundee DD1 4HN, Scotland. [Bennett, A.; McCarthy, M.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Ruokonen, A.] Univ Oulu, Oulu, Finland. [Panicker, V.] Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Bristol BS8 1TH, Avon, England. [Jarvelin, M. -R.] Univ London Imperial Coll Sci Technol & Med, London, England. RI Singleton, Andrew/C-3010-2009; Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 309 BP S131 EP S131 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660200309 ER PT J AU Rayner, NW Prokopenko, I Groves, CJ Zeggini, E Hanson, RL Mitchell, BD Jia, W Ng, M Froguel, P Chan, J Bogardus, C Elbein, SC Shuldiner, AR McCarthy, MI AF Rayner, N. W. Prokopenko, I. Groves, C. J. Zeggini, E. Hanson, R. L. Mitchell, B. D. Jia, W. Ng, M. Froguel, P. Chan, J. Bogardus, C. Elbein, S. C. Shuldiner, A. R. McCarthy, M. I. CA Int Type Diabet lq Consortium TI Large-scale follow-up study does not confirm putative association signals in the NOS1AP and PKLR gene regions on chromosome 1q with type 2 diabetes SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Rayner, N. W.; Prokopenko, I.; Groves, C. J.; Zeggini, E.; McCarthy, M. I.] Univ Oxford, WTCHG, Oxford OX1 2JD, England. [Hanson, R. L.; Bogardus, C.] NIH, NIDDK, Phoenix, AZ USA. [Mitchell, B. D.; Shuldiner, A. R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Jia, W.] Shanghai Diabet Inst, Dept Endocrinol & Metab, Shanghai, Peoples R China. [Ng, M.] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Elbein, S. C.] Univ Arkansas, Div Endocrinol & Metab, Little Rock, AR 72204 USA. RI Hanson, Robert/O-3238-2015; Chan, Juliana /B-7918-2016 OI Hanson, Robert/0000-0002-4252-7068; Chan, Juliana /0000-0003-1325-1194 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 301 BP S128 EP S128 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660200301 ER PT J AU Brynczka, C Merrick, BA AF Brynczka, Christopher Merrick, B. Alex TI The p53 transcriptional target gene wnt7b contributes to NGF-inducible neurite outgrowth in neuronal PC12 cells SO DIFFERENTIATION LA English DT Article DE wnt7b; wnt; p53; PC12; NGF; neurite; JNK; Fzd ID NEURAL PRECURSOR CELLS; BETA-CATENIN; PHEOCHROMOCYTOMA CELLS; INT-1 PROTOONCOGENE; NERVOUS-SYSTEM; DIFFERENTIATION; EXPRESSION; ACTIVATION; PROTEIN; GROWTH AB Differentiation of PC12 cells by nerve growth factor (NGF) is characterized by changes in signal transduction pathways leading to growth arrest and neurite extension. The transcription factor p53, involved in regulating cell cycle and apoptosis, is also activated during PC12 differentiation and contributes to each of these processes but the mechanisms are incompletely understood. NGF signaling stabilizes p53 protein expression, which enables its transcriptional regulation of target genes, including the newly identified target, wnt7b, a member of the wnt family of secreted morphogens. We tested the hypothesis that wnt7b expression is a factor in NGF-dependent neurite outgrowth of differentiating PC12 cells. Wnt7b transcript and protein levels are increased following NGF treatment in a p53-dependent manner, as demonstrated by a reduction in wnt7b protein levels following stable shRNA-mediated silencing of p53. In addition, overexpressed human tp53 was capable of inducing marked wnt7b expression in neuronal PC12 cells but tp53 overexpression did not elevate wnt7b levels in several tested human tumor cell lines. Ectopic wnt7b overexpression was sufficient to rescue neurite outgrowth in NGF-treated p53-silenced PC12 cells, which could be blocked by c-Jun N-terminal kinase (JNK) inhibition with SP600125 and did not involve beta-catenin nuclear translocation. Addition of sFRP1 to differentiation medium inhibited wnt7b-dependent phosphorylation of JNK, demonstrating that wnt7b is secreted and signals through a JNK-dependent mechanism in PC12 cells. We further identify an NGF-inducible subset of wnt receptors that likely supports wnt7b-mediated neurite extension in PC12 cells. In conclusion, wnt7b is a novel p53-regulated neuritogenic factor in PC12 cells that in conjunction with NGF-regulated Fzd expression is involved in p53-dependent neurite outgrowth through noncanonical JNK signaling. C1 [Brynczka, Christopher; Merrick, B. Alex] NIEHS, Natl Ctr Toxicogenom, NIH, Res Triangle Pk, NC 27709 USA. [Brynczka, Christopher] N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27606 USA. RP Merrick, BA (reprint author), NIEHS, Natl Ctr Toxicogenom, NIH, Res Triangle Pk, NC 27709 USA. EM merrick@niehs.nih.gov FU Intramural Research Program of the NIH; National Institute of Environmental Health Sciences FX This work was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We thank Dr. Kevin E. Gerrish and Dr. Serena M. Dudek for critical review of this manuscript. NR 64 TC 9 Z9 10 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD SEP PY 2008 VL 76 IS 7 BP 795 EP 808 DI 10.1111/j.1432-0436.2007.00261.x PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 339MJ UT WOS:000258581400005 PM 18177422 ER PT J AU Chang, MC Grieder, FB AF Chang, Michael C. Grieder, Franziska B. TI The baffling multitude of disease models for the study of human disease - how can the scientist navigate the huge amount of data and receive guidance? SO DISEASE MODELS & MECHANISMS LA English DT Editorial Material ID MEDICINE; HEALTH AB Funding from external sources is the lifeline for most biomedical research scientists. In the USA, the National Institutes of Health (NIH), composed of 27 institutes and centers, is the primary federal agency for conducting and supporting medical research. One of these centers, the National Center for Research Resources (NCRR) provides financial support and resources to clinical or translational scientists working to understand human disease. Through the Division of Comparative Medicine, the NCRR funds projects focused on the development and use of model organisms to understand, diagnose, prevent and treat disease. Here, officials within the NCRR's Division of Comparative Medicine discuss some of the funding opportunities and resources available to researchers who use model organisms, and their perspectives on the future of model organism research. C1 [Chang, Michael C.; Grieder, Franziska B.] NIH, Natl Ctr Res Resources, Div Comparat Med, Bethesda, MD 20892 USA. RP Grieder, FB (reprint author), NIH, Natl Ctr Res Resources, Div Comparat Med, 6701 Democracy Blvd, Bethesda, MD 20892 USA. EM griederf@mail.nih.gov NR 2 TC 1 Z9 1 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD SEP-OCT PY 2008 VL 1 IS 2-3 BP 99 EP 102 DI 10.1242/dmm.001354 PG 4 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 474AH UT WOS:000268254100009 PM 19048071 ER PT J AU Gearhart, PJ AF Gearhart, Patricia J. TI Response to "Mutation frequency vs. mutation patterns: A comparison of the results in spleen and Peyer's patches" SO DNA REPAIR LA English DT Letter ID SOMATIC HYPERMUTATION; IG GENES C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gearhartp@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000732-12] NR 7 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD SEP 1 PY 2008 VL 7 IS 9 BP 1411 EP 1412 DI 10.1016/j.dnarep.2008.06.001 PG 2 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 347JK UT WOS:000259136300003 PM 19727317 ER PT J AU Hwang, JY Smith, S Ceschia, A Torres-Rosell, J Aragon, L Myung, K AF Hwang, Ji-Young Smith, Stephanie Ceschia, Audrey Torres-Rosell, Jordi Aragon, Luis Myung, Kyungjae TI Smc5-Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications SO DNA REPAIR LA English DT Article DE Smc5-Smc6; gross chromosomal rearrangement; break-induced replication; checkpoints; translocations ID DOUBLE-STRAND BREAKS; DNA-DAMAGE CHECKPOINTS; SACCHAROMYCES-CEREVISIAE HOMOLOG; S-PHASE PROGRESSION; GENOME INSTABILITY; SUMO MODIFICATION; SMC PROTEINS; TELOMERE ELONGATION; DEFECTIVE-MUTANTS; BLOOMS-SYNDROME AB Translocations in chromosomes alter genetic information. Although the frequent translocations observed in many tumors suggest the altered genetic information by translocation could promote tumorigenesis, the mechanisms for how translocations are suppressed and produced are poorly understood. The smc6-9 mutation increased the translocation class gross chromosomal rearrangement (GCR). Translocations produced in the smc6-9 strain are unique because they are non-reciprocal and dependent on break-induced replication (BIR) and independent of non-homologous endjoining. The high incidence of translocations near repetitive sequences such as 6 sequences, ARS, tRNA genes, and telomeres in the smc6-9 strain indicates that Smc5-Smc6 suppresses translocations by reducing DNA damage at repetitive sequences. Synergistic enhancements of translocations in strains defective in DNA damage checkpoints by the smc6-9 mutation without affecting de novo telomere addition class GCR suggest that Smc5-Smc6 defines a new pathway to suppress GCR formation. Published by Elsevier B.V. C1 [Hwang, Ji-Young; Smith, Stephanie; Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Ceschia, Audrey; Torres-Rosell, Jordi; Aragon, Luis] Univ London Imperial Coll Sci Technol & Med, Ctr Clin Sci, Cell Cycle Grp, MRC, London, England. RP Myung, K (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Room 4A22, Bethesda, MD 20892 USA. EM kmyung@nhgri.nih.gov RI Torres-Rosell, Jordi/A-4213-2010; OI Torres-Rosell, Jordi/0000-0003-1308-6926; Hwang, Ji-Young/0000-0001-8044-1989 FU National Human Genome Research Institute, National Institutes of Health; Medical Research Council UK FX We thank S. Lee (U. Texas San Antonio) for helpful discussion; X. Zhao (Sloan Kettering Cancer Center) for the mms21-11 strain; the NIH fellows editorial board for comments on the manuscript; J. Fekecs (NHGRI) for figure preparation. K.M. especially thanks E. Cho. This research was supported by the intramural research program of the National Human Genome Research Institute, National Institutes of Health (to K.M.) and the Medical Research Council UK (to L.A.). NR 71 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD SEP 1 PY 2008 VL 7 IS 9 BP 1426 EP 1436 DI 10.1016/j.dnarep.2008.05.006 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 347JK UT WOS:000259136300005 PM 18585101 ER PT J AU Martomo, SA Saribasak, H Yokoi, M Hanaoka, F Gearhart, PJ AF Martomo, Stella A. Saribasak, Huseyin Yokoi, Masayuki Hanaoka, Fumio Gearhart, Patricia J. TI Reevaluation of the role of DNA polymerase theta in somatic hypermutation of immunoglobulin genes SO DNA REPAIR LA English DT Article DE somatic hypermutation; class switch recombination; immunoglobulin gene; DNA polymerase theta; DNA polymerase eta ID CLASS-SWITCH RECOMBINATION; ANTIBODY GENES; IG GENES; MICE; ETA; DIVERSIFICATION; MUTATIONS; MECHANISMS; FREQUENCY; REGIONS AB DNA polymerase theta has been implicated in the process of somatic hypermutation in immunoglobulin variable genes based on several reports of alterations in the frequency and spectra of mutations from Polq(-/-) mice. However, these studies have contrasting results on mutation frequencies and the types of nucleotide substitutions, which question the role of polymerase theta in hypermutation. DNA polymerase eta has a dominant effect on mutation and may substitute in the absence of polymerase theta to affect the pattern. Therefore, we have examined mutation in mice deficient for both polymerases theta and eta. The mutation frequencies in rearranged variable genes from Peyer's patches were similar in wild type, Polq-/-, Polh(-/-), and Polq(-/-) Polh(-/-) mice. The types of substitutions were also similar between wild type and Polq-/- clones, and between Polh(-/-) and Polq(-/-)Polh(-/-) clones. Furthermore, there was no difference in heavy chain class switching in splenic B cells from the four groups of mice. These results indicate that polymerase theta does not play a significant role in the generation of somatic mutation in immunoglobulin genes. Published by Elsevier B.V C1 [Martomo, Stella A.; Saribasak, Huseyin; Gearhart, Patricia J.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Yokoi, Masayuki; Hanaoka, Fumio] Gakushuin Univ, Fac Sci, Toshima Ku, Tokyo 1718588, Japan. RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gearhartp@grc.nia.nih.gov RI Saribasak, Huseyin/C-9331-2012 OI Saribasak, Huseyin/0000-0003-0055-062X FU Intramural Research Program of the NIH, National Institute on Aging FX We thank J. Chrest, C. Morris, and R. Wersto for flow cytometry; the entire staff of the Comparative Medicine Section for mouse breeding; William Yang for technical help, and Robert Maul for comments. mice heterozygous for pol theta were graciously provided by John Schimenti . This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 28 TC 33 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD SEP 1 PY 2008 VL 7 IS 9 BP 1603 EP 1608 DI 10.1016/j.dnarep.2008.04.002 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 347JK UT WOS:000259136300018 PM 18485835 ER PT J AU Ghitza, UE Epstein, DH Preston, KL AF Ghitza, Udi E. Epstein, David H. Preston, Kenzie L. TI Self-report of illicit benzodiazepine use on the Addiction Severity Index predicts treatment outcome SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE contingency management; cocaine abuse; heroin abuse; opiate; benzodiazepine ID METHADONE-MAINTENANCE TREATMENT; SUBSTANCE USE DISORDERS; RISK-TAKING BEHAVIOR; INJECTING DRUG-USERS; COCAINE ABSTINENCE; SOCIAL-ADJUSTMENT; CONTINGENCY MANAGEMENT; FOLLOW-UP; DEPENDENT PATIENTS; RANDOMIZED-TRIAL AB The relationship between pre-treatment illicit benzodiazepine use (days of use in the last 30) assessed on the Addiction Severity Index (ASI) and treatment outcome was investigated by retrospective analysis of data from two controlled clinical trials in 361 methadone maintained cocaine/opiate users randomly assigned to 12-week voucher- or prize-based contingency management (CM) or control interventions. Based on screening ASI, participants were identified as non-users (BZD-N; 0 days of use) or users (BZD-U; >0 days of use). Outcome measures were: urine drug screens (thrice weekly): quality of life and self-reported HIV-risk behaviors (every 2 weeks): and current DSM-IV diagnosis of cocaine and heroin dependence (study exit). In the CM group, BZD-U had significantly worse outcomes on in-treatment cocaine use, quality-of-life scores, needle-sharing behaviors, and current heroin dependence diagnoses at study exit compared to BZD-N. In the control group. BZD-U had significantly higher in-treatment cocaine use but did not differ from BZD-N on psychosocial measures. Thus, in a sample of non-dependent BZD users, self-reported illicit BZD use on the ASI, even at low levels, predicted worse outcome on cocaine use and blunted response to CM. Published by Elsevier Ireland Ltd. C1 [Ghitza, Udi E.; Epstein, David H.; Preston, Kenzie L.] NIDA, Clin Pharmacol & Therapeut Res Branch, Treatment Sect, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Ghitza, UE (reprint author), NIDA, Clin Pharmacol & Therapeut Res Branch, Treatment Sect, Intramural Res Program,NIH, Baltimore, MD 21224 USA. EM ghitzau@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS [Z01 DA000234-15] NR 56 TC 9 Z9 9 U1 1 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2008 VL 97 IS 1-2 BP 150 EP 157 DI 10.1016/j.drugalcdep.2008.04.003 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 335RQ UT WOS:000258308100015 PM 18499354 ER PT J AU Yu, E Miotto, K Akerele, E Montgomery, A Elkashef, A Walsh, R Montoya, I Fischman, MW Collins, J McSherry, F Boardman, K Davies, DK O'Brien, CP Ling, W Kleber, H Herman, BH AF Yu, Elmer Miotto, Karen Akerele, Evaristo Montgomery, Ann Elkashef, Ahmed Walsh, Robert Montoya, Ivan Fischman, Marian W. Collins, Joseph McSherry, Frances Boardman, Kathy Davies, David K. O'Brien, Charles P. Ling, Walter Kleber, Herbert Herman, Barbara H. TI A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE lofexidine; alpha-2-adrenergic agonist; opioid withdrawal treatment; phase 3; placebo-controlled; double-blind; multi-site trail ID RANDOMIZED CONTROLLED-TRIAL; OPIATE WITHDRAWAL; DETOXIFICATION; CLONIDINE; ADDICTION; METHADONE; RAT; MORPHINE; NEURONS; LOCUS AB Context: Lofexidine is an alpha-2-adrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine. Objective: To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally defined opioid withdrawal symptoms in opioid dependent individuals Undergoing medically supervised opioid detoxification as compared to placebo. Design: An inpatient, Phase 3. placebo-controlled. double-blind. randomized mufti-site trial with three phases: (1) opioid agonist stabilization phase (days 1-3), (2) detoxification/medication or placebo phase (clays 4-8). and (3) post detoxification/medication phase (days 9-11). Subjects: Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo. Main outcome measure: Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (second opioid detoxification treatment day). Results: Due to significant findings. the study was terminated early. On the study clay 5 MHOWS. Subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (least squares means 19.5 +/- 2.1 versus 30.9 +/- 2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01). Conclusions: Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification. Published by Elsevier Ireland Ltd. C1 [Yu, Elmer; O'Brien, Charles P.] Univ Penn, Philadelphia, PA 19104 USA. [Miotto, Karen; Ling, Walter] Univ Calif Los Angeles, David Geffen Sch Med, Long Beach Vet Affairs Med Ctr, Los Angeles, CA 90025 USA. [Akerele, Evaristo; Fischman, Marian W.; Kleber, Herbert] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Akerele, Evaristo; Fischman, Marian W.; Kleber, Herbert] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Montgomery, Ann; Elkashef, Ahmed; Walsh, Robert; Montoya, Ivan; Herman, Barbara H.] NIDA, DPMCDA, NIH, Bethesda, MD 20892 USA. [Collins, Joseph; McSherry, Frances] VA Med Ctr, Dept Vet Affairs Cooperat Studies Program, Perry Point, MD 21902 USA. [Boardman, Kathy] VACSPCRPCC, Albuquerque, NM 87106 USA. [Davies, David K.] Britannia Pharmaceut Ltd, Surrey RH1 6YS, England. RP Yu, E (reprint author), Univ Penn, Philadelphia VAMC 116,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM yu_e@mail.trc.upenn.edu FU Intramural NIH HHS [Z99 DA999999]; NIDA NIH HHS [P50 DA 09236, P50 DA009236, P50 DA009236-05S1, P60 DA 005186, P60 DA005186, P60 DA005186-13, Y1 DA 1001] NR 42 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2008 VL 97 IS 1-2 BP 158 EP 168 DI 10.1016/j.drugalcdep.2008.04.002 PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 335RQ UT WOS:000258308100016 PM 18508207 ER PT J AU Eckelman, WC Reba, RC Kellof, GJ AF Eckelman, William C. Reba, Richard C. Kellof, Gary J. TI Targeted imaging: an important biomarker for understanding disease progression in the era of personalized medicine SO DRUG DISCOVERY TODAY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; GASTROINTESTINAL STROMAL TUMOR; IN-VIVO; IMATINIB MESYLATE; DRUG DISCOVERY; GLUCOSE-UTILIZATION; MALIGNANT-TUMORS; HER2 EXPRESSION; RECEPTOR; PET AB The key to applying targeted imaging to personalized medicine is the choice of the right radiolabeled probe for the right target for the right disease following the lead of pharmaceutical development. The imaging approach differs depending on whether the target is a single disease control point (e.g. a specific receptor or transport protein linked to the mechanistic activity of a drug) or a general disease control point applicable to a number of treatment paradigms (e.g. proliferation, angiogenesis,inflammation). But in either case, the number of control points must be small given the time constraints on molecular imaging procedures in the clinic. Regardless of the choice, the radiotracer must be validated as binding the target with the appropriate pharmacokinetics and pharmacodynamics for effective external imaging. Such an imaging agent developed in concert with drug development has a built in synergy that will accelerate the drug development process, targeted imaging and personalized medicine as well. C1 [Eckelman, William C.] Mol Tracer LLC, Bethesda, MD 20814 USA. [Reba, Richard C.] NIH, Bethesda, MD 20892 USA. [Kellof, Gary J.] NCI, Bethesda, MD 20892 USA. RP Eckelman, WC (reprint author), Mol Tracer LLC, Bethesda, MD 20814 USA. EM wceckelman@verizon.net NR 71 TC 30 Z9 31 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD SEP PY 2008 VL 13 IS 17-18 BP 748 EP 759 DI 10.1016/j.drudis.2008.05.009 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 356PP UT WOS:000259790400003 PM 18617011 ER PT J AU Sharma, S Ou, JH Strom, S Mattison, D Caritis, S Venkataramanan, R AF Sharma, Shringi Ou, Junhai Strom, Stephen Mattison, Don Caritis, Steve Venkataramanan, Raman TI Identification of enzymes involved in the metabolism of 17 alpha-hydroxyprogesterone caproate: An effective agent for prevention of preterm birth SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CYTOCHROME-P450 3A4; PREGNANCY; INDUCTION; DELIVERY AB Preterm delivery, that is delivery before 37 completed weeks of gestation, is the major determinant of neonatal morbidity and mortality. Until recently, no effective therapies for prevention of preterm birth existed. In a recent multicentered trial, 17 alpha-hydroxyprogesterone caproate (17-OHPC) reduced the rate of preterm birth by 33% in a group of high-risk women. Limited pharmacologic data exist for this drug. The recommended dose is empiric; the metabolic pathways are not well defined especially in pregnant women; and the fetal exposure has not been quantified. To define the metabolic pathways of 17-OHPC we used human liver microsomes (HLMs), fresh human hepatocytes (FHHs), and expressed enzymes. HLMs in the presence of NADPH generated three metabolites, whereas two major metabolites were observed with FHHs. Metabolism of 17-OHPC was significantly inhibited by the CYP3A4 inhibitors ketoconazole and troleandomycin in HLM and FHH. Metabolism of 17-OHPC was significantly greater in FHH treated with the CYP3A inducers, rifampin and phenobarbital. Furthermore, studies with expressed enzymes showed that 17-OHPC is metabolized exclusively by CYP3A4 and CYP3A5. The caproic acid ester was intact in the major metabolites generated, indicating that 17-OHPC is not converted to the primary progesterone metabolite, 17 alpha-hydroxyprogesterone. In summary, this study shows that 17-OHPC is metabolized by CYP3A. Because CYP3A is involved in the oxidative metabolism of numerous commonly used drugs, 17-OHPC may be involved in clinically relevant metabolic drug interactions with coadministered CYP3A inhibitors or inducers. C1 [Sharma, Shringi; Ou, Junhai; Venkataramanan, Raman] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Strom, Stephen; Venkataramanan, Raman] Univ Pittsburgh, Sch Pharm, Dept Pathol, Pittsburgh, PA 15261 USA. [Mattison, Don] NICHHD, Ctr Res Mothers & Children, OPRU Network, Bethesda, MD 20892 USA. [Caritis, Steve] Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. RP Venkataramanan, R (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, 731 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. EM rv@pitt.edu RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013; OI Mattison, Donald/0000-0001-5623-0874; caritis, steve/0000-0002-2169-0712; Strom, Stephen/0000-0002-2889-3387 FU NICHD NIH HHS [HD-047905-2] NR 17 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 EI 1521-009X J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD SEP PY 2008 VL 36 IS 9 BP 1896 EP 1902 DI 10.1124/dmd.108.021444 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 339WK UT WOS:000258607800019 PM 18573861 ER PT J AU Jessup, CM Bohannan, BJM AF Jessup, Christine M. Bohannan, Brendan J. M. TI The shape of an ecological trade-off varies with environment SO ECOLOGY LETTERS LA English DT Article DE adaptive dynamics; bacteria; bacteriophage; divergent selection; Escherichia coli; microbial ecology; parasitoid-host; pathogen-host; predator-prey; trade-off ID FREQUENCY-DEPENDENT SELECTION; TERM EXPERIMENTAL EVOLUTION; LARVAL COMPETITIVE ABILITY; LOTKA-VOLTERRA SYSTEMS; ESCHERICHIA-COLI K-12; DROSOPHILA-MELANOGASTER; PARASITOID RESISTANCE; RESOURCE ENRICHMENT; QUANTILE REGRESSION; ADAPTIVE DYNAMICS AB Central to most theories that explain the diversity of life is the concept that organisms face trade-offs. Theoretical work has shown that the precise shape of a trade-off relationship affects evolutionary predictions. One common trade-off is that between competitive ability and resistance to predators, parasitoids, pathogens or herbivores. We used a microbial experimental system to elucidate the shape of the relationship between parasitoid resistance and competitive ability. For each of 86 bacteriophage-resistant isolates of the bacterium Escherichia coli B, we measured the degree of resistance to bacteriophage T2 (a viral parasitoid) and relative competitive ability in both the resource environment in which strains were isolated and in two alternate environments. We observed that environmental change can alter trade-off shape, and that different physiological mechanisms can lead to different trade-off shapes and different sensitivities to environmental change. These results highlight the important interaction between environment and trade-off shape in affecting ecological and evolutionary dynamics. C1 [Jessup, Christine M.] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. [Bohannan, Brendan J. M.] Univ Oregon, Ctr Ecol & Evolutionary Biol, Eugene, OR 97403 USA. RP Jessup, CM (reprint author), NIH, Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. EM cjessup@stanfordalumni.org FU National Science Foundation [DEB-0408108, DEB-0515598, DEB-0129942] FX This work was supported by the National Science Foundation (DEB-0408108, DEB-0515598, and DEB-0129942). David Ackerly, Craig Criddle, Samantha Forde and Fiorenza Micheli, and three anonymous referees provided insightful comments on this manuscript. Ellen Edenberg, Weronika Patena, Alike Wiser and Steve Biller assisted with preliminary experiments. Discussions with Mike Quance guided the development of the resistance assay used in these experiments. We are particularly grateful to David Ackerly for valuable suggestions regarding statistical analysis and data interpretation. NR 65 TC 32 Z9 32 U1 4 U2 45 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1461-023X J9 ECOL LETT JI Ecol. Lett. PD SEP PY 2008 VL 11 IS 9 BP 947 EP 959 DI 10.1111/j.1461-0248.2008.01205.x PG 13 WC Ecology SC Environmental Sciences & Ecology GA 349EB UT WOS:000259263000007 PM 18557986 ER PT J AU Costa-Mattioli, M Bidinosti, M Dever, TE AF Costa-Mattioli, Mauro Bidinosti, Michael Dever, Thomas E. TI Getting the message in protein synthesis - Keystone Symposium on Translational Regulatory Mechanisms SO EMBO REPORTS LA English DT Editorial Material DE initiation factor; learning and memory; miRNA; mRNA stability; translational control ID MESSENGER-RNA DECAY; INITIATION-FACTORS; RIBOSOMAL-SUBUNIT; SUBSTRATE RECOGNITION; SYNAPTIC PLASTICITY; EIF2-ALPHA KINASE; PHOSPHORYLATION; NONSENSE; RELEASE; CELLS C1 [Dever, Thomas E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Costa-Mattioli, Mauro; Bidinosti, Michael] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. [Costa-Mattioli, Mauro; Bidinosti, Michael] McGill Univ, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada. RP Dever, TE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM tdever@nih.gov OI Dever, Thomas/0000-0001-7120-9678 NR 37 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD SEP PY 2008 VL 9 IS 10 BP 954 EP 959 DI 10.1038/embor.2008.165 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 355AX UT WOS:000259682100006 PM 18758437 ER PT J AU Csanady, L Mindell, JA AF Csanady, Laszlo Mindell, Joseph A. TI The twain shall meet: channels, transporters and things between - Meeting on Membrane Transport in Flux: The Ambiguous Interface between Channels and Pumps SO EMBO REPORTS LA English DT Editorial Material DE channel; coupling; gates; occluded state; transporter ID ANTHRAX TOXIN; GLUTAMATE TRANSPORTER; PROTEIN TRANSLOCATION; ABC TRANSPORTER; SELECTIVITY; HOMOLOG; DRIVEN; SODIUM C1 [Csanady, Laszlo] Semmelweis Univ, Dept Med Biochem, H-1088 Budapest, Hungary. [Mindell, Joseph A.] NINDS, Membrane Transport Biophys Unit, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Csanady, L (reprint author), Semmelweis Univ, Dept Med Biochem, Puskin U 9, H-1088 Budapest, Hungary. EM csanady@puskin.sote.hu; mindellj@ninds.nih.gov OI Csanady, Laszlo/0000-0002-6547-5889; Mindell, Joseph/0000-0002-6952-8247 NR 17 TC 3 Z9 3 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD SEP PY 2008 VL 9 IS 10 BP 960 EP 965 DI 10.1038/embor.2008.172 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 355AX UT WOS:000259682100007 PM 18772896 ER PT J AU Morens, DM AF Morens, David M. TI In memoriam: Michael B. Gregg (1930-2008) SO EMERGING INFECTIOUS DISEASES LA English DT Biographical-Item C1 NIAID, Natl Inst Hlth, Off Director, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIAID, Natl Inst Hlth, Off Director, Bldg 31,Rm 7A-03,31 Ctr Dr,Mailstop 2520, Bethesda, MD 20892 USA. EM dm270q@nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD SEP PY 2008 VL 14 IS 9 BP 1476 EP 1478 DI 10.3201/eid1409080952 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 345JE UT WOS:000258991700027 PM 18760025 ER PT J AU Usdin, TB Paciga, M Riordan, T Kuo, J Parmelee, A Petukova, G Camerini-Otero, RD Mezey, E AF Usdin, Ted B. Paciga, Mark Riordan, Tim Kuo, Jonathan Parmelee, Alissa Petukova, Galina Camerini-Otero, R. Daniel Mezey, Eva TI Tuberoinfundibular peptide of 39 residues is required for germ cell development SO ENDOCRINOLOGY LA English DT Article ID CHROMOSOME SYNAPSIS; NERVOUS-SYSTEM; FEMALE MICE; EXPRESSION; MEIOSIS; RECEPTOR; RAT; GENE; ENDOCRINE; HOMOLOG AB Tuberoinfundibular peptide of 39 residues (TIP39) was identified as a PTH 2 receptor ligand. We report that mice with deletion of Tifp39, the gene encoding TIP39, are sterile. Testes contained Leydig and Sertoli cells and spermatogonia but no spermatids. Labeling chromosome spreads with antibodies to proteins involved in recombination showed that spermatogonia do not complete prophase of meiosis I. Chromosomes were observed at different stages of recombination in single nuclei, a defect not previously described with mutations in genes known to be specifically involved in DNA replication and recombination. TIP39 was previously shown to be expressed in neurons projecting to the hypothalamus and within the testes. LH and FSH were slightly elevated in Tifp39(-/-) mice, suggesting intact hypothalamic function. We found using in situ hybridization that the genes encoding TIP39 and the PTH 2 receptor are expressed in a stage-specific manner within seminiferous tubules. Using immunohistochemistry and quantitative RT-PCR, TIP39 expression is greatest in mature testes, and appears most abundant in postmeiotic spermatids, but TIP39 protein and mRNA can be detected before any cells have completed meiosis. We used mice that express Cre recombinase under control of a spermatid-specific promoter to express selectively a cDNA encoding TIP39 in the testes of Tifp39(-/-) mice. Spermatid production and fertility were rescued, demonstrating that the defect in Tifp39(-/-) mice was due to the loss of TIP39. These results show that TIP39 is essential for germ cell development and suggest that it may act as an autocrine or paracrine agent within the gonads. C1 [Usdin, Ted B.; Paciga, Mark; Riordan, Tim; Kuo, Jonathan] NIMH, Natl Inst Hlth, Bethesda, MD 20892 USA. [Petukova, Galina; Camerini-Otero, R. Daniel] NIDDK, Bethesda, MD 20892 USA. [Parmelee, Alissa; Mezey, Eva] Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Usdin, TB (reprint author), Bldg 35,35 Convent Dr,MSC 3728, Bethesda, MD 20892 USA. EM usdint@mail.nih.gov FU Intramural Program of the National Institutes of Health; National Institute of Mental Health FX This research was supported by the Intramural Program of the National Institutes of Health, National Institute of Mental Health. NR 44 TC 15 Z9 15 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2008 VL 149 IS 9 BP 4292 EP 4300 DI 10.1210/en.2008-0419 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QT UT WOS:000258660800008 PM 18483145 ER PT J AU Muniyappa, R Iantorno, M Quon, MJ AF Muniyappa, Ranganath Iantorno, Micaela Quon, Michael J. TI An Integrated View of Insulin Resistance and Endothelial Dysfunction SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID NITRIC-OXIDE SYNTHASE; TYPE-2 DIABETES-MELLITUS; MUSCLE GLUCOSE-UPTAKE; C-REACTIVE PROTEIN; CARDIOVASCULAR RISK-FACTORS; POLYCYSTIC-OVARY-SYNDROME; CORONARY-ARTERY-DISEASE; FLOW-MEDIATED DILATION; HUMAN SKELETAL-MUSCLE; ORAL VITAMIN-C AB Endothelial dysfunction and insulin resistance are frequently comorbid states. Vasodilator actions of insulin are mediated by phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathways that stimulate production of nitric oxide from vascular endothelium. This helps to couple metabolic and hemodynamic homeostasis under healthy conditions. In pathologic states, shared causal factors, including glucotoxicity, lipotoxicity, and inflammation selectively impair PI3K-dependent insulin signaling pathways that contribute to reciprocal relationships between insulin resistance and endothelial dysfunction. This article discusses the implications of pathway-selective insulin resistance in vascular endothelium, interactions between endothelial dysfunction and insulin resistance, and therapeutic interventions that may simultaneously improve both metabolic and cardiovascular physiology in insulin-resistant conditions. C1 [Muniyappa, Ranganath; Iantorno, Micaela; Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Quon, MJ (reprint author), NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, 9 Mem Dr,Bldg 9,Room 1N-105,MSC 0920, Bethesda, MD 20892 USA. EM quonm@nih.gov OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Intramural Research Program; NCCAM; NIH FX This work was supported by the Intramural Research Program, NCCAM, NIH. NR 148 TC 76 Z9 79 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 EI 1558-4410 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 2008 VL 37 IS 3 BP 685 EP + DI 10.1016/j.ecl.2008.06.001 PG 29 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 357WJ UT WOS:000259877600010 PM 18775359 ER PT J AU Bjornstad, ON Grenfell, BT AF Bjornstad, Ottar N. Grenfell, Bryan T. TI Hazards, spatial transmission and timing of outbreaks in epidemic metapopulations SO ENVIRONMENTAL AND ECOLOGICAL STATISTICS LA English DT Article; Proceedings Paper CT Spring Meeting of the Eastern North American Region of the International-Biometric-Society CY MAR 20-23, 2005 CL Austin, TX SP Int Biomet Soc, Eastern N Amer Reg DE measles; inter-epidemic periods; TSIR model; disease ecology; population dynamics ID MEASLES METAPOPULATION; COMMUNITY SIZE; TIME-SERIES; DYNAMICS; DISEASES; MODEL; STOCHASTICITY; DETERMINISM; HIERARCHIES; STATES AB Highly infectious, immunizing pathogens can cause violent local outbreaks that are followed by the agent's extinction as it runs out of susceptible hosts. For these pathogens, regional persistence can only be secured through spatial transmission and geographically asynchronous epidemics. In this paper we develop a hazard model for the waiting time between epidemics. We use the model, first, to discuss the predictability in timing of epidemics, and, second, to estimate the strength of spatial transmission. Based on the hazard model, we conclude that highly epidemic pathogens can at times be predictable in the sense that the waiting-time distribution between outbreaks is probabilistically bounded; The greater the spatial transmission the more periodic the outbreak dynamics. When we analyze the historical records of measles outbreaks in England and Wales between 1944 and 1965, we find the waiting-time between epidemics to depend inversely on community size. This is because large communities are much more tightly coupled to the regional metapopulation. The model further help identify the most important areas for spatial transmission. We conclude that the data on absence of these pathogens is the key to understanding spatial spread. C1 [Bjornstad, Ottar N.] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. [Bjornstad, Ottar N.; Grenfell, Bryan T.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Bjornstad, Ottar N.; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Bjornstad, ON (reprint author), Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. EM onb1@psu.edu RI Bjornstad, Ottar/I-4518-2012 NR 30 TC 8 Z9 8 U1 2 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1352-8505 EI 1573-3009 J9 ENVIRON ECOL STAT JI Environ. Ecol. Stat. PD SEP PY 2008 VL 15 IS 3 BP 265 EP 277 DI 10.1007/s10651-007-0059-3 PG 13 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA 334TI UT WOS:000258243700002 ER PT J AU Kan, HD London, SJ Chen, GH Zhang, YH Song, GX Zhao, NQ Jiang, LL Chen, BH AF Kan, Haidong London, Stephanie J. Chen, Guohai Zhang, Yunhui Song, Guixiang Zhao, Naiqing Jiang, Lili Chen, Bingheng TI Season, sex, age, and education as modifiers of the effects of outdoor air pollution on daily mortality in Shanghai, China: The Public Health and Air Pollution in Asia (PAPA) study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollution; modifiers; mortality; time-series studies ID CASE-CROSSOVER ANALYSIS; TIME-SERIES ANALYSIS; PARTICULATE MATTER; SENSITIVITY-ANALYSIS; NATIONAL MORBIDITY; EXPOLIS-HELSINKI; EUROPEAN CITIES; WESTERN-EUROPE; APHEA PROJECT; US CITIES AB BACKGROUND: Various factors can modify the health effects of outdoor air pollution. Prior findings about modifiers are inconsistent, and most of these studies were conducted in developed countries. OBJECTIVES: We conducted a time-series analysis to examine the modifying effect of season, sex, age, and education on the association between outdoor air pollutants [particulate matter < 10 mu m in aerodynamic diameter (PM10), sulfur dioxide, nitrogen dioxide, and ozone] and daily mortality in Shanghai, China, using 4 years of daily data (2001-2004). METHODS: Using a natural spline model to analyze the data, we examined effects of air pollution for the warm season (April-September) and cool season (October-March) separately. For total mortality, we examined the association stratified by sex and age. Stratified analysis by educational attainment was conducted for total, cardiovascular, and respiratory mortality. RESULTS: Outdoor air pollution was associated with mortality from all causes and from cardiorespiratory diseases in Shanghai. An increase of 10 mu g/m(3) in a 2-day average concentration of PM10, SO2, NO2, and O-3 corresponds to increases in all-cause mortality of 0.25% [95% confidence interval (CI), 0.14-0.37), 0.95% (95% CI, 0.62-1.28), 0.97% (95% CI, 0.66-1.27), and 0.31% (95% CI, 0.04-0.58), respectively. The effects of air pollutants were more evident in the cool season than in the warm season, and females and the elderly were more vulnerable to outdoor air pollution. Effects of air pollution were generally greater in residents with low educational attainment (illiterate or primary school) compared with those with high educational attainment (middle school or above). CONCLUSIONS: Season, sex, age, and education may modify the health effects of outdoor air pollution in Shanghai. These findings provide new information about the effects of modifiers on the relationship between daily mortality and air pollution in developing countries mid may have implications for local environmental and social policies. C1 [Kan, Haidong; Zhang, Yunhui; Chen, Bingheng] Fudan Univ, Dept Environm Hlth, Sch Publ Hlth, Shanghai 200032, Peoples R China. [Kan, Haidong; London, Stephanie J.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC USA. [Chen, Guohai] Shanghai Environm Monitoring Ctr, Shanghai, Peoples R China. [Song, Guixiang; Jiang, Lili] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China. [Zhao, Naiqing] Fudan Univ, Sch Publ Hlth, Dept Hlth Stat, Shanghai 200433, Peoples R China. RP Kan, HD (reprint author), Fudan Univ, Dept Environm Hlth, Sch Publ Hlth, Shanghai 200032, Peoples R China. EM haidongkan@gmail.com OI London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS NR 52 TC 177 Z9 205 U1 14 U2 68 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2008 VL 116 IS 9 BP 1183 EP 1188 DI 10.1289/ehp.10851 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 345TP UT WOS:000259020100032 PM 18795161 ER PT J AU Wong, CM Vichit-Vadakan, N Kan, HD Qian, ZM AF Wong, Chit-Ming Vichit-Vadakan, Nuntavarn Kan, Haidong Qian, Zhengmin CA PAPA Project Teams TI Public Health and Air Pollution in Asia (PAPA): A multicity study of short-term effects of air pollution on mortality SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollution; Bangkok; Hong Kong; mortality; Shanghai; time-series analysis; Wuhan ID PARTICULATE MATTER; NITROGEN-DIOXIDE; APHEA PROJECT; TIME-SERIES; EXPOSURE; BANGKOK; CITIES; ASSOCIATIONS; POLLUTANTS; THAILAND AB BACKGROUND AND OBJECTIVES: Although the deleterious effects of air pollution from fossil fuel combustion have been demonstrated in many Western nations, fewer studies have been conducted in Asia. The Public Health and Air Pollution in Asia (PAPA) project assessed the effects of short-term exposure to air pollution on daily mortality in Bangkok, Thailand, and in three cities in China: Hong Kong, Shanghai, and Wuhan. METHODS: Poisson regression models incorporating natural spline smoothing functions were used to adjust for seasonality and other time-varying covariates that might confound the association between air pollution and mortality. Effect estimates were determined for each city and then for the cities combined using a random effects method. RESULTS: In individual cities, associations were detected between most of the pollutants [nitrogen dioxide, sulfur dioxide, particulate matter <= 10 mu m in aerodynamic diameter (PM10), and ozone] and most health outcomes under study (i.e., all natural-cause, cardiovascular, and respiratory mortality). The city-combined effects of the four pollutants tended to be equal or greater than those identified in studies conducted in Western industrial nations. In addition, residents of Asian cities are likely to have higher exposures to air pollution than those in Western industrial nations because they spend more time outdoors and less time in air conditioning. CONCLUSIONS: Although the social and environmental conditions may be quite different, it is reasonable to apply estimates derived from previous health effect of air pollution studies in the West to Asia. C1 [Wong, Chit-Ming] Univ Hong Kong, Dept Community Med, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China. [Vichit-Vadakan, Nuntavarn] Thammasat Univ, Fac Publ Hlth, Pathum Thani, Thailand. [Kan, Haidong] Fudan Univ, Sch Publ Hlth, Shanghai 200433, Peoples R China. [Kan, Haidong] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. [Qian, Zhengmin] Penn State Univ, Coll Med, Hershey, PA USA. [Qian, Zhengmin] Geisinger Ctr Hlth Res, Danville, PA USA. RP Wong, CM (reprint author), Univ Hong Kong, Dept Community Med, Sch Publ Hlth, 5-F William MW Mong Block,21 Sassoon Rd, Hong Kong, Hong Kong, Peoples R China. EM hrmrwcm@hkucc.hku.hk RI Wong, Chit Ming/C-4438-2009; OI Thomas, Graham Neil/0000-0002-2777-1847; London, Stephanie/0000-0003-4911-5290 NR 28 TC 171 Z9 192 U1 10 U2 82 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2008 VL 116 IS 9 BP 1195 EP 1202 DI 10.1289/ehp.11257 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 345TP UT WOS:000259020100034 PM 18795163 ER PT J AU Tinkle, SS AF Tinkle, Sally S. TI Nanotechnology: Collaborative opportunities for ecotoxicology and environmental health SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Editorial Material C1 Natl Inst Environm Hlth Sci, Natl Inst Hlth, Durham, NC USA. RP Tinkle, SS (reprint author), Natl Inst Environm Hlth Sci, Natl Inst Hlth, Durham, NC USA. NR 4 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD SEP PY 2008 VL 27 IS 9 BP 1823 EP 1824 DI 10.1897/08-266.1 PG 2 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 335WT UT WOS:000258325000001 PM 19086312 ER PT J AU Hoffman, CS Mendola, P Savitz, DA Herring, AH Loomis, D Hartmann, KE Singer, PC Weinberg, HS Olshan, AF AF Hoffman, Caroline S. Mendola, Pauline Savitz, David A. Herring, Amy H. Loomis, Dana Hartmann, Katherine E. Singer, Philip C. Weinberg, Howard S. Olshan, Andrew F. TI Drinking water disinfection by-product exposure and fetal growth SO EPIDEMIOLOGY LA English DT Article ID ADVERSE PREGNANCY OUTCOMES; BIRTH-WEIGHT; TRIHALOMETHANE LEVELS; GESTATIONAL-AGE; UNITED-STATES; CONTAMINANTS; ASSOCIATION; CONSUMPTION; POPULATION; CHLOROFORM AB Previous studies suggest that elevated exposure 10 drinking water disinfection by-products (DBPs)-in particular, total trihalomethanes (TTHMs-may lead to fetal growth restriction. We examined the effects of exposure to TTHMs, haloacetic acids, and total organic halide oil the probability of delivering small-for-gestational-age (SGA) infant and on birth weight al term. Methods: Women early fit pregnancy (: 12 weeks' gestation) or planning a pregnancy were enrolled in a prospective pregnancy study conducted in 3 US communities from 2000 through 2004. Weekly (or biweekly) water samples were collected at each site as well as individual-level participant data. Associations between DBP exposures (T-THMs, halolacetic acids. total organic halide) and fetal growth Were assessed Using log-binomial regression for SGA (it 1958) and linear regression For term birth weight (it - 1854). We conducted I Bayesian analysis to examine associations between individual DBP species and fetal growth. Results: Haloacetic acids and total organic halide were not associated with SGA or term birth weight. The probability of delivering an SGA infant was elevated when comparing women with an average third-trimester residential TTHM concentration >= 80 mu g/L to women with exposure <80 mu g/L (risk ratio = 2.0 [95% confidence interval 1.1-3.6]), but not when examining other exposure contrasts. Bayesian analyses did not support l Consistent association,growth although these analyses between any DBP species and fetal g were based oil small sample sizes. Conclusions: Our results do not suggest an adverse effect of haloacetic acid or total organic halide exposure oil fetal growth. All association ol'TTI-INI with SGA was seen only for average r sid tial concentrations above the current( extraordinary standard. C1 [Hoffman, Caroline S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Mendola, Pauline] US EPA, Human Studies Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Savitz, David A.] Mt Sinai Sch Med, Dept Community & Preventat Med, New York, NY USA. [Herring, Amy H.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Herring, Amy H.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA. [Loomis, Dana] Univ Nevada, Sch Publ Hlth, Reno, NV 89557 USA. [Hartmann, Katherine E.] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Nashville, TN 37232 USA. [Hartmann, Katherine E.] Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth, Nashville, TN USA. [Singer, Philip C.; Weinberg, Howard S.; Olshan, Andrew F.] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. RP Hoffman, CS (reprint author), Natl Inst Environm Hlth Sci, POB 12233,MD EC-21, Res Triangle Pk, NC 27709 USA. EM dilworthch@niehs.nih.gov OI Mendola, Pauline/0000-0001-5330-2844 FU NIEHS NIH HHS [5-T32-ES07018]; PHS HHS [P30E510126] NR 41 TC 49 Z9 53 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2008 VL 19 IS 5 BP 729 EP 737 DI 10.1097/EDE.0b013e3181812bd4 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 341KB UT WOS:000258712000014 PM 18633330 ER PT J AU Kinoshita-Moleka, R Smith, JS Atibu, J Tshefu, A Hemingway-Foday, J Hobbs, M Bartz, J Koch, MA Rimoin, AW Ryder, RW AF Kinoshita-Moleka, R. Smith, J. S. Atibu, J. Tshefu, A. Hemingway-Foday, J. Hobbs, M. Bartz, J. Koch, M. A. Rimoin, A. W. Ryder, R. W. TI Low prevalence of HIV and other selected sexually transmitted infections in 2004 in pregnant women from Kinshasa, the Democratic Republic of the Congo SO EPIDEMIOLOGY AND INFECTION LA English DT Article ID SUB-SAHARAN AFRICA; POPULATIONS; SUBTYPES; NIGERIA; SPREAD AB This study examined the prevalence of HIV and other sexually transmitted infections (STIs) in pregnant women in Kinshasa, the Democratic Republic of the Congo (DRC). Between April and July 2004., antenatal attendees at two of the largest maternity clinics in Kinshasa were tested to identify HIV status, syphilis, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). HIV seroprevalence was 1.9 % in 2082 women. With PCR techniques, CT and NG infections were also uncommon in the first 529 women (1.7% and 0.4%, respectively). No active syphilis infection case was identified by Treponema pallidum haemagglutination assay (TPHA) and rapid plasma reagin test (RPR). A woman's risk of HIV infection was significantly associated with her reporting a male partner having had other female sexual partners (OR 2.7, 95 % CI 1.2-6.2). The continuing low seroprevalence of HIV in pregnant women from Kinshasa was confirmed. Understanding factors associated with this phenomenon could help prevent a future HIV epidemic in low HIV transmission areas in Africa. C1 [Kinoshita-Moleka, R.; Smith, J. S.; Ryder, R. W.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA. [Kinoshita-Moleka, R.; Atibu, J.] UNC DRC Program, Kinshasa, Zaire. [Tshefu, A.] Kinshasa Sch Publ Hlth, Kinshasa, Zaire. [Hemingway-Foday, J.; Bartz, J.; Koch, M. A.] RTI Int, Res Triangle Pk, NC USA. [Hobbs, M.; Ryder, R. W.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Rimoin, A. W.] NIH, Bethesda, MD 20892 USA. [Rimoin, A. W.] Univ Calif Los Angeles, Dept Epidemiol, Sch Publ Hlth, Los Angeles, CA USA. RP Smith, JS (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA. EM jennifers@unc.edu FU Global Network for Women's and Children's Health Research [NICHD U01 HD043475-01]; Bill & Melinda Gates Foundation; Center for AIDS Research [5 P30 A1050410-07 NIAID]; North Carolina STI; Topical Microbicide Cooperative Research Center [5 U19 AI031496-14] FX The authors acknowledge K. Rich (UNC-CH Microbiology Laboratory) and S. Edidi (DRC National AIDS Reference Laboratory) for laboratory technical support. G. Mpanya, M. Onyamboko, and K. Mwandagalirwa worked in the planning and implementation phases of the study. This work was financed by the Global Network for Women's and Children's Health Research (NICHD U01 HD043475-01) and the Bill & Melinda Gates Foundation. J. Smith was supported through a Center for AIDS Research grant (5 P30 A1050410-07 NIAID). Logistical support for STI testing was provided by the North Carolina STI and Topical Microbicide Cooperative Research Center grant (5 U19 AI031496-14). NR 28 TC 12 Z9 12 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD SEP PY 2008 VL 136 IS 9 BP 1290 EP 1296 DI 10.1017/S095026S807009818 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 350DI UT WOS:000259332400019 PM 18028581 ER PT J AU Probstfield, JL Wright, JT Einhorn, PT Pressel, S Davis, BR AF Probstfield, J. L. Wright, J. T. Einhorn, P. T. Pressel, S. Davis, B. R. CA ALLHAT Investigators TI ALLHAT findings revisited 5 years later in the context of subsequent analyses SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Probstfield, J. L.] Univ Washington, Seattle, WA 98195 USA. [Wright, J. T.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Einhorn, P. T.] NHLBI, NIH, Bethesda, MD 20892 USA. [Pressel, S.; Davis, B. R.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 511 EP 511 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702502458 ER PT J AU Koh, K Oh, P Quon, M Han, S Chung, W Shin, E AF Koh, K. Oh, P. Quon, M. Han, S. Chung, W. Shin, E. TI Significant differential metabolic effects of lipophilic and hydrophilic statins in hypercholesterolemic patients SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Koh, K.] Gachon Med Sch, Div Cardiol, Gil Heart Ctr, Inchon, South Korea. [Oh, P.; Han, S.; Chung, W.; Shin, E.] Gachon Univ, Gil Med Ctr, Inchon, South Korea. [Quon, M.] NIH, Diabet Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 614 EP 615 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702503163 ER PT J AU Montero, CI Shea, YR Jones, PA Harrington, SM Tooke, NE Witebsky, FG Murray, PR AF Montero, C. I. Shea, Y. R. Jones, P. A. Harrington, S. M. Tooke, N. E. Witebsky, F. G. Murray, P. R. TI Evaluation of Pyrosequencing (R) technology for the identification of clinically relevant non-dematiaceous yeasts and related species SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID MOLECULAR-IDENTIFICATION; CRYPTOCOCCUS-NEOFORMANS; TRICHOSPORON-PULLULANS; CANDIDA-ORTHOPSILOSIS; FUNGAL PATHOGENS; METAPSILOSIS; PARAPSILOSIS; INFECTION; DISEASE; COMPLEX AB Pyrosequencing was used to identify 133 isolates of clinically relevant non-dematiaceous yeasts. These included 97 ATCC strains (42 type strains), seven UAMH strains, and 29 clinical isolates. Isolates belonged to the following genera: Candida (18 species), Trichosporon (10), Cryptococcus (7), Malassezia (3), Rhodotorula (2), Geotrichum (1), Blastoschizomyces (1), and Kodamaea (1). Amplicons of a hyper-variable ITS region were obtained and analyzed using Pyrosequencing technology. The data were evaluated by a BLAST search against the GenBank database and correlated with data obtained by conventional cycle sequencing of the ITS1-5.8S-ITS2 region. Cycle sequencing identified 78.9% of the isolates to the species level. Pyrosequencing technology identified 69.1%. In 90.1% of all of the strains tested, the identification results of both sequencing methods were identical. Most Candida isolates can be identified to the species level by Pyrosequencing. Trichosporon species and some Cryptococcus species cannot be differentiated at the species level. Pyrosequencing can be used for the reliable identification of most commonly isolated non-dematiaceous yeasts, with a reduction of cost per identification compared to conventional sequencing. C1 [Montero, C. I.; Shea, Y. R.; Jones, P. A.; Witebsky, F. G.; Murray, P. R.] NIH, Microbiol Serv, Dept Lab Med, Clin Ctr,US Dept HHS, Bethesda, MD 20892 USA. [Harrington, S. M.] Albany Med Ctr, Dept Clin Microbiol, Albany, NY 12208 USA. [Tooke, N. E.] Biotage AB, S-75318 Uppsala, Sweden. RP Montero, CI (reprint author), NIH, Microbiol Serv, Dept Lab Med, Clin Ctr,US Dept HHS, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM monteroc@cc.nih.gov FU NIH Clinical Center FX We thank Patricia S. Conville, Department of Laboratory Medicine, Warren Grant Magnuson Clinical Center, NIH, for her technical assistance. This research was supported by the Intramural Research Program of the NIH Clinical Center. The views expressed herein are those of the authors and should not be construed as those of the U. S. Department of Health and Human Services. NR 37 TC 26 Z9 30 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD SEP PY 2008 VL 27 IS 9 BP 821 EP 830 DI 10.1007/s10096-008-0510-x PG 10 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 337RK UT WOS:000258453000008 PM 18421488 ER PT J AU de Snoo, FA Hottenga, JJ Gillanders, EM Sandkuijl, LA Jones, MP Bergman, W van der Drift, C van Leeuwen, I van Mourik, L ter Huurne, JAC Frants, RR Willemze, R Breuning, MH Trent, JM Gruis, NA AF de Snoo, Femke A. Hottenga, Jouke-Jan Gillanders, Elizabeth M. Sandkuijl, Loudewijk A. Jones, Mary Pat Bergman, Wilma van der Drift, Clasine van Leeuwen, Inge van Mourik, Lenny ter Huurne, Jeanet A. C. Frants, Rune R. Willemze, Rein Breuning, Martijn H. Trent, Jeffrey M. Gruis, Nelleke A. TI Genome-wide linkage scan for atypical nevi in p16-Leiden melanoma families SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE nevus gene; familial melanoma; linkage ID FAMMM SYNDROME FAMILIES; GERMLINE MUTATION; CDKN2A MUTATIONS; SUSCEPTIBILITY; PENETRANCE; CANCER; GENE; TWIN; COUNT; MAP AB In most Dutch melanoma families, a founder deletion in the melanoma susceptibility gene CDKN2A (which encodes p16) is present. This founder deletion (p16-Leiden) accounts for a significant proportion of the increased melanoma risk. However, it does not account for the Atypical Nevus (AN) phenotype that segregates in both p16-Leiden carriers and non-carriers. The AN-affected p16-Leiden family members are therefore a unique valuable resource for unraveling the genetic etiology of the AN phenotype, which is considered both a risk factor and a precursor lesion for melanoma. In this study, we performed a genome-wide scan for linkage in four p16-Leiden melanoma pedigrees, classifying family members with five or more AN as affected. The strongest evidence for an atypical nevus susceptibility gene was mapped to chromosome band 7q21.3 (two-point LOD score 2.751), a region containing candidate gene CDK6. C1 [de Snoo, Femke A.; van Mourik, Lenny; ter Huurne, Jeanet A. C.; Frants, Rune R.; Breuning, Martijn H.] Leiden Univ, Med Ctr, Dept Human, NL-2333 ZA Leiden, Netherlands. [de Snoo, Femke A.; van Mourik, Lenny; ter Huurne, Jeanet A. C.; Frants, Rune R.; Breuning, Martijn H.] Leiden Univ, Med Ctr, Dept Clin Genet, NL-2333 ZA Leiden, Netherlands. [Hottenga, Jouke-Jan; Gruis, Nelleke A.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Gillanders, Elizabeth M.; Jones, Mary Pat] NHGRI, Inherited Dis Res Branch, NIH, Dept Hlth & Human Serv, Baltimore, MD USA. [Sandkuijl, Loudewijk A.] Leiden Univ, Med Ctr, Dept Med Stat, Leiden, Netherlands. [Bergman, Wilma; van der Drift, Clasine; van Leeuwen, Inge; Willemze, Rein] Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands. [Trent, Jeffrey M.] Translat Genom Res Inst, Phoenix, AZ USA. RP de Snoo, FA (reprint author), Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Dept Clin Genet, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands. EM desnoo@lumc.nl OI Gruis, Nelleke/0000-0002-5210-9150 FU Dutch Cancer Society [RUL 99-1932]; Aspasia fellowship of the Netherlands organization for Scientific Research FX We are indebted to the family members for their past and recent participation in our research. FAS is supported by the Dutch Cancer Society (RUL 99-1932); NAG is a recipient of an Aspasia fellowship of the Netherlands organization for Scientific Research. NR 26 TC 11 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD SEP PY 2008 VL 16 IS 9 BP 1135 EP 1141 DI 10.1038/ejhg.2008.72 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 344LX UT WOS:000258929800016 PM 18398432 ER PT J AU Jatav, V Mishra, P Kashaw, S Stables, JP AF Jatav, Varsha Mishra, Pradeep Kashaw, Sushil Stables, J. P. TI CNS depressant and anticonvulsant activities of some novel 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE Styryl quinazoline-4(3H)-ones; 1,3,4-Thiadiazole; MES; Subcutaneous pentylenetetrazole induced seizure; CNS depressants ID SEMICARBAZONES; DERIVATIVES; AGENTS AB A series of new 3-[5-substituted phenyl-1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones were synthesized and evaluated for anticonvulsant, sedative-hypnotic and CNS depression activities. After i.p. injection to mice or rat at doses of 30, 100, and 300 mg/kg body weight 2-styryl quinazolin-4(3H)-ones derivatives were examined in the maximal electroshock (MES) induced seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Rotorod method was employed to determine the neurotoxicity. Out of 18 compounds only 4a, 4e and 4p showed anticonvulsant activity in one or more test models. All except 4l and 4q exhibited significant sedative-hypnotic activity via actophotometer screen. Forced swim pool method to determine CNS depressant activity resulted in some potent compounds. It can be concluded that synthesized compounds exhibited better sedative-hypnotic and CNS depressant activities than anticonvulsant activity. (C) 2007 Elsevier Masson SAS. All rights reserved. C1 [Jatav, Varsha; Mishra, Pradeep; Kashaw, Sushil] Dr HSG Univ, Pharmaceut Chem Div, Dept Pharmaceut Sci, Sagar 470003, Madhya Pradesh, India. [Stables, J. P.] NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA. RP Kashaw, S (reprint author), Dr HSG Univ, Pharmaceut Chem Div, Dept Pharmaceut Sci, Sagar 470003, Madhya Pradesh, India. EM sushilkashaw@gmail.com NR 22 TC 84 Z9 85 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD SEP PY 2008 VL 43 IS 9 BP 1945 EP 1954 DI 10.1016/j.ejmech.2007.12.003 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 360RC UT WOS:000260074200016 PM 18222569 ER PT J AU Lauretani, F Semba, RD Dayhoff-Brannigan, M Corsi, AM Di Iorio, A Buiatti, E Bandinelli, S Guralnik, JM Ferrucci, L AF Lauretani, Fulvio Semba, Richard D. Dayhoff-Brannigan, Margaret Corsi, Anna Maria Di Iorio, Angelo Buiatti, Eva Bandinelli, Stefania Guralnik, Jack M. Ferrucci, Luigi TI Low total plasma carotenoids are independent predictors of mortality among older persons - The InCHIANTI study SO EUROPEAN JOURNAL OF NUTRITION LA English DT Article DE aging; carotenoids; fruits; mortality; vegetables ID CARDIOVASCULAR-DISEASE MORTALITY; CORONARY-HEART-DISEASE; ALPHA-TOCOPHEROL; ANTIOXIDANT VITAMINS; SERUM CAROTENOIDS; BETA-CAROTENE; ALL-CAUSE; POPULATION; CANCER; NUTRITION AB Background Plasma carotenoids are considered a valid biological marker for fruit and vegetable dietary intake. Recent studies show that low carotenoid levels are associated with a high risk of inflammation, cancer, and cardiovascular disease. Aim of the study To determine whether low plasma carotenoids are associated with increased mortality among older adults. Methods Longitudinal study among 1,043 adults, 65 years and older, in the InCHIANTI study, a population-based cohort of adults living in the community in the Tuscany region, Italy. Results Mean total carotenoid concentration was 1.80 mu mol/l. During eight years of follow-up, 310 (29.7%) of participants died. Eight-year survival was lower in the lowest compared with the highest tertile of total serum carotenoids (P < 0.0001 by Mantel-Haenszel chi-square). In a multivariate Cox proportional hazards model adjusted for age, education, smoking, body mass index, energy intake, and chronic diseases, adults in the highest tertile of plasma carotenoids at enrollment had lower mortality compared to those in the lowest tertile (Hazards Ratio obtained by considering carotenoids level as an ordinal variable 0.81, 95%; CI 0.65-0.99; P for trend = 0.046). Conclusions Low plasma carotenoids are an independent risk factor for mortality among older adults living in the community. C1 [Lauretani, Fulvio] Univ Hosp Parma, Geriatr Unit, Parma, Italy. [Lauretani, Fulvio; Corsi, Anna Maria; Buiatti, Eva] Tuscany Reg Agcy, Florence, Italy. [Semba, Richard D.; Dayhoff-Brannigan, Margaret] Johns Hopkins Sch Med, Baltimore, MD USA. [Di Iorio, Angelo] Univ G dAnnunzio, Lab Clin Epidemiol, Chieti, Italy. [Bandinelli, Stefania] Azienda Sanit Firenze, Florence, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Lauretani, F (reprint author), Univ Hosp Parma, Geriatr Unit, Parma, Italy. EM flauretani@ao.pr.it RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 FU National Institute on Aging [N01-AG-916413, N01-AG-821336, N01-AG5 -0002]; NIA [R01 AG027012]; Intramural Research Program; National Institute on Aging, NIH FX This work was supported by National Institute on Aging Contracts N01-AG-916413, N01-AG-821336, N01-AG5 -0002, and NIA Grant R01 AG027012. This research was supported in part by the Intramural Research Program, National Institute on Aging, NIH. NR 33 TC 26 Z9 26 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1436-6207 J9 EUR J NUTR JI Eur. J. Nutr. PD SEP PY 2008 VL 47 IS 6 BP 335 EP 340 DI 10.1007/s00394-008-0732-9 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 342BA UT WOS:000258758400007 PM 18709473 ER PT J AU Akhmadeeva, L Andreeva, VA Sussman, S Khusnutdinova, Z Simons-Morton, BG AF Akhmadeeva, Leila Andreeva, Valentina A. Sussman, Steve Khusnutdinova, Zolya Simons-Morton, Bruce G. TI Need and possibilities for seat belt use promotion in Bashkortostan, Russia SO EVALUATION & THE HEALTH PROFESSIONS LA English DT Article DE seat belts; health promotion; Bashkortostan; Russia ID TRANSPORTATION SAFETY; ENFORCEMENT; LAWS; LEGISLATION; PROGRAM; RATES; CHILD AB Bashkortostan is a republic in the Russian Federation with a population of 4.1 million. As with other health behaviors, the prevalence of seat belt use is low, which may account in part for the very high rate of motor-vehicle-related mortality in this republic. The authors discuss the need and potential for translating seat belt promotion programming from other Russian regions and other countries to Bashkortostan. The authors conclude that current policies developed in other countries could work well in the republic, if they are enforced. Meanwhile, initiatives such as the Sakhalin Road Safety Partnership offer great potential for translation in Bashkortostan as well as in other regions with similarly low seat belt use prevalence. C1 [Akhmadeeva, Leila] Bashkir State Med Univ, Ufa, Russia. [Andreeva, Valentina A.; Sussman, Steve] Univ So Calif, Los Angeles, CA USA. [Khusnutdinova, Zolya] Bashkir State Pedag Univ, Ufa, Russia. [Simons-Morton, Bruce G.] NICHHD, Bethesda, MD 20892 USA. RP Akhmadeeva, L (reprint author), Bashkir State Med Univ, Ufa, Russia. OI Akhmadeeva, Leila/0000-0002-1177-6424; Simons-Morton, Bruce/0000-0003-1099-6617 FU Intramural NIH HHS [Z99 HD999999] NR 36 TC 4 Z9 4 U1 3 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0163-2787 J9 EVAL HEALTH PROF JI Eval. Health Prof. PD SEP PY 2008 VL 31 IS 3 BP 282 EP 289 DI 10.1177/0163278708320167 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 335KL UT WOS:000258289400005 PM 18559882 ER PT J AU Lopez-Lluch, G Irusta, PM Navas, P de Cabo, R AF Lopez-Lluch, Guillermo Irusta, Pablo M. Navas, Placido de Cabo, Rafael TI Mitochondrial biogenesis and healthy aging SO EXPERIMENTAL GERONTOLOGY LA English DT Review DE aging; calorie restriction; mitochondrial biogenesis; PGC-1 alpha ID ACTIVATED PROTEIN-KINASE; MUSCLE OXIDATIVE CAPACITY; RAT SKELETAL-MUSCLE; THYROID-HORMONE; SACCHAROMYCES-CEREVISIAE; CALORIC RESTRICTION; NITRIC-OXIDE; TRANSCRIPTIONAL REPRESSION; CELLULAR DIFFERENTIATION; NEUROSPORA-CRASSA AB Aging is associated with an overall loss of function at the level of the whole organism that has origins in cellular deterioration. Most cellular components, including mitochondria, require continuous recycling and regeneration throughout the lifespan. Mitochondria are particularly susceptive to damage over time as they are the major bioenergetic machinery and source of oxidative stress in cells. Effective control of mitochondrial biogenesis and turnover, therefore, becomes critical for the maintenance of energy production, the prevention of endogenous oxidative stress and the promotion of healthy aging. Multiple endogenous and exogenous factors regulate mitochondrial biogenesis through the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (KC-1 alpha). Activators of PGC-1 alpha include nitric oxide, CREB and AMPK. Calorie restriction (CR) and resveratrol, a proposed CR mimetic, also increase mitochondrial biogenesis through activation of PGC-1 alpha. Moderate exercise also mimics CR by inducing mitochondrial biogenesis. Negative regulators of PGC-1 alpha such as RIP140 and 160MBP suppress mitochondrial biogenesis. Another mechanism involved in mitochondrial maintenance is mitochondrial fission/fusion and this process also involves an increasing number of regulatory proteins. Dysfunction of either biogenesis or fission/fusion of mitochondria is associated with diseases of the neuromuscular system and aging, and a greater understanding of the regulation of these processes should help us to ultimately control the aging process. Published by Elsevier Inc. C1 [de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Lopez-Lluch, Guillermo; Navas, Placido] Univ Pablo Olavide, CSIC, CABD, Seville 41013, Spain. [Irusta, Pablo M.] Georgetown Univ, Med Ctr, Dept Human Sci, Washington, DC 20057 USA. RP de Cabo, R (reprint author), NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. EM decabora@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; Lopez-Lluch, Guillermo/N-4742-2014; de Cabo, Rafael/J-5230-2016; OI Lopez-Lluch, Guillermo/0000-0001-9830-8502; de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU Intramural NIH HHS [Z01 AG000368-03] NR 84 TC 157 Z9 163 U1 4 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD SEP PY 2008 VL 43 IS 9 BP 813 EP 819 DI 10.1016/j.exger.2008.06.014 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 351QF UT WOS:000259438400002 PM 18662766 ER PT J AU Tang, SC Lathia, JD Selvaraj, PK Jo, DG Mughal, MR Cheng, A Siler, DA Markesbery, WR Arumugam, TV Mattson, MP AF Tang, Sung-Chun Lathia, Justin D. Selvaraj, Pradeep K. Jo, Dong-Gyu Mughal, Mohamed R. Cheng, Aiwu Siler, Dominic A. Markesbery, William R. Arumugam, Thiruma V. Mattson, Mark P. TI Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal SO EXPERIMENTAL NEUROLOGY LA English DT Article DE toll-like receptors; amyloid beta-peptide; 4-hydroxynonenal; neuron; cell death ID FOCAL CEREBRAL-ISCHEMIA; INNATE IMMUNE DEFENSE; ALZHEIMERS-DISEASE; SIGNALING PATHWAYS; OXIDATIVE STRESS; NERVOUS-SYSTEM; COMPLEMENT ACTIVATION; BRAIN-INJURY; INFLAMMATION; TOLL-LIKE-RECEPTOR-4 AB The innate immune system senses the invasion of pathogenic microorganisms and tissue injury through Toll-like receptors (TLR), a mechanism thought to be limited to immune cells. We recently found that neurons express several TLRs, and that the levels of TLR2 and TLR4 are increased in neurons in response to energy deprivation. Here we report that TLR4 expression increases in neurons when exposed to amyloid beta-peptide (A beta 1-42) or the lipid pet-oxidation product 4-hydroxynonenal (HNE). Neuronal apoptosis triggered by A beta and HNE was mediated by jun N-terminal kinase (JNK); neurons from TLR4 mutant mice exhibited reduced JNK and caspase-3 activation and were protected against apoptosis induced by A beta and HNE. Levels of TLR4 were decreased in inferior parietal cortex tissue specimens from end-stage AD patients compared to aged-matched Control Subjects, possibly as the result of loss of neurons expressing TLR4. Our findings Suggest that TLR4 signaling increases the vulnerability of neurons to A beta and oxidative stress in AD, and identify TLR4 as a potential therapeutic target for AD. Published by Elsevier Inc. C1 [Tang, Sung-Chun; Lathia, Justin D.; Jo, Dong-Gyu; Mughal, Mohamed R.; Cheng, Aiwu; Siler, Dominic A.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Tang, Sung-Chun] Natl Taiwan Univ Hosp, Stoke Ctr, Dept Neurol, Taipei, Taiwan. [Tang, Sung-Chun] Natl Taiwan Univ Hosp, Dept Neurol, Yun Liin Branch, Taipei, Taiwan. [Jo, Dong-Gyu] Sungkyunkwan Univ, Coll Pharm, Suwon, South Korea. [Markesbery, William R.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Selvaraj, Pradeep K.; Arumugam, Thiruma V.] Texas Tech Univ, Hlth Sci Ctr, Dept Pharmaceut Sci, Sch Pharm, Amarillo, TX USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; OI Tang, Sung-Chun/0000-0003-3731-5973 FU Intramural Research Program of the National Institute on Aging; National Institutes of Health FX We wish to thank Hiayang Zhu and Ouyang Xin for their excellent technical support. This work was supported by Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 55 TC 134 Z9 144 U1 5 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD SEP PY 2008 VL 213 IS 1 BP 114 EP 121 DI 10.1016/j.expneurol.2008.05.014 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 344QX UT WOS:000258943500014 PM 18586243 ER PT J AU Wolf, RC Sambataro, F Vasic, N Shonfeldt-Lecuona, C Ecker, D Landwehrmeyer, B AF Wolf, Robert Christian Sambataro, Fabio Vasic, Nenad Shoenfeldt-Lecuona, Carlos Ecker, Daniel Landwehrmeyer, Bernhard TI Aberrant connectivity of lateral prefrontal networks in presymptomatic Huntington's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article DE premanifest Huntington's disease; working memory; striatum; independent component analysis; functional magnetic resonance imaging ID INDEPENDENT COMPONENT ANALYSIS; EVENT-RELATED FMRI; WORKING-MEMORY; COGNITIVE DEFICITS; BRAIN; DYSFUNCTION; CORTEX; NEUROPATHOLOGY; ABNORMALITIES; EXPRESSION AB In clinically presymptomatic individuals with the Huntington's disease (HD) gene mutation, functional neuroimaging data have suggested a dysfuuction Of multiple cortical and subcortical regions including the prefrontal and parietal cortex, as well as the striatum. Although it has been hypothesized that these activation differences most likely reflect aberrant corticostriatal circuits, the functional Coupling of neural networks associated with cognitive performance has not been investigated so far. In this Study, we used functional magnetic resonance imaging (fMRI) and multivariate analytic techniques to investigate memory-related patterns of functional connectivity in healthy controls (n = 16) and pre-HD individuals (n = 16). Independent component analyses (ICA) revealed distinct bilateral frontostriatal and frontoparietal networks that were activated during a verbal working memory paradigm in both healthy controls and pre-HD subjects. Compared with healthy controls, pre-HD individuals exhibited lower functional connectivity in left lateral prefrontal and parietal regions as well as in the bilateral putamen. Functional connectivity indices in the left putamen were negatively correlated with the CAG repeat size and the UHDRS behavioral score, and positively correlated with the predicted years to manifest symptom onset. The connectivity of the right putamen was negatively correlated with the UHDRS motor score. In pre-HD individuals, these results suggest ail early frontostriatal and frontoparietal deficit of dissociable functional networks associated with executive processing. (C) 2008 Elsevier Inc. All rights reserved. C1 [Wolf, Robert Christian; Vasic, Nenad; Shoenfeldt-Lecuona, Carlos] Univ Ulm, Dept Psychiat & Psychotherapy 3, D-89075 Ulm, Germany. [Sambataro, Fabio] Univ Bari, Dept Psychiat, I-70121 Bari, Italy. [Ecker, Daniel; Landwehrmeyer, Bernhard] Univ Ulm, Dept Neurol, D-89069 Ulm, Germany. [Sambataro, Fabio] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Wolf, RC (reprint author), Univ Ulm, Dept Psychiat & Psychotherapy 3, Leimgrubenweg 12-14, D-89075 Ulm, Germany. EM christian.wolf@uni-ulm.de RI Sambataro, Fabio/E-3426-2010; OI Sambataro, Fabio/0000-0003-2102-416X; Landwehrmeyer, Georg Bernhard/0000-0003-3375-790X FU European Huntington's Disease Network (EHDN) FX This study was supported by the European Huntington's Disease Network (EHDN). The authors are grateful to Beate Englet and Sebastian Satzinger for their assistance with the data collection. NR 54 TC 58 Z9 58 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD SEP PY 2008 VL 213 IS 1 BP 137 EP 144 DI 10.1016/j.expneurol.2008.05.017 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 344QX UT WOS:000258943500017 PM 18588876 ER PT J AU Ostera, G Tokumasu, F Oliveira, F Sa, J Furuya, T Teixeira, C Dvorak, J AF Ostera, Graciela Tokumasu, Fuyuki Oliveira, Fabiano Sa, Juliana Furuya, Tetsuya Teixeira, Clarissa Dvorak, James TI Plasmodium falciparum: Food vacuole localization of nitric oxide-derived species in intraerythrocytic stages of the malaria parasite SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; nitric oxide ID SYNTHASE; IDENTIFICATION; HEMOGLOBIN; ERYTHROCYTES AB Nitric oxide (NO) has diverse biological functions. Numerous studies have documented NO's biosynthetic pathway in a wide variety of organisms. Little is known, however, about NO production in intraerythrocytic Plasmodium falciparum. Using diaminorhodamine-4-methyl acetoxymethylester (DAR-4M AM), a fluorescent indicator, we obtained direct evidence of NO and NO-derived reactive nitrogen species (RNS) production in intraerythrocytic P.falciparum parasites, as well as in isolated food vacuoles from trophozoite stage parasites. We preliminarily identified two gene sequences that might be implicated in NO synthesis in intra erythrocytic P.falciparum. We showed localization of the protein product of one of these two genes, a molecule that is structurally similar to a plant nitrate reductase, in trophozoite food vacuole membranes. We confirmed previous reports on the antiproliferative effect of NOS (nitric oxide synthase) inhibitors in A falciparum cultures; however, we did not obtain evidence that NOS inhibitors had the ability to inhibit RNS production or that there is an active NOS in mature forms of the parasite. We concluded that a nitrate reductase activity produce NO and NO-derived RNS in or around the food vacuole in A falciparum parasites. The food vacuole is a critical parasitic compartment involved in hemoglobin degradation, heme detoxification and a target for antimalarial drug action. Characterization of this relatively unexplored synthetic activity could provide important clues into poorly understood metabolic processes of the malaria parasite. Published by Elsevier Inc. C1 [Ostera, Graciela; Tokumasu, Fuyuki; Dvorak, James] NIAID, Biophys & Biochem Parasitol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Oliveira, Fabiano; Teixeira, Clarissa] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Sa, Juliana] NIAID, Malaria Genet Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Furuya, Tetsuya] NIAID, Malaria Genom Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Ostera, G (reprint author), NIAID, Biophys & Biochem Parasitol Sect, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Twinbrook 3,Room 2W-09, Rockville, MD 20852 USA. EM gostera@niaid.nih.gov RI Oliveira, Fabiano/B-4251-2009; Furuya, Tetsuya/J-5916-2013; Furuya, Tetsuya/H-2412-2013 OI Oliveira, Fabiano/0000-0002-7924-8038; Tokumasu, Fuyuki/0000-0003-2790-1071; Furuya, Tetsuya/0000-0003-3979-7072 FU Intramural NIH HHS [Z99 AI999999] NR 23 TC 13 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD SEP PY 2008 VL 120 IS 1 BP 29 EP 38 DI 10.1016/j.exppara.2008.04.014 PG 10 WC Parasitology SC Parasitology GA 347DC UT WOS:000259119800005 PM 18504040 ER PT J AU Patterson, LJ Robert-Guroff, M AF Patterson, L. Jean Robert-Guroff, Marjorie TI Replicating adenovirus vector prime/protein boost strategies for HIV vaccine development SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE animal models; HIV vaccine; mucosal immunity; multigenic priming; protein boost; replication competent adenovirus vectors ID SIMIAN-IMMUNODEFICIENCY-VIRUS; VESICULAR STOMATITIS-VIRUS; CELLULAR IMMUNE-RESPONSES; HOST-RANGE MUTANT; CD4(+) T-CELLS; DIPLOID TISSUE CULTURE; RHESUS MACAQUES; NEUTRALIZING ANTIBODIES; RECOMBINANT ADENOVIRUS; AIDS VACCINE AB Background: In recent years the HIV vaccine field introduced a number of promising vaccine candidates into human clinical trials. Objective: To briefly discuss the advances made in vaccine development and HIV pathogenesis and give an overview of the body of work our lab has generated in multiple animal models on replication-competent Adenovirus recombinant vaccines. Methods: Emphasis is placed on comparative examination of vaccine components, routes of immunization and challenge models using replicating Adenovirus vectors. Results/conclusion: The findings make the case that replicating Adenovirus vectors are superior in priming multiple arms of the immune system, and in conjunction with protein boosting, have resulted in dramatic protective efficacy leading to their advancement to Phase I trials. Implications of the recent halting of the Merck Ad5-HIV Phase IIb clinical trial of our vaccine approach and other vectored vaccines are discussed. C1 [Patterson, L. Jean; Robert-Guroff, Marjorie] NCI, Natl Inst Hlth, Vaccine Branch, Bethesda, MD 20892 USA. RP Robert-Guroff, M (reprint author), NCI, Natl Inst Hlth, Vaccine Branch, 41 Medlars Dr Bldg 41,Room D804, Bethesda, MD 20892 USA. EM guroffm@mail.nih.gov FU National Institutes of Health; National Cancer Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 136 TC 28 Z9 28 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD SEP PY 2008 VL 8 IS 9 BP 1347 EP 1363 DI 10.1517/14712590802256991 PG 17 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 348LW UT WOS:000259213000008 PM 18694354 ER PT J AU Zarate, CA Manji, HK AF Zarate, Carlos A., Jr. Manji, Husseini K. TI Riluzole in psychiatry: a systematic review of the literature SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE antidepressant; anxiety disorder; bipolar disorder; depression; glutamate; mania; plasticity; psychiatry; riluzole; treatment ID AMYOTROPHIC-LATERAL-SCLEROSIS; OPEN-LABEL TRIAL; NEUROPROTECTIVE AGENT RILUZOLE; OBSESSIVE-COMPULSIVE DISORDER; MAJOR DEPRESSIVE DISORDER; CELLULAR PLASTICITY CASCADES; GENERALIZED ANXIETY DISORDER; SODIUM-CHANNEL BLOCKERS; SPINAL-CORD-INJURY; UDP-GLUCURONOSYLTRANSFERASES AB Background: The glutamate system seems to be an important contributor to the pathophysiology of mood and anxiety disorders. Thus, glutamatergic modulators are reasonable candidate drugs to test in patients with mood and anxiety disorders. Riluzole, a neuroprotective agent with anticonvulsant properties approved for the treatment of amyotrophic lateral sclerosis (ALS) is one such agent. Objective: To assess the potential risks and benefits of riluzole treatment in psychiatric patients. Methods: A PubMed search was performed using the keywords 'riluzole', 'inhibitor of glutamate release' and 'glutamatergic modulator' to identify all clinical studies and case reports involving riluzole in psychiatric patients. Results/conclusion: Riluzole's side effect profile is favorable and preliminary results regarding riluzole for the treatment of severe mood, anxiety and impulsive disorders are encouraging. C1 [Zarate, Carlos A., Jr.; Manji, Husseini K.] NIMH, Lab Mol Pathophysiol & Expt Therapeut, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), 10 Ctr Dr,Mark O Hatfield CRC,Unit 7 SE,Rm 7-3445, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov FU Intramural NIH HHS [Z01 MH002828-05, Z01 MH002857-03] NR 92 TC 35 Z9 36 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD SEP PY 2008 VL 4 IS 9 BP 1223 EP 1234 DI 10.1517/17425250802340946 PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 348LZ UT WOS:000259213300008 PM 18721116 ER PT J AU Miller, S Stagl, J Wallerstedt, DB Ryan, M Mansky, PJ AF Miller, Scott Stagl, Jamie Wallerstedt, Dawn B. Ryan, Mary Mansky, Patrick J. TI Botanicals used in complementary and alternative medicine treatment of cancer: clinical science and future perspectives SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE botanical; cancer symptoms; cancer treatment; clinical trials; complementary and alternative medicine ID CHRONIC MYELOGENOUS LEUKEMIA; FACTOR-KAPPA-B; TRADITIONAL CHINESE MEDICINE; QUALITY-OF-LIFE; WITHANIA-SOMNIFERA; BREAST-CANCER; ADJUVANT IMMUNOCHEMOTHERAPY; COLORECTAL-CANCER; POLYSACCHARIDE-K; CHRONIC-PHASE AB Background: Botanicals and herbal combinations are among the most common complementary and alternative medicine (CAM) approaches used by cancer patients both for cancer treatment and management of cancer symptoms. Despite their widespread use, however, the safety and efficacy of many botanicals has not been established in controlled clinical trials. Objectives: This article reviews the published evidence for the safety and clinical benefit of botanicals used in the treatment of cancer and cancer symptom management and describes the continuing clinical trials of botanicals with applications in oncology. Methods: Literature searches were conducted in PubMed, EMBASE, Cochrane Clinical Trials databases, Pharmaprojects and CRISP (Computer Retrieval of Information on Scientific Projects) clinical trials databases. Conclusion: A number of botanicals have shown promise for cancer symptom management but need further study. A limited number of multi-agent nutritional supplement approaches are being explored in clinical trials. Botanical immunomodulators and botanical products shown to affect pathways of angiogenesis, apoptosis and cell signaling in vitro have stimulated research interest and may broaden the range of available cancer treatments. C1 [Miller, Scott; Stagl, Jamie; Wallerstedt, Dawn B.; Mansky, Patrick J.] Natl Inst Hlth, DHHS, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Ryan, Mary] Natl Inst Hlth Lib, Bethesda, MD 20892 USA. RP Mansky, PJ (reprint author), Natl Inst Hlth, DHHS, Natl Ctr Complementary & Alternat Med, 10 Ctr Dr,CRC,Room 4-1741,MSC 1302, Bethesda, MD 20892 USA. EM manskyp@mail.nih.gov FU NIH; NCCAM FX This research was supported in part by the Intramural Research Program of the NIH, NCCAM. Conclusions drawn and recommendations for future directions made are the opinions of the authors and do not represent the view of the National Center for Complementary and Alternative Medicine. NR 99 TC 10 Z9 10 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD SEP PY 2008 VL 17 IS 9 BP 1353 EP 1364 DI 10.1517/13543780802323464 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 343VD UT WOS:000258882500007 PM 18694368 ER PT J AU Brown, M Cohen, J Arun, P Chen, Z Van Waes, C AF Brown, Matthew Cohen, Jonah Arun, Pattatheyil Chen, Zhong Van Waes, Carter TI NF-kappa B in carcinoma therapy and prevention SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE aspirin; BMS-345541; bortezomib; carcinoma; CHS-828; dexamethasone; inhibitor-kappaB; MLN-120B; NF-kappa B; NSAIDs; proteasome; sulindac ID SQUAMOUS-CELL CARCINOMA; PROSTATE-CANCER CELLS; PROTEIN-KINASE CK2; PROTEASOME INHIBITOR BORTEZOMIB; MULTIPLE-MYELOMA; BREAST-CANCER; TRANSCRIPTIONAL ACTIVITY; TUMOR-GROWTH; IN-VIVO; SIGNALING PATHWAY AB Background: NF-kappa B includes a family of signal-activated transcription factors that normally regulate responses to injury and infection but which are aberrantly activated in many carcinomas. Objective: To review the activation and role of NF-kappa B in pathogenesis and as a target for treatment and prevention in carcinoma. Methods: Evidence from experimental, epidemiological, preclinical studies and clinical trials cited in the literature are reviewed. Results/conclusion: Cumulative evidence implicates NF-kappa B in cell survival, inflammation, angiogenesis, spread and therapeutic resistance during tumor development, progression and metastasis of carcinomas. Non-specific natural and synthetic agents that inhibit NF-kappa B have demonstrated activity and safety in prevention or therapy. NF-kappa B-activating kinases and the proteasome are under investigation for targeted prevention and therapy of carcinoma. C1 [Brown, Matthew; Cohen, Jonah; Arun, Pattatheyil; Chen, Zhong; Van Waes, Carter] Natl Inst Deafncss & Other Commun Disorders, Head & Neck Surg Branch, Bethesda, MD 20892 USA. [Van Waes, Carter] NCI, Ctr Canc Res, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, NIH, Head & Neck Surg Branch, Bethesda, MD 20892 USA. RP Van Waes, C (reprint author), Natl Inst Deafncss & Other Commun Disorders, Head & Neck Surg Branch, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov FU NIDCD intramural project [ZOI-DC-00016]; NCI-Millennium Pharmaceuticals Cooperative Research and Development Agreement [00676] FX The authors would like to thank Shivaani Kummar and James F Battey for reading the manuscript. This research was supported by NIDCD intramural project ZOI-DC-00016, NCI-Millennium Pharmaceuticals Cooperative Research and Development Agreement 00676 (CM, NIH-Pfizer Clinical Research Training Program (MB), and Howard Hughes Medical Institute Research Scholars Program (JC). NR 122 TC 47 Z9 49 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD SEP PY 2008 VL 12 IS 9 BP 1109 EP 1122 DI 10.1517/14728220802287810 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 343LY UT WOS:000258856500005 PM 18694378 ER PT J AU Arbab, AS Janic, B Knight, RA Anderson, SA Pawelczyk, E Rad, AM Read, EJ Pandit, SD Frank, JA AF Arbab, Ali S. Janic, Branislava Knight, Robert A. Anderson, Stasia A. Pawelczyk, Edyta Rad, Ali M. Read, Elizabeth J. Pandit, Sunil D. Frank, Joseph A. TI Detection of migration of locally implanted AC133(+) stem cells by cellular magnetic resonance imaging with histological findings SO FASEB JOURNAL LA English DT Article DE MRI; magnetically labeled AC133(+) cells; tumors; angiogenesis ID ENDOTHELIAL PROGENITOR CELLS; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; BONE-MARROW; PRECURSOR CELLS; GROWTH-FACTOR; TUMOR ANGIOGENESIS; IN-VITRO; POSTNATAL NEOVASCULARIZATION; BLOOD; CANCER AB This study investigated the factors responsible for migration and homing of magnetically labeled AC133(+) cells at the sites of active angiogenesis in tumor. AC133(+) cells labeled with ferumoxide-protamine sulfate were mixed with either rat glioma or human melanoma cells and implanted in flank of nude mice. An MRI of the tumors including surrounding tissues was performed. Tumor sections were stained for Prussian blue (PB), platelet-derived growth factor (PDGF), hypoxia-inducible factor-1 alpha (HIF-1 alpha), stromal cell derived factor-1 (SDF-1), matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF), and endothelial markers. Fresh snap-frozen strips from the central and peripheral parts of the tumor were collected for Western blotting. MRIs demonstrated hypointense regions at the periphery of the tumors where the PB(+)/AC133(+) cells were positive for endothelial cells markers. At the sites of PB(+)/AC133(+) cells, both HIF-1 alpha and SDF-1 were strongly positive and PDGF and MMP-2 showed generalized expression in the tumor and surrounding tissues. There was no significant association of PB(+)/AC133(+) cell localization and VEGF expression in tumor cells. Western blot demonstrated strong expression of the SDF-1, MMP-2, and PDGF at the peripheral parts of the tumors. HIF-1 alpha was expressed at both the periphery and central parts of the tumor. This work demonstrates that magnetically labeled cells can be used as probes for MRI and histological identification of administered cells. C1 [Arbab, Ali S.; Janic, Branislava; Knight, Robert A.; Rad, Ali M.] Henry Ford Hosp, Dept Radiol, Mol & Cellular Imaging Lab, Detroit, MI 48202 USA. [Anderson, Stasia A.] NHLBI, Mouse Core Imaging Facil, Bethesda, MD 20892 USA. [Pawelczyk, Edyta; Frank, Joseph A.] NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. [Read, Elizabeth J.] NIH, Cell Proc Sect, Dept Transfus Med, Bethesda, MD 20892 USA. [Pandit, Sunil D.] NIH, Mol Imaging Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Arbab, AS (reprint author), Henry Ford Hlth Syst, Dept Radiol, 1 Ford Pl,2F,Box 82, Detroit, MI 48202 USA. EM saali@rad.hfh.edu FU Intramural Research Program; National Institutes of Health [5R01CA122031] FX We thank Gene T. Yocum for help during the labeling of AC133+ cells at the National Institutes of Health. We thank Dr. A. S. M. Iskander for help in sectioning of collected tumor samples and collection of AC133+ cells from cord blood, and Dr. Hanh M. Khuu for supervision during collection of AC133+ from volunteers. This work was supported in part by the Intramural Research Program of the Clinical Center at the National Institutes of Health and an extramural funding grant (5R01CA122031). NR 54 TC 41 Z9 44 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2008 VL 22 IS 9 BP 3234 EP 3246 DI 10.1096/fj.07-105676 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 342CD UT WOS:000258761300016 PM 18556461 ER PT J AU Donzelli, S Espey, MG Flores-Santana, W Switzer, CH Yeh, GC Huang, JM Stuehr, DJ King, SB Miranda, KM Wink, DA AF Donzelli, Sonia Espey, Michael Graham Flores-Santana, Wilmarie Switzer, Christopher H. Yeh, Grace C. Huang, Jinming Stuehr, Dennis J. King, S. Bruce Miranda, Katrina M. Wink, David A. TI Generation of nitroxyl by heme protein-mediated peroxidation of hydroxylamine but not N-hydroxy-L-arginine SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE heme; peroxidase; hydroxylamine; N-hydroxy-L-arginine; nitroxyl; suffinamide ID NITRIC-OXIDE SYNTHASE; CARDIAC SARCOPLASMIC-RETICULUM; DETERRENT AGENT CYANAMIDE; IN-VIVO; ANGELIS SALT; ALDEHYDE DEHYDROGENASE; SODIUM-NITROPRUSSIDE; SUPEROXIDE-DISMUTASE; GUANYLATE-CYCLASE; OXIDATIVE STRESS AB The chemical reactivity, toxicology, and pharmacological responses to nitroxyl (HNO) are often distinctly different from those of nitric oxide (NO). The discovery that HNO donors may have pharmacological Utility for treatment of cardiovascular disorders such as heart failure and ischemia reperfusion has led to increased speculation of potential endogenous pathways for HNO biosynthesis. Here, the ability of heme proteins to utilize H2O2 to oxidize hydroxylamine (NH2OH) or N-hydroxy-L-arginine (NOHA) to HNO was examined. Formation of HNO was evaluated with a recently developed selective assay in which the reaction products ill the presence of reduced glutathione (GSH) were quantified by HPLC. Release of HNO from the heme pocket was indicated by formation of sulfinamide (GS(O)NH2), While the yields of nitrite and nitrate signified the degree of intramolecular recombination of HNO with the heme. Formation of GS(O)NH2 was observed upon oxidation of NH2OH, whereas NOHA, the primary intermediate in oxidation of L-arginine by NO synthase, was apparently resistant to oxidation by the heme proteins utilized. In the presence of NH2OH, the highest yields of GS(O)NH2 were observed with proteins in which the heme was coordinated to a histidine (horseradish peroxidase, lactoperoxidase, myeloperoxidase, myoglobin, and hemoglobin) in contrast to a tyrosine (catalase) or cysteine (cytochrome P450). That peroxidation of NH2OH by horseradish peroxidase produced free HNO, which was able to affect intracellular targets, was verified by conversion of 4,5-diaminofluorescein to the corresponding fluorophore within intact cells. (c) Published by Elsevier Inc. C1 [Donzelli, Sonia; Espey, Michael Graham; Flores-Santana, Wilmarie; Switzer, Christopher H.; Wink, David A.] NCI, Tumor Biol Sect, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Yeh, Grace C.] NCI, Cellular Defense & Carcinogenesis Sect, Lab Metab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Huang, Jinming; King, S. Bruce] Wake Forest Univ, Dept Chem, Winston Salem, NC 27109 USA. [Stuehr, Dennis J.] Lerner Res Inst, Dept Pathobiol, Cleveland, OH 44195 USA. [Miranda, Katrina M.] Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. RP Wink, DA (reprint author), NCI, Tumor Biol Sect, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. EM sdonzell@uke.uni-hamburg.de; wink@mail.nih.gov RI Switzer, Christopher/D-9203-2013; Miranda, Katrina/B-7823-2009 FU National Institutes of Health National Cancer Institute; Center for Cancer Research (DW); National Institutes of Health [R01-GM076247] FX The authors acknowledge the technical assistance of D. Janie Salmon and Derek Hollman (UA). The research was Supported by the Intramural Research Program of the National Institutes of Health National Cancer Institute and the Center for Cancer Research (DW) and National Institutes of Health Grant R01-GM076247 (KIVI). NR 69 TC 46 Z9 46 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 1 PY 2008 VL 45 IS 5 BP 578 EP 584 DI 10.1016/j.freeradbiomed.2008.04.036 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 345KK UT WOS:000258995200005 PM 18503778 ER PT J AU Jeong, YC Walker, NJ Burgin, DE Kissling, G Gupta, M Kupper, L Birnbaum, LS Swenberg, JA AF Jeong, Yo-Chan Walker, Nigel J. Burgin, Deborah E. Kissling, Grace Gupta, Mayetri Kupper, Lawrence Birnbaum, Linda S. Swenberg, James A. TI Accumulation of M(1)dG DNA adducts after chronic exposure to PCBs, but not from acute exposure to polychlorinated aromatic hydrocarbons SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE polychlorinated aromatic hydrocarbons; PCBs; TCDD; oxidative DNA lesion; M(1)dG; carcinogenesis ID TOXIC EQUIVALENCY FACTORS; DIOXIN-LIKE COMPOUNDS; SPRAGUE-DAWLEY RATS; BIPHENYLS PCBS; OXIDATIVE STRESS; RISK ASSESSMENT; FACTORS TEFS; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; 2,2',4,4',5,5'-HEXACHLOROBIPHENYL; TCDD AB Oxidative DNA damage is one of the key events thought to be involved in mutation and cancer. The present study examined the accumulation of M(1)dC, 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)-pyrimido[1,2-a]-purin-10(3H)-one, DNA adducts after single dose or 1-year exposure to polyhalogenated aromatic hydrocarbons (PHAH) in order to evaluate the potential role of oxidative DNA damage in PHAH toxicity and carcinogenicity. The effect of PHAH exposure on the number of M(1)dG adducts was explored initially in female mice exposed to a single dose of either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or a PHAH mixture. This study demonstrated that a single exposure to PHAH had no significant effect on the number of M(1)dG adducts compared to the corn oil control group. The role of M(1)dG adducts in polychlorinated biphenyl (PCB)-inducecl toxicity and carcinogenicity was further investigated in rats exposed for a year to PCB 153, PCB 126, or a mixture of the two. PCB 153, at doses up to 3000 mu g/kg/day. had no significant effect on the number of M(1)dG adducts in liver and brain tissues from the exposed rats compared to controls. However, 1000 ng/kg/day of PCB 126 resulted in M(1)dG adduct accumulation in the liver. More importantly, coadministration of equal proportions of PCB 153 and PCB 126 resulted in dose-dependent increases in M(1)dG adduct accumulation in the liver from 300 to 1000 ng/kg/day of PCB 126 with 300-1000 mu g/kg/day of PCB 153. Interestingly, the coadministration of different amounts of PCB 153 with fixed amounts of PCB 126 demonstrated more M(1)dG adduct accumulation with higher doses of PCB 153. These results are consistent with the results from cancer bioassays that demonstrated a synergistic effect between PCB 126 and PCB 153 on toxicity and tumor development. In summary, the results from the present Study Support the hypothesis that oxidative DNA damage plays a key role in toxicity and carcinogenicity following long-term PCB exposure. (c) 2008 Elsevier Inc. All rights reserved. C1 [Jeong, Yo-Chan; Swenberg, James A.] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Walker, Nigel J.; Kissling, Grace] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Burgin, Deborah E.; Birnbaum, Linda S.] NHEERL, USEPA, ORD, ETD, Res Triangle Pk, NC 27709 USA. [Gupta, Mayetri; Kupper, Lawrence] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. RP Swenberg, JA (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Room 253C,Rosenau Hall,CB 7431, Chapel Hill, NC 27599 USA. EM jswenber@email.unc.edu RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU NIEHS Superfund Basic Research Program [P42-ES05948]; NIH [R42-ESII746, P30-ES10126]; NHEERL-DESE Training in Environmental Sciences Research; EPA [CT902908, T32-ES07126] FX We thank Drs. Barohny Eun, Michael Wyde, and Ivan Rusyn for a critical reading of the manuscript; Dr. Valeriy V. Afonin for his technical assistance in DNA isolation; and Daniela Sotres-Alvarez for her assistance in statistical analyses. This research Was Supported in part by the NIEHS Superfund Basic Research Program P42-ES05948, NIH Grants R42-ESII746 and P30-ES10126, and the Intramural Research Program of the NIH and NIEHS. Partial funding was provided by the NHEERL-DESE Training in Environmental Sciences Research, EPA CT902908 and T32-ES07126. The information in this document has been subjected to review and approved for publication by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and by NIEHS, NIH. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. NR 46 TC 22 Z9 23 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 1 PY 2008 VL 45 IS 5 BP 585 EP 591 DI 10.1016/j.freeradbiomed.2008.04.043 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 345KK UT WOS:000258995200006 PM 18534201 ER PT J AU Pi, JB Diwan, BA Sun, Y Liu, J Qu, W He, YY Styblo, M Waalkes, MP AF Pi, Jingbo Diwan, Bhalchandra A. Sun, Yang Liu, Jie Qu, Wei He, Yuying Styblo, Miroslav Waalkes, Michael P. TI Arsenic-induced malignant transformation of human keratinocytes: Involvement of Nrf2 SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE arsenic; carcinogenesis; Nrf2; oxidative stress; CK2 ID OXIDATIVE DNA-DAMAGE; PROTEIN-KINASE CK2; UROTHELIAL CELLS; LUNG-CANCER; SKIN; APOPTOSIS; ACTIVATION; EXPRESSION; STRESS; MICE AB Arsenic is a well-known human skin carcinogen but the underlying mechanisms of carcinogenesis are unclear. Transcription factor Nrf2-mediated antioxidant response represents a critical cellular defense mechanism, and emerging data suggest that constitutive activation of Nrf2 contributes to malignant phenotype. In the present study when an immortalized. nontumorigenic human keratinocyte cell line (HaCaT) was continuously exposed to an environmentally relevant level of inorganic arsenite (100 nM) for 28 weeks, malignant transformation occurred as evidenced by the formation of highly aggressive squamous cell carcinoma after inoculation into nude mice. To investigate the mechanisms involved, a broad array of biomarkers for transformation were assessed in these arsenic-transformed cells (termed As-TM). In addition to increased secretion of matrix metalloproteinase-9 (MMP-9), a set of markers for squamous differentiation and skin keratinization, including keratin-1, keratin-10, involucrin, and loricrin, were significantly elevated in As-TM cells. Furthermore, As-TM cells showed increased intracellular glutathione and elevated expression of Nrf2 and its target genes, as well as generalized apoptotic resistance. In contrast to increased basal Nrf2 activity in As-TM cells, a diminished Nrf2-mediated antioxidant response induced by acute exposure to high doses of arsenite or tert-butyl hydroxyquinone occurred. The findings that multiple biomarkers for malignant transformation observed in As-TM cells, including MMP-9 and cytokeratins, are potentially regulated by NFf2 suggest that Constitutive Nrf2 activation may be involved in arsenic carcinogenesis of skin. The weakened Nrf2 activation in response to oxidative stressors observed in As-TM cells, coupled with acquired apoptotic resistance, would potentially have increased the likelihood of transmittable oxidative DNA damage and fixation of mutational/DNA damage events. (c) 2008 Elsevier Inc. All rights reserved. C1 [Pi, Jingbo] Hamner Inst Hlth Sci, Div Translat Biol, Res Triangle Pk, NC 27709 USA. [Pi, Jingbo; Sun, Yang; Liu, Jie; Qu, Wei; Waalkes, Michael P.] NIEHS, Comparat Carcinogenesis Lab, NCI, NIH, Res Triangle Pk, NC 27709 USA. [Diwan, Bhalchandra A.] NCI, Basic Res Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. [He, Yuying] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. [Styblo, Miroslav] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. RP Pi, JB (reprint author), Hamner Inst Hlth Sci, Div Translat Biol, Res Triangle Pk, NC 27709 USA. EM jpi@thehamner.org; waalkes@niehs.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-124000]; NIDDK NIH HHS [K01 DK076788, K01 DK076788-01A1] NR 50 TC 79 Z9 88 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 1 PY 2008 VL 45 IS 5 BP 651 EP 658 DI 10.1016/j.freeradbiomed.2008.05.020 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 345KK UT WOS:000258995200014 PM 18572023 ER PT J AU Jia, YP Alayash, AI AF Jia, Yiping Alayash, Abdu I. TI Effects of (-)-epigallocatechin gallate on the redox reactions of human hemoglobin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE (-)-epigallocatechin gallate; blood substitutes; hemoglobin ID CROSS-LINKED HEMOGLOBIN; GREEN TEA EXTRACT; CARRIERS BLOOD SUBSTITUTES; OXIDE PRODUCING REACTIONS; NITRIC-OXIDE; OXYGEN CARRIERS; EPIGALLOCATECHIN GALLATE; HYDROGEN-PEROXIDE; (-)-EPICATECHIN GALLATE; METABOLIC-ACIDOSIS AB The toxicity of a cellular hemoglobin (Hb)-based therapeutics has been attributed in part to the uncontrolled oxidative reactions. A variety of antioxidant Strategies to ameliorate potential oxidative damage in vivo have been suggested. We have examined the effects of (-)-epigallocatechin gallate (EGCG), a green tea polyphenol compound widely regarded as a chain-breaking antioxidant. on the oxidative stability of diaspirin crosslinked Hb (DBBF) and its cytotoxic ferryl intermediate. DBBF (ferrous) was rapidly oxidized to the ferric form in the presence of EGCG relative to the normal spontaneous oxidation of this Hb. The fast elimination of ferrous Hb is probably due to the ability of EGCG to produce hydrogen peroxide (H2O2) as these reactions were almost completely reversed by the addition of catalase and superoxide dismutase to the reaction medium. EGCG, however, effectively reduced ferryl back to ferric Hb in a biphasic kinetic reaction at physiological pH. At acidic pH where the autoreduction of protonated ferryl Hb is enhanced, a monophasic reduction process of the ferry] heme is achieved. A balance between pro and antioxidant properties of EGCG should be taken into account if EGCG is used in combination therapy with redox active acellular Hbs. Published by Elsevier Inc. C1 [Jia, Yiping; Alayash, Abdu I.] US FDA, LBVB, CBER, Div Hematol, Bethesda, MD 20892 USA. RP Jia, YP (reprint author), US FDA, LBVB, CBER, Div Hematol, NIH Campus,8800 Rockville Pike,Bldg 29,Rm 129, Bethesda, MD 20892 USA. EM yiping.jia@fda.hhs.gov NR 68 TC 13 Z9 14 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 1 PY 2008 VL 45 IS 5 BP 659 EP 666 DI 10.1016/j.freeradbiomed.2008.05.010 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 345KK UT WOS:000258995200015 PM 18539156 ER PT J AU Hussain, SP AF Hussain, S. Perwez TI Inflammation and cancer: Is AID aiding? SO GASTROENTEROLOGY LA English DT Editorial Material ID INDUCED CYTIDINE DEAMINASE; ACTIVATION; EXPRESSION; MICRORNA-155; MALIGNANCIES C1 NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hussain, SP (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CA999999] NR 15 TC 2 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2008 VL 135 IS 3 BP 736 EP 737 DI 10.1053/j.gastro.2008.07.035 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 346WC UT WOS:000259099300009 PM 18692057 ER PT J AU Baege, AC Fink, D Baker, C Niederhuber, J AF Baege, A. C. Fink, D. Baker, C. Niederhuber, J. TI Isolation, characterization, and potential role of cervical stem cells in HPV-induced cervical carcinogenesis SO GEBURTSHILFE UND FRAUENHEILKUNDE LA English DT Meeting Abstract DE HPV; HPV infection; carcinogenesis; cervical cancer; stem cells C1 [Baege, A. C.; Fink, D.] Univ Spital Zurich, Klin Gynakol, Zurich, Switzerland. [Baker, C.; Niederhuber, J.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0016-5751 J9 GEBURTSH FRAUENHEILK JI Geburtshilfe Frauenheilkd. PD SEP PY 2008 VL 68 SU 1 BP S143 EP S143 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 353OO UT WOS:000259577500593 ER PT J AU Ortiz, M Kaessmann, H Zhang, K Bashirova, A Carrington, M Quintana-Murci, L Telenti, A AF Ortiz, M. Kaessmann, H. Zhang, K. Bashirova, A. Carrington, M. Quintana-Murci, L. Telenti, A. TI The evolutionary history of the CD209 (DC-SIGN) family in humans and non-human primates SO GENES AND IMMUNITY LA English DT Article DE C-type lectins; HIV; Ebola; mycobacteria; innate immunity; DC-SIGN ID AMINO-ACID SITES; POSITIVE SELECTION; TYPE-1 INFECTION; INNATE-IMMUNITY; POLYMORPHISMS; RECEPTORS; DOMAIN; SUSCEPTIBILITY; TRIM5-ALPHA; LIKELIHOOD AB The CD209 gene family that encodes C-type lectins in primates includes CD209 (DC-SIGN), CD209L (L-SIGN) and CD209L2. Understanding the evolution of these genes can help understand the duplication events generating this family, the process leading to the repeated neck region and identify protein domains under selective pressure. We compiled sequences from 14 primates representing 40 million years of evolution and from three non-primate mammal species. Phylogenetic analyses used Bayesian inference, and nucleotide substitutional patterns were assessed by codon-based maximum likelihood. Analyses suggest that CD209 genes emerged from a first duplication event in the common ancestor of anthropoids, yielding CD209L2 and an ancestral CD209 gene, which, in turn, duplicated in the common Old World primate ancestor, giving rise to CD209L and CD209. K(A)/K(S) values averaged over the entire tree were 0.43 (CD209), 0.52 (CD209L) and 0.35 (CD209L2), consistent with overall signatures of purifying selection. We also assessed the Toll-like receptor (TLR) gene family, which shares with CD209 genes a common profile of evolutionary constraint. The general feature of purifying selection of CD209 genes, despite an apparent redundancy (gene absence and gene loss), may reflect the need to faithfully recognize a multiplicity of pathogen motifs, commensals and a number of self-antigens. C1 [Ortiz, M.; Zhang, K.; Telenti, A.] Univ Lausanne, Inst Microbiol, Lausanne, Switzerland. [Kaessmann, H.] Univ Lausanne, Ctr Integrat Genom, Lausanne, Switzerland. [Bashirova, A.] USA, Med Res Inst Infect Dis, Lab Mol Immunol, Frederick, MD USA. [Carrington, M.] NCI, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA. [Quintana-Murci, L.] Inst Pasteur, CNRS, URA3012, Paris, France. RP Telenti, A (reprint author), CHU Vaudois, Inst Microbiol, Bugnon 48, CH-1011 Lausanne, Switzerland. EM amalio.telenti@chuv.ch RI Kaessmann, Henrik/B-4989-2013; OI Quintana-Murci, Lluis/0000-0003-2429-6320 FU Swiss National Science Foundation; Faculty of Biology and Medicine of the University of Lausanne; National Cancer Institute; National Institutes of Health [N01-CO-12400]; Intramural Research Program of the NIH; Center for Cancer Research FX We thank Keith Mansfield and Kuei-Chin Lin from the New England Primate Center, and Charles Buillard and Eugene Chabloz from the Zoo of Servion for materials. This work was funded by the Swiss National Science Foundation and a grant for interdisciplinary research from the Faculty of Biology and Medicine of the University of Lausanne. 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 US Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 32 TC 18 Z9 19 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD SEP PY 2008 VL 9 IS 6 BP 483 EP 492 DI 10.1038/gene.2008.40 PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 344LM UT WOS:000258928500001 PM 18528403 ER PT J AU Belanger, S Tai, LH Anderson, SK Makrigiannis, AP AF Belanger, S. Tai, L-H Anderson, S. K. Makrigiannis, A. P. TI Ly49 cluster sequence analysis in a mouse model of diabetes: an expanded repertoire of activating receptors in the NOD genome SO GENES AND IMMUNITY LA English DT Article DE Ly49; diabetes; natural killer cells; comparative immunology/evolution; cell surface molecules ID NATURAL-KILLER-CELL; NK CELLS; LY-49D RECEPTOR; MICE; GENE; RECOGNITION; H-2D(D); PHOSPHORYLATION; CYTOMEGALOVIRUS; COMPLEX AB The mouse Ly49 and human killer cell immunoglobulin-like receptors (KIR) gene clusters encode activating and inhibitory class I MHC receptors on natural killer (NK) cells. A direct correlation between the presence of multiple activating KIR and various human autoimmune diseases including diabetes has been shown. Previous studies have implicated NK cell receptors in the development of diabetes in the non-obese diabetic ( NOD) inbred mouse strain. To assess the contribution of Ly49 to NOD disease acceleration the Ly49 gene cluster of these mice was sequenced. Remarkably, the NOD Ly49 haplotype encodes the largest haplotype and the most functional activating Ly49 of any known mouse strain. These activating Ly49 include three Ly49p-related and two Ly49h-related genes. The NOD cluster contains large regions highly homologous to both C57BL/6 and 129 haplotypes, suggesting unequal crossing over as a mechanism of Ly49 haplotype evolution. Interestingly, the 129-like region has duplicated in the NOD genome. Thus, the NOD Ly49 cluster is a unique mix of elements seen in previously characterized Ly49 haplotypes resulting in a disproportionately large number of functional activating Ly49 genes. Finally, the functionality of activating Ly49 in NOD mice was confirmed in cytotoxicity assays. C1 [Belanger, S.; Tai, L-H; Makrigiannis, A. P.] Univ Montreal, Inst Rech Clin Montreal, Lab Mol Immunol, Montreal, PQ H2W 1R7, Canada. [Belanger, S.; Tai, L-H; Makrigiannis, A. P.] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. [Anderson, S. K.] SAIC Frederick Inc, NCI, Basic Res Program, Frederick, MD USA. RP Makrigiannis, AP (reprint author), Univ Montreal, Inst Rech Clin Montreal, Lab Mol Immunol, Rm 1340,110 Ave Pins Ouest, Montreal, PQ H2W 1R7, Canada. EM makriga@ircm.qc.ca RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU Canadian Institutes of Health Research [CIHR MOP 62841]; Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; National Institutes of Health [NO1-CO-12400]; Fonds de la recherche en sante du Quebec; CIHR Cancer Training Program; CIHR FX We thank Christophe Benoist for his essential aid in initiating the sequencing of the NOD Ly49 region. We also thank Dr Silvia Vidal for her help with MCMV plaque assays and reagents. We gratefully acknowledge the genome sequencing efforts of The Wellcome Trust Sanger Institute. This work was supported by an Operating Grant from the Canadian Institutes of Health Research (CIHR MOP 62841). This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project has also been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract no. NO1-CO-12400. SB is supported by a scholarship from the Fonds de la recherche en sante du Quebec. L-HT is supported by a CIHR Cancer Training Program scholarship. APM is supported by a New Investigator Award from the CIHR. NR 51 TC 25 Z9 25 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD SEP PY 2008 VL 9 IS 6 BP 509 EP 521 DI 10.1038/gene.2008.43 PG 13 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 344LM UT WOS:000258928500004 PM 18528402 ER PT J AU Szamecz, B Rutkai, E Cuchalova, L Munzarova, V Herrmannova, A Nielsen, KH Burela, L Hinnebusch, AG Valasek, L AF Szamecz, Bela Rutkai, Edit Cuchalova, Lucie Munzarova, Vanda Herrmannova, Anna Nielsen, Klaus H. Burela, Laxminarayana Hinnebusch, Alan G. Valasek, Leos TI eIF3a cooperates with sequences 5 ' of uORF1 to promote resumption of scanning by post-termination ribosomes for reinitiation on GCN4 mRNA SO GENES & DEVELOPMENT LA English DT Article DE translation initiation; reinitiation; eIF3; 40S ribosomal subunit; GCN4; short uORF ID EUKARYOTIC TRANSLATION INITIATION; START CODON SELECTION; OPEN READING FRAME; IN-VIVO; RECOGNITION MOTIF; 40S SUBUNITS; STOP CODONS; BINDING; YEAST; COMPLEXES AB Yeast initiation factor eIF3 ( eukaryotic initiation factor 3) has been implicated in multiple steps of translation initiation. Previously, we showed that the N-terminal domain (NTD) of eIF3a interacts with the small ribosomal protein RPS0A located near the mRNA exit channel, where eIF3 is proposed to reside. Here, we demonstrate that a partial deletion of the RPS0A-binding domain of eIF3a impairs translation initiation and reduces binding of eIF3 and associated eIFs to native preinitiation complexes in vivo. Strikingly, it also severely blocks the induction of GCN4 translation that occurs via reinitiation. Detailed examination unveiled a novel reinitiation defect resulting from an inability of 40S ribosomes to resume scanning after terminating at the first upstream ORF (uORF1). Genetic analysis reveals a functional interaction between the eIF3a-NTD and sequences 5 ' of uORF1 that is critically required to enhance reinitiation. We further demonstrate that these stimulatory sequences must be positioned precisely relative to the uORF1 stop codon and that reinitiation efficiency after uORF1 declines with its increasing length. Together, our results suggest that eIF3 is retained on ribosomes throughout uORF1 translation and, upon termination, interacts with its 5 ' enhancer at the mRNA exit channel to stabilize mRNA association with post-termination 40S subunits and enable resumption of scanning for reinitiation downstream. C1 [Szamecz, Bela; Rutkai, Edit; Cuchalova, Lucie; Munzarova, Vanda; Herrmannova, Anna; Valasek, Leos] Inst Microbiol AVCR, Lab Regulat Gene Express, Prague 14220, Czech Republic. [Nielsen, Klaus H.] Univ Aarhus, Dept Mol Biol, Ctr mRNP Biogenesis & Metab, DK-8000 Aarhus, Denmark. [Burela, Laxminarayana; Hinnebusch, Alan G.] NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Valasek, L (reprint author), Inst Microbiol AVCR, Lab Regulat Gene Express, Videnska 1083, Prague 14220, Czech Republic. EM valasekl@biomed.cas.cz RI Herrmannova, Anna/I-1745-2014; Valasek, Leos/I-5743-2014; Cuchalova, Lucie/H-4650-2014 FU Wellcome Trusts [076456/Z/05/Z]; Howard Hughes Medical Institute; Fogarty International Center [R01 TW007271]; Purkyne from the Academy of Sciences of the Czech Republic; Institute Research Concept [AV0Z50200510]; National Institutes of Health FX We are thankful to Libor Krasny for critical reading of the manuscript, to the members of the Valasek and Krasny laboratories for helpful suggestions, and to Olga Krydova, Anna Delijannisova, and Ilona Krupickova for technical and administrative assistance. This research was supported for the most part by The Wellcome Trusts Grant 076456/Z/05/Z, and partly also by the Howard Hughes Medical Institute, by NIH Research Grant R01 TW007271 funded by the Fogarty International Center, by the Fellowship of Jan E. Purkyne from the Academy of Sciences of the Czech Republic, by the Institute Research Concept AV0Z50200510, and by the Intramural Research Program of the National Institutes of Health. NR 39 TC 63 Z9 64 U1 1 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 1 PY 2008 VL 22 IS 17 BP 2414 EP 2425 DI 10.1101/gad.480508 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 343TM UT WOS:000258878100012 PM 18765792 ER PT J AU Mackwan, RR Carver, GT Kissling, GE Drake, JW Grogan, DW AF Mackwan, Reena R. Carver, Geraldine T. Kissling, Grace E. Drake, John W. Grogan, Dennis W. TI The rate and character of spontaneous mutation in Thermus thermophilus SO GENETICS LA English DT Article ID ARCHAEON SULFOLOBUS-ACIDOCALDARIUS; DNA-BINDING PROTEIN; EXTREME THERMOPHILE; COMPARATIVE GENOMICS; FRAMESHIFT MUTATION; POLYMERASES; REPAIR; IDENTIFICATION; PURIFICATION; EXPRESSION AB Selection of spontaneous, loss-of-function mutations at two chromosomal loci (pyrF and pyrE) enabled the first molecular-level of replication fidelity in the extremely thermophilic bacterium Thermus thermophilus. Two different methods yielded similar mutation rates, mutational spectra determined by sequencing of independent mutants revealed a variety of replication errors distributed throughout the target genes. The genomic mutation rate estimated from these targets, 0.00097 +/- 0.00052 per replication, was lower than corresponding estimates from mesophilic microorganisms, primarily because of a low rate of base substitution.. However, both the rate and spectrum of spontaneous mutations T. thermophilus resembled those of the thermoacidophilic archaeon Sulfolobus acidocaldarius, despite important molecular differences between these two thermophiles mid their genomes. C1 [Mackwan, Reena R.; Grogan, Dennis W.] Univ Cincinnati, Dept Biol Sci, Cincinnati, OH 45221 USA. [Carver, Geraldine T.; Drake, John W.] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Kissling, Grace E.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Grogan, DW (reprint author), Univ Cincinnati, Dept Biol Sci, 614 Rieveschl Hall ML 0006,Clifton Court, Cincinnati, OH 45221 USA. EM grogandw@email.uc.edu FU National Science Foundation [MCB 9733103, MCB 0543910]; National Institutes of Health National Institute of Environmental Health Sciences FX We thank Marilyn Diaz and Tom Kunkel for critical readings of the manuscript. This work was supported by National Science Foundation grants MCB 9733103 and MCB 0543910 to D.W.G. and by the Intramural Research Program of the National Institutes of Health National Institute of Environmental Health Sciences. NR 39 TC 15 Z9 15 U1 0 U2 5 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 2008 VL 180 IS 1 BP 17 EP 25 DI 10.1534/genetics.108.089086 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 356DI UT WOS:000259758500003 PM 18723895 ER PT J AU Eydmann, T Sommariva, E Inagawa, T Mian, S Klar, AJS Dalgaard, JZ AF Eydmann, T. Sommariva, E. Inagawa, T. Mian, S. Klar, A. J. S. Dalgaard, J. Z. TI Rtf1-mediated eukaryotic site-specific replication termination SO GENETICS LA English DT Article ID RNA-POLYMERASE-I; TRANS-ACTING FACTORS; SACCHAROMYCES-CEREVISIAE; SCHIZOSACCHAROMYCES-POMBE; TRANSCRIPTION TERMINATION; DNA-REPLICATION; FISSION YEAST; RIBOSOMAL DNA; FORK ARREST; ESCHERICHIA-COLI AB The molecular mechanisms mediating eukaryotic replication termination and pausing remain largely unknown. Here we present the molecular characterization of Rtf1 that mediates site-specific replication termination at the polar Schizosaccharomyces pombe barrier RTS1. We show that Rtf1 possesses two chimeric myb/SANT domains: one is able to interact with the repeated motifs encoded by the RTS1 element as well as the elements enhancer region, while the other shows only a weak DNT binding activity. In addition we show that the C-terminal tail of Rtf1 mediates self-interaction, and deletion of this tail has a dominant phenotype. Finally, we identify a point imitation in Rtf1 domain I that converts the RTS1 element into a replication barrier of the opposite polarity. Together our data establish that multiple protein DNA and protein-protein interactions between Rtf1 molecules and both the repeated motifs and the enhancer region of RTS1 are required for site-specific termination at the RTS1 element. C1 [Eydmann, T.; Sommariva, E.; Inagawa, T.; Dalgaard, J. Z.] Marie Curie Res Inst, Oxted RH8 0TL, Surrey, England. [Mian, S.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. [Klar, A. J. S.] NCI, Gene Regulat & Chromosome Biol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Dalgaard, JZ (reprint author), Marie Curie Res Inst, Oxted RH8 0TL, Surrey, England. EM j.dalgaard@mcri.ac.uk RI Sommariva, Elena/K-4078-2016 OI Sommariva, Elena/0000-0003-2172-4051 FU National Cancer Institute of the National Institutes of Health; Marie Curie Cancer Care; Association of International Cancer Research FX We thank our colleagues at the Marie Curie Research Institute for helpful suggestions and interactions. A special thanks to Rob Cross, Natalie Mansfield, S. Jack Carlisle, Doug Drummond, Sonya Vengrova, and Michael Bonaduce for technical assistance. This work was supported by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health (A.J.S.K.), the Marie Curie Cancer Care (J.Z.D.) and the Association of International Cancer Research (J.Z.D.). NR 55 TC 25 Z9 27 U1 0 U2 2 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD SEP PY 2008 VL 180 IS 1 BP 27 EP 39 DI 10.1534/genetics.108.089243 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 356DI UT WOS:000259758500004 PM 18723894 ER PT J AU Frydrychova, RC Mason, JM Archer, TK AF Frydrychova, Radmila Capkova Mason, James M. Archer, Trevor K. TI HP1 is distributed within distinct chromatin domains at drosophila telomeres SO GENETICS LA English DT Article ID POSITION-EFFECT VARIEGATION; HET-A; HETEROCHROMATIN PROTEIN-1; MELANOGASTER TELOMERES; LYSINE-9 METHYLATION; DIFFERENT MECHANISMS; FUNCTIONAL-ANALYSIS; CHROMOSOME ENDS; DNA-SEQUENCES; GENE AB Telomeric regions In Drosophila are Composed of till-cc subdomains. A chromosome cap distinguishes the chromosome end from a DNA double-strand break; an an-ay of retrotransposons, HeT-A, TART, and TAHRE (HTT), maintains telomere length by targeted transposition to chromosome ends; and telomere-associated sequence (TAS), which consists of a mosaic of complex repeated sequences, has been identified as a source of gene silencing. Heterochromatin protein 1 (HP1) and HP1-ORC-associated protein (HOAP) are major protein components of the telomere cap in Drosophila and are required for telomere- protein stability. Besides the chromosome cap, HP1 is also localized along the HTT array and in TAS. Mutants for Su(var)205, the gene encoding HP1, have decreased the HP1 level in the HTT array and increased transcription of individual HeT-A elements. This suggests that HP1 levels directly affect HeT-A activity along, the HTT array, although they have little or no effect on transcription of a while reporter gene in the HTT. Chromatin immunoprecipitation to identify other heterochromatic proteins indicates that TAS and the HTT array may be distinct from either heterochromatin or euchromatin. C1 [Archer, Trevor K.] NIEHS, Mol Carcinogenesis Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Frydrychova, Radmila Capkova; Mason, James M.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, DHHS, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM archer1@niehs.nih.gov RI Capkova Frydrychova, Radmila/H-4187-2014 FU National Institutes of Health National Institute of Environmental Health Sciences FX We thank Karen Adelman and Daniel Menendez for critical reading of: the manuscript. and Harald Biessmann for providing sequences of EY and KG insertions and comments to the manuscript. This research was supported by the Intramural Research Program of National Institutes of Health National Institute of Environmental Health Sciences. NR 56 TC 18 Z9 18 U1 0 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 2008 VL 180 IS 1 BP 121 EP 131 DI 10.1534/genetics.108.090647 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 356DI UT WOS:000259758500012 PM 18723888 ER PT J AU Zaykin, DV Pudovkin, A Weir, BS AF Zaykin, Dmitri V. Pudovkin, Alexander Weir, Bruce S. TI Correlation-based inference for linkage disequilibrium with multiple alleles SO GENETICS LA English DT Article ID GOODNESS-OF-FIT; RANDOMLY MATING POPULATIONS; GAMETIC DISEQUILIBRIUM; TESTS; LOCI; ASSOCIATION; FREQUENCIES; STATISTICS; PREDICTORS; PATTERNS AB The correlation between alleles at a pair of genetic loci is a measure of linkage disequilibrium. The square of the sample correlation multiplied by sample size provides the usual test statistic for the hypothesis of no disequilibrium for loci with two alleles and this relation has proved useful for study design and marker selection. Nevertheless, this relation holds only in a diallelic case, and an extension to multiple alleles has not been made. Here we introduce a similar statistic, R-z, which leads to correlaiton -based test for loci with multiple alleles: for a pair of loci with k and m alleles, and a sample of n individuals, the approximate distribution of n(k-1) (m-1)/(km)R-2 under independence between loci is chi(2)((k-1)(m-1)). One advantage of this statistic is that is can be interpreted as the total correlation between a pair of loci. When the phase of two-locus genotypes is know, the approach is equivalent to a test for the overall correlation between rows and columns in a contingency table. In the phase-known case, R-2 is strong competitor to approaches such as Pearson's chi square, Fisher's exact test, and a test based on Cressie and Read's power divergence statistic. We combine this approach with our previous composite-disequilibrium measures to address the case when the genotypic phase is unknown. Calculation os the new multiallele test statistic and its P-value is very simple and utilizes the approximate distribution of R-2. We provide a computer program that evaluates approximate as well as "exact" permutational P-values. C1 [Zaykin, Dmitri V.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. [Pudovkin, Alexander] Russian Acad Sci, Inst Marine Biol, Vladivostok 690041, Russia. [Weir, Bruce S.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Zaykin, DV (reprint author), Natl Inst Environm Hlth Sci, NIH, MD A3-03,South Bldg 101-B356B,POB 12233, Res Triangle Pk, NC 27709 USA. EM zaykind@niehs.nih.gov FU National Institutes of Health (NIH) [GM 07591]; National Institute of Environmental Health Sciences FX This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences, and by NIH GM 07591. NR 40 TC 41 Z9 41 U1 0 U2 6 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 2008 VL 180 IS 1 BP 533 EP 545 DI 10.1534/genetics.108.089409 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 356DI UT WOS:000259758500043 PM 18757931 ER PT J AU Walser, JC Ponger, L Furano, AV AF Walser, Jean-Claude Ponger, Loic Furano, Anthony V. TI CpG dinucleotides and the mutation rate of non-CpG DNA SO GENOME RESEARCH LA English DT Article ID HUMAN GENOME; LINE-1 RETROTRANSPOSONS; CYTOSINE METHYLATION; MOLECULAR EVOLUTION; NUCLEOTIDE-SEQUENCE; CHIMPANZEE GENOMES; LOCAL SIMILARITY; MAMMALIAN GENOME; FOREIGN DNA; GC-CONTENT AB The neutral mutation rate is equal to the base substitution rate when the latter is not affected by natural selection. Differences between these rates may reveal that factors such as natural selection, linkage, or a mutator locus are affecting a given sequence. We examined the neutral base substitution rate by measuring the sequence divergence of similar to 30,000 pairs of inactive orthologous L1 retrotransposon sequences interspersed throughout the human and chimpanzee genomes. In contrast to other studies, we related ortholog divergence to the time ( age) that the L1 sequences resided in the genome prior to the chimpanzee and human speciation. As expected, the younger orthologs contained more hypermutable CpGs than the older ones because of their conversion to TpGs (and CpAs). Consequently, the younger orthologs accumulated more CpG mutations than the older ones during the similar to 5 million years since the human and chimpanzee lineages separated. But during this same time, the younger orthologs also accumulated more non-CpG mutations than the older ones. In fact, non-CpG and CpG mutations showed an almost perfect (R-2 = 0.98) correlation for similar to 97% of the ortholog pairs. The correlation is independent of G + C content, recombination rate, and chromosomal location. Therefore, it likely reflects an intrinsic effect of CpGs, or mutations thereof, on non-CpG DNA rather than the joint manifestation of the chromosomal environment. The CpG effect is not uniform for all regions of non-CpG DNA. Therefore, the mutation rate of non-CpG DNA is contingent to varying extents on local CpG content. Aside from their implications for mutational mechanisms, these results indicate that a precise determination of a uniform genome-wide neutral mutation rate may not be attainable. C1 [Walser, Jean-Claude; Furano, Anthony V.] NIDDK, Sect Genom Struct & Funct, Lab Mol & Cellular Biol, NIH, Bethesda, MD 20892 USA. [Ponger, Loic] Museum Natl Hist Nat, UMS Regulat & Dynam Genomes 503, F-75005 Paris 5, France. RP Furano, AV (reprint author), NIDDK, Sect Genom Struct & Funct, Lab Mol & Cellular Biol, NIH, Bethesda, MD 20892 USA. EM avf@helix.nih.gov FU NIH; NIDDK; National Museum of Natural History, France FX We thank Deborah M. Hinton and Natalia Wesolowska for their valuable suggestions during the preparation of the manuscript. We are grateful to the UCSC Genome Browser Database group for providing various sequences files and programs. Furthermore, we thank Marcos Antezana (U. Chicago) for stimulating discussions on mutational aspects of the response to foreign DNA in eukaryotes. The Intramural Research Program of the NIH, NIDDK, funded A. V. F. and J.-C.W., and the National Museum of Natural History, France funded L. P. NR 73 TC 30 Z9 30 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD SEP PY 2008 VL 18 IS 9 BP 1403 EP 1414 DI 10.1101/gr.076455.108 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 342AH UT WOS:000258756500003 PM 18550801 ER PT J AU Johnson, CC Kessel, B Riley, TL Ragard, LR Williams, CR Xu, JL Buys, SS AF Johnson, Christine C. Kessel, Bruce Riley, Thomas L. Ragard, Lawrence R. Williams, Craig R. Xu, Jian-Lun Buys, Saundra S. CA PLCO Project Team TI The epidemiology of CA-125 in women without evidence of ovarian cancer in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial SO GYNECOLOGIC ONCOLOGY LA English DT Article DE epidemiology; CA-125; race/ethnicity ID HEALTHY POSTMENOPAUSAL WOMEN; HORMONE REPLACEMENT THERAPY; SERUM CA-125; TUMOR-MARKERS; ANTIGEN CA125; ENDOMETRIUM; RECRUITMENT; RISK; GENE AB Objective. To determine the epidemiology of CA-125 in women without ovarian cancer. Methods. We analyzed demographic, medical and lifestyle characteristics related to CA-125, measured using the Centocor CA-125II RIA assay, among 25,608 multi-ethnic U.S. women aged 55-74 years enrolled in a cancer screening trial and found to have no evidence of ovarian cancer. Results. Mean CA-125 level was 11.9 U/ml (SD 8.3); median 10.0 U/ml, interquartile range 8.0-14.0. High levels, using the clinical cut point of >= 35 U/ml, were associated with increased age (p<0.001) and former smoking (p<0.021), while hysterectomy and obesity were protective (p<0.001). Mean levels were higher with increasing age (p<0.001), ever use of hormone therapy (p<0.001), former smoking (p<0.017) and history of breast cancer (p<0.002), but lower (p<0.001) with non-White status, previous hysterectomy, current smoking, and obesity. Current hormone therapy use was not associated with CA-125 in women without a uterus. Conclusion. In post-menopausal women without ovarian cancer, CA-125 level is influenced by a number of factors, including race/ethnicity, age, hysterectomy, smoking history and obesity. (C) 2008 Elsevier Inc. All rights reserved. C1 [Johnson, Christine C.] Henry Ford Hosp, Josephine Ford Canc Ctr, Detroit, MI 48202 USA. [Kessel, Bruce] Pacific Hlth Res Inst, Honolulu, HI USA. [Kessel, Bruce] Univ Hawaii, Honolulu, HI 96822 USA. [Riley, Thomas L.; Williams, Craig R.] Informat Management Syst, Rockville, MD USA. [Ragard, Lawrence R.] Westat Corp, Rockville, MD USA. [Xu, Jian-Lun] NCI, Biometry Res Grp, Canc Prevent Div, NIH,DHHS, Bethesda, MD 20892 USA. [Buys, Saundra S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. RP Johnson, CC (reprint author), Henry Ford Hosp, Josephine Ford Canc Ctr, 1 Ford Pl,5C, Detroit, MI 48202 USA. EM cjohnso1@hfhs.org OI Kessel, Bruce/0000-0001-9979-2068; Johnson, Christine Cole/0000-0002-6864-6604 FU NCI NIH HHS [N01 CN25404, N01 CN25512, N01 CN25516, N01 CN25522, N01 CN75022] NR 31 TC 40 Z9 42 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2008 VL 110 IS 3 BP 383 EP 389 DI 10.1016/j.ygyno.2008.05.006 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 349XN UT WOS:000259316700018 PM 18586313 ER PT J AU Patel, KV AF Patel, Kushang V. TI Variability and heritability of hemoglobin concentration: an opportunity to improve understanding of anemia in older adults SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Editorial Material ID UNEXPLAINED ANEMIA; MORTALITY; HOSPITALIZATION; ERYTHROPOIETIN; DEFINITION; IMPACT; STATES C1 NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. RP Patel, KV (reprint author), NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. EM patelku@mail.hih.gov FU Intramural NIH HHS NR 20 TC 7 Z9 7 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD SEP PY 2008 VL 93 IS 9 BP 1281 EP 1283 DI 10.3324/haematol.13692 PG 3 WC Hematology SC Hematology GA 347DF UT WOS:000259120100001 PM 18757846 ER PT J AU Salaverria, I Zettl, A Beaa, S Hartmann, EM Dave, SS Wright, GW Boerma, EJ Kluin, PM Ott, G Chan, WC Weisenburger, DD Lopez-Guillermo, A Gascoyne, RD Delabie, J Rimsza, LM Braziel, RM Jaffe, ES Staudt, LM Mueller-Hermelink, HK Campo, E Rosenwald, A AF Salaverria, Itziar Zettl, Andreas Bea, Silvia Hartmann, Elena M. Dave, Sandeep S. Wright, George W. Boerma, Evert-Jan Kluin, Philip M. Ott, German Chan, Wing C. Weisenburger, Dennis D. Lopez-Guillermo, Armando Gascoyne, Randy D. Delabie, Jan Rimsza, Lisa M. Braziel, Rita M. Jaffe, Elaine S. Staudt, Louis M. Mueller-Hermelink, Hans Konrad Campo, Elias Rosenwald, Andreas CA LLMPP TI Chromosomal alterations detected by comparative genomic hybridization in subgroups of gene expression-defined Burkitt's lymphoma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE Burkitt's lymphoma; comparative genomic hybridization; DLBCL; gene expression ID B-CELL LYMPHOMA; MOLECULAR PATHOGENESIS; ABNORMALITIES; ABERRATIONS; ADOLESCENTS; PROGNOSIS; ADULTS AB Background Burkitt's lymphoma is an aggressive B-cell lymphoma characterized by typical morph 0 logical, immunophenotypic and molecular features. Gene expression profiling provided a molecular signature of Burkitt's lymphoma, but also demonstrated that a subset of aggressive B-cell lymphomas not fulfilling the current World Health Organization criteria for the diagnosis of Burkitt's lymphoma nonetheless show a molecular signature of Burkitt's lymphoma ('discrepant Burkitt's lymphoma'). Given the different treatment of Burkitt's lymphoma and diffuse large B-cell lymphomas we investigated molecular differences within gene expression-defined Burkitt's lymphoma. Design and Methods We studied tumors from 51 Burkitt's lymphoma patients, comprising 26 with classic Burkitt's lymphoma, 17 with atypical Burkitt's lymphoma and 8 with 'discrepant Burkitt's lymphoma', by comparative genomic hybridization and gene expression profiling. Results Classic and atypical Burkitt's lymphoma (excluding 'discrepant Burkitt's lymphoma'), in adult and pediatric cases do not differ in underlying genomic imbalances or gene expression suggesting that these subgroups are molecularly homogeneous. 'Discrepant Burkitt's lymphoma', however, differ dramatically in the absolute number of alterations from classic/atypical Burkitt's lymphoma and from diffuse large B-cell lymphoma. Moreover, this category includes lymphomas that carry both the t(14;18) and t(8;14) translocations and are clinically characterized by presentation in adult patients and an aggressive course. Conclusions Pediatric and adult Burkitt's lymphoma are molecularly homogeneous, whereas 'discrepant Burkitt's lymphoma' differ in underlying genetic and clinical features from typical/atypical Burkitt's lymphoma. 'Discrepant Burkitt's lymphoma' may therefore form a distinct genetic subgroup of aggressive B-cell lymphomas, which show poor response to multi-agent chemotherapy. C1 [Zettl, Andreas; Hartmann, Elena M.; Ott, German; Mueller-Hermelink, Hans Konrad; Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, D-97080 Wurzburg, Germany. [Salaverria, Itziar; Bea, Silvia; Campo, Elias] Univ Barcelona, Dept Pathol, Barcelona, Spain. [Dave, Sandeep S.; Staudt, Louis M.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. [Wright, George W.] NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. [Boerma, Evert-Jan; Kluin, Philip M.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, NL-9713 AV Groningen, Netherlands. [Chan, Wing C.; Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. [Lopez-Guillermo, Armando] Univ Barcelona, Hematol Hosp Clin, Barcelona, Spain. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Delabie, Jan] Norwegian Radium Hosp, Norway Hosp Clin, Oslo, Norway. [Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ USA. [Braziel, Rita M.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Jaffe, Elaine S.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Ott, German] Robert Bosch Krankenhaus, Inst Clin Pathol, Stuttgart, Germany. RP Rosenwald, A (reprint author), Univ Wurzburg, Inst Pathol, Josef Schneider Str 2, D-97080 Wurzburg, Germany. EM Rosenwald@mail.uni-wuerzburg.de RI SALAVERRIA, ITZIAR/L-2246-2015; Bea, Silvia/K-7699-2014; OI SALAVERRIA, ITZIAR/0000-0002-2427-9822; Delabie, Jan/0000-0001-5023-0689; Bea, Silvia/0000-0001-7192-2385; Campo, elias/0000-0001-9850-9793 FU Spanish Comision Interministerial de Ciencia y Tecnologia (CICYT) [SAF05/5855]; Instituto de Salud Carlos III Red Tematica de Investigacion Cooperativa de Cancer; Interdisciplinary Center for Clinical Research (IZKF) of the University of Wurzburg, Germany; NIH [U01-CA84967]; National Cancer Institute, Bethesda, MD, USA FX supported by grants from the Spanish Comision Interministerial de Ciencia y Tecnologia (CICYT) SAF05/5855, Instituto de Salud Carlos III Red Tematica de Investigacion Cooperativa de Cancer, by the Interdisciplinary Center for Clinical Research (IZKF) of the University of Wurzburg, Germany (AR, EH), and by an NIH grant (U01-CA84967) from the National Cancer Institute, Bethesda, MD, USA, (WCC, AR, EC, GO, HKMH). NR 20 TC 45 Z9 46 U1 1 U2 5 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD SEP PY 2008 VL 93 IS 9 BP 1327 EP 1334 DI 10.3324/haematol.13071 PG 8 WC Hematology SC Hematology GA 347DF UT WOS:000259120100009 PM 18698080 ER PT J AU Choi, CW Chung, YJ Slape, C Aplan, PD AF Choi, Chul Won Chung, Yang Jo Slape, Christopher Aplan, Peter D. TI Impaired differentiation and apoptosis of hematopoietic precursors in a mouse model of myelodysplastic syndrome SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE myelodysplastic syndromes; mouse model; NUP98; HOXD13; apoptosis ID IN-VITRO PROLIFERATION; PROGENITORS; CELLS; MDS; CULTURES; FAS AB Expression of a NUP98-HOXD13 (NHD13) fusion gene, initially identified in a patient with myelodysplastic syndrome, leads to a highly penetrant myelodysplastic syndrome in mice that recapitulates all of the key features of the human disease. Expansion of undifferentiated lineage negative (lin(neg)) hematopoietic precursors that express NHD13 was markedly inhibited (30-fold) in vitro. Decreased expansion was accompanied by decreased production of terminally differentiated cells, indicating impaired differentiation of NHD13 precursors Rather than differentiate, the majority (80%) of NHD13 lin(neg) precursors underwent apoptotic cell death when induced to differentiate. These findings demonstrate that NHD13 lin(neg) cells provide a tractable in vitro system for studies of myelodysplastic syndrome. C1 [Choi, Chul Won; Chung, Yang Jo; Slape, Christopher; Aplan, Peter D.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Aplan, PD (reprint author), Navy 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM aplanp@mail.nih.gov RI Slape, Christopher/H-8586-2016; Aplan, Peter/K-9064-2016 OI Slape, Christopher/0000-0002-8407-3092; FU NIH; NCI FX we would like to thank Dave Caudell, Helge Hartung, Sarah Beachy, Dwayne Barber, and Eli Estey for helpful discussion. This research was supported by the Intramural Research Program of the NIH, NCI. NR 19 TC 13 Z9 13 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD SEP PY 2008 VL 93 IS 9 BP 1394 EP 1397 DI 10.3324/haematol.13042 PG 4 WC Hematology SC Hematology GA 347DF UT WOS:000259120100020 PM 18603548 ER PT J AU Resnik, DB AF Resnik, David B. TI The Sex Kitten of Bioethics? Research Ethics Comes of Age SO HASTINGS CENTER REPORT LA English DT Letter C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD SEP-OCT PY 2008 VL 38 IS 5 BP 5 EP 6 PG 2 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 357LZ UT WOS:000259848600006 ER PT J AU Schelbert, EB Vaughan-Sarrazin, MS Welke, KF Rosenthal, GE AF Schelbert, E. B. Vaughan-Sarrazin, M. S. Welke, K. F. Rosenthal, G. E. TI Valve type and long-term outcomes after aortic valve replacement in older patients SO HEART LA English DT Article ID PROSTHETIC HEART-VALVES; MEDICARE CLAIMS DATA; ADMINISTRATIVE DATA; PORCINE BIOPROSTHESES; OPERATIVE MORTALITY; MECHANICAL VALVE; RANDOMIZED-TRIAL; NEXT-GENERATION; UNITED-STATES; CABG SURGERY AB Objective: To compare outcomes after aortic valve replacement (AVR) according to valve type specifically in older patients since valve-related risks are age-dependent; two randomised trials comparing mechanical and bioprosthetic valves found better outcomes with mechanical valves, but the samples were small and the patients were considerably younger than most who undergo AVR. Design: Cohort study. Setting: 1199 US hospitals. Patients: Patients 65 years and older undergoing AVR during 1991-2003 (n = 307 054) identified through Medicare claims data. Main outcome measures: Relative hazard ratios associated with bioprosthetic valves of (1) death (n = 131 719); (2) readmission for haemorrhage (n = 31 186), stroke (n = 25 051) or embolism (n = 5870); (3) reoperation (n = 4216); and (4) death or reoperation (reoperation free survival) in Cox regression analyses adjusting for demographic and clinical factors and hospital-level effects. Results: Overall, 36% of AVR patients received bioprosthetic valves. Bioprosthetic valve recipients were older (77 vs 75 years, p<0.001) and generally had higher comorbidity. Bioprosthetic valve recipients had a slightly lower adjusted hazard ratios of death (HR = 0.97; 95% CI 0.95 to 0.98); readmission for haemorrhage, stroke or embolism (HR = 0.90, 95% CI 0.88 to 0.92); and death or reoperation (HR = 0.97, 95% CI 0.96 to 0.98), but a higher hazard ratio of reoperation (HR = 1.25, 95% CI 1.16 to 1.35). However, overall mortality and complication rates were more than 20 and 10 times higher, respectively, than the overall reoperation rate. Conclusions: In older patients undergoing AVR, bioprosthetic valve recipients had slightly lower risks of death and complications, but a higher risk of reoperation. Given the low reoperation rate, these data suggest that bioprosthetic valves may be preferred in older patients. C1 [Schelbert, E. B.] Univ Iowa, Dept Internal Med, Div Cardiovasc Dis, Carver Coll Med, Iowa City, IA 52242 USA. [Vaughan-Sarrazin, M. S.; Rosenthal, G. E.] Univ Iowa, Dept Internal Med, Div Gen Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Vaughan-Sarrazin, M. S.; Rosenthal, G. E.] Iowa City VA Med Ctr, CRIISP, Iowa City, IA USA. [Welke, K. F.] Oregon Hlth & Sci Univ, Div Cardiothorac Surg, Dept Surg, Portland, OR USA. RP Schelbert, EB (reprint author), NHLBI, NIH, 10 Ctr Dr,Room B1D416,MSC 1061, Bethesda, MD 20892 USA. EM schelberteb@nhlbi.nih.gov OI Vaughan Sarrazin, Mary/0000-0001-8717-1061 FU NHLBI NIH HHS [K30HL04117-01A1] NR 40 TC 21 Z9 21 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD SEP PY 2008 VL 94 IS 9 BP 1181 EP 1188 DI 10.1136/hrt.2007.127506 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 337PH UT WOS:000258447500021 PM 18070945 ER PT J AU Hosgood, HD Baris, D Zhang, Y Zhu, Y Zheng, T Yeager, M Welch, R Zahm, S Chanock, S Rothman, N Lan, Q AF Hosgood, H. Dean, III Baris, Dalsu Zhang, Yawei Zhu, Yong Zheng, Tongzhang Yeager, Meredith Welch, Robert Zahm, Shelia Chanock, Stephen Rothman, Nathaniel Lan, Qing TI Caspase polymorphisms and genetic susceptibility to multiple myeloma SO HEMATOLOGICAL ONCOLOGY LA English DT Article DE multiple myeloma; caspase; variant; polymorphism; snp : risk factors ID LUNG-CANCER; CONNECTICUT WOMEN; BREAST-CANCER; IN-VIVO; APOPTOSIS; RISK; ASSOCIATION; DEATH; ACTIVATION; VARIANTS AB Multiple myeloma is a haematological malignency, characterized by clonal expansion of plastma cells. However, little is known about the cause of multiple rnyeloma. Cancer cells must avoid apoptosis to ensure unregulated tumour formation and growth. The highly conserved caspase cascade is essential to the regulation of the apoptotic pathway. To examine if five single nucleotide polymorphisms (SNPs) in four caspase genes [CASP3 Ex8-280 C > A (rs6948), CASP3 Ex8 + 567 T > c (rs1049216), CASP8 Ex14-271 A > T (rs13113). CASP9 Ex5 + 32 G > A (rs1052576), CASPIO Ex3-171 A > G (rs39001150)] alter multiple myeloma risk, we conducted a population-based case-control study of women (128 cases; 516 controls) in Connecticut. Compared to individuals with the TT genotype of CASP3 Ex8 + 567 T > C, subjects with the CC genotype had a five-fold decreased risk of multiple myeloma (odds ratio (OR)(cc) = 0.2, 95% confidence interval (CI)=0.0-1.0). Further, individuals with the AG and AA genotypes of CASP9 Ex5+32 G > A also experienced a decreased risk of multiple myeloma (ORAG=0.8, 95% CI=0.5-1.3; ORAA=0.5, 95% CI=03-0.9, p-trend=0.02). While no previous study has evaluated the association between caspase genes and multiple myeloma, studies have found associations with lung, breast, esophageal, gastric, colorectal and cervical cancers. Our parallel study of non-Hodgkin lymphoma, which utilized the same controls, found strong evidence that caspase genes play a key role in lymphogenesis. The protective associations observed in two key caspase genes suggest that genetic variation in CASP genes may play an important role in the aetiology of multiple myeloma. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Hosgood, H. Dean, III; Baris, Dalsu; Zahm, Shelia; Chanock, Stephen; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Hosgood, H. Dean, III; Zhang, Yawei; Zhu, Yong; Zheng, Tongzhang] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Yeager, Meredith; Welch, Robert] NCI, SAIC Frederick Inc, Adv Technol Program, Div Canc Epidemiol & Genet,Core Genotyping Facil, Frederick, MD 21701 USA. [Chanock, Stephen] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hosgood, HD (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH, 6120 Execut Blvd,EPS 8118,MCS 7240, Bethesda, MD 20892 USA. EM hosgoodd@mail.nihgov RI Zahm, Shelia/B-5025-2015 FU Yale University-National Cancer Institute Partnership Pre-Doctoral Fellowship Training Program [NCI TU2 CA 105666]; National Cancer Institute; National Institutes of Health [N01-CO-12400] FX This work was supported in pan by the Yale University-National Cancer Institute Partnership Pre-Doctoral Fellowship Training Program (NCI TU2 CA 105666). 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 US Government. NR 33 TC 30 Z9 32 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0278-0232 J9 HEMATOL ONCOL JI Hematol. Oncol. PD SEP PY 2008 VL 26 IS 3 BP 148 EP 151 DI 10.1002/hon.852 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 356CQ UT WOS:000259756700004 PM 18381704 ER PT J AU Kato, T Choi, Y Elmowalid, G Sapp, RK Barth, H Furusaka, A Mishiro, S Wakita, T Krawczynski, K Liang, TJ AF Kato, Takanobu Choi, Youkyung Elmowalid, Gamal Sapp, Ronda K. Barth, Heidi Furusaka, Akihiro Mishiro, Shunji Wakita, Takaji Krawczynski, Krzysztof Liang, T. Jake TI Hepatitis C virus JFH-1 strain infection in chimpanzees is associated with low pathogenicity and emergence of an adaptive mutation SO HEPATOLOGY LA English DT Article ID B VIRAL-HEPATITIS; FULMINANT NON-A; CELL-CULTURE; MOLECULAR CLONE; EFFICIENT REPLICATION; HUH-7 CELLS; IN-VIVO; RNA; PARTICLES; NS2 AB The identification of the hepatitis C virus (HCV) strain JFH-1 enabled the successful development of infectious cell culture systems. Although this strain replicates efficiently and produces infectious virus in cell culture, the replication capacity and pathogenesis in vivo are still undefined. To assess the in vivo phenotype of the JFH-1 virus, cell culture-generated JFH-1 virus (JFH-1cc) and patient serum from which JFH-1 was isolated were inoculated into chimpanzees. Both animals became HCV RNA-positive 3 days after inoculation but showed low-level viremia and no evidence of hepatitis. HCV viremia persisted 8 and 34 weeks in JFH-1cc and patient serum-infected chimpanzees, respectively. Immunological analysis revealed that HCV-specific immune responses were similarly induced in both animals. Sequencing of HCV at various times of infection indicated more substitutions in the patient serum-inoculated chimpanzee, and the higher level of sequence variations seemed to be associated with a prolonged infection in this animal. A common mutation G838R in the NS2 region emerged early in both chimpanzees. This mutation enhances viral assembly, leading to an increase in viral production in transfected or infected cells. Conclusion: Our study shows that the HCV JFH-1 strain causes attenuated infection and low pathogenicity in chimpanzees and is capable of adapting in vivo with a unique mutation conferring an enhanced replicative phenotype. C1 [Kato, Takanobu; Elmowalid, Gamal; Sapp, Ronda K.; Barth, Heidi; Liang, T. Jake] NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Kato, Takanobu; Mishiro, Shunji] Toshiba Gen Hosp, Dept Med Sci, Tokyo, Japan. [Kato, Takanobu; Wakita, Takaji] Natl Inst Infect Dis, Dept Virol 2, Shinjuku Ku, Tokyo 1628640, Japan. [Choi, Youkyung; Krawczynski, Krzysztof] Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA USA. [Furusaka, Akihiro] Jikei Univ, Sch Med, Dept Internal Med, Tokyo, Japan. RP Liang, TJ (reprint author), NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. EM JakeL@bdgl0.niddk.nih.gov FU Intramural NIH HHS [Z01 DK054504-11] NR 46 TC 35 Z9 35 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2008 VL 48 IS 3 BP 732 EP 740 DI 10.1002/hep.22422 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 344QJ UT WOS:000258942100006 PM 18712792 ER PT J AU Balan, V Ruppert, K Demetris, AJ Ledneva, T Duquesnoy, RJ Detre, KM Wei, YL Rakela, J Schafer, DF Roberts, JP Everhart, JE Wiesner, RH AF Balan, Vijayan Ruppert, Kris Demetris, A. Jake Ledneva, Tatiana Duquesnoy, Rene J. Detre, Katherine M. Wei, Yuling L. Rakela, Jorge Schafer, Daniel F. Roberts, John P. Everhart, James E. Wiesner, Russell H. TI Long-term outcome of human leukocyte antigen mismatching in liver transplantation: Results of the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database SO HEPATOLOGY LA English DT Article ID HEPATITIS-C; GRAFT-SURVIVAL; HLA COMPATIBILITY; RETROSPECTIVE ANALYSIS; PATIENT SURVIVAL; ACUTE REJECTION; RISK-FACTORS; IMPACT; HISTOCOMPATIBILITY; IDENTIFICATION AB A perfect or nearly perfect human lettkocyte antigen (HI-A) match has been associated with better immediate and long-term survival of diseased donor kidney transplants. However, the effect of HLA matching for hepatic allografts remains poorly defined. Using data from the National Institutes of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database, we investigated the association between HLA mismatches and hepatic allograft survival, disease recurrence, and immunosuppression interactions. A, B, and DR loci were used to calculate total mismatch scores of 0 (no mismatches in any loci) to 6 (mismatches in all loci). Seven hundred ninety-nine adults (male, 55%; female, 45%) underwent 883 liver transplants. The 10-year graft survival according to total mismatch score was as follows: 0-2, 60%; 3-4, 54%; and 5-6, 57%. There was a negative effect of mismatching at the A locus on patient survival, with shorter survival for patients with I or 2 mismatches compared with 0 mismatches [P = 0.05, hazard ratio (HR) = 1.6]. Patients on tacrolimus with I or 2 mismatches at B or DR loci appeared to have increased rates of patient and graft survival compared to patients with 0 mismatches, with the appearance of a protective effect of tacrolimus (HR = 0.67). The effect of HILA mismatching was more pronounced on certain disease recurrences. DR-locus mismatch increased recurrence of autoimmune hepatitis (P = 0.01, HR = 4.2) and primary biliary cirrhosis (P = 0.04, HR = 2). Mismatch in the A locus was associated with more recurrence of hepatitis C virus (P = 0.01, HR = 1.6) and primary sclerosing cholangitis (P = 0.03, HR = 2.9). Conclusion: Mismatching at the A locus decreases patient survival in liver transplant recipients, and mismatching at the DR and A loci affects recurrence of autoimmune liver diseases and hepatitis C, respectively. C1 [Balan, Vijayan; Rakela, Jorge] Mayo Clin, Dept Transplantat Med, Phoenix, AZ USA. [Ruppert, Kris; Demetris, A. Jake; Ledneva, Tatiana; Detre, Katherine M.; Wei, Yuling L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Duquesnoy, Rene J.] Univ Pittsburgh, Sch Med, Div Transplantat Pathol, Pittsburgh, PA USA. [Schafer, Daniel F.] Univ Nebraska Med Ctr, Dept Med, Omaha, NE USA. [Schafer, Daniel F.] Univ Nebraska Med Ctr, Dept Surg, Omaha, NE USA. [Roberts, John P.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Roberts, John P.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Everhart, James E.] NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. [Wiesner, Russell H.] Mayo Clin & Mayo Fdn, Dept Med, Rochester, MN 55905 USA. [Wiesner, Russell H.] Mayo Clin & Mayo Fdn, Dept Surg, Rochester, MN 55905 USA. RP Balan, V (reprint author), Mayo Clin, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM balan.vijayan@mayo.edu RI Ruppert, Kristine/C-2555-2016 OI Ruppert, Kristine/0000-0002-3008-6584 FU National Institute of Diabetey and Digestive and Kidney Diseases [DK 55883] FX This work was supported by National Institute of Diabetey and Digestive and Kidney Diseases grant DK 55883. NR 43 TC 34 Z9 34 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2008 VL 48 IS 3 BP 878 EP 888 DI 10.1002/hep.22435 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 344QJ UT WOS:000258942100021 PM 18752327 ER PT J AU Masson, MJ Carpenter, LD Graf, ML Pohl, LR AF Masson, Mary Jane Carpenter, Leah D. Graf, Mary L. Pohl, Lance R. TI Pathogenic role of natural killer T and natural killer cells in acetaminophen-induced liver injury in mice is dependent on the presence of dimethyl sulfoxide SO HEPATOLOGY LA English DT Article ID INNATE IMMUNE-SYSTEM; NKT CELLS; HEPATIC-INJURY; INDUCED HEPATOTOXICITY; MACROPHAGE-MIGRATION; DEFICIENT MICE; MURINE MODEL; MOUSE MODEL; MAJOR ROLE; DIMETHYLSULFOXIDE AB Dimethyl sulfoxide (DMSO) is commonly used in biological studies to dissolve drugs and enzyme inhibitors with low solubility. Although DMSO is generally thought of as being relatively inert, it can induce biological effects that are often overlooked. An example that highlights this potential problem is found in a recent report demonstrating a pathogenic role for natural killer T (NKT) and natural killer (NK) cells in acetaminophen-induced liver injury (AILI) in C57131/6 mice in which DMSO was used to facilitate acetaminophen (APAP) dissolution. We report that NKT and NK cells do not play a pathologic role in AILI in C57131/6 mice in the absence of DMSO. Although AILI was significantly attenuated in mice depleted of NKT and NK cells prior to APAP treatment in the presence of DMSO, no such effect was observed when APAP was dissolved in saline. Because of this unexpected finding, the effects of DMSO on hepatic NKT and NK cells were subsequently investigated. When given alone, DMSO activated hepatic NKT and NK cells in vivo as evidenced by increased NKT cell numbers and higher intracellular levels of the cytotoxic effector molecules interferon-gamma (IFN-gamma) and granzyme B in both cell types. Similarly, when used as a solvent for APAP, DMSO again increased NKT cell numbers and induced IFN-gamma and granzyme B expression in both cell types. Conclusion: These data demonstrate a previously unappreciated effect of DMSO on hepatic NKT and NK cells, suggesting that DMSO should be used cautiously in experiments involving these cells. C1 [Masson, Mary Jane; Carpenter, Leah D.; Graf, Mary L.; Pohl, Lance R.] NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Masson, MJ (reprint author), NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, 10 Ctr Dr,Bldg 10,Room 8N110, Bethesda, MD 20892 USA. EM massonm@nhlbi.nih.gov FU Intramural Research Program of the National Institutes of Health; National Heart, Lung, and Blood Institute FX Supported by the Intramural Research Program of the National Institutes of Health and the National Heart, Lung, and Blood Institute. NR 49 TC 57 Z9 57 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2008 VL 48 IS 3 BP 889 EP 897 DI 10.1002/hep.22400 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 344QJ UT WOS:000258942100022 PM 18712839 ER PT J AU Yeager, M Xiao, NQ Hayes, RB Bouffard, P Desany, B Burdett, L Orr, N Matthews, C Qi, LQ Crenshaw, A Markovic, Z Fredrikson, KM Jacobs, KB Amundadottir, L Jarvie, TP Hunter, DJ Hoover, R Thomas, G Harkins, TT Chanock, SJ AF Yeager, Meredith Xiao, Nianqing Hayes, Richard B. Bouffard, Pascal Desany, Brian Burdett, Laura Orr, Nick Matthews, Casey Qi, Liqun Crenshaw, Andrew Markovic, Zdenek Fredrikson, Karin M. Jacobs, Kevin B. Amundadottir, Laufey Jarvie, Thomas P. Hunter, David J. Hoover, Robert Thomas, Gilles Harkins, Timothy T. Chanock, Stephen J. TI Comprehensive resequence analysis of a 136 kb region of human chromosome 8q24 associated with prostate and colon cancers SO HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; COLORECTAL-CANCER; GENETIC ALTERATIONS; BREAST-CANCER; RISK LOCUS; SUSCEPTIBILITY; VARIANT; SEQUENCES; INSIGHTS; SCAN AB Recently, genome-wide association studies have identified loci across a segment of chromosome 8q24 ( 128,100,000-128,700,000) associated with the risk of breast, colon and prostate cancers. At least three regions of 8q24 have been independently associated with prostate cancer risk; the most centromeric of which appears to be population specific. Haplotypes in two contiguous but independent loci, marked by rs6983267 and rs1447295, have been identified in the Cancer Genetic Markers of Susceptibility project (http://cgems.cancer.gov), which genotyped more than 5,000 prostate cancer cases and 5,000 controls of European origin. The rs6983267 locus is also strongly associated with colorectal cancer. To ascertain a comprehensive catalog of common single-nucleotide polymorphisms (SNPs) across the two regions, we conducted a resequence analysis of 136 kb (chr8: 128,473,000 128,609,802) using the Roche/454 next-generation sequencing technology in 39 prostate cancer cases and 40 controls of European origin. We have characterized a comprehensive catalog of common (MAF > 1%) SNPs within this region, including 442 novel SNPs and have determined the pattern of linkage disequilibrium across the region. Our study has generated a detailed map of genetic variation across the region, which should be useful for choosing SNPs for fine mapping of association signals in 8q24 and investigations of the functional consequences of select common variants. C1 [Yeager, Meredith] NCI, Adv Technol Ctr, Gaithersburg, MD 20877 USA. [Yeager, Meredith; Xiao, Nianqing; Burdett, Laura; Matthews, Casey; Qi, Liqun; Crenshaw, Andrew; Amundadottir, Laufey] NCI Frederick, SAIC Frederick Inc, Adv Technol Program, Core Genotyping Facil, Ft Detrick, MD 21702 USA. [Yeager, Meredith; Xiao, Nianqing; Hayes, Richard B.; Burdett, Laura; Matthews, Casey; Crenshaw, Andrew; Amundadottir, Laufey; Hunter, David J.; Hoover, Robert; Thomas, Gilles; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Bouffard, Pascal; Desany, Brian; Markovic, Zdenek; Jarvie, Thomas P.] Life Sci 454, Branford, CT USA. [Orr, Nick; Chanock, Stephen J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. [Jacobs, Kevin B.] Bioinformed Consulting Serv, Gaithersburg, MD USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Fredrikson, Karin M.; Harkins, Timothy T.] Roche Appl Sci, Indianapolis, IN USA. RP Yeager, M (reprint author), NCI, Adv Technol Ctr, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM yeagerm@mail.nih.gov RI Amundadottir, Laufey/L-7656-2016; OI Amundadottir, Laufey/0000-0003-1859-8971; Hayes, Richard/0000-0002-0918-661X FU National Cancer Institute; National Institutes of Health [N01-CO-12400] FX The authors would like to recognize the contribution of the late Robert A. Welch to the conception, execution, and analysis of this project. 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 US Government. NR 28 TC 77 Z9 79 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD SEP PY 2008 VL 124 IS 2 BP 161 EP 170 DI 10.1007/s00439-008-0535-3 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 342BJ UT WOS:000258759300006 PM 18704501 ER PT J AU Berndt, SI Potter, JD Hazra, A Yeager, M Thomas, G Makar, KW Welch, R Cross, AJ Huang, WY Schoen, RE Giovannucci, E Chan, AT Chanock, SJ Peters, U Hunter, DJ Hayes, RB AF Berndt, Sonja I. Potter, John D. Hazra, Aditi Yeager, Meredith Thomas, Gilles Makar, Karen W. Welch, Robert Cross, Amanda J. Huang, Wen-Yi Schoen, Robert E. Giovannucci, Edward Chan, Andrew T. Chanock, Stephen J. Peters, Ulrike Hunter, David J. Hayes, Richard B. TI Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; PROSTATE-CANCER RISK; ADENOMATOUS POLYPS; LINKAGE PHASE; COLON-CANCER; C-MYC; METAANALYSIS; VARIANT; LOCUS; POPULATION AB Several different genetic variants at chromosome 8q24 have been related to prostate, breast and colorectal cancer risk with evidence of region-specific risk differentials for various tumor types. We investigated the association between 15 polymorphisms located in 8q24 regions associated with cancer risk in a pooled analysis of 2587 colorectal adenoma cases, 547 colorectal cancer cases and 2798 controls of European descent from four studies. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations. Three polymorphisms (rs10808555, rs6983267 and rs7837328) located between 128.47 and 128.54 Mb were found to be associated with colorectal tumor risk. The association was strongest for the previously reported rs6983267 variant and was similar for both adenoma (OR(per allele) = 1.16, 95% CI: 1.07-1.25, P = 0.0002) and cancer (OR(per allele) = 1.17, 95% CI: 1.01-1.35, P = 0.03). The strength of the association of the regional haplotype containing variant alleles at rs10808555, rs6983267 and rs7837328 but not rs10505476 was greater than that of any single variant of both adenoma (OR = 1.27, P = 0.0001) and cancer (OR = 1.26, P = 0.03). The risk associated with rs6983267 was stronger for multiple adenomas (OR(per allele) = 1.29, P = 5.6 x 10(-6)) than for single adenoma (ORper allele = 1.10, P = 0.03) with P(heterogeneity) = 0.008. This study confirms the association between colorectal neoplasia and the 8q24 polymorphisms located between 128.47 and 128.54 Mb and suggests a role for these variants in the formation of multiple adenomas. C1 [Berndt, Sonja I.; Yeager, Meredith; Thomas, Gilles; Welch, Robert; Cross, Amanda J.; Huang, Wen-Yi; Chanock, Stephen J.; Hayes, Richard B.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Potter, John D.; Makar, Karen W.; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Potter, John D.; Peters, Ulrike] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Hazra, Aditi; Giovannucci, Edward; Hunter, David J.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Yeager, Meredith; Welch, Robert] SAIC Frederick Inc, Adv Technol Program, Natl Canc Inst Frederick, Frederick, MD 21702 USA. [Schoen, Robert E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Schoen, Robert E.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Schoen, Robert E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. [Giovannucci, Edward; Hunter, David J.] Harvard Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward; Chan, Andrew T.; Hunter, David J.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Berndt, SI (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8116,MSC 7240, Bethesda, MD 20892 USA. EM berndts@mail.nih.gov OI Potter, John/0000-0001-5439-1500; Hayes, Richard/0000-0002-0918-661X FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health [N01-CO-12400, CA87969, CA55075, CA059045] FX This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health; National Cancer Institute, National Institutes of Health under contract N01-CO-12400; and National Institutes of Health research grants CA87969, CA55075 and CA059045. NR 35 TC 51 Z9 53 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 1 PY 2008 VL 17 IS 17 BP 2665 EP 2672 DI 10.1093/hmg/ddn166 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 343PW UT WOS:000258867000008 PM 18535017 ER PT J AU Vergarajauregui, S Connelly, PS Daniels, MP Puertollano, R AF Vergarajauregui, Silvia Connelly, Patricia S. Daniels, Mathew P. Puertollano, Rosa TI Autophagic dysfunction in mucolipidosis type IV patients SO HUMAN MOLECULAR GENETICS LA English DT Article ID NEURODEGENERATIVE DISEASE; CATION CHANNEL; FRONTOTEMPORAL DEMENTIA; MEMBRANE-PROTEIN; TRAFFICKING; MUTATIONS; GENE; IDENTIFICATION; MICE; MACROAUTOPHAGY AB Mutations in Mucolipin 1 (MCOLN1) have been linked to mucolipidosis type IV (MLIV), a lysosomal storage disease characterized by several neurological and ophthalmological abnormalities. It has been proposed that MCOLN1 might regulate transport of membrane components in the late endosomal-lysosomal pathway; however, the mechanisms by which defects of MCOLN1 function result in mental and psychomotor retardation remain largely unknown. In this study, we show constitutive activation of autophagy in fibroblasts obtained from MLIV patients. Accumulation of autophagosomes in MLIV cells was due to the increased de novo autophagosome formation and to delayed fusion of autophagosomes with late endosomes/lysosomes. Impairment of the autophagic pathway led to increased levels and aggregation of p62, suggesting that abnormal accumulation of ubiquitin proteins may contribute to the neurodegeneration observed in MLIV patients. In addition, we found that delivery of platelet-derived growth factor receptor to lysosomes is delayed in MCOLN1-deficient cells, suggesting that MCOLN1 is necessary for efficient fusion of both autophagosomes and late endosomes with lysosomes. Our data are in agreement with recent evidence showing that autophagic defects may be a common characteristic of many neurodegenerative disorders. C1 [Vergarajauregui, Silvia; Puertollano, Rosa] NHLBI, Natl Inst Hlth, Cell Biol Lab, Bethesda, MD 20892 USA. [Connelly, Patricia S.; Daniels, Mathew P.] NHLBI, Natl Inst Hlth, Electron Microscopy Core Facil, Bethesda, MD 20892 USA. RP Puertollano, R (reprint author), NHLBI, Natl Inst Hlth, Cell Biol Lab, Bethesda, MD 20892 USA. EM puertolr@mail.nih.gov FU Intramural Research Program of the NIH; National Heart, Lung, and Blood Institute (NHLBI) FX This project was supported by the Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute (NHLBI). NR 57 TC 78 Z9 79 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 1 PY 2008 VL 17 IS 17 BP 2723 EP 2737 DI 10.1093/hmg/ddn174 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 343PW UT WOS:000258867000014 PM 18550655 ER PT J AU Ingelsson, E Pencina, MJ Levy, D Aragam, J Mitchell, GF Benjamin, EJ Vasan, RS AF Ingelsson, Erik Pencina, Michael J. Levy, Daniel Aragam, Jayashri Mitchell, Gary F. Benjamin, Emelia J. Vasan, Ramachandran S. TI Aortic root diameter and longitudinal blood pressure tracking SO HYPERTENSION LA English DT Article DE blood pressure; aorta; hypertension ID TARGET ORGAN DAMAGE; SYSTOLIC HYPERTENSION; PULSE PRESSURE; FLOW RELATIONSHIP; WAVE REFLECTION; DILATATION; SIZE; DETERMINANTS; PATHOGENESIS; HYPERTROPHY AB Proximal aortic diameter, including aortic root ( AoR) diameter, has been inversely related to pulse pressure in cross-sectional studies. So, investigators have hypothesized that a smaller AoR diameter may increase the risk of developing hypertension. Prospective studies are lacking to test this hypothesis. We measured AoR diameter in 3195 Framingham Study participants ( mean age: 49 years; 57% women; 8460 person-examinations) free from hypertension and previous cardiovascular disease who underwent routine echocardiography. We related AoR to hypertension incidence and blood pressure ( BP) progression ( increment of >= 1 category, as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). On follow- up ( median: 4 years), 1267 individuals ( 15%; 661 women) developed hypertension, and 2978 participants experienced BP progression ( 35%; 1588 women). In logistic regression models adjusted for age, sex, and height, AoR was positively associated with hypertension incidence ( odds ratio: 1.15; 95% CI: 1.08 to 1.23) and BP progression ( odds ratio: 1.09; 95% CI: 1.04 to 1.14) on follow- up. However, adjustment for other factors known to influence BP tracking ( baseline systolic and diastolic BP, smoking, diabetes, and weight) rendered these relations statistically nonsignificant ( odds ratio: 1.03; 95% CI: 0.96 to 1.11 for hypertension incidence; odds ratio: 1.03; 95% CI: 0.97 to 1.08 for BP progression). In our large community- based sample of nonhypertensive individuals, AoR diameter was not associated with hypertension incidence or BP progression prospectively after adjustment for potential confounders. Our prospective study does not support the notion that a smaller AoR predisposes to hypertension. C1 [Ingelsson, Erik; Pencina, Michael J.; Levy, Daniel; Aragam, Jayashri; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Framingham Study, Framingham, MA USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Evans Mem Dept Med, Framingham, MA USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Framingham, MA USA. [Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Pencina, Michael J.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Aragam, Jayashri] Vet Adm Hosp, W Roxbury, MA USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Holliston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU Swedish Society of Medicine and the Swedish Heart-Lung Foundation; National Institutes of Health/National Heart, Lung, and Blood Institute [N01-HC-25195, 6R01-NS 17950, HL080124, 2K24HL4334] FX This work was supported by the Swedish Society of Medicine and the Swedish Heart-Lung Foundation (E. I.) and the National Institutes of Health/National Heart, Lung, and Blood Institute contracts N01-HC- 25195, 6R01-NS 17950 (E. J. B.), HL080124, and 2K24HL4334 (R. S. V.). NR 25 TC 12 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2008 VL 52 IS 3 BP 473 EP 477 DI 10.1161/HYPERTENSIONAHA.108.114157 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 339XB UT WOS:000258609500009 PM 18663156 ER PT J AU Erim, Z Lin, W AF Erim, Zeynep Lin, Winsean TI Decomposition of intramuscular EMG signals using a heuristic fuzzy expert system SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE action potential (AP); classification; decomposition; electromyography (EMG); expert system; fuzzy logic; intramuscular; motor unit (MU) ID ACTION-POTENTIALS; RESOLUTION AB Although increasingly sophisticated algorithms have been proposed to decompose intramuscular electromyography signals into the concurrent activities of individual motor units (MUs), the human operator is still able to improve decomposition results by visual inspection. The rationale for this paper was to combine components from previous decomposition procedures in an expert systems approach utilizing fuzzy logic and attempting to replicate the thought process of an accomplished decomposer in order to minimize the user interaction subsequently needed to enhance decomposition results. The decomposition procedure is discussed and examples are given of the type of information it can yield. The method has been used to identify the discharge activities of up to 15 MUs with up to 95% accuracy. C1 [Erim, Zeynep; Lin, Winsean] Rehabil Inst Chicago, Sensory Motor Performance Program, Chicago, IL 60611 USA. [Erim, Zeynep] Northwestern Univ, Feinberg Sch Med, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. RP Erim, Z (reprint author), NIH, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA. EM erimz@mail.nih.gov FU NICHD NIH HHS [K25HD043993] NR 17 TC 15 Z9 16 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD SEP PY 2008 VL 55 IS 9 BP 2180 EP 2189 DI 10.1109/FBME.2008.923915 PG 10 WC Engineering, Biomedical SC Engineering GA 341NW UT WOS:000258722200008 PM 18713687 ER PT J AU Pham, TD Wang, HH Zhou, XB Beck, D Brandl, M Hoehn, G Azok, J Brennan, ML Hazen, SL Li, K Wong, STC AF Pham, Tuan D. Wang, Honghui Zhou, Xiaobo Beck, Dominik Brandl, Miriam Hoehn, Gerard Azok, Joseph Brennan, Marie-Luise Hazen, Stanley L. Li, King Wong, Stephen T. C. TI Computational prediction models for early detection of risk of cardiovascular events using mass spectrometry data SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE LA English DT Article DE cardiovascular risk; early disease detection; mass spectrometry (MS); prediction models; proteomics ID OVARIAN-CANCER; PROTEOMIC PATTERNS; HUMAN SERUM; CLASSIFICATION; IDENTIFICATION; DISCOVERY; SELECTION; MARKERS; SPEECH AB Early prediction of the risk of cardiovascular events in patients with chest pain is critical in order to provide appropriate medical care for those with positive diagnosis. This paper introduces a computational methodology for predicting such events in the context of robust computerized classification using mass spectrometry data of blood samples collected from patients in emergency departments. We applied the computational theories of statistical and geostatistical linear prediction models to extract effective features of the mass spectra and a simple decision logic to classify disease and control samples for the purpose of early detection. While the statistical and geostatistical techniques provide better results than those obtained from some other methods, the geostatistical approach yields superior results in terms of sensitivity and specificity in various designs of the data set for validation, training, and testing. The proposed computational strategies are very promising for predicting major adverse cardiac events within six months. C1 [Pham, Tuan D.; Beck, Dominik; Brandl, Miriam] Univ New S Wales, Sch Informat Technol & Elect Engn, ADFA, Canberra, ACT 2006, Australia. [Wang, Honghui; Hoehn, Gerard; Azok, Joseph; Li, King] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Zhou, Xiaobo; Wong, Stephen T. C.] Harvard Univ, Sch Med, HCNR, Ctr Bioinformat, Boston, MA 02115 USA. [Brennan, Marie-Luise; Hazen, Stanley L.] Cleveland Clin Fdn, Ctr Cardiovasc Diagnost & Prevent, Cleveland, OH 44195 USA. RP Pham, TD (reprint author), Univ New S Wales, Sch Informat Technol & Elect Engn, ADFA, Canberra, ACT 2006, Australia. EM t.pham@adfa.edu.au; hwang2@cc.nih.gov; xiaobo_zhou@hms.harvard.edu; d.beck@adfa.edu.au; m.brandl@adfa.edu.au; ghoehn@cc.nih.gov; brennam@ccf.org; hazens@ccf.org; kli@tmhs.org; stephen_wong@hms.harvard.edu NR 39 TC 11 Z9 11 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1089-7771 J9 IEEE T INF TECHNOL B JI IEEE T. Inf. Technol. Biomed. PD SEP PY 2008 VL 12 IS 5 BP 636 EP 643 DI 10.1109/TITB.2007.908756 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 353MI UT WOS:000259571700010 PM 18779078 ER PT J AU Tan, S Yao, JH Ward, MM Yao, L Summers, RM AF Tan, Sovira Yao, Jianhua Ward, Michael M. Yao, Lawrence Summers, Ronald M. TI Computer aided evaluation of Ankylosing Spondylitis using high-resolution CT SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE level sets on nonplanar manifolds; multiscale vertebra segmentation; ridgelines/crestlines; semi-synthetic digital phantoms ID SEGMENTATION METHOD; 3-D SEGMENTATION; ACTIVE CONTOURS; CREST LINES; IMAGES; SURFACES; MESHES; MODEL; CURVES; SPINE AB Ankylosing Spondylitis is a disease characterized by abnormal bone structures (syndesmophytes) growing at intervertebral disk spaces. Because this growth is so slow as to be undetectable on plain radiographs taken over years, it is desirable to resort to computerized techniques to complement qualitative human judgment with precise quantitative measures. We developed an algorithm with minimal user intervention that provides such measures using high-resolution computed tomography (CT) images. To the best of our knowledge it is the first time that determination of the disease's status is attempted by direct measurement of the syndesmophytes. The first part of our algorithm segments the whole vertebral body using a 3-D multiscale cascade of successive level sets. The second part extracts the continuous ridgeline of the vertebral body where syndesmophytes are located. For that we designed a novel level set implementation capable of evolving on the isosurface of an object represented by a triangular mesh using curvature features. The third part of the algorithm segments the syndesmophytes from the vertebral body using local cutting planes and quantitates them. We present experimental work (lone with 10 patients from each of which we processed five vertebrae. The results of our algorithm were validated by comparison with a semi-quantitative evaluation made by a medical expert who visually inspected the CT scans. Correlation between the two evaluations was found to be 0.936 (p < 10(-18)). C1 [Tan, Sovira; Ward, Michael M.] NIAMSD, NIH, Ctr Clin, Bethesda, MD 20892 USA. [Yao, Jianhua; Yao, Lawrence; Summers, Ronald M.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Tan, S (reprint author), NIAMSD, NIH, Ctr Clin, Bethesda, MD 20892 USA. EM tanso@mail.nih.gov FU National Institutes of Health; Clinical Center; National Institute of Arthritis and Musculoskeletal and Skin diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center and the National Institute of Arthritis and Musculoskeletal and Skin diseases. NR 53 TC 20 Z9 20 U1 1 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD SEP PY 2008 VL 27 IS 9 BP 1252 EP 1267 DI 10.1109/TMI.2008.920612 PG 16 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 344TF UT WOS:000258949500007 PM 18779065 ER PT J AU Hu, CH Zhou, QF Shung, KK AF Hu, Chang-hong Zhou, Qifa Shung, K. Kirk TI Design and implementation of high frequency ultrasound pulsed-wave Doppler using FPGA SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID DIGITAL BEAMFORMER; BLOOD-FLOW; ARRAY; TRANSDUCERS AB The development of a field-programmable gate array (FPGA)-based pulsed-wave Doppler processing approach in pure digital domain is reported in this paper. After the ultrasound signals are digitized, directional Doppler frequency shifts are obtained with a digital-down converter followed by a low-pass filter. A Doppler spectrum is then calculated using the complex fast Fourier transform core inside the FPGA. In this approach, a pulsed-wave Doppler implementation core with reconfigurable and real-time processing capability is achieved. C1 [Hu, Chang-hong] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. RP Hu, CH (reprint author), Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. EM changhoh@usc.edu FU NIBIB NIH HHS [P41 EB002182-12, P41 EB002182, P41-EB2182] NR 9 TC 9 Z9 12 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD SEP PY 2008 VL 55 IS 9 BP 2109 EP 2111 DI 10.1109/TUFFC.904 PG 3 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 344FR UT WOS:000258912800027 PM 18986909 ER PT J AU Catalfamo, M Tai, XG Karpova, T McNally, J Henkart, PA AF Catalfamo, Marta Tai, Xuguang Karpova, Tatiana McNally, James Henkart, Pierre A. TI TcR-induced regulated secretion leads to surface expression of CTLA-4 in CD4(+)CD25(+) T cells SO IMMUNOLOGY LA English DT Article DE cytotoxic T-lymphocyte-associated antigen-4; human CD4(+) T cells; regulated exocytosis; secretory lysosome ID LYMPHOCYTE-ACTIVATION; GRANULE EXOCYTOSIS; SELF-TOLERANCE; CD4(+); PATHWAY; CD28; IDENTIFICATION; STIMULATION; COMPARTMENT; RECEPTOR AB In this study we show that CD4(+) T cells develop a functional regulated secretory compartment after differentiation into effector cells, as shown by their increased expression and T-cell receptor-induced exocytosis of lysosomal and cytotoxic effector proteins. We tested the hypothesis that activation-induced surface cytotoxic T-lymphocyte-associated antigen (CTLA-4) expression in CD4(+)CD25(+) regulatory T cells occurs via a similar regulated secretory pathway. Fluorescence microscopy showed that internal CTLA-4 in these cells was stored in a vesicular compartment distinct from lysosomal vesicles. Rapid activation-induced CTLA-4 surface expression in mouse CD4(+)CD25(+) T cells is independent of protein synthesis and Rab-27a. When antigen-dependent T-cell-antigen-presenting cell (APC) conjugates were analysed for surface distribution of CD86 on APC, a higher concentration of CD86 molecules was observed in the synapse of APC conjugated to CD4(+)CD25(+) cells than APC conjugated to CD4(+)CD25(-) cells. These results demonstrate that fast delivery of mediators by the regulated secretory pathway in CD4(+) T cells can be used to perform other functions that are not involved in cytotoxic function but that can influence/regulate other cells. C1 [Catalfamo, Marta] NIAID, CMRS, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Catalfamo, Marta; Tai, Xuguang; Henkart, Pierre A.] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Karpova, Tatiana; McNally, James] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Catalfamo, M (reprint author), NIAID, CMRS, Immunoregulat Lab, NIH, Bldg 10,Room 11B01, Bethesda, MD 20892 USA. EM catalfam@mail.nih.gov NR 30 TC 14 Z9 14 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2008 VL 125 IS 1 BP 70 EP 79 DI 10.1111/j.1365-2567.2008.02822.x PG 10 WC Immunology SC Immunology GA 335AR UT WOS:000258263700008 PM 18397268 ER PT J AU Yu, SQ Xie, H Datta, A Naidu, N Gu, XX AF Yu, Shengqing Xie, Hang Datta, Anup Naidu, Natasha Gu, Xin-Xing TI Galactose residues on the lipooligosaccharide of Moraxella catarrhalis 26404 form the epitope recognized by the bactericidal antiserum from conjugate vaccination SO INFECTION AND IMMUNITY LA English DT Article ID BRANHAMELLA-CATARRHALIS; MONOCLONAL-ANTIBODY; SEROTYPE-C; LIPOPOLYSACCHARIDE ANTIGENS; HAEMOPHILUS-INFLUENZAE; VACCINES; POLYSACCHARIDE; STRAINS; PROTEIN; OLIGOSACCHARIDES AB Lipooligosaccharide (LOS) from Moraxella catarrhalis has the potential to elicit bactericidal antibodies against the pathogen. We generated LOS-based conjugate vaccines that elicited bactericidal antibodies in animal models. However, epitopes on the LOS recognized by the functional anti-LOS antibodies remain unidentified. In this study, a mutant strain, D4, which lost the recognition by a bactericidal anti-LOS rabbit serum in Western blotting was generated from a serotype C strain 26404 by random transposon mutagenesis. Sequence analysis revealed there was an insertion of a kanamycin resistance gene in the lgt2 gene of D4, which encodes beta(1-4)-galactosyltransferase. An isogenic lgt2 mutant, 26404lgt2, was constructed. Structural analysis indicated that the mutant strain produced a truncated LOS lacking terminal galactoses from 4- and 6-linked oligosaccharide chains of strain 26404. Further studies showed that the antiserum lost the recognition of both mutant cells and LOSs in Western blotting, an enzyme-linked immunosorbent assay (ELISA), or a flow cytometry assay. The antiserum also lost the ability to kill the mutant strain in a bactericidal assay, whereas it showed a bactericidal titer of 1:80 to strain 26404. In an inhibition ELISA, D-(+)-galactose or 26404lgt2 LOS showed no inhibition. However, the 26404 LOS and a serotype A O35E LOS with terminal galactoses on its 6-linked oligosaccharide chain showed > 90% inhibition, while a serotype B 26397 LOS showed > 60% inhibition. These studies suggest that the terminal alpha-Gal-(1 -> 4)-beta-Gal on the 6-linked oligosaccharide chain of 26404 LOS plays a critical role in forming the epitope recognized by the bactericidal antiserum induced by immunization with our conjugate vaccine. C1 [Yu, Shengqing; Xie, Hang; Gu, Xin-Xing] Natl Inst Deafness & Other Commun Disorders, Vaccine Res Facil, Rockville, MD 20850 USA. [Datta, Anup; Naidu, Natasha] Univ Calif San Diego, Glycotechnol Core Resource, Glycobiol Res & Training Ctr, La Jolla, CA 92093 USA. RP Gu, XX (reprint author), 5 Res Court,Room 2A31, Rockville, MD 20850 USA. EM guxx@nidcd.nih.gov OI DATTA, ANUP/0000-0002-3796-6891 FU NIH, NIDCD FX We thank Eric J. Hansen and John C. McMichael (retired from Wyeth Vaccines, New York) for kindly supplying Moraxella catarrhalis strains.; This research was supported by the intramural research program of the NIH, NIDCD. NR 43 TC 9 Z9 13 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2008 VL 76 IS 9 BP 4251 EP 4258 DI 10.1128/IAI.01570-07 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 340TI UT WOS:000258667500047 PM 18559429 ER PT J AU Zhang, Y Murtha, J Roberts, MA Siegel, RM Bliska, JB AF Zhang, Yue Murtha, James Roberts, Margaret A. Siegel, Richard M. Bliska, James B. TI Type III secretion decreases bacterial and host survival following phagocytosis of Yersinia pseudotuberculosis by macrophages SO INFECTION AND IMMUNITY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; NECROSIS-FACTOR-ALPHA; VIRULENCE DETERMINANT; EFFECTOR PROTEIN; KINASE ACTIVATION; INDUCED APOPTOSIS; GAMMA-INTERFERON; OUTER PROTEINS; YOP2B PROTEIN; RHO-GTPASES AB Yersinia pseudotuberculosis uses a plasmid (pYV)-encoded type III secretion system (T3SS) to translocate a set of effectors called Yops into infected host cells. YopJ functions to induce apoptosis, and YopT, YopE, and YopH act to antagonize phagocytosis in macrophages. Because Yops do not completely block phagocytosis and Y. pseudotuberculosis can replicate in macrophages, it is important to determine if the T3SS modulates host responses to intracellular bacteria. Isogenic pYV-cured, pYV(+) wild-type, and yop mutant Y. pseudotuberculosis strains were allowed to infect bone marrow-derived murine macrophages at a low multiplicity of infection under conditions in which the survival of extracellular bacteria was prevented. Phagocytosis, the intracellular survival of the bacteria, and the apoptosis of the infected macrophages were analyzed. Forty percent of cell-associated wild-type bacteria were intracellular after a 20-min infection, allowing the study of the macrophage response to internalized pYV(+) Y. pseudotuberculosis. Interestingly, macrophages restricted survival of pYV(+) but not pYV-cured or Delta yopB Y. pseudotuberculosis within phagosomes: only a small fraction of the pYV(+) bacteria internalized replicated by 24 h. In addition, similar to 20% of macrophages infected with wild-type pYV(+) Y. pseudotuberculosis died of apoptosis after 20 h. Analysis of yop mutants expressing catalytically inactive effectors revealed that YopJ was important for apoptosis, while a role for YopE, YopH, and YopT in modulating macrophage responses to intracellular bacteria could not be identified. Apoptosis was reduced in Toll-like receptor 4-deficient macrophages, indicating that cell death required signaling through this receptor. Treatment of macrophages harboring intracellular pYV(+) Y. pseudotuberculosis with chloramphenicol reduced apoptosis, indicating that the de novo bacterial protein synthesis was necessary for cell death. Our finding that the presence of a functional T3SS impacts the survival of both bacterium and host following phagocytosis of Y. pseudotuberculosis suggests new roles for the T3SS in Yersinia pathogenesis. C1 [Zhang, Yue; Murtha, James; Bliska, James B.] SUNY Stony Brook, Ctr Infect Dis, Stony Brook, NY 11794 USA. [Zhang, Yue; Murtha, James; Bliska, James B.] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. [Roberts, Margaret A.; Siegel, Richard M.] Natl Inst Arthrit, Natl Inst Hlth, Autoimmun Branch, Immunoregulat Unit, Bethesda, MD 20892 USA. RP Zhang, Y (reprint author), SUNY Stony Brook, Ctr Infect Dis, Stony Brook, NY 11794 USA. EM yzhang@ms.cc.sunysb.edu FU National Institutes of Health [AI043389]; NIAID National Institutes of Health intramural biodefense research [Y2-AI-3739]; NIAMS intramural research FX We thank Susan von Horn and Guo-Wei Tian at the Central Microscopy Imaging Center at Stony Brook University for assistance with electron microscopy and confocal microscopy, respectively; Kim Orth at the University of Texas Southwestern Medical Center for providing YopJ proteins used for antibody production; Wei-Xing Zong for stimulating discussion and suggestions; Hana Fukuto, Joseph McPhee, Celine Pujol, Adrianus van der Velden, and Gloria Viboud for comments and suggestions; and Galina Romanov for excellent technical assistance.; This work is supported by grants from the National Institutes of Health (AI043389) awarded to J.B.B., by NIAID National Institutes of Health intramural biodefense research grant Y2-AI-3739 to R.M.S., and by NIAMS intramural research funding to R.M.S. NR 57 TC 22 Z9 23 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2008 VL 76 IS 9 BP 4299 EP 4310 DI 10.1128/IAI.00183-08 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 340TI UT WOS:000258667500052 PM 18591234 ER PT J AU Lehmann, T Diabate, A AF Lehmann, Tovi Diabate, Abdoulaye TI The molecular forms of Anopheles gambiae: A phenotypic perspective SO INFECTION GENETICS AND EVOLUTION LA English DT Review DE Anopheles gambiae; Malaria; Mating behavior; Predation; Reproductive isolation; Divergent selection; Ecological speciation; Swarm ID DNA-SEQUENCE VARIATION; WEST-AFRICA; GENETIC DIFFERENTIATION; CHROMOSOMAL FORMS; BURKINA-FASO; REPRODUCTIVE ISOLATION; INCIPIENT SPECIATION; INSECTICIDE RESISTANCE; SYMPATRIC SPECIATION; MALARIA TRANSMISSION AB The African malaria mosquito Anopheles gambiae is undergoing speciation, being split into the M and S molecular forms. Speciation is the main process promoting biological diversity, thus, new vector species might complicate disease transmission. Genetic differentiation between the molecular forms has been extensively studied, but phenotypic differences between them, the evolutionary forces that generated divergence, and the mechanisms that maintain their genetic isolation have only recently been addressed. Here, we review recent studies suggesting that selection mediated by larval predation and competition promoted divergence between temporary and permanent freshwater habitats. These differences explain the sharp discontinuity in distribution of the molecular forms between rice fields and surrounding savanna, but they can also explain the concurrent cline between humid and and environments due to the dependence on permanent habitats in the latter. Although less pronounced, differences in adult body size, reproductive output, and longevity also suggest that the molecular forms have adapted to distinct niches. Reproductive isolation between the molecular forms is achieved by spatial swarm segregation, although within-swarm mate recognition appears to play a role in certain locations. The implications of these results to disease transmission and control are discussed and many of the gaps in our understanding are highlighted. Published by Elsevier B.V. C1 [Lehmann, Tovi; Diabate, Abdoulaye] NIAID, Lab Malaria & Vector Res, NIH, MS 8132, Rockville, MD USA. RP Lehmann, T (reprint author), NIAID, Lab Malaria & Vector Res, NIH, MS 8132, 12735 Twinbrook Pkwy, Rockville, MD USA. EM tlehmann@niaid.nih.gov FU National Institutes of Health; National Institute of Allergy and Infectious Diseases FX We thank Drs. Frederic Simard, Nicholas Manoukis, Cecilia Coscaron, Frederic Tripet, Adama Dao, Jen Hume, and Bill Hawley, for helpful comments and discussions on earlier versions of this paper. Special thanks to Drs. Nora Besansky, Nicholas Manoukis, Frederic Simard, and to Mr. Adama Dao and colleagues at MRTC, Mali for sharing unpublished data. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 101 TC 84 Z9 86 U1 2 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 EI 1567-7257 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD SEP PY 2008 VL 8 IS 5 BP 737 EP 746 DI 10.1016/j.meegid.2008.06.003 PG 10 WC Infectious Diseases SC Infectious Diseases GA 361XK UT WOS:000260160900029 PM 18640289 ER PT J AU Dworkin, MS Schwan, TG Anderson, DE Borchardt, SM AF Dworkin, Mark S. Schwan, Tom G. Anderson, Donald E. Borchardt, Stephanie M. TI Tick-borne relapsing fever SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID SPIROCHETE BORRELIA-HERMSII; UNITED-STATES; LYME-DISEASE; PHYLOGENETIC ANALYSIS; INTERSTATE OUTBREAK; ANTIGENIC VARIATION; BRITISH-COLUMBIA; NORTH-AMERICA; GRAND-CANYON; IDENTIFICATION AB Each year, many residents of And visitors to endemic regions of the western United States are exposed to the tick vectors of tick-borne relapsing fever (TBRF), Ornithodoros hermsi, Ornithodoros turicata, or Ornithodoros parkeri. This disease is remarkable because the human host is unaware of the tick bite, usually becomes very ill, may experience an exacerbation of symptoms rather than improvement shortly after beginning appropriate treatment, and, despite often high numbers of the etiologic organism in the blood, rarely dies as a result of the illness. Although relapsing fever is acquired in many parts of the world, this article focuses primarily on knowledge about TBRF in North America. C1 [Dworkin, Mark S.] Univ Illinois, Div Epidemiol & Biostat, Sch Publ Hlth, Chicago, IL 60612 USA. [Schwan, Tom G.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Anderson, Donald E.] Washington State Univ, Coll Pharm, Spokane, WA 99223 USA. [Borchardt, Stephanie M.] Fargo Vet Adm Med Ctr, Fargo, ND 58102 USA. RP Dworkin, MS (reprint author), Univ Illinois, Div Epidemiol & Biostat, Sch Publ Hlth, 1603 W Taylor St, Chicago, IL 60612 USA. EM mdworkin@uic.edu FU Intramural NIH HHS [Z01 AI000492-21] NR 67 TC 56 Z9 60 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0891-5520 EI 1557-9824 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 2008 VL 22 IS 3 BP 449 EP + DI 10.1016/j.idc.2008.03.006 PG 21 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 354DN UT WOS:000259619200006 PM 18755384 ER PT J AU Lin, J DiCuccio, M Grigoryan, V Wilbur, WJ AF Lin, Jimmy DiCuccio, Michael Grigoryan, Vahan Wilbur, W. John TI Navigating information spaces: A case study of related article search in PubMed SO INFORMATION PROCESSING & MANAGEMENT LA English DT Article DE MEDLINE; TREC genomics; browsing; interactive IR ID EXPLORATION; RETRIEVAL; NETWORKS AB The concept of an "information space" provides a powerful metaphor for guiding the design of interactive retrieval systems. We present a case study of related article search, a browsing tool designed to help users navigate the information space defined by results of the PubMed (R) search engine. This feature leverages content-similarity links that tie MEDLINE (R) citations together in a vast document network. We examine the effectiveness of related article search from two perspectives: a topological analysis of networks generated from information needs represented in the TREC 2005 genomics track and a query log analysis of real PubMed users. Together, data suggest that related article search is a useful feature and that browsing related articles has become an integral part of how users interact with PubMed. Published by Elsevier Ltd. C1 [Lin, Jimmy] Univ Maryland, iSch, College Pk, MD 20742 USA. [Lin, Jimmy; DiCuccio, Michael; Grigoryan, Vahan; Wilbur, W. John] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Lin, J (reprint author), Univ Maryland, iSch, College Pk, MD 20742 USA. EM jimmylin@umd.edu; dicuccio@ncbi.nlm.nih.gov; grigoryv@ncbi.nlm.nih.gov; wilbur@ncbi.nlm.nih.gov NR 29 TC 6 Z9 6 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4573 J9 INFORM PROCESS MANAG JI Inf. Process. Manage. PD SEP PY 2008 VL 44 IS 5 BP 1771 EP 1783 DI 10.1016/j.ipm.2008.04.002 PG 13 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA 342UA UT WOS:000258807800010 ER PT J AU Mans, BJ Ribeiro, JMC AF Mans, Ben J. Ribeiro, Jose M. C. TI Function, mechanism and evolution of the moubatin-clade of soft tick lipocalins SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Ornithodoros moubata; Ornithodoros savignyi; Moubatin; TSGP2; TSGP3; Platelet aggregation; Thromboxane A(2); Complement C5 inhibitor ID ORNITHODOROS-MOUBATA; PLATELET-AGGREGATION; GRANULE BIOGENESIS; IXODES-SCAPULARIS; BINDING PROTEINS; SALIVARY-GLANDS; FAMILY; INHIBITOR; CLONING; EXPRESSION AB The "moubatin-clade" of soft tick lipocalins, although monophyletic, shows clear signs of paralogy as indicated by the various functions associated with this protein family. This includes anti-platelet (moubatin), anti-complement (OMCI) and toxic (TSGP2) activities in the vertebrate host. In order to understand the evolution of function and how it relates to the various paralogs in this clade, we characterized a number of different proteins in regard to undefined function and mechanism. By utilizing gain-of-function for TSGP2 and loss-of-function for TSGP3, we show that inhibition of collagen-induced platelet aggregation by moubatin and TSGP3 is due to scavenging of thromboxane A(2). Moubatin, TSGP2 and TSGP3 are also able to bind leukotriene B-4 With high affinity. TSGP2 and TSGP3, but not moubatin, binds complement C5, with kinetics that indicates that conformation change occurs during interaction. A conserved loop and histidine residue in the sequences of OMCI, TSGP2 and TSGP3 are implicated in the interaction with complement C5. The data presented suggest that the ancestral function evolved in this clade was aimed at inhibition of vasoconstriction, platelet aggregation and neutrophil aggregation, primarily by scavenging of thromboxane A(2) and leukotriene B-4. C5 complement targeting activity evolved within this clade, probably within the Old World Ornithodorinae. The moubatin-clade itself most probably derived from the related histamine and serotonin-binding lipocalin sub-family that is conserved within the Argasidae. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Mans, Ben J.; Ribeiro, Jose M. C.] NIH, Lab Malaria & Vector Res, Rockville, MD 20852 USA. RP Mans, BJ (reprint author), Agr Res Council, Onderstepoort Vet Inst, ZA-0110 Onderstepoort, South Africa. EM mansb@arc.agric.za OI Mans, Ben/0000-0002-0177-0029; Ribeiro, Jose/0000-0002-9107-0818 FU NIAID; National Institutes of Health FX Dr. Carl Hammer of the Research and Technology Branch of the NIAID is thanked for mass spectrometry analysis of the recombinant proteins. This work was supported by the intramural research program of the NIAID, National Institutes of Health. NR 42 TC 50 Z9 50 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD SEP PY 2008 VL 38 IS 9 BP 841 EP 852 DI 10.1016/j.ibmb.2008.06.007 PG 12 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 358CT UT WOS:000259894900004 PM 18694828 ER PT J AU Mans, BJ Ribeiro, JMC AF Mans, Ben J. Ribeiro, Jose M. C. TI A novel clade of cysteinyl leukotriene scavengers in soft ticks SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Argas monolakensis; Ornithodoros savignyi; TSGP4; AM-33; Vasodilator; Leukotrienes; Mast cell; Basophil ID ORNITHODOROS-SAVIGNYI; HOST INTERACTIONS; BINDING PROTEINS; SALIVARY-GLANDS; SAND TAMPAN; EVOLUTION; FAMILY; PERSPECTIVE; TOXICOSES; HISTAMINE AB Inflammation is an important vertebrate defense mechanism against ecto-parasites for which ticks have evolved numerous mechanisms of modulation. AM-33 and TSGP4, related lipocalins from the soft ticks Argas monolakensis and Ornithodoros savignyi bind cysteinyl leukotrienes with high affinity as measured by isothermal titration calorimetry. This was confirmed in a smooth muscle bioassay that measured contraction of guinea pig ileum induced by leukotriene C-4 where both proteins inhibited contraction effectively. Conservation of this function in two diverse soft tick genera suggests that scavenging of cysteinyl leukotrienes evolved in the ancestral soft tick lineage. In addition soft ticks also evolved mechanisms that target other mediators of inflammation that include scavenging of histamine, serotonin, leukotriene B-4, thromboxane A(2), ATP and inhibition of the complement cascade. Inhibitors of blood-coagulation and platelet aggregation were also present in the ancestral soft tick lineage. Because histamine and cysteinyl leukotrienes are mainly produced by mast cells and basophils, and these cells are important in the mediation of tick rejection reactions, these findings indicate an ancient antagonistic relationship between ticks and the immune system. As such, modulation of the hemostatic system as well as inflammation was important adaptive responses in the evolution of a blood-feeding lifestyle in soft ticks. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Mans, Ben J.; Ribeiro, Jose M. C.] NIH, Lab Malaria & Vector Res, Rockville, MD 20852 USA. RP Mans, BJ (reprint author), Agr Res Council, Onderstepoort Vet Inst, ZA-0110 Onderstepoort, South Africa. EM mansb@arc.agric.za OI Mans, Ben/0000-0002-0177-0029; Ribeiro, Jose/0000-0002-9107-0818 FU MAID; National Institutes of Health FX Dr. Carl Hammer and Mark Garfield of the Research and Technology Branch of the NIAID are thanked for mass spectrometry analysis and Edman sequencing of the recombinant proteins. This work was supported by the intramural research program of the MAID, National Institutes of Health. NR 41 TC 36 Z9 36 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD SEP PY 2008 VL 38 IS 9 BP 862 EP 870 DI 10.1016/j.ibmb.2008.06.002 PG 9 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 358CT UT WOS:000259894900006 PM 18675910 ER PT J AU Hsiao, AF Wong, MD Miller, MF Ambs, AH Goldstein, MS Smith, A Ballard-Barbash, R Becerra, LS Cheng, EM Wenger, NS AF Hsiao, An-Fu Wong, Mitchell D. Miller, Melissa F. Ambs, Anita H. Goldstein, Michael S. Smith, Ashley Ballard-Barbash, Rachel Becerra, Lida S. Cheng, Eric M. Wenger, Neil S. TI Role of religiosity and spirituality in complementary and alternative medicine use among cancer survivors in California SO INTEGRATIVE CANCER THERAPIES LA English DT Article DE CAM; integrative medicine; spirituality; religiosity; survivors ID HEALTH-CARE; ETHNIC-DIFFERENCES; ONCOLOGY; PREVALENCE; ADULTS AB Objectives. Cancer survivors often turn to religion, spirituality, and complementary and alternative medicine (CAM) because they perceive these areas as being more holistic and patient-centered than conventional medicine. Because increased religiosity and spirituality have been found to be associated with higher CAM use in the general population, it was hypothesized that these factors would be important predictors of CAM use in cancer survivors. Design and Subjects. The study included a subsample of 1844 people with cancer or a history of cancer from the 2003 California Health Interview Survey of CAM, a cross-sectional survey of a population-based sample of adults in California. Prevalence and predictors of religious/spiritual forms of CAM (R/S CAM) and nonreligious/nonspiritual forms of CAM (non-R/S CAM) were compared. Multivariate logistic regression was used to identify the predictors of R/S CAM and non-R/S CAM. Results. Nearly two thirds of participants reported using at least 1 type of R/S CAM, and 85% reported ever using non-R/S CAM. The majority of cancer survivors reported that they were very/moderately religious or spiritual. Both religiosity and spirituality were strongly related to non-R/S CAM use, but in opposite directions. Very or moderately religious cancer survivors were less likely (odds ratio = 0.30; 95% confidence interval, 0.12-0.40) than nonreligious cancer survivors to use non-R/S CAM. In contrast, very or moderately spiritual cancer survivors were more likely (odds ratio = 2.42; 95% confidence interval, 1.16-6.02) than nonspiritual cancer survivors to use non-R/S CAM. Conclusions. The use of R/S CAM and non-R/S CAM is very high in cancer survivors. It may be helpful for clinicians to ascertain their patients' use of these types of CAM to integrate all forms of care used to managing their cancer. C1 [Hsiao, An-Fu] VA Long Beach Healthcare Syst, Long Beach, CA 90822 USA. [Hsiao, An-Fu] Univ Calif Irvine, Ctr Hlth Policy Res, Irvine, CA USA. [Wong, Mitchell D.] Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA USA. [Wong, Mitchell D.; Wenger, Neil S.] Univ Calif Los Angeles, Hlth Serv Res, Los Angeles, CA USA. [Miller, Melissa F.; Ambs, Anita H.; Smith, Ashley; Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Goldstein, Michael S.] Univ Calif Los Angeles, Dept Community Hlth Sci, Los Angeles, CA USA. [Becerra, Lida S.] Univ Calif Los Angeles, Ctr Hlth Policy & Res, Los Angeles, CA USA. [Cheng, Eric M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA USA. [Cheng, Eric M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Hsiao, AF (reprint author), VA Long Beach Healthcare Syst, 5901 E 7th St,Mail Code 11-111, Long Beach, CA 90822 USA. EM anfu.hsiao@va.gov OI Wong, Mitchell/0000-0002-4800-8410 FU National Institutes of Health (NIH); National Center of Complementary and Alternative Medicine [R21 AT002248-01]; NCCAM [R21-AT002248-01]; National Cancer institute (NCI) [NO2-PC-95057] FX We thank Victor Gonzalez for his technical assistance. We thank UCLA Center for Health Policy Research for their assistance in carrying out the research. FUNDING/GRANT INFORMATION: Dr. Hsiao was supported by National Institutes of Health (NIH), National Center of Complementary and Alternative Medicine (R21 AT002248-01). This publication was made possible by Grant No. R21-AT002248-01 from NCCAM. The collection of data used in this study was supported by the National Cancer institute (NCI) under contract NO2-PC-95057 awarded to the UCLA Center for Health Policy Research. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM, NCI, or the NIH. NR 36 TC 20 Z9 21 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1534-7354 J9 INTEGR CANCER THER JI Integr. Cancer Ther. PD SEP PY 2008 VL 7 IS 3 BP 139 EP 146 DI 10.1177/1534735408322847 PG 8 WC Oncology; Integrative & Complementary Medicine SC Oncology; Integrative & Complementary Medicine GA 351PQ UT WOS:000259436800004 PM 18815145 ER PT J AU Miller, MA Miller, WA Conrad, PA James, ER Melli, AC Leutenegger, CM Dabritz, HA Packham, AE Paradies, D Harris, M Ames, J Jessup, DA Worcester, K Grigg, ME AF Miller, M. A. Miller, W. A. Conrad, P. A. James, E. R. Melli, A. C. Leutenegger, C. M. Dabritz, H. A. Packham, A. E. Paradies, D. Harris, M. Ames, J. Jessup, D. A. Worcester, K. Grigg, M. E. TI Type X Toxoplasma gondii in a wild mussel and terrestrial carnivores from coastal California: New linkages between terrestrial mammals, runoff and toxoplasmosis of sea otters SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Article DE Toxoplasma gondii; Type X; B1; 18S rDNA; SAG1; GRA6; otter; felid; mussel ID ENHYDRA-LUTRIS-NEREIS; OYSTERS CRASSOSTREA-VIRGINICA; WATERBORNE TOXOPLASMOSIS; SEXUAL RECOMBINATION; DRINKING-WATER; OOCYSTS; MARINE; SPP.; CRYPTOSPORIDIUM; PROTOZOAN AB Sea otters in California are commonly infected with Toxoplasma gondii. A unique Type X strain is responsible for 72% of otter infections, but its prevalence in terrestrial animals and marine invertebrates inhabiting the same area was unknown. Between 2000 and 2005, 45 terrestrial carnivores (lions, bobcats, domestic cats and foxes) and 1396 invertebrates (mussels, clams and worms) were screened for T gondii using PCR and DNA sequencing to determine the phylogeographic distribution of T gondii archetypal 1, 11, 111 and Type X genotypes. Marine bivalves have been shown to concentrate T gondii oocysts in the laboratory, but a comprehensive survey of wild invertebrates has not been reported. A California mussel from an estuary draining into Monterey Bay was confirmed positive for Type X T gondii by multilocus PCR and DNA sequencing at the B1 and SAG1 loci. This mussel was collected from nearshore marine waters just after the first significant rainfall event in the fall of 2002. Of 45 carnivores tested at the B1, SAG1, and GRA6 typing loci, 15 had PCR-confirmed T gondii infection; 11 possessed alleles consistent with infection by archetypal Type I, II or III strains and 4 possessed alleles consistent with Type X T gondii infection. No non-canonical alleles were identified. The four T gondii strains with Type X alleles were identified from two mountain lions, a bobcat and a fox residing in coastal watersheds adjacent to sea otter habitat near Monterey Bay and Estero Bay. Confirmation of Type X T. gondii in coastal-dwelling felids, canids, a marine bivalve and nearshore-dwelling sea otters supports the hypotheses that feline faecal contamination is flowing from land to sea through surface runoff, and that otters can be infected with T gondii via consumption of filter-feeding marine invertebrates. (c) 2008 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. C1 [Miller, M. A.; Harris, M.; Ames, J.; Jessup, D. A.] Marine Wildlife Vet Care & Res Ctr, Calif Dept Fish & Game, Santa Cruz, CA 95060 USA. [Miller, W. A.; Conrad, P. A.; Melli, A. C.; Packham, A. E.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. [James, E. R.] Univ British Columbia, Dept Med, Vancouver, BC V5C 3J5, Canada. [Leutenegger, C. M.] IDEXX Reference Labs, W Sacramento, CA 95605 USA. [Dabritz, H. A.] Infant Botulism Treatment & Prevent Program, Calif Dept Publ Hlth, Richmond, CA 94804 USA. [Paradies, D.] Bay Fdn Morro Bay, Morro Bay, CA 93442 USA. [Worcester, K.] Reg Water Qual Control Board Cent Coast, San Luis Obispo, CA 93401 USA. [Grigg, M. E.] NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Miller, MA (reprint author), Marine Wildlife Vet Care & Res Ctr, Calif Dept Fish & Game, 1451 Shaffer Rd, Santa Cruz, CA 95060 USA. EM mmiller@ospr.dfg.ca.gov RI James, Erick/D-4725-2012 FU Morris Animal Foundation; National Sea Grant; Central Coast Regional Water Quality Control Board; Duke Power and the Morro Bay Water Treatment Plant; National Science Foundation; Intramural Research Program of the NIH; NIAID FX Financial support was provided by the Morris Animal Foundation (MAM, PAC, HAD), National Sea Grant (MAM and PAC), CDFG (MAM and DAJ), the Central Coast Regional Water Quality Control Board, Duke Power and the Morro Bay Water Treatment Plant (MAM, DAJ, PAC and WAM) and the National Science Foundation (MEG). This research was supported in part by the Intramural Research Program of the NIH and NIAID (MEG). We are grateful to the wardens, biologists and staff of CDFG, California State Parks, USDA-Wildlife Protection Services, the Elkhorn Slough Reserve, Monterey SPCA, Moss Landing Yacht Club, Elkhorn Slough Safari Tours, Morro Bay Water Treatment Plant, UC Davis, UC Santa Cruz, the Central Coast Water Quality Control Board and the Morro Bay Harbor Patrol for their enthusiastic collaboration and support. In particular, we thank Adam Schneider, Alexis Fisher, Bruce Keough, Dave Paradies, Debbie Brownstein, Elene Dorfmeier, Eva Berberich, Erin Dodd, Francesca Batac, Larry White, Nancy Wagner, Sara Miller, Sharon Toy-Choutka and Tricia Wilson for assistance with data collection, specimen transport, necropsies and manuscript preparation. We would especially like to thank Ms. Betty White-Ludden for her long-term support of sea otter research.; The cover photo was provided by Mr. Frank Balthis. NR 55 TC 101 Z9 103 U1 5 U2 50 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD SEP PY 2008 VL 38 IS 11 BP 1319 EP 1328 DI 10.1016/j.ijpara.2008.02.005 PG 10 WC Parasitology SC Parasitology GA 345TU UT WOS:000259020700009 PM 18452923 ER PT J AU Ahn, J Moslehi, R Weinstein, SJ Snyder, K Virtamo, J Albanes, D AF Ahn, Jiyoung Moslehi, Roxana Weinstein, Stephanie J. Snyder, Kirk Virtamo, Jarmo Albanes, Demetrius TI Family history of prostate cancer and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE family history; prostate cancer; height; weight; alpha-tocopherol; retinol; beta-carotene ID NATIONWIDE REGISTER COHORT; POPULATION-BASED COHORT; BREAST-CANCER; FOLLOW-UP; SWEDEN; MEN; HEALTH; CARCINOMA; MEAT; AGE AB Prostate cancer family history has been associated with increased risk of the malignancy. Most prior studies have been retrospective and subject to recall bias, however, and data evaluating interactions with other important risk factors are limited. We examined the relationship between a family history of prostate cancer and prostate cancer risk in relation to body size, micronutrients and other exposures in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort of Finnish male smokers. Family history of cancer information was self-reported once during the study in 1991, and anthropometry was measured by trained personnel. Among 19,652 men with complete data, 1,111 incident cases were identified during up to 12.3 years of follow-up. A first-degree family history of prostate cancer was associated with an overall relative risk (RR) of 1.91 (95% CI = 1.49-2.47) and a RR of 4.16 (95% CI = 2.67-6.49) for advanced disease (stage : 3), adjusted for age and trial intervention. Our data also suggest that to some degree, height, body mass index, and serum a-tocopherol and P-carotene modify the family history and prostate cancer association, although the interactions were not statistically significant. Supplementation with vitamin E or beta-carotene did not modify the family history-prostate cancer association. This study provides additional evidence that family history is a significant risk factor for prostate cancer. Published 2008 Wiley-Liss, Inc. C1 [Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Snyder, Kirk] Informat Management Serv Inc, Silver Spring, MD USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Albanes, D (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, EPS-3044,6120 Execut Blvd, Bethesda, MD 20892 USA. EM daa@nih.gov RI Albanes, Demetrius/B-9749-2015 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; Intramural NIH HHS; NCI NIH HHS [N01-CN-45165] NR 38 TC 18 Z9 18 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 2008 VL 123 IS 5 BP 1154 EP 1159 DI 10.1002/ijc.23591 PG 6 WC Oncology SC Oncology GA 334TE UT WOS:000258243300022 PM 18546266 ER PT J AU Shamir, L AF Shamir, Lior TI Evaluation of face datasets as tools for assessing the performance of face recognition methods SO INTERNATIONAL JOURNAL OF COMPUTER VISION LA English DT Article DE face recognition; biometrics; FERET ID QUANTITATIVE-ANALYSIS; INFORMATICS; ALGORITHMS; IMAGES AB Face datasets are considered a primary tool for evaluating the efficacy of face recognition methods. Here we show that in many of the commonly used face datasets, face images can be recognized accurately at a rate significantly higher than random even when no face, hair or clothes features appear in the image. The experiments were done by cutting a small background area from each face image, so that each face dataset provided a new image dataset which included only seemingly blank images. Then, an image classification method was used in order to check the classification accuracy. Experimental results show that the classification accuracy ranged between 13.5% (color FERET) to 99% (YaleB). These results indicate that the performance of face recognition methods measured using face image datasets may be biased. Compilable source code used for this experiment is freely available for download via the Internet. C1 NIA, NIH, Genet Lab, Baltimore, MD 21224 USA. RP Shamir, L (reprint author), NIA, NIH, Genet Lab, 333 Cassell Dr, Baltimore, MD 21224 USA. EM shamirl@mail.nih.gov FU Intramural NIH HHS [NIH0012688432] NR 32 TC 22 Z9 22 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-5691 EI 1573-1405 J9 INT J COMPUT VISION JI Int. J. Comput. Vis. PD SEP PY 2008 VL 79 IS 3 BP 225 EP 230 DI 10.1007/s11263-008-0143-7 PG 6 WC Computer Science, Artificial Intelligence SC Computer Science GA 310KW UT WOS:000256529500001 PM 18776952 ER PT J AU Kretschmer, D Gleske, AK Rautenberg, M van Strijp, J Otto, M Peschel, A AF Kretschmer, D. Gleske, A. K. Rautenberg, M. van Strijp, J. Otto, M. Peschel, A. TI The leukocidal phenol-soluble modulin (PSM) peptides of Staphylococcus aureus represent a novel type of leukocyte attractants SO INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the Deutschen-Gesellschaft-fur-Hygiene-und-Mikrobiologie CY SEP 21-24, 2008 CL Dresden, GERMANY SP Deutsch Gesell Hygiene & Mikrobiol C1 [Kretschmer, D.; Gleske, A. K.; Rautenberg, M.; Peschel, A.] Univ Tubingen, Tubingen, Germany. [van Strijp, J.] Univ Med Ctr Utrecht, Eijkman Winkler Inst, Utrecht, Netherlands. [Otto, M.] NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, US NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1438-4221 J9 INT J MED MICROBIOL JI Int. J. Med. Microbiol. PD SEP PY 2008 VL 298 SU 45 BP 45 EP 45 PG 1 WC Microbiology; Virology SC Microbiology; Virology GA 353SV UT WOS:000259589400175 ER PT J AU Lee, KY Choi, SY Bae, JW Kim, S Chung, KW Drayna, D Kim, UK Lee, SH AF Lee, K. Y. Choi, S. Y. Bae, J. W. Kim, S. Chung, K. W. Drayna, D. Kim, U. K. Lee, S. H. TI Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE connexin; hearing loss; Koreans; mutation; Pendred syndrome ID CONNEXIN 26 GENE; NONSYNDROMIC HEARING-LOSS; PENDRED-SYNDROME; VESTIBULAR AQUEDUCT; RECESSIVE DEAFNESS; CHILDHOOD DEAFNESS; HIGH-FREQUENCY; UNITED-STATES; PDS GENE; MUTATIONS AB Objectives: Mutations in the GJB2, GJB6 and SLC26A4 genes are a frequent cause of hearing toss in a number of populations. However, little is known about the genetic causes of hearing toss in the Korean population. Methods: We sequenced the GJB2 and GJB6 genes to examine the rote of mutations in these genes in 22 hearing loss patients. We also sequenced the SLC26A4 gene in seven patients with inner ear malformations, including enlarged vestibular aqueduct (EVA) revealed by computer tomography. Results: Coding sequence mutations in GJB2 were identified in 13.6% of the patients screened. Two different mutations, 235delC and T86R were found in three unrelated patients. The 235delC was the most prevalent mutation with an allele frequency of 6.9% in our patient group. No mutations, including 342-kb deletion, were found in GJB6 gene. Three different variants of SLC26A4 were identified in the EVA patients, including one novel. mutation. Four EVA patients carried two mutant alleles of SLC26A4, and at least one allele in all patients was the H723R mutation, which accounted for 75% of all mutant alleles. Conclusions: Our results suggest that GJB2 and SLC26A4 mutations together make up a major cause of congenital hearing loss in the Korean population. Further studies may be able to identify other common variants that account for a significant fraction of hearing toss in the Korean population. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Lee, K. Y.; Lee, S. H.] Kyungpook Natl Univ, Coll Med, Dept Otolaryngol, Taegu 702701, South Korea. [Choi, S. Y.; Bae, J. W.; Kim, U. K.] Kyungpook Natl Univ, Coll Nat Sci, Dept Biol, Taegu 702701, South Korea. [Kim, S.] Deagu Fatima Hosp, Dept Otolaryngol, Taegu 701600, South Korea. [Chung, K. W.] Kongju Natl Univ, Dept Biol Sci, Kong Ju 314701, South Korea. [Drayna, D.] Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. RP Lee, KY (reprint author), Kyungpook Natl Univ, Coll Med, Dept Otolaryngol, Taegu 702701, South Korea. EM drlky@hanmail.net; kimuk@knu.ac.kr FU Korea Science and Engineering Foundation (KOSEF); Korean government (MOST) [R01-2008-000-10431-0]; Kyungpook National University Hospital; Korean Ministry of Education FX We thank all the subjects who participated in the present study. We also thank Young-Jun Choi and Jung Ree Lee for collecting:) patients and family members. This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (MOST) (No. R01-2008-000-10431-0). This work was supported by BioMedical Research Institute grant, Kyungpook National University Hospital (2007). SY Choi and JW Bae were supported by the Korean Ministry of Education through the Brain Korea 21 project. NR 46 TC 40 Z9 43 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD SEP PY 2008 VL 72 IS 9 BP 1301 EP 1309 DI 10.1016/j.ijport.2008.05.007 PG 9 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 347IW UT WOS:000259134800001 PM 18585793 ER PT J AU Bondar, IV Leopold, DA Logothetis, NK AF Bondar, I. V. Leopold, D. A. Logothetis, N. K. TI Stability of neuronal representation in inferotemporal cortex: Long-term single neurons study by chronically implanted microelectrodes SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 14th World Congress of Psychophysiology the Olympics of the Brain CY SEP 08-13, 2008 CL St Petersburg, RUSSIA SP Int Org Psychophysiol C1 [Bondar, I. V.] RAS, Inst Higher Nervous Act & Neurophysiol, Moscow 117901, Russia. [Leopold, D. A.] NIMH, Unit Cognit Neurophysiol & Imaging, Bethesda, MD 20892 USA. [Logothetis, N. K.] Max Planck Inst Biol Cybernet, Tubingen, Germany. 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 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2008 VL 69 IS 3 BP 172 EP 172 DI 10.1016/j.ijpsycho.2008.05.447 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 336VU UT WOS:000258393700119 ER PT J AU Furey, ML AF Furey, M. L. TI Influence of muscarinic cholinergic receptors on mood, attention and emotional stimulus processing in affective disorders SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 14th World Congress of Psychophysiology the Olympics of the Brain CY SEP 08-13, 2008 CL St Petersburg, RUSSIA SP Int Org Psychophysiol C1 [Furey, M. L.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2008 VL 69 IS 3 BP 187 EP 187 DI 10.1016/j.ijpsycho.2008.05.499 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 336VU UT WOS:000258393700171 ER PT J AU Pietrini, P Furey, ML AF Pietrini, P. Furey, M. L. TI The role of the cholinergic system in physiological and pathological conditions SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 14th World Congress of Psychophysiology the Olympics of the Brain CY SEP 08-13, 2008 CL St Petersburg, RUSSIA SP Int Org Psychophysiol C1 [Pietrini, P.] Univ Pisa, Dept Expt Pathol Med Biotechnol Infectivol & Epid, Lab Clin Biochem & Mol Biol, Pisa, Italy. [Furey, M. L.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2008 VL 69 IS 3 BP 187 EP 187 DI 10.1016/j.ijpsycho.2008.05.498 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 336VU UT WOS:000258393700170 ER PT J AU Ricciardi, E Pietrini, P Furey, ML AF Ricciardi, E. Pietrini, P. Furey, M. L. TI Cholinergic modulation on brain response to working memory as task difficulty increases in young and older subjects SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 14th World Congress of Psychophysiology the Olympics of the Brain CY SEP 08-13, 2008 CL St Petersburg, RUSSIA SP Int Org Psychophysiol C1 [Ricciardi, E.; Pietrini, P.] Univ Pisa, Dept Expt Pathol Med Biotechnol Infectivol & Epid, Lab Clin Biochem & Mol Biol, Pisa, Italy. [Furey, M. L.] NIMH, NIH, Bethesda, MD 20892 USA. RI Furey, Maura/H-5273-2013; Ricciardi, Emiliano/E-6929-2011 OI Ricciardi, Emiliano/0000-0002-7178-9534 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2008 VL 69 IS 3 BP 187 EP 188 DI 10.1016/j.ijpsycho.2008.05.500 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 336VU UT WOS:000258393700172 ER PT J AU Nugent, AC Bain, EE Sollers, JJ Thayer, JF Drevets, WC AF Nugent, A. C. Bain, E. E. Sollers, J. J. Thayer, J. F. Drevets, W. C. TI Alterations in neural correlates of autonomic control in females with and without major depressive disorder SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 14th World Congress of Psychophysiology the Olympics of the Brain CY SEP 08-13, 2008 CL St Petersburg, RUSSIA SP Int Org Psychophysiol C1 [Nugent, A. C.; Drevets, W. C.] NIMH, Bethesda, MD USA. [Bain, E. E.] Abbott Labs, Abbott Pk, IL 60064 USA. [Sollers, J. J.; Thayer, J. F.] Ohio State Univ, Columbus, OH 43210 USA. 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 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2008 VL 69 IS 3 BP 194 EP 194 DI 10.1016/j.ijpsycho.2008.05.524 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 336VU UT WOS:000258393700196 ER PT J AU Nugent, AC Bain, EE Thayer, JF Sollers, JJ Drevets, WC AF Nugent, A. C. Bain, E. E. Thayer, J. F. Sollers, J. J. Drevets, W. C. TI Alterations in neural correlates of autonomic control in females with major depressive disorder SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 14th World Congress of Psychophysiology the Olympics of the Brain CY SEP 08-13, 2008 CL St Petersburg, RUSSIA SP Int Org Psychophysiol C1 [Nugent, A. C.; Drevets, W. C.] NIMH, NIH, Bethesda, MD 20892 USA. [Bain, E. E.] Abbott Labs, Abbott Pk, IL 60064 USA. [Thayer, J. F.; Sollers, J. J.] Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2008 VL 69 IS 3 BP 195 EP 195 DI 10.1016/j.ijpsycho.2008.05.526 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 336VU UT WOS:000258393700198 ER PT J AU Leopold, DA Wilke, M Maier, A AF Leopold, D. A. Wilke, M. Maier, A. TI Neural correlates of perception measured with fMRl and microelectrodes SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 14th World Congress of Psychophysiology the Olympics of the Brain CY SEP 08-13, 2008 CL St Petersburg, RUSSIA SP Int Org Psychophysiol C1 [Leopold, D. A.; Wilke, M.; Maier, A.] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RI Maier, Alexander/B-7489-2009 OI Maier, Alexander/0000-0002-7250-502X NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2008 VL 69 IS 3 BP 199 EP 200 DI 10.1016/j.ijpsycho.2008.05.543 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 336VU UT WOS:000258393700215 ER PT J AU Duncan, CC Mirsky, AF AF Duncan, C. C. Mirsky, A. F. TI Auditory P300 is more sensitive than visual P300 to the attention impairment in absence epilepsy SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 14th World Congress of Psychophysiology the Olympics of the Brain CY SEP 08-13, 2008 CL St Petersburg, RUSSIA SP Int Org Psychophysiol C1 [Duncan, C. C.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Lab Clin Psychophysiol, Bethesda, MD 20814 USA. [Mirsky, A. F.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2008 VL 69 IS 3 BP 207 EP 207 DI 10.1016/j.ijpsycho.2008.05.011 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 336VU UT WOS:000258393700234 ER PT J AU Rota, G Turicchia, L Veit, R Guazzelli, M Birbaumer, N Dogil, G AF Rota, G. Turicchia, L. Veit, R. Guazzelli, M. Birbaumer, N. Dogil, G. TI Perceptual learning of speech processed by a Cochlear Implant simulator - An fMRI investigation SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 14th World Congress of Psychophysiology the Olympics of the Brain CY SEP 08-13, 2008 CL St Petersburg, RUSSIA SP Int Org Psychophysiol C1 [Rota, G.; Guazzelli, M.] Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. [Turicchia, L.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Rota, G.; Veit, R.; Birbaumer, N.] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany. [Veit, R.] Max Planck Inst Biol Cybernet, Tubingen, Germany. [Birbaumer, N.] NINDS, NIH, Human Cort Physiol Sect, Bethesda, MD 20892 USA. [Rota, G.; Dogil, G.] Univ Stuttgart, Inst Natural Language Proc, Stuttgart, Germany. RI Veit, Ralf/F-8907-2012 OI Veit, Ralf/0000-0001-9860-642X NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2008 VL 69 IS 3 BP 225 EP 226 DI 10.1016/j.ijpsycho.2008.05.072 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 336VU UT WOS:000258393700294 ER PT J AU Cisneros, GA Tholander, SNI Parisel, O Darden, TA Elking, D Perera, L Piquemal, JP AF Cisneros, G. A. Tholander, S. Na-Im Parisel, O. Darden, T. A. Elking, D. Perera, L. Piquemal, J. -P. TI Simple formulas for improved point-charge electrostatics in classical force fields and hybrid quantum mechanical/molecular mechanical embedding SO INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY LA English DT Article; Proceedings Paper CT 3rd International Theoretical Biophysics Symposium CY JUN 16-20, 2007 CL Cetraro, ITALY DE electrostatics; force fields; QM/MM; embedding; penetration energy; reaction path ID INTERMOLECULAR INTERACTION ENERGY; POLARIZABLE MOLECULAR-MECHANICS; FRAGMENT POTENTIAL METHOD; PARTICLE MESH EWALD; 4-OXALOCROTONATE TAUTOMERASE; SIMULATION; DENSITY; HYDROGEN; MODEL; ATOMS AB We present a simple damping scheme for point-charge electrostatics that could be used directly in classical force fields. The approach acts at the charge (or monopole) level only and allows the inclusion of short-range electrostatic penetration effects at a very low cost. Results are compared with density functional theory Coulomb intermolecular interaction energies and with several other methods such as distributed multipoles, damped distributed multipoles, and transferable Hermite-Gaussian densities. Realistic trends in the interactions are observed for atom-centered Mertz-Kollman corrected point-charge distributions. The approach allows increasing the selectivity of parameters in the case of metal complexes. In addition, two QM/MM calculations are presented where the damping function is employed to include the MM atoms located at the QM/MM boundary. The first calculation corresponds to the gas-phase proton transfer of aspartic acid through water and the second is the first step of the reaction catalyzed by the 4-oxalocrotonate tautomerase (4OT) enzyme. First, improved agreement is observed when using the damping approach compared with the conventional excluded charge method or when including all charges in the calculation. Second, in the case of 4OT, the damped charge approach is in agreement with previous calculations, whereas including all charges gives a significantly higher energy barrier. In both cases, no reparameterization of the van der Waals part of the force field was performed. (c) 2008 Wiley Periodicals, Inc. C1 [Tholander, S. Na-Im; Parisel, O.; Piquemal, J. -P.] Univ Paris 06, UPMC, Chim Theor Lab, UMR 7616, F-75005 Paris, France. [Cisneros, G. A.; Darden, T. A.; Elking, D.; Perera, L.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Tholander, S. Na-Im; Parisel, O.; Piquemal, J. -P.] CNRS, Chim Theor Lab, UMR 7616, F-75005 Paris, France. RP Piquemal, JP (reprint author), Univ Paris 06, UPMC, Chim Theor Lab, UMR 7616, Case Courrier 137,4 Pl Jussieu, F-75005 Paris, France. EM jpp@lct.jussieu.fr RI Cisneros, Gerardo/B-3128-2010; Piquemal, Jean-Philip/B-9901-2009; perera, Lalith/B-6879-2012 OI Piquemal, Jean-Philip/0000-0001-6615-9426; perera, Lalith/0000-0003-0823-1631 FU Intramural NIH HHS [NIH0011757912] NR 57 TC 37 Z9 37 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7608 EI 1097-461X J9 INT J QUANTUM CHEM JI Int. J. Quantum Chem. PD SEP PY 2008 VL 108 IS 11 BP 1905 EP 1912 DI 10.1002/qua.21675 PG 8 WC Chemistry, Physical; Mathematics, Interdisciplinary Applications; Physics, Atomic, Molecular & Chemical SC Chemistry; Mathematics; Physics GA 326EY UT WOS:000257642300005 PM 19606279 ER PT J AU Simone, CB Vapiwala, N Hampshire, MK Metz, JM AF Simone, Charles B., II Vapiwala, Neha Hampshire, Margaret K. Metz, James M. TI Internet-based survey evaluating use of pain medications and attitudes of radiation oncology patients toward pain intervention SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE quality of life; pain management; Internet; analgesic; pain ID CANCER PAIN; BREAST-CANCER; HEALTH-CARE; MANAGEMENT; INFORMATION; BARRIERS; PHYSICIANS; THERAPIES; ANXIETY; COMPLEMENTARY AB Purpose: Pain is it common symptom among cancer patients, yet many patients do not receive adequate pain management. Few data exist quantifying analgesic use by radiation oncology patients. This study evaluated the causes of pain in cancer patients and investigated the reasons patients fail to receive optimal analgesic therapy. Methods and Materials: An institutional review board-approved, Internet-based questionnaire assessing analgesic use and pain control was posted on the OncoLink (available at www.oncolink.org) Website. Between November 2005 and April 2006, 243 patients responded. They were predominantly women (73%), white (71%), and educated beyond high school (67%) and had breast (38%), lung (6%), or ovarian (6%) cancer. This analysis evaluated the 106 patients (44%) who underwent radiotherapy. Results: Of the 106 patients, 58% reported pain from their cancer treatment, and 46% reported pain directly from their cancer. The pain was chronic in 51% and intermittent in 33%. Most (80%) did not use medication to manage their pain. Analgesic use was significantly less in patients with greater education levels (11% vs. 36%, p = 0.002), witha trend toward lower use by whites (16% vs. 32%, p = 0.082) and women (17% vs. 29%, p = 0.178). The reasons for not taking analgesics included healthcare provider not recommending medication (87%), fear of addiction or dependence (79%), and inability to pay (79%). Participants experiencing pain, but not taking analgesics, pursued alternative therapies for relief. Conclusions: Many radiation oncology patients experience pain from their disease and cancer treatment. Most study participants did not use analgesics because of concerns of addiction, cost, or failure of the radiation oncologist to recommend medication. Healthcare providers should have open discussions with their patients regarding pain symptoms and treatment. (C) 2008 Elsevier Inc. C1 [Simone, Charles B., II] NCI, Natl Inst Hlth, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Simone, Charles B., II; Vapiwala, Neha; Hampshire, Margaret K.; Metz, James M.] Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Simone, CB (reprint author), NCI, Natl Inst Hlth, Radiat Oncol Branch, Bldg 10-CRC,Rm B2-3500,10 Ctr Dr, Bethesda, MD 20892 USA. EM simonec@mial.nih.gov RI Vapiwala, Neha/A-5445-2010 NR 53 TC 9 Z9 9 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2008 VL 72 IS 1 BP 127 EP 133 DI 10.1016/j.ijrobp.2008.03.071 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 341UX UT WOS:000258741700023 PM 18547743 ER PT J AU Wang, HB Wang, N Chen, RY Sharp, GB Ma, YL Wang, GX Ding, GW Wu, ZL AF Wang, Haibo Wang, Ning Chen, Ray Y. Sharp, Gerald B. Ma, Yanling Wang, Guixiang Ding, Guowei Wu, Zhenglai TI Prevalence and predictors of herpes simplex virus type 2 infection among female sex workers in Yunnan Province, China SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE herpes simplex virus type 2 (HSV-2); female sex worker; condom; sexually transmitted infection; China ID SEXUALLY-TRANSMITTED INFECTIONS; RISK-FACTORS; WOMEN; HIV-1; ACQUISITION; METAANALYSIS; MEN; SEROPREVALENCE; EPIDEMIOLOGY; HIV/AIDS AB The objective of this study was to determine the seroprevalence of herpes simplex virus type 2 (HSV-2), and to evaluate the relationship between HSV-2 infection and sociodemographic factors and the sexual practices of female sex workers (FSWs) in Kaiyuan city, Yunnan Province, China. This cross-sectional study involved 737 FSWs and was carried out from March to May 2006 with confidential interviews and laboratory tests for HSV-2 and other sexually transmitted infections (STI). HSV-2 was the most common STI (68%), followed by Chlamydia trachomatis (26%), Trichomonas vaginalis (11%), Neisseria gonorrhoeae (8%) and syphilis (7%). Prevalence of HIV-1 was 10.3%. Adjusted odds ratios of HSV-2 seroprevalence were 2.6 (95% CI [confidence interval]: 1.30-5.38) for HIV-1 infection, 2.0 (95% CI: 1.33-3.16) for vaginal douching, 2.0 (95% CI: 0.45-0.86) for condom breaking or failing off during sexual intercourse with the ciient in the previous week, 1.8 (95% CI: 1.07-3.18) for >= 5 years of commercial sex work, 1.6 (95% CI: 1.08-2.33) for >= 5 clients in the previous week, 0.6 (95% CI: 0.45-0.86) for >= 9 years of education. This study identifies a very high prevalence of HSV-2 infections among FSWs in Yunnan Province, with only a few who reported a prior history of genital herpes. HSV-2 serological screening and suppressive therapy should be considered for study populations. Education on the importance of diagnosis, treatment and prevention may help control the spread of HSV-2 infection. C1 [Wang, Haibo; Wang, Ning; Ding, Guowei] Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Prevent & Control, Beijing 100050, Peoples R China. [Chen, Ray Y.; Sharp, Gerald B.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Ma, Yanling] Yunnan Ctr Dis Control & Prevent, Dept AIDS, Kaiyuan, Yunnan, Peoples R China. [Wang, Guixiang] Kaiyuan Ctr Dis Control & Prevent, Kaiyuan, Yunnan, Peoples R China. [Wu, Zhenglai] Peking Union Med Coll, Dept Epidemiol, Beijing 100021, Peoples R China. RP Wang, N (reprint author), Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Prevent & Control, 27 Nanwei Rd, Beijing 100050, Peoples R China. EM wangnbj@163.com OI Chen, Ray/0000-0001-6344-1442 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [U19 AI51915-05] FX This study was funded by a grant from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (U19 AI51915-05). NR 33 TC 29 Z9 34 U1 1 U2 8 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD SEP PY 2008 VL 19 IS 9 BP 635 EP 639 DI 10.1258/ijsa.2008.008013 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 350SZ UT WOS:000259374700014 PM 18725558 ER PT J AU Leng, K Lonsdorf, A Hartmann, M AF Leng, K. Lonsdorf, A. Hartmann, M. TI Fatal outcome of nevirapine-associated toxic epidermal necrolysis SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE HIV; nevirapine; TEN; rash ID STEVENS-JOHNSON-SYNDROME; HYPERSENSITIVITY AB The irregular use of antiretroviral therapy (ART) can result in ART-resistance but can also lead to a sensitization between agents with a cross-sensitivity. We report a case of nevirapine-associated toxic epidermal necrolysis resulting in death in an HIV-infected man. C1 [Leng, K.; Hartmann, M.] Univ Heidelberg, Dept Dermatol, D-6900 Heidelberg, Germany. [Lonsdorf, A.] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Leng, K (reprint author), Univ Hautklin, Vossstr 2, D-69115 Heidelberg, Germany. EM katharina.leng@med.uni-heidelberg.de NR 7 TC 4 Z9 5 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD SEP PY 2008 VL 19 IS 9 BP 642 EP 643 DI 10.1258/ijsa.2008.008062 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 350SZ UT WOS:000259374700016 PM 18725560 ER PT J AU Nunez-Troconis, J Velasquez, J Mindiola, R Munroe, D AF Nunez-Troconis, Jose Velasquez, Jesvy Mindiola, Raimy Munroe, David TI Educational level and cervical cancer screening programs in a Venezuelan urban area SO INVESTIGACION CLINICA LA English DT Article DE Pap smear; educational level; cervical cancer screening program; Venezuela ID HUMAN-PAPILLOMAVIRUS; PREVENTION; COVERAGE; WOMEN; CARE AB The purpose of this study was to investigate, in a group of Venezuelan women, the knowledge and understanding of the purpose of the Pap smear and the correlation of this knowledge with their educational level. Women were recruited for a cervical cancer screening program and answered a questionnaire concerning what a Pap smear is used for. Three hundred one women were included in the study. Two hundred eighty six women (95%) answered that they knew about Pap smear. Two hundred sixty eight patients (89%) knew that the Pap smear is used for cervical cancer screening. One hundred sixteen women (38.5%) had a low educational level. One hundred and four of them (89.7%) knew that Pap smear is used to screen cervical cancer. Ninety two percent of women who did not complete elementary school had the knowledge of the purpose of vaginal cytology. Two hundred eighty one patients (93%) mentioned that they had at least one Pap smear. One hundred sixty four patients (58.3%) reported to have >= 4 Pap smears in their life time. Two hundred fifty seven women (91.5%) remembered when the first Pap smear was taken. Twenty one patients (7%) had a Pap smear for the first time. The conclusions are: 1) low educational level in an urban area is not a limitation for knowing about and having a cervical cytology test taken; 2) high percentage of Venezuelan women in an urban area know what the Pap smear is used for. C1 [Nunez-Troconis, Jose] Univ Zulia, Manuel Noriega Trigo Hosp, Dept Obstet & Gynecol, Maracaibo 4011, Venezuela. [Velasquez, Jesvy; Mindiola, Raimy] Univ Zulia, Fac Med, Reg Lab Virol Reference, Maracaibo 4011, Venezuela. [Munroe, David] SAIC Frederick Inc, Natl Canc Inst, Lab Mol Technol, Frederick, MD USA. RP Nunez-Troconis, J (reprint author), Univ Zulia, Fac Med, Dept Obstet & Gynecol, Ave 20, Maracaibo 4011, Venezuela. EM jnunezt@cantv.net FU National Cancer Institute; National Institutes of Health [N01-C0-12400]; Fogarty Foundation/NCI/PAHO 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-C0-12400. The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, nor does mention of trades names, commercial products, or organizations imply endorsement by the U.S. Government. Dr. Nunez-Trocoms is supported by a scholarship from Fogarty Foundation/NCI/PAHO.; We thank all the members of Social Service and nurses who work at the Gynecological Out-Patient Clinic of Manuel Noriega Trigo Hospital for their assistant and help. NR 21 TC 1 Z9 1 U1 0 U2 7 PU INST INVESTIGACION CLINICA PI MARACAIBO PA APARTADO 23, MARACAIBO 4001-A, VENEZUELA SN 0535-5133 J9 INVEST CLIN JI Invest. Clin. PD SEP PY 2008 VL 49 IS 3 BP 331 EP 339 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 349AQ UT WOS:000259251600006 PM 18846774 ER PT J AU Huang, LL Coleman, HR Kim, J de Monasterio, F Wong, WT Schleicher, RL Ferris, FL Chew, EY AF Huang, Lynn L. Coleman, Hanna R. Kim, Jonghyeon de Monasterio, Francisco Wong, Wai T. Schleicher, Rosemary L. Ferris, Frederick L., III Chew, Emily Y. TI Oral supplementation of lutein/zeaxanthin and omega-3 long chain polyunsaturated fatty acids in persons aged 60 years or older, with or without AMD SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MACULAR DEGENERATION; VITAMIN-E; LUTEIN SUPPLEMENTATION; ALPHA-CAROTENE; BETA-CAROTENE; UNITED-STATES; BIOAVAILABILITY; PREVALENCE; DISEASE; HEALTH AB PURPOSE. Increased dietary intake of lutein/zeaxanthin and omega-long-chain polyunsaturated fatty acids (omega-3 LCPUFA) was found to be associated with reduced risk of advanced age-related macular degeneration (AMD). The purpose of the study was to examine the effect of oral supplementation of omega-3 LCPUFA on changes in serum levels of lutein/zeaxanthin during supplementation in persons 60 years of age and older, with or without AMD. METHODS. Forty participants with AMD of various degrees of severity received lutein (10 mg) and zeaxanthin (2 mg) daily and were equally randomized to receive omega-3 LCPUFA (350 mg docosahexaenoic acid [DHA] and 650 mg eicosapentaenoic acid [EPA]) or placebo for 6 months. Serum levels of lutein, zeaxanthin, and omega-3 LCPUFAs and macular pigment optical densities were measured at baseline, 1 week, and 1, 3, 6, and 9 months. RESULTS. By month 6, the median serum levels of lutein/zeaxanthin increased by two- to threefold compared with baseline. Increases in serum levels of lutein/zeaxanthin did not differ by omega-3 LCPUFA treatment (P > 0.5). After 1 month, in the omega-3 LCPUFA-treated group, the median levels of DHA and EPA increased and the placebo group had no changes. At month 6, participants with AMD had a lower increase in serum lutein concentration than did those without AMD (P < 0.05). CONCLUSIONS. The addition of omega-3 LCPUFA to oral supplementation of lutein/zeaxanthin did not change the serum levels of lutein and zeaxanthin. A long-term large clinical trial is necessary to investigate the benefits and adverse effects of these factors for the treatment of AMD. C1 [Chew, Emily Y.] NEI, CRC, NIH, Div Epidemiol & Clin Res,Clin Trials Branch, Bethesda, MD 20892 USA. [de Monasterio, Francisco] NEI, NIH, Off Clin Director, Bethesda, MD 20892 USA. [Kim, Jonghyeon] EMMES Corp, Rockville, MD USA. [Schleicher, Rosemary L.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Chew, EY (reprint author), NEI, CRC, NIH, Div Epidemiol & Clin Res,Clin Trials Branch, Bldg 10,Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov RI Sanguansri, Luz/B-6630-2011; Wong, Wai/B-6118-2017 OI Sanguansri, Luz/0000-0003-1908-7604; Wong, Wai/0000-0003-0681-4016 FU National Eye Institute; Pfizer Pharmaceuticals Group, Bethesda; NIH; Pfizer; National Institutes of Health FX Supported by the intramural funds of the National Eye Institute; and a grant to the Foundation for the NIH from Pfizer Pharmaceuticals Group, Bethesda, MD (LLH), with a public-private partnership supported jointly by the NIH and Pfizer. LLH is a Clinical Research Training Program Scholar at the National Institutes of Health. NR 19 TC 23 Z9 24 U1 4 U2 8 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2008 VL 49 IS 9 BP 3864 EP 3869 DI 10.1167/iovs.07-1420 PG 6 WC Ophthalmology SC Ophthalmology GA 344AB UT WOS:000258896500017 PM 18450596 ER PT J AU Lee, JE Liang, KJ Fariss, RN Wong, WT AF Lee, Jung Eun Liang, Katharine J. Fariss, Robert N. Wong, Wai T. TI Ex vivo dynamic imaging of retinal microglia using time-lapse confocal microscopy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MACULAR DEGENERATION; IN-VIVO; DIABETIC-RETINOPATHY; DENDRITIC CELLS; ACTIVATION; BRAIN; MOUSE; NEUROTOXICITY; BEHAVIOR; DISEASE AB PURPOSE. Retinal microglia have been implicated in the pathogenesis of various retinal diseases, but their basic function and cellular phenotype remain incompletely understood. Here, the authors used a novel ex vivo retinal imaging preparation to examine the behavioral phenotype of living retinal microglia in intact tissue and in response to injury. METHODS. Fluorescence-labeled microglia in retinal explants from CX3CR1(+/GFP) transgenic mice were observed using time-lapse confocal imaging. High spatial and temporal resolution imaging parameters were used to follow dynamic microglial behavior in real time. RESULTS. Under normal conditions, resting retinal microglia are not static in structure but instead exhibit extensive structural dynamism in their cellular processes. Process movements are highly random in direction but are balanced to maintain overall cellular symmetry and arbor size. At rest, however, these exuberant process movements do not result in overt cellular migration. After focal laser injury, microglial processes increase significantly in their motility and direct themselves toward the injury site. Microglia rapidly transition their morphologies from symmetric to polarized toward the laser lesion. Microglia also transition from a fixed to a migratory phenotype, translocating through tissue while retaining their ramified morphology. CONCLUSIONS. Retinal microglia normally occupying uninjured tissue display a continuous, dynamic behavior that suggests functions of tissue surveillance and intercellular communication. Microglial behavior is highly regulated by, and immediately responsive to, focal tissue injury and may constitute a therapeutic cellular response to focal laser photocoagulation. Ex vivo live imaging in the retina is an experimental approach well suited to the study of dynamic aspects of microglial physiology. C1 [Lee, Jung Eun; Liang, Katharine J.; Wong, Wai T.] NEI, Natl Inst Hlth, Off Sci Director, Bethesda, MD 20892 USA. [Lee, Jung Eun; Liang, Katharine J.] NEI, Natl Inst Hlth, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. RP Wong, WT (reprint author), NEI, Natl Inst Hlth, Off Sci Director, Room 217,7 Mem Dr, Bethesda, MD 20892 USA. EM wongw@nei.nih.gov RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU Howard Hughes Medical Institute (JEL); National Eye Institute Intramural Research Program FX Supported by the Howard Hughes Medical Institute (JEL) and the National Eye Institute Intramural Research Program. NR 31 TC 72 Z9 73 U1 2 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2008 VL 49 IS 9 BP 4169 EP 4176 DI 10.1167/iovs.08-2076 PG 8 WC Ophthalmology SC Ophthalmology GA 344AB UT WOS:000258896500057 PM 18487378 ER PT J AU Fontainhas, AM Townes-Anderson, E AF Fontainhas, Aurora M. Townes-Anderson, Ellen TI RhoA and its role in synaptic structural plasticity of isolated salamander photoreceptors SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID GTP-BINDING PROTEINS; MYELIN-ASSOCIATED GLYCOPROTEIN; CENTRAL-NERVOUS-SYSTEM; ENHANCES AXONAL REGENERATION; SPINAL-CORD-INJURY; MYOSIN-II ACTIVITY; RETINAL-DETACHMENT; IN-VITRO; LYSOPHOSPHATIDIC ACID; DEPENDENT MECHANISM AB PURPOSE. Adult salamander photoreceptors retract existing axons and extend new neuritic processes in vitro. In mammalian retina, similar forms of structural plasticity occur in injury and disease. The authors asked whether RhoA is present in photoreceptor axon terminals and whether activity in the RhoA-ROCK pathway contributes to the structural plasticity observed in rod and cone cells. METHODS. Antibodies against RhoA were used to immunolabel Western blots sections and isolated neurons from salamander retina. Isolated photoreceptors were treated with lysophosphatidic acid (LPA; a RhoA activator) or Y27632 (an inhibitor of RhoA effector ROCK) for the first 24 hours, the first 3 days, or the last 24 hours of culture. Growth and retraction were assessed with time-lapse and image analyses. RESULTS. RhoA protein was found throughout the retina, including in rod and cone synaptic terminals. When treated with LPA, photoreceptors significantly reduced the growth of new neuritic processes and presynaptic varicosities and retracted growth at the highest LPA concentrations. When treated with Y27632, rod cells significantly increased the number of varicosities, whereas cone cells increased process growth. Treatment with Y27632 also dramatically reduced retraction of the existing axon, which occurs spontaneously in rod cells during the first 24 hours of culture. CONCLUSIONS. Thus, RhoA-ROCK activity reduces and retracts neuritic growth, but inhibition of activity increases neuritic development and blocks retraction. The results suggest that RhoA activation contributes to axon retraction by rod cells after retinal detachment, whereas inhibition of RhoA contributes to the neuritic sprouting seen in reattached and degenerating retina. C1 [Fontainhas, Aurora M.] UMDNJ Grad Sch Biomed Sci, Program Integrat Neurosci, Newark, NJ USA. [Fontainhas, Aurora M.] Rutgers State Univ, Newark, NJ 07102 USA. [Townes-Anderson, Ellen] UMDNJ New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ USA. RP Fontainhas, AM (reprint author), NEI, Natl Inst Hlth, 7 Mem Dr, Bethesda, MD 20892 USA. EM fontainhasa@nei.nih.gov FU National Eye Institute [EY012031]; F. M. Kirby Foundation FX Supported by National Eye Institute Grant EY012031 and by the F. M. Kirby Foundation. NR 89 TC 11 Z9 11 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2008 VL 49 IS 9 BP 4177 EP 4187 DI 10.1167/iovs.07-1580 PG 11 WC Ophthalmology SC Ophthalmology GA 344AB UT WOS:000258896500058 PM 18503000 ER PT J AU Jones, SD Teigen, PM AF Jones, Susan D. Teigen, Philip M. TI Anthrax in transit - Practical experience and intellectual exchange SO ISIS LA English DT Review ID VACCINE AB Focusing on three Anglo-American outbreaks of industrial anthrax, this essay engages the question of how local circumstances influenced the transmission of scientific knowledge in the late nineteenth century. Walpole (Massachusetts), Glasgow, and Bradford (Yorkshire) served as important nodes of transnational investigation into anthrax. Knowledge about the morphology and behavior of Bacillus anthracis changed little while in transit between these nodes, even during complex debates about the nature of bacterial morphology, disease causation, and spontaneous generation. Working independently of their more famous counterparts (Robert Koch and Louis Pasteur), Anglo-American anthrax investigators used visual representations of anthrax bacilli to persuade their peers that a specific, identifiable cause produced all forms of anthrax-malignant pustule (cutaneous anthrax), intestinal anthrax, and woolsorter's disease (pneumonic anthrax). By the late 1870s, this point of view also supported what we would today call an ecological notion of the disease's origins in the interactions of people, animals, and microorganisms in the context of global commerce. C1 [Jones, Susan D.] Univ Minnesota, Program Hist Sci Technol & Med, St Paul, MN 55108 USA. [Jones, Susan D.] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA. [Teigen, Philip M.] Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. RP Jones, SD (reprint author), Univ Minnesota, Program Hist Sci Technol & Med, 1987 Upper Buford Circle, St Paul, MN 55108 USA. NR 110 TC 6 Z9 8 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0021-1753 J9 ISIS JI Isis PD SEP PY 2008 VL 99 IS 3 BP 455 EP 485 DI 10.1086/591709 PG 31 WC History & Philosophy Of Science SC History & Philosophy of Science GA 357KH UT WOS:000259844200001 PM 18959192 ER PT J AU Konstam, MA AF Konstam, Marvin A. TI Patterns of Ventricular Remodeling After Myocardial Infarction Clues Toward Linkage Between Mechanism and Morbidity SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE myocardial infarction; ventricular remodeling; hypertension; echocardiography; cardiovascular risk C1 [Konstam, Marvin A.] NHLBI, Div Cardiovasc Dis, Bethesda, MD 20892 USA. [Konstam, Marvin A.] Tufts Univ, Boston, MA 02111 USA. [Konstam, Marvin A.] Tufts Med Ctr, Div Cardiol, Boston, MA USA. RP Konstam, MA (reprint author), NHLBI, Div Cardiovasc Dis, MSC 7940,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM konstamm@nhlbi.nih.gov NR 12 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD SEP PY 2008 VL 1 IS 5 BP 592 EP 594 DI 10.1016/j.jcmg.2008.07.005 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA V13EL UT WOS:000207650000006 PM 19356486 ER PT J CA NIHM Multisite HIV STD Prevent Tri TI The role of community advisory boards (CABs) in Project Eban SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE African American couples; community advisory board; culturally congruent; HIV; behavioral prevention ID PROTECTING COMMUNITIES; PREVENTION PROGRAM; PUBLIC-HEALTH; HIV; COLLABORATION; RESEARCHERS; FAMILIES; YOUTH AB Objective: To describe tire theoretical principles that guided the establishment of Project Ebans community Advisory Boards (CABs), their functions, and composition the selection and recruitment processes; lessons learned; and recommendations on the use of CABs in multisite HIV clinical trial Studies. Methods: In the first year of Project Eban's implementation, each of the 4 sites formed a local CAB. Member recruitment took place during the first 6 months of the study. On average, each site's CAB consisted of 13-19 stakeholders, with a total of 62 members for the multisite study, including leaders of HIV-AIDS-related community-based organizations (CBOs), hospital-based HIV/AIDS service providers, HIV/AIDS network leaders in minority communities, CBOs that serve predominantly black communities, and consumers. Results: Each of the CAB members has expressed a strong commitment to assisting in the conduct of the research. CABs are integral to the success of the study and their input is highly respected and used to improve the quality of the research. Conclusions: This article highlights the importance of CABs in the conduct of HIV multisite clinical trials and their roles in making the study culturally congruent to meet the needs of the black community in dealing with the HIV epidemic. C1 [NIHM Multisite HIV STD Prevent Tri] NIMH, Ctr Mental Hlth Res AIDS, Div AIDS & Hlth & Behav Res, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 27 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2008 VL 49 SU 1 BP S68 EP S74 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 343JB UT WOS:000258848300009 ER PT J CA NIHM Multisite HIV STD Prevent Tri TI Supervision of facilitators in a multisite study: Goals, process, and outcomes SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE African American couples; behavioral interventions; cognitive behavior therapy; empowerment; supervision AB Objective: To describe the aims, implementation, and desired Outcomes of facilitator Supervision for both interventions (treatment and control) in Project Eban and to present the Eban Theoretical Framework for Supervision that guided the facilitators' Supervision. The qualifications and training of Supervisors and facilitators are also described. Design: This article provides a detailed description of supervision in a multisite behavioral intervention trial. The Eban Theoretical Framework for Supervision is guided by 3 theories: cognitive behavior therapy, the Model of Life-Long Supervision, and the empowerment model of culturally responsive Supervision. Methods: Supervision is based oil the Eban Theoretical Framework for Supervision, which provides guidelines for implementing both interventions using goals, process, and outcomes. Results: Because of effective supervision, the interventions were implemented with fidelity to the protocol and were standard across the Multiple Sites. Conclusions: Supervision of facilitators is a crucial aspect of multisite intervention research quality assurance. It provides them with expert advice, optimizes the effectiveness of facilitators, and increases adherence to the protocol across Multiple Sites. Based oil the experience in this trial, some of the challenges that arise when conducting a multisite randomized control trial and how they call be handled by implementing the Eban Theoretical Framework for Supervision are described. C1 [NIHM Multisite HIV STD Prevent Tri] NIMH, Ctr Mental Hlth Res AIDS, Div AIDS & Hlth & Behav Res, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2008 VL 49 SU 1 BP S59 EP S67 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 343JB UT WOS:000258848300008 ER PT J CA NIMH Multisite HIV STD Prevent Tri TI Designing an audio computer-assisted self-interview (ACASI) system in a multisite trial: A brief report SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE ACASI; AIDS; Audio Computer-Assisted Self-Interview; HIV; intervention ID REPRODUCTIVE HEALTH RESEARCH; RIO-DE-JANEIRO; DRUG-USE; SEXUAL-BEHAVIOR; RANDOMIZED-TRIAL; RISK BEHAVIORS; HIV RISK; POPULATION; COLLECTION; WOMEN AB Objective: To describe the advantages and limitations of an audio computer-assisted self-interview (ACASI) system in a multisite trial with African American couples and to present the steps in designing, testing, and implementing a system. Methods: The ACASI system evolved from a paper and pencil interview that was pilot tested. Based oil this initial work, the paper and pencil inter-view was translated into storyboards that were the basis of the development of ACASI system. Storyboards consisted of 1 page per question and provided the programmers with the test of the question. valid responses, and any instructions that were to be read to the participants. Storyboards were further translated into flow diagrams representing each module of the survey and illustrating the skip patterns used to navigate a participant through the survey. Provisions were also made to insert a face-to-lace interview into the ACASI assessment process, to elicit sexual abuse history data. which typically requires specially trained data collectors with active listening skills to help participants reframe and coordinate times. places and, emotionally difficult Memories. Results: The ACASI was successfully developed and implemented in the main trial. During an exit interview, respondents indicated that they liked using the ACASI and indicating that they favored it as the method to answer questions. Conclusions: It is feasible to implement an ACASI system in a multisite study in a timely and efficient way. C1 [NIMH Multisite HIV STD Prevent Tri] NIMH, Ctr Mental Hlth Res AIDS, Div AIDS & Hlth & Behav Res, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 43 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2008 VL 49 SU 1 BP S52 EP S58 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 343JB UT WOS:000258848300007 ER PT J CA NIMH Multisite HIV STD Prevent Tri TI Measure of HIV/STD risk-reduction: Strategies for enhancing the utility of behavioral and biological outcome measures for African American couples SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE African American; behavioral and biological outcome measures; biomarkers; couples; heterosexual ID SEXUALLY-TRANSMITTED-DISEASES; LIGASE CHAIN-REACTION; RANDOMIZED CONTROLLED-TRIAL; CONDOM-USE ERRORS; PREVENTION INTERVENTIONS; REACTION ASSAY; INFECTION; HIV; URINE; WOMEN AB Objective: Numerous studies have discussed the value of including biological outcome measures as a complement to behavioral outcome measure to assess the efficacy of HIV risk-reduction interventions. This article highlights strategies used to minimize the limitations of including both self-reported sexual behaviors and biologically confirmed Sexually transmitted diseases as Primary outcome measures in all HIV/sexually transmitted disease (STD) prevention program for African American serodiscordant couples (Eban). Design: Couples receiving all HIV intervention condition (Eban) were compared with couples receiving a time-equivalent General Health Promotion condition oil behavioral and biological outcomes. Both behavioral and biological data were collected at baseline, immediately post intervention, and at 6 and 12 months post-intervention. Methods: Literature reviews, Consulting other researchers who conducted couples studies, Our investigative team's experience in previous HIV interventions, and formative work were used to develop procedures to minimize potential limitations associated with the inclusion of behavioral and biological outcome measures for Eban. Results: Given the strengths Of including behavioral and biological Outcome measures, the Eban study chose to have both measures serve as primary outcomes. The primary behavioral outcome for the trial is the proportion of protected vaginal and anal intercourse episodes that Occurred within the index Couple in 90 days before each follow-tip assessment and over the 12-month postintervention follow-up period. The primary biological outcome is the proportion of participants (male or female study partners,) with an incident STD) (Chlamydia, gonorrhea, or trichomoniasis) over the 12-month postintervention follow-up Period. Conclusions: Employing procedures to minimize limitations of using self-reported Sexual behaviors and STDs as complementary primary Outcomes enhances their utility as measures of the efficacy of HIV/STD prevention interventions. C1 [NIMH Multisite HIV STD Prevent Tri] NIMH, Ctr Mental Hlth Res AIDS, Div AIDS & Hlth & Behav Res, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 46 TC 0 Z9 0 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2008 VL 49 SU 1 BP S35 EP S41 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 343JB UT WOS:000258848300005 ER PT J CA NIMH Multisite HIV STD Prevent Tri TI Eban Health Promotion Intervention: Conceptual basis and procedures SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE African American; behavioral intervention; fruit and vegetable consumption; HIV; medical adherence; physical activity AB Objective: This article concerns the health promotion intervention that served as the comparison condition in Project E-ban, the NIMH Multisite HIV/STD prevention Trial for African American Couples. Considerable research has documented the high rates of chronic diseases, including heart disease, cancer, stroke, and diabetes, among African Americans. Many of these diseases are tied to behavioral risk factors-the things that people do or do not do, their diet, the amount of exercise they get and their substance use practices. Design: The Eban Health Promotion Intervention was designed to increase healthful behaviors, including physical activity. healthful dietary practices, ceasing cigarette smoking and alcohol abuse. practicing early detection and screening behaviors, and improving medication adherence. As a comparison condition, the Eban Health Promotion Intervention was designed to be structurally similar to the Eban HIV/STD Risk Reduction Intervention. Methods: This article describes the intervention and how it was developed, integrating, social cognitive theory with information collected in formative research to ensure that the intervention was appropriate for African Americans affected by HIV Conclusion: Project Eban not only tests the efficacy of an HIV/STD risk reduction intervention for African American serodiscordant couples, but also tests the efficacy of ail intervention addressing many of the other health problems common in this Population. C1 [NIMH Multisite HIV STD Prevent Tri] NIMH, Ctr Mental Hlth Res AIDS, Div AIDS & Hlth & Behav Res, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2008 VL 49 SU 1 BP S28 EP S34 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 343JB UT WOS:000258848300004 ER PT J CA NIMH Multisite HIV STD Prevent Tri TI Formative study to develop the Eban treatment and comparison interventions for couples SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE African American couples; behavioral intervention; culturally congruent; focus groups; HIV; sexual behavior ID SERODISCORDANT HETEROSEXUAL COUPLES; RISK REDUCTION INTERVENTION; AFRICAN-AMERICAN WOMEN; CHILD SEXUAL-ABUSE; HIV-INFECTION; CONDOM USE; PREVENTION; BEHAVIORS; SUPPORT; TRANSMISSION AB Objective: To describe formative and pilot-testing research that generated themes and procedures. curricula, and critical measures for a randomized clinical trial testing a Risk Reduction Intervention for HIV-serodiscordant African American couples (project Eban). Design: This article describes the themes that emerged from discussions with African American serodiscordant couples about HIV-related risks from focus groups with 11 couples and pilot study results with 32 couples across 4 sites. Methods: In step 1, focus groups examined the need for a Risk Reduction Intervention for HIV-serodiscordant African American Couples and confirmed 4 themes that formed the basis for the intervention curriculum and study format. In step 2, a Pilot Study refined the clinical trial procedures, for this population and tested critical measures and selected portions of the curriculum for both the treatment and the comparison interventions. Results: Based oil these findings, stigma and psychological distress, barriers to condom use. insufficient support from community and service organisations,and the lack of skills that emphasize individual and relationship protection were ultimately integrated into the Risk Reduction Intervention. Conclusions: Pilot study findings highlighted the importance of examining gender and ethnicity in HIV-impacted couples along with factors that heightened HIV-related risk behaviors that affect couples' skills and psychological adjustment. The goal was to ensure that a skill-based, culturally congruent, relationship-centered intervention could be understood and of interest to couples. Future analyses in the main trial will be discussed. C1 NIMH, Ctr Mental Hlth Res AIDS, Div AIDS & Hlth & Behav Res, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 43 TC 0 Z9 0 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2008 VL 49 SU 1 BP S42 EP S51 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 343JB UT WOS:000258848300006 ER PT J CA NIMH Multisite HIV STD Prevent Tri TI Eban HIV/STD risk reduction intervention: Conceptual basis and procedures SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE African American; behavioral intervention; couple-level; culturally congruent; HIV sexual behavior ID HUMAN-IMMUNODEFICIENCY-VIRUS; AMERICAN ADOLESCENT GIRLS; HIV-PREVENTION; HETEROSEXUAL COUPLES; CONDOM USE; WOMEN; EFFICACY; BEHAVIOR; SEX; AFRICA AB Objective: To describe the Eban HIV/STD Risk Reduction Intervention being evaluated in the NIMH Multisite HIV/STD Prevention trial for heterosexual African American Couples, including the integrated theoretical framework, the structure, core elements and procedures of the intervention, and how the content was shaped by Culturally congruent concepts to address the needs of the Study target population. Design: The Eban HIV/STD) Risk Reduction Intervention is designed to address multilevel individual, interpersonal-, and community-level factors that contribute to HIV/STD transmission risk behaviors all-tong heterosexual African American couples who are HIV serodiscordant. Methods: The Eban HIV/STD Risk Reduction Intervention employs a mixed modality, couple-based approach that is based oil an integrated ecological Framework incorporating social cognitive theory and uses ail Afrocentric paradigm that is informed by previous evidence-based Couples HIV prevention interventions. For this randomized controlled trial, African American serodiscordant Couples were recruited from 4 urban sites (Atlanta, Los Angeles, New York, and Philadelphia) and were randomized to either the Eban HIV/STD Risk Reduction Intervention (treatment condition) or a Health Promotion Intervention that served as an attentional control condition. Both interventions had 4 individual couple sessions and 4 group) sessions, but only the treatment condition was focused oil reducing HIV/STD risk behaviors. Behavioral and biological data were collected at baseline, immediately after the intervention, and at 6 and 12 months. The theoretical framework, core elements, and content of each session are described and lessons learned from this intervention trial are discussed. Results: Ail HIV prevention intervention combining couple and group sessions can be feasibly implemented with African American HIV-serodiscordant Couples Who remain at high risk of HIV/STD transmission. The lessons carried from the trial Suggest that the participants responded very well to both the couple and the group sessions. Participant feedback Suggests that the cultural congruence of the intervention and use of African American cofacilitators made them feel comfortable disclosing risky behaviors. Participant feedback also Suggests that the intervention's couple-based focus oil enhancing dyadic communication and (decision-making skills was key to helping the couples work together to overcome barriers to using condoms. Conclusions: Participant and facilitator evaluations of the Eban Risk Reduction Intervention suggest that couples responded well to the Afrocentric content and mixed modalities of the intervention sessions. Couple sessions were optimal for enhancing interpersonal and microlevel factors, including communication problem solving and decision making. C1 [NIMH Multisite HIV STD Prevent Tri] NIMH, Ctr Mental Hlth Res AIDS, Div AIDS & Hlth & Behav Res, Natl Inst Hlth, Bethesda, MD 20892 USA. FU NIMH NIH HHS [P50 MH073453, U10 MH078819-03, U10 MH078819] NR 58 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2008 VL 49 SU 1 BP S15 EP S27 DI 10.1097/QAI.0b013e318184255d PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 343JB UT WOS:000258848300003 PM 18724186 ER PT J CA NIMH Multisite HIV STD Prevent Tri TI Methodological overview of an African American couple-based HIV/STD Prevention Trial SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE AIDS; behavioral intervention; clinical trial; HIV; HIV-serodiscordant couples; STDs ID HUMAN-IMMUNODEFICIENCY-VIRUS; RISK REDUCTION INTERVENTION; MAIN SEXUAL PARTNERS; HETEROSEXUAL COUPLES; MINORITY WOMEN; CONDOM USE; HIV; BEHAVIOR; AIDS; TRANSMISSION AB Objective: to provide in overview of the National Institute of Mental Health Multisite HIV/sexually transmitted disease (STD) Prevention Trial for African American Couples conducted in 4 urban areas: Atlanta, Los Angeles, New York, and Philadelphia. The rationale, study design methods, proposed data analyses, and study management are described. Design: This is a 2-arm randomized trial, implementing a modified randomized block design, to evaluate the efficacy of a couples-based intervention designed for HIV-serodiscordant African American Couples. Methods: The Study phases consisted of formative work, pilot Studies, and a randomized clinical trial. The sample is 535 HIV-serodiscordant heterosexual African American Couples. There are 2 theoretically derived behavioral interventions with 8 group and individual sessions: the Eban HIV/STD Risk Reduction Intervention (treatment) versus the Eban Health Promotion Intervention (control). The treatment intervention was Couples based and focused on HIV/STD risk reduction whereas the control was individual based and focused oil health promotion. The 2 study conditions were Structurally similar in length and types of activities. At baseline, participants completed an audio computer assisted self-interview and interviewer-administered questionnaire and provided biological specimens to assess tor STDs. Similar follow-up assessments were conducted immediately after the intervention, at 6 months, and at 12 months. Results: The trial results will be analyzed across the 4 sites by randomization assignment. Generalized estimating equations and mixed-effects modeling are planned to test: (1) file effects of the intervention oil STD incidence and condom use and oil mediator variables of these Outcomes and (2) whether the effects of the intervention differ depending oil key moderator variables (eg, gender of the HIV-seropositive partners, length of relationship, psychological distress, sexual abuse history, and Substance abuse history). Conclusions: The lessons learned From the design and conduct of this clinical trial provide guidelines for future couples-based clinical trials in HIV/STD risk reduction and call be generalized to other couples-based behavioral interventions. C1 NIMH, Ctr Mental Hlth Res AIDS, Div AIDS & Hlth & Behav Res, Natl Inst Hlth, Bethesda, MD 20892 USA. FU NIMH NIH HHS [U10 MH078819, U10 MH078819-03, P50 MH073453] NR 48 TC 0 Z9 0 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP 1 PY 2008 VL 49 SU 1 BP S3 EP S14 DI 10.1097/QAI.0b013e3181842570 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 343JB UT WOS:000258848300002 PM 18724188 ER PT J AU Henderson, WA Fall-Dickson, JM Schlenk, EA Kim, KH Matthews, JT Erlen, JA AF Henderson, Wendy A. Fall-Dickson, Jane M. Schlenk, Elizabeth A. Kim, Kevin H. Matthews, Judith T. Erlen, Judith A. TI Effects of liver disease on the well-being of persons living with HIV SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE HIV; liver disease; quality of life; well-being ID QUALITY-OF-LIFE; CHRONIC HEPATITIS-C; MEDICAL OUTCOMES; VIRUS-INFECTION; COINFECTION; THERAPY; IMPACT AB Clinical evidence suggests that patients with liver disease and HIV have poorer quality of life (QOL). Because little research exists to support this observation, this study examined the relationships between people with HIV and liver disorders and their QOL. Cella's multidimensional (functional, social,emotional, physical) conceptualization of QOL guided this study. The sample included 80 participants with liver disorders and HIV; 48.8% had chronic or permanent hepatitis. Cella's four dimensions significantly correlated with QOL: functional, r = .329, p < .01; social, r = .636, p < .01; emotional, r = -.549, p < .01; and physical, r = -.480, p < .01. Linear regression analysis with QOL as the dependent variable and the four dimensions as predictors resulted in significant associations explaining approximately 50% of the variance (R-2 = .532). Confirmatory factor analysis supported Cella's model with the four subdomains loading on one factor (QOL). Understanding the multiple dimensions of QOL may assist in developing interventions for patients with HIV and comorbid liver disorders. C1 [Henderson, Wendy A.] NINR, Biobehav Unit, Symptom Management Branch, NIH, Bethesda, MD 20892 USA. [Fall-Dickson, Jane M.] NINR, Mucosal Injury Unit, Symptom Management Branch, NIH, Bethesda, MD 20892 USA. [Schlenk, Elizabeth A.; Matthews, Judith T.; Erlen, Judith A.] Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15260 USA. [Kim, Kevin H.] Univ Pittsburgh, Sch Educ, Pittsburgh, PA 15260 USA. RP Henderson, WA (reprint author), NINR, Biobehav Unit, Symptom Management Branch, NIH, Bethesda, MD 20892 USA. OI Schlenk, Elizabeth/0000-0001-7361-1951; Henderson, Wendy/0000-0003-3924-7118 FU National Institute of Nursing Research (NINR); National Institutes of Health (NIH); Department of Health and Human Services [NINR 1R01 NR047491]; Center for Research in Chronic Disorders [P30NR03924]; NIH Clinical and Translational Fellowship [1 TL1 RR 024155-01]; Sigma Theta Tau International and Association for Nurses in AIDS Care 2006 Research Award; Sigma Theta Tau, Epsilon Phi 2006 Research Award FX Sincere gratitude goes to the persons living with HIV who participated in the study. The authors thank Donna Caruthers, PhD, RN, Project Director, Michelle Meyers, BSN, RN, Recruitment Coordinator, Alison Colbert, PhD, MSN, RN, Graduate Student Assistant, and Angela Martino, BSN, student assistant, for their assistance. They also thank Dr. Lisa A. Morrow and Tara J. Taylor for reviewing the manuscript.; Support for this study was provided from a grant to the parent study from the National Institute of Nursing Research (NINR), National Institutes of Health (NIH), Department of Health and Human Services (NINR 1R01 NR047491, Primary Investigator: Dr. Judith A. Erlen), and the NINR-funded Center for Research in Chronic Disorders (P30NR03924). Dr. Wendy A. Henderson's efforts were also supported by the NIH Clinical and Translational Fellowship (1 TL1 RR 024155-01), Sigma Theta Tau International and Association for Nurses in AIDS Care 2006 Research Award, Sigma Theta Tau, Epsilon Phi 2006 Research Award, and by endowed scholarships from Dr. Corrine Barnes, Dr. Rose Constantino, and the Pennsylvania Higher Education Funds for graduate studies in nursing. The opinions expressed are those of the authors and do not represent the position of the NIH or the U.S. Government. NR 27 TC 1 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1055-3290 J9 J ASSOC NURSE AIDS C JI J. Assoc. Nurses Aids Care PD SEP-OCT PY 2008 VL 19 IS 5 BP 368 EP 374 DI 10.1016/j.jana.2008.05.004 PG 7 WC Nursing SC Nursing GA 350XW UT WOS:000259388100006 PM 18762144 ER PT J AU Mahajan, R El-Omar, EM Lissowska, J Grillo, P Rabkin, CS Baccarelli, A Yeager, M Sobin, LH Zatonski, W Channock, SJ Chow, WH Hou, LF AF Mahajan, Rajeev El-Omar, Emad M. Lissowska, Jolanta Grillo, Paolo Rabkin, Charles S. Baccarelli, Andrea Yeager, Meredith Sobin, Leslie H. Zatonski, Witold Channock, Stephen J. Chow, Wong-Ho Hou, Lifang TI Genetic variants in t helper cell type 1, 2 and 3 pathways and gastric cancer risk in a Polish population SO JAPANESE JOURNAL OF CLINICAL ONCOLOGY LA English DT Article DE gastric cancer; T helper cell pathways; polymorphism ID SINGLE NUCLEOTIDE POLYMORPHISMS; HELICOBACTER-PYLORI INFECTION; NON-HODGKIN-LYMPHOMA; CTLA4 GENE; MULTIPLE-SCLEROSIS; KOREAN POPULATION; STOMACH-CANCER; ORAL TOLERANCE; TNF-ALPHA; TGF-BETA AB Host immune responses are known determinants of gastric cancer susceptibility. We previously reported an increased gastric cancer risk associated with common variants of several T helper type 1 (Th1) cytokine genes in a population-based case-control study in Warsaw, Poland. In the present study, we augmented our investigation to include additional Th1 genes as well as key genes in the Th2 and Th3 pathways. Analysis of 378 cases and 435 age- and sex-matched controls revealed associations for polymorphisms in the Th1 IL7R gene and one polymorphism in the Th2 IL5 gene. The odd ratios (ORs) for IL7R rs1494555 were 1.4 [95% confidence interval (CI), 1.0-1.9] for A/G and 1.5 (95% CI, 1.0-2.4) for G/G carriers relative to A/A carriers (P = 0.04). The ORs for IL5 rs2069812 were 0.9 (95% CI, 0.7-1.3) for C/T and 0.6 (95% CI, 0.3-1.0) T/T carriers compared with C/C carriers (P = 0.03). These results suggest that IL5 rs2069812 and IL7R rs1389832, rs1494556 and rs1494555 polymorphisms may contribute to gastric cancer etiology. C1 [Hou, Lifang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Mahajan, Rajeev; Rabkin, Charles S.; Channock, Stephen J.; Chow, Wong-Ho; Hou, Lifang] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [El-Omar, Emad M.] Univ Aberdeen, Dept Med & Therapeut, Inst Med Sci, Aberdeen, Scotland. [Lissowska, Jolanta; Zatonski, Witold] Ctr Canc, Div Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta; Zatonski, Witold] M Sklodowska Curie Inst Oncol, Warsaw, Poland. [Grillo, Paolo; Baccarelli, Andrea] Univ Milan, Maggiore Hosp IRCCS Fdn, EPOCA Epidemiol Res Ctr, Milan, Italy. [Yeager, Meredith; Channock, Stephen J.] Natl Canc Inst, Adv Technol Ctr, Core Genotyping Facil, Gaithersburg, MD USA. [Sobin, Leslie H.] Armed Forces Inst Pathol, Div Gastrointestinal Pathol, Washington, DC 20306 USA. RP Hou, LF (reprint author), Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, 680 N Lake Shore Dr, Chicago, IL 60611 USA. EM l-hou@northwestern.edu RI Kim, Seongman/N-6910-2014; OI Baccarelli, Andrea/0000-0002-3436-0640; Lissowska, Jolanta/0000-0003-2695-5799 FU National Cancer Institute, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 69 TC 17 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0368-2811 J9 JPN J CLIN ONCOL JI Jpn. J. Clin. Oncol. PD SEP PY 2008 VL 38 IS 9 BP 626 EP 633 DI 10.1093/jjco/hyn075 PG 8 WC Oncology SC Oncology GA 348II UT WOS:000259203800008 PM 18687755 ER PT J AU Macones, GA Hankins, GDV Spong, CY Hauth, J Moore, T AF Macones, George A. Hankins, Gary D. V. Spong, Catherine Y. Hauth, John Moore, Thomas TI The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: Update on definitions, interpretation, and research guidelines SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE fetal heart tracings; uterine contractions; electronic fetal heart rate; monitoring AB In April 2008, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine partnered to sponsor a 2-day workshop to revisit nomenclature, interpretation, and research recommendations for intrapartum electronic fetal heart rate monitoring. Participants included obstetric experts and representatives from relevant stakeholder groups and organizations. This article provides a summary of the discussions at the workshop. This includes a discussion of terminology and nomenclature for the description of fetal heart tracings and uterine contractions for use in clinical practice and research. A three-tier system for fetal heart rate tracing interpretation is also described. Lastly, prioritized topics for future research are provided. C1 Washington Univ, Dept Obstet & Gynecol, St Louis, MO 63110 USA. Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Calif San Diego, Dept Obstet & Gynecol, San Diego, CA 92103 USA. RP Macones, GA (reprint author), Washington Univ, Dept Obstet & Gynecol, St Louis, MO 63110 USA. EM maconesg@wustl.edu NR 8 TC 59 Z9 62 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-2175 J9 JOGNN-J OBST GYN NEO JI JOGNN PD SEP-OCT PY 2008 VL 37 IS 5 BP 510 EP 515 DI 10.1111/j.1552-6909.2008.00284.x PG 6 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 347OT UT WOS:000259151600002 PM 18761565 ER PT J AU Freeman, MP Davis, M Sinha, P Wisner, KL Hibbeln, JR Gelenberg, AJ AF Freeman, Marlene P. Davis, Melinda Sinha, Pniti Wisner, Katherine L. Hibbeln, Joseph R. Gelenberg, Alan J. TI Omega-3 fatty acids and supportive psychotherapy for perinatal depression: A randomized placebo-controlled study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE perinatal; depression; postpartum; pregnancy; omega-3; supportive psychotherapy ID SEROTONIN-REUPTAKE INHIBITORS; FATTY-ACID STATUS; POSTPARTUM DEPRESSION; POSTNATAL DEPRESSION; SEAFOOD CONSUMPTION; FISH CONSUMPTION; PREGNANT-WOMEN; BIRTH-DEFECTS; DHA CONTENT; TRIAL AB Background: Perinatal major depressive disorder (MDD), including antenatal and postpartum depression, is common and has serious consequences. This study was designed to investigate the feasibility, safety, and efficacy of omega-3 fatty acids for perinatal depression in addition to supportive psychotherapy. Methods: Perinatal women with MDD were randomized to eicosapentacnoic (EPA) and docosahexaenoic acids (DHA), 1.9g/day, or placebo for 8weeks. A manualized supportive psychotherapy was provided to all subjects. Symptoms were assessed with the Hamilton Rating Scale for Depression (HAM-D) and Edinburgh Postnatal Depression Scale (EPDS) biweekly. Results: Fifty-nine women enrolled; N = 51 had two data collection points that allowed for evaluation of efficacy. Omega-3 fatty acids were well tolerated. Participants in both groups experienced significant decreases in EPDS and HAM-D scores (P < .0001) from baseline. We did not find a benefit of omega-3 fatty acids over placebo. Dietary omega-3 fatty acid intake was low among participants. Limitations: The ability to detect an effect of omega-3 fatty acids may have been limited by sample size, study length, or dose. The benefits of supportive psychotherapy may have limited the ability to detect an effect of omega-3 fatty acids. Conclusions: There was no significant difference between omega-3 fatty acids and placebo in this study in which all participants received supportive psychotherapy. The manualized supportive psychotherapy warrants further study. The low intake of dietary omega-3 fatty acids among participants is of concern, in consideration of the widely established health advantages in utero and in infants. (C) 2007 Elsevier B.V. All rights reserved. C1 [Freeman, Marlene P.] Univ Texas SW Med Ctr Dallas, Womens Mental Hlth Ctr, Dept Psychiat, Dallas, TX 75390 USA. [Freeman, Marlene P.; Sinha, Pniti; Gelenberg, Alan J.] Univ Arizona, Dept Psychiat, Coll Med, Tucson, AZ 85721 USA. [Davis, Melinda] Univ Arizona, Dept Pediat, Coll Med, Tucson, AZ 85721 USA. [Wisner, Katherine L.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15260 USA. [Wisner, Katherine L.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Obstet & Gynecol, Pittsburgh, PA 15260 USA. [Wisner, Katherine L.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Hibbeln, Joseph R.] NIAAA, Bethesda, MD 20892 USA. RP Freeman, MP (reprint author), Univ Texas SW Med Ctr Dallas, Womens Mental Hlth Ctr, Dept Psychiat, Dallas, TX 75390 USA. EM marlene.freeman@utsouthwestern.edu FU NIMH NIH HHS [K23 MH066265, K23MH066265] NR 40 TC 94 Z9 98 U1 1 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 2008 VL 110 IS 1-2 BP 142 EP 148 DI 10.1016/j.jad.2007.12.228 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 343JX UT WOS:000258850600016 PM 18206247 ER PT J AU Rooks, RN Simonsick, EM Klesges, LM Newman, AB Ayonayon, HN Harris, TB AF Rooks, Ronica N. Simonsick, Eleanor M. Klesges, Lisa M. Newman, Anne B. Ayonayon, Hilsa N. Harris, Tamara B. TI Racial disparities in health care access and cardiovascular disease indicators in black and white older adults in the health ABC study SO JOURNAL OF AGING AND HEALTH LA English DT Article DE racial disparities; health insurance; access to care; socioeconomic status; cardiovascular disease ID QUALITY-OF-LIFE; LONG-TERM-CARE; MEXICAN-AMERICANS; NORTH-CAROLINA; MEDICAL-CARE; RACE; HYPERTENSION; MORTALITY; SERVICES; ASSOCIATION AB Objective: Black adults consistently exhibit higher rates of and poorer health outcomes due to cardiovascular disease (CVD) than other racial groups, independent of differences in socioeconomic status (SES). Whether factors related to health care access can further explain racial disparities in CVD has not been thoroughly examined. Method: Using logistic regression, the authors examined racial and health care (i.e., health insurance and access to care) associations with CVD indicators (i.e., hypertension, low ankle-arm index, and left ventricular hypertrophy) in the Health, Aging, and Body Composition Study, a longitudinal study of well-functioning older adults. Results: Older Black versus White adults had significantly worse health care. Overall, health care reduced the significant association between being Black and CVD only slightly, while race remained strongly associated with CVD after adjusting for demographics, SES, body mass index, and comorbidity. Discussion: Research on health care quality may contribute to our understanding of these disparities. C1 [Rooks, Ronica N.] Univ Colorado, Dept Hlth & Behav Sci, Denver, CO 80217 USA. [Simonsick, Eleanor M.; Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. [Klesges, Lisa M.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Ayonayon, Hilsa N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Rooks, RN (reprint author), Univ Colorado, Dept Hlth & Behav Sci, POB 173364,CB 188, Denver, CO 80217 USA. EM ronica.rooks@cudenver.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU Intramural NIH HHS [Z01 AG007390-02]; NIA NIH HHS [N01-AG-6-2106, N01-AG-6-2101, N01-AG-6-2103] NR 49 TC 29 Z9 29 U1 3 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD SEP PY 2008 VL 20 IS 6 BP 599 EP 614 DI 10.1177/0898264308321023 PG 16 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 339IK UT WOS:000258571100001 PM 18625758 ER PT J AU Huang, L Chen, MH Yu, F Neal, PR Anderson, GJ AF Huang, Lan Chen, Ming-Hui Yu, Fang Neal, Paul R. Anderson, Gregory J. TI On modeling repeated binary responses and time-dependent missing covariates SO JOURNAL OF AGRICULTURAL BIOLOGICAL AND ENVIRONMENTAL STATISTICS LA English DT Article DE flower intensity; generalized linear mixed model (GLMM); missing at random; Monte Carlo EM algorithm; model assessment; Tilia; weather conditions ID GENERALIZED LINEAR-MODELS; MIXED MODELS; EM ALGORITHM; REGRESSION; INFERENCE; ECOLOGY; DROPOUT AB We develop a novel modeling strategy for analyzing data with repeated binary responses over time as well as time-dependent missing covariates. We assume that covariates are missing at random (MAR). We use the generalized linear mixed logistic regression model for the repeated binary responses and then propose a joint model for time-dependent missing covariates using information from different sources. A Monte Carlo EM algorithm is developed for computing the maximum likelihood estimates. We propose an extended version of the AlC criterion to identify the important factors that may explain the binary responses, A real plant dataset is used to motivate and illustrate the proposed methodology. C1 [Huang, Lan] NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Yu, Fang] Univ Nebraska Med Ctr, Dept Biostat, Coll Publ Hlth, Omaha, NE 68198 USA. [Anderson, Gregory J.] Univ Connecticut, Dept Ecol & Evolutionary Biol, Storrs, CT 06269 USA. RP Huang, L (reprint author), NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. EM ming-hui.chen@uconn.edu RI Yu, Fang/B-9874-2013 FU NIH [GM 70335, CA 74015] FX The authors thank the editor. an associate editor, and two referees, for their constructive comments and suggestions which led to improvements it) this article. Dr. Chen's research was partially suppoprted by NIH grants #GM 70335 and #CA 74015. NR 27 TC 1 Z9 1 U1 0 U2 4 PU AMER STATISTICAL ASSOC & INT BIOMETRIC SOC PI WASHINGTON PA 1444 I ST NW, STE 700, WASHINGTON, DC 20005 USA SN 1085-7117 J9 J AGR BIOL ENVIR ST JI J. Agric. Biol. Environ. Stat. PD SEP PY 2008 VL 13 IS 3 BP 270 EP 293 DI 10.1198/108571108X338023 PG 24 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 343HC UT WOS:000258843100003 ER PT J AU Ciencewicki, J Trivedi, S Kleeberger, SR AF Ciencewicki, Jonathan Trivedi, Shweta Kleeberger, Steven R. TI Oxidants and the pathogenesis of lung diseases SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE oxidative stress; antioxidant; genetics; susceptibility; infant; reproductive outcome; premature; children; elderly; asthma; chronic obstructive pulmonary disease; ozone; pollutants; particulates; PM; acute respiratory distress syndrome; hyperoxia; SNP; single nucleotide polymorphism ID OBSTRUCTIVE PULMONARY-DISEASE; RESPIRATORY-DISTRESS-SYNDROME; LOW-BIRTH-WEIGHT; EXHALED BREATH CONDENSATE; DIESEL EXHAUST PARTICLES; AMBIENT AIR-POLLUTION; SURFACTANT PROTEIN-A; ACUTE OZONE EXPOSURE; LIPID OZONATION PRODUCTS; GLUTATHIONE-S-TRANSFERASE AB The increasing number of population-based and epiderniologic associations between oxidant pollutant exposures and cardiopulmonary disease exacerbation, decrements in pulmonary function, and mortality underscores the important detrimental effects of oxidants on public health. Because inhaled oxidants initiate a number of pathologic processes, including inflammation of the airways, which may contribute to the pathogenesis and/or exacerbation of airways disease, it is critical to understand the mechanisms through which exogenous and endogenous oxidants interact with molecules in the cells, tissues, and epithelial lining fluid of the lung. Furthermore, it is clear that interindividual variation in response to a given exposure also exists across an individual lifetime. Because of the potential impact that oxidant exposures may have on reproductive outcomes and infant, child, and adult health, identification of the intrinsic and extrinsic factors that may influence susceptibility to oxidants remains an important issue. In this review, we discuss mechanisms of oxidant stress in the lung, the role of oxidants in lung disease pathogenesis and exacerbation (eg, asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome), and the potential risk factors (eg, age, genetics) for enhanced susceptibility to oxidant-induced disease. C1 [Ciencewicki, Jonathan; Trivedi, Shweta; Kleeberger, Steven R.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Kleeberger, SR (reprint author), NIEHS, Lab Resp Biol, NIH, 111 TW Alexander Dr,Bldg 101,Rm D240, Res Triangle Pk, NC 27709 USA. EM kleeber1@niehs.nih.gov FU National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services. FX Supported by the Division of Intramural Research at the National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services. NR 182 TC 164 Z9 168 U1 3 U2 28 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2008 VL 122 IS 3 BP 456 EP 468 DI 10.1016/j.jaci.2008.08.004 PG 13 WC Allergy; Immunology SC Allergy; Immunology GA 348TW UT WOS:000259234000002 PM 18774381 ER PT J AU MacPherson, H Nahin, R Paterson, C Cassidy, CM Lewith, GT Hammerschlag, R AF MacPherson, Hugh Nahin, Richard Paterson, Charlotte Cassidy, Claire M. Lewith, George T. Hammerschlag, Richard TI Developments in Acupuncture Research: Big-Picture Perspectives from the Leading Edge SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article; Proceedings Paper CT Annual Conference of the Society-for-Acupuncture-Research CY NOV 09-11, 2007 CL Univ Maryland, Baltimore, MD SP Soc Acupuncture Res, Natl Ctr Complementary Med, NCCAM HO Univ Maryland ID CHINESE MEDICINE USERS; WHOLE SYSTEMS RESEARCH; ALTERNATIVE MEDICINE; UNITED-STATES; HEALTH-CARE; COMPLEMENTARY; MODEL AB On November 8-9, 2007, the Society for Acupuncture Research (SAR) hosted an international conference to mark the tenth anniversary of the landmark NIH [National Institutes of Health] Consensus Development Conference on Acupuncture. More than 300 acupuncture researchers, practitioners, students, funding agency personnel, and health policy analysts from 20 countries attended the SAR meeting held at the University of Maryland School of Medicine, Baltimore, MD. This paper summarizes important invited lectures in the area of how the field has developed in the past decade, along with a focus on appropriate strategies for advancing the field. Specific topics include: the impact of the 1997 NIH Acupuncture Consensus Conference on acupuncture research; whole-system strategies for developing the evidence without distorting the medicine; use of qualitative research methods to explore acupuncture as a complex intervention; use of qualitative research approaches to explore some "missing" topics in acupuncture research; and the impact of acupuncture research on clinical practice. A concluding section focuses on future directions in acupuncture research. C1 [MacPherson, Hugh] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. [Nahin, Richard] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Paterson, Charlotte] Univ Exeter, Peninsular Med Sch, Exeter, Devon, England. [Cassidy, Claire M.] Windpath Healing Works LLC, Bethesda, MD USA. [Lewith, George T.] Univ Southampton, Southampton, Hants, England. [Hammerschlag, Richard] Oregon Coll Oriental Med, Portland, OR USA. RP MacPherson, H (reprint author), Univ York, Dept Hlth Sci, Seebohm Rowntree Bldg, York YO10 5DD, N Yorkshire, England. EM hm18@york.ac.uk OI Nahin, Richard/0000-0002-3682-4816; Lewith, George/0000-0002-2364-3960; MacPherson, Hugh/0000-0003-4255-4768 FU Medical Research Council [G106/1095] NR 37 TC 15 Z9 15 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD SEP PY 2008 VL 14 IS 7 BP 883 EP 887 DI 10.1089/acm.2008.SAR-5 PG 5 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 363RD UT WOS:000260283500014 PM 18803497 ER PT J AU Riley, W Obermayer, J Jean-Mary, J AF Riley, William Obermayer, Jami Jean-Mary, Jersino TI Internet and mobile phone text messaging intervention for college smokers SO JOURNAL OF AMERICAN COLLEGE HEALTH LA English DT Article DE college health; health education; smoking cessation; text messaging ID SMOKING-CESSATION PROGRAM; RANDOMIZED-TRIAL; COMPUTER; STUDENTS; MODEL; ADOLESCENTS; PREVENTION; TELEPHONE AB Objective: -The authors developed a smoking cessation program using mobile phone text messaging to provide tailored and stage-specific messages to college smokers. Participants and Methods: The authors recruited 31 daily smokers who desired to quit front a college campus and asked them to use an Internet and mobile phone text messaging program to quit smoking. Results: Six weeks after program initiation, 45% reported abstinence with 42% abstinent based on cotinine verification. Continued smokers reported significantly reduced smoking rates and dependence. Overall, participants accepted the text messages. Conclusions: These results replicate findings from ail earlier study and indicate that mobile phone text messaging, is a potentially efficacious and easily disseminated method for providing cessation interventions to young adult smokers. C1 [Riley, William; Obermayer, Jami; Jean-Mary, Jersino] PICS Inc, Reston, VA USA. RP Riley, W (reprint author), NIMH, 6001 Execut Blvd,MSC 9615, Bethesda, MD 20892 USA. EM wiriley@mail.nih.gov RI Emchi, Karma/Q-1952-2016 NR 29 TC 65 Z9 67 U1 3 U2 19 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0744-8481 J9 J AM COLL HEALTH JI J. Am. Coll. Health PD SEP-OCT PY 2008 VL 57 IS 2 BP 245 EP 248 DI 10.3200/JACH.57.2.245-248 PG 4 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 352PH UT WOS:000259508900014 PM 18809542 ER PT J AU Villar, R Vicente, E Solano, B Perez-Silanes, S Aldana, I Maddry, JA Lenaerts, AJ Franzblau, SG Cho, SH Monge, A Goldman, RC AF Villar, Raquel Vicente, Esther Solano, Beatriz Perez-Silanes, Silvia Aldana, Ignacio Maddry, Joseph A. Lenaerts, Anne J. Franzblau, Scott G. Cho, Sang-Hyun Monge, Antonio Goldman, Robert C. TI In vitro and in vivo antimycobacterial activities of ketone and amide derivatives of quinoxaline 1,4-di-N-oxide SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 38th World Conference on Lung Health of the International-Union-Against-Tuberculosis-and-Lung-Disease CY NOV 08-12, 2007 CL Cape Town, SOUTH AFRICA SP Int Union Against Tuberculosis & Lung Dis DE antitubercular drugs; resistance; in vivo efficacy ID EXTENSIVELY DRUG-RESISTANT; MYCOBACTERIUM-TUBERCULOSIS AGENTS; GENE-DISRUPTED MICE; ALAMAR BLUE ASSAY; QUINOXALINE-2-CARBONITRILE 1,4-DI-N-OXIDE; ANTITUBERCULOSIS ACTIVITY; COENZYME F-420; BOVIS BCG; TB; BIOSYNTHESIS AB Objectives: To evaluate a novel series of quinoxaline 1,4-di-N-oxides for in vitro activity against Mycobacterium tuberculosis and for efficacy in a mouse model of tuberculosis (TB). Methods: Ketone and amide derivatives of quinoxaline 1,4-di-N-oxide were evaluated in in vitro and in vivo tests including: (i) activity against M. tuberculosis resistant to currently used antitubercular drugs including multidrug-resistant strains (MDR-TB resistant to isoniazid and rifampicin); (ii) activity against non-replicating persistent (NRP) bacteria; (iii) MBC; (iv) maximum tolerated dose, oral bioavailability and in vivo efficacy in mice; and (v) potential for cross-resistance with another bioreduced drug, PA-824. Results: Ten compounds were tested on single drug-resistant M. tuberculosis. In general, all compounds were active with ratios of MICs against resistant and non-resistant strains of <= 4.00. One compound, 5, was orally active in a murine model of TB, bactericidal, active against NRP bacteria and active on MDR-TB and poly drug-resistant clinical isolates (resistant to 3-5 antitubercular drugs). Conclusions: Quinoxaline 1,4-di-N-oxides represent a new class of orally active antitubercular drugs. They are likely bioreduced to an active metabolite, but the pathway of bacterial activation was different from PA-824, a bioreducible nitroimidazole in clinical trials. Compound 5 was bactericidal and active on NRP organisms indicating that activation occurred in both growing and non-replicating bacteria leading to cell death. The presence of NRP bacteria is believed to be a major factor responsible for the prolonged nature of antitubercular therapy. If the bactericidal activity and activity on non-replicating bacteria in vitro translate to in vivo conditions, quinoxaline 1,4-di-N-oxides may offer a path to shortened therapy. C1 [Goldman, Robert C.] NIAID, Div Aids, Therapeut Res Program, Bethesda, MD 20892 USA. [Villar, Raquel; Vicente, Esther; Solano, Beatriz; Perez-Silanes, Silvia; Aldana, Ignacio; Monge, Antonio] Univ Navarra, CIFA, Unidad Invest & Desarrollo Medicamentos, E-31080 Pamplona, Spain. [Maddry, Joseph A.] So Res Inst, Birmingham, AL 35255 USA. [Lenaerts, Anne J.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Franzblau, Scott G.; Cho, Sang-Hyun] Univ Illinois, Inst TB Res, Chicago, IL 60612 USA. RP Goldman, RC (reprint author), NIAID, Div Aids, Therapeut Res Program, Bethesda, MD 20892 USA. EM rgoldman@niaid.nih.gov RI Perez-Silanes, Silvia/B-5284-2008; Vicente, Esther/P-2308-2016; Lenaerts, Anne/F-1353-2017; OI Perez-Silanes, Silvia/0000-0002-6284-4546; Vicente, Esther/0000-0002-1061-2292; Franzblau, Scott/0000-0002-8698-0243 FU NIAID NIH HHS [N01 AI095385, N01 AI095364, N01-AI-95364, N01-AI-95385] NR 32 TC 37 Z9 39 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD SEP PY 2008 VL 62 IS 3 BP 547 EP 554 DI 10.1093/jac/dkn214 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 337ZD UT WOS:000258473200022 PM 18502817 ER PT J AU Rajter, R French, RH Podgornik, R Ching, WY Parsegian, VA AF Rajter, Rick French, Roger H. Podgornik, Rudi Ching, W. Y. Parsegian, V. Adrian TI Spectral mixing formulations for van der Waals-London dispersion interactions between multicomponent carbon nanotubes SO JOURNAL OF APPLIED PHYSICS LA English DT Article ID ELECTRONIC-STRUCTURE; OPTICAL-PROPERTIES; HAMAKER CONSTANTS; SPECTROSCOPIC ELLIPSOMETRY; DIELECTRIC FUNCTION; WATER; FORCES; SYSTEMS; VACUUM; FIELD AB Recognition of spatially varying optical properties is a necessity when studying the van der Waals-London dispersion (vdW-Ld) interactions of carbon nanotubes (CNTs) that have surfactant coatings, tubes within tubes, and/or substantial core sizes. The ideal way to address these radially dependent optical properties would be to have an analytical add-a-layer solution in cylindrical coordinates similar to the one readily available for the plane-plane geometry. However, such a formulation does not exist nor does it appear trivial to be obtained exactly. The best and most pragmatic alternative for end-users is to take the optical spectra of the many components and to use a spectral mixing formulation so as to create effective solid-cylinder spectra for use in the far-limit regime. The near-limit regime at "contact" is dominated by the optical properties of the outermost layer, and thus no spectral mixing is required. Specifically we use a combination of a parallel capacitor in the axial direction and the Bruggeman effective medium in the radial direction. We then analyze the impact of using this mixing formulation upon the effective vdW-Ld spectra and the resulting Hamaker coefficients for small and large diameter single walled CNTs (SWCNTs) in both the near- and far-limit regions. We also test the spectra of a [16,0,s+7,0,s] muldwalled CNT (MWCNT) with an effective MWCNT spectrum created by mixing its [16, 0, s] and [7, 0, s] SWCNT components to demonstrate nonlinear coupling effects that exist between neighboring layers. Although this paper is primarily on nanotubes, the strategies, implementation, and analysis presented are applicable and likely necessary to any system where one needs to resolve spatially varying optical properties in a, particular Lifshitz formulation. (C) 2008 American Institute of Physics. C1 [Rajter, Rick] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [French, Roger H.] DuPont Co Inc, Cent Res, Expt Stn, Wilmington, DE 19880 USA. [Podgornik, Rudi] Univ Ljubljana, Fac Math & Phys, Ljubljana, Slovenia. [Podgornik, Rudi] Jozef Stefan Inst, Dept Theoret Phys, SI-1000 Ljubljana, Slovenia. [Ching, W. Y.] Univ Missouri, Dept Phys, Kansas City, MO 64110 USA. [Parsegian, V. Adrian] NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Rajter, R (reprint author), MIT, Dept Mat Sci & Engn, Room 13-5046, Cambridge, MA 02139 USA. EM rickrajter@alum.mit.edu RI Ching, Wai-Yim/B-4686-2009; French, Roger/E-1986-2011; Podgornik, Rudolf/C-6209-2008 OI Ching, Wai-Yim/0000-0001-7738-8822; French, Roger/0000-0002-6162-0532; Podgornik, Rudolf/0000-0002-3855-4637 NR 41 TC 10 Z9 10 U1 1 U2 10 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-8979 J9 J APPL PHYS JI J. Appl. Phys. PD SEP 1 PY 2008 VL 104 IS 5 AR 053513 DI 10.1063/1.2975207 PG 13 WC Physics, Applied SC Physics GA 357NO UT WOS:000259853600043 ER PT J AU Scichilone, N La Sala, A Bellia, M Fallano, K Togias, A Brown, RH Midiri, M Bellia, V AF Scichilone, Nicola La Sala, Alba Bellia, Maria Fallano, Katherine Togias, Alkis Brown, Robert H. Midiri, Massimo Bellia, Vincenzo TI The airway response to deep inspirations decreases with COPD severity and is associated with airway distensibility assessed by computed tomography SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE high-resolution computed tomography; methacholine; airway-parenchyma interdependence; bronchoprovocation; hyperinflation ID OBSTRUCTIVE LUNG-DISEASE; SMOOTH-MUSCLE; METHACHOLINE CHALLENGE; ASTHMATIC SUBJECTS; HEALTHY-SUBJECTS; EXPIRATORY FLOW; INFLATION; RESPONSIVENESS; CALIBER AB In patients with mild chronic obstructive pulmonary disease (COPD), the effect of deep inspirations (DIs) to reverse methacholine-induced bronchoconstriction is largely attenuated. In this study, we tested the hypothesis that the effectiveness of DI is reduced with increasing disease severity and that this is associated with a reduction in the ability of DI to distend the airways. Fifteen subjects [Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I-II: n = 7; GOLD stage III-IV: n = 8] underwent methacholine bronchoprovocation in the absence of DI, followed by DI. The effectiveness of DI was assessed by their ability to improve inspiratory vital capacity and forced expiratory volume in 1 s (FEV1). To evaluate airway distensibility, two sets of high-resolution computed tomography scans [at residual volume (RV) and at total lung capacity] were obtained before the challenge. In addition, mean parenchymal density was calculated on the high-resolution computed tomography scans. We found a strong correlation between the response to DI and baseline FEV1 %predicted (r(2) = 0.70, P < 0.0001) or baseline FEV1/forced vital capacity (r(2) = 0.57, P = 0.001). RV % predicted and functional residual capacity %predicted correlated inversely (r(2) = 0.33, P = 0.02 and r(2) = 0.32, P = 0.03, respectively), and parenchymal density at RV correlated directly (r(2) = 0.30, P = 0.03), with the response to DI. Finally, the effect of DI correlated to the change in large airway area from RV to total lung capacity (r(2) = 0.44, P = 0.01). We conclude that loss of the effects of DI is strongly associated with COPD severity and speculate that the reduction in the effectiveness of DI is due to the failure to expand the lungs because of the hyperinflated state and/or the parenchymal damage that prevents distension of the airways with lung inflation. C1 [Scichilone, Nicola; La Sala, Alba; Bellia, Vincenzo] Univ Palermo, Dipartimento Med Pneumol Fisiol & Ntr Umana, Sez Pneumol & Med, I-90146 Palermo, Italy. [Bellia, Maria; Midiri, Massimo] Univ Palermo, Dipartimento Biotecnol & Med Legale, Sez Sci Radiol, I-90146 Palermo, Italy. [Fallano, Katherine; Brown, Robert H.] Johns Hopkins Univ, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. [Togias, Alkis] Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Bethesda, MD USA. RP Scichilone, N (reprint author), Univ Palermo, Dipartimento Med Pneumol Fisiol & Ntr Umana, Sez Pneumol & Med, Via Trabucco 180, I-90146 Palermo, Italy. EM n.scichilone@libero.it OI Scichilone, Nicola/0000-0001-6400-6573 FU University of Palermo, Palermo, Italy FX The study was funded by the University of Palermo, Palermo, Italy. NR 26 TC 12 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2008 VL 105 IS 3 BP 832 EP 838 DI 10.1152/japplphysiol.01307.2007 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 345ZT UT WOS:000259038900009 PM 18617628 ER PT J AU Liu, DM Metter, EJ Ferrucci, L Roth, SM AF Liu, Dongmei Metter, E. Jeffrey Ferrucci, Luigi Roth, Stephen M. TI TNF promoter polymorphisms associated with muscle phenotypes in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE genetics; skeletal muscle; inflammation; cytokine; tumor necrosis factor-alpha ID TUMOR-NECROSIS-FACTOR; SKELETAL-MUSCLE; FACTOR-ALPHA; PROTEIN-SYNTHESIS; CIRCULATING LEVELS; BEHCETS-DISEASE; ELDERLY-MEN; OLDEST-OLD; AGE; SARCOPENIA AB Tumor necrosis factor-alpha (TNF-alpha) is a potent catabolic factor to skeletal muscle. Single-nucleotide polymorphisms (SNPs) in the promoter region of the TNF-alpha coding gene, TNF, have been implicated in the interindividual variation in TNF-alpha production via transcriptional regulation. The present study investigated the association of muscle phenotypes with five TNF promoter SNPs, which potentially have biological significance. Female and male volunteers (n = 1,050) from the Baltimore Longitudinal Study of Aging were genotyped, and their regional and total body muscle mass, and arm and leg muscle strength were measured. Results indicated that putative high-expression alleles at positions -1031 and -863, individually or in combination in the haplotype 1031C-863A-857C-308G-238G, were associated with lower muscle mass in men. Specifically, carriers of -1031C, compared with noncarriers, exhibited lower arm muscle mass (6.4 +/- 0.1 vs. 6.8 +/- 0.1 kg, P = 0.01) and appendicular skeletal muscle mass (ASM) (24.3 +/- 0.4 vs. 25.4 +/- 0.2 kg, P = 0.02), with leg muscle mass and the ASM index (ASMI; kg/m(2)) also tending to be lower (P = 0.06 and 0.07). Similarly, -863A allele carriers (linked with -1031), compared with noncarriers, exhibited lower arm muscle mass (6.4 +/- 0.1 vs. 6.8 +/- 0.1 kg, P = 0.04). Carriers of the haplotype 1031C-863A-857C-308G-238G, compared with noncarriers, exhibited lower arm muscle mass (6.3 +/- 0.2 vs. 6.8 +/- 0.1 kg, P < 0.01), trunk muscle mass (25.7 +/- 0.5 vs. 26.9 +/- 0.3 kg, P < 0.05), and ASM (24.1 +/- 0.5 vs. 25.3 +/- 0.2 kg, P < 0.025), with tendencies for lower leg muscle mass and ASMI (P = 0.07 and 0.08). Results indicate that genetic variation in the TNF locus may contribute to the interindividual variation in muscle phenotypes in men. C1 [Liu, Dongmei; Roth, Stephen M.] Univ Maryland, Sch Publ Hlth, Dept Kinesiol, College Pk, MD 20742 USA. [Metter, E. Jeffrey; Ferrucci, Luigi] Harbor Hosp, Natl Inst Aging, Clin Res Branch, Baltimore, MD USA. RP Roth, SM (reprint author), Univ Maryland, Sch Publ Hlth, Dept Kinesiol, 2134 SPH Bldg, College Pk, MD 20742 USA. EM sroth1@umd.edu RI Liu, Dongmei/C-1525-2012; OI Roth, Stephen/0000-0002-7841-3695 FU National Institutes of Health [AG-021500, AG-022791] FX The BLSA research was conducted as a component of the Intramural Research Program of the National Institute on Aging. This work was further sponsored by National Institutes of Health Grants AG-021500 and AG-022791. NR 51 TC 10 Z9 10 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2008 VL 105 IS 3 BP 859 EP 867 DI 10.1152/japplphysiol.90655.2008 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 345ZT UT WOS:000259038900013 PM 18635873 ER PT J AU Minshew, NJ Hobson, JA AF Minshew, Nancy J. Hobson, Jessica A. TI Sensory sensitivities and performance on sensory perceptual tasks in high-functioning individuals with autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE autism; sensory sensitivities; sensory perception; sensory neglect ID CHILDHOOD AUTISM; INFANTILE-AUTISM; DEVELOPMENTAL DISORDERS; SENTENCE COMPREHENSION; SPECTRUM DISORDERS; DISTURBED-CHILDREN; MOTOR INTEGRATION; ASPERGER-SYNDROME; ABNORMALITIES; CONNECTIVITY AB Most reports of sensory symptoms in autism are second hand or observational, and there is little evidence of a neurological basis. Sixty individuals with high-functioning autism and 61 matched typical participants were administered a sensory questionnaire and neuropsychological tests of elementary and higher cortical sensory perception. Thirty-two percent of autism participants endorsed more sensory sensitivity items than any control participants. Both groups made few errors on elementary sensory perception items. Controls made few errors on higher cortical sensory perception items, but 30% of the autism participants made high numbers of errors. These findings support the common occurrence of sensory symptoms in high functioning autism based on first person report, and the presence of neurological abnormalities in higher cortical sensory perception. C1 [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, NICHD, Collaborat Program Excellence Autism, Pittsburgh, PA 15213 USA. [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Hobson, Jessica A.] UCL, Inst Child Hlth, London, England. RP Minshew, NJ (reprint author), Univ Pittsburgh, Sch Med, NICHD, Collaborat Program Excellence Autism, 3811 OHara St,Suite 300 Webster Hall, Pittsburgh, PA 15213 USA. EM minshewnj@upmc.edu FU NICHD NIH HHS [U19 HD035469-09, P01 HD035469, P50 HD055748, U19 HD035469, U19 HD035469-07, U19 HD035469-10, HD35469, U19 HD035469-06, U19 HD035469-08] NR 85 TC 32 Z9 32 U1 4 U2 21 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD SEP PY 2008 VL 38 IS 8 BP 1485 EP 1498 DI 10.1007/s10803-007-0528-4 PG 14 WC Psychology, Developmental SC Psychology GA 338TI UT WOS:000258531400008 PM 18302014 ER PT J AU Yeh, S Wroblewski, K Buggage, R Li, Z Kurup, SK Sen, HN Dahr, S Sran, P Reed, GF Robinson, R Ragheb, JA Waldmann, TA Nussenblatt, RB AF Yeh, Steven Wroblewski, Keith Buggage, Ronald Li, Zhuqing Kurup, Shree K. Sen, Hatice Nida Dahr, Sam Sran, Pushpa Reed, George F. Robinson, Randy Ragheb, Jack A. Waldmann, Thomas A. Nussenblatt, Robert B. TI High-dose humanized anti-IL-2 receptor alpha antibody (daclizumab) for the treatment of active, non-infectious uveitis SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Daclizumab; Posterior uveitis; Panuveitis; Intermediate uveitis; Interleukin-2 ID PREVENT ACUTE REJECTION; IL-2 RECEPTOR; MYCOPHENOLATE-MOFETIL; TRANSPLANT RECIPIENTS; RENAL-TRANSPLANTATION; LUNG TRANSPLANTATION; POSTERIOR UVEITIS; CLINICAL-TRIAL; T(H)17 CELLS; T-CELLS AB Purpose: This study was designed to provide preliminary data regarding the safety and efficacy of high-dose humanized anti-IL-2 receptor (daclizumab) therapy for the treatment of active intermediate, posterior or panuveitis. Methods: Five patients were recruited into this non-randomized, prospective pilot study of high-dose intravenous induction daclizumab therapy given at doses of 8 mg/kg at day 0 and 4 mg/kg at day 14. Patients who did not meet a safety endpoint at the 3-week follow-up evaluation were given the option of continuing therapy with subcutaneous daclizumab at 2 mg/kg every 4 weeks for 52 weeks. The primary outcome assessed was a two-step decrease in vitreous haze at day 21. Secondary outcomes evaluated included best-corrected visual acuity, retinal thickness as measured by optical coherence tomography, retinal vascular leakage assessed by fluorescein angiography, anterior chamber and vitreous cellular inflammation. Results: Four male patients and one female patient were enrolled. Diagnoses included birdshot retinochoroidopathy (two patients), Vogt-Koyanagi-Harada's disease, bilateral idiopathic panuveitis and bilateral idiopathic intermediate uveitis. By the 4th week, four of five patients demonstrated a two-step decrease in vitreous haze. The other participant did not meet this criterion until week 20, but all five patients maintained stability in vitreous haze grade throughout their follow-up periods. At enrollment, mean visual acuity (10 eyes in 5 patients) was 69.2 ETDRS letters and following treatment was 78.2 letters (p < 0.12). Anterior chamber cell, vitreous cell, and vitreous haze also improved in the majority of eyes. Adverse events were generally mild except for one episode of left-lower lobe pneumonia requiring hospitalization and treatment. Conclusion: This is the first demonstration that high-dose daclizumab can reduce inflammation in active uveitis. Daclizumab was well tolerated but there may be a potential increased risk of infection associated with immunosuppression. All five patients demonstrated a decrease in vitreous haze and measures of intraocular inflammation at final follow-up. The results of this small, non-randomized pilot study support the consideration of high-dose daclizumab therapy in cases of active posterior uveitis. Published by Elsevier Ltd. C1 [Yeh, Steven; Wroblewski, Keith; Buggage, Ronald; Li, Zhuqing; Kurup, Shree K.; Sen, Hatice Nida; Dahr, Sam; Sran, Pushpa; Ragheb, Jack A.; Nussenblatt, Robert B.] NEI, NIH, Immunol Lab, Bethesda, MD 20892 USA. [Reed, George F.] NIH, Dept Biometry & Epidemiol, Bethesda, MD 20892 USA. [Robinson, Randy] BioPharma Inc, Prot Design Lab, Redwood City, CA USA. [Waldmann, Thomas A.] NCI, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, NIH, Immunol Lab, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM drbob@nei.nih.gov FU National Eye Institute; National Institutes of Health; Heed Ophthalmic Foundation FX This research was funded in part by the Intramural Research Program of the National Eye Institute, National Institutes of Health. S.Y. is supported in part by the Heed Ophthalmic Foundation. Daclizumab was provided by PDL BioPharma (Redwood City, CA). NR 26 TC 43 Z9 43 U1 1 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD SEP PY 2008 VL 31 IS 2 BP 91 EP 97 DI 10.1016/j.jaut.2008.05.001 PG 7 WC Immunology SC Immunology GA 357XO UT WOS:000259880700001 PM 18571896 ER PT J AU Hawes, JJ Nerva, JD Reilly, KM AF Hawes, Jessica J. Nerva, John D. Reilly, Karlyne M. TI Novel dual-reporter preclinical screen for antiastrocytoma agents identifies cytostatic and cytotoxic compounds SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE astrocytoma; Nf1; p53; E2F1; luciferase ID NEUROFIBROMATOSIS TYPE-1; GLIOBLASTOMA-MULTIFORME; P53 MUTATIONS; GENE; PROLIFERATION; CHEMOTHERAPY; ASTROCYTOMA; BOUVARDIN; PATHWAY; GLIOMAS AB Astrocytoma/glioblastoma is the most common malignant form of brain cancer and is Often unresponsive to current pharmacological therapies and Surgical interventions. Despite several potential therapeutic agents against astrocytoma and glioblastoma, there are currently no effective therapies for astrocytoma, creating a great need for the identification of effective antitumor agents. The authors have developed a novel dual-reporter system in Trp53/Nf1-null astrocytoma cells to simultaneously and rapidly assay cell viability and cell cycle progression as evidenced by activity of the human E2F1 promoter in vitro. The dual-reporter high-throughput assay was used to screen experimental therapeutics for activity in Trp53/Nf1-null astrocytoma. Several compounds were identified demonstrating selectivity for astrocytoma over primary astrocytes. The dual-reporter system described here may be a valuable tool for identifying potential antitumor treatments that specifically target astrocytoma. C1 [Hawes, Jessica J.; Nerva, John D.; Reilly, Karlyne M.] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Reilly, KM (reprint author), NCI, Mouse Canc Genet Program, W 7th St Ft Detrick,POB B,Bldg 560,Rm 32-20, Frederick, MD 21702 USA. EM kreilly@ncifcrf.gov FU Intralflural Research Program of the National Institutes of Health (NIH); National Cancer Institute FX This research was supported by the Intralflural Research Program of the National Institutes of Health (NIH), National Cancer Institute. This research was performed while JJH held a National Research Council Research Associateship Award at the National Cancer Institute. All experiments were conducted in compliance with the current laws of the United States. NR 28 TC 9 Z9 9 U1 2 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD SEP PY 2008 VL 13 IS 8 BP 795 EP 803 DI 10.1177/1087057108321085 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 352MS UT WOS:000259501900007 PM 18664715 ER PT J AU Aragon, AB Jackson, WM Onodera, J Tuan, RS Nesti, LJ AF Aragon, A. B. Jackson, W. M. Onodera, J. Tuan, R. S. Nesti, L. J. TI Gene Expression in Blast-Injured Muscle: Insights into the Mechanism of Heterotopic Ossification. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Aragon, A. B.; Nesti, L. J.] Walter Reed Army Med Ctr, Dept Orthopaed & Rehabil, Washington, DC 20307 USA. [Jackson, W. M.; Onodera, J.; Tuan, R. S.] NIAMSD, Cartilage Biol & Orthopaed Branch, Bethesda, MD 20892 USA. RI Onodera, Jun/D-7142-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S281 EP S281 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001428 ER PT J AU Cabral, WA Barnes, AM Rotimi, CN Porter, D Bailey-Wilson, J Brody, L Martini, JC AF Cabral, W. A. Barnes, A. M. Rotimi, C. N. Porter, D. Bailey-Wilson, J. Brody, L. Martini, J. C. TI Recurring Mutation Causing Severe/Lethal Recessive Type VIII Osteogenesis Imperfecta in African-Americans Originated in West Africa More than 300 Years Ago SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Cabral, W. A.; Barnes, A. M.; Martini, J. C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA. [Rotimi, C. N.; Bailey-Wilson, J.] NHGRI, Inherited Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Porter, D.] NHGRI, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. [Brody, L.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S183 EP S183 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001058 ER PT J AU Chang, W Barnes, AM Cabral, WA Marini, JC AF Chang, W. Barnes, A. M. Cabral, W. A. Marini, J. C. TI Prolyl 3-Hydroxylase 1 and CRTAP are Mutually Stabilizing in the Endoplasmic Reticulum Collagen Prolyl 3-Hydroxylation Complex SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Chang, W.; Barnes, A. M.; Cabral, W. A.; Marini, J. C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S15 EP S15 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000050 ER PT J AU Chen, J Bi, Y Young, MF Wadhwa, S AF Chen, J. Bi, Y. Young, M. F. Wadhwa, S. TI Identification And Characterization of 3.6 Col I Positive Cells from Mouse Temporomandibular Joint SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Chen, J.; Wadhwa, S.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Bi, Y.; Young, M. F.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, US Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S274 EP S274 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001399 ER PT J AU Collin-Osdoby, P Uveges, TE Cabral, WA Goldberg, L Gronowicz, GA Osdoby, P Marini, JC AF Collin-Osdoby, P. Uveges, T. E. Cabral, W. A. Goldberg, L. Gronowicz, G. A. Osdoby, P. Marini, J. C. TI Increased Osteoclasts in Brtl Mouse Model for Osteogenesis Imperfecta Are Independent of Decreased Osteoblast Matrix Production and RANKL/OPG Ratio, but Are Associated with Increased Osteoclast Precursors in Marrow. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Collin-Osdoby, P.; Goldberg, L.; Osdoby, P.] Washington Univ, Dept Biol, St Louis, MO 63130 USA. [Collin-Osdoby, P.; Goldberg, L.; Osdoby, P.] Washington Univ, Div Bone & Mineral Metab, St Louis, MO 63130 USA. [Uveges, T. E.; Cabral, W. A.; Marini, J. C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA. [Gronowicz, G. A.] Univ Connecticut, Ctr Hlth, Dept Orthopaed Surg, Farmington, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S292 EP S292 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001473 ER PT J AU Daley, ELH McBride, DJ Uveges, TE Kuznetsova, NV Leikin, S Marini, JC Goldstein, SA AF Daley, E. L. H. McBride, D. J. Uveges, T. E. Kuznetsova, N. V. Leikin, S. Marini, J. C. Goldstein, S. A. TI Age-Associated Changes in the Material Properties of the G610C (Amish) OI Mouse Model SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Daley, E. L. H.; Goldstein, S. A.] Univ Michigan, Ann Arbor, MI 48109 USA. [McBride, D. J.] Univ Maryland, Baltimore, MD 21201 USA. [Uveges, T. E.; Kuznetsova, N. V.; Leikin, S.; Marini, J. C.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S182 EP S182 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001051 ER PT J AU Duverger, O Lee, D Hassan, MQ Chen, SX Jaisser, F Lian, JB Morasso, MI AF Duverger, O. Lee, D. Hassan, M. Q. Chen, S. X. Jaisser, F. Lian, J. B. Morasso, M. I. TI Molecular Consequences of a Mutant Dlx3 Affecting Bone Homeostasis in Tricho-Dento-Osseous Syndrome SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Duverger, O.; Lee, D.; Chen, S. X.; Morasso, M. I.] NIAAMS, NIH, Bethesda, MD USA. [Hassan, M. Q.; Lian, J. B.] UMass Med Sch, Worcester, MA USA. [Jaisser, F.] Coll France, F-75231 Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S76 EP S76 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000273 ER PT J AU Gafni, RI Bhattacharyya, N Brahim, JS Dumitrescu, CE Theman, TA Kelly, MH Molinolo, AA Collins, MT AF Gafni, R. I. Bhattacharyya, N. Brahim, J. S. Dumitrescu, C. E. Theman, T. A. Kelly, M. H. Molinolo, A. A. Collins, M. T. TI Evidence Supporting the Necessity of UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyl-transferase 3 (GalNac-T3) in the Processing of Fibroblast Growth Factor 23 (FGF23) in Humans SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Gafni, R. I.; Bhattacharyya, N.; Brahim, J. S.; Dumitrescu, C. E.; Theman, T. A.; Kelly, M. H.; Molinolo, A. A.; Collins, M. T.] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S173 EP S173 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001018 ER PT J AU Gudnason, V Aspelund, T Smith, AV Siggeirsdottir, K Eiriksdottir, G Jonsson, BY Lang, TF Launer, LJ Harris, TB AF Gudnason, V. Aspelund, T. Smith, A. V. Siggeirsdottir, K. Eiriksdottir, G. Jonsson, B. Y. Lang, T. F. Launer, L. J. Harris, T. B. TI Use of Genetic Markers in Prediction of Fractures SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Gudnason, V.; Aspelund, T.; Smith, A. V.; Siggeirsdottir, K.; Eiriksdottir, G.] Iceland Heart Assoc, Kopavogur, Iceland. [Jonsson, B. Y.] Univ Hosp, Malmo, Sweden. [Lang, T. F.] UCSF, San Francisco, CA USA. [Launer, L. J.; Harris, T. B.] NIA, Bethesda, MD 20892 USA. RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S27 EP S27 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000095 ER PT J AU Han, S Makareeva, E Kuznetsova, NV DeRidder, AM Sutter, MB McBride, DJ Phillips, CL Schwartze, U Pace, JM Byers, PH Visse, R Nagase, H Leikin, S AF Han, S. Makareeva, E. Kuznetsova, N. V. DeRidder, A. M. Sutter, M. B. McBride, D. J. Phillips, C. L. Schwartze, U. Pace, J. M. Byers, P. H. Visse, R. Nagase, H. Leikin, S. TI Do Type I Collagen Homotrimers Contribute to Osteoporosis by Altering Bone Remodeling? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Han, S.; Makareeva, E.; Kuznetsova, N. V.; DeRidder, A. M.; Sutter, M. B.; Leikin, S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [McBride, D. J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Phillips, C. L.] Univ Missouri, Dept Biochem, Columbia, MO USA. [Schwartze, U.; Pace, J. M.; Byers, P. H.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Visse, R.; Nagase, H.] Univ London Imperial Coll Sci Technol & Med, Kennedy Inst Rheumatol, London, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S162 EP S162 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000579 ER PT J AU Ichikawa, S Sorenson, AH Fritz, TA Moh, A Mackenzie, DS Hui, SL Econs, MJ AF Ichikawa, S. Sorenson, A. H. Fritz, T. A. Moh, A. Mackenzie, D. S. Hui, S. L. Econs, M. J. TI Ablation of the Galnt3 Gene in Mice Leads to Low Circulating Fgf23 Concentrations and Hyperphosphatemia Despite Increased Fgf23 Gene Expression SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Ichikawa, S.; Sorenson, A. H.; Moh, A.; Mackenzie, D. S.; Hui, S. L.; Econs, M. J.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Fritz, T. A.] NIDDK, Sect Biol Chem, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S6 EP S6 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000019 ER PT J AU Islam, MS Chen, I Adams, D Xi, J Li, H Kronenberg, M Duffin, M Morasso, M Reichenberger, E Lichtler, AC AF Islam, M. S. Chen, I. Adams, D. Xi, J. Li, H. Kronenberg, M. Duffin, M. Morasso, M. Reichenberger, E. Lichtler, A. C. TI High Bone Mass Phenotype in the Bone Specific Dlx3 Knock Out mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Islam, M. S.] Univ Minnesota, Minneapolis, MN USA. [Chen, I.; Adams, D.; Xi, J.; Li, H.; Kronenberg, M.; Duffin, M.; Morasso, M.; Lichtler, A. C.] Univ Connecticut, Farmington, CT USA. [Morasso, M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S380 EP S381 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411002164 ER PT J AU Kiel, DP Hannan, MT Barton, BA Lang, TF Bouxsein, ML Brown, K Shane, E Magaziner, J Zimmerman, S Harris, T Rubin, CT AF Kiel, D. P. Hannan, M. T. Barton, B. A. Lang, T. F. Bouxsein, M. L. Brown, K. Shane, E. Magaziner, J. Zimmerman, S. Harris, T. Rubin, C. T. TI The "Vibes" Trial: Low Magnitude Mechanical Stimulation (LMMS) to Improve Bone Mineral Density (BMD). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Kiel, D. P.; Hannan, M. T.] Hebrew Rehab Ctr, IFAR, Boston, MA USA. [Barton, B. A.; Brown, K.] Maryland Med Res Inst, Baltimore, MD USA. [Lang, T. F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bouxsein, M. L.] BIDMC, Ortho Biomech Lab, Boston, MA USA. [Shane, E.] Columbia Univ, New York, NY USA. [Magaziner, J.] Univ MD, Baltimore, MD USA. [Zimmerman, S.] UNC, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC USA. [Harris, T.] NIA, Washington, DC USA. [Rubin, C. T.] SUNY Stony Brook, Stony Brook, NY 11794 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S474 EP S474 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411002531 ER PT J AU Lang, TF Hughes, T Sigurdsson, S Sigurdsson, G Harris, TB Siggeirsdottir, K Gudnason, V Launer, L AF Lang, T. F. Hughes, T. Sigurdsson, S. Sigurdsson, G. Harris, T. B. Siggeirsdottir, K. Gudnason, V. Launer, L. TI Proximal Femoral Fragility and Age-Related White Matter Lesions by Brain MRI in Elderly Subjects: the Age Gene/Environment Susceptibility Study-Reykjavik SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Lang, T. F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hughes, T.; Harris, T. B.; Launer, L.] NIA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. [Sigurdsson, G.] Landspitali, Endocrinol, Reykjavik, Iceland. [Sigurdsson, S.; Siggeirsdottir, K.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S28 EP S28 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000097 ER PT J AU Marini, JC Abukhaled, MK Cintas, HL Obafemi, AA Troendle, JF Letocha, AD Reynolds, JC Paul, S AF Marini, J. C. Abukhaled, M. K. Cintas, H. L. Obafemi, A. A. Troendle, J. F. Letocha, A. D. Reynolds, J. C. Paul, S. TI Randomized Dose Comparison of Pamidronate in Children with Types III and IV Osteogenesis Imperfecta: 3 vs 6 Month Cycles. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Marini, J. C.; Abukhaled, M. K.; Obafemi, A. A.; Letocha, A. D.] NICHHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. [Cintas, H. L.; Paul, S.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Troendle, J. F.] NICHHD, Biometry & Math Stat Branch, NIH, Bethesda, MD 20892 USA. [Reynolds, J. C.] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S370 EP S370 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411002130 ER PT J AU Matsunobu, T Kulkarni, AB Karlsson, S Yamada, Y AF Matsunobu, T. Kulkarni, A. B. Karlsson, S. Yamada, Y. TI Critical Role of TGF-beta Signaling Pathways in Skeletal Development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Matsunobu, T.; Kulkarni, A. B.; Yamada, Y.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. [Karlsson, S.] Lund Univ, Lund Strateg Ctr Stem Cell Biol & Cell Therapy, Lund, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S24 EP S24 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000080 ER PT J AU Ou, G Isales, C Hamrick, M Ding, K Yang, S Gonzalez, F Kream, B Shi, X AF Ou, G. Isales, C. Hamrick, M. Ding, K. Yang, S. Gonzalez, F. Kream, B. Shi, X. TI Targeted Disruption of PPAR gamma in Bone Marrow Stromal Cells Reveals Its Role in Aging-Induced Bone Loss. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Ou, G.; Isales, C.; Ding, K.; Shi, X.] Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. [Isales, C.] Med Coll Georgia, Dept Orthopaed, Augusta, GA 30912 USA. [Yang, S.] Wayne State Univ, Dept Orthopaed Surg, Detroit, MI USA. [Gonzalez, F.] NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Kream, B.] Univ Connecticut, Ctr Hlth, Dept Med & Genet, Farmington, CT USA. [Kream, B.] Univ Connecticut, Ctr Hlth, Dept Dev Biol, Farmington, CT USA. [Shi, X.] Med Coll Georgia, Dept Pathol, Augusta, GA 30912 USA. RI Isales, Carlos/J-9902-2013; Hamrick, Mark/K-1131-2016 OI Isales, Carlos/0000-0002-4480-3484; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S42 EP S42 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000149 ER PT J AU Oz, OK Hajibeigi, A Korach, K Chambon, P Zerwekh, J AF Oz, O. K. Hajibeigi, A. Korach, K. Chambon, P. Zerwekh, J. TI Regulation of Renal Klotho: The Importance of ER alpha SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Oz, O. K.; Hajibeigi, A.; Zerwekh, J.] UT SW Med Ctr, Dallas, TX USA. [Korach, K.] NIEHS, NIH, Environm Dis Med Program, Res Triangle Pk, NC 27709 USA. [Chambon, P.] Univ Strasbourg 1, CNRS, UMR 7104, INSERM,U596, Strasbourg, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S175 EP S175 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001025 ER PT J AU Panaroni, C Gioia, R Lupi, A Farina, A Casasco, M Perilli, E Baruffaldi, F Cetta, G Goldstein, SA Kreider, J Villa, I Rossi, A Marini, JC Frattini, A Vezzoni, P Forlino, A AF Panaroni, C. Gioia, R. Lupi, A. Farina, A. Casasco, M. Perilli, E. Baruffaldi, F. Cetta, G. Goldstein, S. A. Kreider, J. Villa, I. Rossi, A. Marini, J. C. Frattini, A. Vezzoni, P. Forlino, A. TI In utero Stem Cell Therapy as Treatment for Classical Osteogenesis Imperfecta Using the Knock In Murine Model BrtIIV SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Panaroni, C.; Gioia, R.; Lupi, A.; Baruffaldi, F.; Cetta, G.; Rossi, A.; Forlino, A.] Univ Pavia, Dept Biochem, I-27100 Pavia, Italy. [Farina, A.; Casasco, M.] Univ Pavia, Dept Expt Med, I-27100 Pavia, Italy. [Perilli, E.] Ist Ortoped Rizzoli, Lab Tecnol Med, Bologna, Italy. Univ Michigan, Orthopaed Res Labs, Ann Arbor, MI 48109 USA. [Villa, I.] Ist Sci San Raffaele, Bone Metab Unit, I-20132 Milan, Italy. [Marini, J. C.] NICHD, BEMB, Bethesda, MD USA. [Frattini, A.] Ist Clin Humanitas, Milan, Italy. [Vezzoni, P.] Ist Clin Rozzano, Milan, Italy. RI Rossi, Antonio/E-9935-2012; Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 6 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S129 EP S129 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000464 ER PT J AU Raggio, CL Fishbein, KW Carter, EM Kim, M Pleshko, N Spencer, RG AF Raggio, C. L. Fishbein, K. W. Carter, E. M. Kim, M. Pleshko, N. Spencer, R. G. TI Identification of Skin Abnormalities in Osteogenesis Imperfecta Patients by Magnetic Resonance Imaging-A Pilot Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Carter, E. M.] Hosp Special Surg, Kathryn O & Alan C Greenberg Ctr Skeletal Dysplas, New York, NY 10021 USA. [Spencer, R. G.] NIA, Nucl Magnet Resonance Unit, NIH, Baltimore, MD 21224 USA. [Kim, M.] Hosp Special Surg, Mineralized Tissue Lab, New York, NY 10021 USA. [Pleshko, N.] Exponent, Biomech, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S240 EP S240 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001260 ER PT J AU Rianon, N Lang, T Sigurdsson, G Siggeirsdottir, K Eiriksdottir, G Sigurdsson, S Jonsson, B Gudnason, V Harris, T AF Rianon, N. Lang, T. Sigurdsson, G. Siggeirsdottir, K. Eiriksdottir, G. Sigurdsson, S. Jonsson, B. Gudnason, V. Harris, T. TI A Composite Bone Score with QCT Bone Measurements and Fracture History. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Rianon, N.; Harris, T.] NIA, LEDB, Bethesda, MD 20892 USA. [Lang, T.] UCSF, San Francisco, CA USA. [Sigurdsson, G.; Gudnason, V.] Univ Iceland, Reykjavik, Iceland. [Siggeirsdottir, K.; Eiriksdottir, G.; Sigurdsson, S.] Iceland Heart Assoc, Kopavogur, Iceland. [Jonsson, B.] Orthoped Univ Hosp, Malmo, Sweden. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S314 EP S314 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001552 ER PT J AU Saito, H Ellwanger, K Clement-Lacroix, P Hesse, E Maltry, N Niedermeyer, J Lee, RW Rawadi, G Westphal, H Niehrs, C Baron, R AF Saito, H. Ellwanger, K. Clement-Lacroix, P. Hesse, E. Maltry, N. Niedermeyer, J. Lee, R. W. Rawadi, G. Westphal, H. Niehrs, C. Baron, R. TI Deletion of the Dkk1 Co-receptors Kremen 1 and Kremen 2 in Mice Leads to Increased Bone Formation and Bone Mass SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Saito, H.; Hesse, E.; Baron, R.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Ellwanger, K.; Niedermeyer, J.; Lee, R. W.; Niehrs, C.] DKFZ, Heidelberg, Germany. [Westphal, H.] NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S2 EP S2 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000005 ER PT J AU Samelson, EJ Massaro, JM Fox, CS Tucker, KL Booth, SL Wang, TJ Broe, KE Berry, SD Hannan, MT McLean, RR Cupples, LA O'Donnell, CJ Kiel, DP AF Samelson, E. J. Massaro, J. M. Fox, C. S. Tucker, K. L. Booth, S. L. Wang, T. J. Broe, K. E. Berry, S. D. Hannan, M. T. McLean, R. R. Cupples, L. A. O'Donnell, C. J. Kiel, D. P. TI Calcium Intake Is Not Associated with Increased Coronary Artery Calcification: The Framingham QCT Study. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Samelson, E. J.; Broe, K. E.; Berry, S. D.; Hannan, M. T.; McLean, R. R.; Kiel, D. P.] Harvard Univ, Sch Med, Inst Aging Res, Boston, MA USA. [Massaro, J. M.; Cupples, L. A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Fox, C. S.; O'Donnell, C. J.] NHLBI, Framingham, MA USA. [Tucker, K. L.; Booth, S. L.] Tufts Univ, Boston, MA 02111 USA. [Wang, T. J.] Harvard Univ, Sch Med, MA Gen Hosp, Boston, MA USA. RI Tucker, Katherine/A-4545-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S58 EP S58 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000208 ER PT J AU Sigurdsson, G Aspelund, T Siggeirsdottir, K Jonsson, B Mogensen, B Sigurdsson, S Launer, L Harris, TB Lang, TF Gudnason, V AF Sigurdsson, G. Aspelund, T. Siggeirsdottir, K. Jonsson, B. Mogensen, B. Sigurdsson, S. Launer, L. Harris, T. B. Lang, T. F. Gudnason, V. TI Prediction of Incidental Low Trauma Limb Fractures in Older Men and Women with Quantitative CT(QCT) Variables of Bone and Muscles in Mid-Thigh: The AGES-Reykjavik Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Sigurdsson, G.; Aspelund, T.; Siggeirsdottir, K.; Jonsson, B.; Mogensen, B.; Sigurdsson, S.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Launer, L.; Harris, T. B.] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Gudnason, V.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S118 EP S118 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000424 ER PT J AU Theman, TA Collins, MT Dempster, DW Zhou, H Reynolds, JC Brahim, JS Roschger, P Klaushofer, K Winer, KK AF Theman, T. A. Collins, M. T. Dempster, D. W. Zhou, H. Reynolds, J. C. Brahim, J. S. Roschger, P. Klaushofer, K. Winer, K. K. TI Safety and Efficacy of Long-Term Parathyroid Hormone Replacement in a Pediatric Patient with Inherited Hypoparathyroidism: Skeletal and Renal Outcomes SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Theman, T. A.; Collins, M. T.] NIDCR, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. [Dempster, D. W.; Zhou, H.] Helen Hayes Hosp, Reg Bone Ctr, W Haverstraw, NY USA. [Reynolds, J. C.] NIH, Nucl Med CC, Bethesda, MD 20892 USA. [Roschger, P.; Klaushofer, K.] Hanusch Hosp, Ludwig Boltzmann Inst Osteol, Vienna, Austria. [Winer, K. K.] NICHD, ENGB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S103 EP S103 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000368 ER PT J AU von Marschall, Z Fisher, LW AF von Marschall, Z. Fisher, L. W. TI Specific Forms of DMPI Support Attachment and Haptotactic Migration via alpha V beta 3 but not alpha V beta 5 Integrin SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [von Marschall, Z.; Fisher, L. W.] NIH, CSDB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S97 EP S97 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000348 ER PT J AU Wu, JY Maes, C Chen, M Weinstein, LS Kronenberg, HM AF Wu, J. Y. Maes, C. Chen, M. Weinstein, L. S. Kronenberg, H. M. TI Deletion of the G Protein Subunit Gs alpha in Early Osteoblasts Leads to Accelerated Osteoblast Maturation and Formation of Woven Bone with Abnormal Osteocytes, Resulting in Severe Osteoporosis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Wu, J. Y.; Maes, C.; Kronenberg, H. M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Chen, M.; Weinstein, L. S.] NIDDK, Metab Dis Branch, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S71 EP S71 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000255 ER PT J AU Yang, W Harris, MA Cui, Y Skinner, C Chen, X Lai, Y Lichtler, A Kream, B Mishina, Y Harris, SE AF Yang, W. Harris, M. A. Cui, Y. Skinner, C. Chen, X. Lai, Y. Lichtler, A. Kream, B. Mishina, Y. Harris, S. E. TI Conditional Deletion of BMP2 Gene in Early Osteoblasts Leads to Reduction in the Total Bone Marrow (BM) Mesenchymal Stem Cells and Their Capacity to Form Osteoblast Precursors SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Yang, W.; Harris, M. A.; Cui, Y.; Skinner, C.; Chen, X.; Lai, Y.; Harris, S. E.] U Texas HSC San Antonio, San Antonio, TX USA. [Lichtler, A.; Kream, B.] U Connecticut Med CTR, Farmington, CT USA. [Mishina, Y.] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S33 EP S33 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000115 ER PT J AU Zemel, B Kalkwarf, H Gilsanz, V Lappe, J Oberfield, S Shepherd, J Mahboubi, S Frederick, M Winer, K AF Zemel, B. Kalkwarf, H. Gilsanz, V. Lappe, J. Oberfield, S. Shepherd, J. Mahboubi, S. Frederick, M. Winer, K. TI A Clinical Tool for Adjusting BMD Z-Scores for Body Size in Growing Children? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Zemel, B.] Univ Penn, Philadelphia, PA 19104 USA. [Kalkwarf, H.] Cincinnati Childrens Med Ctr, Cincinnati, OR USA. [Gilsanz, V.] Los Angeles Childrens Hosp, Los Angeles, CA USA. [Lappe, J.] Creighton Univ, Omaha, NE 68178 USA. [Oberfield, S.] Columbia Univ, New York, NY USA. [Shepherd, J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mahboubi, S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Frederick, M.] CTASC, Baltimore, MD USA. [Winer, K.] NICHD, Bethesda, MD USA. RI Zemel, Babette/D-1117-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S30 EP S31 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000106 ER PT J AU Zhao, L Huang, J Guo, R Chen, D Zhang, YE Boyce, BF Xing, L AF Zhao, L. Huang, J. Guo, R. Chen, D. Zhang, Y. E. Boyce, B. F. Xing, L. TI Age-related Bone Loss in Mice Associated with Ubiquitin Ligase Smurf1 Degradation of JunB Protein and Reduced Osteoblast Proliferation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Zhao, L.; Guo, R.; Boyce, B. F.; Xing, L.] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA. [Huang, J.; Chen, D.] Univ Rochester, Med Ctr, Dept Orthopaed, Rochester, NY 14642 USA. [Zhang, Y. E.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RI Huang, Jian/B-3146-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S33 EP S33 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000114 ER PT J AU Touz, MC Ropolo, AS Rivero, MR Vranych, CV Conrad, JT Svard, SG Nash, TE AF Carolina Touz, Maria Silvana Ropolo, Andrea Romina Rivero, Maria Veronica Vranych, Cecilia Conrad, John Thomas Svard, Staffan Gunnar Nash, Theodore Elliott TI Arginine deiminase has multiple regulatory roles in the biology of Giardia lamblia SO JOURNAL OF CELL SCIENCE LA English DT Article DE arginine deiminase; citrullination; sumoylation; antigenic variation; encystation; gene regulation ID INTESTINAL EPITHELIAL-CELLS; SURFACE PROTEIN; ANTIGENIC VARIATION; PERIPHERAL VACUOLES; CITRULLINE RESIDUES; ANTIBODIES; DIFFERENTIATION; PALMITOYLATION; IDENTIFICATION; CYTOTOXICITY AB The protozoan parasite Giardia lamblia uses arginine deiminase (ADI) to produce energy from free L-arginine under anaerobic conditions. In this work, we demonstrate that, in addition to its known role as a metabolic enzyme, it also functions as a peptidylarginine deiminase, converting protein-bound arginine into citrulline. G. lamblia ADI specifically binds to and citrullinates the arginine in the conserved CRGKA tail of variant-specific surface proteins (VSPs), affecting both antigenic switching and antibody-mediated cell death. During encystation, ADI translocates from the cytoplasm to the nuclei and appears to play a regulatory role in the expression of encystation-specific genes. ADI is also sumoylated, which might modulate its activity. Our findings reveal a dual role played by ADI and define novel regulatory pathways used by Giardia for survival. C1 [Carolina Touz, Maria; Silvana Ropolo, Andrea; Romina Rivero, Maria; Veronica Vranych, Cecilia] INIMEC CONICET, Inst Invest Med Mercedes & Martin Ferreyra, Cordoba, Argentina. [Conrad, John Thomas; Nash, Theodore Elliott] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Svard, Staffan Gunnar] Uppsala Univ, Dept Cell & Mol Biol, SE-75124 Uppsala, Sweden. RP Touz, MC (reprint author), INIMEC CONICET, Inst Invest Med Mercedes & Martin Ferreyra, Friuli 2434, Cordoba, Argentina. EM ctouz@immf.uncor.edu FU Agencia Nacional para la Promocion de la Ciencia y Tecnolog a FONCyT Jovenes PICT2004; National Institutes of Allergy and Infectious Diseases, National Institutes of Health FX Adrian Hehl is acknowledged for his collaboration in the production of anti-ADI pAb, and Alfredo Caceres and laboratory members for providing numerous reagents. This work was partially supported by the Agencia Nacional para la Promocion de la Ciencia y Tecnolog a FONCyT Jovenes PICT2004. This research was also supported in part by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases, National Institutes of Health. NR 44 TC 40 Z9 44 U1 0 U2 8 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 SEP 1 PY 2008 VL 121 IS 17 BP 2930 EP 2938 DI 10.1242/jcs.026963 PG 9 WC Cell Biology SC Cell Biology GA 339SC UT WOS:000258596600016 PM 18697833 ER PT J AU Bauge, C Beauchef, G Leclercq, S Kim, SJ Pujol, JP Galera, P Boumediene, K AF Bauge, C. Beauchef, G. Leclercq, S. Kim, S. J. Pujol, J. P. Galera, P. Boumediene, K. TI NF kappa B mediates IL-1 beta-induced down-regulation of T beta RII through the modulation of Sp3 expression SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE interleukin-1; TGF beta receptors; Sp transcription factors; NF kappa B ID GROWTH-FACTOR-BETA; COLLAGEN GENE-EXPRESSION; II RECEPTOR GENE; ARTICULAR CHONDROCYTES; TRANSFORMING GROWTH-FACTOR-BETA-1; TRANSCRIPTION FACTORS; ACTIVATION; PROMOTER; CELLS; RESPONSIVENESS AB We previously showed that interleukin-1 beta (IL-1 beta) down-regulation of type II TGF beta receptor (T beta RII) involves NF kappa B pathway and requires de novo synthesis of a yet unknown protein. Here, we demonstrate that this effect is mediated through Sp1 site located at position -25 of human T beta RII promoter. Inhibition of transcription factors binding (decoy oligonucleotides or mithramycin) abolished IL-1 beta effect. EMSA and ChIP revealed that this treatment induced Sp3 binding to cis-sequence whereby IL-1 beta exerts its transcriptional effects whereas it decreased that of Sp1. Moreover, although the cytokine did not modulate Sp1 expression, it increased that of Sp3 via NF kappa B pathway. Experiments of gain and loss of function clearly showed that Sp3 inhibited T beta RII expression whereas its silencing abolished IL-1 beta effect. In addition, both Sp1 and Sp3 were found to interact with NF kappa B, which therefore may indirectly interact with T beta RII promoter. Altogether, these data suggest that IL-1 beta decreases T beta RII expression by inducing Sp3 via NF kappa B and its binding on core promote at the expense of Sp1, which could explain the loss of cell responsiveness in certain conditions. These findings bring new insights in the knowledge of the interference between two antagonistic transduction pathways involved in multiple physiopathological processes. C1 [Boumediene, K.] Univ Caen, IFR ICORE 146, Lab Connect Tissue Biochem, F-14032 Caen, France. [Leclercq, S.] St Martin Private Clin, Dept Orthopaed Surg, Caen, France. [Pujol, J. P.] NCI, Chemoprevent Lab, Bethesda, MD 20892 USA. RP Boumediene, K (reprint author), Univ Caen, IFR ICORE 146, Lab Connect Tissue Biochem, F-14032 Caen, France. EM karim.boumediene@unicaen.fr OI BOUMEDIENE, Karim/0000-0001-6517-8318; BAUGE, Catherine/0000-0001-5642-998X FU French Ministry of Education and Research (MENRT) FX We thank Dr Jalinot (Laboratoire de Biologie Moleculaire et Cellulaire, ENS, Lyon, France), Dr Suske (Institut fur Molekularbiologie and tumorforschung, Marburg, Germany) and Dr Kim (National Cancer Institute, Bethesda, MD, USA) for providing pEVR2-p65, pEVR2-Sp1, pCMV-Sp3 and T beta RII promoter constructs, respectively. C. Bauge was a recipient of a fellow from French Ministry of Education and Research (MENRT). NR 27 TC 14 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD SEP-OCT PY 2008 VL 12 IS 5A BP 1754 EP 1766 DI 10.1111/j.1582-4934.2007.00173.x PG 13 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 361EB UT WOS:000260109200035 PM 18053089 ER PT J AU Liu, A Yoshioka, KI Salerno, V Hsieh, P AF Liu, Angen Yoshioka, Ken-ichi Salerno, Vincenzo Hsieh, Peggy TI The mismatch repair-mediated cell cycle checkpoint response to fluorodeoxyuridine SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE mismatch repair; 5-Fluouracil; DNA damage; ATR; colorectal cancer ID COLORECTAL-CANCER PROGNOSIS; DNA-DAMAGE-RESPONSE; MICROSATELLITE-INSTABILITY; BASE-EXCISION; TUMOR-CELLS; HMUTS-ALPHA; MUTS-ALPHA; ATR KINASE; CYTOTOXICITY; 5-FLUOROURACIL AB The loss of DNA mismatch repair (MMR) is responsible for hereditary nonpolyposis colorectal cancer and a subset of sporadic tumors. Acquired resistance or tolerance to some anti-cancer drugs occurs when MMR function is impaired. 5-Fluorouracil (FU), an anti-cancer drug used in the treatment of advanced colorectal and other cancers, and its metabolites are incorporated into RNA and DNA and inhibit thymidylate synthase resulting in depletion of dTTP and incorporation in DNA of uracil. Although the MMR deficiency has been implicated in tolerance to FU, the mechanism of cell killing remains unclear. Here, we examine the cellular response to fluorodeoxyuridine (FdU) and the role of the MMR system. After brief exposure of cells to low closes of FdU, MMR mediates DNA damage signaling during S-phase and triggers arrest: in G2/M in the first cell cycle in a manner requiring MctS alpha, MutL alpha, and DNA replication. Cell cycle arrest is mediated by ATR kinase and results in phosphorylation of Chk1 and SMC1. MutS alpha binds FdU:G mispairs in vitro consistent with its being a DNA damage sensor. Prolonged treatment with FdU results in an irreversible arrest in G2 Chat is independent of MMR status and leads to the accumulation of DNA lesions that are targeted by the base excision repair (BER) pathway. Thus, MMR can act as a direct sensor of FdU-mediated DNA lesions eliciting cell cycle arrest via the ATR/Chk1 pathway. However, at higher levels of damage, other damage surveillance pathways such as BER also play important roles. C1 [Liu, Angen; Yoshioka, Ken-ichi; Salerno, Vincenzo; Hsieh, Peggy] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Hsieh, P (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 5,Room 324, Bethesda, MD 20892 USA. EM ph52x@nih.gov FU Baylor University Medical Center; Massachusetts General Hospital; NIEHS, NIH; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases FX We are grateful to Richard Boland (Baylor University Medical Center) for providing us HCT116 3-6 cells, Paul Nghiem (Massachusetts General Hospital) for providing ATR-wt and ATR-kd U20S cells, and Tom Kunkel (NIEHS, NIH) for providing HEC59 and HEC59 2-4 cells used in this study. This work was funded by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. NR 39 TC 31 Z9 31 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD SEP 1 PY 2008 VL 105 IS 1 BP 245 EP 254 DI 10.1002/jcb.21824 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 346ZX UT WOS:000259109200027 PM 18543256 ER PT J AU Deshet, N Lupu-Meiri, M Espinoza, I Fili, O Shapira, Y Lupu, R Gershengorn, MC Oron, Y AF Deshet, Naamit Lupu-Meiri, Monica Espinoza, Ingrid Fili, Oded Shapira, Yuval Lupu, Ruth Gershengorn, Marvin C. Oron, Yoram TI Plasminogen-induced aggregation of PANC-1 cells requires conversion to plasmin and is inhibited by enclogenous plasminogen activator inhibitor-1 SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID UROKINASE RECEPTOR; SERINE-PROTEASE; PRECURSOR CELLS; PAI-1 GENE; SYSTEM; CANCER; PROUROKINASE; FIBRINOLYSIS; PERMEABILITY; VITRONECTIN AB PANC-1 cells express proteinase-activated receptors (PARs)-1, -2, and respond to their activation by transient elevation of cytosolic [Ca2+]and accelerated aggregation (Wei et al., 2006, J Cell Physiol 206:322-328). We studied the effect of plasminogen (PGN), an inactive precursor of the PAR-1-activating protease, plasmin (PN) on aggregation of pancreatic adenocarcinoma (PDAC) cells. A single dose of PGN time- and dose-dependently promoted PANC-1 cells aggregation in serum-free medium, while PN did not. PANC-1 cells express urokinase plasminogen activator (uPA), which continuously converted PGN to PN. This activity and PGN-induced aggregation were inhibited by the uPA inhibitor amiloride. PGN-incluced aggregation was also inhibited by alpha-antiplasmin and by the PN inhibitor epsilon-aminocaproic acid (EACA). Direct assay of uPA activity revealed very low rate, markedly enhanced in the presence of PGN. Moreover, in PGN activator inhibitor I-deficient PANC-1 cells, uPA activity and PGN-induced aggregation were markedly potentiated. Two additional human PDAC cell lines, MiaPaCa and Colo347, were assayed for PGN-induced aggregation. Both cell lines responded by aggregation and exhibited PGN-enhanced uPA activity. We hypothesized that the continuous conversion of PGN to PN by enclogenous uPA is limited by PN's degradation and negatively controlled by enclogenously produced PAI-1. Indeed, we found that PANC-1 cells inactivate PN with t 1/2 of approximately 7 h, while the continuous addition of PN promoted aggregation. Our data suggest that PANC-1 cells possess intrinsic, PAI-1-sensitive mechanism for promotion of aggregation and differentiation by prolonged exposure to PGN and, possibly, additional precursors of PARs agonists. C1 [Deshet, Naamit; Lupu-Meiri, Monica; Fili, Oded; Shapira, Yuval; Oron, Yoram] Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. [Espinoza, Ingrid; Lupu, Ruth] Evanston NW Healthcare Res Inst, Dept Med, Evanston, IL USA. [Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. RP Oron, Y (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. EM medfair@post.tau.ac.il NR 42 TC 5 Z9 5 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2008 VL 216 IS 3 BP 632 EP 639 DI 10.1002/jcp.21441 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 335EK UT WOS:000258273400008 PM 18366077 ER PT J AU Strizzi, L Mancino, M Bianco, C Raafat, A Gonzales, M Booth, BW Watanabe, K Nagaoka, T Mack, DL Howard, B Callahan, R Smith, GH Salomon, DS AF Strizzi, Luigi Mancino, Mario Bianco, Caterina Raafat, Ahmed Gonzales, Monica Booth, Brian W. Watanabe, Kazuhide Nagaoka, Tadahiro Mack, David L. Howard, Beatrice Callahan, Robert Smith, Gilbert H. Salomon, David S. TI Netrin-1 can affect morphogenesis and differentiation of the mouse mammary gland SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; BETA-CASEIN GENE; EPITHELIAL-CELLS; TRANSGENIC MICE; IN-VITRO; HUMAN CRIPTO-1; ADULT STEM; EXPRESSION; GROWTH; PLURIPOTENCY AB Netrin-1 has been shown to regulate the function of the EGF-like protein Cripto-1 (Cr-1) and affect mammary gland development. Since Cr-1 is a target gene of Nanog and Oct4, we investigated the relationship between Netrin-1 and Cr-1, Nanog and Oct4 during different stages of development in the mouse mammary gland. Results from histological analysis show that exogenous Netrin-1 was able to induce formation of alveolar-like structures within the mammary gland terminal end buds of virgin transgenic Cripto-1 mice and enhance mammary gland alveologenesis in early pregnant FVB/N mice. Results from immunostaining and Western blot analysis show that Netrin-1, Nanog and Oct4 are expressed in the mouse embryonic mammary anlage epithelium while Cripto-1 is predominantly expressed outside this structure in the surrounding mesenchyme. We find that in lactating mammary glands of postnatal FVB/N mice, Netrin-1 expression is highest while Cripto-1 and Nanog levels are lowest indicating that Netrin-1 may perform a role in the mammary gland during lactation. HC-II mouse mammary epithelial cells stimulated with lactogenic hormones and exogenous soluble Netrin-1 showed increased beta-casein expression as compared to control thus supporting the potential role for Netrin-1 during functional differentiation of mouse mammary epithelial cells. Finally, mouse ES cells treated with exogenous soluble Netrin-1 showed reduced levels of Nanog and Cripto-1 and higher levels of beta-III tubulin during differentiation. These results suggest that Netrin-1 may facilitate functional differentiation of mammary epithelial cells and possibly affect the expression of Nanog and/or Cripto-1 in multipotent cells that may reside in the mammary gland. C1 [Strizzi, Luigi; Mancino, Mario; Bianco, Caterina; Raafat, Ahmed; Gonzales, Monica; Booth, Brian W.; Watanabe, Kazuhide; Nagaoka, Tadahiro; Mack, David L.; Callahan, Robert; Smith, Gilbert H.; Salomon, David S.] NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. [Howard, Beatrice] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. RP Salomon, DS (reprint author), NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, 37 Convent Dr,Bldg 37,Room 1112, Bethesda, MD 20892 USA. EM salomond@mail.nih.gov OI Nagaoka, Tadahiro/0000-0002-9391-0243 FU Intramural NIH HHS [Z01 BC009003-25] NR 49 TC 13 Z9 13 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2008 VL 216 IS 3 BP 824 EP 834 DI 10.1002/jcp.21462 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 335EK UT WOS:000258273400029 PM 18425773 ER PT J AU Miller, BT Singh, RP Klauda, JB Hodoscek, M Brooks, BR Woodcock, HL AF Miller, Benjamin T. Singh, Rishi P. Klauda, Jeffery B. Hodoscek, Milan Brooks, Bernard R. Woodcock, H. Lee, III TI CHARMMing: A new, flexible web portal for CHARMM SO JOURNAL OF CHEMICAL INFORMATION AND MODELING LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; BINDING-SITES; CONSERVATION; POTENTIALS; ALGORITHMS; PREDICTION; PRESSURE; PROTEINS; QUANTUM; SYSTEMS AB A new web portal for the CHARMM macromolecular modeling package, CHARMMing (CHARMM interface and graphics, http://www.charmming.org), is presented. This tool provides a user-friendly interface for the preparation, submission, monitoring, and visualization of molecular simulations (i.e., energy minimization, solvation, and dynamics). The infrastructure used to implement the web application is described. Two additional programs have been developed and integrated with CHARMMing: GENRTF, which is employed to define structural features not supported by the standard CHARMM force field, and a job broker, which is used to provide a portable method for using grid and Cluster computing with CHARMMing. The use of the program is described with three proteins: 1YJP, 1O1O, and 1UFY. Source code is provided allowing CHARMMing to be downloaded, installed, and used by supercomputing centers and research groups that have a CHARMM license. Although no software can replace a scientist's own judgment and experience, CHARMMing eases the introduction of newcomers to the molecular modeling discipline by providing a graphical method for running simulations. C1 [Miller, Benjamin T.; Singh, Rishi P.; Klauda, Jeffery B.; Brooks, Bernard R.; Woodcock, H. Lee, III] NHLBI, Natl Inst Hlth, Lab Computat Biol, Bethesda, MD 20892 USA. [Hodoscek, Milan] Natl Inst Chem, Ctr Mol Modeling, SI-1000 Ljubljana, Slovenia. RP Woodcock, HL (reprint author), NHLBI, Natl Inst Hlth, Lab Computat Biol, Bldg 10, Bethesda, MD 20892 USA. EM hlwood@nih.gov RI Woodc, Henry/D-9275-2011; OI Woodcock, Henry/0000-0003-3539-273X; Miller, Benjamin/0000-0003-1647-0122 FU NIH; NHLBI FX We wish to acknowledge Richard M. Venable and Xiongwu Wu for their assistance With preparing the CHARMM input scripts. We also wish to thank the developers of Django (an open source web application framework). Jmol (used for visualization). Ajax Tabs (used to provide the tabbed user interface), Bubble tooltips (provides context-sensitive help), Prototype (a Javascript framework), SDMenu (for the side menu), TableKit (For table sorting), and GreyBox (for various display functionality). This research was supported by the Intramural Research Program of the NIH, NHLBI. NR 47 TC 57 Z9 57 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9596 J9 J CHEM INF MODEL JI J. Chem Inf. Model. PD SEP PY 2008 VL 48 IS 9 BP 1920 EP 1929 DI 10.1021/ci800133b PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Chemistry; Computer Science GA 351BH UT WOS:000259398500018 PM 18698840 ER PT J AU Brenner, D Bago, AG Gallatz, K Palkovits, M Usdin, TB Dobolyi, A AF Brenner, David Bago, Attila G. Gallatz, Katallin Palkovits, Miklos Usdin, Ted Bjoern Dobolyi, Arpad TI Tuberoinfundibular peptide of 39 residues in the embryonic and early postnatal rat brain SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Article DE neuropeptide; transient expression; ontogeny; medial paralemniscal nucleus; amygdalo-hippocampal transitional zone; posterior intralaminar thalamic nucleus ID PARATHYROID-HORMONE; PTH2 RECEPTOR; EXPRESSION; FOREBRAIN; NEURONS; TIP39; EJACULATION; IDENTIFICATION; HYPOTHALAMUS; ORGANIZATION AB Tuberoinfundibular peptide of 39 residues (TIP39) was identified as the endogenous ligand of parathyroid hormone 2 receptor. We have recently demonstrated that TIP39 expression in adult rat brain is confined to the subparafascicular area of the thalamus with a few cells extending laterally into the posterior intralaminar thalamic nucleus (PIL), and the medial paralemniscal nucleus (MPL) in the lateral pontomesencephalic tegmentum. During postnatal development, TIP39 expression increases until postnatal (lay 33 (PND-33), then decreases, and almost completely disappears by PND-125. Here, we report the expression of TIP39 during early brain development. TIP39-immunoreactive (TIP39-ir) neurons in the subparafascicular area first appeared at PND-1. In contrast, TIP39-ir neurons were detectable in the MPL at embryonic day 14.5 (ED-14.5), and the intensity of their labeling increased thereafter. We also identified TIP39-ir neurons between ED-16.5 and PND-5 in two additional brain areas, the PIL and the amygdalo-hippocampal transitional zone (AHi). We confirmed the specificity of TIP39 immunolabeling by demonstrating TIP39 mRNA using in situ hybridization histochemistry. In the PIL, TIP39 neurons are located medial to the CGRP group as demonstrated by double immunolabeling. All TIP39-ir neurons in the AHi and most TIP39-ir neurons in the PIL disappear during early postnatal development. The adult pattern of TIP39-ir fibers emerge during postnatal development. However, fibers emanating from PIL can be followed in the supraoptic decussations towards the hypothalamus at ED-18.5. These TIP39-ir fibers disappear by PND-1. The complex pattern of TIP39 expression during early brain development suggests the involvement of TIP39 in transient functions during ontogeny. (c) 2008 Elsevier B.V. All rights reserved. C1 [Brenner, David; Bago, Attila G.; Gallatz, Katallin; Palkovits, Miklos; Dobolyi, Arpad] Semmelweis Univ, Dept Anat Histol & Embryol, Neuromorphol and Neuroendocrine Res Lab, H-1094 Budapest, Hungary. [Brenner, David; Bago, Attila G.; Gallatz, Katallin; Palkovits, Miklos; Dobolyi, Arpad] Hungarian Acad Sci, H-1094 Budapest, Hungary. [Bago, Attila G.] Natl Inst Neurosurg, H-1145 Budapest, Hungary. [Usdin, Ted Bjoern] NIMH, Sect Fundamental Neurosci, Bethesda, MD 20892 USA. RP Dobolyi, A (reprint author), Semmelweis Univ, Dept Anat Histol & Embryol, Neuromorphol and Neuroendocrine Res Lab, H-1094 Budapest, Hungary. EM dobolyi@ana.sote.hu RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 FU Hungarian Science Foundation [OTKA K67646] FX We appreciate the technical assistance of Erzsebet Tarnokne Voros and Frigyesne Helfferich. Support was provided by the Hungarian Science Foundation (OTKA K67646) for A.D. Arpad Dobolyi is a grantee of the Bolyai Janos Scholarship. NR 38 TC 4 Z9 4 U1 0 U2 1 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 SEP PY 2008 VL 36 IS 1 BP 59 EP 68 DI 10.1016/j.jchemneu.2008.04.001 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 337JT UT WOS:000258433100007 PM 18495420 ER PT J AU Winer, KK Sinaii, N Peterson, D Sainz, B Cutler, GB AF Winer, Karen K. Sinaii, Ninet Peterson, Donna Sainz, Bruno, Jr. Cutler, Gordon B., Jr. TI Effects of once versus twice-daily parathyroid hormone 1-34 therapy in children with hypoparathyroidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PARATHYROID-HORMONE 1-34; LONG-TERM TREATMENT; PHOSPHATE-METABOLISM; VITAMIN-D; BONE; CALCIUM; 1,25-DIHYDROXYVITAMIN-D3; CALCITRIOL; HYPERCALCIURIA; OSTEOPOROSIS AB Context: Hypoparathyroidism is among the few hormonal insufficiency states not treated with replacement of the missing hormone. Long-term conventional therapy with vitamin D and analogs may lead to nephrocalcinosis and renal insufficiency. Objective: Our objective was to compare the response of once-daily vs. twice-daily PTH 1-34 treatment in children with hypoparathyroidism. Setting: The study was conducted at a clinical research center. Subjects: Fourteen children ages 4-17 yr with chronic hypoparathyroidism were studied. Study Design: This was a randomized cross-over trial, lasting 28 wk, which compared two dose regimens, once-daily vs. twice-daily PTH1-34. Each 14-wk study arm was divided into a 2-wk inpatient dose-adjustment phase and a 12-wk outpatient phase. Results: Mean predose serum calcium was maintained at levels just below the normal range. Repeated serum measures over a 24-h period showed that twice-daily PTH 1-34 increased serum calcium and magnesium levels more effectively than a once-daily dose. This was especially evident during the second half of the day (12-24 h). PTH 1-34 normalized mean 24-h urine calcium excretion on both treatment schedules. This was achieved with half the PTH 1-34 dose during the twice-daily regimen compared with the once-daily regimen ( twice-daily, 25 +/- 15 mu g/d vs. once-daily, 58 +/- 28 mu g/d; P < 0.001). Conclusions: We conclude that a twice-daily PTH1-34 regimen provides a more effective treatment of hypoparathyroidism compared with once-daily treatment because it reduces the variation in serum calcium levels and accomplishes this at a lower total daily PTH 1-34 dose. The results showed, as in the previous study of adult patients with hypoparathyroidism, that a twice-daily regimen produced significantly improved metabolic control compared with once-daily PTH 1-34. C1 [Winer, Karen K.] NICHHD, NIH, Ctr Res Mothers & Children, Endocrinol Nutr & Growth Branch, Bethesda, MD 20892 USA. [Sinaii, Ninet] Natl Inst Hlth, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD USA. RP Winer, KK (reprint author), NICHHD, NIH, Ctr Res Mothers & Children, Endocrinol Nutr & Growth Branch, Bldg 6100,Room 4B11, Bethesda, MD 20892 USA. EM winerk@mail.nih.gov FU National Institutes of Health Clinical Center FX We thank the National Institutes of Health Clinical Center fellows and nursing staff for their contributions and support. We also thank nutritionist Nancy Sebring for her contributions. NR 23 TC 52 Z9 55 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2008 VL 93 IS 9 BP 3389 EP 3395 DI 10.1210/jc.2007-2552 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 344TV UT WOS:000258951100021 PM 18492754 ER PT J AU Florio, P Romero, R Chaiworapongsa, T Kusanovic, JP Torricelli, M Lowry, PJ Petraglia, F AF Florio, Pasquale Romero, Roberto Chaiworapongsa, Tinnakorn Kusanovic, Juan Pedro Torricelli, Michela Lowry, Phil J. Petraglia, Felice TI Amniotic fluid and umbilical cord plasma corticotropin-releasing factor (CRF), CRF-binding protein, adrenocorticotropin, and cortisol concentrations in intraamniotic infection and inflammation at term SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MATERNAL PLASMA; HUMAN PLACENTA; PREGNANT-WOMEN; HORMONE; PRETERM; LABOR; ASSOCIATION; MECHANISM; CYTOKINES; PEPTIDES AB Context: Pregnant tissues express corticotropin-releasing factor (CRF), a peptide modulating fetal and placental ACTH and cortisol secretion. These actions are modulated by the locally expressed CRF-binding protein (CRF-BP). Objective: The objective of the study was to determine whether CRF, CRF-BP, ACTH, and cortisol concentrations change in amniotic fluid and umbilical cord plasma in the presence of intraamniotic infection/inflammation (IAI) in women with spontaneous labor at term. Design: This was a cross-sectional study. Setting: The study was conducted at a tertiary referral center for obstetric care. Patients: Patients included women in active labor at term with (n = 39) and without (controls; n = 78) IAI. Main Outcome Measures: Amniotic fluid and umbilical cord plasma concentrations of CRF, CRF-BP, ACTH, and cortisol measured by RIA and immunoradiometric assays were measured. Results: In patients with IAI, amniotic fluid CRF (0.97 +/- 0.18 ng/ml) and CRF-BP (33.06 +/- 5.54 nmol/liter) concentrations were significantly (P < 0.001) higher than in controls (CRF: 0.32 +/- 0.04 ng/ml; CRF-BP: 14.69 +/- 2.79 ml). The umbilical cord plasma CRF and CRF-BP concentrations were significantly (P < 0.001 for all) higher in women with IAI than in controls (CRF: 2.96 +/- 0.35 ng/ml vs. 0.38 +/- 0.18 ng/ml; CRF-BP: 152.12 +/- 5.94 nmol/liter vs. 106.9 +/- 5.97 nmol/liter). In contrast, amniotic fluid and umbilical cord plasma ACTH and cortisol concentrations did not differ between groups. Conclusions: Amniotic fluid and umbilical cord plasma CRF and CRF-BP concentrations are increased in women with spontaneous labor at term and IAI. CRF-BP may modulate CRF actions on ACTH and cortisol secretion, playing a pivotal role in limiting the inflammatory process and thus avoiding an overactivation of the fetal/placental hypothalamus-pituitary-adrenal axis at birth. C1 [Florio, Pasquale; Torricelli, Michela; Petraglia, Felice] Univ Siena, Chair Obstet & Gynecol, Dept Pediat Obstet & Reprod Med, I-53100 Siena, Italy. [Romero, Roberto; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20814 USA. [Romero, Roberto; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI 48202 USA. Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Lowry, Phil J.] Univ Reading, Sch Anim & Microbial Sci, Reading RG6 6UR, England. RP Florio, P (reprint author), Univ Siena, Chair Obstet & Gynecol, Dept Pediat Obstet & Reprod Med, Policlin Le Scotte Viale Bracci, I-53100 Siena, Italy. EM florio@unisi.it RI Torricelli, Michela/N-1785-2016; PETRAGLIA, Felice/K-6535-2016 OI Torricelli, Michela/0000-0001-8608-9875; PETRAGLIA, Felice/0000-0002-8851-625X FU Italian Ministry of University and Scientific Research; University of Siena FX The work was partially supported by grants from the Italian Ministry of University and Scientific Research and the University of Siena ( to F. P.). The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. NR 31 TC 6 Z9 6 U1 0 U2 0 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 SEP PY 2008 VL 93 IS 9 BP 3604 EP 3609 DI 10.1210/jc.2007-2843 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 344TV UT WOS:000258951100052 PM 18559919 ER PT J AU Ma, L Hanson, RL Que, LN Mack, JL Franks, PW Infante, AM Kobes, S Bogardus, C Baier, LJ AF Ma, Lijun Hanson, Robert L. Que, Lorem N. Mack, Janel L. Franks, Paul W. Infante, Aniello M. Kobes, Sayuko Bogardus, Clifton Baier, Leslie J. TI Association analysis of Kruppel-like factor 11 variants with type 2 diabetes in Pima Indians SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TRANSCRIPTION FACTOR KLF11; PANCREATIC-CANCER; CELL-GROWTH; BETA; MECHANISM; MELLITUS; LOCI AB Context: Kruppel-like factor 11 (KLF11) is a transcription factor of the zinc finger domain family that has been shown to regulate expression of the insulin gene. An initial study reported that a KLF11 variant predicting a Q62R was associated with type 2 diabetes (T2D) in French Caucasians; however, subsequent studies have failed to identify an association between this variant and T2D in subjects from a similar Northern-European ancestry. Objective: We sought to determine whether the Q62R or other variants within KLF11 were associated with T2D in Pima Indians, a population with an extremely high prevalence of this disease. Design, Setting, and Subjects: KLF11 was sequenced in 24 Pima Indians to identify potentially novel variants. There were 18 variants genotyped in a family-based sample of 1337 Pima Indians to analyze the linkage disequilibrium pattern of this gene and identify representative variants. Four representative variants were further genotyped in a population-based sample of 3501 full-heritage Pima Indians for association analyses. Among these subjects, 413 had undergone metabolic studies when they were nondiabetic to measure traits that predict T2D. Results: Neither the Q62R nor any other common variant in KLF11 was associated with T2D in the Pima population. In addition, no variant was associated with insulin secretion or insulin-stimulated glucose disposal rate. Conclusions: Common variation in KLF11 variation does not appear to influence the population-based risk for developing T2D among full-heritage Pima Indians. Thus, KLF11 is unlikely to play a major role in the etiology of T2D among this Native American population. C1 [Ma, Lijun; Hanson, Robert L.; Que, Lorem N.; Mack, Janel L.; Franks, Paul W.; Infante, Aniello M.; Kobes, Sayuko; Bogardus, Clifton; Baier, Leslie J.] NIDDK, Diabet Mol Genet Sect, Phoenix Epidemiol & Clin Res Branch, NIH,Dept Hlth & Human Serv, Phoenix, AZ 85004 USA. [Franks, Paul W.] Umea Univ Hosp, Genet Epidemiol & Clin Res Grp, Dept Publ Hlth & Clin Med, Div Med, SE-90187 Umea, Sweden. RP Baier, LJ (reprint author), NIDDK, Diabet Mol Genet Sect, Phoenix Epidemiol & Clin Res Branch, NIH,Dept Hlth & Human Serv, 445 N 5th St,Suite 210, Phoenix, AZ 85004 USA. EM lbaier@phx.niddk.nih.gov RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; Franks, Paul/0000-0002-0520-7604 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX This study was also supported by the intramural research program of National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 16 TC 7 Z9 8 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 SEP PY 2008 VL 93 IS 9 BP 3644 EP 3649 DI 10.1210/jc.2008-0546 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 344TV UT WOS:000258951100058 PM 18593768 ER PT J AU Kim, SJ Zhang, ZJ Sarkar, C Tsai, PC Lee, YC Dye, L Mukherjee, AB AF Kim, Sung-Jo Zhang, Zhongjian Sarkar, Chinmoy Tsai, Pei-Chih Lee, Yi-Ching Dye, Louis Mukherjee, Anil B. TI Palmitoyl protein thioesterase-1 deficiency impairs synaptic vesicle recycling at nerve terminals, contributing to neuropathology in humans and mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSIS; MEMBRANE-FUSION; HIPPOCAMPAL-NEURONS; HUNTINGTONS-DISEASE; MOLECULAR-CLONING; SYNAPTOTAGMIN-I; GOLGI MEMBRANES; KNOCKOUT MICE; ENDOCYTOSIS; EXOCYTOSIS AB Neuronal ceroid lipofuscinoses represent the most common childhood neurodegenerative storage disorders. Infantile neuronal ceroid lipofuscinosis (INCL) is caused by palmitoyl protein thioesterase-1 (PPT1) deficiency. Although INCL patients show signs of abnormal neurotransmission, manifested by myoclonus and seizures, the molecular mechanisms by which PPT1 deficiency causes this abnormality remain obscure. Neurotransmission relies on repeated cycles of exo- and endocytosis of the synaptic vesicles (SVs), in which several palmitoylated proteins play critical roles. These proteins facilitate membrane fusion, which is required for neurotransmitter exocytosis, recycling of the fused SV membrane components, and regeneration of fresh vesicles. However, palmitoylated proteins require depalmitoylation for recycling. Using postmortem brain tissues from an INCL patient and tissue from the PPT1-knockout (PPT1-KO) mice that mimic INCL, we report here that PPT1 deficiency caused persistent membrane anchorage of the palmitoylated SV proteins, which hindered the recycling of the vesicle components that normally fuse with the presynaptic plasma membrane during SV exocytosis. Thus, the regeneration of fresh SVs, essential for maintaining the SV pool size at the synapses, was impaired, leading to a progressive loss of readily releasable SVs and abnormal neurotransmission. This abnormality may contribute to INCL neuropathology. C1 [Kim, Sung-Jo; Zhang, Zhongjian; Sarkar, Chinmoy; Tsai, Pei-Chih; Lee, Yi-Ching; Mukherjee, Anil B.] NICHHD, NIH, Sect Dev Genet, Heritable Disorders Branch, Bethesda, MD 20892 USA. [Dye, Louis] NICHHD, NIH, Microscopy & Imaging Core, Bethesda, MD 20892 USA. RP Mukherjee, AB (reprint author), NICHHD, NIH, Sect Dev Genet, Heritable Disorders Branch, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM mukherja@exchange.nih.gov FU NICHD; NIH FX We thank J.Y. Chou, I. Owens,J.T. Russell, and S.W. Levin For critical review of the manuscript and helpful suggestions. The statistical analysis of the SV data by H. Wei is gratefully acknowledged. We are also grateful to V. Schram (Microscopy and Imaging Core, National Institute of Child Health and Human Development [NICHD]) for confocal microscopy and L. Holtzclaw (Section on Cellular and Synaptic Physiology, NICHD) for her expert assistance with the perfusion of the triouse brain. Brain autopsy tissue samples were obtained from the Human Brain and Spinal Fluid Resource Center at the VA West Los Angeles Healthcare Center (Los Angeles, California, USA), which is sponsored by the National institute of Neurological Disorders and Stroke/National Institute of Mental Health, National Multiple Sciences Society, and the Department of Veterans Affairs. This research was supported in whole by the intramural Research Program of the NICHD, NIH. NR 69 TC 52 Z9 52 U1 0 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 SEP PY 2008 VL 118 IS 9 BP 3075 EP 3086 DI 10.1172/JCI33482 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 344OF UT WOS:000258936500012 PM 18704195 ER PT J AU Osei-Hyiaman, D Liu, J Zhou, L Godlewski, G Harvey-White, J Jeong, WI Batkai, S Marsicano, G Lutz, B Buettner, C Kunos, G AF Osei-Hyiaman, Douglas Liu, Jie Zhou, Liang Godlewski, Grzegorz Harvey-White, Judith Jeong, Won-il Batkai, Sandor Marsicano, Giovanni Lutz, Beat Buettner, Christoph Kunos, George TI Hepatic CB(1) receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FATTY-ACID OXIDATION; REDUCED FOOD-INTAKE; INDUCED OBESITY; RISK-FACTORS; ANTAGONIST SR141716; OVERWEIGHT PATIENTS; ENERGY-EXPENDITURE; WISTAR RATS; BODY-WEIGHT; ZUCKER RATS AB Diet-induced obesity is associated with fatty liver, insulin resistance, leptin resistance, and changes in plasma lipid profile. Endocannabinoids have been implicated in the development of these associated phenotypes, because mice deficient for the cannabinoid receptor CB, (CB1(-/-)) do not display these changes in association with diet-induced obesity. The target tissues that mediate these effects, however, remain unknown. We therefore investigated the relative role of hepatic versus extrahepatic CBI receptors in the metabolic consequences of a high-fat diet, using liver-specific CBI knockout (LCB1(-/-)) mice. LCB1(-/-) mice fed a high-fat diet developed a similar degree of obesity as that of wild-type mice, but, similar to CB1(-/-) mice, had less steatosis, hyperglycemia, dyslipidemia, and insulin and leptin resistance than did wild-type mice fed a high-fat diet. CBI agonist-induced increase in de novo hepatic lipogenesis and decrease in the activity of carnitine paimitoyltransferase-1 and total energy expenditure were absent in both CB1(-/-) and LCB1(-/-) mice. We conclude that endocannabinoid activation of hepatic CB, receptors contributes to the diet-induced steatosis and associated hormonal and metabolic changes, but not to the increase in adiposity, observed with high-fat diet feeding. Theses studies suggest that peripheral CBI receptors could be selectively targeted for the treatment of fatty liver, impaired glucose homeostasis, and dyslipidemia in order to minimize the neuropsychiatric side effects of nonselective CB, blockade during treatment of obesity-associated conditions. C1 [Osei-Hyiaman, Douglas; Liu, Jie; Zhou, Liang; Godlewski, Grzegorz; Harvey-White, Judith; Jeong, Won-il; Batkai, Sandor; Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. [Marsicano, Giovanni] Univ Bordeaux 2, U862, INSERM, Magendie Ctr, F-33076 Bordeaux, France. [Lutz, Beat] Johannes Gutenberg Univ Mainz, Dept Physiol Chem, D-6500 Mainz, Germany. [Buettner, Christoph] Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Kunos, G (reprint author), NIAAA, 5625 Fishers Lane, Rockville, MD 20852 USA. EM gkunos@mail.nih.gov RI Batkai, Sandor/G-3889-2010; JEONG, WON IL/B-6615-2011; Batkai, Sandor/H-7983-2014 FU National Institute on Alcohol Abuse and Alcoholism, NIH; AVENIR; INSERM FX We thank Keming Xiong for expert technical assistance. This study was supported by Funds from the intramural research program of the National Institute on Alcohol Abuse and Alcoholism, NIH. G. Marsicano is supported by an AVENIR grant of INSERM in partnership with Foundation Bettencourt-Schueller. NR 42 TC 228 Z9 231 U1 1 U2 12 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 SEP PY 2008 VL 118 IS 9 BP 3160 EP 3169 DI 10.1172/JCI34827 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 344OF UT WOS:000258936500020 PM 18677409 ER PT J AU Mitchell, C Jennings, C Brambilla, D Aldrovandi, G Amedee, AM Beck, I Bremer, JW Coombs, R Decker, D Fiscus, S Fitzgibbon, J Luzuriaga, K Moye, J Palumbo, P Reichelderfer, P Somasundaran, M Stevens, W Frenkel, L AF Mitchell, Caroline Jennings, Cheryl Brambilla, Donald Aldrovandi, Grace Amedee, Angela Martin Beck, Ingrid Bremer, James W. Coombs, Robert Decker, Don Fiscus, Susan Fitzgibbon, Joseph Luzuriaga, Katherine Moye, John Palumbo, Paul Reichelderfer, Patricia Somasundaran, Mohan Stevens, Wendy Frenkel, Lisa CA IMPAACT Network TI Diminished human immunodeficiency virus type 1 DNA yield from dried blood spots after storage in a humid incubator at 37 degrees C compared to-20 degrees C SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; SUBTYPE-B DNA; HIV-INFECTION; FILTER-PAPER; INFANTS; DIAGNOSIS; STABILITY; SAMPLES; MOTHERS; MORTALITY AB Collecting whole blood on filter paper simplifies the processing, transport, and storage of specimens used for the diagnosis of human immunodeficiency virus type 1 (HIV-1) and other tests. Specimens may be collected in tropical or rural areas with minimal facilities for handling specimens. To compare simulated tropical conditions with freezer storage, we examined the stability of HIV-1 DNA in dried blood spots (DBS) stored in humid heat and at -20 degrees C. DBS were created by spotting 50-mu l aliquots of whole blood on 903 filter paper. DNA was extracted from DBS at baseline and after 2, 6, or 12 months of storage at -20 degrees C or at 37 degrees C with similar to 85% humidity. The DNA was tested undiluted or diluted using the Amplicor HIV-1 DNA PCR (Roche), version 1.5. Each reaction was scored positive, negative, or indeterminate based on optical density. Results were compared between storage conditions and over time. A total of 1,832 reactions from 916 DBS were analyzed, including 100 DBS at baseline, 418 stored at -20 degrees C, and 398 stored at 37 degrees C. A chi-square test showed fewer positive reactions for DBS stored at 37 degrees C (55%) than for those stored at -20 degrees C (78%) (P < 0.0001). Samples stored at -20 degrees C showed little change in the probability of detection of HIV-1 DNA over time; the odds ratio (OR) was 0.93 after storage for 1 year. Samples stored at 37 degrees C demonstrated a significant change in detection at 1 year (OR, 0.29). We conclude that exposure of DBS to 37 degrees C and high humidity impaired the recovery of HIV-1 DNA from DBS, whereas DNA recovery was preserved when DBS were stored frozen. C1 [Beck, Ingrid; Frenkel, Lisa] Seattle Childrens Hosp Res Inst, Seattle, WA 98109 USA. [Mitchell, Caroline; Coombs, Robert; Frenkel, Lisa] Univ Washington, Seattle, WA 98195 USA. [Jennings, Cheryl; Bremer, James W.] Rush Univ, Virol Qual Assurance Lab, Chicago, IL 60612 USA. [Brambilla, Donald] New England Res Inst, Watertown, MA 02172 USA. [Luzuriaga, Katherine; Somasundaran, Mohan] Univ Massachusetts, Worcester, MA 01605 USA. [Aldrovandi, Grace] Univ So Calif, Los Angeles, CA USA. [Aldrovandi, Grace; Decker, Don] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Amedee, Angela Martin] Louisiana State Univ, New Orleans, LA USA. [Fiscus, Susan] Univ N Carolina, Chapel Hill, NC USA. [Fitzgibbon, Joseph] NIAID, Bethesda, MD 20892 USA. [Moye, John; Reichelderfer, Patricia] NICHHD, Bethesda, MD 20892 USA. [Palumbo, Paul] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Stevens, Wendy] Univ Witwatersrand, Johannesburg, South Africa. RP Frenkel, L (reprint author), Seattle Childrens Hosp Res Inst, 1900 9th Ave, Seattle, WA 98109 USA. EM lfrenkel@u.washington.edu OI moye, john/0000-0001-9976-8586 FU Children's LA [HD 40777]; NIH [U01 AI068632-01]; DAIDS [N01-AI-5044, U01AI068632, U01 AI068632, NO1-HD-3-3612] FX This project was funded by Children's LA grant HD 40777 (to G. A.) and NIH awards U01 AI068632-01 (to G. A.), N01-AI-5044 DAIDS (to J.W.B.), U01AI068632 (to S. F.), U01 AI068632 (to L. F.), and NO1-HD-3-3612 (to L. F.). NR 16 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2008 VL 46 IS 9 BP 2945 EP 2949 DI 10.1128/JCM.00359-08 PG 5 WC Microbiology SC Microbiology GA 344FS UT WOS:000258912900020 PM 18614660 ER PT J AU Krull, KR Okcu, MF Potter, B Jain, N Dreyer, Z Kamdar, K Brouwers, P AF Krull, Kevin R. Okcu, M. Fatih Potter, Brian Jain, Neelam Dreyer, ZoAnn Kamdar, Kala Brouwers, Pim TI Screening for neurocognitive impairment in pediatric cancer long-term survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; COGNITIVE IMPAIRMENT; INITIAL VALIDATION; CHILDHOOD-CANCER; NORMATIVE DATA; PERFORMANCE; DEMENTIA; CHILDREN; ASSOCIATION; STRATEGIES AB Purpose Recent studies suggest that up to 40% of childhood cancer survivors may experience neurocognitive problems, a finding that has led the Children's Oncology Group to recommend regular evaluation. However, for a variety of reasons, including costs, time restraints, health insurance, and access to professional resources, these guidelines are often difficult to implement. We report reliability and validity data on a brief neurocognitive screening method that could be used to routinely screen patients in need of comprehensive follow-up. Patients and Methods Two hundred forty consecutive patients were screened during their annual visits to a long-term survivor clinic using standard neurocognitive measures and brief parent rating. From this total, 48 patients had a second screening, and 52 patients had a comprehensive follow-up evaluation. Test-retest reliability and predictive and discriminative validity were examined. Results Good test-retest reliability was demonstrated, with an overall r = 0.72 and all individual subtest correlations greater than r = 0.40. Although means tended to improve from first to second testing, no significant changes were detected (all P >.10). The screen accurately predicted global intellect (F-6,F-45 = 11.81, P < .0001), reading skills (F-6,F-45 = 4.74, P < .001), and mathematics (F-6,F-45 = 3.35, P < .008). Parent rating was a marginal indicator of global intellect only. Conclusion The brief neurocognitive screening was a better predictor of child functioning than specific parent rating. This brief measure, which can be completed in 30 minutes, is a practical and reliable method to identify cancer survivors in need of further neurocognitive follow-up. C1 Texas Childrens Hosp, Dept Child Psychol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Texas Childrens Canc Ctr, Houston, TX USA. NIMH, Div AIDS & Hlth & Behav Res, Rockville, MD 20857 USA. RP Krull, KR (reprint author), St Jude Childrens Hosp, Dept Epidemiol & Canc Control, 332 N Lauderdale St,MS 735, Memphis, TN 38105 USA. EM kevin.krull@stjude.org NR 38 TC 39 Z9 39 U1 2 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2008 VL 26 IS 25 BP 4138 EP 4143 DI 10.1200/JCO.2008.16.8864 PG 6 WC Oncology SC Oncology GA 350KB UT WOS:000259350200013 PM 18757327 ER PT J AU Egorin, M Ramanathan, RK Gibbons, J Petros, W Ivy, SP Remick, SC AF Egorin, Merrill Ramanathan, Ramesh K. Gibbons, Joseph Petros, William Ivy, S. Percy Remick, Scot C. TI Inhibition of imatinib transport by uremic toxins during renal failure - In reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID DYSFUNCTION WORKING GROUP; ADVANCED MALIGNANCIES; VARYING DEGREES; PHASE-I; MESYLATE; LIVER C1 [Egorin, Merrill] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. [Ramanathan, Ramesh K.] Scottsdale Clin Res Inst, Translat Genom Inst, Scottsdale, AZ USA. [Gibbons, Joseph] Case Comprehens Canc Ctr, Cleveland, OH USA. [Petros, William; Remick, Scot C.] Mary Babb Randolph Canc Ctr, Morgantown, WV USA. [Ivy, S. Percy] NCI, Bethesda, MD 20892 USA. RP Egorin, M (reprint author), Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2008 VL 26 IS 25 BP 4227 EP 4228 DI 10.1200/JCO.2008.18.5470 PG 2 WC Oncology SC Oncology GA 350KB UT WOS:000259350200035 ER PT J AU Brar, S Leu, J Kim, Y Venitz, J AF Brar, S. Leu, J. Kim, Y. Venitz, J. TI Effects of smoking and gender on tetrahydroisoquinolines (TIQ) and beta-carbolines in a healthy population SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 14-16, 2008 CL Philadelphia, PA SP Amer Coll Clin Pharmacol C1 NIAAA, NIH, Bethesda, MD USA. Virginia Commonwealth Univ, Dept Pharmaceut, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2008 VL 48 IS 9 MA 100 BP 1122 EP 1122 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 341MT UT WOS:000258719300099 ER PT J AU Kim, Y Herion, D George, DT Venitz, J AF Kim, Y. Herion, D. George, D. T. Venitz, J. TI Effects of smoking on R- and S-salsolinol and dopamine in a healthy population and during alcohol detoxification SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 14-16, 2008 CL Philadelphia, PA SP Amer Coll Clin Pharmacol C1 NIAAA, NIH, Bethesda, MD USA. Virginia Commonwealth Univ, Dept Pharmaceut, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2008 VL 48 IS 9 MA 101 BP 1122 EP 1122 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 341MT UT WOS:000258719300100 ER PT J AU Hasin, DS Keyes, KM Alderson, D Wang, S Aharonovich, E Grant, BE AF Hasin, Deborah S. Keyes, Katherine M. Alderson, Donald Wang, Shuang Aharonovich, Efrat Grant, Bridget E. TI Cannabis withdrawal in the United States: Results from NESARC SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ALCOHOL-USE DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; INTERVIEW SCHEDULE AUDADIS; SUBSTANCE USE DISORDERS; GENERAL-POPULATION SAMPLE; DSM-IV ALCOHOL; MARIJUANA WITHDRAWAL; DRUG-USE; ABSTINENCE SYMPTOMS; SMOKED MARIJUANA AB Objective: Although cannabis is the most widely abused illicit drug, little is known about the prevalence of cannabis withdrawal and its factor structure, clinical validity, and psychiatric correlates in the general population. Method: National Epidemiologic Survey on Alcohol and Related Conditions participants were assessed, in 2001-2002, with structured in-person interviews covering substance history, DSM-IV Axis I and 11 disorders, and withdrawal symptoms after cessation of use. Of these, 2613 had been frequent cannabis users (>= 3 times/week), and a "cannabis-only" subset (N = 1119) never binge-drank or used other drugs 3 times/week. Results: In the full sample and subset, 44.3% (SE = 1.19) and 44.2% (SE = 1.75), respectively, experienced ! 2 cannabis withdrawal symptoms, while 34.4% (SE = 1.21) and 34.1% (SE = 1.76), respectively, experienced ! 3 symptoms. The symptoms formed 2 factors, one characterized by weakness, hypersomnia, and psychomotor retardation and the second by anxiety, restlessness, depression, and insomnia. Both symptom types were associated with significant distress/impairment (p < .01), substance use to relieve/avoid cannabis withdrawal symptoms (p < .01), and quantity of cannabis use (among the cannabis-only users p < .05). Panic (p < .01) and personality (p <= .01) disorders were associated with anxiety symptoms in both samples, family history of drug problems was associated with weakness symptoms in the subset (p = .01), and depression was associated with both sets of symptoms in the subset (p < .05). Conclusion: Cannabis withdrawal was prevalent and clinically significant among a representative sample of frequent cannabis users. Similar results in the subset without polysubstance abuse confirmed the specificity of symptoms to cannabis. Cannabis withdrawal should be added to DSM-V, and the etiology and treatment implications of cannabis withdrawal symptoms should be investigated. C1 [Hasin, Deborah S.; Keyes, Katherine M.; Alderson, Donald; Wang, Shuang; Aharonovich, Efrat] Columbia Univ, New York State Psychiat Inst, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Grant, Bridget E.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, US Dept HHS,NIH, Bethesda, MD USA. RP Hasin, DS (reprint author), Columbia Univ, New York State Psychiat Inst, Mailman Sch Publ Hlth, 1051 Riverside Dr,Box 123, New York, NY 10032 USA. EM dsh2@columbia.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Md [K05 AA014223]; National Institute on Drug Abuse (NIDA), Bethesda, Md [R01 DA018652]; National Institutes of Health, NIAAA FX The National epidemiologic Survey on Alcohol and Related Conditions was conducted and funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Md., with supplemental funding by the National Institute on Drug Abuse (NIDA). Bethesda, Md. This study was funded in part by the Intramural Program of the National Institutes of Health, NIAAA. This research was supported in part by grants from the NIAAA (K05 AA014223) and the NIDA (R01 DA018652) and support from New York State Psychiatric Institute.; The authors thank Vialerie Richmond, M.A., New York State Psychiatric Institute, New York, for manuscript preparation and editorial assistance. Ms. Richmond reports no financial or other relationships relevant to the subject of this article.; The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of any sponsoring organization, agencies, or the U.S. government.; The authors report no additional financial or other relationships relevant to the subject of this article. NR 45 TC 63 Z9 65 U1 2 U2 7 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2008 VL 69 IS 9 BP 1354 EP 1363 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 355NV UT WOS:000259716500002 PM 19012815 ER PT J AU Guyer, AE Monk, CS McClure-Tone, EB Nelson, EE Roberson-Nay, R Adler, AD Fromm, SJ Leibenluft, E Pine, DS Ernst, M AF Guyer, Amanda E. Monk, Christopher S. McClure-Tone, Erin B. Nelson, Eric E. Roberson-Nay, Roxann Adler, Abby D. Fromm, Stephen J. Leibenluft, Ellen Pine, Daniel S. Ernst, Monique TI A developmental examination of amygdala response to facial expressions SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID FUSIFORM FACE AREA; EVENT-RELATED FMRI; HUMAN BRAIN; ANTERIOR CINGULATE; PREFRONTAL CORTEX; FUNCTIONAL CONNECTIVITY; EMOTIONAL RESPONSES; NEURAL RESPONSES; ADOLESCENT BRAIN; SOCIAL-BEHAVIOR AB Several lines of evidence implicate the amygdala in face emotion processing, particularly for fearful facial expressions. Related findings suggest that face-emotion processing engages the amygdala within an interconnected circuitry that can be studied using a functional-connectivity approach. Past work also underscores important functional changes in the amygdala during development. Taken together, prior research on amygdala function and development reveals a need for more work examining developmental changes in the amygdala's response to fearful faces and in amygdala functional connectivity during face processing. The present study used event-related functional magnetic resonance imaging to compare 31 adolescents (9-17 years old) and 30 adults (21-40 years old) on activation to fearful faces in the amygdala and other regions implicated in face processing. Moreover, these data were used to compare patterns of amygdala functional connectivity in adolescents and adults. During passive viewing, adolescents demonstrated greater amygdala and fusiform activation to fearful faces than did adults. Functional connectivity analysis revealed stronger connectivity between the amygdala and the hippocampus in adults than in adolescents. Within each group, variability in age did not correlate with amygdala response, and sex-related developmental differences in amygdala response were not found. Eye movement data collected outside of the magnetic resonance imaging scanner using the same task suggested that developmental differences in amygdala activation were not attributable to differences in eye-gaze patterns. Amygdala hyperactivation in response to fearful faces may explain increased vulnerability to affective disorders in adolescence; stronger amygdala - hippocampus connectivity in adults than adolescents may reflect maturation in learning or habituation to facial expressions. C1 [Guyer, Amanda E.] NIMH, MAP, NIH, Bethesda, MD 20892 USA. [Monk, Christopher S.] Univ Michigan, Ann Arbor, MI 48109 USA. [McClure-Tone, Erin B.] Georgia State Univ, Atlanta, GA 30303 USA. [Roberson-Nay, Roxann] Virginia Commonwealth Univ, Richmond, VA 23284 USA. RP Guyer, AE (reprint author), NIMH, MAP, NIH, 15K N Dr,Room 208,MSC 2670, Bethesda, MD 20892 USA. EM amandaguyer@mail.nih.gov RI Nelson, Eric/B-8980-2008 OI Nelson, Eric/0000-0002-3376-2453 FU Intramural Research Program of the National Institute of Mental Health; National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. NR 94 TC 153 Z9 154 U1 8 U2 35 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD SEP PY 2008 VL 20 IS 9 BP 1565 EP 1582 DI 10.1162/jocn.2008.20114 PG 18 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 341EB UT WOS:000258695900004 PM 18345988 ER PT J AU Zhao, Y Flandin, P Long, JE Dela Cuesta, M Westphal, H Rubenstein, JLR AF Zhao, Yangu Flandin, Pierre Long, Jason E. Dela Cuesta, Melissa Westphal, Heiner Rubenstein, John L. R. TI Distinct molecular pathways for development of telencephalic interneuron subtypes revealed through analysis of Lhx6 mutants SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE Lhx6; Dlx; GABAergic; interneuron; NPY ID CORTICAL GABAERGIC INTERNEURONS; FOREBRAIN CHOLINERGIC NEURONS; MEDIAL GANGLIONIC EMINENCE; LIM-HOMEOBOX GENE; CELL-MIGRATION; DLX GENES; TRANSCRIPTION FACTORS; DEVELOPING NEOCORTEX; BASAL FOREBRAIN; CEREBRAL-CORTEX AB Here we analyze the role of the Lhx6 lim-homeobox transcription factor in regulating the development of subsets of neocortical, hippocampal, and striatal interneurons. An Lhx6 loss-of-function allele, which expresses placental alkaline phosphatase (PLAP), allowed analysis of the development and fate of Lhx6-expressing interneurons in mice lacking this homeobox transcription factor. There are Lhx6(+)-;Dlx(+) and Lhx6(-);Dlx(+) subtypes of tangentially migrating interneurons. Most interneurons in Lhx6(PLAP/PLAP) mutants migrate to the cortex, although less efficiently, and exhibit defects in populating the marginal zone and superficial parts of the neocortical plate. By contrast, migration to superficial parts of the hippocampus is not seriously affected. Furthermore, whereas parvalbumin(+) and somatostatin(+) interneurons do not differentiate, NPY(+) interneurons are present; we suggest that these NPY(+) interneurons are derived from the Lhx6(-);Dlx(+) subtype. Striatal interneurons show deficits distinct from pallial interneurons, including a reduction in the NPY(+) subtype. We provide evidence that Lhx6 mediates these effects through promoting expression of receptors that regulate interneuron migration (ErbB4, CXCR4, and CXCR7), and through promoting the expression of transcription factors either known (Arx) or implicated (bMaf, Cux2, and NPAS1) in controlling interneuron development. C1 [Rubenstein, John L. R.] Univ Calif San Francisco, Nina Ireland Lab Dev Neurobiol, Dept Psychiat, San Francisco, CA 94143 USA. [Zhao, Yangu; Dela Cuesta, Melissa; Westphal, Heiner] NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. RP Rubenstein, JLR (reprint author), Univ Calif San Francisco, Nina Ireland Lab Dev Neurobiol, Dept Psychiat, 2nd Floor S,Room GD 284C,1550 4th St, San Francisco, CA 94143 USA. EM john.rubenstein@ucsf.edu FU Nina Ireland; Larry L. Hillblom Foundation; National Institute of Mental Health [RO1 MH49428-01, K05 MH065670]; Swiss National Science Foundation [PA00A-117463, PBGEA-112882]; Intramural Research Program of the National Institute of Child Health and Human Development FX Grant sponsor: Nina Ireland (to J.L.R.R.); Grant sponsor: the Larry L. Hillblom Foundation (to J.L.R.R.); Grant sponsor: the National Institute of Mental Health; Grant numbers: RO1 MH49428-01 and K05 MH065670 (to J.L.R.R.); Grant sponsor: the Swiss National Science Foundation; Grant numbers: PA00A-117463 and PBGEA-112882 (to P.F.); Grant sponsor: the Intramural Research Program of the National Institute of Child Health and Human Development (to H.W.). NR 71 TC 113 Z9 114 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 1 PY 2008 VL 510 IS 1 BP 79 EP 99 DI 10.1002/cne.21772 PG 21 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 338CG UT WOS:000258481900005 PM 18613121 ER PT J AU Schneidman-Duhovny, D Dror, O Inbar, Y Nussinov, R Wolfson, HJ AF Schneidman-Duhovny, Dina Dror, Oranit Inbar, Yuval Nussinov, Ruth Wolfson, Haim J. TI Deterministic pharmacophore detection via multiple flexible alignment of drug-like molecules SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article; Proceedings Paper CT 11th Annual International Conference on Research in Computational Molecular Biology CY APR 21-25, 2007 CL Oakland, CA SP AFFYMETRIX, BioNovo, Genentech, Int Soc Computat Biol, Helicos, Merck, Roche, Wyeth, ARIADNE, QB3 Calif Inst Quantitat Biomed Res DE computer-aided drug design (CADD); rational drug discovery; 3D molecular similarity; 3D molecular superposition ID SIZED MOLECULES; IDENTIFICATION; SUPERPOSITION; 3D; SETS; SUBSTRUCTURES; SEARCH; DESIGN AB We present a novel highly efficient method for the detection of a pharmacophore from a set of drug-like ligands that interact with a target receptor. A pharmacophore is a spatial arrangement of physico-chemical features in a ligand that is essential for the interaction with a specific receptor. In the absence of a known three-dimensional (3D) receptor structure, a pharmacophore can be identified from a multiple structural alignment of ligand molecules. The key advantages of the presented algorithm are: (a) its ability to multiply align flexible ligands in a deterministic manner, (b) its ability to focus on subsets of the input ligands, which may share a large common substructure, resulting in the detection of both outlier molecules and alternative binding modes, and (c) its computational efficiency, which allows to detect pharmacophores shared by a large number of molecules on a standard PC. The algorithm was extensively tested on a dataset of almost 80 ligands acting on 12 different receptors. The results, which were achieved using a set of standard default parameters, were consistent with reference pharmacophores that were derived from the bound ligand-receptor complexes. The pharmacophores detected by the algorithm are expected to be a key component in the discovery of new leads by screening large databases of drug-like molecules. A user-friendly web interface is available at http://bioinfo3d.cs.tau.ac.il/pharma. Supplementary material can be found at http://bioinfo3d.cs.tau.ac.il/pharma/reduction/. C1 [Schneidman-Duhovny, Dina; Dror, Oranit; Inbar, Yuval; Wolfson, Haim J.] Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. [Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. [Nussinov, Ruth] NCI, Ctr Canc Res, SAIC Frederick Inc, Basic Res Program,Nanobiol Program, Frederick, MD 21701 USA. RP Dror, O (reprint author), Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, Haim Levanon St, IL-69978 Tel Aviv, Israel. EM oranit@post.tau.ac.il RI Wolfson, Haim/A-1837-2011 FU Intramural NIH HHS [Z01 BC010442-06]; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [1UC1AI067231, UC1 AI067231] NR 32 TC 18 Z9 19 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PD SEP PY 2008 VL 15 IS 7 BP 737 EP 754 DI 10.1089/cmb.2007.0130 PG 18 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 351TW UT WOS:000259449800007 PM 18662104 ER PT J AU Mabley, JG Pacher, P Murthy, KGK Williams, W Southan, GJ Salzman, AL Szabo, C AF Mabley, Jon G. Pacher, Pal Murthy, Kanneganti G. K. Williams, William Southan, Garry J. Salzman, Andrew L. Szabo, Csaba TI The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; BETA-CELL DESTRUCTION; ADP-RIBOSE POLYMERASE; NITRIC-OXIDE SYNTHASE; NOD MICE; MYCOPHENOLATE-MOFETIL; DOWN-REGULATION; REPERFUSION INJURY; RADICAL SCAVENGER; IMPROVES SURVIVAL AB Endogenous purines including inosine have been shown to exert immunomodulatory and anti-inflammatory effects in a variety of disease models. The dosage of inosine required for protection is very high because of the rapid metabolism of inosine in vivo. The aim of this study was to determine whether a metabolic-resistant purine analogue, INO-2002, exerts anti-inflammatory effects in two animal models of type I diabetes. Type I diabetes was induced chemically with streptozotocin or genetically using the non-obese diabetic (NOD) female mouse model. Mice were treated with INO-2002 or inosine as required at 30, 100, or 200 mg/kg per day, while blood glucose and diabetes incidence were monitored. The effect of INO-2002 on the pancreatic cytokine profile was also determined. INO-2002 reduced both the hyperglycaemia and incidence of diabetes in both streptozotocin-induced and spontaneous diabetes in NOD mice. INO-2002 proved to be more effective in protecting against diabetes than the naturally occurring purine, inosine, when administered at the same dose. INO-2002 treatment decreased pancreatic levels of interleukin (IL)-12 and tumour necrosis factor-alpha, while increasing levels of IL-4 and IL-10. INO-2002 also reduced pancreatic levels of the chemokine MIP-1 alpha. The inosine analogue, INO-2002, was protected more effectively than the naturally occurring purine, inosine, against development of diabetes in two separate animal models. INO-2002 exerts protective effects by changing the pancreatic cytokine expression from a destructive Th1 to a protective Th2 profile. The use of analogues of inosine such as INO-2002 should be considered as a potential preventative therapy in individuals susceptible to developing type I diabetes. C1 [Mabley, Jon G.] Univ Brighton, Sch Pharm & Biomol Sci, Brighton BN2 4GJ, E Sussex, England. [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Murthy, Kanneganti G. K.; Williams, William; Southan, Garry J.; Salzman, Andrew L.] Inotek Pharmaceut Corp, Beverly, MA 01915 USA. [Szabo, Csaba] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. RP Mabley, JG (reprint author), Univ Brighton, Sch Pharm & Biomol Sci, Cockcroft Bldg,Lewes Rd, Brighton BN2 4GJ, E Sussex, England. EM j.g.mabley@brighton.ac.uk RI Mabley, Jon/D-2296-2010; Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU National Institutes of Health [1R43 DK59676] FX This study was supported by a grant from the National Institutes of Health (1R43 DK59676) to G J S. NR 51 TC 6 Z9 6 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 EI 1479-6805 J9 J ENDOCRINOL JI J. Endocrinol. PD SEP PY 2008 VL 198 IS 3 BP 581 EP 589 DI 10.1677/JOE-07-0511 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 365OL UT WOS:000260416500014 PM 18562629 ER PT J AU Cooper, R Hardy, R Guralnik, J Richards, M Kuh, D AF Cooper, R. Hardy, R. Guralnik, J. Richards, M. Kuh, D. TI Cognitive function across life and mid-life physical performance: Findings from a British birth cohort study SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Meeting Abstract C1 [Cooper, R.; Hardy, R.; Richards, M.; Kuh, D.] UCL Royal Free & Univ Coll Med Sch, Dept Epidemiol & Publ Hlth, MRC Unit Lifelong Hlth Ageing, London, England. [Guralnik, J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD SEP PY 2008 VL 62 MA 021 BP A8 EP A8 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 343CG UT WOS:000258829600022 ER PT J AU Tom, SE Kuh, D Guralink, JM Mishra, G AF Tom, S. E. Kuh, D. Guralink, J. M. Mishra, G. TI Patterns in trouble sleeping among women at midlife: Results from a British prospective cohort study SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Meeting Abstract C1 [Tom, S. E.; Guralink, J. M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. [Tom, S. E.; Kuh, D.; Mishra, G.] UCL Royal Free & Univ Coll Med Sch, MRC Unit Lifelong Hlth & Ageing, London, England. RI Mishra, Gita/F-8052-2011 OI Mishra, Gita/0000-0001-9610-5904 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 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD SEP PY 2008 VL 62 MA 022 BP A8 EP A9 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 343CG UT WOS:000258829600023 ER PT J AU Takizawa, M Tolarova, H Li, Z Dubois, W Lim, S Callen, E Franco, S Mosaico, M Feigenbaum, L Alt, FW Nussenzweig, A Potter, M Casellas, R AF Takizawa, Makiko Tolarova, Helena Li, Zhiyu Dubois, Wendy Lim, Susan Callen, Elsa Franco, Sonia Mosaico, Maria Feigenbaum, Lionel Alt, Frederick W. Nussenzweig, Andre Potter, Michael Casellas, Rafael TI AID expression levels determine the extent of cMyc oncogenic translocations and the incidence of B cell tumor development SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CLASS-SWITCH RECOMBINATION; INDUCED CYTIDINE DEAMINASE; ACTIVATION-INDUCED DEAMINASE; SOMATIC HYPERMUTATION; DNA BREAKS; CHROMOSOME BREAKS; PATHWAY; REGION; MICRORNA-155; MECHANISMS AB Immunoglobulin (Ig) isotype switching is a recombination event that changes the constant domain of antibody genes and is catalyzed by activation-induced cytidine deaminase (AID). Upon recruitment to Ig genes, AID deaminates cytidines at switch (S) recombination sites, leading to the formation of DNA breaks. In addition to their role in isotype switching, AID-induced lesions promote Igh-cMyc chromosomal translocations and tumor development. However, cMyc translocations are also present in lymphocytes from healthy humans and mice, and thus, it remains unclear whether AID directly contributes to the dynamics of B cell transformation. Using a plasmacytoma mouse model, we show that AID(+/-) mice have reduced AID expression levels and display haploinsufficiency both in the context of isotype switching and plasmacytomagenesis. At the Ig loci, AID(+/-) lymphocytes show impaired intra- and inter-switch recombination, and a substantial decrease in the frequency of S mutations and chromosomal breaks. In AID(+/-) mice, these defects correlate with a marked decrease in the accumulation of B cell clones carrying Igh-cMyc translocations during tumor latency. These results thus provide a causality link between the extent of AID enzymatic activity, the number of emerging Igh-cMyc-translocated cells, and the incidence of B cell transformation. C1 [Dubois, Wendy; Potter, Michael] NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. [Takizawa, Makiko; Tolarova, Helena; Li, Zhiyu; Lim, Susan; Casellas, Rafael] NIAMSD, NIH, Bethesda, MD 20892 USA. [Franco, Sonia; Alt, Frederick W.] Childrens Hosp, CBR Inst Biomed Res, Boston, MA 02115 USA. [Franco, Sonia; Alt, Frederick W.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Mosaico, Maria; Feigenbaum, Lionel] NCI, Lab Anim Sci Program, SAIC, NIH, Frederick, MD 21702 USA. RP Potter, M (reprint author), NCI, Genet Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM potter@helix.nih.gov; casellar@mail.nih.gov FU NIAMS; NCI; NIH FX This research was supported in part by the Intramural Research Program of NIAMS and NCI of the NIH. NR 35 TC 90 Z9 93 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 2008 VL 205 IS 9 BP 1949 EP 1957 DI 10.1084/jem.20081007 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 354RI UT WOS:000259656300002 PM 18678733 ER PT J AU Andersson, J Tran, DQ Pesu, M Davidson, TS Ramsey, H O'Shea, JJ Shevach, EM AF Andersson, John Tran, Dat Q. Pesu, Marko Davidson, Todd S. Ramsey, Heather O'Shea, John J. Shevach, Ethan M. TI CD4(+)FoxP3(+) regulatory T cells confer infectious tolerance in a TGF-beta-dependent manner SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; GROWTH-FACTOR-BETA; DENDRITIC CELLS; CUTTING EDGE; INDUCTION; EXPRESSION; MICE; AUTOIMMUNITY; SUPPRESSION; SCURFIN AB CD4(+)FoxP3(+) regulatory T (T reg) cells comprise a separate lineage of T cells that are essential for maintaining immunological tolerance to self. The molecular mechanism(s) by which T reg cells mediate their suppressive effects remains poorly understood. One molecule that has been extensively studied in T reg cell suppression is transforming growth factor (TGF)-beta, but its importance remains controversial. We found that TGF-beta complexed to latency-associated peptide (LAP) is expressed on the cell surface of activated but not resting T reg cells. T reg cell LAP-TGF-beta plays an important role in the suppression of the proliferation of activated T cells, but it is not required for the suppression of naive T cell activation. More importantly, T reg cell-derived TGF-beta could generate de novo CD4(+)FoxP3(+) T cells in vitro from naive precursors in a cell contact-dependent, antigen-presenting cell-independent and alpha(V) integrin-independent manner. The newly induced CD4(+)FoxP3(+) T cells are suppressive both in vitro and in vivo. Transfer of activated antigen-specific T reg cells with naive antigen-specific responder T cells to normal recipients, followed by immunization, also results in induction of FoxP3 expression in the responder cells. T reg cell-mediated generation of functional CD4(+)FoxP3(+) cells via this TGF-beta-dependent pathway may represent a major mechanism as to how T reg cells maintain tolerance and expand their suppressive abilities. C1 [Andersson, John; Tran, Dat Q.; Davidson, Todd S.; Ramsey, Heather; Shevach, Ethan M.] NIAID, Immunol Lab, Bethesda, MD 20892 USA. [Pesu, Marko; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, Bldg 10, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov RI Andersson, John/A-4436-2009; Pesu, marko/L-6344-2013; OI Andersson, John/0000-0003-2799-6349 FU NIAID Intramural Research Program FX The NIAID Intramural Research Program has supported this work. NR 31 TC 172 Z9 179 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 2008 VL 205 IS 9 BP 1975 EP 1981 DI 10.1084/jem.20080308 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 354RI UT WOS:000259656300005 PM 18710931 ER PT J AU Kirk, KL AF Kirk, Kenneth L. TI Editorial for special issue of JFC on Biomedicinal Chemistry SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Editorial Material C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kennethk@bdg8.niddk.nih.gov FU Intramural NIH HHS [Z01 DK031134-01] NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD SEP PY 2008 VL 129 IS 9 SI SI BP 730 EP 730 DI 10.1016/j.jfluchem.2008.07.007 PG 1 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 357ZO UT WOS:000259886100001 PM 19727326 ER PT J AU Kiesewetter, DO Kramer-Marek, G Ma, Y Capala, J AF Kiesewetter, Dale O. Kramer-Marek, Gabriela Ma, Ying Capala, Jacek TI Radiolabeling of HER2-specific Affibody (R) molecule with F-18 SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE Fluorine-18; HER2; Breast cancer; Affibody (R) molecule ID REACTIVE F-18-LABELING AGENT; HER2 EXPRESSION; BREAST-CANCER; MALIGNANT-TUMORS; TRIS(2-CARBOXYETHYL)PHOSPHINE; MALEIMIDE; PEPTIDES; PROTEINS; THERAPY; TRACER AB The presence of human epidermal growth factor type 2 (HER2)on 20-30% of human breast cancer is a prognostic indicator of more rapid disease progression and a therapeutic indicator for anti-HER2 monoclonal antibodies. Because the literature has demonstrated some discordance between primary and metastatic tumors in the same patient for expression of the HER2 marker, we set out to develop an imaging agent that could be used to assess the marker concentration in vivo in an individual patient. The pharmaceutical company Affibody (R) AB has optimized the specificity of Affibody (R) molecules for HER2. Two Affibody" molecules, a 7 kDa and an 8 kDa protein, were designed with a single carboxy terminal cysteine in order to provide a specific location for the purposes of labeling for various types of imaging. We have prepared [(18)F]FBEM utilizing a coupling reaction between [(18)F]fluorobenzoic acid and aminoethylmaleimide. We then optimized the conjugation of this radiolabeled maleimide to the free sulfhydryl of cysteine by incubating at pH 7.4 in phosphate buffered saline containing 0.1% sodium ascorbate. An overall uncorrected yield of radiolabeled Affibody (R) molecule of approximately 10% from [(18)F]fluoride was achieved in a 2 h synthesis. These conjugated Affibody (R) molecules were obtained with a specific activity of 2.51 +/- 0.92 MBq/mu g. Characterization of the product by HPLC-MS Supported the conjugation of [(18)F]FBEM with the Affibody (R) molecule. The radiolabeled Affibody" molecule retained its binding specificity as demonstrated by successful imaging of xenografts expressing HER2. Published by Elsevier B.V. C1 [Kiesewetter, Dale O.; Ma, Ying] NIBIB, PRG, IR, Positron Emiss Tomog Radiochem Grp, Bethesda, MD 20892 USA. [Kramer-Marek, Gabriela; Capala, Jacek] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kiesewetter, DO (reprint author), NIBIB, PRG, IR, Positron Emiss Tomog Radiochem Grp, 10 Ctr Dr,MSC 1180,10-1C401, Bethesda, MD 20892 USA. EM dk7k@nih.gov FU NIH; National Cancer Institute (NCI); National Institute of Biomedical Imaging and Bioengineering (NIBIB); Affibody AB (Sweden) FX This research was supported in part by the intramural research program of the NIH, including the National Cancer Institute (NCI) and the National Institute of Biomedical Imaging and Bioengineering (NIBIB). In addition, partial support was provided by a co-operative research and development agreement with Affibody AB (Sweden). The authors acknowledge the NIH/CC cyclotron facility for isotope production and Dr. Jurgen Seidel for assistance with the ATLAS. The contents of this publication do 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 24 TC 29 Z9 29 U1 3 U2 8 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD SEP PY 2008 VL 129 IS 9 SI SI BP 799 EP 806 DI 10.1016/j.jfluchem.2008.06.021 PG 8 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 357ZO UT WOS:000259886100009 PM 19727427 ER PT J AU Hajduch, J Cramer, JC Kirk, KL AF Hajduch, Jan Cramer, John C. Kirk, Kenneth L. TI An enantioselective synthesis of (S)-4-fluorohistidine SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE Schollkopf diasteroselective alkylation; Photochemical Schiemann reaction; Fluoroimidazole; Microwave reaction ID DIAZONIUM SALTS; PHOTOCHEMISTRY AB We report a new synthesis of enantiomerically pure (S)-4-fluorohisitidine based on diastereoselective alkylation of MOM-protected 4-fluoro-5-bromomethyl imidazole using the Schollkopf bis-lactim amino acid synthesis. Improvements in procedures for preparation of key intermediates are also described. (S)4-Fluorohisitidine prepared by this new method was identical in all respects to material prepared by previous procedures. Published by Elsevier B.V. C1 [Hajduch, Jan; Cramer, John C.; Kirk, Kenneth L.] NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM kennethk@bdg8.niddk.nih.gov FU NIDDK FX This research was supported by the intramural research funds of NIDDK. NR 12 TC 3 Z9 3 U1 1 U2 14 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD SEP PY 2008 VL 129 IS 9 BP 807 EP 810 DI 10.1016/j.jfluchem.2008.04.011 PG 4 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 357ZO UT WOS:000259886100010 PM 19727329 ER PT J AU Fujiwara, T Yin, B Jin, MX Kirk, KL Takeuchi, Y AF Fujiwara, Tomoya Yin, Bin Jin, Meixiang Kirk, Kenneth L. Takeuchi, Yoshio TI Synthetic studies of 3-(3-fluorooxindol-3-yl)-L-alanine SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE Epimerization; Fluorooxindole; Hydroxyoxindole; Indole; Oxindole; Oxindolylalanine; Selectfluor (TM); Tryptophan ID GROWTH-HORMONE SECRETAGOGUES; TRYPTOPHAN INDOLE-LYASE; OXINDOLYL-L-ALANINE; SACC. TC 1093; 2-ARYL-2-FLUOROPROPIONIC ACIDS; PROTEASOME INHIBITORS; PYRIDOXAL-PHOSPHATE; ANALOGS; ALKALOIDS; 2,3-DIHYDRO-L-TRYPTOPHAN AB Oxidative fluorination of several protected tryptophans 8b-g with Selectfluor (TM) proceeded smoothly in aqueous media to give a diastereomeric mixture of the corresponding 3-fluorooxindoles 9b-g. Attempted deprotection of the 3-fluorooxindoles 9b-g under various conditions did not afford 3-(3-fluorooxindol-3-yl)-L-alanine (6). Reaction of the suitably protected tryptophan derivative 16 with Selectfluor (TM) produced the fluorinated product 17. Simultaneous cleavage of all protective groups of 17 under acidic conditions successfully gave the target compound 6 in excellent yield. (c) 2008 Elsevier B.V. All rights reserved. C1 [Fujiwara, Tomoya; Yin, Bin; Jin, Meixiang; Takeuchi, Yoshio] Toyama Univ, Grad Sch Med & Pharmaceut Sci Res, Toyama 9300194, Japan. [Kirk, Kenneth L.] NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Fujiwara, T (reprint author), Toyama Univ, Grad Sch Med & Pharmaceut Sci Res, Sugitani 2630, Toyama 9300194, Japan. EM tfuji@pha.u-toyama.ac.jp FU NIDDK, NIH FX KLK acknowledges support from the intramural research funds of NIDDK, NIH. NR 38 TC 12 Z9 12 U1 0 U2 4 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD SEP PY 2008 VL 129 IS 9 BP 829 EP 835 DI 10.1016/j.jfluchem.2008.06.026 PG 7 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 357ZO UT WOS:000259886100013 PM 19122889 ER PT J AU Hruschka, S Yoshida, S Kirk, KL Haufe, G AF Hruschka, Svenja Yoshida, Shinichi Kirk, Kenneth L. Haufe, Guenter TI Fluorinated phenylcyclopropylamines Part 6. Effects of electron withdrawing or donating aryl substituents on the inhibition of tyramine oxidase from Arthrobacter sp by diastereomeric 2-aryl-2-fluoro-cyclopropylamines SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE Cyclopropylamines; Fluorine; Monoamine oxidase inhibitors; Microbial tyramine oxidase; Arthrobacter sp ID ANTIDEPRESSANT DRUG TRANYLCYPROMINE; DEPENDENT AMINE OXIDASES; CATALYTIC MECHANISM; MONOAMINE OXIDASES; QUINONE; MODEL; RING; SSAO AB Diastereomeric arylcyclopropylamines substituted with fluorine in the 2-position and with electron donating or electron withdrawing groups at the aromatic ring were evaluated as inhibitors of microbial tyramine oxidase. The trans-isomers were consistently more potent inhibitors of the enzyme than the cis-isomers. Electron donating substituents increased the potency of tyramine oxidase inhibition, while electron withdrawing substituents decreased the activity. The results obtained are discussed in terms of pK(a) and log D values of the inhibitors as well as the mechanism of action of tranylcypromines and the geometry of the active site of the enzyme. (c) 2008 Elsevier B.V. All rights reserved. C1 [Hruschka, Svenja; Haufe, Guenter] Univ Munster, Inst Organ Chem, D-48149 Munster, Germany. [Hruschka, Svenja; Haufe, Guenter] Univ Munster, Int NRW Grad Sch Chem, D-48149 Munster, Germany. [Yoshida, Shinichi] Tottori Inst Ind Technol, Tottori 6891112, Japan. [Kirk, Kenneth L.] NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Haufe, G (reprint author), Univ Munster, Inst Organ Chem, Corrensstr 40, D-48149 Munster, Germany. EM haufe@uni-muenster.de FU DFG; International NRW Graduate School of Chemistry; Intramural Research Funds of NIDDK, NIH; Tottoti Prefectural Government, Japan FX This research was partially supported by the DFG as a contribution from the Sonderforschungsbereich 424, the International NRW Graduate School of Chemistry, the Intramural Research Funds of NIDDK, NIH, and the research grant of Tottoti Prefectural Government, Japan. NR 28 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD SEP PY 2008 VL 129 IS 9 SI SI BP 875 EP 880 DI 10.1016/j.jfluchem.2008.06.023 PG 6 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 357ZO UT WOS:000259886100018 PM 19727324 ER PT J AU Marotta, F Yadav, H Gumaste, U Signorelli, P Minelli, E Marandola, P AF Marotta, F. Yadav, H. Gumaste, U. Signorelli, P. Minelli, E. Marandola, P. TI Protective nutragenomic effect of a phytocompound on oxidative stress and DNA fragmentation against paracetamol-induced liver damage SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 [Marotta, F.; Signorelli, P.; Marandola, P.] GAIA Age Management Fdn, Nutraceut Nutrigenom Unit, Pavia, Italy. [Yadav, H.] NIDDK, NIH, Bethesda, MD USA. [Gumaste, U.] Agharkar Res Inst, Pune, Maharashtra, India. [Marotta, F.; Minelli, E.] Univ Milan, WHO, Cntr Biotech & Nat Med, I-20122 Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD SEP PY 2008 VL 23 SU 5 BP A48 EP A48 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 350OD UT WOS:000259361200165 ER PT J AU Kronman, AC Ash, AS Freund, KM Hanchate, A Emanuel, EJ AF Kronman, Andrea C. Ash, Arlene S. Freund, Karen M. Hanchate, Amresh Emanuel, Ezekiel J. TI Can primary care visits reduce hospital utilization among medicare beneficiaries at the end of life? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE end-of-life care; health services research; primary care AB BACKGROUND: Medical care at the end of life is often expensive and ineffective. OBJECTIVE: To explore associations between primary care and hospital utilization at the end of life. DESIGN: Retrospective analysis of Medicare data. We measured hospital utilization during the final 6 months of life and the number of primary care physician visits in the 12 preceding months. Multivariate cluster analysis adjusted for the effects of demographics, comorbidities, and geography in end-of-life healthcare utilization. SUBJECTS: National random sample of 78,356 Medicare beneficiaries aged 66+ who died in 2001. Non-whites were over-sampled. All subjects with complete Medicare data for 18 months prior to death were retained, except for those in the End Stage Renal Disease program. MEASUREMENTS: Hospital days, costs, in-hospital death, and presence of two types of preventable hospital admissions (Ambulatory Care Sensitive Conditions) during the final 6 months of life. RESULTS: Sample characteristics: 38% had 0 primary care visits; 22%, 1-2; 19%, 3-5; 10%, 6-8; and 11%, 9+ visits. More primary care visits in the preceding year were associated with fewer hospital days at end of life (15.3 days for those with no primary care visits vs. 13.4 for those with >= 9 visits, P < 0.001), lower costs ($24,400 vs. $23,400, P < 0.05), less in-hospital death (44% vs. 40%, P < 0.01), and fewer preventable hospitalizations for those with congestive heart failure (adjusted odds ratio, aOR = 0.82, P < 0.001) and chronic obstructive pulmonary disease (aOR = 0.81, P = 0.02). CONCLUSIONS: Primary care visits in the preceding year are associated with less, and less costly, end-of-life hospital utilization. Increased primary care access for Medicare beneficiaries may decrease costs and improve quality at the end of life. C1 [Kronman, Andrea C.; Ash, Arlene S.; Freund, Karen M.; Hanchate, Amresh] Boston Univ, Med Ctr, Evans Dept Med, Gen Internal Med Sect,Womens Hlth & Hlth Care Res, Boston, MA 02118 USA. [Kronman, Andrea C.; Ash, Arlene S.; Freund, Karen M.; Hanchate, Amresh] Boston Univ, Med Ctr, Womens Interdisciplinary Res Ctr, Boston, MA 02118 USA. [Emanuel, Ezekiel J.] NIH, Dept Clin Bioeth, Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Kronman, AC (reprint author), Boston Univ, Med Ctr, Evans Dept Med, Gen Internal Med Sect,Womens Hlth & Hlth Care Res, 801 Massachusetts Ave,Suite 470, Boston, MA 02118 USA. EM Andrea.Kronman@bmc.org OI Hanchate, Amresh/0000-0002-7038-4463; Freund, Karen/0000-0002-9049-5574 FU Mentored Clinical Scientist Development Program Award (Building Interdisciplinary Careers in Women's Health Research); National Institutes of Health [K12 HD04344, T32 HP 10028]; National Institutes of Health FX This work was presented at the Academy Health Annual Research Meeting in Orlando, FL, on 4 June 2006 and received the Mack Lipkin Sr. Associate Member Award for Outstanding Scientific Presentation at the National Meeting for the Society of General Internal Medicine in Los Angeles, CA, on 26 April 2006. The authors thank Drs. Jim Burgess and John Pagliaro for their support with manuscript preparation, and Jenn Fonda for support with computer programming. Dr. Kronman is supported by a Mentored Clinical Scientist Development Program Award ( Building Interdisciplinary Careers in Women's Health Research) from the National Institutes of Health (K12 HD04344, Karen Freund, Principal Investigator). Dr. Kronman was supported by an Institutional National Research Service Award from the National Institutes of Health (T32 HP 10028, Rob Friedman, Principal Investigator) when this research was performed. NR 37 TC 28 Z9 29 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2008 VL 23 IS 9 BP 1330 EP 1335 DI 10.1007/s11606-008-0638-5 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 339LJ UT WOS:000258578800006 PM 18506545 ER PT J AU Tilburt, JC Emanuel, EJ Miller, FG AF Tilburt, Jon C. Emanuel, Ezekiel J. Miller, Franklin G. TI Does the evidence make a difference in consumer behavior? Sales of supplements before and after publication of negative research results SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE complementary therapies; health behaviors; dietary supplements ID RANDOMIZED CONTROLLED-TRIAL; ST-JOHNS-WORT; BENIGN PROSTATIC HYPERPLASIA; VITAMIN-E; HYPERICUM EXTRACT; MAJOR DEPRESSION; CLINICAL-TRIALS; SAW PALMETTO; DOUBLE-BLIND; EFFICACY AB OBJECTIVE: To determine if the public consumption of herbs, vitamins, and supplements changes in light of emerging negative evidence. METHODS: We describe trends in annual US sales of five major supplements in temporal relationship with publication of research from three top US general medical journals published from 2001 through early 2006 and the number of news citations associated with each publication using the Lexus-Nexis database. RESULTS: In four of five supplements (St. John's wort, echinacea, saw palmetto, and glucosamine), there was little or no change in sales trends after publication of research results. In one instance, however, dramatic changes in sales occurred following publication of data suggesting harm from high doses of vitamin E. CONCLUSION: Results reporting harm may have a greater impact on supplement consumption than those demonstrating lack of efficacy. In order for clinical trial evidence to influence public behavior, there needs to be a better understanding of the factors that influence the translation of evidence in the public. C1 [Tilburt, Jon C.; Emanuel, Ezekiel J.; Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Tilburt, Jon C.] Mayo Clin, Div Gen Internal Med, Rochester, MN USA. [Tilburt, Jon C.] Mayo Clin, Program Professionalism & Bioeth, Rochester, MN USA. RP Tilburt, JC (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. EM tilburt.jon@mayo.edu FU Department of Bioethics, National Institutes of Health, Bethesda FX Funding for this research was provided by the Department of Bioethics, National Institutes of Health, Bethesda, MD. Statistical support was provided by Joel Verter and Heidi Christ-Schmidt at Statistic Collaborative, Inc., Washington, D. C. NR 28 TC 14 Z9 14 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2008 VL 23 IS 9 BP 1495 EP 1498 DI 10.1007/s11606-008-0704-z PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 339LJ UT WOS:000258578800033 PM 18618194 ER PT J AU Hoelzer, K Shackelton, LA Parrish, CR Holmes, EC AF Hoelzer, Karin Shackelton, Laura A. Parrish, Colin R. Holmes, Edward C. TI Phylogenetic analysis reveals the emergence, evolution and dispersal of carnivore parvoviruses SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID FELINE PANLEUKOPENIA VIRUS; CANINE TRANSFERRIN RECEPTOR; POLYMERASE-CHAIN-REACTION; HOST-RANGE; MINUTE VIRUS; MURINE CELLS; RNA VIRUS; NS2; MICE; DNA AB Canine parvovirus (CPV), first recognized as an emerging virus of dogs in 1978, resulted from a successful cross-species transmission. CPV emerged from the endemic feline panleukopenia virus (FPV), or from a closely related parvovirus of another host. Here we refine our current understanding of the evolution and population dynamics of FPV and CPV. By analysing nearly full-length viral sequences we show that the majority of substitutions distinguishing CPV from FPV are located in the capsid protein gene, and that this gene is under positive selection in CPV, resulting in a significantly elevated rate of molecular evolution. This provides strong phylogenetic, evidence for a prominent role of the viral capsid in host adaptation. In addition, an analysis of the population dynamics of more recent CPV reveals, on a global scale, a strongly spatially subdivided CPV population with little viral movement among countries and a relatively constant population size. Such limited viral migration contrasts with the global spread of the virus observed during the early phase of the CPV pandemic, but corresponds to the more endemic nature of current CPV infections. C1 [Hoelzer, Karin; Parrish, Colin R.] Cornell Univ, Dept Microbiol & Immunol, Coll Vet Med, Baker Inst Anim Hlth, Ithaca, NY 14853 USA. [Shackelton, Laura A.; 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. RP Hoelzer, K (reprint author), Cornell Univ, Dept Microbiol & Immunol, Coll Vet Med, Baker Inst Anim Hlth, Ithaca, NY 14853 USA. EM kh294@cornell.edu RI Hoelzer, Karin/A-8230-2010; OI Holmes, Edward/0000-0001-9596-3552 FU NIH [GM080533, AI028385] FX Leland E. Carmichael and Edward Dubovi provided clinical samples, and Wendy S. Weichert and Nell Bond provided excellent technical support. Christian Nelson provided valuable help with the three-dimensional representation of the positively selected capsid residues. This work was supported by NIH grants GM080533 to E. C. H. and AI028385 to C. R. P. NR 45 TC 72 Z9 78 U1 0 U2 10 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD SEP PY 2008 VL 89 BP 2280 EP 2289 DI 10.1099/vir.0.2008/002055-0 PN 9 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 349MT UT WOS:000259285600025 PM 18753238 ER PT J AU Marques, R Antunes, I Eksmond, U Stoye, J Hasenkrug, K Kassiotis, G AF Marques, Rute Antunes, Ines Eksmond, Urszula Stoye, Jonathan Hasenkrug, Kim Kassiotis, George TI B lymphocyte activation by coinfection prevents immune control of Friend virus infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DEHYDROGENASE-ELEVATING VIRUS; MURINE LEUKEMIA VIRUSES; FOCUS-FORMING VIRUS; INDUCED ERYTHROLEUKEMIA; POLYCLONAL ACTIVATION; RETROVIRAL INFECTION; VIRAL-INFECTIONS; RESISTANT MICE; SENDAI VIRUS; T-CELLS AB Although the adaptive immune response almost invariably fails to completely eliminate retroviral infections, it can exert significant protection from disease and long-term control of viral replication. Friend virus (FV), a mouse retrovirus, causes persistent infection in all strains of mice and erythroleukaemia in susceptible strains, the course of which can be strongly influenced by both genetic and extrinsic factors. In this study we examine the impact of coinfection on the requirements for immune control of FV infection. We show that congenic C57BL/6 mice, in which the introduction of an allele of the Friend virus susceptibility 2 gene provides the potential for FV-induced leukemia development, effectively resist FV infection, and both T cell- and Ab-dependent mechanisms contribute to their resistance. However, we further demonstrate that coinfection with lactate dehydrogenase-elevating virus (LDV) renders these otherwise immunocompetent mice highly susceptible to FV infection and subsequent disease. The presence of LDV delays induction of FV-specific neutralizing Abs and counteracts the protective contribution of adaptive immunity. Importantly, the disease-enhancing effect of LDV coinfection requires the presence of a polyclonal B cell repertoire and is reproduced by direct polyclonal B cell activation. Thus, immune activation by coinfecting pathogens or their product's can contribute to the pathogenicity of retroviral infection. C1 [Marques, Rute; Antunes, Ines; Eksmond, Urszula; Kassiotis, George] Natl Inst Med Res, MRC, Div Immunoregulat, London NW7 1AA, England. [Stoye, Jonathan] Natl Inst Med Res, MRC, Div Virol, London NW7 1AA, England. [Hasenkrug, Kim] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Kassiotis, G (reprint author), Natl Inst Med Res, MRC, Div Immunoregulat, Ridgeway,Mill Hill, London NW7 1AA, England. EM gkassio@nimr.mrc.ac.uk FU U.K.'s Medical Research Council; Portuguese Foundation of Science and Technology [SFRH/BD/15208/2004] FX This work was supported by the U.K.'s Medical Research Council and the Portuguese Foundation of Science and Technology (SFRH/BD/15208/2004 to I.A.). NR 59 TC 23 Z9 25 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2008 VL 181 IS 5 BP 3432 EP 3440 PG 9 WC Immunology SC Immunology GA 352QJ UT WOS:000259511800053 PM 18714015 ER PT J AU Permar, SR Kang, HH Carville, A Mansfield, KG Gelman, RS Rao, SS Whitney, JB Letvin, NL AF Permar, Sallie R. Kang, Helen H. Carville, Angela Mansfield, Keith G. Gelman, Rebecca S. Rao, Srinivas S. Whitney, James B. Letvin, Norman L. TI Potent simian immunodeficiency virus-specific cellular immune responses in the breast milk of simian immunodeficiency virus-infected, lactating rhesus monkeys SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TO-CHILD TRANSMISSION; LYMPHOCYTE-RESPONSES; HUMAN COLOSTRUM; HIV-1-INFECTED WOMEN; HIV TRANSMISSION; DENDRITIC CELLS; POOLED ANALYSIS; MACACA-MULATTA; TYPE-1; MASTITIS AB Breast milk transmission of HIV is a leading cause of infant HIV/AIDS in the developing world. Remarkably, only a small minority of breastfeeding infants born to HIV-infected mothers contract HIV via breast milk exposure, raising the possibility that immune factors in the breast milk confer protection to the infants who remain uninfected. To model HIV-specific immunity in breast milk, lactation was pharmacologically induced in Mamu-A*01(+) female rhesus monkeys. The composition of lymphocyte subsets in hormone-induced lactation breast milk was found to be similar to that in natural lactation breast milk. Hormone-induced lactating monkeys were inoculated i.v. with SIVmac251 and CD8(+) T lymphocytes specific for two immunodominant SIV epitopes, Gag p11C and Tat TL8, and SIV viral load were monitored in peripheral blood and breast milk during acute infection. The breast milk viral load was 1-2 logs lower than plasma viral load through peak and set point of viremia. Surprisingly, whereas the kinetics of the SIV-specific cellular immunity in breast milk mirrored that of the blood, the peak magnitude of the SIV-specific CD8(+) T lymphocyte response in breast milk was more than twice as high as the cellular immune response in the blood. Furthermore, the appearance of the SIV-specific CD8(+) T lymphocyte response in breast milk was associated with a reduction in breast milk viral load, and this response remained higher than that in the blood after viral set point. This robust viral-specific cellular immune response in breast milk may contribute to control of breast milk virus replication. C1 [Permar, Sallie R.; Kang, Helen H.; Whitney, James B.; Letvin, Norman L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. [Permar, Sallie R.] Harvard Univ, Sch Med, Div Infect Dis, Childrens Hosp Boston, Boston, MA 02115 USA. [Carville, Angela; Mansfield, Keith G.] Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. [Gelman, Rebecca S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rao, Srinivas S.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Permar, SR (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, 330 Brookline Ave,Res E, Boston, MA 02115 USA. EM sallie.permar@childrens.harvard.edu FU Center for HIV/AIDS Vaccine Immunology [R01AI067854]; Fred Lovejoy Research and Education Fund; Children's Hospital House Officer Research Award; Pediatric Infectious Disease Society/St. Jude Children's Hospital Basic Science Research Award; Harvard Center for AIDS Research [P30AI060354] FX This work was supported by the Center for HIV/AIDS Vaccine Immunology (to S.R.P. and N.L.L.; R01AI067854), the Fred Lovejoy Research and Education Fund (to S.R.P.), the Children's Hospital House Officer Research Award (to S.R.P.), the Pediatric Infectious Disease Society/St. Jude Children's Hospital Basic Science Research Award (to S.R.P.), and the Harvard Center for AIDS Research (to R.S.G.: P30AI060354). NR 55 TC 23 Z9 23 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2008 VL 181 IS 5 BP 3643 EP 3650 PG 8 WC Immunology SC Immunology GA 352QJ UT WOS:000259511800077 PM 18714039 ER PT J AU Kutty, G Maldarelli, F Achaz, G Kovacs, JA AF Kutty, Geetha Maldarelli, Frank Achaz, Guillaume Kovacs, Joseph A. TI Variation in the major surface glycoprotein genes in Pneumocystis jirovecii SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIGENIC VARIATION; EXPRESSION SITE; TRYPANOSOMA-BRUCEI; CARINII; IDENTIFICATION; MICE; VARIANTS; MULTIPLE; RECOMBINATION AB The genome of Pneumocystis, which causes life-threatening pneumonia in immunosuppressed patients, contains a multicopy gene family that encodes the major surface glycoprotein (Msg). Pneumocystis can vary the expressed Msg, presumably as a mechanism to avoid host immune responses. Analysis of 24 msg-gene sequences obtained from a singlehumanisolate of Pneumocystis demonstrated that the sequences segregate into 2 branches. Results of a number of analyses suggest that recombination between msg genes is an important mechanism for generating msg diversity. Intrabranch recombination occurred more frequently than interbranch recombination. Restriction-fragment length polymorphism analysis of human isolates of Pneumocystis demonstrated substantial variation in the repertoire of the msg-gene family, variation that was not observed in laboratory isolates of Pneumocystis in rats or mice; this may be the result of examining outbred versus captive populations. Increased diversity in the Msg repertoire, generated in part by recombination, increases the potential for antigenic variation in this abundant surface protein. C1 [Kutty, Geetha; Kovacs, Joseph A.] Natl Inst Hlth, Ctr Clin, Dept Crit Care Med, Bethesda, MD USA. [Maldarelli, Frank] NCI, Natl Inst Hlth, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Achaz, Guillaume] UMR 7138, Paris, France. [Achaz, Guillaume] Atelier Bioinformat, Paris, France. [Achaz, Guillaume] Univ Paris 06, Paris, France. RP Kovacs, JA (reprint author), Bldg 10,Rm 2C145,MSC 1662, Bethesda, MD 20892 USA. EM jkovacs@nih.gov FU Intramural NIH HHS [Z01 BC010819-01, Z01 CL000146-14] NR 45 TC 20 Z9 20 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2008 VL 198 IS 5 BP 741 EP 749 DI 10.1086/590433 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 336KW UT WOS:000258363700017 PM 18627244 ER PT J AU Miller, FG AF Miller, Franklin G. TI Research on medical records without informed consent SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID SELECTION BIAS; INFORMATION; PRIVACY AB Observational research involving access to personally identifiable data in medical records has often been conducted without informed consent, owing to practical barriers to soliciting consent and concerns about selection bias. Nevertheless, medical records research without informed consent appears to conflict with basic ethical norms relating to clinical research and personal privacy. This article analyzes the scope of these norms and provides an ethical justification for research using personally identifiable medical information without consent. C1 Natl Inst Hlth, Dept Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), Natl Inst Hlth, Dept Bioeth, Bethesda, MD 20892 USA. NR 27 TC 21 Z9 21 U1 3 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD FAL PY 2008 VL 36 IS 3 BP 560 EP + DI 10.1111/j.1748-720X.2008.304.x PG 8 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 341AC UT WOS:000258685100016 PM 18840249 ER PT J AU Johnson, TR Rothenberg, ME Graham, BS AF Johnson, Teresa R. Rothenberg, Marc E. Graham, Barney S. TI Pulmonary eosinophilia requires interleukin-5, eotaxin-1, and CD4+T cells in mice immunized with respiratory syncytial virus G glycoprotein SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE vaccine; pathogenesis; cytokines; chemokines; immunoregulation ID AIRWAY EPITHELIAL-CELLS; BALB/C MICE; TISSUE EOSINOPHILIA; T-CELLS; CATIONIC PROTEIN; SUPEROXIDE ANION; RSV CHALLENGE; LUNG-DISEASE; IFN-GAMMA; INFECTION AB Severe illness, type 2 cytokine production, and pulmonary eosinophilia are adverse immune responses resulting from respiratory syncytial virus (RSV) challenge of vvGs-immunized mice. We have shown IL-4 and IL-13 activity must be simultaneously inhibited to reduce disease severity. We now address the contributions of IL-5, eotaxin-1, and CD4+ and CD8+ T cells to the induction of disease-enhancing immune responses. Depletion of CD4+ T cells during immunization prevented IL-4, IL-13, and eotaxin-1 production, diminished eosinophilia, and reduced weight loss. Conversely, CD8+ T cell depletion did not decrease eosinophilia, weight loss, or type 2 cytokines but did dramatically reduce mucus production and increase eotaxin production. Anti-IL-5 administration at immunization or challenge significantly decreased pulmonary eosinophilia. Strikingly, there were not concomitant decreases in weight loss. Following RSV challenge eotaxin-1-deficient mice immunized with vvGs exhibited significantly less eosinophilia without decreased weight loss or type 2 cytokine production. We conclude CD4+ T cell production of IL-5 and induction of eotaxin-1 are required for vvGs-induced eosinophilia following RSV challenge, while CD8+ T cells appear to down-regulate eotaxin-1 and mucus production. In summary, we demonstrate that pulmonary eosinophilia 1) is a by-product of memory CD4+ T cell activation, 2) does not necessarily correlate with mucus production, and, most importantly, 3) is not required for the RSV G-induced illness in mice. These findings have important implications for the evaluation of candidate RSV vaccines. C1 [Johnson, Teresa R.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Rothenberg, Marc E.] Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Div Allergy & Immunol, Cincinnati, OH USA. RP Johnson, TR (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Rm 2614,40 Convent Dr,MSC 3017, Bethesda, MD 20892 USA. EM teresaj@nih.gov NR 65 TC 14 Z9 15 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 SEP 1 PY 2008 VL 84 IS 3 BP 748 EP 759 DI 10.1189/jlb.0907621 PG 12 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 338RH UT WOS:000258525500021 PM 18519743 ER PT J AU Demar, JC DiMartino, C Baca, AW Lefkowitz, W Salem, N AF Demar, James C., Jr. DiMartino, Carmine Baca, Adam W. Lefkowitz, William Salem, Norman, Jr. TI Effect of dietary docosahexaenoic acid on biosynthesis of docosahexaenoic acid from alpha-linolenic acid in young rats SO JOURNAL OF LIPID RESEARCH LA English DT Article DE essential fatty acids; lipid metabolism; early development; infant formula composition ID N-3 FATTY-ACIDS; TERM INFANTS; EICOSAPENTAENOIC ACID; DOCOSAPENTAENOIC ACID; DEVELOPING BRAIN; VISUAL-ACUITY; PEROXISOMAL RETROCONVERSION; NUTRITIONAL DEPRIVATION; DELTA-6 DESATURASE; LIVER CONVERSION AB Docosahexaenoic acid (DHA), a crucial nervous system n-3 PUFA, may be obtained in the diet or synthesized in vivo from dietary alpha-linolenic acid (LNA). We addressed whether DHA synthesis is regulated by the availability of dietary DHA in artificially reared rat pups, during p8 to p28 development. Over 20 days, one group of rat pups was continuously fed deuterium-labeled LNA (d5-LNA) and no other n-3 PUFA (d5-LNA diet), and a second group of rat pups was fed a d5-LNA diet with unlabeled DHA (d5-LNA + DHA diet). The rat pups were then euthanized, and the total amount of deuterium-labeled docosahexaenoic acid (d5-DHA) (synthesized DHA) as well as other n-3 fatty acids present in various body tissues, was quantified. In the d5-LNA 1 DHA group, the presence of dietary DHA led to a marked decrease (3- to 5-fold) in the total amount of d5-DHA that accumulated in all tissues that we examined, except in adipose. Overall, DHA accretion from d5-DHA was generally diminished by availability of dietary preformed DHA, inasmuch as this was found to be the predominant source of tissue DHA. When preformed DHA was unavailable, d5-DHA and unlabeled DHA were preferentially accreted in some tissues along with a net loss of unlabeled DHA from other organs.-DeMar, Jr., J. C., C. DiMartino, A. W. Baca, W. Lefkowitz, and N. Salem, Jr. Effect of dietary docosahexaenoic acid on biosynthesis of docosahexaenoic acid from alpha-linolenic acid in young rats. C1 [Demar, James C., Jr.; DiMartino, Carmine; Baca, Adam W.; Salem, Norman, Jr.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. [Lefkowitz, William] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Salem, N (reprint author), NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. EM nsalem@niaaa.nih.gov FU Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism FX This project was supported by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism. NR 96 TC 23 Z9 25 U1 3 U2 8 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 SEP PY 2008 VL 49 IS 9 BP 1963 EP 1980 DI 10.1194/jlr.M800117-JLR200 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 337YX UT WOS:000258472500012 PM 18469302 ER PT J AU Farias, SE Basselin, M Chang, L Heidenreich, KA Rapoport, SI Murphy, RC AF Farias, Santiago E. Basselin, Mireille Chang, Lisa Heidenreich, Kim A. Rapoport, Stanley I. Murphy, Robert C. TI Formation of eicosanoids, E-2/D-2 isoprostanes, and docosanoids following decapitation-induced ischemia, measured in high-energy-microwaved rat brain SO JOURNAL OF LIPID RESEARCH LA English DT Article DE arachidonic; docosahexaenoic; eicosanoids; docosanoids; isoprostanes; brain ischemia ID FREE FATTY-ACIDS; ALPHA-LINOLENIC ACID; DOCOSAHEXAENOIC ACID; CEREBRAL-ISCHEMIA; ARACHIDONIC-ACID; MOUSE-BRAIN; LIPID-PEROXIDATION; MASS-SPECTROMETRY; OXIDATIVE STRESS; GENE-EXPRESSION AB Inflammatory lipid mediators derived from arachidonic acid (AA) and docosahexaenoic acid (DHA) modify the pathophysiology of brain ischemia. The goal of this work was to investigate the formation of eicosanoids and docosanoids generated from AA and DHA, respectively, during no-flow cerebral ischemia. Rats were subjected to head-focused microwave irradiation 5 min following decapitation (complete ischemia) or prior to decapitation (controls). Brain lipids were extracted and analyzed by reverse-phase liquid chromatography-tandem mass spectrometry. After complete ischemia, brain AA, DHA, and docosapentaenoic acid concentrations increased 18-, 5- and 4-fold compared with controls, respectively. Prostaglandin E-2 (PGE(2)) and PGD(2) could not be detected in control microwaved rat brain, suggesting little endogenous PGE(2)/D-2 production in the brain in the absence of experimental manipulation. Concentrations of thromboxane B-2, E-2/D-2-isoprostanes, 5-hydroxyeicosatetraenoic acid (5-HETE), 5-oxo-eicosatetraenoic acid, and 12-HETE were significantly elevated in ischemic brains. In addition, DHA products such as mono-, di- and trihydroxy-DHA were detected in control and ischemic brains. Monohydroxy-DHA, identified as 17-hydroxy-DHA and thought to be the immediate precursor of neuroprotectin D-1, was 6.5-fold higher in ischemic than in control brain. The present study demonstrated increased formation of eicosanoids, E-2/D-2-IsoPs, and docosanoids following cerebral ischemia. A balance of these lipid mediators may mediate immediate events of ischemic injury and recovery.-Farias, S. E., M. Basselin, L. Chang, K. A. Heidenreich, S. I. Rapoport, and R. C. Murphy. Formation of eicosanoids, E-2/D-2 isoprostanes, and docosanoids following decapitation-induced ischemia, measured in high-energy-microwaved rat brain. C1 [Farias, Santiago E.; Heidenreich, Kim A.; Murphy, Robert C.] Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Aurora, CO 80045 USA. [Basselin, Mireille; Chang, Lisa; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Murphy, RC (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Aurora, CO 80045 USA. EM Robert.Murphy@uchsc.edu FU Heart, Lung and Blood Institute; National Institutes of Health [HL-025785]; General Medical Sciences [GM-069338]; Intramural Research Program of the National Institute on Aging FX This work was supported in part by the Heart, Lung and Blood Institute, National Institutes of Health, Grant HL-025785, and a grant from General Medical Sciences (GM-069338) (Lipid Maps), as well as by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. No author has a conflict of interest or financial interest with regard to this work. NR 61 TC 47 Z9 48 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2008 VL 49 IS 9 BP 1990 EP 2000 DI 10.1194/jlr.M800200-JLR200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 337YX UT WOS:000258472500014 PM 18503030 ER PT J AU Detsky, JS Graham, JJ Vijayaraghavan, R Biswas, L Stainsby, JA Guttman, MA Wright, GA Dick, AJ AF Detsky, Jay S. Graham, John J. Vijayaraghavan, Ram Biswas, Labonny Stainsby, Jeffrey A. Guttman, Michael A. Wright, Graham A. Dick, Alexander J. TI Free-breathing, nongated real-time delayed enhancement MRI of myocardial infarcts: A comparison with conventional delayed enhancement SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MRI; delayed enhancement; real-time; myocardial infarct; SSFP ID INVERSION-RECOVERY TRUEFISP; STATE FREE PRECESSION; MAGNETIC-RESONANCE; CONTRAST AB Purpose: To compare a free-breathing, nongated, and black-blood real-time delayed enhancement (RT-DE) sequence to the conventional inversion recovery gradient echo (IR-GRE) sequence for delayed enhancement MRI. Materials and Methods: Twenty-three patients with suspected myocardial infarct (MI) were examined using both the IR-GRE and RT-DE imaging sequences. The sensitivity and specificity of RT-DE for detecting MI, using IR-GRE as the gold standard, was determined. The contrast-to-noise ratios (CNR) between the two techniques were also compared. Results: RT-DE had a high sensitivity and specificity (94% and 98%, respectively) for identifying MI. The total acquisition time to image the entire left ventricle was significantly shorter using RT-DE than IR-GRE (5.6 +/- 0.9 versus 11.5 +/- 1.9 min). RT-DE had a slightly lower infarct-myocardium CNR but a higher infarct-blood CNR than IR-GRE imaging. Compared with IR-GRE, RT-DE accurately measured total infarct sizes. Conclusion: RT-DE can be used for delayed enhancement imaging during free-breathing and without cardiac gating. C1 [Detsky, Jay S.; Biswas, Labonny; Wright, Graham A.; Dick, Alexander J.] Sunnybrook Hlth Sci Ctr, Imaging Res Program, Toronto, ON M4N 3M5, Canada. [Detsky, Jay S.; Wright, Graham A.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Graham, John J.; Vijayaraghavan, Ram; Dick, Alexander J.] Sunnybrook Hlth Sci Ctr, Schulich Heart Program, Toronto, ON M4N 3M5, Canada. [Stainsby, Jeffrey A.] GE Healthcare, Mississauga, ON, Canada. [Guttman, Michael A.] NIH, Bethesda, MD 20892 USA. RP Detsky, JS (reprint author), Sunnybrook Hlth Sci Ctr, Imaging Res Program, S605,2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM jay.detsky@sri.utoronto.ca FU Canadian Institutes of Health Research Grant [CIHR-MOP-36477] FX Contract grant sponsor: the Canadian Institutes of Health Research Grant #CIHR-MOP-36477. NR 17 TC 5 Z9 5 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD SEP PY 2008 VL 28 IS 3 BP 621 EP 625 DI 10.1002/jmri.21505 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 346ZA UT WOS:000259106900009 PM 18777543 ER PT J AU Callahan, R Smith, GH AF Callahan, Robert Smith, Gilbert H. TI The mouse as a model for mammary tumorigenesis: History and current aspects SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Editorial Material C1 [Callahan, Robert; Smith, Gilbert H.] NCI, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, Bethesda, MD 20892 USA. EM smithg@mail.nih.gov NR 0 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD SEP PY 2008 VL 13 IS 3 BP 269 EP 269 DI 10.1007/s10911-008-9094-4 PG 1 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 342RZ UT WOS:000258802500001 PM 18712586 ER PT J AU Callahan, R Smith, GH AF Callahan, Robert Smith, Gilbert H. TI Common integration sites for MMTV in viral induced mouse mammary tumors SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE mammary tumors; cancer; mouse mammary tumor virus ID HUMAN BREAST-CANCER; POLYMERASE CHAIN-REACTION; TEMPLATE DNA STRANDS; TRUNCATED INT3 GENE; TRANSGENIC MICE; INSERTIONAL MUTAGENESIS; EPITHELIAL-CELLS; NOTCH-GENE; GLAND ADENOCARCINOMAS; STEM-CELLS AB The paradigm of mammary cancer induction by the mouse mammary tumor virus (MMTV) is used to illustrate the body of evidence that supports the hypothesis that mammary epithelial stem/progenitor cells represent targets for oncogenic transformation. It is argued that this is not a special case applicable only to MMTV-induced mammary cancer, because MMTV acts as an environmental mutagen producing random interruptions in the somatic DNA of infected cells by insertion of proviral DNA copies. In addition to disrupting the host genome, the proviral DNA also influences gene expression through its associated enhancer sequences over significant inter-genomic distances. Genes commonly affected by MMTV insertion in multiple individual tumors include, the Wnt, FGF, RSpo gene families as well as eIF3e and Notch4. All of these gene families are known to play essential roles in stem cell maintenance and behavior in a variety of organs. The MMTV-induced mutations accumulate in cells that are long-lived and possess the properties of stem cells, namely, self-renewal and the capacity to produce divergent epithelial progeny through asymmetric division. The evidence shows that epithelial cells with these properties are present in normal mammary glands, may be infected with MMTV, become transformed to produce epithelial hyperplasia through MMTV-induced mutagenesis and progress to frank mammary malignancy. Retroviral marking via MMTV proviral insertion demonstrates that this process progresses from a single mammary epithelial cell that possesses all of the features ascribed to tissue-specific stem cells. C1 [Smith, Gilbert H.] NCI, Bethesda, MD 20892 USA. [Callahan, Robert] NCI, Mammary Gland Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, Bldg 37 Room 1112A,MSC 4254, Bethesda, MD 20892 USA. EM gs4d@nih.gov FU NIH; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 86 TC 26 Z9 26 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD SEP PY 2008 VL 13 IS 3 BP 309 EP 321 DI 10.1007/s10911-008-9092-6 PG 13 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 342RZ UT WOS:000258802500006 PM 18709449 ER PT J AU Winter, SF Hunter, KW AF Winter, Scott F. Hunter, Kent W. TI Mouse modifier genes in mammary tumorigenesis and metastasis SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE breast cancer; mouse models; metastasis; genetics; polymorphism; quantitative trait loci ID BREAST-CANCER METASTASIS; PEUTZ-JEGHERS-SYNDROME; TUMOR PROGRESSION; GLAND DEVELOPMENT; COWDEN DISEASE; SUSCEPTIBILITY; MUTATIONS; BRCA1; RISK; DISSEMINATION AB Tumorigenesis and metastasis are complex multistep processes. In addition to the numerous somatic mutations that facilitate cancer progression, there is abundant evidence that an individual's genetic background not only contributes to overall cancer risk, but also specifically influences metastatic potential. The handful of human susceptibility genes that have been identified thus far do not fully account for hereditary cancer risk, and the discovery of additional susceptibility loci using population based studies is complex, time-consuming and expensive. Therefore, we and others have used a variety of mouse models to identify novel candidate susceptibility genes. Here we review how these mouse models have contributed to our understanding of the role of genetic background in modifying tumorigenesis and metastasis susceptibility. C1 [Winter, Scott F.; Hunter, Kent W.] NCI, Lab Canc Biol & Genet, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hunter, KW (reprint author), 37 Convent Dr,Rm 5046, Bethesda, MD 20892 USA. EM hunterk@mail.nih.gov NR 57 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD SEP PY 2008 VL 13 IS 3 BP 337 EP 342 DI 10.1007/s10911-008-9089-1 PG 6 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 342RZ UT WOS:000258802500008 PM 18661105 ER PT J AU Wertheimer, A Miller, FG AF Wertheimer, A. Miller, F. G. TI Payment for research participation: a coercive offer? SO JOURNAL OF MEDICAL ETHICS LA English DT Article AB Payment for research participation has raised ethical concerns, especially with respect to its potential for coercion. We argue that characterising payment for research participation as coercive is misguided, because offers of benefit cannot constitute coercion. In this article we analyse the concept of coercion, refute mistaken conceptions of coercion and explain why the offer of payment for research participation is never coercive but in some cases may produce undue inducement. C1 [Wertheimer, A.; Miller, F. G.] NCI, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NCI, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 13 TC 44 Z9 44 U1 1 U2 3 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 SEP 1 PY 2008 VL 34 IS 5 BP 389 EP 392 DI 10.1136/jme.2007.021857 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 294PS UT WOS:000255418600019 PM 18448723 ER PT J AU Resnick, DB AF Resnick, D. B. TI Increasing the amount of payment to research subjects SO JOURNAL OF MEDICAL ETHICS LA English DT Article AB This article discusses some ethical issues that can arise when researchers decide to increase the amount of payment offered to research subjects to boost enrollment. Would increasing the amount of payment be unfair to subjects who have already consented to participate in the study? This article considers how five different models of payment-the free market model, the wage payment model, the reimbursement model, the appreciation model, and the fair benefits model-would approach this issue. The article also considers several practical problems related to changing the amount of payment, including determining whether there is enough money in the budget to offer additional payments to subjects who have already enrolled, ascertaining how difficult it will be to re-contact subjects, and developing a plan of action for responding to subjects who find out they are receiving less money and demand an explanation. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnick, DB (reprint author), NIEHS, NIH, Box 12233,NH06, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU NIEHS/NIH FX This research was supported by the intramural programme of the NIEHS/NIH. It does not represent the views of the NIEHS or NIH. I am a grateful to C Grady and an anonymous reviewer for helpful comments. NR 16 TC 5 Z9 5 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD SEP PY 2008 VL 34 IS 9 AR e14 DI 10.1136/jme.2007.022699 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 343CE UT WOS:000258829400031 PM 18757614 ER PT J AU Shalowitz, DI Miller, FG AF Shalowitz, D. I. Miller, F. G. TI The search for clarity in communicating research results to study participants SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID CLINICAL-RESEARCH; DUTY AB Current guidelines on investigators' responsibilities to communicate research results to study participants may differ on (1) whether investigators should proactively re-contact participants, (2) the type of results to be offered, (3) the need for clinical relevance before disclosure, and (4) the stage of research at which results should be offered. Lack of consistency on these issues, however, does not undermine investigators' obligation to offer to disclose research results: an obligation rooted firmly in the principle of respect for research participants. C1 [Shalowitz, D. I.] Univ Michigan, Sch Med, Bioeth Program, Ann Arbor, MI 48109 USA. [Miller, F. G.] NIH, Dept Bioeth, Bethesda, MD USA. RP Shalowitz, DI (reprint author), Univ Michigan, Sch Med, Bioeth Program, N17C27 SPC 5429,300 N Ingalls St, Ann Arbor, MI 48109 USA. EM dshalowi@med.umich.edu RI Shalowitz, David/A-7432-2009; OI Shalowitz, David/0000-0002-5189-4687 NR 13 TC 20 Z9 20 U1 0 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 SEP PY 2008 VL 34 IS 9 AR e17 DI 10.1136/jme.2008.025122 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 343CE UT WOS:000258829400034 PM 18757617 ER PT J AU Muenke, M AF Muenke, Maximilian TI Hedgehog signaling and normal and abnormal brain development in humans SO JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT British Human Genetics Conference CY SEP 15-17, 2008 CL Univ York, York, ENGLAND HO Univ York C1 [Muenke, Maximilian] NHGRI, Med Genet Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD USA. EM mmuenke@nhgri.nih.gov NR 5 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 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 2008 VL 45 BP S15 EP S15 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 351PM UT WOS:000259436400003 ER PT J AU Murray, JC Shi, M Mostowska, A Mansilla, MA Christensen, K Marazita, M Cooper, M Lidral, A Rahimov, F Suzuki, S AF Murray, Jeffrey C. Shi, M. Mostowska, A. Mansilla, M. A. Christensen, K. Marazita, M. Cooper, M. Lidral, A. Rahimov, F. Suzuki, S. TI Cleft Palate SO JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT British Human Genetics Conference CY SEP 15-17, 2008 CL Univ York, York, ENGLAND HO Univ York C1 [Murray, Jeffrey C.; Mansilla, M. A.; Rahimov, F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Shi, M.] NIEHS, Natl Inst Hlth, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Mostowska, A.] Univ Med Sci, Dept Biochem & Mol Biol, PL-60781 Poznan, Poland. [Christensen, K.] Univ So Denmark, Inst Publ Hlth, DK-5000 Odense, Denmark. [Marazita, M.; Cooper, M.] Sch Dent Med, Ctr Craniofacial & Dent Genet, Dept Oral Biol, Pittsburgh, PA 15219 USA. [Lidral, A.] Univ Iowa, Dept Orthodont, Iowa City, IA 52242 USA. [Suzuki, S.] Aichi Gakuin Univ, Sch Dent, Nagoya, Aichi 4648651, Japan. EM jeff-murray@uiowa.edu RI Mostowska, Adrianna/J-6719-2012 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 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 2008 VL 45 BP S15 EP S15 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 351PM UT WOS:000259436400002 ER PT J AU Garcia, GL Parent, CA AF Garcia, G. L. Parent, C. A. TI Signal relay during chemotaxis SO JOURNAL OF MICROSCOPY LA English DT Article; Proceedings Paper CT 6th Abercrombie Symposium on Cell Motility CY SEP 09-12, 2007 CL St Catherines Coll, Oxford, ENGLAND HO St Catherines Coll DE cAMP; chemotaxis; Dictyostelium discoideum ID PROTEIN-MEDIATED ACTIVATION; ADENYLYL-CYCLASE; DICTYOSTELIUM-DISCOIDEUM; CHEMOATTRACTANT RECEPTOR; CELL POLARITY; CYTOSOLIC REGULATOR; LEUKOTRIENE B-4; CAMP SYNTHESIS; LEADING-EDGE; LIVING CELLS AB The ability of cells to migrate in response to external cues, a process known as chemotaxis, is a fundamental phenomenon in biology. It is exhibited by a wide variety of cell types in the context of embryogenesis, angiogenesis, inflammation, wound heating and many other complex physiological processes. Here, we discuss the signals that control the directed migration of the social amoebae Dictyostelium discoideum both as single cells and in the context of group migration. This multi-cellular organism has served as an excellent model system to decipher amoeboid-like leukocyte migration and has played a key role in establishing signalling paradigms in the chemotaxis field. We envision that Dictyostelium will continue to bring forward basic knowledge as we seek to understand the mechanisms regulating group cell migration. C1 [Garcia, G. L.; Parent, C. A.] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, NIH, 37 Convent Dr,Bldg 37,Rm 2066, Bethesda, MD 20892 USA. EM parentc@mail.nih.gov FU Intramural NIH HHS [Z01 BC010418-08] NR 62 TC 20 Z9 20 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-2720 EI 1365-2818 J9 J MICROSC-OXFORD JI J. Microsc.. PD SEP PY 2008 VL 231 IS 3 BP 529 EP 534 DI 10.1111/j.1365-2818.2008.02066.x PG 6 WC Microscopy SC Microscopy GA 354AJ UT WOS:000259611000020 PM 18755009 ER PT J AU Schinkovitz, A Pro, SM Main, M Chen, SN Jaki, BU Lankin, DC Pauli, GF AF Schinkovitz, Andreas Pro, Samuel M. Main, Matthew Chen, Shao-Nong Jaki, Birgit U. Lankin, David C. Pauli, Guido F. TI Dynamic nature of the ligustilide complex SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID ANGELICA-SINENSIS; COUNTERCURRENT SEPARATION; MASS-SPECTROMETRY; CHUANXIONG; CHROMATOGRAPHY; EXTRACTION; PHTHALIDE; PRODUCTS; ROOTS; VASODILATATION AB Monomeric phthalides such as Z-ligustilide (1) and Z-butylidenephthalide (2) are major constituents of medicinal plants of the Apiaceae family. While I has been associated with a variety of observed biological effects, it is also known for its instability and rapid chemical degradation. For the purpose of isolating pure 1 and 2, a gentle and rapid two-step countercurrent isolation procedure was developed. From a supercritical CO(2) fluid extract of Angelica sinensis roots, the phthalides were isolated with high GC-MS purities of 99.4% for 1 and 98.9% for 2 and consistently lower qHNMR purities of 98.1 % and 96.4%, respectively. Taking advantage of molarity-based qHNMR methodology, a time-resolved study of the dynamic changes and residual complexity of pure 1 was conducted. GC-MS and (qH)NMR analysis of artificially degraded 1 provided evidence for the phthalide degradation pathways and optimized storing conditions. Parallel qHNMR analysis led to the recognition of variations in time- and process-dependent sample purity and has impact on the overall assessment of time-dependent changes in complex natural products systems. The study underscores the importance of independent quantitative monitoring as a prerequisite for the biological evaluation of labile natural products such as monomeric phthalides. C1 [Schinkovitz, Andreas; Main, Matthew; Chen, Shao-Nong; Lankin, David C.; Pauli, Guido F.] Univ Illinois, NIH, Ctr Bot Dietary Supplements Res, Chicago, IL 60612 USA. [Schinkovitz, Andreas; Main, Matthew; Chen, Shao-Nong; Lankin, David C.; Pauli, Guido F.] Univ Illinois, Program Collaborat Res Pharmaceut Sci, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. [Pro, Samuel M.; Jaki, Birgit U.; Pauli, Guido F.] Univ Illinois, Inst TB Res, Coll Pharm, Chicago, IL 60612 USA. RP Pauli, GF (reprint author), Univ Illinois, NIH, Ctr Bot Dietary Supplements Res, Chicago, IL 60612 USA. EM gfp@uic.edu OI Pauli, Guido/0000-0003-1022-4326 FU the National Center for Complementary and Alternative Medicine (NCCAM) [P50 AT00 155]; the Office of Dietary Supplements (ODS) FX Research was supported by grant number P50 AT00 155 from the National Center for Complementary and Alternative Medicine (NCCAM) and the Office of Dietary Supplements (ODS). NR 38 TC 17 Z9 17 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD SEP PY 2008 VL 71 IS 9 BP 1604 EP 1611 DI 10.1021/np800137n PG 8 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 353NO UT WOS:000259574900019 PM 18781813 ER PT J AU Bokesch, HR Wamiru, A Le Grice, SFJ Beutler, JA Mckee, TC McMahon, JB AF Bokesch, Heidi R. Wamiru, Antony Le Grice, Stuart F. J. Beutler, John A. McKee, Tawnya C. McMahon, James B. TI HIV-1 ribonuclease H inhibitory phenolic glycosides from Eugenia hyemalis SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID FLAVONOL GLYCOSIDES; GALLOTANNINS; CONSTITUENTS; PLANT AB Three new galloyl arbutins, hyemalosides A-C (1-3), along with nine known compounds were isolated from the evergreen tree Eugenia hyemalis. The structures of compounds 1-3 were determined by analysis of NMR and MS data. Compounds 1-3 inhibited HIV-1 RNase H in vitro with IC(50) values of 1.46, > 18, and 1.19 mu M, respectively. However, in a XTT-based cell viability assay using the human T-cell line CEM-SS infected with HIV-1(RT), none of the compounds inhibited the cytopathic effect of HIV-1 infection at the highest dose tested (20 mu g/mL). C1 [Bokesch, Heidi R.; Wamiru, Antony; Beutler, John A.; McKee, Tawnya C.; McMahon, James B.] NCI, Mol Targets Dev Program, Frederick, MD 21702 USA. [Bokesch, Heidi R.; Wamiru, Antony] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA. [Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Mckee, TC (reprint author), NCI, Mol Targets Dev Program, Frederick, MD 21702 USA. EM mckee@ncifcrf.gov RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU National Cancer Institute; National Institutes of Health [N01-CO-12400]; NIH; Center for Cancer Research 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. We thank N. Trushell (NYBG) and G. Cragg (NPB) for the contract collection, T. McCloud for extractions, and J. Wilson for the HIV cytopathicity assay. NR 16 TC 19 Z9 20 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD SEP PY 2008 VL 71 IS 9 BP 1634 EP 1636 DI 10.1021/np8002518 PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 353NO UT WOS:000259574900026 PM 18763827 ER PT J AU Agnati, LF Baldelli, E Andreoli, N Woods, AS Vellani, V Marcellino, D Guidolin, D Fuxe, K AF Agnati, L. F. Baldelli, E. Andreoli, N. Woods, A. S. Vellani, V. Marcellino, D. Guidolin, D. Fuxe, K. TI On the key role played by altered protein conformation in Parkinson's disease SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE Parkinson's disease; disordered proteins; protein mosaics ID CENTRAL-NERVOUS-SYSTEM; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; AMYLOID-BETA; NEURODEGENERATIVE DISEASES; MITOCHONDRIAL DYSFUNCTION; INTRINSIC DISORDER; SUBSTANTIA-NIGRA; BRAIN PATHOLOGY; BODY FORMATION AB On the basis of the previously proposed hierarchic organisation of the central nervous system (CNS) and of its syntropic behaviour, a view of neurodegenerative diseases focusing on the assemblage of abnormal multimeric proteins (pathologic protein mosaics (PMs)) is proposed. Thus, the main focus of the present paper is on Parkinson's disease (PD) as a neurodegenerative disease, which has as crucial feature protein conformational alterations and formation of pathological PMs. Two interconnected cellular dysfunctions are discussed as main pathogenic factors of PD syndromes, namely mitochondrial deficits (i.e. energy failure, especially critical for Substantia Nigra DA neurons) and conformational protein alterations (due to genetic or environmental causes). Conformational protein alterations can trigger pathological phenomena via the loss and/or the gain of new functions. In particular, altered proteins can lead to the formation of abnormal PMs, which can, inter alia, cause distortion of cellular structures, toxic functions and/or formation of improper membrane ion channels. In view of the fact that disordered proteins can easily acquire unwanted conformation, the "disorder index" (DI) for proteins involved in PD has been evaluated. It has been found that both alpha-synuclein and tau-protein have high DI. This datum is in agreement with the observation that these two proteins synergistically promote polymerisation of each other into amyloid fibrils, favouring the formation of Lewy bodies. C1 [Agnati, L. F.; Baldelli, E.; Andreoli, N.; Vellani, V.] Univ Modena, Dept Biomed Sci, Physiol Sect, I-41100 Modena, Italy. [Woods, A. S.] Natl Inst Drug Abuse, Behav Neurosci Branch, NIH, DHHS, Baltimore, MD 20817 USA. [Marcellino, D.; Fuxe, K.] Karolinska Inst, Div Cellular & Mol Neurochem, Dept Neurosci, S-17177 Stockholm, Sweden. [Guidolin, D.] Univ Padua, Dept Anat & Physiol, I-35121 Padua, Italy. [Agnati, L. F.] IRCCS, I-30126 Venice, Italy. RP Agnati, LF (reprint author), Univ Modena, Dept Biomed Sci, Physiol Sect, I-41100 Modena, Italy. EM luigiagnati@tin.it RI Vellani, Vittorio/H-1100-2016; OI Vellani, Vittorio/0000-0002-3581-6654; Fuxe, Kjell/0000-0001-8491-4288; Guidolin, Diego/0000-0003-2133-3552; Marcellino, Daniel/0000-0002-4618-7267 FU IRCCS; PRIN FX The work has been supported by an IRCCS and a PRIN grant. Thanks to Dott. A. Percesepe (Dep. of Medical Genetic) for suggestions on the Table. NR 93 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD SEP PY 2008 VL 115 IS 9 BP 1285 EP 1299 DI 10.1007/s00702-008-0072-1 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 342BO UT WOS:000258759800008 PM 18528629 ER PT J AU Fadul, CE Wen, PY Kim, L Olson, JJ AF Fadul, Camilo E. Wen, Patrick Y. Kim, Lyndon Olson, Jeffrey J. TI Cytotoxic chemotherapeutic management of newly diagnosed glioblastoma multiforme SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article ID HIGH-GRADE GLIOMAS; OPERATED ASTROCYTOMAS GRADE-3; EXTERNAL-BEAM-RADIOTHERAPY; RESISTANCE IN-VITRO; FACTOR-KAPPA-B; MALIGNANT GLIOMA; PHASE-II; RADIATION-THERAPY; RANDOMIZED TRIAL; POSTOPERATIVE TREATMENT C1 [Olson, Jeffrey J.] Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA 30322 USA. [Fadul, Camilo E.] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Neurooncol Program, Dartmouth Med Sch, Lebanon, NH 03766 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Kim, Lyndon] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. RP Olson, JJ (reprint author), Emory Univ, Sch Med, Dept Neurosurg, 1365B Clifton Rd,NE,Ste 6200, Atlanta, GA 30322 USA. EM jeffrey.olson@emoryhealthcare.org RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 NR 79 TC 12 Z9 12 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD SEP PY 2008 VL 89 IS 3 BP 339 EP 357 DI 10.1007/s11060-008-9615-4 PG 19 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 339XW UT WOS:000258611600006 PM 18712284 ER PT J AU Kanungo, J Zheng, YL Amin, ND Pant, HC AF Kanungo, Jyotshnabala Zheng, Ya-Li Amin, Niranjana D. Pant, Harish C. TI The Notch signaling inhibitor DAPT down-regulates cdk5 activity and modulates the distribution of neuronal cytoskeletal proteins SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cdk5; neurofilament; Notch signaling; tau ID CYCLIN-DEPENDENT KINASE-5; NEUROFILAMENT AXONAL-TRANSPORT; GAMMA-SECRETASE INHIBITOR; TAU-PROTEIN; ALZHEIMERS-DISEASE; ACTIVATOR P35; UP-REGULATION; PHOSPHORYLATION; DIFFERENTIATION; CELLS AB Notch signaling is critical for the development of the nervous system. Cyclin-dependent kinase 5 (cdk5) is a neuronal kinase involved in neuronal development and phosphorylates a number of neuronal cytoskeletal proteins. To determine the relationship between Notch and cdk5 signaling, we tested the effects of the Notch inhibitor, N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT) on cdk5 expression, activity and cytoskeletal protein distribution in the rat cortical neurons in primary cultures. Neurons treated with 10 mu M DAPT showed attenuated cdk5 activity in spite of an up-regulation of cdk5 protein level, consistent with a phenomenon reported in the cdk5 transgenic mice. Immunoblot and immunofluorescence analyses showed an increased level of cdk5, but not p35. Phospho-tau and phospho-neurofilament showed a shift from axons to cell bodies in DAPT-treated cells. DAPT-induced attenuation of cdk5 activity was restored by over-expression of p35 indicating that it interacted with cdk5 and up-regulated nascent cdk5 activity. p35 over-expression also rescued DAPT-induced translocation of phospho-tau and phospho-neurofilament. Immunoprecipitation followed by immunoblotting demonstrated that DAPT does not disrupt cdk5 and p35 interaction. Moreover, DAPT up-regulated neurogenin that is negatively regulated by Notch, and down-regulated Hes1, a downstream target of Notch, suggesting that Notch signaling in the cortical neurons was disrupted. Semi-quantitative and quantitative RT-PCR analyses confirmed that DAPT up-regulated cdk5 expression at the transcriptional level. These results establish a link between Notch signaling and cdk5 expression regulating neuronal cytoskeletal protein dynamics. C1 [Kanungo, Jyotshnabala; Zheng, Ya-Li; Amin, Niranjana D.; Pant, Harish C.] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Pant, HC (reprint author), NINDS, Neurochem Lab, NIH, Bldg 49,Rm 2A28,9000 Rockville Pike, Bethesda, MD 20892 USA. EM panth@ninds.nih.gov FU Intramural NIH HHS [Z01 NS002725-21] NR 48 TC 16 Z9 17 U1 2 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2008 VL 106 IS 5 BP 2236 EP 2248 DI 10.1111/j.1471-4159.2008.05551.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 336JL UT WOS:000258360000022 PM 18662245 ER PT J AU Sveinbjornsdottir, S Sigurdsson, S Aspelund, T Kjartansson, O Eiriksdottir, G Valtysdottir, B Lopez, OL van Buchem, MA Jonsson, PV Gudnason, V Launer, LJ AF Sveinbjornsdottir, S. Sigurdsson, S. Aspelund, T. Kjartansson, O. Eiriksdottir, G. Valtysdottir, B. Lopez, O. L. van Buchem, M. A. Jonsson, P. V. Gudnason, V. Launer, L. J. TI Cerebral microbleeds in the population based AGES-Reykjavik study: prevalence and location SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID T2-ASTERISK-WEIGHTED MR-IMAGES; INTRACEREBRAL HEMORRHAGE; ASYMPTOMATIC MICROBLEEDS; AMYLOID ANGIOPATHY; ALZHEIMERS-DISEASE; ISCHEMIC-STROKE; MICROHEMORRHAGES; ASSOCIATION; LEUKOARAIOSIS; SEVERITY AB Background and purpose: Incidental foci of signal loss suggestive of cerebral microbleeds (CMBs) are frequent findings on gradient echo T2* weighted MRI (T2* MRI) of patients with haemorrhagic or ischaemic stroke. There are few prevalence data on older populations. This paper reports on the prevalence and location of CMBs in a community based cohort of older men and women (born 1907-1935) who participated in the Age Gene/ Environment Susceptibility (AGES)-Reykjavik Study, a population based cohort study that followed the Reykjavik Study Methods: As part of the examination, all eligible and consenting cohort members underwent a full brain MRI, and blood was drawn for genotyping. Results are based on the first 1962 men (n= 820) and women (n= 1142), mean age 76 years, with complete MRI and demographic information available. Results: Evidence of CMBs was found in 218 participants (11.1% (95% CI 9.8% to 12.6%)); men had significantly more CMBs than women (14.4% vs 8.8%; p= 0.0002, age adjusted). The prevalence of CMBs increased with age (p= 0.0001) in both men (p= 0.006) and women (p= 0.007). CMBs were located in the cerebral lobes (70%), the basal ganglia region (10.5%) and infratentorium (18.6%). Having a CMB was significantly associated with a homozygote Apo E epsilon 4 epsilon 4 genotype (p= 0.01). Conclusion: Cerebral microbleeds are common in older persons. The association with homozygote Apo E epsilon 4 genotype and finding a relative predominance in the parietal lobes might indicate an association with amyloid angiopathy. C1 [Sveinbjornsdottir, S.; Kjartansson, O.; Jonsson, P. V.] Landspitali Univ Hosp, Dept Neurol, IS-108 Reykjavik, Iceland. [Sveinbjornsdottir, S.; Kjartansson, O.; Jonsson, P. V.] Landspitali Univ Hosp, Dept Radiol, IS-108 Reykjavik, Iceland. [Sveinbjornsdottir, S.; Jonsson, P. V.; Gudnason, V.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Sveinbjornsdottir, S.; Sigurdsson, S.; Aspelund, T.; Kjartansson, O.; Eiriksdottir, G.; Valtysdottir, B.; Jonsson, P. V.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Lopez, O. L.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Lopez, O. L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [van Buchem, M. A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. [Launer, L. J.] NIA, Bethesda, MD 20892 USA. RP Sveinbjornsdottir, S (reprint author), Landspitali Univ Hosp, Dept Neurol, C12, IS-108 Reykjavik, Iceland. EM sigurls@landspitali.is RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-1-2100] NR 33 TC 90 Z9 92 U1 0 U2 3 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 SEP PY 2008 VL 79 IS 9 BP 1002 EP 1006 DI 10.1136/jnnp.2007.121913 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 337ZG UT WOS:000258473600008 PM 18270235 ER PT J AU Isoda, M Hikosaka, O AF Isoda, Masaki Hikosaka, Okihide TI A neural correlate of motivational conflict in the superior colliculus of the macaque SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SUPPLEMENTARY EYE FIELD; ANTERIOR CINGULATE CORTEX; MEDIAL FRONTAL-CORTEX; PRIMATE CAUDATE-NUCLEUS; VISUAL-SEARCH TASK; BASAL GANGLIA; NEURONAL-ACTIVITY; CORTICOSTRIATAL PROJECTIONS; RESPONSE BIAS; MONKEY AB Behavior is controlled by both external instructions and internal motives, but the actions demanded by each may be different. A common consequence of such a conflict is a delay in decision making and subsequent motor responses. It is unknown, however, what neural mechanisms underlie motivational conflict and associated response delay. To answer this question, we recorded single-neuron activity in the superior colliculus (SC) as macaque monkeys performed a visually guided, asymmetrically rewarded saccade task. A peripheral spot of light at one of two opposing positions was illuminated to indicate a saccade target. In a given block of trials, one position was associated with a big reward and the other with a small reward. The big-reward position was alternated across blocks. Behavioral analyses revealed that small-reward trials created a conflict between the instructed saccade to one position and the internally motivated, yet invalid saccade to the opposite position. We found that movement neurons in the SC temporally exhibited bursting activity after the appearance of the small-reward target opposite their movement field. This transient activity predicted the amount of response delay for upcoming saccades. Our data suggest that motivational conflict activates movement neurons in both colliculi, thereby delaying saccade initiation through intercollicular inhibitory interactions. C1 [Isoda, Masaki] RIKEN, Lab Symbol Cognit Dev, Brain Sci Inst, Wako, Saitama 3510198, Japan. [Isoda, Masaki; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Isoda, M (reprint author), RIKEN, Lab Symbol Cognit Dev, Brain Sci Inst, 2-1 Hirosawa, Wako, Saitama 3510198, Japan. EM isodam@brain.riken.jp FU National Eye Institute FX This work was supported by the intramural research program of the National Eye Institute. NR 60 TC 11 Z9 12 U1 3 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2008 VL 100 IS 3 BP 1332 EP 1342 DI 10.1152/jn.90275.2008 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 345YR UT WOS:000259034900017 PM 18596188 ER PT J AU Huey, ED Zahn, R Krueger, F Moll, J Kapogiannis, D Wassermann, EM Grafman, J AF Huey, Edward D. Zahn, Roland Krueger, Frank Moll, Jorge Kapogiannis, Dimitrios Wassermann, Eric M. Grafman, Jordan TI A Psychological and Neuroanatomical Model of Obsessive-Compulsive Disorder SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Review ID ANTERIOR CINGULATE CORTEX; CEREBRAL-BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; HUMAN ORBITOFRONTAL CORTEX; BASAL GANGLIA LESIONS; MAGNETIC-RESONANCE; SYMPTOM PROVOCATION; PREFRONTAL CORTEX; MATTER ABNORMALITIES; ANXIETY DISORDERS AB Imaging, surgical, and lesion studies suggest that the prefrontal cortex (orbitofrontal and anterior cingulate cortexes), basal ganglia, and thalamus are involved in the pathogenesis of obsessive-compulsive disorder (OCD). On the basis of these findings several models of OCD have been developed, but have had difficulty fully integrating the psychological and neuroanatomical findings of OCD. Recent research in the field of cognitive neuroscience on the normal function of these brain areas demonstrates the role of the orbitofrontal cortex in reward, the anterior cingulate cortex in error detection, the basal ganglia in affecting the threshold for activation of motor and behavioral programs, and the prefrontal cortex in storing memories of behavioral sequences (called "structured event complexes" or SECs). The authors propose that the initiation of these SECs can be accompanied by anxiety that is relieved with completion of the SEC, and that a deficit in this process could be responsible for many of the symptoms of OCD. Specifically, the anxiety can form the basis of an obsession, and a compulsion can be an attempt to receive relief from the anxiety by repeating parts of, or an entire, SEC. The authors discuss empiric support for, and specific experimental predictions of, this model. The authors believe that this model explains the specific symptoms, and integrates the psychology and neuroanatomy of OCD better than previous models. C1 [Huey, Edward D.; Zahn, Roland; Krueger, Frank; Moll, Jorge; Kapogiannis, Dimitrios; Wassermann, Eric M.; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Huey, Edward D.] Litwin Zucker Res Ctr, Study Alzheimers Dis & Memory Disorders, Great Neck, NY USA. [Moll, Jorge] LABS Or Hosp Network, Cognit & Behav Neurosci Unit, Rio De Janeiro, Brazil. [Wassermann, Eric M.] NINDS, Brain Stimulat Unit, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Rm 7D43,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov RI Zahn, Roland/C-4665-2008; Moll, Jorge/B-2654-2013; OI Zahn, Roland/0000-0002-8447-1453; Grafman, Jordan H./0000-0001-8645-4457 FU NIH; NINDS; NIMH FX We thank Ben Greenberg and Anthony Pinto of Brown University for their very helpful comments and Nicole Armstrong for her help with manuscript preparation. This research was supported by the Intramural Research Program of NIH, NINDS, and NIMH. NR 155 TC 60 Z9 60 U1 7 U2 21 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2008 VL 20 IS 4 BP 390 EP 408 PG 19 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 399CV UT WOS:000262778900002 PM 19196924 ER PT J AU Li, J Okamoto, H Yin, C Jagannathan, J Takizawa, J Aoki, S Glasker, S Rushing, EJ Vortmeyer, AO Oldfield, EH Yamanaka, R Zhuang, ZP AF Li, Jie Okamoto, Hiroaki Yin, Chunyue Jagannathan, Jay Takizawa, Jun Aoki, Sadao Glaesker, Sven Rushing, Elisabeth J. Vortmeyer, Alexander O. Oldfield, Edward H. Yamanaka, Ryuya Zhuang, Zhengping TI Proteomic characterization of primary diffuse large B-cell lymphomas in the central nervous system - Laboratory investigation SO JOURNAL OF NEUROSURGERY LA English DT Article DE B-cell lymphoma; gel electrophoresis; proteomics; sporadic systemic lymphoma; Western blot ID PROTEIN DISULFIDE-ISOMERASE; CLASSICAL HODGKINS-DISEASE; PRIMARY MALIGNANT-LYMPHOMA; REED-STERNBERG CELLS; PRIMARY CNS LYMPHOMA; IMMUNOGLOBULIN TRANSCRIPTION; ENERGY-METABOLISM; WHITE-MATTER; IMMUNOCOMPETENT PATIENTS; GLIOBLASTOMA-MULTIFORME AB Object. The lack of primary lymphoid tissue within the central nervous system (CNS) confounds our understanding of the pathogenesis of primary CNS lymphomas (PCNSLs). Comparing the protein expression of PCNSLs and sporadic systemic lymphomas (SSLs) provides a useful strategy for identifying a molecular signature that characterizes disease-associated features and provides information regarding tumor initiation and progression. Methods. Seven diffuse large B-cell PCNSLs were selected to undergo 2D gel electrophoresis, and profiled proteomes from these PCNSLs were compared with those from 7 diffuse large B-cell SSLs. Distinguishing proteins were sequenced using mass spectrometry. Results. Two-dimensional get electrophoresis identified an average of 706 proteins from each specimen. Computerized gel analysis and manual reconfirmation revealed a 96% similarity in the proteomes of PCNSLs and SSLs. Comparative analysis identified 9 proteins significantly overexpressed (p < 0.05) and 16 proteins downregulated in PCNSLs. The proteomic findings were further validated using Western blot and immunohistochemical staining. Conclusions. The similarities in proteomic patterns between PCNSLs and SSLs suggest that these tumor types share structural similarities, acquired during differentiation. The ultimate fate of lymphomatous cells (CNS vs systemic) may be related to differentially expressed proteins, which function in homing and host processing. Elucidating the roles of these differentially expressed proteins will prove valuable in understanding the pathogenesis of PCNSL. C1 [Li, Jie; Okamoto, Hiroaki; Yin, Chunyue; Jagannathan, Jay; Glaesker, Sven; Vortmeyer, Alexander O.; Oldfield, Edward H.; Zhuang, Zhengping] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD USA. [Takizawa, Jun; Aoki, Sadao] Niigata Univ, Div Hematol, Grad Sch Med & Dent Sci, Niigata, Japan. [Rushing, Elisabeth J.] USAF, Inst Pathol, Dept Neuropathol & Ophthalm Pathol, Washington, DC 20330 USA. [Yamanaka, Ryuya] Niigata Univ, Brain Res Inst, Dept Neurosurg, Niigata 95021, Japan. [Jagannathan, Jay] Univ Virginia Hlth Syst, Dept Neurosurg, Charlottesville, VA USA. RP Zhuang, ZP (reprint author), Room 5D37,10 Ctr Dr, Bethesda, MD 20892 USA. EM zhuangp@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke; National Institutes of Health, Bethesda, Maryland FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. NR 66 TC 4 Z9 5 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2008 VL 109 IS 3 BP 536 EP 546 DI 10.3171/JNS/2008/109/9/0536 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 344CX UT WOS:000258904400027 PM 18759588 ER PT J AU Jagannathan, J Walbridge, S Butman, JA Oldfield, EH Lonser, RR AF Jagannathan, Jay Walbridge, Stuart Butman, John A. Oldfield, Edward H. Lonser, Russell R. TI Effect of ependymal and pial surfaces on convection-enhanced delivery. Laboratory investigation SO JOURNAL OF NEUROSURGERY LA English DT Article DE cerebrospinal fluid; convection-enhanced delivery; ependyma; imaging; Macaca fascicularis; Macaca mulatta; pia mater; ventricle ID PRIMATE BRAIN; COMPUTERIZED-TOMOGRAPHY; REAL-TIME; INFUSION; STEM; GLUCOCEREBROSIDASE; MACROMOLECULES; PERFUSION; PROTEIN; DISEASE AB Object. Convection-enhanced delivery (CED) is increasingly used to investigate new treatments for central nervous system disorders. Although the properties of CED are well established in normal gray and white matter central nervous system structures, the effects on drug distribution imposed by ependymal and pial surfaces are not precisely defined. To determine the effect of these anatomical boundaries on CED, the authors infused low MW and high MW tracers for MR imaging near ependymal (periventricular) and pial (pericisternal) surfaces. Methods. Five primates underwent CED of Gd-diethylenetriamine pentaacetic acid (Gd-DTPA; MW 590 D) or Gd-bound albumin (Gd-albumin; MW 72,000 D) during serial real-time MR imaging (FLAIR and T1-weighted sequences). Periventricular (caudate) infusions were performed unilaterally in I animal (volume of infusion [Vi] 57 mu l) and bilaterally in 1 animal with Gd-DTPA (Vi = 40 mu l on each side), and bilaterally in 1 animal with Gd-albumin (Vi = 80 mu l on each side). Pericisternal infusions were performed in 2 animals with Gd-DTPA (Vi = 190 mu l) or with Gd-albumin (Vi = 185 mu l) (1 animal each). Clinical effects, MR imaging, and histology were analyzed. Results. Large regions of the brain and brainstem were perfused with both tracers. Intraparenchymal distribution was successfully tracked in real time by using T1-weighted MR imaging. During infusion, the volume of distribution (Vd) increased linearly (R-2 = 0.98) with periventricular (mean Vd/Vi ratio +/- standard deviation; 4.5 +/- 0.5) and pericisternal (5.2 +/- 0.3) Vi, but did so only until the leading edge of distribution reached the ependymal or pial surfaces, respectively. After the infusate reached either surface, the Vd/Vi decreased significantly (ependyma 2.9 +/- 0.8, pia mater 3.6 +/- 1.0; p < 0.05) and infusate entry into the ventricular or cisternal cerebrospinal fluid (CSF) was identified on FLAIR but not on T1-weighted MR images. Conclusions. Ependymal and pial boundaries are permeable to small and large molecules delivered interstitially by convection. Once infusate reaches these surfaces, a portion enters the adjacent ventricular or cisternal CSF and the tissue Vd/Vi ratio decreases. Although T1-weighted MR imaging is best for tracking intraparenchymal infusate distribution, FLAIR MR imaging is the most sensitive and accurate for detecting entry of Gd-labeled imaging compounds into CSF during CED. C1 [Jagannathan, Jay; Walbridge, Stuart; Oldfield, Edward H.; Lonser, Russell R.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Butman, John A.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD USA. [Jagannathan, Jay; Oldfield, Edward H.] Univ Virginia, Dept Neurosurg, Univ Virginia Hlth Syst, Charlottesville, VA USA. RP Lonser, RR (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 FU National Institute of Neurological Disorders; Stroke at the National Institutes of Health FX Support for this research was provided by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. NR 20 TC 24 Z9 24 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2008 VL 109 IS 3 BP 547 EP 552 DI 10.3171/JNS/2008/109/9/0547 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 344CX UT WOS:000258904400028 PM 18759589 ER PT J AU Lonser, RR AF Lonser, Russell R. TI Metastasis in von Hippel-Lindau disease - Response SO JOURNAL OF NEUROSURGERY LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Lonser, RR (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 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 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2008 VL 109 IS 3 BP 568 EP 569 DI 10.3171/JNS/2008/109/9/0568 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 344CX UT WOS:000258904400032 ER PT J AU Lonser, RR Kim, HJ AF Lonser, Russell R. Kim, H. Jeffrey TI Endolymphatic sac tumors - Response SO JOURNAL OF NEUROSURGERY LA English DT Letter ID HIPPEL-LINDAU-DISEASE C1 [Lonser, Russell R.; Kim, H. Jeffrey] NIH, Bethesda, MD 20892 USA. [Kim, H. Jeffrey] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Lonser, RR (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 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 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2008 VL 109 IS 3 BP 570 EP 570 DI 10.3171/JNS/2008/109/9/0569 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 344CX UT WOS:000258904400034 ER PT J AU Esposito, G Giovacchini, G Liow, JS Bhattacharjee, AK Greenstein, D Schapiro, M Hallett, M Herscovitch, P Eckelman, WC Carson, RE Rapoport, SI AF Esposito, Giuseppe Giovacchini, Giampiero Liow, Jeih-San Bhattacharjee, Abesh K. Greenstein, Dede Schapiro, Mark Hallett, Mark Herscovitch, Peter Eckelman, William C. Carson, Richard E. Rapoport, Stanley I. TI Imaging neuroinflammation in Alzheimer's disease with radiolabeled arachidonic acid and PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE arachidonic; neuroinflammation; PET; Alzheimer's imaging ID POSITRON-EMISSION-TOMOGRAPHY; FALSE DISCOVERY RATE; PHOSPHOLIPASE A(2); NEURODEGENERATIVE DISEASES; BRAIN PHOSPHOLIPIDS; BLOOD-FLOW; ACTIVATED MICROGLIA; RAT; METABOLISM; VOLUME AB Incorporation coefficients (K(star)) of arachidonic acid (AA) in the brain are increased in a rat model of neuroinflammation, as are other markers of AA metabolism. Data also indicate that neuroinflammation contributes to Alzheimer's disease (AD). On the basis of these observations, K(star) for AA was hypothesized to be elevated in patients with AD. Methods: A total of 8 patients with AD with an average (+/-SD) Mini-Mental State Examination score of 14.7 +/- 8.4 (mean age, 71.7 +/- 11.2 y) and 9 controls with a normal Mini-Mental State Examination score (mean age, 68.7 +/- 5.6 y) were studied. Each subject received a (15)O-water PET scan of regional cerebral blood flow, followed after 15 min by a 1-(11)C-AA scan of regional K(star) for AA. Results: In the patients with AD, compared with control subjects, global gray matter K(star) for AA (corrected or uncorrected for the partial-volume error [PVE]) was significantly elevated, whereas only PVE-uncorrected global cerebral blood flow was reduced significantly (P < 0.05). A false-discovery-rate procedure indicated that PVE-corrected K(star) for AA was increased in 78 of 90 identified hemispheric gray matter regions. PVE-corrected regional cerebral blood flow, although decreased in 12 regions at P < 0.01 by an unpaired t test, did not survive the false-discovery-rate procedure. The surviving K(star) increments were widespread in the neocortex but were absent in caudate, pallidum, and thalamic regions. Conclusion: These preliminary results show that K(star) for AA is widely elevated in the AD brain, particularly in regions reported to have high densities of senile (neuritic) plaques with activated microglia. To the extent that the elevations represent upregulated AA metabolism associated with neuroinflammation, PET with 1-(11)C-AA could be used to examine neuroinflammation in patients with AD and other brain diseases. C1 [Esposito, Giuseppe; Giovacchini, Giampiero; Liow, Jeih-San; Bhattacharjee, Abesh K.; Schapiro, Mark; Rapoport, Stanley I.] NIA, Natl Inst Hlth, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. [Giovacchini, Giampiero] Univ Milano Bicocca, Ctr Mol Bioimaging, Milan, Italy. [Liow, Jeih-San] NIMH, Natl Inst Hlth, Mol Imaging Branch, Bethesda, MD 20892 USA. [Greenstein, Dede] NIMH, Natl Inst Hlth, Child Psychiat Branch, Bethesda, MD 20892 USA. [Schapiro, Mark] Cincinnati Childrens Hosp, Med Ctr, Dept Pediat Neurol, Cincinnati, OH USA. [Hallett, Mark] NINDS, Natl Inst Hlth, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20892 USA. [Herscovitch, Peter; Eckelman, William C.; Carson, Richard E.] Natl Inst Hlth, Ctr Clin, Dept Positron Emiss Tomog, Bethesda, MD USA. [Eckelman, William C.] Mol Tracer LLC, Bethesda, MD USA. [Carson, Richard E.] Yale Univ, Sch Med, Yale PET Ctr, New Haven, CT USA. RP Rapoport, SI (reprint author), NIA, Natl Inst Hlth, Brain Physiol & Metab Sect, Bldg 9,Room IS128, Bethesda, MD 20892 USA. EM sir@helix.nih.gov RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 FU Intramural Programs of the National Institute on Aging; National Institute of Neurological Disorders and Stroke; National Institute of Mental Health; National Institutes of Health, Bethesda, Maryland FX We thank Dr. Madhav Thambisetty for his helpful comments about the manuscript. This work was supported by the Intramural Programs of the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, the National Institute of Mental Health, and the PET Department of the Clinical Center at the National Institutes of Health, Bethesda, Maryland. NR 46 TC 74 Z9 76 U1 0 U2 6 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 SEP PY 2008 VL 49 IS 9 BP 1414 EP 1421 DI 10.2967/jnumed.107.049619 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 346CQ UT WOS:000259046400020 PM 18703605 ER PT J AU Sojkova, J Beason-Held, L Zhou, Y An, Y Kraut, MA Ye, W Ferrucci, L Mathis, CA Klunk, WE Wong, DF Resnick, SM AF Sojkoval, Jitka Beason-Held, Lori Zhou, Yun An, Yang Kraut, Michael A. Ye, Weigo Ferrucci, Luigi Mathis, Chester A. Klunk, William E. Wong, Dean F. Resnick, Susan M. TI Longitudinal cerebral blood flow and amyloid deposition: An emerging pattern? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PIB; CBF; longitudinal; positron emission tomography; aging ID MILD COGNITIVE IMPAIRMENT; EARLY ALZHEIMERS-DISEASE; PITTSBURGH COMPOUND-B; REFERENCE TISSUE MODEL; SPATIAL CONSTRAINT; ELDERLY SUBJECTS; OLDER-ADULTS; PET; DEMENTIA; BRAIN AB Although cerebral amyloid deposition may precede cognitive impairment by decades, the relationship between amyloid deposition and longitudinal change in neuronal function has not, to our knowledge, been studied. The aim of this article was to determine whether individuals without dementia with high and low amyloid burden show different patterns of longitudinal regional cerebral blood flow (rCBF) changes in the years preceding measurement of amyloid deposition. Methods: Twenty-eight participants without dementia (mean age +/- SD, 82.5 +/- 4.8 y; 6 mildly impaired) from the Baltimore Longitudinal Study of Aging underwent yearly resting-state (15)O-H(2)O PET scans for up to 8 y. (11)C-PIB images of amyloid deposition were acquired on average 10.8 +/- 0.8 y after the first CBF scan. (11)C-PIB distribution volume ratios of regions of interest were estimated by fitting a reference-tissue model to the measured time-activity curves. On the basis of mean cortical distribution volume ratios, participants were divided into groups with high or low (11)C-PIB retention. Differences in longitudinal rCBF changes between high-and low-(11)C-PIB groups were investigated by voxel-based analysis. Results: Longitudinal rCBF changes differed significantly between high- (n = 10) and low- (n = 18) (11)C-PIB groups (P <= 0.001). Greater longitudinal decreases in rCBF in the high-(11)C-PIB group than in the low-(11)C-PIB group were seen in right anterior to middle cingulate, right supramarginal gyrus, left thalamus, and midbrain bilaterally. Greater increases in rCBF overtime in the high-(11)C-PIB group were found in left medial and inferior frontal gyri, right precuneus, left inferior parietal lobule, and left postcentral gyrus. Conclusion: In this group of older adults without dementia, those with high (11)C-PIB show greater longitudinal declines in rCBF in certain areas, representing regions with greater decrements in neuronal function. Greater longitudinal increases in rCBF are also observed in those with higher amyloid load and may represent an attempt to preserve neuronal function in these regions. C1 [Sojkoval, Jitka; Beason-Held, Lori; An, Yang; Ferrucci, Luigi; Resnick, Susan M.] NIA, Lab Personal & Cognit, NIH, Biomed Ctr,IRP, Baltimore, MD 21224 USA. [Sojkoval, Jitka; Zhou, Yun; Kraut, Michael A.; Ye, Weigo; Wong, Dean F.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Mathis, Chester A.] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. [Klunk, William E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Wong, Dean F.] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. [Wong, Dean F.] Johns Hopkins Univ, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. RP Resnick, SM (reprint author), NIA, Lab Personal & Cognit, NIH, Biomed Ctr,IRP, Suite 100,Room 04B336,251 Bayview Blvd, Baltimore, MD 21224 USA. EM susan.resnick@nih.gov OI Klunk, William/0000-0001-5512-0251 FU National Institutes of Health (NIH) [N01-AG-3-2124, K24 DA00412]; NIA; PIB FX We thank the staff of the PET facility at Johns Hopkins University and the neuroimaging staff of the National Institute on Aging (NIA) for their assistance. This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), by the NIA, and by NIH grants N01-AG-3-2124 and K24 DA00412. GE Healthcare holds a license agreement with the University of Pittsburgh based on the PIB technology described in this manuscript. Drs. Klunk and Mathis are co-inventors of PIB and, as such, have a financial interest in this license agreement. NR 38 TC 33 Z9 33 U1 0 U2 0 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 SEP PY 2008 VL 49 IS 9 BP 1465 EP 1471 DI 10.2967/jnumed.108.051946 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 346CQ UT WOS:000259046400027 PM 18703614 ER PT J AU Yang, K Lamprecht, SA Shinozaki, H Fan, K Yan, W Newmark, HL Kopelovich, L Edelmann, W Jin, B Gravaghi, C Augenlicht, L Kucherlapati, R Lipkin, M AF Yang, Kan Lamprecht, Sergio A. Shinozaki, Hiroharu Fan, Kunhua Yan, WanCai Newmark, Harold L. Kopelovich, Levy Edelmann, Winfried Jin, Bo Gravaghi, Claudia Augenlicht, Leonard Kucherlapati, Raju Lipkin, Martin TI Dietary calcium and cholecalciferol modulate cyclin D1 expression, apoptosis, and tumorigenesis in intestine of adenomatous polyposis coli1638N/+ mice SO JOURNAL OF NUTRITION LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; VITAMIN-D; COLON-CANCER; COLORECTAL-CANCER; SENSING RECEPTOR; GENE-EXPRESSION; MOUSE MODELS; APC; PREVENTION; CELLS AB Both epidemiological and experimental findings have indicated that components of Western diets influence colonic tumorigenesis. Among dietary constituents, calcium and cholecalciferol have emerged as promising chemopreventive agents. We have demonstrated that a Western-style diet (WD) with low levels of calcium and cholecalciferol and high levels of (n-6) PUFA, increased the incidence of neoplasia in mouse intestine compared with a standard AIN-76A diet; models included wild-type mice and mice with targeted mutations. In the present study, adenomatous polyposis coli (Apc)(1638N/+) mice carrying a heterozygous Apc mutation were fed either an AIN-76A diet, a WD, or a WD supplemented with calcium and cholecalciferol (WD/Ca/VitD3). Diets were fed for 24 wk and effects on cellular and molecular events were assessed by performing immunohistochemistry in colonic epithelium along the crypt-to-surface continuum. Feeding WD to Apc(1638N/+) mice not only enhanced cyclin D1 expression in colonic epithelium compared with AIN-76A treatment as previously reported but also significantly increased the expression of the antiapoptotic protein B-cell lymphoma 2(Bcl-2) concomitantly with a decrease in the proapoptotic Bcl2-associated X protein and the number of apoptotic epithelial cells. WD treatment enhanced mutant Apc-driven small intestinal carcinogenesis and also resulted in the formation of a small number of colonic adenomas (0.16 +/- 0.09; P < 0.05). By contrast, the WD/Ca/VitD3 diet reversed WD-induced growth, promoting changes in colonic epithelium. Importantly, Apc(1638N/+) mice fed the WD/Ca/VitD3 diet did not develop colonic tumors, further indicating that dietary calcium and cholecalciferol have a key role in the chemoprevention of colorectal neoplasia in this mouse model of human colon cancer. C1 [Yang, Kan; Lamprecht, Sergio A.; Shinozaki, Hiroharu; Fan, Kunhua; Gravaghi, Claudia; Lipkin, Martin] Cornell Univ, Weill Med Coll, Dept Med Gastroenterol & Hepatol, Strang Canc Res Lab, New York, NY 10065 USA. [Yan, WanCai; Edelmann, Winfried; Jin, Bo; Augenlicht, Leonard] Albert Einstein Coll Med, Bronx, NY 10461 USA. [Newmark, Harold L.] Rutgers State Univ, Dept Biol Chem, Piscataway, NJ 08854 USA. [Kopelovich, Levy] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Kucherlapati, Raju] Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. RP Lipkin, M (reprint author), Cornell Univ, Weill Med Coll, Dept Med Gastroenterol & Hepatol, Strang Canc Res Lab, New York, NY 10065 USA. EM lipkin@mail.rockefeller.edu FU NO [N01-CN-43302, N01-CN-43308, U54-CA100926, CA84301, ES-11040] FX Supported by NO awards N01-CN-43302, N01-CN-43308, U54-CA100926, CA84301, and ES-11040, NR 39 TC 27 Z9 27 U1 0 U2 1 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 SEP PY 2008 VL 138 IS 9 BP 1658 EP 1663 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 342RU UT WOS:000258802000012 PM 18716166 ER PT J AU Freedman, LS Guenther, PN Krebs-Smith, SM Kott, PS AF Freedman, Laurence S. Guenther, Patricia N. Krebs-Smith, Susan M. Kott, Phillip S. TI A population's mean Healthy Eating Index-2005 scores are best estimated by the score of the population ratio when one 24-hour recall is available SO JOURNAL OF NUTRITION LA English DT Article ID FOODS AB he USDA Healthy Eating Index-2005 (HEI-2005) is a tool to quantify and evaluate the quality of diet consumed by the U.S. population. It comprises 12 components, expressed as ratios of a food group or nutrient to energy intake. The components are scored on a scale from 0 to M, where M is 5, 10, or 20. Ideally, the HEI-2005 is calculated or the basis of the usual dietary intake of an individual. Intake data, collected via a 24-h recall, are often available for only 1 d for each individual. In this article, we examine how best to estimate a population's mean usual HEI-2005 component and total scores when 1 d of dietary information is available for a sample of individuals from the population. Three methods are considered: the mean of individual scores, the score of the mean of individual ratios, and the score of the ratio of total food group or nutrient intake to total energy intake, which we call the Population ratio. We investigate via computer simulation which method is the least biased. The simulations are based on statistical modeling of the distributions of intakes reported by 738 women participating in the Eating at America's Table Study. The results show that overall, the score of the population ratio is the preferred method. We therefore recommend that the quality of the U.S. population's diet be assessed and monitored using this method. C1 [Freedman, Laurence S.] Gertner Inst Epidemiol & Hlth Policy Res, IL-52161 Tel Hashomer, Israel. [Guenther, Patricia N.] USDA, Ctr Nutr Policy & Promot, Alexandria, VA 22302 USA. [Krebs-Smith, Susan M.] NCI, Bethesda, MD 20892 USA. [Kott, Phillip S.] Natl Agr Stat Serv, Fairfax, VA 22030 USA. RP Freedman, LS (reprint author), Gertner Inst Epidemiol & Hlth Policy Res, IL-52161 Tel Hashomer, Israel. EM lsf@actcom.co.il FU Intramural NIH HHS [Z99 CA999999] NR 8 TC 33 Z9 34 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 SEP PY 2008 VL 138 IS 9 BP 1725 EP 1729 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 342RU UT WOS:000258802000022 PM 18716176 ER PT J AU McGrath, PJ Walco, GA Turk, DC Dworkin, RH Brown, MT Davidson, K Eccleston, C Finley, GA Goldschneider, K Haverkos, L Hertz, SH Ljungman, G Palermo, T Rappaport, BA Rhodes, T Schechter, N Scott, J Sethna, N Svensson, OK Stinson, J von Baeyer, CL Walker, L Weisman, S White, RE Zajicek, A Zeltzer, L AF McGrath, Patrick J. Walco, Gary A. Turk, Dennis C. Dworkin, Robert H. Brown, Mark T. Davidson, Karina Eccleston, Christopher Finley, G. Allen Goldschneider, Kenneth Haverkos, Lynne Hertz, Sharon H. Ljungman, Gustaf Palermo, Tonya Rappaport, Bob A. Rhodes, Thomas Schechter, Neil Scott, Jane Sethna, Navil Svensson, Ola K. Stinson, Jennifer von Baeyer, Carl L. Walker, Lynn Weisman, Steven White, Richard E. Zajicek, Anne Zeltzer, Lonnie TI Core outcome domains and measures for pediatric acute and chronic/recurrent pain clinical trials: PedIMMPACT recommendations SO JOURNAL OF PAIN LA English DT Article DE acute pain; chronic pain; children; adolescents; pediatric; clinical trials; randomized controlled trials; assessment; outcomes; health-related quality of life; physical functioning; emotional functioning; global ratings; adverse events; IMMPACT ID QUALITY-OF-LIFE; FUNCTIONAL DISABILITY INVENTORY; SCHOOL-AGED CHILDREN; SICKLE-CELL-DISEASE; POSTOPERATIVE PAIN; PSYCHOMETRIC PROPERTIES; SELF-REPORT; IMMPACT RECOMMENDATIONS; BEHAVIORAL DISTRESS; INITIAL VALIDATION AB Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 26 professionals from academia, governmental agencies, and the pharmaceutical industry participated in a 2-stage Delphi poll and a consensus meeting that identified core outcome domains and measures that should be considered in clinical trials of treatments for acute and chronic pain in children and adolescents. Consensus was refined by consultation with the international pediatric pain community through announcement of our recommendations on the Pediatric Pain List and inviting and incorporating comments from external sources. There was consensus that investigators conducting pediatric acute pain clinical trials should consider assessing outcomes in pain intensity; global judgment of satisfaction with treatment; symptoms and adverse events; physical recovery; emotional response; and economic factors. There was also agreement that investigators conducting pediatric clinical trials in chronic and recurrent pain should consider assessing outcomes in pain intensity; physical functioning; emotional functioning; role functioning; symptoms and adverse events; global judgment of satisfaction with treatment; sleep; and economic factors. Specific measures or measurement strategies were recommended for different age groups for each domain. Perspective: Based on systematic review and consensus of experts, core domains and measures for clinical trials to treat pain in children and adolescents were defined. This will assist in comparison and pooling of data and promote evidence-based treatment, encourage complete reporting of outcomes, simplify the review of proposals and manuscripts, and facilitate clinicians making informed decisions regarding treatment. (C) 2008 by the American Pain Society. C1 [Walco, Gary A.] Hackensack Univ, Joseph M Sanzari Childrens Hosp, Med Ctr, Hackensack, NJ 07601 USA. [McGrath, Patrick J.; Finley, G. Allen] Dalhousie Univ, Halifax, NS, Canada. [McGrath, Patrick J.; Finley, G. Allen] IWK Hlth Ctr, Halifax, NS, Canada. [Turk, Dennis C.] Univ Washington, Seattle, WA 98195 USA. [Dworkin, Robert H.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Brown, Mark T.] Pfizer Inc, Ann Arbor, MI USA. [Davidson, Karina] Columbia Univ, New York, NY USA. [Eccleston, Christopher] Univ Bath, Bath BA2 7AY, Avon, England. [Goldschneider, Kenneth] Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. [Haverkos, Lynne; Zajicek, Anne] NIH NICHD, Bethesda, MD USA. [Hertz, Sharon H.; Rappaport, Bob A.; Scott, Jane] US FDA, Rockville, MD 20857 USA. [Ljungman, Gustaf] Uppsala Univ, Childrens Hosp, Uppsala, Sweden. [Palermo, Tonya] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Rhodes, Thomas] Merck & Co Inc, Blue Bell, PA USA. [Schechter, Neil] St Francis Hosp & Med Ctr, Hartford, CT USA. [Sethna, Navil] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. [Svensson, Ola K.] AstraZeneca, Stockholm, Sweden. [Stinson, Jennifer] Univ Toronto, Toronto, ON, Canada. [Stinson, Jennifer] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [von Baeyer, Carl L.] Univ Saskatchewan, Saskatoon, SK, Canada. [Walker, Lynn] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Weisman, Steven] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Weisman, Steven] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [White, Richard E.] Endo Pharmaceut, Chadds Ford, PA USA. [White, Richard E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Walco, GA (reprint author), Hackensack Univ, Joseph M Sanzari Childrens Hosp, Med Ctr, 30 Prospect Ave, Hackensack, NJ 07601 USA. EM gwalco@humed.com OI Ljungman, Gustaf/0000-0002-4949-2494; von Baeyer, Carl/0000-0002-6308-1966; Zeltzer, Lonnie/0000-0001-9306-9450; Eccleston, Christopher/0000-0003-0698-1543; McGrath, Patrick/0000-0002-9568-2571 NR 80 TC 271 Z9 274 U1 4 U2 17 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD SEP PY 2008 VL 9 IS 9 BP 771 EP 783 DI 10.1016/j.jpain.2008.04.007 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 347WN UT WOS:000259172200002 PM 18562251 ER PT J AU Wysocki, T Iannotti, R Weissberg-Benchell, J Laffel, L Hood, K Anderson, B Chen, R AF Wysocki, Tim Iannotti, Ronald Weissberg-Benchell, Jill Laffel, Lori Hood, Korey Anderson, Barbara Chen, Rusan CA Family Management Childhood Diabet TI Diabetes problem solving by youths with type 1 diabetes and their caregivers: Measurement, validation, and longitudinal associations with glycemic control SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE adolescents; children; diabetes; problem solving ID BLOOD-GLUCOSE DATA; SELF-MANAGEMENT; CHILDREN; ADOLESCENTS; ADHERENCE; MELLITUS; IDDM AB Objectives This article introduces a new measure of problem-solving skills of youths with type 1 diabetes (T1DM) and adult caregivers in correcting glycemic fluctuations. Methods The Diabetes Problem Solving Interview (DPSI), a structured interview, was validated during a pilot study of a behavioral intervention. DPSI data and measures of diabetes management were obtained at baseline from 114 youths (ages 9-14.5) and 109 caregivers. Glycosylated hemoglobin (HbA(1c)) was measured quarterly over 9 months. Results Results confirmed the psychometric adequacy of the DPSI. For caregivers, but not youths, low DPSI scores (indicating poor problem-solving skills) were significantly associated with worse HbA(1c) over 9 months. Conclusions The DPSI has clinical and research utility as a measure of diabetes problem-solving skills. Identification and targeted remediation of caregivers deficient diabetes problem-solving skills or promotion of youths utilization of these skills could possibly enhance glycemic control in youths with T1DM. C1 [Wysocki, Tim] Nemours Childrens Clin, Ctr Pediat Psychol Res, Jacksonville, FL 32207 USA. [Iannotti, Ronald] NICHHD, Bethesda, MD 20892 USA. [Weissberg-Benchell, Jill] Childrens Mem Hosp, Chicago, IL 60614 USA. [Anderson, Barbara] Texas Childrens Hosp, Houston, TX 77030 USA. [Chen, Rusan] Georgetown Univ, Washington, DC 20057 USA. RP Wysocki, T (reprint author), Nemours Childrens Clin, Ctr Pediat Psychol Res, 807 Childrens Way, Jacksonville, FL 32207 USA. EM twysocki@nemours.org RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 FU Intramural NIH HHS; NICHD NIH HHS [N01 HD003364] NR 27 TC 43 Z9 46 U1 4 U2 12 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 SEP PY 2008 VL 33 IS 8 BP 875 EP 884 DI 10.1093/jpepsy/jsn024 PG 10 WC Psychology, Developmental SC Psychology GA 333GP UT WOS:000258141300009 PM 18346973 ER PT J AU Oh, W Perritt, R Shankaran, S Merritts, M Donovan, EF Ehrenkranz, RA O'Shea, TM Tyson, JE Laptook, AR Das, A Higgins, RD AF Oh, William Perritt, Rebecca Shankaran, Seetha Merritts, Matthew Donovan, Edward F. Ehrenkranz, Richard A. O'Shea, T. Michael Tyson, Jon E. Laptook, Abbot R. Das, Abhik Higgins, Rosemary D. TI Association between urinary lactate to creatinine ratio and neurodevelopmental outcome in term infants with hypoxic-ischemic encephalopathy SO JOURNAL OF PEDIATRICS LA English DT Article ID NEWBORN-INFANTS; ASPHYXIA AB Objective To assess the association between urinary lactate to creatinine ratio (ULCR) and neurodevelopmental outcome in term infants with hypoxic ischemic encephalopathy and examine the effect of hypothermia on the change in ULCR. Study design Spot urine samples were collected in 58 term infants (28 hypothermia, 30 control subjects) with hypoxic ischemic encephalopathy. Urinary lactate and creatinine were measured by using (1)H nuclear magnetic, resonance spectroscopy and expressed as ULCR. Survivors were examined at 18 months of age. Results The ULCR was significantly higher in infants who died or had moderate/severe neurodevelopmental disability. Logistic regression analysis controlling for hypothermia and severity of encephalopathy confirmed the association (aqjusted odds ratio, 5.52; 95% CI, 1.36, 22.42; P < .02). Considerable overlap in ULCR was observed between infants with normal/mild disability and those who died or survived with moderate/severe disability. ULCR fell significantly between 6 and 24 hours and 48 and 72 hours of age for all infants. The magnitude of decline did not differ between hypothermia and control groups. Conclusions High ULCR is associated with death or moderate/severe neurodevelopmental disability. Significant overlap in values between the normal/mild and moderate/severe disability groups limits predictive value of this measure. Whole-body hypothermia did not affect the decline in ULCR. C1 [Oh, William] Brown Univ, Dept Pediat, Warren Alpert Med Sch, Providence, RI 02912 USA. [Perritt, Rebecca; Das, Abhik] Res Triangle Int, Res Triangle Pk, NC USA. [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Merritts, Matthew] Southwestern Univ, Dept Nucl Imaging, Dallas, TX USA. [Donovan, Edward F.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. [Ehrenkranz, Richard A.] Yale Univ, Dept Pediat, New Haven, CT 06520 USA. [O'Shea, T. Michael] Wake Forest Univ, Dept Pediat, Wake Forest, NC USA. [Tyson, Jon E.] Univ Texas Houston, Dept Pediat, Providence, RI USA. [Laptook, Abbot R.] Brown Univ, Dept Pediat, Warren Alpert Med Sch, Providence, RI 02912 USA. [Higgins, Rosemary D.] NICHD, NIH, NICHD Neonatal Res Network, Bethesda, MD USA. RP Oh, W (reprint author), Women & Infants Hosp Rhode Isl, Brown Med Sch, Dept Pediat, 101 Dudley St,Suite 1100, Providence, RI 02905 USA. EM woh@wihri.org FU Neonatal Research Network NICHD FX Supported by Neonatal Research Network NICHD. The list of grant support for each participating center is available at WWW. jpeds.com. Authors declare no conflict of interest. NR 10 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2008 VL 153 IS 3 BP 375 EP 378 DI 10.1016/j.jpeds.2008.03.041 PG 4 WC Pediatrics SC Pediatrics GA 348JV UT WOS:000259207700017 PM 18534246 ER PT J AU Flanigan, EY Aros, S Bueno, MF Conley, M Troendle, JF Cassorla, F Mills, JL AF Flanigan, Elizabeth Y. Aros, Sofia Ferraz Bueno, Maria Conley, Mary Troendle, James F. Cassorla, Fernando Mills, James L. TI Eye malformations in children with heavy alcohol exposure in utero SO JOURNAL OF PEDIATRICS LA English DT Article ID EYEGROUND MALFORMATIONS; OCULAR MANIFESTATIONS; IMAGE-ANALYSIS; OPTIC-NERVE; FETAL; MOTHERS; INVOLVEMENT AB Objective To determine whether children who do not develop fetal alcohol syndrome (FAS) despite heavy alcohol exposure are at risk for eye abnormalities. Study design We screened 9628 pregnant women and identified 101 women who were drinking >= 2 oz of absolute alcohol per day and 101 nondrinking control women. We followed 43 exposed and 55 control offspring between age 4 and 9 years, performing masked standardized ophthalomologic examinations. Results The groups did not differ in their rates of impaired visual acuity, refractory errors, ptosis, epicanthal folds, or short palpebral fissures. Biomicroscopy examination was normal in all exposed subjects; cataracts were detected in 2 control subjects (4%) but in no exposed subjects. Arterial tortuosity was seen in 7 exposed subjects (16%) and in 8 control subjects (15%). Optic nerve hypoplasia was not detected in any subject. Conclusions Previous research has found that children with FAS have a high incidence of serious ophthalmologic defects; our data indicate that the risk is limited to children with FAS and does not extend to children exposed to high levels of alcohol prenatally who do not develop FAS. Eye examinations are unlikely to clarify the diagnosis in children suspected of having alcohol-related damage. C1 [Flanigan, Elizabeth Y.; Conley, Mary; Troendle, James F.; Mills, James L.] NICHD, NIH, DHHS, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Aros, Sofia] Univ Chile, San Borja Arriaran Clin Hosp, Sch Med, Dept Pediat, Santiago, Chile. [Ferraz Bueno, Maria] Univ Chile, JJ Aguirre Hosp, Santiago, Chile. [Flanigan, Elizabeth Y.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. [Flanigan, Elizabeth Y.] Walter Reed Army Med Ctr, Dept Pediat, Washington, DC 20307 USA. [Cassorla, Fernando] Univ Chile, Sch Med, Inst Maternal & Child Res, Santiago, Chile. RP Flanigan, EY (reprint author), NICHD, NIH, DHHS, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA. EM eflanigan@usuhs.mil FU National Institute of Child Health; Human Development's Intramural Research Program [OHSR-96-04] FX Supported by the National Institute of Child Health and Human Development's Intramural Research Program and protocol/project OHSR-96-04. NR 35 TC 8 Z9 9 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2008 VL 153 IS 3 BP 391 EP 395 DI 10.1016/j.jpeds.2008.04.024 PG 5 WC Pediatrics SC Pediatrics GA 348JV UT WOS:000259207700020 PM 18571671 ER PT J AU Roeloffs, R Wickenden, AD Crean, C Werness, S McNaughton-Smith, G Stables, J McNamara, JO Ghodadra, N Rigdon, GC AF Roeloffs, Rosemarie Wickenden, Alan D. Crean, Christopher Werness, Stephen McNaughton-Smith, Grant Stables, James McNamara, James O. Ghodadra, Neil Rigdon, Greg C. TI In vivo profile of ICA-27243 [N-(6-Chloro-pyridin-3-yl)-3,4-difluoro-benzamide], a potent and selective KCNQ2/Q3 (Kv7.2/Kv7.3) activator in rodent anticonvulsant models SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID POTASSIUM CHANNEL GENE; PRECLINICAL EVALUATION; SEIZURE MODEL; DUP 996; EPILEPSY; RETIGABINE; LINOPIRDINE; MUTATION; D-23129; DRUG AB Openers or activators of neuronal KCNQ2/Q3 potassium channels decrease neuronal excitability and may provide benefit in the treatment of disorders of neuronal excitability such as epilepsy. In the present study, we evaluate the effects of ICA-27243 [N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide], an orally bioavailable, potent, and selective KCNQ2/Q3 opener, in a broad range of rodent seizure models. ICA-27243 was effective against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures in both rats (MES, ED(50) = 1.5 mg/kg p.o.; PTZ, ED(50) = 2.2 mg/kg p.o.) and mice (MES, ED(50) = 8.6 mg/kg p.o.; PTZ, ED(50) = 3.9 mg/kg p.o.) in the rat amygdala kindling model of partial seizures (full protection from seizure at 9 mg/kg p.o.) and in the 6-Hz model of psychomotor seizures in mice (active at 10 mg/kg i.p.). Antiseizure efficacy in all models was observed at doses significantly less than those shown to effect open-field locomotor activity (rat ED(50) = 40 mg/kg p.o.) or ability to remain on a Rotorod (no effect in rat at doses up to 100 mg/kg p. o.). There was no evidence of cognition impairment as measured in the Morris water maze in the rat (10 and 30 mg/kg p. o.), nor was there evidence of the development of tolerance after multiple doses of ICA-27243. Our findings suggest that selective KCNQ2/Q3 opening activity in the absence of effects on KCNQ3/Q5 or GABA-activated channels may be sufficient for broad-spectrum antiepileptic activity in rodents. C1 [Roeloffs, Rosemarie; Wickenden, Alan D.; Crean, Christopher; Werness, Stephen; McNaughton-Smith, Grant; Rigdon, Greg C.] Icagen Inc, Durham, NC 27703 USA. [Stables, James] NINDS, Anticonvulsant Screening Program, NIH, Rockville, MD USA. [McNamara, James O.; Ghodadra, Neil] Duke Univ, Sch Med, Dept Neurobiol, Durham, NC USA. RP Roeloffs, R (reprint author), Icagen Inc, 4222 Emperor Blvd,Suite 350, Durham, NC 27703 USA. EM rroeloffs@icagen.com FU Icagen FX R.R., S.W., and G.C.R. are employees of Icagen, Inc. and are owners of Icagen stock and Icagen stock options. A. D. W., G. M.-S., and C. C. are former Icagen employees who received Icagen stock option grants as part of their compensation. Rat amygdala kindling studies were conducted in the laboratory of J.O.M. by N.G. (Duke University Medical School, Durham, NC), and these studies were supported by a grant from Icagen. In addition, J.O.M. declares that he has served as an advisor to Icagen, that his compensation has included options for shares in Icagen, and that he currently owns shares in the company. NR 41 TC 37 Z9 38 U1 1 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2008 VL 326 IS 3 BP 818 EP 828 DI 10.1124/jpet.108.137794 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 338RB UT WOS:000258524400016 PM 18577704 ER PT J AU Witkin, JM Levant, B Zapata, A Kaminski, R Gasior, M AF Witkin, J. M. Levant, B. Zapata, A. Kaminski, R. Gasior, M. TI The dopamine D(3)/D(2) agonist (+)-PD-128,907 [(R-(+)-trans3,4a, 10b-tetrahydro-4-propyl-2H, 5H-[1] benzopyrano[4,3-b]1,4-oxazin-9-ol)] protects against acute and cocaine-kindled seizures in mice: Further evidence for the involvement of D(3) receptors SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID WILD-TYPE MICE; LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; BODY-TEMPERATURE; BRAIN REWARD; D3; SENSITIZATION; RATS; ANTAGONISTS; ANTICONVULSANT AB Previous findings have demonstrated a protective role for dopamine D(3)/D(2) receptor agonists in the convulsant and lethal effects of acutely administered cocaine. Data are provided here to establish that the protection occurs through a D(3) linked mechanism and that protection is extended to seizure kindling. The D(3) antagonist SB-277011-A [4-quinolinecarboxamide, N[ trans-4-[2-(6-cyano-3,4-dihydro-2(1H)-isoquinolinyl) ethyl]cyclohexyl]-(9CI)] prevented the anticonvulsant effect of the D(3)/D(2) receptor agonist (+)-PD-128,907 [(R-(+)-trans-3,4a, 10-btetrahydro4-propyl-2H, 5H-[1] benzopyrano[4,3-b]-1,4-oxazin-9-ol)] on cocaine-induced seizures. The protection afforded by the D(3)/D(2) agonist, (+)-PD-128,907, was eliminated in D(3) receptor-deficient mice. In D 2 receptor knockout mice, the anticonvulsant effects of (+)-PD-128,907 were preserved. (+)PD-128,907 also prevented the acquisition and expression of cocaine-kindled seizures engendered by repeated daily dosing with 60 mg/ kg cocaine. (+)-PD-128,907 also blocked the seizures induced in mice fully seizure kindled to cocaine. Although repeated dosing with cocaine increased the potency of cocaine to produce seizures and lethality (decreased ED 50 values), daily coadministration of (+)-PD-128,907 significantly prevented this potency shift. In mice treated daily with cocaine and (+)-PD128,907, the density, but not the affinity, of D 3 receptors was increased. The specificity with which (+)-PD-128,907 acts upon this cocaine-driven process was demonstrated by the lack of a significant effect of (+)-PD-128,907 on seizure kindling to a GABA A receptor antagonist, pentylenetetrazol. Taken together and with literature findings, the data indicate that dopamine D 3 receptors function in the initiation of a dampening mechanism against the toxic effects of cocaine, a finding that might have relevance to psychiatric disorders of drug dependence, schizophrenia, and bipolar depression. C1 [Witkin, J. M.] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. [Levant, B.] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. [Zapata, A.; Kaminski, R.; Gasior, M.] NIDA, Behav Neurosci Branch, NIH, Baltimore, MD USA. RP Witkin, JM (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. EM jwitkin@lilly.com NR 50 TC 8 Z9 8 U1 1 U2 3 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 SEP PY 2008 VL 326 IS 3 BP 930 EP 938 DI 10.1124/jpet.108.139212 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 338RB UT WOS:000258524400029 PM 18566292 ER PT J AU Do Carmo, GP Polt, R Bilsky, EJ Rice, KC Negus, SS AF Do Carmo, Gail Pereira Polt, Robin Bilsky, Edward J. Rice, Kenner C. Negus, S. Stevens TI Behavioral pharmacology of the mu/delta opioid glycopeptide MMP2200 in rhesus monkeys SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BLOOD-BRAIN-BARRIER; CAPSAICIN-INDUCED ALLODYNIA; TAIL-WITHDRAWAL PROCEDURE; THERMAL NOCICEPTION; UNANESTHETIZED PRIMATES; AGONIST SNC80; RECEPTORS; MORPHINE; RAT; ANTINOCICEPTION AB H(2)N-Tyr-D-Thr-Gly-Phe-Leu-Ser-(O-beta-D-lactose)-CONH(2) (MMP2200) is a novel glycopeptide opioid agonist with similar affinities for mu and delta receptors. Glycosylation promoted brain penetration and production of centrally mediated behavioral effects in mice; however, it is unknown whether the magnitude of enhanced brain penetration is sufficient to permit central mediation of drug effects and production of synergistic mu/delta antinociceptive interactions after systemic administration in primates. To address this issue, the present study compared the effects of MMP2200 and the mu-agonist morphine in four behavioral procedures in rhesus monkeys. In an assay of thermal nociception, morphine (1.0-5.6 mg/kg) produced dose-dependent antinociception, whereas MMP2200 (10-56 mg/kg) was ineffective. In an assay of capsaicin-induced thermal allodynia, both morphine (0.01-1.0 mg/kg) and MMP2200 (0.032 -3.2 mg/ kg) produced dose-dependent antiallodynic effects. MMP2200-induced antiallodynia was blocked by the moderately mu-selective antagonist naltrexone (0.01 mg/kg), the delta-selective antagonist naltrindole (1.0 mg/kg), and the peripherally selective opioid antagonist quaternary naltrexone ( 0.32 mg/ kg). In an assay of schedulecontrolled behavior, both morphine (0.01 -1.0 mg/kg) and MMP2200 (10-56 mg/kg) decreased response rates. Morphine effects were antagonized by naltrexone (0.001-0.01 mg/ kg); however, the effects of MMP2200 were not antagonized by either naltrexone ( 0.01 mg/ kg) or naltrindole ( 1.0 mg/kg). In an assay of drug self-administration, morphine (0.0032-0.32 mg/kg/injection) produced reinforcing effects, whereas MMP2200 (0.032 -0.32 mg/kg/injection) did not. These results suggest that systemically administered MMP2200 acted as a peripheral, mu/delta-opioid agonist with limited distribution to the central nervous system in rhesus monkeys. These results also suggest the existence of species differences in the pharmacokinetics and brain penetration of glycopeptides. C1 [Negus, S. Stevens] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. [Do Carmo, Gail Pereira; Negus, S. Stevens] Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02178 USA. [Polt, Robin] Univ Arizona, Tucson, AZ USA. [Bilsky, Edward J.] Univ New England, Biddeford, ME USA. [Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Bethesda, MD USA. [Rice, Kenner C.] NIAAA, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA. RP Negus, SS (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 N 12th St,POB 980613, Richmond, VA 23298 USA. EM ssnegus@vcu.edu OI Bilsky, Edward/0000-0002-4664-5256 FU Intramural NIH HHS; NIDA NIH HHS [R01 DA011460-09, R01 DA011460, R01-DA11460]; NINDS NIH HHS [R01 NS052727, R01-NS052727, R01 NS052727-01A2] NR 39 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2008 VL 326 IS 3 BP 939 EP 948 DI 10.1124/jpet.108.138180 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 338RB UT WOS:000258524400030 PM 18511649 ER PT J AU Wu, T Chan, P Hallett, M AF Wu, Tao Chan, Piu Hallett, Mark TI Modifications of the interactions in the motor networks when a movement becomes automatic SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; FUNCTIONAL MRI; EFFECTIVE CONNECTIVITY; BRAIN ACTIVATION; FRONTAL-CORTEX; SEQUENTIAL-PROCEDURES; VISUOMOTOR SEQUENCE; MEDIAL WALL; AREAS; FMRI AB A crucial feature of the motor system is the ability to control some movements automatically. We have previously shown that all parts of the motor networks reduce their activity with automaticity, and, while this change may indicate increased efficiency in terms of neural processing, it is not clear how motor skill can be maintained after a reduction of neural activity. In the current study, we used functional MRI (fMRI) to investigate influences on the effective connectivity of the brain motor networks when movements become automatic. Subjects practiced a sequential movement until they could execute it automatically, and task-related brain fMRI activation was measured before and after they achieved automaticity. Using the psychophysiological interaction (PPI) method, we found that the cerebellum, cingulate motor area, supplementary motor area, and putamen had significantly greater connectivity, whereas the precuneus had less connectivity in the motor networks at the automatic stage. Our findings demonstrate that the importance of the attention networks decrease when movements become automatic. Moreover, the process of automaticity is accompanied by a strengthened interaction of central motor networks even though the magnitude of the activation is decreased. We speculate that this increase in connectivity reflects more efficient neural coding of movement at the automatic stage. C1 [Wu, Tao; Chan, Piu] Capital Med Univ, Xuanwu Hosp, Minist Educ,Dept Neurol, Key Lab Neurodegenerate Disorder,Beijing Inst Ger, Beijing, Peoples R China. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), Bldg 10,Rm 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke Intramural Competitive Fellowship; National Science Foundation of China [30570530]; NINDS, NIH FX T. Wu was supported by a National Institute of Neurological Disorders and Stroke Intramural Competitive Fellowship. This work was partially supported by the National Science Foundation of China, Grant no. 30570530. In addition, this work was supported in part by the Intramural Research Program of the NINDS, NIH. NR 66 TC 44 Z9 44 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP 1 PY 2008 VL 586 IS 17 BP 4295 EP 4304 DI 10.1113/jphysiol.2008.153445 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 347NO UT WOS:000259148500024 PM 18617569 ER PT J AU Jin, GX Zhou, XB Wang, HH Zhao, H Cui, K Zhang, XS Chen, LN Hazen, SL Li, K Wong, STC AF Jin, Guangxu Zhou, Xiaobo Wang, Honghui Zhao, Hong Cui, Kemi Zhang, Xiang-Sun Chen, Luonan Hazen, Stanley L. Li, King Wong, Stephen T. C. TI The knowledge-integrated network biomarkers discovery for Major Adverse Cardiac Events SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE proteomics; mass spectrometry; MACE; network biomarker; cross validation; systems biology ID PROSTATE-CANCER PROGRESSION; METASTATIC BREAST-CANCER; CROSS-VALIDATION; PROTEIN-INTERACTION; MASS-SPECTROMETRY; PROTEOMICS; IDENTIFICATION; SERUM; COMPLEX; HER2 AB The mass spectrometry (MS) technology in clinical proteomics is very promising for discovery of new biomarkers for diseases management. To overcome the obstacles of data noises in MS analysis, we proposed a new approach of knowledge-integrated biomarker discovery using data from Major Adverse Cardiac Events (MACE) patients. We first built up a cardiovascular-related network based on protein information coming from protein annotations in Uniprot, protein-protein interaction (PPI), and signal transduction database. Distinct from the previous machine learning methods in MS data processing, we then used statistical methods to discover biomarkers in cardiovascular-related network. Through the tradeoff between known protein information and data noises in mass spectrometry data, we finally could firmly identify those high-confident biomarkers. Most importantly, aided by protein-protein interaction network, that is, cardiovascular-related network, we proposed a new type of biomarkers, that is, network biomarkers, composed of a set of proteins and the interactions among them. The candidate network biomarkers can classify the two groups of patients more accurately than current single ones without consideration of biological molecular interaction. C1 [Zhou, Xiaobo] Methodist Hosp, Inst Res, Ctr Biotechnol & Informat, Houston, TX 77030 USA. Cornell Univ, Houston, TX 77030 USA. [Jin, Guangxu; Zhang, Xiang-Sun] Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100080, Peoples R China. [Li, King] Methodist Hosp, Dept Radiol, Houston, TX 77030 USA. [Wang, Honghui] Natl Inst Hlth, Ctr Clin, Bethesda, MD 20892 USA. [Chen, Luonan] Osaka Sangyo Univ, Dept Elect Engn, Osaka 5748530, Japan. [Hazen, Stanley L.] CCF, Ctr Cardiovasc Diagnost & Prevent, Cleveland, OH 44195 USA. RP Zhou, XB (reprint author), Methodist Hosp, Inst Res, Ctr Biotechnol & Informat, 6535 Fannin, Houston, TX 77030 USA. EM XZhou@thms.org RI Jin, Guangxu/B-4627-2012 OI Jin, Guangxu/0000-0002-6616-6981 FU Methodist Research Institute, Cornell University; The Methodist Hospital; NIH [R01LM08696, R01LM009161, R01AG028928] FX This research is funded by the Bioinformatics Core Research Grant at The Methodist Research Institute, Cornell University. Dr. Zhou is partially funded by The Methodist Hospital Scholarship Award. He and Dr. Wong are also partially funded by NIH grants R01LM08696, R01LM009161, and R01AG028928. NR 37 TC 27 Z9 27 U1 0 U2 5 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 SEP PY 2008 VL 7 IS 9 BP 4013 EP 4021 DI 10.1021/pr8002886 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 345RZ UT WOS:000259015500036 PM 18665624 ER PT J AU Cascella, NG Testa, SM Meyer, SM Rao, VA Diaz-Asper, CM Pearlson, GD Schretlen, DJ AF Cascella, Nicola G. Testa, S. Marc Meyer, Stephen M. Rao, Vani A. Diaz-Asper, Catherine M. Pearlson, Godfrey D. Schretlen, David J. TI Neuropsychological impairment in deficit vs. non-deficit schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE schizophrenia; deficit syndrome; cognitive testing; neuropsychology ID NEGATIVE SYMPTOMS; NONDEFICIT FORMS; COGNITIVE DEFICITS; BIPOLAR DISORDER; VERBAL FLUENCY; PERFORMANCE; VALIDATION; PATTERNS AB This study aimed to assess the severity and specificity of cognitive impairments that affect individuals with deficit versus non-deficit schizophrenia. We compared 26 patients with the deficit subtype of schizophrenia (SZ-D) and 79 with non-deficit schizophrenia (SZ-ND) to 316 healthy adults (NC). All study participants completed a battery with 19 individual cognitive measures. After adjusting their test performance for age, sex, race, education and estimated premorbid IQ, we derived regression-based T-scores for each measure and the six derived cognitive domains including attention, psychomotor speed, executive function, verbal fluency, visual memory, and verbal memory. Multivariate analyses of variance revealed Significant group effects for every individual measure and domain of cognitive functioning (all ps < 0.001). Post hoc comparisons revealed that patients with SZ-D performed significantly worse than NCs in every cognitive domain. They also produced lower scores than the SZ-ND group in every domain, but only the difference for verbal fluency reached statistical significance. The correlations of the effect sizes shown by the SZ-D and SZ-ND patients were of intermediate magnitude for the individual tests (r = 0.56, p < 0.01) and higher, but not statistically significant for the cognitive domains (r = 0.79, p = 0.06). Patients with SZ-D demonstrate cognitive deficits that are both common and distinct from those shown by patients with SZ-ND. Their impairment of verbal fluency is consistent with the observation that poverty of speech is a clinically significant feature of patients with SZ-D. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Cascella, Nicola G.; Testa, S. Marc; Meyer, Stephen M.; Rao, Vani A.; Diaz-Asper, Catherine M.; Pearlson, Godfrey D.; Schretlen, David J.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Schretlen, David J.] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [Diaz-Asper, Catherine M.] NIMH, NIH, Bethesda, MD 20892 USA. [Pearlson, Godfrey D.] Hartford Hosp Inst Living, Olin Neuropsychiat Res Ctr, Hartford, CT USA. [Pearlson, Godfrey D.] Yale Univ, Sch Med, New Haven, CT USA. RP Cascella, NG (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 144, Baltimore, MD 21287 USA. EM cascella@jhmi.edu FU NARSAD; NIH [MH60504, MH43775]; NIMH; Stanley Foundation FX Funding for this study was provided by NARSAD Young Investigator Award to NGC, NARSAD award to DJS, Stanley Foundation to NGC and NIH (MH60504 and MH43775) to GDP and DJS.; NARSAD, NIMH, and Stanley Foundation had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 42 TC 14 Z9 14 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD SEP PY 2008 VL 42 IS 11 BP 930 EP 937 DI 10.1016/j.jpsychires.2007.10.002 PG 8 WC Psychiatry SC Psychiatry GA 342QJ UT WOS:000258798300007 PM 18021807 ER PT J AU Dye, BA Nowjack-Raymer, R Barker, LK Nunn, JH Steele, JG Tan, S Lewis, BG Beltran-Aguilar, ED AF Dye, B. A. Nowjack-Raymer, R. Barker, L. K. Nunn, J. H. Steele, J. G. Tan, S. Lewis, B. G. Beltran-Aguilar, E. D. TI Overview and Quality Assurance for the Oral Health Component of the National Health and Nutrition Examination Survey (NHANES), 2003-04 SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE NHANES; oral health; dental public health; epidemiology; data reliability; quality assurance ID DENTAL EROSION; TOOTH WEAR; ETIOLOGY AB The 2003-04 National Health and Nutrition Examination Survey (NHANES) was a collaborative effort involving 28 federal funding partners with the National Center for Health Statistics. The collaborators for the 2003-04 NHANES oral health component included the National Institute of Dental and Craniofacial Research and the National Center for Chronic Disease Prevention and Health Promotion, Division of Oral Health. Oral health data are available on 8,272 persons aged 2 years or older. This report provides an overview of the 2003-04 oral health component including content descriptions and procedures for oral health assessments conducted for the first time in a national survey in the United States. These assessments include posterior functional contacts, tooth wear, and oral health-related quality of life. This report also provides evaluations of data quality in terms of examiner reliability statistics (percent agreements, kappas, and correlation coefficients) for various NHANES 2003-04 oral health examination components and analytical recommendations for producing 6-year estimates using the previous two NHANES data collection components (1999-2000 and 2001-02). C1 [Dye, B. A.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, CDC, NHANES Program, Hyattsville, MD 20782 USA. [Dye, B. A.] Univ Maryland, Sch Dent, Baltimore, MD 21201 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Barker, L. K.; Beltran-Aguilar, E. D.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Oral Hlth, Atlanta, GA USA. [Nunn, J. H.] Univ Dublin, Trinity Coll, Dent Sch & Hosp, Dept Publ & Child Dent Hlth, Dublin, Ireland. [Steele, J. G.] Newcastle Univ, Sch Dent, Dept Restorat Dent, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Dye, BA (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, CDC, NHANES Program, 3311 Toledo Rd,RM 4416, Hyattsville, MD 20782 USA. EM bfd1@cdc.gov OI Nunn, June/0000-0003-4481-544X FU NHANES; NIH/NIDCR; CDC/National Center for Health Promotion and Disease Prevention; Division of Oral Health; CDC/NCHS FX The 2003-04 NHANES oral health component was a funding and content collaborative effort between the NIH/NIDCR, the CDC/National Center for Health Promotion and Disease Prevention, Division of Oral Health, and the CDC/NCHS. NR 24 TC 31 Z9 31 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD FAL PY 2008 VL 68 IS 4 BP 218 EP 226 DI 10.1111/j.1752-7325.2007.00076.x PG 9 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 380BU UT WOS:000261441400006 PM 18248340 ER PT J AU Arnold, JI Gray, NE Jacobowitz, K Viswanathan, L Cheung, PW McFann, KK Le, H Blackman, MR AF Arnold, Julia I. Gray, Nora E. Jacobowitz, Ketzela Viswanathan, Lavanya Cheung, Pui W. McFann, Kimberly K. Le, Hanh Blackman, Marc R. TI Human prostate stromal cells stimulate increased PSA production in DHEA-treated prostate cancer epithelial cells SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE DHEA; stromal; prostate; PSA; coculture ID PERIPHERAL TARGET TISSUES; GROWTH-FACTOR; COCULTURE MODEL; DEHYDROEPIANDROSTERONE; ANDROGENS; MEN; PROGRESSION; EXPRESSION; ESTROGENS; INTRACRINOLOGY AB Dehydroepiandrosterone (DHEA) is commonly used as a dietary supplement and may affect prostate pathophysiology when metabolized to androgens and/or estrogens. Human prostate LAPC-4 cancer cells with a wild type androgen receptor (AR) were treated with DHEA, androgens dihydrotestosterone (DHT), T, or R1881), and E-2 and assayed for prostate specific antigen (PSA) protein and gene expression. In LAPC-4 monocultures, DHEA and E-2 induced little or no increase in PSA protein or mRNA expression compared to androgen-treated cells. When prostate cancer-associated (6S) stromal cells were added in coculture, DHEA stimulated LAPC-4 cell PSA protein secretion to levels approaching induction by DHT. Also, DHEA induced 15-fold more PSA mRNA in LAPC-4 cocultures than in monocultures. LAPC-4 proliferation was increased 2-3-fold when cocultured with 6S stromal cells regardless of hormone treatment. DHEA-treated 6S stromal cells exhibited a dose- and time-dependent increase in T secretion, demonstrating stromal cell metabolism of DHEA to T. Coculture with non-cancerous stroma did not induce LAPC-4 PSA production, suggesting a differential modulation of DHEA effect in a cancer-associated prostate stromal environment. This coculture model provides a research approach to reveal detailed endocrine. intracrine, and paracrine signaling between stromal and epithelial cells that regulate tissue homeostasis within the prostate, and the role of the tumor microenvironment in cancer progression. Published by Elsevier Ltd. C1 [Arnold, Julia I.; Gray, Nora E.; Jacobowitz, Ketzela; Viswanathan, Lavanya; Cheung, Pui W.; Le, Hanh; Blackman, Marc R.] NCCAM, Endocrinol Sect, LCI, Div Intramural Res,NIH, Bethesda, MD 20892 USA. [McFann, Kimberly K.] Univ Colorado, Hlth Sci Ctr, Denver, CO 80232 USA. RP Arnold, JI (reprint author), NCCAM, Endocrinol Sect, LCI, Div Intramural Res,NIH, 9000 Rockville Pike 10-2B47, Bethesda, MD 20892 USA. EM jarnold@mail.nih.gov FU Intramural Research Program; National Center for Complementary and Alternative Medicine; National Institutes of Health, Bethesda, MD FX The authors thank Dr. Charles Sawyers (UCLA) for providing the LAPC-4 cells, Dr. John Isaacs (Johns Hopkins School of Medicine) for providing the primary prostate stromal cells (5S, 6S, 9S, 12S) and Dr. Vernon Steele (NIH-NCI) and Dr. Angela Brodie (University of Maryland) for their constructive comments upon reviewing this manuscript. This work was supported by the Intramural Research Program, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD. NR 40 TC 33 Z9 34 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD SEP PY 2008 VL 111 IS 3-5 BP 240 EP 246 DI 10.1016/j.jsbmb.2008.06.008 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 351YO UT WOS:000259462100011 PM 18621129 ER PT J AU Condon, TP Miner, LL Balmer, CW Pintello, D AF Condon, Timothy P. Miner, Lucinda L. Balmer, Curtis W. Pintello, Denise TI Blending addiction research and practice: Strategies for technology transfer SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE addiction treatment; technology transfer; evidence-based practices; Clinical Trials Network (CTN); Addiction Technology Transfer Center (ATTC) ID CLINICAL-TRIALS NETWORK; SUBSTANCE-ABUSE; DETOXIFICATION; INCENTIVES; PROGRAMS AB Consistent with traditional conceptions of technology transfer, efforts to translate substance abuse and addiction research into treatment practice have typically relied on the passive dissemination of research findings. The large gap between addiction research and practice, however, indicates that there are many barriers to successful technology transfer and that dissemination alone is not sufficient to produce lasting changes in addiction treatment. To accelerate the translation of research into practice, the National Institute on Drug Abuse launched the Blending Initiative in 2001. In part a collaboration with the Substance Abuse and Mental Health Services Administration/Center for Substance Abuse Treatment's Addiction Technology Transfer Center program, this initiative aims to improve the development, effectiveness, and usability of evidence-based practices and reduce the obstacles to their timely adoption and implementation. (C) 2008 Published by Elsevier Inc. C1 [Condon, Timothy P.; Miner, Lucinda L.; Pintello, Denise] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. [Balmer, Curtis W.] JRS Int Inc, Silver Spring, MD 20910 USA. RP Condon, TP (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Rm 5274, Bethesda, MD 20892 USA. EM tc52x@nih.gov NR 14 TC 24 Z9 24 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD SEP PY 2008 VL 35 IS 2 BP 156 EP 160 DI 10.1016/j.jsat.2007.09.004 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 342QR UT WOS:000258799100007 PM 18337054 ER PT J AU Janjanin, S Li, WJ Morgan, MT Shanti, RA Tuan, RS AF Janjanin, Sasa Li, Wan-Ju Morgan, Meredith T. Shanti, Rabie A. Tuan, Rocky S. TI Mold-shaped, nanofiber scaffold-based cartilage engineering using human mesenchymal stem cells and bioreactor SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE mesenchymal stem cells; tissue engineering; cartilage; nanofibers; nanofibrous scaffolds; mold; bioreactor; plastic and reconstructive surgery ID CHONDROGENIC DIFFERENTIATION; TISSUE; CHONDROCYTES; AGAROSE; FABRICATION; EXPRESSION AB Background. Mesenchymal stem cell (MSC)-based tissue engineering is a promising future alternative to autologous cartilage grafting. This study evaluates the potential of using MSCs, seeded into electrospun, biodegradable polymeric nanofibrous scaffolds, to engineer cartilage with defined dimensions and shape, similar to grafts used for subcutaneous implantation in plastic and reconstructive surgery. Materials and methods. Human bone marrow derived MSCs seeded onto nanofibrous scaffolds and placed in custom-designed molds were cultured for up to 42 days in bioreactors. Chondrogenesis was induced with either transforming growth factor-beta 1 (TGF-beta I) alone or in combination with insulin-like growth factor-I (IGF-I). Results. Constructs exhibited hyaline cartilage histology with desired thickness and shape as well as favorable tissue integrity and shape retention, suggesting the presence of elastic tissue. Time-dependent increase in cartilage matrix gene expression was seen in both types of culture: at Day 42, TGF-beta 1/IGF-I treated cultures showed higher collagen Type 2 and aggrecan expression. Both culture conditions showed significant time-dependent increase in sulfated glycosaminoglycan and hydroxyproline contents. TGF-beta 1/IGF-I-treated samples were significantly stiffer; with equilibrium compressive Young's modulus values reaching 17 kPa by Day 42. Conclusions. The successful ex vivo development of geometrically defined cartilaginous construct using customized molding suggests the potential of cell-based cartilage tissue for reconstructive surgery. (c) 2008 Elsevier Inc. All rights reserved. C1 [Janjanin, Sasa; Li, Wan-Ju; Morgan, Meredith T.; Shanti, Rabie A.; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Janjanin, Sasa] Zagreb Clin Hosp Ctr, Dept Otorhinolaryngol Head & Neck Surg, Zagreb, Croatia. [Shanti, Rabie A.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bldg 50,Room 1523,MSC 8022, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU NIH [ZO1 41131]; U.S. Department of State FX This work is supported by the Intramural Research Program of NIAMS, NIH (Grant ZO1 41131). Sasa Janjanin is a recipient of the Fulbright Scholarship of the U.S. Department of State. NR 31 TC 56 Z9 64 U1 4 U2 23 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD SEP PY 2008 VL 149 IS 1 BP 47 EP 56 DI 10.1016/j.jss.2007.12.788 PG 10 WC Surgery SC Surgery GA 340GD UT WOS:000258633200008 PM 18316094 ER PT J AU Iwasa, KH Sul, B AF Iwasa, Kuni H. Sul, Bora TI Effect of the cochlear microphonic on the limiting frequency of the mammalian ear SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID OUTER HAIR CELL; GUINEA-PIG COCHLEA; BASILAR-MEMBRANE; MOTILITY; CURRENTS; ELECTROMOTILITY; AMPLIFICATION; POTENTIALS; AMPLIFIER; TRANSDUCTION AB Electromotility is a basis for cochlear amplifier, which controls the sensitivity of the mammalian ear and contributes to its frequency selectivity. Because it is driven by the receptor potential, its frequency characteristics are determined by the low-pass RC filter intrinsic to the cell, which has a corner frequency about 1/10th of the operating frequency. This filter significantly decreases the efficiency of electromotility as an amplifier. The present paper examines a proposal that the cochlear microphonic, the voltage drop across the extracellular medium by the receptor current, contributes to overcome this problem. It is found that this effect can improve frequency dependence. However, this effect alone is too small to enhance the effectiveness of electromotility beyond 10 kHz in the mammalian ear. (C) 2008 Acoustical Society of America. C1 [Iwasa, Kuni H.; Sul, Bora] NIDCD, Biophys Sect, NIH, Rockville, MD 20850 USA. RP Iwasa, KH (reprint author), NIDCD, Biophys Sect, NIH, 5 Res Ct,Rm 1B03, Rockville, MD 20850 USA. EM kits@nih.gov; Bulb@nidcd.nih.gov OI Iwasa, Kuni/0000-0002-9397-7704 FU NIDCD; NIH FX The authors thank Richard Chadwick and two anonymous reviewers for valuable comments. This research was supported by the Intramural Research Program of the NIDCD, NIH. NR 29 TC 3 Z9 4 U1 0 U2 3 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 2008 VL 124 IS 3 BP 1607 EP 1612 DI 10.1121/1.2953317 PN 1 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 356PQ UT WOS:000259790500023 PM 19045652 ER PT J AU Towbin, K AF Towbin, Kenneth TI Paying attention to stimulants: Height, weight, and cardiovascular monitoring in clinical practice SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID AMERICAN-HEART-ASSOCIATION; SUDDEN-DEATH; GROWTH; DISORDER; CHILDREN; METHYLPHENIDATE; ADOLESCENTS; STATEMENT; CLONIDINE; COUNCIL C1 [Towbin, Kenneth] NIMH, Emot & Dev Branch, Mood & Anxiety Disorder Program, NIH, Bethesda, MD 20892 USA. [Towbin, Kenneth] US Dept HHS, Washington, DC 20201 USA. RP Towbin, K (reprint author), NIMH, Emot & Dev Branch, Mood & Anxiety Disorder Program, NIH, CRC Room 1-3633,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Kenneth.Towbin@nih.gov NR 20 TC 7 Z9 7 U1 0 U2 1 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 SEP PY 2008 VL 47 IS 9 BP 977 EP 980 DI 10.1097/CHI.0b013e31817e0eb9 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 341VE UT WOS:000258742500001 PM 18580503 ER PT J AU Perdue, KA Copeland, MK Karjala, Z Cheng, LI Ward, JM Elkins, WR AF Perdue, Kathy A. Copeland, Michelle K. Karjala, Zuzana Cheng, Lily I. Ward, Jerrold M. Elkins, William R. TI Suboptimal Ability of Dirty-bedding Sentinels to Detect Spironucleus muris in a Colony of Mice with Genetic Manipulations of the Adaptive Immune System SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID T-CELL DEVELOPMENT; LABORATORY MICE; GIARDIA-MURIS; SYPHACIA-OBVELATA; HOST SPECIFICITY; MOUSE COLONY; NUDE-MICE; HEXAMITIASIS; INFECTION; TCR AB Spironucleus muris is an unacceptable infectious agent for most rodent colonies. Exposure of sentinel mice to dirty bedding and examination of sentinel intestinal smears was not sufficient for identification of the extent of spironucleosis within 1 mouse room. Clinical abnormalities were not reported in the animals housed in the room despite extensive breeding and a preponderance of mice genetically engineered to have nonfunctional T and B cells. In addition, researchers reported that the infection had not altered their research data. During investigation of the outbreak, direct intestinal smears performed on related animals (conspecifics, offspring, or siblings) revealed that immunodeficient mice often tested negative whereas the immunocompetent cohort tested positive. In this study, we used culled colony animals and compared direct intestinal exam test results with histologic results. The comparison showed the extent of false negatives that may occur when direct intestinal exam alone is used to detect this protozoon. Sensitivity of the direct intestinal exam for detection of S. muris was calculated to be 71%, while histology sensitivity was 91%. In light of the study results and an extensive literature review, we revised our health surveillance plan so that the age and duration of exposure to dirty bedding among sentinel mice is varied at the time of testing. C1 [Perdue, Kathy A.; Copeland, Michelle K.; Cheng, Lily I.; Ward, Jerrold M.; Elkins, William R.] NIAID, Comparat Med Branch, Div Intramural Res, Bethesda, MD 20892 USA. [Karjala, Zuzana] NIH, Hlth Surveillance Lab, Diagnost & Res Serv Branch, Div Vet Resources,Off Res Serv, Bethesda, MD 20892 USA. RP Perdue, KA (reprint author), NIAID, Comparat Med Branch, Div Intramural Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kperdue@niaid.nih.gov FU National Institute of Allergy and Infectious Disease FX We wish to thank Dr BJ Fowlkes, Dr Karen Laky, and Ms Sharron Evans, RSSIII, for providing cull animals for testing, assisting with the animal submission, and providing individual animal data needed for the study; Ms Remina Greenfield for Figure 1; Ms. Elizabeth M. Williams and Mr. Lawrence J. Faucette for tissue processing assistance; and Mr Omar Feliciano, Senior Technician, and the rest of the 14B South caretaking and technical staff for all of their hard work and assistance with this study. This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Disease and the Office of Research Services (National Institutes of Health, Bethesda, MD). The views and opinions provided are those of the authors and do not reflect the official policy or positions of the National Institutes of Health, the Department of Health and Human Services, or the United States Government. NR 45 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 10 EP 17 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500003 PM 18947164 ER PT J AU Fain, MA Karjala, Z Perdue, KA Copeland, MK Cheng, LI Elkins, WR AF Fain, Michele A. Karjala, Zuzana Perdue, Kathy A. Copeland, Michelle K. Cheng, Lily I. Elkins, William R. TI Detection of Spironucleus muris in Unpreserved Mouse Tissue and Fecal Samples by Using a PCR Assay SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID LABORATORY MICE; GIARDIA-MURIS; HEXAMITIASIS; EXCYSTATION; INFECTIONS; STRAINS AB The purpose of this study was to develop a rapid DNA isolation method and a sensitive and specific PCR assay for detecting Spironucleus muris in mouse tissue and fecal samples. A PCR assay based on the carboxy terminus of the elongation factor la gene was developed; the PCR product was confirmed by nucleic acid sequencing and nested PCR. The new PCR assay then was used to test feces from animals that had been screened for S. muris by using direct intestinal examination and histology. The PCR assay was determined to be a more sensitive test than either direct intestinal examination or intestinal histology. To our knowledge, this assay represents the first use of a PCR-based diagnostic screening method to confirm the presence of S. muris in murine tissue and fecal samples. C1 [Fain, Michele A.; Perdue, Kathy A.; Copeland, Michelle K.; Cheng, Lily I.; Elkins, William R.] NIAID, Comparat Med Branch, Bethesda, MD 20892 USA. [Karjala, Zuzana] NIH, Hlth Surveillance Lab, Diagnost & Res Serv Branch, Div Vet Resources,Off Res Serv, Bethesda, MD 20892 USA. RP Perdue, KA (reprint author), NIAID, Comparat Med Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kperdue@niaid.nih.gov FU National Institute of Allergy and Infectious Disease FX We wish to think Dr BJ Fowlkes, Dr Karen Laky, Ms Sharron Evans, RSSIIl, for providing cull animals for testing; Ms Elizabeth M Williams for tissue processing assistance; Mr Jeremy Dathe of Lofstrand Labs for his superior service; Ms Roman Tesfaye for her help with the figures; and Dr Gerry Shea for his scientific assistance. This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Disease (National Institutes of Health, Bethesda, MD). The views and opinions provided are those of the authors and do not reflect the official policy or positions of the National Institutes of Health, the Department of Health and Human Services, or the United States Government. NR 26 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 39 EP 43 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500008 PM 18947169 ER PT J AU DeMuro, K AF DeMuro, K. TI New Approach to Quality Assurance SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [DeMuro, K.] SoBran, Bethesda, MD USA. [DeMuro, K.] NIH, DVR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 92 EP 92 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500071 ER PT J AU McGee, K Patel, D McKenna, J Banks, F Sekou, S Prevost, K Barnard, D Skopets, B AF McGee, K. Patel, D. McKenna, J. Banks, F. Sekou, S. Prevost, K. Barnard, D. Skopets, B. TI Use of Dietary Fiber in the Management of Chronic and Reoccurring Diarrhea in Pigtail Macaques (Macaca nemestrina) SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [McGee, K.; Patel, D.; McKenna, J.; Banks, F.; Sekou, S.] NIH, SoBran Inc, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 104 EP 105 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500104 ER PT J AU Caviness, GF Thigpen, JE Locklear, J Whiteside, TE Grant, MG Forsythe, DB AF Caviness, G. F. Thigpen, J. E. Locklear, J. Whiteside, T. E. Grant, M. G. Forsythe, D. B. TI Incidence of Mycoplasma Contaminants in Cell Cultures: Detection and Growth on Trypticase Soy Agar Containing 5% Sheep Blood SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Caviness, G. F.; Thigpen, J. E.; Locklear, J.; Whiteside, T. E.; Grant, M. G.; Forsythe, D. B.] NIH, Res Triangle Pk, NC USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 106 EP 106 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500108 ER PT J AU Locklear, J Caviness, GF Thigpen, JE Whiteside, TE Grant, MG Forsythe, DB AF Locklear, J. Caviness, G. F. Thigpen, J. E. Whiteside, T. E. Grant, M. G. Forsythe, D. B. TI Arthropod Detection during Screening of Sentinel Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Locklear, J.; Caviness, G. F.; Thigpen, J. E.; Whiteside, T. E.; Grant, M. G.; Forsythe, D. B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 106 EP 107 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500110 ER PT J AU Thigpen, JE Hobbs, BA Cliffordz, CB Grant, MG Myers, MB Forsythe, DB AF Thigpen, J. E. Hobbs, B. A. Cliffordz, C. B. Grant, M. G. Myers, M. B. Forsythe, D. B. TI Background Lesions in Homozygous and Heterozygous Mice of Two Stocks, Crl:NU-Fox(nu) and CA:CD1-Foxn1(nu), Used as Sentinels SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Thigpen, J. E.; Hobbs, B. A.; Grant, M. G.; Myers, M. B.; Forsythe, D. B.] NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. [Cliffordz, C. B.] Charles River, Wilmington, DE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 107 EP 107 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500112 ER PT J AU Davis, BA Graninger, H Hitt, ND AF Davis, B. A. Graninger, H. Hitt, N. D. TI Novel Cage Flag System for Identifying Special Husbandry Requests SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Davis, B. A.; Graninger, H.; Hitt, N. D.] NINDS, AHCS, Germantown, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 117 EP 117 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500141 ER PT J AU Pinkney, J Smith, D Burkholder, T AF Pinkney, J. Smith, D. Burkholder, T. TI Fur Mite Treatment 101: Labor, Time Management, and Project Coordination SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Pinkney, J.] SoBran, Bethesda, MD USA. [Pinkney, J.; Smith, D.; Burkholder, T.] NIH, DVR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 127 EP 127 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500170 ER PT J AU Mensch, J AF Mensch, J. TI Supplemental Care for ERCC-1-deficient Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Mensch, J.] SoBran Inc, Rockville, MD USA. [Mensch, J.] FLAC, NIAAA, OLAS, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 130 EP 130 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500177 ER PT J AU Rosa, MC Perez, D Sabol-Jones, M Hitt, ND AF Rosa, M. C. Perez, D. Sabol-Jones, M. Hitt, N. D. TI Systematic Approach to Solving Breeding Colony Problems SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Rosa, M. C.; Perez, D.; Sabol-Jones, M.; Hitt, N. D.] NINDS, NIH, AHCS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 134 EP 135 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500190 ER PT J AU Huntsberry, M AF Huntsberry, M. TI Enhancements to the Canine Socialization and Training Program SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Huntsberry, M.] SoBran, Bethesda, MD USA. [Huntsberry, M.] NIH, DVR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 135 EP 135 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500191 ER PT J AU Savane, S AF Savane, S. TI Use of Flashlights in Old World Nonhuman Primate Health Monitoring SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Savane, S.] SoBran, Bethesda, MD USA. [Savane, S.] NIH, DVR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 140 EP 140 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500206 ER PT J AU Thigpen, JE Padilla-Banks, E Kissling, G Caviness, GF WIuteside, TE Locklear, J Grant, MG Forsythe, DB AF Thigpen, J. E. Padilla-Banks, E. Kissling, G. Caviness, G. F. WIuteside, T. E. Locklear, J. Grant, M. G. Forsythe, D. B. TI Commercially Available Corn-cob Bedding Naturally Contaminated with Zearalenone Significantly Advances the Time of Vaginal Opening in Immature CD-1 Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Thigpen, J. E.; Padilla-Banks, E.; Kissling, G.; Caviness, G. F.; WIuteside, T. E.; Locklear, J.; Grant, M. G.; Forsythe, D. B.] NIH, Res Triangle Pk, NC USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 159 EP 159 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500255 ER PT J AU Hagelin, K Young, J Mattison, J Ingram, D AF Hagelin, K. Young, J. Mattison, J. Ingram, D. TI Locomotor Activity in Rhesus Macaques (Macaca mulatta) on Long-term Calorie Restriction SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Hagelin, K.; Young, J.] NIHAC SoBran Inc, Div Vet Resources, Poolesville, MD USA. [Mattison, J.] NIA, Lab Expt Gerontol, Poolesville, MD USA. [Ingram, D.] Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 161 EP 161 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500260 ER PT J AU Blair, R Hoogstraten-Miller, SL Mueller, K Schwartzberg, P AF Blair, R. Hoogstraten-Miller, S. L. Mueller, K. Schwartzberg, P. TI Alternative Method for Intrathymic Injections in Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Hoogstraten-Miller, S. L.] NHGRI, Off Lab Anim Med, NIH, Bethesda, MD 20892 USA. [Blair, R.; Mueller, K.; Schwartzberg, P.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 171 EP 171 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500286 ER PT J AU Goode, PS FitzGerald, MP Richter, HE Whitehead, WE Nygaard, I Wren, PA Zyczynski, HM Cundiff, G Menefee, S Senka, JM Gao, X Weber, AM AF Goode, Patricia S. FitzGerald, Mary P. Richter, Holly E. Whitehead, William E. Nygaard, Ingrid Wren, Patricia A. Zyczynski, Halina M. Cundiff, Geoffrey Menefee, Shawn Senka, Judith M. Gao, Xin Weber, Anne M. CA Pelvic Floor Disorders Network TI Enhancing participation of older women in surgical trials SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID PELVIC ORGAN PROLAPSE; RECRUITMENT STRATEGIES; CLINICAL-TRIAL; STRESS-INCONTINENCE; ADULTS; DYSFUNCTION; DEPRESSION; EXCLUSION; PEOPLE AB BACKGROUND: Older participants are often excluded from clinical trials, precluding a representative sample. STUDY DESIGN: Using qualitative and quantitative methods, we examined recruitment and retention of older women with pelvic organ prolapse in two surgical trials: the randomized Colpopexy And Urinary Reduction Efforts (CARE) study and the Longitudinal Pelvic Symptoms and Patient Satisfaction After Colpocleisis cohort study. Using focus groups, we developed a questionnaire addressing factors facilitating and impeding the recruitment and retention of older study participants and administered it to research staff. Enrollment-to-surgery ratios, missed visit rates, and dropout rates for older and younger participants were compared using Fisher's exact test, with cut-points of 70 and 80 years for the CARE and Colpocleisis studies, respectively. RESULTS: Questionnaires were completed by 23 physician investigators and I I nurses or coordinators (92% response rate). Respondents indicated it was more difficult to recruit older research participants (32%), obtain informed con sent (56%), and retain participants to study completion (50%). Challenges to recruitment included caregiver involvement in the decision to participate and participant comorbidities. Perceived barriers to retention were transportation, caregiver availability, and participant fatigue. Data quality was challenged by sensory and cognitive impairment, resulting in a change from telephone inter-views to in-person visits in the Colpocleisis study. Older participants did not have higher dropout rates than younger participants. There were no differences in missed in-person visits or telephone interview rates between age groups. CONCLUSIONS: Strategies, albeit unstudied, could assist investigators in planning surgical trials-that successfully enroll and retain older women. C1 [Goode, Patricia S.] Univ Alabama, Birmingham VA Med Ctr, Dept Med, Birmingham, AL 35233 USA. [Richter, Holly E.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35233 USA. [Goode, Patricia S.] Vet Affairs Med Ctr, Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. [FitzGerald, Mary P.] Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. [Whitehead, William E.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Nygaard, Ingrid] Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Wren, Patricia A.] Oakland Univ, Dept Hlth Behav Hlth Educ, Rochester, MI 48063 USA. [Zyczynski, Halina M.] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet & Gynecol, Pittsburgh, PA 15213 USA. [Cundiff, Geoffrey] Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC V5Z 1M9, Canada. [Menefee, Shawn] Univ Calif San Diego, Dept Obstet & Gynecol, San Diego, CA 92103 USA. [Senka, Judith M.] Northwestern Univ, Evanston Hosp, Dept Obstet & Gynecol, Evanston, IL 60201 USA. [Gao, Xin] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Weber, Anne M.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Goode, PS (reprint author), Univ Alabama, Birmingham VA Med Ctr, Dept Med, 11G,700 S 19th St, Birmingham, AL 35233 USA. FU National Institute of Child Health and Human Development [U01 HD41249, U10 HD41268, U10 HD41248, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41269, U10 HD41267] FX Supported by grants from the National Institute of Child Health and Human Development (U01 HD41249, U10 HD41268, U10 HD41248, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41269, and U10 HD41267). NR 26 TC 10 Z9 11 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2008 VL 207 IS 3 BP 303 EP 311 DI 10.1016/j.jamcollsurg.2008.03.012 PG 9 WC Surgery SC Surgery GA 349FD UT WOS:000259265800001 PM 18722933 ER PT J AU Heaton, TE Peranteau, WH Bauer, TR Zoltick, PW Hickstein, DD Flake, AW AF Heaton, Todd Erin Peranteau, William H. Bauer, Thomas R. Zoltick, Philip W. Hickstein, Dennis D. Flake, Alan W. TI High level chimerism and donor specific tolerance achieved in the canine model by in utero hematopoietic cell transplantation followed by postnatal minimal conditioning bone marrow transplantation SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 94th Annual Clinical Congress of the American-College-of-Surgeons/63rd Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 12-16, 2008 CL San Francisco, CA SP Amer Coll Surg C1 [Heaton, Todd Erin; Peranteau, William H.; Bauer, Thomas R.; Zoltick, Philip W.; Hickstein, Dennis D.; Flake, Alan W.] Childrens Hosp Philadelphia, NIH, Bethesda, MD USA. RI Heaton, Todd/E-5197-2016 OI Heaton, Todd/0000-0003-3515-0028 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2008 VL 207 IS 3 SU S BP S105 EP S105 DI 10.1016/j.jamcollsurg.2008.06.268 PG 1 WC Surgery SC Surgery GA 349NV UT WOS:000259288500234 ER PT J AU Rovner, AJ Stallings, VA Kawchak, DA Schall, JI Ohene-Frempong, K Zemel, BS AF Rovner, Alisha J. Stallings, Virginia A. Kawchak, Deborah A. Schall, Joan I. Ohene-Frempong, Kwakij Zemel, Babette S. TI High risk of vitamin D deficiency in children with sickle cell disease SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID ADOLESCENT GIRLS; 25-HYDROXYVITAMIN-D; OUTCOMES AB Vitamin D is a particularly concerning nutrient for children with homozygous SS sickle cell disease (SCD-SS) due to their increased skin melanin concentrations, reduced levels of physical activity, and poor vitamin D intake. The goal of this study was to compare the vitamin D status of children with SCD-SS to healthy African-American children living in the same geographic area. Growth, dietary intake, serum 25-hydroxyvitamin D [25(OH)D], and intact parathyroid hormone (iPTH) concentrations were measured in 61 African-American subjects with SCD-SS and 89 healthy African-American control subjects age 5 to 18 years from the Philadelphia, PA, region (latitude 39.95 degrees N). Median serum 25(OH)D concentrations were 15 ng/mL (95% confidence interval [Cl]: 13, 17) in subjects with SCD-SS and 21 ng/mL (95% CI: 18, 22) in healthy control subjects (P<0.0002). Vitamin D deficiency [25(OH)D<11 mg/mL] was found in 33% of subjects with SCD-SS and 9% of healthy control subjects (P<0.001); 25% of subjects with SCD-SS and 17% of healthy control subjects had elevated iPTH [(>59 rho g/mL), P<0.05]. Ninety-three percent of subjects with SCD-SS and 90% of healthy subjects had vitamin D insufficiency [25(OH)D<30 mg/mL]. The risk of vitamin D deficiency among subjects with SCD-SS was 5.3 (95% CI: 2.5, 8.2) times greater than control subjects, adjusted for season and age. Poor vitamin D status was prevalent in children with SCD-SS and healthy African-American children living in the same geographic area. However, children with SCD-SS were at greater risk for vitamin D deficiency than healthy African-American children. C1 [Zemel, Babette S.] Childrens Hosp Philadelphia, Div Gastroenterol Hepatol, Philadelphia, PA 19104 USA. [Rovner, Alisha J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent, Rockville, MD USA. [Schall, Joan I.] Childrens Hosp Philadelphia, Nutr & Growth Lab, Philadelphia, PA 19104 USA. [Zemel, Babette S.] Childrens Hosp Philadelphia, Div Gastroenterol Hepatol, Philadelphia, PA 19104 USA. [Ohene-Frempong, Kwakij] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. RP Zemel, BS (reprint author), Childrens Hosp Philadelphia, Div Gastroenterol Hepatol, CHOP N,Room 1560,34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM zemel@email.chop.edu RI Zemel, Babette/D-1117-2009 FU General Clinical Research Center [5-MO1-RR-000240]; Comprehensive Sickle Cell Center [1354 HL 70596-3]; Nutrition Center at The Children's Hospital of Philadelphia; American Society for Parenteral and Enteral Nutrition FX Funding for this research was provided by the General Clinical Research Center (5-MO1-RR-000240), Comprehensive Sickle Cell Center (1354 HL 70596-3), the Nutrition Center at The Children's Hospital of Philadelphia, and the Richard Fleming Grant from the American Society for Parenteral and Enteral Nutrition.; We greatly appreciate the children and their families from the Comprehensive Sickle Cell Center at The Children's Hospital of Philadelphia for participating in this study. We acknowledge the staff of the General Clinical Research Center for drawing the blood and storing and shipping the samples, Richard Reitz, MD, and his lab staff at Quest Nichols Institute (San Juan Capistrano, CA) for conducting the vitamin D and PTH analyses, Kimberly O'Brien, PhD, for serving as thesis advisor for Alisha Rovner, PhD (these data were collected as part of a doctoral dissertation), and Dei Macleod for her assistance in the manuscript preparation. NR 23 TC 29 Z9 32 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 2008 VL 108 IS 9 BP 1512 EP 1516 DI 10.1016/j.jada.2008.06.433 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 346DR UT WOS:000259049100023 PM 18755325 ER PT J AU Bassim, CW Gibson, G Ward, T Paphides, BM DeNucci, DJ AF Bassim, Carol W. Gibson, Gretchen Ward, Timothy Paphides, Brian M. DeNucci, Donald J. TI Modification of the risk of mortality from pneumonia with oral hygiene care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE long-term care; nursing home; oral hygiene; oral care; pneumonia ID LONG-TERM-CARE; VENTILATOR-ASSOCIATED PNEUMONIA; HOME-ACQUIRED PNEUMONIA; NURSING-HOME; ASPIRATION PNEUMONIA; RESPIRATORY PATHOGENS; NOSOCOMIAL INFECTIONS; DENTAL PLAQUE; OLDER-ADULTS; HEALTH-CARE AB OBJECTIVES: To investigate the associations between the assignment of an oral hygiene aide staff member and risk factors for mortality from pneumonia in a nursing home and to test the hypothesis that this care would affect the incidence of mortality from pneumonia. DESIGN: Electronic medical records. SETTING:Nursing home. PARTICIPANTS: One hundred forty-three residents of a Veterans Affairs Medical Center (VAMC) nursing home. METHODS: The electronic medical records of 143 residents of a VAMC nursing home were analyzed for risk factors for pneumonia. A certified nursing assistant had been assigned to provide oral hygiene care for residents on two of four nursing home wards. Researchers performed a longitudinal analysis of resident's medical records to investigate the association between the assignment of an oral hygiene aide with the risk of mortality from pneumonia. RESULTS: Initially, the group that received oral care, an older and less functionally able group, showed approximately the same incidence of mortality from pneumonia as the group that did not receive oral care, but when the data were adjusted for the risk factors found to be significant for mortality from pneumonia, the odds of dying from pneumonia in the group that did not receive oral care was more than three times that of the group that did receive oral care (odds ratio=3.57, P=.03). Modified risk factors included age, functionality, cognitive function, and clinical concern about aspiration pneumonia. CONCLUSION: Oral hygiene nursing aide intervention may be an efficient risk factor modifier of mortality from nursing home-associated pneumonia. C1 [Bassim, Carol W.; DeNucci, Donald J.] Dental Serv, Washington, DC USA. [Bassim, Carol W.; DeNucci, Donald J.] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Gibson, Gretchen] Fayetteville Vet Affaires Med Ctr, Dent Serv, Fayetteville, AR USA. [Ward, Timothy; DeNucci, Donald J.] Dept Vet Affairs, Off Dent, Washington, DC USA. [Paphides, Brian M.] N Florida S Georgia Vet Hlth Syst, Vet Affairs Med Ctr, Dent Serv, Lake City, FL USA. RP Bassim, CW (reprint author), NIH NIDCR CRC, 10 Ctr Dr Bldg 10,Rm 1N-118,MSC 1191, Bethesda, MD 20892 USA. EM bassimc@mail.nih.gov FU Dental Research Fellowship FX This work was supported by a Dental Research Fellowship through the Veterans Affairs Office of Academic Affiliations. We would like to thank the dental and long-term care staff of the Lake City, Florida, VAMC for their service for our veterans. NR 51 TC 36 Z9 36 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2008 VL 56 IS 9 BP 1601 EP 1607 DI 10.1111/j.1532-5415.2008.01825.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 347PC UT WOS:000259152500002 PM 18691286 ER PT J AU Unruh, ML Newman, AB Larive, B Dew, MA Miskulin, DC Greene, T Beddhu, S Rocco, MV Kusek, JW Meyer, KB AF Unruh, Mark L. Newman, Anne B. Larive, Brett Dew, Mary Amanda Miskulin, Dana C. Greene, Tom Beddhu, Srinivasan Rocco, Michael V. Kusek, John W. Meyer, Klemens B. CA Hemodialysis Study Grp TI The influence of age on changes in health-related quality of life over three years in a cohort undergoing hemodialysis SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hemodialysis; quality of life; aging; chronic health conditions ID STAGE RENAL-DISEASE; CHRONIC DIALYSIS; MEMBRANE FLUX; PSYCHOSOCIAL FACTORS; FUNCTIONAL HEALTH; KIDNEY-DISEASE; SURVIVAL; HEMO; ADEQUACY; OUTCOMES AB OBJECTIVES: To assess the extent to which persons aged 70 and older undergoing hemodialysis (HD) had greater changes in health-related quality of life (HRQOL) over 3 years than younger patients undergoing HD. DESIGN: Longitudinal. SETTING: The Hemodialysis Study (HEMO Study) was a randomized, clinical trial of the effects of HD dose and membrane flux on mortality and morbidity in patients undergoing chronic dialysis. PARTICIPANTS: Secondary analysis of the HEMO Study. MEASUREMENTS: Participants completed the Index of Well-Being (IWB) and the Kidney Disease Quality of Life-Long Form (KDQOL-LF), which also includes the Medical Outcomes Study 36-item Short Form Questionnaire (SF-36) annually. Changes in subjects those aged 70 and older were compared with changes in subjects aged 55 to 69 and 18 to 54. RESULTS: At baseline, 1,813 (98%) of HEMO participants completed HRQOL surveys. Their mean age was 58, 56% were female, 64% were black, and mean duration of dialysis was 3.8 years. In subjects with HRQOL data at the first three annual assessments, there were no substantial mean declines in the SF-36 Physical or Mental Component Summary scales over 3 years. In models incorporating effects of attrition, the differences in average change over 3 years between patients undergoing HD aged 70 and older and the younger cohorts were small in magnitude. There were high rates of adverse HRQOL events in all age groups and significantly higher composite event rates of death or clinically significant decline in HRQOL over 3 years was found in subjects aged 70 and older. CONCLUSION: Although HRQOL was impaired in the population undergoing HD, HRQOL scores at baseline reflect a better-preserved multidimensional quality of life in respondents in the HEMO Study aged 70 and older than in younger patients undergoing HD. There was no substantial relationship between age and average decline in HRQOL score over 3 years in participants in the HEMO Study. C1 [Unruh, Mark L.; Newman, Anne B.; Dew, Mary Amanda] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Med Ctr, Dept Epidemiol, Pittsburgh, PA USA. [Larive, Brett; Greene, Tom] Cleveland Clin Fdn, Dept Biostat, Cleveland, OH 44195 USA. [Miskulin, Dana C.; Meyer, Klemens B.] Tufts Univ New England Med Ctr, Div Kidney Dis & Hypertens, Boston, MA USA. [Beddhu, Srinivasan] Univ Utah, Div Nephrol & Hypertens, Salt Lake City, UT USA. [Beddhu, Srinivasan] Vet Affairs Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. [Rocco, Michael V.] Wake Forest Univ, Bowman Gray Sch Med, Div Nephrol & Hypertens, Winston Salem, NC USA. [Kusek, John W.] NIDDK, Bethesda, MD USA. RP Unruh, ML (reprint author), Renal Electrolyte Div, A908 Scaife Hall, Pittsburgh, PA 15261 USA. EM unruh@pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Meyer, Klemens/0000-0001-5253-4950 FU National Kidney Foundation; Baxter Extramural Grant Program [DK077785, DK66006]; National Institutes of Diabetes; Digestive and Kidney Diseases (NIDDK) [U01DK 46109, U01 DK 46114, U01DK 46126, U01DK 46143, U01DK 49240, U01DK 49241, UO1DK 49242, U01DK 49243, U01DK49244, U01DK 49249, U01DK 49252, U01DK 49254, U01DK 49259, U01DK 49261, U01DK 49264, U01DK 49271]; Dialysis Clinics Incorporated, Baxter; Consultants Merck and Qualitymetric KBM; Dialysis Clinic Inc; ESRD Network of New England, Inc., Amgen; Board of Directors of ESRD Network of New England; Forum of ESRD Networks; Merck; GersonLehrman; NIDDK; Covidien FX Conflict of Interest: Dr. Unruh was supported by Fresenius Medical Care Young Investigator Grant of the National Kidney Foundation, Baxter Extramural Grant Program, DK077785 and DK66006.; TheHEMOStudy is supported by the National Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK) via cooperative agreements: U01DK 46109, U01 DK 46114, U01DK 46126, U01DK 46143, U01DK 49240, U01DK 49241, UO1DK 49242, U01DK 49243, U01DK, 49244, U01DK 49249, U01DK 49252, U01DK 49254, U01DK 49259, U01DK 49261, U01DK 49264, U01DK 49271.; MLU: Grant support from Dialysis Clinics Incorporated, Baxter Extramural Grant Fund; Consultants Merck and Qualitymetric KBM: Salary support from Dialysis Clinic Inc.; honoraria from ESRD Network of New England, Inc., Amgen, National Kidney Foundation; member of Board of Directors of ESRD Network of New England and Forum of ESRD Networks; consulting for Merck, GersonLehrman, Primary Insight; grant support from the NIDDK and Covidien. DCM: Salary support from Dialysis Clinic Inc. MVR: Grant support from NIDDK; consultant for Amgen, DaVita, Hoffman LaRoche, Rennaissance Health Care. NR 57 TC 45 Z9 52 U1 0 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2008 VL 56 IS 9 BP 1608 EP 1617 DI 10.1111/j.1532-5415.2008.01849.x PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 347PC UT WOS:000259152500003 PM 18721224 ER PT J AU Chaves, PHM Varadhan, R Lipsitz, LA Stein, PK Windham, G Tian, J Fleisher, LA Guralnik, JM Fried, LP AF Chaves, Paulo H. M. Varadhan, Ravi Lipsitz, Lewis A. Stein, Phyllis K. Windham, Gwen Tian, Jing Fleisher, Lee A. Guralnik, Jack M. Fried, Linda P. TI Physiological complexity underlying heart rate dynamics and frailty status in community-dwelling older women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE frailty; approximate entropy; heart rate variability; elderly; physiological complexity ID RATE-VARIABILITY; MYOCARDIAL-INFARCTION; APPROXIMATE ENTROPY; CHAOS THEORY; DISEASE; HEALTH; PREDICTOR; MORTALITY; INFLAMMATION; DYSFUNCTION AB OBJECTIVES: To assess whether less physiological complexity underlying regulation of heart rate dynamics, as indicated by lower approximate entropy for heart rate (ApEn(HR)), is associated with frailty. For supporting validity, relationships between frailty and traditional linear indices of heart rate variability (HRV) were also assessed. DESIGN: Cross-sectional. SETTING: Women's Health and Aging Study I, a community-based observational study, 1992 to 1995. PARTICIPANTS: Subset of 389 community-dwelling women aged years and older with moderate to severe disability with ApEn(HR) data (convenience sampling). MEASUREMENTS: Electrocardiographic Holter recordings obtained over 2- to 3-hour periods were processed for ApEn(HR) and HRV measures. ApEn(HR) is a nonlinear statistic that quantifies the regularity of heart rate fluctuations over time. Lower ApEn(HR) is characteristic of heart rate time series containing a high proportion of repetitive patterns. Frailty was defined according to validated phenotype criteria. RESULTS: Median ApEn(HR) was lower in frail than in nonfrail subjects (P=.02). Lower ApEn(HR) (top quartile) was associated with lower likelihood of frailty than higher ApEn(HR) (bottom three quartiles) (odds ratio=0.47, 95% confidence interval=0.26-0.86), even after adjustment for major confounders. Frailty was consistently associated with lower HRV as assessed using time- and frequency-domain indices. CONCLUSION: This study supports the notion that less physiological complexity marks frailty and provides an empirical basis to the concept of frailty as a syndrome of homeostatic impairment. Future research will determine whether noninvasive measures of physiological complexity underlying heart rate dynamics might be useful for screening and monitoring of clinical vulnerability in older adults. C1 [Chaves, Paulo H. M.; Varadhan, Ravi; Tian, Jing] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA. [Chaves, Paulo H. M.; Varadhan, Ravi; Tian, Jing] Johns Hopkins Univ, Div Geriatr Med & Gerontol, Baltimore, MD USA. [Chaves, Paulo H. M.; Varadhan, Ravi; Tian, Jing] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Chaves, Paulo H. M.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Chaves, Paulo H. M.] Univ Estado Rio De Janeiro, UNATI Ctr Studies Aging & Care Elderly, Rio De Janeiro, Brazil. [Lipsitz, Lewis A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Lipsitz, Lewis A.] Hebrew Senior Life, Dept Geriatr Med, Boston, MA USA. [Stein, Phyllis K.] Washington Univ, Sch Med, St Louis, MO USA. [Windham, Gwen] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. [Fleisher, Lee A.] Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Fried, Linda P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. RP Chaves, PHM (reprint author), Johns Hopkins Ctr Aging & Hlth, 2024 E Monument St,Suite 2-700, Baltimore, MD 21205 USA. EM pchaves@jhsph.edu FU Johns Hopkins Older Americans Independence Center-National Institute on Aging (NIA) [P30 AG021334]; National Institutes of Health (NIH)-NIA [R37 AG19905]; Intramural Research Program, NIA, NIH; NIA [AG025037] 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. This research supported by Johns Hopkins Older Americans Independence Center-National Institute on Aging (NIA) Grant P30 AG021334; National Institutes of Health (NIH)-NIA Grant R37 AG19905; the Intramural Research Program, NIA, NIH; and NIA Grant AG025037. NR 30 TC 27 Z9 27 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2008 VL 56 IS 9 BP 1698 EP 1703 DI 10.1111/j.1532-5415.2008.01858.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 347PC UT WOS:000259152500016 PM 19166446 ER PT J AU Young, CLE Chaon, BC Shan, QA Lobo, NF Collins, FH AF Young, Catherine L. E. Chaon, Benjamin C. Shan, Qiuqi A. Lobo, Neil F. Collins, Frank H. TI A checklist of the mosquitoes of Indiana with notes on the cryptic species complexes Anopheles quadrimaculatus s.l. and Anopheles punctipennis SO JOURNAL OF THE AMERICAN MOSQUITO CONTROL ASSOCIATION LA English DT Article DE mosquito; Indiana; cryptic species; Anopheles; new state records ID WEST-NILE-VIRUS; OCHLEROTATUS-J.-JAPONICUS; EXPERIMENTAL TRANSMISSION; ENCEPHALITIS-VIRUS; VECTOR COMPETENCE; AEDES-ALBOPICTUS; NEARCTIC REGION; UNITED-STATES; CULICIDAE; DIPTERA AB The checklist of the mosquito species reported to occur in the state of Indiana is updated to include a number of new records and new classifications. Specimens of the cryptic species complex Anopheles quadrimaculatus s.l. are identified as An. quadrimaculatus s.s., and specimens of An. punctipennis are identified as the Eastern form of the species. C1 [Young, Catherine L. E.; Lobo, Neil F.; Collins, Frank H.] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. [Chaon, Benjamin C.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Shan, Qiuqi A.] Princeton Univ, Frist Campus Ctr 3593, Princeton, NJ 08544 USA. RP Young, CLE (reprint author), Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. NR 33 TC 0 Z9 0 U1 0 U2 3 PU AMER MOSQUITO CONTROL ASSOC PI MOUNT LAUREL PA 15000 COMMERCE PARKWAY, SUITE C, MOUNT LAUREL, NJ 08054 USA SN 8756-971X EI 1943-6270 J9 J AM MOSQUITO CONTR JI J. Am. Mosq. Control Assoc. PD SEP PY 2008 VL 24 IS 3 BP 450 EP 452 DI 10.2987/5669.1 PG 3 WC Entomology SC Entomology GA 351XX UT WOS:000259460400018 PM 18939701 ER PT J AU Chen, JB Ayyagari, R Chatterjee, N Pee, DY Schairer, C Byrne, C Benichou, J Gail, MH AF Chen, Jinbo Ayyagari, Rajeev Chatterjee, Nilanjan Pee, David Y. Schairer, Catherine Byrne, Celia Benichou, Jacques Gail, Mitchell H. TI Breast Cancer Relative Hazard Estimates From Case-Control and Cohort Designs With Missing Data on Mammographic Density SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Missing at random; Piecewise exponential model; Pseudo-likelihood; Two-phase stratified case-control study ID 2-STAGE CASE-CONTROL; MAXIMUM-LIKELIHOOD; LOGISTIC-REGRESSION; RISK; MODELS; VALIDATION; 2-PHASE; DISEASE; WOMEN AB We analyzed data from the Breast Cancer Detection Demonstration Project (BCDDP) to obtain multivariate relative hazard models for breast cancer that included mammographic density (MD) in addition to standard risk factors. Data from the BCDDP were collected from a stratified case-control study in the screening phase (1973-1980) and from follow-up of three subcohorts in the follow-up phase (1980-1995). For both phases. MD measurements were only available for about half the women who developed breast cancer (cases) and a small fraction of noncases. We used a logistic regression model for the stratified case-control study and developed a general pseudo-likelihood approach to accommodate missing covariate data (MD) by adapting the method of Scott and Wild and Breslow and Holubkov. We showed that this method was substantially more efficient than a previously proposed weghted-likelihood method. We assumed piecewise exponential models for the analysis of each subcohort, with the missing covariate (MD) distribution conditional on the observed information modeled with polytomous logistic regression. We developed an EM algorithm for estimation, which allowed for time-varying covariates, incomplete follow-up, and left truncation. We analyzed the three follow-up subcohorts separately and then combined the relative hazard models from the case-control and cohort data. The final model included main effects for MD, weight, age at first live birth, number of previous breast biopsies, and number of sisters or mother with breast cancer and was more discriminating (higher concordance) than the original model of Gail et al., which included standard risk jfactors but not MD. In a spearate work, we combined this relative hazard model with other data to project absolute breast cancer risk. C1 [Chen, Jinbo] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Chatterjee, Nilanjan; Schairer, Catherine; Gail, Mitchell H.] Natl Canc Inst, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA. [Ayyagari, Rajeev; Pee, David Y.] Informat Management Serv Inc, Rockville, MD 20852 USA. [Byrne, Celia] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Benichou, Jacques] Univ Rouen, Rouen, France. RP Chen, JB (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. EM jinboche@mail.med.upenn.edu RI Byrne, Celia/K-2964-2015 OI Byrne, Celia/0000-0001-8289-4252 NR 26 TC 3 Z9 3 U1 0 U2 6 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2008 VL 103 IS 483 BP 976 EP 988 DI 10.1198/016214508000000120 PG 13 WC Statistics & Probability SC Mathematics GA 362JJ UT WOS:000260193700007 ER PT J AU Luo, S Crainiceanu, CM Louis, TA Chatterjee, N AF Luo, Sheng Crainiceanu, Ciprian M. Louis, Thomas A. Chatterjee, Nilanjan TI Analysis of Smoking Cessation Patterns Using a Stochastic Mixed-Effects Model With a Latent Cured State SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Cure model; Mixed-effects model; Recurrent events; Smoking cessation; Stochastic transition model ID 2-STATE MARKOV-PROCESSES; MIXTURE-MODELS; CENSORED SAMPLE; SURVIVAL-DATA; RISK-FACTORS; MORTALITY; CANCER; RATES; EPIDEMIOLOGY; INDIVIDUALS AB We develop a mixed model to capture the complex stochastic nature of tobacco abuse and dependence. This model describes transition processes among addiction and nonaddiction stages. An important innovation of our model is allowing an unobserved cure state, or permanent quitting, in contrast to transient quitting. This distinction is necessary to model data from situations where censoring prevents unambiguous determination that a person has been "cured," Moreover, the processes that described transient and permanent quitting are likely to be different and have different policy-making implications. For example, when analyzing factors that influence smoking and can be targeted by interventions, it is more important to target those factors that are associated with permanent quitting rather than transient quitting. We apply our methodology to the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, a large (29,133 participants) longitudinal cohort study. While ATBC was designed as a cancer prevention study. It contains unique information about the smoking status of each participant during every 4-month period of the study. These data are used to model smoking cessation patterns using a discrete-time stochastic mixed-effects model with threee states: smoking, transient cessation, and permanent cessation (absorbent state). Random participant-specific transition probabilities among these states are used to account for participant-to-participant heterogeneity. Another important innovation in our article is to design computationally practical methods for dealing with the size of the dataset and complexity of the models. This is achieved using the marginal likelihood obtained by integrating over the Beta distribution of random effects C1 [Luo, Sheng; Crainiceanu, Ciprian M.; Louis, Thomas A.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Chatterjee, Nilanjan] NCI, NIH, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Luo, S (reprint author), Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. EM sluo@jhsph.edu FU NIDDK NIH HHS [R01 DK061662, R01 DK061662-05] NR 47 TC 5 Z9 5 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2008 VL 103 IS 483 BP 1002 EP 1013 DI 10.1198/016214507000001030 PG 12 WC Statistics & Probability SC Mathematics GA 362JJ UT WOS:000260193700009 PM 19305513 ER PT J AU Rodriguez, A Dunson, DB Gelfand, AE AF Rodriguez, Abel Dunson, David B. Gelfand, Alan E. TI The Nested Dirichlet Process SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE In multicenter studies subjects in different centers may have different outcome distribution. This article is motivated by the problem of nonparametric modeling of these distributions, borrowing information across centers while also allowing centers to be clustered, Starting with a stick-breaking representation of the Dricichlet process (DP). we replace that random atoms with random probability measures drawn from a DP. This results in a nested DP prior, which can be placed on the collection of distributions for the different centers with centers drawn from the same DP component authomatically clustered together. Theorectical properties are discussed and an efficient Markov chain Monte Carlo algorithm is developed for computation. The methods are illustrated using a simulation study and an application to quality of care in U.S hospitals. ID FINITE NORMAL MIXTURES; PROBABILITY-MEASURES; BAYESIAN-INFERENCE; SAMPLING METHODS; PROCESS MODELS; DISTRIBUTIONS; HETEROGENEITY; REGRESSION; PRIORS C1 [Rodriguez, Abel] Univ Calif Santa Cruz, Dept Appl Math & Stat, Santa Cruz, CA 95064 USA. [Dunson, David B.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Gelfand, Alan E.] Duke Univ, Inst Stat & Decis Sci, Durham, NC 27708 USA. RP Rodriguez, A (reprint author), Univ Calif Santa Cruz, Dept Appl Math & Stat, Santa Cruz, CA 95064 USA. EM abel@soe.ucsc.edu; dunson1@niehs.nih.gov; alan@isds.duke.edu NR 55 TC 64 Z9 65 U1 0 U2 5 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2008 VL 103 IS 483 BP 1131 EP 1144 DI 10.1198/016214508000000553 PG 14 WC Statistics & Probability SC Mathematics GA 362JJ UT WOS:000260193700019 ER PT J AU Rodriguez, A Dunson, DB Gelfand, AE AF Rodriguez, Abel Dunson, David B. Gelfand, Alan E. TI The Nested Dirichlet Process Rejoinder SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Editorial Material C1 [Rodriguez, Abel] Univ Calif Santa Cruz, Dept Appl Math & Stat, Santa Cruz, CA 95064 USA. [Dunson, David B.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Gelfand, Alan E.] Duke Univ, Inst Stat & Decis Sci, Durham, NC 27708 USA. RP Rodriguez, A (reprint author), Univ Calif Santa Cruz, Dept Appl Math & Stat, Santa Cruz, CA 95064 USA. EM abel@soe.ucsc.edu; dunson1@niehs.nih.gov; alan@isds.duke.edu NR 7 TC 0 Z9 0 U1 1 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2008 VL 103 IS 483 BP 1153 EP 1154 DI 10.1198/016214508000000616 PG 2 WC Statistics & Probability SC Mathematics GA 362JJ UT WOS:000260193700025 ER PT J AU Huang, CY Qin, J Follmann, DA AF Huang, Chiung-Yu Qin, Jing Follmann, Dean A. TI Empirical Likelihood-Based Estimation of the Treatment Effect in a Pretest- Posttest Study SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Auxiliary information; Biased sampling; Casual inference; Observational study; Survey sampling ID MISSING RESPONSE; AUXILIARY INFORMATION; RESEARCH DESIGNS; INFERENCE AB The pretest-posttest study design is commonly used in medical and social science research to assess the effect of a treatment or an intervention. Recently, interest has been rising in developing inference procedures that improve efficiency while relaxing assumptions used in the pretest-posttest data analysis, especially when the posttest measurement might be missing. In this article we propose a semiparametric estimation procedure based on empirical likelihood (EL) that incorporates the common baseline covariate information to improve efficiency. The proposed method also yields an asymptotically unbiased estimate of the response distribution. Thus functions of the response distribution, such as the median, can be estimated straightforwardly, and the EL method can provide a more appealing estimate of the treatment effect for skewed data.We show that, compared with existing methods, the proposed EL estimator has appealing theoretical properties, especially when the working model for the underlying relationship between the pretest and posttest measurements is misspecified. A series of simulation studies demonstrates that the EL-based estimator outerperforms its competitors when the working model is misspecified and the data are missing at random. We illustrate the methods by analyzing data from an AIDS clinical trial (ACTG 175). C1 [Huang, Chiung-Yu; Qin, Jing; Follmann, Dean A.] NIAID, NIH, Biostat Res Branch, Bethesda, MD 20892 USA. RP Huang, CY (reprint author), NIAID, NIH, Biostat Res Branch, Bethesda, MD 20892 USA. EM huangchi@niaid.nih.gov; jingqin@niaid.nih.gov; dfollmann@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 30 TC 6 Z9 6 U1 0 U2 3 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2008 VL 103 IS 483 BP 1270 EP 1280 DI 10.1198/016214508000000625 PG 11 WC Statistics & Probability SC Mathematics GA 362JJ UT WOS:000260193700036 PM 23729942 ER PT J AU Goedert, JJ Scoppio, BM Pfeiffer, R Neve, L Federici, AB Long, LR Dolan, BM Brambati, M Bellinvia, M Lauria, C Preiss, L Boneschi, V Whitby, D Brambilla, L AF Goedert, J. J. Scoppio, B. M. Pfeiffer, R. Neve, L. Federici, A. B. Long, L. R. Dolan, B. M. Brambati, M. Bellinvia, M. Lauria, C. Preiss, L. Boneschi, V. Whitby, D. Brambilla, L. TI Treatment of classic Kaposi sarcoma with a nicotine dermal patch: a phase II clinical trial SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY LA English DT Article DE drug delivery systems; Kaposi sarcoma; smoking ID ACTIVE ANTIRETROVIRAL THERAPY; 0.1-PERCENT ALITRETINOIN GEL; TRANSDERMAL NICOTINE; 9-CIS-RETINOIC ACID; ULCERATIVE-COLITIS; VERRUCA-VULGARIS; DUCT TAPE; AIDS; CHEMOTHERAPY; EFFICACY AB Background Kaposi sarcoma (KS), a malignancy of dermal endothelial cells that is caused by human herpesvirus 8 (HHV8) infection, is sensitive to perturbations of immunity. Nicotine might be effective against KS because of its immunologic and vascular effects and because smoking is associated with a low risk of KS. Objective and study design We conducted a masked, randomized phase 2 clinical trial of transdermal nicotine and placebo patches to assess the safety and efficacy of nicotine against classic KS (cKS). Subjects and methods Three cKS lesions, predominantly nodules, in each of 24 non-smoking patients were randomly assigned to 15 weeks continuous treatment with nicotine patch (escalated to 7 mg), identical masked placebo patch or no patch. Changes in lesion area and elevation from baseline through six follow-up visits, by direct measurement and by two independent readers using digital photographs of the lesions, were compared using non-parametric and regression methods. Changes in longitudinal levels of HHV8 antibodies and DNA in blood cells were similarly assessed. Results There were no systemic or serious adverse events, and compliance was good. One patient resumed smoking and discontinued patches, and two patients withdrew at week 12 for unrelated indications. Six (29%) of the remaining 21 suspended use of patches to relieve local skin irritation; four of these six completed the trial at reduced dose. Treatment assignment was not associated with significant or consistent changes in cKS lesion area or elevation, HHV8 viral load or antibodies. Conclusion Transdermal nicotine and placebo patches caused no serious toxicities but had no demonstrable effect on nodular cKS lesions or HHV8 levels. C1 [Goedert, J. J.; Pfeiffer, R.; Dolan, B. M.] NCI, Viral Epidemiol Branch, Div Canc Epidemiol and Genet, Rockville, MD 20852 USA. [Goedert, J. J.; Pfeiffer, R.; Dolan, B. M.] NCI, Biostat Branch, Div Canc Epidemiol and Genet, Rockville, MD 20852 USA. [Scoppio, B. M.; Federici, A. B.; Brambati, M.; Bellinvia, M.; Boneschi, V.; Brambilla, L.] Regina Elena Fdn, IRCCS Fdn Maggiore Policlin Hosp, Dept Med & Med Specialties, Angelo Bianchi Bonomi Hemophilia Thrombosis Ctr, Milan, Italy. [Scoppio, B. M.; Federici, A. B.; Brambati, M.; Bellinvia, M.; Boneschi, V.; Brambilla, L.] Regina Elena Fdn, IRCCS Fdn Maggiore Policlin Hosp, Dept Med & Med Specialties, Inst Dermatol Sci, Milan, Italy. [Neve, L.; Long, L. R.] Natl Lib Med, Commun Engn Branch, Bethesda, MD USA. [Lauria, C.] Lega Italiana Lotta Contro I Tumori RG, Ragusa, Italy. [Preiss, L.] RTI Int, Rockville, MD USA. [Preiss, L.] RTI Int, Buenos Aires, DF, Argentina. [Whitby, D.] NCI, SAIC Frederick, AIDS Vaccine Program, Viral Oncol Sect, Frederick, MD 21701 USA. RP Goedert, JJ (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol and Genet, 6120 Execut Blvd Room 7066, Rockville, MD 20852 USA. EM goedertj@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 FU NIH Intramural Research Program [N02-CP-55504, N01-CO-12400] FX We thank the Data and Safety Monitoring Board: Drs Damiano Abeni ( Chair), Gianni Baliva and Paolo Marchetti, all of whom are at the Istituto Dermatopatico Dell'Immacolata, Rome, Italy. We are grateful to Joseph A. Matthias and Dr Carolyn M. Dresler, GlaxoSmithKline Consumer Healthcare, for donation of the patches; to Mss. Julie Russell Grey and Judith Lichaa for random allocation and masking of the nicotine and placebo patches; to Noelle Richa (RTI International) for masking and randomization of the digital photograph files; to Marianne Ardini ( RTI International) for forms development and operations management; and to Georgina Mbisa and Vickie Marshall, Viral Oncology Section, SAIC-Frederick, for HHV8 antibody titres and for HHV8 and EBV viral load measurements, respectively. This study is supported in part by the NIH Intramural Research Program through contracts N02-CP-55504 and N01-CO-12400. NR 43 TC 7 Z9 7 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0926-9959 J9 J EUR ACAD DERMATOL JI J. Eur. Acad. Dermatol. Venereol. PD SEP PY 2008 VL 22 IS 9 BP 1101 EP 1109 DI 10.1111/j.1468-3083.2008.02720.x PG 9 WC Dermatology SC Dermatology GA 337NS UT WOS:000258443400011 PM 18384551 ER PT J AU Choong, NW Mauer, AM Haraf, DJ Lester, E Hoffman, PC Kozloff, M Lin, S Dancey, JE Szeto, L Grushko, T Olopade, OI Salgia, R Vokes, EE AF Choong, Nicholas W. Mauer, Ann M. Haraf, Daniel J. Lester, Eric Hoffman, Philip C. Kozloff, Mark Lin, Shang Dancey, Janet E. Szeto, Livia Grushko, Tatyana Olopade, Olufunmilayo I. Salgia, Ravi Vokes, Everett E. TI Phase I trial of erlotinib-based multimodality therapy for inoperable stage III non-small cell lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol DE non-small cell lung cancer; chemoradiotherapy; multimodality therapy; erlotinib; epidermal-growth factor inhibitor ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CARCINOMA-CELLS; PHARMACODYNAMIC SEPARATION; RADIATION RESPONSE; GEFITINIB; GENE; CHEMOTHERAPY; COMBINATION; CISPLATIN AB Introduction: This Phase I trial aimed to determine the maximum-tolerated-dose of erlotinib administered with two standard chemoradiotherapy regimens for non-small cell lung cancer. Methods: Unresectable stage III non-small cell lung cancer patients were enrolled in this 2-arm close-escalation Study. Erlotinib, given only during chemoradiotherapy, was escalated front 50 to 150 mg/d in 3 to 6 patient cohorts. Arm A: erlotinib with cisplatin (50 mg/m(2) IV days 1, 8, 29, 36), etoposide (50 mg/m(2) IV days 1-5, 29-33) and chest radiotherapy (66 Gy, 2 Gy/d) followed by docetaxel (75 mg/m(2) 2 IV Q21 d) for 3 cycles. Arm B: induction carboplatin (AUC 6) and paclitaxel (200 mg/m(2)) for two 21-d cycles then radiotherapy with erlotinib, carboplatin (AUC = 2/wk) and paclitaxel (50 mg/m(2)/wk). Results: Seventeen patients were treated in each arm. Patient characteristics: performance status 0 to 24 patients, I to 10 patients, median age 63 years. adenocarcinoma 21% and female 14 patients. Dose-escalation of erlotinib to 150 mg/d was possible oil both chemoradiotherapy regimens. Grade 3/4 leukopenia and neutropenia were predominant toxicities in both arms. Grade 3 chemoradiotherapy toxicities in at-in A were esophagitis (3 patients), vomiting (1), ototoxicity (1), diarrhea (2), dehydration (3), pneumonitis (1) and arm B was esophagitis (6). Seven patients (21%) developed rash (all grade 1/2). Median survival times for patients oil Ann A and B were 10.2 and 13.7 months, respectively. Three-year overall survival in patients with and Without rash were 53% and 10%, respectively (log-rank P = 0.0807). Epidermal growth factor receptor IHC or FISH positive patients showed no significant overall survival difference. Conclusion: Addition of standard-dose erlotinib to chemoradiotherapy is feasible Without evident increase in toxicities. However, the survival data are disappointing ill this unselected patient Population and does not Support further investigation of this approach. C1 [Choong, Nicholas W.; Hoffman, Philip C.; Szeto, Livia; Grushko, Tatyana; Olopade, Olufunmilayo I.; Salgia, Ravi; Vokes, Everett E.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60615 USA. [Choong, Nicholas W.; Hoffman, Philip C.; Szeto, Livia; Grushko, Tatyana; Olopade, Olufunmilayo I.; Salgia, Ravi; Vokes, Everett E.] Univ Chicago, Med Ctr, Phase Network 2, Chicago, IL 60615 USA. [Choong, Nicholas W.] Med Coll Wisconsin, Div Neoplast Dis, Milwaukee, WI 53226 USA. [Mauer, Ann M.] Advocate Illinois Mason Med Ctr, Creticos Canc Ctr, Chicago, IL USA. [Haraf, Daniel J.; Vokes, Everett E.] Univ Chicago, Med Ctr, Dept Radiat Biol & Cellular Oncol, Chicago, IL 60615 USA. [Lester, Eric] Oncol Care Associates, St Joseph, MI USA. [Kozloff, Mark] Ingalls Hosp, Harvey, IL USA. [Lin, Shang] Univ Chicago, Dept Hlth Studies, Chicago, IL 60615 USA. [Dancey, Janet E.] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatments & Diag, Rockville, MD USA. RP Vokes, EE (reprint author), Univ Chicago, Med Ctr, Hematol Oncol Sect, MC 2115,5841 S Maryland Ave, Chicago, IL 60615 USA. EM evokes@medicine.bsd.uchicago.edu FU NCI NIH HHS [N01 CM-07003-74, T32 CA009566-15, T32 CA009566, P30 CA14599-32, P30 CA014599, N01 CM007003] NR 44 TC 40 Z9 43 U1 0 U2 1 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 SEP PY 2008 VL 3 IS 9 BP 1003 EP 1011 DI 10.1097/JTO.0b013e31818396a4 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 347TV UT WOS:000259164900011 PM 18758303 ER PT J AU Gill, JM Page, GG Sharps, P Campbell, JC AF Gill, Jessica M. Page, Gayle G. Sharps, Phyllis Campbell, Jacquelyn C. TI Experiences of traumatic events and associations with PTSD and depression development in urban health care-seeking women SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE PTSD; depression; trauma; urban; women ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER VIOLENCE; CHILD SEXUAL-ABUSE; PERSONALITY-DISORDER; GENDER-DIFFERENCES; AFRICAN-AMERICANS; MAJOR DEPRESSION; SUBSTANCE-ABUSE; MENTAL-HEALTH; COMORBIDITY AB Posttraumatic stress disorder (PTSD) is an anxiety disorder that occurs after a traumatic event and has been linked to psychiatric and physical health declines. Rates of PTSD are far higher in individuals with low incomes and who reside in urban areas compared to the general population. In this study, 250 urban health care-seeking women were interviewed for a diagnosis of PTSD, major depressive disorder, and also the experience of traumatic events. Multivariate logistic regressions were used to determine the associations between traumatic events and PTSD development. Survival analysis was used to determine if PTSD developed from assaultive and nonassaultive events differed in symptom duration. Eighty-six percent of women reported at least one traumatic event, 14.8% of women were diagnosed with current PTSD, and 19.6% with past PTSD. More than half of women with PTSD had comorbid depression. Assaultive traumatic events were most predictive of PTSD development. More than two thirds of the women who developed PTSD developed chronic PTSD. Women who developed PTSD from assaultive events experienced PTSD for at least twice the duration of women who developed PTSD from nonassaultive events. In conclusion, PTSD was very prevalent in urban health care-seeking women. Assaultive violence was most predictive of PTSD development and also nonremittance. C1 [Gill, Jessica M.] NINR, NIH, Bethesda, MD 20892 USA. [Page, Gayle G.; Sharps, Phyllis; Campbell, Jacquelyn C.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. RP Gill, JM (reprint author), NINR, NIH, 10 Ctr Dr,10 CRC 2-1339, Bethesda, MD 20892 USA. EM gillj@mail.nih.gov FU National Institute for Nursing Research (NINR) [F31 NR009166, T32 NR 07968] FX Funding for this research was provided by the following sources: Individual National Research Service Award (NRSA) F31 NR009166 funded through the National Institute for Nursing Research (NINR); Institutional Training Grant funded through NINR T32 NR 07968: Health Disparities in Underserved Populations; The Freedom from Fear Sharon Davies Memorial Grant; Sigma Theta Tau, Beta Nu Chapter, Small Grant Award. NR 57 TC 11 Z9 12 U1 7 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD SEP PY 2008 VL 85 IS 5 BP 693 EP 706 DI 10.1007/s11524-008-9290-y PG 14 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 343GS UT WOS:000258842000006 PM 18581238 ER PT J AU Kaplan, SA Roehrborn, CG McConnell, JD Meehan, AG Surynawanshi, S Lee, JY Rotonda, J Kusek, JW Nyberg, LM AF Kaplan, Steven A. Roehrborn, Claus G. McConnell, John D. Meehan, Alan G. Surynawanshi, Shailaja Lee, Jeannette Y. Rotonda, Jennifer Kusek, John W. Nyberg, Leroy M., Jr. CA Med Therapy Prostat Symptoms Res G TI Long-term treatment with finasteride results in a clinically significant reduction in total prostate volume compared to placebo over the full range of baseline prostate sizes in men enrolled in the MTOPS trial SO JOURNAL OF UROLOGY LA English DT Article DE prostatic hyperplasia; urinary tract; doxazosin; finasteride; combined modality therapy ID THERAPY AB Purpose: In the present analysis we examined data from the MTOPS (Medical Therapy of Prostatic Symptoms) trial to determine the effect of long-term finasteride treatment, either alone or in combination with doxazosin, on total prostate volume across the full range of baseline total prostate volume values in men enrolled in this study. Materials and Methods: In this trial a total of 3,047 patients with lower urinary tract symptoms were randomized to placebo, doxazosin (4 to 8 mg), finasteride (5 mg) or the combination of doxazosin and finasteride (average length of treatment 4.5 years). Total prostate volume was measured by transrectal ultrasound in all patients at baseline, yearly and at study end or at termination of participation. Results: Long-term treatment with finasteride led to a consistent reduction of approximately 25% in total prostate volume compared to placebo in men with a relatively small prostate (less than 25 to 30 ml), as well as in those with a moderate size (30 to less than 40 ml) or enlarged prostate (40 ml or greater) at baseline. Conclusions: In this MTOPS data analysis long-term (more than 4 years) treatment with finasteride, either alone or in combination with doxazosin, led to a consistent, clinically significant reduction in total prostate volume compared to placebo in patients with lower urinary tract symptoms and benign prostatic hyperplasia whose baseline prostate size ranged from relatively small (less than 25 to 30 ml) to enlarged (40 ml or greater). C1 [Kaplan, Steven A.] Cornell Univ, Inst Bladder & Prostate Hlth, Weill Cornell Med Coll, New York, NY 10021 USA. [Roehrborn, Claus G.; McConnell, John D.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Meehan, Alan G.; Surynawanshi, Shailaja; Rotonda, Jennifer] Merck Res Labs, Rahway, NJ USA. [Lee, Jeannette Y.] Univ Alabama, Birmingham, AL USA. [Kusek, John W.; Nyberg, Leroy M., Jr.] NIDDK, Bethesda, MD USA. RP Kaplan, SA (reprint author), Cornell Univ, Inst Bladder & Prostate Hlth, Weill Cornell Med Coll, 1300 York Ave,F9 W,Box 261, New York, NY 10021 USA. EM kaplans@med.cornell.edu FU NIDDK NIH HHS [U01 DK46468, U01 DK 49912, U01 DK41418, U01 DK46416, U01 DK46429, U01 DK46431, U01 DK46437, U01 DK46472, U01 DK49880, U01 DK49921, U01 DK49951, U01 DK49954, U01 DK49960, U01 DK49961, U01 DK49963, U01 DK49964, U01 DK49971, U01 DK49977, U01 DK49980] NR 3 TC 32 Z9 34 U1 1 U2 4 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 SEP PY 2008 VL 180 IS 3 BP 1030 EP 1032 DI 10.1016/j.juro.2008.05.004 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 337TV UT WOS:000258459300061 PM 18639298 ER PT J AU Elagha, AA Kocaturk, O Guttman, MA Ozturk, C Kim, AH Burton, GW Kim, JH Raman, VK Raval, AN Wright, VJ Schenke, WH McVeigh, ER Lederman, RJ AF Elagha, Abdalla A. Kocaturk, Ozgur Guttman, Michael A. Ozturk, Cengizhan Kim, Ann H. Burton, George W. Kim, June H. Raman, Venkatesh K. Raval, Amish N. Wright, Victor J. Schenke, William H. McVeigh, Elliot R. Lederman, Robert J. TI Real-time MR imaging-guided laser atrial septal puncture in swine SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID LEFT-HEART CATHETERIZATION; TRANSSEPTAL PUNCTURE; RESONANCE; EXPERIENCE; ANGIOPLASTY; FLUOROSCOPY; SAFETY; FEASIBILITY; COARCTATION AB PURPOSE: The authors performed this study to report their initial preclinical experience with real-time magnetic resonance (MR) imaging-guided atrial septal puncture by using a MR imaging-conspicuous blunt laser catheter that perforates only when energized. MATERIALS AND METHODS: The authors customized a 0.9-mm clinical excimer laser catheter with a receiver coil to impart MR imaging visibility at 1.5 T. Seven swine underwent laser transseptal puncture under real-time MR imaging. MR imaging signal-to-noise ratio profiles of the device were obtained in vitro. Tissue traversal force was tested with a calibrated meter. Position was corroborated with pressure measurements, oximetry, angiography, and necropsy. Intentional non-target perforation simulated serious complication. RESULTS: Embedded MR imaging antennae accurately reflected the position of the laser catheter tip and profile in vitro and in vivo. Despite having an increased profile from the microcoil, the 0.9-mm laser catheter traversed in vitro targets with similar force (0.22 N +/- 0.03) compared with the unmodified laser. Laser puncture of the atrial septum was successful and accurate in all animals. The laser was activated an average of 3.8 seconds +/- 0.4 before traversal. There were no sequelae after 6 hours of observation. Necropsy revealed 0.9-mm holes in the fossa ovalis in all animals. Intentional perforation of the aorta and atrial free wall was evident immediately. CONCLUSIONS: MR imaging-guided laser puncture of the interatrial septum is feasible in swine and offers controlled delivery of perforation energy by using an otherwise blunt catheter. Instantaneous soft tissue imaging provides immediate feedback on safety. C1 [Elagha, Abdalla A.; Kocaturk, Ozgur; Guttman, Michael A.; Ozturk, Cengizhan; Kim, Ann H.; Kim, June H.; Raman, Venkatesh K.; Raval, Amish N.; Wright, Victor J.; Schenke, William H.; McVeigh, Elliot R.; Lederman, Robert J.] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Burton, George W.] Spectranetics, Colorado Springs, CO USA. RP Lederman, RJ (reprint author), NHLBI, Div Intramural Res, NIH, Bldg 10,Rm 2C713, Bethesda, MD 20892 USA. EM ledermar@nhlbi.nih.gov RI Ozturk, Cengizhan/A-6177-2016; OI Ozturk, Cengizhan/0000-0002-6966-0774; lederman, robert/0000-0003-1202-6673; Elagha, Abdalla/0000-0003-3136-2293 FU NHLBI Division of Intramural Research [Z01-HL005062-04 CVB] FX The authors thank Kathy Lucas and Joni Taylor for their animal care and support and Parag V. Karmarkar for assistance with decoupling circuitry. Spectranetics customized laser catheters under a Collaborative Research and Development Agreement with the National Heart Lung and Blood Institute. Supported by the NHLBI Division of Intramural Research (Z01-HL005062-04 CVB), NR 36 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2008 VL 19 IS 9 BP 1347 EP 1353 DI 10.1016/j.jvir.2008.05.007 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 346FU UT WOS:000259054900013 PM 18725098 ER PT J AU Tseng, FC Edlin, BR Zhang, M Kral, A Busch, MP Ortiz-Conde, BA Welzel, TM O'Brien, TR AF Tseng, F. -C. Edlin, B. R. Zhang, M. Kral, A. Busch, M. P. Ortiz-Conde, B. A. Welzel, T. M. O'Brien, T. R. TI The inverse relationship between chronic HBV and HCV infections among injection drug users is associated with decades of age and drug use SO JOURNAL OF VIRAL HEPATITIS LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/106th Annual Meeting of the American-Gastroenterological-Association CY MAY 14-19, 2005 CL Chicago, IL SP Amer Gastroenterol Assoc DE epidemiology; hepatitis B virus; hepatitis C virus; injection drug use; United States; viral suppression ID HEPATITIS-C VIRUS; B-VIRUS; SAN-FRANCISCO; HEPATOCELLULAR-CARCINOMA; LIVER-DISEASE; DELTA VIRUSES; CORE PROTEIN; FOLLOW-UP; PREVALENCE; RISK AB Infection with hepatitis C virus (HCV) may suppress co-infection with hepatitis B virus (HBV) during acute or chronic HBV infection. We examined relationships between HBV infection, HCV infection and other factors among injection drug users (IDUs) with antibodies to both viruses. Participants enrolled in a cross-sectional study during 1998-2000 were considered to have been infected with HBV if they had core antibody, to be chronically infected if they had hepatitis B surface antigen (HBsAg), to have been infected with HCV if they had HCV antibody and to be chronically infected if they had HCV RNA. Among 1694 participants with antibody to both viruses, HBsAg prevalence decreased with increasing age among those positive for HCV RNA [from 4.55% in those 18-29 years to 1.03% in those >= 50 years old (P(trend) = 0.02)], but not among those who were negative for HCV RNA. Chronic HBV infection was less common overall among those with chronic HCV infection (odds ratio [OR], 0.25; P < 0.0001), but this inverse relationship was much stronger in the oldest (> 50 years; OR = 0.15) than the youngest (18-29 years; OR = 0.81) participants (P(trend) = 0.03). Similar results were obtained when duration of injection drug use was substituted for age (P(trend) = 0.05). Among IDUs who have acquired both HBV and HCV, chronic HBV infection is much less common among those with chronic HCV infection, but this inverse relationship increases markedly with increasing years of age and injection drug use. Co-infection with HCV may enhance the resolution of HBsAg during the chronic phases of these infections. C1 [O'Brien, T. R.] Natl Canc Inst, Div Canc Epidemiol & Genet, Adv Technol Ctr, Bethesda, MD 20892 USA. [Edlin, B. R.; Kral, A.; Busch, M. P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Edlin, B. R.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Kral, A.] RTI Int, San Francisco Reg Off, San Francisco, CA USA. [Busch, M. P.] Blood Syst Res Inst, San Francisco, CA USA. [Ortiz-Conde, B. A.] NCI, Viral Oncol Sect, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21701 USA. RP O'Brien, TR (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Adv Technol Ctr, Room 225A,MSC 4605 8717,Grovemont Circle, Bethesda, MD 20892 USA. EM obrient@mail.nih.gov RI Tseng, Fan-Chen/D-2097-2010; OI Edlin, Brian/0000-0001-8172-8797 FU CSAT SAMHSA HHS [H79-TI12103]; Intramural NIH HHS; NCI NIH HHS [N01CO12400, N02-CP-91027, N01-CO-12400]; NIDA NIH HHS [R01 DA009532, R01 DA012109, R01-DA16159, R01-DA09532, R01 DA016159, R01 DA013245, R01 DA009532-08, R01-DA13245] NR 43 TC 11 Z9 12 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD SEP PY 2008 VL 15 IS 9 BP 690 EP 698 DI 10.1111/j.1365-2893.2008.01005.x PG 9 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 336QX UT WOS:000258380800010 PM 18507757 ER PT J AU Chen, JB Pathak, VK Peng, WQ Hu, WS AF Chen, Jianbo Pathak, Vinay K. Peng, Weiqun Hu, Wei-Shau TI Capsid proteins from human immunodeficiency virus type 1 and simian immunodeficiency virus SIVmac can coassemble into mature cores of infectious viruses SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; HIV-1 INFECTION; RETROVIRAL RESTRICTION; NONDIVIDING CELLS; VIRAL REPLICATION; TRIM5-ALPHA; REF1; RECONSTRUCTIONS; ORGANIZATION; LENTIVIRUS AB We have recently shown that the Gag polyproteins from human immunodeficiency virus type 1 (HIV-1) and HIV-2 can coassemble and functionally complement each other. During virion maturation, the Gag polyproteins undergo proteolytic cleavage to release mature proteins including capsid (CA), which refolds and forms the outer shell of a cone-shaped mature core. Less than one-half of the CA proteins present within the HIV-1 virion are required to form the mature core. Therefore, it is unclear whether the mature core in virions containing both HIV-1 and HIV-2 Gag consists of CA proteins from a single virus or from both viruses. To determine whether CA proteins from two different viruses can coassemble into mature cores of infectious viruses, we exploited the specificity of the tripartite motif 5 alpha protein from the rhesus monkey (rhTRIM5 alpha) for cores containing HIV-1 CA (hCA) but not the simian immunodeficiency virus SIVmac CA protein (sCA). If hCA and sCA cannot coassemble into the same core when equal amounts of sCA and hCA are coexpressed, the infectivities of such virus preparations in cells should be inhibited less than twofold by rhTRIM5 alpha.. However, if hCA and sCA can coassemble into the same core structure to form a mixed core, rhTRIM5 alpha would be able to recognize such cores and significantly restrict virus infectivity. We examined the restriction phenotypes of viruses containing both hCA and sCA. Our results indicate that hCA and sCA can coassemble into the same mature core to produce infectious virus. To our knowledge, this is the first demonstration of functional coassembly of heterologous CA protein into the retroviral core. C1 [Chen, Jianbo; Pathak, Vinay K.; Hu, Wei-Shau] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535,Room 336, Frederick, MD 21702 USA. EM whu@ncifcrf.gov RI Chen, Jianbo/N-3737-2014 OI Chen, Jianbo/0000-0001-6491-6577 FU NIH [IATAP]; Center for Cancer Research, National Cancer Institute FX We thank Anne Arthur for her expert editorial help, Matthew Stremlau and Joseph Sodroski for the generous gifts of TRIM5 alpha and control cell lines, and Eric Freed and Alan Rein for their input and critical reading of the manuscript. This research was supported by the Intramural Research Program of the NIH, including an IATAP grant, and the Center for Cancer Research, National Cancer Institute. NR 55 TC 1 Z9 1 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 SEP PY 2008 VL 82 IS 17 BP 8253 EP 8261 DI 10.1128/JVI.02663-07 PG 9 WC Virology SC Virology GA 339UU UT WOS:000258603600002 PM 18579598 ER PT J AU Liu, MH Yang, LP Zhang, L Liu, BY Merling, R Xia, Z Giam, CZ AF Liu, Meihong Yang, Liangpeng Zhang, Ling Liu, Baoying Merling, Randall Xia, Zheng Giam, Chou-Zen TI Human T-cell leukemia virus type 1 infection leads to arrest in the G(1) phase of the cell cycle SO JOURNAL OF VIROLOGY LA English DT Article ID HTLV-I TAX; ANAPHASE-PROMOTING COMPLEX; ONCOGENE PRODUCT TAX; NF-KAPPA-B; CENTROSOME OVERDUPLICATION; MOLECULAR MECHANISM; DEPENDENT KINASES; CDK INHIBITORS; ONCOPROTEIN; ACTIVATION AB Infection by the human T-cell leukemia virus type 1 (HTLV-1) is thought to cause dysregulated T-cell proliferation, which in turn leads to adult T-cell leukemia/lymphoma. Early cellular changes after HTLV-1 infection have been difficult to study due to the poorly infectious nature of HTLV-1 and the need for cell-to-cell contact for HTLV-1 transmission. Using a series of reporter systems, we show that HeLa cells cease proliferation within one or two division cycles after infection by HTLV-1 or transduction of the HTLV-1 tax gene. HTLV-1-infected HeLa cells, like their tax-transduced counterparts, expressed high levels of p21(CIP1/WAF1) and p27(KIP1), developed mitotic abnormalities, and became arrested in G, in senescence. In contrast, cells of a human osteosarcoma lineage (HOS) continued to divide after HTLV-1 infection or Tax expression, albeit at a reduced growth rate and with mitotic aberrations. Unique to HOS cells is the dramatic reduction of p21(CIP1/WAF1) and p27(KIP1) expression, which is in part associated with the constitutive activation of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) pathway. The loss of p21(CIP1/WAF1) and p27(KIP1) in HOS cells apparently allows HTLV-1- and Tax-induced G, arrest to be bypassed. Finally, HTLV-1 infection and Tax expression also cause human SupT1 T cells to arrest in the G, phase of the cell cycle. These results suggest that productive HTLV-1 infection ordinarily leads to Tax-mediated G, arrest. However, T cells containing somatic mutations that inactivate p21(CIP1/WAF1) and p27(KIP1) may continue to proliferate after HTLV-I infection and Tax expression. These infected cells can expand clonally, accumulate additional chromosomal abnormalities, and progress to cancer. C1 [Liu, Meihong; Yang, Liangpeng; Zhang, Ling; Merling, Randall; Xia, Zheng; Giam, Chou-Zen] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Liu, Baoying] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Giam, CZ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM cgiam@usuhs.mil FU National Institutes of Health [R01CA115884] FX We thank K. Wolcott and K. Lund of the Uniformed Services University Biomedical Instrumentation Center for help with flow cytometry and K. S. Jones of SAIC-Frederick of National Cancer Institute for helpful discussions.; This work was supported by a grant (R01CA115884) from the National Institutes of Health. NR 45 TC 35 Z9 37 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2008 VL 82 IS 17 BP 8442 EP 8455 DI 10.1128/JVI.00091-08 PG 14 WC Virology SC Virology GA 339UU UT WOS:000258603600020 PM 18596104 ER PT J AU Jung, KJ Dasgupta, A Huang, K Jeong, SJ Pise-Masison, C Gurova, KV Brady, JN AF Jung, Kyung-Jin Dasgupta, Arindam Huang, Keven Jeong, Soo-Jin Pise-Masison, Cynthia Gurova, Katerina V. Brady, John N. TI Small-molecule inhibitor which reactivates p53 in human T-cell leukemia virus type 1-transformed cells SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; I TAX PROTEIN; TRANSGENIC MICE; HTLV-1-TRANSFORMED CELLS; GENE-EXPRESSION; ACTIVATION; TRANSFORMATION; PHOSPHORYLATION; ONCOPROTEIN; HTLV-1 AB Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of the aggressive and fatal disease adult T-cell leukemia. Previous studies have demonstrated that the HTLV-1-encoded Tax protein inhibits the function of tumor suppressor p53 through a Tax-induced NF-kappa B pathway. Given these attributes, we were interested in the activity of small-molecule inhibitor 9-aminoacridine (9AA), an anticancer drug that targets two important stress response pathways, NF-kappa B and p53. In the present study, we have examined the effects of 9AA on HTLV-1 -transformed cells. Treatment of HTLV-1-transformed cells with 9AA resulted in a dramatic decrease in cell viability. Consistent with these results, we observed an increase in the percentage of cells in sub-G, and an increase in the number of cells positive by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay following treatment of HTLV-1-transformed cells with 9AA. In each assay, HTLV-1-transformed cells C8166, Hut102, and MT2 were more sensitive to treatment with 9AA than control CEM and peripheral blood mononuclear cells. Analyzing p53 function, we demonstrate that treatment of HTLV-1 -transformed cells with 9AA resulted in an increase in p53 protein and activation of p53 transcription activity. Of significance, 9AA-induced cell death could be blocked by introduction of a p53 small interfering RNA, linking p53 activity and cell death. These results suggest that Tax-repressed p53 function in HTLV-1-transformed cells is "druggable" and can be restored by treatment with 9AA. The fact that 9AA induces p53 and inhibits NF-kappa B suggests a promising strategy for the treatment of HTLV-1-transformed cells. C1 [Jung, Kyung-Jin; Dasgupta, Arindam; Huang, Keven; Jeong, Soo-Jin; Pise-Masison, Cynthia; Brady, John N.] NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Gurova, Katerina V.] Cleveland Biolabs Inc, Anticanc Drug Discovery Lab, Buffalo, NY 14203 USA. RP Brady, JN (reprint author), NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bldg 41,Room B201, Bethesda, MD 20892 USA. EM bradyj@exchange.nih.gov NR 49 TC 19 Z9 20 U1 1 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 SEP PY 2008 VL 82 IS 17 BP 8537 EP 8547 DI 10.1128/JVI.00690-08 PG 11 WC Virology SC Virology GA 339UU UT WOS:000258603600029 PM 18550670 ER PT J AU Chang, KW Oh, J Alvord, WG Hughes, SH AF Chang, Kevin W. Oh, Jangsuk Alvord, W. Gregory Hughes, Stephen H. TI The effects of alternate polypurine tracts (PPTs) and mutations of sequences adjacent to the PPT on viral replication and cleavage specificity of the Rous sarcoma virus reverse transcriptase SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNASE-H CLEAVAGE; STRAND DNA-SYNTHESIS; PRIMER BINDING-SITE; IN-VIVO; RIBONUCLEASE-H; CRYSTAL-STRUCTURE; CELL-LINE; TYPE-1; INTEGRATION AB We previously reported that a mutant Rous sarcoma virus (RSV) with an alternate polypurine tract (PPT), DuckHepBFlipPPT, had unexpectedly high titers and that the PPT was miscleaved primarily at one position following a GA dinucleotide by the RNase H of reverse transcriptase (RT). This miscleavage resulted in a portion of the 3' end of the PPT (5'-ATGTA) being added to the end of U3 of the linear viral DNA. To better understand the RNase H cleavage by RSV RT, we made a number of mutations within the DuckHepBFlipPPT and in the sequences adjacent to the PPT. Deleting the entire ATGTA sequence from the DuckHepBFlipPPT increased the relative titer to wild-type levels, while point mutations within the ATGTA sequence reduced the relative titer but had minimal effects on the cleavage specificity. However, mutating a sequence 5' of ATGTA affected the relative titer of the virus and caused the RNase H of RSV RT to lose the ability to cleave the PPT specifically. In addition, although mutations in the conserved stretch of thymidine residues upstream of the PPT did not affect the relative titer or cleavage specificity, the mutation of some of the nucleotides immediately upstream of the PPT did affect the titer and cleavage specificity. Taken together, our studies show that the structure of the PPT in the context of the cognate RT, rather than a specific sequence, is important for the proper cleavage by RSV RT. C1 [Chang, Kevin W.; Oh, Jangsuk; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Alvord, W. Gregory] NCI, Data Management Serv, Frederick, MD 21702 USA. [Oh, Jangsuk] NHLBI, Bethesda, MD 20892 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, POB 8,Bldg 539,Rm 130A, Frederick, MD 21702 USA. EM hughes@ncifcrf.gov FU NIH; National Cancer Institute; Center for Cancer Research FX We thank Teresa Burdette for help with the preparation of the manuscript and Tammy L. Schroyer from the Scientific Publications Graphics and Media, SAIC-Frederick office for help with the preparation of the figures.; Research was Supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 35 TC 2 Z9 2 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 SEP PY 2008 VL 82 IS 17 BP 8592 EP 8604 DI 10.1128/JVI.00499-08 PG 13 WC Virology SC Virology GA 339UU UT WOS:000258603600034 PM 18562520 ER PT J AU Bisht, H Weisberg, AS Moss, B AF Bisht, Himani Weisberg, Andrea S. Moss, Bernard TI Vaccinia virus L1 protein is required for cell entry and membrane fusion SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE PROTEIN; VIRION MEMBRANE; MATURE VIRION; GENE; IDENTIFICATION; POXVIRUSES; EXPRESSION; ANTIBODIES; COMPONENT; TOPOLOGY AB Genetic and biochemical studies have provided evidence for an entry/fusion complex (EFC) comprised of at least eight viral proteins (A16, A21, A28, G3, G9, H2, J5, and L5) that together with an associated protein (F9) participates in entry of vaccinia virus (VACV) into cells. The genes encoding these proteins are conserved in all poxviruses, are expressed late in infection, and are components of the mature virion membrane but are not required for viral morphogenesis. In addition, all but one component has intramolecular disulfides that are formed by the poxvirus cytoplasmic redox system. The L1 protein has each of the characteristics enumerated above except that it has been reported to be essential for virus assembly. To further investigate the role of L1, we constructed a recombinant VACV (vL1Ri) that inducibly expresses L1. In the absence of inducer, L1 synthesis was repressed and vL1Ri was unable to form plaques or produce infectious progeny. Unexpectedly, assembly and morphogenesis appeared normal and the noninfectious virus particles were indistinguishable from wild-type VACV as determined by transmission electron microscopy and analysis of the component polypeptides. Notably, the L1-deficient virions were able to attach to cells but the cores failed to penetrate into the cytoplasm. In addition, cells infected with vL1Ri in the absence of inducer did not form syncytia following brief low-pH treatment even though extracellular virus was produced. Coimmunoprecipitation experiments demonstrated that L1 interacted with the EFC and indirectly with F9, suggesting that L1 is an additional component of the viral entry apparatus. C1 [Bisht, Himani; Weisberg, Andrea S.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 33 N Dr, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Division of Intramural Research; MAID; NIH FX We thank Mariano Esteban, Geoffrey Smith, and Gary Cohen for their generosity in providing antibodies; Norman Cooper and Catherine Cotter for tissue Culture cells; Timothy R. Wagenaar for vA28i/F9TAP virus; Arban Domi for help in confocal microscopy and the entry assay; and Tatiana G. Scrikevich for useful discussions.; The study was Supported by the Division of Intramural Research, MAID, NIH. NR 41 TC 42 Z9 44 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 SEP PY 2008 VL 82 IS 17 BP 8687 EP 8694 DI 10.1128/JVI.00852-08 PG 8 WC Virology SC Virology GA 339UU UT WOS:000258603600042 PM 18596103 ER PT J AU McCormack, JC Yuan, XF Yingling, YG Kasprzak, W Zamora, RE Shapiro, BA Simon, AE AF McCormack, John C. Yuan, Xuefeng Yingling, Yaroslava G. Kasprzak, Wojciech Zamora, Rodolfo E. Shapiro, Bruce A. Simon, Anne E. TI Structural domains within the 3 ' untranslated region of Turnip crinkle virus SO JOURNAL OF VIROLOGY LA English DT Article ID MINUS-STRAND SYNTHESIS; PARALLEL GENETIC ALGORITHM; CHLOROTIC-RINGSPOT VIRUS; RNA STRUCTURE-ANALYSIS; 3' END; TRANSLATIONAL ENHANCEMENT; VIRAL REPLICATION; STEM-LOOP; REGION; INITIATION AB The genomes of positive-strand RNA viruses undergo conformational shifts that complicate efforts to equate structures with function. We have initiated a detailed analysis of secondary and tertiary elements within the 3' end of Turnip crinkle virus (TCV) that are required for viral accumulation in vivo. MPGAfold, a massively parallel genetic algorithm, suggested the presence of five hairpins (H4a, H4b, and previously identified hairpins H4, H5, and Pr) and one H-type pseudoknot (Psi(3)) within the 3 '-terminal 194 nucleotides (nt). In vivo compensatory mutagenesis analyses confirmed the existence of H4a, H4b, Psi(3) and a second pseudoknot (Psi(2)) previously identified in a TCV satellite RNA. In-line structure probing of the 194-nt fragment supported the coexistence of H4, H4a, H4b, Psi(3) and a pseudoknot that connects H5 and the 3' end (Psi(1)). Stepwise replacements of TCV elements with the comparable elements from Cardamine chlorotic fleck virus indicated that the complete 142-nt 3' end, and subsets containing Psi(3), H4a, and H4b or Psi(3), H4a, H4b, H5, and Psi(2), form functional domains for virus accumulation in vivo. A new 3-D molecular modeling protocol (RNA2D3D) predicted that H4a, H4b, H5, Psi(3), and Psi(2) are capable of simultaneous existence and bears some resemblance to a tRNA. The related Japanese iris necrotic ring virus does not have comparable domains. These results provide a framework for determining how interconnected elements participate in processes that require 3' untranslated region sequences such as translation and replication. C1 [McCormack, John C.; Yuan, Xuefeng; Zamora, Rodolfo E.; Simon, Anne E.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Yingling, Yaroslava G.; Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Kasprzak, Wojciech] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Simon, AE (reprint author), Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. EM simona@umd.edu RI Yingling, Yaroslava/B-2901-2008 OI Yingling, Yaroslava/0000-0002-8557-9992 FU U.S. Public Health Service [GM 061515-05A2/G120CD, GM 61515-01]; National Science Foundation [MCB-0086952]; NIH Institutional Training [T32-AI51967-01]; Intramural Research Program; National Cancer Institute; Center for Cancer Research; National Institutes of Health [NO1-CO-12400]; National Cancer Institute's Advanced Biomedical Computing Center FX We are very grateful 10 Ping Yu for providing LIS with T7 RNA polymerase.; This work was supported by grants from the U.S. Public Health Service (GM 061515-05A2/G120CD and GM 61515-01) and the National Science Foundation (MCB-0086952) to A.E.S. J.C.M. was Supported by NIH Institutional Training Grant no. T32-AI51967-01. This research was Supported in part by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research. This publication has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. NO1-CO-12400. The computational support was provided in part by the National Cancer Institute's Advanced Biomedical Computing Center.; The content Of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NR 47 TC 40 Z9 40 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 SEP PY 2008 VL 82 IS 17 BP 8706 EP 8720 DI 10.1128/JVI.00416-08 PG 15 WC Virology SC Virology GA 339UU UT WOS:000258603600044 PM 18579599 ER PT J AU Munir, S Le Nouen, C Luongo, C Buchholz, UJ Collins, PL Bukreyev, A AF Munir, Shirin Le Nouen, Cyril Luongo, Cindy Buchholz, Ursula J. Collins, Peter L. Bukreyev, Alexander TI Nonstructural proteins 1 and 2 of respiratory syncytial virus suppress maturation of human dendritic cells SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; INTERFERON REGULATORY FACTOR-3; HUMAN ALVEOLAR MACROPHAGES; AIRWAY EPITHELIAL-CELLS; TUMOR-NECROSIS-FACTOR; WILD-TYPE SV5; CD4 T-CELLS; I INTERFERON; ADAPTIVE IMMUNITY; CYTOKINE PRODUCTION AB Human respiratory syncytial virus (RSV) is the most important agent of serious pediatric respiratory tract disease worldwide. One of the main characteristics of RSV is that it readily reinfects and causes disease throughout life without the need for significant antigenic change. The virus encodes nonstructural protein 1 (NS1) and NS2, which are known to suppress type I interferon (IFN) production and signaling. In the present study, we monitored the maturation of human monocyte-derived myeloiel dendritic cells (DC) following inoculation with recombinant RSVs bearing deletions of the NS1 and/or NS2 proteins and expressing enhanced green fluorescent protein. Deletion of the NS1 protein resulted in increased expression of cell surface markers of DC maturation and an increase in the expression of multiple cytokines and chemokines. This effect was enhanced somewhat by further deletion of the NS2 protein, although deletion of NS2 alone did not have a significant effect. The upregulation was largely inhibited by pretreatment with a blocking antibody against the type I IFN receptor, suggesting that suppression of DC maturation by NS1/2 is, at least in part, a result of IFN antagonism mediated by these proteins. Therefore, this study identified another effect of the NS1 and NS2 proteins. The observed suppression of DC maturation may result in decreased antigen presentation and T-lymphocyte activation, leading to incomplete and/or weak immune responses that might contribute to RSV reinfection. C1 [Munir, Shirin; Le Nouen, Cyril; Luongo, Cindy; Buchholz, Ursula J.; Collins, Peter L.; Bukreyev, Alexander] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Bukreyev, A (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 50,Room 6505,50 S Dr,MSC 8007, Bethesda, MD 20892 USA. EM AB176v@nih.gov FU Intramural Research Program of NIAID, NIH FX We thank Ronald Rabin and Brian Murphy for reviewing the manuscript and for useful suggestions. We also thank Christine Winter for sequencing of the viral constructs, Lijuan Yang for ELISAs, and David Stephany for help with flow cytometry.; This study was funded as a part of the Intramural Research Program of NIAID, NIH. NR 91 TC 50 Z9 54 U1 1 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 SEP PY 2008 VL 82 IS 17 BP 8780 EP 8796 DI 10.1128/JVI.00630-08 PG 17 WC Virology SC Virology GA 339UU UT WOS:000258603600050 PM 18562519 ER PT J AU Sun, Y Santra, S Schmitz, JE Roederer, M Letvin, NL AF Sun, Yue Santra, Sampa Schmitz, Joern E. Roederer, Mario Letvin, Norman L. TI Magnitude and quality of vaccine-elicited T-cell responses in the control of immunodeficiency virus replication in rhesus monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID LYMPHOCYTE RESPONSES; HIV VACCINES; AIDS VACCINE; DNA; VECTORS; IMMUNOGENICITY; IMMUNIZATION; VOLUNTEERS; PHENOTYPE; INFECTION AB While a diversity of immunogens that elicit qualitatively different cellular immune responses are being assessed in clinical human immunodeficiency virus vaccine trials, the consequences of those varied responses for viral control remain poorly understood. In the present study, we evaluated the induction (if virus-specific T-cell responses in rhesus monkeys using a series of diverse vaccine vectors. We assessed both the magnitude and the functional profile of the virus-specific CD8(+) T cells by measuring gamma interferon, interleukin-2, and tumor necrosis factor alpha production. We found that the different vectors generated virus-specific T-cell responses of different magnitudes and with different functional profiles. Heterologous prime-boost vaccine regimens induced particularly high-frequency virus-specific T-cell responses with polyfunctional repertoires. Yet, immediately after a pathogenic simian-human immunodeficiency virus (SHIV) challenge, no significant differences were observed between these cohorts of vaccinated monkeys in the magnitudes or the functional profiles of their virus-specific CD8(+) T cells. This finding suggests that the high viral load shapes the functional repertoire of the cellular immune response during primary infection. Nevertheless, in all vaccination regimens, higher frequency and more polyfunctional vaccine-elicited virus-specific CD8(+) T-cell responses were associated with better viral control after SHIV challenge. These observations highlight the contributions of both the quality and the magnitude (of vaccine-elicited cellular immune responses in the control of immunodeficiency virus replication. C1 [Sun, Yue; Santra, Sampa; Schmitz, Joern E.; Letvin, Norman L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Viral Pathogenesis, Boston, MA 02215 USA. [Roederer, Mario; Letvin, Norman L.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Letvin, NL (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Viral Pathogenesis, RE113,POB 15732, Boston, MA 02215 USA. EM nletvin@bidmc.harvard.edu FU Vaccine Research Centerr, NIAID, NIH; Harvard Medical School [A1060354]; NIH [NOI-AI30033] FX We are grateful to Mark Cavabyab, Avi-Hai Hovav, Robert Seder, John Mascola, and Gary Nabel for helpful conversations and Michelle Lifton for technical assistance.; This work wits supported in part by funds front the intramural research program of the Vaccine Research Center, NIAID, NIH; the Harvard Medical School CFAR grant A1060354; and the NIH grant NOI-AI30033. NR 23 TC 27 Z9 28 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 SEP PY 2008 VL 82 IS 17 BP 8812 EP 8819 DI 10.1128/JVI.00204-08 PG 8 WC Virology SC Virology GA 339UU UT WOS:000258603600052 PM 18579590 ER PT J AU Peterson, KE Pourciau, S Du, M LaCasse, R Pathmajeyan, M Poulsen, D Agbandje-McKenna, M Wehrly, K Chesebro, B AF Peterson, Karin E. Pourciau, Susan Du, Min LaCasse, Rachel Pathmajeyan, Melissa Poulsen, David Agbandje-McKenna, Mavis Wehrly, Kathy Chesebro, Bruce TI Neurovirulence of polytropic murine retrovirus is influenced by two separate regions on opposite sides of the envelope protein receptor binding domain SO JOURNAL OF VIROLOGY LA English DT Article ID INDUCED SPONGIFORM NEURODEGENERATION; ENDOPLASMIC-RETICULUM STRESS; LEUKEMIA-VIRUS-TB; NEUROLOGIC DISEASE; SYNCYTIUM FORMATION; MICROGLIAL CELLS; BRAIN; INDUCTION; INFECTION; GENE AB Changes in the envelope proteins of retroviruses can alter the ability of these viruses to infect the central nervous system (CNS) and induce neurological disease. In the present study, nine envelope residues were found to influence neurovirulence of the Friend murine polytropic retrovirus Fr98. When projected on a three-dimensional model, these residues were clustered in two spatially separated groups, one in variable region B of the receptor binding site and the other on the opposite side of the envelope. Further studies indicated a role for these residues in virus replication in the CNS, although the residues did not affect viral entry. C1 [Peterson, Karin E.; Pourciau, Susan; Du, Min] Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA. [LaCasse, Rachel; Pathmajeyan, Melissa; Wehrly, Kathy; Chesebro, Bruce] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. [Poulsen, David] Univ Montana, Ctr Struct & Funct Neurosci, Dept Biomed & Pharmaceut Sci, Missoula, MT 59801 USA. [Agbandje-McKenna, Mavis] Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL USA. RP Peterson, KE (reprint author), Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Skip Bertman Dr, Baton Rouge, LA 70803 USA. EM petersonka@niaid.nih.gov RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 FU Intramural Research Program of the NIAID, NIH; National Center for Research Resources [IP20RRO20159] FX We thank Scott Hughes for technical assistance, Anita Mora and Gary Hettrick for graphics assistance, and Kim Hasenkrug and John Portis for helpful suggestions with the manuscript.; This research was supported in part by the Intramural Research Program of the NIAID, NIH, and in part by the National Center for Research Resources (grant IP20RRO20159). NR 24 TC 5 Z9 5 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 SEP PY 2008 VL 82 IS 17 BP 8906 EP 8910 DI 10.1128/JVI.02134-07 PG 5 WC Virology SC Virology GA 339UU UT WOS:000258603600064 PM 18579597 ER PT J AU Schmidt, M Govindasamy, L Afione, S Kaludov, N Agbandje-McKenna, M Chiorini, JA AF Schmidt, Michael Govindasamy, Lakshmanan Afione, Sandra Kaludov, Nick Agbandje-McKenna, Mavis Chiorini, John A. TI Molecular characterization of the heparin-dependent transduction domain on the capsid of a novel adeno-associated virus isolate, AAV(VR-942) SO JOURNAL OF VIROLOGY LA English DT Article ID EFFICIENT TRANSDUCTION; SULFATE PROTEOGLYCAN; AAV SEROTYPES; BINDING; TYPE-2; IDENTIFICATION; SPECIFICITY; VECTORS; CLONING; STOCKS AB A new adeno-associated virus (AAV), referred to as AAV(VR-942), has been isolated as a contaminant of adenovirus strain simian virus 17. The sequence of the rep gene places it in the AAV serotype 2 (AAV2) complementation group, while the capsid is only 88% identical to that of AAV2. High-level AAV(VR-942) transduction activity requires cell surface heparan sulfate proteoglycans, although AAV(VR-942) lacks residues equivalent to the AAV2 R585 and R588 amino acid residues essential for mediating the interaction of AAV2 with the heparan sulfate proteoglycan receptor. Instead, AAV(VR-942) uses a distinct transduction region. This finding shows that distinct domains on different AAV isolates can be responsible for the same activities. C1 [Govindasamy, Lakshmanan; Agbandje-McKenna, Mavis] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Struct Biol Ctr,McKnight Brain Inst, Gainesville, FL 32610 USA. [Schmidt, Michael; Afione, Sandra; Kaludov, Nick; Chiorini, John A.] Natl Inst Dent & Cranifacial Res, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. RP Agbandje-McKenna, M (reprint author), Univ Florida, Coll Med, Dept Biochem & Mol Biol, Struct Biol Ctr,McKnight Brain Inst, Gainesville, FL 32610 USA. EM jchiorini@dir.nidcr.nih FU Intramural Research Program of the NIH and NIDCR [NIH R01 GM082946, NIH P01 HL51811] FX We thank the NIDCR sequencing core facility and Danielle Mandikian for their excellent assistance.; This research was supported by funds from the Intramural Research Program of the NIH and NIDCR to J.A.C. and grants NIH R01 GM082946 and NIH P01 HL51811 to M.A.-M. NR 19 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2008 VL 82 IS 17 BP 8911 EP 8916 DI 10.1128/JVI.00672-08 PG 6 WC Virology SC Virology GA 339UU UT WOS:000258603600065 PM 18524816 ER PT J AU Young, NS Zhi, N Wong, S AF Young, Neal S. Zhi, Ning Wong, Susan TI Human B19 erythrovirus in vitro replication: What's new? Authors' reply SO JOURNAL OF VIROLOGY LA English DT Letter ID HUMAN PARVOVIRUS B19; CELLS; INVITRO; PROTEIN C1 [Young, Neal S.; Zhi, Ning; Wong, Susan] NHLBI, NIH, Bethesda, MD 20892 USA. RP Young, NS (reprint author), NHLBI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM youngn@nhlbi.nih.gov NR 12 TC 0 Z9 0 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 SEP PY 2008 VL 82 IS 17 BP 8952 EP 8953 PG 2 WC Virology SC Virology GA 339UU UT WOS:000258603600074 ER PT J AU Bartlett, EJ Cruz, AM Esker, J Castano, A Schomacker, H Surman, SR Hennessey, M Boonyaratanakornkit, J Pickles, RJ Collins, PL Murphy, BR Schmidt, AC AF Bartlett, Emmalene J. Cruz, Ann-Marie Esker, Janice Castano, Adam Schomacker, Henrick Surman, Sonja R. Hennessey, Margaret Boonyaratanakornkit, Jim Pickles, Raymond J. Collins, Peter L. Murphy, Brian R. Schmidt, Alexander C. TI Human parainfluenza virus type 1 C proteins are nonessential proteins that inhibit the host interferon and apoptotic responses and are required for efficient replication in nonhuman primates SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; ACUTE OTITIS-MEDIA; NF-KAPPA-B; SENDAI-VIRUS; VACCINE CANDIDATES; NS1 PROTEIN; REVERSE GENETICS; EPITHELIAL-CELLS; YOUNG-CHILDREN; RNA-SYNTHESIS AB Recombinant human parainfluenza virus type 1 (rHPIV1) was modified to create rHPIV1-P(C-), a virus in which expression of the C proteins (C ', C, Y1, and Y2) was silenced without affecting the amino acid sequence of the P protein. Infectious rHPIV1-P(C-) was readily recovered from cDNA, indicating that the four C proteins were not essential for virus replication. Early during infection in vitro, rHPIV1-P(C-) replicated as efficiently as wild-type (wt) HPIV1, but its titer subsequently decreased coincident with the onset of an extensive cytopathic effect not observed with wt rHPIV1. rHPIV1-P(C-) infection, but not wt rHPIV1 infection, induced caspase 3 activation and nuclear fragmentation in LLC-MK2 cells, identifying the HPIV1 C proteins as inhibitors of apoptosis. In contrast to wt rHPIV1, rHPIV1-P(C-) and rHPIV1-C(F170S), a mutant encoding an F170S substitution in C, induced interferon (IFN) and did not inhibit IFN signaling in vitro. However, only rHPIV1-P(C-) induced apoptosis. Thus, the anti-IFN and antiapoptosis activities of HPIV1 were separable: both activities are disabled in rHPIV1-P(C-), whereas only the anti-IFN activity is disabled in rHPIV1-C(F170S). In African green monkeys (AGMs), rHPIV1-P(C-) was considerably more attenuated than rHPIV1-C(F170S), suggesting that disabling the anti-IFN and antiapoptotic activities of HPIV1 had additive effects on attenuation in vivo. Although rHPIV1-P(C-) protected against challenge with wt HPIV1, its highly restricted replication in AGMs and in primary human airway epithelial cell cultures suggests that it might be overattenuated for use as a vaccine. Thus, the C proteins of HPIV1 are nonessential but have anti-IFN and antiapoptosis activities required for virulence in primates. C1 [Bartlett, Emmalene J.; Cruz, Ann-Marie; Esker, Janice; Castano, Adam; Schomacker, Henrick; Surman, Sonja R.; Boonyaratanakornkit, Jim; Collins, Peter L.; Murphy, Brian R.; Schmidt, Alexander C.] NIAID, Infect Dis Lab, Resp Viruses Sect, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hennessey, Margaret; Pickles, Raymond J.] Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. [Hennessey, Margaret; Pickles, Raymond J.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. RP Schmidt, AC (reprint author), NIAID, Infect Dis Lab, Resp Viruses Sect, NIH,US Dept Hlth & Human Serv, Bldg 50,Room 6511,50 S Dr,MSC 8007, Bethesda, MD 20892 USA. EM schmidta@niaid.nih.gov FU NIAID Intramural Program; National Institutes of Health (NIH) [NIH R01 HL77844-1] FX We thank Brad Finneyfrock and Marisa St. Claire, Bioqual, Inc., for carrying out the primate studies. We are grateful to the bioimaging and flow cytometry groups, especially Lily Koo and David Stephany, within the Research Technology Branch at NIAID for their excellent support. We are also grateful to the directors and teams of the UNC Cystic Fibrosis Center Tissue Culture Core and to Susan Burkett for technical assistance. John Hiscott, McGill University, provided the VSV-GFP, and Yasuhiko Ito, Mie University School of Medicine, Mie, Japan, provided the mouse anti-HPIV1 HN (8.2.2A and 4.5) antibodies.; This project was funded as a part of the NIAID Intramural Program and National Institutes of Health (NIH) and by grant NIH R01 HL77844-1. NR 73 TC 27 Z9 27 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2008 VL 82 IS 18 BP 8965 EP 8977 DI 10.1128/JVI.00853-08 PG 13 WC Virology SC Virology GA 347OX UT WOS:000259152000002 PM 18614629 ER PT J AU Brumme, ZL Brumme, CJ Carlson, J Streeck, H John, M Eichbaum, Q Block, BL Baker, B Kadie, C Markowitz, M Jessen, H Kelleher, AD Rosenberg, E Kaldor, J Yuki, Y Carrington, M Allen, TM Mallal, S Altfeld, M Heckerman, D Walker, BD AF Brumme, Zabrina L. Brumme, Chanson J. Carlson, Jonathan Streeck, Hendrik John, Mina Eichbaum, Quentin Block, Brian L. Baker, Brett Kadie, Carl Markowitz, Martin Jessen, Heiko Kelleher, Anthony D. Rosenberg, Eric Kaldor, John Yuki, Yuko Carrington, Mary Allen, Todd M. Mallal, Simon Altfeld, Marcus Heckerman, David Walker, Bruce D. TI Marked epitope- and allele- specific differences in rates of mutation in human immunodeficiency type 1 (HIV-1) Gag, Pol, and Nef cytotoxic T-lymphocyte epitopes in acute/early HIV-1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM NONPROGRESSORS; VIRUS TYPE-1; CELL RESPONSES; VIRAL LOAD; VACCINE DESIGN; P24 GAG; DISEASE PROGRESSION; ESCAPE MUTATIONS; IMMUNE-RESPONSES; POPULATION-LEVEL AB During acute human immunodeficiency virus type 1 (HIV-1) infection, early host cellular immune responses drive viral evolution. The rates and extent of these mutations, however, remain incompletely characterized. In a cohort of 98 individuals newly infected with HIV-1 subtype B, we longitudinally characterized the rates and extent of HLA-mediated escape and reversion in Gag, Pol, and Nef using a rational definition of HLA-attributable mutation based on the analysis of a large independent subtype B data set. We demonstrate rapid and dramatic HIV evolution in response to immune pressures that in general reflect established cytotoxic T-lymphocyte (CTL) response hierarchies in early infection. On a population level, HLA-driven evolution was observed in similar to 80% of published CTL epitopes. Five of the 10 most rapidly evolving epitopes were restricted by protective HLA alleles (HLA-B* 13/B* 51/B* 57/B* 5801; P = 0.01), supporting the importance of a strong early CTL response in HIV control. Consistent with known fitness costs of escape, B* 57-associated mutations in Gag were among the most rapidly reverting positions upon transmission to non-B* 57-expressing individuals, whereas many other HLA-associated polymorphisms displayed slow or negligible reversion. Overall, an estimated minimum of 30% of observed substitutions in Gag/Pol and 60% in Nef were attributable to HLA-associated escape and reversion events. Results underscore the dominant role of immune pressures in driving early within-host HIV evolution. Dramatic differences in escape and reversion rates across codons, genes, and HLA restrictions are observed, highlighting the complexity of viral adaptation to the host immune response. C1 [Brumme, Zabrina L.; Brumme, Chanson J.; Streeck, Hendrik; Eichbaum, Quentin; Block, Brian L.; Baker, Brett; Rosenberg, Eric; Allen, Todd M.; Altfeld, Marcus; Walker, Bruce D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. [Carlson, Jonathan; Kadie, Carl; Heckerman, David] Microsoft Res, Redmond, WA USA. [Carlson, Jonathan] Univ Washington, Dept Comp Sci, Seattle, WA 98195 USA. [John, Mina; Mallal, Simon] Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia. [John, Mina; Mallal, Simon] Murdoch Univ, Perth, WA, Australia. [Markowitz, Martin] Aaron Diamond AIDS Res Ctr, New York, NY USA. [Jessen, Heiko] Jessen Praxis, Berlin, Germany. [Kelleher, Anthony D.; Kaldor, John] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. [Yuki, Yuko; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Brumme, ZL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM zbrumme@partners.org RI Allen, Todd/F-5473-2011; Kaldor, John /D-4545-2011; OI Brumme, Chanson/0000-0003-2722-5288 FU Howard Hughes Medical Institute; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [R01AI50429, P30 AI060354, R01 AI050429, U01 AI052403, U01AI052403] NR 78 TC 127 Z9 131 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2008 VL 82 IS 18 BP 9216 EP 9227 DI 10.1128/JVI.01041-08 PG 12 WC Virology SC Virology GA 347OX UT WOS:000259152000026 PM 18614631 ER PT J AU Shaw, LJ Merz, CNB Bittner, V Kip, K Johnson, BD Reis, SE Kelsey, SF Olson, M Mankad, S Sharaf, BL Rogers, WJ Pohost, GM Sopko, G Pepine, CJ AF Shaw, Leslee J. Merz, C. Noel Bairey Bittner, Vera Kip, Kevin Johnson, B. Delia Reis, Steven E. Kelsey, Sheryl F. Olson, Marian Mankad, Sunil Sharaf, Barry L. Rogers, William J. Pohost, Gerald M. Sopko, George Pepine, Carl J. CA WISE Investigators TI Importance of socioeconomic status as a predictor of cardiovascular outcome and costs of care in women with suspected myocardial ischemia. Results from the National Institutes of Health, National Heart, Lung and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) SO JOURNAL OF WOMENS HEALTH LA English DT Article ID CORONARY-ARTERY DISEASE; FUNCTIONAL-CAPACITY; ETHNIC-DIFFERENCES; RISK-FACTORS; SOCIAL-CLASS; CHEST PAIN; ATHEROSCLEROSIS; INEQUALITIES; MORTALITY; POSITION AB Background: For women, who are more likely to live in poverty, defining the clinical and economic impact of socioeconomic factors may aid in defining redistributive policies to improve healthcare quality. Methods. The NIH-NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) enrolled 819 women referred for clinically indicated coronary angiography. This study's primary end point was to evaluate the independent contribution of socioeconomic factors on the estimation of time to cardiovascular death or myocardial infarction (MI) (n = 79) using Cox proportional hazards models. Secondary aims included an examination of cardiovascular costs and quality of life within socioeconomic subsets of women. Results: In univariable models, socioeconomic factors associated with an elevated risk of cardiovascular death or MI included an annual household income <$20,000 (p = 0.0001), <9th grade education (p = 0.002), being African American, Hispanic, Asian, or American Indian (p = 0.016), on Medicaid, Medicare, or other public health insurance (p < 0.0001), unmarried (p = 0.001.), unemployed or employed part-time (p < 0.0001), and working in a service job (p = 0.003). Of these socioeconomic factors, income (p = 0.006) remained a significant predictor of cardiovascular death or MI in risk-adjusted models that controlled for angiographic coronary disease, chest pain symptoms, and cardiac risk factors. Low-income women, with an annual household income <$20,000, were more often uninsured or on public insurance (p < 0.0001) yet had the highest 5-year hospitalization and drug treatment costs (p < 0.0001). Only 17% of low-income women had prescription drug coverage (vs. >= 50% of higher-income households, p < 0.0001), and 64% required >= 2 anti-ischemic medications during follow-up (compared with 45% of those earning >=$50,000, p < 0.0001). Conclusions: Economic disadvantage prominently affects cardiovascular disease outcomes for women with chest pain symptoms. These results further support a profound intertwining between poverty and poor health. Cardiovascular disease management strategies should focus on policies that track unmet healthcare needs and worsening clinical status for low-income women. C1 [Shaw, Leslee J.] Emory Univ, Sch Med, Dept Med, Div Cardiol,Emory Program Cardiovasc Outcome Res, Atlanta, GA 30306 USA. [Merz, C. Noel Bairey] Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Los Angeles, CA 90048 USA. [Bittner, Vera; Rogers, William J.] Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Kip, Kevin; Johnson, B. Delia; Kelsey, Sheryl F.; Olson, Marian] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Reis, Steven E.] Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA USA. [Mankad, Sunil] Allegheny Univ Hlth Sci, Dept Med, Div Cardiol, Pittsburgh, PA USA. [Sharaf, Barry L.] Rhode Isl Hosp, Div Cardiol, Providence, RI USA. [Pohost, Gerald M.] Univ So Calif, Div Cardiol, Los Angeles, CA USA. [Sopko, George] NHLBI, NIH, Bethesda, MD 20892 USA. [Pepine, Carl J.] Univ Florida, Dept Med, Div Cardiol, Gainesville, FL USA. RP Shaw, LJ (reprint author), Emory Univ, Sch Med, Dept Med, Div Cardiol,Emory Program Cardiovasc Outcome Res, Suite 1 North,1256 Briarcliff Rd NE, Atlanta, GA 30306 USA. EM leslee.shaw@emory.edu RI Reis, Steven/J-3957-2014 FU National Heart, Lung and Blood Institutes [N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164]; National Center for Research Resources [MO1-RR00425]; Gustavus and Louis Pfeiffer Research Foundation, Denville, New Jersey; The Women's Guild of Cedars-Sinai Medical Center, Los Angeles, California; The Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, Pennsylvania; QMED, Inc., Laurence Harbor, New Jersey; [U0164829]; [U01 HL649141]; [U01 HL649241] FX This work was supported by contracts from the National Heart, Lung and Blood Institutes, Nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, and N01-HV-68164, grants U0164829, U01 HL649141, and U01 HL649241, a GCRC grant MO1-RR00425 from the National Center for Research Resources, and grants from the Gustavus and Louis Pfeiffer Research Foundation, Denville, New Jersey, The Women's Guild of Cedars-Sinai Medical Center, Los Angeles, California, The Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, Pennsylvania, and QMED, Inc., Laurence Harbor, New Jersey. NR 38 TC 14 Z9 14 U1 2 U2 10 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 SEP PY 2008 VL 17 IS 7 BP 1081 EP 1092 DI 10.1089/jwh.2007.0596 PG 12 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 354KT UT WOS:000259639200005 PM 18774893 ER PT J AU Augustson, EM Barzani, D Rutten, LJF Marcus, S AF Augustson, Erik M. Barzani, Dilyara Rutten, Lila J. Finney Marcus, Stephen TI Gender differences among hardcore smokers: An analysis of the Tobacco Use Supplement of the Current Population Survey SO JOURNAL OF WOMENS HEALTH LA English DT Article ID SMOKING-CESSATION; NICOTINE DEPENDENCE; WORKPLACE SMOKING; MATERNAL SMOKING; SYNDROME SCALE; BIRTH-WEIGHT; INTERVENTION; RESTRICTIONS; PREVALENCE; HOUSEHOLD AB Background: Despite significant declines in smoking rates in the United States, a substantial percentage of adults continue to smoke. Improved understanding of current smokers and their contact with sources of cessation support future tobacco control efforts. Recent evidence suggests that hardcore smokers, established smokers without a history of quit attempts, have less contact with cessation support. Although gender is among the major factors that influence smoking cessation, no research is available on gender differences among hardcore smokers. Methods: Demographic, environmental, and smoking-related characteristics of female hardcore smokers and male hardcore smokers and other female smokers were examined. Data from 17,777smokers from the 2003 Current Population Survey Tobacco Use Supplement were analyzed. Results. Compared with female hardcore smokers, male hardcore smokers were more likely to have contact with smoking restrictions at work (OR = 1.69) and at home (OR = 1.45). Compared with female hardcore smokers, female other smokers were more likely to have seen a healthcare provider during the past year who advised them to quit smoking (OR = 1.39) and more likely to have smoking restrictions at work (OR = 1.25) and at home (OR = 2.32)). Measures of nicotine dependence suggested that female hardcore smokers were less dependent than male hardcore smokers but more dependent than other female smokers. Conclusions: The sociodemographic and healthcare access variations in tobacco use identified in our analyses have significant public health implications and underscore the vital need for clinical and scientific advances in tobacco use prevention and control efforts. C1 [Augustson, Erik M.] NCI, Tobacco Control Res Branch, DCCPS EPN 4039B, Bethesda, MD 20892 USA. [Barzani, Dilyara] Kurdistan Reg Govt, Minist Hlth, Kurdistan, Iraq. [Rutten, Lila J. Finney] NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. RP Augustson, EM (reprint author), NCI, Tobacco Control Res Branch, DCCPS EPN 4039B, 6130 Execut Blvd,MSC 7337, Bethesda, MD 20892 USA. EM augustse@mail.nih.gov NR 38 TC 11 Z9 11 U1 1 U2 6 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 SEP PY 2008 VL 17 IS 7 BP 1167 EP 1173 DI 10.1089/jwh.2007.0535 PG 7 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 354KT UT WOS:000259639200013 PM 18707532 ER PT J AU McCarthy, EP Pencina, MJ Kelly-Hayes, M Evans, JC Oberacker, EJ D'Agostino, RB Burns, RB Murabito, JM AF McCarthy, Ellen P. Pencina, Michael J. Kelly-Hayes, Margaret Evans, Jane C. Oberacker, Elizabeth J. D'Agostino, Ralph B., Sr. Burns, Risa B. Murabito, Joanne M. TI Advance Care Planning and Health Care Preferences of Community-Dwelling Elders: The Framingham Heart Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc Gen Internal Med DE Advance directives; Geriatrics; End-of-life care; Patient-centered care; Decision making ID OF-LIFE CARE; SERIOUSLY ILL PATIENTS; DECISION-MAKING; CARDIOPULMONARY-RESUSCITATION; CANCER-PATIENTS; DIRECTIVES; COMMUNICATION; ETHNICITY; DISCUSSIONS; DISPARITIES AB Objective. The study objective was to describe self-reported advance care planning, health care preferences, use of advance directives, and health perceptions in a very elderly community-dwelling sample. Methods. We interviewed surviving participants of the original cohort of the Framingham Heart Study who were cognitively intact and attended a routine research examination between February 2004 and October 2005. Participants were queried about discussions about end-of-life care, preferences for care, documentation of advance directives, and health perceptions. Results. Among 220 community-dwelling respondents, 67% were women with a mean age of 88 years (range 84-100 years). Overall, 69% discussed their wishes for medical care at the end of life with someone, but only 17% discussed their wishes with a physician or health care provider. Two thirds had a health care proxy, 55% had a living will, and 41% had both. Most (80%) respondents preferred comfort care over life-extending care, and 71% preferred to die at home; however, substantially fewer respondents said they would rather die than receive specific life-prolonging interventions (chronic ventilator [63%] or feeding tube [64%]). Many were willing to endure distressing health states, with fewer than half indicating that they would rather die than live out their life in a great deal of pain (46%) or be confused and/or forgetful (45%) all of the time. Conclusions. Although the vast majority of very elderly community-dwellers in this sample appear to prefer comfort measures at the end of life, many said they were willing to endure specific life-prolonging interventions and distressing health states to avoid death. Our results highlight the need for physicians to better understand patients' preferences and goals of care to help them make informed decisions at the end of life. C1 [McCarthy, Ellen P.; Burns, Risa B.] Harvard Univ, Sch Med, Dept Med, Div Gen Med & Primary Care,Beth Israel Deaconess, Boston, MA USA. [Pencina, Michael J.; Kelly-Hayes, Margaret; Evans, Jane C.; Oberacker, Elizabeth J.; D'Agostino, Ralph B., Sr.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Pencina, Michael J.; Evans, Jane C.; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Stat Consulting Unit, Boston, MA 02215 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Dept Med,Boston Med Ctr, Boston, MA 02215 USA. RP McCarthy, EP (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Dept Med, 1309 Beacon St,Suite 220, Brookline, MA 02446 USA. EM emccarth@bidmc.harvard.edu FU NHLBI NIH HHS [N01 HC025195, N01-HC-25195, N01HC25195]; NIA NIH HHS [R01 AG008122, R01 AG008122-19, R01 AG08122]; NINDS NIH HHS [R01 NS017950, R01 NS017950-27, R01 NS17950] NR 54 TC 29 Z9 29 U1 2 U2 12 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 SEP PY 2008 VL 63 IS 9 BP 951 EP 959 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 360RI UT WOS:000260074800008 PM 18840800 ER PT J AU Miller, FG Gluck, JP Wendler, D AF Miller, Franklin G. Gluck, John P., Jr. Wendler, David TI Debriefing and accountability in deceptive research SO KENNEDY INSTITUTE OF ETHICS JOURNAL LA English DT Article ID PSYCHOLOGICAL-RESEARCH; RESEARCH PARTICIPANTS; INFORMED CONSENT; ETHICAL ISSUES; PAIN AB Debriefing is a standard ethical requirement for human research involving the use of deception. Little systematic attention, however, has been devoted to explaining the ethical significance of debriefing and the specific ethical functions that it serves. In this article, we develop an account of debriefing as a tool of moral accountability for the prima facie wrong of deception. Specifically, we contend that debriefing should include a responsibility to promote transparency by explaining the deception and its rationale, to provide an apology to subjects for infringing the principle of respect for persons, and to offer subjects an opportunity to withdraw their data. We also present recommendations concerning the discussion of deception in scientific articles reporting the results of research using deception. C1 [Miller, Franklin G.] NIMH, Bethesda, MD 20892 USA. [Miller, Franklin G.; Gluck, John P., Jr.] Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA. [Gluck, John P., Jr.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Miller, Franklin G.; Wendler, David] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. NR 30 TC 16 Z9 16 U1 0 U2 6 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1054-6863 J9 KENNEDY INST ETHIC J JI Kennedy Inst. Ethics J. PD SEP PY 2008 VL 18 IS 3 BP 235 EP 251 PG 17 WC Ethics; Philosophy; Social Issues SC Social Sciences - Other Topics; Philosophy; Social Issues GA 355WC UT WOS:000259738900002 PM 18935922 ER PT J AU Zhou, H Cheruvanky, A Hu, XZ Matsumoto, T Hiramatsu, N Cho, ME Berger, A Leelahavanichkul, A Doi, K Chawla, LS Illei, GG Kopp, JB Balow, JE Austin, HA Yuen, PST Star, RA AF Zhou, Hua Cheruvanky, Anita Hu, Xuzhen Matsumoto, Takayuki Hiramatsu, Noriyuki Cho, Monique E. Berger, Alexandra Leelahavanichkul, Asada Doi, Kent Chawla, Lakhmir S. Illei, Gabor G. Kopp, Jeffrey B. Balow, James E. Austin, Howard A., III Yuen, Peter S. T. Star, Robert A. TI Urinary exosomal transcription factors, a new class of biomarkers for renal disease SO KIDNEY INTERNATIONAL LA English DT Article DE exosomes; transcription factor; ATF3; AKI; WT-1; FSGS ID ACUTE KIDNEY INJURY; GELATINASE-ASSOCIATED LIPOCALIN; GLOMERULAR-FILTRATION-RATE; MESSENGER-RNA EXPRESSION; GENE-EXPRESSION; CARDIAC-SURGERY; CYSTATIN-C; ISCHEMIA-REPERFUSION; DIAGNOSTIC MARKER; SERUM CREATININE AB Urinary exosomes are excreted from all nephron segments and constitute a rich source of intracellular kidney injury biomarkers. To study whether they contain transcription factors, we collected urine from two acute kidney injury models (cisplatin or ischemia-reperfusion), two podocyte injury models (puromycin-treated rats or podocin-Vpr transgenic mice) and from patients with focal segmental glomerulosclerosis, acute kidney injury and matched controls. Exosomes were isolated by differential centrifugation and found to contain activating transcription factor 3 (ATF3) and Wilms Tumor 1 (WT-1) proteins detected by Western blot. These factors were found in the concentrated exosomal fraction, but not in whole urine. ATF3 was continuously present in urine exosomes of the rat models following acute injury at times earlier than the increase in serum creatinine. ATF3 was found in exosomes isolated from patients with acute kidney injury but not from patients with chronic kidney disease or controls. Urinary WT-1 was present in animal models before significant glomerular sclerosis and in 9/10 patients with focal segmental glomerulosclerosis but not in 8 controls. Our findings suggest that transcription factor ATF3 may provide a novel renal tubular cell biomarker for acute kidney injury while WT-1 may detect early podocyte injury. Measurement of urinary exosomal transcription factors may offer insight into cellular regulatory pathways. C1 [Zhou, Hua; Cheruvanky, Anita; Hu, Xuzhen; Leelahavanichkul, Asada; Doi, Kent; Yuen, Peter S. T.; Star, Robert A.] NIDDK, Renal Diagnost & Therapeut Unit, Natl Inst Hlth, Bethesda, MD 20892 USA. [Matsumoto, Takayuki; Hiramatsu, Noriyuki; Cho, Monique E.; Kopp, Jeffrey B.; Balow, James E.; Austin, Howard A., III] NIDDK, Kidney Dis Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. [Berger, Alexandra; Chawla, Lakhmir S.] George Washington Univ, Dept Med, Div Renal Dis & Hypertens, Washington, DC USA. [Illei, Gabor G.] NIDCR, Gene Therapy & Therapeut Branch, Natl Inst Hlth, Bethesda, MD USA. RP Star, RA (reprint author), NIDDK, Renal Diagnost & Therapeut Unit, Natl Inst Hlth, 10 Ctr Dr,Bldg 10,Room 3N108, Bethesda, MD 20892 USA. EM Robert_Star@nih.gov RI Yuen, Peter/B-1954-2008; OI Yuen, Peter/0000-0001-9557-3909; Kopp, Jeffrey/0000-0001-9052-186X FU Intramural Research Program of NIH; NIDDK FX This research was supported by the Intramural Research Program of NIH, NIDDK. We thank Bertrand Jaber and Orfeas Liangos for insightful suggestions. NR 62 TC 89 Z9 94 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2008 VL 74 IS 5 BP 613 EP 621 DI 10.1038/ki.2008.206 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 338TM UT WOS:000258531800013 PM 18509321 ER PT J AU Murkunde, YV Kalaiselvan, P Vijayakumar, S Hemalatha, K Maronpot, RR Herbert, RA Wells, MY AF Murkunde, Yogeshkumar V. Kalaiselvan, Ponnusamy Vijayakumar, Subramaniyan Hemalatha, Kuppusamy Maronpot, Robert R. Herbert, Ronald A. Wells, Monique Y. TI Brain lesion in a Wistar rat SO LAB ANIMAL LA English DT Article C1 [Murkunde, Yogeshkumar V.; Kalaiselvan, Ponnusamy; Vijayakumar, Subramaniyan; Hemalatha, Kuppusamy] Int Inst Biotechnol & Toxicol, Dept Pathol, Padappai 601301, Tamil Nadu, India. [Maronpot, Robert R.; Herbert, Ronald A.] Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. [Wells, Monique Y.] Toxicol Pathol Serv Inc, F-75005 Paris, France. RP Murkunde, YV (reprint author), Int Inst Biotechnol & Toxicol, Dept Pathol, Padappai 601301, Tamil Nadu, India. EM fippat@giasmd01.vsnl.net.in RI pasuvalingam, visha/B-5717-2012 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 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD SEP PY 2008 VL 37 IS 9 BP 401 EP 401 DI 10.1038/laban0908-401 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 340QW UT WOS:000258661100005 PM 18719690 ER PT J AU Huntsberry, ME Charles, D Adams, KM Weed, JL AF Huntsberry, Mary E. Charles, Debbie Adams, Kristina M. Weed, James L. TI The foraging ball as a quick and easy enrichment device for pigs (Sus scrofa) SO LAB ANIMAL LA English DT Article ID ENVIRONMENTAL ENRICHMENT; AGGRESSIVE-BEHAVIOR; FINISHING PIGS; GROWING PIGS; WEANED PIGS; SYSTEMS; TOY AB Providing research pigs with enrichment objects can encourage species-typical behavior such as rooting and foraging. The authors gave pigs hard plastic 'foraging balls' that resembled enrichment devices commonly used for nonhuman primates. Holes were custom-drilled into the balls, and animal caretakers filled them with palatable food items such as jellybeans, unsalted peanuts, cereal, Beggin' Strips, primate biscuits and dog biscuits. Staff members suspended the balls from chains in pigs' enclosures, ensuring that toys did not touch the floor. All pigs manipulated the balls and were able to obtain treats that were supplemental to their standard diet. The simple and effective enrichment device was easily incorporated into the daily routines of research facilities, with little disruption to schedules. C1 [Huntsberry, Mary E.] SoBran Inc, Bethesda, MD USA. [Huntsberry, Mary E.; Weed, James L.] NIH, Div Vet Resources, ORS, DHHS, Bethesda, MD USA. [Charles, Debbie] Tuskegee Univ, Coll Vet Med, Tuskegee, AL 36088 USA. [Adams, Kristina M.] ARS, USDA, NAL, AWIC, Beltsville, MD USA. RP Huntsberry, ME (reprint author), SoBran Inc, Bethesda, MD USA. EM huntsmar@mail.nih.gov FU Intramural NIH HHS NR 28 TC 0 Z9 0 U1 2 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD SEP PY 2008 VL 37 IS 9 BP 411 EP 414 DI 10.1038/laban0908-411 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 340QW UT WOS:000258661100007 PM 18719693 ER PT J AU Qiu, J Ai, L Ramachandran, C Yao, B Gopalakrishnan, S Fields, CR Delmas, AL Dyer, LM Melnick, SJ Yachnis, AT Schwartz, PH Fine, HA Brown, KD Robertson, KD AF Qiu, Jingxin Ai, Lingbao Ramachandran, Cheppail Yao, Bing Gopalakrishnan, Suhasni Fields, C. Robert Delmas, Amber L. Dyer, Lisa M. Melnick, Steven J. Yachnis, Anthony T. Schwartz, Philip H. Fine, Howard A. Brown, Kevin D. Robertson, Keith D. TI Invasion suppressor cystatin E/M (CST6): high-level cell type-specific expression in normal brain and epigenetic silencing in gliomas SO LABORATORY INVESTIGATION LA English DT Article DE cell invasion; CST6; cystatin E/M; DNA methylation; glioma; neural stem cell ID HUMAN GLIOBLASTOMA CELLS; CATHEPSIN-B EXPRESSION; HISTONE DEACETYLASE INHIBITION; CYSTEINE PROTEINASE-INHIBITOR; ABERRANT DNA METHYLATION; TUMOR STEM-CELLS; GENE-EXPRESSION; MALIGNANT GLIOMA; BREAST-CANCER; DOWN-REGULATION AB DNA hypermethylation-mediated gene silencing is a frequent and early contributor to aberrant cell growth and invasion in cancer. Malignant gliomas are the most common primary brain tumors in adults and the second most common tumor in children. Morbidity and mortality are high in glioma patients because tumors are resistant to treatment and are highly invasive into surrounding brain tissue rendering complete surgical resection impossible. Invasiveness is regulated by the interplay between secreted proteases ( eg, cathepsins) and their endogenous inhibitors ( cystatins). In our previous studies we identified cystatin E/ M ( CST6) as a frequent target of epigenetic silencing in glioma. Cystatin E/ M is a potent inhibitor of cathepsin B, which is frequently overexpressed in glioma. Here, we study the expression of cystatin E/ M in normal brain and show that it is highly and moderately expressed in oligodendrocytes and astrocytes, respectively, but not in neurons. Consistent with this, the CST6 promoter is hypomethylated in all normal samples using methylation- specific PCR, bisulfite genomic sequencing, and pyrosequencing. In contrast, 78% of 28 primary brain tumors demonstrated reduced/ absent cystatin E/ M expression using a tissue microarray and this reduced expression correlated with CST6 promoter hypermethylation. Interestingly, CST6 was expressed in neural stem cells ( NSC) and markedly induced upon differentiation, whereas a glioma tumor initiating cell ( TIC) line was completely blocked for CST6 expression by promoter methylation. Analysis of primary pediatric brain tumor- derived lines also showed CST6 downregulation and methylation in nearly 100% of 12 cases. Finally, ectopic expression of cystatin E/ M in glioma lines reduced cell motility and invasion. These results demonstrate that epigenetic silencing of CST6 is frequent in adult and pediatric brain tumors and occurs in TICs, which are thought to give rise to the tumor. CST6 methylation may therefore represent a novel prognostic marker and therapeutic target specifically altered in TICs. C1 [Ai, Lingbao; Yao, Bing; Gopalakrishnan, Suhasni; Fields, C. Robert; Delmas, Amber L.; Dyer, Lisa M.; Brown, Kevin D.; Robertson, Keith D.] Univ Florida, Dept Biochem & Mol Biol, UF Shands Canc Ctr, Program Canc Genet Epigenet & Tumor Virol,Coll Me, Gainesville, FL 32610 USA. Univ Florida, Dept Pathol, UF Shands Canc Ctr, Program Canc Genet Epigenet & Tumor Virol,Coll Me, Gainesville, FL 32610 USA. [Ramachandran, Cheppail; Melnick, Steven J.] Miami Childrens Hosp, Dept Pathol, Miami, FL USA. [Schwartz, Philip H.] Childrens Hosp Orange Cty, Res Inst, Orange, CA 92668 USA. [Fine, Howard A.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. RP Robertson, KD (reprint author), Univ Florida, Dept Biochem & Mol Biol, UF Shands Canc Ctr, Program Canc Genet Epigenet & Tumor Virol,Coll Me, 1600 SW Archer Rd, Gainesville, FL 32610 USA. EM keithr@ufl.edu FU NCI NIH HHS [R01CA114229, R01CA102289, R01 CA114229, R01 CA102289, R01 CA114229-03, R01 CA114229-04] NR 68 TC 30 Z9 32 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD SEP PY 2008 VL 88 IS 9 BP 910 EP 925 DI 10.1038/labinvest.2008.66 PG 16 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 340HK UT WOS:000258636500001 PM 18607344 ER PT J AU Davis, AR Shields, AD Brigman, JL Norcross, M McElligott, ZA Holmes, A Winder, DG AF Davis, Adeola R. Shields, Angela D. Brigman, Jonathan L. Norcross, Maxine McElligott, Zoe A. Holmes, Andrew Winder, Danny G. TI Yohimbine impairs extinction of cocaine-conditioned place preference in an alpha(2)-adrenergic receptor independent process SO LEARNING & MEMORY LA English DT Article ID SYMPATHETIC-NERVOUS-SYSTEM; RAT RELAPSE MODEL; STRIA TERMINALIS; FEAR EXTINCTION; BED NUCLEUS; FACILITATES EXTINCTION; POTENTIATED STARTLE; INFRALIMBIC CORTEX; RECEPTOR SUBTYPES; 5-HT1A RECEPTORS AB Extinction, a form of learning that has the ability to reshape learned behavior based on new experiences, has been heavily studied utilizing fear learning paradigms. Mechanisms underlying extinction of positive-valence associations, such as drug self-administration and place preference, are poorly understood yet may have important relevance to addiction treatment. Data suggest a major role for the noradrenergic system in extinction of fear-based learning. Employing both pharmacological and genetic approaches, we investigated the role of the alpha(2)-adrenergic receptor (alpha(2)-AR) in extinction of cocaine-conditioned place preference (CPP) and glutamatergic transmission in the bed nucleus of the stria terminalis (BNST). We found that pre-extinction systemic treatment with the alpha(2)-AR antagonist yohimbine impaired cocaine CPP extinction in C57BL/6J mice, an effect that was not mimicked by the more selective alpha(2)-AR antagonist, atipamezole. Moreover, alpha(2)A-AR knockout mice exhibited similar cocaine CPP extinction and exacerbated extinction impairing effects of yohimbine. Using acute brain slices and electrophysiological approaches, we found that yohimbine produces a slowly evolving depression of glutamatergic transmission in the BNST that was not mimicked by atipamezole. Further, this action was extant in slices from alpha(2)A-AR knockout mice. Our data strongly suggest that extinction-modifying effects of yohimbine are unlikely to be due to actions at alpha(2)A-ARs. C1 [Davis, Adeola R.; McElligott, Zoe A.; Winder, Danny G.] Vanderbilt Univ, Med Ctr, Vanderbilt Brain Inst, Nashville, TN 37232 USA. [Shields, Angela D.; Winder, Danny G.] Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Brigman, Jonathan L.; Norcross, Maxine; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. [Winder, Danny G.] Vanderbilt Univ, Med Ctr, Kennedy Ctr Human Dev, Nashville, TN 37232 USA. RP Winder, DG (reprint author), Vanderbilt Univ, Med Ctr, Vanderbilt Brain Inst, Nashville, TN 37232 USA. EM danny.winder@vanderbilt.edu RI Winder, Danny/H-4857-2013; Brigman, Jonathan/O-4978-2016 FU NIDA; National Institute on Alcohol Abuse and Alcoholism FX We thank Dr. Chris Olsen for a critical reading of the manuscript and William Nobis for writing a helpful script to gather data. Research was supported by NIDA (D. G. W.), NIDA supplement (A. D. and D. G. W.), and the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism (A. H., J. B., and M. N.). NR 54 TC 21 Z9 22 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD SEP PY 2008 VL 15 IS 9 BP 667 EP 676 DI 10.1101/lm.1079308 PG 10 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 355HW UT WOS:000259701000008 PM 18772254 ER PT J AU Yong, ASM Keyvanfar, K Eniafe, R Savani, BN Rezvani, K Sloand, EM Goldman, JM Barrett, AJ AF Yong, A. S. M. Keyvanfar, K. Eniafe, R. Savani, B. N. Rezvani, K. Sloand, E. M. Goldman, J. M. Barrett, A. J. TI Hematopoietic stem cells and progenitors of chronic myeloid leukemia express leukemia-associated antigens: implications for the graft-versus-leukemia effect and peptide vaccine-based immunotherapy SO LEUKEMIA LA English DT Article DE chronic myeloid leukemia; CD34+progenitor cells; leukemia-associated antigens; graft-versus-leukemia effect ID CYTOTOXIC T-LYMPHOCYTES; CHRONIC MYELOGENOUS LEUKEMIA; CD34(+) CELLS; GENE TRANSCRIPTS; CD7 EXPRESSION; CML PATIENTS; TRANSPLANTATION; WT1; RESPONSES; PROTEINASE-3 AB The cure of chronic myeloid leukemia (CML) patients following allogeneic stem cell transplantation (SCT) is attributed to graft-versus-leukemia (GVL) effects targeting alloantigens and/or leukemia-associated antigens (LAA) on leukemia cells. To assess the potential of LAA-peptide vaccines in eliminating leukemia in CML patients, we measured WT1, PR3, ELA2 and PRAME expression in CD34+ progenitor subpopulations in CML patients and compared them with minor histocompatibility antigens (mHAgs) HA1 and SMCY. All CD34+ subpopulations expressed similar levels of mHAgs irrespective of disease phase, suggesting that in the SCT setting, mHAgs are the best target for GVL. Furthermore, WT1 was consistently over-expressed in advanced phase (AdP) CML in all CD34+ subpopulations, and mature progenitors of chronic phase (CP) CML compared to healthy individuals. PRAME overexpression was limited to more mature AdP-CML progenitors only. Conversely, only CP-CML progenitors had PR3 overexpression, suggesting that PR1-peptide vaccines are only appropriate in CP-CML. Surface expression of WT1 protein in the most primitive hematopoietic stem cells in AdP-CML suggest that they could be targets for WT1 peptide-based vaccines, which in combination with PRAME, could additionally improve targeting differentiated progeny, and benefit patients responding suboptimally to tyrosine kinase inhibitors, or enhance GVL effects in SCT patients. C1 [Yong, A. S. M.; Keyvanfar, K.; Eniafe, R.; Savani, B. N.; Rezvani, K.; Sloand, E. M.; Goldman, J. M.; Barrett, A. J.] NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Yong, ASM (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bldg 10-CRC,Rm 3-5140,10 Ctr Dr,MSC 1202, Bethesda, MD 20892 USA. EM yonga@nhlbi.nih.gov FU Intramural Research Program of the National Heart, Lung and Blood Institute of the NIH FX We thank Ms Loretta Pfannes for technical advice on the assessment of WT1 surface protein by flowcytometry. This research was supported by the Intramural Research Program of the National Heart, Lung and Blood Institute of the NIH. NR 33 TC 33 Z9 35 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD SEP PY 2008 VL 22 IS 9 BP 1721 EP 1727 DI 10.1038/leu.2008.161 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 346KH UT WOS:000259066900010 PM 18548092 ER PT J AU Arons, E Suntum, T Margulies, I Yuan, C Stetler-Stevenson, M Kreitman, RJ AF Arons, Evgeny Suntum, Tara Margulies, Inger Yuan, Constance Stetler-Stevenson, Maryalice Kreitman, Robert J. TI PRAME expression in hairy cell leukemia SO LEUKEMIA RESEARCH LA English DT Article DE hairy cell leukemia; real-time PCR; chronic lymphocytic leukemia; PRAME; TaqMan; minimal residual disease ID MINIMAL RESIDUAL DISEASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; POLYMERASE-CHAIN-REACTION; TUMOR-ASSOCIATED ANTIGENS; ACUTE MYELOID-LEUKEMIA; MESSENGER-RNA LEVELS; GENE-EXPRESSION; CLINICAL IMPORTANCE; MALIGNANCIES; MELANOMA AB PRAME has been proposed as a useful marker for solid tumors and acute B-cell malignancies. Several studies demonstrate expression in CLL. To further examine its B-cell tumor distribution, we studied PRAME in both CLL and hairy cell leukemia (HCL). While by conventional PCR only 8% of 37 HCL and 27% of 22 CLL patients were positive, nearly all patients and normal donors expressed PRAME by real-time quantitative (TaqMan) PCR. We conclude that HCL and CLL differ in PRAME overexpression, and that basal normal expression of PRAME may limit its usefulness for following patients with minimal residual CLL or HCL. Published by Elsevier Ltd. C1 [Kreitman, Robert J.] NCI, Mol Biol Lab, Ctr Canc Res, Clin Immunotherapy Sect,NIH, Bethesda, MD 20892 USA. NCI, Clin Pathol Lab, Ctr Canc Res, Clin Immunotherapy Sect,NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, Clin Immunotherapy Sect,NIH, 9000 Rockville Pike,Bldg 37,Room 5124B, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov FU Intramural NIH HHS [Z01 BC010301-10, Z99 CA999999] NR 41 TC 4 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD SEP PY 2008 VL 32 IS 9 BP 1400 EP 1406 DI 10.1016/j.leukres.2007.12.010 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 312EB UT WOS:000256650800010 PM 18295331 ER PT J AU Adams, DK Mullineaux, LS AF Adams, Diane K. Mullineaux, Lauren S. TI Supply of gastropod larvae to hydrothermal vents reflects transport from local larval sources SO LIMNOLOGY AND OCEANOGRAPHY LA English DT Article ID EAST PACIFIC RISE; COMMUNITY STRUCTURE; MUSSEL BEDS; DISPERSAL; RECRUITMENT; PATTERNS; SETTLEMENT; ECOLOGY; WATERS; RIDGE AB Variation in larval supply to disjunct marine populations can provide insight into larval transport and delivery mechanisms, especially when compared with observations of physical transport. Daily variability in larval supply at two mussel-dominated hydrothermal vents, East Wall and Choo Choo, near 9 degrees 50'N, East Pacific Rise, was quantified concurrently with hydrodynamic observations to investigate local dispersal processes. The magnitude and temporal variation in supply differed between the two vent sites despite their close proximity, 1.6 km. Larval supply was relatively high and uninterrupted at East Wall compared to low and episodic at Choo Choo. Observed variation in larval supply was compared to predictions based on advective transport from larval sources at neighboring vents. Variation in larval supply at Choo Choo correlated with along-axis southward currents, consistent with larval transport from a northern larval source. Larval supply to East Wall appeared to be independent of current velocities, suggesting that larvae came from multiple sources north of and south of and possibly including East Wall. Transport of larvae from discrete local sources can explain differences in larval supply to vent communities, even on spatial scales of kilometers. C1 [Adams, Diane K.; Mullineaux, Lauren S.] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA. [Adams, Diane K.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Adams, DK (reprint author), Woods Hole Oceanog Inst, 266 Woods Hole Rd, Woods Hole, MA 02543 USA. EM adamsdi@mail.nih.gov RI Adams, Diane/E-7831-2015 OI Adams, Diane/0000-0001-6638-5781 FU Woods Hole Oceanographic Institution Deep Ocean Exploration Institute; S. Beaulieu, National Science Foundation [OCE-0424953]; National Defense Science and Engineering Graduate FX Funding was provided by a Woods Hole Oceanographic Institution Deep Ocean Exploration Institute grant to L. M. and S. Beaulieu, National Science Foundation grant OCE-0424953 to L. M., and a National Defense Science and Engineering Graduate fellowship to D. A. NR 38 TC 23 Z9 23 U1 2 U2 12 PU AMER SOC LIMNOLOGY OCEANOGRAPHY PI WACO PA 5400 BOSQUE BLVD, STE 680, WACO, TX 76710-4446 USA SN 0024-3590 J9 LIMNOL OCEANOGR JI Limnol. Oceanogr. PD SEP PY 2008 VL 53 IS 5 BP 1945 EP 1955 DI 10.4319/lo.2008.53.5.1945 PG 11 WC Limnology; Oceanography SC Marine & Freshwater Biology; Oceanography GA 350MG UT WOS:000259356000021 ER PT J AU Campsen, J Blei, AT Emond, JC Everhart, JE Freise, CE Lok, AS Saab, S Wisniewski, KA Trotter, JF AF Campsen, Jeffrey Blei, Andres T. Emond, Jean C. Everhart, James E. Freise, Chris E. Lok, Anna S. Saab, Sammy Wisniewski, Karen A. Trotter, James F. CA Adult-to-Adult Living Donor Liver TI Outcomes of living donor liver transplantation for acute liver failure: The adult-to-adult living donor liver transplantation cohort study SO LIVER TRANSPLANTATION LA English DT Article ID FULMINANT HEPATIC-FAILURE; UNITED-STATES AB For acute liver failure (ALF), living donor liver transplantation (LDLT) may reduce waiting time and provide better timing compared to deceased donor liver transplantation (DDLT). However, there are concerns that a partial graft would result in reduced survival of critically ill LDLT recipients and that the rapid evolution of ALF would lead to selection of inappropriate donors. We report outcomes for ALF patients (and their donors) evaluated for LDLT between 1998 and April 2007 from the Adult-to-Adult Living Donor Liver Transplantation Cohort. Of the 1201 potential LDLT recipients, 14 had ALF, only 6 of whom had an identified cause. The median time from listing to first donor evaluation was 1.5 days, and the median time from evaluation to transplantation was 1 day. One patient recovered without liver transplant, 3 of 10 LDLT recipients died, and 1 of 3 DDLT recipients died. Five of the 10 living donors had a total of 7 posttransplant complications. In conclusion, LDLT is rarely performed for ALF, but in selected patients it may be associated with acceptable recipient mortality and donor morbidity. C1 [Campsen, Jeffrey; Trotter, James F.] Univ Colorado, Div Transplant Surg, Aurora, CO USA. [Blei, Andres T.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Emond, Jean C.] Columbia Presbyterian Med Ctr, Dept Surg, New York, NY 10032 USA. [Everhart, James E.] NIDDK, NIH, Bethesda, MD USA. [Freise, Chris E.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Lok, Anna S.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Saab, Sammy] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Saab, Sammy] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Wisniewski, Karen A.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. RP Trotter, JF (reprint author), Univ Colorado Hosp, 1635 N Ursula,Campus Box 154, Aurora, CO 80262 USA. EM james.trotter@uchsc.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU National Institutes of Health [U01-DK62536, U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531]; American Society of Transplant Surgeons; Health Resources and Services Administration; U.S. Department of Health and Human Services FX This study was supported in part by the National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases grant numbers U01-DK62536, U01-DK62444. U01-DK62467. U01-DK62483, U01-DK62484. U01-DK62494, U01-DK62496, U01-DK62498. U01-DK62505. and U01-DK62531), the American Society of Transplant Surgeons, and the Health Resources and Services Administration. U.S. Department of Health and Human Services. NR 20 TC 40 Z9 41 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD SEP PY 2008 VL 14 IS 9 BP 1273 EP 1280 DI 10.1002/lt.21500 PG 8 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 346NY UT WOS:000259076700009 PM 18756453 ER PT J AU Shen, M Chapman, RS He, XZ Liu, LZ Lai, H Chen, W Lan, Q AF Shen, Min Chapman, Robert S. He, Xingzhou Liu, Larry Z. Lai, Hong Chen, Wei Lan, Qing TI Dietary factors, food contamination and lung cancer risk in Xuanwei, China SO LUNG CANCER LA English DT Article DE risk factor; lung cancer; indoor air pollution; case-control study; food contamination; polycyclic aromatic hydrocarbon ID POLYCYCLIC AROMATIC-HYDROCARBONS; DNA ADDUCT FORMATION; COAL-TAR; BIOREMEDIATION; METABOLISM AB Background: In rural. Xuanwei County, China, the high incidence of Lung cancer is attributable largely to burning smoky coal indoors for heating and cooking without adequate ventilation. Such burning generates very high levels of indoor air pollutants, including carcinogenic polycyclic aromatic hydrocarbons, which could contaminate foodstuffs in the home. Thus, residents could be exposed to carcinogenic coat emissions not only via inhalation but also via ingestion of these foodstuffs. Methods: A population-based case-control. study of 498 Lung cancer patients and 498 controls was conducted from 1985 through 1990 in Xuanwei. The interviewer-administered study questionnaire queried the frequency of food items commonly consumed in this region. Overall and sex-specific multiple logistic regression models were constructed to estimate Odds ratios (OR) and 95% confidence intervals (CI) for consumption of these foods. Results: Intake of rice, green vegetables, mushrooms and fresh meat was associated with an increased risk of lung cancer. In contrast, intake of corn, buckwheat, radishes, peppers, melons, pickled vegetables, and salt-preserved meats was associated with reduced risk. The detrimental. effect of ingesting green vegetables (OR, 2.39; 95% CI, 1.28-4.48) is consistent with previous reports. Conclusions: These findings suggest that in Xuanwei, food contamination by environmental polycyclic aromatic hydrocarbons may be an important risk factor for Lung cancer, and that differential contamination of foods by polycyclic aromatic hydrocarbons possibly explained the different associations with lung cancer risk. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Shen, Min] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Chapman, Robert S.] Chulalongkorn Univ, Coll Publ Hlth, Bangkok, Thailand. [He, Xingzhou] Chinese Ctr Dis Control & Prevent, Inst Environm Hlth & Engn, Beijing, Peoples R China. [Liu, Larry Z.] Cornell Univ, Weill Med Coll, Dept Publ Hlth, New York, NY 10021 USA. [Lai, Hong] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. [Chen, Wei] Forest Labs Inc, Harborside Financial Ctr, Jersey City, NJ USA. RP Shen, M (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 8122,MSC 7240, Bethesda, MD 20892 USA. EM shenmi@mail.nih.gov NR 18 TC 15 Z9 17 U1 2 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD SEP PY 2008 VL 61 IS 3 BP 275 EP 282 DI 10.1016/j.lungcan.2007.12.024 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 356TN UT WOS:000259800600001 PM 18304686 ER PT J AU Hagberg, GE Bianciardi, M Brainovich, V Cassara, AM Maraviglia, B AF Hagberg, Gisela E. Bianciardi, Marta Brainovich, Valentina Cassara, Antonino Mario Maraviglia, Bruno TI The effect of physiological noise in phase functional magnetic resonance imaging: from blood oxygen level-dependent effects to direct detection of neuronal currents SO MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT International School on Magnetic Resonance and Brain Function CY MAY 06-13, 2007 CL Erice, ITALY DE fMRI; phase; physiological noise; BOLD; nc-MRI; human; brain ID INDUCED B-0 FLUCTUATIONS; ECHO-PLANAR; HUMAN BRAIN; MRI DETECTION; 1.5 T; FMRI; BOLD; RESPIRATION; COMPLEX; SIGNAL AB Recently, the possibility to use both magnitude and phase image sets for the statistical evaluation of fMRI has been proposed, with the prospective of increasing both statistical power and the spatial specificity. In the present work, several issues that affect the spatial and temporal stability in fMRI phase time series in the presence of physiologic noise processes are reviewed, discussed and illustrated by experiments performed at 3 T. The observed phase value is a fingerprint of the underlying voxel averaged magnetic field variations. Those related to physiological processes can be considered static or dynamic in relation to the temporal scale of a 2D acquisition and will play out on different spatial scales as well: globally across the entire images slice, and locally depending on the constituents and their relative fractions inside the MRI voxel. The 'static' respiration-induced effects lead to magneto-mechanic scan-to-scan variations in the global magnetic field but may also contribute to local BOLD fluctuations due to respiration-related variations in arterial carbon dioxide. Likewise, the 'dynamic' cardiac-related effects will lead to global susceptibility effects caused by pulsatile motion of the brain as well as local blood pressure-related changes in BOLD and changes in blood flow velocity. Finally, subject motion may lead to variations in both local and global tissue susceptibility that will be especially pronounced close to air cavities. Since dissimilar manifestations of physiological processes can be expected in phase and in magnitude images, a direct relationship between phase and magnitude scan-to-scan fluctuations cannot be assumed a priori. Therefore three different models were defined for the phase stability, each dependent on the relation between phase and magnitude variations and the best will depend on the underlying noise processes. By experiments on healthy volunteers at rest, we showed that phase stability depends on the type of post-processing and can be improved by reducing the low-frequency respiration-induced mechano-magnetic effects. Although the manifestations of physiological noise were in general more pronounced in phase than in magnitude images, due to phase wraps and global Bo effects, we Suggest that a phase stability similar to that found in magnitude could theoretically be achieved by adequate correction methods. Moreover, as suggested by out-experimental data regarding BOLD-related phase effects, phase stability could even supersede magnitude stability in voxels covering dense microvascular networks with BOLD-related fluctuations as the dominant noise contributor. In the interest of the quality of both BOLD-based and nc-MRI methods, future studies are required to find alternative methods that can improve phase stability, designed to match the temporal and spatial scale of the underlying neuronal activity. (c) 2008 Elsevier Inc. All rights reserved. C1 [Hagberg, Gisela E.; Bianciardi, Marta; Brainovich, Valentina] Fdn Santa Lucia IRCCS, Lab Neuroimaging, I-00179 Rome, Italy. [Cassara, Antonino Mario; Maraviglia, Bruno] Univ Roma La Sapienza, Dept Phys, I-00185 Rome, Italy. [Cassara, Antonino Mario; Maraviglia, Bruno] Museo Storico Fis, I-00184 Rome, Italy. [Cassara, Antonino Mario; Maraviglia, Bruno] Ctr Studi & Ric, I-00184 Rome, Italy. [Bianciardi, Marta] NINDS, Adv MRI Sect, NIH, Bethesda, MD 20892 USA. RP Hagberg, GE (reprint author), Fdn Santa Lucia IRCCS, Lab Neuroimaging, I-00179 Rome, Italy. EM g.hagberg@hsantalucia.it RI Hagberg, Gisela/A-2134-2010; OI Hagberg, Gisela/0000-0003-2176-7086; Cassara, Antonino Mario/0000-0003-3375-7440; Maraviglia, Bruno/0000-0003-2354-8039 NR 39 TC 20 Z9 20 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD SEP PY 2008 VL 26 IS 7 BP 1026 EP 1040 DI 10.1016/j.mri.2008.01.010 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 342TN UT WOS:000258806500022 PM 18479875 ER PT J AU Goelman, G Pelled, G Dodd, S Koretsky, A AF Goelman, Gadi Pelled, Galit Dodd, Steve Koretsky, Alan TI Tracking the effects of crusher gradients on gradient-echo BOLD signal in space and time during rat sensory stimulation SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE spatiotemporal dynamic; BOLD signal; somatosensory stimulation; rat; extravascular/intravascular weighting; CBV versus CBF ID RADIAL CORRELATION CONTRAST; CEREBRAL BLOOD-VOLUME; FUNCTIONAL MRI; WEIGHTED FMRI; IN-VIVO; SOMATOSENSORY CORTEX; SPATIAL LOCALIZATION; COLUMNAR RESOLUTION; NEURONAL-ACTIVITY; BRAIN ACTIVATION AB A unique method to map the effect of crusher gradients in space and time on the gradient echo blood oxygen level dependent (BOLD) signal is introduced. Using the Radial Correlation Contrast (RCC) analysis method, amplitude-RCC maps at different time segments and different gradient strengths were obtained. The ratio of amplitude-RCC cluster volumes, with and without crusher gradients, showed a temporal dependency with stronger volume reduction for stimulation-onset versus stimulation-decline. Aside from signal-to-noise ratio reduction in diffusion weighted images, the average temporal patterns were equal. Comparison of the data with and without crushers showed a stronger reduction in local coherence for stimulationon-set times. We hypothesize that the stimulation decline was weighted by extravascular effects originating in expanded veins due to their larger volume and long range susceptibility which couples neighboring voxels. The ratio of amplitude-RCC with and without crushers calculated for each voxel at each time segment yielded a spatial-temporal mapping of the crusher effect. These maps suggest that early stimulation-onset (similar to 9 s) is weighted by flow; later a dynamic steady-state between intra- and extravascular effects is obtained. Stimulation-decline was dominated by extravascular effects, and at late stimulation decline as well as at early stimulation onset, clusters were small and localized to expected site of neuronal activity. C1 [Goelman, Gadi] Hadassah Hebrew Univ, Med Ctr, Dept Med Biophys & Nucl Med, IMRI MRS Lab,Human Biol Res Ctr, IL-91120 Jerusalem, Israel. [Pelled, Galit; Dodd, Steve; Koretsky, Alan] NINDS, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. RP Goelman, G (reprint author), Hadassah Hebrew Univ, Med Ctr, Dept Med Biophys & Nucl Med, IMRI MRS Lab,Human Biol Res Ctr, POB 1200, IL-91120 Jerusalem, Israel. EM gadig@hadassah.org.il RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU Israel Science Foundation [184/05] FX Grant sponsor: the Israel Science Foundation; Grant number: 184/05. NR 34 TC 2 Z9 2 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 SEP PY 2008 VL 60 IS 3 BP 548 EP 554 DI 10.1002/mrm.21666 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 346FL UT WOS:000259053900007 PM 18727038 ER PT J AU Bennett, KM Zhou, H Sumner, JP Dodd, SJ Bouraoud, N Doi, K Star, RA Koretsky, AP AF Bennett, Kevin M. Zhou, Hua Sumner, James P. Dodd, Stephen J. Bouraoud, Nadia Doi, Kent Star, Robert A. Koretsky, Alan P. TI MRI of the basement membrane using charged nanoparticles as contrast agents SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE basement membrane; cationic contrast agents; nanoparticles; kidney ID NEPHROGENIC SYSTEMIC FIBROSIS; CELL-SURFACE CHARGE; ANIONIC SITES; ENHANCED MRI; AMINONUCLEOSIDE NEPHROSIS; PREFERENTIAL DISTRIBUTION; CAPILLARY ENDOTHELIUM; CATIONIZED FERRITIN; LUMINAL SURFACE; KIDNEY-FUNCTION AB The integrity of the basement membrane is essential for tissue cellular growth and is often altered in disease. In this work a method for noninvasively detecting the structural integrity of the basement membrane, based on the delivery of cationic iron-oxide nanoparticles, was developed. Cationic particles accumulate due to the highly negative charge of proteoglycans in the basement membrane. The kidney was used to test this technique because of its highly fenestrated endothelia and well-established disease models to manipulate the basement membrane charge barrier. After systemic injection of cationic or native ferritin (CF or NF) in rats, ex vivo and in vivo MRI showed selective accumulation of CF, but not NF, causing a 60% reduction in signal intensity in cortex at the location of individual glomeruli. Immunofluorescence and electron microscopy demonstrated that this CF accumulation was localized to the glomerular basement membrane (GBM). In a model of GBM breakdown during focal and segmental glomerulosclerosis, MRI showed reduced single glomerular accumulation of CIF, but a diffuse accumulation of CIF in the kidney tubules caused by leakage of CIF through the glomerulus. Cationic contrast agents can be used to target the basement membrane and detect the breakdown of the basement membrane in disease. C1 [Bennett, Kevin M.; Sumner, James P.; Dodd, Stephen J.; Bouraoud, Nadia; Koretsky, Alan P.] NINDS, Natl Inst Hlth, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. [Zhou, Hua; Doi, Kent; Star, Robert A.] NINDS, Natl Inst Hlth, Renal Diagnost & Therapeut Unit, Bethesda, MD 20892 USA. RP Bennett, KM (reprint author), Arizona State Univ, Dept Bioengn, 501 E Tyler,ECG Bldg,Room 334, Tempe, AZ 85286 USA. EM kevin.m.bennett@asu.edu RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU Intramural Research Programs of the NIH/NINDS; NIDDK FX Grant sponsor: Intramural Research Programs of the NIH/NINDS and NIDDK. NR 46 TC 36 Z9 36 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 SEP PY 2008 VL 60 IS 3 BP 564 EP 574 DI 10.1002/mrm.21684 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 346FL UT WOS:000259053900009 PM 18727041 ER PT J AU Dahnke, H Liu, W Herzka, D Frank, JA Schaeffter, T AF Dahnke, Hannes Liu, Wei Herzka, Daniel Frank, Joseph A. Schaeffter, Tobias TI Susceptibility gradient mapping (SGM): A new postprocessing method for positive contrast generation applied to superparamagnetic iron oxide particle (SPIO)-labeled cells SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE susceptibility; positive contrast; SPIO; labeled cells ID ATHEROSCLEROTIC PLAQUE; LYMPH-NODES; MRI; AGENT; CATHETERS; TRACKING; SYSTEM AB Local susceptibility gradients result in a dephasing of the precessing magnetic moments and thus in a fast decay of the NMR signals. In particular, cells labeled with superparamagnetic iron oxide particles (SPIOs) induce hypointensities, making the in vivo detection of labeled cells from such a negative image contrast difficult. In this work, a new method is proposed to selectively turn this negative contrast into a positive contrast. The proposed method calculates the susceptibility gradient and visualizes it in a parametric map directly from a regular gradient-echo image dataset. The susceptibility gradient map is determined in a postprocessing step, requiring no dedicated pulse sequences or adaptation of the sequence before and during image acquisition. Phantom experiments demonstrated that local susceptibility differences can be quantified. In vivo experiments showed the feasibility of the method for tracking of SPIO-labeled cells. The method bears the potential also for usage in other applications, including the detection of contrast agents and interventional devices as well as metal implants. C1 [Dahnke, Hannes] Philips Res Europe, Sector Med Imaging Syst, D-22335 Hamburg, Germany. [Liu, Wei; Herzka, Daniel] Philips Res N Amer, Briarcliff Manor, NY USA. [Frank, Joseph A.] Natl Inst Hlth, Bethesda, MD USA. [Schaeffter, Tobias] Kings Coll London, Div Imaging Sci, London WC2R 2LS, England. RP Dahnke, H (reprint author), Philips Res Europe, Sector Med Imaging Syst, Roentgenstr 24-26, D-22335 Hamburg, Germany. EM hannes.dahnke@philips.com OI Herzka, Daniel/0000-0002-9400-7814; Schaeffter, Tobias/0000-0003-1310-2631 FU Intramural Program of the Clinical Center; German BMBF [13N8896] FX Grant sponsor: Intramural Program of the Clinical Center at the NIH; Grant sponsor: German BMBF; Grant number: 13N8896. NR 27 TC 75 Z9 75 U1 1 U2 13 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 SEP PY 2008 VL 60 IS 3 BP 595 EP 603 DI 10.1002/mrm.21478 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 346FL UT WOS:000259053900013 PM 18727097 ER PT J AU Watkins, SM Reich, A Fleming, LE Hammond, R AF Watkins, Sharon M. Reich, Andrew Fleming, Lora E. Hammond, Roberta TI Neurotoxic shellfish poisoning SO MARINE DRUGS LA English DT Review DE neurotoxic shellfish Poisoning; NSP; brevetoxins; harmful algal blooms (HABs); Karenia brevis; epidemiology; human health; red tide ID FLORIDA RED TIDE; OYSTER CRASSOSTREA-VIRGINICA; HARMFUL ALGAL BLOOMS; KARENIA-BREVIS; NEW-ZEALAND; BREVETOXIN METABOLISM; GYMNODINIUM-BREVE; AEROSOLIZED BREVETOXINS; AUSTROVENUS-STUTCHBURYI; DINOFLAGELLATE TOXINS AB Neurotoxic shellfish poisoning (NSP) is caused by consumption of molluscan shellfish contaminated with brevetoxins primarily produced by the dinoflagellate, Karenia brevis. Blooms of K. brevis, called Florida red tide, occur frequently along the Gulf of Mexico. Many shellfish beds in the US (and other nations) are routinely monitored for presence of K. brevis and other brevetoxin-producing organisms. As a result, few NSP cases are reported annually from the US. However, infrequent larger outbreaks do occur. Cases are usually associated with recreationally-harvested shellfish collected during or post red tide blooms. Brevetoxins are neurotoxins which activate voltage-sensitive sodium channels causing sodium influx and nerve membrane depolarization. No fatalities have been reported, but hospitalizations occur. NSP involves a cluster of gastrointestinal and neurological symptoms: nausea and vomiting, paresthesias of the mouth, lips and tongue as well as distal paresthesias, ataxia, slurred speech and dizziness. Neurological symptoms can progress to partial paralysis; respiratory distress has been recorded. Recent research has implicated new species of harmful algal bloom organisms which produce brevetoxins, identified additional marine species which accumulate brevetoxins, and has provided additional information on the toxicity and analysis of brevetoxins. A review of the known epidemiology and recommendations for improved NSP prevention are presented. C1 [Watkins, Sharon M.; Reich, Andrew] Florida Dept Hlth, Div Environm Hlth, Aquat Toxins Program, Tallahassee, FL 32399 USA. [Fleming, Lora E.] Univ Miami, NSF, NIEHS, Oceans & Human Hlth Ctr,Rosenstiel Sch Marine & A, Miami, FL 33136 USA. [Hammond, Roberta] Florida Dept Hlth, Div Environm Hlth, Food & Waterborne Dis Program, Tallahassee, FL 32399 USA. RP Watkins, SM (reprint author), Florida Dept Hlth, Div Environm Hlth, Aquat Toxins Program, Tallahassee, FL 32399 USA. EM Sharon_Watkins@doh.state.fl.us FU the Florida Department of Health; the Centers for Disease Control and Prevention (CDC); National Science Foundation; National Institute of Environmental Health Sciences Oceans and Human Health Center at the University of Miami Rosenstiel School [NSF 0CE0432368, NIEHS 1 P50 ES12736]; National Institute of Environmental Health Sciences Red Tide POI [P01 ES 10594] FX The funding for this study was provided by the Florida Department of Health and the Centers for Disease Control and Prevention (CDC), as well as the National Science Foundation and National Institute of Environmental Health Sciences Oceans and Human Health Center at the University of Miami Rosenstiel School (NSF 0CE0432368; NIEHS 1 P50 ES12736) and the National Institute of Environmental Health Sciences Red Tide POI (P01 ES 10594). NR 136 TC 77 Z9 79 U1 10 U2 40 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-3397 J9 MAR DRUGS JI Mar. Drugs PD SEP PY 2008 VL 6 IS 3 BP 431 EP 455 DI 10.3390/md20080021 PG 25 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 354RO UT WOS:000259656900003 PM 19005578 ER PT J AU Friedman, MA Fleming, LE Fernandez, M Bienfang, P Schrank, K Dickey, R Bottein, MY Backer, L Ayyar, R Weisman, R Watkins, S Granade, R Reich, A AF Friedman, Melissa A. Fleming, Lora E. Fernandez, Mercedes Bienfang, Paul Schrank, Kathleen Dickey, Robert Bottein, Marie-Yasmine Backer, Lorraine Ayyar, Ram Weisman, Richard Watkins, Sharon Granade, Ray Reich, Andrew TI Ciguatera fish poisoning: Treatment, prevention and management SO MARINE DRUGS LA English DT Review DE ciguatera fish poisoning; ciguatoxin; harmful algal bloom (HAB); treatment human health; marine toxins ID COMMON-SOURCE OUTBREAK; STATES VIRGIN-ISLANDS; INDIAN-OCEAN; SYMPTOMATIC IMPROVEMENT; CARIBBEAN CIGUATOXINS; PACIFIC CIGUATOXIN-1; CLINICAL-FEATURES; BREVETOXINS; TOXINS; DISEASE AB Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world, and it causes substantial physical and functional impact. It produces a myriad of gastrointestinal, neurologic and/or cardiovascular symptoms which last days to weeks, or even months. Although there are reports of symptom amelioration with some interventions ( e. g. IV mannitol), the appropriate treatment for CFP remains unclear to many physicians. We review the literature on the treatments for CFP, including randomized controlled studies and anecdotal reports. The article is intended to clarify treatment options, and provide information about management and prevention of CFP, for emergency room physicians, poison control information providers, other health care providers, and patients. C1 [Friedman, Melissa A.] Mt Sinai Med Ctr, Miami Beach, FL 33140 USA. [Friedman, Melissa A.; Fleming, Lora E.] NIEHS, NSF, Oceans & Human Hlth Ctr, Rosenstiel Sch Marine & Atmospher Sci, Miami, FL 33136 USA. [Fernandez, Mercedes] Carlos Albizu Univ, Miami, FL 33172 USA. [Bienfang, Paul] Univ Hawaii, Honolulu, HI 96822 USA. [Schrank, Kathleen] Univ Miami, Dept Med, Jackson Mem Med Ctr, Miami, FL 33136 USA. [Dickey, Robert; Granade, Ray] US FDA, Div Seafood Sci & Technol, Ctr Food Safety & Nutr, Dauphin Isl, AL 36528 USA. [Bottein, Marie-Yasmine] NOAA, Natl Ocean Serv, Ctr Coastal Environm Hlth & Biomol Res, Charleston, SC 29412 USA. [Backer, Lorraine] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. [Ayyar, Ram] Univ Miami, Dept Neurol, Miami, FL 33136 USA. [Weisman, Richard] Florida Poison Informat Ctr, Miami, FL 33136 USA. [Watkins, Sharon; Reich, Andrew] Florida Dept Hlth, Div Environm Hlth, Aquat Toxins Program, Tallahassee, FL 32399 USA. RP Friedman, MA (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NSF, NIEHS,Oceans & Human Hlth Ctr, 4600 Rickenbacker Causeway,E Grosvenor Bldg,E211, Key Biscayne, FL 33149 USA. EM melissafried@yahoo.com FU National Science Foundation (NSF) [NSF 0CE0432368]; National Institute of Environmental Health Sciences [NIEHS P50 ES12736]; Florida Dept of Health Aquatic Toxins Program; Centers for Disease Control and Prevention (CDC) FX This publication was made possible through the National Science Foundation (NSF) National Institute of Environmental Health Sciences Center for Oceans and Human Health (COHH) program at the University of Miami (NSF 0CE0432368; NIEHS P50 ES12736), as well as with funding from the Florida Dept of Health Aquatic Toxins Program and the Centers for Disease Control and Prevention (CDC). NR 106 TC 86 Z9 91 U1 6 U2 35 PU MOLECULAR DIVERSITY PRESERVATION INT PI BASEL PA MATTHAEUSSTRASSE 11, CH-4057 BASEL, SWITZERLAND SN 1660-3397 J9 MAR DRUGS JI Mar. Drugs PD SEP PY 2008 VL 6 IS 3 BP 456 EP 479 DI 10.3390/md20080022 PG 24 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 354RO UT WOS:000259656900004 PM 19005579 ER PT J AU Macchi, C Molino-Lova, R Polcaro, P Guarducci, L Lauretani, F Cecchi, F Bandinelli, S Guralnik, JM Ferrucci, L AF Macchi, Claudio Molino-Lova, Raffaele Polcaro, Paola Guarducci, Lorenzo Lauretani, Fulvio Cecchi, Francesca Bandinelli, Stefania Guralnik, Jack M. Ferrucci, Luigi TI Higher circulating levels of uric acid are prospectively associated with better muscle function in older persons SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE uric acid; antioxidants; sarcopenia; muscle strength; elderly ID CORONARY-HEART-DISEASE; LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE; CARDIOVASCULAR RISK; INSULIN-RESISTANCE; BLOOD-PRESSURE; GRIP STRENGTH; MORTALITY; DISABILITY; SARCOPENIA AB Background: Previous studies have shown that oxidative protein damage is independently associated with low grip strength and that dietary intake and circulating levels of antioxiclant vitamins are positive predictors of muscle strength among older persons. Since uric acid (LIA), has strong antioxidant properties, we tested the hypothesis that UA levels is cross-sectionaly associated with muscle strength and protective against the decline of strength over the aging process. Subjects and methods: 789 InCHIANTI Study participants underwent baseline serum UA, handgrip and knee extension torque measurements. Of these, 497 participants (226 men and 271 women, mean age 76.0 +/- 5.4 years) also had follow-up strength measures. Lifestyle, comorbidities, nutritional profile, inflammatory markers and other laboratory measures were considered as potential confounders. Results: Follow-up strength measures significantly increased across baseline UA tertiles. After adjusting for potential confounders and analogous baseline strength measures, higher baseline UA levels still remained significantly associated with higher follow-up strength measures. Conclusions: Our findings suggest that higher levels ofUA might represent a protective reaction aimed at counteracting the excessive production offree radicals that cause muscle protein damage and eventually contribute to the decline of muscle mass and strength. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Macchi, Claudio; Molino-Lova, Raffaele; Polcaro, Paola; Guarducci, Lorenzo; Cecchi, Francesca] Fdn Don C Gnocchi, I-50020 Florence, Italy. [Lauretani, Fulvio] Tuscany Hlth Reg Agcy, Florence, Italy. [Bandinelli, Stefania] ASF, Geriatr Rehabil Unit, Florence, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Molino-Lova, R (reprint author), Fdn Don C Gnocchi, Via Imprunetana 124, I-50020 Florence, Italy. EM rmolino@dongnocchi.it RI Lauretani, Fulvio/K-5115-2016; OI Lauretani, Fulvio/0000-0002-5287-9972; Cecchi, Franco/0000-0002-2035-5621 FU Intramural NIH HHS [Z99 HD999999]; NIA NIH HHS [N01 AG050002, N01 AG821336, N01 AG916413, N01-AG-821336, Z01 AG000971-01]; NIMHD NIH HHS [263 MD821336, 263 MD9164 13, R01 MD009164] NR 48 TC 14 Z9 15 U1 0 U2 2 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 SEP PY 2008 VL 129 IS 9 BP 522 EP 527 DI 10.1016/j.mad.2008.04.008 PG 6 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 334QT UT WOS:000258237000003 PM 18534661 ER PT J AU Shamir, L Orlov, N Eckley, DM Macura, TJ Goldberg, IG AF Shamir, Lior Orlov, Nikita Eckley, David Mark Macura, Tomasz J. Goldberg, Ilya G. TI IICBU 2008: a proposed benchmark suite for biological image analysis SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE biological imaging; image analysis; image datasets; benchmarks ID SUBCELLULAR STRUCTURES; ELECTRON-MICROSCOPY; DATABASE; PATTERNS AB New technology for automated biological image acquisition has introduced the need for effective biological image analysis methods. These algorithms are constantly being developed by pattern recognition and machine vision experts, who tailor general computer vision techniques to the specific needs of biological imaging. However, computer scientists do not always have access to biological image datasets that can be used for computer vision research, and biologist collaborators who can assist in defining the biological questions are not always available. Here, we propose a publicly available benchmark suite of biological image datasets that can be used by machine vision experts for developing and evaluating biological image analysis methods. The suite represents a set of practical real-life imaging problems in biology, and offers examples of organelles, cells and tissues, imaged at different magnifications and different contrast techniques. All datasets are available for free download at http://ome.grc.nia.nih.gov/iicbu2008. C1 [Shamir, Lior; Orlov, Nikita; Eckley, David Mark; Macura, Tomasz J.; Goldberg, Ilya G.] NIA, Genet Lab, Image Informat & Computat Biol Unit, NIH, Baltimore, MD 21224 USA. [Macura, Tomasz J.] Univ Cambridge, Comp Lab, Cambridge CB2 3QG, England. RP Shamir, L (reprint author), NIA, Genet Lab, Image Informat & Computat Biol Unit, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM shamirl@mail.nih.gov RI Goldberg, Ilya/H-5307-2011; OI Goldberg, Ilya/0000-0001-8514-6110; Eckley, D. Mark/0000-0003-2296-5164 FU NIH; National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. The datasets Hela and CHO are from Murphy lab, CMU. The dataset Pollen was contributed by Andrew Duller, Henry Lamb and Ian France, and the dataset Binucleate was provided by Aaron Straight, Stanford U. We would also like to thank Cathy Wolkow and Wendy Iser for their assistance with the acquisition and definition of the Terminal Bulb Aging and C. elegans Muscle Aging datasets, and Elaine Jaffe for providing the data for the Lymphoma dataset. NR 8 TC 42 Z9 42 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0140-0118 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD SEP PY 2008 VL 46 IS 9 BP 943 EP 947 DI 10.1007/s11517-008-0380-5 PG 5 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA 343GY UT WOS:000258842700012 PM 18668273 ER PT J AU Carney, PA Hoffman, RM Lieberman, DA Hornbrook, MC Dietrich, AJ Klabunde, CN AF Carney, Patricia A. Hoffman, Richard M. Lieberman, David A. Hornbrook, Mark C. Dietrich, Allen J. Klabunde, Carrie N. TI Data systems to evaluate colorectal cancer screening practices and outcomes at the population level SO MEDICAL CARE LA English DT Editorial Material ID NATIONAL ENDOSCOPIC DATABASE; UNITED-STATES; MAMMOGRAPHY; PERFORMANCE; COLONOSCOPY; CONSORTIUM; SURVEILLANCE; GUIDELINES; RATIONALE; SETTINGS C1 [Carney, Patricia A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97239 USA. [Carney, Patricia A.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Lieberman, David A.] Oregon Hlth & Sci Univ, Div Gastroenterol, Dept Med, Portland, OR 97239 USA. [Hoffman, Richard M.] Univ New Mexico, Hlth Sci Ctr, New Mexico Vet Adm Hlth Care Syst, Albuquerque, NM 87131 USA. [Hornbrook, Mark C.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Dietrich, Allen J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. [Klabunde, Carrie N.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Carney, PA (reprint author), Oregon Hlth & Sci Univ, Dept Family Med, 3181 Sam Jackson Pk Rd, Portland, OR 97239 USA. EM carneyp@ohsu.edu NR 25 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 2008 VL 46 IS 9 SU 1 BP S132 EP S137 DI 10.1097/MLR.0b013e31817f7355 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 344RR UT WOS:000258945500019 PM 18725825 ER PT J AU Klabunde, CN Lanier, D Meissner, HI Breslau, ES Brown, ML AF Klabunde, Carrie N. Lanier, David Meissner, Helen I. Breslau, Erica S. Brown, Martin L. TI Improving colorectal cancer screening through research in primary care settings - Introduction SO MEDICAL CARE LA English DT Editorial Material ID PREVENTIVE SERVICES; UNITED-STATES; GUIDELINES; FUTURE; RATIONALE; DELIVERY; MEDICINE C1 [Klabunde, Carrie N.; Brown, Martin L.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Lanier, David] Agcy Healthcare Res & Qual, Ctr Primary Care Prevent & Clin Partnerships, Rockville, MD USA. [Meissner, Helen I.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Breslau, Erica S.] NCI, Div Canc Control & Populat Sci, Behav Res Program, Appl Canc Screening Res Branch, Bethesda, MD 20892 USA. RP Klabunde, CN (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N Room 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. EM klabundc@mail.nih.gov NR 50 TC 11 Z9 11 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 2008 VL 46 IS 9 SU 1 BP S1 EP S4 DI 10.1097/MLR.0b013e3181805e2a PG 4 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 344RR UT WOS:000258945500001 PM 18725819 ER PT J AU Miglioretti, DL Rutter, CM Bradford, SC Zauber, AG Kessler, LG Feuer, EJ Grossman, DC AF Miglioretti, Diana L. Mutter, Carolyn M. Bradford, Susan Carol Zauber, Ann G. Kessler, Larry G. Feuer, Eric J. Grossman, David C. TI Improvement in the Diagnostic Evaluation of a Positive Fecal Occult Blood Test in an Integrated Health Care Organization SO MEDICAL CARE LA English DT Article DE fecal occult blood test; colorectal cancer screening; diagnostic follow-up ID IMPROVING PRIMARY-CARE; COLORECTAL-CANCER; FOLLOW-UP; CLINICAL GUIDELINES; CHRONIC ILLNESS; UNITED-STATES; PREVENTION; RATIONALE; MORTALITY; TRIAL AB Background: Screening for fecal occult blood can be effective in reducing colorectal cancer mortality only if positive tests are appropriately followed up with complete diagnostic evaluation (ie, colonoscopy or flexible sigmoidoscopy with double contrast barium enema) and treatment. Objectives: To examine whether rates of complete diagnostic evaluation after a positive fecal occult blood test (FOBT) have improved over time after the implementation of tracking systems and physician guidelines within a large integrated health care organization. Research Design: From 1993 to 2005, 8513 positive FOBTs were identified on 8291 enrollees aged 50-79 of a large health care system. Automated records were used to identify repeat FOBTs, colonoscopy, flexible sigmoidoscopy, and double-contrast barium enema within 1 year after the positive FOBT. National rates of complete diagnostic evaluation were estimated from the 2005 National Health Interview Survey. Results: In this integrated health care organization, the percentage of positive FOBTs followed by complete diagnostic evaluation within 1 year increased from 57-64% in 1993-1996 to 82-86% from 2000-2005. Use of repeat FOBT after a positive FOBT decreased from 28-31% in 1993-1996 to 6-11% in 2000-2005. Based on the National Health Interview Survey, only 52% of positive FOBTs in 2000-2005 were followed by omplete diagnostic evaluation nationally. Conclusions: Adherence to recommendations for complete diagnostic evaluation after a positive FOBT has greatly improved over time in an integrated group medical practice. Through the use of tracking systems and screening guidelines, it may be possible to reach levels of follow-up that are comparable to those observed in randomized trials. C1 [Miglioretti, Diana L.; Mutter, Carolyn M.; Grossman, David C.] Grp Hlth Ctr Hlth Studies, Seattle, WA 98101 USA. [Bradford, Susan Carol; Grossman, David C.] Grp Hlth Cooperat Puget Sound, Dept Clin Improvement & Prevent, Seattle, WA USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA. [Kessler, Larry G.] Ctr Devices & Radiol Hlth Food & Drug Adm, Off Sci & Engn Labs, Silver Spring, MD USA. [Feuer, Eric J.] Natl Canc Inst, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD USA. RP Miglioretti, DL (reprint author), Grp Hlth Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM miglioretti.d@ghc.org FU National Cancer Institute [U01 CA-97427, U01 CA-97426] FX Supported by the National Cancer Institute grants U01 CA-97427 and U01 CA-97426. NR 27 TC 28 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD SEP PY 2008 VL 46 IS 9 SU 1 BP S91 EP S96 DI 10.1097/MLR.0b013e31817946c8 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 344RR UT WOS:000258945500022 PM 18725839 ER PT J AU Srinivasan, S Kerner, J AF Srinivasan, Shobha Kerner, Jon TI Meeting the needs of diverse populations - An overview and commentary SO MEDICAL CARE LA English DT Editorial Material ID CANCER SCREENING RATES; COLORECTAL-CANCER; UNITED-STATES; RACIAL-DISCRIMINATION; INTERVENTION RESEARCH; SOCIOECONOMIC-STATUS; PREVENTIVE CARE; HEALTH-CARE; DISPARITIES; BARRIERS C1 [Srinivasan, Shobha; Kerner, Jon] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Srinivasan, S (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 6126, Bethesda, MD 20892 USA. EM ss688k@nih.gov NR 52 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 2008 VL 46 IS 9 SU 1 BP S30 EP S35 DI 10.1097/MLR.0b013e31817f0d12 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 344RR UT WOS:000258945500006 PM 18725830 ER PT J AU Taplin, SH Haggstrom, D Jacobs, T Determan, A Granger, J Montalvo, W Snyder, WM Lockhart, S Calvo, A AF Taplin, Stephen H. Haggstrom, David Jacobs, Tracy Determan, Ada Granger, Jennifer Montalvo, Wanda Snyder, William M. Lockhart, Susan Calvo, Ahmed TI Implementing colorectal cancer screening in community health centers - Addressing cancer health disparities through a Regional Cancer Collaborative SO MEDICAL CARE LA English DT Article DE colorectal cancer screening; quality improvement; health disparities ID CHRONIC CARE MODEL; INCREASE MAMMOGRAPHY USE; IMPROVING DIABETES CARE; SERVICES TASK-FORCE; CERVICAL-CANCER; QUALITY IMPROVEMENT; CHRONIC ILLNESS; BREAST; INTERVENTIONS; SYSTEM AB Background: The population served by Federally Qualified Health Centers (FQHCs) has lower levels of cancer screening compared with the general population and suffers a disproportionate cancer burden. To address these disparities, 3 federal agencies and a primary care association established and tested the feasibility of a Regional Cancer Collaborative (RCC) in 2005. Methods: RCC faculty implemented a learning model to improve cancer screening across 4 FQHCs that met explicit organizational readiness criteria. Regional faculty trained "care process leaders," who worked with primary care teams to plan and implement practice changes. FQHCs monitored progress across the following measures of screening implementation: self-management goal-setting; number and percent screened for breast, cervical, and colorectal cancer; percent timely results notification; and percent abnormal screens evaluated within 90 days. Progress and plans were reviewed in regular teleconferences. FQHCs were encouraged to create local communities of practice (LCOP) involving community resources to support cancer screening and to participate in a monthly teleconference that linked the LCOPs into a regional community of practice. Summary reports and administrative data facilitated a process evaluation of the RCC. chi(2) test and test of trends compared baseline and follow-up screening rates. Results: The RCC taught the collaborative process using process leader training, teleconferences, 2 regional meetings, and local process improvement efforts. All organizations created clinical tracking capabilities and 3 of the 4 established LCOPs, which met monthly in an regional community of practice. Screening documentation increased for all 3 cancers from 2005 to 2007. Colorectal cancer screening increased from 8.6% to 21.2%. Conclusions: A regional plan to enable collaborative learning for cancer screening implementation is feasible, and improvements in screening rates can occur among carefully selected organizations. C1 [Taplin, Stephen H.] NCI, Bethesda, MD 20892 USA. [Haggstrom, David] Indiana Univ, Ctr Hlth Serv & Outcomes Res, Regenstrief Inst, Bloomington, IN 47405 USA. [Haggstrom, David] Indiana Univ, Sch Med, Dept Internal Med, Div Gen Internal Med & Geriatr, Bloomington, IN 47405 USA. [Haggstrom, David] Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. [Jacobs, Tracy] IHI, Cambridge, MA USA. [Determan, Ada; Calvo, Ahmed] HRSA, Rockville, MD USA. [Granger, Jennifer] CHCACT, Newington, CT USA. [Montalvo, Wanda] Community Hlth Ctr Assoc New York, New York, NY USA. [Snyder, William M.] Social Capital Grp, Cambridge, MA USA. [Lockhart, Susan] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. RP Taplin, SH (reprint author), 6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM taplins@mail.nih.gov FU Inter-Agency-Agreement between HRSA; CDC FX Supported by an Inter-Agency-Agreement between HRSA and the CDC for support of the teams, faculty, and infrastructure; in-kind contributions from the National Cancer Institute for the time, travel, and activity of Dr. Taplin; from HRSA for the infrastructure of the internet based Knowledge Management System for sharing of insights and data as well as in kind contribution of staff time, travel, and activity of Dr Calvo and Ada Determan; and in kind support from CDC with regards to staff time,, travel, and activity of Dr. Susan Lockhart. NR 43 TC 36 Z9 37 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD SEP PY 2008 VL 46 IS 9 SU 1 BP S74 EP S83 DI 10.1097/MLR.0b013e31817fdf68 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 344RR UT WOS:000258945500012 PM 18725837 ER PT J AU Vernon, SW Meissner, HI AF Vernon, Sally W. Meissner, Helen I. TI Evaluating approaches to increase uptake of colorectal cancer screening - Lessons learned from pilot studies in diverse primary care settings SO MEDICAL CARE LA English DT Editorial Material ID CERVICAL-CANCER; UNITED-STATES; TASK-FORCE; INTERVENTIONS; METAANALYSIS; FUTURE; HEALTH; RISK; STRATEGIES; MEDICINE C1 [Vernon, Sally W.] Univ Texas Houston, Sch Publ Hlth, Ctr Hlth Promot & Prevent Res, Div Hlth Promot & Behav Sci, Houston, TX 77030 USA. [Meissner, Helen I.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Vernon, SW (reprint author), Univ Texas Houston, Sch Publ Hlth, Ctr Hlth Promot & Prevent Res, Div Hlth Promot & Behav Sci, 7000 Fannin,Suite 2560, Houston, TX 77030 USA. EM sally.w.vemon@uth.tmc.edu NR 27 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 2008 VL 46 IS 9 SU 1 BP S97 EP S102 DI 10.1097/MLR.0b013e31817eb346 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 344RR UT WOS:000258945500014 PM 18725840 ER PT J AU Zauber, AG Levin, TR Jaffe, CC Galen, BA Ransohoff, DF Brown, ML AF Zauber, Ann G. Levin, Theodore R. Jaffe, C. Carl Galen, Barbara A. Ransohoff, David F. Brown, Martin L. TI Implications of new colorectal cancer screening technologies for primary care practice SO MEDICAL CARE LA English DT Editorial Material ID FECAL-OCCULT-BLOOD; SOCIETY-TASK-FORCE; PROXIMAL COLONIC NEOPLASIA; COLLEGE-OF-RADIOLOGY; ASYMPTOMATIC ADULTS; ADENOMATOUS POLYPS; CLINICAL GUIDELINES; JOINT GUIDELINE; UNITED-STATES; HUMAN DNA C1 [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Levin, Theodore R.] Kaiser Permanente, Med Ctr, Dept Gastroenterol, Walnut Creek, CA USA. [Jaffe, C. Carl; Galen, Barbara A.] NCI, Canc Imaging Program, Bethesda, MD 20892 USA. [Ransohoff, David F.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Brown, Martin L.] NCI, Div Canc Control & Populat Sci, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. RP Zauber, AG (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 307 E 63rd St, New York, NY 10065 USA. EM zaubera@mskcc.org FU NCI NIH HHS [U01 CA097426] NR 70 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 2008 VL 46 IS 9 SU 1 BP S138 EP S146 DI 10.1097/MLR.0b013e31818192ef PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 344RR UT WOS:000258945500020 PM 18725826 ER PT J AU Yao, JH Chen, D AF Yao, Jianhua Chen, David TI Live level set: A hybrid method of livewire and level set for medical image segmentation SO MEDICAL PHYSICS LA English DT Article DE livewire; level set; medical image segmentation ID SHAPE; LANE AB Livewire and level set are popular methods for medical image segmentation. In this article, the authors propose a hybrid method of livewire and level set, termed the live level set (LLS). The LLS replaces the one graph update iteration in the classic livewire with two iterations of graph updates. The first iteration generates an initial contour for a level set computation. The level set distance is then factored back into the cost function in the second iteration of graph update. The authors validated LLS using synthetic images. The results show that the performance of the LLS is superior to both the classic live wire and traditional level set methods in terms of accuracy, reproducibility, smoothness and running time. They also qualitatively evaluated the LLS using real clinical data. (C) 2008 American Association of Physicists in Medicine. C1 [Yao, Jianhua; Chen, David] NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Chen, David] Stanford Univ, Stanford, CA 94305 USA. RP Yao, JH (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bldg 10, Bethesda, MD 20892 USA. EM jyao@cc.nih.gov FU Intramural Research Program of the National Institutes of Health; Warren G. Magnuson Clinical Center FX The authors thank Dr. Ronald Summers for support of the project and critical reviews of the article. This research was supported by the Intramural Research Program of the National Institutes of Health, Warren G. Magnuson Clinical Center. NR 25 TC 4 Z9 5 U1 0 U2 1 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 SEP PY 2008 VL 35 IS 9 BP 4112 EP 4120 DI 10.1118/1.2968876 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 342GQ UT WOS:000258773000033 PM 18841864 ER PT J AU Steiner, AZ Baird, DD Kesner, JS AF Steiner, Anne Z. Baird, Donna D. Kesner, James S. TI Mother's menopausal age is associated with her daughter's early follicular phase urinary follicle-stimulating hormone level SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE follicle-stimulating hormone; menopause; maternal age at menopause ID PREMATURE OVARIAN FAILURE; LUTEINIZING-HORMONE; REPRODUCTIVE LIFE; WOMEN; RESERVE; PERIMENOPAUSE; VARIABILITY; POPULATION; TRANSITION; SMOKING AB Objective: Early follicular phase follicle-stimulating hormone (FSH), a marker of ovarian reserve, has been used to predict time to menopause. A mother's age at menopause is related to her daughter's age at menopause, possibly because of genetic factors. In this study we sought to determine the relationship between maternal age at menopause and early follicular phase FSH of premenopausal daughters. Design: The Uterine Fibroid Study enrolled women randomly selected from a prepaid health plan, collected questionnaire data, and obtained earl), follicular phase urine samples for a Subset of participants. For this secondary analysis, premenopausal women between the ages of 35 and 46 years, who provided a urine sample on cycle day 2, 3, 4, or 5 and their mother's age at natural menopause (n = 182) were selected from the original cohort. Initially bivariate analysis and subsequently regression modeling were performed to assess the independent relationship between maternal age at menopause and urinary creatinine-corrected FSH. Results: Unadjusted analyses and those adjusting for age (mean +/- SD, 405 +/- 3.2 y), smoking status (16% current smokers), and body mass index (26.8 +/- 6.9 kg/m(2)) showed a significant association between maternal age at menopause and daughter's urinary FSH level (P < 0.04). Women whose mothers experienced earlier menopause had higher urinary FSH levels. Conclusions: The significantly increased FSH values among women whose mothers experienced early menopause is consistent with previously reported associations between mother's and daughter's age of menopause. FSH, a marker of ovarian reserve, is influenced by both genetic and environmental factors. Future epidemiologic studies on FSH should include collection of information on maternal age at menopause. C1 [Steiner, Anne Z.] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC 27515 USA. [Baird, Donna D.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Kesner, James S.] NIOSH, Biomonitoring & Hlth Assessment Branch, Div Appl Res & Technol, Cincinnati, OH 45226 USA. RP Steiner, AZ (reprint author), Univ N Carolina, Sch Med, Dept Obstet & Gynecol, CB 7570,Old Clin Bldg, Chapel Hill, NC 27515 USA. EM asteiner@med.unc.edu RI Baird, Donna/D-5214-2017 OI Baird, Donna/0000-0002-5544-2653 FU National Institutes of Health; National Institute of Environmental Health Sciences; Office of Research on Minority Health; Reproductive Health Research Career Development Center [5K12 HD050113-02] FX This study was funded as intramural research at the National Institutes of Health, National Institute of Environmental Health Sciences with support from the Office of Research on Minority Health and by Women's Reproductive Health Research Career Development Center Grant 5K12 HD050113-02 at the University of North Carolina. NR 31 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SEP-OCT PY 2008 VL 15 IS 5 BP 940 EP 944 DI 10.1097/gme.0b013e31816429e5 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 347BJ UT WOS:000259113500022 PM 18779679 ER PT J AU Parrish, CR Holmes, EC Morens, DM Park, EC Burke, DS Calisher, CH Laughlin, CA Saif, LJ Daszak, P AF Parrish, Colin R. Holmes, Edward C. Morens, David M. Park, Eun-Chung Burke, Donald S. Calisher, Charles H. Laughlin, Catherine A. Saif, Linda J. Daszak, Peter TI Cross-species virus transmission and the emergence of new epidemic diseases SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID INFLUENZA-A VIRUS; RESPIRATORY SYNDROME CORONAVIRUS; EMERGING INFECTIOUS-DISEASES; CANINE TRANSFERRIN RECEPTOR; HOST-RANGE; AVIAN INFLUENZA; SARS CORONAVIRUS; PUBLIC-HEALTH; RNA VIRUSES; FELINE PARVOVIRUSES AB Host range is a viral property reflecting natural hosts that are infected either as part of a principal transmission cycle or, less commonly, as "spillover" infections into alternative hosts. Rarely, viruses gain the ability to spread efficiently within a new host that was not previously exposed or susceptible. These transfers involve either increased exposure or the acquisition of variations that allow them to overcome barriers to infection of the new hosts. In these cases, devastating outbreaks can result. Steps involved in transfers of viruses to new hosts include contact between the virus and the host, infection of an initial individual leading to amplification and an outbreak, and the generation within the original or new host of viral variants that have the ability to spread efficiently between individuals in populations of the new host. Here we review what is known about host switching leading to viral emergence from known examples, considering the evolutionary mechanisms, virus-host interactions, host range barriers to infection, and processes that allow efficient host-to-host transmission in the new host population. C1 [Parrish, Colin R.] Cornell Univ, Coll Vet Med, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA. [Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Park, Eun-Chung; Laughlin, Catherine A.] NIAID, NIH, Virol Branch, Bethesda, MD 20892 USA. [Burke, Donald S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Calisher, Charles H.] Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Arthropod Borne & Infect Dis Lab, Ft Collins, CO 80523 USA. [Saif, Linda J.] Ohio State Univ, Ohio Agr Res & Dev Ctr, Food Anim Hlth Res Program, Wooster, OH 44691 USA. [Daszak, Peter] Consortium Conservat Med, New York, NY 10001 USA. RP Parrish, CR (reprint author), Cornell Univ, Coll Vet Med, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA. EM crp3@cornell.edu OI /0000-0002-5704-8094; Holmes, Edward/0000-0001-9596-3552 FU National Institutes of Allergy and Infectious Diseases; U. S. National Institutes of Health FX This review in part summarizes a meeting (Emergence of new epidemic viruses through host switching, 6 to 8 September 2005, Washington, DC) sponsored by the National Institutes of Allergy and Infectious Diseases and the Office of Rare Diseases of the U. S. National Institutes of Health. NR 157 TC 219 Z9 226 U1 12 U2 120 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1092-2172 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD SEP PY 2008 VL 72 IS 3 BP 457 EP + DI 10.1128/MMBR.00004-08 PG 15 WC Microbiology SC Microbiology GA 344TW UT WOS:000258951200004 PM 18772285 ER PT J AU To, KKW Zhan, ZR Litman, T Bates, SE AF To, Kenneth K. W. Zhan, Zhirong Litman, Thomas Bates, Susan E. TI Regulation of ABCG2 expression at the 3 ' untranslated region of its mRNA through modulation of transcript stability and protein translation by a putative MicroRNA in the s1 colon cancer cell line SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AU-RICH ELEMENT; 3'-UNTRANSLATED REGION; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; DOWN-REGULATION; GENE; IDENTIFICATION; BINDING; OVEREXPRESSION; TRANSPORTER AB ABCG2 is recognized as an important efflux transporter in clinical pharmacology and is potentially important in resistance to chemotherapeutic drugs. To identify epigenetic mechanisms regulating ABCG2 mRNA expression at its 3' untranslated region (3'UTR), we performed 3' rapid amplification of cDNA ends with the S1 parental colon cancer cell line and its drug-resistant ABCG2-overexpressing counterpart. We found that the 3'UTR is > 1,500 bp longer in parental cells and, using the miRBase TARGETs database, identified a putative microRNA (miRNA) binding site, distinct from the recently reported hsa-miR520h site, in the portion of the 3'UTR missing from ABCG2 mRNA in the resistant cells. We hypothesized that the binding of a putative miRNA at the 3'UTR of ABCG2 suppresses the expression of ABCG2. In resistant S1MI80 cells, the miRNA cannot bind to ABCG2 mRNA because of the shorter 3'UTR, and thus, mRNA degradation and/or repression on protein translation is relieved, contributing to overexpression of ABCG2. This hypothesis was rigorously tested by reporter gene assays, mutational analysis at the miRNA binding sites, and forced expression of miRNA inhibitors or mimics. The removal of this epigenetic regulation by miRNA could be involved in the overexpression of ABCG2 in drug-resistant cancer cells. C1 [To, Kenneth K. W.; Zhan, Zhirong; Bates, Susan E.] NCI, Mol Therapeut Sect, Med Oncol Branch, Ctr Canc Res,Natl Inst Hlth, Bethesda, MD 20892 USA. [Litman, Thomas] Exiqon AS, DK-2950 Vedboek, Denmark. RP To, KKW (reprint author), NCI, Mol Therapeut Sect, Med Oncol Branch, Ctr Canc Res,Natl Inst Hlth, Bldg 10,Room 13N220,10 Ctr Dr, Bethesda, MD 20892 USA. EM tok@mail.nih.gov RI To, Kenneth /M-4500-2013 OI To, Kenneth /0000-0003-2755-0283 FU NIH; National Cancer Institute; Center for Cancer Research FX This research was supported by the intramural research program of the NIH, National Cancer Institute, Center for Cancer Research. NR 56 TC 95 Z9 106 U1 0 U2 10 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 SEP PY 2008 VL 28 IS 17 BP 5147 EP 5161 DI 10.1128/MCB.00331-08 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 341DY UT WOS:000258695600002 PM 18573883 ER PT J AU Shao, JY Welch, WJ DiProspero, NA Diamond, MI AF Shao, Jieya Welch, William J. DiProspero, Nicholas A. Diamond, Marc I. TI Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSGENIC MOUSE MODEL; RHO-ASSOCIATED KINASE; ACTIN-BINDING SITE; HUNTINGTONS-DISEASE; PROTEIN-KINASE; MOTOR DEFICITS; LIM-KINASE; INHIBITOR; RECEPTOR; DYNAMICS AB Y-27632, an inhibitor of the Rho-associated kinase ROCK, is a therapeutic lead for Huntington disease (HD). The downstream targets that mediate its inhibitory effects on huntingtin (Htt)aggregation and toxicity are unknown. We have identified profilin, a small actin-binding factor that also interacts with Htt, as being a direct target of the ROCK1 isoform. The overexpression of profilin reduces the aggregation of polyglutamine-expanded Htt and androgen receptor (AR) peptides. This requires profilin's G-actin binding activity and its direct interaction with Htt, which are both inhibited by the ROCK1-mediated phosphorylation of profilin at Ser-137. Y-27632 blocks the phosphorylation of profilin in HEK293 cells and primary neurons, which maintains profilin in an active state. The knockdown of profilin blocks the inhibitory effect of Y-27632 on both AR and Htt aggregation. A signaling pathway from ROCK1 to profilin thus controls polyglutamine protein aggregation and is targeted by a promising therapeutic lead for HD. C1 [Shao, Jieya; Diamond, Marc I.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Shao, Jieya; Diamond, Marc I.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. [Welch, William J.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [DiProspero, Nicholas A.] NIH, Neurogenet Branch, Bethesda, MD 20892 USA. RP Diamond, MI (reprint author), Univ Calif San Francisco, Dept Neurol, GH-S572B,600 16th St, San Francisco, CA 94143 USA. EM marc.diamond@ucsf.edu NR 54 TC 61 Z9 64 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2008 VL 28 IS 17 BP 5196 EP 5208 DI 10.1128/MCB.00079-08 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 341DY UT WOS:000258695600006 PM 18573880 ER PT J AU Maceyka, M Alvarez, SE Milstien, S Spiegel, S AF Maceyka, Michael Alvarez, Sergio E. Milstien, Sheldon Spiegel, Sarah TI Filamin A links sphingosine kinase 1 and sphingosine-1-phosphate receptor 1 at lamellipodia to orchestrate cell migration SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; EPIDERMAL-GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; PLASMA-MEMBRANE; DEPENDENT TRANSLOCATION; P21-ACTIVATED KINASES; LYMPHOID ORGANS; PHOSPHORYLATION; ACTIVATION; BINDING AB Sphingosine kinase 1 (SphK1) catalyzes the phosphorylation of sphingosine to produce the potent lipid mediator sphingosine-1-phosphate (S1P), which plays a critical role in cell motility via its cell surface receptors. Here, we have identified filamin A (FLNa), an actin-cross-linking protein involved in cell movement, as a bona fide SphK1-interacting protein. Heregulin stimulated SphK1 activity only in FLNa-expressing A7 melanoma cells but not in FLNa-deficient cells and induced its translocation and colocalization with FLNa at lamellipodia. SphK1 was required for heregulin-induced migration, lamellipodia formation, activation of PAK1, and subsequent FLNa phosphorylation. S1P directly stimulated PAK1 kinase, suggesting that it may be a target of intracellularly generated S1P. Heregulin also induced colocalization of S1P(1) (promotility S1P receptor) but not S1P(2), with SphK1 and FLNa at membrane ruffles. Moreover, an S1P1 antagonist inhibited the lamellipodia formation induced by heregulin. Hence, FLNa links SphK1 and S1P1 to locally influence the dynamics of actin cytoskeletal structures by orchestrating the concerted actions of the triumvirate of SphK1, FLNa, and PAK1, each of which requires and/or regulates the actions of the others, at lamellipodia to promote cell movement. C1 [Maceyka, Michael; Alvarez, Sergio E.; Spiegel, Sarah] Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. [Maceyka, Michael; Alvarez, Sergio E.; Spiegel, Sarah] Virginia Commonwealth Univ, Sch Med, Massey Canc Ctr, Richmond, VA 23298 USA. [Milstien, Sheldon] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, POB 980614,1101 E Marshall St, Richmond, VA 23298 USA. EM sspiegel@vcu.edu FU NCI [R01CA61774, 5T32 CA085159-04]; NIMH Intramural Research; NIH [P30 CA16059] FX This work was supported by NCI grants R01CA61774 (to S. S.) and 5T32 CA085159-04 (to M. M.) and the NIMH Intramural Research Program (S. M.). Confocal microscopy was supported in part by NIH grant P30 CA16059 to the Massey Cancer Center. NR 47 TC 51 Z9 52 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 SEP PY 2008 VL 28 IS 18 BP 5687 EP 5697 DI 10.1128/MCB.00465-08 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 344TU UT WOS:000258951000011 PM 18644866 ER PT J AU Bandyopadhyay, U Kaushik, S Varticovski, L Cuervo, AM AF Bandyopadhyay, Urmi Kaushik, Susmita Varticovski, Lyuba Cuervo, Ana Maria TI The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RAT-LIVER LYSOSOMES; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; MOLECULAR CHAPERONE; SELECTIVE UPTAKE; DEGRADATION; FIBROBLASTS AB Chaperone-mediated autophagy (CMA) is a selective type of autophagy by which specific cytosolic proteins are sent to lysosomes for degradation. Substrate proteins bind to the lysosomal membrane through the lysosome-associated membrane protein type 2A (LAMP-2A), one of the three splice variants of the lamp2 gene, and this binding is limiting for their degradation via CMA. However, the mechanisms of substrate binding and uptake remain unknown. We report here that LAMP-2A organizes at the lysosomal membrane into protein complexes of different sizes. The assembly and disassembly of these complexes are a very dynamic process directly related to CMA activity. Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. The two major chaperones related to CMA, hsc70 and hsp90, play critical roles in the functional dynamics of the LAMP-2A complexes at the lysosomal membrane. Thus, we have identified a novel function for hsc70 in the disassembly of LAMP-2A from these complexes, whereas the presence of lysosome-associated hsp90 is essential to preserve the stability of LAMP-2A at the lysosomal membrane. C1 [Bandyopadhyay, Urmi; Kaushik, Susmita; Cuervo, Ana Maria] Albert Einstein Coll Med, Dept Dev & Mol Biol, Marion Bessin Liver Res Ctr, Bronx, NY 10461 USA. [Bandyopadhyay, Urmi; Kaushik, Susmita; Cuervo, Ana Maria] Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Dept Anat & Struct Biol, Bronx, NY 10461 USA. [Varticovski, Lyuba] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Cuervo, AM (reprint author), Albert Einstein Coll Med, Dept Dev & Mol Biol, Marion Bessin Liver Res Ctr, Ullmann Bldg Room 611D,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM amcuervo@aecom.yu.edu RI Bandyopadhyay, Urmi/A-3944-2015 OI Bandyopadhyay, Urmi/0000-0003-3438-8923 FU NIH/NIA [AG021904, AG25355, DK041918]; Ellison Medical Foundation FX This work was supported by NIH/NIA grants AG021904, AG25355, and DK041918 and by an Ellison Medical Foundation award. NR 37 TC 142 Z9 145 U1 3 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2008 VL 28 IS 18 BP 5747 EP 5763 DI 10.1128/MCB.02070-07 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 344TU UT WOS:000258951000016 PM 18644871 ER PT J AU Park, JJ Cawley, NX Loh, YP AF Park, Joshua J. Cawley, Niamh X. Loh, Y. Peng TI A bi-directional carboxypeptidase E-driven transport mechanism controls BDNF vesicle homeostasis in hippocampal neurons SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE carboxypeptidase E; cytoplasmic tail; BDNF vesicle transport; dynactin ID RETROGRADE AXONAL-TRANSPORT; ACTIVITY-DEPENDENT SECRETION; PROHORMONE SORTING RECEPTOR; NEUROTROPHIC FACTOR; VESICULAR TRANSPORT; CAENORHABDITIS-ELEGANS; CYTOPLASMIC DYNEIN; CORTICAL-NEURONS; DYNACTIN; GRANULES AB Anterograde transport of brain-derived neurotrophic factor (BDNF) vesicles from the soma to neurite terminals is necessary for activity-dependent secretion of BDNF to mediate synaptic plasticity, memory and learning, and retrograde BDNF transport back to the soma for recycling. in our study, overexpression of the cytoplasmic tail of the carboxypeptidase E (CPE) found in BDNF vesicles significantly reduced localization of BDNF in neurites of hippocampal neurons. Live-cell imaging showed that the velocity and distance of movement of fluorescent protein-tagged CPE- or BDNF-containing vesicles were reduced in both directions. in pulldown assays, the CPE tail interacted with dynactin along With kinesin-2 and kinesin-3. and cytoplasmic dynein. Competition assays using a CPE tail peptide verified specific interaction between the CPE tail and dynactin. Thus, the CPE cytoplasmic tail binds dynactin that recruits kinesins or dynein for driving bidirectional transport of BDNF vesicle to maintain vesicle homeostasis and secretion in hippocampal neurons. Published by Elsevier Inc. C1 [Park, Joshua J.; Cawley, Niamh X.; Loh, Y. Peng] NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Program, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Program, NIH, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov FU NICHD; NIH FX We thank Dr. Bai Lu (NICHD, NIH), Dr. Joel Rosenbaum (Yale University), Dr.Trina Schroer(Johns Hopkins University),and Dr. Jennifer Lippincott-Schwartz (NICHD, NIH) for their suggestions and critical reading of the manuscript. We also thank Drs. Hong Lou, Guhan Nagappan and Hisatsugu Koshimizu, all from NICHD for their technical assistance and helpful discussions. We thank Dr. Vincent Schram and Chip Dye in the NICHD Microscopy Imaging Core for their technical support. This research was supported by the Intramural Research Program of the NICHD, NIH. NR 39 TC 32 Z9 32 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD SEP PY 2008 VL 39 IS 1 BP 63 EP 73 DI 10.1016/j.mcn.2008.05.016 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 346EX UT WOS:000259052500007 PM 18573344 ER PT J AU Wang, PY Seabold, GK Wenthold, R AF Wang, Philip Y. Seabold, Gail K. Wenthold, Robert. TI Synaptic adhesion-like molecules (SALMs) promote neurite outgrowth SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; LEUCINE-RICH REPEATS; N-CADHERIN; EXCITATORY SYNAPSES; NMDA RECEPTOR; TRANSMEMBRANE PROTEINS; HIPPOCAMPAL-NEURONS; SURFACE EXPRESSION; AXONAL GROWTH; FAMILY AB SALMs are a family of five adhesion molecules whose expression is largely restricted to the CNS. Initial reports showed that SALM1 functions in neurite Outgrowth while SALM2 is involved in synapse formation. To investigate the function of SALMs in detail, we asked if all five are involved in neurite outgrowth. Expression of epitope-tagged Proteins in cultured hippocampal neurons showed that SALMs are distributed throughout neurons, including axons, dendrites, and growth cones. Over-expression of each SALM resulted in enhanced neurite outgrowth, but with different phenotypes. Neurite Outgrowth could be reduced by applying antibodies targeting the extracellular leucine rich regions of SALMs and with RNAi. Through over-expression of deletion constructs, we found that the C-terminal PDZ binding domains of SALMs 1-3 are required for most aspects Of neurite outgrowth. In addition, by using a chimera of SALMs 2 and 4, we found that the N-terminus is also-involved in neurite outgrowth. Published by Elsevier Inc. C1 [Wang, Philip Y.; Seabold, Gail K.; Wenthold, Robert.] NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. [Wang, Philip Y.] Univ Maryland, Dept Biol, Coll Chem & Life Sci, College Pk, MD 20742 USA. [Wang, Philip Y.] Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA. RP Wenthold, R (reprint author), NIDCD, Neurochem Lab, NIH, 50 S Dr,MSC 8027,Bldg 50,Room 4140, Bethesda, MD 20892 USA. EM wenthold@nidcd.nih.gov FU National Institute on Deafness and Other Communication Disorders (NIDCD) FX We are grateful to Dr. Kai Chang, Dr. Ya-Xian Wang, and Ms. Linna Ge for their excellent technical assistance. We would like to thank Dr. Ronald Petralia, Dr. Rana Al-Hallaq, and members of the Wenthold lab for their invaluable discussions and suggestions on the preparation of this manuscript. This work was supported by the National Institute on Deafness and Other Communication Disorders (NIDCD) Intramural Research Program. NR 47 TC 22 Z9 28 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD SEP PY 2008 VL 39 IS 1 BP 83 EP 94 DI 10.1016/j.mcn.2008.05.019 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 346EX UT WOS:000259052500009 PM 18585462 ER PT J AU Prasad, AB Allard, MW Green, ED AF Prasad, Arjun B. Allard, Marc W. Green, Eric D. CA NISC Comparat Sequencing Program TI Confirming the phylogeny of mammals by use of large comparative sequence data sets SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE Placentalia; Eutheria; Mammalia; mammalian phylogeny; phylogenomics; Atlantogenata; molecular systematics ID NEW-WORLD MONKEYS; PLACENTAL MAMMALS; MITOCHONDRIAL GENOMES; MAXIMUM-LIKELIHOOD; EUTHERIAN RELATIONSHIPS; BAYESIAN PHYLOGENETICS; EVOLUTIONARY HISTORY; MULTIPLE ALIGNMENTS; MOLECULAR EVIDENCE; PRIMATE PHYLOGENY AB The ongoing generation of prodigious amounts of genomic sequence data from myriad vertebrates is providing unparalleled opportunities for establishing definitive phylogenetic relationships among species. The size and complexities of such comparative sequence data sets not only allow smaller and more difficult branches to be resolved but also present unique challenges, including large computational requirements and the negative consequences of systematic biases. To explore these issues and to clarify the phylogenetic relationships among mammals, we have analyzed a large data set of over 60 megabase pairs (Mb) of high-quality genomic sequence, which we generated from 41 mammals and 3 other vertebrates. All sequences are orthologous to a 1.9-Mb region of the human genome that encompasses the cystic fibrosis transmembrane conductance regulator gene (CFTR). To understand the characteristics and challenges associated with phylogenetic analyses of such a large data set, we partitioned the sequence data in several ways and utilized maximum likelihood, maximum parsimony, and Neighbor-Joining algorithms, implemented in parallel on Linux clusters. These studies yielded well-supported phylogenetic trees, largely confirming other recent molecular phylogenetic analyses. Our results provide support for rooting the placental mammal tree between Atlantogenata (Xenarthra and Afrotheria) and Boreoeutheria (Euarchontoglires and Laurasiatheria), illustrate the difficulty in resolving some branches even with large amounts of data (e.g., in the case of Laurasiatheria), and demonstrate the valuable role that very large comparative sequence data sets can play in refining our understanding of the evolutionary relationships of vertebrates. C1 [Prasad, Arjun B.; Green, Eric D.] NHGRI, Gen Technol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Green, Eric D.; NISC Comparat Sequencing Program] NHGRI, NIH Intramural Sequencing Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. [Prasad, Arjun B.] George Washington Univ, Integrated Biosci Program, Washington, DC 20052 USA. [Allard, Marc W.] George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. RP Green, ED (reprint author), NHGRI, Gen Technol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. EM egreen@nhgri.nih.gov RI Prasad, Arjun/C-6736-2008; OI Prasad, Arjun/0000-0002-1343-8664 FU Intramural NIH HHS [Z01 HG000196-07, Z99 HG999999] NR 95 TC 166 Z9 170 U1 9 U2 49 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 EI 1537-1719 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD SEP PY 2008 VL 25 IS 9 BP 1795 EP 1808 DI 10.1093/molbev/msn104 PG 14 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 337ZF UT WOS:000258473400002 PM 18453548 ER PT J AU Chen, J Xiao, L Rao, JN Zou, T Liu, L Bellavance, E Gorospe, M Wang, JY AF Chen, Jie Xiao, Lan Rao, Jaladanki N. Zou, Tongtong Liu, Lan Bellavance, Emily Gorospe, Myriam Wang, Jian-Ying TI JunD represses transcription and translation of the tight junction protein zona occludens-1 modulating intestinal epithelial barrier function SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ANTIGEN-RELATED PROTEIN; AU-RICH-ELEMENT; MESSENGER-RNA; POLYAMINE DEPLETION; OXIDATIVE STRESS; GENE-EXPRESSION; HUMAN-CELLS; C-JUN; BINDING; ZO-1 AB The AP-1 transcription factor JunD is highly expressed in intestinal epithelial cells, but its exact role in maintaining the integrity of intestinal epithelial barrier remains unknown. The tight junction (TJ) protein zonula occludens (ZO)-1 links the intracellular domain of TJ-transmembrane proteins occludin, claudins, and junctional adhesion molecules to many cytoplasmic proteins and the actin cytoskeleton and is crucial for assembly of the TJ complex. Here, we show that JunD negatively regulates expression of ZO-1 and is implicated in the regulation of intestinal epithelial barrier function. Increased JunD levels by ectopic overexpression of the junD gene or by depleting cellular polyamines repressed ZO-1 expression and increased epithelial paracellular permeability. JunD regulated ZO-1 expression at the levels of transcription and translation. Transcriptional repression of ZO-1 by JunD was mediated through cAMP response element-binding protein-binding site within its proximal region of the ZO-1-promoter, whereas induced JunD inhibited ZO- 1 mRNA translation by enhancing the interaction of the ZO-13'-untranslated region with RNA-binding protein T cell-restricted intracellular antigen 1-related protein. These results indicate that JunD is a biological suppressor of ZO- 1 expression in intestinal epithelial cells and plays a critical role in maintaining epithelial barrier function. C1 [Chen, Jie; Xiao, Lan; Rao, Jaladanki N.; Zou, Tongtong; Liu, Lan; Bellavance, Emily; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA. [Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Chen, Jie; Xiao, Lan; Rao, Jaladanki N.; Zou, Tongtong; Liu, Lan; Bellavance, Emily; Wang, Jian-Ying] Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA. [Gorospe, Myriam] NIA, Natl Inst Hlth, Intramural Res Program, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. RP Wang, JY (reprint author), Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA. EM jwang@smail.umaryland.edu FU Department of Veterans Affairs; National Institutes of Health [DK-57819, DK-61972, DK-68491]; National Institute on Aging-Intramural Research Program, National Institutes of Health FX This work was supported by a Merit Review grant (to J.-Y.W.) from the Department of Veterans Affairs and by National Institutes of Health grants DK-57819, DK-61972, and DK-68491 (to J.-Y.W.). J.-Y.W. is a Research Career Scientist, Medical Research Service, U. S. Department of Veterans Affairs. M. G. is supported by the National Institute on Aging-Intramural Research Program, National Institutes of Health. NR 65 TC 36 Z9 39 U1 1 U2 3 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 SEP PY 2008 VL 19 IS 9 BP 3701 EP 3712 DI 10.1091/mbc.E08-02-0175 PG 12 WC Cell Biology SC Cell Biology GA 348AM UT WOS:000259183200008 PM 18562690 ER PT J AU Yeh, CH Hung, LY Hsu, C Le, SY Lee, PT Liao, WL Lin, YT Chang, WC Tseng, JT AF Yeh, Chiu-Hung Hung, Liang-Yi Hsu, Chin Le, Shu-Yun Lee, Pin-Tse Liao, Wan-Lin Lin, Yi-Tseng Chang, Wen-Chang Tseng, Joseph T. TI RNA-binding protein HuR interacts with thrombomodulin 5 ' untranslated region and represses internal ribosome entry site-mediated translation under IL-1 beta treatment SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID TUMOR-NECROSIS-FACTOR; ENDOTHELIAL-CELLS; 5'-UNTRANSLATED REGION; SECONDARY STRUCTURE; GENE-EXPRESSION; TISSUE-FACTOR; INITIATION; SEPSIS; INFLAMMATION; MECHANISM AB Reduction in host-activated protein C levels and resultant microvascular thrombosis highlight the important functional role of protein C anticoagulant system in the pathogenesis of sepsis and septic shock. Thrombomodulin (TM) is a critical factor to activate protein C in mediating the anticoagulation and anti-inflammation effects. However, TM protein content is decreased in inflammation and sepsis, and the mechanism is still not well defined. In this report, we identified that the TM 5' untranslated region (UTR) bearing the internal ribosome entry site (IRES) element controls TM protein expression. Using RNA probe pulldown assay, HuR was demonstrated to interact with the TM 5'UTR. Overexpression of HuR protein inhibited the activity of TM IRES, whereas on the other hand, reducing the HuR protein level reversed this effect. When cells were treated with IL-1 beta, the IRES activity was suppressed and accompanied by an increased interaction between HuR and TM 5'UTR. In the animal model of sepsis, we found the TM protein expression level to be decreased while concurrently observing the increased interaction between HuR and TM mRNA in liver tissue. In summary, HuR plays an important role in suppression of TM protein synthesis in IL-1 beta treatment and sepsis. C1 [Yeh, Chiu-Hung; Hung, Liang-Yi; Chang, Wen-Chang; Tseng, Joseph T.] Natl Cheng Kung Univ, Dept Pharmacol, Tainan 701, Taiwan. [Lee, Pin-Tse] Natl Cheng Kung Univ, Inst Basic Med Sci, Coll Med, Tainan 701, Taiwan. [Hung, Liang-Yi; Liao, Wan-Lin] Natl Cheng Kung Univ, Inst Biosignal Transduct, Tainan 701, Taiwan. [Tseng, Joseph T.] Natl Cheng Kung Univ, Inst Bioinformat, Coll Biosci & Biotechnol, Tainan 701, Taiwan. [Tseng, Joseph T.] Natl Cheng Kung Univ, Ctr Gene Regulat & Signal Transduct Res, Tainan 701, Taiwan. [Hsu, Chin] Kaohsiung Med Univ, Dept Physiol, Grad Inst Physiol & Mol Med, Kaohsiung, Taiwan. [Lin, Yi-Tseng] Kaohsiung Med Univ, Grad Inst Med, Sch Med, Kaohsiung, Taiwan. [Le, Shu-Yun] Natl Canc Inst, Natl Inst Hlth, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. RP Tseng, JT (reprint author), Natl Cheng Kung Univ, Dept Pharmacol, Tainan 701, Taiwan. EM wcchang@mail.ncku.edu.tw; tctseng@mail.ncku.edu.tw RI Hsu, Chin/C-7283-2009 FU National Science Council [NSC 94-2311-B-006-004, NSC 95-2320-B-006-066MY3]; National Cheng-Kung University Project of Promoting Academic Excellence and Developing World Class Research Center; Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank Professor Anne Willis (School of Pharmacy, The University of Nottingham, United Kingdom) for kindly providing the pRF, pRMF, pRHRVF, and phpRF constructs. This work was supported by National Science Council Grant NSC 94-2311-B-006-004 and NSC 95-2320-B-006-066MY3 of Taiwan, National Cheng-Kung University Project of Promoting Academic Excellence and Developing World Class Research Center, and in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 48 TC 25 Z9 25 U1 0 U2 2 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 SEP PY 2008 VL 19 IS 9 BP 3812 EP 3822 DI 10.1091/mbc.E07-09-0962 PG 11 WC Cell Biology SC Cell Biology GA 348AM UT WOS:000259183200018 PM 18579691 ER PT J AU Cheng, WH Muftic, D Muftuoglu, M Dawut, L Morris, C Helleday, T Shiloh, Y Bohr, VA AF Cheng, Wen-Hsing Muftic, Diana Muftuoglu, Meltem Dawut, Lale Morris, Christa Helleday, Thomas Shiloh, Yosef Bohr, Vilhelm A. TI WRN is required for ATM activation and the S-phase checkpoint in response to interstrand cross-link-induced DNA double-strand breaks SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID WERNER-SYNDROME PROTEIN; COLLAPSED REPLICATION FORKS; TELANGIECTASIA-MUTATED ATM; SYNDROME GENE-PRODUCT; HOMOLOGOUS RECOMBINATION; ATAXIA-TELANGIECTASIA; CELLULAR-RESPONSE; SYNDROME CELLS; CHROMATIN-STRUCTURE; TOPOISOMERASE-I AB Werner syndrome (WS)is a human genetic disorder characterized by extensive clinical features of premature aging. Ataxia-telengiectasia (A-T) is a multisystem human genomic instability syndrome that includes premature aging in some of the patients. WRN and ATM, the proteins defective in WS and A-T, respectively, play significant roles in the maintenance of genomic stability and are involved in several DNA metabolic pathways. A role for WRN in DNA repair has been proposed; however, this study provides evidence that WRN is also involved in ATM pathway activation and in a S-phase checkpoint in cells exposed to DNA interstrand cross-link-induced double-strand breaks. Depletion of WRN in such cells by RNA interference results in an intra-S checkpoint defect, and interferes with activation of ATM as well as downstream phosphorylation of ATM target proteins. Treatment of cells under replication stress with the ATM kinase inhibitor KU 55933 results in a S-phase checkpoint defect similar to that observed in WRN shRNA cells. Moreover, gamma H2AX levels are higher in WRN shRNA cells than in control cells 6 and 16 h after exposure to psoralen DNA cross-links. These results suggest that WRN and ATM participate in a replication checkpoint response, in which WRN facilitates ATM activation in cells with psoralen DNA cross-link-induced collapsed replication forks. C1 [Cheng, Wen-Hsing; Muftic, Diana; Muftuoglu, Meltem; Dawut, Lale; Bohr, Vilhelm A.] NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. [Morris, Christa] NIA, NIH, Flow Cytometry Unit, Baltimore, MD 21224 USA. [Cheng, Wen-Hsing] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Muftic, Diana; Helleday, Thomas] Stockholm Univ, Dept Genet Microbiol & Toxicol, Arrhenius Lab, S-10691 Stockholm, Sweden. [Shiloh, Yosef] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, David & Inez Myers Lab Genet Res, IL-69978 Tel Aviv, Israel. RP Bohr, VA (reprint author), NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. EM vbohr@nih.gov RI Helleday, Thomas/D-5224-2013; OI Helleday, Thomas/0000-0002-7384-092X FU Intramural Research Program of the National Institutes of Health; National Institute on Aging; Lilly Lawski Foundation FX We thank G. Smith and A. May for materials and technical support; F. Indig and R. Earley for confocal microscope; and S. A. Martomo, A. Balajan, R. Wersto, and Y. Liu for comments. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, and Lilly Lawski Foundation (D.M.). NR 77 TC 46 Z9 46 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 SEP PY 2008 VL 19 IS 9 BP 3923 EP 3933 DI 10.1091/mbc.E07-07-0698 PG 11 WC Cell Biology SC Cell Biology GA 348AM UT WOS:000259183200027 PM 18596239 ER PT J AU Guirouilh-Barbat, J Redon, C Pommier, Y AF Guirouilh-Barbat, Josee Redon, Christophe Pommier, Yves TI Transcription-coupled DNA double-strand breaks are mediated via the nucleotide excision repair and the Mre11-Rad50-Nbs1 complex SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID DEPENDENT PROTEIN-KINASE; BLOOMS-SYNDROME HELICASE; SOFT-TISSUE SARCOMAS; HISTONE H2AX; HOMOLOGOUS RECOMBINATION; CARIBBEAN TUNICATE; DAMAGE RESPONSE; ATM ACTIVATION; MRE11 COMPLEX; ECTEINASCIDIN-743 ET-743 AB The cellular activity of Yondelis (trabectedin, Ecteinascidin 743, Et743) is known to depend on transcription-coupled nucleotide excision repair (TCR). However, the subsequent cellular effects of Et743 are not fully understood. Here we show that Et743 induces both transcription-and replication-coupled DNA double-strand breaks (DSBs) that are detectible by neutral COMET assay and as gamma-H2AX foci that colocalize with 53BP1, Mre11, Ser(1981)-pATM, and Thr(68)-pChk2. The transcription coupled-DSBs (TC-DSBs) induced by Et743 depended both on TCR and Mre11-Rad50-Nbs1 (MRN) and were associated with DNA-PK-dependent gamma-H2AX foci. In contrast to DNA-PK, ATM phosphorylated H2AX both in NER-proficient and -deficient cells, but its full activation was dependent on H2AX as well as DNA-PK, suggesting a positive feedback loop: DNA-PK-gamma-H2AX-ATM. Knocking-out H2AX or inactivating DNA-PK reduced Et743's antiproliferative activity, whereas ATM and MRN tended to act as survival factors. Our results highlight the interplays between ATM and DNA-PK and their impacts on H2AX phosphorylation and cell survival. They also suggest that gamma-H2AX may serve as a biomarker in patients treated with Et743 and that molecular profiling of tumors for TCR, MRN, ATM, and DNA-PK might be useful to anticipate tumor response to Et743 treatment. C1 [Guirouilh-Barbat, Josee; Redon, Christophe; Pommier, Yves] NCI, NIH, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, NIH, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA. EM pommier@nih.gov FU National Cancer Institute (NCI) Intramural Program; Center for Cancer Research, NCI; National Institutes of Health FX We thank Drs. Chiara Conti, Andrew Jobson, Olivier Sordet, and Kurt W. Kohn for critical reading of the manuscript and suggestions during the course of these experiments. We also thank Dr. Roger Griffin, Department of Chemistry, University of Newcastle, and Dr. Ian Hickson, KuDos Pharmaceuticals. for generously providing the ATM and DNA-PK small molecule inhibitors. This work was supported by the National Cancer Institute (NCI) Intramural Program, Center for Cancer Research, NCI, National Institutes of Health. NR 70 TC 45 Z9 47 U1 0 U2 5 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 SEP PY 2008 VL 19 IS 9 BP 3969 EP 3981 DI 10.1091/mbc.E08-02-0215 PG 13 WC Cell Biology SC Cell Biology GA 348AM UT WOS:000259183200031 PM 18632984 ER PT J AU Bryan, L Paugh, BS Kapitonov, D Wilczynska, KM Alvarez, SM Singh, SK Milstien, S Spiegel, S Kordula, T AF Bryan, Lauren Paugh, Barbara S. Kapitonov, Dmitri Wilczynska, Katarzyna M. Alvarez, Silvina M. Singh, Sandeep K. Milstien, Sheldon Spiegel, Sarah Kordula, Tomasz TI Sphingosine-1-phosphate and interleukin-1 independently regulate plasminogen activator inhibitor-1 and urokinase-type plasminogen activator receptor expression in glioblastoma cells: Implications for invasiveness SO MOLECULAR CANCER RESEARCH LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; HUMAN-BRAIN-TUMORS; PROTEIN-COUPLED RECEPTOR; GASTRIC-CANCER CELLS; SPHINGOSINE KINASE-1; SIGNALING PATHWAYS; GENE AMPLIFICATION; XENOGRAFT MODEL; INVASION; MULTIFORME AB Glioblastoma multiforme is an invasive primary brain tumor, which evades the current standard treatments. The invasion of glioblastoma cells into healthy brain tissue partly depends on the proteolytic and nonproteolytic activities of the plasminogen activator system proteins, including the urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1), and a receptor for uPA (uPAR). Here we show that sphingosine-1-phosphate (S1P) and the inflammatory mediator interleukin-1 (IL-1) increase the mRNA and protein expression of PAI-1 and uPAR and enhance the invasion of U373 glioblastoma cells. Although IL-1 enhanced the expression of sphingosine kinase 1 (Sphk1), the enzyme that produces S1P, down-regulation of SphK1 had no effect on the IL-1-induced uPAR or PAI-1 mRNA expression, suggesting that these actions of IL-1 are independent of S1P production. Indeed, the S1P-induced mRNA expression of uPAR and PAI-1 was blocked by the S1P(2) receptor antagonist JTE013 and by the down-regulation Of S1P2 using siRNA. Accordingly, the inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 and Rho-kinase, two downstream signaling cascades activated by S1P(2), blocked the activation of PAI-1 and uPAR mRNA expression by S1P. More importantly, the attachment of glioblastoma cells was inhibited by the addition of exogenous PAI-1 or siRNA to uPAR, whereas the invasion of glioblastoma cells induced by S1P or IL-1 correlated with their ability to enhance the expression of PAI-1 and uPAR. Collectively, these results indicate that S1P and IL-1 activate distinct pathways leading to the mRNA and protein expression of PAI-1 and uPAR, which are important for glioblastoma invasiveness. C1 [Bryan, Lauren; Paugh, Barbara S.; Kapitonov, Dmitri; Wilczynska, Katarzyna M.; Alvarez, Silvina M.; Singh, Sandeep K.; Spiegel, Sarah; Kordula, Tomasz] Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. [Milstien, Sheldon] NIMH, Bethesda, MD 20892 USA. RP Kordula, T (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. EM tkordula@vcu.edu RI Paugh, Barbara/B-3625-2009 FU NIH [R01 NS044118]; Massey Cancer Center, Virginia Commonwealth University [R01 CA61774]; National Institute of Mental Health Intramural Research Program FX NIH grant R01 NS044118 (T. Kordula); the Pilot Project grant from the Massey Cancer Center, Virginia Commonwealth University (T. Kordula); grant R01 CA61774 (S. Spiegel); and the National Institute of Mental Health Intramural Research Program (S. Milstien). NR 55 TC 29 Z9 30 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD SEP PY 2008 VL 6 IS 9 BP 1469 EP 1477 DI 10.1158/1541-7786.MCR-08-0082 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 359WB UT WOS:000260017800009 PM 18819934 ER PT J AU Liang, XJ Finkel, T Shen, DW Yin, JJ Aszalos, A Gottesman, MM AF Liang, Xing-Jie Finkel, Toren Shen, Ding-Wu Yin, Jun-Jie Aszalos, Adorjan Gottesman, Michael M. TI SIRT1 contributes in part to cisplatin resistance in cancer cells by altering mitochondrial metabolism SO MOLECULAR CANCER RESEARCH LA English DT Article ID LIFE-SPAN EXTENSION; CALORIE RESTRICTION; CELLULAR PHARMACOLOGY; MULTIDRUG-RESISTANCE; REDUCED EXPRESSION; CROSS-RESISTANCE; REGULATES SIRT1; LINES; DEACETYLASE; PROTEINS AB Tumors frequently develop resistance to cisplatin, a platinum drug used as a cornerstone of present-day chemotherapy regimens, significantly decreasing its usefulness in the clinic. Although it is known that cisplatin-resistant (CP-r) cancer cells commonly grow more slowly and exhibit reduced uptake of various compounds, including nutrients, the effect of tumor metabolism on cisplatin resistance is unclear. It was found that in CP-r cells, uptake of 2-deoxyglucose was reduced due to dysfunction and altered morphology of mitochondria compared with cisplatin-sensitive parental cancer cells. The CP-r cells overexpressed SIRT1, a histone deacetylase that plays a central role in DNA damage response and transcriptional silencing. Incubation of drug-sensitive cells in low glucose medium induced the expression of SIRT1 and increased cellular resistance to cisplatin. Reduced SIRT1 expression by a SIRT1 SMART small interfering RNA duplex sensitized the >20-fold resistant CP-r cells to cisplatin treatment 1.5- to 2-fold, and SIRT1 overexpression by SIRT1 cDNA transfection increased cisplatin resistance in cisplatin-sensitive cells by 2- to 3-fold. Our findings therefore suggest that reduced glucose use and altered mitochondrial metabolism mediated by SIRT1 is one of several alterations that contribute to cellular resistance to cisplatin. C1 [Liang, Xing-Jie] Natl Ctr Nanosci & Technol China, Div Nanomed & Nanobiol, Lab Nanobiomed & Nanosafety, Beijing 100190, Peoples R China. [Finkel, Toren] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. [Liang, Xing-Jie; Shen, Ding-Wu; Aszalos, Adorjan; Gottesman, Michael M.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. [Yin, Jun-Jie] US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Liang, XJ (reprint author), Natl Ctr Nanosci & Technol China, Div Nanomed & Nanobiol, Lab Nanobiomed & Nanosafety, Beijing 100190, Peoples R China. EM liangxj@nanoctr.cn RI Yin, Jun Jie /E-5619-2014 FU NIH; National Cancer Institute; Chinese Academy of Sciences [07165111ZX] FX Intramural Research Program of the NIH, National Cancer Institute and Chinese Academy of Sciences "Hundred Talents Program" (07165111ZX). NR 34 TC 51 Z9 52 U1 0 U2 9 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 SEP PY 2008 VL 6 IS 9 BP 1499 EP 1506 DI 10.1158/1541-7786.MCR-07-2130 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 359WB UT WOS:000260017800012 PM 18723829 ER PT J AU Paccione, RJ Miyazaki, H Patel, V Waseern, A Gutkind, JS Zehner, ZE Yeudall, WA AF Paccione, Rachel J. Miyazaki, Hiroshi Patel, Vyomesh Waseern, Ahmad Gutkind, J. Silvio Zehner, Zendra E. Yeudall, W. Andrew TI Keratin down-regulation in vimentin-positive cancer cells is reversible by vimentin RNA interference, which inhibits growth and motility SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN BREAST-CANCER; NF-KAPPA-B; GENE-EXPRESSION; INTERMEDIATE FILAMENTS; TUMOR PROGRESSION; CARCINOMA-CELLS; IN-VITRO; METASTASIS; INVASION AB At later stages of tumor progression, epithelial carcinogenesis is associated with transition to a mesenchymal phenotype, which may contribute to the more aggressive properties of cancer cells and may be stimulated by growth factors such as epidermal growth factor and transforming growth factors-beta. Previously, we found that cells derived from a nodal metastatic squamous cell carcinoma are highly proliferative and motile in vitro and tumorigenic in vivo. In the current study, we have investigated the role of vimentin in proliferation and motility. Cells derived from nodal metastasis express high levels of vimentin, which is undetectable in tumor cells derived from a synchronous primary lesion of tongue. Vimentin expression was enhanced by epidermal growth factor and transforming growth factor-beta both independently and in combination. Use of RNA interference resulted in the generation of stable cell lines that express constitutively low levels of vimentin. RNA interference-mediated vimentin knockdown reduced cellular proliferation, migration, and invasion through a basement membrane substitute by 3-fold compared with nontargeting controls. In addition, cells with reduced vimentin reexpressed differentiation-specific keratins K 13, K 14, and K 15 as a result of increased gene transcription as judged by quantitative PCR and promoter-reporter assays. Furthermore, cells in which vimentin expression was reduced showed a greatly decreased tumorigenic potential, as tumors developing from these cells were 70% smaller than those from control cells. The data suggest that reversal of the mesenchymal phenotype by inhibiting vimentin expression results in reexpression of epithelial characteristics and reduced tumor aggressiveness. C1 [Paccione, Rachel J.; Miyazaki, Hiroshi; Yeudall, W. Andrew] Philips Inst Oral & Craniofacial Mol Biol, Richmond, VA 23298 USA. [Paccione, Rachel J.; Zehner, Zendra E.; Yeudall, W. Andrew] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA USA. [Zehner, Zendra E.; Yeudall, W. Andrew] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD USA. [Waseern, Ahmad] Barts & London Queen Marys Sch Med & Dent, Inst Cell & Mol Sci, Ctr Clin & Diagnost Oral Sci, London, England. RP Yeudall, WA (reprint author), Philips Inst Oral & Craniofacial Mol Biol, POB 980566, Richmond, VA 23298 USA. EM wayeudall@vcu.edu RI Gutkind, J. Silvio/A-1053-2009 FU Philip Morris External Research Program UK Medical Research Council [COSB1A1R]; Medical Research Council FX Philip Morris External Research Program UK Medical Research Council (COSB1A1R); Philip Morris USA (W.A. Yeudall) and Medical Research Council (A. Waseem). NR 50 TC 47 Z9 53 U1 0 U2 2 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 SEP PY 2008 VL 7 IS 9 BP 2894 EP 2903 DI 10.1158/1535-7163.MCT-08-0450 PG 10 WC Oncology SC Oncology GA 350XP UT WOS:000259387300031 PM 18790770 ER PT J AU Okabe, M Szakacs, G Reimers, MA Suzuki, T Hall, MD Abe, T Weinstein, JN Gottesman, MM AF Okabe, Mitsunori Szakacs, Gergely Reimers, Mark A. Suzuki, Toshihiro Hall, Matthew D. Abe, Takaaki Weinstein, John N. Gottesman, Michael M. TI Profiling SLCO and SLC22 genes in the NCI-60 cancer cell lines to identify drug uptake transporters SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ORGANIC CATION TRANSPORTERS; MULTIDRUG-RESISTANCE; MOLECULAR PHARMACOLOGY; MEMBRANE TRANSPORTERS; EXPRESSION; CISPLATIN; CHEMOSENSITIVITY; SENSITIVITY; FAMILY; CHEMORESISTANCE AB Molecular and pharmacologic profiling of the NCI-60 cell panel offers the possibility of identifying pathways involved in drug resistance or sensitivity. Of these, decreased uptake of anticancer drugs mediated by efflux transporters represents one of the best studied mechanisms. Previous studies have also shown that uptake transporters can influence cytotoxicity by altering the cellular uptake of anticancer drugs. Using quantitative real-time PCR, we measured the mRNA expression of two solute carrier (SLC) families, the organic cation/zwitterion transporters (SLC22 family) and the organic anion transporters (SLCO family), totaling 23 genes in normal tissues and the NCI-60 cell panel. By correlating the mRNA expression pattern of the SLCO and SLC22 family member gene products with the growth-inhibitory profiles of 1,429 anticancer drugs and drug candidate compounds tested on the NCI-60 cell lines, we identified SLC proteins that are likely to play a dominant role in drug sensitivity. To substantiate some of the SLC-drug pairs for which the SLC member was predicted to be sensitizing, follow-up experiments were performed using engineered and characterized cell lines overexpressing SLC22A4 (OCTN1). As predicted by the statistical correlations, expression of SLC22A4 resulted in increased cellular uptake and heightened sensitivity to mitoxantrone and doxorubicin. Our results indicate that the gene expression database can be used to identify SLCO and SLC22 family members that confer sensitivity to cancer cells. C1 [Okabe, Mitsunori; Szakacs, Gergely; Suzuki, Toshihiro; Hall, Matthew D.; Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Reimers, Mark A.; Weinstein, John N.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Szakacs, Gergely] Hungarian Acad Sci, Inst Enzymol, Biol Res Ctr, Budapest, Hungary. [Reimers, Mark A.] Virginia Commonwealth Univ, Dept Biostat, Richmond, VA USA. [Suzuki, Toshihiro] Meiji Pharmaceut Univ, Dept Analyt Biochem, Tokyo, Japan. [Abe, Takaaki] Tohoku Univ, Grad Sch Med, Dept Med, Div Nephrol Endocrinol & Vasc Med, Sendai, Miyagi, Japan. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Szakacs, Gergely/A-2580-2009; Hall, Matthew/B-2132-2010 OI Szakacs, Gergely/0000-0002-9311-7827; FU NIH, National Cancer Institute; Japan Society for the Promotion of Science; Leukemia and Lymphoma Society FX Intramural Research Program of the NIH, National Cancer Institute, and Japan Society for the Promotion of Science. G. Szakacs is a Bolyai fellow and a special fellow of the Leukemia and Lymphoma Society. NR 40 TC 73 Z9 75 U1 3 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD SEP PY 2008 VL 7 IS 9 BP 3081 EP 3091 DI 10.1158/1535-7163.MCT-08-0539 PG 11 WC Oncology SC Oncology GA 350XP UT WOS:000259387300050 PM 18790787 ER PT J AU Risek, B Bilski, P Rice, AB Schrader, WT AF Risek, Boris Bilski, Piotr Rice, Annette B. Schrader, William T. TI Androgen receptor-mediated apoptosis is regulated by photoactivatable androgen receptor ligands SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID INDEPENDENT PROSTATE-CANCER; LONG-LIVED RADICALS; CELL-DEATH; VITAMIN-C; SINGLET OXYGEN; LNCAP CELLS; OXIDATIVE STRESS; BYSTANDER CELLS; BINDING DOMAIN; MUTATION AB We have studied nonsteroidal ligands of the human androgen receptor (hAR) and have shown elsewhere that when photoactivated by visible light they collide with O(2) to yield singlet oxygens ((1)O(2)) in vitro. Here we report cell killing after brief light activation ( 405 nm) of 1,2,3,4-tetrahydro-2,2-dimethyl-6-( trifluoromethyl)-8- pyridono[ 5,6-g] quinoline (TDPQ) in human prostate tumor cells. TDPQ/AR complexes were required for the death response because AR-positive LNCaP cells were killed, whereas AR-negative PC-3 cells were resistant. Excess dihydrotestosterone (DHT) blocked the TDPQ effect when the two were added together; irradiation of cells containing DHT alone had no effect. When LNCaP AR expression was suppressed using small interfering oligonucleotides targeting AR, photocytotoxicity was diminished. Conversely, stable transfection of hAR into PC-3 results were obtained using a structural isomer of TDPQ, and also the synthetic steroidal AR ligand R1881. Cell death occurred via apoptosis as demonstrated by annexin V immunostaining, nuclear condensation, and caspase inhibition. Death involved oxidative stress, because it was prevented by addition of the antioxidant ascorbic acid during photoactivation. Detection of elevated levels of 8-hydroxy-2'-deoxyguanosine in nuclei of irradiated cells indicated oxidative DNA damage. Apoptosis spread into adjacent nonirradiated cells by direct cell-cell contacts, indicative of a bystander effect. Other photoactivatable ligands are described, implying a general method for ablation of cells bearing specific nuclear hormone receptors. C1 [Risek, Boris; Rice, Annette B.; Schrader, William T.] NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Bilski, Piotr] NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Schrader, WT (reprint author), NIEHS, Reprod & Dev Toxicol Lab, 3 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM schrader@niehs.nih.gov FU Intramural Research Program of the National Institutes of Health; National Institute of Environmental Health Sciences FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 54 TC 5 Z9 5 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 SEP PY 2008 VL 22 IS 9 BP 2099 EP 2115 DI 10.1210/me.2007-0426 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 343LX UT WOS:000258856400009 PM 18562628 ER PT J AU Schoser, B Bruno, C Schneider, HC Shin, YS Podskarbi, T Goldfarb, L Muller-Felber, W Muller-Hocker, J AF Schoser, Benedikt Bruno, Claudio Schneider, Hans-Christian Shin, Yoon S. Podskarbi, Teodor Goldfarb, Lev Mueller-Felber, Wolfgang Mueller-Hoecker, Josef TI Unclassified polysaccharidosis of the heart and skeletal muscle in siblings SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE glycogenosis type 4; idiopathic polysaccharide storage disease; polyglucosan body; cardiomyopathy; heart transplantation ID GLYCOGEN-STORAGE-DISEASE; HYPERTROPHIC CARDIOMYOPATHY; IV GLYCOGENOSIS; AMYLOPECTINOSIS; MYOPATHY; SEQUENCE; LIGHT AB We describe a 15-year-old boy and his 19-year-old sister with progressive dilated cardiomyopathy and mild non-progressive proximal lower limb myopathy, secondary to the accumulation of amylopectin-like fibrillar glycogen, (polyglucosan) bodies, in heart and skeletal muscle. Evidence of idiopathic amylopectinosis or polysaccharidosis was demonstrated in heart and skeletal muscle tissue by histology, electron microscopy, biochemical, and genetic analysis. In both siblings the heart muscle stored PAS-positive, proteinase-k resistant and partly diastase resistant granulo-filamentous material, simulating polyglucosan bodies. Glycogen branching enzyme activity, and phosphofructokinase enzyme activity, measured in skeletal muscle tissue and explanted heart tissue were all within the normal limits, however glycogen content was elevated. Furthermore, GBE1, PRKAG2, desmin, alpha beta-crystallin, ZASP, myotilin, and LAMP-2 gene sequencing revealed no mutation, excluding e.g. glycogen storage disease type 4 and desmin-related myofibrillar cardiomyopathies. In both patients the diagnosis of an idiopathic polysaccharidosis with progressive dilated cardiomyopathy was made, requiring heart transplantation at age 13 and 14, respectively. Both patients belong to an autosomal recessive group of biochemically and genetically unclassified severe vacuolar glycogen storage disease of the heart and skeletal muscle. Up to now unidentified glycogen synthesis or glycogen degradation pathways are supposed to contribute to this idiopathic glycogen storage disease. (C) 2008 Elsevier Inc. All rights reserved. C1 [Schoser, Benedikt] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-80336 Munich, Germany. [Bruno, Claudio] Univ Genoa, Dept Pediat, Neuromuscular Dis Unit, Genoa, Italy. [Schneider, Hans-Christian] Community Hosp Reutlingen, Dept Pediat, Reutlingen, Germany. [Shin, Yoon S.; Podskarbi, Teodor] Mol Genet & Metab Lab, Munich, Germany. [Goldfarb, Lev] NIH, Bethesda, MD 20892 USA. [Mueller-Felber, Wolfgang] Univ Munich, Dept Neuropediat, Friedrich Baur Inst, D-80336 Munich, Germany. [Mueller-Hoecker, Josef] Univ Munich, Dept Pathol, D-80336 Munich, Germany. RP Schoser, B (reprint author), Univ Munich, Dept Neurol, Friedrich Baur Inst, Ziemssenstr 1A, D-80336 Munich, Germany. EM bschoser@med.uni-muenchen.de RI Bruno, Claudio/A-3148-2015; OI Bruno, Claudio/0000-0002-3426-2901; Schoser, Benedikt/0000-0002-2757-8131 FU Intramural NIH HHS [Z01 NS002973-09] NR 20 TC 7 Z9 7 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 SEP-OCT PY 2008 VL 95 IS 1-2 BP 52 EP 58 DI 10.1016/j.ymgme.2008.07.005 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 358TS UT WOS:000259941000009 PM 18691923 ER PT J AU Buccafusca, R Venditti, CP Kenyon, LC Johanson, RA Van Bockstaele, E Ren, J Pagliardini, S Minarcik, J Golden, JA Coady, MJ Greer, JJ Berry, GT AF Buccafusca, Roberto Venditti, Charles P. Kenyon, Lawrence C. Johanson, Roy A. Van Bockstaele, Elisabeth Ren, Jun Pagliardini, Silvia Minarcik, Jeremy Golden, Jeffrey A. Coady, Michael J. Greer, John J. Berry, Gerard T. TI Characterization of the null murine sodium/myo-inositol cotransporter 1 (Smit1 or Slc5a3) phenotype: Myo-inositol rescue is independent of expression of its cognate mitochondrial ribosomal protein subunit 6 (Mrps6) gene and of phosphatidylinositol levels in neonatal brain SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE myo-inositol; phosphatidylinositol; Slc5a3 or Smit1; Mprs6; knockout; MALDI-TOF MS; central apnea; development; lithium; galactosemia ID ARTHROGRYPOSIS MULTIPLEX CONGENITA; DOWN-SYNDROME; LITHIUM; MONOPHOSPHATASE; IDENTIFICATION; MECHANISM; HYPERTONICITY; GALACTOSEMIA; METABOLISM; PHOSPHATES AB Ablation of the murine Slc5a3 gene results in severe myo-inositol (Ins) deficiency and congenital central apnea due to abnormal respiratory rhythmogenesis. The lethal knockout phenotype may be rescued by supplementing the maternal drinking water with 1% Ins. In order to test the hypothesis that Ins deficiency leads to inositide deficiencies, which are corrected by prenatal treatment, we measured the effects of Ins rescue on Ins, phosphatidylinositol (PtdIns) and myo-inositol polyphosphate levels in brains of E18.5 knockout fetuses. As the Slc5a3 gene structure is unique in the sodium/solute cotransporter (SLC5) family, and exon 1 is shared with the mitochondrial ribosomal protein subunit 6 (Mrps6) gene, we also sought to determine whether expression of its cognate Mrps6 gene is abnormal in knockout fetuses. The mean level of Ins was increased by 92% in brains of rescued Slc5a3 knockout fetuses (0.48 versus 0.25 nmol/mg), but was still greatly reduced in comparison to wildtype (6.97 nmol/mg). The Ptdlns, InSP(5) and InsP(6) levels were normal without treatment. Mrps6 gene expression was unaffected in the E18.5 knockout fetuses. This enigmatic model is not associated with neonatal PtdIns deficiency and rescue of the phenotype may be accomplished without restoration of Ins. The biochemical mechanism that both uniformly leads to death and allows for Ins rescue remains unknown. In conclusion, in neonatal brain tissue, Mrps6 gene expression may not be contingent on function of its embedded Slc5a3 gene, while inositide deficiency may not be the mechanism of lethal apnea in null Slc5a3 mice. (C) 2008 Elsevier Inc. All rights reserved. C1 [Buccafusca, Roberto; Berry, Gerard T.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Buccafusca, Roberto; Johanson, Roy A.; Berry, Gerard T.] Thomas Jefferson Univ, Dept Pediat, Philadelphia, PA 19107 USA. [Venditti, Charles P.] NHGRI, NIH, Bethesda, MD 20892 USA. [Van Bockstaele, Elisabeth] Thomas Jefferson Univ, Farber Inst Neurosci, Philadelphia, PA 19107 USA. [Ren, Jun; Pagliardini, Silvia; Greer, John J.] Univ Alberta, Dept Physiol, Edmonton, AB T6G 2M7, Canada. [Minarcik, Jeremy; Golden, Jeffrey A.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pathol, Philadelphia, PA 19104 USA. [Coady, Michael J.] Univ Montreal, Dept Phys, Montreal, PQ H3C 3J7, Canada. RP Berry, GT (reprint author), Childrens Hosp, Div Genet, Enders Bldg,Room 507,300 Longwood Ave, Boston, MA 02115 USA. EM gerard.berry@childrens.harvard.edu NR 77 TC 15 Z9 15 U1 1 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 SEP-OCT PY 2008 VL 95 IS 1-2 BP 81 EP 95 DI 10.1016/j.ymgme.2008.05.008 PG 15 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 358TS UT WOS:000259941000013 PM 18675571 ER PT J AU Sameni, M Dosescu, J Yamada, KM Sloane, BF Cavallo-Medved, D AF Sameni, Mansoureh Dosescu, Julie Yamada, Kenneth M. Sloane, Bonnie F. Cavallo-Medved, Dora TI Functional Live-Cell Imaging Demonstrates that beta(1)-Integrin Promotes Type IV Collagen Degradation by Breast and Prostate Cancer Cells SO MOLECULAR IMAGING LA English DT Article ID COLORECTAL-CARCINOMA CELLS; CATHEPSIN-B; PLASMINOGEN-ACTIVATOR; IN-VIVO; MATRIX-METALLOPROTEINASE; PERICELLULAR PROTEOLYSIS; 3-DIMENSIONAL COLLAGEN; INTEGRIN EXPRESSION; MMP-13 EXPRESSION; BETA(1) INTEGRIN AB The ability of tumor cells to adhere to, migrate on, and remodel extracellular matrices is mediated by cell surface receptors such as beta(1)-integrins. Here we conducted functional live-cell imaging in real time to investigate the effects of modulating beta(1)-integrin expression and function on proteolytic remodeling of the extracellular matrix. Human breast and prostate cancer cells were grown on reconstituted basement membrane containing a quenched fluorescent form of collagen IV. Generation of cleavage products and the resulting increases in fluorescence were imaged and quantified. Decreases in the expression and activity of beta(1)-integrin reduced digestion of quenched fluorescent-collagen IV by the breast and prostate cancer cells and correspondingly their invasion through and migration on reconstituted basement membrane. Decreased extracellular matrix degradation also was associated with changes in the constituents of proteolytic pathways: decreases in secretion of the cysteine protease cathepsin B, the matrix metalloproteinase (MMP)-13, and tissue inhibitors of metalloproteinases (TIMP)-1 and 2; a decrease in expression of MMP-14 or membrane type 1 MMP; and an increase in secretion of TIMP-3. This is the first study to demonstrate through functional live-cell imaging that downregulation of beta(1)-integrin expression and function reduces proteolysis of collagen IV by breast and prostate cancer cells. C1 [Cavallo-Medved, Dora] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Cavallo-Medved, D (reprint author), Wayne State Univ, Sch Med, Dept Pharmacol, 540 E Canfield, Detroit, MI 48201 USA. EM dcavallo@med.wayne.edu FU National Institutes of Health (NIH) [CA 56586, P30 CA 22453, P30 ES 06639, U54 RR02084330]; Department of Defense [PC991261] FX This work was supported by National Institutes of Health (NIH) grant CA 56586 and Department of Defense Award PC991261. The Microscopy and Imaging Resource Center is supported, in part, by NIH Center grants P30 CA 22453, P30 ES 06639, and U54 RR02084330. K.M.Y. was supported in part by the intramural Research Program of the NIH, National Institute of Dental and Craniofacial Research. NR 49 TC 23 Z9 23 U1 0 U2 3 PU B C DECKER INC PI HAMILTON PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD SEP-OCT PY 2008 VL 7 IS 5 BP 199 EP 213 DI 10.2310/7290.2008.00019 PG 15 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 389EI UT WOS:000262073300001 PM 19123990 ER PT J AU Bar, C Zabel, R Liu, SH Stark, MJR Schaffrath, R AF Baer, Christian Zabel, Rene Liu, Shihui Stark, Michael J. R. Schaffrath, Raffael TI A versatile partner of eukaryotic protein complexes that is involved in multiple biological processes: Kti11/Dph3 SO MOLECULAR MICROBIOLOGY LA English DT Article ID KLUYVEROMYCES-LACTIS ZYMOCIN; SACCHAROMYCES-CEREVISIAE REVEALS; ADP-RIBOSYLATING TOXINS; DIPHTHERIA-TOXIN; TRANSFER-RNA; TRANSLATION ELONGATION-FACTOR-2; ELONGATOR COMPLEX; TRANSCRIPTIONAL ELONGATION; DIPHTHAMIDE BIOSYNTHESIS; GAMMA-TOXIN AB The Kluyveromyces lactis killer toxin zymocin insensitive 11 (KTI11) gene from Saccharomyces cerevisiae is allelic with the diphthamide synthesis 3 (DPH3) locus. Here, we present evidence that the KTI11 gene product is a versatile partner of proteins and operates in multiple biological processes. Notably, Kti11 immune precipitates contain Elp2 and Elp5, two subunits of the Elongator complex which is involved in transcription, tRNA modification and zymocin toxicity. KTI11 deletion phenocopies Elongator-minus cells and causes antisuppression of nonsense and missense suppressor tRNAs (SUP4, SOE1), zymocin resistance and protection against the tRNase attack of zymocin. In addition and unlike Elongator mutants, kti11 mutants resist diphtheria toxin (DT), protect against ADP-ribosylation of eukaryotic translation elongation factor 2 (eEF2) by DT and induce resistance against sordarin, an eEF2 poisoning antifungal. The latter phenotype applies to all diphthamide mutants (dph1-dph5) tested and Kti11/Dph3 physically interacts with diphthamide synthesis factors Dph1 and Dph2, presumably as part of a trimeric complex. Moreover, we present a separation of function mutation in KTI11, kti11-1, which dissociates zymocin resistance from DT sensitivity. It encodes a C-terminal Kti11 truncation that almost entirely abolishes Elongator interaction without affecting association with Kti13, another Kti11 partner protein. C1 [Baer, Christian; Zabel, Rene; Schaffrath, Raffael] Univ Halle Wittenberg, Inst Genet, D-06120 Halle, Germany. [Liu, Shihui] Natl Inst Allergy & Infect Dis, Bacteria Toxins & Therapeut Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. [Stark, Michael J. R.] Univ Dundee, Coll Life Sci, Wellcome Trust Ctr Gene Regulat & Express, Dundee DD1 5EH, Scotland. RP Schaffrath, R (reprint author), Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. EM rs240@le.ac.uk RI Stark, Michael/B-2815-2014 OI Stark, Michael/0000-0001-9086-191X NR 59 TC 22 Z9 22 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 2008 VL 69 IS 5 BP 1221 EP 1233 DI 10.1111/j.1365-2958.2008.06350.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 334LG UT WOS:000258222700011 PM 18627462 ER PT J AU Zhang, A Rosner, JL Martin, RG AF Zhang, Aixia Rosner, Judah L. Martin, Robert G. TI Transcriptional activation by MarA, SoxS and Rob of two tolC promoters using one binding site: a complex promoter configuration for tolC in Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID EFFLUX PUMP; MICROARRAY DATA; REGULON; PROTEIN; SYSTEM; ORIENTATION; RESISTANCE; SEQUENCE; OPERON; K-12 AB The Escherichia coli tolC encodes a major outer membrane protein with multiple functions in export (e.g. diverse xenobiotics, haemolysin) and as an attachment site for phage and colicins. tolC is regulated in part by MarA, SoxS and Rob, three paralogous transcriptional activators which bind a sequence called the marbox and which activate multiple antibiotic and superoxide resistance functions. Two previously identified tolC promoters, p1 and p2, are not regulated by MarA, SoxS or Rob but p2 is activated by EvgAS and PhoPQ which also regulate other functions. Using transcriptional fusions and primer extension assays, we show here that tolC has two additional strong overlapping promoters, p3 and p4, which are downstream of p1, p2 and the marbox and are activated by MarA, SoxS and Rob. p3 and p4 are configured so that a single marbox suffices to activate transcription from both promoters. At the p3 promoter, the marbox is separated by 20 bp from the -10 hexamer for RNA polymerase but at the p4 promoter, the same marbox is separated by 30 bp from the -10 hexamer. The multiple tolC promoters may allow the cell to respond to diverse environments by co-ordinating tolC transcription with other appropriate functions. C1 [Rosner, Judah L.; Martin, Robert G.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Zhang, Aixia] NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Rosner, JL (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM jlrosner@helix.nih.gov FU NIH FX We thank G. Storz for discussions. This research was supported by the Intramural Research Program of the NIH. NR 29 TC 16 Z9 17 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 2008 VL 69 IS 6 BP 1450 EP 1455 DI 10.1111/j.1365-2958.2008.06371.x PG 6 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 339VX UT WOS:000258606500012 PM 18673442 ER PT J AU Ge, Y Byun, JS De Luca, P Gueron, G Yabe, IM Sadiq-Ali, SG Figg, WD Quintero, J Haggerty, CM Li, QQ De Siervi, A Gardner, K AF Ge, Yun Byun, Jung S. De Luca, Paola Gueron, Geraldine Yabe, Idalia M. Sadiq-Ali, Sara G. Figg, William D. Quintero, Jesse Haggerty, Cynthia M. Li, Quentin Q. De Siervi, Adriana Gardner, Kevin TI Combinatorial antileukemic disruption of oxidative homeostasis and mitochondrial stability by the redox reactive thalidomide 2-(2,4-difluoro-phenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3(2H)-dione (CPS49) and flavopiridol SO MOLECULAR PHARMACOLOGY LA English DT Article ID DEPENDENT KINASE INHIBITOR; NF-KAPPA-B; INDUCED APOPTOSIS; CANCER-CELLS; S-PHASE; CYCLIN; ANALOGS; TRANSCRIPTION; MECHANISM; NECROSIS AB 2-(2,4-Difluoro-phenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3(2H)-dione (CPS49) is a member of a recently identified class of redox-reactive thalidomide analogs that show selective killing of leukemic cells by increasing intracellular reactive oxygen species (ROS) and targeting multiple transcriptional pathways. Flavopiridol is a semisynthetic flavonoid that inhibits cyclin-dependent kinases and also shows selective lethality against leukemic cells. The purpose of this study is to explore the efficacy and mechanism of action of the combinatorial use of the redox-reactive thalidomide CPS49 and the cyclin-dependent kinase inhibitor flavopiridol as a selective antileukemic therapeutic strategy. In combination, CPS49 and flavopiridol were found to induce selective cytotoxicity associated with mitochondrial dysfunction and elevations of ROS in leukemic cells ranging from additive to synergistic activity at low micromolar concentrations. Highest synergy was observed at the level of ROS generation with a strong correlation between cell-specific cytotoxicity and reciprocal coupling of drug-induced ROS elevation with glutathione depletion. Examination of the transcriptional targeting of CPS49 and flavopiridol combinations reveals that the drugs act in concert to initiate a cell specific transcriptional program that manipulates nuclear factor-kappa B (NF-kappa B), E2F-1, and p73 activity to promote enhanced mitochondrial instability by simultaneously elevating the expression of the proapoptotic factors BAX, BAD, p73, and PUMA while depressing expression of the antiapoptotic genes MCL1, XIAP, BCL-xL, SURVIVIN, and MDM2. The coadministration of CPS49 and flavopiridol acts through coordinate targeting of transcriptional pathways that enforce selective mitochondrial dysfunction and ROS elevation and is therefore a promising new therapeutic combination that warrants further preclinical exploration. C1 [Ge, Yun; Byun, Jung S.; Yabe, Idalia M.; Sadiq-Ali, Sara G.; Quintero, Jesse; Haggerty, Cynthia M.; Li, Quentin Q.; De Siervi, Adriana; Gardner, Kevin] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. [Figg, William D.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [De Luca, Paola; Gueron, Geraldine; De Siervi, Adriana] Univ Buenos Aires, Dept Biochem, RA-1053 Buenos Aires, DF, Argentina. RP Gardner, K (reprint author), NCI, Lab Receptor Biol & Gene Express, Bldg 41,Rm 41-D305, Bethesda, MD 20892 USA. EM gardnerk@mail.nih.gov RI Figg Sr, William/M-2411-2016 FU National Cancer Institutes; National Institutes of Health FX This work was funded through intramural research program of the National Cancer Institutes, National Institutes of Health. NR 42 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 2008 VL 74 IS 3 BP 872 EP 883 DI 10.1124/mol.107.040808 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 340HU UT WOS:000258637500033 PM 18556456 ER PT J AU Surapureddi, S Rana, R Reddy, JK Goldstein, JA AF Surapureddi, Sailesh Rana, Ritu Reddy, Janardan K. Goldstein, Joyce A. TI Nuclear receptor coactivator 6 mediates the synergistic activation of human cytochrome P-4502C9 by the constitutive androstane receptor and hepatic nuclear factor-4 alpha SO MOLECULAR PHARMACOLOGY LA English DT Article ID PREGNANE-X-RECEPTOR; INTERACTING PROTEIN PRIP; HUMAN CYP2B6 GENE; NUCLEAR-RECEPTOR; CROSS-TALK; TRANSCRIPTIONAL REGULATION; COACTIVATOR PRIP; MOUSE-LIVER; GLUCOCORTICOID RECEPTOR; SIGNAL COINTEGRATOR-2 AB Nuclear receptor coactivator 6 (NCOA6) also known as PRIP/RAP250/ASC-2 anchors a steady-state complex of cofactors and function as a transcriptional coactivator for certain nuclear receptors. This is the first study to identify NCOA6 as a hepatic nuclear factor 4 alpha (HNF4 alpha)-interacting protein. CYP2C9 is an important enzyme that metabolizes both commonly used therapeutic drugs and important endogenous compounds. We have shown previously that constitutive androstane receptor (CAR) (a xenobiotic-sensing receptor) up-regulates the CYP2C9 promoter through binding to a distal site, whereas HNF4 alpha transcriptionally up-regulates CYP2C9 via proximal sites. We demonstrate ligand-enhanced synergistic cross-talk between CAR and HNF4 alpha. We identify NCOA6 as crucial to the underlying mechanism of this cross-talk. NCOA6 was identified as an HNF4 alpha-interacting protein in this study using a yeast two-hybrid screen and GST pull-down assays. Furthermore, we identified NCOA6, CAR, and other coactivators as part of a mega complex of cofactors associated with HNF4 alpha in HepG2 cells. Although the interaction of NCOA6 with CAR is specifically through the first LXXLL motif of NCOA6, both LXXLL motifs are involved in its interaction with HNF4 alpha. Silencing of NCOA6 abrogated the synergistic activation of the CYP2C9 promoter and the synergistic induction of the CYP2C9 gene by CAR-HNF4 alpha. Chromatin immunoprecipitation analysis revealed that NCOA6 can pull down both the proximal HNF4 alpha and distal CAR binding sites of the CYP2C9 promoter and provides the basis for the recruitment of other cofactors. We conclude that the coactivator NCOA6 mediates the mechanism of the synergistic activation of the CYP2C9 gene by CAR and HNF4 alpha. C1 [Surapureddi, Sailesh; Rana, Ritu; Goldstein, Joyce A.] NIEHS, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Reddy, Janardan K.] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL USA. RP Goldstein, JA (reprint author), NIEHS, Pharmacol Lab, NIH, A3-02,POB 12233, Res Triangle Pk, NC 27709 USA. EM goldste1@niehs.nih.gov RI Rana, Ritu/F-2591-2011; Goldstein, Joyce/A-6681-2012 FU National Institutes of Health [CA104578]; National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the National Institutes of Health and National Institute of Environmental Health Sciences (to S. S., R. R., and J. A. G.) and in part by National Institutes of Health grant CA104578 (to J. K. R.). NR 59 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 2008 VL 74 IS 3 BP 913 EP 923 DI 10.1124/mol.108.048983 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 340HU UT WOS:000258637500037 PM 18552123 ER PT J AU Phillips, M Ladouceur, C Drevets, W AF Phillips, M. L. Ladouceur, C. D. Drevets, W. C. TI A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder SO MOLECULAR PSYCHIATRY LA English DT Review DE emotion regulation; voluntary emotion regulation; automatic emotion regulation; affective neuroscience; neurodevelopment; bipolar disorder ID MEDIAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; VOXEL-BASED MORPHOMETRY; GRAY-MATTER VOLUME; EVENT-RELATED FMRI; COMPARATIVE CYTOARCHITECTONIC ANALYSIS; CORTICOCORTICAL CONNECTION PATTERNS; HUMAN FRONTAL-CORTEX; WORKING-MEMORY TASK; FACIAL EXPRESSIONS AB The ability to regulate emotions is an important part of adaptive functioning in society. Advances in cognitive and affective neuroscience and biological psychiatry have facilitated examination of neural systems that may be important for emotion regulation. In this critical review we first develop a neural model of emotion regulation that includes neural systems implicated in different voluntary and automatic emotion regulatory subprocesses. We then use this model as a theoretical framework to examine functional neural abnormalities in these neural systems that may predispose to the development of a major psychiatric disorder characterized by severe emotion dysregulation, bipolar disorder. C1 [Phillips, M. L.; Ladouceur, C. D.; Drevets, W. C.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Phillips, M. L.] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales. [Drevets, W. C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. RP Phillips, M (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, 121 Meyran Ave, Pittsburgh, PA 15213 USA. EM phillipsml@upmc.edu RI Ladouceur, C/H-3124-2016 FU NIMH [R01( MH076971-01)]; NARSAD Independent Investigator Award; NARSAD Young Investigator Award; NIMH DIRP FX This study was supported by NIMH, R01( MH076971-01) to MLP; NARSAD Independent Investigator Award to MLP; NARSAD Young Investigator Award to CDL and NIMH DIRP support for WCD. NR 213 TC 481 Z9 490 U1 17 U2 89 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 SEP PY 2008 VL 13 IS 9 BP 833 EP 857 DI 10.1038/mp.2008.65 PG 25 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 339IJ UT WOS:000258571000003 PM 18574483 ER PT J AU Shaltiel, G Maeng, S Malkesman, O Pearson, B Schloesser, R Tragon, T Rogawski, M Gasior, M Luckenbaugh, D Chen, G Manji, H AF Shaltiel, G. Maeng, S. Malkesman, O. Pearson, B. Schloesser, R. J. Tragon, T. Rogawski, M. Gasior, M. Luckenbaugh, D. Chen, G. Manji, H. K. TI Evidence for the involvement of the kainate receptor subunit GluR6 (GRIK2) in mediating behavioral displays related to behavioral symptoms of mania SO MOLECULAR PSYCHIATRY LA English DT Article DE glutamate receptor 6 (GluR6); kainate receptors (KARs); mood-related behaviors; bipolar disorder (BPD); knockout mice (KO); lithium ID BIPOLAR AFFECTIVE-DISORDER; METABOTROPIC REGULATION; SYNAPTIC PLASTICITY; SURFACE EXPRESSION; SUICIDAL-BEHAVIOR; MAJOR DEPRESSION; CHROMOSOMES 6Q; ANIMAL-MODELS; MICE LACKING; MAP KINASE AB The glutamate receptor 6 (GluR6 or GRIK2, one of the kainate receptors) gene resides in a genetic linkage region (6q21) associated with bipolar disorder (BPD), but its function in affective regulation is unknown. Compared with wild-type (WT) and GluR5 knockout ( KO) mice, GluR6 KO mice were more active in multiple tests and super responsive to amphetamine. In a battery of specific tests, GluR6 KO mice also exhibited less anxious or more risk-taking type behavior and less despair-type manifestations, and they also had more aggressive displays. Chronic treatment with lithium, a classic antimanic mood stabilizer, reduced hyperactivity, aggressive displays and some risk-taking type behavior in GluR6 KO mice. Hippocampal and prefrontal cortical membrane levels of GluR5 and KA-2 receptors were decreased in GluR6 KO mice, and chronic lithium treatment did not affect these decreases. The membrane levels of other glutamatergic receptors were not significantly altered by GluR6 ablation or chronic lithium treatment. Together, these biochemical and behavioral results suggest a unique role for GluR6 in controlling abnormalities related to the behavioral symptoms of mania, such as hyperactivity or psychomotor agitation, aggressiveness, driven or increased goal-directed pursuits, risk taking and supersensitivity to psychostimulants. Whether GluR6 perturbation is involved in the mood elevation or thought disturbance of mania and the cyclicity of BPD are unknown. The molecular mechanism underlying the behavioral effects of lithium in GluR6 KO mice remains to be elucidated. C1 [Shaltiel, G.; Maeng, S.; Malkesman, O.; Pearson, B.; Schloesser, R. J.; Tragon, T.; Luckenbaugh, D.; Chen, G.; Manji, H. K.] NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. [Rogawski, M.; Gasior, M.] NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. RP Manji, H (reprint author), NIMH, Mol Pathophysiol Lab, NIH, Bldg 35,Room 1C-912,35 Convent Dr MSC-3711, Bethesda, MD 20892 USA. EM manjih@mail.nih.gov RI Rogawski, Michael/B-6353-2009; Chen, Guang/A-2570-2017; OI Rogawski, Michael/0000-0002-3296-8193; Pearson, Brandon/0000-0003-4807-137X FU Intramural Program of the NIMH FX We thank Ioline Henter for providing outstanding editorial assistance. This work was supported by the Intramural Program of the NIMH. NR 58 TC 90 Z9 91 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2008 VL 13 IS 9 BP 858 EP 872 DI 10.1038/mp.2008.20 PG 15 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 339IJ UT WOS:000258571000004 PM 18332879 ER PT J AU Nicodemus, KK Marenco, S Batten, AJ Vakkalanka, R Egan, MF Straub, RE Weinberger, DR AF Nicodemus, K. K. Marenco, S. Batten, A. J. Vakkalanka, R. Egan, M. F. Straub, R. E. Weinberger, D. R. TI Serious obstetric complications interact with hypoxia-regulated/vascular-expression genes to influence schizophrenia risk SO MOLECULAR PSYCHIATRY LA English DT Article DE schizophrenia; obstetric complications; hypoxia; AKT1; genes ID FETAL GENOTYPE INCOMPATIBILITY; INDIVIDUAL PATIENT DATA; HIPPOCAMPAL VOLUME; PROSPECTIVE COHORT; MATERNAL RECALL; EARLY-ONSET; BIRTH; SIBLINGS; METAANALYSIS; SUSCEPTIBILITY AB The etiology of schizophrenia is thought to include both epistasis and gene-environment interactions. We sought to test whether a set of schizophrenia candidate genes regulated by hypoxia or involved in vascular function in the brain (AKT1, BDNF, CAPON, CHRNA7, COMT, DTNBP1, GAD1, GRM3, NOTCH4, NRG1, PRODH, RGS4, TNF-alpha) interacted with serious obstetric complications to influence risk for schizophrenia. A family-based study of transmission disequilibrium was conducted in 116 trios. Twenty-nine probands had at least one serious obstetric complication (OC) using the McNeil-Sjostrom Scale, and many of the OCs reported were associated with the potential for fetal hypoxia. Analyses were conducted using conditional logistic regression and a likelihood ratio test (LRT) between nested models was performed to assess significance. Of the 13 genes examined, four (AKT1 (three SNPs), BDNF (two SNPs), DTNBP1 (one SNP) and GRM3 (one SNP)) showed significant evidence for gene-by-environment interaction (LRT P-values ranged from 0.011 to 0.037). Although our sample size was modest and the power to detect interactions was limited, we report significant evidence for genes involved in neurovascular function or regulated by hypoxia interacting with the presence of serious obstetric complications to increase risk for schizophrenia. C1 [Nicodemus, K. K.; Marenco, S.; Batten, A. J.; Vakkalanka, R.; Egan, M. F.; Straub, R. E.; Weinberger, D. R.] NIMH, Cognit & Psyhcosis Program, IRP, NIH, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Cognit & Psyhcosis Program, IRP, NIH, Room 4S-235,10 Ctr Dr, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 39 TC 96 Z9 97 U1 2 U2 11 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 SEP PY 2008 VL 13 IS 9 BP 873 EP 877 DI 10.1038/sj.mp.4002153 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 339IJ UT WOS:000258571000005 PM 18195713 ER PT J AU Hu, JQ Renaud, G Golmes, T Ferris, A Hendrie, PC Donahue, RE Hughes, SH Wolfsberg, TG Russell, DW Dunbar, CE AF Hu, Jingqiong Renaud, Gabriel Golmes, Theotonius Ferris, Andrea Hendrie, Paul C. Donahue, Robert E. Hughes, Stephen H. Wolfsberg, Tyra G. Russell, David W. Dunbar, Cynthia E. TI Reduced genotoxicity of avian sarcoma leukosis virus vectors in rhesus long-term repopulating cells compared to standard murine retrovirus vectors SO MOLECULAR THERAPY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; GENE-THERAPY; HEMATOPOIETIC-CELLS; INSERTIONAL MUTAGENESIS; PROGENITOR CELLS; MACAQUE GENOME; HOT-SPOTS; INTEGRATION; SCID-X1; STEM AB Insertional mutagenesis continues to be a major concern in hematopoietic stem-cell gene therapy. Nonconventional gene transfer vectors with more favorable integration features in comparison with conventional retrovirus and lentivirus vectors are being developed and optimized. In this study, we report for the first time a systematic analysis of 198 avian sarcoma leukosis virus (ASLV) insertion sites identified in rhesus long-term repopulating cells, and a comparison of ASLV insertion patterns to Moloney murine leukemia virus (MLV) (n = 396) and simian immunodeficiency virus (SIV) (n = 289) using the newly released rhesus genome databank. Despite a weak preference toward gene-coding regions, ASLV integration is nonclustered, does not favor gene-rich regions, transcription start sites, or CpG islands. There was no propensity for ASLV insertions within or near proto-oncogenes, and most importantly, no insertions close to or within the Mds1-Evi1 locus, which is in contrast to the significant over-representation of this insertion site for MLV vectors in the same transplantation model. Furthermore, ASLV long terminal repeats (LTRs) do not have detectable promoter and enhancer activity in a quantitative luciferase assay to measure neighboring gene activation. The combination of these features is unique for ASLV and suggests that optimized vectors based on this virus could be useful and safe for gene transfer to hematopoietic stem cells and progenitor cells. C1 [Hu, Jingqiong; Golmes, Theotonius; Donahue, Robert E.; Dunbar, Cynthia E.] NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Renaud, Gabriel; Wolfsberg, Tyra G.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Ferris, Andrea; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Hendrie, Paul C.; Russell, David W.] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. RP Dunbar, CE (reprint author), NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bldg 10 CRC,Room 4-5132,10 Ctr Dr, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov FU National Heart, Lung, Blood Institute; National Human Genome Research Institute; National Cancer Institute of the National Institutes of Health FX The authors thank Stephanie Sellers for assistance with CD34+ cell purification and culture, and the staff of the 5 Research Court primate facility for excellent animal care. This work is supported by intramural research program of National Heart, Lung, Blood Institute, National Human Genome Research Institute, and National Cancer Institute of the National Institutes of Health. NR 34 TC 28 Z9 29 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD SEP PY 2008 VL 16 IS 9 BP 1617 EP 1623 DI 10.1038/mt.2008.135 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 342KG UT WOS:000258782400016 PM 18578011 ER PT J AU Ma, ZZ Xu, W Jensen, NH Roth, BL Liu-Chen, LY Lee, DYW AF Ma, Zhong-Ze Xu, Wei Jensen, Niels H. Roth, Bryan L. Liu-Chen, Lee-Yuan Lee, David Y. W. TI Isoquinoline alkaloids isolated from Corydalis yanhusuo and their binding affinities at the dopamine D(1) receptor SO MOLECULES LA English DT Article DE Corydalis yanhusuo; isoquinoline alkaloids; d/l ratio; chiral HPLC; dopamine receptor ID TETRAHYDROPALMATINE; BUPRENORPHINE; RATS; TETRAHYDROPROTOBERBERINES; CHROMATOGRAPHY; OPIATE; ENANTIOMERS; ADDICTION; STRIATUM; EXTRACT AB Bioactivity-guided fractionation of Corydalis yanhusuo has resulted in the isolation of eight known isoquinoline alkaloids - tetrahydropalmatine, isocorypalmine, stylopine, corydaline, columbamine, coptisin, 13-methylpalmatine, and dehydrocorybulbine. The tertiary alkaloids were further analyzed by chiral HPLC to determine the ratios of d-and l-isomers. The isolated compounds were screened for their binding affinities at the dopamine D(1) receptor. Isocorypalmine had the highest affinity (K(i) = 83 nM). The structure-affinity relationships of these alkaloids are discussed. C1 [Ma, Zhong-Ze; Lee, David Y. W.] Harvard Univ, McLean Hosp, Sch Med, Bioorgan & Nat Prod Lab, Belmont, MA 02478 USA. [Xu, Wei; Liu-Chen, Lee-Yuan] Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19140 USA. [Xu, Wei; Liu-Chen, Lee-Yuan] Temple Univ, Sch Med, Ctr Subst Abuse Res, Philadelphia, PA 19140 USA. [Jensen, Niels H.; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Jensen, Niels H.; Roth, Bryan L.] Univ N Carolina, Sch Med, Ctr Neurobiol, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. [Jensen, Niels H.; Roth, Bryan L.] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Sch Med, Chapel Hill, NC 27599 USA. RP Lee, DYW (reprint author), Harvard Univ, McLean Hosp, Sch Med, Bioorgan & Nat Prod Lab, 115 Mill St, Belmont, MA 02478 USA. EM wxu00001@temple.edu; niels_h_jensen@hotmail.com; bryan_roth@med.unc.edu; lliuche@temple.edu; dlee@mclean.harvard.edu RI Roth, Bryan/F-3928-2010 FU NCCAM/NIAAA [P01-AT-002038-04] FX This work was supported by Center of Excellence Research Program (P01-AT-002038-04, NCCAM/NIAAA) to D.Y.L. NR 40 TC 32 Z9 35 U1 5 U2 26 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1420-3049 J9 MOLECULES JI Molecules PD SEP PY 2008 VL 13 IS 9 BP 2303 EP 2312 DI 10.3390/molecules13092303 PG 10 WC Chemistry, Organic SC Chemistry GA 355UY UT WOS:000259735800018 PM 18830156 ER PT J AU Blumberg, RS Li, L Nusrat, A Parkos, CA Rubin, DC Carrington, JL AF Blumberg, R. S. Li, L. Nusrat, A. Parkos, C. A. Rubin, D. C. Carrington, J. L. TI Recent insights into the integration of the intestinal epithelium within the mucosal environment in health and disease SO MUCOSAL IMMUNOLOGY LA English DT Article ID MOUSE SMALL-INTESTINE; STEM-CELLS; CROHNS-DISEASE; IMMUNE HOMEOSTASIS; ULCERATIVE-COLITIS; EXPRESSION; SUSCEPTIBILITY; PATHOGENESIS; INFLAMMATION; ASSOCIATION C1 [Carrington, J. L.] NIDDK, Bethesda, MD 20892 USA. [Blumberg, R. S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Gastroenterol Div, Boston, MA USA. [Li, L.] Stowers Inst Med Res, Kansas City, MO USA. [Nusrat, A.; Parkos, C. A.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Rubin, D. C.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. RP Carrington, JL (reprint author), NIDDK, Bethesda, MD 20892 USA. EM carringj@mail.nih.gov RI Nusrat, Asma/B-3887-2009; Parkos, Charles/B-3896-2009 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health, the Public Health Service; Department of Health and Human Services FX The Workshop on Local Influences on Health and Repair of Intestinal Epithelium was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The following speakers contributed to the research presentations and discussions described in this manuscript: Maria Abreu, James M. Anderson, David Artis, Jean-Francois Beaulieu, Jeffrey Brown, Sean Colgan, Deborah Gumucio, Susan J. Henning, Calvin Kuo, Andrew Leiter, W. James Nelson, Andre Ouellette, Charalabos Pothoulakis, Don Powell, Derek Radisky, John Rioux, R. Balfour Sartor, Ramesh Shivdasani, Thaddeus Stappenbeck, Makoto Taketo, and Melissa Wong. The opinions expressed herein are those of the authors and do not necessarily reflect the views of the National Institutes of Health, the Public Health Service, or the Department of Health and Human Services. NR 38 TC 10 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2008 VL 1 IS 5 BP 330 EP 334 DI 10.1038/mi.2008.29 PG 5 WC Immunology SC Immunology GA 366HK UT WOS:000260471200002 PM 19079196 ER PT J AU Sheth, PM Chege, D Shin, LYY Huibner, S Yue, FY Loutfy, M Halpenny, R Persad, D Kovacs, C Chun, TW Kandel, G Ostrowski, M Kaul, R AF Sheth, P. M. Chege, D. Shin, L. Y. Y. Huibner, S. Yue, F-Y Loutfy, M. Halpenny, R. Persad, D. Kovacs, C. Chun, T-W Kandel, G. Ostrowski, M. Kaul, R. TI Immune reconstitution in the sigmoid colon after long-term HIV therapy SO MUCOSAL IMMUNOLOGY LA English DT Article ID T-CELL DEPLETION; VIRUS TYPE-1 INFECTION; GASTROINTESTINAL-TRACT; LYMPHOID-TISSUE; ANTIRETROVIRAL THERAPY; SIV INFECTION; MUCOSAL; CD4(+); RESPONSES; DISEASE AB Early and profound CD4+ T-cell depletion in gut-associated lymphoid tissue (GALT) may drive Human Immunodeficiency Virus (HIV) immunopathogenesis, and GALT immune reconstitution on highly active antiretroviral therapy (HAART) may be suboptimal. Blood and sigmoid colon biopsies were collected from HAART-treated individuals with undetectable blood HIV RNA for >= 4 years and from uninfected controls. HIV proviral levels and T-cell phenotype/function were examined in both compartments. CD4+ T-cell reconstitution in the sigmoid, including CD4+ T cells expressing CCR5, exceeded that in blood and did not differ from uninfected controls. Sigmoid HIV proviral load was not correlated with CD4+ reconsitution, but was correlated with the degree of mucosal CD8+ T-cell immune activation. Colonic Gag-specific T-cell responses were common, but were not associated with proviral load or immune activation. In this select study population, long-term HAART was associated with complete CD4+ T-cell reconstitution in sigmoid colon. However, colonic immune activation may drive ongoing HIV replication. C1 [Sheth, P. M.; Chege, D.; Shin, L. Y. Y.; Huibner, S.; Kaul, R.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Yue, F-Y; Ostrowski, M.] Univ Toronto, Dept Immunol, Toronto, ON, Canada. [Yue, F-Y; Loutfy, M.; Halpenny, R.; Persad, D.; Kovacs, C.] Canadian Immunodeficiency Res Collaborat, Toronto, ON, Canada. [Chun, T-W] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Chun, T-W] NIAID, Off Clin Res, NIH, Bethesda, MD 20892 USA. [Kandel, G.] St Michaels Hosp, Div Gastroenterol, Toronto, ON M5B 1W8, Canada. [Kaul, R.] Univ Hlth Network, Dept Med, Toronto, ON, Canada. RP Sheth, PM (reprint author), Univ Toronto, Dept Med, Toronto, ON, Canada. EM prameet.sheth@utoronto.ca FU Ontario HIV Treatment Network; CIHR [HOP-81735, HET-85518]; Canadian Research Chair Program; Gilead Pharmaceuticals FX This work was supported in part by the Ontario HIV Treatment Network (P. S., salary award); the CIHR (R. K., HOP-81735 and HET-85518); the Canadian Research Chair Program (R. K., salary support); and an unrestricted research grant from Gilead Pharmaceuticals (M. O., C. K., and T. C.). Study sponsors played no role in study design, collection or analysis of data, interpretation of results, writing of the manuscript, or decision to submit for publication. NR 37 TC 41 Z9 41 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2008 VL 1 IS 5 BP 382 EP 388 DI 10.1038/mi.2008.23 PG 7 WC Immunology SC Immunology GA 366HK UT WOS:000260471200008 PM 19079202 ER PT J AU Abrahamsson, S Packer, A Oh, U Burt, RK Muraro, PA AF Abrahamsson, Sofia Packer, Amy Oh, Unsong Burt, Richard K. Muraro, Paolo A. TI Dose matters: different immunological effects following a reduced- or high-intensity autologous hematopoietic stem cell transplantation regimen in patients with multiple sclerosis SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 13th Annual Meeting of the Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/24th Congress of the European-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/5th Congress of the Latin-Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis CY SEP 17-20, 2008 CL Montreal, CANADA SP Amer Comm Treatment & Res Multiple Scleros, European Comm Treatment & Res Multiple Scleros, Latin Amer Comm Treatment & Res Multiple Scleros C1 [Abrahamsson, Sofia; Muraro, Paolo A.] Univ London Imperial Coll Sci Technol & Med, London, England. [Packer, Amy; Oh, Unsong] NIH, Bethesda, MD 20892 USA. [Burt, Richard K.] Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 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 SEP PY 2008 VL 14 BP S23 EP S23 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 354YL UT WOS:000259675700065 ER PT J AU Ohayon, J Oh, U Richert, ND McFarland, H AF Ohayon, Joan Oh, Unsong Richert, Nancy D. McFarland, Henry TI central nervous system vasculitis in a Subject with multiple sclerosis on daclizumab monotherapy SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 13th Annual Meeting of the Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/24th Congress of the European-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/5th Congress of the Latin-Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis CY SEP 17-20, 2008 CL Montreal, CANADA SP Amer Comm Treatment & Res Multiple Scleros, European Comm Treatment & Res Multiple Scleros, Latin Amer Comm Treatment & Res Multiple Scleros C1 [Ohayon, Joan; Oh, Unsong; Richert, Nancy D.; McFarland, Henry] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 SEP PY 2008 VL 14 BP S170 EP S170 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 354YL UT WOS:000259675700558 ER PT J AU Richert, ND Dinacci, D Ostuni, J McFarland, H AF Richert, Nancy D. Dinacci, Daria Ostuni, John McFarland, Henry TI Whole brain magnetization transfer histogram metrics predict clinical disability in multiple sclerosis patients: a 5-year follow-up study SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 13th Annual Meeting of the Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/24th Congress of the European-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/5th Congress of the Latin-Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis CY SEP 17-20, 2008 CL Montreal, CANADA SP Amer Comm Treatment & Res Multiple Scleros, European Comm Treatment & Res Multiple Scleros, Latin Amer Comm Treatment & Res Multiple Scleros C1 [Richert, Nancy D.; Ostuni, John; McFarland, Henry] NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. [Dinacci, Daria] Univ Naples 2, Naples, Italy. NR 4 TC 0 Z9 0 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 SEP PY 2008 VL 14 BP S17 EP S18 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 354YL UT WOS:000259675700046 ER PT J AU Salman, Z Evangelou, I Talagala, SL Ikonomidou, V Stern, S Hill, R Gallo, A Ohayon, J Kane, R McFarland, H Bagnato, F AF Salman, Zeena Evangelou, Iordanis Talagala, S. Lalith Ikonomidou, Vasiliki Stern, Susan Hill, Rence Gallo, Antonio Ohayon, Joan Kane, Robert McFarland, Henry Bagnato, Francesca TI Cortical lesions in patients with multiple sclerosis: their relation with cortical atrophy and impact on Physical and cognitive impairment SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 13th Annual Meeting of the Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/24th Congress of the European-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/5th Congress of the Latin-Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis CY SEP 17-20, 2008 CL Montreal, CANADA SP Amer Comm Treatment & Res Multiple Scleros, European Comm Treatment & Res Multiple Scleros, Latin Amer Comm Treatment & Res Multiple Scleros C1 [Salman, Zeena; Evangelou, Iordanis; Talagala, S. Lalith; Ikonomidou, Vasiliki; Stern, Susan; Hill, Rence; Gallo, Antonio; Ohayon, Joan; Kane, Robert; McFarland, Henry; Bagnato, Francesca] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 SEP PY 2008 VL 14 BP S217 EP S217 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 354YL UT WOS:000259675700714 ER PT J AU Sormani, MP Bonzano, L Roccatagliata, L Bruzzi, P AF Sormani, Maria Pia Bonzano, Laura Roccatagliata, Luca Bruzzi, Paolo TI Imaging metrics that predict outcomes SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 13th Annual Meeting of the Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/24th Congress of the European-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/5th Congress of the Latin-Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis CY SEP 17-20, 2008 CL Montreal, CANADA SP Amer Comm Treatment & Res Multiple Scleros, European Comm Treatment & Res Multiple Scleros, Latin Amer Comm Treatment & Res Multiple Scleros C1 [Sormani, Maria Pia] Univ Genoa, Dept Hlth Sci, Genoa, Italy. [Bonzano, Laura; Roccatagliata, Luca] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. [Bonzano, Laura; Roccatagliata, Luca] Univ Genoa, Magnet Resonance Ctr Nervous Syst Dis, Genoa, Italy. [Bruzzi, Paolo] Natl Canc Inst, Dept Epidemiol & Prevent, Genoa, Italy. NR 0 TC 0 Z9 0 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 SEP PY 2008 VL 14 BP S19 EP S19 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 354YL UT WOS:000259675700051 ER PT J AU Cofield, SS Jenkins, TM Conwit, R Cutter, G Wolinsky, J Lublin, F AF Cofield, Stacey S. Jenkins, Todd M. Conwit, Robin Cutter, Gary Wolinsky, Jerry Lublin, Fred TI Optic neuritis and contrast letter acuity at baseline in CombiRx SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 13th Annual Meeting of the Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/24th Congress of the European-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/5th Congress of the Latin-Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis CY SEP 17-20, 2008 CL Montreal, CANADA SP Amer Comm Treatment & Res Multiple Sclerosis, European Comm Treatment & Res Multiple Sclerosis, Latin Amer Comm Treatment & Res Multiple Sclerosis C1 [Cofield, Stacey S.; Jenkins, Todd M.; Cutter, Gary] Univ Alabama, Birmingham, AL USA. [Lublin, Fred] Mt Sinai Sch Med, New York, NY USA. [Wolinsky, Jerry] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 J JI Mult. Scler. J. PD SEP PY 2008 VL 14 SU 1 BP S62 EP S62 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 354YL UT WOS:000259675700190 ER PT J AU Cofield, SS Cutter, G Conwit, R Wolinsky, J Lublin, F AF Cofield, Stacey S. Cutter, Gary Conwit, Robin Wolinsky, Jerry Lublin, Fred TI Race, ethnicity, country of origin and infections in CombiRx SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 13th Annual Meeting of the Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/24th Congress of the European-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/5th Congress of the Latin-Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis CY SEP 17-20, 2008 CL Montreal, CANADA SP Amer Comm Treatment & Res Multiple Sclerosis, European Comm Treatment & Res Multiple Sclerosis, Latin Amer Comm Treatment & Res Multiple Sclerosis C1 [Cofield, Stacey S.; Cutter, Gary] Univ Alabama, Birmingham, AL USA. [Lublin, Fred] Mt Sinai Sch Med, New York, NY USA. [Wolinsky, Jerry] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 J JI Mult. Scler. J. PD SEP PY 2008 VL 14 SU 1 BP S62 EP S62 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 354YL UT WOS:000259675700191 ER PT J AU Ahn, J Berndt, SI Wacholder, S Kraft, P Kibel, AS Yeager, M Albanes, D Giovannucci, E Stampfer, MJ Virtamo, J Thun, MJ Feigelson, HS Cancel-Tassin, G Cussenot, O Thomas, G Hunter, DJ Fraumeni, JF Hoover, RN Chanock, SJ Hayes, RB AF Ahn, Jiyoung Berndt, Sonja I. Wacholder, Sholom Kraft, Peter Kibel, Adam S. Yeager, Meredith Albanes, Demetrius Giovannucci, Edward Stampfer, Meir J. Virtamo, Jarmo Thun, Michael J. Feigelson, Heather Spencer Cancel-Tassin, Geraldine Cussenot, Olivier Thomas, Gilles Hunter, David J. Fraumeni, Joseph F., Jr. Hoover, Robert N. Chanock, Stephen J. Hayes, Richard B. TI Variation in KLK genes, prostate-specific antigen and risk of prostate cancer SO NATURE GENETICS LA English DT Letter ID SUSCEPTIBILITY; POLYMORPHISM; ASSOCIATION; PROMOTER C1 [Ahn, Jiyoung; Berndt, Sonja I.; Wacholder, Sholom; Yeager, Meredith; Albanes, Demetrius; Thomas, Gilles; Hunter, David J.; Fraumeni, Joseph F., Jr.; Hoover, Robert N.; Chanock, Stephen J.; Hayes, Richard B.] Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Dept Epidemiol, Boston, MA 02115 USA. [Kibel, Adam S.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Giovannucci, Edward; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward; Stampfer, Meir J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Giovannucci, Edward; Stampfer, Meir J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, FIN-0030 Helsinki, Finland. [Thun, Michael J.; Feigelson, Heather Spencer] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [Cancel-Tassin, Geraldine; Cussenot, Olivier] CeRePP Hop Tenon, AP HP, F-75020 Paris, France. RP Hayes, RB (reprint author), Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM Hayesr@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; OI Hayes, Richard/0000-0002-0918-661X; Cancel-Tassin, Geraldine/0000-0002-9583-6382 FU CCR NIH HHS [N01RC37004, N01-RC-45035]; Intramural NIH HHS [ZIA CP010152-11]; NCI NIH HHS [CA55075, N01 CN045165, N01-CO-12400, U01CA098233, N01CO12400, P01 CA055075, R01 CA112028, R01CA112028, U01 CA098233, U01 CA098710] NR 10 TC 61 Z9 62 U1 0 U2 2 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 SEP PY 2008 VL 40 IS 9 BP 1032 EP 1034 DI 10.1038/ng0908-1032 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 342CC UT WOS:000258761200002 PM 19165914 ER PT J AU O'Donovan, MC Craddock, N 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 Hartmann, AM Moller, HJ Morris, DW Shi, YY Feng, GY Hoffmann, P Propping, P Vasilescu, C Maier, W Rietschel, M Zammit, S Schumacher, J Quinn, EM Schulze, TG Williams, NM Giegling, I Iwata, N Ikeda, M Darvasi, A Shifman, S He, L Duan, J Sanders, AR Levinson, DF Gejman, PV Cichon, S Nothen, MM Gill, M Corvin, A Rujescu, D Kirov, G Owen, MJ AF O'Donovan, Michael C. Craddock, Nicholas Norton, Nadine Williams, Hywel Peirce, Timothy Moskvina, Valentina Nikolov, Ivan Hamshere, Marian Carroll, Liam Georgieva, Lyudmila Dwyer, Sarah Holmans, Peter Marchini, Jonathan L. Spencer, Chris C. A. Howie, Bryan Leung, Hin-Tak Hartmann, Annette M. Moeller, Hans-Juergen Morris, Derek W. Shi, YongYong Feng, GuoYin Hoffmann, Per Propping, Peter Vasilescu, Catalina Maier, Wolfgang Rietschel, Marcella Zammit, Stanley Schumacher, Johannes Quinn, Emma M. Schulze, Thomas G. Williams, Nigel M. Giegling, Ina Iwata, Nakao Ikeda, Masashi Darvasi, Ariel Shifman, Sagiv He, Lin Duan, Jubao Sanders, Alan R. Levinson, Douglas F. Gejman, Pablo V. Cichon, Sven Noethen, Markus M. Gill, Michael Corvin, Aiden Rujescu, Dan Kirov, George Owen, Michael J. CA Mol Genetics Of Schizophrenia Coll TI Identification of loci associated with schizophrenia by genome-wide association and follow-up SO NATURE GENETICS LA English DT Article AB We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10(-5) in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 x 10(-4)), and the overall pattern of replication was unlikely to occur by chance (P < 9 x 10(-8)). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 x 10(-7)) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 x 10(-9)). C1 [O'Donovan, Michael C.; Craddock, Nicholas; Norton, Nadine; Williams, Hywel; Peirce, Timothy; Moskvina, Valentina; Nikolov, Ivan; Hamshere, Marian; Carroll, Liam; Georgieva, Lyudmila; Dwyer, Sarah; Holmans, Peter; Zammit, Stanley; Williams, Nigel M.; Kirov, George; Owen, Michael J.] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff CF14 4XN, England. [Marchini, Jonathan L.; Spencer, Chris C. A.; Howie, Bryan] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Leung, Hin-Tak] Univ Cambridge, Dept Med Genet, Wellcome Trust Diabet & Inflammat Lab, Juvenile Diabet Res Fdn, Cambridge CB2 0XY, England. [Hartmann, Annette M.; Giegling, Ina; Rujescu, Dan] Univ Munich, Div Mol & Clin Neurbiol, D-80336 Munich, Germany. [Moeller, Hans-Juergen] Univ Munich, Dept Psychiat, D-80336 Munich, Germany. [Morris, Derek W.; Quinn, Emma M.; Gill, Michael; Corvin, Aiden] Univ Dublin Trinity Coll, Sch Med, Neuropsychiat Genet Res Grp, Dublin 8, Ireland. [Shi, YongYong] Shanghai Jiao Tong Univ, BioX Ctr, Shanghai 200030, Peoples R China. [Feng, GuoYin] Shanghai Inst Mental Hlth, Shanghai 200030, Peoples R China. [Hoffmann, Per; Vasilescu, Catalina; Cichon, Sven; Noethen, Markus M.] Univ Bonn, Dept Gen, Life & Brain Ctr, D-53105 Bonn, Germany. [Propping, Peter; Cichon, Sven; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-53105 Bonn, Germany. [Maier, Wolfgang] Univ Bonn, Dept Psychiat, D-53105 Bonn, Germany. [Rietschel, Marcella] Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-68159 Mannheim, Germany. [Schumacher, Johannes; Schulze, Thomas G.] US Natl Inst Mental Hlth, Natl Inst Hlth, Bethesda, MD 20892 USA. [Iwata, Nakao; Ikeda, Masashi] Fujita Hlth Univ, Sch Med, Dept Psychiat, Aichi 4701192, Japan. [Iwata, Nakao; Ikeda, Masashi] Japan Sci & Technol Agcy, CREST, Saitama 3320012, Japan. [Darvasi, Ariel; Shifman, Sagiv] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. [He, Lin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China. [Duan, Jubao; Sanders, Alan R.; Gejman, Pablo V.] Northwestern Univ, Ctr Psychiat Genet, Evanston, IL 60201 USA. [Duan, Jubao; Sanders, Alan R.; Gejman, Pablo V.] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60201 USA. [Levinson, Douglas F.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP O'Donovan, MC (reprint author), Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff CF14 4XN, England. EM wpcmod@cf.ac.uk; wpcmjo@cf.ac.uk RI turton, miranda/F-4682-2011; 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 Buccola, Nancy/0000-0003-1378-4636; Escott-Price, Valentina/0000-0003-1784-5483; Nothen, Markus/0000-0002-8770-2464; Hoffmann, Per/0000-0002-6573-983X; 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; Corvin, Aiden/0000-0001-6717-4089; O'Donovan, Michael/0000-0001-7073-2379; Zammit, Stanley/0000-0002-2647-9211 FU MRC; Wellcome Trust; Science Foundation Ireland; Health Research Board (Ireland); National Genomic Network of the 'Bundesministerium fur Bildung und Forschung' (BMBF); Alfried Krupp von Bohlen und Halbach-Stiftung; GlaxoSmithKline. FX The UK research was supported by grants from the MRC and the Wellcome Trust. We are grateful to the Wellcome Trust Case Control Consortium for access to control genotypes (and to the individuals acknowledged in that respect in ref. 4) and their contribution to the genome-wide study, and to the Welsh e-Science Centre at Cardiff University for access to computing resources for some of this work. In Dublin, the research was supported by Science Foundation Ireland, the Health Research Board (Ireland) and the Wellcome Trust. We are grateful to J. Waddington for sample recruitment. Irish controls were supplied by J. 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) and the Alfried Krupp von Bohlen und Halbach-Stiftung. 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. NR 10 TC 628 Z9 652 U1 6 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 SEP PY 2008 VL 40 IS 9 BP 1053 EP 1055 DI 10.1038/ng.201 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 342CC UT WOS:000258761200014 PM 18677311 ER PT J AU Zody, MC Jiang, Z Fung, HC Antonacci, F Hillier, LW Cardone, MF Graves, TA Kidd, JM Cheng, Z Abouelleil, A Chen, L Wallis, J Glasscock, J Wilson, RK Reily, AD Duckworth, J Ventura, M Hardy, J Warren, WC Eichler, EE AF Zody, Michael C. Jiang, Zhaoshi Fung, Hon-Chung Antonacci, Francesca Hillier, LaDeana W. Cardone, Maria Francesca Graves, Tina A. Kidd, Jeffrey M. Cheng, Ze Abouelleil, Amr Chen, Lin Wallis, John Glasscock, Jarret Wilson, Richard K. Reily, Amy Denise Duckworth, Jaime Ventura, Mario Hardy, John Warren, Wesley C. Eichler, Evan E. TI Evolutionary toggling of the MAPT 17q21.31 inversion region SO NATURE GENETICS LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; RECENT SEGMENTAL DUPLICATIONS; HUMAN-GENOME; COPY-NUMBER; HUMAN-POPULATIONS; COMMON INVERSION; GENE-EXPRESSION; DNA-SEQUENCE; TAU-GENE; HAPLOTYPE AB Using comparative sequencing approaches, we investigated the evolutionary history of the European-enriched 17q21.31 MAPT inversion polymorphism. We present a detailed, BAC-based sequence assembly of the inverted human H2 haplotype and compare it to the sequence structure and genetic variation of the corresponding 1.5-Mb region for the noninverted H1 human haplotype and that of chimpanzee and orangutan. We found that inversion of the MAPT region is similarly polymorphic in other great ape species, and we present evidence that the inversions occurred independently in chimpanzees and humans. In humans, the inversion breakpoints correspond to core duplications with the LRRC37 gene family. Our analysis favors the H2 configuration and sequence haplotype as the likely great ape and human ancestral state, with inversion recurrences during primate evolution. We show that the H2 architecture has evolved more extensive sequence homology, perhaps explaining its tendency to undergo microdeletion associated with mental retardation in European populations. C1 [Hillier, LaDeana W.; Graves, Tina A.; Wallis, John; Glasscock, Jarret; Wilson, Richard K.; Reily, Amy Denise; Warren, Wesley C.] Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA. [Zody, Michael C.] MIT, Broad Inst, Cambridge, MA 02142 USA. [Zody, Michael C.] Harvard Univ, Cambridge, MA 02142 USA. [Zody, Michael C.] Uppsala Univ, Dept Med Biochem & Microbiol, SE-75124 Uppsala, Sweden. [Jiang, Zhaoshi; Antonacci, Francesca; Kidd, Jeffrey M.; Cheng, Ze; Chen, Lin; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Dept Genome Sci, Seattle, WA 98195 USA. [Fung, Hon-Chung; Hardy, John] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Fung, Hon-Chung; Hardy, John] UCL, Reta Lila Weston Labs, London WC1N 3BG, England. [Fung, Hon-Chung] Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Taipei 10591, Taiwan. [Fung, Hon-Chung] Chang Gung Univ, Coll Med, Taipei 10591, Taiwan. [Cardone, Maria Francesca; Ventura, Mario] Univ Bari, Dept Genet & Microbiol, I-70126 Bari, Italy. [Duckworth, Jaime] Natl Inst Aging, Natl Inst Hlth, Neurogenet Lab, Bethesda, MD 20892 USA. RP Warren, WC (reprint author), Washington Univ, Sch Med, Genome Sequencing Ctr, Campus Box 8501,4444 Forest Pk Ave, St Louis, MO 63108 USA. EM wwarren@watson.wustl.edu; eee@gs.washington.edu RI Ventura, Mario/E-6420-2011; Hardy, John/C-2451-2009; Cardone, Maria Francesca/G-8818-2012; Antonacci, Francesca/F-5457-2013; OI Ventura, Mario/0000-0001-7762-8777; Cardone, Maria Francesca/0000-0002-7597-7313; Antonacci, Francesca/0000-0002-5833-6186; Kidd, Jeffrey/0000-0002-9631-1465 FU National Human Genome Research Institute; National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000957-05]; NIH [GM058815, HG002385]; Rosetta Inpharmatics Fellowship (Merck Laboratories); Howard Hughes Medical Institute FX We thank T. Marques, D. Reich, A. Navarro, N. Patterson, S. McCarroll, T. Brown and K. Augustyn for critical comments and valuable discussions in the preparation of this manuscript; C. Alkan for providing computational assistance; and members of the Broad Institute Sequence Platform (BISP) and Washington University Genome Sequencing Center (WUGSC) for generating clone-based sequencing data for this project. M. C. Z., A. A., W. C. W., L. W. H., T. A. G., R. K. W., A. D. R., J. W., J. G. and the BISP and WUGSC were supported by grants from the National Human Genome Research Institute. This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services, project number Z01 AG000957-05. This work was supported by NIH grants GM058815 and HG002385 to E. E. E. and a Rosetta Inpharmatics Fellowship (Merck Laboratories) to Z. J. E. E. E. is an investigator of the Howard Hughes Medical Institute. NR 45 TC 101 Z9 101 U1 1 U2 5 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 SEP PY 2008 VL 40 IS 9 BP 1076 EP 1083 DI 10.1038/ng.193 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 342CC UT WOS:000258761200020 PM 19165922 ER PT J AU Kim, C Sano, Y Todorova, K Carlson, BA Arpa, L Celada, A Lawrence, T Otsu, K Brissette, JL Arthur, JSC Park, JM AF Kim, Chun Sano, Yasuyo Todorova, Kristina Carlson, Bradley A. Arpa, Luis Celada, Antonio Lawrence, Toby Otsu, Kinya Brissette, Janice L. Arthur, J. Simon C. Park, Jin Mo TI The kinase p38 alpha serves cell type-specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression SO NATURE IMMUNOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; INNATE IMMUNE-RESPONSES; P38 MAP KINASE; NF-KAPPA-B; SUBSTRATE-SPECIFICITY; MACROPHAGE APOPTOSIS; INHIBITION; STRESS; INTERLEUKIN-10; PHOSPHATASE-1 AB The mitogen-activated protein kinase p38 mediates cellular responses to injurious stress and immune signaling. Among the many p38 isoforms, p38 alpha is the most widely expressed in adult tissues and can be targeted by various pharmacological inhibitors. Here we investigated how p38 alpha activation is linked to cell type-specific outputs in mouse models of cutaneous inflammation. We found that both myeloid and epithelial p38 alpha elicit inflammatory responses, yet p38 alpha signaling in each cell type served distinct inflammatory functions and varied depending on the mode of skin irritation. In addition, myeloid p38 alpha limited acute inflammation via activation of anti-inflammatory gene expression dependent on mitogen -and stress-activated kinases. Our results suggest a dual function for p38 alpha in the regulation of inflammation and show mixed potential for its inhibition as a therapeutic strategy. C1 [Kim, Chun; Sano, Yasuyo; Todorova, Kristina; Brissette, Janice L.; Park, Jin Mo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Kim, Chun; Sano, Yasuyo; Todorova, Kristina; Brissette, Janice L.; Park, Jin Mo] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Carlson, Bradley A.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,Natl Inst Hlth, Bethesda, MD 20892 USA. [Arpa, Luis; Celada, Antonio] Univ Barcelona, E-08028 Barcelona, Spain. [Arpa, Luis; Celada, Antonio] Inst Biomed Res, Macrophage Biol Grp, Barcelona 08028, Spain. [Lawrence, Toby] Barts & London Queen Marys Sch Med & Dent, Ctr Translat Oncol, Inst Canc, London EC1M 6BQ, England. [Lawrence, Toby] Barts & London Queen Marys Sch Med & Dent, Ctr Translat Oncol, CR UK Clin Ctr, London EC1M 6BQ, England. [Otsu, Kinya] Osaka Univ, Grad Sch Med, Dept Cardiovasc Med, Suita, Osaka 5650871, Japan. [Arthur, J. Simon C.] Univ Dundee, MRC, Prot Phosphorylat Unit, Sir James Black Ctr, Dundee DD1 5EH, Scotland. RP Park, JM (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM jmpark@cbrc2.mgh.harvard.edu RI Arthur, J. Simon/B-8058-2010; Lawrence, Toby/F-4461-2015 OI Arthur, J. Simon/0000-0002-8135-1958; FU Cutaneous Biology Research Center; US National Institutes of Health [DK043351]; Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital FX We thank S. Krane (Massachusetts General Hospital) for the MMP-13-specific antibody and advice on its use; D. Ginsburg (University of Michigan School of Medicine) for the PAI-2-specific antibody; R. Bravo (Bristol-Myers Squibb Pharmaceutical Research Institute) and C. Caelles (Institute for Research in Biomedicine, Barcelona) for Dusp1-KO mice; and M. Karin for discussion about Jnk-activation mechanisms in p38 alpha-deficient cells. Supported by the Cutaneous Biology Research Center through the Massachusetts General Hospital-Shiseido Agreement (J. M. P.), the US National Institutes of Health (DK043351 to D. Podolsky) and the Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital (J. M. P.). NR 50 TC 126 Z9 128 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD SEP PY 2008 VL 9 IS 9 BP 1019 EP 1027 DI 10.1038/ni.1640 PG 9 WC Immunology SC Immunology GA 339DZ UT WOS:000258559600014 PM 18677317 ER PT J AU Pobezinskaya, YL Kim, YS Choksi, S Morgan, MJ Li, T Liu, CY Liu, ZG AF Pobezinskaya, Yelena L. Kim, You-Sun Choksi, Swati Morgan, Michael J. Li, Tao Liu, Chengyu Liu, Zhenggang TI The function of TRADD in signaling through tumor necrosis factor receptor 1 and TRIF-dependent Toll-like receptors SO NATURE IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; INDUCED CELL-DEATH; DOMAIN KINASE RIP; TNF RECEPTOR; MEDIATED APOPTOSIS; ACTIVATION; PROTEIN; MICE; PATHWAY; TRANSDUCTION AB The physiological function of the adaptor protein TRADD remains unclear because of the unavailability of a TRADD-deficient animal model. By generating TRADD-deficient mice, we found here that TRADD serves an important function in tumor necrosis factor receptor 1 (TNFR1) signaling by orchestrating the formation of TNFR1 signaling complexes. TRADD was essential for TNFR1 signaling in mouse embryonic fibroblasts but was partially dispensable in macrophages; abundant expression of the adaptor RIP in macrophages may have allowed some transmission of TNFR1 signals in the absence of TRADD. Although morphologically normal, TRADD-deficient mice were resistant to toxicity induced by TNF, lipopolysaccharide and polyinosinic-polycytidylic acid. TRADD was also required for TRIF-dependent Toll-like receptor signaling in mouse embryonic fibroblasts but not macrophages. Our findings definitively establish the biological function of TRADD in TNF signaling. C1 [Pobezinskaya, Yelena L.; Kim, You-Sun; Choksi, Swati; Morgan, Michael J.; Li, Tao; Liu, Zhenggang] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Liu, Chengyu] NHLBI, Transgen Core Facil, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Liu, ZG (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM zgliu@helix.nih.gov FU Center for Cancer Research (US National Cancer Institute) FX We thank W. C. Yeh and T. W. Mak (University of Toronto, Canada) for Traf2-/- MEFs; H. Nakano (Juntento University, Japan) for Traf5-/- and Traf2-/- Traf5-/- MEFs; L. Tessarollo (US National Cancer Institute) for the pLTM260 vector; A. Singer (US National Cancer Institute) for the pKO Scrambler 917 TK vector; and L. Pobezinsky for suggestions. Supported by the Intramural Research Program of Center for Cancer Research (US National Cancer Institute). NR 40 TC 106 Z9 110 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD SEP PY 2008 VL 9 IS 9 BP 1047 EP 1054 DI 10.1038/ni.1639 PG 8 WC Immunology SC Immunology GA 339DZ UT WOS:000258559600017 PM 18641653 ER PT J AU Drew, PJ Duyn, JH Golanov, E Kleinfeld, D AF Drew, Patrick J. Duyn, Jeff H. Golanov, Eugene Kleinfeld, David TI Finding coherence in spontaneous oscillations SO NATURE NEUROSCIENCE LA English DT Editorial Material ID VISUAL-CORTEX; BOLD SIGNAL; FLUCTUATIONS; RESPONSES; BEHAVIOR; NEURONS C1 [Drew, Patrick J.; Kleinfeld, David] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA. [Golanov, Eugene] NINDS, Extramural Res Program, Bethesda, MD 20892 USA. RP Drew, PJ (reprint author), Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA. EM dk@physics.ucsd.edu RI Duyn, Jozef/F-2483-2010; Golanov, Eugene/B-6462-2011; OI Golanov, Eugene/0000-0003-0220-822X; Drew, Patrick/0000-0002-7483-7378 NR 15 TC 21 Z9 21 U1 1 U2 7 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 SEP PY 2008 VL 11 IS 9 BP 991 EP 993 DI 10.1038/nn0908-991 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 341NA UT WOS:000258720000004 PM 18725901 ER PT J AU Hasko, G Linden, J Cronstein, B Pacher, P AF Hasko, Gyorgy Linden, Joel Cronstein, Bruce Pacher, Pal TI Adenosine receptors: therapeutic aspects for inflammatory and immune diseases SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID ISCHEMIA-REPERFUSION INJURY; MARROW-DERIVED CELLS; REGULATORY T-CELLS; SUPEROXIDE ANION GENERATION; MURINE SEPTIC PERITONITIS; ENDOTHELIAL GROWTH-FACTOR; HUMAN DENDRITIC CELLS; IFN-GAMMA PRODUCTION; TNF-ALPHA PRODUCTION; HUMAN MAST-CELLS AB Adenosine is a key endogenous molecule that regulates tissue function by activating four G-protein-coupled adenosine receptors: A(1), A(2A), A(2B) and A(3). Cells of the immune system express these receptors and are responsive to the modulatory effects of adenosine in an inflammatory environment. Animal models of asthma, ischaemia, arthritis, sepsis, inflammatory bowel disease and wound healing have helped to elucidate the regulatory roles of the various adenosine receptors in dictating the development and progression of disease. This recent heightened awareness of the role of adenosine in the control of immune and inflammatory systems has generated excitement regarding the potential use of adenosine-receptor-based therapies in the treatment of infection, autoimmunity, ischaemia and degenerative diseases. C1 [Hasko, Gyorgy] Univ Med & Dent New Jersey, Dept Surg, New Jersey Med Sch, Newark, NJ 07103 USA. [Linden, Joel] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA. [Linden, Joel] Univ Virginia, Cardiovasc Res Ctr, Charlottesville, VA 22908 USA. [Cronstein, Bruce] NYU, Sch Med, Dept Med, New York, NY 10016 USA. [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, Bethesda, MD 20892 USA. RP Hasko, G (reprint author), Univ Med & Dent New Jersey, Dept Surg, New Jersey Med Sch, 185 S Orange Ave, Newark, NJ 07103 USA. EM haskoge@umdnj.edu RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU National Institutes of Health (NIH) [R01GM66189]; Intramural Research Program of NIH; National Institute on Alcohol Abuse and Alcoholism FX This work was supported by the National Institutes of Health (NIH) Grant R01GM66189 and the Intramural Research Program of NIH, National Institute on Alcohol Abuse and Alcoholism. NR 130 TC 478 Z9 490 U1 4 U2 45 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD SEP PY 2008 VL 7 IS 9 BP 759 EP 770 DI 10.1038/nrd2638 PG 12 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 344GV UT WOS:000258915800018 PM 18758473 ER PT J AU Singh, K Gittis, AG Nguyen, P Gowda, DC Miller, LH Garboczi, DN AF Singh, Kavita Gittis, Apostolos G. Nguyen, Phuc Gowda, D. Channe Miller, Louis H. Garboczi, David N. TI Structure of the DBL3x domain of pregnancy-associated malaria protein VAR2CSA complexed with chondroitin sulfate A SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID FALCIPARUM-INFECTED ERYTHROCYTES; N-TERMINAL DOMAIN; PLASMODIUM-FALCIPARUM; HUMAN PLACENTA; VACCINE CANDIDATE; DIFFRACTION DATA; ADHERENCE; RECEPTOR; BINDING; SURFACE AB Plasmodium falciparum-infected erythrocytes bind to chondroitin sulfate A (CSA) in the placenta via the VAR2CSA protein, a member of the P. falciparum erythrocyte membrane protein-1 family, leading to life-threatening malaria in pregnant women with severe effects on their fetuses and newborns. Here we describe the structure of the CSA binding DBL3x domain, a Duffy binding-like (DBL) domain of VAR2CSA. By forming a complex of DBL3x with CSA oligosaccharides and determining its structure, we have identified the CSA binding site to be a cluster of conserved positively charged residues on subdomain 2 and subdomain 3. Mutation or chemical modification of lysine residues at the site markedly diminished CSA binding to DBL3x. The location of the CSA binding site is an important step forward in the molecular understanding of pregnancy-associated malaria and offers a new target for vaccine development. C1 [Singh, Kavita; Gittis, Apostolos G.; Nguyen, Phuc; Garboczi, David N.] NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Gowda, D. Channe] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. [Miller, Louis H.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. RP Singh, K (reprint author), NIAID, Struct Biol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM ksingh@niaid.nih.gov; dgarboczi@niaid.nih.gov FU US Department of Energy; Office of Science; Office of Basic Energy Sciences [W-31-109-Eng-38]; US National Institutes of Health; National Institute of Allergy and Infectious Diseases [AI45086] FX We thank A. Diouf and C. A. Long (Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases) for screening monoclonal antibodies, J.F. Andersen for helping with ITC, S. Madala for giving assistance with flow cytometry, H.-P. Su for advising on molecular biology, J.M. Moore for helping with initial protein purification and J.D. Smith (Seattle Biomedical Research Institute) for giving us the A4 genomic DNA. X-ray data were collected at the SBC-CAT and SER-CAT beamlines at the Advanced Photon Source supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract W-31-109-Eng-38. This work was supported by the Intramural Research Program of the US National Institutes of Health, National Institute of Allergy and Infectious Diseases and by grant AI45086 for work performed in the laboratory of D. C. Gowda. NR 39 TC 61 Z9 62 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD SEP PY 2008 VL 15 IS 9 BP 932 EP 938 DI 10.1038/nsmb.1479 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 344LL UT WOS:000258928400012 PM 19172746 ER PT J AU Downs, JL Mattison, JA Ingram, DK Urbanski, HF AF Downs, Jodi L. Mattison, Julie A. Ingram, Donald K. Urbanski, Henryk F. TI Effect of age and caloric restriction on circadian adrenal steroid rhythms in rhesus macaques SO NEUROBIOLOGY OF AGING LA English DT Article DE adrenal steroids; aging; caloric restriction; circadian; cortisol; DHEAS; endocrine rhythms; primate ID DEHYDROEPIANDROSTERONE-SULFATE; LIFE-SPAN; IDENTIFYING BIOMARKERS; DIETARY RESTRICTION; NUTRITIONAL-STATUS; OXIDATIVE STRESS; FOOD RESTRICTION; BLOOD-CHEMISTRY; MONKEYS; LONGEVITY AB Dietary caloric restriction (CR) slows aging, extends lifespan, and reduces the occurrence of age-related diseases in short-lived species. However, it is unclear whether CR can exert similar beneficial effects in long-lived species, like primates. Our objective was to determine if CR could attenuate purported age-related changes in the 24-h release of adrenal steroids. To this end, we examined 24-h plasma profiles of cortisol, and dehydroepiandrosterone sulfate (DHEAS) in young and old, mate and female rhesus macaques (Macaca mulatta) subjected to either ad libitum (AL)-feeding or CR (70% of AL) for 2-4 years. Hormone profiles from young monkeys showed pronounced 24-h rhythms. 'Cortisol concentrations were higher in old mates but not females, whereas DHEAS rhythms were dampened with age in both sexes. The cortisol rhythms of old CR males resembled those of young control males. However, CR failed to prevent age-related declines in DHEAS and further dampened DHEAS rhythms in both sexes. Apart from the partial attenuation of the age-related cortisol elevation in the old males, 24-h adrenal steroid rhythms did not benefit from late-onset CR. Published by Elsevier Inc. C1 [Downs, Jodi L.; Urbanski, Henryk F.] Oregon Reg Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA. [Downs, Jodi L.; Urbanski, Henryk F.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Downs, Jodi L.; Urbanski, Henryk F.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Mattison, Julie A.; Ingram, Donald K.] NIA, Intramural Res Program, Lab Expt Gerontol, Baltimore, MD 21224 USA. [Ingram, Donald K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA. RP Urbanski, HF (reprint author), Oregon Reg Primate Res Ctr, Div Neurosci, 505 NW 185th Ave, Beaverton, OR 97006 USA. EM urbanski@ohsu.edu FU NCRR NIH HHS [P51 RR000163, K01 RR000163, P51 RR000163-450158, P51 RR000163-486757, RR-00163]; NIA NIH HHS [AG-023477, AG-029612, AG-19914, R01 AG019914, R01 AG019914-04, R01 AG029612, R01 AG029612-01A1, T32 AG023477]; NICHD NIH HHS [HD-29186, R01 HD029186, R01 HD029186-09] NR 53 TC 26 Z9 26 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP PY 2008 VL 29 IS 9 BP 1412 EP 1422 DI 10.1016/j.neurobiolaging.2007.03.01 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 331UF UT WOS:000258037400012 PM 17420071 ER PT J AU Nolte, MW Loscher, W Herden, C Freed, WJ Gernert, M AF Nolte, Marc W. Loescher, Wolfgang Herden, Christiane Freed, William J. Gernert, Manuela TI Benefits and risks of intranigral transplantation of GABA-producing cells subsequent to the establishment of kindling-induced seizures SO NEUROBIOLOGY OF DISEASE LA English DT Article DE substantia nigra pars reticulata; basal ganglia; seizures; genetically engineered cells; gene therapy; neural transplantation; grafting; kindling ID TEMPORAL-LOBE EPILEPSY; LARGE T-ANTIGEN; FETAL GABAERGIC NEURONS; SUBSTANTIA-NIGRA; ELECTRICAL STIMULATION; BEHAVIORAL SEIZURES; PIRIFORM CORTEX; BASAL GANGLIA; TSA58 ALLELE; RATS AB Neural transplantation has been investigated experimentally and clinically for the purpose of developing new treatment options for intractable epilepsy. In the present study we assessed the anticonvulsant efficacy and safety of bilateral allotransplantation of genetically engineered striatal GABAergic rat cell lines into the substantia nigra pars reticulata (SNr). Rats with previously-established seizures, induced by amygdala kindling, were used as a model of temporal lobe epilepsy. Three cell lines were transplanted: (1) immortalized GABAergic cells (M213-20) derived from embryonic rat striatum; (2) M213-20 cells (CL4) transfected with human GAD67 cDNA to obtain higher GABA synthesis than the parent cell line; and (3) control cells (121-11), also derived from embryonic rat striatum, but which did not show GAD expression. A second control group received injections of medium alone. Transplantation of M213-20 cells into the SNr of kindled rats resulted in significant but transient anticonvulsant effects. Neither control cells nor medium induced anticonvulsant effects. Strong tissue reactions were, however, induced in the host brain of kindled but not of non-kindled rats, and only in animals that received grafts of genetically modified CL4 cells. These tissue reactions included graft rejection, massive infiltration of inflammatory immune cells, and gliosis. The anticonvulsant effect of M213-20 cells emphasizes the feasibility of local manipulations of seizures by intranigral transplantation of GABA-producing cells. On the other hand, the present data suggest that kindling-induced activation of microglia in the SNr can enhance immune reactions to transplanted cells. In this case, under conditions of further immunological stimulation by CL4 cells, transfected with a human cDNA, substantial immune reactions occurred. Thus, it appears that the condition of the host brain and the production of foreign proteins by transplanted cells have to be considered in estimating the risks of rejection of transplants into the brain. (C) 2008 Elsevier Inc. All rights reserved. C1 [Loescher, Wolfgang; Gernert, Manuela] Univ Vet Med Hannover, Dept Pharmacol Toxicol & Pharm, D-30559 Hannover, Germany. [Herden, Christiane] Univ Vet Med Hannover, Inst Pathol, D-30559 Hannover, Germany. [Loescher, Wolfgang; Gernert, Manuela] Ctr Syst Neurosci, Hannover, Germany. [Nolte, Marc W.] Abbott GmbH & Co KG, Dept Pharmacol, D-67061 Ludwigshafen, Germany. [Freed, William J.] NIDA, IRP, NIH, DHHS, Baltimore, MD 21224 USA. RP Gernert, M (reprint author), Univ Vet Med Hannover, Dept Pharmacol Toxicol & Pharm, Bunteweg 17, D-30559 Hannover, Germany. EM manuela.gernert@tiho-hannover.de FU German National Academic Foundation; NIDA IRP; NIH; DHHS FX We are grateful to Michael Wei beta ing for excellent help in cell culture. We thank Holger Volk for crucial help in immunohistology. Horst Briese did a wonderful job in adapting a probe holder needed during the stereotaxic transplantation procedure. The assistance of Christiane Bartling is gratefully acknowledged. We thank Prof. Dr. Claudia Grothe and Marco Timmer (both Dept. of Neuroanatomy, Medical School Hannover, Germany) for methodological advice with the microtransplantation technique. The research was supported in part by a grant of the German National Academic Foundation to MWN and in part by the NIDA IRP, NIH, DHHS. NR 69 TC 17 Z9 17 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 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD SEP PY 2008 VL 31 IS 3 BP 342 EP 354 DI 10.1016/j.nbd.2008.05.010 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 343NY UT WOS:000258862000007 PM 18632280 ER PT J AU Stranahan, AM Lee, K Pistell, PJ Nelson, CM Readal, N Miller, MG Spangler, EL Ingram, DK Mattson, MP AF Stranahan, Alexis M. Lee, Kim Pistell, Paul J. Nelson, Christopher M. Readal, Nathaniel Miller, Marshall G. Spangler, Edward L. Ingram, Donald K. Mattson, Mark P. TI Accelerated cognitive aging in diabetic rats is prevented by lowering corticosterone levels SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Article DE stress; streptozocin; hippocampus; stone maze; aging ID ADRENAL-STEROID RECEPTORS; MEMORY; IMPAIRMENT; ANTAGONISM; STRESS AB Diabetes and normal aging are both characterized by increases in levels of glucocorticoids. Because long-term exposure to elevated glucocorticoids can be detrimental to hippocampal function, we evaluated the performance of young diabetic rats in the 14-unit T-maze, a task that is sensitive to hippocampal deficits. To assess the contribution of diabetes-induced elevations in corticosterone levels, we examined maze learning in diabetic rats that had levels of corticosterone 'clamped' through adrenalectomy and low-dose corticosterone replacement. For comparison, we also tested a separate group of young and aged rats in the maze. Adrenally intact diabetic rats learned poorly in the 14-unit T-maze. Preventing the increases in corticosterone levels that accompanies the onset of experimental diabetes also prevented deficits in complex maze learning. The pattern of errors made by adrenally intact diabetic rats was similar to the pattern of errors made by aged rats, suggesting that the cognitive profiles of diabetic and aged rats share common features. Published by Elsevier Inc. C1 [Stranahan, Alexis M.; Lee, Kim; Mattson, Mark P.] Natl Inst Aging Intramural Res Program, Neurosci Lab, Cellular & Mol Neurosci Sect, Baltimore, MD USA. [Pistell, Paul J.; Nelson, Christopher M.; Readal, Nathaniel; Miller, Marshall G.; Spangler, Edward L.; Ingram, Donald K.] Natl Inst Aging Intramural Res Program, Lab Expt Gerontol, Baltimore, MD USA. [Pistell, Paul J.; Ingram, Donald K.] Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA USA. RP Mattson, MP (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. EM mattsonm@grc.nia.gov RI Mattson, Mark/F-6038-2012; OI Lee, Kim/0000-0002-5675-1896 FU National Institute on Aging Intramural Research FX This research was supported by the National Institute on Aging Intramural Research Program. NR 13 TC 32 Z9 32 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD SEP PY 2008 VL 90 IS 2 BP 479 EP 483 DI 10.1016/j.nlm.2008.05.005 PG 5 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 347BT UT WOS:000259114700025 PM 18579418 ER PT J AU Goldstein, DS Holmes, C Axelrod, FB AF Goldstein, David S. Holmes, Courtney Axelrod, Felicia B. TI Plasma catechols in familial dysautonomia: A long-term follow-up study SO NEUROCHEMICAL RESEARCH LA English DT Article DE familial dysautonomia; dihydroxyphenylglycol; norepinephrine; DOPA; sympathetic nervous system ID DOPAMINE-BETA-HYDROXYLASE; NOREPINEPHRINE; HUMANS; DIHYDROXYPHENYLALANINE AB This study tested whether familial dysautonomia (FD) involves progressive loss of noradrenergic nerves. Plasma levels of catechols, including dihydroxyphenylglycol (DHPG), norepinephrine (NE), dopamine (DA), and DOPA, were measured in 7 adult patients with FD and 50 healthy control subjects. FD patients were re-tested after a mean follow-up period of 13 years. Compared to controls, FD patients had low plasma levels of DHPG (P < 0.001), high DOPA and DA levels (P = 0.01, P = 0.0002), and high NE:DHPG (P < 0.0001), DA:NE (P = 0.0003), and DOPA:DHPG (P < 0.0001) ratios. At follow-up there were no changes in plasma levels of individual catechols; however, there were further increases in DOPA:DHPG ratios (mean 24 +/- 7%, P = 0.01). In FD, plasma catechol profiles are sufficiently stable, at least over a decade, to be used as a biomarker of disease involvement. An increasing DOPA:DHPG ratio suggests slight but consistent, progressive loss of noradrenergic neurons. C1 [Goldstein, David S.; Holmes, Courtney] NINDS, NIH, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. [Axelrod, Felicia B.] NYU, Sch Med, Dysauton Ctr, Dept Pediat, New York, NY USA. RP Goldstein, DS (reprint author), NINDS, NIH, Clin Neurocardiol Sect, Bldg 10 Room 6N252,10 Ctr Dr MSC-1620, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU Intramural NIH HHS [Z01 NS003033-02, Z01 NS003034-01, , Z99 NS999999] NR 20 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD SEP PY 2008 VL 33 IS 9 BP 1889 EP 1893 DI 10.1007/s11064-008-9662-4 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 332EJ UT WOS:000258064900028 PM 18357519 ER PT J AU Wu, CWW Gu, H Lu, HB Stein, EA Chen, JH Yang, YH AF Wu, Changwei W. Gu, Hong Lu, Hanbing Stein, Elliot A. Chen, Jyh-Horng Yang, Yihong TI Frequency specificity of functional connectivity in brain networks SO NEUROIMAGE LA English DT Article ID RESTING-STATE NETWORKS; MONKEY VISUAL-CORTEX; FLUCTUATIONS; OSCILLATIONS; FMRI; MRI; CORRELATE; DISEASE; SIGNAL AB Synchronized low-frequency spontaneous fluctuations of the functional MRI (fMRI) signal have been shown to be associated with electroencephalography (EEG) power fluctuations in multiple brain networks within predefined frequency bands. However, it remains unclear whether frequency-specific characteristics exist in the resting-state fMRI signal. in this study, fMRI signals in five functional brain networks (sensorimotor, 'default mode', visual, amygdala, and hippocampus) were decomposed into various frequency bands within a low-frequency range (0-0.24 Hz). Results show that the correlations in cortical networks concentrate within ultra-low frequencies (0.01-0.06 Hz) while connections within limbic networks distribute over a wider frequency range (0.01-0.14 Hz), suggesting distinct frequency-specific features in the resting-state PORI signal within these functional networks. Moreover, the connectivity decay rates along the frequency bands are positively Correlated with the physical distances between connected brain regions and seed points. This distance-frequency relationship might be attributed to a larger attenuation of synchrony of brain regions separated with longer distance and/or connected with more synaptic steps. Published by Elsevier Inc. C1 [Wu, Changwei W.; Gu, Hong; Lu, Hanbing; Stein, Elliot A.; Yang, Yihong] Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. [Wu, Changwei W.; Chen, Jyh-Horng] Natl Taiwan Univ, Dept Elect Engn, Interdisciplinary MRI MRS Lab, Taipei, Taiwan. RP Yang, YH (reprint author), Natl Inst Drug Abuse, Neuroimaging Branch, NIH, Room 7A709,Suite 200,251 Bayview Blvd, Baltimore, MD 21224 USA. EM jhchen@ntu.edu.tw; YihongYang@intra.nida.nih.gov FU National Institute on Drug Abuse (NIDA); National Institute of Health (NIH) FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIDA), National Institute of Health (NIH). We would like to thank Mark Lowe and Erik Beall of the Cleveland Clinic Foundation for providing software to correct for physiological noise, Thomas Ross of the National Institute on Drug Abuse and Michael Fox of Washington University for their helpful discussions on data analysis. NR 28 TC 52 Z9 54 U1 2 U2 2 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 SEP PY 2008 VL 42 IS 3 BP 1047 EP 1055 DI 10.1016/j.neuroimage.2008.05.035 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 343PA UT WOS:000258864800001 PM 18632288 ER PT J AU Tavares, JVT Clark, L Furey, ML Williams, GB Sahakian, BJ Drevets, WC AF Tavares, Joana V. Taylor Clark, Luke Furey, Maura L. Williams, Guy B. Sahakian, Barbara J. Drevets, Wayne C. TI Neural basis of abnormal response to negative feedback in unmedicated mood disorders SO NEUROIMAGE LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol ID MEDIAL PREFRONTAL CORTEX; MAJOR DEPRESSIVE DISORDER; EVENT-RELATED FMRI; UNIPOLAR DEPRESSION; BIPOLAR DISORDER; GLUCOSE-METABOLISM; BLOOD-FLOW; PERFORMANCE; AMYGDALA; EMOTION AB Depressed individuals show hypersensitivity to negative feedback during cognitive testing, which can precipitate subsequent errors and thereby impair a broad range of cognitive abilities. We studied the neural mechanisms underlying this feedback hypersensitivity using functional magnetic resonance imaging (fMRI) with a reversal learning task that required subjects to ignore misleading negative feedback on some trials. Thirteen depressed subjects with major depressive disorder (MDD), 12 depressed subjects with bipolar disorder (BD) and 15 healthy controls participated. The MDD group, but not the BD group, demonstrated enhanced sensitivity to negative feedback compared to controls, as indicated by the rates of rule reversal following misleading negative feedback. In the control and BD groups, hemodynamic activity was significantly higher in the dorsomedial and ventrolateral prefrontal cortices during reversal shifting, and significantly lower in the right amygdala in response to negative feedback. The extent to which the amygdala showed less activity during negative feedback correlated inversely with the behavioral tendency to reverse after misleading feedback. This effect was not present in the MDD group, who also failed to recruit the prefrontal cortex during behavioral reversal. Hypersensitivity to negative feedback is present in unmedicated depressed patients with MDD. Disrupted top-down control by the prefrontal cortex of the amygdala may underlie this abnormal response to negative feedback in unipolar depression. (c) 2008 Elsevier Inc. All rights reserved. C1 [Clark, Luke] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. [Tavares, Joana V. Taylor; Sahakian, Barbara J.] Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England. [Tavares, Joana V. Taylor; Williams, Guy B.] Univ Cambridge, Wolfson Brain Imaging Ctr, Cambridge CB2 2QQ, England. [Tavares, Joana V. Taylor; Clark, Luke; Sahakian, Barbara J.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 2QQ, England. [Tavares, Joana V. Taylor; Furey, Maura L.; Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. RP Clark, L (reprint author), Univ Cambridge, Dept Expt Psychol, Downing St, Cambridge CB2 3EB, England. EM lc260@cam.ac.uk RI Furey, Maura/H-5273-2013 NR 45 TC 95 Z9 96 U1 5 U2 18 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 SEP PY 2008 VL 42 IS 3 BP 1118 EP 1126 DI 10.1016/j.neuroimage.2008.05.049 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 343PA UT WOS:000258864800007 ER PT J AU Tang, H Pavel, J Saavedra, JM Brimijoin, S AF Tang, Hui Pavel, Jaroslav Saavedra, Juan M. Brimijoin, Stephen TI Angiotensin II type 1 receptors may not influence response of spinal autonomic neurons to axonal damage SO NEUROLOGICAL RESEARCH LA English DT Article DE Candesartan; immunohistochemistry; sympathetic nervous system; neurodegeneration; primary sensory neurons ID SPONTANEOUSLY HYPERTENSIVE-RATS; ACETYLCHOLINESTERASE ANTIBODIES; AT(1) RECEPTORS; BINDING-SITES; BRAIN; ANTAGONIST; BLOCKADE; CORD; HYPERTROPHY; ISCHEMIA AB Objectives: Angiotensin II can promote cell stress, and the expression of its AT(1) receptor is characteristic of neuronal populations that die off in multiple systems atrophy and Parkinson's disease. To explore the possible significance of these facts, we undertook to: (1) clarify the distribution of AT(1) in rat neurons; (2) use selective antagonists as a means of determining whether AT(1) activation predisposes stressed neurons to die. Methods: AT(1)-expression was examined by immunohistochemistry and by autoradiography for [(125) I]-sarcosine(1)-angiotensin II binding in sensory, motor and autonomic neurons. To induce cell loss in a specific neuronal population, rats were given systemic i.v. injection of antiacetylcholinesterase antibodies, which cause a delayed death of pre-ganglionic sympathetic neurons in the intermediolateral nucleus (IML). As pharmacologic intervention, some immunolesioned rats were treated with the selective AT(1) antagonist, Candesartan. Results: Immunohistochemistry and autoradiography revealed AT(1) expression in dorsal root ganglia, superior cervical ganglion. In the dorsal horn of the spinal cord, AT(1) immunostainining and angiotensin binding were both prominent. In ventral horn and IML, immunoreactivity for AT(1) and choline acetyltransferase co-localized in pre-ganglionic sympathetic and somatic motor neurons. Immunolesion caused over 50% loss of IML perikarya within 3 months. Concurrent treatment with the AT(1) antagonist, Candesartan, did not affect the outcome. Discussion: AT(1) expression is surprisingly widespread in sensory, autonomic and somatic motor neurons of the rat. This expression may be important to the normal physiology of these systems. Present data, however, do not support the concept that AT(1) activation contributes to the loss of autonomic neurons after axonal damage. [Neurol Res 2008; 30: 751-760] C1 [Tang, Hui; Brimijoin, Stephen] Mayo Fdn, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA. [Pavel, Jaroslav; Saavedra, Juan M.] NIMH, Clin Sci Lab, Pharmacol Sect, Bethesda, MD 20892 USA. RP Brimijoin, S (reprint author), Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, 200 1st St SW, Rochester, MN 55905 USA. EM Brimijoin@mayo.edu FU NINDS [NS 32352] FX We thank Professor B. K. Hartman for supplying the antiChAT antibody. This work was supported by an NINDS Program Project Grant on Autonomic Disorders (grant no. NS 32352). NR 27 TC 5 Z9 5 U1 0 U2 4 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD SEP PY 2008 VL 30 IS 7 BP 751 EP 760 DI 10.1179/174313208X298020 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 358FE UT WOS:000259901700016 PM 18498681 ER PT J AU Mattson, MP Wan, RQ AF Mattson, Mark P. Wan, Ruiqian TI Neurotrophic factors in autonomic nervous system plasticity and dysfunction SO NEUROMOLECULAR MEDICINE LA English DT Review DE BDNF; NGF; CNTF; sympathetic; parasympathetic; Parkinson's disease; Alzheimer's disease ID HEART-RATE-VARIABILITY; FIBROBLAST-GROWTH-FACTOR; SYMPATHETIC PREGANGLIONIC NEURONS; TRANSGENIC MOUSE MODEL; GDNF FAMILY LIGANDS; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; DIETARY RESTRICTION; HUNTINGTONS-DISEASE; CALORIC RESTRICTION AB During development, neurotrophic factors are known to play important roles in regulating the survival of neurons in the autonomic nervous system (ANS) and the formation of their synaptic connectivity with their peripheral targets in the cardiovascular, digestive, and other organ systems. Emerging findings suggest that neurotrophic factors may also affect the functionality of the ANS during adult life and may, in part, mediate the effects of environmental factors such as exercise and dietary energy intake on ANS neurons and target cells. In this article, we describe the evidence that ANS neurons express receptors for multiple neurotrophic factors, and data suggesting that activation of those receptors can modify plasticity in the ANS. Neurotrophic factors that may regulate ANS function include brain-derived neurotrophic factor, nerve growth factor, insulin-like growth factors, and ciliary neurotrophic factor. The possibility that perturbed neurotrophic factor signaling is involved in the pathogenesis of ANS dysfunction in some neurological disorders is considered, together with implications for neurotrophic factor-based therapeutic interventions. C1 [Mattson, Mark P.; Wan, Ruiqian] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 154 TC 11 Z9 12 U1 0 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PD SEP PY 2008 VL 10 IS 3 BP 157 EP 168 DI 10.1007/s12017-007-8021-y PG 12 WC Neurosciences SC Neurosciences & Neurology GA 337SR UT WOS:000258456300003 PM 18172785 ER PT J AU McBain, CJ AF McBain, C. J. TI mGluR7: A fulcrum for state-dependent presynaptic metaplasticity SO NEUROPHARMACOLOGY LA English DT Meeting Abstract CT 6th International mGluR Meeting CY SEP 14-19, 2008 CL Taormina, ITALY C1 [McBain, C. J.] NICHD, Program Dev Neurobiol, NIH, Ctr Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD SEP PY 2008 VL 55 IS 4 MA 84 BP 610 EP 610 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 353CX UT WOS:000259544800114 ER PT J AU Pelkey, KA Topolnik, L Yuan, XQ Lacaille, JC McBaiin, CJ AF Pelkey, K. A. Topolnik, L. Yuan, X. Q. Lacaille, J. C. McBaiin, C. J. TI State-dependent cAMP sensitivity of presynaptic function controlled by mGluR7 activation and internalization SO NEUROPHARMACOLOGY LA English DT Meeting Abstract CT 6th International mGluR Meeting CY SEP 14-19, 2008 CL Taormina, ITALY C1 [Pelkey, K. A.; Yuan, X. Q.; McBaiin, C. J.] NICHHD, Natl Inst Hlth, Lab Cellular & Synapt Neurophysiol, Bethesda, MD 20892 USA. [Topolnik, L.; Lacaille, J. C.] Univ Montreal, Nerveux Cent, Dept Physiol, Grp Rech Syst, Montreal, PQ H3C 3J7, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD SEP PY 2008 VL 55 IS 4 MA 106 BP 617 EP 617 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 353CX UT WOS:000259544800136 ER PT J AU Gardiner, JM Brandt, KR Baddeley, AD Vargha-Khadem, F Mishkin, M AF Gardiner, John M. Brandt, Karen R. Baddeley, Alan D. Vargha-Khadem, Faraneh Mishkin, Mortimer TI Charting the acquisition of semantic knowledge in a case of developmental amnesia SO NEUROPSYCHOLOGIA LA English DT Article DE developmental amnesia; episodic memory; semantic memory; hippocampus; learning ID RECOGNITION MEMORY; HIPPOCAMPAL PATHOLOGY; INFORMATION AB We report the acquisition and recall of novel facts by Jon, a young adult with early onset developmental amnesia whose episodic memory is gravely impaired due to selective bilateral hippocampal damage. Jon succeeded in learning some novel facts but compared with a control group his intertrial retention was impaired during acquisition and, except for the most frequently repeated facts, he was also less accurate in correctly sourcing these facts to the experiment. The results further support the hypothesis that despite a severely compromised episodic memory and hippocampal system, there is nevertheless the capacity to accrue semantic knowledge available to recall. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Brandt, Karen R.] Univ Keele, Dept Psychol, Keele ST5 5BG, Staffs, England. [Gardiner, John M.] Univ Sussex, Brighton BN1 9RH, E Sussex, England. [Baddeley, Alan D.] Univ York, York YO10 5DD, N Yorkshire, England. [Vargha-Khadem, Faraneh] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Vargha-Khadem, Faraneh] UCL, London, England. [Mishkin, Mortimer] NIMH, NIH, DHHS, Bethesda, MD, England. RP Brandt, KR (reprint author), Univ Keele, Dept Psychol, 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]; NIMH/NIH FX We are grateful to Jon and to his parents for their very willing cooperation. This research was supported by a grant from the Economic and Social Research Council (ESRC Grant R000223887). It was also supported in part by the Intramural Program of the NIMH/NIH. We thank them for their support. NR 15 TC 23 Z9 23 U1 3 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD SEP PY 2008 VL 46 IS 11 BP 2865 EP 2868 DI 10.1016/j.neuropsychologia.2008.05.021 PG 4 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 339YB UT WOS:000258612100030 PM 18589461 ER PT J AU Jensen, NH Rodriguiz, RM Caron, MG Wetsel, WC Rothman, RB Roth, BL AF Jensen, Niels H. Rodriguiz, Ramona M. Caron, Marc G. Wetsel, William C. Rothman, Richard B. Roth, Bryan L. TI N-Desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE quetiapine; N-Desalkylquetiapine; norepinephrine reuptake inhibitor; antidepressant; antipsychotic ID ATYPICAL ANTIPSYCHOTIC-DRUGS; BIPOLAR-II DEPRESSION; INDUCED WEIGHT-GAIN; CLINICAL PHARMACOKINETICS; DOUBLE-BLIND; MICE; SCHIZOPHRENIA; RECEPTORS; SEROTONIN; BLOCKADE AB Quetiapine is an atypical antipsychotic drug that is also US FDA approved for treating bipolar depression, albeit by an unknown mechanism. To discover the potential mechanism for this apparently unique action, we screened quetiapine, its metabolite N-Desalkylquetiapine, and dibenzo[b,f][ 1,4] thiazepine-11(10-H)-one (DBTO) against a large panel of G-protein - coupled receptors, ion channels, and neurotransmitter transporters. DBTO was inactive at all tested molecular targets. N-Desalkylquetiapine had a high affinity (3.4 nM) for the histamine H-1 receptor and moderate affinities (10 - 100 nM) for the norepinephrine reuptake transporter (NET), the serotonin 5-HT1A, 5-HT1E, 5-HT2A, 5-HT2B, 5-HT7 receptors, the alpha(1B)-adrenergic receptor, and the M-1, M-3, and M-5 muscarinic receptors. The compound had low affinities (100-1000 nM) for the 5-HT1D, 5-HT2C, 5-HT3, 5-HT5, 5-HT6, alpha(1A), alpha(2A), alpha(2B), alpha(2C), H-2, M-2, M-4, and dopamine D-1, D-2, D-3, and D-4 receptors. N-Desalkylquetiapine potently inhibited human NE transporter with a K-i of 12 nM, about 100-fold more potent than quetiapine itself. N-Desalkylquetiapine was also 10-fold more potent and more efficacious than quetiapine at the 5-HT1A receptor. N-Desalkylquetiapine was an antagonist at 5-HT2A, 5-HT2B, 5-HT2C, alpha(1A), alpha(1D), alpha(2A), alpha(2C), H-1, M-1, M-3, and M-5 receptors. In the mouse tail suspension test, N-Desalkylquetiapine displayed potent antidepressant-like activity in VMAT2 heterozygous mice at doses as low as 0.1 mg/kg. These data strongly suggest that the antidepressant activity of quetiapine is mediated, at least in part, by its metabolite N-Desalkylquetiapine through NET inhibition and partial 5-HT1A agonism. Possible contributions of this metabolite to the side effects of quetiapine are discussed. C1 [Jensen, Niels H.; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Rodriguiz, Ramona M.; Wetsel, William C.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Rodriguiz, Ramona M.; Wetsel, William C.] Duke Univ, Med Ctr, Mouse Behav & Neuroendocrine Anal Core Facil, Durham, NC USA. [Caron, Marc G.; Wetsel, William C.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. [Caron, Marc G.; Wetsel, William C.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. [Rothman, Richard B.] NIDA, NIH, Intramural Res Program, Clin Psychopharmacol Sect, Baltimore, MD USA. [Roth, Bryan L.] Univ N Carolina, Sch Med, NIMH Psychoact Drug Screening Program, Chapel Hill, NC USA. RP Roth, BL (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, 8032 Burnett Womack Bldg,CB 7365, Chapel Hill, NC 27599 USA. EM bryan_roth@med.unc.edu RI Roth, Bryan/F-3928-2010 FU Intramural NIH HHS; NIMH NIH HHS [R01MH60451, R01MH61887, UF1MH 082441, N01MH32004, R01MH57635] NR 43 TC 181 Z9 185 U1 1 U2 11 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 SEP PY 2008 VL 33 IS 10 BP 2303 EP 2312 DI 10.1038/sj.npp.1301646 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 336WM UT WOS:000258395600001 PM 18059438 ER PT J AU Floel, A Hummel, F Duque, J Knecht, S Cohen, LG AF Floel, Agnes Hummel, Friedhelm Duque, Julie Knecht, Stefan Cohen, Leonardo G. TI Influence of somatosensory input on interhemispheric interactions in patients with chronic stroke SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE anesthesia; interhemispheric inhibition; neurorehabilitation; motor; stroke ID TRANSCRANIAL MAGNETIC STIMULATION; PRIMARY MOTOR CORTEX; TRANSCALLOSAL INHIBITION; INTRACORTICAL CIRCUITS; CLINICAL-APPLICATION; DORSAL PREMOTOR; HAND; RECOVERY; MUSCLE; EXCITABILITY AB Background. Ischemia-induced Cutaneous anesthesia of the healthy hand in patients with chronic stroke elicits transient improvements of motor performance in the contralateral, paretic hand. Objective. The present Study was designed to investigate one of the possible mechanisms underlying this effect. Methods. The authors evaluated the effects of transient ischemic Cutaneous anesthesia of the healthy hand (target intervention) and healthy foot (control intervention) on transcranial magnetic stimulation-induced interhemispheric inhibition from the contralesional onto the ipsilesional primary motor cortex (M1). Ten subjects with chronic, predominantly subcortical stroke with motor impairment were assessed. Results. Cutaneous anesthesia of the intact hand but not the intact leg resulted in reduction of the inhibitory drive from the contralesional to the ipsilesional M1 both at rest and immediately preceding movements of the paretic hand. Changes in premovement interhemispheric inhibition showed a trend for correlation with improvements in finger-tapping speed in the paretic hand. Conclusion. The findings Suggest that modulation of interhemispheric inhibitory interactions between the contralesional and ipsilesional M1, either primarily or secondary to intrahemispheric excitability changes in either hemisphere, may contribute to performance improvements with cutaneous anesthesia of the intact hand. The present Study provides additional insight into the mechanisms by which rehabilitative interventions focused on training one hand and restraining the other may operate after chronic stroke. C1 [Floel, Agnes; Hummel, Friedhelm; Duque, Julie; Cohen, Leonardo G.] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20817 USA. [Floel, Agnes; Hummel, Friedhelm; Duque, Julie; Cohen, Leonardo G.] NINDS, Stroke Neurorehabil Clin, NIH, Bethesda, MD 20817 USA. [Floel, Agnes; Knecht, Stefan] Univ Munster, Dept Neurol, Munster, Germany. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20817 USA. EM cohenl@ninds.nih.gov RI Floel, Agnes/A-9426-2017; OI Knecht, Stefan/0000-0003-1056-9228 FU National Institute of Neurological Disorders and Stroke; Deutsche Forschungsgemeinschaft [Fl 379-1/1, Fl 379-4/1]; Bundesministerium for Bildung und Forschung [01GW0520]; Nordrhein-Westfalen Ministry of Education and Research; Innovative Medizinische Forschung Munster [FL110605] FX We thank S. Ravindran for help with patient recruitment, N. Dang for providing technical help, and C. Breitenstein for helpful discussions on the manuscript.; This work was supported by the intramural research program of the National Institute of Neurological Disorders and Stroke, the Deutsche Forschungsgemeinschaft to AF (Fl 379-1/1, Fl 379-4/1), the Bundesministerium for Bildung und Forschung to AF (01GW0520, part 4), the Nordrhein-Westfalen Ministry of Education and Research to AF (Lise Meitner Stipendium), and the Innovative Medizinische Forschung Munster to AF (FL110605).; None of the authors reports any potential conflict of interest. NR 55 TC 30 Z9 30 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD SEP-OCT PY 2008 VL 22 IS 5 BP 477 EP 485 DI 10.1177/1545968308316388 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 343QE UT WOS:000258867900006 PM 18645188 ER PT J AU Adamec, R Holmes, A Blundell, J AF Adamec, Robert Holmes, Andrew Blundell, Jacqueline TI Vulnerability to lasting anxiogenic effects of brief exposure to predator stimuli: Sex, serotonin and other factors-Relevance to PTSD SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Article; Proceedings Paper CT Satellite Symposium on Olfaction and Aversive Emotions held in Conjunction with the International-Behavioral-Neuroscience-Society CY JUN, 2007 CL Rio de Janeiro, BRAZIL SP Int Behav Neurosci Soc DE Amygdala; Anxiety; Cat exposure; Cat odor exposure; Elevated plus maze; Lasting effects; 5-HTT knockout mice; Limbic neuroplasticity; mPFC; Mice; 5-HT1A; 5-HT2A; PTSD; Startle; SERT ID POSTTRAUMATIC-STRESS-DISORDER; TRANSPORTER KNOCKOUT MICE; LONG-TERM POTENTIATION; ANXIETY-LIKE BEHAVIOR; NATIONAL COMORBIDITY SURVEY; 5-HT TRANSPORTER; TRAUMATIC STRESS; CAT ODOR; NEUROENDOCRINE RESPONSES; SYSTEMIC INJECTIONS AB Lasting anxiogenic effects of predator stress in rodents may model aspects of post-traumatic stress disorder (PTSD). There is a link between genetic variation in the serotonin (5-HT) transporter (SERT) and anxiety in humans, promoting the generation of SERT knockout mice. This review brings together studies of SERT knockout male mice, normal female mice, and different 5-HT receptors in predator stress effects on anxiety. These studies provide for a link between vulnerability to the anxiogenic effects of predator stress and abnormalities of 5-HT transmission induced by a life long reduction in 5-HT reuptake in male mice, which creates a vulnerability like that seen in normal female mice. Data reviewed suggest abnormalities in 5-HT transmission contribute to vulnerability to lasting anxiogenic effects of species relevant stressors. To the extent to which predator stress effects model aspects of PTSD, and in the light of relevant human literature, these considerations implicate abnormalities of 5-HT transmission in vulnerability to PTSD per se, and as a potential contributor to enhanced female vulnerability to PTSD. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Adamec, Robert; Blundell, Jacqueline] Mem Univ Newfoundland, Dept Psychol, St John, NF A1B 3X9, Canada. [Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIMH,NIH, Bethesda, MD 20892 USA. RP Adamec, R (reprint author), Mem Univ Newfoundland, Dept Psychol, 232 Elizabeth Ave, St John, NF A1B 3X9, Canada. EM radamec@mun.ca FU Intramural NIH HHS [Z01 AA000411-04] NR 96 TC 38 Z9 38 U1 4 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD SEP PY 2008 VL 32 IS 7 SI SI BP 1287 EP 1292 DI 10.1016/j.neubiorev.2008.05.005 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 363PK UT WOS:000260279000010 PM 18550167 ER PT J AU Holmes, A AF Holmes, Andrew TI Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Article; Proceedings Paper CT Satellite Symposium on Olfaction and Aversive Emotions held in Conjunction with the International-Behavioral-Neuroscience-Society CY JUN, 2007 CL Rio de Janeiro, BRAZIL SP Int Behav Neurosci Soc DE Stress; Gene; Strain; Mouse; Inbred; Serotonin; Serotonin transporter; Tryptophan hydroxylase; VMAT2; MAOA; 5-HT1A; 5-HT1B; 5-HT2A; 5-HT2C; 5-HT3; Prefrontal cortex; Hippocampus; Amygdala; Anxiety; Depression; Emergence test; Forced swim test; Restraint ID DORSAL RAPHE NUCLEUS; MEDIAL PREFRONTAL CORTEX; RECEPTOR KNOCKOUT MICE; ELEVATED PLUS-MAZE; RAT BASOLATERAL AMYGDALA; CENTRAL-NERVOUS-SYSTEM; ANXIETY-LIKE BEHAVIOR; PITUITARY-ADRENAL AXIS; FORCED SWIMMING TEST; POSTSYNAPTIC 5-HT1A RECEPTORS AB The serotonin system is strongly implicated in the pathophysiology and therapeutic alleviation of stress-related disorders such as anxiety and depression. Serotonergic modulation of the acute response to stress and the adaptation to chronic stress is mediated by a myriad of molecules controlling serotonin neuron development (Pet-1), synthesis (tryptophan hydroxylase I and 2 isozymes), packaging (vesicular monoamine transporter 2), actions at presynaptic and postsynaptic receptors (5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT3A, 5-HT4, 5-HT5A, 5-HT6, 5-HT7), reuptake (serotonin transporter), and degradation (monoamine oxidase A). A growing body of evidence from preclinical rodents models, and especially genetically modified mice and inbred mouse strains, has provided significant insight into how genetic variation in these molecules can affect the development and function of a key neural circuit between the dorsal raphe nucleus, medial prefrontal cortex and amygdala. By extension, such variation is hypothesized to have a major influence on individual differences in the stress response and risk for stress-related disease in humans. The current article provides an update on this rapidly evolving field of research. Published by Elsevier Ltd. C1 NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA. EM holmesan@mail.nih.gov FU Intramural NIH HHS [Z01 AA000411-04] NR 489 TC 155 Z9 158 U1 6 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD SEP PY 2008 VL 32 IS 7 SI SI BP 1293 EP 1314 DI 10.1016/j.neubiorev.2008.03.006 PG 22 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 363PK UT WOS:000260279000011 PM 18439676 ER PT J AU Liu, YX Qin, LY Wilson, B Wu, XF Qian, L Granholm, AC Crews, FT Hong, JS AF Liu, Yuxin Qin, Liya Wilson, Belinda Wu, Xuefei Qian, Li Granholm, Ann-Charlotte Crews, Fulton T. Hong, Jau-Shyong TI Endotoxin induces a delayed loss of TH-IR neurons in substantia nigra and motor behavioral deficits SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 24th International Neurotoxicology Conference on Environmental Etiologies of Neurological Disorders - Modifiers of Risk CY NOV 11-14, 2007 CL San Antonio, TX SP Natl Inst Environm Hlth Sci, EOHSI, ASA, ATSDR, March Dimes, Autism Speaks, Elsevier, Charles River Lab, John Merch Fund, CTEH, Soc Toxicol, INND, Inst Childrens Environm Hlth, Hammer, Inst Hlth Sci, Morris Cranmer, UAMS, VA Res Dev, Arkansas Childrens Hosp DE Lipopolysaccharide; Neurodegeneration; Parkinson's disease; TH-IR neurons; Rotarod test ID PARKINSONS-DISEASE; MICROGLIAL ACTIVATION; DOPAMINERGIC-NEURONS; ESTROGEN; EXPOSURE; NEUROTOXICITY; INFLAMMATION; MECHANISMS; EXPRESSION; SEPSIS AB We have previously reported that a single injection of endotoxin, lipopolysaccharide (LPS, 5 mg/kg, i.p.), causes a delayed and progressive loss of TH-IR neurons in the substantia nigra (SN) in C57BL/six male mice. In this study, we determined sex differences and behavioral deficits accompanying the loss of TH-IR neurons in response to peripheral LPS injection. A single injection of LPS (5 mg/kg, i.p.) failed to produce any loss of TH-IR neurons in the SN of female mice over a 12-month period. To determine if multiple-injections were required, female mice received five injections of LPS (5 mg/kg, i.p.) at either weekly or monthly intervals. Behavioral motor ability and TH-IR neuronal loss were determined after the first injection of LPS. We found significant differences in both behavioral activities and neuronal loss between these two injection paradigms. Between 7 and 20 months after the first injection of LPS, progressive behavioral changes, measured by rotor-rod and open-field activities, and neuronal loss in SN were observed in monthly injected, but not in weekly injected mice. In addition, reduced rotor-rod ability in monthly injected mice were restored following treatment of L-dopa/carbidopa (30 mg/3 mg/kg), i.p.). Approximately 40 and 50% loss of TH-IR neurons at 9 and 20 months, respectively, was observed after exposure to LPS, suggesting that the behavioral deficit is related to loss of dopamine function in the nigra-striatal pathway. More intense immuno-staining of alpha-synuclein and inflammatory markets were detected in brain sections exposed to LPS. In conclusion, these results show that multi-LPS monthly injections can induce a delayed and progressive loss of TH-IR neurons and motor deficits which resemble the progressive nature of Parkinson's disease. Further, the present study reveals a clear sex difference: female mice are more resistant to LPS than male mice. Repeated monthly LPS injections are required to cause both motor behavioral deficits and DA neuronal loss in female mice. Published by Elsevier Inc. C1 [Liu, Yuxin; Wilson, Belinda; Wu, Xuefei; Qian, Li; Hong, Jau-Shyong] Natl Inst Environm Hlth Sci, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. [Liu, Yuxin; Qin, Liya; Crews, Fulton T.] Univ N Carolina, Sch Med, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. [Qian, Li] Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. [Granholm, Ann-Charlotte] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. RP Hong, JS (reprint author), Natl Inst Environm Hlth Sci, Neuropharmacol Sect, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM hong3@niehs.nih.gov FU Intramural NIH HHS; NIA NIH HHS [AG023630, P01 AG023630, P01 AG023630-03] NR 32 TC 28 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2008 VL 29 IS 5 SI SI BP 864 EP 870 DI 10.1016/j.neuro.2008.02.014 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 366XE UT WOS:000260516100014 PM 18471886 ER PT J AU Wink, DA Ridnour, LA Hussain, SP Harris, CC AF Wink, David A. Ridnour, Lisa A. Hussain, S. Perwez Harris, Curtis C. TI The reemergence of nitric oxide and cancer - Preface SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Editorial Material ID WOODCHUCK HEPATITIS-VIRUS; ENDOTHELIAL GROWTH-FACTOR; BLOOD-PRESSURE; NITRATE BIOSYNTHESIS; SYNTHASE ACTIVITY; MUTATION SPECTRA; DIETARY NITRATE; MARMOTA-MONAX; TUMOR-GROWTH; HUMAN-CELLS C1 [Wink, David A.; Ridnour, Lisa A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Hussain, S. Perwez; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Wink, DA (reprint author), NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. EM wink@mail.nih.gov FU Intramural NIH HHS [Z01 BC010033-12] NR 52 TC 60 Z9 61 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD SEP PY 2008 VL 19 IS 2 BP 65 EP 67 DI 10.1016/j.niox.2008.05.003 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 330UW UT WOS:000257969300001 PM 18638716 ER PT J AU Ridnour, LA Thomas, DD Switzer, C Flores-Santana, W Isenberg, JS Ambs, S Roberts, DD Wink, DA AF Ridnour, Lisa A. Thomas, Douglas D. Switzer, Christopher Flores-Santana, Wilmarie Isenberg, Jeffrey S. Ambs, Stefan Roberts, David D. Wink, David A. TI Molecular mechanisms for discrete nitric oxide levels in cancer SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Review DE nitric oxide; cancer; angiogenesis; treatment; nitrosative stress ID SIGNAL-REGULATED KINASE; HUMAN BREAST-CANCER; CELL RESPONSES; POOR SURVIVAL; WOUND REPAIR; THROMBOSPONDIN-1; MACROPHAGE; PATHWAY; P53; ANGIOGENESIS AB Nitric oxide (NO) has been invoked in nearly every normal and pathological condition associated with human physiology. in tumor biology, nitrogen oxides have both positive and negative affects as they have been implicated in both promoting and preventing cancer. Our work has focused on NO chemistry and how it correlates with cytotoxicity and cancer. Toward this end, we have studied both concentration- and time-dependent NO regulation of specific signaling pathways in response to defined nitrosative stress levels that may occur within the tumor microenvironment. Threshold levels of NO required for activation and stabilization of key proteins involved in carcinogenesis including p53, ERK, Akt and HIF have been identified. Importantly, threshold NO levels are further influenced by reactive oxygen species (ROS) including superoxide, which can shift or attenuate NO-mediated signaling as observed in both tumor and endothelial cells. Our studies have been extended to determine levels of NO that are critical during angiogenic response through regulation of the anti-angiogenic agent thrombospondin-1 (TSP-1) and pro-angiogenic agent matrix metalloproteinase-9 (MMP-9). The quantification of redox events at the cellular level has revealed potential mechanisms that may either limit or potentiate tumor growth, and helped define the positive and negative function of nitric oxide in cancer. Published by Elsevier Inc. C1 [Ridnour, Lisa A.; Switzer, Christopher; Flores-Santana, Wilmarie; Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Thomas, Douglas D.] Univ Illinois, Sch Pharm, Dept Med Chem & Pharmacol, Chicago, IL USA. [Isenberg, Jeffrey S.; Roberts, David D.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Ambs, Stefan] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Ridnour, LA (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3-B35, Bethesda, MD 20892 USA. EM ridnourl@mail.nih.gov; wink@mail.nih.gov RI Roberts, David/A-9699-2008; Switzer, Christopher/D-9203-2013 OI Roberts, David/0000-0002-2481-2981; FU Intramural NIH HHS [Z01 SC007281-14] NR 34 TC 66 Z9 69 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD SEP PY 2008 VL 19 IS 2 BP 73 EP 76 DI 10.1016/j.niox.2008.04.006 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 330UW UT WOS:000257969300003 PM 18472020 ER PT J AU Li, JT Zhang, Y Kong, L Liu, QR Wei, LP AF Li, Jiong-Tang Zhang, Yong Kong, Lei Liu, Qing-Rong Wei, Liping TI Trans-natural antisense transcripts including noncoding RNAs in 10 species: implications for expression regulation SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI; HUMAN-GENOME; MESSENGER-RNA; MOUSE OOCYTES; MAMMALIAN GENOME; GENE-EXPRESSION; PREDICTION; PROTEIN; SENSE; EVOLUTION AB Natural antisense transcripts are at least partially complementary to their sense transcripts. Cis-Sense/Antisense pairs (cis-SAs) have been extensively characterized and known to play diverse regulatory roles, whereas trans-Sense/Antisense pairs (trans-SAs) in animals are poorly studied. We identified long trans-SAs in human and nine other animals, using ESTs to increase coverage significantly over previous studies. The percentage of transcriptional units (TUs) involved in trans-SAs among all TUs was as high as 4.13%. Particularly 2896 human TUs (or 2.89% of all human TUs) were involved in 3327 trans-SAs. Sequence complementarities over multiple segments with predicted RNA hybridization indicated that some trans-SAs might have sophisticated RNA-RNA pairing patterns. One-fourth of human trans-SAs involved noncoding TUs, suggesting that many noncoding RNAs may function by a trans-acting antisense mechanism. TUs in trans-SAs were statistically significantly enriched in nucleic acid binding, ion/protein binding and transport and signal transduction functions and pathways; a significant number of human trans-SAs showed concordant or reciprocal expression pattern; a significant number of human trans-SAs were conserved in mouse. This evidence suggests important regulatory functions of trans-SAs. In 30 cases, trans-SAs were related to cis-SAs through paralogues, suggesting a possible mechanism for the origin of trans-SAs. All trans-SAs are available at http://trans.cbi.pku.edu.cn/. C1 [Li, Jiong-Tang; Zhang, Yong; Kong, Lei; Wei, Liping] Peking Univ, Ctr Bioinformat, Natl Lab Prot Engn & Plant Genet Engn, Coll Life Sci, Beijing 100871, Peoples R China. [Liu, Qing-Rong] NIDA IRP, DHHS, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. RP Wei, LP (reprint author), Peking Univ, Ctr Bioinformat, Natl Lab Prot Engn & Plant Genet Engn, Coll Life Sci, Beijing 100871, Peoples R China. EM weilp@mail.cbi.pku.edu.cn RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU China Ministry of Science and Technology [2006AA02Z334, 2006AA0 2Z314, 2006AA02A312, 2007AA02Z165]; Basic Research Programs [2006CB910404, 2007CB946904]; China Ministry of Education [B06001]; National Institutes of Health (NIH)-Intramural Research Program; National Institute on Drug Abuse FX We are grateful to Drs Manyuan Long, Jane Wu, Louis Tao, Zicai Liang and Ge Gao for insightful suggestions. We thank Dr Laurie Goodman for proofreading the manuscript. This work was supported by China Ministry of Science and Technology 863 Hi-Tech Research and Development Programs (No. 2006AA02Z334, 2006AA0 2Z314, 2006AA02A312, 2007AA02Z165) and 973 Basic Research Programs (No. 2006CB910404, 2007CB946904), and China Ministry of Education 111 project (No. B06001). This study was also supported in part by the National Institutes of Health (NIH)-Intramural Research Program, National Institute on Drug Abuse. Funding to pay the Open Access publication charges for this article was provided by China Ministry of Education 111 Project (No. B06001). NR 75 TC 27 Z9 31 U1 0 U2 8 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 SEP PY 2008 VL 36 IS 15 BP 4833 EP 4844 DI 10.1093/nar/gkn470 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 343OW UT WOS:000258864400009 PM 18653530 ER PT J AU Bukowy, Z Harrigan, JA Ramsden, DA Tudek, B Bohr, VA Stevnsner, T AF Bukowy, Zuzanna Harrigan, Jeanine A. Ramsden, Dale A. Tudek, Barbara Bohr, Vilhelm A. Stevnsner, Tinna TI WRN Exonuclease activity is blocked by specific oxidatively induced base lesions positioned in either DNA strand SO NUCLEIC ACIDS RESEARCH LA English DT Article ID WERNER-SYNDROME PROTEIN; ABASIC SITE RECOGNITION; ESCHERICHIA-COLI; FUNCTIONAL INTERACTION; DAMAGED DNA; MAJOR HUMAN; APURINIC/APYRIMIDINIC ENDONUCLEASE; CRYSTAL-STRUCTURE; EXCISION-REPAIR; RECQ HELICASES AB Werner syndrome (WS) is a premature aging disorder caused by mutations in the WS gene (WRN). Although WRN has been suggested to play an important role in DNA metabolic pathways, such as recombination, replication and repair, its precise role still remains to be determined. WRN possesses ATPase, helicase and exonuclease activities. Previous studies have shown that the WRN exonuclease is inhibited in vitro by certain lesions induced by oxidative stress and positioned in the digested strand of the substrate. The presence of the 70/86 Ku heterodimer (Ku), participating in the repair of double-strand breaks (DSBs), alleviates WRN exonuclease blockage imposed by the oxidatively induced DNA lesions. The current study demonstrates that WRN exonuclease is inhibited by several additional oxidized bases, and that Ku stimulates the WRN exonuclease to bypass these lesions. Specific lesions present in the non-digested strand were shown also to inhibit the progression of the WRN exonuclease; however, Ku was not able to stimulate WRN exonuclease to bypass these lesions. Thus, this study considerably broadens the spectrum of lesions which block WRN exonuclease progression, shows a blocking effect of lesions in the non-digested strand, and supports a function for WRN and Ku in a DNA damage processing pathway. C1 [Bukowy, Zuzanna; Stevnsner, Tinna] Univ Aarhus, Dept Mol Biol, Danish Ctr Mol Gerontol, DK-8000 Aarhus C, Denmark. [Harrigan, Jeanine A.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Natl Inst Hlth, Baltimore, MD 21224 USA. [Ramsden, Dale A.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. [Tudek, Barbara] Polish Acad Sci, Inst Biochem & Biophys, Warsaw, Poland. [Tudek, Barbara] Warsaw Univ, Inst Genet & Biotechnol, Warsaw, Poland. RP Stevnsner, T (reprint author), Univ Aarhus, Dept Mol Biol, Danish Ctr Mol Gerontol, DK-8000 Aarhus C, Denmark. EM tvs@mb.au.dk FU National Institute of Health/National Institute on Aging Intramural Program; European Union Research Training Network [HPRN-CT-2002-00240]; Danish Research Council [22-03-0253]; Danish Cancer Society [DP05024]; NovoNordisk Foundation; The Danish Aging Research Center FX We thank Susanne Trillingsgaard Veno for help with performing the assays with Fapy lesions. This work was supported in part by the National Institute of Health/National Institute on Aging Intramural Program. It was furthermore supported by the European Union Research Training Network programme (contract no. HPRN-CT-2002-00240), as well as the Danish Research Council (22-03-0253), the Danish Cancer Society (DP05024), The NovoNordisk Foundation, and The Danish Aging Research Center. Funding to pay the Open Access publication charges for this article was provided by Danish Cancer Society. NR 67 TC 18 Z9 20 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP PY 2008 VL 36 IS 15 BP 4975 EP 4987 DI 10.1093/nar/gkn468 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 343OW UT WOS:000258864400021 PM 18658245 ER PT J AU Tozluoglu, M Karaca, E Haliloglu, T Nussinov, R AF Tozluoglu, Melda Karaca, Ezgi Haliloglu, Turkan Nussinov, Ruth TI Cataloging and organizing p73 interactions in cell cycle arrest and apoptosis SO NUCLEIC ACIDS RESEARCH LA English DT Review ID MOLECULAR INTERACTION MAP; TRANSCRIPTION FACTOR FAMILY; TUMOR-SUPPRESSOR PROTEIN; YES-ASSOCIATED PROTEIN; ABL TYROSINE KINASE; P53 HOMOLOG P73; VIRUS TYPE-I; DNA-DAMAGE; C-ABL; PHYSICAL INTERACTION AB We have compiled the p73-mediated cell cycle arrest and apoptosis pathways. p73 is a member of the p53 family, consisting of p53, p63 and p73. p73 exists in several isoforms, presenting different domain structures. p73 functions not only as a tumor suppressor in apoptosis but also as differentiator in embryo development. p53 mutations are responsible for half of the human cancers; p73 can partially substitute mutant p53 as tumor suppressor. The pathways we assembled create a p73-centered network consisting of 53 proteins and 176 interactions. We clustered our network into five functional categories: Upregulation, Activation, Suppression, ranscriptional Activity and Degradation. Our literature searches led to discovering proteins (c-Jun and pRb) with apparent opposing functional effects; these indicate either currently missing proteins and interactions or experimental misidentification or functional annotation. For convenience, here we present the p73 network using the molecular interaction map (MIM) notation. The p73 MIM is unique amongst MIMs, since it further implements detailed domain features. We highlight shared pathways between p53 and p73. We expect that the compiled and organized network would be useful to p53 family-based studies. C1 [Tozluoglu, Melda; Karaca, Ezgi; Haliloglu, Turkan] Bogazici Univ, Polymer Res Ctr, TR-80815 Bebek, Turkey. [Tozluoglu, Melda; Karaca, Ezgi; Haliloglu, Turkan] Bogazici Univ, Dept Chem Engn, TR-80815 Bebek, Turkey. [Nussinov, Ruth] SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, NCI Frederick, Basic Res Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Haliloglu, T (reprint author), Bogazici Univ, Polymer Res Ctr, TR-80815 Bebek, Turkey. EM turkan@prc.boun.edu.tr; ruthn@ncifcrf.gov FU Turkish Academy of Sciences (TUBA); Scientific and Technological Research Council of Turkey [TUBITAK, 107T382]; National Cancer Institute; National Institutes of Health [N01-CO-12400]; Center for Cancer Research; NCI [N01-CO-12400]; NIH; [EU FP6-2004-ACC-SSA-2 (517991)] FX We are grateful to Dr Kurt Kohn for suggesting the project to us. Moreover, Dr Kohn and Dr Mirit Aladjem followed the project making many useful comments. We would like to acknowledge financial support from the following sources: EU FP6-2004-ACC-SSA-2 (517991); Turkish Academy of Sciences (TUBA); The Scientific and Technological Research Council of Turkey (TUBITAK, 107T382). This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health (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. Funding to pay the Open Access publication charges for this article was provided by NCI contract N01-CO-12400. NR 125 TC 15 Z9 16 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 SEP PY 2008 VL 36 IS 15 BP 5033 EP 5049 DI 10.1093/nar/gkn481 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 343OW UT WOS:000258864400026 PM 18660513 ER PT J AU Bauman, JD Das, K Ho, WC Baweja, M Himmel, DM Clark, AD Oren, DA Boyer, PL Hughes, SH Shatkin, AJ Arnold, E AF Bauman, Joseph D. Das, Kalyan Ho, William C. Baweja, Mukta Himmel, Daniel M. Clark, Arthur D., Jr. Oren, Deena A. Boyer, Paul L. Hughes, Stephen H. Shatkin, Aaron J. Arnold, Eddy TI Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design SO NUCLEIC ACIDS RESEARCH LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIGH-RESOLUTION STRUCTURES; PROTEIN CRYSTALLIZATION; POSITIONAL ADAPTABILITY; ANGSTROM RESOLUTION; OVERLAP EXTENSION; INHIBITORS; CRYSTALLOGRAPHY; RESISTANCE; FRAGMENT AB HIV-1 reverse transcriptase (RT) is a primary target for anti-AIDS drugs. Structures of HIV-1 RT, usually determined at 2.53.0 resolution, are important for understanding enzyme function and mechanisms of drug resistance in addition to being helpful in the design of RT inhibitors. Despite hundreds of attempts, it was not possible to obtain the structure of a complex of HIV-1 RT with TMC278, a nonnucleoside RT inhibitor (NNRTI) in advanced clinical trials. A systematic and iterative protein crystal engineering approach was developed to optimize RT for obtaining crystals in complexes with TMC278 and other NNRTIs that diffract X-rays to 1.8 resolution. Another form of engineered RT was optimized to produce a high-resolution apo-RT crystal form, reported here at 1.85 resolution, with a distinct RT conformation. Engineered RTs were mutagenized using a new, flexible and cost effective method called methylated overlap-extension ligation independent cloning. Our analysis suggests that reducing the solvent content, increasing lattice contacts, and stabilizing the internal low-energy conformations of RT are critical for the growth of crystals that diffract to high resolution. The new RTs enable rapid crystallization and yield high-resolution structures that are useful in designing/developing new anti-AIDS drugs. C1 [Bauman, Joseph D.; Das, Kalyan; Ho, William C.; Baweja, Mukta; Himmel, Daniel M.; Clark, Arthur D., Jr.; Oren, Deena A.; Shatkin, Aaron J.; Arnold, Eddy] Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. [Bauman, Joseph D.; Das, Kalyan; Ho, William C.; Himmel, Daniel M.; Clark, Arthur D., Jr.; Oren, Deena A.; Arnold, Eddy] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. [Boyer, Paul L.; Hughes, Stephen H.] NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Arnold, E (reprint author), Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. EM arnold@cabm.rutgers.edu FU NIH FX We acknowledge personnel at the Cornell High Energy Synchrotron Source (CHESS), Brookhaven National Laboratory (BNL), Advanced Photon Source Argonne National Laboratory (APS) and Liang Tong of Columbia University for support of data collection. Members of our laboratories provided valuable discussions and assistance, including Stefan Sara. anos, Chhaya Dharia, Chun Chu, Rajiv Bandwar, ThomasActon, Sergio Martinez and Jason Schifano. E. A. is grateful to the National Institutes of Health (Grants AI 27690 MERIT Award and P01 GM 066671) for support of RT structural studies. S. H. H. was supported by the Intramural Research Program of National Institutes of Health, National Cancer Institute, Center for Cancer Research and National Institute of General Medical Sciences. Funding to pay Open Access publication charges for this article was provided by the NIH. NR 31 TC 54 Z9 58 U1 0 U2 7 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 SEP PY 2008 VL 36 IS 15 BP 5083 EP 5092 DI 10.1093/nar/gkn464 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 343OW UT WOS:000258864400030 PM 18676450 ER PT J AU Kulkarni, A McNeill, DR Gleichmann, M Mattson, MP Wilson, DM AF Kulkarni, Avanti McNeill, Daniel R. Gleichmann, Marc Mattson, Mark P. Wilson, David M., III TI XRCC1 protects against the lethality of induced oxidative DNA damage in nondividing neural cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID STRAND BREAK REPAIR; BASE EXCISION-REPAIR; OXYGEN FREE-RADICALS; CHROMOSOMAL-ABERRATIONS; SPINOCEREBELLAR ATAXIA; NEUROBLASTOMA SH-SY5Y; GENE-PRODUCT; MUTANT-CELLS; APRATAXIN; RESISTANCE AB XRCC1 is a critical scaffold protein that orchestrates efficient single-strand break repair (SSBR). Recent data has found an association of XRCC1 with proteins causally linked to human spinocerebellar ataxiasaprataxin and tyrosyl-DNA phosphodiesterase 1implicating SSBR in protection against neuronal cell loss and neurodegenerative disease. We demonstrate herein that shRNA lentiviral-mediated XRCC1 knockdown in human SH-SY5Y neuroblastoma cells results in a largely selective increase in sensitivity of the nondividing (i.e. terminally differentiated) cell population to the redox-cycling agents, menadione and paraquat; this reduced survival was accompanied by an accumulation of DNA strand breaks. Using hypoxanthinexanthine oxidase as the oxidizing method, XRCC1 deficiency affected both dividing and nondividing SH-SY5Y cells, with a greater effect on survival seen in the former case, suggesting that the spectrum of oxidative DNA damage created dictates the specific contribution of XRCC1 to cellular resistance. Primary XRCC1 heterozygous mouse cerebellar granule cells exhibit increased strand break accumulation and reduced survival due to increased apoptosis following menadione treatment. Moreover, knockdown of XRCC1 in primary human fetal brain neurons leads to enhanced sensitivity to menadione, as indicated by increased levels of DNA strand breaks relative to control cells. The cumulative results implicate XRCC1, and more broadly SSBR, in the protection of nondividing neuronal cells from the genotoxic consequences of oxidative stress. C1 [Kulkarni, Avanti; McNeill, Daniel R.; Wilson, David M., III] NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. [Gleichmann, Marc; Mattson, Mark P.] NIA, NIH, Neurosci Lab, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Wilson, DM (reprint author), NIA, NIH, Lab Mol Gerontol, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM wilsonda@mail.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural Research Program of the NIH; National Institute on Aging FX We thank P. Pistell (Pennington Research Institute) for supervising the animal behavioral studies, A. Nath (Johns Hopkins) for providing the human mixed glialneuronal cell populations, H. Nguyen (Stanford University) for assisting in some of the early mouse brain cell studies, and Z. Guo (NIA) for helpful discussion. We also thank Drs L. Weissman and J- L. Yang (NIA) for critical reading of the manuscript. Funding to pay Open Access publication charges for this article was provided by the Intramural Research Program of the NIH, National Institute on Aging. NR 51 TC 26 Z9 26 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 SEP PY 2008 VL 36 IS 15 BP 5111 EP 5121 DI 10.1093/nar/gkn480 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 343OW UT WOS:000258864400033 PM 18682529 ER PT J AU Jothi, R Cuddapah, S Barski, A Cui, K Zhao, K AF Jothi, Raja Cuddapah, Suresh Barski, Artem Cui, Kairong Zhao, Keji TI Genome-wide identification of in vivo protein-DNA binding sites from ChIP-Seq data SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RESTRICTIVE SILENCER FACTOR; TRANSCRIPTIONAL REPRESSOR; ZINC FINGERS; CTCF; CHROMATIN; GENES; EPIGENETICS; INSULATORS; MOTIFS; CELLS AB ChIP-Seq, which combines chromatin immunoprecipitation (ChIP) with ultra high-throughput massively parallel sequencing, is increasingly being used for mapping proteinDNA interactions in-vivo on a genome scale. Typically, short sequence reads from ChIP-Seq are mapped to a reference genome for further analysis. Although genomic regions enriched with mapped reads could be inferred as approximate binding regions, short read lengths (similar to 25-50 nt) pose challenges for determining the exact binding sites within these regions. Here, we present SISSRs ((S) under bar ite Identification from (S) under bar hort (S) under bar equence (R) under bar Reads), a novel algorithm for precise identification of binding sites from short reads generated from ChIP-Seq experiments. The sensitivity and specificity of SISSRs are demonstrated by applying it on ChIP-Seq data for three widely studied and well-characterized human transcription factors: CTCF (CCCTC-binding factor), NRSF (neuron-restrictive silencer factor) and STAT1 (signal transducer and activator of transcription protein 1). We identified 26 814, 5813 and 73 956 binding sites for CTCF, NRSF and STAT1 proteins, respectively, which is 32, 299 and 78 more than that inferred previously for the respective proteins. Motif analysis revealed that an overwhelming majority of the identified binding sites contained the previously established consensus binding sequence for the respective proteins, thus attesting for SISSRs accuracy. SISSRs sensitivity and precision facilitated further analyses of ChIP-Seq data revealing interesting insights, which we believe will serve as guidance for designing ChIP-Seq experiments to map in vivo proteinDNA interactions. We also show that tag densities at the binding sites are a good indicator of proteinDNA binding affinity, which could be used to distinguish and characterize strong and weak binding sites. Using tag density as an indicator of DNA-binding affinity, we have identified core residues within the NRSF and CTCF binding sites that are critical for a stronger DNA binding. C1 [Jothi, Raja; Cuddapah, Suresh; Barski, Artem; Cui, Kairong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20894 USA. RP Zhao, K (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20894 USA. EM zhaok@nhlbi.nih.gov RI Jothi, Raja/G-3780-2015; OI Barski, Artem/0000-0002-1861-5316 FU National Heart Lung and Blood Institute, National Institutes of Health FX The authors would like to thank Dustin E Schones for suggestions and critical reading of the article, and Warren J Leonard, Tae-Young Roh, Gang Wei and Zhibin Wang for useful comments. This study was funded by Intramural Research Program of the National Heart Lung and Blood Institute, National Institutes of Health. Funding to pay the Open Access publication charges for this article was provided by the Intramural Research Program of the National Institutes of Health. NR 29 TC 343 Z9 356 U1 4 U2 42 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 SEP PY 2008 VL 36 IS 16 BP 5221 EP 5231 DI 10.1093/nar/gkn488 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 348JA UT WOS:000259205600016 PM 18684996 ER PT J AU Newlin, K Melkus, GD Tappen, R Chyun, D Koenig, HG AF Newlin, Kelley Melkus, Gail D. Tappen, Ruth Chyun, Deborah Koenig, Harold G. TI Relationships of religion and spirituality to glycemic control in Black women with type 2 diabetes SO NURSING RESEARCH LA English DT Article DE glycemic control; religion; spirituality; type 2 diabetes ID SOCIAL SUPPORT; AFRICAN-AMERICANS; SELF-MANAGEMENT; DEPRESSIVE SYMPTOMS; PHYSICAL HEALTH; BLOOD-PRESSURE; CARE PROFILE; STRESS; INVOLVEMENT; ADULTS AB Background: Although religion and spirituality are prominent in the lives of Black women with type 2 diabetes (T2DM), there is little research on the relationships of religion and spirituality to glycemic control (GC) in this population. Objective: To examine the relations of religion and spirituality to GC. Methods: Using a cross-sectional, descriptive, correlational design, a convenience sample of 109 Black women with T2DM was recruited. Measures of demographic (age, income, and education), clinical (body mass index and use of diabetes medications), psychosocial (emotional distress and social support), religion and spirituality (religious and existential wellbeing), and GC (hemoglobin A1c) factors were collected. A theoretical model, based on the work of Koenig, McCullough, and Larson (2001), informed linear regression analyses to examine the relations of religion and spirituality to GC, with psychosocial factors as putative mediators. Results: With age (beta = -.133, SE = .020, p = .145), income (beta = .020, SE = .139, p = .853), education (beta = -.221, SE = .204, p = .040), body mass index (beta = .237, SE = .031, p = .011), and diabetes medications (beta = .338, SE = .216, p < .001) held constant, religion and spirituality demonstrated significant relations with GC (beta = .289, SE = .032, p = .028 and beta = -.358, SE = .030, p = .006, respectively). Evidence of emotional distress and social support as mediators in the relationships of religion and spirituality to GC was lacking. Discussion: Religion and spirituality were related to GC, with 4 evidence of psychosocial mediation lacking, thereby forcing revision of the model for the study population. Research is warranted to validate the findings, with further examination of theoretical mediators linking religion and spirituality to GC. Findings suggest that religion and spirituality be addressed in diabetes care to improve GC in Black women with T2DM. C1 [Newlin, Kelley] Florida Atlantic Univ, Christine E Lynn Coll Nursing, Natl Inst Nursing Res Postdoctoral Fellow, Boca Raton, FL 33431 USA. [Melkus, Gail D.] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Chyun, Deborah] Yale Univ, Coll Nursing, New Haven, CT 06536 USA. [Koenig, Harold G.] Duke Univ, Med Ctr, Durham, NC USA. RP Newlin, K (reprint author), Florida Atlantic Univ, Christine E Lynn Coll Nursing, Natl Inst Nursing Res Postdoctoral Fellow, 777 Glades Rd, Boca Raton, FL 33431 USA. EM knewlin@fau.edu RI Koenig, Harold/F-7379-2011 FU National Institute of Nursing Research [F31 NR008190, F32 NR010043, R01NR05341] FX This study was supported by the National Institute of Nursing Research (Grant F31 NR008190, F32 NR010043, and R01NR05341). NR 41 TC 22 Z9 22 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD SEP-OCT PY 2008 VL 57 IS 5 BP 331 EP 339 DI 10.1097/01.NNR.0000313497.10154.66 PG 9 WC Nursing SC Nursing GA 352CG UT WOS:000259472200005 PM 18794717 ER PT J AU Erichsen, HC Peters, U Eck, P Welch, R Schoen, RE Yeager, M Levine, M Hayes, RB Chanock, S AF Erichsen, Hans Christian Peters, Ulrike Eck, Peter Welch, Robert Schoen, Robert E. Yeager, Meredith Levine, Mark Hayes, Richard B. Chanock, Stephen TI Genetic Variation in Sodium-Dependent Vitamin C Transporters SLC23A1 and SLC23A2 and Risk of Advanced Colorectal Adenoma SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID ASCORBIC-ACID; DEHYDROASCORBIC ACID; HAPLOTYPE FREQUENCIES; ANTIOXIDANT VITAMINS; HUMAN NEUTROPHILS; RANDOMIZED TRIAL; RECURRENCE; POLYPS; PREVENTION AB Previous observational studies suggest that vitamin C may reduce risk of colorectal cancer. Vitamin C transport is facilitated by membrane bound sodium-dependent transporters, SVCT1 (encoded by SLC23A1) and SVCT2 (encoded by SLC23A2). To investigate if common genetic variants in these two genes are associated with risk of colorectal tumor development, we conducted a case-control study of 656 Caucasian advanced distal colorectal adenoma cases and 665 Caucasian sigmoidoscopy-negative controls nested within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The analysis of common single nucleotide polymorphisms in SLC23A1 revealed no association. For SLC23A2, overall, there was no association with baplotypes, but two SNPs located in intron 8 and exon 11 could be associated (odds ratio = 0.49, 95% confidence interval = 0.25-0.95 for haplotype G-C vs. haplotype C-C). The findings should be confirmed in follow-up studies, and further investigation is required to probe the functional basis of this finding. C1 [Erichsen, Hans Christian] NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Peters, Ulrike; Hayes, Richard B.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Peters, Ulrike] Univ Washington, Seattle, WA 98195 USA. [Eck, Peter; Levine, Mark] NIDDKD, Mol & Clin Nutr Sect, Bethesda, MD 20892 USA. [Welch, Robert; Yeager, Meredith; Chanock, Stephen] NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Schoen, Robert E.] Univ Pittsburgh, Pittsburgh, PA USA. RP Chanock, S (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM sc83a@nih.gov OI Eck, Peter/0000-0003-2371-9774; Hayes, Richard/0000-0002-0918-661X FU Intramural NIH HHS [Z01 DK053211-01] NR 35 TC 19 Z9 20 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PD SEP-OCT PY 2008 VL 60 IS 5 BP 652 EP 659 DI 10.1080/01635580802033110 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 359ES UT WOS:000259969800014 PM 18791929 ER PT J AU Watters, JL Satia, JA Kupper, LL AF Watters, Joanne L. Satia, Jessie A. Kupper, Lawrence L. TI Correlates of antioxidant nutrients and oxidative DNA damage differ by race in a cross-sectional study of healthy African American and white adults SO NUTRITION RESEARCH LA English DT Article DE oxidative stress; carotenoids; vitamin C; vitamin E; African Americans; humans ID SERUM CONCENTRATIONS; BETA-CAROTENE; VEGETABLE CONSUMPTION; DISEASE MORTALITY; ALPHA-TOCOPHEROL; VITAMIN-C; BASE-LINE; SMOKING; CANCER; FRUIT AB Although antioxidant nutrients and oxidative DNA damage have been associated with carcinogenesis, few studies have investigated the factors that influence antioxidant intake and oxidative DNA damage in racially diverse populations. Demographic, behavioral, and diet-related psychosocial correlates of plasma antioxidant (carotenoids, vitamin C, and vitamin E) concentrations and oxidative DNA damage were examined using data from a cross-sectional study of 147 generally healthy, nonsmoking African American and white adults in North Carolina, aged 20 to 45 years. All participants completed self-administered demographic, diet, and health questionnaires and provided semifasting (>= 6hours) blood samples. Multivariate regression analyses were computed separately for each race to determine associations between the potential correlates with plasma antioxidant concentrations and oxidative DNA damage, separately. Our findings suggest appreciable differences by race. Only a few factors (age, supplement use, and several psychosocial factors) were associated with antioxidant concentrations in African Americans, whereas these and additional factors, including physical activity, waist circumference, and passive smoke exposure, were associated with antioxidant concentrations in whites. For oxidative DNA damage, passive smoke exposure was significantly associated with oxidative DNA damage in African Americans, and age and alcohol were significant in whites. In addition, the regression models generally explained more of the variance in plasma antioxidant concentrations and oxidative DNA damage in whites than in African Americans. Considering the salient correlates differed by race, this work has important implications for the design and implementation of future research studies investigating antioxidant nutrients and/or oxidative stress, especially those in racially diverse populations. Published by Elsevier Inc. C1 [Watters, Joanne L.] Natl Canc Inst, Canc Prevent Fellowship Program, Off Prevent Oncol, Canc Prevent Div, Rockville, MD 20852 USA. [Satia, Jessie A.] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. [Satia, Jessie A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Satia, Jessie A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Satia, Jessie A.] Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Div Digest Dis & Nutr, Chapel Hill, NC 27599 USA. [Kupper, Lawrence L.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. EM wattersj@mail.nih.gov FU [R03 CA108276]; [K22 CA96556]; [T32 CA72319]; [P30ES010126]; [DK56350]; [RROO046] FX This study was supported in part by the following grants: R03 CA108276, K22 CA96556, T32 CA72319, P30ES010126, DK56350, and RROO046. NR 50 TC 8 Z9 8 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD SEP PY 2008 VL 28 IS 9 BP 565 EP 576 DI 10.1016/j.nutres.2008.06.005 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 344SD UT WOS:000258946700001 PM 19083461 ER PT J AU Koska, J Stefan, N Votruba, SB Smith, SR Krakoff, J Bunt, JC AF Koska, Juraj Stefan, Norbert Votruba, Susanne B. Smith, Steven R. Krakoff, Jonathan Bunt, Joy C. TI Distribution of subcutaneous fat predicts insulin action in obesity in sex-specific manner SO OBESITY LA English DT Article ID VISCERAL ADIPOSE-TISSUE; PIMA-INDIANS; REGIONAL DIFFERENCES; BODY-FAT; METABOLIC COMPLICATIONS; ABDOMINAL ADIPOSITY; MUSCLE COMPOSITION; GLUCOSE-TOLERANCE; RESISTANCE; WOMEN AB The pattern of adipose tissue (AT) distribution is an important predictor of metabolic risk. The aim of this study was to analyze the association of peripheral (insulin-mediated glucose disposal - M) and hepatic (suppression of endogenous glucose production - EGP) insulin action with abdominal (subcutaneous abdominal AT-SAAT, intraabdominal AT - IAA70 and thigh AT depots in obese individuals. Fifty-seven Pima Indians with normal glucose tolerance underwent magnetic resonance imaging (MRI) and euglycemic-hyperinsulinemic clamp. M was negatively related to intraperitoneal IAAT (P = 0.02) and deep SAAT (P = 0.03). Suppression of EGP was negatively related to total (P < 0.05) or deep SAAT (P < 0.05 and P = 0.01, respectively), and total or intraperitoneal IAAT (P = 0.009 and P = 0.002, respectively). A significant interaction with sex was found in the association between superficial SAAT and M, so that in women, but not men, M negatively correlated with superficial SAAT (P = 0.02). In stepwise regression analysis, both M (r(2) = 0.09) and EGP suppression (r(2) = 0.17) were associated only with intraperitoneal IAAT in the whole group. In the sex-specific analysis (because of the significant interaction), lower M was associated with higher deep SAAT (r(2) = 0.15) in combination with lower superficial SAAT (r(2) = 0.09) in men, and with higher superficial SAAT (r(2) = 0.29) in combination with lower thigh subcutaneous AT (r(2) = 0.16) in women. Although intraperitoneal IAAT and deep SAAT were major predictors of peripheral and hepatic insulin action in obese Pima Indians, the largest variance in M rate was explained in a sex-specific manner by relative size of subcutaneous AT depots. C1 [Koska, Juraj; Stefan, Norbert; Votruba, Susanne B.; Krakoff, Jonathan; Bunt, Joy C.] NIDDK, Obes & Diabet Clin Res Sect, NIH, DHHS, Phoenix, AZ 85014 USA. [Stefan, Norbert] Univ Tubingen, Div Endocrinol, Dept Internal Med, Tubingen, Germany. [Smith, Steven R.] Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Koska, J (reprint author), NIDDK, Obes & Diabet Clin Res Sect, NIH, DHHS, Phoenix, AZ 85014 USA. EM jkrakoff@mail.nih.gov OI Stefan, Norbert/0000-0002-2186-9595 FU NIDDK/NIH/DHHS FX This work was funded by the intramural research program of the NIDDK/NIH/DHHS We gratefully acknowledge Thomas Brookshire, PA; Kathy Trinidad, RN; and nursing and dietary staff of the National Institutes of Health (NIH) metabolic unit for the care of the volunteers. We thank Ann Nelson and magnetic resonance imaging (MRI) staff at The Banner Health Good Samaritan Medical Center for help in MRI data acquisition. We are grateful to the members and leaders of the Gila River Indian Community for their continuing cooperation in our studies. We thank Jeff Curtis, MD for helpful comments on the manuscript. NR 40 TC 20 Z9 20 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD SEP PY 2008 VL 16 IS 9 BP 2003 EP 2009 DI 10.1038/oby.2008.292 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 345KP UT WOS:000258996000004 PM 18551127 ER PT J AU El-Mohandes, AAE Kiely, M Joseph, JG Subramanian, S Johnson, AA Blake, SM Gantz, MG El-Khorazaty, MN AF El-Mohandes, Ayman A. E. Kiely, Michele Joseph, Jill G. Subramanian, Siva Johnson, Allan A. Blake, Susan M. Gantz, Marie G. El-Khorazaty, M. Nabil TI An intervention to improve postpartum outcomes in African-American mothers - A randomized controlled trial SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies/Society-of-Pediatric-Research CY MAY 05-08, 2007 CL Toronto, CANADA SP Pediat Acad Soc ID INTIMATE PARTNER VIOLENCE; ENVIRONMENTAL TOBACCO-SMOKE; LOW-BIRTH-WEIGHT; BEHAVIORAL INTERVENTION; DOMESTIC VIOLENCE; PREGNANT-WOMEN; PRIMARY-CARE; DEPRESSION; CESSATION; PREVENTION AB OBJECTIVE: To evaluate the efficacy of an integrated multiple risk intervention, delivered mainly during pregnancy, in reducing such risks (cigarette smoking, environmental tobacco smoke exposure, depression, and intimate partner violence) postpartum. METHODS: Data from this randomized controlled trial were collected prenatally and on average 10 weeks postpartum in six prenatal care sites in the District of Columbia. African Americans were screened, recruited, and randomly assigned to the behavioral intervention or usual care. Clinic-based, individually tailored counseling was delivered to intervention women. The outcome measures were number of risks reported postpartum and reduction of these risks between baseline and postpartum. RESULTS: The intervention was effective in significantly reducing the number of risks reported in the postpartum period. In bivariate analyses, the intervention group was more successful in resolving all risks (47% compared with 35%, P=.007, number needed to treat=9, 95% confidence interval [CI] 5-31) and in resolving some risks (63% compared with 54%, P=.009, number needed to treat=11, 95% CI 7-43) as compared with the usual care group. In logistic regression analyses, women in the intervention group were more likely to resolve all risks (odds ratio 1.86, 95% CI 1.25-2.75, number needed to treat=7, 95% CI 4-19) and resolve at least one risk (odds ratio 1.60, 95% CI 1.15-2.22, number needed to treat=9, 95% CI 6-29). CONCLUSION: An integrated multiple risk factor intervention addressing psychosocial and behavioral risks delivered mainly during pregnancy can have beneficial effects in risk reduction postpartum. C1 [El-Mohandes, Ayman A. E.] George Washington Univ, Dept Prevent & Community Hlth, Sch Publ Hlth & Hlth Serv, Med Ctr, Washington, DC 20037 USA. Georgetown Univ, Washington, DC USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NIH, Bethesda, MD 20892 USA. Howard Univ, Washington, DC 20059 USA. Res Triangle Inst Int, Rockville, MD USA. RP El-Mohandes, AAE (reprint author), George Washington Univ, Dept Prevent & Community Hlth, Sch Publ Hlth & Hlth Serv, Med Ctr, 2175 K St, Washington, DC 20037 USA. EM sphaxe@gwumc.edu FU Intramural NIH HHS [Z99 HD999999]; NICHD NIH HHS [U18 HD031206-07, 3U18HD030445, 3U18HD030447, 3U18HD031919, 5U18HD036104, 5U18HD31206, U18 HD030445, U18 HD030445-07, U18 HD030447, U18 HD030447-07, U18 HD031206, U18 HD031919, U18 HD031919-07, U18 HD036104, U18 HD036104-02] NR 55 TC 35 Z9 36 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 2008 VL 112 IS 3 BP 611 EP 620 DI 10.1097/AOG.0b013e3181834b10 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 347YZ UT WOS:000259179100016 PM 18757660 ER PT J AU Castle, PE Cox, JT Schiffman, M Wheeler, CM Solomon, D AF Castle, Philip E. Cox, J. Thomas Schiffman, Mark Wheeler, Cosette M. Solomon, Diane TI Factors influencing histologic confirmation of high-grade squamous intraepithelial lesion cytology SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID HUMAN-PAPILLOMAVIRUS DNA; CERVICAL-CANCER; CONSENSUS GUIDELINES; WOMEN; MANAGEMENT; CARCINOGENICITY; PARTICIPANTS; METAANALYSIS; COLPOSCOPY; NEOPLASIA AB OBJECTIVE: To examine the predictors of histologic confirmation of high-grade squamous intraepithelial lesion (HSIL) cytology occurring in follow-up of young women originally referred into a trial because of less severe cytology. METHODS: We used enrollment HSIL cytology (N=411) as read by clinical center pathologists for women participating in the ASCUS-LSIL Triage Study (ALTS). The primary outcome was histologic cervical intraepithelial neoplasia (CIN) grade 3 and early cancer (n = 195; 191 CIN 3 and four cancers) as diagnosed by the Pathology Quality Control Group during the 2-year duration of ALTS. RESULTS: The 2-year absolute risk of CIN 3 or worse after an HSIL cytology was 47.4% (95% confidence interval 42.5-52.4%). The 2-year absolute risk of CIN 3 or worse was lowest (14.3%) for women who were human papillomavirus (HPV)-16-negative, had colposcopic impression of less than low-grade, and whose HSIL cytology as called by the clinical center was not also called HSIL or equivocal HSIL cytology by the Pathology Quality Control Group. The 2-year absolute risk of CIN 3 or worse was highest (82.4%) for women who were HPV16-positive, had colposcopic impression of low-grade or worse, and whose HSIL cytology also was called HSIL or equivocal HSIL cytology by the Pathology Quality Control Group. CONCLUSION: Histologic confirmation of precancer among young women with HSIL cytology was more likely when other risk factors (eg, HPV16) for cervical precancer were present. C1 [Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Calif Santa Barbara, Gynecol & Colposcopy Clin, Student Hlth Serv, Santa Barbara, CA 93106 USA. Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Sch Med, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Sch Med, Albuquerque, NM 87131 USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,Room 5004,MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov FU National Institutes of Health (NIH); National Cancer Institute; NIH Department of Health and Human Services [CN-55753, CN-55754, CN-55155, CN55156, CN-55157, CN-55758, CN-55159, CN-55105] FX Supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute. The ASCUS-LSIL Triage Study was supported by the National Cancer Institute, NIH Department of Health and Human Services contracts CN-55753, CN-55754, CN-55155, CN55156, CN-55157, CN-55758, CN-55159, and CN-55105. Some of the equipment and supplies used in these studies was donated or provided at reduced cost by Digene Corporation (Gaithersburg, AID), Cytyc Corporation (Marlborough, MAI), National Testing Laboratories (Fenton, MO), DenVu (Tucson, AZ), BD Diagnostics-TriPath (Burlington, NC), and Roche Molecular Systems Inc. (Alameda, CA). NR 21 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 2008 VL 112 IS 3 BP 637 EP 645 DI 10.1097/AOG.0b013e3181834637 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 347YZ UT WOS:000259179100019 PM 18757663 ER PT J AU Gibson, M Spong, CY Simonsen, SE Martin, S Scott, JR AF Gibson, Mark Spong, Catherine Y. Simonsen, Sara Ellis Martin, Sheryl Scott, James R. TI Author perception of peer review SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; QUALITY; MANUSCRIPTS; ACCEPTANCE; FEEDBACK; EDITORS; IMPACT AB OBJECTIVE: To survey authors submitting manuscripts to a leading specialty journal regarding their assessment of editorial review. The study sought factors affecting authors' satisfaction and whether authors rated the journal review processes differently from the commentary provided by different reviewers. METHODS: Participation in an online survey was offered to 445 corresponding authors of research manuscripts submitted consecutively during a 7-month period. All manuscripts received full editorial review. The survey instrument asked authors to rate six aspects of editorial comments from each of two to four reviewers and three aspects of the review process. in addition, the survey queried overall satisfaction and likelihood of submission of future manuscripts based on review experience. RESULTS: Higher ratings for overall satisfaction with manuscript review were given by authors of accepted compared with rejected manuscripts (98% compared with 80%, P<.001). Authors rated processes for submission and review more highly than editorial commentary (88% compared with 69%, P<.001), and this difference was greater among authors of rejected manuscripts. The extent to which reviewers focused on important aspects of submitted manuscripts received the lowest ratings from authors. Authors' ratings of reviewers' comments differentiated between reviewers and did not correlate with ratings of reviews by the journal's senior editors. CONCLUSION: Author feedback was more favorable among authors of accepted manuscripts, and responses differentiated among aspects of editorial review and reviewers. Author feedback may provide a means for monitoring and improvement of processes for editorial review and reviewer commentary. C1 [Gibson, Mark] Univ Utah, Dept Obstet & Gynecol, Sch Med, Salt Lake City, UT 84132 USA. NICHHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. Univ Utah, Dept Family & Prevent Med, Sch Med, Publ Hlth Program, Salt Lake City, UT 84132 USA. RP Gibson, M (reprint author), Univ Utah, Dept Obstet & Gynecol, Sch Med, 30 N 1900 E,Room 2B200, Salt Lake City, UT 84132 USA. EM mark.gibson@hsc.ulah.edu NR 14 TC 8 Z9 9 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 2008 VL 112 IS 3 BP 646 EP 651 DI 10.1097/AOG.0b013e31818425d4 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 347YZ UT WOS:000259179100020 PM 18757664 ER PT J AU Macones, GA Hankins, GDV Spong, CY Hauth, J Moore, T AF Macones, George A. Hankins, Gary D. V. Spong, Catherine Y. Hauth, John Moore, Thomas TI The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring - Update on definitions, interpretation, and research guidelines SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 [Macones, George A.] Washington Univ, Dept Obstet & Gynecol, St Louis, MO 63110 USA. Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Calif San Diego, Dept Obstet & Gynecol, San Diego, CA 92103 USA. RP Macones, GA (reprint author), Washington Univ, Dept Obstet & Gynecol, St Louis, MO 63110 USA. EM maconesg@wustl.edu NR 8 TC 235 Z9 253 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 2008 VL 112 IS 3 BP 661 EP 666 DI 10.1097/AOG.0b013e3181841395 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 347YZ UT WOS:000259179100022 PM 18757666 ER PT J AU Browne, H Manipalviratn, S Armstrong, A AF Browne, Hyacinth Manipalviratn, Somjate Armstrong, Alicia TI Using an intrauterine device in immunocompromised women SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; HIV-1-INFECTED WOMEN; HIV AB Intrauterine devices (IUDs) are a viable treatment option for immunocompromised women who need contraception or menses suppression. They may also be an alternative treatment for women who have a contraindication to estrogen use. A review of the literature on IUD use in this population is sparse, but currently available data suggest that immunocompromised women are not at greater risk of developing pelvic infections. C1 [Browne, Hyacinth; Manipalviratn, Somjate; Armstrong, Alicia] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. RP Browne, H (reprint author), NICHD, Program Reprod & Adult Endocrinol, NIH, CRC 1 E,Rm 1-E-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM brownehy@mail.nih.gov FU Intramural NIH HHS [NIH0012449348]; PHS HHS [NIH0012449348] NR 13 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 2008 VL 112 IS 3 BP 667 EP 669 DI 10.1097/AOG.0b013e318183464e PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 347YZ UT WOS:000259179100023 PM 18757667 ER PT J AU Levens, ED Nieman, LK AF Levens, Eric D. Nieman, Lynnette K. TI CDB-2914 for uterine leiomyomata treatment: A randomized controlled trial - Reply SO OBSTETRICS AND GYNECOLOGY LA English DT Letter ID MIFEPRISTONE C1 [Levens, Eric D.; Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA. RP Levens, ED (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 2008 VL 112 IS 3 BP 707 EP 708 DI 10.1097/AOG.0b013e318186496b PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 347YZ UT WOS:000259179100038 ER PT J AU Aquino-Jarquin, G Benitez-Hess, ML DiPaolo, JA Alvarez-Salas, LM AF Aquino-Jarquin, Guillermo Benitez-Hess, Maria Luisa DiPaolo, Joseph A. Alvarez-Salas, Luis M. TI A triplex ribozyme expression system based on a single hairpin ribozyme SO OLIGONUCLEOTIDES LA English DT Article ID RNA; INHIBITION; HAMMERHEAD; CLEAVAGE; VIRUS; GENE; REPLICATION; SEQUENCES; DESIGN; AGENTS AB Triplex ribozyme (RZ) con C gurations allow for the individual activity of trans-acting RZs in multiple expression cassettes (multiplex), thereby increasing target cleavage relative to conventionally expressed RZs. Although hairpin RZs have been advantageously compared to hammerhead RZs, their longer size and structural features complicated triplex design. We present a triplex expression system based on a single hairpin RZ with trans-cleavage capability and simple engineering. The system was tested in vitro using cis-and trans-cleavage kinetic assays against a known target RNA from HPV-16 E6/E7 mRNA. Single and multiplex triplex RZ constructs were more efficient in cleaving the target than tandem-cloned hairpin RZs, suggesting that the release of individual RZs enhanced trans-cleavage kinetics. Multiplex systems constructed with two different hairpin RZs resulted in better trans-cleavage compared to standard double-RZ constructs. In addition, the triplex RZ performed cis-and trans-cleavage in cervical cancer cells. The use of triplex con C gurations with multiplex RZs permit differential targeting of the same or different RNA, thus improving potential use against unstable targets. This prototype will provide the basis for the development of future RZ-based therapies and technologies. C1 [Aquino-Jarquin, Guillermo; Benitez-Hess, Maria Luisa; Alvarez-Salas, Luis M.] CINVESTAV, Lab Terapia Genica, Dept Genet & Mol Biol, Mexico City 07360, DF, Mexico. [DiPaolo, Joseph A.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Alvarez-Salas, LM (reprint author), CINVESTAV, Lab Terapia Genica, Dept Genet & Mol Biol, Mexico City 07360, DF, Mexico. EM lalvarez@cinvestav.mx FU CONACyT [45715Z]; Intramural Research Program of the Center for Cancer Research; NCI/NIH FX We thank Victor Hugo Rosales-Garcia for cell sorting. This research was partially supported by CONACyT (Grant No. 45715Z) and by the Intramural Research Program of the Center for Cancer Research, NCI/NIH. NR 24 TC 3 Z9 3 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1545-4576 J9 OLIGONUCLEOTIDES JI Oligonucleotides PD SEP PY 2008 VL 18 IS 3 BP 213 EP 223 DI 10.1089/oli.2008.0130 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 360JU UT WOS:000260054600002 PM 18707243 ER PT J AU Abu-Asab, MS Chaouchi, M Amri, H AF Abu-Asab, Mones S. Chaouchi, Mohamed Amri, Hakima TI Phylogenetic modeling of heterogeneous gene-expression microarray data from cancerous specimens SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article ID B-CELL LYMPHOMA; MOLECULAR CLASSIFICATION; DIFFERENTIAL EXPRESSION; COLORECTAL-CANCER; LIKELIHOOD; REVEALS; TUMORS; PATHOGENESIS; PARSIMONY; PATHWAYS AB The qualitative dimension of gene expression data and its heterogeneous nature in cancerous specimens can be accounted for by phylogenetic modeling that incorporates the directionality of altered gene expressions, complex patterns of expressions among a group of specimens, and data-based rather than specimen-based gene linkage. Our phylogenetic modeling approach is a double algorithmic technique that includes polarity assessment that brings out the qualitative value of the data, followed by maximum parsimony analysis that is most suitable for the data heterogeneity of cancer gene expression. We demonstrate that polarity assessment of expression values into derived and ancestral states, via outgroup comparison, reduces experimental noise; reveals dichotomously expressed asynchronous genes; and allows data pooling as well as comparability of intra- and interplatforms. Parsimony phylogenetic analysis of the polarized values produces a multidimensional classification of specimens into clades that reveal shared derived gene expressions (the synapomorphies); provides better assessment of ontogenic pathways and phyletic relatedness of specimens; efficiently utilizes dichotomously expressed genes; produces highly predictive class recognition; illustrates gene linkage and multiple developmental pathways; provides higher concordance between gene lists; and projects the direction of change among specimens. Further implication of this phylogenetic approach is that it may transform microarray into diagnostic, prognostic, and predictive tool. C1 [Chaouchi, Mohamed; Amri, Hakima] Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. [Abu-Asab, Mones S.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Amri, H (reprint author), Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. EM amrih@georgetwon.edu OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z99 CA999999] NR 39 TC 6 Z9 6 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 EI 1557-8100 J9 OMICS JI OMICS PD SEP PY 2008 VL 12 IS 3 BP 183 EP 199 DI 10.1089/omi.2008.0010 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 348TI UT WOS:000259232600003 PM 18699725 ER PT J AU Wei, JS Song, YK Durinck, S Chen, QR Cheuk, ATC Tsang, P Zhang, Q Thiele, CJ Slack, A Shohet, J Khan, J AF Wei, J. S. Song, Y. K. Durinck, S. Chen, Q-R Cheuk, A. T. C. Tsang, P. Zhang, Q. Thiele, C. J. Slack, A. Shohet, J. Khan, J. TI The MYCN oncogene is a direct target of miR-34a SO ONCOGENE LA English DT Article DE microRNA; miR-34a; MYCN; 1p36 LOH; neuroblastoma; translation regulation ID TUMOR-SUPPRESSOR GENE; HUMAN NEUROBLASTOMA-CELLS; N-MYC; EXPRESSION PROFILES; FREQUENT DELETIONS; CONSENSUS REGION; TRANSGENIC MICE; NERVOUS-SYSTEM; CHROMOSOME 1P; APOPTOSIS AB Loss of 1p36 heterozygosity commonly occurs with MYCN amplification in neuroblastoma tumors, and both are associated with an aggressive phenotype. Database searches identified five microRNAs that map to the commonly deleted region of 1p36 and we hypothesized that the loss of one or more of these microRNAs contributes to the malignant phenotype of MYCN-amplified tumors. By bioinformatic analysis, we identified that three out of the five microRNAs target MYCN and of these miR-34a caused the most significant suppression of cell growth through increased apoptosis and decreased DNA synthesis in neuroblastoma cell lines with MYCN amplification. Quantitative RT-PCR showed that neuroblastoma tumors with 1p36 loss expressed lower level of miR-34a than those with normal copies of 1p36. Furthermore, we demonstrated that MYCN is a direct target of miR-34a. Finally, using a series of mRNA expression pro. ling experiments, we identified other potential direct targets of miR-34a, and pathway analysis demonstrated that miR- 34a suppresses cell-cycle genes and induces several neural-related genes. This study demonstrates one important regulatory role of miR-34a in cell growth and MYCN suppression in neuroblastoma. C1 [Wei, J. S.; Song, Y. K.; Durinck, S.; Chen, Q-R; Cheuk, A. T. C.; Tsang, P.; Zhang, Q.; Khan, J.] Natl Canc Inst, Oncogenom Sect, Pediat Oncol Branch, Adv Technol Ctr, Gaithersburg, MD 20892 USA. [Chen, Q-R] NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21701 USA. [Thiele, C. J.] Natl Canc Inst, Cell & Mol Biol Sect, Pediat Oncol Branch, Bethesda, MD USA. [Slack, A.; Shohet, J.] Baylor Coll Med, Dept Pediat, Hematol Oncol Sect, Houston, TX 77030 USA. RP Khan, J (reprint author), Natl Canc Inst, Oncogenom Sect, Pediat Oncol Branch, Adv Technol Ctr, Room 134E,8717 Grovemont Circle, Gaithersburg, MD 20892 USA. EM khanjav@mail.nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank Dr Joon-Yong Chung and Xinyu Wen, MS for their excellent technical support. We also thank Dr John Maris, Dr Wendy London (Children's Oncology Group, Philadelphia, PA, USA) and Dr Steven Qualman (Cooperative Human Tissue Network, Columbus, OH, USA) for the NB tumor samples, and for invaluable discussion of this study with Dr John Maris and his group. This study is supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. 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 66 TC 159 Z9 166 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 2008 VL 27 IS 39 BP 5204 EP 5213 DI 10.1038/onc.2008.154 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 344GO UT WOS:000258915100004 PM 18504438 ER PT J AU Parchen, DA Castro, K Herringa, C Ness, E Bevans, M AF Parchen, Debra A. Castro, Kathleen Herringa, Cynthia Ness, Elizabeth Bevans, Margaret TI Developing outcomes for an oncology nurse internship program SO ONCOLOGY NURSING FORUM LA English DT Editorial Material C1 [Parchen, Debra A.; Castro, Kathleen; Herringa, Cynthia] NIH, Nursing & Patient Care Serv Clin Ctr, Bethesda, MD 20892 USA. [Ness, Elizabeth] Natl Canc Inst, Ctr Canc Res, NIH, Bethesda, MD USA. NIH, Nursing & Patient Care Serv, Ctr Clin, Bethesda, MD USA. RP Parchen, DA (reprint author), NIH, Nursing & Patient Care Serv Clin Ctr, Bethesda, MD 20892 USA. EM dparchen@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 22 TC 1 Z9 1 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD SEP PY 2008 VL 35 IS 5 BP 753 EP 756 DI 10.1188/08.ONF.753-756 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA 347BB UT WOS:000259112700005 PM 18765321 ER PT J AU Cecchi, F Mannoni, A Molino-Lova, R Ceppatelli, S Benvenuti, E Bandinelli, S Lauretani, F Macchi, C Ferrucci, L AF Cecchi, F. Mannoni, A. Molino-Lova, R. Ceppatelli, S. Benvenuti, E. Bandinelli, S. Lauretani, F. Macchi, C. Ferrucci, L. TI Epidemiology of hip and knee pain in a community based sample of Italian persons aged 65 and older SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE hip pain; knee pain; older persons; prevalence; correlates ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; QUALITY-OF-LIFE; MUSCULOSKELETAL PAIN; DISABLED WOMEN; JOINT PAIN; BACK-PAIN; OSTEOARTHRITIS; DISABILITY; ADULTS AB Objective: To describe prevalence, characteristics and correlates of hip pain (HP) and knee pain (KP) in an Italian community based cohort aged 65 and older (65+). Method: Baseline survey (1998-2000), population-based study in the Chianti area (Tuscany, Italy); 1299 persons aged 65+ were selected from the city registry of Greve in Chianti and Bagno a Ripoli (multistage sampling method); 1006 participants (564 women and 442 men, age 75.2 +/- 7.1) provided information for this analysis. Persons reporting HP/KP in the past 4 weeks were recorded and their Western Ontario and M Master University Osteoarthritis Index pain score (WPS-range 0-20) calculated. Potential correlates of HP/KP, including clinical, lifestyle c and psycho-social features and physical measures, were tested in age- and gender-adjusted regression analyses and then entered a multivariate regression model. Results: HP was reported by 11.9% participants, while 22.4% reported KP and 7.2% both conditions. Climbing/descending stairs and walking Were the activities eliciting more severe pain in either condition. Average WPSs were 5.6 +/- 3.5 for HP and 5.4 +/- 10.4 for KP. Both HP and KP wore related to back pain, reduced hip abduction, reduced muscle power and increased trunk flexibility. HP was also related to KP and poor self-rated health (SRH), while KP to HP, foot pain, high body mass index, reduced knee passive flexion and knee extension torque, low education. Conclusion: In a community sample of an Italian persons aged 65+, the prevalence of KP almost doubled that of HP. While both conditions were related to pain in other joints and specific joint impairment, only HP was related to poor SRH, and only KP to mechanical overload. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Cecchi, F.; Molino-Lova, R.; Ceppatelli, S.; Macchi, C.] Sci Inst Recovery & Care, Fdn Don Carlo Gnocchi, Outpatient Rehabil Dept, IRCCS, I-50141 Florence, Italy. [Mannoni, A.] ASF, Qual Improvement Network, Rheumatol Unit, Florence, Italy. [Benvenuti, E.; Bandinelli, S.] ASF, Geriatr Unit, Florence, Italy. [Lauretani, F.] Tuscany Hlth Reg Agcy, Florence, Italy. [Macchi, C.] Univ Florence, Dept Crit Care Med & Surg, I-50121 Florence, Italy. [Ferrucci, L.] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD USA. RP Cecchi, F (reprint author), Sci Inst Recovery & Care, Fdn Don Carlo Gnocchi, Outpatient Rehabil Dept, IRCCS, Caccini 18, I-50141 Florence, Italy. EM francescacec-chi2002@libero.it RI Lauretani, Fulvio/K-5115-2016; OI Lauretani, Fulvio/0000-0002-5287-9972; Cecchi, Franco/0000-0002-2035-5621 FU Italian Ministry of Health [ICS 110.1\RS97.71]; U.S. National Institute on Aging [N01-AG-916413, N01-AG-821336, 263 MID 9164 13, 263 MID 821336]; NIH, USA FX The manuscript submitted does not contain information about medical device(s)/drug(s). Funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript. The InCHIANTI Study was supported as a "targeted project" (ICS 110.1\RS97.71) by the Italian Ministry of Health, by the U.S. National Institute on Aging (Contracts N01-AG-916413, N01-AG-821336 and Contracts 263 MID 9164 13 and 263 MID 821336) and in part by the Intramural Research Program, National Institute on Aging, NIH, USA. NR 50 TC 13 Z9 17 U1 2 U2 7 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD SEP PY 2008 VL 16 IS 9 BP 1039 EP 1046 DI 10.1016/j.joca.2008.01.008 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 350UT UT WOS:000259379400011 PM 18343164 ER PT J AU Schisterman, EF Vexler, A AF Schisterman, Enrique F. Vexler, Albert TI To pool or not to pool, from whether to when: applications of pooling to biospecimens subject to a limit of detection SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE biological samples; pooling design; sampling strategy; detection threshold; Monte Carlo simulations ID MEASUREMENT ERROR; EXPOSURE; SAMPLES; CURVE AB Pooling of biological specimens has been utilised as a cost-efficient sampling strategy, but cost is not the unique limiting factor in biomarker development and evaluation. We examine the effect of different sampling strategies of biospecimens for exposure assessment that cannot be detected below a detection threshold (DT). The paper compares use of pooled samples to a randomly selected sample from a cohort in order to evaluate the efficiency of parameter estimates. The proposed approach shows that a pooling design is more efficient than a random sample strategy under certain circumstances. Moreover, because pooling minimises the amount of information lost below the DT, the use of pooled data is preferable (in a context of a parametric estimation) to using all available individual measurements, for certain values of the DT. We propose a combined design, which applies pooled and unpooled biospecimens, in order to capture the strengths of the different sampling strategies and overcome instrument limitations (i.e. DT). Several Monte Carlo simulations and an example based on actual biomarker data illustrate the results of the article. C1 [Schisterman, Enrique F.; Vexler, Albert] NICHHD, NIH, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. RP Schisterman, EF (reprint author), NICHHD, NIH, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,7B03N, Rockville, MD 20852 USA. EM schistee@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS [Z01 HD008761-05] NR 19 TC 23 Z9 23 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-5022 EI 1365-3016 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD SEP PY 2008 VL 22 IS 5 BP 486 EP 496 DI 10.1111/j.1365-3016.2008.00956.x PG 11 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 349ED UT WOS:000259263200008 PM 18782255 ER PT J AU Keir, ST Morton, CL Billups, C Smith, MA Houghton, PJ Gururangan, S AF Keir, Stephen T. Morton, Christopher L. Billups, Catherine Smith, Malcolm A. Houghton, Peter J. Gururangan, Sridharan TI Initial testing of VNP40101M (Cloretazine (R)) by the pediatric preclinical testing program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE developmental therapeutics; preclinical testing; VNP40101 M ID SULFONYLHYDRAZINE ALKYLATING AGENT; PHASE-I; REFRACTORY LEUKEMIA; CANCER MODELS; CELL-LINES; CYTOTOXICITY; TUMORS; VIVO AB VNP40101M is a novel alkylating agent that yields two reactive compounds (a chloroethylating species and methylisocyanate) and has demonstrated activity against a wide spectrum of tumor xenografts. VNP40101M was tested against an in vivo panel of five pediatric brain tumor xenografts at a dose of 18 mg/kg/day administered for 5 days. O-6-methylguanine-DNA methyltransferase (MGMT) levels of xenografts were assessed by Western blot analysis. Only one xenograft (GBM2), which lacked detectable MGMT expression, demonstrated an objective response to VNP40101M. VNP4010M antitumor activity was observed only in the absence of MGMT expression, with resistance to VNP4010M seen even with low MGMT expression. C1 [Gururangan, Sridharan] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Dept Pediat, Durham, NC 27710 USA. [Morton, Christopher L.; Billups, Catherine; Houghton, Peter J.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Gururangan, Sridharan] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Gururangan, S (reprint author), Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Dept Pediat, 047 Baker House,Trent Dr, Durham, NC 27710 USA. EM gurur002@mc.duke.edu RI Houghton, Peter/E-3265-2011 FU NCI NIH HHS [CA108786, N01 CM042216, N01-CM-42216, N01CM42216, P30 CA021765, CA21765, P50 CA108786] NR 16 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2008 VL 51 IS 3 BP 439 EP 441 DI 10.1002/pbc.21620 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 329YU UT WOS:000257907300029 PM 18493996 ER PT J AU Chilongozi, D Wang, L Brown, L Taha, T Valentine, M Emel, L Sinkala, M Kafulafula, G Noor, RA Read, JS Brown, ER Goldenberg, RL Hoffman, I AF Chilongozi, Duvid Wang, Lei Brown, Lillian Taha, Taha Valentine, Melgan Emel, Lynda Sinkala, Moses Kafulafula, George Noor, Ramadhani A. Read, Jennifer S. Brown, Elizabeth R. Goldenberg, Robert L. Hoffman, Irving CA HIVNET 024 Study Team TI Morbidity and mortality among a cohort of human immunodeficiency virus type 1-infected and uninfected pregnant women and their infants from Malawi, Zambia, and Tanzania SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE HIV-1 infection; infant mortality; maternal morbidity and mortality; sub-Saharan Africa; pregnant women ID ANTIRETROVIRAL THERAPY; SCALING-UP; CHORIOAMNIONITIS; TRANSMISSION; ANTIBIOTICS; OUTCOMES; MOTHERS; AFRICA; UGANDA; TRIAL AB Background: Morbidity and mortality patterns among pregnant women and their infants (before antiretroviral therapy was widely available) determines HIV-1 diagnostic, monitoring, and care interventions. Methods: Data from mothers and their infants enrolled in a trial of antibiotics to reduce mother-to-child-transmission of HIV-1 at 4 sub-Saharan African sites were analyzed. Women were enrolled during pregnancy and follow-up continued until the infants reached 12 months of age. We describe maternal and infant morbidity and mortality in a cohort of HIV-1-infected and HIV-1-uninfected mothers. Maternal and infant factors associated with mortality risk in the infants were assessed using Cox proportional hazard modeling. Results: Among 2292 HIV-1-infected mothers, 166 (7.2%) had a serious adverse event (SAE) and 42 (1.8%) died, whereas no deaths Occurred among the 331 HIV-1 uninfected mothers. Four hundred twenty-four (17.8%) of 2383 infants had an SAE and 349 (16.4%) died before the end of follow-up. Infants with early HIV-1 infection (birth to 4-6 weeks) had the highest mortality. Among infants born to HIV-1-infected women, maternal morbidity and mortality (P 0.0001), baseline CD4 Count (P = 0.0002), and baseline plasma HIV-1 RNA concentration (P < 0.0001) were significant predictors of infant mortality in multivariate analyses. Conclusions: The high mortality among infants with early HIV-1 infection supports access to HIV-1 diagnostics and appropriate early treatment for all infants of HIV-1-infected mothers. The significant association between stage of maternal HIV-1 infection and infant mortality supports routine CD4 Counts at the time of prenatal HIV-1 testing. C1 [Chilongozi, Duvid] Univ N Carolina Project, Lilongwe, Malawi. [Wang, Lei; Emel, Lynda] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. [Brown, Lillian] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. [Hoffman, Irving] Univ N Carolina, Div Infect Dis, Chapel Hill, NC 27599 USA. [Taha, Taha] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Valentine, Melgan] Family Hlth Int, Res Triangle Pk, NC 27709 USA. [Sinkala, Moses] Ctr Infect Dis Res Zambia, Lusaka, Zambia. [Sinkala, Moses; Goldenberg, Robert L.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL USA. [Kafulafula, George] Univ Malawi, Coll Med, Dept Obstet & Gynaecol, Blantyre, Malawi. [Noor, Ramadhani A.] Muhimbili Univ, Dar Es Salaam, Tanzania. [Read, Jennifer S.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, Seattle, WA USA. [Brown, Elizabeth R.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Hoffman, I (reprint author), Univ N Carolina, Div Infect Dis, 130 Mason Farm Rd, Chapel Hill, NC 27599 USA. EM hoffmani@med.unc.edu RI Brown, Elizabeth/A-8984-2008 FU HIV Network for Prevention Trials (HIVNET); U.S. National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health; Department of Health and Human Services [N01-Al-35173, N01-Al-45200, N01-Al-35173-117/412]; U.S. National Institute of Allergy and Infectious Diseases; National Institute of Child Health and Human Development National Institute Oil Drug Abuse; National Institute of Mental Health; Harvard University [U01-Al-48006]; Johns Hopkins University [U01-Al-48005]; University of Alabama Birmingham [U01-Al-47972] FX This study was supported by the HIV Network for Prevention Trials (HIVNET) and sponsored by the U.S. National Institute of Allergy and Infectious Diseases (NIAID), the National Institutes of Health, and Department of Health and Human Services, through contract #N01-Al-35173 with Family Health International: contract #N01-Al-45200 with Fred Hutchinson Cancer Research Center, and subcontract #N01-Al-35173-117/412 with Johns Hopkins University. This work was also sponsored by the U.S. National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development National Institute Oil Drug Abuse. National Institute Of Mental Health and the Office of AIDS Research at the National Institutes of Health.. U.S. Department of Health aid Human Services, Harvard University (U01-Al-48006), Johns Hopkins University (U01-Al-48005), and the University of Alabama Birmingham (U01-Al-47972). Boehringer Ingelheim GMBH, Ingelheim, Germany) for the study provided by Boehringer Ingelheim Pharmaceuticals, Incorporated. NR 16 TC 59 Z9 59 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD SEP PY 2008 VL 27 IS 9 BP 808 EP 814 DI 10.1097/INF.0b013e31817109a4 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 343OE UT WOS:000258862600007 PM 18679152 ER PT J AU Hayden, R Pounds, S Knapp, K Petraitiene, R Schaufele, RL Sein, T Walsh, TJ AF Hayden, Randall Pounds, Stanley Knapp, Katherine Petraitiene, Ruta Schaufele, Robert L. Sein, Tin Walsh, Thomas J. TI Galactomannan antigenemia in pediatric oncology patients with invasive aspergillosis SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE aspergillosis; galactomannan; pediatric oncology ID LINKED-IMMUNOSORBENT-ASSAY; CHRONIC GRANULOMATOUS-DISEASE; CELL TRANSPLANT RECIPIENTS; TIME PCR ASSAY; PULMONARY ASPERGILLOSIS; FUNGAL-INFECTIONS; ENZYME-IMMUNOASSAY; ANTIFUNGAL THERAPY; NEUTROPENIC PATIENTS; EARLY-DIAGNOSIS AB Background: Diagnosing invasive aspergillosis is difficult but might be improved by detection of circulating galactomannan. Although galactomannan antigenemia has been well studied ill the detection of invasive aspergillosis ill adult patients, little is known about the expression of circulating galactomannan in immunocompromised children with invasive aspergillosis. Methods: We studied the expression of galactomannan antigen by enzyme immunoassay (EIA) ill 990 sserum samples from 56 pediatric oncology patients (ages 3 months to 18 years) of whom 17 had proven or probable invasive aspergillosis defined by the European Organization for Research and Treatment of Cancer-Mycoses Study Group criteria. Any sample with a galactomannan EIA Galactomannan index value of >= 0.5 was considered positive. Results: At least 1 serum sample was positive for 11 of 17 pediatric oncology patients (65.7% sensitivity, 95% confidence interval: 38.3-85.7) with invasive aspergillosis. Galactomannan HA was positive in 99 of 304 samples from patients with proven or probable invasive aspergillosis, and 7 of 686 (1.0%) samples from 39 control subjects resulted in a positive galactomannan EIA result. At least I sample tested positive in 5 of the 39 controls (12.8%. 95% confidence interval: 4.3-27.4). No significant association between accuracy and patient age vas observed. Among the 7 evaluable galactomannan-positive patients with IA, the galactomannan EIA produced a positive result before clinical or radiographic evidence of infection in 6 cases, with a lead-time to diagnosis ranging from 1 day to 34 days (median: 10 clays). In the remaining case, a positive galactomannan vas observed on the same clay as diagnosis by non-EIA methods. Conclusions: The presence of circulating galactomannan is predictive of invasive aspergillosis in most pediatric oncology patients. Galactomannan antigenemia may precede clinical, microbiologic, oradiographic evidence of invasive aspergillosis. C1 [Petraitiene, Ruta; Schaufele, Robert L.; Sein, Tin; Walsh, Thomas J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Hayden, Randall] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38101 USA. [Pounds, Stanley] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38101 USA. [Knapp, Katherine] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38101 USA. SAIC Frederick Inc, Lab Anim Sci Program, Frederick, MD USA. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, CRC 1-5750,10 Ctr Dr, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov OI Pounds, Stanley/0000-0002-9167-2114 FU American Lebanese Syrian Associated Charities (ALSAC); National Cancer Institute, Bethesda, MD FX The authors thank Diane Brand for assistance in clinical data extraction and the staff of the Clinical Microbiology Laboratory of St. Jude Children's Research Hospital. This study was supported in part by the American Lebanese Syrian Associated Charities (ALSAC) and by the Intramural Research Program of the National Cancer Institute, Bethesda, MD. NR 52 TC 39 Z9 40 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD SEP PY 2008 VL 27 IS 9 BP 815 EP 819 DI 10.1097/INF.0b013e31817197ab PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 343OE UT WOS:000258862600008 PM 18703991 ER PT J AU Chang, M Parker, EA Muller, TJM Haenen, C Mistry, M Finkielstain, GP Murphy-Ryan, M Barnes, KM Sundaram, R Baron, J AF Chang, Maria Parker, Elizabeth A. Muller, Tessa J. M. Haenen, Caroline Mistry, Maanasi Finkielstain, Gabriela P. Murphy-Ryan, Maureen Barnes, Kevin M. Sundaram, Rajeshwari Baron, Jeffrey TI Changes in cell-cycle kinetics responsible for limiting somatic growth in mice SO PEDIATRIC RESEARCH LA English DT Article ID POSTNATAL GROWTH; RAT; BROMODEOXYURIDINE; CHILDREN; LENGTHS; NUMBER AB In mammals, the rate of somatic growth is rapid ill early postnatal life but then slows with age, approaching zero as the animal approaches adult body size. To investigate the underlying changes in cell-cycle kinetics, [methyl-H-3]thymidine and 5'-bromo-2'deoxyuridine were used to double-label proliferating cells in 1-, 2-, and 3-wk-old mice for four weeks. Proliferation of renal tubular epithelial cells and hepatocytes decreased with age. The average cell-cycle time did not increase in liver and increased only 1.7 fold in kidney. The fraction of cells in S-phase that will divide again declined approximately 10 fold with age. Concurrently, average cell area increased approximately 2 told. The findings suggest that somatic growth deceleration primarily results not from an increase in cell-cycle time but from a decrease in growth fraction (fraction of cells that continue to proliferate). During the deceleration phase. cells appear to reach it proliferative limit and undergo their final cell divisions, staggered over time. Concomitantly, cells enlarge to a greater volume, perhaps because they are relieved of the size constraint imposed by cell division. In conclusion. a decline in growth fraction with age causes somatic growth deceleration and thus Sets a fundamental limit on adult body size. C1 [Baron, Jeffrey] NICHD, NIH, Sect Growth & Dev, Bethesda, MD 20892 USA. [Sundaram, Rajeshwari] NIH, Biometry & Math Stat Branch, Bethesda, MD 20892 USA. RP Baron, J (reprint author), NICHD, NIH, Sect Growth & Dev, Bldg CRC,Room 1-3330,10 Ctr Dr MSC 1103, Bethesda, MD 20892 USA. EM jeffrey.baron@nih.gov OI Sundaram, Rajeshwari/0000-0002-6918-5002 FU National Institute of Child Health and Human Development; NIH FX This research was supported by the Intramural Research Program of the National Institute of Child Health and Human Development, NIH. NR 18 TC 17 Z9 17 U1 0 U2 3 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD SEP PY 2008 VL 64 IS 3 BP 240 EP 245 DI 10.1203/PDR.0b013e318180e47a PG 6 WC Pediatrics SC Pediatrics GA 344DR UT WOS:000258906700005 PM 18535488 ER PT J AU Kahana, SY Frazier, TW Drotar, D AF Kahana, Shoshana Y. Frazier, Thomas W. Drotar, Dennis TI Preliminary quantitative investigation of predictors of treatment non-adherence in pediatric transplantation: A brief report SO PEDIATRIC TRANSPLANTATION LA English DT Article DE non-adherence; transplantation; pediatric; predictor ID HEART-LUNG TRANSPLANTATION; LIVER-TRANSPLANT; RENAL-TRANSPLANTATION; MEDICATION ADHERENCE; RECIPIENTS; NONCOMPLIANCE; CHILDREN; ADOLESCENTS; VARIABLES AB The examination of predictors of non-adherence in transplantation populations offers the potential to identify high-risk individuals and concomitantly generate effective adherence-promoting interventions. The present paper aggregated quantitative estimates of various correlates of treatment adherence in studies of pediatric transplantation. Seventeen studies and three classes of predictors of non-adherence, including demographic, psychosocial, and treatment-related predictors, were included in the current analyses. The weighted means effect sizes for the demographic factors were in the small to medium range (female gender mean d = 0.35, 95% CI = 0.32-0.38, n = 8; mean age d = 0.55, 95% CI = 0.52-0.58, n = 7), suggesting that older youth and males tended to display more non-adherence behaviors than younger youth and females, respectively. Several psychosocial factors exhibited large to very large relationships with non-adherence, in particular comorbid psychiatric conditions (mean d = 1.04, 95% CI = 0.66-1.42, n = 3) and child self-responsibility for medication (mean d = 0.88, 95% CI = 0.53-1.23, n = 3). Finally, prior treatment/grafts (mean d = 0.17, 95% CI = -0.15-0.49, n = 3) and donor source (mean d = 0.33, 95% CI = -0.10-0.76, n = 4) exhibited small, non-significant relationships with non-adherence. Limitations of the study are discussed as are future directions for research. C1 [Kahana, Shoshana Y.; Drotar, Dennis] Cincinnati Childrens Hosp, Med Ctr, Div Behav Med & Clin Psychol, Ctr Promot Adherence & Self Management, Cincinnati, OH USA. [Frazier, Thomas W.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Kahana, SY (reprint author), NIMH, Div Dev Translat Res, 6001 Execut Blvd,MSC 9617,Room 6190, Bethesda, MD 20892 USA. EM sykahana@gmail.com NR 33 TC 25 Z9 26 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PD SEP PY 2008 VL 12 IS 6 BP 656 EP 660 DI 10.1111/j.1399-3046.2007.00864.x PG 5 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 335JW UT WOS:000258287900009 PM 18798360 ER PT J AU Laptook, A Tyson, J Shankaran, S McDonald, S Ehrenkranz, R Fanaroff, A Donovan, E Goldberg, R O'Shea, TM Higgins, RD Poole, WK AF Laptook, Abbot Tyson, Jon Shankaran, Seetha McDonald, Scott Ehrenkranz, Richard Fanaroff, Avroy Donovan, Edward Goldberg, Ronald O'Shea, T. Michael Higgins, Rosemary D. Poole, W. Kenneth CA Natl Inst Child Hlth Human Dev Neo TI Elevated temperature after hypoxic-ischemic encephalopathy: Risk factor for adverse outcomes SO PEDIATRICS LA English DT Article DE hypoxic-ischemic encephalopathy; neurologic outcome; temperature ID NEONATAL ENCEPHALOPATHY; BRAIN TEMPERATURE; FOREBRAIN ISCHEMIA; CEREBRAL-ISCHEMIA; BIRTH-WEIGHT; ACUTE STROKE; HYPERTHERMIA; HYPOTHERMIA; INFANTS; INJURY AB OBJECTIVE. The goal was to determine whether the risk of death or moderate/severe disability in term infants with hypoxic-ischemic encephalopathy increases with relatively high esophageal or skin temperature occurring between 6 and 78 hours after birth. METHODS. This was an observational secondary study within the National Institute of Child Health and Human Development Neonatal Research Network randomized trial comparing whole-body cooling and usual care (control) for term infants with hypoxic-ischemic encephalopathy. Esophageal and skin temperatures were recorded serially for 72 hours. Each infant's temperatures for each site were rank ordered. The high temperature was defined for each infant as the mean of all temperature measurements in the upper quartile. The low temperature was similarly defined as the mean of the lower quartile. Outcomes were related to temperatures in 3 logistic regression analyses for the high, median, and low temperatures at each temperature site for each group, with adjustment for the level of encephalopathy, gender, gestational age, and race. RESULTS. In control infants, the mean esophageal temperature was 37.2 +/- 0.7 degrees C over the 72-hour period, and 63%, 22%, and 8% of all temperatures were >37 degrees C, > 37.5 degrees C, and >38 degrees C, respectively. The mean skin temperature was 36.5 +/- 0.8 degrees C, and 12%, 5%, and 2% of all temperatures were >37 degrees C, >37.5 degrees C, and >38 degrees C, respectively. The odds of death or disability were increased 3.6-4 fold for each 1 degrees C increase in the highest quartile of skin or esophageal temperatures. There were no associations between temperatures and outcomes in the cooling-treated group. CONCLUSIONS. Relatively high temperatures during usual care after hypoxia-ischemia were associated with increased risk of adverse outcomes. The results may reflect underlying brain injury and/or adverse effects of temperature on outcomes. C1 [Laptook, Abbot] Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI 02906 USA. [Tyson, Jon] Univ Texas Houston, Dept Pediat, Houston, TX USA. [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [McDonald, Scott; Poole, W. Kenneth] RTI Int, Dept Stat & Epidemiol, Res Triangle Pk, NC USA. [Ehrenkranz, Richard] Yale Univ, Dept Pediat, New Haven, CT 06520 USA. [Fanaroff, Avroy] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. [Donovan, Edward] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. [Goldberg, Ronald] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [O'Shea, T. Michael] Wake Forest Univ, Dept Pediat, Winston Salem, NC 27109 USA. [Higgins, Rosemary D.] NICHHD, Bethesda, MD 20892 USA. RP Laptook, A (reprint author), Women & Infants Hosp Rhode Isl, Dept Pediat, 101 Dudley St, Providence, RI 02906 USA. EM alaptook@wihri.org RI Myers , Gary /I-4901-2013 OI Myers , Gary /0000-0003-4317-015X FU National Institutes of Health [U10 HD34216, U10 HD27853, U10 HD27871, U10 HD40461, U10 HD40689, U10 HD27856, U10 HD27904, U10 HD40498, U10 HD40521, U10 HD36790, U10 HD21385, U10 HD27880, U10 HD27851, U10 HD 21373]; General Clinical Research Center [M01 RR 08084, M01 RR 00125, M01 RR 00750, M01 RR 00070, M01 RR 0039-43, M01RR 00039, 5 M01 RR00044] FX This work was supported in part by National Institutes of Health grants U10 HD34216, U10 HD27853, U10 HD27871, U10 HD40461, U10 HD40689, U10 HD27856, U10 HD27904, U10 HD40498, U10 HD40521, U10 HD36790, U10 HD21385, U10 HD27880, U10 HD27851, and U10 HD 21373 and General Clinical Research Center grants M01 RR 08084, M01 RR 00125, M01 RR 00750, M01 RR 00070, M01 RR 0039-43, M01RR 00039, and 5 M01 RR00044. NR 36 TC 71 Z9 72 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2008 VL 122 IS 3 BP 491 EP 499 DI 10.1542/peds.2007-1673 PG 9 WC Pediatrics SC Pediatrics GA 342ZR UT WOS:000258822600003 PM 18762517 ER PT J AU Cole, CR Hansen, NI Higgins, RD Ziegler, TR Stoll, BJ AF Cole, Conrad R. Hansen, Nellie I. Higgins, Rosemary D. Ziegler, Thomas R. Stoll, Barbara J. CA Eunice Kennedy Shriver NICHD Neona TI Very low birth weight preterm infants with surgical short bowel syndrome: Incidence, morbidity and mortality, and growth outcomes at 18 to 22 months SO PEDIATRICS LA English DT Article DE short bowel syndrome; preterm; necrotizing enterocolitis; nutrition ID NEONATAL RESEARCH NETWORK; HOME PARENTERAL-NUTRITION; NECROTIZING ENTEROCOLITIS; INTESTINAL RESECTION; UNITED-STATES; CHILDREN; MANAGEMENT; EPIDEMIOLOGY; DEPENDENCE; DURATION AB OBJECTIVES. The objective of this study was to determine the (1) incidence of short bowel syndrome in very low birth weight (< 1500 g) infants, (2) associated morbidity and mortality during initial hospitalization, and (3) impact on short-term growth and nutrition in extremely low birth weight (< 1000 g) infants. METHODS. Infants who were born from January 1, 2002, through June 30, 2005, and enrolled in the National Institute of Child Health and Human Development Neonatal Research Network were studied. Risk factors for developing short bowel syndrome as a result of partial bowel resection (surgical short bowel syndrome) and outcomes were evaluated for all neonates until hospital discharge, death, or 120 days. Extremely low birth weight survivors were further evaluated at 18 to 22 months' corrected age for feeding methods and growth. RESULTS. The incidence of surgical short bowel syndrome in this cohort of 12 316 very low birth weight infants was 0.7%. Necrotizing enterocolitis was the most common diagnosis associated with surgical short bowel syndrome. More very low birth weight infants with short bowel syndrome (20%) died during initial hospitalization than those without necrotizing enterocolitis or short bowel syndrome (12%) but fewer than the infants with surgical necrotizing enterocolitis without short bowel syndrome (53%). Among 5657 extremely low birth weight infants, the incidence of surgical short bowel syndrome was 1.1%. At 18 to 22 months, extremely low birth weight infants with short bowel syndrome were more likely to still require tube feeding (33%) and to have been rehospitalized (79%). Moreover, these infants had growth delay with shorter lengths and smaller head circumferences than infants without necrotizing enterocolitis or short bowel syndrome. CONCLUSIONS. Short bowel syndrome is rare in neonates but has a high mortality rate. At 18 to 22 months' corrected age, extremely low birth weight infants with short bowel syndrome were more likely to have growth failure than infants without short bowel syndrome. C1 [Cole, Conrad R.] Emory Univ, Sch Med, Div Pediat Gastroenterol Hepatol & Nutr, Dept Pediat, Atlanta, GA 30322 USA. [Cole, Conrad R.; Stoll, Barbara J.] Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA. [Hansen, Nellie I.] RTI Int, Res Triangle Pk, NC USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Cole, CR (reprint author), Emory Univ, Sch Med, Div Pediat Gastroenterol Hepatol & Nutr, Dept Pediat, 2015 Uppergate Dr, Atlanta, GA 30322 USA. EM conrad_cole@oz.ped.emory.edu RI Myers , Gary /I-4901-2013 OI Myers , Gary /0000-0003-4317-015X FU NCATS NIH HHS [KL2 TR000455, UL1 TR000454]; NCRR NIH HHS [M01 RR6022, 1KL2RR025009, 5K12RR017643, K12 RR017643, K24 RR023356, K24 RR023356-03, KL2 RR025009, M01 RR000039, M01 RR000039-475518, M01 RR006022, M01 RR007122, M01 RR008084, M01 RR016587, M01 RR16587, M01 RR30, M01 RR39, M01 RR44, M01 RR633, M01 RR70, M01 RR7122, M01 RR750, M01 RR80, M01 RR8084, UL1 RR024139, UL1 RR24139]; NICHD NIH HHS [U01 HD036790, U01 HD36790, U10 HD021364, U10 HD021373, U10 HD021385, U10 HD021397, U10 HD027851, U10 HD027853, U10 HD027856, U10 HD027871, U10 HD027880, U10 HD027904, U10 HD034216, U10 HD040461, U10 HD040492, U10 HD040498, U10 HD040521, U10 HD040689, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27904, U10 HD34216, U10 HD40461, U10 HD40492, U10 HD40498, U10 HD40521, U10 HD40689] NR 37 TC 54 Z9 55 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2008 VL 122 IS 3 BP E573 EP E582 DI 10.1542/peds.2007-3449 PG 10 WC Pediatrics SC Pediatrics GA 342ZR UT WOS:000258822600058 PM 18762491 ER PT J AU Ferreira-Gonzalez, A Teutsch, S Williams, MS Au, SM FitzGerald, KT Miller, PS Fomous, C AF Ferreira-Gonzalez, Andrea Teutsch, Steven Williams, Marc S. Au, Sylvia M. FitzGerald, Kevin T. Miller, Paul Steven Fomous, Cathy CA Secretarys Advisory Comm Genetics TI US system of oversight for genetic testing: a report from the Secretary's Advisory Committee on Genetics, Health and Society SO PERSONALIZED MEDICINE LA English DT Article DE analytical validity; CLIA; clinical decision support; clinical utility; clinical validity; genetic testing; health communication; oversight; proficiency testing; USFDA AB As genetic testing technology is integrated into healthcare, increasingly detailed information about individual and population genetic variation is available to patients and providers. Health professionals use genetic testing to diagnose or assess the risk of disease in individuals, families and populations and to guide healthcare decisions. Consumers are beginning to explore personalized genomic services in an effort to learn more about their risk for common diseases. Scientific and technological advances in genetic testing, as with any newly introduced medical technology, present certain challenges to existing frameworks of oversight. in addition, the growing use of genetic testing will require a significant investment in evidence-based assessments to understand the validity and utility of these tests in clinical and personal decisionmaking. To optimize the use of genetic testing in healthcare, all sectors of the oversight system need to be strengthened and yet remain flexible in order to adapt to advances that will inevitably increase the range of genetic tests and methodologies. C1 [Fomous, Cathy] NIH, Off Biotechnol Act, Bethesda, MD 20892 USA. [Ferreira-Gonzalez, Andrea] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Teutsch, Steven] Merck & Co Inc, Whitehouse Stn, NJ USA. [FitzGerald, Kevin T.] Georgetown Univ, Washington, DC 20057 USA. [Miller, Paul Steven] Univ Washington, Sch Law, Seattle, WA 98195 USA. RP Fomous, C (reprint author), NIH, Off Biotechnol Act, 6705 Rockledge Dr,Suite 750, Bethesda, MD 20892 USA. EM cfomous@od.nih.gov OI Williams, Marc/0000-0001-6165-8701 FU Intramural NIH HHS [Z99 OD999999] NR 3 TC 6 Z9 6 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD SEP PY 2008 VL 5 IS 5 BP 521 EP 528 DI 10.2217/17410541.5.5.521 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 349JZ UT WOS:000259278400019 PM 20490368 ER PT J AU Janakiram, NB Indranie, C Malisetty, SV Jagan, P Steele, VE Rao, CV AF Janakiram, Naveena B. Indranie, Cooma Malisetty, Swamy V. Jagan, Patlolla Steele, Vernon E. Rao, Chinthalapally V. TI Chemoprevention of Colon Carcinogenesis by Oleanolic Acid and Its Analog in Male F344 Rats and Modulation of COX-2 and Apoptosis in Human Colon HT-29 Cancer Cells SO PHARMACEUTICAL RESEARCH LA English DT Article DE chemoprevention; colon cancer; COX-2; iNOS; triterpenoids ID ABERRANT CRYPT FOCI; NITRIC-OXIDE; URSOLIC ACID; CYCLOOXYGENASE-2 INHIBITOR; INCREASED EXPRESSION; COLORECTAL-CANCER; AZOXYMETHANE; RISK; PREVENTION; CELECOXIB AB Purpose. To assess the chemopreventive effect of oleanolic acid (ONA) and its synthetic analog 18 alpha-olean-12-ene-3 beta-23,28-triol (OT) on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in F344 rats and understand anti-inflammatory properties and apoptosis effects in HT29 colon cancer cells and Raw 264.7 macrophage cell lines. Methods. Five week-old male F344 rats were fed a control diet or experimental diets containing two doses of ONA (750 and 1,500 ppm) and OT (250 and 500 ppm). After 1 week, all animals were s.c. injected with AOM (15 mg/kg body weight, once weekly for 2 weeks). At 14 weeks of age, all rats were killed and colons were evaluated for ACF. Cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expressions and apoptosis were assessed in cell lines exposed to OT using western blots and 4',6-diamidino-2-phenylindole staining. Results. Administration of ONA and OT inhibited mean colonic ACF and multi-crypt AC/foci in a dose dependent manner (p < 0.001-0.0001). OT blocked the COX-2 expression induced by phorbol 12-myristate 13-acetate in a dose-dependent manner and induced apoptosis in HT-29 cancer cells, and suppressed iNOS activation in RAW264.7 macrophages. Conclusions. ONA and OT possess chemopreventive activity against colon carcinogenesis in rat and OT inhibits the COX-2 and iNOS and induces apoptosis in cell lines. C1 [Janakiram, Naveena B.; Indranie, Cooma; Malisetty, Swamy V.; Jagan, Patlolla; Rao, Chinthalapally V.] Univ Oklahoma, Hlth Sci Ctr, OU Canc Inst, Hem Onc Sect,Dept Med, Oklahoma City, OK 73104 USA. [Steele, Vernon E.] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Rao, CV (reprint author), Univ Oklahoma, Hlth Sci Ctr, OU Canc Inst, Hem Onc Sect,Dept Med, Oklahoma City, OK 73104 USA. EM cv-rao@ouhsc.edu RI Chinthalapally, Rao/B-3633-2010 FU NCI FX We gratefully acknowledge NCI chemoprevention drug development repository for providing oleanolic acid analog OT. We also extend our thanks to Ms. Alyson Atchison for editing this article. NR 36 TC 29 Z9 31 U1 1 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORD JI Pharm. Res. PD SEP PY 2008 VL 25 IS 9 BP 2151 EP 2157 DI 10.1007/s11095-008-9582-7 PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 337AR UT WOS:000258408400019 PM 18408893 ER PT J AU Shin, SH Kluepfel-Stahl, S Cooney, AM Kaneski, CR Quirk, JM Schiffmann, R Brady, RO Murray, GJ AF Shin, Sang H. Kluepfel-Stahl, Stefanie Cooney, Adele M. Kaneski, Christine R. Quirk, Jane M. Schiffmann, Raphael Brady, Roscoe O. Murray, Gary J. TI Prediction of response of mutated alpha-galactosidase A to a pharmacological chaperone SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE alpha-galactosidase A; Fabry disease; lysosomal storage disorders; molecular chaperone; molecular mechanisms of pharmacological action; pharmacological chaperone ID FABRY-DISEASE; ENZYME-ACTIVITY; DEFECT; GENE; MUTATIONS; STORAGE; STROKE AB Objective To examine the relationship between types and locations of mutations of the enzyme alpha-galactosidase (Gal) A in Fabry disease and the response to the pharmacological chaperone 1-deoxygalactonojirimycin (DGJ) Methods T cells grown from normal individuals or from patients with Fabry disease were tested for response to treatment with DGJ by increased activity of alpha-Gal A. Results Cells from normal controls responded with a 28% increase in alpha-Gal A activity, whereas response in Fabry individuals was mutation dependent ranging from no increase to fully normal activity. Nine truncation mutations (all nonresponsive) and 31 missense mutations were tested. Three groups of missense mutations were categorized: responders with activity more than 25% of normal, nonresponders, with less than 7% and an intermediate response group. In normal cells and in responders an increase in the mature lysosomal form of alpha-Gal A was observed after DGJ treatment. Nonresponders showed little or no protein with or without DGJ. The intermediate response group showed an increase in band intensity but incomplete processing of the enzyme to the mature form. Conclusion Mapping the missense mutations to the structure of alpha-Gal A identified several factors that may influence response. Mutations in regions that are not in alpha-helix or beta-sheets, neither involved in disulfide bonds nor with an identified functional or structural role were more likely to respond. Predictability is, however, not precise and testing of each mutation for response to pharmacological chaperone therapy is necessary for Fabry disease and related lysosomal storage disorders. C1 [Shin, Sang H.; Kluepfel-Stahl, Stefanie; Cooney, Adele M.; Kaneski, Christine R.; Quirk, Jane M.; Schiffmann, Raphael; Brady, Roscoe O.; Murray, Gary J.] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, Bethesda, MD USA. RP Murray, GJ (reprint author), NIH, Bldg 10,Room 3D04, Bethesda, MD 20891 USA. EM murrayg@mail.nih.gov OI Kaneski, Christine/0000-0003-1453-2502 FU National Institute of Neurologic Disorders and Stroke; National Institutes of Health; The Public Health Service and Amicus Therapeutics, Inc [01956] FX This study was supported in part by the Intramural Program of the National Institute of Neurologic Disorders and Stroke, National Institutes of Health. The Public Health Service and Amicus Therapeutics, Inc. have a Cooperative Research and Development Agreement, #01956. The authors thank Dr Greg Pastores at New York University for genotyping some of the patients' samples. The authors appreciate Gregory Zirzow at NINDS for technical assistance. The contribution of both the patients and volunteers who participated in this study is gratefully acknowledged. NR 22 TC 30 Z9 31 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD SEP PY 2008 VL 18 IS 9 BP 773 EP 780 DI 10.1097/FPC.0b013e32830500f4 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 342GE UT WOS:000258771800004 PM 18698230 ER PT J AU Mamedova, LK Wang, R Besada, P Liang, BT Jacobson, KA AF Mamedova, Liaman K. Wang, Ruibo Besada, Pedro Liang, Bruce T. Jacobson, Kenneth A. TI Attenuation of apoptosis in vitro and ischemia/reperfusion injury in vivo in mouse skeletal muscle by P2Y(6) receptor activation SO PHARMACOLOGICAL RESEARCH LA English DT Article DE Ischemia; Uracil nucleotide; G protein-coupled receptor; Tumor necrosis factor; Skeletal muscle; UDP ID PROTEIN-KINASE-C; NF-KAPPA-B; NUCLEOTIDE RECEPTORS; MUSCULAR-DYSTROPHY; DERIVATIVES; ALPHA; CELLS; ASTROCYTES; PATHWAYS; SURVIVAL AB Activation of the G(q)-coupled P2Y(6) receptor heterologously expressed in astrocytes significantly attenuates apoptosis induced by tumor necrosis factor alpha (TNF alpha). We have extended the analysis of P2Y(6) receptor-induced cytoprotection to mouse skeletal muscle cells endogenously expressing this receptor. The endogenous P2Y(6) receptor agonist UDP and synthetic agonist MRS2693 protected C2C12 skeletal muscle cells against apoptosis in a concentration-dependent manner (0.1-10 nM) as determined by propidium iodide staining, histochemical analysis using hematoxylin and Hoechst 33258, and DNA fragmentation. The insurmountable P2Y(6) receptor antagonist MRS2578 blocked the protection. TNF alpha-induced apoptosis in C2C12 cells correlated with activation of the transcription factor NF-kappa B. The NF-kappa B activation was attenuated by 10 nM MRS2693, which activated the antiapoptic ERK1/2 pathway. In an in vivo mouse hindlimb model, MRS2693 protected against skeletal muscle ischemia/reperfusion injury. The P2Y(6) receptor is a novel cytoprotective receptor that deserves further exploration in ameliorating skeletal muscle injury. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Mamedova, Liaman K.; Besada, Pedro; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Mamedova, Liaman K.] Kansas State Univ, Dept Anim Sci & Ind, Manhattan, KS 66506 USA. [Wang, Ruibo; Liang, Bruce T.] Univ Connecticut, Ctr Hlth, Pat & Jim Calhoun Cardiol Ctr, Farmington, CT 06030 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A 19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Besada Pereira, Pedro/E-6051-2012; Jacobson, Kenneth/A-1530-2009 OI Besada Pereira, Pedro/0000-0002-9985-9063; Jacobson, Kenneth/0000-0001-8104-1493 FU NIH; National Institute of Diabetes and Digestive and Kidney Diseases FX This research was supported by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. We thank Cara Heller (NIDDK) for proofreading this manuscript. NR 29 TC 18 Z9 20 U1 1 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD SEP-OCT PY 2008 VL 58 IS 3-4 BP 232 EP 239 DI 10.1016/j.phrs.2008.08.004 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 375RT UT WOS:000261131700009 PM 18805489 ER PT J AU Zhao, BZ Bilski, PJ He, YY Feng, L Chignell, CF AF Zhao, Baozhong Bilski, Piotr J. He, Yu-Ying Feng, Li Chignell, Colin F. TI Photo-induced reactive oxygen species generation by different water-soluble fullerenes (C(60)) and their cytotoxicity in human keratinocytes SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID SINGLET OXYGEN; GAMMA-CYCLODEXTRIN; MOLECULAR-OXYGEN; C60; IRRADIATION; OXIDATION; SYSTEM; AZIDE; ACID; NADH AB In this study we report the phototoxicity toward HaCaT keratinocytes that results from the photogeneration of superoxide and singlet oxygen ((1)O(2)) by four different "water-soluble" fullerene (C(60)) preparations-monomeric (gamma-CyD)(2)/C(60) (gamma-cyclodextrin bicapped C(60)) and three aggregated forms-THF/nC(60) (prepared by solvent exchange from THF solution); Son/nC(60) (prepared by sonication of a toluene/water mixture); and gamma-CyD/nC(60) (prepared by heating the [gamma-CyD](2)/C(60) aqueous solution). Our results demonstrate that all four C(60) preparations photogenerate (1)O(2) efficiently. However, the properties of C(60)-generated (1)O(2), including its availability for reactions in solution, are markedly different for the monomeric and aggregated forms. (1)O(2) produced by monomeric (gamma-CyD)(2)/C(60) is quenchable by NaN(3) and its quantum yield in D(2)O, which is only weakly dependent on oxygen concentration, is as high as C(60) in toluene. In contrast, (1)O(2) generated from aggregated C(60) is not quenchable by NaN(3), exhibits a solvent-independent short-lived lifetime (ca 2.9 mu s), is highly sensitive to oxygen concentration while its phosphorescence is redshifted. All these features indicate that (1)O(2) is sequestered inside the C(60) aggregates, which may explain why these preparations were not phototoxic toward HaCaT cells. Electron paramagnetic resonance studies demonstrated the generation of the C(60) anion radical (C(60)(center dot-)) when (gamma-CyD)(2)/C(60) was irradiated (lambda > 300 nm) in the presence of a reducing agent (NADH); spin trapping experiments (lambda > 400 nm) with 5,5-dimethyl-1-pyrroline N-oxide clearly showed the generation of superoxide resulting from the reaction of C(60)(center dot-) with oxygen. In vitro tests with HaCaT keratinocytes provided evidence that (gamma-CyD)(2)/C(60) phototoxicity is mainly mediated by (1)O(2) (Type II mechanism) with only a minor contribution from free radicals (Type I mechanism). C1 [Zhao, Baozhong; Bilski, Piotr J.; He, Yu-Ying; Feng, Li; Chignell, Colin F.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Zhao, BZ (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM zhaob2@niehs.nih.gov RI Zhao, Baozhong/B-5865-2011 FU Intramural Research Program of the NIH; National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. The authors are indebted to Dr. Ann Motten and Dr. Albert Wielgus, NIEHS, for critical reading of the manuscript, to Ms. D. Sutton and Mr. J. Horton, NIEHS, for the TEM pictures and to Mr. Wayneho Kam for Matrox Inspector analysis of the TEM particle size. NR 37 TC 30 Z9 30 U1 2 U2 23 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2008 VL 84 IS 5 BP 1215 EP 1223 DI 10.1111/j.1751-1097.2008.00333.x PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 342LL UT WOS:000258785500021 PM 18399919 ER PT J AU Chignell, CF Sik, RH Bilski, PJ AF Chignell, Colin F. Sik, Robert H. Bilski, Piotr J. TI The photosensitizing potential of compact fluorescent vs incandescent light bulbs SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PORPHYRIA-CUTANEA-TARDA; SKIN-LESIONS; IRRADIATION AB Recently an article about the new energy-saving compact fluorescent light (CFL) bulbs appeared in Parade magazine [Rosenfeld, I. (2008) ParadeFeb 3, 22]. Under the heading "Bright Lights, Bad Headache?" the writer states that "new research suggests some dangers" involving these lights because they are fluorescent and "can aggravate skin rashes in people with lups, eczema, dermatitis or porphyria." We measured the emission spectrum of a 14 W compact fluorescent bulb (with the same luminous flux as a 60 W incandescent bulb) and compared it to 60 W soft white incandescent and cool white fluorescent (CWF) bulbs. Our results clearly show that the spectral irradiance of the compact fluorescent bulb is similar to that of the CWF bulb; both exhibit sharp Hg emission lines at 365 nm (very weak), 404 nm (weak), 435 nm (moderate) and 543 nm (strong). In contrast, the emission of the incandescent bulb begins at 375 nm and then increases monotonically to above 750 nm. From their respective absorption spectra we calculated the potential photosensitization indices of protoporphyrin IX (PPIX; a prototypic porphyria skin photosensitizer) and riboflavin (a putative lens photosensitizer) vs 14 W compact fluorescent, CWF and 60 W incandescent bulbs. A higher photosensitization index would indicate a greater chance that the light/photosensitizer combination would cause photosensitization of the skin or eyes. We found that for PPIX and riboflavin the photosensitization index of the compact fluorescent bulb is less than half that of the 60 W incandescent bulb. These results suggest that substitution of a compact fluorescent bulb for an incandescent bulb of the same luminous flux should not increase the phototoxicity of skin porphyrins or lens riboflavin. C1 [Chignell, Colin F.; Sik, Robert H.; Bilski, Piotr J.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Chignell, CF (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM chignell@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. The authors are indebted to Dr. Ann Motten, Dr. Albert Wielgus, NIEHS, for critical reading of the manuscript. NR 12 TC 11 Z9 11 U1 2 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2008 VL 84 IS 5 BP 1291 EP 1293 DI 10.1111/j.1751-1097.2008.00366.x PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 342LL UT WOS:000258785500032 PM 18494761 ER PT J AU Munday, JN Capasso, F Parsegian, VA Bezrukov, SM AF Munday, J. N. Capasso, Federico Parsegian, V. Adrian Bezrukov, Sergey M. TI Measurements of the Casimir-Lifshitz force in fluids: The effect of electrostatic forces and Debye screening SO PHYSICAL REVIEW A LA English DT Article ID MICROELECTROMECHANICAL SYSTEMS; ATTRACTIVE FORCES; HAMAKER CONSTANTS; MU-M; SPHERE; SOLIDS; RANGE AB We present detailed measurements of the Casimir-Lifshitz force between two gold surfaces (a sphere and a plate) immersed in ethanol and study the effect of residual electrostatic forces, which are dominated by static fields within the apparatus and can be reduced with proper shielding. Electrostatic forces are further reduced by Debye screening through the addition of salt ions to the liquid. Additionally, the salt leads to a reduction of the Casimir-Lifshitz force by screening the zero-frequency contribution to the force; however, the effect is small between gold surfaces at the measured separations and within experimental error. An improved calibration procedure is described and compared with previous methods. Finally, the experimental results are compared with Lifshitz's theory and found to be consistent for the materials used in the experiment. C1 [Munday, J. N.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Capasso, Federico] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Parsegian, V. Adrian; Bezrukov, Sergey M.] NIH, Bethesda, MD 20892 USA. RP Munday, JN (reprint author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. RI Munday, Jeremy/E-6512-2016 OI Munday, Jeremy/0000-0002-0881-9876 FU NSEC [PHY-0117795]; Center for Nanoscale Systems at Harvard University; Intramural Research Program of the NIH; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NSF FX The authors would like to acknowledge R. Podgornik, J. Zimmerberg, G. Carugno, and M. B. Romanowsky for helpful discussions. This project was partially supported by NSEC, under NSF Contract No. PHY-0117795, the Center for Nanoscale Systems at Harvard University, and the Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development. J.N.M. gratefully acknowledges financial support from the NSF. NR 40 TC 21 Z9 21 U1 2 U2 16 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1050-2947 J9 PHYS REV A JI Phys. Rev. A PD SEP PY 2008 VL 78 IS 3 AR 032109 DI 10.1103/PhysRevA.78.032109 PG 8 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA 355DO UT WOS:000259689400021 ER PT J AU Imudia, AN Kilburn, BA Petkova, A Edwin, SS Romero, R Armant, DR AF Imudia, A. N. Kilburn, B. A. Petkova, A. Edwin, S. S. Romero, R. Armant, D. R. TI Expression of heparin-binding EGF-like growth factor in term chorionic villous explants and its role in trophoblast survival SO PLACENTA LA English DT Article DE trophoblast; term villous explants; cell death; growth factors; hypoxia; preeclampsia ID OXYGEN-TENSION; IN-VITRO; APOPTOSIS; PREECLAMPSIA; ENDOMETRIAL; CELLS; CYTOTROPHOBLASTS; DIFFERENTIATION; PLACENTATION; IMPLANTATION AB Heparin-bincling EGF-like growth factor (HBEGF) induces trophoblast extravillous differentiation and prevents apoptosis. These functions are compromised in preeclampsia. Because HBEGF is downregulated in placentas delivered by women with preeclampsia, we have examined its expression and cytoprotective activity in term villous explants. Chorionic villous explants prepared from non-pathological placentas collected by cesarean section at term were cultured at either 20% or 2% O(2) and treated with the HBEGF antagonist CRM197 or recombinant HBEGF. Paraffin sections were assayed for trophoblast death, proliferation and HBEGF expression using the TUNEL method, immunohistochemistry for nuclear Ki67 expression and semi-quantitative immunohistochemistry with image analysis, respectively. Trophoblast cell death was increased significantly after 8 h of culture with CRM 197 or by culture for 2 h at 2% O(2). Exogenous HBEGF prevented cell death due to hypoxia. Proliferative capacity was not affected by culture at either 20% or 2% O(2). Contrary to first trimester placenta, term trophoblasts do not elevate HBEGF expression in response to hypoxia. However, low endogenous levels of HBEGF are required to maintain survival. Therefore, HBEGF-mediated signaling significantly reduces trophoblast cell death at term and its deficiency in preeclampsia could negatively impact trophoblast survival. Published by Elsevier Ltd. C1 [Armant, D. R.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, Detroit, MI 48201 USA. [Edwin, S. S.; Romero, R.] NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA. [Romero, R.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Armant, D. R.] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Armant, DR (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, 275 E Hancock Ave, Detroit, MI 48201 USA. EM d.armant@wayne.edu OI Armant, D. Randall/0000-0001-5904-9325 FU National Institute of Child Health and Human Development; National Institutes of Health; DHHS FX We thank Mr. Michael Kruger for conducting the statistical analyses. This work was supported by the intramural research program of the National Institute of Child Health and Human Development, National Institutes of Health, DHHS. NR 36 TC 13 Z9 14 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD SEP PY 2008 VL 29 IS 9 BP 784 EP 789 DI 10.1016/j.placenta.2008.06.013 PG 6 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 355MI UT WOS:000259712600003 PM 18691754 ER PT J AU Antonellis, A Huynh, JL Lee-Lin, SQ Vinton, RM Renaud, G Loftus, SK Elliot, G Wolfsberg, TG Green, ED McCallion, AS Pavan, WJ AF Antonellis, Anthony Huynh, Jimmy L. Lee-Lin, Shih-Queen Vinton, Ryan M. Renaud, Gabriel Loftus, Stacie K. Elliot, Gene Wolfsberg, Tyra G. Green, Eric D. McCallion, Andrew S. Pavan, William J. TI Identification of Neural Crest and Glial Enhancers at the Mouse Sox10 Locus through Transgenesis in Zebrafish SO PLOS GENETICS LA English DT Article ID TRANSCRIPTION FACTOR SOX10; DORSAL-ROOT GANGLIA; HIRSCHSPRUNG-DISEASE; REGULATORY ELEMENTS; GENE DESERTS; EXPRESSION; SEQUENCE; CELLS; DIFFERENTIATION; MUTATIONS AB Sox10 is a dynamically regulated transcription factor gene that is essential for the development of neural crest-derived and oligodendroglial populations. Developmental genes often require multiple regulatory sequences that integrate discrete and overlapping functions to coordinate their expression. To identify Sox10 cis-regulatory elements, we integrated multiple model systems, including cell-based screens and transposon-mediated transgensis in zebrafish, to scrutinize mammalian conserved, noncoding genomic segments at the mouse Sox10 locus. We demonstrate that eight of 11 Sox10 genomic elements direct reporter gene expression in transgenic zebrafish similar to patterns observed in transgenic mice, despite an absence of observable sequence conservation between mice and zebrafish. Multiple segments direct expression in overlapping populations of neural crest derivatives and glial cells, ranging from pan-Sox10 and pan-neural crest regulatory control to the modulation of expression in subpopulations of Sox10-expressing cells, including developing melanocytes and Schwann cells. Several sequences demonstrate overlapping spatial control, yet direct expression in incompletely overlapping developmental intervals. We were able to partially explain neural crest expression patterns by the presence of head to head SoxE family binding sites within two of the elements. Moreover, we were able to use this transcription factor binding site signature to identify the corresponding zebrafish enhancers in the absence of overall sequence homology. We demonstrate the utility of zebrafish transgenesis as a high-fidelity surrogate in the dissection of mammalian gene regulation, especially those with dynamically controlled developmental expression. C1 [Antonellis, Anthony; Lee-Lin, Shih-Queen; Renaud, Gabriel; Wolfsberg, Tyra G.; Green, Eric D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Loftus, Stacie K.; Elliot, Gene; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Huynh, Jimmy L.; Vinton, Ryan M.; McCallion, Andrew S.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA. RP Antonellis, A (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM andy@jhmi.edu FU National Human Genome Research Institute's (NHGRI) Intramural Research Program (WJP); NIH (NIGMS) (ASM) FX This work was supported by the National Human Genome Research Institute's (NHGRI) Intramural Research Program (WJP) and by sponsored funds from the NIH (NIGMS) (ASM). NR 41 TC 64 Z9 65 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2008 VL 4 IS 9 AR e1000174 DI 10.1371/journal.pgen.1000174 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 365MR UT WOS:000260411200025 PM 18773071 ER PT J AU Buac, K Watkins-Chow, DE Loftus, SK Larson, DM Incao, A Gibney, G Pavan, WJ AF Buac, Kristina Watkins-Chow, Dawn E. Loftus, Stacie K. Larson, Denise M. Incao, Arturo Gibney, Gretchen Pavan, William J. TI A Sox10 Expression Screen Identifies an Amino Acid Essential for Erbb3 Function SO PLOS GENETICS LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; TRANSCRIPTIONAL REGULATION; WAARDENBURG-SYNDROME; CRYSTAL-STRUCTURE; GLIAL-CELLS; MUTATIONS; RECEPTOR; PROTEIN; MOUSE; HEREGULIN AB The neural crest (NC) is a population of embryonic stem cells that gives rise to numerous cell types, including the glia and neurons of the peripheral and enteric nervous systems and the melanocytes of the skin and hair. Mutations in genes and genetic pathways regulating NC development lead to a wide spectrum of human developmental disorders collectively called neurocristopathies. To identify molecular pathways regulating NC development and to understand how alterations in these processes lead to disease, we established an N-ethyl-N-nitrosourea (ENU) mutagenesis screen utilizing a mouse model sensitized for NC defects, Sox10(LacZ/+). Out of 71 pedigrees analyzed, we identified and mapped four heritable loci, called modifier of Sox10 expression pattern 1-4 (msp1-4), which show altered NC patterning. In homozygous msp1 embryos, Sox10(LacZ) expression is absent in cranial ganglia, cranial nerves, and the sympathetic chain; however, the development of other Sox10-expressing cells appears unaffected by the mutation. Linkage analysis, sequencing, and complementation testing confirmed that msp1 is a new allele of the receptor tyrosine kinase Erbb3, Erbb3(msp1), that carries a single amino acid substitution in the extracellular region of the protein. The ENU-induced mutation does not alter protein expression, however, it is sufficient to impair ERBB3 signaling such that the embryonic defects observed in msp1 resemble those of Erbb3 null alleles. Biochemical analysis of the mutant protein showed that ERBB3 is expressed on the cell surface, but its ligand-induced phosphorylation is dramatically reduced by the msp1 mutation. These findings highlight the importance of the mutated residue for ERBB3 receptor function and activation. This study underscores the utility of using an ENU mutagenesis to identify genetic pathways regulating NC development and to dissect the roles of discrete protein domains, both of which contribute to a better understanding of gene function in a cellular and developmental setting. C1 [Buac, Kristina; Watkins-Chow, Dawn E.; Loftus, Stacie K.; Larson, Denise M.; Incao, Arturo; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Buac, Kristina] George Washington Univ, Washington, DC USA. [Gibney, Gretchen] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Buac, K (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. EM bpavan@mail.nih.gov OI Watkins-Chow, Dawn/0000-0002-4355-0868 FU National Institutes of Health [N01-HG-65403]; National Human Genome Research Institute; National Institutes of Health (USA) FX CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number N01-HG-65403. This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health (USA). NR 44 TC 10 Z9 10 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2008 VL 4 IS 9 AR e1000177 DI 10.1371/journal.pgen.1000177 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 365MR UT WOS:000260411200028 PM 18773073 ER PT J AU Karp, DR Carlin, S Cook-Deegan, R Ford, DE Geller, G Glass, DN Greely, H Guthridge, J Kahn, J Kaslow, R Kraft, C MacQueen, K Malin, B Scheuerman, RH Sugarman, J AF Karp, David R. Carlin, Shelley Cook-Deegan, Robert Ford, Daniel E. Geller, Gail Glass, David N. Greely, Hank Guthridge, Joel Kahn, Jeffrey Kaslow, Richard Kraft, Cheryl MacQueen, Kathleen Malin, Bradley Scheuerman, Richard H. Sugarman, Jeremy TI Ethical and Practical Issues Associated with Aggregating Databases SO PLOS MEDICINE LA English DT Review ID INFORMATION; GENOMICS; PRIVACY; PROJECT C1 [Karp, David R.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Carlin, Shelley] Univ Texas SW Med Ctr Dallas, Inst Review Board, Dallas, TX 75390 USA. [Cook-Deegan, Robert] Duke Univ, Inst Genome Sci & Policy, Durham, NC USA. [Sugarman, Jeremy] Johns Hopkins Univ, Berman Inst Bioeth, Dept Med, Baltimore, MD USA. [Glass, David N.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. [Greely, Hank] Stanford Law Sch, Stanford, CA USA. [Guthridge, Joel] Oklahoma Med Res Fdn, Arthrit & Immunol Res Program, Oklahoma City, OK 73104 USA. [Kahn, Jeffrey] Univ Minnesota, Ctr Bioeth, Minneapolis, MN USA. [Kaslow, Richard] Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. [Kraft, Cheryl] NIAID, Div Allergy Immunol & Transplantat, NIH, Rockville, MD USA. [MacQueen, Kathleen] Family Hlth Int, Res Triangle Pk, NC 27709 USA. [Malin, Bradley] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA. [Scheuerman, Richard H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Scheuerman, Richard H.] Univ Texas SW Med Ctr Dallas, Div Biomed Informat, Dallas, TX 75390 USA. [Sugarman, Jeremy] Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA. [Ford, Daniel E.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Karp, DR (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. EM david.karp@utsouthwestern.edu OI Cook-Deegan, Robert/0000-0002-8251-4237 FU NIAID NIH HHS [N01-AI40076, N01AI40076] NR 21 TC 21 Z9 21 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD SEP PY 2008 VL 5 IS 9 BP 1333 EP 1337 AR e190 DI 10.1371/journal.pmed.0050190 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 365XG UT WOS:000260442300008 PM 18816162 ER PT J AU Ingavale, SS Chang, YC Lee, H McClelland, CM Leong, ML Kwon-Chung, KJ AF Ingavale, Susham S. Chang, Yun C. Lee, Hyeseung McClelland, Carol M. Leong, Madeline L. Kwon-Chung, Kyung J. TI Importance of mitochondria in survival of Cryptococcus neoformans under low oxygen conditions and tolerance to cobalt chloride SO PLOS PATHOGENS LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; HYPOXIA-MIMICKING AGENT; INDUCIBLE FACTOR-I; OXIDATIVE STRESS; SUPEROXIDE-PRODUCTION; STEROL HOMEOSTASIS; NEUROSPORA CRASSA; ADP/ATP CARRIER; NITRIC-OXIDE; COMPLEX-III AB Cryptococcus neoformans is an environmental fungal pathogen that requires atmospheric levels of oxygen for optimal growth. For the fungus to be able to establish an infection, it must adapt to the low oxygen concentrations in the host environment compared to its natural habitat. In order to investigate the oxygen sensing mechanism in C. neoformans, we screened T-DNA insertional mutants for hypoxia-mimetic cobalt chloride (CoCl(2))-sensitive mutants. All the CoCl(2)-sensitive mutants had a growth defect under low oxygen conditions at 37 degrees C. The majority of mutants are compromised in their mitochondrial function, which is reflected by their reduced rate of respiration. Some of the mutants are also defective in mitochondrial membrane permeability, suggesting the importance of an intact respiratory system for survival under both high concentrations of CoCl(2) as well as low oxygen conditions. In addition, the mutants tend to accumulate intracellular reactive oxygen species (ROS), and all mutants show sensitivity to various ROS generating chemicals. Gene expression analysis revealed the involvement of several pathways in response to cobalt chloride. Our findings indicate cobalt chloride sensitivity and/or sensitivity to low oxygen conditions are linked to mitochondrial function, sterol and iron homeostasis, ubiquitination, and the ability of cells to respond to ROS. These findings imply that multiple pathways are involved in oxygen sensing in C. neoformans. C1 [Ingavale, Susham S.; Chang, Yun C.; Lee, Hyeseung; McClelland, Carol M.; Leong, Madeline L.; Kwon-Chung, Kyung J.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM June_Kwon-Chung@nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America FX This study was supported by funds from the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America. NR 69 TC 33 Z9 34 U1 2 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD SEP PY 2008 VL 4 IS 9 AR e1000155 DI 10.1371/journal.ppat.1000155 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 356MW UT WOS:000259783300012 PM 18802457 ER PT J AU Klein, MM Gittis, AG Su, HP Makobongo, MO Moore, JM Singh, S Miller, LH Garboczi, DN AF Klein, Michael M. Gittis, Apostolos G. Su, Hua-Poo Makobongo, Morris O. Moore, Jaime M. Singh, Sanjay Miller, Louis H. Garboczi, David N. TI The cysteine-rich interdomain region from the highly variable Plasmodium falciparum erythrocyte membrane protein-1 exhibits a conserved structure SO PLOS PATHOGENS LA English DT Article ID FALCIPARUM-INFECTED ERYTHROCYTES; INTERCELLULAR-ADHESION MOLECULE-1; PARASITE PLASMODIUM-FALCIPARUM; PREGNANCY-ASSOCIATED MALARIA; MEMBRANE PROTEIN-1 FAMILY; BINDING-LIKE DOMAINS; RED-BLOOD-CELLS; VAR GENES; ANTIGENIC VARIATION; SEVERE DISEASE AB Plasmodium falciparum malaria parasites, living in red blood cells, express proteins of the erythrocyte membrane protein-1 (PfEMP1) family on the red blood cell surface. The binding of PfEMP1 molecules to human cell surface receptors mediates the adherence of infected red blood cells to human tissues. The sequences of the 60 PfEMP1 genes in each parasite genome vary greatly from parasite to parasite, yet the variant PfEMP1 proteins maintain receptor binding. Almost all parasites isolated directly from patients bind the human CD36 receptor. Of the several kinds of highly polymorphic cysteine-rich interdomain region (CIDR) domains classified by sequence, only the CIDR1 alpha domains bind CD36. Here we describe the CD36-binding portion of a CIDR1 alpha domain, MC179, as a bundle of three alpha-helices that are connected by a loop and three additional helices. The MC179 structure, containing seven conserved cysteines and 10 conserved hydrophobic residues, predicts similar structures for the hundreds of CIDR sequences from the many genome sequences now known. Comparison of MC179 with the CIDR domains in the genome of the P. falciparum 3D7 strain provides insights into CIDR domain structure. The CIDR1 alpha three-helix bundle exhibits less than 20% sequence identity with the three-helix bundles of Duffy-binding like (DBL) domains, but the two kinds of bundles are almost identical. Despite the enormous diversity of PfEMP1 sequences, the CIDR1 alpha and DBL protein structures, taken together, predict that a PfEMP1 molecule is a polymer of three-helix bundles elaborated by a variety of connecting helices and loops. From the structures also comes the insight that DBL1 alpha domains are approximately 100 residues larger and that CIDR1 alpha domains are approximately 100 residues smaller than sequence alignments predict. This new understanding of PfEMP1 structure will allow the use of better-defined PfEMP1 domains for functional studies, for the design of candidate vaccines, and for understanding the molecular basis of cytoadherence. C1 [Klein, Michael M.; Gittis, Apostolos G.; Su, Hua-Poo; Moore, Jaime M.; Garboczi, David N.] NIAID, Immunogenet Lab, Struct Biol Sect, NIH, Rockville, MD 20852 USA. [Makobongo, Morris O.; Singh, Sanjay; Miller, Louis H.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. RP Garboczi, DN (reprint author), NIAID, Immunogenet Lab, Struct Biol Sect, NIH, Rockville, MD 20852 USA. EM dgarboczi@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 64 TC 31 Z9 31 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD SEP PY 2008 VL 4 IS 9 AR e1000147 DI 10.1371/journal.ppat.1000147 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 356MW UT WOS:000259783300005 PM 18773118 ER PT J AU Schelhaas, M Ewers, H Rajamaki, ML Day, PM Schiller, JT Helenius, A AF Schelhaas, Mario Ewers, Helge Rajamaki, Minna-Liisa Day, Patricia M. Schiller, John T. Helenius, Ari TI Human papillomavirus type 16 entry: Retrograde cell surface transport along actin-rich protrusions SO PLOS PATHOGENS LA English DT Article ID VIRUS-LIKE PARTICLES; HEPARAN-SULFATE PROTEOGLYCANS; NEURONAL GROWTH CONES; MURINE POLYOMA-VIRUS; HUMAN KERATINOCYTES; HOST-CELLS; RECEPTORS; NEUTRALIZATION; ENDOCYTOSIS; FILOPODIA AB The lateral mobility of individual, incoming human papillomavirus type 16 pseudoviruses (PsV) bound to live HeLa cells was studied by single particle tracking using fluorescence video microscopy. The trajectories were computationally analyzed in terms of diffusion rate and mode of motion as described by the moment scaling spectrum. Four distinct modes of mobility were seen: confined movement in small zones (30-60 nm in diameter), confined movement with a slow drift, fast random motion with transient confinement, and linear, directed movement for long distances. The directed movement was most prominent on actin-rich cell protrusions such as filopodia or retraction fibres, where the rate was similar to that measured for actin retrograde flow. It was, moreover, sensitive to perturbants of actin retrograde flow such as cytochalasin D, jasplakinolide, and blebbistatin. We found that transport along actin protrusions significantly enhanced HPV-16 infection in sparse tissue culture, cells suggesting a role for in vivo infection of basal keratinocytes during wound healing. C1 [Schelhaas, Mario; Ewers, Helge; Helenius, Ari] ETH, Inst Biochem, Zurich, Switzerland. [Rajamaki, Minna-Liisa] Univ Helsinki, Dept Appl Biol, Helsinki, Finland. [Day, Patricia M.; Schiller, John T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Helenius, A (reprint author), ETH, Inst Biochem, Zurich, Switzerland. EM ari.helenius@bc.biol.ethz.ch RI Ewers, Helge/I-3455-2012; OI Ewers, Helge/0000-0003-3948-4332 FU German Science Foundation (DFG) [SCHE 1552/1-1]; Academy of Finland [204104]; ETH Zurich; Fondation Andromac (Liechtenstein); Swiss National Science Foundation (SNF) FX M. S. was supported by the German Science Foundation (DFG, grant SCHE 1552/1-1). M. L. R. was supported by the Academy of Finland (grant 204104). A. H. was supported by the ETH Zurich, the Fondation Andromac (Liechtenstein), and by the Swiss National Science Foundation (SNF). NR 49 TC 78 Z9 79 U1 3 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD SEP PY 2008 VL 4 IS 9 AR e1000148 DI 10.1371/journal.ppat.1000148 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 356MW UT WOS:000259783300006 PM 18773072 ER PT J AU Signore, C Mills, JL Qian, C Yu, KF Rana, S Karmnanchi, SA Levine, RJ AF Signore, Caroline Mills, James L. Qian, Cong Yu, Kai F. Rana, Sarosh Karmnanchi, S. Ananth Levine, Richard J. TI Circulating soluble endoglin and placental abruption SO PRENATAL DIAGNOSIS LA English DT Article DE abruptio placentae; preclampsia; gestational hypertension; endoglin; angiogenic factors ID GROWTH-FACTOR; ANGIOGENIC FACTORS; UNITED-STATES; ANTIANGIOGENIC FACTORS; TYROSINE KINASE-1; PREECLAMPSIA; RISK; PREGNANCIES AB Objective Our objective was to investigate whether serum concentrations of a novel anti-angiogenic factor, soluble endoglin (sEng), could predict placental abruption. Methods In a nested case-control study of nulliparous pregnancies, we examined levels of sEng in serum collected prospectively from 31 women who later developed placental abruption and from 31 normal controls. All serum specimens were collected before the onset of hypertension or abruption and before labor or delivery. Serum sEng was compared within three gestational age intervals: early- (< 20 weeks), mid- (21-32 weeks), and late (>= 33 weeks) pregnancy. Results There was no significant difference in sEng between abruption cases and controls in early pregnancy. sEng was significantly elvated among abruption cases at 21-32 weeks (10.7 vs 5.9 ng/mL, P < 0.01). Subgroup analyses revealed no differences in sEng concentrations at any gestational age interval between cases with abruption without hypertension and healthy controls. Among women who developed hypertension and palcental abruption. sEng was not significantly increased in early pregnancy, but was in mid-pregnancy (19.3 vs 5.5 ng/mL, P=0.002) and in late pregnancy (15.6 vs 9.5 ng/mL, P=0.04). Conclusions Serum levels of the anti-angiogenic factor sEng are elevated prior to the development of hypertension and placental abruption. These elevations are not apparent until the late second trimester (26-27 weeks, on average), but they persist from this time in gestation onward. sEng may be useful for identifying pregnant women at risk for abruption and hypertension. Published in 2008 by John Wiley & Sons, Ltd. C1 [Signore, Caroline; Mills, James L.; Levine, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NICHD,NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Qian, Cong] Allied Technol Grp, Rockville, MD USA. [Yu, Kai F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Rana, Sarosh] Women & Infants Hosp Rhode Isl, Dept Obstet & Gynecol, Div Maternal Fetal Med, Providence, RI 02908 USA. [Rana, Sarosh; Karmnanchi, S. Ananth] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Karmnanchi, S. Ananth] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. RP Levine, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NICHD,NIH,Dept Hlth & Human Serv, Bldg 6100,Rm 7B03, Bethesda, MD 20892 USA. EM LevineRJ@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; National Institute of Child Health and Human Development [N01-HD-1-3121, -3122, -3123, -3124, -3125, 3126, N01-HD-3154, N01-HD-5-3246]; National Heart, lung and Blood Institute [HL079594] FX This research was supported by funds from the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The CPEP trial was supported by contracts (N01-HD-1-3121, -3122, -3123 -3124, -3125, and -3126, N01-HD-3154; and N01-HD-5-3246) with the National Institute of Child Health and Human Development, with cofunding from the National Heart, Lung, and Blood Institute. Dr. Karumanchi is supported by R01 grant HL079594 from the National Heart, lung and Blood Institute.; Dr. Karumanchi reports being named the coinventor of multiple provisional patents that have been filed by Beth Israel Deaconess Medical Center for the diagnosis and treatment of preeclampsia. These patents have been nonexclusively licensed to several companies. Dr. Karumanchi reports having served as a consultant to Abbott, Beckman Coulter, and Johnson & Johnson. NR 20 TC 24 Z9 24 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD SEP PY 2008 VL 28 IS 9 BP 852 EP 858 DI 10.1002/pd.2065 PG 7 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 355PE UT WOS:000259720000012 PM 18702104 ER PT J AU Berrigan, D McKinnon, RA AF Berrigan, David McKinnon, Robin A. TI Built environment and health SO PREVENTIVE MEDICINE LA English DT Editorial Material ID LESSONS C1 [Berrigan, David] NCI, Off Assoc Director, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [McKinnon, Robin A.] NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Berrigan, D (reprint author), NCI, Off Assoc Director, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N, Bethesda, MD 20892 USA. EM berrigad@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 11 TC 9 Z9 9 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 2008 VL 47 IS 3 BP 239 EP 240 DI 10.1016/j.ypmed.2008.07.010 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 355MG UT WOS:000259712400001 PM 18694780 ER PT J AU Kruger, J Ham, SA Berrigan, D Ballard-Barbash, R AF Kruger, Judy Ham, Sandra A. Berrigan, David Ballard-Barbash, Rachel TI Prevalence of transportation and leisure walking among US adults SO PREVENTIVE MEDICINE LA English DT Article DE walking; physical activity; transportation ID PHYSICAL-ACTIVITY; PUBLIC-HEALTH; UNITED-STATES; RECOMMENDATIONS AB Objective. This paper aims to contrast the demographic correlates of leisure and transportation walking. Methods. Using data from the 2005 National Health Interview Survey (n=31,482), this paper reports on the prevalence of transportation walking and leisure walking for U.S. adults and examines the variation in prevalence across different socio-demographic groups. The prevalence of transportation walking and leisure walking for U.S. adults (>= 5 days/week for >= 30 min/day) was calculated using data from the 2005 National Health Interview Survey. Results. In the United States, 41.5% of adults walked for leisure and 28.2% walked for transportation in intervals of at least 10 min. The highest prevalence of transportation walking was among black non-Hispanic men (36.0%) and Asian/Native Hawaiian/Pacific Islander women (40.5%). The highest prevalence of leisure walking was among Asian/Native Hawaiian/Pacific Islander men (42.0%) and white non-Hispanic women (46.6%). Leisure walking was most prevalent among respondents with higher incomes and education levels, whereas transportation walking increased in prevalence with education level but decreased with income level. Based on the findings, 6% of U.S. adults were considered regularly active (>= 5 days/week for >= 30 min/day) by walking for transportation and 9% were regularly active by walking for leisure. Conclusion. Leisure and transportation walking have distinctly different demographic correlates. These differences should guide interventions aimed at influencing walking for different purposes. Published by Elsevier Inc. C1 [Kruger, Judy; Ham, Sandra A.] Ctr Dis Control & Prevent, Phys Act & Hlth Branch, Div Nutr, Phys Act & Obes, Atlanta, GA 30341 USA. [Berrigan, David; Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD USA. RP Kruger, J (reprint author), Ctr Dis Control & Prevent, Phys Act & Hlth Branch, Div Nutr, Phys Act & Obes, 4770 Buford Highway,NE MS K-46, Atlanta, GA 30341 USA. EM ezk0@cdc.gov NR 19 TC 50 Z9 53 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 2008 VL 47 IS 3 BP 329 EP 334 DI 10.1016/j.ypmed.2008.02.018 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 355MG UT WOS:000259712400018 PM 18445507 ER EF