FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Paulos, CM Kaiser, A Wrzesinski, C Hinrichs, CS Cassard, L Boni, A Muranski, P Sanchez-Perez, L Palmer, DC Yu, ZY Antony, PA Gattinoni, L Rosenberg, SA Restifo, NP AF Paulos, Chrystal M. Kaiser, Andrew Wrzesinski, Claudia Hinrichs, Christian S. Cassard, Lyclie Boni, Andrea Muranski, Pawel Sanchez-Perez, Luis Palmer, Douglas C. Yu, Zhiya Antony, Paul A. Gattinoni, Luca Rosenberg, Steven A. Restifo, Nicholas P. TI Toll-like receptors in tumor immunotherapy SO CLINICAL CANCER RESEARCH LA English DT Review ID CD8(+) T-CELLS; VERSUS-HOST-DISEASE; DISSEMINATED MURINE LEUKEMIA; MONOCLONAL-ANTIBODY THERAPY; NON-HODGKINS-LYMPHOMA; DENDRITIC CELLS; METASTATIC MELANOMA; IN-VIVO; ANTITUMOR IMMUNITY; ADAPTIVE IMMUNITY AB Lymphodepletion with chemotherapeutic agents or total body irradiation (TBI) before adoptive transfer of tumor-specific T cells is a critical advancement in the treatment of patients with melanoma. More than 50% of patients that are refractory to other treatments experience an objective or curative response with this approach. Emerging data indicate that the key mechanisms underlying how TBI augments the functions of adoptively transferred T cells include (a) the depletion of regulatory T cells (T-reg) and myeloid-derived suppressor cells that limit the function and proliferation of adoptively transferred cells; (b) the removal of immune cells that act as "sinks" for homeostatic cytokines, whose levels increase after lymphodepletion; and (c) the activation of the innate immune system via Toll-like receptor 4 signaling, which is engaged by microbial lipopolysaccharide that translocated across the radiation -injured gut. Here, we review these mechanisms and focus on the effect of Toll-like receptor agonists in adoptive immunotherapy. We also discuss alternate regimens to chemotherapy or TBI, which might be used to safely treat patients with advanced disease and promote tumor regression. C1 Natl Canc Inst, Mark O Hatfield Clin Res Ctr, NIH, Bethesda, MD 20892 USA. RP Paulos, CM (reprint author), Natl Canc Inst, Mark O Hatfield Clin Res Ctr, NIH, Room 3-5762,10 Ctr Dr, Bethesda, MD 20892 USA. EM chrystalp@hotmail.com; restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Wrzesinski, Claudia/A-3077-2008; Palmer, Douglas/B-9454-2008; Restifo, Nicholas/A-5713-2008; Muranski, Pawel/E-5572-2010; Kaiser, Andrew/C-2617-2012; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z01 SC003811-32, Z99 CA999999] NR 156 TC 75 Z9 78 U1 2 U2 7 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 15 PY 2007 VL 13 IS 18 BP 5280 EP 5289 DI 10.1158/1078-0432.CCR-07-1378 PN 1 PG 10 WC Oncology SC Oncology GA 214JV UT WOS:000249734700011 PM 17875756 ER PT J AU Kummar, S Gutierrez, M Gardner, ER Donovan, E Hwang, K Chung, EJ Lee, MJ Maynard, K Kalnitskiy, M Chen, A Melillo, G Ryan, QC Conley, B Figg, WD Trepel, JB Zwiebel, J Doroshow, JH Murgo, AJ AF Kummar, Shivaani Gutierrez, Martin Gardner, Erin R. Donovan, Erin Hwang, Kyunghwa Chung, Eun Joo Lee, Min-Jung Maynard, Kim Kalnitskiy, Mikhail Chen, Alice Melillo, Giovanni Ryan, Qin C. Conley, Barbara Figg, William D. Trepel, Jane B. Zwiebel, James Doroshow, James H. Murgo, Anthony J. TI Phase I trial of MS-275, a histone deacetylase inhibitor, administered weekly in refractory solid tumors and lymphoid malignancies SO CLINICAL CANCER RESEARCH LA English DT Article ID PHARMACODYNAMIC ANALYSIS; CELL; PLASMA AB Purpose: MS-275 is a histone deacetylase inhibitor that has shown potent and unique anticancer activity in preclinical models. The aims of this phase I trial were to determine the dose-limiting toxicities and maximum tolerated dose of oral MS-275 in humans administered with food on a once weekly schedule and to study the pharmacokinetics of oral MS-275. Experimental Design: Patients with refractory solid tumors and lymphoid malignancies were treated with oral MS-275 on a once weekly schedule for 4 weeks of a 6-week cycle. Samples for pharmacokinetic and pharmacodynamic analyses were collected during cycle 1. Protein acetylation in subpopulations of peripheral blood mononuclear cells was measured using a multivariable flow cytometry assay. Results: A total of 22 patients were enrolled, and 19 were considered evaluable for toxicity. The maximum tolerated dose was 6 mg/m(2). No National Cancer Institute Common Toxicity Criteria grade 4 toxicities were observed. Dose-limiting grade 3 toxicities were reversible and consisted of hypophosphatemia, hyponatremia, and hypoalbuminemia. Non - dose-limiting grade 3 myelosuppression was also observed, The mean terminal half-life of MS-275 was 33.9 +/- 26.2 and the T-max ranged from 0.5 to 24 h. Although there was considerable interpatient variability in pharmacokinetics, the area under the plasma concentration versus time curve increased linearly with dose. Conclusions: MS-275 is well tolerated at a dose of 6 mg/m(2) administered weekly with food for 4 weeks every 6 weeks. Drug exposure increases linearly with dose, and protein acetylation increased in all the subpopulations of peripheral blood mononuclear cells following MS-275 administration. C1 NCI, Med Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Clin Pharmacol Program, Frederick, MD 21701 USA. RP Kummar, S (reprint author), NCI, Med Oncol Branch, Canc Res Ctr, 10 Ctr Dr,10-12N226, Bethesda, MD 20892 USA. EM kummars@exchange.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS [, NIH0011335962]; PHS HHS [N01-C0-12400, NIH0011335962] NR 19 TC 75 Z9 77 U1 0 U2 7 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 15 PY 2007 VL 13 IS 18 BP 5411 EP 5417 DI 10.1158/1078-0432.CCR-07-0791 PN 1 PG 7 WC Oncology SC Oncology GA 214JV UT WOS:000249734700028 PM 17875771 ER PT J AU Christov, K Grubbs, CJ Shilkaitis, A Juliana, MM Lubet, RA AF Christov, Konstantin Grubbs, Clinton J. Shilkaitis, Anne Juliana, M. Margaret Lubet, Ronald A. TI Short-term modulation of cell proliferation and apoptosis and preventive/Therapeutic efficacy of various agents in a mammary cancer model SO CLINICAL CANCER RESEARCH LA English DT Article ID ESTROGEN-RECEPTOR MODULATOR; SPRAGUE-DAWLEY RATS; BREAST-CANCER; AROMATASE INHIBITORS; TUMORS; PREVENTION; COMBINATION; EXPRESSION; TAMOXIFEN; BIOMARKER AB Purpose: The methylnitrosourea (MNU)-induced mammary cancer model in rats is similar to estrogen receptor-positive breast cancer in women. In prevention studies using this model, tumor incidence and multiplicity were typically primary end points. The ability of various agents administered for a short period to modulate cell proliferation [proliferation index (PI)] and apoptosis [apoptotic index (AI)] in mammary cancers was compared with their efficacy in long-term prevention and therapy studies. Experimental Design: Rats were injected with MNU to induce mammary cancers. For the prevention studies, agents were administered by gavage or in the diet beginning 5 days after MNU. For proliferation (PI) and apoptosis (AI) experiments, animals with a palpable mammary cancer were treated with the agents for only 4 to 7 days. PI was determined following 5-bromo-deoxyuricline labeling whereas AI was determined using the terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay. Therapeutic efficacy was evaluated by measuring cancer size over a 6-week period. Results: Treatments with differing chemopreventive efficacy and mechanism (s) of action were examined: (a) hormonal treatments [tamoxifen, vorozole (an aromatase inhibitor), and ovariectomy]; (b) retinoid X receptor agonists (targretin, 9-cis retinoic acid, and UAB30); (c) inducers of drug-metabolizing enzymes (indole-3-carbinol, 5,6 benzoflavone, and diindoylmethane); (d) agents that alter signal transduction (R115777, a farnesyltransferase inhibitor); Iressa (an epidermal growth factor receptor inhibitor); sulindac and celecoxib (cyclooxygenase 1/2 and cyclooxygenase 2 inhibitors); and (e) diverse agents including meclizine, vitamin C, and sodium phenylbutyrate. Correlations between inhibition of PI, increase of AI, and chemopreventive efficacy were observed. Although most agents with moderate or low preventive efficacy suppressed PI, they minimally affected AI. Conclusions: The data confirmed that the short-term effects of various agents on cell proliferation and apoptosis in small mammary cancers can predict their preventive/therapeutic efficacy. Thus, these biomarkers can be used to help determine the efficacy of compounds in phase 11 clinical prevention trials. C1 NCI, Div Canc Prevent, Bethesda, MD 20852 USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama, Dept Genet, Birmingham, AL USA. Univ Illinois, Dept Surg Oncol, Chicago, IL USA. RP Lubet, RA (reprint author), NCI, Div Canc Prevent, Execut Plaza N,Suite 2110,6130 Execut Blvd, Bethesda, MD 20852 USA. EM lubetr@mail.nih.gov FU NCI NIH HHS [N01-CN-25003, N01-CN-15128, N01-CN-25115, N01-CN-43301] NR 35 TC 35 Z9 37 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2007 VL 13 IS 18 BP 5488 EP 5496 DI 10.1158/1078-0432.CCR-07-0404 PN 1 PG 9 WC Oncology SC Oncology GA 214JV UT WOS:000249734700037 PM 17875779 ER PT J AU Kelly, MP Lee, FT Tahtis, K Smyth, FE Brechbiel, MW Scott, AM AF Kelly, Marcus P. Lee, Fook T. Tahtis, Kiki Smyth, Fiona E. Brechbiel, Martin W. Scott, Andrew M. TI Radioimmunotherapy with alpha-particle - Emitting Bi-213-C-functionalized trans-cyclohexyl-diethylenetriaminepentaacetic acid-humanized 3S193 is enhanced by combination with paclitaxel chemotherapy SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 11th Conference on Cancer Therapy with Antibodies and Immunoconjugates CY OCT 12-14, 2006 CL Parsippany, NJ SP Ctr Mol Med & Immunol, Garden State Canc Ctr ID DISSEMINATED PERITONEAL DISEASE; MONOCLONAL-ANTIBODY HU3S193; ACTIVATOR INHIBITOR TYPE-2; HUMAN PROSTATE-CANCER; BREAST-CANCER; IN-VITRO; SOLID TUMORS; THERAPEUTIC-EFFICACY; METASTATIC PROSTATE; ANTITUMOR-ACTIVITY AB Purpose: Previous experience in solid tumor radioimmunotherapy studies has indicated that greatest therapeutic efficacy is achieved in the treatment of small-volume disease. alpha-Particle-emitting radioisotopes possess several physical characteristics ideally suited to the treatment of minimal residual disease. Therefore, we have investigated the efficacy of the alpha-particle-emitting bismuth-213 (Bi-213) radioimmunotherapy using the humanized anti-Lewis Y (Le(y)) monoclonal antibody humanized 3S193 (hu3S193). Experimental Design: The intracellular localization of hu3S193 in Le(y)-positive MCF-7 breast carcinoma cells was assessed by confocal microscopy. Cytotoxicity of Bi-213-hu3S193 and apoptosis was assessed using [3 H] thymidine incorporation assay and ELISA, respectively. Immunoblotting for gamma-H2AX assessed DNA strand breaks. In vivo efficacy of Bi-213-hu3S193 was assessed using a minimal residual disease model in BALB/c nude mice, with radioconjugate [15, 30, and 60 mu Ci (9.2 mu g)] injected 2 days after s.c. implantation of MCF-7 cells. Radioimmunotherapy was also combined with a single injection of 300 lug paclitaxel to explore improved efficacy. Further, mice with established tumors received 30, 60, or 120 mu Ci (14.5 mu g) of Bi-213-hu3S193 to assess the effect of tumor volume on treatment efficacy. Results: hu3S193 is internalized via an endosomal and lysosomal trafficking pathway. Treatment with Bi-213-hu3S193 results in >90% cytotoxicity in vitro and induces apoptosis and increased gamma-112AX expression, Bi-213-hu3S193 causes specific and significant retardation of tumor growth even in established tumors, and efficacy was enhanced by paclitaxel to produce defined complete responses. Conclusions: These studies show the potency of alpha-particle radioimmunotherapy and warrant its further exploration in the treatment of micrometastatic disease in Le(y)-positive malignancies. C1 Austin Hosp, Ludwig Inst Canc Res, Tumour Targeting Program, Heidelberg, Vic 3084, Australia. NCI, NIH, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Scott, AM (reprint author), Austin Hosp, Ludwig Inst Canc Res, Tumour Targeting Program, Studley Rd, Heidelberg, Vic 3084, Australia. EM andrew.scott@ludwig.edu.au FU Intramural NIH HHS NR 49 TC 17 Z9 19 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 15 PY 2007 VL 13 IS 18 SU S BP 5604S EP 5612S DI 10.1158/1078-0432.CCR-07-1071 PN 2 PG 9 WC Oncology SC Oncology GA 216PD UT WOS:000249889900016 PM 17875796 ER PT J AU Siddiqui, S Anderson, VL Hilligoss, DM Abinun, M Kuijpers, TW Masur, H Witebsky, FG Shea, YR Gallin, JI Malech, HL Holland, SM AF Siddiqui, Sophia Anderson, Victoria L. Hilligoss, Diane M. Abinun, Mario Kuijpers, Taco W. Masur, Henry Witebsky, Frank G. Shea, Yvonne R. Gallin, John I. Malech, Henry L. Holland, Steven M. TI Fulminant mulch pneumonitis: An emergency presentation of chronic granulomatous disease SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID EMPIRICAL ANTIFUNGAL THERAPY; LIPOSOMAL AMPHOTERICIN-B; INVASIVE ASPERGILLOSIS; PERSISTENT FEVER; PULMONARY ASPERGILLOSIS; HOST-DEFENSE; INFECTION; MICE; VORICONAZOLE; NEUTROPENIA AB Background. Chronic granulomatous disease (CGD) is associated with multiple and recurrent infections. In patients with CGD, invasive pulmonary infection with Aspergillus species remains the greatest cause of mortality and is typically insidious in onset. Acute fulminant presentations of fungal pneumonia are catastrophic. Methods. Case records, radiograph findings, and microbiologic examination findings of patients with CGD who had acute presentations of dyspnea and diffuse pulmonary infiltrates caused by invasive fungal infection were reviewed and excerpted onto a standard format. Results. From 1991 through 2004, 9 patients who either were known to have CGD or who received a subsequent diagnosis of CGD presented with fever and new onset dyspnea. Eight patients were hypoxic at presentation; bilateral pulmonary infiltrates were noted at presentation in 6 patients and developed within 2 days after initial symptoms in 2 patients. All patients received diagnoses of invasive filamentous fungi; 4 patients had specimens that also grew Streptomyces species on culture. All patients had been exposed to aerosolized mulch or organic material 1-10 days prior to the onset of symptoms. Cases did not occur in the winter. Five patients died. Two patients, 14 years of age and 23 years of age, who had no antecedent history of recognized immunodeficiency, were found to have p47(phox)- deficient CGD. Conclusions. Acute fulminant invasive fungal pneumonia in the absence of exogenous immunosuppression is a medical emergency that is highly associated with CGD. Correct diagnosis has important implications for immediate therapy, genetic counseling, and subsequent prophylaxis. C1 NIAID, NIH, Clin Infect Dis, Bethesda, MD 20892 USA. NIH, Lab Immune Regulat, Bethesda, MD 20892 USA. NIH, Host Def Lab, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Microbiol Serv, Bethesda, MD 20892 USA. Newcastle Gen Hosp, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Emma Childrens Hosp, Amsterdam, Netherlands. RP Holland, SM (reprint author), NIH, Lab Clin Infect Dis, Bldg 10,CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov OI Malech, Harry/0000-0001-5874-5775 FU Intramural NIH HHS NR 33 TC 67 Z9 72 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 15 PY 2007 VL 45 IS 6 BP 673 EP 681 DI 10.1086/520985 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 202DG UT WOS:000248881600005 PM 17712749 ER PT J AU Di-Gregorio, A Sancho, M Stuckey, DW Crompton, LA Godwin, J Mishina, Y Rodriguez, TA AF Di-Gregorio, Aida Sancho, Margarida Stuckey, Daniel W. Crompton, Lucy A. Godwin, Jonathan Mishina, Yuji Rodriguez, Tristan A. TI BMP signalling inhibits premature neural differentiation in the mouse embryo SO DEVELOPMENT LA English DT Article DE neural induction; Bmpr1a; BMP signalling ID BONE MORPHOGENETIC PROTEIN-4; PRIMORDIAL GERM-CELLS; ANTERIOR-POSTERIOR AXIS; STEM-CELLS; TRANSCRIPTION FACTOR; I RECEPTORS; SMAD1 PHOSPHORYLATION; PRIMITIVE ENDODERM; MESODERM FORMATION; VISCERAL ENDODERM AB The specification of a subset of epiblast cells to acquire a neural fate constitutes the first step in the generation of the nervous system. Little is known about the signals required for neural induction in the mouse. We have analysed the role of BMP signalling in this process. We demonstrate that prior to gastrulation, Bmp2/4 signalling via Bmpr1a maintains epiblast pluripotency and prevents precocious neural differentiation of this tissue, at least in part by maintaining Nodal signalling. We find that during gastrulation, BMPs of the 60A subgroup cooperate with Bmp2/4 to maintain pluripotency. The inhibition of neural fate by BMPs is independent of FGF signalling, as inhibition of FGF signalling between 5.5 and 7.5 days post-coitum does not block neural differentiation in the mouse embryo. Together, our results demonstrate that inhibition of BMP signalling has a central role during neural induction in mammals and suggest that FGFs do not act as neural inducers in the post-implantation mouse embryo. C1 Univ London Imperial Coll Sci Technol & Med, Mol Embryol Grp, London W12 0NN, England. Univ London Imperial Coll Sci Technol & Med, Transgen Facil, MRC, Ctr Clin Sci, London W12 0NN, England. NIEHS, Reprod & Dev Toxicol Lab, Mol Dev Biol Sect, Res Triangle Pk, NC 27709 USA. RP Rodriguez, TA (reprint author), Univ London Imperial Coll Sci Technol & Med, Mol Embryol Grp, Hammersmith Hosp Campus,Cane Rd, London W12 0NN, England. EM tristan.rodriguez@csc.mrc.ac.uk FU Intramural NIH HHS; Medical Research Council [MC_U120081320] NR 78 TC 80 Z9 84 U1 3 U2 15 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 15 PY 2007 VL 134 IS 18 BP 3359 EP 3369 DI 10.1242/dev.005967 PG 11 WC Developmental Biology SC Developmental Biology GA 203ZX UT WOS:000249013700013 PM 17699604 ER PT J AU Tanaka-Matakatsu, M Thomas, BJ Du, W AF Tanaka-Matakatsu, Miho Thomas, Barbara J. Du, Wei TI Mutation of the Apcl homologue shattered disrupts normal eye development by disrupting G1 cell cycle arrest and progression through mitosis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE anaphase-promoting complex/cyclosome; APC/C; Cdc25; drosophila; shattered; string; CycA; eye development ID ANAPHASE-PROMOTING COMPLEX; DEVELOPING DROSOPHILA EYE; PATTERN-FORMATION; S-PHASE; DOWN-REGULATION; PRONEURAL GENE; AXONAL GROWTH; PROLIFERATION; COMPLEX/CYCLOSOME; DIFFERENTIATION AB The shattered(1) (shtd(1)) mutation disrupts Drosophila compound eye structure. In this report, we show that the shtd(1) eye defects are due to a failure to establish and maintain G1 arrest in the morphogenetic, furrow (MF) and a defect in progression through mitosis. The observed cell cycle defects were correlated with an accumulation of cyclin A (CycA) and String (Stg) proteins near the ME Interestingly, the failure to maintain G1 arrest in the MF led to the specification of R8 photoreceptor cells that undergo mitosis, generating R8 doublets in shtd(1) mutant eye discs. We demonstrate that shtd encodes Apc1, the largest subunit of the anaphase-promoting complex/cyclosome (APC/C). Furthermore, we show that reducing the dosage of either CycA or stg suppressed the shtd(1) phenotype. While reducing the dosage of CycA is more effective in suppressing the premature S phase entry in the MF, reducing the dosage of stg is more effective in suppressing the progression through mitosis defect. These results indicate the importance of not only G1 arrest in the MF but also appropriate progression through mitosis for normal eye development during photoreceptor differentiation. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA. NIH, Genes Genomes & Genet IRG, Ctr Sci Review, Off Extramural Res, Bethesda, MD 20817 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Tanaka-Matakatsu, M (reprint author), Univ Chicago, Ben May Dept Canc Res, 924 E 57th St, Chicago, IL 60637 USA. EM mmatakat@huggins.bsd.uchicago.edu; bthomas@csr.nih.gov; wdu@huggins.bsd.uchicago.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM074197, R01 GM074197-01A1, R01 GM074197-02, R01 GM074197] NR 67 TC 15 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 15 PY 2007 VL 309 IS 2 BP 222 EP 235 DI 10.1016/j.ydbio.2007.07.007 PG 14 WC Developmental Biology SC Developmental Biology GA 211IO UT WOS:000249517700006 PM 17689521 ER PT J AU Chiquet, BT Lidral, AC Stal, S Mulliken, JB Moreno, LM Arco-Burgos, M Valencia-Ramirez, C Blanton, SH Hecht, JT AF Chiquet, Brett T. Lidral, Andrew C. Stal, Samuel Mulliken, John B. Moreno, Lina M. Arco-Burgos, Mauricio Valencia-Ramirez, Consuelo Blanton, Susan H. Hecht, Jacqueline T. TI CRISPLD2: a novel NSCLP candidate gene SO HUMAN MOLECULAR GENETICS LA English DT Article ID NONSYNDROMIC CLEFT-LIP; GENOME-SCAN; CRANIOFACIAL DEVELOPMENT; LINKAGE DISEQUILIBRIUM; MACULAR DEGENERATION; PALATE; LOCI; FAMILIES; MICE; IDENTIFICATION AB Non-syndromic cleft lip with or without cleft palate (NSCLP) results from the complex interaction between genes and environmental factors. Candidate gene analysis and genome scans have been employed to identify the genes contributing to NSCLP. In this study, we evaluated the 16q24.1 chromosomal region, which has been identified by multiple genome scans as an NSCLP region of interest. Two candidate genes were found in the region: interferon regulatory factor 8 (IRF8) and cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2). Initially, Caucasian and Hispanic NSCLP multiplex families and simplex parent-child trios were genotyped for single nucleotide polymorphisms (SNPs) in both IRF8 and CRISPLD2. CRISPLD2 was subsequently genotyped in a data set comprised of NSCLP families from Colombia, South America. Linkage disequilibrium analysis identified a significant association between CRISPLD2 and NSCLP in both our Caucasian and Hispanic NSCLP cohorts. SNP rs1546124 and haplotypes between rs1546124 and either rs4783099 or rs16974880 were significant in the Caucasian multiplex population (P = 0.01, P = 0.002 and P = 0.001, respectively). An altered transmission of CRISPLD2 SNPs rs8061351 (P = 0.02) and rs2326398 (P = 0.06) was detected in the Hispanic population. No association was found between CRISPLD2 and our Colombian population or IRF8 and NSCLP. In situ hybridization showed that CRISPLD2 is expressed in the mandible, palate and nasopharynx regions during craniofacial development at E13.5-E17.5, respectively. Altogether, these data suggest that genetic variation in CRISPLD2 has a role in the etiology of NSCLP. C1 Univ Texas, Sch Med, Dept Pediat, Houston, TX 77030 USA. Univ Texas, Dent Branch, Houston, TX 77030 USA. Univ Iowa, Dows Inst Dent Res, Iowa City, IA 52242 USA. Univ Iowa, Dept Orthodont, Iowa City, IA 52242 USA. Texas Childrens Hosp, Houston, TX 77030 USA. Childrens Hosp, Boston, MA 02115 USA. NIH, NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. Univ Antioquia, Coll Dent, Medllin, Colombia. Univ Miami, Miller Sch Med, Miami, FL 33101 USA. RP Hecht, JT (reprint author), Univ Texas, Sch Med, Dept Pediat, Houston, TX 77030 USA. EM ejacqueline.t.hecht@uth.tmc.edu FU NIDCR NIH HHS [K02 DE015291-02, 5 T32DE015355-04, K02 DE015291, K02 DE015291-01, K02 DE015291-03, K02 DE015291-04, K02 DE015291-05, K02DE015291, R01 DE011931, R01 DE014667, R01 DE014667-01, R01 DE014667-02, R01 DE014667-03, R01 DE014667-04, R01 DE014667-05, R01 DE014667-06, R01 DE014667-07, R01 DE014667-08, R01-DE011931-07, R01DE14677, T32 DE015355] NR 56 TC 46 Z9 47 U1 0 U2 2 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 15 PY 2007 VL 16 IS 18 BP 2241 EP 2248 DI 10.1093/hmg/ddm176 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 219LL UT WOS:000250086600011 PM 17616516 ER PT J AU Donninger, H Vos, MD Clark, GJ AF Donninger, Howard Vos, Michele D. Clark, Geoffrey J. TI The RASSF1A tumor suppressor SO JOURNAL OF CELL SCIENCE LA English DT Review DE epigenetic; RASSF1A; Ras; tumor suppressor ID ASSOCIATION DOMAIN FAMILY-1; CELL LUNG-CANCER; FREQUENT EPIGENETIC INACTIVATION; MICROTUBULE-ASSOCIATED PROTEIN; ANAPHASE-PROMOTING COMPLEX; CPG ISLAND HYPERMETHYLATION; HUMAN-CHROMOSOME 3P21.3; K-RAS MUTATIONS; COLORECTAL-CANCER; NASOPHARYNGEAL CARCINOMA AB RASSF1A (Ras association domain family 1 isoform A) is a recently discovered tumor suppressor whose inactivation is implicated in the development of many human cancers. Although it can be inactivated by gene deletion or point mutations, the most common contributor to loss or reduction of RASSF1A function is transcriptional silencing of the gene by inappropriate promoter methylation. This epigenetic mechanism can inactivate numerous tumor suppressors and is now recognized as a major contributor to the development of cancer. RASSF1A lacks apparent enzymatic activity but contains a Ras association (RA) domain and is potentially an effector of the Ras oncoprotein. RASSF1A modulates multiple apoptotic and cell cycle checkpoint pathways. Current evidence supports the hypothesis that it serves as a scaffold for the assembly of multiple tumor suppressor complexes and may relay pro-apoptotic signaling by K-Ras. C1 Univ Louisville, JG Brown Canc Ctr, Dept Med, Mol Targets Grp, Louisville, KY 40202 USA. NCI, Res Anal & Evaluat Branch, Rockville, MD USA. RP Clark, GJ (reprint author), Univ Louisville, JG Brown Canc Ctr, Dept Med, Mol Targets Grp, 119C Baxter Blvd,580 S Preston St, Louisville, KY 40202 USA. EM gjclar01@louisville.edu NR 134 TC 208 Z9 224 U1 0 U2 13 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 15 PY 2007 VL 120 IS 18 BP 3163 EP 3172 DI 10.1242/jcs.010389 PG 10 WC Cell Biology SC Cell Biology GA 211YF UT WOS:000249559400002 PM 17878233 ER PT J AU Rothfuchs, AG Bafica, A Feng, CG Egen, JG Williams, DL Brown, GD Sher, A AF Rothfuchs, Antonio Gigliotti Bafica, Andre Feng, Carl G. Egen, Jackson G. Williams, David L. Brown, Gordon D. Sher, Alan TI Dectin-1 interaction with mycobacterium tuberculosis leads to enhanced IL-12p40 production by splenic dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BETA-GLUCAN RECEPTOR; C-TYPE LECTINS; MACROPHAGE RECEPTORS; PATHOGEN RECOGNITION; IMMUNE RECOGNITION; ADAPTIVE IMMUNITY; INNATE IMMUNITY; INFECTION; RESPONSES; INDUCTION AB Dectin-1 is a fungal pattern recognition receptor that binds to beta-glucans and triggers cytokine production by facilitating interaction with TLR2 or by directly activating spleen tyrosine kinase (Syk). To assess the possible role of Dectin-1 in the innate response to mycobacteria, we used an in vitro system in which IL-12p40 production is measured in splenic dendritic cells (SpDC) following exposure to live Mycobacterium tuberculosis bacilli. Treatment of SpDC with laminarin or glucan phosphate, two molecules known to block Dectin-1-dependent activity, led to a reduction in M. tuberculosis-induced IL-12p40 as well as IL-12p70 production. Moreover, SpDC from Dectin-1(-/-) chimeric mice displayed reduced IL-12p40 production in response to mycobacteria when compared with Dectin-sufficient DC. Laminarin treatment also inhibited mycobacterial-induced IL-12p40 production in DC from TLR2(-/-) mice, arguing that Dectin-1 functions independently of TLR2 signaling in this system. Importantly, a Dectin-1 fusion protein was found to directly bind to live mycobacteria in a laminarin-inhabitable manner indicating the presence of ligands for the receptor in the bacterium and laminarin pretreatment resulted in reduced association of mycobacteria to SpDC. In additional experiments, mycobacterial stimulation was shown to be associated with increased phosphorylation of Syk and this response was inhibited by laminarin. Furthermore, pharmacologic inhibition of Syk reduced the M. tuberculosis-induced IL-12p40 response. Together, these findings support a role for Dectin-1 in promoting M. tuberculosis-induced IL-12p40 production by DC in which the receptor augments bacterial-host cell interaction and enhances the subsequent cytokine response through an unknown mechanism involving Syk signaling. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Fed Santa Catarina, Dept Microbiol & Parasitol, Div Immunol, Florianopolis, SC, Brazil. E Tennessee State Univ, James H Quillen Coll Med, Dept Surg, Johnson City, TN 37614 USA. Univ Cape Town, Inst Infect Dis & Mol Med, Div Immunol, ZA-7700 Rondebosch, South Africa. RP Rothfuchs, AG (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Room 6148,Bldg 50,50 South Dr, Bethesda, MD 20892 USA. EM rothfuchsa@niaid.nih.gov RI brown, gordon/B-4249-2012; Rothfuchs, Antonio/F-5981-2013; OI Rothfuchs, Antonio/0000-0001-6001-7240; Egen, Jackson/0000-0003-2053-0837 FU Intramural NIH HHS NR 57 TC 108 Z9 111 U1 0 U2 12 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 15 PY 2007 VL 179 IS 6 BP 3463 EP 3471 PG 9 WC Immunology SC Immunology GA 210ON UT WOS:000249465600012 PM 17785780 ER PT J AU Mostbock, S Vidal, S Schlom, J Sabzevari, H AF Mostbock, Sven Vidal, Silvia Schlom, Jeffrey Sabzevari, Helen TI Enhanced levels of costimulation lead to reduced Effector/Memory CD8(+) T cell functionality SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ALTERED PEPTIDE LIGANDS; DENDRITIC CELLS; TCR AFFINITY; INFLUENZA NUCLEOPROTEIN; SELF-RECOGNITION; 2-SIGNAL MODEL; CLONAL ANERGY; TARGET-CELLS; ACTIVATION; MEMORY AB The role of different levels of costimulation in conjunction with signal 1 in the activation of memory CD8(+) T cells remains elusive. In this study, we demonstrate, in a mouse model with the influenza nucleoprotein epitope NP68, that mouse early memory (effector/memory) CD8(+) T cells that were generated with high levels of costimulation have reduced CTL functionality compared with those that were generated with low levels of costimulation. This reduction is associated with increased phosphorylation of the negative regulatory site 292 on Zap70 and a decrease in granzyme B levels. Furthermore, we show that enhanced costimulation reduces proliferation and cytokine production of effector/memory CD8(+) T cells in response to intermediate and weak TCR stimulation, in contrast to previously described positive effects of costimulation on naive CD8(+) T cells. This effect is associated with the expression of ICAM-1 on APCs. Together, our results indicate that enhanced costimulation can lead to reduced functionality in effector/memory CD8(+) T cells. This compromised effector function of effector/memory CD8(+) T cells in response to high levels of costimulation can have important implications for designing immunotherapeutic strategies to enhance immune responses. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Hosp Sant Pau, Dept Immunol, Barcelona, Spain. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10 Room 8B09,10 Ctr Dr, Bethesda, MD 20892 USA. EM js141c@nih.gov FU Intramural NIH HHS NR 65 TC 4 Z9 4 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2007 VL 179 IS 6 BP 3524 EP 3534 PG 11 WC Immunology SC Immunology GA 210ON UT WOS:000249465600019 PM 17785786 ER PT J AU Hystad, ME Myklebust, JH Bo, TH Sivertsen, EA Rian, E Forfang, L Munthe, E Rosenwald, A Chiorazzi, M Jonassen, I Staudt, LM Smeland, EB AF Hystad, Marit E. Myklebust, June H. Bo, Trond H. Sivertsen, Einar A. Rian, Edith Forfang, Lise Munthe, Else Rosenwald, Andreas Chiorazzi, Michael Jonassen, Inge Staudt, Louis M. Smeland, Erlend B. TI Characterization of early stages of human B cell development by gene expression profiling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN BONE-MARROW; NATURAL-KILLER-CELLS; J-CHAIN PROMOTER; TRANSCRIPTION FACTOR; HEMATOPOIETIC STEM; T-CELLS; PROGENITOR CELLS; DENDRITIC CELLS; V(D)J RECOMBINATION AB We have characterized several stages of normal human B cell development in adult bone marrow by gene expression profiling of hemopoietic stem cells, early B (E-B), pro-B, pre-B, and immature B cells, using RNA amplification and Lymphochip cDNA microarrays (n = 6). Hierarchical clustering of 758 differentially expressed genes clearly separated the five populations. We used gene sets to investigate the functional assignment of the differentially expressed genes. Genes involved in VDJ recombination as well as B lineage-associated transcription factors (TCF3 (E2A), EBF, BCL11A, and PAX5) were turned on in E-B cells, before acquisition of CD19. Several transcription factors with unknown roles in B lymphoid cells demonstrated interesting expression patterns, including ZCCHC7 and ZHX2. Compared with hemopoietic stem cells and pro-B cells, E-B cells had increased expression of 18 genes, and these included IGJ, IL1RAP, BCL2, and CD62L. In addition, E-B cells expressed T/NK lineage and myeloid-associated genes including CD2, NOTCH1, CD99, PECAM1, TNFSF13B, and MPO. Expression of key genes was confirmed at the protein level by FACS analysis. Several of these Ags were heterogeneously expressed, providing a basis for further subdivision of E-B cells. Altogether, these results provide new information regarding expression of genes in early stages of human B cell development. C1 Natl Hosp Norway, Radiumhosp Med Ctr, Inst Canc Res, Dept Immunol, N-0310 Oslo, Norway. Univ Bergen, Dept Informat, N-5008 Bergen, Norway. Univ Oslo, Fac Div Rikshosp, Inst Pathol, N-0027 Oslo, Norway. Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. NCI, Metab Branch, Bethesda, MD 20892 USA. Univ Oslo, Ctr Biomed, Oslo, Norway. RP Smeland, EB (reprint author), Natl Hosp Norway, Radiumhosp Med Ctr, Inst Canc Res, Dept Immunol, N-0310 Oslo, Norway. EM erlend.bremertun.smeland@rr-research.no NR 59 TC 74 Z9 75 U1 0 U2 9 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 15 PY 2007 VL 179 IS 6 BP 3662 EP 3671 PG 10 WC Immunology SC Immunology GA 210ON UT WOS:000249465600035 PM 17785802 ER PT J AU Packard, BZ Telford, WG Koxlloriya, A Henkart, PA AF Packard, Beverly Z. Telford, William G. Koxlloriya, Akira Henkart, Pierre A. TI Granzye B activity in target cells detects attack by cytotoxic lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEDIATED CYTOTOXICITY; T-LYMPHOCYTES; APOPTOSIS; PERFORIN; BCL-2; DEGRANULATION; DEATH; STIMULATION; PROTECTION; CYTOMETRY AB Lymphocyte-mediated cytotoxicity via granule exocytosis operates by the perforin-mediated transfer of granzymes from CTLs and NK cells into target cells where caspase activation and other death pathways are triggered. Granzyme B (GzB) is a major cytotoxic effector in this pathway, and its fate in target cells has been studied by several groups using immunodetection. In this study, we have used a newly developed cell-permeable fluorogenic GzB substrate to measure this protease activity in three different living targets following contact with cytotoxic effectors. Although no GzB activity is measurable in CTL or NK92 effector cells, this activity rapidly becomes detectable throughout the target cytoplasm after effector-target engagement. We have combined the GzB substrate with a second fluorogenic substrate selective for caspase 3 to allow both flow cytometry and fluorescence confocal microscopy studies of cytotoxicity. With both effectors, caspase 3 activity appears subsequent to that of GzB inside all three targets. Overexpression of Bcl-2 in target cells has minimal effects on lysis, NK- or CTL-delivered GzB activity, or activation of target caspase 3. Detection of target GzB activity followed by caspase 3 activation provides a unique readout of a potentially lethal injury delivered by cytotoxic lymphocytes. C1 NCI, Expt Immunol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Packard, BZ (reprint author), 207A Perry Pkwy,Suite 6, Gaithersburg, MD 20877 USA. EM BPackard@PhiPhiLux.com NR 34 TC 37 Z9 38 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2007 VL 179 IS 6 BP 3812 EP 3820 PG 9 WC Immunology SC Immunology GA 210ON UT WOS:000249465600051 PM 17785818 ER PT J AU Ishaq, M DeGray, G Mou, K Aguilera, A Yang, J Lempicki, RA Hazen, A Natarajan, V AF Ishaq, Mohammad DeGray, Gerald Mou, Kathy Aguilera, Angelica Yang, Jun Lempicki, Richard A. Hazen, Allison Natarajan, Ven TI Zap70 signaling pathway mediates glucocorticoid receptor-dependent transcriptional activation: role in the regulation of annexin 1 expression in T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; TYROSINE-PHOSPHORYLATION; ANTIGEN RECEPTOR; RXR-ALPHA; ZAP-70; KINASE; LYMPHOCYTES; TRANSACTIVATION; GENE; TRANSDUCTION AB We have recently shown that Zap70 is important in retinoid receptor-dependent transactivation in T lymphocytes. We report that Zap70 signaling is also essential in dexamethasone-inducible glucocorticoid receptor (GR)-mediated transactivation in T lymphocytes. Zap70-negative Jurkat T cells and cells reconstituted with inactive Zap70 exhibited attenuated GR-mediated activation as compared with Zap70 reconstituted and wild-type cells. Lck-lacking Jurkat cells were also found to show markedly reduced GR activation, and reconstitution with Lck restored the activation. Gene array and protein analysis showed that the level of annexin 1 (ANXA1), an anti-inflammatory protein known to be induced and released by the glucocorticoid action, was significantly. reduced in Zap70-negative and Zap70-inactive Jurkat cells as compared with wildtype cells. Lck-lacking cells were also found to have markedly reduced ANXA1 levels and reconstitution with Lck restored the ANXA1 expression. RNA interference-induced knockdown of Zap70 or Lck in Jurkat cells and peripheral blood T lymphocytes also resulted in the loss of ANXA1 expression. Transcriptional analysis revealed that dexamethasone-inducible GR-mediated activation of ANXA1 promoter was compromised in both Zap70 knocked down peripheral blood T cells and Zap70 or Lck-deficient/Lck-inactive Jurkat cells, indicating an essential role of these kinases in GR-mediated ANXA1 promoter activation in T lymphocytes. To summarize, our data demonstrate an important role for Zap70 signaling in GR-mediated transactivation in T lymphocytes and also point out a crucial role of this kinase in maintaining normal ANXA1 levels in these cells. C1 NCI, SAIC Frederick, Mol Cell Biol Lab, Frederick, MD 21702 USA. RP Ishaq, M (reprint author), NCI, SAIC Frederick, Mol Cell Biol Lab, Frederick, MD 21702 USA. EM mishaq@mail.nih.gov; vnatarajan@mail.nih.gov RI Lempicki, Richard/E-1844-2012; OI Lempicki, Richard/0000-0002-7059-409X; Mou, Kathy/0000-0002-3950-3778 FU NCI NIH HHS [N01-CO-12400] NR 38 TC 8 Z9 8 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2007 VL 179 IS 6 BP 3851 EP 3858 PG 8 WC Immunology SC Immunology GA 210ON UT WOS:000249465600055 PM 17785822 ER PT J AU Garantziotis, S Hollingsworth, JW Ghanayem, RB Timberlake, S Zhuo, LS Kimata, K Schwartzt, DA AF Garantziotis, Stavros Hollingsworth, John W. Ghanayem, Rami B. Timberlake, Sarah Zhuo, Lisheng Kimata, Koji Schwartzt, David A. TI Inter-alpha-trypsin inhibitor attenuates complement activation and complement-induced lung injury SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SHAP-HYALURONAN COMPLEX; INFLAMMATORY RESPONSES; RHEUMATOID-ARTHRITIS; BINDING-SITE; A DOMAIN; SEPSIS; C5A; BIKUNIN; MACROPHAGES; EXPRESSION AB Complement activation is a central component of inflammation and sepsis and can lead to significant tissue injury. Complement factors are serum proteins that work through a cascade of proteolytic reactions to amplify proinflammatory signals. Inter-alpha-trypsin inhibitor (IaI) is an abundant serum protease inhibitor that contains potential complement-binding domains, and has been shown to improve survival in animal sepsis models. We hypothesized that IaI can bind complement and inhibit complement activation, thus ameliorating complement-dependent inflammation. We evaluated this hypothesis with in vitro complement activation assays and in vivo in a murine model of complement-dependent lung injury. We found that IaI inhibited complement activation through the classical and alternative pathways, inhibited complement-dependent phagocytosis in vitro, and reduced complement-dependent lung injury in vivo. This novel function of IaI provides a mechanistic explanation for its observed salutary effects in sepsis and opens new possibilities for its use as a treatment agent in inflammatory diseases. C1 Duke Univ, Med Ctr, Durham, NC 27710 USA. NIEHS, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Raleigh, NC 27695 USA. Aichi Med Univ, Inst Mol Sci Med, Aichi, Japan. RP Garantziotis, S (reprint author), Duke Univ, Med Ctr, Box 3683, Durham, NC 27710 USA. EM garan001@mc.duke.edu RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU Intramural NIH HHS NR 27 TC 29 Z9 30 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2007 VL 179 IS 6 BP 4187 EP 4192 PG 6 WC Immunology SC Immunology GA 210ON UT WOS:000249465600091 PM 17785858 ER PT J AU Damjanovic, AK Yang, YH Glaser, R Kiecolt-Glaser, JK Nguyen, H Laskowski, B Zou, YX Beversdorf, DQ Weng, NP AF Damjanovic, Amanda K. Yang, Yinhua Glaser, Ronald Kiecolt-Glaser, Janice K. Nguyen, Huy Laskowski, Bryon Zou, Yixiao Beversdorf, David Q. Weng, Nan-ping TI Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE; T-CELLS; CHRONIC STRESS; DYSKERATOSIS-CONGENITA; HTERT GENE; LIFE-SPAN; LYMPHOCYTES; LENGTH; CYTOKINE; RNA AB Caregivers of Alzheimer's disease patients endure chronic stress associated with a decline of immune function. To assess the psychological and immunological changes of caregivers, we compared depressive symptoms, PBMC composition, in vitro activation-induced proliferation and cytokine production, and telomere length and telomerase activity of 82 individuals (41 caregivers and 41 age- and gender-matched controls). We found depressive symptoms were significantly higher in caregivers than in controls (p < 0.001). Correspondingly, caregivers had significantly lower T cell proliferation but higher production of immune-regulatory cytokines (TNF-alpha and IL-10) than controls in response to stimulation in vitro. We examined the impact of these changes on cellular replicative lifespan and found that caregivers had significantly shorter telomere lengths in PBMC than controls (6.2 and 6.4 kb, respectively, p < 0.05) with similar shortening in isolated T cells and monocytes and that this telomere attrition in caregivers was not due to an increase of shorter telomere possessing T cell subsets in PBMC. Finally, we showed that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls (p < 0.0001), pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers. These findings demonstrate that chronic stress is associated with altered T cell function and accelerated immune cell aging as suggested by excessive telomere loss. C1 NIH, NIA, Immunol Lab, Baltimore, MD 21224 USA. Ohio State Univ, Coll Med, Columbus, OH 43210 USA. Ohio State Univ, Coll Med, Inst Behav Med Res, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA. Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA. RP Glaser, R (reprint author), NIH, NIA, Immunol Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Ronald.Glaser@osumc.edu; Wengn@mail.nih.gov RI Kiecolt-Glaser, Janice/A-3236-2009; Glaser, Ronald/E-3124-2011; Beversdorf, David/M-2786-2016 OI Kiecolt-Glaser, Janice/0000-0003-4900-9578; Beversdorf, David/0000-0002-0298-0634 FU Intramural NIH HHS [Z01 AG000756-10]; NCI NIH HHS [CA16058, P30 CA016058]; NCRR NIH HHS [M01 RR000034, M01-RR-0034]; NIA NIH HHS [AG025732, R21 AG025732] NR 36 TC 203 Z9 211 U1 1 U2 26 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 15 PY 2007 VL 179 IS 6 BP 4249 EP 4254 PG 6 WC Immunology SC Immunology GA 210ON UT WOS:000249465600098 PM 17785865 ER PT J AU Dimitrov, DS Wang, LF AF Dimitrov, Dimiter S. Wang, Lin-Fa TI In utero transmission of Nipah virus: Role played by pregnancy and vertical transmission in henipavirus epidemiology - Editorial commentary SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID HENDRA VIRUS; PIG-FARMERS; ENCEPHALITIS; INFECTION; PARAMYXOVIRUS; CONSEQUENCES; MALAYSIA; DISEASE; BATS C1 NCI, Prot Interact Grp, Nanobiol Program, Canc Res Ctr,NIH, Ft Detrick, MD 21702 USA. Commonwealth Sci & Ind Res Org, Australian Anim Hlth Lab, Geelong, Vic, Australia. Australian Biosecur Cooperat Res Ctr, Geelong, Vic, Australia. RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, Nanobiol Program, Canc Res Ctr,NIH, POB B,Bldg 469,Rm 105, Ft Detrick, MD 21702 USA. EM dimitrov@ncifcrf.gov FU Intramural NIH HHS NR 32 TC 1 Z9 1 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 15 PY 2007 VL 196 IS 6 BP 807 EP 809 DI 10.1086/520822 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 207LE UT WOS:000249251800001 PM 17703408 ER PT J AU Genovesio, A Mitz, AR AF Genovesio, Aldo Mitz, Andrew R. TI MatOFF: A tool for analyzing behaviorally complex neurophysiological experiments SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE neurophysiology; behavior; single unit; data mining; primate; software ID PREFRONTAL CORTEX AB The simple operant conditioning originally used in behavioral neurophysiology 30 years ago has given way to complex and sophisticated behavioral paradigms; so much so, that early general purpose programs for analyzing neurophysiological data are ill-suited for complex experiments. The trend has been to develop custom software for each class of experiment, but custom software can have serious drawbacks. We describe here a general purpose software tool for behavioral and electrophysiological studies, called MatOFF, that is especially suited for processing neurophysiological data gathered during the execution of complex behaviors. Written in the MATLAB programming language, MatOFF solves the problem of handling complex analysis requirements in a unique and powerful way. While other neurophysiological programs are either a loose collection of tools or append MATLAB as a post-processing step, MatOFF is an integrated environment that supports MATLAB scripting within the event search engine safely isolated in a programming sandbox. The results from scripting are stored separately, but in parallel with the raw data, and thus available to all subsequent MatOFF analysis and display processing. An example from a recently published experiment shows how all the features of MatOFF work together to analyze complex experiments and mine neurophysiological data in efficient ways. Published by Elsevier B.V. C1 NIMH, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA. RP Mitz, AR (reprint author), NIMH, Lab Syst Neurosci, NIH, Bldg 49,Rm B1EE17 MSC 4401, Bethesda, MD 20892 USA. EM arm@nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 7 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD SEP 15 PY 2007 VL 165 IS 1 BP 38 EP 48 DI 10.1016/j.jneumeth.2007.05.026 PG 11 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 201YP UT WOS:000248868800005 PM 17604115 ER PT J AU Bazin, PL Cuzzocreo, JL Yassa, MA Gandler, W McAuliffe, MJ Bassett, SS Pham, DL AF Bazin, Pierre-Louis Cuzzocreo, Jennifer L. Yassa, Michael A. Gandler, William McAuliffe, Matthew J. Bassett, Susan S. Pham, Dzung L. TI Volumetric neuroimage analysis extensions for the MIPAV software package SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE segmentation; magnetic resonance imaging; talairach atlas ID MR-IMAGES; TISSUE CLASSIFICATION; BRAIN; SEGMENTATION; ATLAS; MODEL; ALGORITHM AB We describe a new collection of publicly available software tools for performing quantitative neuroimage analysis. The tools perform semiautomaticrain extraction, tissue classification, Talairach alignment, and atlas-based measurements within a user-friendly graphical environment. They are implemented as plug-ins for MIPAV, a freely available medical image processing software package from the National Institutes of Health. Because the plug-ins and MIPAV are implemented in Java, both can be utilized on nearly any operating system platform. In addition to the software plug-ins. we have also released a digital version of the Talairach atlas that can be used to perform regional volumetric analyses. Several studies are conducted applying the new tools to simulated and real neuroimaging data sets. (c) 2007 Elsevier B.V. All rights reserved. C1 Johns Hopkins Univ, Dept Radiol & Radiol Sci, Lab Med Image Comp, Neuroradiol Div, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Psychiat & Behav Sci, Div Psychiat Neuroimaging, Baltimore, MD 21218 USA. NIH, Ctr Imaging Technol, Biomed Imaging Res Serv Sect, Bethesda, MD 20892 USA. RP Pham, DL (reprint author), 600 N Wolfe St,Phipps B100, Baltimore, MD 21287 USA. EM pham@jhu.edu RI Yassa, Michael/A-8474-2013; OI Yassa, Michael/0000-0002-8635-1498; Bazin, Pierre-Louis/0000-0002-0141-5510 FU NIA NIH HHS [AG016324, R01 AG016324, R01 AG016324-04]; NIDA NIH HHS [DA017231-01, R01 DA017231, R01 DA017231-01A1]; NINDS NIH HHS [R01 NS054255, R01 NS054255-01, R01NS054255-01] NR 35 TC 61 Z9 61 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD SEP 15 PY 2007 VL 165 IS 1 BP 111 EP 121 DI 10.1016/j.jneumeth.2007.05.024 PG 11 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 201YP UT WOS:000248868800014 PM 17604116 ER PT J AU Wheaton, LA Hallett, M AF Wheaton, Lewis A. Hallett, Mark TI Ideomotor apraxia: A review SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Review DE ideomotor apraxia; motor control; rehabilitation; parictofrontal; apraxia; higher-order motor control ID PROGRESSIVE SUPRANUCLEAR PALSY; POSTERIOR PARIETAL CORTEX; MULTIPLE SYSTEM ATROPHY; LEFT-HEMISPHERE STROKE; EVENT-RELATED FMRI; LIMB APRAXIA; CORTICOBASAL DEGENERATION; PARKINSONS-DISEASE; PRAXIS MOVEMENTS; PREMOTOR AREAS AB Ideornotor apraxia (IMA) is a disorder traditionally characterized by deficits in properly performing tool-use pantomirnes (e.g., pretending to use a hammer) and communicative gestures (e.g., waving goodbye). These deficits are typically identified with movements made to verbal command or imitation. Questions about this disorder relate to its diagnosis, anatomical correlates, physiological mechanisms involved, and the patients in whom IMA is best characterized. In this review, utilizing information presented at an international workshop, we summarize the present state of knowledge about IMA. We include insights on how to distinguish IMA from the other motor apraxias and confounding disorders. We discuss testing for IMA and the need for more rigorous tests that examine more elements, such as imitation, actual use, task selection, and recognizing proper use. From neurophysiological insights, we propose hypotheses of the necessity of networks in praxis performance. We also point out that more neurophysiological knowledge in humans might lead to a better understanding of how different brain structures may aid in the rehabilitation of praxis. While little is known about exactly how rehabilitation may be pursued, biological evidence warrants the further exploration of this issue. (C) 2007 Elsevier B.V. All rights reserved. C1 NIH, Natl Inst Neurol Disorders & Stroke, Med Neurol Branch, Human Motor Control Sect, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Baltimore, MD USA. Ctr Geriatr Res Educ & Clin, Div Gerontol, Baltimore, MD USA. RP Hallett, M (reprint author), NIH, Natl Inst Neurol Disorders & Stroke, Med Neurol Branch, Human Motor Control Sect, Bldg 10,Room 5N244,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov RI Wheaton, Lewis /B-4482-2009 OI Wheaton, Lewis /0000-0003-0771-0294 NR 92 TC 39 Z9 44 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD SEP 15 PY 2007 VL 260 IS 1-2 BP 1 EP 10 DI 10.1016/j.jns.2007.04.014 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 208JG UT WOS:000249315000001 PM 17507030 ER PT J AU Bara-Jimenez, W Aksu, M Leon-Sarmiento, FE Malone, MF Lai, RYK Chizh, BA Maltby, K Hallett, M Chase, TN AF Bara-Jimenez, W. Aksu, M. Leon-Sarmiento, F. E. Malone, M. F. Lai, R. Y. K. Chizh, B. A. Maltby, K. Hallett, M. Chase, T. N. TI Effects of dopamine agonist treatment on spinal cord excitability in patients with restless legs syndrome SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 21st Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinsons Disease and Other Movement Disorders CY OCT 07, 2007 CL Washington, DC SP Parkinson Study Grp, Huntinton Study Grp, Dystonia Study Grp, Myoclonus Study Grp, Tourette Syndrome Study Grp, Cooperat Ataxia Grp, Tremor Res Grp, Movement Disorder Soc C1 Natl Inst Neurol Disorders & Stroke, NIH, Expt Therapeut Branch, Bethesda, MD USA. Natl Inst Neurol Disorders & Stroke, NIH, Human Motor Control Sect, Bethesda, MD USA. Bethesda Neurosci Clin, Bethesda, MD USA. Erciyes Univ, Dept Neurol, Kayseri, Turkey. Univ Nacl Fundac Santa Fe, Uniciencia Res Grp, Bogota, Colombia. GlaxoSmithKline Inc, Neurol Ctr Excellence Drug Discovery, Essex Jct, VT USA. GlaxoSmithKline Inc, Cambridge Clin Unit, Cambridge, England. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2007 VL 22 IS 12 MA 1 BP IV EP IV PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 218CD UT WOS:000249992700043 ER PT J AU Ross, GW Abbott, RD Petrovitch, H Tanner, CM Popper, J McMurtray, A Masaki, K Launer, L White, LR AF Ross, G. W. Abbott, R. D. Petrovitch, H. Tanner, C. M. Popper, J. McMurtray, A. Masaki, K. Launer, L. White, L. R. TI Association of mid-life physical activity with risk of future Parkinson's disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 21st Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinsons Disease and Other Movement Disorders CY OCT 07, 2007 CL Washington, DC SP Parkinson Study Grp, Huntinton Study Grp, Dystonia Study Grp, Myoclonus Study Grp, Tourette Syndrome Study Grp, Cooperat Ataxia Grp, Tremor Res Grp, Movement Disorder Soc C1 Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA. Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. Univ Hawaii, John A Burns Sch Med, Dept Geriatr, Honolulu, HI 96822 USA. Pacific Hlth Res Inst, Honolulu, HI USA. Kuakini Med Ctr, Honolulu Asia Aging Study, Honolulu, HI USA. Univ Virginia, Sch Med, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA. Shiga Univ Med Sci, Dept Hlth Sci, Otsu, Shiga 52021, Japan. Parkinsons Inst, Sunnyvale, CA USA. NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2007 VL 22 IS 12 MA 26 BP XI EP XII PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 218CD UT WOS:000249992700068 ER PT J AU Leijnse, JNAL Hallett, M AF Leijnse, Joris N. A. L. Hallett, Mark TI Etiological musculo-skeletal factor in focal, dystonia in a musician's hand: A case study of the right hand of a guitarist SO MOVEMENT DISORDERS LA English DT Article DE dystonia; focal; hand; musician; guitarist; overuse; biomechanics AB A case study is presented in which a focal hand dystonia seems to have developed in the right hand of a classical guitarist as a result of a neuromuscular peripheral defect caused by trauma. The trauma was a near total perforation of the first web space by a splinter. Healing was uneventful without apparent functional complications. Two years later the patient noticed difficulties in extending the index in playing, for which he received various unsuccessful treatments during seven years. However, we found more severe dystonic symptoms (cocontractions) in the thumb than in the index during playing, which correlated with an undiagnosed insufficiency in the flexor pollicis brevis (FPB). This defect allowed proposing a biomechanical analysis of compensations for diminished thumb control in playing, which would explain the dysfunction in the index in playing as overcompensation for the thumb problem. If this analysis is correct, the etiology of the case can be traced back to underlying multiarticular control problems in the thumb caused by an insufficient FPB. This defect was considered irrepairable. It was concluded that even with knowledge of the underlying cause, a potentially successful treatment of the dystonia might not exist in this case. The case would demonstrate that task-specific hand dystonias can arise as overcompensations for (peripheral) neuro-musculoskeletal defects. The case is illustrated by videos of playing and functional thumb tests. (C) 2007 Movement Disorder Society. C1 Univ Louisville, Dept Mech Engn, Lab Clin Biomech & Reconstruct Surg Hand & Upper, Speed Sch Engn & Price Inst Surg Res,Dept Surg, Louisville, KY 40292 USA. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Leijnse, JNAL (reprint author), Univ Louisville, Dept Mech Engn, Lab Clin Biomech & Reconstruct Surg Hand & Upper, Speed Sch Engn & Price Inst Surg Res,Dept Surg, 200 Sackett Hall, Louisville, KY 40292 USA. EM jnleij01@louisville.edu NR 2 TC 9 Z9 11 U1 3 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2007 VL 22 IS 12 BP 1803 EP 1808 DI 10.1002/mds.21636 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 218CD UT WOS:000249992700019 PM 17659635 ER PT J AU Nigam, P Earl, PL Americo, JL Sharma, S Wyatt, LS Edghill-Spano, Y Chennareddi, LS Silvera, P Moss, B Robinson, HL Amara, RR AF Nigam, Pragati Earl, Patricia L. Americo, Jeffrey L. Sharma, Sunita Wyatt, Linda S. Edghill-Spano, Yvette Chennareddi, Lakshmi S. Silvera, Peter Moss, Bernard Robinson, Harriet L. Amara, Rama Rao TI DNA/MVA HIV-1/AIDS vaccine elicits long-lived vaccinia virus-specific immunity and confers protection against a lethal monkeypox challenge SO VIROLOGY LA English DT Article DE HIV; modified vaccinia virus Ankara; DNA/MVA vaccine; smallpox; monkeypox; CD8 T cells; rhesus macaque ID SMALLPOX VACCINE; HIV TYPE-1; RECOMBINANT VECTOR; POXVIRUS INFECTION; MUCOSAL CHALLENGE; 89.6P CHALLENGE; CELL MEMORY; STRAIN MVA; GAG-POL; ANKARA AB Modified vaccinia Ankara (MVA) is being tested in humans as an alternative to the current smallpox vaccine Dryvax. Here, we compare the magnitude and longevity of protective immune responses elicited by a DNA/MVA HIV-1 vaccine with those elicited by Dryvax using a monkeypox virus/macaque model. The DNA/MVA vaccine elicited similar levels of vaccinia virus (VV)-specific antibody and 5-10-fold lower levels of VV-specific cellular responses than Dryvax. This MVA-elicited cellular and humoral immunity was long-lived. A subset of the DNA/MVA- and Dryvax-vaccinated macaques were subjected to a lethal monkeypox virus challenge at 3 years after vaccination. All of the vaccinated monkeys survived, whereas the unvaccinated controls succumbed to monkeypox. The viral control correlated with early postchallenge levels of monkeypox-specific neutralizing antibody but not with VV-specific cellular immune response. Thus, our results demonstrate the elicitation of long lasting protective immunity for a lethal monkeypox challenge by a DNA/MVA HIV-1 vaccine. (c) 2007 Elsevier Inc. All rights reserved. C1 Emory Univ, Emory Vaccine Ctr, Dept Microbiol & Immunol, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. Natl Inst Hlth, NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. So Res Inst, Frederick, MD 21701 USA. RP Amara, RR (reprint author), Emory Univ, Emory Vaccine Ctr, Dept Microbiol & Immunol, Yerkes Natl Primate Res Ctr, 954 Gatewood Rd,NE, Atlanta, GA 30329 USA. EM rama@rmy.emory.edu FU Intramural NIH HHS; NCRR NIH HHS [P51 RR00165, P51 RR000165]; NIAID NIH HHS [R01 AI57029, R01 AI057029-03, R01 AI057029, R21 AI053488-01, R21 AI53488, P01 AI49364, R01 AI057029-01, R01 AI057029-04, R21 AI053488, R21 AI053488-02, R01 AI057029-05, R01 AI057029-02, P01 AI049364] NR 46 TC 22 Z9 22 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 0042-6822 J9 VIROLOGY JI Virology PD SEP 15 PY 2007 VL 366 IS 1 BP 73 EP 83 DI 10.1016/j.virol.2007.04.010 PG 11 WC Virology SC Virology GA 209VA UT WOS:000249414900009 PM 17507071 ER PT J AU Earl, PL Americo, JL Wyatt, LS Eller, LA Montefiori, DC Byrum, R Piatak, M Lifson, JD Amara, RR Robinson, HL Huggins, JW Moss, B AF Earl, Patricia L. Americo, Jeffrey L. Wyatt, Linda S. Eller, Leigh Anne Montefiori, David C. Byrum, Russ Piatak, Michael Lifson, Jeffrey D. Amara, Rama Rao Robinson, Harriet L. Huggins, John W. Moss, Bernard TI Recombinant modified vaccinia virus Ankara provides durable protection against disease caused by an immunodeficiency virus as well as long-term immunity to an orthopoxvirus in a non-human primate SO VIROLOGY LA English DT Article DE SHIV/89.6P; recombinant modified vaccinia virus Ankara; monkeypox virus; smallpox; rhesus macaque ID CYTOTOXIC T-LYMPHOCYTES; RHESUS-MONKEYS; GAG-POL; SMALLPOX VACCINE; IN-VIVO; CYNOMOLGUS MONKEYS; MUCOSAL CHALLENGE; IMMUNOGENICITY; MACAQUES; MVA AB Recombinant and non-recombinant modified vaccinia virus Ankara (MVA) strains are currently in clinical trials as human immunodeficiency virus-1 (HIV) and attenuated smallpox vaccines, respectively. Here we tested the ability of a recombinant MVA delivered by alternative needlefree routes (intramuscular, intradennal, or into the palatine tonsil) to protect against immunodeficiency and orthopoxvirus diseases in a non-human primate model. Rhesus macaques were immunized twice I month apart with MVA expressing 5 genes from a pathogenic simian human immunodeficiency virus (SHIV)/89.6P and challenged intrarectally 9 months later with the pathogenic SHIV/89.6P and intravenously 2.7 years later with monkeypox virus. Irrespective of the route of vaccine delivery, binding and neutralizing antibodies and CD8 responses to SHIV and orthopoxvirus proteins were induced and the monkeys were successively protected against the diseases caused by the challenge viruses in unimmunized controls as determined by viral loads and clinical signs. These non-human primate studies support the clinical testing of recombinant MVA as an HIV vaccine and further demonstrate that MVA can provide long-term poxvirus immunity, essential for use as an alternative smallpox vaccine. (c) 2007 Elsevier Inc. All rights reserved. C1 Natl Inst Hlth, NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. Henry M Jackson Fdn, Rockville, MD 20852 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Bioqual, Rockville, MD 20850 USA. Natl Canc Inst, AIDS Vaccine Program, Sci Appl Int Corp, Ft Detrick, MD 21702 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Vaccine Res Ctr, Dept Microbiol Immunol, Atlanta, GA 30329 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. RP Earl, PL (reprint author), Natl Inst Hlth, NIAID, Viral Dis Lab, Bldg 33,Room 1E19,33 N Dr, Bethesda, MD 20892 USA. EM pearl@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000416-24] NR 62 TC 34 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 15 PY 2007 VL 366 IS 1 BP 84 EP 97 DI 10.1016/j.virol.2007.02.041 PG 14 WC Virology SC Virology GA 209VA UT WOS:000249414900010 PM 17499326 ER PT J AU Schwartz, JA Buonocore, L Roberts, A Suguitan, A Kobasa, D Kobinger, G Feldmann, H Subbarao, K Rose, JK AF Schwartz, Jennifer A. Buonocore, Linda Roberts, Anjeanette Suguitan, Amorsolo, Jr. Kobasa, Darwyn Kobinger, Gary Feldmann, Heinz Subbarao, Kanta Rose, John K. TI Vesicular stomatitis virus vectors expressing avian influenza H5HA induce cross-neutralizing antibodies and long-term protection SO VIROLOGY LA English DT Article DE VSV; AIV; vaccine; H5N1; cross neutralizing antibody ID ATTENUATED RECOMBINANT VACCINE; PROVIDES COMPLETE PROTECTION; A H5N1 VIRUSES; REPLICATION-COMPETENT; NEWCASTLE-DISEASE; IMMUNE-RESPONSES; L1 PROTEIN; LIVE; CHALLENGE; MICE AB Given the lethality of H5N1 avian influenza viruses (AIV) and the recurring spread from poultry to humans, an effective vaccine against H5N1 viruses may be needed to prevent a pandemic. We generated experimental vaccine vectors based on recombinant vesicular stomatitis virus (VSV) expressing the H5 hemagglutinin (HA) from an H5N1 virus isolated in 1997. The HA gene was expressed either from an attenuated wild-type VSV vector or from a single-cycle vector containing a deletion of the VSV G gene. We found that all of the vectors induced potent neutralizing antibody titers against the homologous and antigenically heterologous H5N1 viruses isolated in 2004 and 2005. Vaccination of mice with any combination of prime or prime/boost vectors provided long-lasting protection (> 7 months) against challenge with AIV, even in animals receiving a single dose of single-cycle vaccine. Our data indicate that these recombinants are promising vaccine candidates for pandemic influenza. (c) 2007 Elsevier Inc. All rights reserved. C1 Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. NIH, Natl Inst Allergy & Infect Dis, Infect Dis Lab, Bethesda, MD 20892 USA. Canadian Sci Ctr Human & Animal Hlth, Natl Microbiol Lab, Winnipeg, MB, Canada. RP Rose, JK (reprint author), Univ Virginia, Dept Microbiol Immunol & Infect Dis, PO Box 800734, Charlottesville, VA 22908 USA. EM john.rose@yale.edu OI Schwartz, Jennifer/0000-0001-8239-8857 FU Intramural NIH HHS; NIAID NIH HHS [AI057158, U54 AI057158-05S1, U54 AI057158-05, U54 AI057158] NR 41 TC 43 Z9 44 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 0042-6822 J9 VIROLOGY JI Virology PD SEP 15 PY 2007 VL 366 IS 1 BP 166 EP 173 DI 10.1016/j.virol.2007.04.021 PG 8 WC Virology SC Virology GA 209VA UT WOS:000249414900017 PM 17524441 ER PT J AU Bene, L Kanyari, Z Bodnar, A Kappelmayer, J Waldmann, TA Vamosi, G Damjanovich, L AF Bene, Laszlo Kanyari, Zsolt Bodnar, Andrea Kappelmayer, Janos Waldmann, Thomas A. Vamosi, Gyoergy Damjanovich, Laszlo TI Colorectal carcinoma rearranges cell surface protein topology and density in CD4(+) T cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE MHC I; MHC II; IL-2R; IL-15R; ICAM-1; receptor clustering; FRET; flow cytometry; confocal microscopy; membrane protein association; CD4(+) T cells; colorectal carcinoma; draining lymph node ID HLA CLASS-I; ENERGY-TRANSFER MEASUREMENTS; HUMAN LYMPHOBLASTOID-CELLS; MHC CLASS-II; PLASMA-MEMBRANE; LIPID RAFTS; ANTIGEN PRESENTATION; TARGET-CELLS; MOLECULES; ICAM-1 AB Previously, we described conserved protein clusters including MHCI and II glycoproteins, ICAM-1 adhesion molecules, and interleukin-2 and -15 receptors in lipid rafts of several human cell types. Differential protein-protein interactions can modulate function, thus influence cell fate. Therefore, we analyzed supramolecular clusters of CD4(+) T cells from draining lymph nodes and peripheral blood of colorectal carcinoma patients, and compared these to healthy controls. Superclusters of MHC I and II with IL-2/15 receptors were identified by confocal microscopy on all cell types. Flow-cytometric FRET revealed molecular associations of these proteins with each other and with ICAM-1 as well. In draining lymph nodes expression levels of all these proteins were lower, and interactions, particularly between IL-2/15 receptors and MHC molecules weakened or disappeared as compared to the control. Stimuli/local conditions can rearrange cell surface protein patterns on the same cell type in the same patient, having important implications on further function and cell fate. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Debrecen, Res Ctr Mol Med, Hungarian Acad Sci, Cell Biol & Signaling Res Grp, Debrecen, Hungary. Univ Debrecen, Res Ctr Mol Med, Dept Biophys & Cell Biol, Debrecen, Hungary. Univ Debrecen, Dept Surg 1, Debrecen, Hungary. Univ Debrecen, Med & Hlth Sci Ctr, Dept Clin Biochem & Mol Pathol, Debrecen, Hungary. NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. RP Vamosi, G (reprint author), Univ Debrecen, Res Ctr Mol Med, Hungarian Acad Sci, Cell Biol & Signaling Res Grp, Debrecen, Hungary. EM vamosig@dote.hu RI Vamosi, Gyorgy/C-9351-2009; Bodnar, Andrea/A-9286-2011 NR 24 TC 12 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 14 PY 2007 VL 361 IS 1 BP 202 EP 207 DI 10.1016/j.bbrc.2007.07.013 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 198WU UT WOS:000248659000034 PM 17658476 ER PT J AU Kalueff, AV Keisala, T Minasyan, A Tuohimaa, P AF Kalueff, A. V. Keisala, T. Minasyan, A. Tuohimaa, P. TI Pharmacological modulation of anxiety-related behaviors in the murine Suok test SO BRAIN RESEARCH BULLETIN LA English DT Article DE anxiety; mice; drug-evoked alterations; suok test; light-dark niodification ID ELEVATED PLUS-MAZE; BALANCE CONTROL; VESTIBULAR COMPENSATION; ANIMAL-MODELS; GENETIC-BASIS; MICE; MOUSE; DIAZEPAM; RESPONSES; NOVELTY AB We have recently introduced a new model of anxiety - the Suck test and its light-dark modification - for behavioral characterization in mice and rats, including simultaneous assessment of their anxiety, activity, and neurological phenotypes. In the present study, testing different inbred (129S1, BALB/c) and hybrid (C57-129S1) mouse strains in both Suok test modifications, we examined the effects on anxiety-related behaviours produced by traditional anxiogenic and anxiolytic drugs. Here we show dose-dependent increases in anxiety-related behaviors produced by anxiogenic drug pentylenetetrazole (10 and 20 mg/kg). In contrast, anxiolytic drugs ethanol (0.75 and 1.5 g/kg) and diazepam (0.5 mg/kg) reduced anxiety and increased mouse exploration in this test. Hyperemotional anxious BALB/c mice were particularly sensitive to pharmacogenic anxiety in Suok test, also showing robust light-dark shifts in the light-dark version of this test. Overall, the results of this study confirm the potential utility of both murine Suok tests, especially when used in selected "sensitive" mouse strains, for high-throughput screening of potential anxiotropic drugs. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Tampere, Sch Med, Dept Anat, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Dept Clin Chem, FIN-33521 Tampere, Finland. RP Kalueff, AV (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. EM kalueva@mail.nih.gov NR 57 TC 3 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD SEP 14 PY 2007 VL 74 IS 1-3 BP 45 EP 50 DI 10.1016/j.brainresbull.2007.05.002 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 207DH UT WOS:000249231300006 PM 17683788 ER PT J AU Mravec, B Lukackova, R Bodnar, L Kiss, A Pacak, K Palkovits, M Kvetnansky, R AF Mravec, Boris Lukackova, Renata Bodnar, Lbolya Kiss, Alexander Pacak, Karel Palkovits, Miklos Kvetnansky, Richard TI Stress-induced alterations in catecholamine enzymes gene expression in the hypothalamic dorsomedial nucleus are modulated by caudal brain and not hypothalamic paraventricular nucleus neurons SO BRAIN RESEARCH BULLETIN LA English DT Article DE aromatic L-amino acid decarboxylase; dopainine-beta-hydroxylase; phenylethanolamine N-methyltransferase; tyrosine hydroxylase; norepinephrine; immobilization stress ID CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; ASCENDING PROJECTIONS; IMMOBILIZATION STRESS; LESIONS; CORTICOSTERONE; NOREPINEPHRINE; ORGANIZATION; QUANTITATION; CONNECTIONS AB The hypothalamic dorsomedial nucleus (DMN) represents an important coordinate center for regulation of autonomic and neuroendocrine systems, especially during stress response. The present study was focused on the gene expression of catecholamine-synthesizing enzymes and the protein levels of tyrosine hydroxylase in DMN, both in control and stressed rats. Moreover, pathways modulating the gene expression of tyrosine hydroxylase in DMN during immobilization (IMO) stress were also investigated. Gene expressions of all catecholamine-synthesizing enzymes were detected in DMN samples. While the levels of tyrosine hydroxylase and phenyl ethanol ami ne N-methyltransferase mRNA were increased in IMO rats, aromatic L-amino acid decarboxylase and dopamine-beta-hydroxylase mRNA remained unchanged. Tyrosine hydroxylase protein levels were significantly elevated in the DMN only after repeated IMO stress. Postero-lateral deafferentations of the DMN, or transections of the ascending catecholaminergic pathways originating in the lower brainstem abolished the IMO-induced increase of tyrosine hydroxylase gene expression in the DMN. Nevertheless, postero-lateral deafferentations of the hypothalamic paraventricular nucleus (PVN), which separate the DMN from the PVN, had no effect on IMO-induced elevation of tyrosine hydroxylase mRNA in the DMN. The present data indicate that certain DMN neurons synthesize mRNA of catecholamine enzymes. The stress-induced increase of tyrosine hydroxylase and phenylethanolamine N-methyltransferase mRNA in DMN neurons indicates the involvement of these catecholaminergic neurons in stress response. The gene expression of tyrosine hydroxylase in DMN is modulated by lower brainsterm and/or spinal cord, but not by PVN afferents. (c) 2007 Elsevier Inc. All rights reserved. C1 Slovak Acad Sci, Inst Expt Endocrinol, SK-83306 Bratislava, Slovakia. Comenius Univ, Fac Med, Inst Pathophysiol, Bratislava, Slovakia. Hungarian Acad Sci, Neuromorphol & Neuroendocrine Res Lab, Budapest, Hungary. Semmelweis Univ, H-1085 Budapest, Hungary. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Mravec, B (reprint author), Slovak Acad Sci, Inst Expt Endocrinol, Vlarska 3, SK-83306 Bratislava, Slovakia. EM ueeninrav@savba.sk RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 53 TC 3 Z9 4 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 EI 1873-2747 J9 BRAIN RES BULL JI Brain Res. Bull. PD SEP 14 PY 2007 VL 74 IS 1-3 BP 147 EP 154 DI 10.1016/j.brainresbull.2007.06.005 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 207DH UT WOS:000249231300019 PM 17683801 ER PT J AU Chopra, N Kannankeril, PJ Yang, T Hlaing, T Holinstat, I Ettensohn, K Pfeifer, K Akin, B Jones, LR Franzini-Armstrong, C Knollmann, BC AF Chopra, Nagesh Kannankeril, Prince J. Yang, Tao Hlaing, Thinn Holinstat, Izabela Ettensohn, Kristen Pfeifer, Karl Akin, Brandy Jones, Larry R. Franzini-Armstrong, Clara Knollmann, Bjorn C. TI Modest reductions of cardiac calsequestrin increase sarcoplasmic reticulum Ca2+ leak independent of luminal Ca2+ and trigger ventricular arrhythmias in mice SO CIRCULATION RESEARCH LA English DT Article DE calsequestrin; ventricular arrhythmia; SR Ca2+ leak; SR free luminal Ca2+; catecholaminergic polymorphic ventricular tachycardia ID RYANODINE RECEPTOR; CALCIUM-RELEASE; TACHYCARDIA; MYOCYTES; MUSCLE; PURIFICATION; TRIADIN; JUNCTIN; IDENTIFICATION; CONTRACTION AB Cardiac calsequestrin-null mice (Casq2(-/-)) display catecholaminergic ventricular tachycardia akin to humans with CASQ2 mutations. However, the specific contribution of Casq2 deficiency to the arrhythmia phenotype is difficult to assess because Casq2(-/-) mice also show significant reductions in the sarcoplasmic reticulum (SR) proteins junctin and triadin-1 and increased SR volume. Furthermore, it remains unknown whether Casq2 regulates SR Ca2+ release directly or indirectly by buffering SR luminal Ca2+. To address both questions, we examined heterozygous (Casq2(+/-\)) mice, which have a 25% reduction in Casq2 but no significant decrease in other SR proteins. Casq2(-/-) mice (n = 35) challenged with isoproterenol displayed 3-fold higher rates of ventricular ectopy than Casq2(-/-) mice (n = 31; P < 0.05). Programmed stimulation induced significantly more ventricular tachycardia in Casq2(-/-) mice than in Casq2(+/+) mice. Field-stimulated Ca2+ transients, cell shortening, L-type Ca2+ current, and SR volume were not significantly different in Casq2(+/-) and Casq2(+/+) myocytes. However, in the presence of isoproterenol, SR Ca2+ leak was significantly increased in Casq2(+/-) myocytes (Casq2(+/+) 0.18 +/- 0.02 F-ratio versus Casq2(+/+) 0.11 +/- 0.01 F-ratio, n = 57, 60; P < 0.01), resulting in a significantly higher rate of spontaneous SR Ca2+ releases and triggered beats. SR luminal Ca2+ measured using Mag-Fura-2 was not altered by Casq2 reduction. As a result, the relationship between SR Ca2+ leak and SR luminal Ca2+ was significantly different between Casq2(+/-) and Casq2(+/+) myocytes ( P < 0.01). Thus, even modest reductions in Casq2 increase SR Ca2+ leak and cause ventricular tachycardia susceptibility under stress. The underlying mechanism is likely the direct regulation of SR Ca2+ release channels by Casq2 rather than altered luminal Ca2+. C1 Vanderbilt Univ, Med Ctr, Oates Inst Expt Therapeut, Div Clin Pharmacol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. Washington Hosp Ctr, Cardiovasc Res Inst, Washington, DC 20010 USA. NICHHD, NIH, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. Krannert Cardiovasc Res Inst, Dept Med, Indianapolis, IN USA. Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. RP Knollmann, BC (reprint author), Vanderbilt Univ, Med Ctr, Oates Inst Expt Therapeut, Div Clin Pharmacol, 1265 Med Res Bldg IV, Nashville, TN 37232 USA. EM bjorn.knollmann@vanderbilt.edu OI Knollmann, Bjorn/0000-0003-4956-9735; Pfeifer, Karl/0000-0002-0254-682X FU Intramural NIH HHS; NHLBI NIH HHS [HL28556, HL46681, HL48093, HL71670, HL88635] NR 30 TC 82 Z9 84 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP 14 PY 2007 VL 101 IS 6 BP 617 EP 626 DI 10.1161/CIRCRESAHA.107.157552 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 211IS UT WOS:000249518100012 PM 17656677 ER PT J AU Berkhout, B Jeang, KT AF Berkhout, Ben Jeang, Kuan-Teh TI RISCy business: MicroRNAs, pathogenesis, and viruses SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID X MENTAL-RETARDATION; RNA-BINDING PROTEIN; B-CELL LYMPHOMAS; EXPRESSION PROFILES; ONCOGENIC MICRORNA; SILENCING PATHWAY; MOUSE DEVELOPMENT; BURKITT-LYMPHOMA; MAMMALIAN-CELLS; GENE-EXPRESSION C1 Acad Med Centrum, NL-1105 AZ Amsterdam, Netherlands. NIAID, Mol Microbiol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), Acad Med Centrum, Meibergdreef 15, NL-1105 AZ Amsterdam, Netherlands. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 103 TC 61 Z9 66 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 14 PY 2007 VL 282 IS 37 BP 26641 EP 26645 DI 10.1074/jbc.R700023200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208FJ UT WOS:000249304900002 PM 17627941 ER PT J AU Athanasopoulos, AN Schneider, D Keiper, T Alt, V Pendurthi, UR Liegibel, UM Sommer, U Nawroth, PP Kasperk, C Chavakis, T AF Athanasopoulos, Athanasios N. Schneider, Darius Keiper, Tanja Alt, Volker Pendurthi, Usha R. Liegibel, Ute M. Sommer, Ulrike Nawroth, Peter P. Kasperk, Christian Chavakis, Triantafyllos TI Vascular endothelial growth factor (VEGF)-induced up-regulation of CCN1 in Osteoblasts mediates proangiogenic activities in endothelial cells and promotes fracture healing SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMEDIATE-EARLY GENE; BONE-FORMATION; EXTRACELLULAR-MATRIX; CYR61 CCN1; ANGIOGENESIS; EXPRESSION; VEGF; PRODUCT; REPAIR; MECHANISMS AB Angiogenesis is indispensable during fracture repair, and vascular endothelial growth factor ( VEGF) is critical in this process. CCN1 ( CYR61) is an extracellular matrix signaling molecule that has been implicated in neovascularization through its interactions with several endothelial integrin receptors. CCN1 has been shown to be up-regulated during the reparative phase of fracture healing; however, the role of CCN1 therein remains unclear. Here, the regulation of CCN1 expression in osteoblasts and the functional consequences thereof were studied. Stimulation of osteoblasts with VEGF resulted in a dose- and time-dependent up-regulation of CCN1 mRNA and protein. An up-regulation of both cell surface-associated CCN1 as well as extracellular matrix-associated CCN1 in osteoblasts was found. The supernatant of VEGF-prestimulated osteoblasts was chemotactic for endothelial cells, increasing their migration and stimulated capillary-like sprout formation. These effects could be attributed to the presence of CCN1 in the osteoblast supernatant as they were prevented by an antibody against CCN1 or by small interfering RNA-mediated knockdown of osteoblast CCN1. Moreover, the supernatant of VEGF-prestimulated osteoblasts induced angiogenesis in Matrigel plugs in vivo in a CCN1-dependent manner. In addition, blockade of CCN1 prevented bone fracture healing in mice. Taken together, the present work demonstrates a potential paracrine loop consisting of the VEGF-mediated up-regulation of CCN1 in osteoblasts that attracts endothelial cells and promotes angiogenesis. Such a loop could be operative during fracture healing. C1 NCI, EIB, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Heidelberg, Dept Internal Med 1, D-69120 Heidelberg, Germany. Univ Hosp Giessen Marburg, Dept Trauma Surg, D-35385 Giessen, Germany. Univ Texas, Hlth Ctr Tyler, Biomed Res Div, Tyler, TX USA. RP Chavakis, T (reprint author), NCI, EIB, Natl Inst Hlth, 10 Ctr Dr,Rm 4B17, Bethesda, MD 20892 USA. EM chavakist@mail.nih.gov FU NHLBI NIH HHS [R01 HL058869, R01 HL058869-05A3, R01 HL058869-06] NR 45 TC 46 Z9 60 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 14 PY 2007 VL 282 IS 37 BP 26746 EP 26753 DI 10.1074/jbc.M705200200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208FJ UT WOS:000249304900013 PM 17626014 ER PT J AU Calvo, E Tokumasu, F Marinotti, O Villeval, JL Ribeiro, JMC Francischetti, IMB AF Calvo, Eric Tokumasu, Fuyuki Marinotti, Osvaldo Villeval, Jean-Luc Ribeiro, Jose M. C. Francischetti, Ivo M. B. TI Aegyptin, a novel mosquito salivary gland protein, specifically binds to collagen and prevents its interaction with platelet glycoprotein VI, integrin alpha 2 beta 1, and von Willebrand factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN ATHEROSCLEROTIC PLAQUES; ADULT FEMALE MOSQUITO; THROMBUS FORMATION; FLOW CONDITIONS; AEDES-AEGYPTI; IN-VIVO; INTEGRIN ALPHA(2)BETA(1); AGGREGATION INHIBITOR; ACTIVATION; ADHESION AB Blood-sucking arthropods have evolved a number of inhibitors of platelet aggregation and blood coagulation. In this study we have molecularly and functionally characterized aegyptin, a member of the family of 30-kDa salivary allergens from Aedes aegypti, whose function remained elusive thus far. Aegyptin displays a unique sequence characterized by glycine, glutamic acid, and aspartic acid repeats and was shown to specifically block collagen-induced human platelet aggregation and granule secretion. Plasmon resonance experiments demonstrate that aegyptin binds to collagen types I-V (Kd approximate to 1 nM) but does not interact with vitronectin, fibronectin, laminin, fibrinogen, and von Willebrand factor (vWf). In addition, aegyptin attenuates platelet adhesion to soluble or fibrillar collagen. Furthermore, aegyptin inhibits vWf interaction with collagen type III under static conditions and completely blocks platelet adhesion to collagen under flow conditions at high shear rates. Notably, aegyptin prevents collagen but not convulxin binding to recombinant glycoprotein VI. These findings suggest that aegyptin recognizes specific binding sites for glycoprotein VI, integrin alpha 2 beta 1, and vWf, thereby preventing collagen interaction with its three major ligands. Aegyptin is a novel tool to study collagen-platelet interaction and a prototype for development of molecules with antithrombotic properties. C1 NIH, NIAID, Biol Sect, Lab Malaria & Vector, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. Univ Paris 11, INSERM, Inst Gustave Roussy, F-94805 Villejuif, France. RP Francischetti, IMB (reprint author), NIH, NIAID, Biol Sect, Lab Malaria & Vector, 12735 Twinbrook Pkwy Rm 2E-28, Bethesda, MD 20892 USA. EM ifrancischetti@niaid.nih.gov OI Villeval, Jean-Luc/0000-0002-0562-925X; Tokumasu, Fuyuki/0000-0003-2790-1071; Calvo, Eric/0000-0001-7880-2730 FU Intramural NIH HHS [Z01 AI000810-11, Z99 AI999999] NR 64 TC 58 Z9 61 U1 2 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 14 PY 2007 VL 282 IS 37 BP 26928 EP 26938 DI 10.1074/jbc.M705669200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208FJ UT WOS:000249304900032 PM 17650501 ER PT J AU Wang, YL Stieglitz, KA Bubunenko, M Court, DL Stec, B Roberts, MF AF Wang, Yanling Stieglitz, Kimberly A. Bubunenko, Mikhail Court, Donald L. Stec, Boguslaw Roberts, Mary F. TI The structure of the R184A mutant of the inositol monophosphatase encoded by suhB and implications for its functional interactions in Escherichia coli SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; SENSITIVE GROWTH; GENE-PRODUCT; PROTEIN; MUTATION; DOCKING; RECOMBINATION; REPLACEMENT; SUPPRESSES; BACTERIAL AB The Escherichia coli product of the suhB gene, SuhB, is an inositol monophosphatase (IMPase) that is best known as a suppressor of temperature-sensitive growth phenotypes in E. coli. To gain insights into these biological diverse effects, we determined the structure of the SuhB R184A mutant protein. The structure showed a dimer organization similar to other IMPases, but with an altered interface suggesting that the presence of Arg-184 in the wild-type protein could shift the monomer-dimer equilibrium toward monomer. In parallel, a gel shift assay showed that SuhB forms a tight complex with RNA polymerase (RNA pol) that inhibits the IMPase catalytic activity of SuhB. A variety of SuhB mutant proteins designed to stabilize the dimer interface did not show a clear correlation with the ability of a specific mutant protein to complement the Delta suhB mutation when introduced extragenically despite being active IMPases. However, the loss of sensitivity to RNA pol binding, i.e. in G173V, R184I, and L96F/R184I, did correlate strongly with loss of complementation of Delta suhB. Because residue 184 forms the core of the SuhB dimer, it is likely that the interaction with RNA polymerase requires monomeric SuhB. The exposure of specific residues facilitates the interaction of SuhB with RNA pol (or another target with a similar binding surface) and it is this heterodimer formation that is critical to the ability of SuhB to rescue temperature-sensitive phenotypes in E. coli. C1 Boston Coll, Merkert Chem Ctr, Chestnut Hill, MA 02467 USA. NIH, NCI, Ctr Canc Res, Gene Regulat & Chrosome Biol Lab, Ft Detrick, MD 21702 USA. SAIC Frederick, Basic Res Program, Chestnut Hill, MA 02467 USA. Burnham Inst, Med Res, La Jolla, CA 92037 USA. RP Roberts, MF (reprint author), Boston Coll, Merkert Chem Ctr, 2609 Beacon St, Chestnut Hill, MA 02467 USA. EM mary.roberts@bc.edu FU Intramural NIH HHS; NCI NIH HHS [N01 CO 12400]; NIGMS NIH HHS [GM 64481] NR 29 TC 13 Z9 13 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 14 PY 2007 VL 282 IS 37 BP 26989 EP 26996 DI 10.1074/jbc.M701210200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208FJ UT WOS:000249304900039 PM 17652087 ER PT J AU Gills, JJ Castillo, SS Zhang, CY Petukhov, PA Memmott, RM Hollingshead, M Warfel, N Han, JH Kozikowski, AP Dennis, PA AF Gills, Joell J. Castillo, S. Sianna Zhang, Chunyu Petukhov, Pavel A. Memmott, Regan M. Hollingshead, Melinda Warfel, Noel Han, Jiahuai Kozikowski, Alan P. Dennis, Phillip A. TI Phosphatidylinositol ether lipid analogues that inhibit AKT also independently activate the stress kinase, p38 alpha, through MKK3/6-independent and -dependent mechanisms SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID P38 MAP KINASE; PLECKSTRIN HOMOLOGY DOMAIN; CYCLE CHECKPOINT PATHWAY; PROTEIN-KINASE; CANCER-CELLS; ENDOTHELIAL-CELLS; ATAXIA-TELANGIECTASIA; SIGNAL-TRANSDUCTION; ANTITUMOR-ACTIVITY; APOPTOSIS AB Previously, we identified five active phosphatidylinositol ether lipid analogues (PIAs) that target the pleckstrin homology domain of Akt and selectively induce apoptosis in cancer cells with high levels of Akt activity. To examine specificity, PIAs were screened against a panel of 29 purified kinases. No kinase was inhibited, but one isoform of p38, p38 alpha, was uniformly activated 2-fold. Molecular modeling of p38 alpha revealed the presence of two regions that could interact with PIAs, one in the activation loop and a heretofore unappreciated region in the upper lobe that resembles a pleckstrin homology domain. In cells, two phases of activation were observed, an early phase that was independent of the upstream kinase MKK3/6 and inhibited by the p38 inhibitor SB203580 and a latter phase that was coincident with MKK3/6 activation. In short term xenograft experiments that employed immunohistochemistry and immunoblotting, PIA administration increased phosphorylation of p38 but not MKK3/6 in tumors in a statistically significant manner. Although PIAs rapidly activated p38 with similar time and dose dependence as Akt inhibition, p38 activation and Akt inhibition were independent events induced by PIAs. Using SB203580 or p38 alpha(-/-) cells, we showed that p38 alpha is not required for PIA-induced apoptosis but is required forH(2)O(2)- and anisomycin-induced apoptosis. Nonetheless, activation of p38a contributes to PIA-induced apoptosis, because reconstitution of p38a into p38 alpha(-/-) cells increased apoptosis. These studies indicate that p38 alpha is activated by PIAs through a novel mechanism and show that p38 alpha activation contributes to PIA-induced cell death. Independent modulation of Akt and p38 alpha could account for the profound cytotoxicity of PIAs. C1 NIH, NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20889 USA. Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. NIH, NCI, Div Canc Treatment & Diagnosis, Dev Therapeut Program, Frederick, MD 21701 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 94080 USA. RP Dennis, PA (reprint author), NIH, NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20889 USA. EM pdennis@nih.gov RI Han, J/G-4671-2010 FU Intramural NIH HHS; NCI NIH HHS [N01 CO 12400] NR 40 TC 32 Z9 34 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 14 PY 2007 VL 282 IS 37 BP 27020 EP 27029 DI 10.1074/jbc.M701108200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208FJ UT WOS:000249304900043 PM 17631503 ER PT J AU Walker, EA Ahmed, A Lavery, GG Tomlinson, JW Kim, SY Cooper, MS Ride, JP Hughes, BA Shackleton, CHL McKiernan, P Elias, E Chou, JY Stewart, PM AF Walker, Elizabeth A. Ahmed, Adeeba Lavery, Gareth G. Tomlinson, Jeremy W. Kim, So Youn Cooper, Mark S. Ride, Jonathan P. Hughes, Beverly A. Shackleton, Cedric H. L. McKiernan, Patrick Elias, Elwyn Chou, Janice Y. Stewart, Paul M. TI 11 beta-hydroxysteroid dehydrogenase type 1 regulation by intracellular glucose 6-phosphate provides evidence for a novel link between glucose metabolism and Hypothalamo-Pituitary-Adrenal axis function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOGEN-STORAGE-DISEASE; BONE-MINERAL DENSITY; HEXOSE-6-PHOSPHATE DEHYDROGENASE; ENDOPLASMIC-RETICULUM; SELECTIVE-INHIBITION; PYRIDINE-NUCLEOTIDES; CUSHINGS-DISEASE; CORTISOL; MICE; OBESITY AB Microsomal glucose-6-phosphatase-alpha (G6Pase-alpha) and glucose 6-phosphate transporter (G6PT) work together to increase blood glucose concentrations by performing the terminal step in both glycogenolysis and gluconeogenesis. Deficiency of the G6PT in liver gives rise to glycogen storage disease type 1b (GSD1b), whereas deficiency of G6Pase-alpha leads to GSD1a. G6Pase-alpha shares its substrate (glucose 6-phosphate; G6P) with hexose-6-phosphate-dehydrogenase (H6PDH), a microsomal enzyme that regenerates NADPH within the endoplasmic reticulum lumen, thereby conferring reductase activity upon 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). 11 beta-HSD1 interconverts hormonally active C11 beta-hydroxy steroids (cortisol in humans and corticosterone in rodents) to inactive C11-oxo steroids (cortisone and 11-dehydrocorticosterone, respectively). In vivo reductase activity predominates, generating active glucocorticoid. We hypothesized that substrate (G6P) availability to H6PDH in patients with GSD1b and GSD1a will decrease or increase 11 beta-HSD1 reductase activity, respectively. We investigated 11 beta-HSD1 activity in GSD1b and GSD1a mice and in two patients with GSD1b and five patients diagnosed with GSD1a. We confirmed our hypothesis by assessing 11 beta-HSD1 in vivo and in vitro, revealing a significant decrease in reductase activity in GSD1b animals and patients, whereas GSD1a patients showed a marked increase in activity. The cellular trafficking of G6P therefore directly regulates 11 beta-HSD1 reductase activity and provides a novel link between glucose metabolism and function of the hypothalamo-pituitary-adrenal axis. C1 Univ Birmingham, Div Med Sci & Biol Sci, Birmingham B15 2TH, W Midlands, England. NIH, NICHD, Bethesda, MD 20892 USA. Birmingham Childrens Hosp, Liver Unit, Birmingham B4 6NH, W Midlands, England. Queen Elizabeth Hosp, Liver & Hepatobiliary Unit, Birmingham B15 2TH, W Midlands, England. RP Stewart, PM (reprint author), Univ Birmingham, Div Med Sci & Biol Sci, Birmingham B15 2TH, W Midlands, England. EM p.m.stewart@bham.ac.uk RI Lavery, Gareth/F-9346-2010; Cooper, Mark/C-9529-2012 FU Medical Research Council [G0100729, G84/6638]; NICHD NIH HHS [1Z01 HD 000912-27]; Wellcome Trust [074088] NR 48 TC 35 Z9 35 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 14 PY 2007 VL 282 IS 37 BP 27030 EP 27036 DI 10.1074/jbc.M704144200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208FJ UT WOS:000249304900044 PM 17588937 ER PT J AU Madsen, DH Engelholm, LH Ingvarsen, S Hillig, T Wagenaar-Miller, RA Kjoller, L Gardsvoll, H Hoyer-Hansen, G Holmbeck, K Bugge, TH Behrendt, N AF Madsen, Daniel H. Engelholm, Lars H. Ingvarsen, Signe Hillig, Thore Wagenaar-Miller, Rebecca A. Kjoller, Lars Gardsvoll, Henrik Hoyer-Hansen, Gunilla Holmbeck, Kenn Bugge, Thomas H. Behrendt, Niels TI Extracellular Collagenases and the Endocytic receptor, urokinase plasminogen activator receptor-associated Protein/Endo180, cooperate in fibroblast-mediated collagen degradation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX-METALLOPROTEINASE; MANNOSE RECEPTOR; I COLLAGEN; TRANSMEMBRANE GLYCOPROTEIN; BINDING-PROPERTIES; LECTIN RECEPTOR; ENDO180; CELLS; CANCER; FIBRONECTIN AB The collagens of the extracellular matrix are the most abundant structural proteins in the mammalian body. In tissue remodeling and in the invasive growth of malignant tumors, collagens constitute an important barrier, and consequently, the turnover of collagen is a rate-limiting process in these events. A recently discovered turnover route with importance for tumor growth involves intracellular collagen degradation and is governed by the collagen receptor, urokinase plasminogen activator receptor-associated protein (uPARAP or Endo 180). The interplay between this mechanism and extracellular collagenolys is is not known. In this report, we demonstrate the existence of a new, composite collagen breakdown pathway. Thus, fibroblast-mediated collagen degradation proceeds preferentially as a sequential mechanism in which extracellular collagenolysis is followed by uPARAP/Endo180-mediated endocytosis of large collagen fragments. First, we show that collagen that has been pre-cleaved by a mammalian collagenase is taken up much more efficiently than intact, native collagen by uPARAP/Endo 180-positive cells. Second, we demonstrate that this preference is governed by the acquisition of a gelatin-like structure by the collagen, occurring upon collagenase-mediated cleavage under native conditions. Third, we demonstrate that the growth of uPARAP/Endo 180-deficient fibroblasts on a native collagen matrix leads to substantial extracellular accumulation of well defined collagen fragments, whereas, wild-type fibroblasts possess the ability to direct an organized and complete degradation sequence comprising both the initial cleavage, the endocytic uptake, and the intracellular breakdown of collagen. C1 Finsen Lab, DK-2200 Copenhagen, Denmark. NIH, NIDCR, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. RP Behrendt, N (reprint author), Finsen Lab, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark. EM niels.behrendt@finsenlab.dk OI Madsen, Daniel Hargboel/0000-0002-3183-6201; Engelholm, Lars/0000-0002-6616-1232 FU Intramural NIH HHS NR 59 TC 62 Z9 63 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 14 PY 2007 VL 282 IS 37 BP 27037 EP 27045 DI 10.1074/jbc.M701088200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208FJ UT WOS:000249304900045 PM 17623673 ER PT J AU Chi, YH Haller, K Peloponese, JM Jeang, KT AF Chi, Ya-Hui Haller, Kerstin Peloponese, Jean-Marie, Jr. Jeang, Kuan-Teh TI Histone acetyltransferase hALP and nuclear membrane protein hsSUN1 function in de-condensation of mitotic chromosomes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE-EXPRESSION; LAMIN-A; ENDOPLASMIC-RETICULUM; CHROMATIN-STRUCTURE; BUILDING-BLOCKS; LIVING CELLS; ENVELOPE; MITOSIS; ACETYLATION; LOCALIZATION AB Replicated mammalian chromosomes condense to segregate during anaphase, and they de-condense at the conclusion of mitosis. Currently, it is not understood what the factors and events are that specify de-condensation. Here, we demonstrate that chromosome de-condensation needs the function of an inner nuclear membrane (INM) protein hsSUN1 and a membrane-associated histone acetyltransferase ( HAT), hALP. We propose that nascently reforming nuclear envelope employs hsSUN1 and hALP to acetylate histones for de-compacting DNA at the end of mitosis. C1 NIAID, NIH, Mol Microbiol Lab, Mol Virol Sect, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), Bldg 4,Rm 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008; Chi, Ya-Hui/B-1080-2010 NR 59 TC 53 Z9 56 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 14 PY 2007 VL 282 IS 37 BP 27447 EP 27458 DI 10.1074/jbc.M703098200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208FJ UT WOS:000249304900086 PM 17631499 ER PT J AU Olivares, I Mulky, A Boross, PI Tozser, J Kappes, JC Lopez-Galindez, C Menendez-Arias, L AF Olivares, Isabel Mulky, Alok Boross, Peter I. Tozser, Jozsef Kappes, John C. Lopez-Galindez, Cecilio Menendez-Arias, Luis TI HIV-1 protease dimer interface mutations that compensate for viral reverse transcriptase instability in infectious virions SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV; reverse transcriptase; protease; retrovirus; fitness ID IMMUNODEFICIENCY-VIRUS TYPE-1; TRYPTOPHAN-REPEAT MOTIF; AMINO-ACID; DRUG-RESISTANCE; REPLICATION CAPACITY; ANGSTROM RESOLUTION; POLYMERASE-ACTIVITY; CLEAVAGE SITES; DNA-SYNTHESIS; P66 SUBUNIT AB Mature enzymes encoded within the human immunodeficiency virus type I (HIV-1) genome (protease (PR), reverse transcriptase (RT) and integrase (IN)) derive from proteolyfic processing of a large polyprotein (Gag-Pol). Gag-Pol processing is catalyzed by the viral PR, which is active as a homodimer. The HIV-1 RT functions as a heterodimer (p66/p51) composed of subunits of 560 and 440 amino acid residues, respectively. Both subunits have identical amino acid sequence, but p51 lacks 120 residues that are removed by the HIV-1 PR during viral maturation. While p66 is the catalytic subunit, p51 has a primarily structural role. Amino acid substitutions affecting the stability of p66/p51 (i.e. F130W) have a deleterious effect on viral fitness. Previously, we showed that the effects of F130W are mediated by p51 and can be compensated by mutation T58S. While studying the dynamics of emergence of the compensatory mutation, we observed that mutations in the viral PR-coding region were selected in HIV clones containing the RT substitution F130W, before the imposition of T58S/ F130W mutations. The PR mutations identified (G94S and T96S) improved the replication capacity of the F130W mutant virus. By using a transcomplementation assay, we demonstrate that the loss of p66/p51 heterodimer stability caused by Trp130 can be attributed to an increased susceptibility of RT to viral PR degradation. Recombinant HIV-1 PRs bearing mutations G94S or T96S showed decreased dimer stability and reduced catalytic efficiency. These results were consistent with crystallographic data showing the location of both residues in the PR dimerization interface. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Autonoma Madrid, CSIC, Ctr Mol Biol, E-28049 Madrid, Spain. Inst Salud Carlos III, Ctr Nacl Microbiol, E-28220 Madrid, Spain. Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. Univ Debrecen, Res Ctr Mol Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. Vet Adm Med Ctr, Res Serv, Birmingham, AL 35233 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Menendez-Arias, L (reprint author), Univ Autonoma Madrid, CSIC, Ctr Mol Biol, E-28049 Madrid, Spain. EM Imenendez@cbm.uam.es RI Tozser, Jozsef/A-7840-2008; Lopez-Galindez, Cecilio/A-3603-2008; Menendez Arias, Luis /G-2436-2016; Menendez Arias, Luis/N-7447-2016; OI Tozser, Jozsef/0000-0003-0274-0056; Lopez-Galindez, Cecilio/0000-0002-2324-9584; Menendez Arias, Luis/0000-0002-1251-6640; Tozser, Jozsef/0000-0001-5076-8729 FU NCI NIH HHS [CA73470, R01 CA073470, R01 CA073470-03, R01 CA073470-04]; NIAID NIH HHS [R01 AI047714, AI47714, P30 AI027767, P30 AI27767, R01 AI047714-01, R01 AI047714-02, R01 AI047714-03, R01 AI047714-04] NR 54 TC 12 Z9 12 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 14 PY 2007 VL 372 IS 2 BP 369 EP 381 DI 10.1016/j.jmb.2007.06.073 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 209EQ UT WOS:000249372200008 PM 17651754 ER PT J AU Zhang, SY Jouanguy, E Ugolini, S Smahi, A Elain, G Romero, P Segal, D Sancho-Shimizu, V Lorenzo, L Puel, A Picard, C Chapgier, A Plancoulaine, S Titeux, M Cognet, C von Bernuth, H Ku, CL Casrouge, A Zhang, XX Barreiro, L Leonard, J Hamilton, C Lebon, P Heron, B Vallee, L Quintana-Murci, L Hovnanian, A Rozenberg, F Vivier, E Geissmann, F Tardieu, M Abel, L Casanova, JL AF Zhang, Shen-Ying Jouanguy, Emmanuelle Ugolini, Sophie Smahi, Asma Elain, Gaelle Romero, Pedro Segal, David Sancho-Shimizu, Vanessa Lorenzo, Lazaro Puel, Anne Picard, Capucine Chapgier, Ariane Plancoulaine, Sabine Titeux, Matthias Cognet, Celine von Bernuth, Horst Ku, Cheng-Lung Casrouge, Armanda Zhang, Xin-Xin Barreiro, Luis Leonard, Joshua Hamilton, Claire Lebon, Pierre Heron, Benedicte Vallee, Louis Quintana-Murci, Lluis Hovnanian, Alain Rozenberg, Flore Vivier, Eric Geissmann, Frederic Tardieu, Marc Abel, Laurent Casanova, Jean-Laurent TI TLR3 deficiency in patients with herpes simplex encephalitis SO SCIENCE LA English DT Article ID TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; IMMUNE-RESPONSES; VIRUS-INFECTION; T-LYMPHOCYTES; NK CELLS; GENE; RECOGNITION; EXPRESSION; INTERFERON AB Some Toll and Toll-like receptors (TLRs) provide immunity to experimental infections in animal models, but their contribution to host defense in natural ecosystems is unknown. We report a dominant-negative TLR3 allele in otherwise healthy children with herpes simplex virus 1 (HSV-1) encephalitis. TLR3 is expressed in the central nervous system (CNS), where it is required to control HSV-1, which spreads from the epithelium to the CNS via cranial nerves. TLR3 is also expressed in epithelial and dendritic cells, which apparently use TLR3-independent pathways to prevent further dissemination of HSV-1 and to provide resistance to other pathogens in TLR3-deficient patients. Human TLR3 appears to be redundant in host defense to most microbes but is vital for natural immunity to HSV-1 in the CNS, which suggests that neurotropic viruses have contributed to the evolutionary maintenance of TLR3. C1 Fac Med Necker Enfants Malad, INSERM, U550, F-75015 Paris, France. Univ Paris 05, F-75015 Paris, France. Shanghai Jiao Tong Univ, Rui Jin Hosp, French Chinese Lab Genet & Life Sci, Shanghai 200025, Peoples R China. Marseille Luminy Immunol Inst, F-13288 Marseille, France. Hop Necker Enfants Malad, INSERM, U781, Dept Genet, F-75015 Paris, France. Hop Necker Enfants Malad, INSERM, U838, Lab Mononucl Cell Biol, F-75015 Paris, France. Univ Lausanne Hosp, Lausanne Branch, Ludwig Inst Canc Res, CH-1005 Lausanne, Switzerland. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Hop Necker Enfants Malad, Ctr Study Immunodeficiencies, F-75015 Paris, France. Univ Toulouse 3, INSERM, U563, F-31000 Toulouse, France. Inst Pasteur, CNRS, URA3012, F-75015 Paris, France. Univ Paris 05, Cochin St Vincent de Paul Hosp, F-75014 Paris, France. Trousseau Hosp, F-75012 Paris, France. Ctr Hosp Reg & Univ Lille, F-59037 Lille, France. Univ Paris Sud, Hop Bicetre, F-94720 Le Kremlin Bicetre, France. RP Casanova, JL (reprint author), Fac Med Necker Enfants Malad, INSERM, U550, F-75015 Paris, France. EM casanova@necker.fr RI Leonard, Joshua/B-7649-2009; Barreiro, Luis/I-7772-2015; KU, Cheng-Lung/L-6073-2015; Gouel-Plancoulaine, Sabine/E-2824-2017; OI KU, Cheng-Lung/0000-0002-0643-2256; geissmann, frederic/0000-0001-5029-2468; Picard, Capucine/0000-0001-8788-5056; Quintana-Murci, Lluis/0000-0003-2429-6320; Plancoulaine, Sabine/0000-0003-0725-8306 FU Medical Research Council [G0900867] NR 39 TC 526 Z9 544 U1 4 U2 56 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 14 PY 2007 VL 317 IS 5844 BP 1522 EP 1527 DI 10.1126/science.1139522 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 210PK UT WOS:000249467900034 PM 17872438 ER PT J AU Khaliullin, RZ Cobar, EA Lochan, RC Bell, AT Head-Gordon, M AF Khaliullin, Rustarn Z. Cobar, Erika A. Lochan, Rohini C. Bell, Alexis T. Head-Gordon, Martin TI Unravelling the origin of intermolecular interactions using absolutely localized molecular orbitals SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Review ID ENERGY DECOMPOSITION ANALYSIS; DENSITY-FUNCTIONAL THEORY; SUBSTITUTED (ETA-6-ARENE)CR(CO)3 COMPLEXES; HYDROGEN-BONDING INTERACTIONS; DONOR-ACCEPTOR INTERACTIONS; METAL-ORGANIC FRAMEWORKS; WATER DIMER; AB-INITIO; PERTURBATION-THEORY; CHARGE-TRANSFER AB An energy decomposition analysis (EDA) method is proposed to isolate physically relevant components of the total intermolecular interaction energies such as the contribution from interacting frozen monomer densities, the energy lowering due to polarization of the densities, and the further energy lowering due to charge-transfer effects. This method is conceptually similar to existing EDA methods such as Morokuma analysis but includes several important new features. The first is a fully self-consistent treatment of the energy lowering due to polarization, which is evaluated by a self-consistent field calculation in which the molecular orbital coefficients are constrained to be block-diagonal (absolutely localized) in the interacting molecules to prohibit charge transfer. The second new feature is the ability to separate forward and back-donation in the charge-transfer energy term using a perturbative approximation starting from the optimized block-diagonal reference. The newly proposed EDA method is used to understand the fundamental aspects of intermolecular interactions such as the degree of covalency in the hydrogen bonding in water and the contributions of forward and back-donation in synergic bonding in metal complexes. Additionally, it is demonstrated that this method can be used to identify the factors controlling the interaction of the molecular hydrogen with open metal centers in potential hydrogen storage materials and the interaction of methane with rhenium complexes. C1 Univ Calif Berkeley, Lawrence Berkeley Lab, Div Chem Sci, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. NHLBI, Lab Computat Biol, Computat Biophys Sect, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Dept Chem Engn, Berkeley, CA 94720 USA. RP Khaliullin, RZ (reprint author), Univ Calif Berkeley, Lawrence Berkeley Lab, Div Chem Sci, Berkeley, CA 94720 USA. EM rustam@khaliullin.com RI Khaliullin, Rustam/B-2672-2009; OI Khaliullin, Rustam/0000-0002-9073-6753; Bell, Alexis/0000-0002-5738-4645 NR 109 TC 217 Z9 217 U1 8 U2 61 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD SEP 13 PY 2007 VL 111 IS 36 BP 8753 EP 8765 DI 10.1021/jp073685z PG 13 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 208OO UT WOS:000249329300002 PM 17655284 ER PT J AU Allen, NPC Donninger, H Vos, MD Eckfeld, K Hesson, L Gordon, L Birrer, MJ Latif, F Clark, GJ AF Allen, N. P. C. Donninger, H. Vos, M. D. Eckfeld, K. Hesson, L. Gordon, L. Birrer, M. J. Latif, F. Clark, G. J. TI RASSF6 is a novel member of the RASSF family of tumor suppressors SO ONCOGENE LA English DT Article DE Ras; RASSF6; tumor suppressor ID NF-KAPPA-B; EPIGENETIC INACTIVATION; EPITHELIAL-CELLS; ONCOGENIC RAS; HUMAN CANCERS; EFFECTOR; ACTIVATION; GENE; ASSOCIATION; APOPTOSIS AB RASSF family proteins are tumor suppressors that are frequently downregulated during the development of human cancer. The best-characterizedmember of the family is RASSF1A, which is downregulated by promoter methylation in 40-90% of primary human tumors. We now identify and characterize a novel member of the RASSF family, RASSF6. Like the other family members, RASSF6 possesses a Ras Association domain and binds activated Ras. Exogenous expression of RASSF6 promotedapoptosis, synergized with activated K-Ras to induce cell death and inhibited the survival of specific tumor cell lines. Suppression of RASSF6 enhanced the tumorigenic phenotype of a human lung tumor cell line. Furthermore, RASSF6 is often downregulated in primary human tumors. RASSF6 shares some similar overall properties as other RASSF proteins. However, there are significant differences in biological activity between RASSF6 and other family members including a discrete tissue expression pro. le, cell killing specificity and impact on signaling pathways. Moreover, RASSF6 may play a role in dictating the degree of in. ammatory response to the respiratory syncytial virus. Thus, RASSF6 is a novel RASSF family member that demonstrates the properties of a Ras effector and tumor suppressor but exhibits biological properties that are unique and distinct from those of other family members. C1 Natl Canc Inst, Dept Cell Canc Biol, Rockville, MD USA. Univ Louisville, JG Brown Canc Ctr, Dept Med, Mol Targets Grp, Louisville, KY USA. Univ Birmingham, Med Sect Mol Genet, Birmingham, W Midlands, England. RP Clark, GJ (reprint author), Univ Louisville, Dept Med, Targets Grp, 580 S Preston Str, Louisville, KY 40202 USA. EM gjclar01@louisville.edu FU Intramural NIH HHS; NCRR NIH HHS [RR018733] NR 39 TC 59 Z9 69 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 13 PY 2007 VL 26 IS 42 BP 6203 EP 6211 DI 10.1038/sj.onc.1210440 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 209PU UT WOS:000249401300011 PM 17404571 ER PT J AU Neumann, AU Polis, MA Rozenberg, L Jackson, JO Reitano, KN McLaughlin, M Koratich, C Dewar, RL Masur, H Haagmans, BL Kottilil, S AF Neumann, A. U. Polis, M. A. Rozenberg, L. Jackson, J. O. Reitano, K. N. McLaughlin, M. Koratich, C. Dewar, R. L. Masur, H. Haagmans, B. L. Kottilil, Shyam TI Differential antiviral effect of PEG-interferon-alpha-2b on HIV and HCV in the treatment of HIV/HCV co-infected patients SO AIDS LA English DT Article DE antiviral effect; HCV; HIV; interferon ID CHRONIC HEPATITIS-C; HUMAN-IMMUNODEFICIENCY-VIRUS; INTERFERON-ALPHA-2B PLUS RIBAVIRIN; DYNAMICS IN-VIVO; CD4(+) T-CELLS; PEGYLATED INTERFERON-ALPHA-2B; ANTIRETROVIRAL THERAPY; VIF PROTEIN; REPLICATION; CLEARANCE AB Objective: The major antiviral effect of interferon (IFN)-alpha on hepatitis C virus (HCV) is blocking of virion production from infected cells. We now investigate the previously unknown mechanism of action of IFN-alpha against HIV. Methods: HIV kinetics in parallel to HCV kinetics and IFN pharmacokinetics during pegylated-IFN-alpha-2b (1.5 mu g/Kg q.w., PEG-IFN) and ribavirin (1-1.2 g daily) treatment in nine HIV patients co-infected with HCV genotype 1 were analyzed. In vivo modeling predictions of suppression of HIV replication by PEG-IFN in CD8-depleted peripheral blood mononuclear cells were verified by in vitro experiments. Results: HCV and HIV show different viral decline patterns after administration of PEG-IFN. Unlike the bi-phasic decline shown by HCV, HIV shows a slow continuous decline cluring the first week, with no rebound when PEG-IFN levels decline. Fitting of HIV kinetics with known half-lives of free virus and infected cells indicates that the major effect of IFN on HIV is to block de novo infection rather than to block virion production. The magnitude of the antiviral effect is similar (mean 1.1 log(10)) decline at 7 days) to those of direct anti-HIV drugs, but shows an inverse correlation with baseline viremia. In vitro studies show that preincubation with IFN renders a suppression of HIV replication superior to that of treatment postinfection, thus corroborating the mathematical analysis in vivo. Conclusion: The complimentary antiviral properties of IFN-alpha and antiretroviral therapy suggest a role for pharmacokinetically improved formulations of IFN as part of salvage therapy for HIV-infected individuals. (C) 2007 Lippincott Williams & Wilkins. C1 Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. Dept Hlth & Human Serv, Natl Inst Hlth, Natl Inst Digest Dis & Kidney, Lab Biol Modeling, Bethesda, MD USA. Dept Hlth & Human Serv, Natl Inst Hlth, NIAID, Immunoregulat Lab, Bethesda, MD USA. NCI, SAIC Frederick, Frederick, MD 21701 USA. Dept Hlth & Human Serv, NIH, Clin Res Ctr, Dept Crit Care Med, Bethesda, MD USA. Erasmus MC, Dept Virol, Rotterdam, Netherlands. RP Kottilil, S (reprint author), NIH, NIAID, Immunoregulat Lab, Immunopathogen Sect, Bldg 10,Rm 11N204, Bethesda, MD 20892 USA. EM skottilil@niaid.nih.gov OI Polis, Michael/0000-0002-9151-2268 FU Intramural NIH HHS NR 43 TC 25 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD SEP 12 PY 2007 VL 21 IS 14 BP 1855 EP 1865 DI 10.1097/QAD.0b013e32825eaba7 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 213DA UT WOS:000249645000005 PM 17721093 ER PT J AU Kalueff, AV Jensen, CL Murphy, DL AF Kalueff, Allan V. Jensen, Catherine L. Murphy, Dennis L. TI Locomotory patterns, spatiotemporal organization of exploration and spatial memory in serotonin transporter knockout mice SO BRAIN RESEARCH LA English DT Article DE serotonin transporter knockout; mice; patterns of locomotion; habituation; spatiotemporal distribution; meandering; open field test; elevated plus maze ID ELEVATED PLUS-MAZE; ANXIETY-RELATED TRAITS; OPEN-FIELD; OUT MICE; TRYPTOPHAN DEPLETION; BEHAVIORAL-PHENOTYPE; DEFICIENT MICE; MOTOR-ACTIVITY; MUTANT MICE; GENE AB Serotonin transporter knockout (SERT-/-) mice are extensively used as a genetic model of several neuropsychiatric disorders, and consistently display anxiety-like behaviors and inactivity in different tests. To better understand how these mice organize their behavior, we assessed the open field and elevated plus maze spatiotemporal patterning of activity in adult male SERT wild type (+/+), heterozygous (+/-) and -/- mice on C57BL/6J genetic background using new videotracking and analytic procedures. In addition, we analyzed their spatial memory, assessing within- and between-trial habituation, and examined specific motor characteristics of their movement in these two tests. In the open field test, SERT-/- mice showed reduced vertical exploration throughout the arena, reduced central (but not peripheral) horizontal exploration, unaltered within-trial habituation, and slightly poorer between-trial habituation for horizontal activity. In the elevated plus maze, SERT-/-mice demonstrated anxiety-like avoidance of open arms, hypoactivity, as well as unaltered within-trial and between-trial habituation (except for poorer between-trial habituation of total horizontal activity). In both tests, SERT-/- mice showed greater prevalence of horizontal over vertical dimension of their exploration in the areas protected by the walls (open field periphery, plus maze closed arms), but not in open aversive areas, such as the center of the open field or center or open arms of the maze. In both arenas, SERT-/- mice consistently displayed increased turning behavior, potentially representing a perseverance-like phenotype or aberrant spatial strategies in novel environments. Overall, using a finegraded behavioral analysis in two different novelty tests, this study revealed alterations in motor and spatiotemporal patterning of activity in SERT-/- mice. Given the relevance of exploratory strategies to human personality traits and brain disorders, our data may be useful for developing further neurobehavioral models using these mice. Published by Elsevier B.V. C1 NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Kalueff, AV (reprint author), NIMH, Clin Sci Lab, Bldg 10,Room 3D41,10 Ctr Dr, Bethesda, MD 20892 USA. EM kalueva@mail.nih.gov FU Intramural NIH HHS NR 81 TC 50 Z9 52 U1 4 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 12 PY 2007 VL 1169 BP 87 EP 97 DI 10.1016/j.brainres.2007.07.009 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 222IG UT WOS:000250289000010 PM 17692295 ER PT J AU Gong, SC Doughty, M Harbaugh, CR Cummins, A Hatten, ME Heintz, N Gerfen, CR AF Gong, Shiaoching Doughty, Martin Harbaugh, Carroll R. Cummins, Alexander Hatten, Mary E. Heintz, Nathaniel Gerfen, Charles R. TI Targeting cre recombinase to specific neuron Populations with bacterial artificial chromosome constructs SO JOURNAL OF NEUROSCIENCE LA English DT Article ID SITE-SPECIFIC RECOMBINATION; TRANSGENIC MICE; GENE-EXPRESSION; STRIATOPALLIDAL NEURONS; SEROTONIN NEURONS; MOUSE-BRAIN; FOREBRAIN; DOPAMINE; MIDBRAIN; SYSTEM C1 Rockefeller Univ, Gene Express Nervous Syst Atlas Project, New York, NY 10021 USA. Rockefeller Univ, Dev Neurobiol Lab, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, Mol Biol Lab, New York, NY 10021 USA. NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Gerfen, CR (reprint author), NIH, Ctr Anim Hlth, Bldg 111,16701 Elmer Sch Rd, Dickerson, MD 20842 USA. EM gerfenc@mail.nih.gov FU Intramural NIH HHS; NINDS NIH HHS [N01 NS-0-2331, N01 NS-7-2370] NR 23 TC 270 Z9 273 U1 5 U2 22 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 12 PY 2007 VL 27 IS 37 BP 9817 EP 9823 DI 10.1523/JNEUROSCI.2707-07.2007 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 209VB UT WOS:000249415000001 PM 17855595 ER PT J AU Jenkins, LMM Hara, T Durell, SR Hayashi, R Inman, JK Piquemal, JP Gresh, N Appella, E AF Jenkins, Lisa M. Miller Hara, Toshiaki Durell, Stewart R. Hayashi, Ryo Inman, John K. Piquemal, Jean-Philip Gresh, Nohad Appella, Ettore TI Specificity of acyl transfer from 2-mercaptobenzamide thioesters to the HIV-1 nucleocapsid protein SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLARIZABLE MOLECULAR-MECHANICS; TERMINAL ZINC-FINGER; IN-VITRO; PYRIDINIOALKANOYL THIOESTERS; BIOLOGICAL-PROPERTIES; INTERACTION ENERGIES; BINDING DOMAINS; TYPE-1; INHIBITORS AB The HIV-1 nucleocapsid protein (NCp7) is a small, highly conserved protein with two zinc-binding domains that are essential for the protein's function. Molecules that bind to and inactivate NCp7 are currently being evaluated as new antiviral drugs. In particular, derivatives based on a 2-mercaptobenzamide thioester template have been shown to specifically eject zinc from the C-terminal zinc-binding domain (ZD2) of NCp7 via acyl transfer from the thioester to a cysteine sulfur. In this study, mutational analysis of the NCp7 amino acid sequence has been used to investigate the specificity of the interaction between ZD2 and a 2-mercaptobenzamide thioester compound using UV-vis spectroscopy and mass spectrometry to monitor the rate of metal ejection from NCp7 mutant peptides and sites of acylation, respectively. We were able to extend the previously reported mechanism of action of these thioester compounds to include a secondary S to N intramolecular acyl transfer that occurs after the primary acyl transfer from the thioester to a cysteine side chain in the protein. Structural models of the thioester/ZD2 complex were then examined to identify the most likely binding orientation. We determined that position x + 1 (where x is CYs(36)) needs to be an aromatic residue for reactivity and a hydrogen-bond donor in position x+9 is important for optimal reactivity. A basic residue (lysine or arginine) is required at position x + 2 for the correct fold, while a lysine residue is needed for reactivity involving S to N acyl transfer. We report highly specific interactions between 2-mercaptobenzamide thioester compounds and NCp7 that offer a structural basis for refining and designing new antiretroviral therapeutics, directed toward a target that is resistant to viral mutation. C1 NCI, Cell Biol Lab, Bethesda, MD 20892 USA. NIAID, Natl Inst Hlth, Immunol Lab, Bethesda, MD 20892 USA. Univ Paris 06, CNRS, UMR7616 CC137, Lab Chem Theorique, F-75005 Paris, France. INSERM, Lab Pharmacochim Mol Cell, U648, F-75006 Paris, France. RP Appella, E (reprint author), NCI, Cell Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM appellae@pop.nci.nih.gov RI Piquemal, Jean-Philip/B-9901-2009 OI Piquemal, Jean-Philip/0000-0001-6615-9426 NR 70 TC 39 Z9 40 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 12 PY 2007 VL 129 IS 36 BP 11067 EP 11078 DI 10.1021/ja071254o PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 209ES UT WOS:000249372400041 ER PT J AU Lafite, P Andre, F Zeldin, DC Dansette, PM Mansuy, D AF Lafite, Pierre Andre, Francois Zeldin, Darryl C. Dansette, Patrick M. Mansuy, Daniel TI Unusual regioselectivity and active site topology of human cytochrome p450 2J2 SO BIOCHEMISTRY LA English DT Article ID POTENTIAL FUNCTIONAL-SIGNIFICANCE; EPOXYEICOSATRIENOIC ACIDS; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; PROTEIN STRUCTURES; SUBSTRATE-BINDING; CYP2J2; METABOLISM; INHIBITORS; 3A4 AB The oxidation of six derivatives of terfenadone by recombinant human CYP2J2 (CYP = cytochrome P450) was studied by high-performance liquid chromatography coupled to mass spectrometry (MS) using tandem MS techniques and by H-1 NMR spectroscopy. CYP2J2 exhibited a surprising regioselectivity in favor of the hydroxylation of the substrate terminal chain at the weakly reactive homobenzylic position. In contrast, hydroxylation of the same substrates by CYP3A4 mainly occurred on the most chemically reactive sites of the substrates (N-oxidation and benzylic hydroxylation). A 3D homology model of CYP2J2 was constructed using recently published structures of CYP2A6, CYP2B4, CYP2C8, CYP2C9, and CYP2D6 as templates. In contrast with other CYP2 structures, it revealed an active site cavity with a severely restricted access of substrates to the heme through a narrow hydrophobic channel. Dynamic docking of terfenadone derivatives in the CYP2J2 active site allowed one to interpret the unexpected regioselectivity of the hydroxylation of these substrates by CYP2J2, which is mainly based on this restricted access to the iron. The structural features that have been found to be important for recognition of substrates or inhibitors by CYP2J2 were also interpreted on the basis of CYP2J2- substrate interactions in this model. C1 Univ Paris 05, CNRS, UMR 8601, Chim & Biochim Pharmacol & Toxicol Lab, F-75270 Paris, France. CEA Saclay, CNRS, URA 2096, Lab Stress Oxydant & Detoxicat,DSV, F-91191 Gif Sur Yvette, France. NIH, Res Triangle Pk, NC 27709 USA. RP Mansuy, D (reprint author), Univ Paris 05, CNRS, UMR 8601, Chim & Biochim Pharmacol & Toxicol Lab, 45 Rues St Peres, F-75270 Paris, France. EM daniel.mansuy@univ-paris5.fr RI DANSETTE, Patrick/B-8384-2014; Le Discorde, Magali/A-5127-2009; ANDRE, Francois/E-5555-2015; Lafite, Pierre/F-6806-2011 OI Le Discorde, Magali/0000-0001-5126-0900; Lafite, Pierre/0000-0003-1637-4966 FU Intramural NIH HHS [Z01 ES025034-13] NR 59 TC 27 Z9 27 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 11 PY 2007 VL 46 IS 36 BP 10237 EP 10247 DI 10.1021/bi700876a PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 207HG UT WOS:000249241600001 PM 17705402 ER PT J AU Xu, W Soga, S Beebe, K Lee, MJ Kim, YS Trepel, J Neckers, L AF Xu, W. Soga, S. Beebe, K. Lee, M-J Kim, Y. S. Trepel, J. Neckers, L. TI Sensitivity of epidermal growth factor receptor and ErbB2 exon 20 insertion mutants to Hsp90 inhibition SO BRITISH JOURNAL OF CANCER LA English DT Article DE Hsp90; epidermal growth factor receptor mutation; ErbB2 mutation; kinase inhibition; non-small cell lung cancer ID CELL LUNG-CANCER; HER2 KINASE DOMAIN; ACTIVATING MUTATIONS; GENE; GEFITINIB; CHAPERONE; FEATURES; EGFR; ADENOCARCINOMAS; GELDANAMYCIN AB The mature epidermal growth factor receptor ( EGFR) neither associates with nor requires the molecular chaperone heat-shock protein 90 ( Hsp90). Mutations in EGFR exons 18, 19, and 21 confer Hsp90 chaperone dependence. In non-small cell lung cancer (NSCLC), these mutations are associated with enhanced sensitivity to EGFR inhibitors in vitro and with clinical response in vivo. Although less prevalent, insertions in EGFR exon 20 have also been described in NSCLC. These mutations, however, confer resistance to EGFR inhibitors. In NSCLC, exon 20 insertions have also been identified in the EGFR family member ErbB2. Here, we examined the sensitivity of exon 20 insertion mutants to an Hsp90 inhibitor currently in the clinic. Our data demonstrate that both EGFR and ErbB2 exon 20 insertion mutants retain dependence on Hsp90 for stability and downstream-signalling capability, and remain highly sensitive to Hsp90 inhibition. Use of Hsp90 inhibitors should be considered in NSCLC harbouring exon 20 insertions in either EGFR or ErbB2. C1 NCI, Canc Res Ctr, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Med Oncol Branch, Bethesda, MD USA. RP Neckers, L (reprint author), NCI, Canc Res Ctr, Urol Oncol Branch, Bldg 10 Clin Res Ctr,Room I-5940,9000 Rockville P, Bethesda, MD 20892 USA. EM len@helix.nih.gov NR 24 TC 22 Z9 24 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 11 PY 2007 VL 97 IS 6 BP 741 EP 744 DI 10.1038/sj.bjc.6603950 PG 4 WC Oncology SC Oncology GA 209MH UT WOS:000249392100007 PM 17712310 ER PT J AU Agalliu, I Karlins, E Kwon, EM Iwasaki, LM Diamond, A Ostrander, EA Stanford, JL AF Agalliu, I. Karlins, E. Kwon, E. M. Iwasaki, L. M. Diamond, A. Ostrander, E. A. Stanford, J. L. TI Rare germline mutations in the BRCA2 gene are associated with early-onset prostate cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE BRCA2 gene; protein-truncating BRCA2 mutations; prostate cancer; early-onset disease ID BREAST-CANCER; HOMOLOGOUS RECOMBINATION; ASHKENAZI-JEWS; DNA-REPAIR; RISK; FAMILIES; SUSCEPTIBILITY; RAD51; TRANSCRIPTION; PREVALENCE AB Studies of families who segregate BRCA2 mutations have found that men who carry disease-associated mutations have an increased risk of prostate cancer, particularly early-onset disease. A study of sporadic prostate cancer in the UK reported a prevalence of 2.3% for protein-truncating BRCA2 mutations among patients diagnosed at ages <= 55 years, highlighting the potential importance of this gene in prostate cancer susceptibility. To examine the role of protein-truncating BRCA2 mutations in relation to early-onset prostate cancer in a US population, 290 population-based patients from King County, Washington, diagnosed at ages < 55 years were screened for germline BRCA2 mutations. The coding regions, intron-exon boundaries, and potential regulatory elements of the BRCA2 gene were sequenced. Two distinct protein-truncating BRCA2 mutations were identified in exon 11 in two patients. Both cases were Caucasian, yielding a mutation prevalence of 0.78% (95% confidence interval (95%CI) 0.09-2.81%) and a relative risk (RR) of 7.8(95%CI 1.8-9.4) for early-onset prostate cancer in white men carrying a protein-truncating BRCA2 mutation. Results suggest that protein-truncating BRCA2 mutations confer an elevated RR of early-onset prostate cancer. However, we estimate that < 1% of early-onset prostate cancers in the general US Caucasian population can be attributed to these rare disease-associated BRCA2 mutations. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. NIH, NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. Western Gen Hosp, Mol Med Ctr, Edinburgh Mol Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B874, Seattle, WA 98109 USA. EM jstanfor@fhcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU NCI NIH HHS [N01 CN005230, N01 CN05230, R01 CA056678, R01 CA092579, R01 CA56678] NR 35 TC 42 Z9 42 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 11 PY 2007 VL 97 IS 6 BP 826 EP 831 DI 10.1038/sj.bjc.6603929 PG 6 WC Oncology SC Oncology GA 209MH UT WOS:000249392100018 PM 17700570 ER PT J AU Savage, SA Chanock, SJ Lissowska, J Brinton, LA Richesson, D Peplonska, B Bardin-Mikolajczak, A Zatonski, W Szeszenia-Dabrowska, N Garcia-Closas, M AF Savage, S. A. Chanock, S. J. Lissowska, J. Brinton, L. A. Richesson, D. Peplonska, B. Bardin-Mikolajczak, A. Zatonski, W. Szeszenia-Dabrowska, N. Garcia-Closas, M. TI Genetic variation in five genes important in telomere biology and risk for breast cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; telomere; TERT; TERF2; haplotype; single nucleotide polymorphism ID COMPARATIVE GENOMIC HYBRIDIZATION; HAPLOTYPE RECONSTRUCTION; PROTEIN; LENGTH; POLYMORPHISM; ASSOCIATION; MAINTENANCE; HTERT; TRF1 AB Telomeres, consisting of TTAGGG nucleotide repeats and a protein complex at chromosome ends, are critical for maintaining chromosomal stability. Genomic instability, following telomere crisis, may contribute to breast cancer pathogenesis. Many genes critical in telomere biology have limited nucleotide diversity, thus, single nucleotide polymorphisms (SNPs) in this pathway could contribute to breast cancer risk. In a population-based study of 1995 breast cancer cases and 2296 controls from Poland, 24 SNPs representing common variation in POT1, TEP1, TERF1, TERF2 and TERT were genotyped. We did not identify any significant associations between individual SNPs or haplotypes and breast cancer risk; however, data suggested that three correlated SNPs in TERT (-1381C > T, -244C > T, and Ex2-659G > A) may be associated with reduced risk of breast cancer among individuals with a family history of breast cancer (odds ratios 0.73, 0.66, and 0.57, 95% confidence intervals 0.53-1.00, 0.46-0.95 and 0.39-0.84, respectively). In conclusion, our data do not support substantial overall associations between SNPs in telomere pathway genes and breast cancer risk. Intriguing associations with variants in TERT among women with a family history of breast cancer warrant follow-up in independent studies. C1 NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD 20852 USA. NIH, NCI, Canc Res Ctr, Pediat Oncol Branch, Bethesda, MD 20892 USA. NIH, NCI, Div Canc Epidemiol & Genet, Core Genotyping Facil, Gaithersburg, MD 20877 USA. M Sklodowska Curie Inst Oncol, Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland. NIH, NCI, Div Canc Epidemiol & Genet Hormonal, Reprod Epidemiol Branch, Bethesda, MD 20892 USA. Nofer Inst Occupat Med, Dept Epidemiol, Lodz, Poland. RP Savage, SA (reprint author), NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, 6120 Executive Blvd,EPS 7018, Rockville, MD 20852 USA. EM savagesh@mail.nih.gov RI Peplonska, Beata/F-6004-2010; Szeszenia-Dabrowska, Neonila/F-7190-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Savage, Sharon/B-9747-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Savage, Sharon/0000-0001-6006-0740; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS NR 28 TC 51 Z9 53 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 11 PY 2007 VL 97 IS 6 BP 832 EP 836 DI 10.1038/sj.bjc.6603934 PG 5 WC Oncology SC Oncology GA 209MH UT WOS:000249392100019 PM 17848914 ER PT J AU Pou, KM Massaro, JM Hoffmann, U Vasan, RS Maurovich-Horvat, P Larson, MG Keaney, JF Meigs, JB Lipinska, I Kathiresan, S Murabito, JM O'Donnell, CJ Benjamin, EJ Fox, CS AF Pou, Karla M. Massaro, Joseph M. Hoffmann, Udo Vasan, Ramachandran S. Maurovich-Horvat, Pal Larson, Martin G. Keaney, John F., Jr. Meigs, James B. Lipinska, Izabella Kathiresan, Sekar Murabito, Joanne M. O'Donnell, Christopher J. Benjamin, Emelia J. Fox, Caroline S. TI Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress - The framingham heart study SO CIRCULATION LA English DT Article DE obesity; abdominal visceral fat; inflammation; computed tomography; epidemiology ID TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; MONOCYTE CHEMOATTRACTANT PROTEIN-1; INSULIN-RESISTANCE; METABOLIC SYNDROME; FACTOR-ALPHA; BODY-FAT; RISK-FACTORS; OBESE WOMEN; WEIGHT-LOSS AB Background-Excess adiposity is associated with greater systemic inflammation. Whether visceral adiposity is more proinflammatory than subcutaneous abdominal adiposity is unclear. Methods and Results-We examined the relations of abdominal subcutaneous adipose tissue ( SAT) and visceral adipose tissue ( VAT), assessed by multidetector computerized tomography, to circulating inflammatory and oxidative stress biomarkers in 1250 Framingham Heart Study participants (52% women; age 60 +/- 9 years). Biomarkers were examined in relation to increments of SAT and VAT after adjustment for age, sex, smoking, physical activity, menopause, hormone replacement therapy, alcohol, and aspirin use; additional models included body mass index and waist circumference. SAT and VAT were positively and similarly ( with respect to strength of association) related to C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, P-selectin, and tumor necrosis factor receptor-2 (multivariable model R-2 0.06 to 0.28 [ SAT] and 0.07 to 0.29 [ VAT]). However, compared with SAT, VAT was more highly associated with urinary isoprostanes and monocyte chemoattractant protein-1 ( SAT versus VAT comparison: isoprostanes, R2 0.07 versus 0.10, P = 0.002; monocyte chemoattractant protein-1, R2 0.07 versus 0.08, P = 0.04). When body mass index and waist circumference were added to the models, VAT remained significantly associated with only C-reactive protein ( P = 0.0003 for women; P = 0.006 for men), interleukin-6 ( P = 0.01), isoprostanes ( P = 0.0002), and monocyte chemoattractant protein-1 ( P = 0.008); SAT only remained associated with fibrinogen ( P = 0.01). Conclusions-The present cross-sectional data support an association between both SAT and VAT with inflammation and oxidative stress. The data suggest that the contribution of visceral fat to inflammation may not be completely accounted for by clinical measures of obesity ( body mass index and waist circumference). C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Brigham & Womens Hosp, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA 02115 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Dept Cardiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Dept Prevent Med, Boston, MA 02118 USA. Semmelweis Univ, H-1085 Budapest, Hungary. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Murabito, Joanne/0000-0002-0192-7516; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Maurovich-Horvat, Pal/0000-0003-0885-736X FU NHLBI NIH HHS [R01-HL076784, 2K24HL04334, N01-HC-25195, R01-HL064753]; NIA NIH HHS [R01-AG028321]; NIDDK NIH HHS [T32 DK007529] NR 52 TC 409 Z9 419 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 11 PY 2007 VL 116 IS 11 BP 1234 EP 1241 DI 10.1161/CIRCULATIONAHA.107.710509 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 208QL UT WOS:000249334200006 PM 17709633 ER PT J AU Collard, CD Shernan, SK Fox, AA Bernig, T Chanock, SJ Vaughn, WK Takahashi, K Ezekowitz, AB Jarolim, P Body, SC AF Collard, Charles D. Shernan, Stanton K. Fox, Amanda A. Bernig, Toralf Chanock, Stephen J. Vaughn, William K. Takahashi, Kazue Ezekowitz, Alan B. Jarolim, Petr Body, Simon C. TI The MBL2 'LYQA secretor' haplotype is an independent predictor of postoperative myocardial infarction in whites undergoing coronary artery bypass graft surgery SO CIRCULATION LA English DT Article; Proceedings Paper CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc DE genetics; myocardial infarction; immunology; inflammation; surgery ID MANNOSE-BINDING LECTIN; COMPLEMENT ACTIVATION; GENETIC-VARIATION; OXIDATIVE STRESS; EARLY RESTENOSIS; PROTEIN GENE; PATHWAY; GENOTYPE; RISK; ENDARTERECTOMY AB Background - Mannose-binding lectin (MBL) is an important component of innate immunity and activator of the lectin complement pathway. Within the MBL2 gene are seven 5' "secretor" haplotypes that code for altered serum MBL levels and complement activation. However, recent evidence suggests that 3' MBL2 haplotypes may also modify MBL function and circulating levels. Because MBL and the lectin complement pathway have been implicated in cardiovascular injury, we investigated whether MBL2 haplotypes are independently associated with an increased risk of postoperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft surgery. Methods and Results - Genotyping of 18 polymorphic sites within the MBL2 gene was performed in a prospective, longitudinal multi-institutional study of 978 patients undergoing primary coronary artery bypass graft-only surgery with cardiopulmonary bypass between August 2001 and May 2005. After adjustment for multiple comparisons by permutation testing, multivariate, stepwise logistic regression, including a score test, was performed controlling for patient demographics, preoperative risk factors, medications, and intraoperative variables to determine if MBL2 secretor haplotypes are independent predictors of PMI in whites undergoing primary coronary artery bypass graft surgery. Neither the 5' nor 3' MBL2 haplotypes alone were associated with an increased incidence of PMI. However, the incidence of PMI in whites (n = 843) expressing the combined MBL2 5' LYQA secretor haplotype (CGTCGG) and 3' haplotype (CGGGT) was significantly higher than in whites not expressing the haplotype (38% versus 10%; P < 0.007). Moreover, the combined MBL2 LYQA secretor haplotype was an independent predictor of PMI in whites after primary coronary artery bypass graft surgery after adjustment for other covariates (P < 0.02; adjusted OR: 3.97; 95% CI: 1.30 to 12.07). The combined MBL2 LYQA secretor haplotype in whites was also an independent predictor of postoperative CKMB levels exceeding 60 ng/mL (P < 0.02; adjusted OR: 4.48; 95% CI: 1.95 to 16.80). Inclusion of the combined MBL2 LYQA secretor haplotype improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.715 versus 0.705). Conclusions - The combined MBL2 LYQA secretor haplotype is a novel independent predictor of PMI and may aid in preoperative risk stratification of whites undergoing primary coronary artery bypass graft surgery. C1 St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiovasc Anesthesiol, Houston, TX 77030 USA. Harvard Univ, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Div Biostat & Epidemiol, Houston, TX 77030 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Lab Dev Immunol, Boston, MA USA. Merck Res Labs, Rahway, NJ USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. RP Collard, CD (reprint author), St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiovasc Anesthesiol, 6720 Bertner Ave, Houston, TX 77030 USA. EM ccollard@heart.thi.tmc.edu FU NHLBI NIH HHS [K23 HL068774, HL-068774, K23 HL068774-01A1]; PHS HHS [M01 02558] NR 33 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 11 PY 2007 VL 116 IS 11 SU S BP I106 EP I112 DI 10.1161/CIRCULATIONAHA.106.679530 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 209BY UT WOS:000249364500015 PM 17846289 ER PT J AU Hubner, J Sprenger, A Klein, C Hagenah, J Rambold, H Zuhlke, C Kompf, D Rolfs, A Kimmig, H Helmchen, C AF Huebner, J. Sprenger, A. Klein, C. Hagenah, J. Rambold, H. Zuehlke, C. Koempf, D. Rolfs, A. Kimmig, H. Helmchen, C. TI Eye movement abnormalities in spinocerebellar ataxia type 17 (SCA17) SO NEUROLOGY LA English DT Article ID DOMINANT CEREBELLAR-ATAXIA; SMOOTH-PURSUIT; SACCADE VELOCITY; OCULOMOTOR ABNORMALITIES; PARKINSONIAN SYNDROMES; HUNTINGTON-DISEASE; CLINICAL-FEATURES; DEFICITS; LESIONS; INITIATION AB Background: Spinocerebellar ataxia type 17 ( SCA17) is associated with an expansion of CAG/ CAA trinucleotide repeats in the gene encoding the TATA- binding protein. In this quantitative characterization of eye movements in SCA17 mutation carriers, we investigated whether eye movement abnormalities originate from multiple lesion sites as suggested by their phenotypic heterogeneity. Methods: Eye movements ( saccades, smooth pursuit) of 15 SCA17 mutation carriers ( mean age 36.9 years, range 20 to 54 years; mean disease duration 7.3 years, range 0 to 20 years; 2 clinically unaffected, 13 affected) were compared with 15 age- matched control subjects using the video- based two- dimensional EYELINK II system. Results: Smooth pursuit initiation ( step- ramp paradigm) and maintenance were strongly impaired, i. e., pursuit latency was increased and acceleration decreased, whereas latency and position error of the first catch- up saccade were normal. Visually guided saccades were hypometric but had normal velocities. Gaze- evoked nystagmus was found in one- third of the mutation carriers, including downbeat and rebound nystagmus. There was a pathologic increase in error rates of antisaccades ( 52%) and memory- guided saccades ( 42%). Oculomotor disorders were not correlated with repeat length. Smooth pursuit impairment and saccadic disorders increased with disease duration. Conclusions: Several oculomotor deficits of spinocerebellar ataxia type 17 ( SCA17) mutation carriers are compatible with cerebellar degeneration. This is consistent with histopathologic and imaging ( morphometric) data. In contrast, increased error rates in antisaccades and memory-guided saccades point to a deficient frontal inhibition of reflexive movements, which is probably best explained by cortical dysfunction and may be related to other phenotypic SCA17 signs, e. g., dementia and parkinsonism. C1 Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Univ Lubeck, Inst Human Genet, Lubeck, Germany. NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. Univ Rostock, Dept Neurol, D-2500 Rostock, Germany. RP Helmchen, C (reprint author), Univ Lubeck, Dept Neurol, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM christoph.helmchen@neuro.uni-luebeck.de RI Sprenger, Andreas/C-7612-2009; OI Sprenger, Andreas/0000-0001-9255-7911; Rambold, Holger/0000-0002-8056-9429 NR 45 TC 17 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 11 PY 2007 VL 69 IS 11 BP 1160 EP 1168 DI 10.1212/01.wnl.0000276958.91986.89 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 208VA UT WOS:000249346100013 PM 17846415 ER PT J AU Drayna, DT AF Drayna, Dennis T. TI Absolute pitch: A special group of ears SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material C1 NIH, Natl Inst Deafness & Other Commun Disorder, Rockville, MD 20850 USA. RP Drayna, DT (reprint author), NIH, Natl Inst Deafness & Other Commun Disorder, 5 Res Court, Rockville, MD 20850 USA. EM drayna@nidcd.nih.gov NR 7 TC 7 Z9 7 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 11 PY 2007 VL 104 IS 37 BP 14549 EP 14550 DI 10.1073/pnas.0707287104 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 211GT UT WOS:000249513000002 PM 17846431 ER PT J AU Mizuuchi, M Rice, PA Wardle, SJ Haniford, DB Mizuuchi, K AF Mizuuchi, Michiyo Rice, Phoebe A. Wardle, Simon J. Haniford, David B. Mizuuchi, Kiyoshi TI Control of transposase activity within a transpososome by the configuration of the flanking DNA segment of the transposon SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA transposition; phage Mu; recombination ID V(D)J RECOMBINATION; STRAND TRANSFER; MU-TRANSPOSASE; SYNAPTIC COMPLEX; IMMUNE-SYSTEM; CLEAVAGE; INTEGRATION; SITE; INTERMEDIATE; RAG1 AB The multiple steps of DNA transposition take place within a large complex called the transpososome, in which a pair of transposon DNA ends are synapsed by a multimer of the transposase protein. The final step, a DNA strand transfer reaction that joins the transposon ends to the target DNA strands, entails no net change in the number of high-energy chemical bonds. Physiology demands that, despite remaining stably associated with the transpososome, the strand transfer products undergo neither the reverse reaction nor any further cleavage reactions. Accordingly, when the Mu or Tn10 strand transfer complex was produced in vitro through transposase-catalyzed reaction steps, reverse reactions were undetectable. In contrast, when the Mu or Tn10 strand transfer complexes were assembled from DNA already having the structure of the strand transfer product, we detected a reaction that resembled reversal of target DNA strand transfer. The stereoselectivity of phosphorothioate-containing substrates indicated that this reaction proceeds as the pseudoreversal of the normal target DNA strand transfer step. Comparison of the reactivity of closely related Mu substrate DNA structures indicated that the configuration of the flanking DNA outside of the transposon sequence plays a key role in preventing the transposon end cleavage reaction after the strand transfer step. C1 NCI, NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. Univ Western Ontario, Dept Biochem, London, ON N6A 5C1, Canada. RP Mizuuchi, K (reprint author), NCI, NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. EM kmizu@helix.nih.gov FU Intramural NIH HHS NR 41 TC 3 Z9 3 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 11 PY 2007 VL 104 IS 37 BP 14622 EP 14627 DI 10.1073/pnas.0706556104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 211GT UT WOS:000249513000016 PM 17785414 ER PT J AU Varma, S Wendler, D AF Varma, Sumeeta Wendler, David TI Medical decision making for patients without surrogates SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PATIENTS RESUSCITATION PREFERENCES; LIFE-SUSTAINING TREATMENT; SELF-DETERMINATION ACT; ADVANCE DIRECTIVES; PRIMARY-CARE; PHYSICIANS; PREDICTIONS; SUPPORT; PROXY AB Patients who lose decision-making capacity and lack advance directives and next of kin present a quandary for physicians. Current mechanisms for making treatment decisions for these patients rely on decision makers, such as courts, public guardians, committees, and physicians, who typically do not have sufficient knowledge to predict the patients' preferences. Thus, these mechanisms likely yield decisions that are inconsistent with patients' treatment preferences in many cases. A population-based treatment indicator is a computer-based tool that predicts which treatment a given patient would prefer based on the treatment preferences of similar patients in similar situations. A recent analysis suggests that a population-based treatment indicator could predict patient preferences as accurately as patient-appointed surrogates and next of kin. This analysis suggests that a population-based treatment indicator may provide a mechanism to respect the treatment preferences of patients without surrogates and ensure that their treatment preferences are respected as much as the preferences of patients who have surrogates. Collection of data on patients' treatment preferences, especially those without surrogates, incorporation of these data into a treatment indicator, and exploration of ways to implement this approach for patients without surrogates are called for. C1 NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Ctr Clin, Dept Bioeth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@mail.nih.gov NR 25 TC 16 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 10 PY 2007 VL 167 IS 16 BP 1711 EP 1715 DI 10.1001/archinte.167.16.1711 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 208TV UT WOS:000249343000002 PM 17846389 ER PT J AU Corti, MC Baggio, G Sartori, L Barbato, G Manzato, E Musacchio, E Ferrucci, L Cardinali, G Donato, D Launer, LJ Zambon, S Crepaldi, G Guralnik, JM AF Corti, Maria-Chiara Baggio, Giovannella Sartori, Leonardo Barbato, Gianmaria Manzato, Enzo Musacchio, Estella Ferrucci, Luigi Cardinali, Giulia Donato, Daniele Launer, Lenore J. Zambon, Sabina Crepaldi, Gaetano Guralnik, Jack M. TI White matter lesions and the risk of incident hip fracture in older persons - Results from the Progetto Veneto Anziani study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID LOWER-EXTREMITY FUNCTION; ELDERLY-PEOPLE; BRAIN; MORTALITY; STROKE; AGE; LEUKOARAIOSIS; DISABILITY; HYPERINTENSITIES; ABNORMALITIES AB Background: White matter lesions (WMLs) are associated with hypertension, an increased risk of falling, and impaired physical and cognitive performance that may affect the mechanical effect of falls. Methods: We hypothesized that WMLs are a risk factor for hip fracture (HF). We studied a sample of 820 community dwelling Italian persons 65 years and older from the cohort of the Progetto Veneto Anziani Study who underwent brain magnetic resonance imaging at baseline. Subjects were classified as having no lesions, focal lesions, or diffuse WMLs. Results: Compared with those with no lesions, participants with diffuse WMLs were older, reported more falls, and had worse physical and cognitive performance, all factors implicated in the causal pathway to HF. During 9 years of follow-up, 51 HFs occurred. Hip fracture risk associated with diffuse WMLs markedly differed between participants younger than 80 years vs those 80 years and older. After adjustment among participants younger than 80 years, diffuse WMLs compared with no lesions were associated with a 2.7-fold (95% confidence interval, 1.1-7.1) increase in the risk of HF. Focal lesions were not statistically significantly associated with an increased risk of HF in the same age group ( hazard ratio, 2.0; 95% confidence interval, 0.6-7.6). No associations between diffuse WMLs, focal lesions, and HF were evident among participants 80 years and older, possibly because of the limited sample size. Conclusions: White matter lesions represent an independent risk factor for HF in persons younger than 80 years. Older persons with diffuse WMLs should be considered candidates for multifactorial interventions aimed at reducing the risk of falling and fractures. C1 Azienda Unita Locale Socio Sanitaria 16, I-35131 Padua, Italy. Univ Padua, Sch Med, Azienda Osped, Padua, Italy. Univ Padua, Sch Med, Dept Med & Surg Sci, Padua, Italy. CNR, Aging Sect, Inst Neurosci, Padua, Italy. Azienda ULSS12, Venice, Italy. NIA, Ctr Gerontol Res, Baltimore Longitudinal Study Aging, Baltimore, MD 21224 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Corti, MC (reprint author), Azienda Unita Locale Socio Sanitaria 16, Via Scrovegni 14, I-35131 Padua, Italy. EM chiara.corti@sanita.padova.it FU Intramural NIH HHS [Z99 AG999999] NR 42 TC 22 Z9 23 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 10 PY 2007 VL 167 IS 16 BP 1745 EP 1751 DI 10.1001/archinte.167.16.1745 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 208TV UT WOS:000249343000007 PM 17846393 ER PT J AU D'Souza, T Indig, FE Morin, PJ AF D'Souza, Theresa Indig, Fred E. Morin, Patrice J. TI Phosphorylation of claudin-4 by PKC epsilon regulates tight junction barrier function in ovarian cancer cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE claudin; tight junction; ovarian cancer; phosphorylation; PKC ID PROTEIN-KINASE-C; CLOSTRIDIUM-PERFRINGENS ENTEROTOXIN; PARACELLULAR CHLORIDE PERMEABILITY; DIFFERENTIAL GENE-EXPRESSION; EPITHELIAL-CELLS; CARCINOMA CELLS; PANCREATIC-CANCER; ATYPICAL PKC; MAP KINASE; CYCLIC-AMP AB Claudin proteins belong to a large family of transmembrane proteins essential to the formation and maintenance of tight junctions (TJs). In ovarian cancer, TJ protein claudin-4 is frequently overexpressed and may have roles in survival and invasion, but the molecular mechanisms underlying its regulation are poorly understood. In this report, we show that claudin-4 can be phosphorylated by protein kinase C (PKC) at Thr189 and Ser194 in ovarian cancer cells and overexpression of a claudin-4 mutant protein mimicking the phosphorylated state results in the disruption of the barrier function. Furthermore, upon phorbol ester-mediated PKC activation of OVCA433 cells, TJ strength is decreased and claudin-4 localization is altered. Analyses using PKC inhibitors and siRNA suggest that PKC epsilon, an isoform typically expressed in ovarian cancer cells, may be important in the TPA-mediated claudin-4 phosphorylation and weakening of the TJs. Furthermore, immunofluorescence studies showed that claudin-4 and PKC epsilon: are co-localized at the TJs in these cells. The modulation of claudin-4 activity by PKC epsilon may not only provide a mechanism for disrupting TJ function in ovarian cancer, but may also be important in the regulation of TJ function in normal epithelial cells. Published by Elsevier Inc. C1 NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, Res Resources Branch, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA. RP Morin, PJ (reprint author), NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM morinp@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000512-10] NR 67 TC 52 Z9 52 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD SEP 10 PY 2007 VL 313 IS 15 BP 3364 EP 3375 DI 10.1016/j.yexcr.2007.06.026 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 206RT UT WOS:000249201300018 PM 17678893 ER PT J AU Camphausen, K Tofilon, PJ AF Camphausen, Kevin Tofilon, Philip J. TI Inhibition of histone deacetylation: A strategy for tumor radiosensitization SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID HYDROXAMIC ACID SAHA; DOUBLE-STRAND BREAKS; HUMAN LEUKEMIA-CELLS; DNA-DAMAGE RESPONSE; SODIUM-BUTYRATE; PHASE-I; IONIZING-RADIATION; ANTITUMOR-ACTIVITY; GAMMA-H2AX FOCI; SOLID TUMORS AB Recently, strategies to enhance tumor radiosensitivity have begun to focus on targeting the molecules and processes that regulate cellular radioresponse. A molecular target that has begun to receive considerable attention is histone acetylation. Histone acetylation is determined by the dynamic interaction of two families of enzymes: histone acetylases and histone deacetylases (HDACs). Histone acetylation plays a role in regulating chromatin structure and gene expression two parameters that have long been considered determinants of radioresponse. As a means of modifying histone acetylation status, considerable effort has been put into the development of inhibitors of HDAC activity. This has led to the generation of a relatively large number of structurally diverse compounds that can inhibit HDAC activity resulting in histone hyperacetylation. Many of the newer HDAC inhibitor compounds have been designed with better bioavailability or pharmacology than the first-generation compounds. Whereas a number of these second-generation HDAC inhibitors have antitumor activity in preclinical cancer models when delivered as single agents, early clinical data demonstrate only cytostasis when used as monotherapy. However, recent preclinical studies have indicated that HDAC inhibitors from structurally diverse classes can enhance both the in vitro and in vivo radiosensitivity of human tumor cell lines generated from a spectrum of solid tumors. HDAC inhibitors are in clinical trials as single modalities, in combination with chemotherapeutic agents, and recently, in combination with radiotherapy. C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Drug Discovery Program, Tampa, FL USA. RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, 10 Ctr Dr,Bldg 10 CRC B2-3562, Bethesda, MD 20892 USA. EM camphauk@mail.nih.gov FU Intramural NIH HHS NR 63 TC 107 Z9 111 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2007 VL 25 IS 26 BP 4051 EP 4056 DI 10.1200/JCO.2007.11.6202 PG 6 WC Oncology SC Oncology GA 233EK UT WOS:000251073000004 PM 17827453 ER PT J AU Fuxe, K Ferre, S Genedani, S Franco, R Agnati, LF AF Fuxe, Kjell Ferre, Sergi Genedani, Susanna Franco, Rafael Agnati, Luigi F. TI Adenosine receptor-dopamine receptor interactions in the basal ganglia and their relevance for brain function SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE dopamine D-1 receptor; dopamine D-2 receptor; adenosine A(1) receptor; adenosine A(2A) receptor; heteromeric receptor complexes; Parkinson's disease; schizophrenia; drug addiction ID BIOLUMINESCENCE ENERGY-TRANSFER; COTRANSFECTED FIBROBLAST CELLS; A(2A) RECEPTORS; A(1) RECEPTOR; PARKINSONS-DISEASE; D-1 RECEPTORS; ANTAGONISTIC INTERACTION; QUANTITATIVE ASSESSMENT; MOLECULAR-MECHANISMS; MEDIATED MODULATION AB The dopamine D-1 and D-2 receptors are major receptors in the regulation of striatal function and striatal adenosine A(1) and A(2A) receptors are major modulators of their signaling. The evidence suggests the existence of antagonistic A(1)-D-1 heteromeric receptor complexes in the basal ganglia and prefrontal cortex and especially in the direct striatonigral-striatoentopeduncular GABA pathways. The neurochemical and behavioral findings showing antagonistic A(1)-D-1 receptor interactions can be explained by the existence of such A(1)-D-1 heteromeric receptor complexes and of antagonistic interactions at the level of the second messengers. In contrast, A(2A)-D-2 receptor heteromers may exist in the dorsal and ventral striato-pallidal GABA pathways, where activation of A(2A) receptors reduces D-2 receptor recognition, coupling and signaling. As a result of the A(2A) receptor-induced reduction of D-2 receptor signaling, the activity of these GABA neurons is increased resulting in reduced motor and reward functions mediated via the indirect pathway, causing a reduced glutamate drive to the prefrontal and motor areas of the cerebral cortex. Thus, A(2A) receptor antagonists and A(2A) receptor agonists, respectively, may offer novel treatments of Parkinson's disease (reduced D-2 receptor signaling) and of schizophrenia and drug addiction (increased D-2 receptor signaling). (c) 2007 Elsevier Inc. All rights reserved. C1 Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. Univ Barcelona, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. Univ Modena, Univ Barcelona, I-41100 Modena, Italy. RP Fuxe, K (reprint author), Karolinska Inst, Dept Neurosci, Retzus Vag 8, S-17177 Stockholm, Sweden. EM kiell.fuxe@ki.se RI Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015; Genedani, Susanna/K-4370-2016; OI Ferre, Sergi/0000-0002-1747-1779; Franco, Rafael/0000-0003-2549-4919; Genedani, Susanna/0000-0003-1526-153X; Fuxe, Kjell/0000-0001-8491-4288 NR 55 TC 130 Z9 132 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD SEP 10 PY 2007 VL 92 IS 1-2 BP 210 EP 217 DI 10.1016/j.physbeh.2007.05.034 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 219QL UT WOS:000250099600036 PM 17572452 ER PT J AU Haugen, P Bhattacharya, D Palmer, JD Turner, S Lewis, LA Pryer, KM AF Haugen, Peik Bhattacharya, Debashish Palmer, Jeffrey D. Turner, Sean Lewis, Louise A. Pryer, Kathleen M. TI Cyanobacterial ribosomal RNA genes with multiple, endonuclease-encoding group 1 introns SO BMC EVOLUTIONARY BIOLOGY LA English DT Article ID GROUP-I INTRONS; RIBONUCLEOTIDE REDUCTASE GENES; HOMING ENDONUCLEASE; HYPERTHERMOPHILIC BACTERIA; BACILLUS-ANTHRACIS; PHAGE TWORT; SP-NOV; SEQUENCE; DNA; SUPERFAMILY AB Background: Group I introns are one of the four major classes of introns as defined by their distinct splicing mechanisms. Because they catalyze their own removal from precursor transcripts, group I introns are referred to as autocatalytic introns. Group I introns are common in fungal and protist nuclear ribosomal RNA genes and in organellar genomes. In contrast, they are rare in all other organisms and genomes, including bacteria. Results: Here we report five group I introns, each containing a LAGLIDADG homing endonuclease gene (HEG), in large subunit (LSU) rRNA genes of cyanobacteria. Three of the introns are located in the LSU gene of Synechococcus sp.C9, and the other two are in the LSU gene of Synechococcus lividus strain CI. Phylogenetic analyses show that these introns and their HEGs are closely related to introns and HEGs located at homologous insertion sites in organellar and bacterial rDNA genes. We also present a compilation of group I introns with homing endonuclease genes in bacteria. Conclusion: We have discovered multiple HEG-containing group I introns in a single bacterial gene. To our knowledge, these are the first cases of multiple group I introns in the same bacterial gene (multiple group I introns have been reported in at least one phage gene and one prophage gene). The HEGs each contain one copy of the LAGLIDADG motif and presumably function as homodimers. Phylogenetic analysis, in conjunction with their patchy taxonomic distribution, suggests that these intron-HEG elements have been transferred horizontally among organelles and bacteria. However, the mode of transfer and the nature of the biological connections among the intron-containing organisms are unknown. C1 Univ Iowa, Dept Biol Sci, Iowa City, IA 52242 USA. Univ Iowa, Roy J Carver Ctr Comparat Genom, Iowa City, IA 52242 USA. Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. Univ Connecticut, Dept Ecol & Evolutionary Biol, Storrs, CT 06269 USA. Duke Univ, Dept Biol, Durham, NC 27708 USA. Univ Tromso, Dept Mol Biotechnol, Inst Med Biol, N-9037 Tromso, Norway. RP Haugen, P (reprint author), Univ Iowa, Dept Biol Sci, 446 Biol Bldg, Iowa City, IA 52242 USA. EM peik.haugen@fagmed.uit.no; debashi-bhattacharya@uiowa.edu; jpalmer@indiana.edu; turner@ncbi.nlm.nih.gov; louise.lewis@uconn.edu; kathleen.pryer@duke.edu RI Palmer, Jeffrey/P-6747-2014 OI Palmer, Jeffrey/0000-0002-4626-2220 FU Intramural NIH HHS; NIGMS NIH HHS [GM-70612, R01 GM070612] NR 47 TC 16 Z9 17 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD SEP 8 PY 2007 VL 7 AR 159 DI 10.1186/1471-2148-7-159 PG 9 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 216UJ UT WOS:000249904200001 PM 17825109 ER PT J AU Wang, PS Aguilar-Gaxiola, S Alonso, J Angermeyer, MC Borges, G Bromet, EJ Bruffaerts, R de Girolamo, G de Graaf, R Gureje, O Haro, JM Karam, EG Kessler, RC Kovess, V Lane, MC Lee, S Levinson, D Ono, Y Petukhova, M Posada-Villa, J Seedat, S Wells, JE AF Wang, Philip S. Aguilar-Gaxiola, Sergio Alonso, Jordi Angermeyer, Matthias C. Borges, Guilherme Bromet, Evelyn J. Bruffaerts, Ronny de Girolamo, Giovanni de Graaf, Ron Gureje, Oye Haro, Josep Maria Karam, Elie G. Kessler, Ronald C. Kovess, Viviane Lane, Michael C. Lee, Sing Levinson, Daphna Ono, Yutaka Petukhova, Maria Posada-Villa, Jose Seedat, Soraya Wells, J. Elisabeth TI Use of mental health services for anxiety, mood, and substance disorders in 17 countries in the WHO world mental health surveys SO LANCET LA English DT Article ID SELF-REPORTED USE; UNITED-STATES; ADMINISTRATIVE RECORDS; PRIMARY-CARE; PREVALENCE; PRIORITIES; SCALE; ORGANIZATION; SEVERITY; CIDI AB Background Mental disorders are major causes of disability worldwide, including in the low-income and middle-income countries least able to bear such burdens. We describe mental health care in 17 countries participating in the WHO world mental health (WMH) survey initiative and examine unmet needs for treatment. Methods Face-to-face household surveys were undertaken with 84850 community adult respondents in low-income or middle-income (Colombia, Lebanon, Mexico, Nigeria, China, South Africa, Ukraine) and high-income countries (Belgium, France, Germany, Israel, Italy, Japan, Netherlands, New Zealand, Spain, USA). Prevalence and severity of mental disorders over 12 months, and mental health service use, were assessed with the WMH composite international diagnostic interview. Logistic regression analysis was used to study sociodemographic predictors of receiving any 12-month services. Findings The number of respondents using any 12-month mental health services (57 [2%; Nigeria] to 1477 [18%; USA]) was generally lower in developing than in developed countries, and the proportion receiving services tended to correspond to countries' percentages of gross domestic product spent on health care. Although seriousness of disorder was related to service use, only five (11%; China) to 46 (61%; Belgium) of patients with severe disorders received any care in the previous year. General medical sectors were the largest sources of mental health services. For respondents initiating treatments, 152 (70%; Germany) to 129 (95%; Italy) received any follow-up care, and one (10%; Nigeria) to 113 (42%; France) received treatments meeting minimum standards for adequacy. Patients who were male, married, less-educated, and at the extremes of age or income were treated less. Interpretation Unmet needs for mental health treatment are pervasive and especially concerning in less-developed countries. Alleviation of these unmet needs will require expansion and optimum allocation of treatment resources. C1 NIMH, Div Serv & Intervent Res, Rockville, MD 20857 USA. Univ Calif Davis, Ctr Reduct Hlth Disparities, Davis, CA 95616 USA. Inst Municipal Invest Med, Hlth Serv Res Unit, E-08003 Barcelona, Spain. Univ Leipzig, Dept Psychiat, D-7010 Leipzig, Germany. Univ Autonoma Metropolitana, Inst Nacl Psiquiatria, Mexico City, DF, Mexico. SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. Univ Hosp Gasthuisberg, Dept Neurosci & Psychiat, Gasthuisberg, Belgium. AUSL Bologna, Dept Mental Hlth, Bologna, Italy. Netherlands Inst Mental Hlth & Addict, Utrecht, Netherlands. Univ Coll Ibadan Hosp, Dept Psychiat, Ibadan, Nigeria. Fdn Sant Joan de Deu, Sant Joan de Deu SSM, Barcelona, Spain. Balamand Univ, Fac Med, St George Hosp Univ Med Ctr, Dept Psychiat & Clin Psychol, Beirut, Lebanon. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Fdn MGEN Sante Publ, Paris, France. Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Minist Hlth, Mental Hlth Serv, Jerusalem, Israel. Keio Univ, Ctr Hlth, Tokyo, Japan. Colegio Mayor Cundinamarca Univ, Saidarriaga Concha Fdn, Bogota, Colombia. MRC, Res Unit Anxiety & Stress Disorders, Cape Town, South Africa. Christchurch Sch Med, Dept Publ Hlth & Gen Practice, Christchurch, New Zealand. RP Wang, PS (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd,Rm 7141,MSC 9629, Bethesda, MD 20892 USA. EM wangphi@mail.nih.gov RI Alonso, Jordi/A-5514-2010; Lee, Sing/O-2136-2015; Haro, Josep Maria/D-1423-2011; OI Alonso, Jordi/0000-0001-8627-9636; Haro, Josep Maria/0000-0002-3984-277X; Borges, Guilherme/0000-0002-3269-0507 FU FIC NIH HHS [R01-TW006481, R03 TW006481, R03 TW006481-03]; NIDA NIH HHS [R01 DA016558, R01 DA016558-04]; NIMH NIH HHS [U13 MH066849, R01 MH059575, R01 MH059575-07, R01 MH061905, R01 MH061905-05, R01 MH069864, R01 MH069864-03, R01 MH070884, R01 MH070884-01A2, R01-MH059575, R01-MH069864, R01-MH61905, R01MH070884, R13 MH066849, R13 MH066849-04, R13-MH066849, U01 MH060220, U01 MH060220-06A1, U01-MH60220] NR 36 TC 416 Z9 423 U1 8 U2 66 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD SEP 8 PY 2007 VL 370 IS 9590 BP 841 EP 850 DI 10.1016/S0140-6736(07)61414-7 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 214JH UT WOS:000249733300029 PM 17826169 ER PT J AU Schiffman, M Castle, PE Jeronimo, J Rodriguez, AC Wacholder, S AF Schiffman, Mark Castle, Philip E. Jeronimo, Jose Rodriguez, Ana C. Wacholder, Sholom TI Human papillomavirus and cervical cancer SO LANCET LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; SQUAMOUS INTRAEPITHELIAL LESION; LIQUID-BASED CYTOLOGY; ASCUS-LSIL TRIAGE; CARCINOMA IN-SITU; INTERNATIONAL INCIDENCE RATES; FEMALE UNIVERSITY-STUDENTS; VIRUS-LIKE PARTICLES; HYBRID CAPTURE 2; FOLLOW-UP AB Cervical cancer is the second most common cancer in women, worldwide, and knowledge regarding its cause and pathogenesis is expanding rapidly. Persistent infection with one of about 15 genotypes of carcinogenic human papillomavirus (HPV) causes almost all cases. There are four major steps in cervical cancer development: infection of metaplastic epithelium at the cervical transformation zone, viral persistence, progression of persistently infected epithelium to cervical precancer, and invasion through the basement membrane of the epithelium. Infection is extremely common in young women in their first decade of sexual. activity. Persistent infections and precancer are established, typically within 5-10 years, from less than 10% of new infections. Invasive cancer arises over many years, even decades, in a minority of women with precancer, with a peak or plateau in risk at about 35-55 years of age. Each genotype of HPV acts as an independent infection, with differing carcinogenic risks linked to evolutionary species. Our understanding has led to improved prevention and clinical management strategies, including improved screening tests and vaccines. The new HPV-oriented model of cervical carcinogenesis should gradually replace older morphological models based only on cytology and histology. If applied wisely, HPV-related technology can minimise the incidence of cervical cancer, and the morbidity and mortality it causes, even in low-resource settings. C1 NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Schiffman, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM schiffmm@mail.nih.gov NR 171 TC 1016 Z9 1067 U1 42 U2 204 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP 8 PY 2007 VL 370 IS 9590 BP 890 EP 907 DI 10.1016/S0140-6736(07)61416-0 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 214JH UT WOS:000249733300033 PM 17826171 ER PT J AU Schaetzlein, S Kodandaramireddy, NR Ju, ZY Lechel, A Stepczynska, A Lilli, DR Clark, AB Rudolph, C Kuhnel, F Wei, KC Schlegelberger, B Schirmacher, P Kunkel, TA Greenberg, RA Edelmann, W Rudolph, KL AF Schaetzlein, Sonja Kodandaramireddy, N. R. Ju, Zhenyu Lechel, Andre Stepczynska, Anna Lilli, Dana R. Clark, Alan B. Rudolph, Cornelia Kuhnel, Florian Wei, Kaichun Schlegelberger, Brigitte Schirmacher, Peter Kunkel, Thomas A. Greenberg, Roger A. Edelmann, Winfried Rudolph, K. Lenhard TI Exonuclease-1 deletion impairs DNA damage signaling and prolongs lifespan of telomere-dysfunctional mice SO CELL LA English DT Article ID DOUBLE-STRAND BREAKS; CELL-CYCLE; PULMONARY-FIBROSIS; HUMAN FIBROBLASTS; BUDDING YEAST; IN-VIVO; CANCER; CHECKPOINT; SENESCENCE; REPAIR AB Exonuclease-1 (EXO1) mediates checkpoint induction in response to telomere dysfunction in yeast, but it is unknown whether EXO1 has similar functions in mammalian cells. Here we show that deletion of the nuclease domain of Exo1 reduces accumulation of DNA damage and DNA damage signal induction in telomeredysfunctional mice. Exo1 deletion improved organ maintenance and lifespan of telomeredysfunctional mice but did not increase chromosomal instability or cancer formation. Deletion of Exo1 also ameliorated the induction of DNA damage checkpoints in response to g-irradiation and conferred cellular resistance to 6-thioguanine-induced DNA damage. Exo1 deletion impaired upstream induction of DNA damage responses by reducing ssDNA formation and the recruitment of Replication Protein A (RPA) and ATR at DNA breaks. Together, these studies provide evidence that EXO1 contributes to DNA damage signal induction in mammalian cells, and deletion of Exo1 can prolong survival in the context of telomere dysfunction. C1 Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30625 Hannover, Germany. Hannover Med Sch, Inst Cell & Mol Pathol, D-30625 Hannover, Germany. Univ Penn, Sch Med, Abramson Famuly Canc Res Inst, Dept Canc Biol, Philadelphia, PA 19104 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Univ Hosp, Inst Pathol, D-69120 Heidelberg, Germany. RP Rudolph, KL (reprint author), Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30625 Hannover, Germany. EM lenhard.rudolph@uni-ulm.de OI Nalapareddy, Kodandaramireddy/0000-0003-3290-5114; Rudolph, Karl Lenhard/0000-0002-4839-2862 FU Intramural NIH HHS [Z99 ES999999]; NCI NIH HHS [R01CA093484] NR 60 TC 105 Z9 107 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD SEP 7 PY 2007 VL 130 IS 5 BP 863 EP 877 DI 10.1016/j.cell.2007.08.029 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 212GI UT WOS:000249581500018 PM 17803909 ER PT J AU Mckay, MM Morrison, DK AF Mckay, Melissa M. Morrison, Deborah K. TI Caspase-dependent cleavage disrupts the ERK cascade scaffolding function of KSR1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; SIGNAL-REGULATED KINASE; CYTOCHROME-C RELEASE; MAMMARY-GLAND; MAPK SCAFFOLD; GENE ENCODES; CELL-DEATH; APOPTOSIS; RAS; PATHWAY AB Kinase suppressor of Ras 1 (KSR1) is a protein scaffold that facilitates ERK cascade activation at the plasma membrane, a critical step in the signal transduction process that allows cells to respond to survival, proliferative, and differentiative cues. Here, we report that KSR1 undergoes caspase-dependent cleavage in apoptotic cells and that cleavage destroys the scaffolding function of the full-length KSR1 protein and generates a stable C-terminal fragment that can inhibit ERK activation. KSR1 is cleaved in response to multiple apoptotic stimuli and occurs in vivo during the involution of mouse mammary tissues, a morphogenic process requiring cellular apoptosis. In addition, we find that in comparison with KSR1 (-/-) mouse embryonic fibroblasts expressing wild type KSR1 (WT-KSR1), cells expressing a cleavage-resistant KSR1 protein (DEVA-KSR1) exhibit reduced apoptotic signaling in response to tumor necrosis factor- alpha/ cycloheximide treatment. The effect of DEVA-KSR1 expression was found to correlate with increased levels of active phosphoERK and could be significantly reversed by treating cells with the MEK inhibitor U0126. In contrast, reduced phosphoERK levels and enhanced apoptotic signaling were observed in cells constitutively expressing the C-terminal KSR1 fragment (CTF-KSR1). Moreover, we find that cleavage of WTKSR1 correlates with a dramatic reduction in active phosphoERK levels. These findings identify KSR1 as a caspase target and suggest that cleavage of the KSR1 scaffold represents another mechanism whereby caspases down-regulate ERK survival signaling to promote cellular apoptosis. C1 NCI Frederick, Natl Inst Hlth, Ctr Canc Res, Lab Cell & Dev Signaling, Ft Detrick, MD 21702 USA. RP Morrison, DK (reprint author), NCI Frederick, Natl Inst Hlth, Ctr Canc Res, Lab Cell & Dev Signaling, POB B, Ft Detrick, MD 21702 USA. EM dmorrison@ncifcrf.gov NR 47 TC 10 Z9 11 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 7 PY 2007 VL 282 IS 36 BP 26225 EP 26234 DI 10.1074/jbc.M702692200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 207GM UT WOS:000249239600027 PM 17613518 ER PT J AU Li, JH Han, SJ Hamdan, FF Kim, SK Jacobson, KA Bloodworth, LM Zhang, XH Wess, J AF Li, Jian Hua Han, Sung-Jun Hamdan, Fadi F. Kim, Soo-Kyung Jacobson, Kenneth A. Bloodworth, Lanh M. Zhang, Xiaohong Wess, Juergen TI Distinct structural changes in a g protein-coupled receptor caused by different classes of agonist ligands SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; BETA(2) ADRENERGIC-RECEPTOR; DISULFIDE CROSS-LINKING; CONFORMATIONAL-CHANGES; INVERSE AGONISM; CYTOPLASMIC END; MOLECULAR-BASIS; IN-SITU; SULFHYDRYL REACTIVITY; CONSTITUTIVE ACTIVITY AB The activity of Gprotein-coupled receptors can be modulated by different classes of ligands, including agonists that promote receptor signaling and inverse agonists that reduce basal receptor activity. The conformational changes in receptor structure induced by different agonist ligands are not well understood at present. In this study, we employed an in situ disulfide crosslinking strategy to monitor ligand-induced conformational changes in a series of cysteine-substituted mutant M-3 muscarinic acetylcholine receptors. The observed disulfide cross-linking patterns indicated that muscarinic agonists trigger a separation of the N-terminal segment of the cytoplasmic tail ( helix 8) from the cytoplasmic end of transmembrane domain I. In contrast, inverse muscarinic agonists were found to increase the proximity between these two receptor regions. These findings provide a structural basis for the opposing biological effects of muscarinic agonists and inverse agonists. This study also provides the first piece of direct structural information as to how the conformations induced by these two functionally different classes of ligands differ at the molecular level. Given the high degree of structural homology found among most G protein-coupled receptors, our findings should be of broad general relevance. C1 NIDDK, Natl Inst Hlth, Bioorgan Chem Lab, Mol Signaling Sect, Bethesda, MD 20892 USA. NIDDK, Natl Inst Hlth, Mol Recognit Sect, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDK, Natl Inst Hlth, Bioorgan Chem Lab, Mol Signaling Sect, Bldg 8A,Rm B1A-05,8 Ctr Dr,MSC 0810, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Li, Jianhua/B-7671-2011; Han, Sung-Jun/B-9547-2012 OI Jacobson, Kenneth/0000-0001-8104-1493; Li, Jianhua/0000-0002-5744-3182; FU Intramural NIH HHS NR 49 TC 36 Z9 38 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 7 PY 2007 VL 282 IS 36 BP 26284 EP 26293 DI 10.1074/jbc.M704875200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 207GM UT WOS:000249239600033 PM 17623649 ER PT J AU Das, A Boldogh, I Lee, JW Harrigan, JA Hegde, ML Piotrowski, J Pinto, ND Ramos, W Greenberg, MM Hazra, TK Mitra, S Bohr, VA AF Das, Aditi Boldogh, Istvan Lee, Jae Wan Harrigan, Jeanine A. Hegde, Muralidhar L. Piotrowski, Jason Pinto, Nadja de Souza Ramos, William Greenberg, Marc M. Hazra, Tapas K. Mitra, Sankar Bohr, Vilhelm A. TI The human Werner syndrome protein stimulates repair of oxidative DNA base damage by the DNA glycosylase NEIL1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXCISION-REPAIR; MAMMALIAN-CELLS; POLYMERASE-BETA; HELICASE ACTIVITY; WRN HELICASE; POLY(ADP-RIBOSE) POLYMERASE-1; FLAP ENDONUCLEASE-1; IDENTIFICATION; 8-OXOGUANINE; ACETYLATION AB The mammalian DNA glycosylase, NEIL1, specific for repair of oxidatively damaged bases in the genome via the base excision repair pathway, is activated by reactive oxygen species and prevents toxicity due to radiation. We show here that the Werner syndrome protein (WRN), a member of the RecQ family of DNA helicases, associates with NEIL1 in the early damage-sensing step of base excision repair. WRN stimulates NEIL1 in excision of oxidative lesions from bubble DNA substrates. The binary interaction between NEIL1 and WRN (K(D) = 60 nM) involves C-terminal residues 288-349 of NEIL1 and the RecQ C-terminal (RQC) region of WRN, and is independent of the helicase activity WRN. Exposure to oxidative stress enhances the NEIL-WRN association concomitant with their strong nuclear co-localization. WRN-depleted cells accumulate some prototypical oxidized bases (e. g. 8-oxoguanine, FapyG, and FapyA) indicating a physiological function of WRN in oxidative damage repair in mammalian genomes. Interestingly, WRN deficiency does not have an additive effect on in vivo damage accumulation in NEIL1 knockdown cells suggesting that WRN participates in the same repair pathway as NEIL1. C1 NIH, NIA, LAb Mol Gerontol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Chem, Baltimore, MD 21224 USA. Univ Texas, Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. RP Bohr, VA (reprint author), NIH, NIA, LAb Mol Gerontol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov RI Souza-Pinto, Nadja/C-3462-2013; OI Souza-Pinto, Nadja/0000-0003-4206-964X; Hegde, Muralidhar/0000-0001-7333-8123 FU Intramural NIH HHS; NCI NIH HHS [R01 CA81063, R01 CA102271, P01 CA 092584, R01 CA-074954]; NIA NIH HHS [P01 AG 021803, P01 AG021830]; NIAID NIH HHS [P01 AI062885]; NIEHS NIH HHS [P30 ES006676, ES06676] NR 66 TC 61 Z9 64 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 7 PY 2007 VL 282 IS 36 AR 26591 DI 10.1074/jbc.M703343200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 207GM UT WOS:000249239600062 PM 17611195 ER PT J AU Lowe, RH Karschner, EL Schwilke, EW Barnes, AJ Huestis, MA AF Lowe, Ross H. Karschner, Erin L. Schwilke, Eugene W. Barnes, Allan J. Huestis, Marilyn A. TI Simultaneous quantification of Delta 9-tetrahydrocannabinol, 11-hydroxy-Delta 9-tetrahydrocannabinol, and 11-nor-Delta 9-tetrahydrocannabinol-9-carboxylic acid in human plasma using two-dimensional gas chromatography, cryofocusing, and electron impact-mass spectrometry SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE tetrahydrocannabinol; plasma; gas chromatography-mass spectrometry; two-dimensional chromatography; cryofocusing ID CANNABIS-BASED MEDICINE; SOLID-PHASE EXTRACTION; DELTA(9)-TETRAHYDROCANNABINOL THC; CHEMICAL-IONIZATION; MULTIPLE-SCLEROSIS; ORAL APPLICATION; VALIDATED METHOD; DOUBLE-BLIND; MARIJUANA; HAIR AB A two-dimensional (2D) gas chromatography/electron impact-mass spectrometry (GC/EI-MS) method for simultaneous quantification of Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC), and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in human plasma was developed and validated. The method employs 2D capillary GC and cryofocusing for enhanced resolution and sensitivity. THC, 11-OH-THC, and THCCOOH were extracted by precipitation with acetonitrile followed by solid-phase extraction. GC separation of trimethylsilyl derivatives of analytes was accomplished with two capillary columns in series coupled via a pneumatic Deans switch system. Detection and quantification were accomplished with a bench-top single quadrupole mass spectrometer operated in electron impact-selected ion monitoring mode. Limits of quantification (LOQ) were 0.125, 0.25 and 0.125 ng/mL for THC, 11-OH-THC, and THCCOOH, respectively. Accuracy ranged from 86.0 to 113.0% for all analytes. Intra- and inter-assay precision, as percent relative standard deviation, was less than 14.1% for THC, 11-OH-THC, and THCCOOH. The method was successfully applied to quantification of THC and its 11-OH-THC and THCCOOH metabolites in plasma specimens following controlled administration of THC. (C) 2007 Elsevier B.V. All rights reserved. C1 Natl Inst Drug Abuse, Intramural Res Program, Chem & Drug Metab Sect, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Chem & Drug Metab Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000412-10, Z01 DA000413-10, Z01 DA000415-10] NR 35 TC 49 Z9 50 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD SEP 7 PY 2007 VL 1163 IS 1-2 BP 318 EP 327 DI 10.1016/j.chroma.2007.06.069 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 208HQ UT WOS:000249310800033 PM 17640656 ER PT J AU Malecki, M Jedrzejczak, R Stepien, PP Golik, P AF Malecki, Michal Jedrzejczak, Robert Stepien, Piotr P. Golik, Pawel TI In vitro reconstitution and characterization of the yeast mitochondrial degradosome complex unravels tight functional interdependence SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE mitochondria; RNA degradation; mitochondrial degradosome; exoribonuclease; helicase ID MESSENGER-RNA TURNOVER; DEAD-BOX PROTEINS; SACCHAROMYCES-CEREVISIAE; HELICASE ACTIVITY; TRANSLATION INITIATION; GENE-EXPRESSION; RIBONUCLEASE-II; POSTTRANSCRIPTIONAL PROCESSES; ARABIDOPSIS-THALIANA; REACTION-MECHANISM AB The mitochondrial degradosome (mtEXO), the main RNA-degrading complex of yeast mitochondria, is composed of two subunits: an exoribonuclease encoded by the DSS1 gene and an RNA helicase encoded by the SUV3 gene. We expressed both subunits of the yeast mitochondrial degradosome in Escherichia coli, reconstituted the complex in vitro and analyzed the RNase, ATPase and helicase activities of the two subunits interdependence. For every enzymatic activity, we observed significant changes when the relevant protein was present in the complex, compared to the activity measured for the protein alone. The ATPase activity of Suv3p is stimulated by RNA and its background activity in the absence of RNA is reduced greatly when the protein is in the complex with Dss1p. The Suv-3 protein alone does not display RNA-unwinding activity and the 3' to 5' directional helicase activity requiring a free 3' single-stranded substrate becomes apparent only when Suv3p is in complex with Dss1p. The Dssl protein alone does have some basal exoribonuclease activity, which is not ATP-dependent, but in the presence of Suv3p the activity of the entire complex is enhanced greatly and is entirely ATP-dependent, with no residual activity observed in the absence of ATP. Such absolute ATP-dependence is unique among known exoribonuclease complexes. On the basis of these results, we propose a model in which the Suv3p RNA helicase acts as a molecular motor feeding the substrate to the catalytic centre of the RNase subunit. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ Warsaw, Dept Genet & Biotechnol, PL-02106 Warsaw, Poland. Argonne Natl Lab, MCL Natl Canc Inst, Synchrotron Radiat Res Stn, Argonne, IL 60439 USA. Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. RP Golik, P (reprint author), Univ Warsaw, Dept Genet & Biotechnol, Pawinskiego 5A, PL-02106 Warsaw, Poland. EM pgolik@igib.uw.edu.pl RI Golik, Pawel/D-7788-2011 OI Golik, Pawel/0000-0001-7814-482X FU Intramural NIH HHS NR 74 TC 32 Z9 33 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 7 PY 2007 VL 372 IS 1 BP 23 EP 36 DI 10.1016/j.jmb.2007.06.074 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 207TN UT WOS:000249274100004 PM 17658549 ER PT J AU Purkiss, AG Bateman, OA Wyatt, K Wilmarth, PA David, LL Wistow, GJ Slingsby, C AF Purkiss, Andrew G. Bateman, Orval A. Wyatt, Keith Wilmarth, Phillip A. David, Larry L. Wistow, Graeme J. Slingsby, Christine TI Biophysical properties of gamma C-Crystallin in human and mouse eye lens: The role of molecular dipoles SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE crystallin; cysteine; eye lens; protein solubility; solution interactions ID X-RAY STRUCTURES; CATARACT FORMATION; BETA-CRYSTALLIN; GENE FAMILY; ANGSTROM; MUTATION; RESOLUTION; PROTEINS; YOUNG; AGE AB The eye lens is packed with soluble crystallin proteins, providing a lifetime of transparency and light refraction. gamma-Crystallins are major components of the dense, high refractive index central regions of the lens and generally have high solubility, high stability and high levels of cysteine residues. Human gamma C belongs to a group of gamma-crystallins with a pair of cysteine resi- dues at positions 78 and 79. Unlike other gamma-crystallins it has relatively low solubility, whereas mouse gamma C, which has the exposed C79 replaced with arginine, and a novel mouse splice variant, gamma Cins, are both highly soluble. Furthermore, human gamma C is extremely stable, while the mouse orthologs are less stable. Evolutionary pressure may have favoured stability over solubility for human gamma C and the reverse for the orthologs in the mouse. Mutation of C79 to R79, in human gamma C, greatly increased solubility, however, neither form produced crystals. Remarkably, when the human gamma D R36S crystallization cataract mutation was mimicked in human gamma C-crystallin, the, solubility of gamma C was dramatically increased, although it still did not crystallize. The highly soluble mouse gamma C-crystallin did crystallize. Its X-ray structure was solved and used in homology modelling of human gamma C, and its,, mutants C79R and R36S. The human gamma D R36S mutant was also modelled from human gamma D coordinates. Molecular dynamics simulation of the six molecules in the solution state showed that the human gamma Cs differed from gamma Ds in domain pairing, behaviour that correlates with interface sequence changes. When the fluctuations of the calculated molecular dipoles, for the six structures, over time were analysed, characteristic patterns for soluble gamma C and gamma D proteins were observed. Individual sequence changes that increase or decrease solubility correlated well with changes in the magnitude and direction of these dipoles. It is suggested that changes in surface residues have allowed adaptation for the differing needs of human and mouse lenses. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ London, Birkbeck Coll, Inst Struct Mol Biol, Dept Crystallog, London WC1E 7HX, England. NEI, Sect Mol Struct & Funct Gen, Bethesda, MD 20892 USA. Oregon Hlth & Sci Univ, Sch Dent, Dept Integrat Biosci, Portland, OR 97239 USA. RP Slingsby, C (reprint author), Univ London, Birkbeck Coll, Inst Struct Mol Biol, Dept Crystallog, London WC1E 7HX, England. EM C.Slingsby@mail.cryst.bbk.ac.uk FU Intramural NIH HHS [Z01 EY000320-09, Z01 EY000255-19]; Medical Research Council [G8303198]; NEI NIH HHS [Z01 EY000320, EY007755, R01 EY007755, Z01 EY000255, EY10572, P30 EY010572] NR 52 TC 18 Z9 18 U1 2 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 7 PY 2007 VL 372 IS 1 BP 205 EP 222 DI 10.1016/j.jmb.2007.06.049 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 207TN UT WOS:000249274100018 PM 17659303 ER PT J AU Prasad, R Liu, Y Deterding, LJ Poltoratsky, VP Kedar, PS Horton, JK Kanno, SI Asagoshi, K Hou, EW Khodyreva, SN Lavrik, OI Tomer, KB Yasui, A Wilson, SH AF Prasad, Rajendra Liu, Yuan Deterding, Leesa J. Poltoratsky, Vladimir P. Kedar, Padmini S. Horton, Julie K. Kanno, Shin-Ichiro Asagoshi, Kenjiro Hou, Esther W. Khodyreva, Svetlana N. Lavrik, Olga I. Tomer, Kenneth B. Yasui, Akira Wilson, Samuel H. TI HMGB1 is a cofactor in mammalian base excision repair SO MOLECULAR CELL LA English DT Article ID DNA-POLYMERASE-BETA; CELL NUCLEAR ANTIGEN; INDUCED CYTOTOXICITY; MISMATCH REPAIR; LYASE ACTIVITY; PROTEIN HMG1; SITE; DAMAGE; IDENTIFICATION; ACCUMULATION AB Deoxyribose phosphate (dRP) removal by DNA polymerase beta (Pol beta) is a pivotal step in base excision repair (BER). To identify BER cofactors, especially those with dRP lyase activity, we used a Pol 0 null cell extract and BER intermediate as bait for sodium borohydride crosslinking. Mass spectrometry identified the high-mobility group box 1 protein (HMGB1) as specifically interacting with the BER intermediate. Purified HMGB1 was found to have weak dRP lyase activity and to stimulate AP endonuclease and FEN1 activities on BER substrates. Coimmunoprecipitation experiments revealed interactions of HMGB1 with known BER enzymes, and GFP-tagged HMGB1 was found to accumulate at sites of oxidative DNA damage in living cells. HMGB1(-/-) mouse cells were slightly more resistant to MMS than wild-type cells, probably due to the production of fewer strand-break BER intermediates. The results suggest HMGB1 is a BER cofactor capable of modulating BER capacity in cells. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Tohoku Univ, Inst Dev Aging & Canc, Dept Mol Genet, Sendai, Miyagi 9808575, Japan. Russian Acad Sci, Siberian Div, Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013; Khodyreva, Svetlana/G-4659-2013; Lavrik, Olga /G-4641-2013 FU Intramural NIH HHS [Z01 ES050158-11, Z01 ES050159-11] NR 60 TC 72 Z9 77 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD SEP 7 PY 2007 VL 27 IS 5 BP 829 EP 841 DI 10.1016/j.molcel.2007.06.029 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 216AK UT WOS:000249849900012 PM 17803946 ER PT J AU Chakraborty, T Chowdhury, D Keyes, A Jani, A Subrahmanyam, R Ivanova, I Sen, R AF Chakraborty, Tirtha Chowdhury, Dipanjan Keyes, Amanda Jani, Anant Subrahmanyam, Ramesh Ivanova, Irina Sen, Ranjan TI Repeat organization and epigenetic regulation of the D-H-C-mu domain of the immunoglobulin heavy-chain gene locusi SO MOLECULAR CELL LA English DT Article ID CHROMATIN DOMAINS; V(D)J RECOMBINATION; HISTONE; HETEROCHROMATIN; METHYLATION; REARRANGEMENTS; BOUNDARIES; ELEMENT; SEGMENT; FETAL AB The first steps of murine immunoglobulin heavy-chain (IgH) gene recombination take place within a chromosomal domain that contains diversity (D-H) and joining (J(H)) gene segments, but not variable (V-H) gene segments. Here we show that the chromatin state of this domain is markedly heterogeneous. Specifically, only 5'- and 3'-most D-H gene segments carry active chromatin modifications, whereas intervening D(H)s are associated with heterochromatic marks that are maintained by ongoing histone deacetylation. The intervening D(H)s form part of a tandemly repeated sequence that expresses tissue-specific, antisense oriented transcripts. We propose that the intervening DH genes are actively suppressed by repeat-induced epigenetic silencing, which is reflected in their infrequent representation in DJ(H) junctions compared to the flanking D-H genes. C1 NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Yale Univ, Dept Chem Engn, New Haven, CT 06511 USA. Yale Univ, Sch Med, Program Immunol, New Haven, CT 06510 USA. RP Sen, R (reprint author), NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. EM rs465z@nih.gov RI Subrahmanyam, Ramesh/K-5503-2012 FU Intramural NIH HHS; NIGMS NIH HHS [GM38925] NR 31 TC 56 Z9 56 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD SEP 7 PY 2007 VL 27 IS 5 BP 842 EP 850 DI 10.1016/j.molcel.2007.07.010 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 216AK UT WOS:000249849900013 PM 17803947 ER PT J AU Albus, JS Bekey, GA Holland, JH Kanwisher, NG Krichmar, JL Mishkin, M Modha, DS Raichle, ME Shepherd, GM Tononi, G AF Albus, James S. Bekey, George A. Holland, John H. Kanwisher, Nancy G. Krichmar, Jeffrey L. Mishkin, Mortimer Modha, Dharmendra S. Raichle, Marcus E. Shepherd, Gordon M. Tononi, Giulio TI A proposal for a decade of the mind initiative SO SCIENCE LA English DT Letter C1 Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. Univ So Calif, Los Angeles, CA 90089 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. MIT, McGovern Inst, Cambridge, MA 02139 USA. Inst Neurosci, San Diego, CA 92121 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. IBM Corp, Almaden Res Ctr, San Jose, CA 95120 USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. Yale Univ, Sch Med, New Haven, CT 06510 USA. Univ Wisconsin, Dept Psychiat, Madison, WI 53719 USA. RP Albus, JS (reprint author), Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. RI Tononi, Giulio/B-8387-2009 NR 2 TC 25 Z9 27 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 7 PY 2007 VL 317 IS 5843 BP 1321 EP 1321 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 209GR UT WOS:000249377500014 PM 17823330 ER PT J AU El-Khorazaty, MN Johnson, AA Kiely, M El-Mohandes, AA Subramanian, S Laryea, HA Murray, KB Thornberry, JS Joseph, JG AF El-Khorazaty, M. Nabil Johnson, Allan A. Kiely, Michele El-Mohandes, Ayman Ae Subramanian, Siva Laryea, Haziel A. Murray, Kennan B. Thornberry, Jutta S. Joseph, Jill G. TI Recruitment and retention of low-income minority women in a behavioral intervention to reduce smoking, depression, and intimate partner violence during pregnancy SO BMC PUBLIC HEALTH LA English DT Article ID COMMUNITY-BASED RESEARCH; AFRICAN-AMERICAN; CLINICAL-TRIALS; HEALTH; PARTICIPATION; TUSKEGEE; BARRIERS; ISSUES; KENYA AB Background: Researchers have frequently encountered difficulties in the recruitment and retention of minorities resulting in their under-representation in clinical trials. This report describes the successful strategies of recruitment and retention of African Americans and Latinos in a randomized clinical trial to reduce smoking, depression and intimate partner violence during pregnancy. Socio-demographic characteristics and risk profiles of retained vs. non-retained women and lost to follow-up vs. dropped-out women are presented. In addition, subgroups of pregnant women who are less ( more) likely to be retained are identified. Methods: Pregnant African American women and Latinas who were Washington, DC residents, aged 18 years or more, and of 28 weeks gestational age or less were recruited at six prenatal care clinics. Potentially eligible women were screened for socio-demographic eligibility and the presence of the selected behavioral and psychological risks using an Audio Computer-Assisted Self-Interview. Eligible women who consented to participate completed a baseline telephone evaluation after which they were enrolled in the study and randomly assigned to either the intervention or the usual care group. Results: Of the 1,398 eligible women, 1,191 (85%) agreed to participate in the study. Of the 1,191 women agreeing to participate, 1,070 completed the baseline evaluation and were enrolled in the study and randomized, for a recruitment rate of 90%. Of those enrolled, 1,044 were African American women. A total of 849 women completed the study, for a retention rate of 79%. Five percent dropped out and 12% were lost-to-follow up. Women retained in the study and those not retained were not statistically different with regard to socio-demographic characteristics and the targeted risks. Retention strategies included financial and other incentives, regular updates of contact information which was tracked and monitored by a computerized data management system available to all project staff, and attention to cultural competence with implementation of study procedures by appropriately selected, trained, and supervised staff. Single, less educated, alcohol and drug users, non-working, and non-WIC women represent minority women with expected low retention rates. Conclusion: We conclude that with targeted recruitment and retention strategies, minority women will participate at high rates in behavioral clinical trials. We also found that women who drop out are different from women who are lost to follow-up, and require different strategies to optimize their completion of the study. C1 NICHD, NIH, DESPR, Collaborat Studies Unit, Rockville, MD 20852 USA. RTI Int, Stat & Epidemiol Unit, Rockville, MD 20852 USA. Howard Univ, Coll Pharm Nursing & Allied Hlth Sci, Div Allied Hlth Sci, Washington, DC 20059 USA. George Washington Univ, Med Ctr, Sch Publ Hlth & Hlth Serv, Dept Prevent & Community Hlth, Washington, DC 20037 USA. Georgetown Univ Hosp, Div Neonatol, Washington, DC 20007 USA. Care Of Allan A Johnson, Howard Univ, Coll Pharm Nursing & Allied Hlth Sci, Div Allied Hlth Sci, Washington, DC 20059 USA. Res Triangle Inst Int, Stat & Epidemiol Unit, Rockville, MD 20852 USA. Childrens Natl Med Ctr, Ctr Hlth Serv & Community Res, Washington, DC 20010 USA. RP Kiely, M (reprint author), NICHD, NIH, DESPR, Collaborat Studies Unit, 6100 Execut Blvd,Rm 7B05, Rockville, MD 20852 USA. EM nek@rti.org; ajohnson@Howard.edu; kielym@nih.gov; sphaxe@gwumc.edu; SUBRAMAS@gunet.georgetown.edu; hlaryea@howard.edu; kennan17@yahoo.com; jps@rti.org; JJoseph@cnmc.org FU NICHD NIH HHS [5U18HD036104, 3U18HD030447, U18 HD030445, U18 HD036104, U18 HD031206, U18 HD031919, 5U18HD31206, 3U18HD030445, 3U18HD031919, U18 HD030447] NR 40 TC 73 Z9 73 U1 0 U2 18 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD SEP 6 PY 2007 VL 7 AR 233 DI 10.1186/1471-2458-7-233 PG 18 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 225FR UT WOS:000250503000001 PM 17822526 ER PT J AU Verdejo-Garcia, A Benbrook, A Funderburk, F David, P Cadet, JL Bolla, KI AF Verdejo-Garcia, Antonio Benbrook, Amy Funderburk, Frank David, Paula Cadet, Jean-Lud Bolla, Karen I. TI The differential relationship between cocaine use and marijuana use on decision-making performance over repeat testing with the Iowa Gambling Task SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine; marijuana; decision-making; learning; Iowa gambling task; repeated testing ID METHAMPHETAMINE-DEPENDENT SUBJECTS; VENTROMEDIAL PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX; DRUG-ABUSERS; NEUROPSYCHOLOGICAL PERFORMANCE; FUTURE CONSEQUENCES; TISSUE COMPOSITION; SUBSTANCE-ABUSE; ACTIVATION; ABSTINENCE AB Decision-making deficits area robust cognitive correlate of substance abuse, but few studies have addressed the long-term differential associations of cocaine use and marijuana (MJ) use on decision-making. This study utilized the Iowa Gambling Task (IGT), a widely used measure of decision-making, to investigate the relationship between cocaine and MJ use and IGT learning. We analyzed between and within group differences across two consecutive testing sessions in abstinent users of either Nil or cocaine. We assessed long-term correlates of the use of these drugs by evaluating users after 25 days of enforced abstinence. Results showed that both cocaine users and MJ users performed worse than controls on the total IGT net score. All groups showed learning between Session 1 and Session 2, but the cocaine users showed the smallest increase in performance. The pattern of learning from the beginning to the end (block x block) of the IGT (Session 2) was different for the drug groups, with the cocaine group showing more learning than the MJ group. Dose-related measures of cocaine use (g/week) and MJ use (joints/week) predicted IGT performance (the heavier the drug use the lower the performance). Differential correlates of cocaine use and MJ use on decision-making learning may have important implications for the development of novel treatment interventions. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21224 USA. Inst Municipal Invest Med, Pharmacol Res Unit, Barcelona 08003, Spain. InCompass Syst, Baltimore, MD 21224 USA. NIDA, Mol Neuropsychiat Branch, DHHS, NIH,Intermural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. RP Bolla, KI (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21224 USA. EM kbolla@jhmi.edu OI Verdejo-Garcia, Antonio/0000-0001-8874-9339 FU Intramural NIH HHS; NCRR NIH HHS [M01 RR002719, M01 RR02719]; NIDA NIH HHS [DA 11426, R01 DA011426-02] NR 58 TC 95 Z9 100 U1 5 U2 13 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 6 PY 2007 VL 90 IS 1 BP 2 EP 11 DI 10.1016/j.drugalcdep.2007.02.004 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 191PW UT WOS:000248144500001 PM 17367959 ER PT J AU Fishbein, DH Krupitsky, E Flannery, BA Langevin, DJ Bobashev, G Verbitskaya, E Augustine, CB Bolla, KI Zvartau, E Schech, B Egorova, V Bushara, N Tsoy, M AF Fishbein, Diana H. Krupitsky, Evgeny Flannery, Barbara A. Langevin, Doris J. Bobashev, Georgiy Verbitskaya, Elena Augustine, Cynthia B. Bolla, Karen I. Zvartau, Edwin Schech, Barry Egorova, Valentina Bushara, Natali Tsoy, Marina TI Neurocognitive characterizations of Russian heroin addicts without a significant history of other drug use SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE heroin addiction; cognition; neuropsychology; alcoholism; Russia ID ANTERIOR CINGULATE CORTEX; RISKY DECISION-MAKING; HIGHER DISCOUNT RATES; MATCHING-TO-SAMPLE; PREFRONTAL CORTEX; SUBSTANCE-USE; METHADONE-MAINTENANCE; CHRONIC AMPHETAMINE; DEPENDENT PATIENTS; NUCLEUS-ACCUMBENS AB Research on the neurocognitive characteristics of heroin addiction is sparse and studies that do exist include polydrug abusers; thus, they are unable to distinguish neurocognitive effects of heroin from those of other drugs. To identify neurocognitive correlates specific to heroin addiction, the present study was conducted in St. Petersburg, Russia where individuals typically abuse and/or become addicted to only one substance, generally alcohol or heroin. Heroin addicts were recruited from an inpatient treatment facility in St. Petersburg. Three comparison groups included alcoholics. addicts who used both alcohol and heroin, and non-abusers. Psychiatric, background, and drug history evaluations were administered after detoxification to screen for exclusion criteria and characterize the sample. Executive Cognitive Functions (ECF) that largely activate areas of the prefrontal cortex and its circuitry measured include complex visual pattern recognition (Paired Associates Learning), working memory (Delayed Matching to Sample), problem solving (Stockings of Cambridge), executive decision making (Cambridge Decision Making Task), cognitive flexibility (Stroop Color-Word Task) and response shifting (Stop Change Task). In many respects, the heroin addicts were similar to alcohol and alcohol + heroin dependent groups in neuroeognitive deficits relative to controls. The primary finding was that heroin addicts exhibited significantly more disadvantageous decision making and longer deliberation times while making risky decisions than the other groups. Because the nature and degree of recovery from drug abuse are likely a function of the type or pattern of neurocognitive impairment, differential drug effects must be considered. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 RTI Int, Transdisciplinary Behav Sci Program, Baltimore, MD 21224 USA. Pavlov State Med Univ St Petersburg, Lab Clin Pharmacol Addict, St Petersburg 197022, Russia. Pacific Inst Res & Evaluat, Calverton, MD 20904 USA. RTI Int, Res Triangle Pk, NC 27709 USA. Johns Hopkins Med Inst, Dept Neurol & Psychiat & Behav Sci, Bloomberg Sch Publ Hlth, Baltimore, MD USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Fishbein, DH (reprint author), RTI Int, Transdisciplinary Behav Sci Program, 6801 Eastern Ave,Suite 203, Baltimore, MD 21224 USA. EM dfishbein@rti.org RI Verbitskaya, Elena/N-3867-2015 OI Verbitskaya, Elena/0000-0003-3770-993X FU NIDA NIH HHS [R01 DA015528-01A1, 1 R01 DA15528-01A1, R01 DA015528] NR 90 TC 54 Z9 60 U1 5 U2 10 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 6 PY 2007 VL 90 IS 1 BP 25 EP 38 DI 10.1016/j.drugalcdep.2007.02.015 PG 14 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 191PW UT WOS:000248144500003 PM 17382488 ER PT J AU Morrell, A Placzek, M Parmley, S Grella, B Antony, S Pommier, Y Cushman, M AF Morrell, Andrew Placzek, Michael Parmley, Seth Grella, Brian Antony, Smitha Pommier, Yves Cushman, Mark TI Optimization of the indenone ring of indenoisoquinoline topoisomerase I inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PLANT ANTITUMOR AGENTS; BIOLOGICAL EVALUATION; CAMPTOTHECIN ANALOGS; NITRATED INDENOISOQUINOLINES; ANTILEUKEMIC ACTIVITY; MJ-III-65 NSC-706744; ANTICANCER ACTIVITY; THIONYL CHLORIDE; DESIGN; TOPOTECAN AB Two series of indenoisoquinoline topoisomerase I inhibitors have been prepared to investigate optimal substituents on the indenone ring at the 9-position. The more exhaustive series was prepared using a nitrated isoquinoline ring that has been previously demonstrated to enhance biological activity. After preliminary biological evaluation, a more focused series of inhibitors was prepared utilizing a 2,3-dimethoxy-substituted isoquinoline ring. The results of the two series indicate the existence of superior functional groups such as methoxy, fluorine, and cyano for the indenoisoquinoline 9-position. Interestingly, these functional groups coincide with established structure-activity relationships for the 11-position of camptothecin. C1 Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu FU Intramural NIH HHS; NCI NIH HHS [T32 CA09634-12, U01 CA89566, N01-CO-56000] NR 45 TC 49 Z9 51 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 6 PY 2007 VL 50 IS 18 BP 4388 EP 4404 DI 10.1021/jm070307+ PG 17 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 205YI UT WOS:000249150700013 PM 17676830 ER PT J AU Morrell, A Placzek, M Parmley, S Antony, S Dexheimer, TS Pommier, Y Cushman, M AF Morrell, Andrew Placzek, Michael Parmley, Seth Antony, Smitha Dexheimer, Thomas S. Pommier, Yves Cushman, Mark TI Nitrated indenoisoquinolines as topoisomerase I inhibitors: A systematic study and optimization SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DNA COVALENT COMPLEX; BIOLOGICAL EVALUATION; MJ-III-65 NSC-706744; ANTICANCER ACTIVITY; CAMPTOTHECIN; MECHANISM; DESIGN; TOPOTECAN; CHLORIDE; INDUCTION AB The biological activity of indenoisoquinoline topoisomerase I (Topl) inhibitors can be greatly enhanced depending on the choice of substituents on the aromatic rings and lactam side chain. Previously, it was discovered that a 3-nitro group and a 9-methoxy group afforded enhanced biological activity. In the present investigation, indenoisoquinoline analogues were systematically prepared using combinations of nitro groups, methoxy groups, and hydrogen atoms in an effort to understand the contribution of each group toward cytotoxicity and Top I inhibition. Analysis of the biological results suggests that the nitro group is important for Top I inhibition and the methoxy group improves cytotoxicity. In addition, previously identified structure-activity relationships were utilized to select favorable lactam side chain functionalities for incorporation on the aromatic skeleton of analogues in this study. As a result, this investigation has provided optimal Topl inhibitors equipotent to camptothecin that demonstrate low nanomolar cytotoxicities toward cancer cells. C1 Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu FU Intramural NIH HHS; NCI NIH HHS [N01-CO-56000, T32 CA09634-12, U01 CA89566]; PHS HHS [C06-14499] NR 40 TC 50 Z9 51 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 6 PY 2007 VL 50 IS 18 BP 4419 EP 4430 DI 10.1021/jm070361q PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 205YI UT WOS:000249150700015 PM 17696418 ER PT J AU Remsberg, JR Lou, H Tarasov, SG Dean, M Tarasova, NI AF Remsberg, Jarrett R. Lou, Hong Tarasov, Sergey G. Dean, Michael Tarasova, Nadya I. TI Structural analogues of smoothened intracellular loops as potent inhibitors of hedgehog pathway and cancer cell growth SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CYCLOPAMINE; PEPTIDE; MEDULLOBLASTOMA; PROLIFERATION; TUMORIGENESIS; THERAPEUTICS; INTERFERENCE; REQUIREMENT; CARCINOMAS; ACTIVATION AB Smoothened is a critical component of the Hedgehog pathway that is essential for stem cell renewal and is dysregulated in many cancer types. We have found synthetic analogues of the second and third intracellular loops of smoothened to be potent inhibitors of the Hedgehog pathway. Palmitoylated peptides as short as 10 residues inhibited melanoma cells growth with IC50 in the low nanomolar range. The compounds are promising drug candidates and convenient tools for solving mechanisms of Hedgehog signaling. C1 NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, Frederick, MD 21701 USA. NCI, Human Genet Sect, Lab Genom Divers, Frederick, MD 21701 USA. NCI, Struct Biophys Lab, Frederick, MD 21701 USA. RP Tarasova, NI (reprint author), NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, Frederick, MD 21701 USA. EM tarasova@ncifcrf.gov RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU Intramural NIH HHS [Z01 BC005652-17] NR 39 TC 31 Z9 32 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 6 PY 2007 VL 50 IS 18 BP 4534 EP 4538 DI 10.1021/jm0705657 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 205YI UT WOS:000249150700026 PM 17685505 ER PT J AU Curco, D Nussinov, R Aleman, C AF Curco, David Nussinov, Ruth Aleman, Carlos TI Coarse-grained representation of beta-helical protein building blocks SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID MOLECULAR-DYNAMICS; AMORPHOUS POLYMERS; ATOMISTIC MODELS; COMPUTER-SIMULATIONS; REPEAT PROTEINS; MONTE-CARLO; AMINO-ACIDS; DESIGN; MEMBRANES; POLYETHYLENE AB A general strategy to develop coarse-grained models of beta-helical protein fragments is presented. The procedure has been applied to a building block formed by a two-turn repeat motif from E. coli galactoside acetyltransferase, which is able to provide a very stable self-assembled tubular nanoconstruct upon stacking of its replicas. For this purpose, first, we have developed a computational scheme to sample very efficiently the configurational space of the building block. This method, which is inspired by a strategy recently designed to study amorphous polymers and by an advanced Monte Carlo algorithm, provides a large ensemble of uncorrelated configurations at a very reasonable computational cost. The atomistic configurations provided by this method have been used to obtain a coarse-grained model that describes the amino acids with fewer particles than those required for full atomistic detail, i.e., two, three, or four depending on the chemical nature of the amino acid. Coarse-grained potentials have been developed considering the following types of interactions: (i) electrostatic and van der Waals interactions between residues i and i + n with n >= 2; (ii) interactions between residues i and i + 1; and (c) intra-residue interactions. The reliability of the proposed model has been tested by comparing the atomistic and coarse-grained energies calculated for a large number of independent configurations of the beta-helical building block. C1 Univ Barcelona, Fac Quim, Dept Engn Quim, E-08028 Barcelona, Spain. NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. Univ Politecn Catalunya, ETS Engn Ind Barcelona, Dept Engn Quim, E-08028 Barcelona, Spain. RP Aleman, C (reprint author), Univ Barcelona, Fac Quim, Dept Engn Quim, Marti i Franquees 1, E-08028 Barcelona, Spain. EM carlos.aleman@upc.es FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 63 TC 11 Z9 11 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD SEP 6 PY 2007 VL 111 IS 35 BP 10538 EP 10549 DI 10.1021/jp072832q PG 12 WC Chemistry, Physical SC Chemistry GA 206FR UT WOS:000249169800026 PM 17691836 ER PT J AU Mascola, JR AF Mascola, John R. TI HIV/AIDS - Allied responses SO NATURE LA English DT Editorial Material ID HIV-1/SIV CHIMERIC VIRUS; ANTIBODY; NEUTRALIZATION; MACAQUES; VACCINE C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3015, Bethesda, MD 20892 USA. EM jmascola@nih.gov NR 13 TC 13 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 6 PY 2007 VL 449 IS 7158 BP 29 EP 30 DI 10.1038/449029a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 207ED UT WOS:000249233500025 PM 17805280 ER PT J AU Kazmierczak, P Sakaguchi, H Tokita, J Wilson-Kubalek, EM Milligan, RA Muller, U Kachar, B AF Kazmierczak, Piotr Sakaguchi, Hirofumi Tokita, Joshua Wilson-Kubalek, Elizabeth M. Milligan, Ronald A. Mueller, Ulrich Kachar, Bechara TI Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells SO NATURE LA English DT Article ID SYNDROME TYPE 1D; C-CADHERIN; TRANSDUCTION; MUTATIONS; STEREOCILIA; CDH23; EAR; COMPONENT; ADHESION; WALTZER AB Hair cells of the inner ear are mechanosensors that transduce mechanical forces arising from sound waves and head movement into electrochemical signals to provide our sense of hearing and balance. Each hair cell contains at the apical surface a bundle of stereocilia. Mechanoelectrical transduction takes place close to the tips of stereocilia in proximity to extracellular tip-link filaments that connect the stereocilia and are thought to gate the mechanoelectrical transduction channel(1-3). Recent reports on the composition(4-8), properties and function(9-11) of tip links are conflicting(29). Here we demonstrate that two cadherins that are linked to inherited forms of deafness in humans(12-15) interact to form tip links. Immunohistochemical studies using rodent hair cells show that cadherin 23 (CDH23) and protocadherin 15 (PCDH15) localize to the upper and lower part of tip links, respectively. The amino termini of the two cadherins co-localize on tip-link filaments. Biochemical experiments show that CDH23 homodimers interact in trans with PCDH15 homodimers to form a filament with structural similarity to tip links. Ions that affect tip-link integrity and a mutation in PCDH15 that causes a recessive form of deafness(16) disrupt interactions between CDH23 and PCDH15. Our studies define the molecular composition of tip links and provide a conceptual base for exploring the mechanisms of sensory impairment associated with mutations in CDH23 and PCDH15. C1 Scripps Res Inst, Inst Dept Cell Biol, La Jolla, CA 92037 USA. Inst Childhood & Neglected Dis, La Jolla, CA 92037 USA. NIDCD, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. RP Muller, U (reprint author), Scripps Res Inst, Inst Dept Cell Biol, La Jolla, CA 92037 USA. EM umueller@scripps.edu; kacharb@nidcd.nih.gov FU Intramural NIH HHS NR 29 TC 292 Z9 300 U1 2 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 6 PY 2007 VL 449 IS 7158 BP 87 EP U59 DI 10.1038/nature06091 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 207ED UT WOS:000249233500041 PM 17805295 ER PT J AU Remmers, EF Plenge, RM Lee, AT Graham, RR Hom, G Behrens, TW de Bakker, PIW Le, JM Lee, HS Batliwalla, F Li, W Masters, SL Booty, MG Carulli, JP Padyukov, L Alfredsson, L Klareskog, L Chen, WV Amos, CI Criswell, LA Seldin, MF Kastner, DL Gregersen, PK AF Remmers, Elaine F. Plenge, Robert M. Lee, Annette T. Graham, Robert R. Hom, Geoffrey Behrens, Timothy W. de Bakker, Paul I. W. Le, Julie M. Lee, Hye-Soon Batliwalla, Franak Li, Wentian Masters, Seth L. Booty, Matthew G. Carulli, John P. Padyukov, Leonid Alfredsson, Lars Klareskog, Lars Chen, Wei V. Amos, Christopher I. Criswell, Lindsey A. Seldin, Michael F. Kastner, Daniel L. Gregersen, Peter K. TI STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GENOME-WIDE ASSOCIATION; GENETIC ASSOCIATION; TYROSINE-PHOSPHATASE; SUSCEPTIBILITY; LINKAGE; DISEASE; PTPN22; SCAN; POLYMORPHISM; METAANALYSIS AB Background Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q. Methods We tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus. Results A SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P=2.81 x 10(-7); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P=0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P=1.87 x 10(-9); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis. Conclusions A haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses. C1 Feinstein Inst Med Res, Manhasset, NY 11030 USA. NIAMSD, Bethesda, MD 20892 USA. Broad Inst, Cambridge, MA USA. Brigham & Womens Hosp, Manhasset, NY USA. Genentech Inc, San Francisco, CA 94080 USA. Hanyang Univ, Coll Med, Seoul 133791, South Korea. Biogen Idec, Cambridge, MA USA. Karolinska Inst, Stockholm, Sweden. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif Davis, San Francisco, CA USA. RP Gregersen, PK (reprint author), Feinstein Inst Med Res, 350 Community Dr, Manhasset, NY 11030 USA. EM peterg@nshs.edu RI Padyukov, Leonid/A-4890-2009; Masters, Seth/N-2886-2013; de Bakker, Paul/B-8730-2009; OI Padyukov, Leonid/0000-0003-2950-5670; Masters, Seth/0000-0003-4763-576X; de Bakker, Paul/0000-0001-7735-7858; Booty, Matthew/0000-0002-0835-3439; Li, Wentian/0000-0003-1155-110X FU NCRR NIH HHS [5-M01-RR-00079, M01 RR000079, M01 RR018535]; NIAID NIH HHS [N01-AI95386, K08 AI055314, K08 AI055314-01A1, K08 AI055314-02, K08 AI055314-03, K08 AI055314-04, K08 AI055314-05, N01AI95386]; NIAMS NIH HHS [N01-AR-1-2256, N01-AR-2-2263, R01 AR-44804, R01 AR044422, R01 AR050267, R01 AR052300, R01 AR44422] NR 51 TC 580 Z9 601 U1 2 U2 23 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 6 PY 2007 VL 357 IS 10 BP 977 EP 986 DI 10.1056/NEJMoa073003 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 206VK UT WOS:000249210800004 PM 17804842 ER PT J AU McWhinney, SR Pasini, B Stratakis, CA AF McWhinney, Sarah R. Pasini, Barbara Stratakis, Constantine A. CA Int Carney Triad Carney Strata TI Familial gastrointestinal stromal tumors and germ-line mutations SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Ohio State Univ, Columbus, OH 43210 USA. Univ Turin, I-10126 Turin, Italy. NICHHD, Bethesda, MD 20892 USA. RP McWhinney, SR (reprint author), Ohio State Univ, Columbus, OH 43210 USA. EM stratakc@mail.nih.gov NR 5 TC 109 Z9 113 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 6 PY 2007 VL 357 IS 10 BP 1054 EP 1056 DI 10.1056/NEJMc071191 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 206VK UT WOS:000249210800029 PM 17804857 ER PT J AU Dirikoc, S Priola, SA Marella, M Zsurger, N Chabry, J AF Dirikoc, Sevda Priola, Suzette A. Marella, Mathieu Zsuerger, Nicole Chabry, Joelle TI Nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE prion; cannabinoid; neuroprotection; scrapie-infected mice; cell-free conversion; microglia ID CREUTZFELDT-JAKOB-DISEASE; CENTRAL-NERVOUS-SYSTEM; MICROGLIA RECRUITMENT; SCRAPIE STRAINS; PRP; CANNABINOIDS; MICE; NEUROPROTECTION; PROPAGATION; INHIBITION AB Prion diseases are transmissible neurodegenerative disorders characterized by the accumulation in the CNS of the protease-resistant prion protein ( PrPres), a structurally misfolded isoform of its physiological counterpart PrPsen. Both neuropathogenesis and prion infectivity are related to PrPres formation. Here, we report that the nonpsychoactive cannabis constituent cannabidiol ( CBD) inhibited PrPres accumulation in both mouse and sheep scrapie-infected cells, whereas other structurally related cannabinoid analogs were either weak inhibitors or noninhibitory. Moreover, after intraperitoneal infection with murine scrapie, peripheral injection of CBD limited cerebral accumulation of PrPres and significantly increased the survival time of infected mice. Mechanistically, CBD did not appear to inhibit PrPres accumulation via direct interactions with PrP, destabilization of PrPres aggregates, or alteration of the expression level or subcellular localization of PrPsen. However, CBD did inhibit the neurotoxic effects of PrPres and affected PrPres-induced microglial cell migration in a concentration-dependent manner. Our results suggest that CBD may protect neurons against the multiple molecular and cellular factors involved in the different steps of the neurodegenerative process, which takes place during prion infection. When combined with its ability to target the brain and its lack of toxic side effects, CBD may represent a promising new anti-prion drug. C1 Univ Nice Sophia Antipolis, CNRS UMR 6097, Inst Pharmacol Mol & Cellulaire, F-06560 Valbonne, France. NIAID, Lab Persistent Viral Dis, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. Scripps Res Inst, La Jolla, CA 92037 USA. RP Chabry, J (reprint author), Univ Nice Sophia Antipolis, CNRS UMR 6097, Inst Pharmacol Mol & Cellulaire, 660 Route Lucioles, F-06560 Valbonne, France. EM chabry@ipmc.cnrs.fr RI Chabry, Joelle/O-2101-2016 NR 33 TC 32 Z9 34 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 5 PY 2007 VL 27 IS 36 BP 9537 EP 9544 DI 10.1523/JNEUROSCI.1942-07.2007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 209MZ UT WOS:000249393900002 PM 17804615 ER PT J AU Saul, A Fay, MP AF Saul, Allan Fay, Michael P. TI Human Immunity and the Design of Multi-Component, Single Target Vaccines SO PLOS ONE LA English DT Article AB Background. Inclusion of multiple immunogens to target a single organism is a strategy being pursued for many experimental vaccines, especially where it is difficult to generate a strongly protective response from a single immunogen. Although there are many human vaccines that contain multiple defined immunogens, in almost every case each component targets a different pathogen. As a consequence, there is little practical experience for deciding where the increased complexity of vaccines with multiple defined immunogens vaccines targeting single pathogens will be justifiable. Methodology/Principal Findings. A mathematical model, with immunogenicity parameters derived from a database of human responses to established vaccines, was used to predict the increase in the efficacy and the proportion of the population protected resulting from addition of further immunogens. The gains depended on the relative protection and the range of responses in the population to each immunogen and also to the correlation of the responses between immunogens. In most scenarios modeled, the gain in overall efficacy obtained by adding more immunogens was comparable to gains obtained from a single immunogen through the use of better formulations or adjuvants. Multi-component single target vaccines were more effective at decreasing the proportion of poor responders than increasing the overall efficacy of the vaccine in a population. Conclusions/Significance. Inclusion of limited number of antigens in a vaccine aimed at targeting a single organism will increase efficacy, but the gains are relatively modest and for a practical vaccine there are constraints that are likely to limit multi-component single target vaccines to a small number of key antigens. The model predicts that this type of vaccine will be most useful where the critical issue is the reduction in proportion of poor responders. C1 [Saul, Allan] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Rockville, MD USA. RP Saul, A (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. EM ASaul@niaid.nih.gov RI Saul, Allan/I-6968-2013; OI Saul, Allan/0000-0003-0665-4091; Fay, Michael P./0000-0002-8643-9625 FU National Institute for Allergy and Infectious Diseases, National Institutes of Health FX The study was supported by the Intramural Research Program of the National Institute for Allergy and Infectious Diseases, National Institutes of Health. The funder played no role in the study or preparation, review or approval of the manuscript. NR 29 TC 13 Z9 15 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 5 PY 2007 VL 2 IS 9 AR e850 DI 10.1371/journal.pone.0000850 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10HQ UT WOS:000207455500033 PM 17786221 ER PT J AU Thiel, M Caldwell, CC Kreth, S Kuboki, S Chen, P Smith, P Ohta, A Lentsch, AB Lukashev, D Sitkovsky, MV AF Thiel, Manfred Caldwell, Charles C. Kreth, Simone Kuboki, Satoshi Chen, P. Smith, Patrick Ohta, Akio Lentsch, Alex B. Lukashev, Dmitry Sitkovsky, Michail V. TI Targeted Deletion of HIF-1 alpha Gene in T Cells Prevents their Inhibition in Hypoxic Inflamed Tissues and Improves Septic Mice Survival SO PLOS ONE LA English DT Article AB Background. Sepsis patients may die either from an overwhelming systemic immune response and/or from an immunoparalysis-associated lack of anti-bacterial immune defence. We hypothesized that bacterial superantigen-activated T cells may be prevented from contribution into anti-bacterial response due to the inhibition of their effector functions by the hypoxia inducible transcription factor (HIF-1 alpha) in inflamed and hypoxic areas. Methodology/ Principal Findings. Using the Cre-lox-P-system we generated mice with a T-cell targeted deletion of the HIF-1 alpha gene and analysed them in an in vivo model of bacterial sepsis. We show that deletion of the HIF-1 alpha gene leads to higher levels of pro-inflammatory cytokines, stronger anti-bacterial effects and much better survival of mice. These effects can be at least partially explained by significantly increased NF-kappa B activation in TCR activated HIF-1 alpha deficient T cells. Conclusions/Significance. T cells can be recruited to powerfully contribute to anti-bacterial response if they are relieved from inhibition by HIF-1 alpha in inflamed and hypoxic areas. Our experiments uncovered the before unappreciated reserve of anti-bacterial capacity of T cells and suggest novel therapeutic anti-pathogen strategies based on targeted deletion or inhibition of HIF-1 alpha in T cells. C1 [Thiel, Manfred; Caldwell, Charles C.; Chen, P.; Smith, Patrick; Ohta, Akio; Lukashev, Dmitry; Sitkovsky, Michail V.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Thiel, Manfred; Kreth, Simone] Univ Munich, Klinikum Grosshadern, Dept Anaesthesiol, D-8000 Munich, Germany. [Caldwell, Charles C.; Kuboki, Satoshi; Lentsch, Alex B.] Univ Cincinnati, Coll Med, Dept Surg, Trauma Sepsis & Inflammat Res Grp, Cincinnati, OH 45267 USA. [Caldwell, Charles C.] Shriners Hosp Children, Dept Res, Cincinnati, OH USA. [Ohta, Akio; Lukashev, Dmitry; Sitkovsky, Michail V.] Northeastern Univ, New England Inflammat & Tissue Protect Inst, Boston, MA 02115 USA. RP Sitkovsky, MV (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM m.sitkovsky@neu.edu RI Lukashev, Dmitriy/F-8133-2010; OI Caldwell, Charles/0000-0003-1692-4550 FU New England Inflammation and Tissue Protection Institute at Northeastern University, Boston [1R21 AT002788-01]; National Institutes of Health; Shriner's Hospital for Children [8560]; German National Research Foundation [TH733/2-1]; National Institute of Allergy and Infectious Diseases Intramural program FX This work was supported by New England Inflammation and Tissue Protection Institute at Northeastern University, Boston, 1R21 AT002788-01(MS), National Institutes of Health grants, and Shriner's Hospital for Children Project 8560 (CCC) as well as by the German National Research Foundation Grant TH733/2-1 and National Institute of Allergy and Infectious Diseases Intramural program. NR 26 TC 77 Z9 81 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 5 PY 2007 VL 2 IS 9 AR e853 DI 10.1371/journal.pone.0000853 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10HQ UT WOS:000207455500036 PM 17786224 ER PT J AU Lee, CH Ito, Y Yanagiba, Y Yamanoshita, O Kim, H Zhang, SY Kamijima, M Gonzalez, FJ Nakajima, T AF Lee, Chul-Ho Ito, Yuki Yanagiba, Yukie Yamanoshita, Osamu Kim, Heon Zhang, Shu-Yun Kamijima, Michihiro Gonzalez, Frank J. Nakajima, Tamie TI Pyrene-induced CYP1A2 and SULT1A1 may be regulated by CAR and not by AhR SO TOXICOLOGY LA English DT Article DE pyrene; cytochrome p450 1A2; sulfotransferase; UDP-glucuronosyltransferase; aryl hydrocarbon receptor; constitutive androstane receptor ID ARYL-HYDROCARBON RECEPTOR; POLYCYCLIC AROMATIC-HYDROCARBONS; HUMAN UDP-GLUCURONOSYLTRANSFERASES; CYTOCHROMES P450 1A1; PREGNANE-X-RECEPTOR; DNA-ADDUCTS; TRANSCRIPTIONAL ACTIVATION; PIPERONYL BUTOXIDE; NUCLEAR RECEPTORS; LIVER-MICROSOMES AB Aryl hydrocarbon receptor (AhR) plays important roles in the regulation and induction of xenobiotic-metabolizing enzymes including the cytochromes P450 1 family (CYP1) and UDP-glucuronosyltransferases 1A (UGT1As) by polycyclic aromatic hydrocarbons as well as chlorinated aromatic hydrocarbons. To determine whether pyrene-induced xenobiotic-metabolizing enzymes are regulated by AhR, male AhR (+/+) and (-/-) mice were used. Both genotyped mice were exposed to 0, 205, 300 or 410 mg/(kg day pyrene), once daily, for four consecutive days by gavage. Exposure to pyrene did not influence hepatic CYP1A1-mRNA in mice of both genotypes, whereas it induced hepatic CYP1A2 protein and mRNA expression and associated 7-ethoxyresorufin O-deethylase and pyrene 1-hydroxylation activities in both AhR (+/+) and (-/-) mice. Similar effects were also found with sulfotransferase 1A1 expression and the associated 1-hydroxypyrene sulfation activity. In contrast, pyrene exposure increased expression of the UGT1A1 and 1A6, and glucuronidation activities associated with 1-hydroxypyrene and 1-naphthol in the liver only in AhR (-/-) mice, although pyrene treatment dose-dependently decreased the latter activity. Pyrene exposure did not increase AhR-mRNA expression in AhR (+/+) mice. In contrast, pyrene-induced expression of the hepatic constitutive androstane receptor (CAR) and one of its target genes, CYP2B10, in both AhR (+/+) and (-/-) mice. These results strongly suggest that pyrene-induced CYP1A2 and SULT1A1 are regulated by CAR, not by AhR. However, the mechanisms of UGT1A1 and 1A6 induction by pyrene were not elucidated in this study. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Nagoya Univ, Grad Sch Med, Dept Environm & Occupat Hlth, Showa Ku, Aichi 4668550, Japan. Chungbuk Natl Univ, Coll Med, Dept Prevent Med, Cheongju 361763, South Korea. Chubu Univ, Coll Life & Hlth Sci, Dept Biomed Sci, Aichi 4878501, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Nakajima, T (reprint author), Nagoya Univ, Grad Sch Med, Dept Environm & Occupat Hlth, Showa Ku, 65 Tsurumai Cho, Aichi 4668550, Japan. EM tnasu23@med.nagoya-u.acjp RI Ito, Yuki/C-3698-2008; OI Kim, Heon/0000-0003-0329-5249 NR 54 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD SEP 5 PY 2007 VL 238 IS 2-3 BP 147 EP 156 DI 10.1016/j.tox.2007.05.026 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 211SA UT WOS:000249542400008 PM 17618724 ER PT J AU Newman, JD AF Newman, John D. TI Neural circuits underlying crying and cry responding in mammals SO BEHAVIOURAL BRAIN RESEARCH LA English DT Review DE mammals; vocalization; behavior; brain; evolution ID MEDIAL PREOPTIC AREA; MIDBRAIN PERIAQUEDUCTAL GRAY; STIMULATE MATERNAL-BEHAVIOR; NULLIPAROUS FEMALE RATS; ULTRASONIC VOCALIZATIONS; SQUIRREL-MONKEYS; ISOLATION CALL; COMMON MARMOSETS; AUDITORY-CORTEX; SEPARATION DISTRESS AB Crying is a universal vocalization in human infants, as well as in the infants of other mammals. Little is known about the neural structures underlying cry production, or the circuitry that mediates a caregiver's response to cry sounds. In this review, the specific structures known or suspected to be involved in this circuit are identified, along with neurochemical systems and hormones for which evidence suggests a role in responding to infants and infant cries. In addition, evidence that crying elicits parental responses in different mammals is presented. An argument is made for including 'crying' as a functional category in the vocal repertoire of all mammalian infants (and the adults of some species). The prevailing neural model for crying production considers forebrain structures to be dispensable. However, evidence for the anterior cingulate gyrus in cry production. and this structure along with the amygdala and some other forebrain areas in responding to cries is presented. (c) 2007 Elsevier B.V. All rights reserved. C1 NICHHD, Comparat Ethol Lab, NIH, DHHS, Poolesville, MD 20837 USA. RP Newman, JD (reprint author), NICHHD, Comparat Ethol Lab, NIH, DHHS, Box 529, Poolesville, MD 20837 USA. EM jdnewman@helix.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 126 TC 55 Z9 55 U1 1 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD SEP 4 PY 2007 VL 182 IS 2 SI SI BP 155 EP 165 DI 10.1016/j.bbr.2007.02 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 208GI UT WOS:000249307400003 PM 17363076 ER PT J AU Hefner, K Cameron, HA Karlsson, RM Holmes, A AF Hefner, Kathryn Cameron, Heather A. Karlsson, Rose-Marie Holmes, Andrew TI Short-term and long-term effects of postnatal exposure to an adult male in C57BL/6J mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE mouse; stress; ultrasonic vocalization; early life; predation; child abuse; anxiety; depression ID ULTRASONIC VOCALIZATION; RAT PUPS; SEROTONIN TRANSPORTER; PREWEANLING RATS; KNOCKOUT MICE; ANXIETY; STRESS; RESPONSES; BEHAVIOR; MOUSE AB Rodent models provide a valuable approach to elucidating the pathophysiological mechanisms underlying the deleterious effects of childhood trauma and stress. Neonatal rats and mice emit ultrasonic vocalizations (USVs) when separated from the dam and litter. USVs are suppressed in rat pups by exposure to the putatively infanticidal threat of an adult male. In the present study, C57BL/6J mouse pups were exposed to an anaesthetized (non-sire) adult C57BL/6J male for 3-min/day from postnatal days 2-14, and subsequently tested for anxiety-related behaviors (using the novel open field, elevated plus-maze, light/dark exploration tests) and depression-related behavior (using the forced swim test) at I I weeks of age. In a separate cohort, hypothalamic-pituitary-adrenal-axis activation was measured via plasma corticosterone levels following either a single male-exposure or separation episode. Results showed that pups exposed to an adult male emitted significantly fewer USVs than separation-only counterparts. Corticosterone levels were significantly lower following single exposure to the adult male than separation alone. Repeated neonatal male-exposure did not lead to significant alterations in anxiety- or depression-related behaviors in adulthood. Taken together, present data suggest that the form of adult male-exposure employed did not act as a significant stressor, at least in this mouse strain. Further studies will be needed to determine whether alternative mouse strains, exposure protocols or adult behavioral assays will produce a different pattern of short-term and long-term effects. (c) 2007 Published by Elsevier B.V. C1 NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. NIMH, Univ Neuroplast Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 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 RI Cameron, Heather/E-6221-2011; OI Cameron, Heather/0000-0002-3245-5777; Hefner, Kathryn/0000-0002-5208-7860 FU Intramural NIH HHS; NIAAA NIH HHS [Z01-AA000411]; NIMH NIH HHS [Z01-MH002784] NR 36 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD SEP 4 PY 2007 VL 182 IS 2 SI SI BP 344 EP 348 DI 10.1016/j.bbr.2007.03.032 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 208GI UT WOS:000249307400021 PM 17482287 ER PT J AU Blain, KY Kwiatkowski, W Zhao, Q La Fleur, D Naik, C Chun, TW Tsareva, T Kanakaraj, P Laird, MW Shah, R George, L Sanyal, I Moore, PA Demeler, B Choe, S AF Blain, Katherine Y. Kwiatkowski, Witek Zhao, Qinghai La Fleur, David Naik, Chethana Chun, Tae-Wook Tsareva, Tatiana Kanakaraj, Palanisamy Laird, Michael W. Shah, Rutul George, Lisa Sanyal, Indra Moore, Paul A. Demeler, Borries Choe, Senyon TI Structural and functional characterization of CC chemokine CCL14 SO BIOCHEMISTRY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; T-CELLS; HEMOFILTRATE CC-CHEMOKINE-1; CRYSTAL-STRUCTURE; NMR ASSIGNMENTS; HIV-1 ENTRY; RECEPTOR; RANTES; BETA; INFECTION AB CC chemokine ligand 14, CCL14, is a human CC chemokine that is of recent interest because of its natural ability, upon proteolytic processing of the first eight NH2-terminal residues, to bind to and signal through the human immunodeficiency virus type-1 (HIV-1) co-receptor, CC chemokine receptor 5 (CCR5). We report X-ray crystallographic structures of both full-length CCL14 and signaling-active, truncated CCL14 [9-74] determined at 2.23 and 1.8 A, respectively. Although CCL14 and CCL14 [9-74] differ in their ability to bind CCR5 for biological signaling, we find that the NH2-terminal eight amino acids (residues 1 through 8) are completely disordered in CCL14 and both show the identical mode of the dimeric assembly characteristic of the CC type chemokine structures. However, analytical ultracentrifugation studies reveal that the CCL14 is stable as a dimer at a concentration as low as 100 nM, whereas CCL14 [9-74] is fully monomeric at the same concentration. By the same method, the equilibrium between monomers of CCL14 [9-74] and higher order oligomers is estimated to be of EC1,4 = 4.98 mu M for monomer-tetramer conversion. The relative instability of CCL14 [9-74] oligomers as compared to CCL14 is also reflected in the K-d's that are estimated by the surface plasmon resonance method to be similar to 9.84 and 667 nM for CCL14 and CCL14 [9-74], respectively. This similar to 60-fold difference in stability at a physiologically relevant concentration can potentially account for their different signaling ability. Functional data from the activity assays by intracellular calcium flux and inhibition of CCR5-mediated HIV-1 entry show that only CCL14 [9-74] is fully active at these near-physiological concentrations where CCL14 [9-74] is monomeric and CCL14 is dimeric. These results together suggest that the ability of CCL14 [9-74] to monomerize can play a role for cellular activation. C1 Salk Inst Biol Studies, Struct Biol Lab, La Jolla, CA 92037 USA. Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. Human Genome Sci Inc, Rockville, MD 20850 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. RP Choe, S (reprint author), Salk Inst Biol Studies, Struct Biol Lab, La Jolla, CA 92037 USA. EM choe@salk.edu FU NICHD NIH HHS [HD 013527]; PHS HHS [RRR022200] NR 63 TC 19 Z9 20 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 4 PY 2007 VL 46 IS 35 BP 10008 EP 10015 DI 10.1021/bi700936w PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 204CN UT WOS:000249021100015 PM 17691823 ER PT J AU Alam, MR Majumdar, A Thazhathveetil, AK Liu, ST Liu, JL Puri, N Cuenoud, B Sasaki, S Miller, PS Seidman, MM AF Alam, Md. Rowshon Majumdar, Alokes Thazhathveetil, Arun Kalliat Liu, Su-Ting Liu, Ji-Lan Puri, Nitin Cuenoud, Bernard Sasaki, Shigeki Miller, Paul S. Seidman, Michael M. TI Extensive sugar modification improves triple helix forming oligonucleotide activity in vitro but reduces activity in Vivo SO BIOCHEMISTRY LA English DT Article ID LOCKED NUCLEIC-ACID; TARGETED GENE KNOCKOUT; DOUBLE-STRANDED DNA; DUPLEX DNA; 2'-AMINOETHOXY-MODIFIED OLIGONUCLEOTIDES; 2'-O-(2-AMINOETHYL) RESIDUES; DUAL RECOGNITION; PHYSIOLOGICAL PH; BASE-PAIRS; 3RD STRAND AB We are developing triple helix forming oligonucleotides (TFOs) for gene targeting. Previously, we synthesized bioactive TFOs containing 2'-O-methylribose (2'-OMe) and 2'-O-aminoethylribose (2'-AE) residues. Active TFOs contained four contiguous 2'-AE residues and formed triplexes with high thermal stability and rapid association kinetics. In an effort to further improve bioactivity, we synthesized three series of TFOs containing the 2'-AE patch and additional ribose modifications distributed throughout the remainder of the oligonucleotide. These were either additional 2'-AE residues, the conformationally locked BNA/LNA ribose with a 2'-O,4'-C-methylene bridge, or the 2'-O,4'-C-ethylene analogue (ENA). The additionally modified TFOs formed triplexes with greater thermal stability than the reference TFO, and some had improved association kinetics. However, the most active TFOs in the biochemical and biophysical assays were the least active in the bioassay. We measured the thermal stability of triplexes formed by the TFOs in each series on duplex targets containing a change in sequence at a single position. The T-m value of the variant sequence triplexes increased as the number of all additional modifications increased. A simple explanation for the failure of the improved TFOs in the bioassay was that the increased affinity for nonspecific targets lowered the effective nuclear concentration. Enhancement of TFO bioactivity will require chemical modifications that improve interaction with the specific targets while retaining selectivity against mismatched sequences. C1 NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. Nova Pharmaceut Ltd, CH-4002 Basel, Switzerland. Kyushu Univ, Grad Sch Pharmaceut Sci, Fukuoka 8128582, Japan. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA. RP Seidman, MM (reprint author), NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. EM seidmanm@grc.nia.nih.gov FU Intramural NIH HHS NR 42 TC 24 Z9 25 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 4 PY 2007 VL 46 IS 35 BP 10222 EP 10233 DI 10.1021/bi7003153 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 204CN UT WOS:000249021100038 PM 17691818 ER PT J AU Newton-Cheh, C Guo, CY Larson, MG Musone, SL Surti, A Camargo, AL Drake, JA Benjamin, EJ Levy, D D'Agostino, RB Hirschhorn, JN O'Donnell, CJ AF Newton-Cheh, Christopher Guo, Chao-Yu Larson, Martin G. Musone, Stacy L. Surti, Aarti Camargo, Amy L. Drake, Jared A. Benjamin, Emelia J. Levy, Daniel D'Agostino, Ralph B. Hirschhorn, Joel N. O'Donnell, Christopher J. TI Common genetic variation in KCNH2 is associated with QT interval duration - The framingham heart study SO CIRCULATION LA English DT Article; Proceedings Paper CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent, Natl Heart, Lung & Blood Inst, Amer Heart Assoc, Council Nutr, Phys Activ & Metab DE arrhythmia; electrocardiography; genetics; ion channels; long-QT syndrome ID SUDDEN CARDIAC DEATH; EXONIC SPLICING ENHANCERS; FUNCTIONAL-CHARACTERIZATION; CARDIOVASCULAR MORTALITY; HEALTHY POPULATION; RISK-FACTOR; PROLONGATION; DISEASE; HERG; POLYMORPHISM AB Background-QT prolongation is associated with increased risk of sudden cardiac death in the general population and in people exposed to QT-prolonging drugs. Mutations in the KCNH2 gene encoding the HERG potassium channel cause 30% of long-QT syndrome, and binding to this channel leads to drug-induced QT prolongation. We tested common KCNH2 variants for association with continuous QT interval duration. Methods and Results-We selected 17 single nucleotide polymorphisms and rs1805123, a previously associated missense single nucleotide polymorphism, for genotyping in 1730 unrelated men and women from the Framingham Heart Study. rs3807375 genotypes were associated with continuous QT interval duration in men and women (2-df P=0.002), with a dominant model suggested (P=0.0004). An independent sample of 871 Framingham Heart Study men and women replicated the association (1-sided dominant P=0.02). On combined analysis of 2123 subjects, individuals with AA or AG genotypes had a 0.14-SD (SE, 0.04) or 3.9-ms higher age-, sex- and RR-adjusted QT interval compared with GG individuals (P=0.00006). The previously reported association of rs1805123 (K897T) replicated under a dominant (AA/AC, 0.06 SD [SE, 0.07] or 3.1 ms higher versus CC; 1-sided P=0.04) or additive model (0.06 SD [SE, 0.03] or 1.6 ms higher per A allele; 1-sided P=0.01). Conclusions-Two common genetic variants at the KCNH2 locus are associated with continuous QT interval duration in an unselected community-based sample. Studies to determine the influence of these variants on risk of sudden cardiac death and drug-induced arrhythmias should be considered. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. MIT, Cambridge, MA 02139 USA. Broad Inst Harvard, Cambridge, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. RP Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,GRB847, Boston, MA 02114 USA. EM cnewtoncheh@partners.org; odonnellc@nhlbi.nih.gov OI Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [HL66582, K23HL080025, N01-HC-25195, T32HL07575] NR 54 TC 58 Z9 58 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 4 PY 2007 VL 116 IS 10 BP 1128 EP 1136 DI 10.1161/CIRCULATIONAHA.107.710780 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 207FZ UT WOS:000249238300005 PM 17709632 ER PT J AU London, B Albert, C Anderson, ME Giles, WR Van Wagoner, DR Balk, E Billman, GE Chung, M Lands, W Leaf, A McAnulty, J Martens, JR Costello, RB Lathrop, DA AF London, Barry Albert, Christine Anderson, Mark E. Giles, Wayne R. Van Wagoner, David R. Balk, Ethan Billman, George E. Chung, Mei Lands, William Leaf, Alexander McAnulty, John Martens, Jeffrey R. Costello, Rebecca B. Lathrop, David A. TI Omega-3 fatty acids and cardiac arrhythmias: Prior studies and recommendations for future research - A report from the national heart, lung, and blood institute and office of dietary supplements omega-3 fatty acids and their role in cardiac arrhythmogenesis workshop SO CIRCULATION LA English DT Review DE arrhythmia; death; sudden; diet; electrophysiology; fatty acids ID POLYUNSATURATED FATTY-ACIDS; ALPHA-LINOLENIC ACID; RAT VENTRICULAR MYOCYTES; SARCOPLASMIC-RETICULUM FUNCTION; RANDOMIZED CONTROLLED-TRIAL; ACTION-POTENTIAL DURATION; FISH-OIL SUPPLEMENTATION; SODIUM-CHANNEL BLOCKADE; ADULT GUINEA-PIG; NF-KAPPA-B C1 Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA 15213 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Iowa, Dept Med, Iowa City, IA 52242 USA. Univ Calgary, Dept Kinesiol, Calgary, AB, Canada. Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. Tufts Univ, New England Med Ctr, Dept Med, Boston, MA 02111 USA. Ohio State Univ, Dept Physiol & Cell Biol, College Pk, MD USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Good Samaritan Hosp, Portland, OR 97210 USA. Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP London, B (reprint author), Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Scaife S-572,200 Lothrop St, Pittsburgh, PA 15213 USA. EM londonb@upmc.edu RI LATHROP, David/A-2758-2008; Van Wagoner, David/C-6783-2008; Billman, George/E-2758-2011 OI Van Wagoner, David/0000-0001-8250-9828; NR 167 TC 108 Z9 109 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 4 PY 2007 VL 116 IS 10 BP E320 EP E335 DI 10.1161/CIRCULATIONAHA.107.712984 PG 16 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 207FZ UT WOS:000249238300015 PM 17768297 ER PT J AU McDermott, MM Guralnik, JM Tian, L Ferrucci, L Liu, K Liao, Y Criqui, MH AF McDermott, Mary M. Guralnik, Jack M. Tian, Lu Ferrucci, Luigi Liu, Kiang Liao, Yihua Criqui, Michael H. TI Baseline functional performance predicts the rate of mobility loss in persons with peripheral arterial disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ANKLE BRACHIAL INDEX; PHYSICAL-ACTIVITY; LOWER-EXTREMITY; 6-MINUTE WALK; LEG SYMPTOMS; ASSOCIATION; PREVALENCE; CRITERIA; CLASSIFICATION; OSTEOARTHRITIS AB We compared rates of mobility loss among persons with versus without peripheral arterial disease (PAD). Associations between baseline functional performance and mobility loss in persons with and without PAD were studied. Background Persons with PAD have poorer functional performance than persons without PAD. The prognostic value of poorer performance in persons with PAD is unknown. Methods Participants were 398 persons with and 240 without PAD who were free of mobility impairment at baseline. Participants were followed for a median of 50 months. Baseline measures included the 6-min walk and the Short Physical Performance Battery score. Mobility status, assessed annually, was defined as the self-reported loss of the ability to walk one-quarter mile or walk up and down one flight of stairs without assistance. Results Adjusting for age and gender, we found that PAD participants had a greater rate of mobility loss than persons without PAD (hazard ratio [HR] 1.63; 95% confidence interval [Cl] 1.03 to 2.56). This difference was not statistically significant after additional adjustment for baseline performance. Among PAD participants, risk of mobility loss in the lowest versus the 2 highest quartiles of baseline performance were as follows: HR 9.65 (95% Cl 3.35 to 27.77, p < 0.001) for the 6-min walk and HR 12.84 (95% Cl 4.64 to 35.55, p < 0.001) for the Short Physical Performance Battery when adjusting for confounders. Conclusions Persons with PAD experience greater mobility loss than persons without PAD. This association was explained by poorer baseline functional performance among participants with PAD. Poorer lower extremity performance predicts increased mobility loss in persons with and without PAD. C1 Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Lab Clin Epidemiol, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. RP McDermott, MM (reprint author), 676 N St Clair,Suite 200, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU Intramural NIH HHS [Z99 AG999999]; NCRR NIH HHS [M01 RR000048, RR-00048]; NHLBI NIH HHS [R01 HL071223, R01 HL064739, R01-HL071223, R01-HL58099, R01-HL64739] NR 22 TC 53 Z9 53 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 4 PY 2007 VL 50 IS 10 BP 974 EP 982 DI 10.1016/j.jacc.2007.05.030 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 207MH UT WOS:000249254700009 PM 17765125 ER PT J AU Xi, SC Zhu, HM Xu, H Schmidtmann, A Geiman, TM Muegge, K AF Xi, Sichuan Zhu, Heming Xu, Hong Schmidtmann, Anja Geiman, Theresa M. Muegge, Kathrin TI Lsh controls Hox gene silencing during development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chromatin; DNA methylation; polycomb; Lsh ID CELL FATE; GENOME; CANCER; DNA; METHYLATION; COMPLEXES; PROTEIN; FAMILY; MEMBER AB Polycomb-mediated repression and DNA methylation are important epigenetic mechanisms of gene silencing. Recent evidence suggests a functional link between the polycomb repressive complex (PRC) and Dnmts in cancer cells. Here we provide evidence that Lsh, a regulator of DNA methylation, is also involved in normal control of PRC-mediated silencing during embryogenesis. We demonstrate that Lsh, a SNF2 homolog, can associate with some Hox genes and regulates Dnmt3b binding, DNA methylation, and silencing of Hox genes during development. Moreover, Lsh can associate with PRO components and influence PRC-mediated histone modifications. Thus Lsh is part of a physiological feedback loop that reinforces DNA methylation and silencing of PRC targets. C1 NCI, Lab Canc Prevent, SAIC Frederick, Frederick, MD 21702 USA. RP Muegge, K (reprint author), NCI, Lab Canc Prevent, SAIC Frederick, Frederick, MD 21702 USA. EM muegge@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 27 TC 51 Z9 54 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 4 PY 2007 VL 104 IS 36 BP 14366 EP 14371 DI 10.1073/pnas.0703669104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 208QF UT WOS:000249333600035 PM 17726103 ER PT J AU Wildman, DE Uddin, M Opazo, JC Liu, G Lefort, V Guindon, S Gascuel, O Grossman, LI Romero, R Goodman, M AF Wildman, Derek E. Uddin, Monica Opazo, Juan C. Liu, Guozhen Lefort, Vincent Guindon, Stephane Gascuel, Olivier Grossman, Lawrence I. Romero, Roberto Goodman, Morris TI Genomics, biogeography, and the diversification of placental mammals SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE atlantogenata; eutheria; notolegia; phylogeny; vicariance ID BAYESIAN PHYLOGENETIC INFERENCE; MAXIMUM-LIKELIHOOD; SISTER GROUP; SEQUENCE; EVOLUTION; TREE; PHYLOGENOMICS; PARSIMONY; ALIGNMENT; INSIGHTS AB Previous molecular analyses of mammalian evolutionary relationships involving a wide range of placental mammalian taxa have been restricted in size from one to two dozen gene loci and have not decisively resolved the basal branching order within Placentalia. Here, on extracting from thousands of gene loci both their coding nucleotide sequences and translated amino acid sequences, we attempt to resolve key uncertainties about the ancient branching pattern of crown placental mammals. Focusing on approximate to 1, 700 conserved gene loci, those that have the more slowly evolving coding sequences, and using maximum-likelihood, Bayesian inference, maximum parsimony, and neighbor-joining (NJ) phylogenetic tree reconstruction methods, we find from almost all results that a clade (the southern Atlantogenata) composed of Afrotheria and Xenarthra is the sister group of all other (the northern Boreoeutheria) crown placental mammals, among boreoeutherians Rodentia groups with Lagomorpha, and the resultant Glires is close to Primates. Only the NJ tree for nucleotide sequences separates Rodentia (murids) first and then Lagomorpha (rabbit) from the other placental mammals. However, this nucleotide NJ tree still depicts Atlantogenata and Boreoeutheria but minus Rodentia and Lagomorpha. Moreover, the NJ tree for amino acid sequences does depict the basal separation to be between Atlantogenata and a Borecleutheria that includes Rodentia and Lagomorpha. Crown placental mammalian diversification appears to be largely the result of ancient plate tectonic events that allowed time for convergent phenotypes to evolve in the descendant clades. C1 NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Dept Anat & Cell Biol, Detroit, MI 48201 USA. Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA. Univ Montpellier 2, CNRS, Lab Comp Sci Robot & Microelect, F-34392 Montpellier, France. RP Wildman, DE (reprint author), NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM dwildman@med.wayne.edu; mgoodwayne@aol.com RI Opazo, Juan/A-9363-2009; OI Opazo, Juan/0000-0001-7938-4083 FU Intramural NIH HHS NR 54 TC 113 Z9 114 U1 3 U2 36 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 4 PY 2007 VL 104 IS 36 BP 14395 EP 14400 DI 10.1073/pnas.0704342104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 208QF UT WOS:000249333600040 PM 17728403 ER PT J AU Gragerov, A Horie, K Pavlova, M Madisen, L Zeng, H Gragerova, G Rhode, A Dolka, I Roth, P Ebbert, A Moe, S Navas, C Finn, E Bergmann, J Vassilatis, DK Pavlakis, GN Gaitanaris, GA AF Gragerov, Alexander Horie, Kyoji Pavlova, Maria Madisen, Linda Zeng, Hongkui Gragerova, Galina Rhode, Alex Dolka, Io Roth, Patricia Ebbert, Amanda Moe, Stephanie Navas, Christopher Finn, Eric Bergmann, John Vassilatis, Demetrios K. Pavlakis, George N. Gaitanaris, George A. TI Large-scale, saturating insertional mutagenesis of the mouse genome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE G protein-coupled receptor; retroviral vector; ES cell; knockout mice ID EMBRYONIC STEM-CELLS; MICE; GENES; EXPRESSION; MUTATE; LINE AB We describe the construction of a large-scale, orderly assembly of mutant ES cells, generated with retroviral insertions and having mutational coverage in > 90% of mouse genes. We also describe a method for isolating ES cell clones with mutations in specific genes of interest from this library. This approach, which combines saturating random mutagenesis with targeted selection of mutations in the genes of interest, was successfully applied to the gene families of G protein-coupled receptors (GPCRs) and nuclear receptors. Mutant mouse strains in 60 different GPCRs were generated. Applicability of the technique for the GPCR genes, which on average represent fairly small targets for insertional mutagenesis, indicates the general utility of our approach for the rest of the genome. The method also allows for increased scale and automation for the large-scale production of mutant mice, which could substantially expedite the functional characterization of the mouse genome. C1 Omeros Corp, Seattle, WA 98101 USA. NCI, Human Retrovirus Sect, Vaccine Branch, Canc Res Ctr, Frederick, MD 21702 USA. RP Gragerova, G (reprint author), Omeros Corp, 1420 5th Ave,Suite 2600, Seattle, WA 98101 USA. EM sgragerov@omeros.com FU NIMH NIH HHS [R44 MH070241, MH070241] NR 28 TC 10 Z9 10 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 4 PY 2007 VL 104 IS 36 BP 14406 EP 14411 DI 10.1073/pnas.0700608104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 208QF UT WOS:000249333600042 PM 17720809 ER PT J AU Pozsgay, V Kubler-Kielb, J Schneerson, R Robbins, JB AF Pozsgay, Vince Kubler-Kielb, Joanna Schneerson, Rachel Robbins, John B. TI Effect of the nonreducing end of Shigella dysenteriae type 10-specific oligosaccharides on their immunogenicity as conjugates in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE vaccine; glycoconjugate; oligosaccharide synthesis; bioconjugation; dysentery ID O-SPECIFIC POLYSACCHARIDE; INFLUENZAE TYPE-B; GLYCOCONJUGATE VACCINE; BIOCHEMICAL-ANALYSIS; PROTEIN; LIPOPOLYSACCHARIDE; ANTIBODIES; ANTIGEN; BIOSYNTHESIS; SEROTYPE-1 AB Endemic and epidemic shigellosis, an acute invasive disease of the lower intestines, afflicts millions of people worldwide with an estimated one million fatalities per annum at a low infectious dose. Our approach to vaccine development against Shigella is based on the hypothesis that serum IgG antibodies to the O-specific polysaccharide (O-SP) domains of the LPS of these organisms confer protection to infection. The synthetic oligosaccharides corresponding to the tetrasaccharide repeating unit of the O-SP of Shigella dysenteriae type 1 covalently linked to human serum albumin elicited O-SP-specific IgG in mice. The antibody levels were a function of both the saccharide chain length and their loading on the protein. These synthetic saccharide conjugates elicited significantly higher levels of IgG anti O-SP than conjugates prepared with the O-SP from the bacteria. Here, we evaluated the influence of the nonreducing terminal monosaccharide on the serum antibody response. To this end, we prepared synthetic oligosaccharides comprising hexa- to tridecasaccharide fragments of the native O-SP, having one of the four monosaccharide residues that constitute the repeating unit at their termini and bound them to BSA by a single-point attachment. The conjugates contained an average of 19 saccharide chains per BSA. The synthetic oligosaccharides inhibited the binding of serum raised against whole bacteria to its LPS to a similar extent but lower than the native O-SP. The highest anti-LPS levels were elicited by conjugates having N-acetylglucosamine (10-mer) or galactose residues (7- and 11-mers) at their nonreducing termini. C1 NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. RP Pozsgay, V (reprint author), NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. EM pozsgayv@mail.nih.gov; robbinsjo@mail.nih.gov FU Intramural NIH HHS NR 42 TC 32 Z9 32 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 4 PY 2007 VL 104 IS 36 BP 14478 EP 14482 DI 10.1073/pnas.0706969104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 208QF UT WOS:000249333600054 PM 17726093 ER PT J AU Shiva, S Sack, MN Greer, JJ Duranski, M Ringwood, LA Burwell, L Wang, XD MacArthur, PH Shoja, A Raghavachari, N Calvert, JW Brookes, PS Lefer, DJ Gladwin, MT AF Shiva, Sruti Sack, Michael N. Greer, James J. Duranski, Mark Ringwood, Lorna A. Burwell, Lindsay Wang, Xunde MacArthur, Peter H. Shoja, Amir Raghavachari, Nalini Calvert, John W. Brookes, Paul S. Lefer, David J. Gladwin, Mark T. TI Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CYTOCHROME-C RELEASE; HYDROGEN-PEROXIDE PRODUCTION; ISCHEMIA-REPERFUSION INJURY; COMPLEX-I; PERMEABILITY TRANSITION; S-NITROSOTHIOLS; OXIDE SYNTHASE; MYOCARDIAL REPERFUSION; PROTECTS MITOCHONDRIA; CONSCIOUS RABBITS AB Nitrite ( NO2-) is an intrinsic signaling molecule that is reduced to NO during ischemia and limits apoptosis and cytotoxicity at reperfusion in the mammalian heart, liver, and brain. Although the mechanism of nitrite-mediated cytoprotection is unknown, NO is a mediator of the ischemic preconditioning cell-survival program. Analogous to the temporally distinct acute and delayed ischemic preconditioning cytoprotective phenotypes, we report that both acute and delayed ( 24 h before ischemia) exposure to physiological concentrations of nitrite, given both systemically or orally, potently limits cardiac and hepatic reperfusion injury. This cytoprotection is associated with increases in mitochondrial oxidative phosphorylation. Remarkably, isolated mitochondria subjected to 30 min of anoxia followed by reoxygenation were directly protected by nitrite administered both in vitro during anoxia or in vivo 24 h before mitochondrial isolation. Mechanistically, nitrite dose-dependently modifies and inhibits complex I by posttranslational S-nitrosation; this dampens electron transfer and effectively reduces reperfusion reactive oxygen species generation and ameliorates oxidative inactivation of complexes II-IV and aconitase, thus preventing mitochondrial permeability transition pore opening and cytochrome c release. These data suggest that nitrite dynamically modulates mitochondrial resilience to reperfusion injury and may represent an effector of the cell-survival program of ischemic preconditioning and the Mediterranean diet. C1 NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Univ Rochester, Med Ctr, Dept Anesthesiol, Rochester, NY 14642 USA. RP Gladwin, MT (reprint author), NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. EM mgladwin@nih.gov RI Lefer, David/A-6372-2012; Calvert, John/F-4497-2014 OI Calvert, John/0000-0001-6858-6042 FU NHLBI NIH HHS [R01 HL 60849, R01 HL060849]; NIDDK NIH HHS [F32 DK 077380-01, F32 DK077380] NR 64 TC 310 Z9 317 U1 2 U2 28 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 3 PY 2007 VL 204 IS 9 BP 2089 EP 2102 DI 10.1084/jem.20070198 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 207AW UT WOS:000249225000010 PM 17682069 ER PT J AU Laky, K Fowlkes, BJ AF Laky, Karen Fowlkes, B. J. TI Presenilins regulate alpha beta T cell development by modulating TCR signaling SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NF-KAPPA-B; THYMOCYTE DEVELOPMENT; POSITIVE SELECTION; LINEAGE DECISION; CD8 LINEAGE; IN-VIVO; IMMATURE THYMOCYTES; TRANSGENIC MICE; GENE-EXPRESSION; PRE-TCR AB TCR alpha beta signaling is crucial for the maturation of CD4 and CD8 T cells, but the role of the Notch signaling pathway in this process is poorly understood. Genes encoding Presenilin ( PS) 1/ 2 were deleted to prevent activation of the multiple Notch receptors expressed by developing thymocytes. PS1/ 2 knockout thymocyte precursors inefficiently generate CD4 T cells, a phenotype that is most pronounced when thymocytes bear a single major histocompatibility complex ( MHC) class II-restricted T cell receptor ( TCR). Diminished T cell production correlated with evidence of impaired TCR signaling, and could be rescued by manipulations that enhance MHC recognition. Although Notch appears to directly regulate binary fate decisions in many systems, these findings suggest a model in which PS-dependent Notch signaling influences positive selection and the development of alpha beta T cells by modifying TCR signal transduction. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Fowlkes, BJ (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. EM bfowlkes@nih.gov FU Intramural NIH HHS NR 85 TC 25 Z9 25 U1 0 U2 1 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 3 PY 2007 VL 204 IS 9 BP 2115 EP 2129 DI 10.1084/jem.20070550 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 207AW UT WOS:000249225000012 PM 17698590 ER PT J AU Okoye, A Meier-Schellersheim, M Brenchley, JM Hagen, SI Walker, JM Rohankhedkar, M Lum, R Edgar, JB Planer, SL Legasse, A Sylwester, AW Piatak, M Lifson, JD Maino, VC Sodora, DL Douek, DC Axthelm, MK Grossman, Z Picker, LJ AF Okoye, Afam Meier-Schellersheim, Martin Brenchley, Jason M. Hagen, Shoko I. Walker, Joshua M. Rohankhedkar, Mukta Lum, Richard Edgar, John B. Planer, Shannon L. Legasse, Alfred Sylwester, Andrew W. Piatak, Michael, Jr. Lifson, Jeffrey D. Maino, Vernon C. Sodora, Donald L. Douek, Daniel C. Axthelm, Michael K. Grossman, Zvi Picker, Louis J. TI Progressive CD4(+) central-memory T cell decline results in CD4(+) effector-memory insufficiency and overt disease in chronic SIV infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; HIV-INFECTION; ANTIRETROVIRAL THERAPY; GASTROINTESTINAL-TRACT; IMMUNE ACTIVATION; RHESUS MACAQUE; VIRAL LOAD; PREDICTIVE-VALUE; DEPLETION; MONKEYS AB Primary simian immunodeficiency virus ( SIV) infections of rhesus macaques result in the dramatic depletion of CD4(+) CCR5(+) effector-memory T ( T-EM) cells from extra-lymphoid effector sites, but in most infections, an increased rate of CD4(+) memory T cell proliferation appears to prevent collapse of effector site CD4(+) T-EM cell populations and acute-phase AIDS. Eventually, persistent SIV replication results in chronic-phase AIDS, but the responsible mechanisms remain controversial. Here, we demonstrate that in the chronic phase of progressive SIV infection, effector site CD4(+) T-EM cell populations manifest a slow, continuous decline, and that the degree of this depletion remains a highly significant correlate of late-onset AIDS. We further show that due to persistent immune activation, effector site CD4(+) T-EM cells are predominantly short-lived, and that their homeostasis is strikingly dependent on the production of new CD4(+) T-EM cells from central -memory T ( T-CM) cell precursors. The instability of effector site CD4(+) T-EM cell populations over time was not explained by increasing destruction of these cells, but rather was attributable to progressive reduction in their production, secondary to decreasing numbers of CCR5-CD4(+) T-CM cells. These data suggest that although CD4(+) T-EM cell depletion is a proximate mechanism of immuno-deficiency, the tempo of this depletion and the timing of disease onset are largely determined by destruction, failing production, and gradual decline of CD4(+) T-CM cells. C1 Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Pathol, Beaverton, OR 97006 USA. Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. NIAID, Immunol Lab, Bethesda, MD 20892 USA. Vaccine Res Ctr, Human Immunol Sect, Bethesda, MD 20892 USA. Natl Canc Inst, Sci Applicat Int Corp Frederick Inc, AIDS Vaccine Program, Ft Detrick, MD 21702 USA. Becton Dickinson Biosci, San Jose, CA 95131 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. RP Picker, LJ (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Pathol, Beaverton, OR 97006 USA. EM pickerl@ohsu.edu RI Grossman, Zvi/A-9643-2008 FU NCI NIH HHS [N01 CO 124000]; NCRR NIH HHS [P51 RR 00163, P51 RR000163, U24 RR 018107, U24 RR018107, U42 RR 016025, U42 RR016025]; NIAID NIH HHS [R01 AI 054292, R01 AI054292] NR 66 TC 182 Z9 187 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 3 PY 2007 VL 204 IS 9 BP 2171 EP 2185 DI 10.1084/jem.20070567 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 207AW UT WOS:000249225000016 PM 17724130 ER PT J AU McKinstry, KK Golech, S Lee, WH Huston, G Weng, NP Swain, SL AF McKinstry, K. Kai Golech, Susanne Lee, Won-Ha Huston, Gail Weng, Nan-Ping Swain, Susan L. TI Rapid default transition of CD4 T cell effectors to functional memory cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID GENE-EXPRESSION; IMMUNOLOGICAL MEMORY; PROTECTIVE IMMUNITY; LEISHMANIA-MAJOR; CLASS-II; IN-VIVO; GENERATION; NAIVE; ACTIVATION; ABSENCE AB The majority of highly activated CD4 T cell effectors die after antigen clearance, but a small number revert to a resting state, becoming memory cells with unique functional attributes. It is currently unclear when after antigen clearance effectors return to rest and acquire important memory properties. We follow well-defined cohorts of CD4 T cells through the effector-to-memory transition by analyzing phenotype, important functional properties, and gene expression profiles. We find that the transition from effector to memory is rapid in that effectors rested for only 3 d closely resemble canonical memory cells rested for 60 d or longer in the absence of antigen. This is true for both Th1 and Th2 lineages, and occurs whether CD4 T cell effectors rest in vivo or in vitro, suggesting a default pathway. We find that the effector -memory transition at the level of gene expression occurs in two stages: a rapid loss of expression of a myriad of effector-associated genes, and a more gradual gain of expression of a cohort of genes uniquely associated with memory cells rested for extended periods. C1 Trudeau Inst Inc, Saranac Lake, NY 12983 USA. NIA, NIH, Baltimore, MD 21224 USA. RP McKinstry, KK (reprint author), Trudeau Inst Inc, POB 59, Saranac Lake, NY 12983 USA. EM kmckinstry@trudeauinstitute.org FU Intramural NIH HHS; NIAID NIH HHS [AI 46530, P01 AI046530] NR 66 TC 64 Z9 65 U1 1 U2 1 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 3 PY 2007 VL 204 IS 9 BP 2199 EP 2211 DI 10.1084/jem.20070041 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 207AW UT WOS:000249225000018 PM 17724126 ER PT J AU Petralia, RS Yao, PJ AF Petralia, Ronald S. Yao, Pamela J. TI AP180 and CALM in the developing hippocampus: Expression at the nascent synapse and localization to trafficking organelles SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE clathrin adaptor; clathrin-coated vesicle; neuron ID CLATHRIN ASSEMBLY PROTEIN; AMPA RECEPTOR TRAFFICKING; CENTRAL-NERVOUS-SYSTEM; VESICLE ENDOCYTOSIS; DIFFERENTIAL EXPRESSION; GLUTAMATERGIC SYNAPSES; DENDRITIC SPINES; ALPHA-APPENDAGE; PLASMA-MEMBRANE; COATED VESICLES AB Genetic and biochemical evidence has established that clathrin assembly protein AP180 is required for the proper assembly of synaptic vesicles via clathrin-mediated endocytosis. The assembly protein CALM, the ubiquitously expressed homolog of AP180, also regulates the formation of clathrin-coated vesicles. In this study we found high expression levels of AP180 and CALM in hippocampal tissues as early as embryonic day 18, before the expression of synaptophysin. We also used immunoelectron microscopy to establish the distribution of AP180 and CALM in the developing hippocampal synapses. We found AP180 and CALM in synapses at all developmental stages and in nonsynaptic growing processes. In addition to localization on the plasma membrane and clathrin-coated vesicles that originated from the plasma membrane, we also report the presence of AP180 and CALM on other types of membrane structures. Our observations link AP180 and CALM to multiple vesicular organelles and raise the possibility that these proteins may play additional roles in developing neurons. C1 NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Yao, PJ (reprint author), NIA, Neurosci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM yaopa@grc.nia.nih.gov FU Intramural NIH HHS NR 59 TC 11 Z9 11 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 2 PY 2007 VL 504 IS 3 BP 314 EP 327 DI 10.1002/cne.21454 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 203SI UT WOS:000248993900008 PM 17640037 ER PT J AU Davis, CD Milner, JA AF Davis, Cindy D. Milner, John A. TI Biomarkers for diet and cancer prevention research: potentials and challenges SO ACTA PHARMACOLOGICA SINICA LA English DT Review DE exposure biomarker; effect biomarker; susceptibility biomarker; nutrigenomics ID MANGANESE SUPEROXIDE-DISMUTASE; ENDOTHELIAL GROWTH-FACTOR; ONE-CARBON METABOLISM; TUMOR-NECROSIS-FACTOR; CELL-CYCLE ARREST; PROSTATE-CANCER; DNA-DAMAGE; MOLECULAR TARGETS; GENE-EXPRESSION; BREAST-CANCER AB As cancer incidence is projected to increase for decades there is a need for effective preventive strategies. Fortunately, evidence continues to mount that altering dietary habits is an effective and cost-efficient approach for reducing cancer risk and for modifying the biological behavior of tumors. Predictive, validated and sensitive biomarkers, including those that reliably evaluate "intake" or exposure to a specific food or bioactive component, that assess one or more specific biological "effects" that are linked to cancer, and that effectively predict individual "susceptibility" as a function of nutrient-nutrient interactions and genetics, are fundamental to evaluating who will benefit most from dietary interventions. These biomarkers must be readily accessible, easily and reliably assayed, and predictive of a key process(es) involved in cancer. The response to a food is determined not only by the effective concentration of the bioactive food component(s) reaching the target tissue, but also by the amount of the target requiring modification. Thus, this threshold response to foods and their components will vary from individual to individual. The key to understanding a personalized response is a greater knowledge of nutrigenomics, proteomics and metabolomics. C1 NCI, Nutr Sci Res Grp, Bethesda, MD 20892 USA. RP Davis, CD (reprint author), NCI, Nutr Sci Res Grp, Bethesda, MD 20892 USA. EM davisci@mail.nih.gov NR 91 TC 28 Z9 30 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD SEP PY 2007 VL 28 IS 9 BP 1262 EP 1273 DI 10.1111/j.1745-7254.2007.00678.x PG 12 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 206ZH UT WOS:000249220900002 PM 17723162 ER PT J AU Manaye, KF Wang, PC O'Neil, JN Huang, SY Xu, T Lei, DL Tizabi, Y Ottinger, MA Ingram, DK Mouton, PR AF Manaye, Kebreten F. Wang, Paul C. O'Neil, Jahn N. Huang, Sophia Y. Xu, Tao Lei, De-Liang Tizabi, Yousef Ottinger, Mary Ann Ingram, Donald K. Mouton, Peter R. TI Neuropathological quantification of dtg APP/PS1: neuroimaging, stereology, and biochemistry SO AGE LA English DT Article DE MRI; Alzheimer's disease; hippocampal formation; amygdala; unbiased stereology ID ALZHEIMERS-DISEASE; COGNITIVE DECLINE; NEURITIC PLAQUES; CEREBRAL ATROPHY; LOCUS-COERULEUS; SYNAPSE LOSS; DEMENTIA; HIPPOCAMPUS; MICE; EFFICIENCY AB Murine models that mimic the neuropathology of Alzheimer's disease (AD) have the potential to provide insight into the pathogenesis of the disease and lead to new strategies for the therapeutic management of afflicted patients. We used magnetic resonance imaging (MRI), design-based stereology, and high performance liquid chromatography (HPLC) to assess the age-related neuropathology in double transgenic mice that overexpress two AD-related proteins-amyloid precursor protein (APP) and presenilin 1 (PS1)-and age- and gender-matched wild-type (WT) controls. In mice ranging in age from 4-28 months, total volumes of the hippocampal formation (V-HF) and whole brain (V-brain) were quantified by the Cavalieri-point counting method on a systematic-random sample of coronal T2-weighted MRI images; the same stereological methods were used to quantify V-HF and V-brain after perfusion and histological processing. To assess changes in AD-type beta-amyloid (A beta) plaques, sections from the hippocampal formation and amylgdaloid complex of mice aged 5, 12, and 15 months were stained by Congo Red histochemistry. In aged mice with large numbers of amyloid plaques, systematic-random samples of sections were stained by GFAP immunocytochemistry to assess gender and genotype effects on total numbers of astrocytes. In addition, levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and 5-HT metabolites were assayed by HPLC in fresh-frozen samples from neocortex, striatum, hippocampus, and brainstem. We confirmed age-related increases in amyloid plaques, beginning with a few plaques at 5 months of age and increasing densities by 12 and 15 months. At 15 months of age, there were robust genotype effects, but no gender effects, on GFAP-immunopositive astrocytes in the amygdaloid complex and hippocampus. There were no effects on monoamine levels in all brain regions examined, and no volume changes in hippocampal formation or whole brain as quantified on either neuroimages or tissue sections. Strong correlations were present between volume estimates from MRI images and histological sections, with about 85% reduction in mean V-HF or mean V-brain between MRI and processed histological sections. In summary, these findings show that the double transgenic expression of AD-type mutations is associated with age-related increases in amyloid plaques and astrocytosis; however, this model does not recapitulate the cortical atrophy or neurochemical changes that are characteristic of AD. C1 Howard Univ, Coll Med, Dept Physiol & Biophys, Washington, DC 20059 USA. Howard Univ, Coll Med, Dept Radiol, Washington, DC 20059 USA. Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. Univ Maryland, College Pk, MD 20742 USA. NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. Louisiana State Univ, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70803 USA. Stereol Resource Ctr, Chester, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Manaye, KF (reprint author), Howard Univ, Coll Med, Dept Physiol & Biophys, 520 W St,NW,Suite 2305,Adams Bldg, Washington, DC 20059 USA. EM kmanaye@howard.edu FU NCRR NIH HHS [G12 RR003048]; NIMH NIH HHS [R44 MH076541]; NINDS NIH HHS [U54 NS039407] NR 42 TC 21 Z9 24 U1 2 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD SEP PY 2007 VL 29 IS 2-3 BP 87 EP 96 DI 10.1007/s11357-007-9035-y PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 201KK UT WOS:000248829900004 PM 19424834 ER PT J AU Nadon, NL AF Nadon, Nancy L. TI The national institute on aging interventions testing program SO AGE LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD SEP PY 2007 VL 29 IS 2-3 BP 129 EP 130 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 201KK UT WOS:000248829900063 ER PT J AU Zou, S Carey, JR Liedo, P Oropeza, A Ingram, DK AF Zou, Sige Carey, James R. Liedo, Pablo Oropeza, Azucena Ingram, Donald K. TI A large-scale screen system for prolongevity interventions using the mexican fruit fly Anastrepha ludens SO AGE LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. El Colegio Frontera Sur, Tapachula, Chiapas, Mexico. RI Trejo, Yesenia/D-9257-2012; Liedo, Pablo/E-9313-2010 OI Liedo, Pablo/0000-0002-0004-1721 NR 0 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD SEP PY 2007 VL 29 IS 2-3 BP 129 EP 129 PG 1 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 201KK UT WOS:000248829900062 ER PT J AU Strong, R Nelson, J Javors, M Sharp, D Peralba, J Miller, R Harrison, D Nadon, N AF Strong, R. Nelson, J. Javors, M. Sharp, D. Peralba, J. Miller, R. Harrison, D. Nadon, N. TI Long-term administration of compounds to rodents: Technical challenges and solutions SO AGE LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Psychait, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Barshop Aging Inst, San Antonio, TX USA. Univ Michigan, Dept Pathol & Geriat Ctr, Ann Arbor, MI 48109 USA. VA Med Ctr, Ann Arbor, MI 48109 USA. Jackson Lab, Bar Harbor, ME 04609 USA. NIA, Biol Aging Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD SEP PY 2007 VL 29 IS 2-3 BP 130 EP 130 PG 1 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 201KK UT WOS:000248829900064 ER PT J AU de Cabo, R AF de Cabo, Rafael TI Lifespan extension by resveratrol SO AGE LA English DT Meeting Abstract C1 NIA, Lab Expt Gerontol, NIH, Gerontol Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD SEP PY 2007 VL 29 IS 2-3 BP 131 EP 131 PG 1 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 201KK UT WOS:000248829900066 ER PT J AU Levintova, M AF Levintova, Marya TI Russian alcohol policy in the making SO ALCOHOL AND ALCOHOLISM LA English DT Article ID MORTALITY; FEDERATION AB Aims: This paper examines implementation of the 2005 federal alcohol control law in the Russian Federation. Methods: The documents on the Russian Federation federal legislation on the control of the production and turnover of ethyl alcohol, and ethyl alcohol containing products, news reports, research, and historical documents were gathered and analysed for implementation barriers. Results: Consumption of alcoholic beverages, especially spirits, has been one the most significant public health problems in Russia for many centuries. Prior attempts to control alcohol consumption have been unsuccessful, in part due to the governments reliance on alcohol revenue, and its inability to implement creative and manageable solutions in the light of the high drinking rates. Implementation of this legislation has been a challenge in Russia because of administrative oversight, lack of organizational preparation, and corruption. Conclusions: The law discussed in this paper presented a window of opportunity to ameliorate the deteriorating health status and reverse the impending mortality crisis. However, a number of barriers presented substantial setbacks toward realization of this legislation. C1 Natl Inst Hlth, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Levintova, M (reprint author), Natl Inst Hlth, Fogarty Int Ctr, 31 Ctr Dr,Room B2C11, Bethesda, MD 20892 USA. EM levintovam@mail.nih.gov FU NIAAA NIH HHS [T32 AA 07240] NR 52 TC 30 Z9 30 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD SEP-OCT PY 2007 VL 42 IS 5 BP 500 EP 505 DI 10.1093/alcalc/agm040 PG 6 WC Substance Abuse SC Substance Abuse GA 227MX UT WOS:000250661900016 PM 17537829 ER PT J AU Donohue, TM Cederbaum, AI French, SW Barve, S Gao, B Osna, NA AF Donohue, Terrence M., Jr. Cederbaum, Arthur I. French, Samuel W. Barve, Shirish Gao, Bin Osna, Natalia A. TI Role of the proteasome in ethanol-induced liver pathology SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism DE ethanol metabolism; proteolysis; ubiquitin proteasome system; alcoholic liver disease; signal transduction; antigen presentation. ID CYTOKERATIN AGGRESOME FORMATION; ISOLATED RAT HEPATOCYTES; NF-KAPPA-B; HEPG2 CELLS; ALCOHOLIC HEPATITIS; OXIDATIVE STRESS; MALLORY BODIES; IN-VITRO; ANTIGEN PRESENTATION; GENE-EXPRESSION AB The ubiquitin-proteasome system has come to be known as a vital constituent of mammalian cells. The proteasome is a large nonlysosomal enzyme that acts in concert with an 8.5 kDa polypeptide called ubiquitin and a series of conjugating enzymes, known as E1, E2 and E3, that covalently bind multiple ubiquitin moieties in a polyubiquitin chain to protein substrates in a process called ubiquitylation. The latter process targets protein substrates for unfolding and degradation by the 26S proteasome. This enzyme system specically recognizes and degrades polyubiquitylated proteins, many of which are key proteins involved in cell cycle regulation, apoptosis, signal transduction, and antigen presentation. The 26S proteasome contains a cylinder-shaped 20S catalytic core that, itself, degrades proteins in an ATP- and ubiquitin-independent manner. The 20S form is actually the predominant enzyme form in mammalian cells. Proteolysis by the constitutive 20S proteasome is vital in removing oxidized, misfolded and otherwise modified proteins. Such degradation is critical as a means of cellular detoxication, as intracellular accumulation of damaged and misfolded proteins is potentially lethal. Studies have shown that inhibition of proteasome activity can lead to cell death. Ethanol and its metabolism cause partial inhibition of the proteasome. This leads to a number of pleiotropic effects that can affect a variety of cellular processes. This critical review describes important aspects of ethanol metabolism and its influence on the proteasome. The review will summarize recent findings on: ( 1) the interactions between the proteasome and the ethanol metabolizing enzyme, CYP2E1; ( 2) the dynamics of proteasome inhibition by ethanol in animal models and cultured cells; ( 3) ethanol-elicited suppression of proteasome activity and its effect on signal transduction; ( 4) The role of proteasome inhibition in cytokine production by liver cells; and ( 5) ethanol elicited suppression of peptide hydrolysis and the potential effects on antigen presentation. While the principal focus is on alcohol-induced liver injury, the authors foresee that the findings presented in this review will prompt further research on the role of this proteolytic system in other tissues injured by excessive alcohol consumption. C1 Vet Affairs Med Ctr, Res Serv, Liver Study Unit, Omaha, NE 68105 USA. Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA. Mt Sinai Med Ctr, Dept Pharmacol, New York, NY 10029 USA. Mt Sinai Med Ctr, Dept Biol Chem, New York, NY 10029 USA. Univ Calif Los Angeles, Harbor Med Ctr, Dept Anat Pathol, Torrance, CA 90509 USA. Univ Louisville, Med Ctr, Dept Internal Med, Louisville, KY 40292 USA. NIH, Sect Liver Biol, Bethesda, MD 20892 USA. RP Donohue, TM (reprint author), Vet Affairs Med Ctr, Res Serv, Liver Study Unit, 4101 Woolworth Ave, Omaha, NE 68105 USA. EM tdonohue@unmc.edu NR 92 TC 27 Z9 27 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2007 VL 31 IS 9 BP 1446 EP 1459 DI 10.1111/j.1530-0277.2007.00454.x PG 14 WC Substance Abuse SC Substance Abuse GA 203EL UT WOS:000248957800002 PM 17760783 ER PT J AU Salloum, JB Ramchandani, VA Bodurka, J Rawlings, R Momenan, R George, D Hommer, DW AF Salloum, Jasmin B. Ramchandani, Vijay A. Bodurka, Jerzy Rawlings, Robert Momenan, Reza George, David Hommer, Daniel W. TI Blunted rostral anterior cingulate response during a simplified decoding task of negative emotional facial expressions in alcoholic patients SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcoholism; fMRI; faces; anterior Cingulate cortex; emotion; cognition ID CEREBRAL-BLOOD-FLOW; GO/NO-GO TASK; COUNTING STROOP; FUNCTIONAL MRI; RECOGNITION; DISORDER; STIMULI; FMRI; DEFICITS; CORTEX AB Background: Alcoholism is characterized by deficits in emotional functioning as well as by deficits in cognitive functioning. However, most brain imaging research on alcoholism has focused on cognition rather than emotion. Method:We used an event-related functional magnetic imaging approach to examine alcoholics' brain blood oxygenation level dependent (BOLD) response to evaluation of emotional stimuli and to compare their response to that of nonalcoholic controls. The task used was a simplified variant of a facial emotion-decoding task in which subjects determined the intensity level of a target emotion displayed as a facial expression. Facial expressions of happy, sad, anger, disgust, and fear were used as stimuli. Results: Alcoholics and controls did not differ in accurately identifying the intensity level on the simple emotional decoding task but there were significant differences in their BOLD response during evaluation of facial emotion. In general, alcoholics showed less brain activation than nonalcoholic controls. The greatest differences in activation were during decoding of facial expressions of fear and disgust during which alcoholics had significantly less activation than controls in the affective division of the anterior cingulate cortex (ACC). Alcoholics also had significantly less activation than controls in the affective division of the ACC, while viewing sad faces. Only to facial expressions of anger did the alcoholics show significant activation in the affective ACC and in this case, their BOLD response did not significantly differ from that of the controls. Conclusion: Alcoholics show a deficit in the function of the affective division of the ACC during evaluation of negative facial emotions that can serve as cues for flight or avoidance. This deficit may underlie some of the behavioral dysfunction in alcoholism. C1 NIAAA, Lab Clin Translat Studies, NIH, Bethesda, MD USA. NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA. RP Salloum, JB (reprint author), NIAAA, Lab Clin Translat Studies, NIH, 10 Ctr Dr, Bethesda, MD USA. EM jasmins@mail.nih.gov FU Intramural NIH HHS NR 63 TC 56 Z9 56 U1 3 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2007 VL 31 IS 9 BP 1490 EP 1504 DI 10.1111/j.1530-0277.2007.00447.x PG 15 WC Substance Abuse SC Substance Abuse GA 203EL UT WOS:000248957800007 PM 17624997 ER PT J AU Le, DSNT Pannacciulli, N Chen, K Salbe, AD Hill, JO Wing, RR Reiman, EM Krakoff, J AF Le, Duc Son N. T. Pannacciulli, Nicola Chen, Kewei Salbe, Arline D. Hill, James O. Wing, Rena R. Reiman, Eric M. Krakoff, Jonathan TI Less activation in the left dorsolateral prefrontal cortex in the reanalysis of the response to a meal in obese than in lean women and its association with successful weight loss SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE dorsolateral prefrontal cortex; neuronal activity; fixture of obesity; weight loss; satiety; formerly obese; positron emission tomography; PET ID POSITRON-EMISSION-TOMOGRAPHY; PERCEPTUAL DECISION-MAKING; BAYESIAN-INFERENCE; BRAIN RESPONSES; SATIATION; HUMANS; HUNGER; APPETITE; SATIETY AB Background: We previously found that obese men have less activation in the left dorsolateral prefrontal cortex (LDLPFC) in response to a meal than do lean men, which indicates an association between this altered neuronal response and the pathophysiology of obesity. Objectives: The objectives of the study were to extend this finding in obese women and to investigate activity in this region in women with a history of severe obesity who have successfully lost weight (ie, formerly obese women, sometimes called postobese women). Design: We reanalyzed previously collected data to compare postmeal (after receiving a liquid meal) with premeal (after a 36-h fast) regional cerebral blood flow, a marker of neuronal activity, by using O-15-water positron emission tomography in 10 lean [26 +/- 6% body fat (1317)], 9 obese (39 +/- 3%BF) and 8 formerly obese (28 +/- 4%BF) right-handed women. Data were analyzed by using a 2-level, random-effect analysis of variance. Results: The regional cerebral blood flow in the LDLPFC differed in response to the meal across the 3 groups (P < 0.001, uncorrected for multiple comparisons). Post hoe group comparisons showed that obese women had significantly less activation in this area than did lean and formerly obese women. No significant difference between formerly obese and lean women was found. Conclusions: These results extend our previous findings, indicating that obese women have less activation in the LDLPFC in response to a meal than do lean or formerly obese women. Neuronal activity in this region did not differ significantly between the latter 2 groups. Longitudinal studies are needed to determine whether these differences in neuronal activity change with or predict weight change. C1 NIDDKD, DHHS, NIDDK, ODCRS,PECRB,DSNT Le, Phoenix, AZ 85016 USA. Alzheimer Inst, Banner Good Samaritan Med Ctr, Phoenix, AZ USA. Alzheimer Inst, Med Ctr, Banner Positron Emiss Tomography Ctr, Phoenix, AZ USA. Univ Colorado, Hlth Sci Ctr, Ctr Human Nutr, Denver, CO 80202 USA. Brown Univ, Miriam Hosp Weigth Control, Providence, RI 02912 USA. Brown Univ, Diabet Res Ctr, Providence, RI 02912 USA. RP Le, DSNT (reprint author), NIDDKD, DHHS, NIDDK, ODCRS,PECRB,DSNT Le, 4212 N 16Th St,Room 5-35, Phoenix, AZ 85016 USA. EM leds@mail.nih.gov RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 FU Intramural NIH HHS [Z01 DK069015-25] NR 41 TC 52 Z9 53 U1 1 U2 4 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2007 VL 86 IS 3 BP 573 EP 579 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 210WC UT WOS:000249485300008 PM 17823419 ER PT J AU Pannacciulli, N Salbe, AD Ortega, E Venti, CA Bogardus, C Krakoff, J AF Pannacciulli, Nicola Salbe, Arline D. Ortega, Emilio Venti, Colleen A. Bogardus, Clifton Krakoff, Jonathan TI The 24-h carbohydrate oxidation rate in a human respiratory chamber predicts ad libitum food intake SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE substrate oxidation; nutrient balance; food intake; body weight regulation ID BODY-WEIGHT GAIN; ENERGY-EXPENDITURE; SUBSTRATE OXIDATION; PIMA-INDIANS; FUEL UTILIZATION; GLYCOGEN STORES; CAFETERIA DIET; FAT GAIN; MEN; MANIPULATION AB Background: The 24-h respiratory quotient (24-h RQ) and 24-h carbohydrate balance (24-h CHO-Bal) are predictors of weight change. Whether these relations are mediated by the effects of substrate oxidation and balance on food intake is not known. Objective: We tested whether substrate oxidation and balance predict future ad libitum food intake. Design: Substrate oxidation and balance were measured in a respiratory chamber in 112 normoglycemic subjects (83 Pima Indians and 29 whites; 67 men and 45 women) in energy balance for 3 d before tests were performed. The subjects then self-selected their food ad libitum for the following 3 d. Results: The 24-h RQ, 24-h carbohydrate oxidation (24-h CHO-Ox), and 24-h CHO-Bal in the respiratory chamber predicted subsequent ad libitum food intake over 3 d (as a percentage of weight maintenance energy needs; %EN-WM). The 24-h CHO-Ox explained 15% of the variance in %EN-WM. The weight change over the 3-d ad libitum period was associated positively with 24-h CHO-Ox and negatively with 24-h CHO-Bal in the chamber; these associations were no longer significant after adjustment for %EN-WM. Conclusion: Carbohydrate oxidation and balance predict subsequent ad libitum food intake and can influence short-term weight changes, which indicates that carbohydrate balance is a contributing metabolic factor affecting food intake. C1 NIDDK, Obesity & Diabet Clin Res Sect, Phoenix Expidemiol & Clin Res Branch, NIH,Dept Hlth & Human Serv, Phoenix, AZ USA. RP Pannacciulli, N (reprint author), Amylin Pharmaceut Inc, 9360 Towne Ctr Dr, San Diego, CA 92121 USA. EM nico.pannacciulli@amylin.com FU Intramural NIH HHS [Z01 DK069015-25] NR 42 TC 55 Z9 56 U1 1 U2 8 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2007 VL 86 IS 3 BP 625 EP 632 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 210WC UT WOS:000249485300015 PM 17823426 ER PT J AU Pfeiffer, CM Johnson, CL Jain, RB Yetley, EA Picciano, MF Rader, JI Fisher, KD Mulinare, J Osterloh, JD AF Pfeiffer, Christine M. Johnson, Clifford L. Jain, Ram B. Yetley, Elizabeth A. Picciano, Mary Frances Rader, Jeanne I. Fisher, Kenneth D. Mulinare, Joseph Osterloh, John D. TI Trends in blood folate and vitamin B-12 concentrations in the United States, 1988-2004 SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE nutrition survey; age; sex; race; ethnic groups; National Health and Nutrition Examination Survey; NHANES; fortification; neural tube defects ID FOLIC-ACID FORTIFICATION; TOTAL HOMOCYSTEINE CONCENTRATIONS; FOOD FORTIFICATION; NATIONAL-HEALTH; MYOCARDIAL-INFARCTION; COGNITIVE IMPAIRMENT; CONTROLLED-TRIAL; DIETARY-FOLATE; SERUM FOLATE; B-VITAMINS AB Background: Monitoring the folate status of US population groups over time has been a public health priority for the past 2 decades, and the focus has been enhanced since the implementation of a folic acid fortification program in the mid-1990s. Objective: We aimed to determine how population concentrations of serum and red blood cell (RBC) folate and serum vitamin B-12 have changed over the past 2 decades. Design: Measurement of blood indicators of folate and vitamin B-12 status was conducted in approximate to 23 000 participants in the prefortification third National Health and Nutrition Examination Survey (NHANES 111; 1988-1994) and in approximate to 8000 participants in 3 postfortification NHANES periods (together covering 1999-2004). Results: Serum and RBC folate concentrations increased substantially (by 119-161 % and 44-64%, respectively) in each age group in the first postfortification survey period and then declined slightly (by 5-13% and 6-9%, respectively) in most age groups between the first and third postfortification survey periods. Serum vitamin 13-12 concentrations did not change appreciably. Prevalence estimates of low serum and RBC folate concentrations declined in women of childbearing age from before to after fortification (from 21 % to < 1 % and from 38% to 5%, respectively) but remained unchanged thereafter. Prevalence estimates of high serum folate concentrations increased in children and older persons from before to after fortification (from 5% to 42% and from 7% to 38%, respectively) but decreased later after fortification. Conclusions: The decrease in folate concentrations observed longer after fortification is small compared with the increase soon after the introduction of fortification. The decrease is not at the low end of concentrations and therefore does not raise concerns about inadequate status. C1 Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Natl Ctr Birth Defects & Dev Disabilities, Atlanta, GA USA. US FDA, College Pk, MD USA. Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD USA. RP Pfeiffer, CM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, 4770 Buford Hwy,NE MS F55, Atlanta, GA 30341 USA. EM cpfeiffer@cdc.gov NR 47 TC 172 Z9 176 U1 3 U2 12 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2007 VL 86 IS 3 BP 718 EP 727 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 210WC UT WOS:000249485300027 PM 17823438 ER PT J AU Hsing, AW Sakoda, LC Chua, SC AF Hsing, Ann W. Sakoda, Lori C. Chua, Streamson C., Jr. TI Obesity, metabolic syndrome, and prostate cancer SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT 8th Postgraduate Nutrition Symposium on Metabolic Syndrome and the Onset of Cancer CY MAR 15-16, 2006 CL Boston, MA SP Harvard Med Sch, Div Nutr & Harvard Clin Nutr Res Ctr, Harvard Sch Public Hlth, Dept Nutr, Coca Cola Co, Beverage Inst Hlth & Wellness, Pharmavite, LLC, ConAgra Foods, Natl Dairy Council, Peanut Inst, Conrad Taff Teaching, S Daniel Abraham Teaching Fund, Harvard Ctr Healthy Living DE obesity; abdominal obesity; metabolic syndrome; insulin resistance; prostate cancer ID BODY-MASS INDEX; HORMONE-BINDING GLOBULIN; AFRICAN-AMERICAN MEN; FACTOR-KAPPA-B; DIABETES-MELLITUS; INSULIN-RESISTANCE; UNITED-STATES; NUCLEAR-LOCALIZATION; TOTAL TESTOSTERONE; NORWEGIAN MEN AB Although obesity has been consistently linked to an increased risk of several malignancies, including cancers of the colon, gallbladder, kidney, and pancreas, its role in prostate cancer etiology remains elusive. Data on the association between obesity and prostate cancer incidence are inconsistent, and in some studies obesity is associated with an increase in risk of high-grade prostate cancer but with a decrease in risk of low-grade tumors. In contrast, obesity has been consistently associated with an increased risk of prostate cancer aggressiveness and mortality. The differential effects of obesity on subtypes of prostate cancer suggest etiologic heterogeneity in these tumors and complex interactions between androgen metabolism and several putative risk factors, including insulin resistance, diabetes, inflammation, and genetic susceptibility, on prostate cancer risk. Data on the role of abdominal obesity, insulin resistance, and metabolic syndrome in prostate cancer etiology are limited. Obesity has been shown to be associated with a state of low-grade chronic inflammation, and insulin resistance and the metabolic syndrome are associated with adverse metabolic profiles and with higher circulating concentrations of inflammation-related markers, including leptin, interleukin-6, and tumor necrosis factor-a, many of which have been shown to enhance tumor growth. Thus, whether obesity and metabolic syndrome modulate the risk of prostate cancer through chronic inflammation needs to be investigated further. Given that the prevalence of obesity and metabolic syndrome is increasing worldwide and that the world population is aging, the roles of obesity and metabolic syndrome in prostate carcinogenesis warrant further clarification. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Albert Einstein Coll Med, Dept Med, New York, NY USA. Albert Einstein Coll Med, Dept Neurosci, New York, NY USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 5024,MSC 7234, Rockville, MD 20852 USA. EM hsinga@mail.nih.gov FU Intramural NIH HHS; NIDDK NIH HHS [9P01DK26687] NR 84 TC 153 Z9 158 U1 3 U2 18 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2007 VL 86 IS 3 BP 843S EP 857S PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 210WC UT WOS:000249485300052 PM 18265478 ER PT J AU Ross, SA Milner, JA AF Ross, Sharon A. Milner, John A. TI Epigenetic modulation and cancer: effect of metabolic syndrome? SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT 8th Postgraduate Nutrition Symposium on Metabolic Syndrome and the Onset of Cancer CY MAR 15-16, 2006 CL Boston, MA SP Harvard Med Sch, Div Nutr & Harvard Clin Nutr Res Ctr, Harvard Sch Public Hlth, Dept Nutr, Coca Cola Co, Beverage Inst Hlth & Wellness, Pharmavite, LLC, ConAgra Foods, Natl Dairy Council, Peanut Inst, Conrad Taff Teaching, S Daniel Abraham Teaching Fund, Harvard Ctr Healthy Living DE epigenetics; cancer; nutrition; maternal diet; metabolic syndrome ID HISTONE DEACETYLASE INHIBITORS; THRIFTY PHENOTYPE HYPOTHESIS; DEPENDENT DIABETES-MELLITUS; DNA METHYLATION; GENE-EXPRESSION; LIFE-SPAN; DEFICIENCY; HEPATOCARCINOGENESIS; DISEASE; MICE AB The importance of epigenetics in the etiology of disease, including cancer development and progression, is increasingly being recognized. However, the relevance of epigenetics to the metabolic syndrome, and how it may affect cancer, is only beginning to capture the interest of the scientific community. This review focuses on data supporting the hypothesis that, in addition to the "thrifty genotype" and "thrifty phenotype" hypotheses, diet-induced changes in "epigenetic programming" during fetal and postnatal development may precipitate the metabolic syndrome. Thus, epigenetics may bridge both the thrifty genotype and thrifty phenotype hypotheses and provide a link between genes and the environment concerning disease predisposition to metabolic syndrome and its associated diseases. C1 NCI, Nutr Sci Res Grp, Div Canc Prevent, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ross, SA (reprint author), NCI, Nutr Sci Res Grp, Div Canc Prevent, NIH,Dept Hlth & Human Serv, 6130 Execut Blvd,EPN 3157 MSC 7328, Bethesda, MD 20892 USA. EM rosssha@mail.nih.gov NR 50 TC 29 Z9 29 U1 1 U2 7 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2007 VL 86 IS 3 BP 872S EP 877S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 210WC UT WOS:000249485300055 PM 18265481 ER PT J AU Saydah, S Graubard, B Ballard-Barbash, R Berrigan, D AF Saydah, Sharon Graubard, Barry Ballard-Barbash, Rachel Berrigan, David TI Insulin-like growth factors and subsequent risk of mortality in the United States SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE heart diseases; insulin-like growth factor 1; insulin-like growth factor binding protein 3; mortality; neoplasms; nutrition surveys ID FACTOR-BINDING PROTEIN-3; ISCHEMIC-HEART-DISEASE; TOTAL IGF-I; SERUM-LEVELS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK; CALORIE RESTRICTION; ELDERLY POPULATION; RANCHO-BERNARDO; IGFBP-1 LEVELS AB Although numerous studies have explored the relation of insulin-like growth factor (IGF)-I and IGF-binding protein (BP) 3 with cancer and cardiovascular disease, only two previous studies are known to have looked at the association of IGF-I and IGF-BP3 with risk of mortality. The objective of this US study was to examine the risk of all-cause, heart disease, and cancer mortality associated with IGF-I and IGF-BP3 levels using data from the Third National Health and Nutrition Examination Survey (NHANES 111) and NHANES III Mortality Study (n = 6,061) (1988-2000). The authors constructed proportional hazards models with age as the time scale to determine the association of baseline IGF-I and IGF-BP3 levels with subsequent mortality. After adjustment for baseline measures, there was no increased risk of all-cause, heart disease, or cancer mortality for the lower quartiles of IGF-I compared with the highest quartile. The adjusted relative hazard of all-cause mortality for the lowest quartile of IGFBP3 compared with the highest quartile was 1.57 (95% confidence interval: 0.98, 2.52), and the trend for risk was significant (p = 0.0364), but there was no increased risk of heart disease or cancer mortality. Results suggest that the association of IGF-I and IGF-BP3 with mortality may differ from associations with incidence of disease. C1 Natl Ctr Hlth Stat, Off Anal & Epidemiol, Ctr Dis Control & Prevent, Hyattsville, MD 20782 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Saydah, S (reprint author), Natl Ctr Hlth Stat, Off Anal & Epidemiol, Ctr Dis Control & Prevent, 3311 Toledo Rd, Hyattsville, MD 20782 USA. EM sharon@saydah.com NR 39 TC 38 Z9 38 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2007 VL 166 IS 5 BP 518 EP 526 DI 10.1093/aje/kwm124 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 203YT UT WOS:000249010700005 PM 17602136 ER PT J AU Weisskopf, MG O'Reilly, E Chen, H Schwarzschild, MA Ascherio, A AF Weisskopf, M. G. O'Reilly, E. Chen, H. Schwarzschild, M. A. Ascherio, A. TI Plasma urate and risk of Parkinson's disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Parkinson disease; prospective studies; uric acid ID URIC-ACID LEVELS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; BRAIN-BARRIER DYSFUNCTION; MULTIPLE-SCLEROSIS; SUBSTANTIA-NIGRA; PEROXYNITRITE; BLOOD; IRON; CONSUMPTION; PROTECTION AB Oxidative stress contributes to dopaminergic neuron degeneration in Parkinson's disease. Urate, a potent antioxidant, could be neuroprotective. To determine whether higher plasma concentrations of urate predict a reduced risk of Parkinson's disease, the authors conducted a nested case-control study among participants in the Health Professionals Follow-up Study, a cohort comprising over 18,000 men who provided blood samples in 1993-1995. Eighty-four incident cases of Parkinson's disease were diagnosed through 2000, and each was randomly matched to two controls by year of birth, race, and time of blood collection. Rate ratios of Parkinson's disease according to quartile of uricemia were estimated by use of conditional logistic regression. The mean urate concentration was 5.7 mg/dl among cases and 6.1 mg/dl among controls (p = 0.01). After adjustment for age, smoking, and caff eine, the rate ratio of Parkinson's disease for the highest quartile of uricemia compared with the lowest was 0.43 (95% confidence interval: 0.18, 1.02; P-trend = 0.017). This association was stronger in analyses excluding cases diagnosed within 4 years (median) from blood collection (rate ratio = 0.17, 95% confidence interval: 0.04, 0.69; P-trend = 0.010). These results suggest that high plasma urate concentrations may decrease the risk of Parkinson's disease, and they raise the possibility that interventions to increase plasma urate may reduce the risk and delay the progression of Parkinson's disease. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Weisskopf, MG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Ctr,3rd Floor E,POB 15697, Boston, MA 02215 USA. EM mweissko@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS [Z01 ES101986-02]; NIEHS NIH HHS [K01 ES012653, K01 ES012653-01]; NINDS NIH HHS [R01 NS048517, R01 NS048517-01A2] NR 39 TC 156 Z9 168 U1 1 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2007 VL 166 IS 5 BP 561 EP 567 DI 10.1093/aje/kwm127 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 203YT UT WOS:000249010700010 PM 17584757 ER PT J AU Burgio, KL Borello-France, D Richter, HE FitzGerald, MP Whitehead, W Handa, VL Nygaard, I Fine, P Zyczynski, H Visco, AG Brown, MB Weber, AM AF Burgio, Kathryn L. Borello-France, Diane Richter, Holly E. FitzGerald, Mary Pat Whitehead, William Handa, Victoria L. Nygaard, Ingrid Fine, Paul Zyczynski, Halina Visco, Anthony G. Brown, Morton B. Weber, Anne M. CA Pelvic Floor Disorders Network TI Risk factors for fecal and urinary incontinence after childbirth: The childbirth and pelvic symptoms study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ANAL-SPHINCTER DISRUPTION; VAGINAL DELIVERY; WOMEN; PREVALENCE; PREGNANCY; OLDER; MODE AB OBJECTIVE: To identify risk factors for postpartum FI and UI. METHODS: Secondary analysis of data from the CAPS study, which estimated the prevalence of postpartum FI and UI in primiparous women with clinically recognized anal sphincter tears after vaginal delivery, compared with women who delivered vaginally without recognized tears or by cesarean before labor. A total of 921 women were enrolled while in the hospital and 759 (82%) were interviewed by telephone 6 months postpartum. FI was assessed using the FISI and UI using the Medical, Epidemiological, and Social Aspects of Aging Questionnaire. FI risk factor analyses were conducted within each group, because of higher prevalence in the tear group. UI analyses were conducted with the groups combined. RESULTS: In women with sphincter tears, FI at 6 months was associated with white race (OR 6.1, 95% CI 1.3-29.4), antenatal UI (OR 2.2, CI 1.1-4.3), 4th versus 3rd degree tear (OR 2.0, CI 1.0-4.0), older age at delivery (OR 1.6 per 5 yr, CI 1.2-2.1), and higher body mass index (BMI) (OR 1.3 per 5 kg/m(2), CI 1.0-1.7). No factors were associated with FI in the vaginal or cesarean control groups. Across all groups, risk factors for postpartum UI were antenatal UI (OR 3.5, CI 2.4-5.2), less education (OR 2.0, CI 1.4-2.8), and higher BMI (OR 1.2 per 5 kg/m(2), CI 1.1-1.4); cesarean delivery was protective (OR 0.5, CI 0.3-0.9). CONCLUSIONS: Postpartum FI and UI are associated with few modifiable risk factors. However, the presence of antenatal UI and high BMI may help clinicians target at-risk women for early intervention. C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. Duquesne Univ, Pittsburgh, PA 15219 USA. Loyola Univ, Chicago, IL 60611 USA. Univ N Carolina, Chapel Hill, NC USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Utah, Salt Lake City, UT USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Michigan, Ann Arbor, MI 48109 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Burgio, KL (reprint author), Univ Alabama, Birmingham, AL 35294 USA. FU NICHD NIH HHS [U10 HD41268, U10 HD41250, U10 HD041263, U10 HD41263, U10 HD41248, U10 HD041261, U01 HD41249, U10 HD41269, U10 HD41261, U10 HD41267] NR 21 TC 43 Z9 46 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2007 VL 102 IS 9 BP 1998 EP 2004 DI 10.1111/j.1572-0241.2007.01364.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 202SA UT WOS:000248922500024 PM 17573795 ER PT J AU Tsai, CJ Leitzmann, M Willett, W Giovannucci, E AF Tsai, Chung-Jyi Leitzmann, Michael Willett, Walter Giovannucci, Edward TI Statin use and the risk of cholecystectomy in women SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 12-17, 2007 CL Philadelphia, PA SP Amer Coll Gastroengerol C1 Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY 40506 USA. NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2007 VL 102 SU 2 MA 842 BP S428 EP S429 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 209OL UT WOS:000249397800840 ER PT J AU Obarzanek, E Vollmer, WM Lin, PH Cooper, LS Young, DR Ard, JD Stevens, VJ Simons-Morton, DG Svetkey, LP Harsha, DW Elmer, PJ Appel, LJ AF Obarzanek, Eva Vollmer, William M. Lin, Pao-Hwa Cooper, Lawton S. Young, Deborah R. Ard, Jamy D. Stevens, Victor J. Simons-Morton, Denise G. Svetkey, Laura P. Harsha, David W. Elmer, Patricia J. Appel, Lawrence J. TI Effects of individual components of multiple behavior changes: The PREMIERTrial SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE blood pressure; nutrition; physical activity; fitness; lifestyle ID LIFE-STYLE MODIFICATION; HIGH BLOOD-PRESSURE; JOINT NATIONAL COMMITTEE; WEIGHT-LOSS; HYPERTENSION PREVENTION; CLINICAL-TRIAL; NONPHARMACOLOGIC INTERVENTIONS; SODIUM REDUCTION; PUBLIC-HEALTH; UNITED-STATES AB Objectives: To assess contributions of individual lifestyle changes on systolic blood pressure (SBP) changes. Methods: We examined associations between lifestyle behavior changes and SBP after 6 and 18 months in 782 PREMIER trial participants. Results: In multivariate models omitting weight, predicted SBP reductions ranged from 1/2 to 11/2 mm Hg for reduced urinary sodium, improved fitness, and adherence to the DASH diet (except sodium at 18 months). With weight included, only fitness change additionally predicted SBP at 18 months. Conclusions: Several lifestyle behavior changes are important for BP lowering, but are difficult to detect when weight is included in multivariate models. C1 NHLBI, Bethesda, MD 20892 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Duke Univ, Med Ctr, Nutr & Metab Ctr, Durham, NC 27708 USA. Univ Alabama, Birmingham, AL USA. Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Obarzanek, E (reprint author), NHLBI, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM obarzane@nhlbi.nih.gov FU NCRR NIH HHS [M01 RR00052]; NHLBI NIH HHS [U01 HL60573, U01 HL60571, U01 HL60570, U01 HL60574, U01HL62828] NR 33 TC 33 Z9 33 U1 0 U2 1 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD SEP-OCT PY 2007 VL 31 IS 5 BP 545 EP 560 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 203PQ UT WOS:000248986900010 PM 17555385 ER PT J AU Horne, MK Merryman, PK Cullinane, AM Nghiem, K Alexander, HR AF Horne, McDonald K., III Merryman, Paula K. Cullinane, Ann M. Nghiem, Khanh Alexander, H. Richard TI The impact of major surgery on blood coagulation factors and thrombin generation SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID HUMAN-PLASMA; PROTEIN-S; INHIBITION; CELLS; FIBRINOLYSIS; COAGULOPATHY; ACTIVATION; FIBRINOGEN; KINETICS; SYSTEM AB We studied the blood coagulation system of 14 patients with metastatic malignancies before and after they had undergone major surgery. In addition to measuring a battery of coagulation factors, we assessed the function of the system with assays of whole blood thrombin generation. With the exceptions of factor VIII (fVIII), which increased, and fibrinogen and fIX, which did not change, the activities of all the pro- and anticoagulant proteins were significantly lower postoperatively. However, the thrombin generating capacity of the system was relatively preserved. Although the integral of thrombin activity over time was lower after surgery, the mean peak thrombin concentration was unchanged and the time to clot formation was shortened. Similar changes could be reproduced by lowering the concentrations of pro- and anticoagulant factors together in control blood samples. Therefore, simultaneous reductions in pro- and anticoagulant proteins postoperatively worked to maintain the functional integrity of the blood coagulation C1 NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Rm 2C306,Bldg 10, Bethesda, MD 20892 USA. EM mhorne@mail.cc.nih.gov FU Intramural NIH HHS NR 27 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2007 VL 82 IS 9 BP 815 EP 820 DI 10.1002/ajh.20963 PG 6 WC Hematology SC Hematology GA 208AX UT WOS:000249293300010 PM 17570509 ER PT J AU Aue, G Austein, T AF Aue, Georg Austein, Thorsten TI Streptococcus pneumoniae sepsis in concurrently diagnosed multiple myeloma SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. St Bernhard Hosp, Brake, Germany. RP Aue, G (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC Room 3-3216,10 Ctr Dr MSC 1202, Bethesda, MD 20892 USA. EM aueg@nhibi.nih.gov NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2007 VL 82 IS 9 BP 858 EP 858 DI 10.1002/ajh.20911 PG 1 WC Hematology SC Hematology GA 208AX UT WOS:000249293300022 PM 17506071 ER PT J AU Yu, K Chatterjee, N Wheeler, W Li, QZ Wang, S Rothman, N Wacholder, S AF Yu, Kai Chatterjee, Nilanjan Wheeler, William Li, Qizhai Wang, Sophia Rothman, Nathaniel Wacholder, Sholom TI Flexible design for following up positive findings SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENERALIZED LINEAR-MODELS; GENE-DISEASE ASSOCIATION; SAMPLE-SIZE CALCULATIONS; GENOME-WIDE ASSOCIATION; LIKELIHOOD RATIO TESTS; NON-HODGKIN-LYMPHOMA; CROSS-VALIDATION; 2-STAGE DESIGNS; SELECTION BIAS; POWER AB As more population-based studies suggest associations between genetic variants and disease risk, there is a need to improve the design of follow-up studies (stage II) in independent samples to confirm evidence of association observed at the initial stage (stage I). We propose to use flexible designs developed for randomized clinical trials in the calculation of sample size for follow-up studies. We apply a bootstrap procedure to correct the effect of regression to the mean, also called "winner's curse," resulting from choosing to follow up the markers with the strongest associations. We show how the results from stage I can improve sample size calculations for stage II adaptively. Despite the adaptive use of stage I data, the proposed method maintains the nominal global type I error for final analyses on the basis of either pure replication with the stage II data only or a joint analysis using information from both stages. Simulation studies show that sample-size calculations accounting for the impact of regression to the mean with the bootstrap procedure are more appropriate than is the conventional method. We also find that, in the context of flexible design, the joint analysis is generally more powerful than the replication analysis. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Informat Management Serv Inc, Rockville, MD USA. Chinese Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China. RP Yu, K (reprint author), 6120 Exevut Blvd,EPS 8050, Rockville, MD 20852 USA. EM yuka@mail.nih.gov FU Intramural NIH HHS NR 37 TC 35 Z9 37 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 2007 VL 81 IS 3 BP 540 EP 551 DI 10.1086/520678 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 205PX UT WOS:000249128200010 PM 17701899 ER PT J AU Madero, M Sarnak, MJ Wang, X Sceppa, CC Greene, T Beck, GJ Kusek, JW Collins, AJ Levey, AS Menon, A AF Madero, Magdalena Sarnak, Mark J. Wang, Xuelei Sceppa, Carmen Castaneda Greene, Tom Beck, Gerald J. Kusek, John W. Collins, Allan J. Levey, Andrew S. Menon, Vandana TI Body mass index and mortality in CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE kidney disease; outcomes; cardiovascular mortality AB Background: Greater body mass index (BMI) is associated with worse survival in the general population, but appears to confer a survival advantage in patients with kidney failure treated by hemodiaiysis. Data are limited on the relationship of BMI with mortality in patients in the earlier stages of chronic kidney disease (CKD). Study Design: Cohort study. Setting & Participants: The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and blood pressure control on progression of kidney disease. This analysis includes 1,759 subjects. Predictor: BMI. Outcomes & Measurements: Cox models were used to evaluate the relationship of quartiles of BMI with all-cause and cardiovascular disease (CVD) mortality. Results: Mean GFR and BMI were 39 +/- 21 (SD) mL/min/1.73 m(2) and 27.1 +/- 4.7 kg/m(2), respectively. During a mean follow-up of 10 years, there were 453 deaths (26%), including 272 deaths (16%) from CVD. In unadjusted Cox models, quartiles 3 (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.11 to 1.90) and 4 (HR, 1.58; 95% Cl, 1.21 to 2.06) were associated with increased risk of all-cause mortality compared with quartile 1. Adjustment for demographic, CVD, and kidney disease risk factors and randomization status attenuated this relationship for quartiles 3 (HR, 0.81; 95% Cl, 0.60 to 1.09) and 4 (HR, 0.83; 95% Cl, 0.61 to 1.20). In unadjusted Cox models, quartiles 3 (HR, 1.66; 95% Cl, 1.17 to 2.36) and 4 (HR, 1.63; 95% Cl, 1.15 to 2.33) were associated with increased risk of CVD mortality. Multivariable adjustment attenuated this relationship for quartiles 3 (HR, 0.92; 95% Cl, 0.63 to 1.36) and 4 (HR, 0.85; 95% Cl, 0.57 to 1.27). Limitations: Primary analyses were based on single measurement of BMI. Because the MDRD Study cohort included relatively young white subjects with predominantly nondiabetic CKD, results may not be generalizable to all patients with CKD. Conclusions: In this cohort of subjects with predominantly nondiabetic CKD, BMI does not appear to be an independent predictor of all-cause or CKD mortality. C1 Tufts Univ New England Med Ctr, Dept Med, Div Nephrol, Boston, MA 02111 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Univ Utah, Div Clin Epidemiol, Salt Lake City, UT USA. NIH, Bethesda, MD 20892 USA. Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN USA. RP Menon, A (reprint author), Tufts Univ New England Med Ctr, Dept Med, Div Nephrol, 750 Washington St,NEMC 391, Boston, MA 02111 USA. EM vmenon@tufts-nemc.org FU NIDDK NIH HHS [UO1 DK 35073, K23 DK02904, K23 DK067303] NR 0 TC 32 Z9 34 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2007 VL 50 IS 3 BP 404 EP 411 DI 10.1053/j.ajkd.2007.06.004 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 206YR UT WOS:000249219300011 PM 17720519 ER PT J AU Kunos, G AF Kunos, George TI Understanding metabolic homeostasis and imbalance: What is the role of the endocannabinoid system? SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the American-Diabetes-Association CY JUN 09-13, 2006 CL Washington, DC SP Amer Diabet Assoc DE adiponectin; cannabinoid-1 receptors; endocannabinoid system; fatty liver disease; leptin; rimonabant ID CB1 RECEPTOR ANTAGONIST; STEAROYL-COA DESATURASE-1; CANNABINOID RECEPTOR; ADIPOSE-TISSUE; ENERGY-BALANCE; DIET; SR141716; BRAIN; LIPOGENESIS; EXPRESSION AB neural circuitry involved in appetite regulation. One of the sites of the orexigenic action of ECs involves activation of cannabinoid-1 (CB1) receptors in the lateral hypothalamus, from which neurons involved in mediating food reward project into the limbic system. In animal models of obesity, pharmacologic blockade or genetic ablation of CB1 receptors causes a transient reduction in food intake accompanied by sustained weight loss, reduced adiposity, and reversal of hormonal/metabolic changes, such as elevated levels of plasma leptin, insulin, glucose, and triglyceride, and reduced levels of plasma adiponectin (Acrp30). However, the beneficial effects of CB1 blockade on weight and metabolism cannot be explained by appetite suppression alone. Animal studies suggest that CB1 blockade exerts a direct peripheral as well as a central effect on fat metabolism. CB1 receptor blockade with rimonabant has been shown to not only reduce weight and adiposity but also to directly modulate fat metabolism at peripheral sites in skeletal muscle, adipose tissue, and the liver. Preclinical animal studies suggest that CB1 blockade acts on adipocytes to increase Acrp30 expression, on hepatocytes to decrease de novo lipogenesis and increase fatty acid oxidation, and on skeletal muscle to reduce blood glucose and insulin levels. Extrapolating from animal studies to the clinic, CB1 receptor blockade offers a promising strategy not only for reducing weight and abdominal adiposity but also for preventing and reversing its metabolic consequences. (C) 2007 Elsevier Inc. All rights reserved. C1 NIAAA, NIH, Bethesda, MD 20817 USA. RP Kunos, G (reprint author), NIAAA, NIH, 6606 Marywood Rd, Bethesda, MD 20817 USA. EM gkunos@mail.nih.gov NR 24 TC 19 Z9 19 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 2007 VL 120 IS 9 SU 1 BP 18 EP 24 DI 10.1016/j.amjmed.2007.06.007 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 205CG UT WOS:000249090100006 ER PT J AU Sharifi, N Kramer, BS AF Sharifi, Nima Kramer, Barnett S. TI Screening for prostate cancer: Current status and future prospects SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 Natl Canc Inst, Med Oncol Branch, Bethesda, MD 20892 USA. Natl Inst Hlth, Off Dis Prevent, Bethesda, MD USA. RP Sharifi, N (reprint author), Natl Canc Inst, Med Oncol Branch, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 16 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 2007 VL 120 IS 9 BP 743 EP 745 DI 10.1016/j.amjmed.2006.12.014 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 205ON UT WOS:000249123800001 PM 17765037 ER PT J AU Gleeson, TD Decker, CF Johnson, MD Hartzell, JD Mascola, JR AF Gleeson, Todd D. Decker, Catherine F. Johnson, Mark D. Hartzell, Joshua D. Mascola, John R. TI Q fever in US military returning from Iraq SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 Natl Naval Med Ctr, Div Infect Dis, Dept Internal Med, Bethesda, MD 20899 USA. Walter Reed Army Med Ctr, Div Infect Dis, Dept Internal Med, Washington, DC 20307 USA. NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Gleeson, TD (reprint author), Natl Naval Med Ctr, Div Infect Dis, Dept Internal Med, 8901 Wisconsin Ave, Bethesda, MD 20899 USA. EM tdgleeson@bethesda.med.navy.mil NR 4 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 2007 VL 120 IS 9 BP E11 EP E12 DI 10.1016/j.amjmed.2007.03.020 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 205ON UT WOS:000249123800025 PM 17765028 ER PT J AU Romero, R Tromp, G AF Romero, Roberto Tromp, Gerard TI Commentary on microarray analysis for gynecologists and obstetricians SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 NIH, NICHD, DHHS, Perinatol Res Branch, Detroit, MI 48201 USA. RP Romero, R (reprint author), NIH, NICHD, DHHS, Perinatol Res Branch, 3990 John R, 4 Brush, Detroit, MI 48201 USA. EM nichdprbchiefstaff@mail.nih.gov RI Tromp, Gerard/B-2677-2017 OI Tromp, Gerard/0000-0002-7761-0806 NR 4 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2007 VL 197 IS 3 BP 331 EP 331 DI 10.1016/j.ajog.2007.05.026 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 211NU UT WOS:000249531300052 ER PT J AU Dao, H Mofenson, LM Ekpini, R Gilks, CF Barnhart, M Bolu, O Shaffer, N AF Dao, Halima Mofenson, Lynne M. Ekpini, Rene Gilks, Charles F. Barnhart, Matthew Bolu, Omotayo Shaffer, Nathan TI International recommendations on antiretroviral drugs for treatment of HIV-infected women and prevention of mother-to-child HIV transmission in resource-limited settings: 2006 update SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE antiretroviral; HIV; prevention of mother-to-child transmission ID SINGLE-DOSE NEVIRAPINE; IMMUNODEFICIENCY-VIRUS TYPE-1; RANDOMIZED CONTROLLED-TRIAL; SHORT-COURSE ZIDOVUDINE; NEURAL-TUBE DEFECTS; RESISTANT HIV-1; BREAST-MILK; POSTEXPOSURE PROPHYLAXIS; VERTICAL TRANSMISSION; ORAL ZIDOVUDINE AB The World Health Organization recommends that countries adopt more effective antiretroviral regimens to increase the effectiveness of the prevention of mother-to-child human immunodeficiency virus (HIV) transmission programs. The 2006 guidelines recommend a tiered approach for the delivery of antiretroviral to pregnant women who are infected with HIV and include triple-drug antiretroviral treatment for those women who are eligible. Those women who are not eligible for antiretroviral treatment should receive a combination prophylaxis antiretroviral regimen, preferably zidovudine from 28 weeks of gestation; zidovudine, lamivudine, and a single dose of nevirapine during delivery; and zidovudine and lamivudine for 7 days after delivery to reduce the development of nevirapine resistance. Newborn infants should receive a single dose of nevirapine and 1-4 weeks of zidovudine, depending on the duration of the regimen received by the mother. Although steps are being taken to provide more effective regimens, the use of single-dose nevirapine alone should still be used in situations in which more effective regimens are not yet feasible or available. HIV transmission through breastfeeding remains a problem, and several interventions are under evaluation that include maternal and/or infant antiretroviral prophylaxis during breastfeeding. C1 Ctr Dis Control & Prevent, Natl Ctr HIV Hepatitis STD TB Prevent, Global AIDS Progam, Prevent Mother To Child Transmiss HIV Team, Atlanta, GA USA. NICHHD, Pediat Adolescent & Mat AIDS Branch, NIH, Bethesda, MD 20892 USA. World Hlth Org, HIV Dept, Geneva, Switzerland. USAID, Off HIV AIDS, Div Tech Leadership & Res, Washington, DC USA. RP Dao, H (reprint author), Ctr Dis Control & Prevent, Natl Ctr HIV Hepatitis STD TB Prevent, Global AIDS Progam, Prevent Mother To Child Transmiss HIV Team, 1600 Clifton Rd,MS E-04, Atlanta, GA USA. EM hcd1@cdc.gov RI Gilks, Charles/B-4184-2012 NR 65 TC 44 Z9 44 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2007 VL 197 IS 3 SU 1 BP S42 EP S55 DI 10.1016/j.ajog.2007.03.001 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 212GR UT WOS:000249582700007 PM 17825650 ER PT J AU Jamieson, DJ Read, JS Kourtis, AP Durant, TM Lampe, MA Dominguez, KL AF Jamieson, Denise J. Read, Jennifer S. Kourtis, Athena P. Durant, Tonji M. Lampe, Margaret A. Dominguez, Kenneth L. TI Cesarean delivery for HIV-infected women: recommendations and controversies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cesarean delivery; HIV transmission ID HUMAN-IMMUNODEFICIENCY-VIRUS; MOTHER-TO-CHILD; 15 PROSPECTIVE COHORT; VERTICAL TRANSMISSION; COST-EFFECTIVENESS; PERINATAL TRANSMISSION; HIV-1-INFECTED WOMEN; INFANTS TRANSMISSION; POSTPARTUM MORBIDITY; VAGINAL DELIVERY AB Two studies that were published in 1999 demonstrated that cesarean delivery before labor and before the rupture of membranes (elective cesarean delivery) reduces the risk of mother-to-child transmission of the human immunodeficiency virus (HIV). On the basis of these results, the American College of Obstetricians and Gynecologists and the US Public Health Service recommend that HIV-infected pregnant women with plasma viral loads of > 1000 copies per milliliter be counseled regarding the benefits of elective cesarean delivery. Since the release of these guidelines, the cesarean delivery rate among HIV-infected women in the United States has increased dramatically. Major postpartum morbidity is uncommon, and cesarean delivery among HIV-infected women is relatively safe and cost-effective. However, a number of important questions remain unanswered, including whether cesarean delivery has a role among HIV-infected women with low plasma viral loads or who receive combination antiretroviral regimens. C1 Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr HIV Aids Viral Hepatitis STD & TB Preven, Div HIV AIDS Prevent, Atlanta, GA 30333 USA. RP Jamieson, DJ (reprint author), Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Hwy,Mallstop K-34, Atlanta, GA 30333 USA. EM djj0@cdc.gov NR 55 TC 10 Z9 13 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2007 VL 197 IS 3 SU 1 BP S96 EP S100 DI 10.1016/j.ajog.2007.02.034 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 212GR UT WOS:000249582700013 PM 17825656 ER PT J AU Jamieson, DJ Clark, J Kourtis, AP Taylor, AW Lampe, MA Fowler, MG Mofenson, LM AF Jamieson, Denise J. Clark, Jill Kourtis, Athena P. Taylor, Allan W. Lampe, Margaret A. Fowler, Mary Glenn Mofenson, Lynne M. TI Recommendations for human immunodeficiency virus screening, prophylaxis, and treatment for pregnant women in the United States SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE HIV testing and treatment; pregnancy ID PERINATAL TRANSMISSION; ZIDOVUDINE; INFECTION; REDUCTION; TYPE-1; HIV-1 AB In the United States, current human immunodeficiency virus (HIV) testing guidelines recommend an opt-out approach for pregnant women, whereby HIV testing is incorporated routinely into the standard panel of prenatal tests with the option to decline. Current recommendations for the initiation of treatment of HIV infection in pregnant women are the same as those for nonpregnant women. However, the special circumstances of pregnancy raise additional issues that are related to potential drug toxicity to the mother and fetus, which affect the choice of antiretroviral drugs to be used. For HIV-infected pregnant women who do not require therapy for their own health, antiretroviral drugs are recommended for prevention of mother-to-child transmission. Highly active antiretroviral therapy is recommended for all women with HIV RNA levels of >= 1000 copies/mL, along with consideration of elective cesarean delivery. For women with HIV RNA levels of >= 1000 copies/mL, a 3-part zidovudine prophylaxis regimen (prenatal, intrapartum, and neonatal) should be used alone or in combination with other antiretroviral drugs. C1 Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, Atlanta, GA 30341 USA. Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TD Preven, Atlanta, GA USA. CDC Informat Technol Support, Atlanta, GA USA. Makerere Univ, Johns Hopkins Univ Res Collaborat, Johns Hopkins Med Sch, Dept Pathol, Kampala, Uganda. NICHHD, Pediat Adolescent & Mat AIDS Branch, NIH, Bethesda, MD 20892 USA. RP Jamieson, DJ (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, 4770 Buford Highway,Mailstop K34, Atlanta, GA 30341 USA. EM djj0@cdc.gov NR 27 TC 28 Z9 31 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2007 VL 197 IS 3 SU 1 BP S26 EP S32 DI 10.1016/j.ajog.2007.03.087 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 212GR UT WOS:000249582700005 PM 17825647 ER PT J AU Bradley, CS Richter, HE Gutman, RE Brown, MB Whitehead, WE Fine, PM Hakim, C Harford, F Weber, AM AF Bradley, Catherine S. Richter, Holly E. Gutman, Robert E. Brown, Morton B. Whitehead, William E. Fine, Paul M. Hakim, Christiane Harford, Frank Weber, Anne M. CA Pelvic Floor Disorders Network TI Risk factors for sonographic internal anal sphincter gaps 6-12 months after delivery complicated by anal sphincter tear SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med DE anal sphincter laceration; endoanal ultrasound; postpartum fecal incontinence ID VAGINAL DELIVERY; URINARY-INCONTINENCE; FECAL INCONTINENCE; WOMEN; SYMPTOMS; LACERATIONS; DISRUPTION; PROLAPSE; REPAIR AB OBJECTIVE: The objective of the study was to identify risk factors for internal anal sphincter (IAS) gaps on postpartum endoanal ultrasound in women with obstetric anal sphincter tear. STUDY DESIGN: This prospective study included 106 women from the Childbirth and Pelvic Symptoms Imaging Supplementary Study who had third- or fourth-degree perineal laceration at delivery and endoanal ultrasound 6-12 months postpartum. Data were analyzed using Fisher's exact and t tests and logistic regression. RESULTS: Mean (+/- SD) age was 27.7 ( +/- 6.2) years. Seventy-nine women (76%) were white and 22 (21%) black. Thirty-seven (35%) had sonographic IAS gaps. Risk factors for gaps included fourth-vs third-degree perineal laceration (odds ratio [OR] 15.4, 95% confidence interval [CI] 4.8, 50) and episiotomy (OR 3.3, 95% CI 1.2, 9.1). Black race (OR 0.23, 95% CI 0.05, 0.96) was protective. CONCLUSION: In women with obstetric anal sphincter repairs, fourth-degree tears and episiotomy are associated with more frequent sonographic IAS gaps. C1 Univ Iowa, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. Univ Alabama, Birmingham, AL USA. Johns Hopkins Sch Med, Baltimore, MD USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Pittsburgh, Dept Radiol, Ctr Med, Magee Womens Hosp, Pittsburgh, PA 15260 USA. Loyola Univ, Dept Surg, Chicago, IL 60611 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Bradley, CS (reprint author), Univ Iowa, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. FU NICHD NIH HHS [U10 HD41248, U10 HD41269, U10 HD041261, U10 HD41267, U10 HD41263, U10 HD41250, U01 HD41249, U10 HD41261, U10 HD41268] NR 18 TC 1 Z9 2 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2007 VL 197 IS 3 AR 310.e1-310.e5 DI 10.1016/j.ajog.2007.06.034 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 211NU UT WOS:000249531300035 PM 17826433 ER PT J AU Hassan, SS Romero, R Tarca, AL Draghici, S Pineles, B Bugrim, A Khalek, N Camacho, N Mittal, P Yoon, BH Espinoza, J Kim, CJ Sorokin, Y Malone, J AF Hassan, Sonia S. Romero, Roberto Tarca, Adi L. Draghici, Sorin Pineles, Beth Bugrim, Andrej Khalek, Nahla Camacho, Natalia Mittal, Pooja Yoon, Bo Hyun Espinoza, Jimmy Kim, Chong Jai Sorokin, Yoram Malone, John, Jr. TI Signature pathways identified from gene expression profiles in the human uterine cervix before and after spontaneous term parturition SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med DE cervical dilation; cervical remodeling; cervix; gene signature network; labor; microarray; parturition; pathway analysis; plasmin; systems biology ID MIGRATION INHIBITORY FACTOR; SYSTEMS BIOLOGY; FUNCTIONAL GENOMICS; PRETERM PARTURITION; FETAL MEMBRANES; LABOR; INTERLEUKIN-8; COLLAGEN; DILATATION; MYOMETRIUM AB OBJECTIVE: This study aimed to discover "signature pathways" that characterize biologic processes, based on genes differentially expressed in the uterine cervix before and after spontaneous labor. STUDY DESIGN: The cervical transcriptome was characterized previously from biopsy specimens taken before and after term labor. Pathway analysis was used to study the differentially expressed genes, based on 2 gene-to-pathway annotation databases ( Kyoto Encyclopedia of Genes and Genomes [Kanehisa Laboratories, Kyoto University, Kyoto, Japan] and Metacore software [GeneGo, Inc, St. Joseph, MI]). Overrepresented and highly impacted pathways and connectivity nodes were identified. RESULTS: Fifty-two pathways in the Metacore database were enriched significantly in differentially expressed genes. Three of the top 5 pathways were known to be involved in cervical remodeling. Two novel pathways were plasmin signaling and plasminogen activator urokinase signaling. The same analysis with the Kyoto Encyclopedia of Genes and Genomes database identified 4 significant pathways that the impact analysis confirmed. Multiple nodes that provide connectivity within the plasmin and plasminogen activator urokinase signaling pathways were identified. CONCLUSION: Three strategies for pathway analysis were consistent in their identification of novel, unexpected, and expected pathways, which suggests that this approach is both valid and effective for the elucidation of biologic mechanisms that are involved in cervical dilation and remodeling. C1 Wayne State Univ, Perinatol Res Branch, Hutzel Womens Hosp, NICHD,DHHS,NIH, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Dept Comp Sci, Detroit, MI USA. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. RP Hassan, SS (reprint author), Wayne State Univ, Perinatol Res Branch, Hutzel Womens Hosp, NICHD,DHHS,NIH, 3990 John R,Box 4, Detroit, MI 48201 USA. EM shassan@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011; Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 FU Intramural NIH HHS [Z01 HD002400-16]; NCI NIH HHS [P30 CA022453-24, U01 CA117478, 1U01CA117478-01, R21 CA100740-01, 2P30CA022453-24, 1R21CA 100740-01, U01 CA117478-01, R21 CA100740]; NHGRI NIH HHS [1RH01HG003491-01A1, R01 HG003491, R01 HG003491-01A1]; NIBIB NIH HHS [R21 EB000990, 5R21EB000990-03, R21 EB000990-03]; NINDS NIH HHS [R01 NS045207, 1R01NS045207-01, R01 NS045207-01] NR 37 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2007 VL 197 IS 3 AR 250.e1 DI 10.1016/j.ajog.2007.07.008 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 211NU UT WOS:000249531300009 PM 17826407 ER PT J AU Jehan, I McClure, EM Salat, S Rizvi, S Pasha, O Harris, H Moss, N Goldenberg, RL AF Jehan, Imtiaz McClure, Elizabeth M. Salat, Sohail Rizvi, Sameera Pasha, Omrana Harris, Hillary Moss, Nancy Goldenberg, Robert L. TI Stillbirths in an urban community in Pakistan SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med DE developing country; obstetric care; stillbirth ID MATERNAL MORTALITY; PERINATAL-MORTALITY; OBSTETRIC CARE; SERVICES; BIRTH; NEWBORN; DEATHS; ACCESS; LEVEL AB OBJECTIVE: The purpose of this study was to determine stillbirth risk factors and gestational age at delivery in a prospective developing country birth cohort. STUDY DESIGN: At 20-26 weeks of gestation, 1369 Pakistani women were prospectively enrolled in the study; the gestational age was determined by ultrasound evaluation, and risk factors and pregnancy outcomes were assessed. RESULTS: The stillbirth rate was 33.6 of 1000 births, despite the fact that 96% of the women received prenatal care, 83% of the women were attended by skilled providers in the hospital, and a 20% of the women underwent cesarean delivery. Fifty-one percent of stillbirths occurred at >= 37 weeks of gestation and 19% occurred from 34-36 weeks of gestation. Only 4% of the births had congenital anomalies. Hemoglobin of <8 g/dL, vaginal bleeding, and preeclampsia were associated with increased stillbirth risk. CONCLUSION: In this developing country with reasonable technical resources defined by hospital delivery and a high cesarean delivery rate, stillbirth rates were much higher than rates in the United States. That most of the stillbirths were term and did not have congenital anomalies and that the death appeared to be recent suggests that many Pakistani stillbirths may be preventable with higher quality obstetric care. C1 Aga Khan Univ, Karachi, Pakistan. RTI Int, Durham, NC USA. NICHD, Rockville, MD USA. Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. RP Jehan, I (reprint author), Aga Khan Univ, Karachi, Pakistan. FU NICHD NIH HHS [U01 HD040636, U01 HD040607, U01 HD040607-07] NR 22 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2007 VL 197 IS 3 AR 257.e1 DI 10.1016/j.ajog.2007.07.012 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 211NU UT WOS:000249531300012 PM 17826410 ER PT J AU McClure, EM Wright, LL Goldenberg, RL Goudar, SS Parida, SN Jehan, I Tshefu, A Chomba, E Althabe, F Garces, A Harris, H Derman, RJ Panigrahi, P Engmann, C Buekens, P Hambidge, M Carlo, WA AF McClure, Elizabeth M. Wright, Linda L. Goldenberg, Robert L. Goudar, Shivaprasad S. Parida, Sailajanandan N. Jehan, Imtiaz Tshefu, Antoinette Chomba, Elwyn Althabe, Fernando Garces, Ana Harris, Hillary Derman, Richard J. Panigrahi, Pinaki Engmann, Cyril Buekens, Pierre Hambidge, Michael Carlo, Waldemar A. CA NICHD FIRST BREATH Study Grp TI The global network: a prospective study of stillbirths in developing countries SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med DE developing country; intrapartum stillbirth; stillbirth ID PERINATAL-MORTALITY; BIRTH; DEATHS; RATES; LABOR AB OBJECTIVE: Our goal was to determine stillbirth rates in a multisite population-based study in community settings in the developing world. STUDY DESIGN: Outcomes of all community deliveries in 5 resource-poor countries ( Democratic Republic of Congo, Guatemala, India, Zambia, and Pakistan) and in 1 mid-level country ( Argentina) were evaluated prospectively over an 18-month period. Births of > 1000 g with no signs of life were defined as stillbirth. RESULTS: Outcomes of 60,324 deliveries were included. Stillbirth rates ranged from 34 per 1000 in Pakistan to 9 per 1000 births in Argentina. Increased stillbirth rates were associated significantly with lower skilled providers, out-of-hospital births, and low cesarean section rates. Maceration was present in 17.2% of stillbirths. CONCLUSION: The stillbirth rates among births of >= 1000 g in these developing countries were substantially higher than reported stillbirth rates in developed countries (3-5/1000 births). Because most developed countries define stillbirth as >= 20 weeks of gestation or >= 500 g and because almost one-half of all stillbirths are < 1000 g, the developing/ developed country difference is actually larger than apparent from this study. Maceration was uncommon, which indicates that most of the deaths probably occurred during labor. The low rates of physician attendance, hospital delivery, and cesarean section deliveries suggest that stillbirth rates could be reduced by access to higher quality institutional deliveries. C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Drexel Univ, Philadelphia, PA 19104 USA. Jawaharlal Nehru Med Coll, Belgaum, India. SCB Med Coll, Orissa, India. Aga Khan Univ, Karachi, Pakistan. Kinshasa Sch Publ Hlth, Kinshasa, Zaire. Univ Zambia, Lusaka, Zambia. Univ Buenos Aires, Buenos Aires, DF, Argentina. San Carlos Univ, Ceby City, Philippines. Univ Missouri, Kansas City, MO 64110 USA. Univ Maryland, Baltimore, MD 21201 USA. Univ N Carolina, Chapel Hill, NC USA. Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Univ Alabama, Birmingham, AL USA. RP McClure, EM (reprint author), Res Triangle Inst, 3040 Cornwallis Rd, Durham, NC 27709 USA. EM mcclure@rti.org OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053 FU NICHD NIH HHS [U01 HD040477, U01 HD040607, U01 HD040607-02, U01 HD040636, U01 HD040657, U01 HD042372, U01 HD0434475, U01 HD043464] NR 18 TC 12 Z9 13 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2007 VL 197 IS 3 AR 247.e1 DI 10.1016/j.ajog.2007.07.004 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 211NU UT WOS:000249531300008 PM 17826406 ER PT J AU Montenegro, D Romero, R Pineles, BL Tarca, AL Kim, YM Draghici, S Kusanovic, JP Kim, JS Erez, O Mazaki-Tovi, S Hassan, S Espinoza, J Kim, CJ AF Montenegro, Daniel Romero, Roberto Pineles, Beth L. Tarca, Adi L. Kim, Yeon Mee Draghici, Sorin Kusanovic, Juan Pedro Kim, Jung-Sun Erez, Offer Mazaki-Tovi, Shali Hassan, Sonia Espinoza, Jimmy Kim, Chong Jai TI Differential expression of microRNAs with progression of gestation and inflammation in the human chorioamniotic membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE chorioamniotic membranes; gestation; inflammation; labor; microRNA; real-time qRT-PCR ID CORTICOTROPIN-RELEASING HORMONE; GENE-EXPRESSION; FETAL MEMBRANES; SPONTANEOUS LABOR; BINDING-PROTEIN; HUMAN PLACENTA; ONTO-EXPRESS; PRETERM; TERM; TISSUE AB OBJECTIVE: The aim of this study was to identify differential expression of microRNAs ( miRNAs) in chorioamniotic membranes with advancing gestation, labor, and inflammation. STUDY DESIGN: Expression profiles of 157 miRNAs in the chorioamniotic membranes were obtained from patients in the following groups: 1) term not in labor (n = 10); 2) term in labor (n = 10); 3) preterm labor with histologic chorioamionitis (n = 9); and 4) without histologic chorioamnionitis (n = 10). RESULTS: More than 95% of the miRNAs screened were expressed. Gestational age-dependent changes in expression were observed for 13 miRNAs. No differences in miRNA expression were observed between women without labor and women in labor. Membranes with chorioamnionitis displayed increased expression of miR-223 and miR-338. Gene Ontology analysis of genes targeted by differentially expressed miRNAs revealed enrichment for specific biological process categories. CONCLUSION: Chorioamniotic membranes with advancing gestational age and chorioamnionitis are associated with the differential expression of a subset of miRNAs. C1 Wayne State Univ, DHHS, NICHD, NIH,Hutzel Womens Hosp,Perinatol Res Branch, Detroit, MI 48201 USA. Wayne State Univ, DHHS, NICHD, NIH,Hutzel Womens Hosp,Perinatol Res Branch, Bethesda, MD USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, DHHS, NICHD, NIH,Hutzel Womens Hosp,Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM nichdprbchiefstaff@mail.nih.gov RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 FU Intramural NIH HHS [Z01 HD002400-16] NR 35 TC 3 Z9 4 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2007 VL 197 IS 3 AR 289.e1-289.e6 DI 10.1016/j.ajog.2007.06.027 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 211NU UT WOS:000249531300026 PM 17826424 ER PT J AU Sawady, J Mercer, BM Wapner, RJ Zhao, Y Sorokin, Y Johnson, F Dudley, DJ Spong, CY Peaceman, AM Leveno, KJ Harper, M Caritis, SN Miodovnik, M Thorp, JM Ramin, S Carpenter, MW Rouse, DJ AF Sawady, Joram Mercer, Brian M. Wapner, Ronald J. Zhao, Yuan Sorokin, Yoram Johnson, Francee Dudley, Donald J. Spong, Catherine Y. Peaceman, Alan M. Leveno, Kenneth J. Harper, Margaret Caritis, Steve N. Miodovnik, Menachem Thorp, John M. Ramin, Susan Carpenter, Marshall W. Rouse, Dwight J. CA Natl Inst Child Hlth Human Dev Mat TI The national institute of child health and human development maternal-fetal medicine units network beneficial effects of antenatal repeated steroids study: impact of repeated doses of antenatal corticosteroids on placental growth and histologic findings SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med DE antenatal corticosteroid; histopathologic finding; placenta; preterm birth ID MEMBRANE RUPTURE; WEEKLY COURSES; PRETERM BIRTH; EXPRESSION; SINGLE; GLUCOCORTICOIDS; RETARDATION; THERAPY; RISK AB OBJECTIVE: In utero exposure to repeated doses of antenatal corticosteroids (ACSs) has been shown to reduce fetal growth. Our goal was to evaluate whether weekly betamethasone (R-ACS) alters placental growth and histologic findings. STUDY DESIGN: In a multicenter randomized controlled trial of R-ACS vs a single course of ACS followed by weekly placebo (S-ACS), placentas were weighed after removal of the membranes and umbilical cord. A single pathologist who was masked to study group and pregnancy outcomes performed histologic evaluation for placental calcifications, infarction, fibrin deposition, and hemorrhage or thrombus formation, acute and chronic chorioamnionitis, fibromuscular vascular hyperplasia, nucleated red blood cells, and villous crowding, edema, fibrosis, or fibrinoid necrosis. Findings were compared between study groups and according to the number of courses of ACS. RESULTS: One hundred ninety-four placentas were available for evaluation. Univariable analyses revealed no differences between study groups in any of the 19 evaluated histologic parameters between R-ACS and S-ACS groups overall or in analyses that were restricted to deliveries at < 32 or >= 32 weeks of gestation. Calcifications were more common (P = .045) in the R-ACS group after controlling for other factors. Multivariable analysis revealed increasing gestational age at delivery, but not increasing ACS courses, to be associated with decreasing chorionic inflammation, villous edema, and fibrosis and with increasing villus crowding, fibrin deposition, and calcifications. Ninety-three placentas were weighed before formalin fixation. After controlling for delivery gestation and infant gender, placental weight was significantly lower in the R-ACS group (P = .017) and was related inversely to the number of ACS courses (P = .037). This finding was confirmed only for deliveries at >= 32 weeks of gestation (525 vs 441 g for R-ACS and S-ACS group, respectively; P = .036). CONCLUSION: Repeated antenatal corticosteroid treatments in pregnancy are associated with decreased placental growth in a dose-dependent fashion, but not with evident differences in histologic markers of placental inflammation, ischemia, or infarction. Histologic placental abnormalities should not be attributed to repeated courses of corticosteroids. C1 Case Western Reserve Univ, Metro Hlth Med Ctr, Dept Pathol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Metro Hlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Wayne State Univ, Dept Obstet, Detroit, MI USA. Wayne State Univ, Dept Gynecol, Detroit, MI USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Utah, Salt Lake City, UT USA. NICHHD, Bethesda, MD 20892 USA. Northwestern Univ, Dept Obstet, Chicago, IL 60611 USA. Northwestern Univ, Dept Gynecol, Chicago, IL 60611 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Magee Womens Hosp, Pittsburgh, PA USA. Columbia Univ, New York, NY USA. Univ N Carolina, Chapel Hill, NC USA. Univ Texas, Houston, TX USA. Brown Univ, Providence, RI 02912 USA. Univ Alabama, Birmingham, AL USA. RP Sawady, J (reprint author), Case Western Reserve Univ, Metro Hlth Med Ctr, Dept Pathol, Cleveland, OH 44106 USA. FU NCRR NIH HHS [M01 RR000080]; NICHD NIH HHS [HD27905, HD34116, HD40500, HD40545, HD36801, HD40560, HD27860, HD40512, HD21414, HD34122, HD27915, HD27869, HD34136, HD27861, HD40485, HD40544, HD27917, HD21410, HD34208] NR 25 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2007 VL 197 IS 3 AR 281.e1 DI 10.1016/j.ajog.2007.06.041 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 211NU UT WOS:000249531300023 PM 17826421 ER PT J AU Toso, L Johnson, A Bissell, S Roberson, R Abebe, D Spong, CY AF Toso, Laura Johnson, Andrea Bissell, Stephanie Roberson, Robin Abebe, Daniel Spong, Catherine Y. TI Understanding the mechanism of learning enhancement: NMDA and GABA receptor expression SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) DE activity-dependent neurotrophic factor (ADNF); activity-dependent neuroprotective protein (ADNP); gamma-aminobutyric acid (GABA); learning; N-methyl-D-aspartate (NMDA) ID FETAL ALCOHOL SYNDROME; DEPENDENT NEUROTROPHIC FACTOR; MOUSE MODEL; PREVENTION; PEPTIDES; HIPPOCAMPUS; DEFICITS; NEURONS; GROWTH; MICE AB OBJECTIVE: The administration of neurotrophic peptides NAPVSIPQ (NAP) + SALLRSIPA (SAL) to aged mice resulted in significant learning enhancement. N-methyl-D-aspartate ( NMDA) and gamma-aminobutyric acid (GABA) receptors are fundamental for learning because they are the major modulators of the long-term potentiation, the electrophysiologic mechanism for learning. Also, these receptors have been shown to be involved in NAP + SAL prevention of learning deficit in a mouse model for fetal alcohol syndrome, when administered prenatally during development. Our objective was to test whether NMDA and GABA receptors contribute to the learning enhancement that is induced by the peptides after adult administration. STUDY DESIGN: Aged (14.5 months) male mice were treated for 10 consecutive days with placebo or D-NAP + D-SAL ( 20 mu g, by gavage). At the end of the treatment, brains were harvested. Calibrator-normalized relative real-time polymerase chain reaction was performed with primers for GABA-(A)beta 3, GABA- (A)alpha 5, and the NMDA receptor subunits NR2A and NR2B, with GAPDH standardization. Statistical analysis included analysis of variance, with a probability value that was considered significant at < .05. RESULTS: Five control brains and 6 brains from animals that were treated with NAP + SAL were collected. There was no difference in GABA-(A)beta 3, GABA-(A)alpha 5, NR2A, and NR2B subunits after adult administration of NAP + SAL, as compared with the controls (P > .05). CONCLUSION: Postnatal treatment with NAP + SAL induced learning enhancement in aged mice with a mechanism that does not involve alteration in NMDA and GABA receptor expression. Thus, the mechanism of learning enhancement might be different for a developing fetus than an adult or in the absence of a perturbing agent. C1 UPDN, NICHD, Bethesda, MD 20892 USA. NIAAA, NIH, Bethesda, MD USA. RP Toso, L (reprint author), UPDN, NICHD, Room 1W125,Blg 9,9 Mem Dr, Bethesda, MD 20892 USA. EM tosol@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 22 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2007 VL 197 IS 3 AR 267.e4 DI 10.1016/j.ajog.2007.05.049 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 211NU UT WOS:000249531300016 PM 17826414 ER PT J AU van Laar, JM Melchers, M Teng, YKO van der Zouwen, B Mohammadi, R Fischer, R Margolis, L Fitzgerald, W Grivel, JC Breedveld, FC Lipsky, PE Grammer, AC AF van Laar, Jacob M. Melchers, Marc Teng, Y. K. Onno van der Zouwen, Boris Mohammadi, Rozbeh Fischer, Randy Margolis, Leonid Fitzgerald, Wendy Grivel, Jean-Charles Breedveld, Ferdinand C. Lipsky, Peter E. Grammer, Amrie C. TI Sustained secretion of immunoglobulin by long-lived human tonsil plasma cells SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MARROW STROMAL CELLS; HUMAN BONE-MARROW; ADHESION MOLECULE EXPRESSION; HUMAN LYMPHOID-TISSUE; B-CELLS; BLIMP-1 EXPRESSION; MESSENGER-RNA; HIV-INFECTION; IN-VIVO; DIFFERENTIATION AB immunoglobulin-secreting cells comprise both short-lived proliferating plasmablasts and long-lived non-proliferating plasma cells. To determine the phenotype and functional activity of Ig-secreting cells in human lymphoid tissue, we used a tonsillar organ culture model. A significant proportion of IgA and IgG secretion was shown to be mediated by long-lived, non-proliferating plasma cells that coexpressed high levels of CD27 and CD38. The presence of such cells was further corroborated by the finding of enhanced expression in the CD19(+) B-cell population of XBP-1, IRF-4, and particularly Blimp-1 genes involved in the differentiation of plasma cells. intact tissue seemed to be necessary for optimal functional activity of plasma cells. A strong correlation was found between concentrations of interleukin-6 and IgA or IgG, but not IgM, in culture supernatants suggesting a role for interleukin-6 in the survival of long-lived plasma cells. Taken together, the present study demonstrates that human lymphoid tissue harbors a population of non-proliferating plasma cells that are dependent on an intact microenviromnent for ongoing Ig secretion. C1 Leiden Univ, Med Ctr, Dept Rheumatol, NL-2300 RC Leiden, Netherlands. Natl Inst Musculoskeletal & Skin Dis, B Cell Biol Grp, Leiden, Netherlands. Natl Inst Musculoskeletal & Skin Dis, Autoimmun Branch, Leiden, Netherlands. NICHHD, Lab Cellular & Mol Biophys, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP van Laar, JM (reprint author), Leiden Univ, Med Ctr, Dept Rheumatol, POB 9600, NL-2300 RC Leiden, Netherlands. EM j.m.van_laar@lumc.nl RI Melchers, Mark/C-1438-2008 FU Intramural NIH HHS NR 42 TC 14 Z9 15 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2007 VL 171 IS 3 BP 917 EP 927 DI 10.2353/ajpath.2007.070005 PG 11 WC Pathology SC Pathology GA 205WV UT WOS:000249146200020 PM 17690187 ER PT J AU Muniyappa, R Sorkin, JD Veldhuis, JD Harman, SM Munzer, T Bhasin, S Blackman, MR AF Muniyappa, Ranganath Sorkin, John D. Veldhuis, Johannes D. Harman, S. Mitchell Muenzer, Thomas Bhasin, Shalender Blackman, Marc R. TI Long-term testosterone supplementation augments overnight growth hormone secretion in healthy older men SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE pulsatility; testosterone replacement; aging ID RANDOMIZED CONTROLLED-TRIAL; VIRUS-INFECTED WOMEN; FACTOR-I; SOMATOTROPIC AXIS; AGED WOMEN; HYPOGONADOTROPIC HYPOGONADISM; SERUM TESTOSTERONE; RECEPTOR BLOCKADE; BODY-COMPOSITION; ELDERLY-MEN AB Long-term testosterone supplementation augments overnight growth hormone secretion in healthy older men. Am J Physiol Endocrinol Metab 293:E769-E775, 2007. First published June 5, 2007; doi:10.1152/ajpendo.00709.2006. - Circulating testosterone ( T) and GH/IGF-I are diminished in healthy aging men. Short-term administration of high doses of T augments GH secretion in older men. However, effects of long-term, low-dose T supplementation on GH secretion are unknown. Our objective was to evaluate effects of long-term, low-dose T administration on nocturnal GH secretory dynamics and AM concentrations of IGF-I and IGFBP-3 in healthy older men ( 65 - 88 yr, n = 34) with low-normal T and IGF-I. In a double-masked, placebo-controlled, randomized study we assessed effects of low-dose T supplementation ( 100 mg im every 2 wk) for 26 wk on nocturnal GH secretory dynamics [ 8 PM to 8 AM, Q(20) min sampling, analyzed by multiparameter deconvolution and approximate entropy (ApEn) algorithms]. The results were that T administration increased serum total T by 33% ( P = 0.004) and E-2 by 31% ( P = 0.009) and decreased SHBG by 17% ( P = 0.002) vs. placebo. T supplementation increased nocturnal integrated GH concentrations by 60% ( P = 0.02) and pulsatile GH secretion by 79% ( P = 0.05), primarily due to a twofold increase in GH secretory burst mass ( P = 0.02) and a 1.9-fold increase in basal GH secretion rate ( P = 0.05) vs. placebo. There were no significant changes in GH burst frequency or orderliness of GH release ( ApEn). IGF-I levels increased by 22% ( P = 0.02), with no significant change in IGFBP-3 levels after T vs. placebo. We conclude that low-dose T supplementation for 26 wk increases spontaneous nocturnal GH secretion and morning serum IGF-I concentrations in healthy older men. C1 Washington DC Vet Affairs Med Ctr, Res Serv 151, Washington, DC 20422 USA. Natl Inst Hlth, NAtl Ctr Complementary & Alternat Med, Clin Invest Lab, Endocrine Sect, Bethesda, MD USA. NIA, Natl Inst Hlth, Endocrine Sect, Bethesda, MD 20892 USA. NIA, Natl Inst Hlth, Metab Sect, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Vet Affairs,Dept Med, Div Geriatr & Gerontol, Baltimore, MD USA. Univ Maryland, Sch Med, Vet Affairs Med Ctr, Baltimore Geriat Res Educ & Clin Ctr, Baltimore, MD USA. Univ Maryland, Sch Med, Div Gerontol, Baltimore, MD 21201 USA. Mayo Clin Res Ctr, Dept Internal Med, Div Endocrinol & Metab, Rochester, MN USA. Kronos Longev Res Inst, Phoenix, AZ USA. Burgerspital, St Gallen, Switzerland. Boston Univ, Sch Med, Dept Med, Endocrine Diabet & Nutr Sect, Boston, MA USA. RP Blackman, MR (reprint author), Washington DC Vet Affairs Med Ctr, Res Serv 151, 50 Irving St, Washington, DC 20422 USA. EM Marc.Blackman@va.gov RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU Intramural NIH HHS; NCRR NIH HHS [M01 RR002719, M01-RR-02719]; NIA NIH HHS [P60 AG012583, P60-AG-12583, R01 AG014369, R01-AG-11005, R01-AG-14369, R01-AG-19695]; NIDDK NIH HHS [P30-DK-072488] NR 48 TC 12 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 2007 VL 293 IS 3 BP E769 EP E775 DI 10.1152/ajpendo.00709.2006 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 208YJ UT WOS:000249354800017 PM 17550998 ER PT J AU Batkai, S Mukhopadhyay, P Harvey-White, J Kechrid, R Pacher, P Kunos, G AF Batkai, Sandor Mukhopadhyay, Partha Harvey-White, Judith Kechrid, Raouf Pacher, Pal Kunos, George TI Endocannabinoids acting at CB1 receptors mediate the cardiac contractile dysfunction in vivo in cirrhotic rats SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cirrhosis; cannabinoid CB1 receptors; endocannabinoids; cardiac contractility; pressure-volume loops ID ENDOGENOUS CANNABINOIDS; HYPERDYNAMIC CIRCULATION; ANANDAMIDE; CARDIOMYOPATHY; PRESSURE; PEROXYNITRITE; MACROPHAGES; HYPOTENSION; ACTIVATION; DISEASE AB Advanced liver cirrhosis is associated with hyperdynamic circulation consisting of systemic hypotension, decreased peripheral resistance, and cardiac dysfunction, termed cirrhotic cardiomyopathy. Previous studies have revealed the role of endocannabinoids and vascular CB1 receptors in the development of generalized hypotension and mesenteric vasodilation in animal models of liver cirrhosis, and CB1 receptors have also been implicated in the decreased beta-adrenergic responsiveness of isolated heart tissue from cirrhotic rats. Here we document the cardiac contractile dysfunction in vivo in liver cirrhosis and explore the role of the endocannabinoid system in its development. Rats with CCl4-induced cirrhosis developed decreased cardiac contractility, as documented through the use of the Millar pressure-volume microcatheter system, low blood pressure, and tachycardia. Bolus intravenous injection of the CB1 antagonist AM251 ( 3 mg/kg) acutely increased mean blood pressure, as well as both load-dependent and -independent indexes of systolic function, whereas no such changes were elicited by AM251 in control rats. Furthermore, tissue levels of the endocannabinoid anandamide increased 2.7-fold in the heart of cirrhotic compared with control rats, without any change in 2-arachidonoylglycerol levels, whereas, in the cirrhotic liver, both 2-arachidonoylglycerol (6-fold) and anandamide (3.5-fold) were markedly increased. CB1-receptor expression in the heart was unaffected by cirrhosis, as verified by Western blotting. Activation of cardiac CB1 receptors by endogenous anandamide contributes to the reduced cardiac contractility in liver cirrhosis, and CB1-receptor antagonists may be used to improve contractile function in cirrhotic cardiomyopathy and, possibly, in other forms of heart failure. C1 NIAAA, Lab Physiol Studies, NIH, Sect Neuroendocrinol, Bethesda, MD 20892 USA. NIAAA, Lab Physiol Studies, NIH, Sect Oxidat Stress & Tissue Injury, Bethesda, MD 20892 USA. RP Batkai, S (reprint author), NIAAA, Lab Physiol Studies, NIH, Sect Neuroendocrinol, MSC 9413,Rm 2N17,5625 Fishers Lane, Bethesda, MD 20892 USA. EM sbatkai@mail.nih.gov RI Batkai, Sandor/G-3889-2010; MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; FU Intramural NIH HHS [Z01 AA000375-02, Z01 AA000351-07] NR 35 TC 65 Z9 67 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2007 VL 293 IS 3 BP H1689 EP H1695 DI 10.1152/ajpheart.00538.2007 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 207FU UT WOS:000249237800047 PM 17557913 ER PT J AU Ohayon, J Dubreuil, O Tracqui, P Le Floc'h, S Rioufol, G Chalabreysse, L Thivolet, F Pettigrew, RI Finet, G AF Ohayon, Jacques Dubreuil, Olivier Tracqui, Philippe Le Floc'h, Simon Rioufol, Gilles Chalabreysse, Lara Thivolet, Francoise Pettigrew, Roderic I. Finet, Gerard TI Influence of residual stress/strain on the biomechanical stability of vulnerable coronary plaques: potential impact for evaluating the risk of plaque rupture SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE atherosclerosis; zero-stress state; lipid core; plaque growth; finite element analysis ID 3-VESSEL INTRAVASCULAR ULTRASOUND; HUMAN ATHEROSCLEROTIC PLAQUES; OPTICAL COHERENCE TOMOGRAPHY; CIRCUMFERENTIAL STRESS; MECHANICAL-PROPERTIES; INTRAPLAQUE HEMORRHAGE; STRUCTURAL-ANALYSIS; CAP THICKNESS; SHEAR-STRESS; IN-VIVO AB Influence of residual stress/strain on the biomechanical stability of vulnerable coronary plaques: potential impact for evaluating the risk of plaque rupture. Am J Physiol Heart Circ Physiol 293: H1987-H1996, 2007. First published June 29, 2007; doi:10.1152/ajpheart.00018.2007.-In a vulnerable plaque ( VP), rupture often occurs at a site of high stress within the cap. It is also known that vessels do not become free of stress when all external loads are removed. Previous studies have shown that such residual stress/strain ( RS/ S) tends to make the stress distribution more uniform throughout the media of a normal artery. However, the influence of RS/S on the wall stress distribution in pathological coronaries remains unclear. The aim of this study was to investigate the effects of RS/ S on the biomechanical stability of VPs. RS/ S patterns were studied ex vivo in six human vulnerable coronary plaque samples. Because the existence of RS/ S can only be assessed by releasing it, the opening angle technique was the experimental approach used to study the geometrical opening configurations of the diseased arteries, producing an arterial wall in a near-zero stress state. Reciprocally, these opening geometries were used in finite element simulations to reconstruct the RS/ S distributions in closed arteries. It was found that the RS/S 1) is not negligible, 2) dramatically affects the physiological peak stress amplitude in the thin fibrous cap, 3) spotlights some new high stress areas, and 4) could be a landmark of the lipid core's developmental process within a VP. This study demonstrates that plaque rupture is not to be viewed as a consequence of intravascular pressure alone, but rather of a subtle combination of external loading and intraplaque RS/ S. C1 NHLBI, NIH, Pettigrews Lab, Bethesda, MD 20892 USA. CNRS, UMR 5525, Inst Ingn & Informat Sante In 3 S, Lab Tech Imagerie Modelisat, Grenoble, France. CNRS, UMR 5525, Inst Ingn & Informat Sante In 3 S, Cognit Inst Math Grenoble,DynaCell, Grenoble, France. Hosp Civils Lyon, Dept Hemodynam & Intervent Cardiol, Lyon, France. Univ Lyon 1, Lyon 1, France. Inst Natl Sante & Rech Med, E0226 Unit, Lyon, France. RP Ohayon, J (reprint author), NHLBI, NIH, Pettigrews Lab, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM ohayonj2@mail.nih.gov NR 58 TC 53 Z9 54 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2007 VL 293 IS 3 BP H1987 EP H1996 DI 10.1152/ajpheart.00018.2007 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 207FU UT WOS:000249237800083 PM 17604326 ER PT J AU Atkinson, JJ Toennies, HM Holmbeck, K Senior, RM AF Atkinson, Jeffrey J. Toennies, Holly M. Holmbeck, Kenn Senior, Robert M. TI Membrane type 1 matrix metalloproteinase is necessary for distal airway epithelial repair and keratinocyte growth factor receptor expression after acute injury SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE naphthalene; proliferation; Clara ID CLARA CELL INJURY; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; IN-VIVO; PROLIFERATION; MT1-MMP; ACTIVATION; MICE; CANCER; CHAIN AB Membrane type 1 matrix metalloproteinase (MT1-MMP) is a protease produced by airway epithelial cells in various diseases. Since other MMPs are involved in bronchial epithelial repair, we investigated the role of MT1-MMP in naphthalene-induced small airway injury and repair in wild-type (WT) and MT1-MMP-knockout (KO) mice. The degree of injury was similar in both strains, but the MT1-MMP KO mice were unable to reconstitute a normal, fully differentiated airway epithelium 28 days after injury. MT1-MMP was required for the proliferative response in distal airway epithelial cells, resulting in decreased cell density and airway epithelial cell differentiation in MT1-MMP KO mice. Surprisingly, EGF-mediated signaling was unaltered in MT1-MMP KO mice and therefore unrelated to the proliferative response. However, keratinocyte growth factor receptor (KGFR) expression was significantly upregulated before the proliferative response and markedly less evident in the distal airway epithelium of MT1-MMP KO mice. These results indicate MT1-MMP is involved in KGFR expression and epithelial cell proliferation after acute airway injury. C1 Washington Univ, Sch Med, Div Pulm & Crit Care, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Senior, RM (reprint author), Washington Univ, Sch Med, Div Pulm & Crit Care, 216 S Kingshighway Blvd,Campus Box 8052, St Louis, MO 63110 USA. FU PHS HHS [P01-56419, R01-47328] NR 51 TC 21 Z9 21 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD SEP PY 2007 VL 293 IS 3 BP L600 EP L610 DI 10.1152/ajplung.00028.2007 PG 11 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 205OV UT WOS:000249125100015 PM 17557804 ER PT J AU Steagall, WK Glasgow, CG Hathaway, OM Avila, NA Taveira-DaSilva, AM Rabel, A Stylianou, MP Lin, JP Chen, XL Moss, J AF Steagall, Wendy K. Glasgow, Connie G. Hathaway, Olanda M. Avila, Nilo A. Taveira-DaSilva, Angelo M. Rabel, Antoinette Stylianou, Mario P. Lin, Jing-Ping Chen, Xiaoling Moss, Joel TI Genetic and morphologic determinants of pneumothorax in lymphangioleiomyomatosis SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE cystic lung disease; collagen; matrix metalloproteinases; elastin ID MATRIX METALLOPROTEINASE-1 PROMOTER; SINGLE NUCLEOTIDE POLYMORPHISM; EHLERS-DANLOS SYNDROME; TUBEROUS SCLEROSIS COMPLEX; SP1 BINDING-SITE; COLLAGEN TYPE-I; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; MATRIX-METALLOPROTEINASE-1 GENE; MARFAN-SYNDROME; BONE-DENSITY AB Genetic and morphologic determinants of pneumothorax in lymphangioleiomyomatosis. Am J Physiol Lung Cell Mol Physiol 293: L800-L808, 2007. First published July 6, 2007; doi:10.1152/ajplung.00176.2007. Lymphangioleiomyomatosis, a multisystem disease affecting women, is characterized by proliferation of abnormal smooth muscle-like cells in the lungs, leading to cystic destruction of the parenchyma and recurrent pneumothoraces. Clinical characteristics of lymphangioleiomyomatosis patients were analyzed to determine the relationship of pneumothoraces to disease progression. Patients were genotyped for polymorphisms in genes of extracellular matrix proteins collagen, elastin, and matrix metalloproteinase-1 to assess their association with pneumothoraces. Clinical data and polymorphisms in the genes for types I and III collagen, elastin, and matrix metalloproteinase-1 were compared with the prevalence of pneumothorax. Of 227 patients, 57% reported having had at least one pneumothorax. Cyst size on high-resolution computed tomography scans was associated with pneumothorax; patients with a history of pneumothorax were more likely to have larger cysts than patients who had no pneumothoraces. In patients with mild disease, those with a history of pneumothorax had a faster rate of decline in forced expiratory volume in 1 s ( FEV1; P = 0.001, adjusted for age) than those without. Genotype frequencies differed between patients with and without pneumothorax for polymorphisms in the types I and III collagen and matrix metalloproteinase-1 genes. Larger cysts may predispose lymphangioleiomyomatosis patients to pneumothorax, which, in early stages of disease, correlates with a more rapid rate of decline in FEV1. Polymorphisms in types I and III collagen and matrix metalloproteinase-1 genes may cause differences in lung extracellular matrix that result in greater susceptibility to pneumothorax. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Rm 6D03,MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov FU Intramural NIH HHS NR 53 TC 16 Z9 19 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD SEP PY 2007 VL 293 IS 3 BP L800 EP L808 DI 10.1152/ajplung.00176.2007 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 205OV UT WOS:000249125100036 PM 17616646 ER PT J AU Garcia, AN Patel, KV Guralnik, JM AF Garcia, Andrea N. Patel, Kushang V. Guralnik, Jack M. TI Seat belt use among American Indians/Alaska natives and non-hispanic whites SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID VEHICLE CRASH FATALITIES; SAFETY BELTS; ENFORCEMENT; DISPARITIES; SECONDARY; URBAN; RISK; LAWS AB Background: Accidents (including motor vehicle injuries) are a leading cause of death among American Indians/Alaskan Natives (AI/AN). The purpose of this study was to examine geographic variation and the existence of a seat belt law on seat belt use among AI/AN and non-Hispanic whites (NHW). Methods: Self-reported seat belt behavior data from the 1997 and 2002 Behavioral Risk Factor Surveillance System were analyzed in 2006-2007 and were restricted to AI/AN (n = 4310 for 2002, and n = 1758 for 1997) and NHW (n = 193,617 for 2002, and n = 108,551 for 1997) aged 18 years and older. Results: Seat belt non-use varied significantly across geographic regions for both AI/AN and NHW. For example, AI/AN living in the Northern Plains (odds ratio [OR] = 12.4, 95% confidence interval [CI] =6.5-23.7) and Alaska (OR = 10.3, 95%CI=5.3-19.9) had significantly higher seat belt non-use compared to AI/AN living in the West. In addition, compared to those residing in urban areas, those living in rural areas were 60% more likely in NHW and 2.6 times more likely in AI/AN not to wear a seat belt. Both AI/AN and NHW living in states without primary seat belt laws were approximately twice as likely to report seat belt non-use in 2002 as those living in states with primary laws. In states with primary laws enacted between 1997 and 2002, AI/AN experienced greater decline in seat belt non-use than NHW. Conclusions: Seat belt use among AI/AN and NHW varied significantly by region and urban-rural residency in 2002. Primary seat belt laws appear to help reduce regional and racial disparities in seat belt non-use. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Guralnik, JM (reprint author), NIA, Lab Epidemiol Demog & Biometry, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave,MSC, Bethesda, MD 20892 USA. EM Guralnij@mail.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 24 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD SEP PY 2007 VL 33 IS 3 BP 200 EP 206 DI 10.1016/j.amerpe.2007.04.032 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 210JO UT WOS:000249452700005 PM 17826579 ER PT J AU Roma, PG Silberberg, A Huntsberry, ME Christensen, CJ Ruggier, AM Suomi, SJ AF Roma, Peter G. Silberberg, Alan Huntsberry, Mary E. Christensen, Chesley J. Ruggier, Angela M. Suomi, Stephen J. TI Mark tests for mirror self-recognition in Capuchin monkeys (Cebus apella) trained to touch marks SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE mirror self-recognition; mark test; operant training capuchin monkeys; Cebus apella ID CHIMPANZEES PAN-TROGLODYTES; MACACA-FUSCATA-FUSCATA; FASCICULARIS; AWARENESS; RESPONSES; GORILLAS; BEHAVIOR; PRIMATES; IMAGES AB In Experiment 1, three capuchin monkeys (Cebus apella) were exposed to a mirror in their home cage for 3 days and then given food treats for touching orange marks located on the surface of an experimental chamber. Following training, a mirror was added to the chamber to see if the monkeys would use it to guide non-reinforced contacts with an orange mark on their foreheads that was only visible as a mirror reflection (mark test). Two monkeys touched the head-mark more often with the mirror present than absent, but no mark touches were emitted while looking at the mirror. In Experiment 2, the monkeys were rewarded for touching orange marks on their bodies that were directly visible, followed by another head-mark test. Again, two monkeys touched the mark more often with the mirror present than absent, but these contacts were not emitted while looking at the mirror. Since facing the mirror while mark touching was not required for reinforcement during training, Experiment 3 further tested the possibility that increased mark touching in the presence of the mirror during Experiments 1 and 2 was the result of a memorial process. For this, a final, novel mark test was conducted using an orange mark on the neck that was only visible as a reflection (Experiment 3). No monkeys passed this test. These are the first mark tests given to capuchin monkeys. The results are consistent with the finding that no monkey species is capable of spontaneous mirror self-recognition. The implications of sequential training and mark testing for comparative evaluations of mirror self-recognition capacity are discussed. C1 American Univ, Dept Psychol, Washington, DC 20016 USA. NICHHD, Comparat Ethol Lab, Poolesville, MD USA. RP Roma, PG (reprint author), American Univ, Dept Psychol, 4400 Massachusetts Ave,NW, Washington, DC 20016 USA. EM PeteRoma@gmail.com FU Intramural NIH HHS NR 36 TC 12 Z9 14 U1 3 U2 19 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD SEP PY 2007 VL 69 IS 9 BP 989 EP 1000 DI 10.1002/ajp.20404 PG 12 WC Zoology SC Zoology GA 204ZT UT WOS:000249083200004 PM 17253635 ER PT J AU Danis, M Lovett, F Sabik, L Aclikes, K Cheng, G Aomo, T AF Danis, Marion Lovett, Francis Sabik, Lindsay Aclikes, Katherin Cheng, Glen Aomo, Tom TI Low-income employees' choices regarding employment benefits aimed at improving the socioeconomic determinants of health SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PROMOTION AB Objectives. Socioeconomic factors are associated with reduced health status in low-income populations. We sought to identify affordable employment benefit packages that might ameliorate these socioeconomic factors and would be consonant with employees' priorities. Methods. Working in groups (n=53), low-income employees (n=408; 62% women, 65% Black) from the Washington, DC, and Baltimore, Md, metropolitan area, participated in a computerized exercise in which they expressed their preference for employment benefit packages intended to address socioeconomic determinants of health. The hypothetical costs of these benefits reflected those of the average US benefit package available to low-income employees. Questionnaires ascertained sociodemographic information and attitudes. Descriptive statistics and logistic regression analysis were used to examine benefit choices. Results. Groups chose offered benefits in the following descending rank order: health care, retirement, vacation, disability pay, training, job flexibility, family time, dependent care, monetary advice, anxiety assistance, wellness, housing assistance, and nutrition programs. Participants varied in their personal choices, but 78% expressed willingness to abide by their groups' choices. Conclusions. It is possible to design employment benefits that ameliorate socioeconomic determinants of health and are acceptable to low-income employees. These benefit packages can be provided at the cost of benefit packages currently available to some low-income employees. C1 [Danis, Marion; Lovett, Francis; Sabik, Lindsay; Aclikes, Katherin] NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20982 USA. [Cheng, Glen] Univ Med & Dent New Jersey, Dept Clin Bioeth, Newark, NJ USA. RP Danis, M (reprint author), NIH, Ctr Clin, Dept Clin Bioeth, Bldg 10,Rm 1c118, Bethesda, MD 20982 USA. EM mdanis@nih.gov OI Sabik, Lindsay/0000-0002-0613-4929 NR 20 TC 7 Z9 7 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2007 VL 97 IS 9 BP 1650 EP 1657 DI 10.2105/AJPH.2006.091033 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 297WM UT WOS:000255648100028 PM 17666702 ER PT J AU Nabel, EG Shurin, SB AF Nabel, Elizabeth G. Shurin, Susan B. TI Notes from the NHLBI director - National Heart, Lung, and Blood Institute core values and shaping the 2007 budget SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 1 PY 2007 VL 176 IS 5 BP 430 EP 430 DI 10.1164/rccm.200705-706ED PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 206HE UT WOS:000249173700004 PM 17715382 ER PT J AU Card, JW Voltz, JW Carey, MA Bradbury, A DeGraff, LM Lih, FB Bonner, JC Morgan, DL Flake, GP Zeldin, DC AF Card, Jeffrey W. Voltz, James W. Carey, Michelle A. Bradbury, Alyce DeGraff, Laura M. Lih, Fred B. Bonner, James C. Morgan, Daniel L. Flake, Gordon P. Zeldin, Darryl C. TI Cyclooxygenase-2 deficiency exacerbates bleomycin-induced lung dysfunction but not fibrosis SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE cyclooxygenase; fibrosis; respiratory mechanics; prostaglandin; transgenic ID INDUCED PULMONARY-FIBROSIS; AIRWAY RESPONSIVENESS; MICE; INFLAMMATION; SEVERITY; INJURY; FIBROBLASTS; PHYSIOLOGY; MEDIATORS; MECHANICS AB Cyclooxygenase (COX)-derived eicosanoids have been implicated in the pathogenesis of pulmonary fibrosis. Uncertainty regarding the influence of COX-2 on experimental pulmonary fibrosis prompted us to clarify the fibrotic and functional effects of intratracheal bleomycin administration in mice genetically deficient in COX-2. Further, the effects of airway-specific COX-1 overexpression on fibrotic and functional outcomes in wild-type and COX-2 knockout mice were assessed. Equivalent increases in airway cell influx, lung Collagen content, and histopathologic evidence of fibrosis were observed in wild-type and COX-2 knockout mice 21 d after bleomycin treatment, suggesting that COX-2 deficiency did not alter the extent or severity of fibrosis in this model. However, bleomycin-induced alterations in respiratory mechanics were more severe in COX-2 knockout mice than in wild-type mice, as illustrated by a greater decrease in static compliance compared with genotype-matched, saline-treated control mice (26 +/not superset of 3% versus 11 +/not superset of 4% decreases for COX-2 knockout and wild-type mice, respectively; P < 0.05). The influence of COX-1 overexpression in airway Clara cells was also examined. Whereas the fibrotic effects of bleomycin were not altered in wild-type or COX-2 knockout mice overexpressing COX-1, the exaggerated lung function decrement in bleomycin-treated COX-2 knockout mice was prevented by COX-1 overexpression and coincided with decreased airway cysteinyl leukotriene levels. Collectively, these data suggest an important regulatory role for COX-2 in the maintenance of lung function in the setting of lung fibrosis, but not in the progression of the fibrotic process per se. C1 NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. CIIT Ctr Hlth Res, Res Triangle Pk, NC USA. RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, NIH, 111 TW Alexander Dr,Bldg 101,Room D236, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov FU Intramural NIH HHS [Z01 ES025043-08] NR 28 TC 27 Z9 27 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD SEP PY 2007 VL 37 IS 3 BP 300 EP 308 DI 10.1165/rcmb.2007-00570C PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 208MC UT WOS:000249322400005 PM 17496151 ER PT J AU Garrison, AR Alakbarova, S Kulesh, DA Shezmukhamedova, D Khodjaev, S Endy, TP Paragas, J AF Garrison, A. R. Alakbarova, S. Kulesh, D. A. Shezmukhamedova, D. Khodjaev, S. Endy, T. P. Paragas, J. TI Development of a TaqMan((R))-Minor groove binding protein assay for the detection and quantification of crimean-congo hemorrhagic fever virus SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID TIME RT-PCR; EXPERIMENTAL-INFECTION; NOSOCOMIAL OUTBREAK; SEGMENT; AFRICA; BINDER; DIAGNOSIS; RUSSIA; ASIA AB Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus of the genus Nairovirus and the family Bunyaviridae. It is a negative-strand RNA virus comprised of small (S), medium (M), and large (L) genome segments. The S segment encodes for nucleocapsid protein, the M segment codes for envelope glycoproteins (Gn and Gc), and the L segment codes for the RNA-dependent RNA polymerase. Currently, there are a limited number of methods for rapidly diagnosing CCHFV infections. We developed a real-time, reverse transcription-polymerase chain reaction assay for the rapid detection of CCHFV by using the TaqMan((R))-minor groove binding protein probe technology. The primers and probes were designed to amplify and detect a region in the S segment of CCHFV that is conserved across multiple strains. The limit of detection of the assay was 10 genome copies of RNA. This primer and probe set was specific to 18 strains of CCHFV tested and did not cross-react with either a DNA panel of 78 organisms or a panel of 28 diverse RNA viruses. This will rapidly and specifically detect CCHFV, and it has been used to detect CCHFV infection in samples from humans, animals, and ticks. C1 NIAID, NIH, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. Minist Hlth, Inst Virol, Tashkent, Uzbekistan. USA, Med Res Inst Infect Dis, Diagnost Syst Div, Ft Detrick, MD 21702 USA. RP Paragas, J (reprint author), NIAID, NIH, 33 N Dr,Room 2E19A, Bethesda, MD 20892 USA. EM paragasj@niaid.nih.gov NR 27 TC 22 Z9 23 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 2007 VL 77 IS 3 BP 514 EP 520 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 208IE UT WOS:000249312200020 PM 17827370 ER PT J AU Ostrander, EA AF Ostrander, Elaine A. TI Genetics and the shape of dogs - Studying the new sequence of the canine genome shows how tiny genetic changes can create enormous variation within a single species SO AMERICAN SCIENTIST LA English DT Article ID DOMESTIC DOG; SIZE C1 NHGRI, Bethesda, MD 20892 USA. RP Ostrander, EA (reprint author), NHGRI, 50 S Dr,MSC 8000, Bethesda, MD 20892 USA. OI Ostrander, Elaine/0000-0001-6075-9738 NR 8 TC 14 Z9 14 U1 0 U2 14 PU SIGMA XI-SCI RES SOC PI RES TRIANGLE PK PA PO BOX 13975, RES TRIANGLE PK, NC 27709 USA SN 0003-0996 J9 AM SCI JI Am. Scientist PD SEP-OCT PY 2007 VL 95 IS 5 BP 406 EP 413 DI 10.1511/2007.67.3724 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 200AB UT WOS:000248735200017 ER PT J AU Lipsky, RH Hu, X Jiang, X Tian, F Xu, K Marini, AM AF Lipsky, R. H. Hu, X. Jiang, X. Tian, F. Xu, K. Marini, A. M. TI Genes and neuropsychiatric disorders SO AMINO ACIDS LA English DT Meeting Abstract C1 NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD SEP PY 2007 VL 33 IS 3 BP XXIV EP XXIV PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 206UH UT WOS:000249207900074 ER PT J AU Marini, AM Jiang, X Tian, F Du, Y Copeland, NG Jenkins, NA Wu, X Pan, H Xu, K Kenney, H Egan, SE Harris, A Turley, H Lipsky, RH AF Marini, A. M. Jiang, X. Tian, F. Du, Y. Copeland, N. G. Jenkins, N. A. Wu, X. Pan, H. Xu, K. Kenney, H. Egan, S. E. Harris, A. Turley, H. Lipsky, R. H. TI The sharp-2 transcription factor: a new candidate for protecting the brain against ischemia SO AMINO ACIDS LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. NIAAA, Mol Genet Sect, NIH, Bethesda, MD USA. NIAAA, Sect Human Genet, NIH, Bethesda, MD USA. NCI, Mouse Canc Genet Program, Canc Res Ctr, Frederick, MD 21701 USA. Univ Toronto, Hosp Sick Children, Programs Canc Res, Toronto, ON M5G 1X8, Canada. Univ Toronto, Hosp Sick Children, Program Dev Biol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Mol Oncol Lab, Oxford OX3 9DU, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD SEP PY 2007 VL 33 IS 3 BP XXV EP XXV PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 206UH UT WOS:000249207900078 ER PT J AU Paddock, S Laje, G Charney, D Rush, AJ Wilson, AF Sorant, AJM Lipsky, R Wisniewski, SR Manji, H McMahon, FJ AF Paddock, S. Laje, G. Charney, D. Rush, A. J. Wilson, A. F. Sorant, A. J. M. Lipsky, R. Wisniewski, S. R. Manji, H. McMahon, F. J. TI Association of GRIK4 with outcome of antidepressant treatment in the STAR* D cohort SO AMINO ACIDS LA English DT Meeting Abstract C1 NIMH, Dept Hlth & Human Serv, Genet Basis Mood & Anxiety Disorders Mood & Anxie, NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. Mt Sinai Sch Med, Dept Pharmacol, New York, NY USA. Mt Sinai Sch Med, Dept Biol Chem, New York, NY USA. Univ Texas, SW Med Ctr, Dept Clin Sci & Psychiat, Dallas, TX 75230 USA. NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH,DHHS, Baltimore, MD USA. NIAAA, Mol Genet Sect, Neurogenet Lab, NIH,DHHS, Rockville, MD 20852 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. NIMH, Mol Pathophysiol Lab, Mood & Anxiety Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD SEP PY 2007 VL 33 IS 3 BP XXVIII EP XXVIII PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 206UH UT WOS:000249207900088 ER PT J AU Westermark, P Benson, MD Buxbaum, JN Cohen, AS Frangione, B Ikeda, SI Masters, CL Merlini, G Saraiva, MJ Sipeo, JD AF Westermark, Per Benson, Merrill D. Buxbaum, Joel N. Cohen, Alan S. Frangione, Blas Ikeda, Shu-Ichi Masters, Colin L. Merlini, Giampaolo Saraiva, Maria J. Sipeo, Jean D. TI A primer of amyloid nomenclature SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Article DE amyloidosis; amyloid protein; nomenclature ID DISEASE AB The increasing knowledge of the exact biochemical nature of the localized and systemic amyloid disorders has made a logical and easily understood nomenclature absolutely necessary. Such a nomenclature, biochemically based, has been used for several years but the current literature is still mixed up with many clinical and histochemically based designations from the time when amyloid in general was poorly understood. All amyloid types are today preferably named by their major fibril protein. This makes a simple and rational nomenclature for the increasing number of amyloid disorders known in humans and animals. C1 Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden. Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indianapolis, IN USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NYU, Sch Med, Dept Pathol, New York, NY USA. Shinshu Univ, Sch Med, Dept Med 3, Matsumoto, Nagano 390, Japan. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Univ Pavia, Policlin San Matteo, Hosp Fdn, IRCCS,Biotechnol Res Labs,Amyloidosis Ctr, I-27100 Pavia, Italy. Inst Mol & Cellular Biol, Unidade Amiloide, Oporto, Portugal. NIH, Ctr Sci Review, Bethesda, MD 20892 USA. RP Westermark, P (reprint author), Rudbeck Lab, SE-75185 Uppsala, Sweden. EM per.westermark@genpat.uu.se RI Merlini, Giampaolo/A-3817-2008; Saraiva, Maria Joao/K-3907-2013 OI Merlini, Giampaolo/0000-0001-7680-3254; Saraiva, Maria Joao/0000-0002-3360-6899 NR 7 TC 171 Z9 178 U1 0 U2 11 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD SEP PY 2007 VL 14 IS 3 BP 179 EP 183 DI 10.1080/13506120701460923 PG 5 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 212WN UT WOS:000249627800001 PM 17701465 ER PT J AU Betz, JM Fisher, KD Saldanha, LG Coates, PM AF Betz, Joseph M. Fisher, Kenneth D. Saldanha, Leila G. Coates, Paul M. TI The NIH analytical methods and reference materials program for dietary supplements SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Review DE bioanalytical methods; natural products; quality assurance; control; reference materials ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SINGLE-LABORATORY VALIDATION; STANDARD REFERENCE MATERIALS; RANDOMIZED CLINICAL-TRIALS; HERBAL MEDICINAL PRODUCTS; ST-JOHNS-WORT; RAW-MATERIALS; ULTRAVIOLET DETECTION; EPHEDRINE ALKALOIDS; CONSORT STATEMENT AB Quality of botanical products is a great uncertainty that consumers, clinicians, regulators, and researchers face. Definitions of quality abound, and include specifications for sanitation, adventitious agents (pesticides, metals, weeds), and content of natural chemicals. Because dietary supplements (DS) are often complex mixtures, they pose analytical challenges and method validation may be difficult. In response to product quality concerns and the need for validated and publicly available methods for DS analysis, the US Congress directed the Office of Dietary Supplements (ODS) at the National Institutes of Health (NIH) to accelerate an ongoing methods validation process, and the Dietary Supplements Methods and Reference Materials Program was created. The program was constructed from stakeholder input and incorporates several federal procurement and granting mechanisms in a coordinated and interlocking framework. The framework facilitates validation of analytical methods, analytical standards, and reference materials. C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Betz, JM (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd, Bethesda, MD 20892 USA. EM betzj@od.nih.gov NR 44 TC 26 Z9 26 U1 1 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD SEP PY 2007 VL 389 IS 1 BP 19 EP 25 DI 10.1007/s00216-007-1342-8 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 203KU UT WOS:000248974300005 PM 17541565 ER PT J AU Dwyer, JT Holden, J Andrews, K Roseland, J Zhao, C Schweitzer, A Perry, CR Harnly, J Wolf, WR Picciano, MF Fisher, KD Saldanha, LG Yetley, EA Betz, JM Coates, PM Milner, JA Whitted, J Burt, V Radimer, K Wilger, J Sharpless, KE Hardy, CJ AF Dwyer, Johanna T. Holden, Joanne Andrews, Karen Roseland, Janet Zhao, Cuiwei Schweitzer, Amy Perry, Charles R. Harnly, James Wolf, Wayne R. Picciano, Mary Frances Fisher, Kenneth D. Saldanha, Leila G. Yetley, Elizabeth A. Betz, Joseph M. Coates, Paul M. Milner, John A. Whitted, Jackie Burt, Vicki Radimer, Kathy Wilger, Jaime Sharpless, Katherine E. Hardy, Constance J. TI Measuring vitamins and minerals in dietary supplements for nutrition studies in the USA SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Review DE dietary supplements; dietary supplement ingredient database; multivitamin mineral supplements; analytical values ID MULTIVITAMIN-MULTIMINERAL SUPPLEMENTS; ACCURACY; HEALTH AB This article illustrates the importance of having analytical data on the vitamin and mineral contents of dietary supplements in nutrition studies, and describes efforts to develop an analytically validated dietary supplement ingredient database (DSID) by a consortium of federal agencies in the USA. Preliminary studies of multivitamin mineral supplements marketed in the USA that were analyzed as candidates for the DSID are summarized. Challenges are summarized, possible future directions are outlined, and some related programs at the Office of Dietary Supplements, National Institutes of Health are described. The DSID should be helpful to researchers in assessing relationships between intakes of vitamins and minerals and health outcomes. C1 US Dept HHS, Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD 20892 USA. US Dept HHS, Natl Canc Inst, Nutr Sci Res Grp, Bethesda, MD 20892 USA. US Dept HHS, Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Natl Hlth & Nutr Examinat Survey, Hyattsville, MD 20782 USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. USDA, Agr Res Serv, Beltsville Human Nutr Res Ctr, Nutr Data Lab, Beltsville, MD 20705 USA. USDA, Agr Res Serv, Beltsville Human Nutr Res Ctr, Food Composit Lab, Beltsville, MD 20705 USA. USDA, Natl Agr Stat Serv, Div Res & Dev, Fairfax, VA 22030 USA. US Dept HHS, US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20850 USA. RP Dwyer, JT (reprint author), US Dept HHS, Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD 20892 USA. EM dwyerj1@od.nih.gov OI Sharpless, Katherine/0000-0001-6569-198X; Dwyer, Johanna/0000-0002-0783-1769 NR 29 TC 26 Z9 26 U1 3 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD SEP PY 2007 VL 389 IS 1 BP 37 EP 46 DI 10.1007/s00216-007-1456-z PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 203KU UT WOS:000248974300007 PM 17641882 ER PT J AU Rimmer, CA Howerton, SB Sharpless, KE Sander, LC Long, SE Murphy, KE Porter, BJ Putzbach, K Rearick, MS Wise, SA Wood, LJ Zeisler, R Hancock, DK Yen, JH Betz, JM NguyenPho, A Yang, L Scriver, C Willie, S Sturgeon, R Schaneberg, B Nelson, C Skamarack, J Pan, M Levanseler, K Gray, D Waysek, EH Blatter, A Reich, E AF Rimmer, Catherine A. Howerton, Samuel B. Sharpless, Katherine E. Sander, Lane C. Long, Stephen E. Murphy, Karen E. Porter, Barbara J. Putzbach, Karsten Rearick, Michael S. Wise, Stephen A. Wood, Laura J. Zeisler, Rolf Hancock, Diane K. Yen, James H. Betz, Joseph M. NguyenPho, Agnes Yang, Lu Scriver, Christine Willie, Scott Sturgeon, Ralph Schaneberg, Brian Nelson, Christina Skamarack, Jules Pan, Meide Levanseler, Kerri Gray, Dean Waysek, Edward H. Blatter, Anne Reich, Eike TI Characterization of a suite of ginkgo-containing standard reference materials SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE liquid chromatography; mass spectrometry; Ginkgo biloba; standard reference material; dietary supplements ID PERFORMANCE LIQUID-CHROMATOGRAPHY; EVAPORATIVE LIGHT-SCATTERING; PLASMA-MASS SPECTROMETRY; ID ICP-MS; BILOBA LEAVES; FLAVONOL AGLYCONES; EXTRACTS; CERTIFICATION; PHYTOPHARMACEUTICALS; TERPENELACTONES AB A suite of three ginkgo-containing dietary supplement Standard Reference Materials (SRMs) has been issued by the National Institute of Standards and Technology (NIST) with certified values for flavonoid aglycones, ginkgolides, bilobalide, and selected toxic trace elements. The materials represent a range of matrices (i.e., plant, extract, and finished product) that provide different analytical challenges. The constituents have been determined by at least two independent analytical methods with measurements performed by NIST and at least one collaborating laboratory. The methods utilized different extractions, chromatographic separations, modes of detection, and approaches to quantitation. The SRMs are primarily intended for method validation and for use as control materials to support the analysis of dietary supplements and related botanical materials. C1 NIST, Gaithersburg, MD 20899 USA. NIH, Off Dietary Supplement, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Natl Res Council Canada, Ottawa, ON K1A 0R9, Canada. ChromaDex Inc, Boulder, CO 80301 USA. Eurofins, Petaluma, CA 94952 USA. NSF Int, Ann Arbor, MI 48105 USA. Midwest Res Inst, Kansas City, MO 64110 USA. Caravan Prod, Totowa, NJ 07512 USA. CAMAG, Muttenz, Switzerland. RP Rimmer, CA (reprint author), NIST, Gaithersburg, MD 20899 USA. EM Catherine.Rimmer@nist.gov OI Yang, Lu/0000-0002-4351-2503; Sharpless, Katherine/0000-0001-6569-198X; Sturgeon, Ralph/0000-0001-7304-3034; Willie, Scott/0000-0002-3376-0722 NR 33 TC 17 Z9 17 U1 0 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD SEP PY 2007 VL 389 IS 1 BP 179 EP 196 DI 10.1007/s00216-007-1398-5 PG 18 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 203KU UT WOS:000248974300019 PM 17619180 ER PT J AU Andrews, KW Schweitzer, A Zhao, C Holden, JM Roseland, JM Brandt, M Dwyer, JT Picciano, MF Saldanha, LG Fisher, KD Yetley, E Betz, JM Douglass, L AF Andrews, Karen W. Schweitzer, Amy Zhao, Cuiwei Holden, Joanne M. Roseland, Janet M. Brandt, Mary Dwyer, Johanna T. Picciano, Mary Frances Saldanha, Leila G. Fisher, Kenneth D. Yetley, Elizabeth Betz, Joseph M. Douglass, Larry TI The caffeine contents of dietary supplements commonly purchased in the US: analysis of 53 products with caffeine-containing ingredients SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE caffeine; HPLC; UV; VIS; Dietary supplement; reference material ID CAMELLIA-SINENSIS; PURINE ALKALOIDS; HPLC; TEA; THEOBROMINE; CATECHINS; SAMPLES; COLUMN; SYSTEM AB As part of a study initiating the development of an analytically validated Dietary Supplement Ingredient Database (DSID) in the United States (US), a selection of dietary supplement products were analyzed for their caffeine content. Products sold as tablets, caplets, or capsules and listing at least one caffeine-containing ingredient (including botanicals such as guarana, yerba mate, kola nut, and green tea extract) on the label were selected for analysis based on market share information. Two or three lots of each product were purchased and analyzed using high-pressure liquid chromatography (HPLC). Each analytical run included one or two National Institute of Standards and Technology (NIST) Standard Reference Materials (SRMs) and two products in duplicate. Caffeine intake per serving and per day was calculated using the maximum recommendations on each product label. Laboratory analysis for 53 products showed product means ranging from 1 to 829 mg caffeine/day. For products with a label amount for comparison (n=28), 89% (n=25) of the products had analytically based caffeine levels/day of between -16% and +16% of the claimed levels. Lot-to-lot variability (n=2 or 3) for caffeine in most products (72%) was less than 10%. C1 USDA, Agr Res Serv, Beltsville Human Nutr Res Ctr, Nutrient Data Lab, Beltsville, MD 20705 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. US Dept HHS, Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD USA. Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. RP Andrews, KW (reprint author), USDA, Agr Res Serv, Beltsville Human Nutr Res Ctr, Nutrient Data Lab, Beltsville, MD 20705 USA. EM karen.andrews@ars.usda.gov OI Dwyer, Johanna/0000-0002-0783-1769 NR 19 TC 34 Z9 35 U1 0 U2 17 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD SEP PY 2007 VL 389 IS 1 BP 231 EP 239 DI 10.1007/s00216-007-1437-2 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 203KU UT WOS:000248974300023 PM 17676317 ER PT J AU Lee, MY Trent, JM Bittner, ML AF Lee, Myoyong Trent, Jeffrey M. Bittner, Michael L. TI Optimization of oligonucleotide microarray fabricated by spotting 65-mer SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE oligonucleotide; microarray; spotting; gene expression ID GENE-EXPRESSION PROFILES; DNA MICROARRAYS; MOLECULAR CLASSIFICATION; CDNA MICROARRAYS; BREAST-CANCER; VALIDATION; DISCOVERY; PLATFORMS AB DNA microarrays currently provide measurements of sufficiently high quality to allow a wide variety of sound inferences about gene regulation and the coordination of cellular processes to be drawn. Nonetheless, a desire for greater precision in the measurements continues to drive the microarray research community to seek higher measurement quality through improvements in array fabrication and sample labeling and hybridization. We prepared oligonucleotide microarrays by printing 65-mer on aldehyde functional group-derivatized slides as described in a previous study. We could improve the reliability of data by removing enzymatic bias during probe labeling and hybridizing under a more stringent condition. This optimized method was used to profile gene expression patterns for nine different mouse tissues and organs, and multidimensional scaling (MDS) analysis of data showed both strong similarity between like samples and a clear, highly reproducible separation between different tissue samples. Three other microarrays were fabricated on commercial substrates and hybridized following the manufacturer's instructions. The data were then compared with in-house microarray data and reverse transcription-polymerase chain reaction (RT-PCR) data. The microarray printed on the custom aldehyde slide was superior to microarrays printed on commercially available substrate slides in terms of signal intensities, background, and hybridization characteristics. The data from the custom substrate microarray generally showed good agreement in quantitative changes up to 100-fold changes of transcript abundance with RT-PCR data. However, more accurate comparisons will be made as more genomic sequence information is gathered in the public data domain. Published by Elsevier Inc. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Lee, MY (reprint author), Samsung Adv Inst Technol, Bio Lab, Yongin 446712, Kyoungki Do, South Korea. EM myoyong.lee@samsung.com FU NCI NIH HHS [R01 CA129447-01, R01 CA129447] NR 23 TC 6 Z9 7 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD SEP 1 PY 2007 VL 368 IS 1 BP 61 EP 69 DI 10.1016/j.ab.2007.06.005 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 194SP UT WOS:000248364400007 PM 17618862 ER PT J AU Lee, MY Xiang, CC Trent, JM Bittner, ML AF Lee, Myoyong Xiang, Charlie C. Trent, Jeffrey M. Bittner, Michael L. TI Performance characteristics of 65-mer oligonucleotide microarrays SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE oligonucleotide; microarray; gene expression ID GENE-EXPRESSION PATTERNS; IMMOBILIZATION; ARRAYS; GLASS; HYBRIDIZATION; SILANIZATION; COATINGS; CANCER; BONDS AB Microarray fabrication using presynthesized long oligonucleotide is becoming increasingly important, but a study of large-scale array productions has not yet been published. We addressed the issue of fabricating oligonucleotide microarrays by spotting commercial presynthesized 65-mers with 5 ' amines representing 7500 murine genes. Amine-modified oligonucleotides were immobilized on glass slides having aldehyde groups via transient Schiff base formation followed by reduction to produce a covalent conjugate. When RNA derived from the same source was used for Cy3 and Cy5 labeling and hybridized to the same array, signal intensities spanning three orders of magnitude were observed and the coefficient of variance (CV) between the two channels for all spots was 8 to 10%. To ascertain the reproducibility of ratio determination of these arrays, two triplicate hybridizations (with fluorochrome reversal) comparing RNAs from a fibroblast (NIHM3T3) and a breast cancer (JC) cell line were carried out. The 95% confidence interval for all spots in the six hybridizations was 0.60 to 1.66. This level of reproducibility allows use of the full range of pattern finding and discriminant analysis typically applied to complementary DNA (cDNA) microarrays. Further comparative testing was carried out with oligonucleotide microarrays, cDNA microarrays, and reverse transcription (RT)-PCR assays to examine the comparability of results across these different methodologies. Published by Elsevier Inc. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Lee, MY (reprint author), Samsung Adv Inst Technol, Bio Lab, Yongin 446712, Kyoungki Do, South Korea. EM myoyong.lee@samsung.com FU NCI NIH HHS [R01 CA129447, R01 CA129447-01] NR 28 TC 8 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD SEP 1 PY 2007 VL 368 IS 1 BP 70 EP 78 DI 10.1016/j.ab.2007.05.010 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 194SP UT WOS:000248364400008 PM 17617369 ER PT J AU Belluco, C Petricoin, EF Mammano, E Facchiano, F Ross-, S Nitti, D Di Maggio, C Liu, CW Lise, M Liotta, LA Whiteley, G AF Belluco, Claudio Petricoin, Emanuel F. Mammano, Enzo Facchiano, Francesco Ross-Rucker, Sally Nitti, Donato Di Maggio, Cosimo Liu, Chenwei Lise, Mario Liotta, Lance A. Whiteley, Gordon TI Serum proteomic analysis identifies a highly sensitive and specific discriminatory pattern in stage 1 breast cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE breast cancer; early detection; serum proteomics; SELDI-TOF; biomarkers ID OVARIAN-CANCER; MASS-SPECTROMETRY; PROSTATE-CANCER; MORTALITY; BIOMARKERS; DIAGNOSIS AB Background: Mass spectrometry (MS)-based profiling was used to determine whether ion fingerprints could distinguish women with stage 1 breast cancer from women without breast cancer. Methods: The initial study population consisted of 310 subjects: 155 women with yearly negative breast examination and negative mammography findings for at least 4 years, and 155 women undergoing surgery for pathology-proven stage 1 invasive ductal carcinoma. High-resolution SELDI-TOF (surface-enhanced laser desorption ionization-time of flight) analysis was performed on serum obtained from blood samples collected before mammography in controls, and before surgery in patients with breast cancer. Samples were divided into a training (109 controls and 109 cancers) and blinded (46 controls and 46 cancers) testing set; each group had similar age demographics. In addition, an independent study set of 46 serum samples was analyzed 14 months after the initial study to validate the robustness of the classifier. Results: A discriminatory profile consisting of seven ion peaks found in the training set, when applied to the blinded test set, achieved a sensitivity and specificity of 95.6% and 86.5%, respectively. This same seven-peak profile achieved a 96.5% sensitivity and 85.7% specificity, with correct identification of all of 17 T1a tumors when applied to the validation study set. Conclusions: Mass spectrometry profiling of human serum generated a robust classifier composed of seven low-molecular-weight ions that yielded a highly sensitive and specific diagnostic procedure for the discrimination of women with stage 1 breast cancer compared with women without breast cancer in this research study set. C1 IRCCS, Natl Canc Inst, Dept Surg, CRO, I-33081 Aviano, Italy. George Mason Univ, Ctr Appl Proteom & Mol Med, Manassas, VA 20110 USA. Univ Padua, Dept Oncol & Surg Sci, I-35128 Padua, Italy. Ist Super Sanita, Dept Hematol, I-00161 Rome, Italy. SAIC Frederick Inc, Natl Canc Inst, Clin Proteom Reference Lab, Gaithersburg, MD 20878 USA. RP Belluco, C (reprint author), IRCCS, Natl Canc Inst, Dept Surg, CRO, Via Franco Gallini 2, I-33081 Aviano, Italy. EM cbelluco@cro.it RI Facchiano, Francesco/K-8716-2016; OI Facchiano, Francesco/0000-0003-4313-0617; belluco, claudio/0000-0001-5972-9574 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 26 TC 60 Z9 63 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD SEP PY 2007 VL 14 IS 9 BP 2470 EP 2476 DI 10.1245/s10434-007-9354-3 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 209PN UT WOS:000249400600010 PM 17594124 ER PT J AU LoPiccolo, J Granville, CA Gills, JJ Dennis, PA AF LoPiccolo, Jaclyn Granville, Courtney A. Gills, Joell J. Dennis, Phillip A. TI Targeting Akt in cancer therapy SO ANTI-CANCER DRUGS LA English DT Review DE Akt inhibitors; cancer therapy; drug development; molecular targets ID PROTEIN-KINASE-B; SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR-RECEPTOR; PLECKSTRIN-HOMOLOGY-DOMAIN; SMALL-MOLECULE INHIBITOR; PHASE-II TRIAL; TRICYCLIC NUCLEOSIDE PHOSPHATE; ACUTE MYELOGENOUS LEUKEMIA; GLYCOGEN-SYNTHASE KINASE; SIGNAL-REGULATED KINASE AB In an effort to improve therapeutic options in cancer, many investigational drugs are being developed to inhibit signaling pathways that promote the survival of cancer cells. The prototypic pathway that promotes cellular survival is the phosphoinositide 3'-kinase/Akt/mammalian target of rapamycin pathway, which is constitutively activated in many types of cancers. Mechanisms for activation of the serine/threonine kinase, Akt, include loss of tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) function, amplification or mutation of phosphoinositide 3'-kinase, amplification of Akt, activation of growth factor receptors and exposure to carcinogens. Activation of Akt promotes cellular survival as well as resistance to treatment with chemotherapy and/or radiation therapy. Immunohistochemical analyses have shown that Akt is activated in many types of cancers and preneoplastic lesions, and Akt activation is a poor prognostic factor in various cancers. Taken together, these data demonstrate that Akt is a valid target for inhibition. This review will focus on published data using different approaches to inhibit Akt. We will also consider how the complex regulation of the phosphoinositide 3'-kinase/Akt/mammalian target of rapamycin pathway poses practical issues concerning the design of clinical trials, potential toxicities and the likelihood of finding a therapeutic index when targeting such a critical cellular pathway. C1 USN, Med Oncol Branch, Canc Res Ctr, NCI, Gaithersburg, MD 20899 USA. RP Dennis, PA (reprint author), USN, Med Oncol Branch, Canc Res Ctr, NCI, Bldg 8,Room 5101,8901 Wisconsin Ave, Gaithersburg, MD 20899 USA. EM pdennis@nih.gov NR 144 TC 92 Z9 97 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD SEP PY 2007 VL 18 IS 8 BP 861 EP 874 PG 14 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 200XE UT WOS:000248795300001 PM 17667591 ER PT J AU Acosta, EP Kendall, MA Gerber, JG Alston-Smith, B Koletar, SL Zolopa, AR Agarwala, S Child, M Bertz, R Hosey, L Haas, DW AF Acosta, Edward P. Kendall, Michelle A. Gerber, John G. Alston-Smith, Beverly Koletar, Susan L. Zolopa, Andrew R. Agarwala, Sangeeta Child, Michael Bertz, Richard Hosey, Lara Haas, David W. TI Effect of concomitantly administered rifampin on the pharmacokinetics and safety of atazanavir administered twice daily SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MULTIPLE VIROLOGICAL FAILURES; CLINICAL-TRIAL; NAIVE SUBJECTS; LOPINAVIR/RITONAVIR; LAMIVUDINE; STAVUDINE; POLYMORPHISM; COMBINATION; SAQUINAVIR; RITONAVIR AB The potent induction of hepatic cytochrome P450 3A isoforms by rifampin complicates therapy for coinfection with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis. We performed an open-label, single-arm study to assess the safety and pharmacokinetic interactions of the HIV protease inhibitor atazanavir coadministered with rifampin. Ten healthy HIV-negative subjects completed pharmacokinetic sampling at steady state while receiving 300 mg atazanavir every 12 111 without rifampin (period 1), 300 mg atazanavir every 12 h with 600 mg rifampin every 24 111 (period 2), and 400 mg atazanavir every 12 111 with 600 mg rifampin every 24 h (period 3). During period 1, the mean concentration of drug in serum at 12 h (C-12 h) was 811 ng/ml (range, 363 to 2,484 ng/ml) for atazanavir, similar to historic seronegative data for once-daily treatment with 300 mg atazanavir boosted with 100 mg ritonavir. During periods 2 and 3, the mean C-12 h values for atazanavir were 44 ng/ml (range, <25 to 187 ng/ml) and 113 ng/ml (range, 39 to 260 ng/ml), respectively, well below historic seronegative data for once-daily treatment with 400 mg atazanavir without ritonavir. Although safe and generally well tolerated, 300 mg or 400 mg atazanavir administered every 12 h did not maintain adequate plasma exposure when coadministered with rifampin. C1 Univ Alabama, Birmingham, AL USA. Harvard Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. NIH, NIAID, DAIDS, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. Stanford Univ, Stanford, CA 94305 USA. Bristol Myers Squibb Co, Princeton, NJ USA. Social & Sci Syst Inc, Silver Spring, MD USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. RP Haas, DW (reprint author), Vanderbilt Univ, Sch Med, Div Infect Dis, 345 24th Ave N,Suite 105, Nashville, TN 37203 USA. EM david.w.haas@vanderbilt.edu RI Kendall, Michelle/B-7665-2016 OI Kendall, Michelle/0000-0001-9160-4544 FU NCRR NIH HHS [RR000034, M01 RR000034, RR00095, M01 RR000095]; NIAID NIH HHS [AI068636, U01 AI069439, UM1 AI069439, UM1 AI068636, U01 AI068636, U01 AI038858, U01 AI038855, AI68636, AI38858, AI38855, AI069474, U01 AI069474, U01 AI032775, UM1 AI069474, AI069439, AI32775] NR 18 TC 26 Z9 26 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2007 VL 51 IS 9 BP 3104 EP 3110 DI 10.1128/AAC.00341-07 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 206HV UT WOS:000249175400009 PM 17576825 ER PT J AU Meletiadis, J Antachopoulos, C Stergiopoulou, T Pournaras, S Roilides, E Walsh, TJ AF Meletiadis, Joseph Antachopoulos, Charalampos Stergiopoulou, Theodouli Pournaras, Spyros Roilides, Emmanuel Walsh, Thomas J. TI Differential fungicidal activities of amphotericin B and voriconazole against Aspergillus species determined by microbroth methodology SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE PULMONARY ASPERGILLOSIS; ESTABLISHED ANTIFUNGAL AGENTS; IN-VITRO ACTIVITY; GUINEA-PIG MODEL; FILAMENTOUS FUNGI; TESTING CONDITIONS; ITRACONAZOLE; EFFICACY; SUSCEPTIBILITIES; TERREUS AB Antifungal agents may differ in their fungicidal activities against Aspergillus spp. In order to compare the fungicidal activities of voriconazole and amphotericin B against 40 isolates of Aspergillus fumigatus, A. flavus, and A. terreus, we developed a new microbroth colorimetric method for assessing fungicidal activities and determining minimal fungicidal concentrations (MFCs). This methodology follows the antifungal susceptibility testing reference method M-38A for MIC determination. After drug removal and addition of fresh medium, growth of viable conidia adhering to the bottoms of the microtitration wells was assessed by a colorimetric assay of metabolic activity after 24 It of incubation. The new method was faster (six times), reproducible (92 to 97%), and in agreement with culture-based MFCs (91 to 100%). Differential fungicidal activities of voriconazole and amphotericin B were found among the three Aspergillus species, with A. fumigatus and A. flavus having the lowest (1 and 2 mg/liter, respectively) and A. terreus the highest (> 16 mg/liter) median amphotericin B MFCs; A. flavus had a lower median voriconazole MFC (4 mg/liter) than the other species (> 8 mg/liter; P < 0.05). Amphotericin B was fungicidal (MFC/MIC <= 4) against all A. fumigatus and A. flavus isolates but no A. terreus isolates, whereas voriconazole was fungicidal against 82% of A. flavus isolates and fungistatic (MFC/MIC > 4) against 94% of A. fumigatus and 84% of A. terreus isolates. The new methodology revealed a concentration-dependent sigmoid pattern of fungicidal effects, indicating that fungicidal activity is not an all-or-nothing phenomenon and that some degree of fungicidal action can be found even for agents considered fungistatic based on the MFC/MIC ratio. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. Univ Thessaloniki, Dept Clin Microbiol, Larisa, Greece. Aristotle Univ Thessaloniki, Dept Pediat 3, Thessaloniki, Greece. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, 10 Ctr Dr,Bldg 10-Rm 1-5750, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov FU Intramural NIH HHS NR 27 TC 29 Z9 29 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2007 VL 51 IS 9 BP 3329 EP 3337 DI 10.1128/AAC.00345-07 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 206HV UT WOS:000249175400042 PM 17576838 ER PT J AU Chapman, J Abbott, E Alber, DG Baxter, RC Bithell, SK Henderson, EA Carter, MC Chambers, P Chubb, A Cockerill, GS Collins, PL Dowdell, VCL Keegan, SJ Kelsey, RD Lockyer, MJ Luongo, C Najarro, P Pickles, RJ Simmonds, M Taylor, D Tyms, S Wilson, LJ Powell, KL AF Chapman, Joanna Abbott, Elizabeth Alber, Dagmar G. Baxter, Robert C. Bithell, Sian K. Henderson, Elisa A. Carter, Malcolm C. Chambers, Phil Chubb, Ann Cockerill, G. Stuart Collins, Peter L. Dowdell, Verity C. L. Keegan, Sally J. Kelsey, Richard D. Lockyer, Michael J. Luongo, Cindy Najarro, Pilar Pickles, Raymond J. Simmonds, Mark Taylor, Debbie Tyms, Stan Wilson, Lara J. Powell, Kenneth L. TI RSV604, a novel inhibitor of respiratory syncytial virus replication SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID NUCLEOPROTEIN-RNA COMPLEX; INFECTION; CHILDREN; PROTEIN; 1,4-BENZODIAZEPINES; HOSPITALIZATION; TRANSCRIPTION; ADULTS AB Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections worldwide, yet no effective vaccine or antiviral treatment is available. Here we report the discovery and initial development of RSV604, a novel benzodiazepine with submicromolar anti-RSV activity. It proved to be equipotent against all clinical isolates tested of both the A and B subtypes of the virus. The compound has a low rate of in vitro resistance development. Sequencing revealed that the resistant virus had mutations within the nucleocapsid protein. This is a novel mechanism of action for anti-RSV compounds. In a three-dimensional human airway epithelial cell model, RSV604 was able to pass from the basolateral side of the epithelium effectively to inhibit virus replication after mucosal inoculation. RSV604, which is currently in phase II clinical trials, represents the first in a new class of RSV inhibitors and may have significant potential for the effective treatment of RSV disease. C1 Arrow Therapeut Ltd, London SE1 1DB, England. Virogen Ltd, MRC Technol, London NW7 1AD, England. Natl Inst Allergy & Infect Dis, Lab Infect Dis, Bethesda, MD USA. Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27515 USA. RP Chapman, J (reprint author), Arrow Therapeut Ltd, Britanniai House,7 Trin St, London SE1 1DB, England. EM jchapman@arrowt.co.uk FU Intramural NIH HHS NR 26 TC 72 Z9 78 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2007 VL 51 IS 9 BP 3346 EP 3353 DI 10.1128/AAC.00211-07 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 206HV UT WOS:000249175400044 PM 17576833 ER PT J AU Lynn, EG Lu, ZP Minerbi, D Sack, MN AF Lynn, Edward G. Lu, Zhongping Minerbi, Diane Sack, Michael N. TI The regulation, control, and consequences of mitochondrial oxygen utilization and disposition in the heart and skeletal muscle during hypoxia SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID HIGH-ALTITUDE HYPOXIA; K-ATP CHANNEL; PROLIFERATOR-ACTIVATED RECEPTOR; GENE-EXPRESSION; RAT-HEART; PERMEABILITY TRANSITION; OXIDATIVE STRESS; CYTOCHROME-C; INDUCIBLE FACTOR-1-ALPHA; HYPOBARIC HYPOXIA AB The major oxygen-dependent function of mitochondria partitions molecular oxygen between oxidative phosphorylation and reactive oxygen species generation. When oxygen becomes limiting, the modulation of mitochondrial function plays an important role in overall biologic adaptation. This review focuses on mitochondrial biology in the heart and skeletal muscle during hypoxia. The disparate mitochondrial responses discussed appear to be dependent on the degree of hypoxia, on the age at exposure to hypoxia, and on the duration of exposure. These hypoxia-induced changes include modulation in mitochondrial respiratory capacity; activation of the mitochondrial biogenesis regulatory program; induction of mitochondrial antioxidant defense systems; regulation of antiapoptotic mitochondrial proteins, and modulation of mitochondrial sensitivity to permeability transition. The mitochondria-derived reactive oxygen species signal-transduction events in response to hypoxia also are reviewed. The cardiac and skeletal muscle phenotypic signatures that result from mitochondrial adaptations include an amelioration of resistance to cardiac ischemia and modulations in exercise capacity and oxidative fuel preference. Overall, the data demonstrate the plasticity in mitochondrial regulation and function that facilitates adaptations to a limited oxygen supply. Moreover, data supporting the role of mitochondria as oxygen-sensing organelles, integrated into global cellular signal transduction are discussed. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Sack, MN (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10 CRC,Rm 5-3150,10 Ctr Dr, Bethesda, MD 20892 USA. EM sackm@nhlbi.nih.gov OI Lynn, Edward/0000-0002-8011-5558 FU Intramural NIH HHS NR 99 TC 15 Z9 15 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD SEP PY 2007 VL 9 IS 9 BP 1353 EP 1361 DI 10.1089/ars.2007.1700 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 197JT UT WOS:000248552000006 PM 17627469 ER PT J AU Morgan, MJ Kim, YS Liu, ZG AF Morgan, Michael J. Kim, You-Sun Liu, Zhenggang TI Lipid rafts and oxidative stress-induced cell death SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; RECEPTOR-INTERACTING PROTEIN; SIGNAL-TRANSDUCTION PATHWAY; APO-1/FAS LIGAND EXPRESSION; TERMINAL KINASE ACTIVATION; ALPHA-INDUCED APOPTOSIS; FAS-MEDIATED APOPTOSIS; GROWTH-FACTOR-RECEPTOR; SRC TYROSINE KINASE AB Reactive oxygen species (ROS) are generated in response to a number of physiologic or pathologic conditions. In addition to ROS produced extrinsically, a cell may produce ROS as a result of normal metabolism and signaling processes. When sufficient quantities of ROS are present within the cell, this oxidative stress may have profound effects on the cell, including the induction of cell death. Various signaling pathways are initiated in response to oxidative stress, through which the cell's demise is assured. Many of these signaling pathways involve cholesterol-enriched domains of the cell membrane known as lipid rafts. These lipid rafts are platforms for initiation or transduction of the signal and may modulate protein activity through a direct change in local membrane structure or by allowing protein-protein interactions to occur with higher affinity/specificity or both. Among the examples discussed in this review are death-receptor signaling, induction of membrane-associated tyrosine kinase activation, and activation of transient receptor protein (TRP) channels. Special attention also is given to the RIP1/TRAF2 pathway, which involves the downstream activation of the stress-activated protein kinase JNK. The activation of the JNK pathway plays a key role in the induction of cellular death in response to ROS. C1 NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD USA. RP Liu, ZG (reprint author), 37 Convent Dr,RM1066A, Bethesda, MD 20892 USA. EM zgliu@helix.nih.gov FU Intramural NIH HHS NR 125 TC 30 Z9 36 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD SEP PY 2007 VL 9 IS 9 BP 1471 EP 1483 DI 10.1089/ars.2007.1658 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 197JT UT WOS:000248552000019 PM 17576159 ER PT J AU Negrete, A Esteban, G Kotin, RM AF Negrete, Alejandro Esteban, Geoffrey Kotin, Robert M. TI Process optimization of large-scale production of recombinant adeno-associated vectors using dielectric spectroscopy SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE adeno-associated vectors; gene therapy; dielectric spectroscopy; large-scale; bioprocessing; harvesting time ID INSECT-CELL CULTURES; VIRUS VECTORS; GENE-TRANSFER; BIOREACTOR CULTURES; SYSTEMIC DELIVERY; VIRAL VECTORS; AAV VECTORS; WILD-TYPE; FACTOR-IX; BACULOVIRUS AB A well-characterized manufacturing process for the large-scale production of recombinant adeno-associated vectors (rAAV) for gene therapy applications is required to meet current and future demands for pre-clinical and clinical studies and potential commercialization. Economic considerations argue in favor of suspension culture-based production. Currently, the only feasible method for large-scale rAAV production utilizes baculovirus expression vectors and insect cells in suspension cultures. To maximize yields and achieve reproducibility between batches, online monitoring of various metabolic and physical parameters is useful for characterizing early stages of baculovirus-infected insect cells. In this study, rAAVs were produced at 40-l scale yielding similar to 1 x 10(15) particles. During the process, dielectric spectroscopy was performed by real time scanning in radio frequencies between 300 kHz and 10 MHz. The corresponding permittivity values were correlated with the rAAV production. Both infected and uninfected reached a maximum value; however, only infected cell cultures permittivity profile reached a second maximum value. This effect was correlated with the optimal harvest time for rAAV production. Analysis of rAAV indicated the harvesting time around 48 h post-infection (hpi), and 72 hpi produced similar quantities of biologically active rAAV. Thus, if operated continuously, the 24-h reduction in the production process of rAAV gives sufficient time for additional 18 runs a year corresponding to an extra production of similar to 2 x 10(16) particles. As part of large-scale optimization studies, this new finding will facilitate the bioprocessing scale-up of rAAV and other bioproducts. C1 NHLBI, NIH, Lab Biochem Genet, Bethesda, MD 20892 USA. FOGALE Nanotech, F-30900 Nimes, France. RP Kotin, RM (reprint author), NHLBI, NIH, Lab Biochem Genet, Bldg 10, Bethesda, MD 20892 USA. EM kotinr@mail.nih.gov RI kotin, robert/B-8954-2008 NR 45 TC 19 Z9 22 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD SEP PY 2007 VL 76 IS 4 BP 761 EP 772 DI 10.1007/s00253-007-1030-9 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 205MH UT WOS:000249117500004 PM 17680241 ER PT J AU Zhukovsky, MA Markovic, I Bailey, AL AF Zhukovsky, Mikhail A. Markovic, Ingrid Bailey, Austin L. TI Influence of calcium on lipid mixing mediated by influenza hemagglutinin SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL MEMBRANE-FUSION; CONFORMATIONAL CHANGE; CRYSTAL-STRUCTURE; CYTOPLASMIC TAIL; TEMPERATURE; EXOCYTOSIS; LIPOSOMES; MECHANISM; PROTEINS AB We studied the influence of calcium on lipid mixing mediated by influenza hemagglutinin (HA). Lipid mixing between HA-expressing cells and liposomes containing disialoganglioside, influenza virus receptor, was studied at 37 C and neutral pH after a low-pH pulse at 4 C. With DSPC/cholesterol liposomes, calcium present after raising the temperature significantly promoted lipid mixing only when it was triggered by a short low-pH application. In case of DOPC/cholesterol liposomes, calcium promotion was observed regardless of the duration of the low-pH pulse. Calcium present during a short, but not long, low-pH application to HA-expressing cells with bound DSPC/cholesterol liposomes at 4 C inhibited subsequent lipid mixing. We hypothesize that calcium influences lipid mixing because it binds to a vestigial esterase domain of hemagglutinin or causes expulsion of the fusion peptide from an electronegative cavity. We suggest that calcium promotes the transition from early and reversible conformation(s) of low pH-activated HA towards an irreversible conformation that underlies both HA-mediated lipid mixing and HA inactivation. (c) 2007 Elsevier Inc. All rights reserved. C1 Sci Commuicat Cephalon Inc, Hoboken, NJ 07030 USA. Max Planck Inst Biophys Chem, Abt Spektroskopie & Photochem Kinetik Struckturdy, D-37077 Gottingen, Germany. NICHHD, Natl Inst Hlth, Lab Cellular & Mol Biol, Sect Membrane Biol, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Zhukovsky, MA (reprint author), Ctr Drug Evaluat & Res, US FDA, Bethesda, MD 20892 USA. EM mzhukov@gwdg.de FU Intramural NIH HHS [Z01 HD001501-16] NR 58 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 2007 VL 465 IS 1 BP 101 EP 108 DI 10.1016/j.abb.2007.05.005 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 206IF UT WOS:000249176400012 PM 17585869 ER PT J AU Moreno, C Laje, G Blanco, C Jiang, H Schmidt, AB Olfson, M AF Moreno, Carmen Laje, Gonzalo Blanco, Carlos Jiang, Huiping Schmidt, Andrew B. Olfson, Mark TI National trends in the outpatient diagnosis and treatment of bipolar disorder in youth SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CHILD-BEHAVIOR CHECKLIST; COMMUNITY MENTAL-HEALTH; I-DISORDER; MANIC SYMPTOMS; SPECTRUM DISORDERS; ADOLESCENT INPATIENTS; MEDICATION TREATMENT; PARENT REPORT; DOUBLE-BLIND; FOLLOW-UP AB Context: Although bipolar disorder may have its onset during childhood, little is known about national trends in the diagnosis and management of bipolar disorder in young people. Objectives: To present national trends in outpatient visits with a diagnosis of bipolar disorder and to compare the treatment provided to youth and adults during those visits. Design: We compare rates of growth between 19941995 and 2002-2003 in visits with a bipolar disorder diagnosis by individuals aged 0 to 19 years vs those aged 20 years or older. For the period of 1999 to 2003, we also compare demographic, clinical, and treatment characteristics of youth and adult bipolar disorder visits. Setting: Outpatient visits to physicians in office-based practice. Participants: Patient visits from the National Ambulatory Medical Care Survey (1999-2003) with a bipolar disorder diagnosis (n=962). Main Outcome Measures: Visits with a diagnosis of bipolar disorder by youth ( aged 0-19 years) and by adults (aged >= 20 years). Results: The estimated annual number of youth office-based visits with a diagnosis of bipolar disorder increased from 25 (1994-1995) to 1003 (2002-2003) visits per 100 000 population, and adult visits with a diagnosis of bipolar disorder increased from 905 to 1679 visits per 100 000 population during this period. In 1999 to 2003, most youth bipolar disorder visits were by males (66.5%), whereas most adult bipolar disorder visits were by females (67.6%); youth were more likely than adults to receive a comorbid diagnosis of attention-deficit/hyperactivity disorder (32.2% vs 3.0%, respectively; P <. 001); and most youth (90.6%) and adults (86.4%) received a psychotropic medication during bipolar disorder visits, with comparable rates of mood stabilizers, antipsychotics, and antidepressants prescribed for both age groups. Conclusions: There has been a recent rapid increase in the diagnosis of youth bipolar disorder in office-based medical settings. This increase highlights a need for clinical epidemiological reliability studies to determine the accuracy of clinical diagnoses of child and adolescent bipolar disorder in community practice. C1 Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. Hosp Gen Univ Gregorio Maranon, Serv Psiauiatria, Unidad Adolescentes, Madrid, Spain. Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA. NIMH, Genet Basis Mood & Anxiety Disorders Mood & Anxie, Bethesda, MD 20892 USA. RP Olfson, M (reprint author), Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@columbia.edu RI Blanco, Carlos/I-4906-2013; Laje, Gonzalo/L-2654-2014 OI Blanco, Carlos/0000-0001-6187-3057; Laje, Gonzalo/0000-0003-2763-3329 FU AHRQ HHS [U18 HS016097]; Intramural NIH HHS; NIDA NIH HHS [DA00482, DA015559, DA019606]; NIMHD NIH HHS [MD000206] NR 76 TC 332 Z9 336 U1 3 U2 23 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2007 VL 64 IS 9 BP 1032 EP 1039 DI 10.1001/archpsyc.64.9.1032 PG 8 WC Psychiatry SC Psychiatry GA 206AS UT WOS:000249156900005 PM 17768268 ER PT J AU Schlesinger, T Appukuttan, B Hwang, T Atchaneeyakasul, L Chan, CC Zhuang, Z Stout, T Wilson, DJ AF Schlesinger, Thomas Appukuttan, Binoy Hwang, Thomas Atchaneeyakasul, La-ongsri Chan, Chi-Chao Zhuang, Zhengping Stout, Timothy Wilson, David J. TI Internal en bloc resection and genetic analysis of retinal capillary Hemangioblastoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; HIPPEL-LINDAU-DISEASE; RECEPTOR INHIBITOR SU5416; CENTRAL-NERVOUS-SYSTEM; SOMATIC MUTATIONS; CEREBELLAR HEMANGIOBLASTOMA; PHOTODYNAMIC THERAPY; HEMANGIOMA; VERTEPORFIN; HYDROXYPROLINE AB Objective: To report the clinical outcomes and molecular genetics of nongermline retinal hemangioblastoma managed by surgical resection. Methods: Retrospective case series of 3 patients aged 16 to 46 years treated at a tertiary care referral center (Casey Eye Institute, Portland, Oregon). Tumors 7 to 9 mm in diameter were removed from 3 consecutive eyes ( in 3 patients) via internal en bloc surgical resection using a bimanual technique. Samples of DNA from 2 of 3 tumors were tested for von Hippel-Lindau gene (VHL) mutations as a clue to the molecular basis for spontaneously occurring hemangioblastoma. Main outcome measures were morbidity, visual acuity, resolution of macular exudates, and presence of VHL markers. Results: Visual acuity improved or remained stable in all patients. All 3 developed cataracts, extracted in 2 instances. Histopathological findings were typical of retinal hemangioblastoma in all cases. The cells from one patient's DNA sample showed loss of heterozygosity for the VHL gene, while no genetic abnormalities were detected in the other patient's DNA sample. Conclusions: Our patients' favorable outcomes suggest that surgical resection is an option for patients with large retinal hemangioblastomas. In addition, ours may be the first report of retinal hemangioblastoma unassociated with a VHL mutation. C1 Oregon Hlth & Sci Univ, Case Eye Inst, Portland, OR 97239 USA. NEI, Immunopathol Sect, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Wilson, DJ (reprint author), Oregon Hlth & Sci Univ, Case Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM wilsonda@ohsu.edu FU Intramural NIH HHS [Z01 EY000222-22] NR 29 TC 8 Z9 9 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 2007 VL 125 IS 9 BP 1189 EP 1193 DI 10.1001/archopht.125.9.1189 PG 5 WC Ophthalmology SC Ophthalmology GA 208TM UT WOS:000249342100005 PM 17846357 ER PT J AU Henson, DE Schwartz, AM Tilara, A Grimley, PM Anderson, WF AF Henson, Donald Earl Schwartz, Arnold M. Tilara, Amy Grimley, Philip M. Anderson, William F. TI Population-based analysis of pathologic data - A new approach to the investigation of uterine endometrial and ovarian endometrioid carcinomas SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol ID EXTRAOVARIAN ENDOMETRIOSIS; STROMAL SARCOMAS; AGE DISTRIBUTION; BREAST-CANCER; EPIDEMIOLOGY; SURVEILLANCE; TUMORS; WOMEN AB Context.-Population- based analysis of the histopathology of endometrioid adenocarcinoma of the endometrium and ovary combined with epidemiologic techniques offer a new approach to exploring the relationship of tumors that share a similar range of morphologic phenotypes. Objective. - To evaluate the contribution of the Surveillance, Epidemiology, and End Results database to our understanding of gynecologic pathology. Specifically, to test and compare whether the etiology/pathogenesis of ovarian endometrioid cancer is as dependent upon the reproductive environment as uterine endometrial carcinoma. Design. - Graphic plots of the epidemiologic patterns were analyzed relating to incidence and age-specific rates of ovarian and uterine endometrioid carcinomas. The graphic analysis included evaluation of age frequency density plots and logarithmic plots (log-log) of age-specific incidence rates. Results. - At all ages, uterine endometrioid carcinomas have higher incidence rates than their ovarian homologues. Up to the age of 50 years, the log-log plots of age-specific incidence rates for each of these tumors remain essentially parallel. In contrast, after age 50 ( menopause), the incidence rates begin to diverge: the rates for uterine endometrial carcinomas continue to rise, whereas the rates for ovarian endometrioid carcinomas plateau. This divergence persists even when the age-specific incidence is stratified according to histologic grade. Interestingly, endometrial stromal sarcomas follow an incidence rate pattern nearly identical to that of ovarian endometrioid carcinomas. Conclusions. - The continuum of cellular and molecular events predisposing to gynecologic cancers of endometrioid phenotype apparently cease to operate in the ovary after menopause, but additional cellular and molecular events appear to occur in the ageing uterine endometrium. C1 George Washington Univ, Inst Canc, Off Canc Prevent & Control, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20052 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Henson, DE (reprint author), George Washington Univ, Inst Canc, Off Canc Prevent & Control, Ross Hall,Room 502,2300 Eye St NW, Washington, DC 20037 USA. EM patdeh@gwumc.edu NR 34 TC 4 Z9 4 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 2007 VL 131 IS 9 BP 1337 EP 1342 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 209NE UT WOS:000249394400005 PM 17824787 ER PT J AU Chen, Z Tato, CM Muul, L Laurence, A O'Shea, JJ AF Chen, Zhi Tato, Cristina M. Muul, Linda Laurence, Arian O'Shea, John J. TI Distinct regulation of interleukin-17 in human T helper lymphocytes SO ARTHRITIS AND RHEUMATISM LA English DT Article ID AUTOIMMUNE INFLAMMATION; MULTIPLE-SCLEROSIS; CYTOKINE MILIEU; CELLS; IL-23; EXPRESSION; IL-17; DIFFERENTIATION; ARTHRITIS; LINEAGE AB Objective. Interleukin-17 (IL-17)-producing T helper cells have been proposed to represent a separate lineage of CD4+ cells, designated Th17 cells, which are regulated by the transcription factor retinoic acid-related orphan receptor -gamma t (ROR gamma t). However, despite advances in understanding murine Th17 differentiation, a systematic assessment of factors that promote the differentiation of naive human T cells to Th17 cells has not been reported. The present study was undertaken to assess the effects on naive human CD4+ T cells of cytokines known to promote murine Th17 cells. Methods. Human naive and memory CD4+ T cells isolated from peripheral blood were activated and cultured with various cytokines. Cytokine production was measured by enzyme-linked immunosorbent assay and flow cytometry. Messenger RNA was measured by quantitative polymerase chain reaction. Results. In response to anti-CD3/anti-CD28 stimulation alone, human memory T cells rapidly produced IL-17, whereas naive T cells expressed low levels. Transforming growth factor beta 1 and IL-6 up-regulated ROR gamma t expression but did not induce Th17 differentiation of naive CD4+ T cells. However, IL-23 up-regulated its own receptor and was an important inducer of IL-17 and IL-22. Conclusion. The present data demonstrate the differential regulation of IL-17 and ROR gamma t expression in human CD4+ T cells compared with murine cells. Optimal conditions for the development of IL-17-producing T cells from murine naive precursors are ineffective in human T cells. Conversely, IL-23 promoted the generation of human Th17 cells but was also a very potent inducer of other proinflammatory cytokines. These findings may have important implications in the pathogenesis of human autoimmunity as compared with mouse models. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Chen, Z (reprint author), NIAMSD, NIH, Bldg 10,Room 9N262,10 Ctr Dr,MSC-1820, Bethesda, MD 20892 USA. EM chenzhi@mail.nih.gov RI Laurence, Arian/A-8770-2009 OI Laurence, Arian/0000-0003-0942-8292 FU Intramural NIH HHS [Z01 AR041106-13] NR 50 TC 239 Z9 262 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2007 VL 56 IS 9 BP 2936 EP 2946 DI 10.1002/art.22866 PG 11 WC Rheumatology SC Rheumatology GA 215TT UT WOS:000249832600015 PM 17763419 ER PT J AU Koh, KK Quon, MJ Han, SH Ahn, JY Lee, Y Shin, EK AF Koh, Kwang Kon Quon, Michael J. Han, Seung Hwan Ahn, Jeong Yeal Lee, Yonghee Shin, Eak Kyun TI Combined therapy with ramipril and simvastatin has beneficial additive effects on tissue factor activity and prothrombin fragment 1+2 in patients with type 2 diabetes SO ATHEROSCLEROSIS LA English DT Article; Proceedings Paper CT Congress of the European-Society-of-Cardiology CY SEP, 2006 CL Barcelona, SPAIN SP European Soc Cardiol DE ACE inhibitor; statins; hemostasis; inflammation ID SMOOTH-MUSCLE-CELLS; FACTOR PATHWAY INHIBITOR; ACUTE CORONARY SYNDROMES; CONVERTING ENZYME-INHIBITION; HORMONE REPLACEMENT THERAPY; LOW-DENSITY-LIPOPROTEIN; FACTOR VA INACTIVATION; C-REACTIVE PROTEIN; FACTOR EXPRESSION; HYPERCHOLESTEROLEMIC PATIENTS AB Tissue factor (TF) plays a pivotal role in thrombus formation. Statins and angiotensin converting enzyme inhibitors attenuate expression of TF by distinct mechanism. Therefore, we hypothesized that combined therapy with sitnvastatin and ramipril may have additive beneficial anti-atherogenic effects to lower TF activity when compared with either drug alone. This was a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Fifty patients with type 2 diabetes were given sirrvastatin 20 mg and placebo, simvastatin 20 mg and ramipril 10 mg, or ramipril 10 mg and placebo daily during each treatment period. Simvastatin and ramipril monotherapy tended to reduce TF activity (0.53 to 0.46 nM, P = 0.056; 0.54 to 0.50 nM, P = 0. 167, respectively) while combined therapy had a significant effect (0.64 to 0.43 nM, P < 0.00 1). All three therapies significantly reduced prothrombin fragment 1 + 2 (F1 + 2) levels from their respective baselines (P = 0.037, P < 0.00 1, and P = 0.057, respectively). Combined therapy significantly reduced TF activity and F I + 2 levels to a greater extent than either simvastatin or ramipril alone (P = 0.029 and P = 0.040 by ANOVA, respectively). Percent changes in TF activity and percent changes in F1 + 2 levels were significantly correlated. All three therapies reduced CD40 ligand levels from their respective baselines (P = 0.098, P < 0.001, and P = 0.002, respectively) with no significant differences among these three therapies (P = 0.204 by ANOVA). Ramipril combined with simvastatin significantly reduces plasma TF activity and F1 + 2 levels to a greater extent than monotherapy with either drug in patients with type 2 diabetes. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Gachon Med Sch, Gil Heart Ctr, Vasc Med & Atherosclerosis Unit, Inchon 405760, South Korea. NIH, Diabet Unit, Clin Invest Lab, NCCAM, Bethesda, MD 20892 USA. Ewha Womans Univ, Dept Stat, Seoul, South Korea. RP Koh, KK (reprint author), Gachon Med Sch, Gil Heart Ctr, Vasc Med & Atherosclerosis Unit, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@gilhospital.com RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 56 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD SEP PY 2007 VL 194 IS 1 BP 230 EP 237 DI 10.1016/j.atherosclerosis.2006.07.031 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 228OD UT WOS:000250738300024 PM 16965776 ER PT J AU Koya, E Simmons, DE Bossert, JM Uejima, JL Berkow, A Mitchell, L Farquhar, D Mattson, BJ Hope, BT AF Koya, E. Simmons, D. E. Bossert, J. M. Uejima, J. L. Berkow, A. Mitchell, L. Farquhar, D. Mattson, B. J. Hope, B. T. TI Reversal of cocaine locomotor sensitization by Daun02-mediated lesions of activated neuronal ensembles in rat nucleus accumbens SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT 12th Biennial Meeting of the European-Pharmacology-Society CY AUG 31-SEP 03, 2007 CL Tubingen, GERMANY SP European Pharmacol Soc C1 [Koya, E.; Simmons, D. E.; Bossert, J. M.; Uejima, J. L.; Berkow, A.; Mitchell, L.; Mattson, B. J.; Hope, B. T.] NIH, DHHS, IRP, NIDA,Behav Neuroaxi Branch, Baltimore, MD 21224 USA. [Farquhar, D.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2007 VL 18 SU 1 BP S65 EP S65 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 221CA UT WOS:000250203800160 ER PT J AU Molander, A Karlsson, RM Schuler, A Heilig, M Spanagel, R AF Molander, A. Karlsson, R-M. Schuler, A. Heilig, M. Spanagel, R. TI Alcohol consumption in GLAST knockout mice SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT 12th Biennial Meeting of the European-Pharmacology-Society CY AUG 31-SEP 03, 2007 CL Tubingen, GERMANY SP European Pharmacol Soc C1 [Molander, A.; Schuler, A.; Spanagel, R.] Cent Inst Mental Hlth, Dept Psychopharmacol, D-6800 Mannheim, Germany. [Karlsson, R-M.; Heilig, M.] NIAAA, Bethesda, MD USA. EM anna.molander@zi-mannheim.de NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2007 VL 18 SU 1 BP S86 EP S86 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 221CA UT WOS:000250203800214 ER PT J AU Pugliese, AM Coppi, E Volpini, R Cristalli, G Corradetti, R Jeong, LS Jacobson, KA Pedata, F AF Pugliese, Anna Maria Coppi, Elisabetta Volpini, Rosaria Cristalli, Gloria Corradetti, Renato Jeong, Lak Shin Jacobson, Kenneth A. Pedata, Felicita TI Role of adenosine A(3) receptors on CA1 hippocampal neurotransmission during oxygen-glucose deprivation episodes of different duration SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Purines; G protein-coupled receptors; cerebral ischemia; hippocampal slices; field EPSP; desensitization ID AGONIST-DEPENDENT PHOSPHORYLATION; ISCHEMIA-LIKE CONDITIONS; IN-VITRO ISCHEMIA; PROTEIN-KINASE-C; RAT HIPPOCAMPUS; SELECTIVE LIGANDS; EXTRACELLULAR ADENOSINE; SYNAPTIC-TRANSMISSION; SPREADING DEPRESSION; ACTIVATION AB The role of adenosine A(3) receptors in synaptic transmission under severe (7 min) and shorter (2-5 min) ischemic conditions, obtained by oxygen and glucose deprivation (OGD), was investigated in rat hippocampal slices. The effects of selective A(3) agonists or antagonists were examined on field excitatory postsynaptic potentials (fEPSPs) extracellularly recorded at the dendritic level of the CA1 pyramidal region. The novel, selective A(3) antagonist LJ1251 ((2R,3R,4S)-2-(2-chloro-6-(3-iodobenzylamino)-9H-purin-9-yl)tetrahydrothiophene-3,4-diol, 0.1-10 nM) protected hippocampal slices from irreversible fEPSP depression induced by severe OGD and prevented or delayed the appearance of anoxic depolarization. Similar results were obtained when severe OGD was carried out with a long, receptor- desensitizing exposure to various selective A(3) agonists: 5'-N-methylcarboxamidoadenosine derivatives Cl-IB-MECA (N-6-(3-iodobenzyl)-2-chloro), VT72 (N-6-methoxy-2phenylethynyl), VT158 (N-6-methoxy-2-phenylethynyl), VT160 (N-6-methoxy-2-(2-pyridinyl)-ethynyl), and VT163 (N-6-methoxy-2-p-acetylphenylethynyl) and AR132 (N-6-methyl-2-phenylethynyladenosine). The selective A(3) antagonist MRS1523 (3 -propyl-6- ethyl- 5 - [(ethylthio) carbonyl] -2 -phenyl-4-propyl-3-pyridine carboxylate, 100 nM) reduced fEPSP depression evoked by 2-min OGD and induced a faster recovery of fEPSP amplitude after 5-min OGD. Similar results were obtained for 2- or 5-min OGD applied in the presence of each of the A(3) agonists tested. Shorter exposure to A(3) agonists significantly delayed the recovery of fEPSP amplitude after 5min OGD. This indicates that A(3) receptors, stimulated by selective A(3) agonists, undergo desensitization during OGD. It is inferred that CA1 hippocampal A(3) receptors stimulated by adenosine released during brief ischemia (2 and 5 min) might exert A(1)-like protective effects on neuro-transmission. Severe ischemia would transform the A(3) receptor-mediated effects from protective to injurious. C1 NIDDK, Bioorgan Chem Lab, Mol Recognit Sect, Bethesda, MD 20892 USA. Univ Florence, Dept Preclin & Clin Pharmacol, I-50139 Florence, Italy. Univ Camerino, Dept Chem Sci, I-62032 Camerino, Italy. Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. Natl Inst Hlth, Natl Inst Diabet & Digest & Kidney Dis, Bioorgan Chem Lab, Mol Recognit Sect, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDK, Bioorgan Chem Lab, Mol Recognit Sect, Bldg 8A,Rm B1A 19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov; felicita.pedata@unifi.it RI Corradetti, Renato/A-1604-2008; Jacobson, Kenneth/A-1530-2009 OI Corradetti, Renato/0000-0002-2588-0484; Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 50 TC 37 Z9 39 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 1 PY 2007 VL 74 IS 5 BP 768 EP 779 DI 10.1016/j.bcp.2007.06.003 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 204ID UT WOS:000249036300012 PM 17626785 ER PT J AU Tuukkanen, A Kaila, VRI Laakkonen, L Hummer, G Wikstrom, M AF Tuukkanen, Anne Kaila, Ville R. I. Laakkonen, L'isa Hummer, Gerhard Wikstrom, Marten TI Dynamics of the glutamic acid 242 side chain in cytochrome c oxidase SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article DE molecular dynamics; nonpolar cavity; proton transfer; proton pump; water ID HEME-COPPER OXIDASES; MOLECULAR-DYNAMICS; PROTON TRANSLOCATION; PARACOCCUS-DENITRIFICANS; RHODOBACTER-SPHAEROIDES; WILD-TYPE; WATER; RESOLUTION; OXYGEN; BACTERIORHODOPSIN AB In many cytochrome c oxidases glutamic acid 242 is required for proton transfer to the binuclear heme a(3)/CUB site, and for proton pumping. When present, the side chain of Glu-242 is orientated "down" towards the proton-transferring D-pathway in all available crystal structures. A nonpolar cavity "above" Glu-242 is empty in these structures. Yet, proton transfer from Glu-242 to the binuclear site, and for proton-pumping, is well established, and the cavity has been proposed to at least transiently contain water molecules that would mediate proton transfer. Such proton transfer has been proposed to require isomerisation of the Glu-242 side chain into an "up" position pointing towards the cavity. Here, we have explored the molecular dynamics of the protonated Glu-242 side chain. We find that the "up" position is preferred energetically when the cavity contains four water molecules, but the "down" position is favoured with less water. We conclude that the cavity might be deficient in water in the crystal structures, possibly reflecting the "resting" state of the enzyme, and that the "up/down" equilibrium of Glu-242 may be coupled to the presence of active-site water molecules produced by O-2 reduction. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Helsinki, Inst Biotechnol, Helsinki Bioenerget Grp, Struct Biol & Biophys Programme, FIN-00014 Helsinki, Finland. NIDDK, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. RP Wikstrom, M (reprint author), Univ Helsinki, Inst Biotechnol, Helsinki Bioenerget Grp, Struct Biol & Biophys Programme, PB 65 Viikinkaari 1, FIN-00014 Helsinki, Finland. EM marten.wikstrom@helsinki.fi RI Wikstrom, Marten/A-4403-2008; Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU Intramural NIH HHS NR 29 TC 26 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 EI 0006-3002 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD SEP PY 2007 VL 1767 IS 9 BP 1102 EP 1106 DI 10.1016/j.bbabio.2007.06.010 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 213MJ UT WOS:000249671400002 PM 17706938 ER PT J AU Lee, JY Gavrilova, O Davani, B Na, R Robinson, GW Hennighausen, L AF Lee, Ji-Yeon Gavrilova, Oksana Davani, Behrous Na, Risu Robinson, Gertraud W. Hennighausen, Lothar TI The transcription factors Stat5a/b are not required for islet development but modulate pancreatic beta-cell physiology upon aging SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Stat5; RIP-Cre; Pdx1-Cre; islets of langerhans; beta-cells; glucose homeostasis ID PROLACTIN-INDUCED PROLIFERATION; GROWTH-HORMONE; SIGNAL TRANSDUCER; VEGF-A; RAT; ACTIVATION; GENE; RECEPTOR; MOUSE; LANGERHANS AB In insulinoma cell lines proliferation and insulin gene transcription are stimulated by growth hormone and prolactin, which convey their signals through the transcription factors Stat5a and 5b (referred to as Stat5). However, the contribution of Stat5 to the physiology of p-cells in vivo could not be assessed directly since Stat5-null mice die perinataly. To explore the physiological role of Stat5 in the mouse, the corresponding gene locus targeted with loxP sites was inactivated in beta-cells using two lines of Cre recombinase expressing transgenic mice. While the RIP-Cre transgene is active in pancreatic beta-cells and the hypothalamus, the Pdx1-Cre transgene is active in precursor cells of the endocrine and exocrine pancreas. Mice carrying two floxed Stat5alleles and a RIP-Cre transgene developed mild obesity, were hyperglycemic and exhibited impaired glucose tolerance. Since RIP-Cre transgenic mice by themselves display some glucose intolerance, the significance of these data is unclear. In contrast, mice, in which the Stat5 locus had been deleted with the Pdx1-Cre transgene, developed functional islets and were glucose tolerant. Mild glucose intolerance occurred with age. We conclude that Stat5 is not essential for islet development but may modulate beta-cell function. (C) 2007 Elsevier B.V. All rights reserved. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. NIDDKD, Mouse Metab Core Facil, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, 8 Ctr Dr,Room 101, Bethesda, MD 20892 USA. EM hennighausen@nih.gov RI Robinson, Gertraud/I-2136-2012 FU Intramural NIH HHS [Z01 DK061000-10] NR 25 TC 19 Z9 19 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD SEP PY 2007 VL 1773 IS 9 BP 1455 EP 1461 DI 10.1016/j.bbamcr.2007.05.010 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 220PN UT WOS:000250168800008 PM 17599554 ER PT J AU Xu, H Regino, CAS Koyama, Y Hama, Y Gunn, AJ Bernardo, M Kobayashi, H Choyke, PL Brechbiel, MW AF Xu, Heng Regino, Celeste A. S. Koyama, Yoshinori Hama, Yukihiro Gunn, Andrew J. Bernardo, Marcelino Kobayashi, Hisataka Choyke, Peter L. Brechbiel, Martin W. TI Preparation and preliminary evaluation of a biotin-targeted, lectin-targeted dendrimer-based probe for dual-modality magnetic resonance and fluorescence Imaging SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MRI CONTRAST AGENTS; OVARIAN-CANCER; AVIDIN; CHEMISTRY; SURVIVAL; SHAPE; SIZE AB A novel approach for the preparation of a biotinylated dendrimer-based MRI agent 5 is described, in which a unique disulfide bond in the core of the Gd(III)-1B4M-DTPA chelated G2 PAMAM dendrimer was reduced and then attached to a maleimide-functionalized biotin. The new MRI agent 5 features a well-defined dendron structure and a unique biotin functionality. Immobilization of up to four copies of biotinylated dendrimer 5 to fluorescently labeled avidin yields a supramolecular avidin-biotin-dendrimer-Gd(III) complex. Validation of the complex in mice bearing ovarian cancer tumors demonstrates that the avidin-biotin-dendrimer targeting system efficiently targets and delivers sufficient amounts of chelated Gd(III) and fluorophores (e.g., Rhodamine green) to ovarian tumors to produce visible changes in the tumors by both MRI and optical imaging, respectively. Thus, the avidin-biotin-dendrimer complex may be used as a tumor-targeted probe for dual-modality magnetic resonance and fluorescence imaging. C1 NIH, NCI, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Inc, Res Technol Program, Frederick, MD 21702 USA. RP Brechbiel, MW (reprint author), NIH, NCI, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bldg 10,Room 1B40,10Ctr Dr, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov FU Intramural NIH HHS NR 24 TC 85 Z9 88 U1 2 U2 33 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP-OCT PY 2007 VL 18 IS 5 BP 1474 EP 1482 DI 10.1021/bc0701085 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 213GY UT WOS:000249656100016 PM 17711320 ER PT J AU Zhao, MR Li, D Shimazu, K Zhou, YX Lu, B Deng, CX AF Zhao, Mingrui Li, Dan Shimazu, Kazuhiro Zhou, Yong-Xing Lu, Bai Deng, Chu-Xia TI Fibroblast growth factor receptor-1 is required for long-term potentiation, memory consolidation, and neurogenesis SO BIOLOGICAL PSYCHIATRY LA English DT Article DE dentate gyrus; FGFR1; gene knockout; memory consolidation; neurogenesis; proliferation; synaptic plasticity ID IN-VIVO NEUROGENESIS; RAT DENTATE GYRUS; ADULT NEUROGENESIS; SYNAPTIC PLASTICITY; HIPPOCAMPAL-NEURONS; CEREBRAL-CORTEX; ENRICHED ENVIRONMENT; CELL-PROLIFERATION; PROGENITOR CELLS; STEM-CELLS AB Background: Although substantial evidence supports the view that adult neurogenesis is involved in learning and memory, how newly generated neurons contribute to the cognitive process remains unknown. Fibroblast growth factor 2 (FGF-2) is known to stimulate the proliferation of neuronal progenitor cells (NPCs) in adult brain. Using conditional knockout micethat lack brain expression of FGFR1, a major receptor for FGF-2, we have investigated the role of adult neurogenesis in hippocampal synaptic plasticity and learning and memory. Methods: The Fgfr1 conditional knockout mice were generated by crossing the Fgfr1-null line, the Fgfr1-flox line, and the Nestin-Cre transgenic mice. Bromodeoxyuricline (BrdU) labeling, slice electrophysiology, and Morris Water Maze experiments were performed with the Fgfrl conditional mutant mice. Results: Bromodeoxyuridine labeling experiments demonstrate that FGFR1 is required for the proliferation of NPCs as well as generation of new neurons in the adult clentate gyrus (DG). Moreover, deficits in neurogenesis in Fgfrl mutant mice are accompanied by a severe impairment of long-term potentiation (LTP) at the medial perforant path (MPP)-granule neuron synapses in the hippocampal clentate. Moreover, the Fgfr1 mutant mice exhibit significant deficits in memory consolidation but not spatial learning. Conclusions: Our study suggests a critical role of FGFR1 in adult neurogenesis in vivo, provides a potential link between proliferative neurogenesis and clentate LTP, and raises the possibility that adult neurogenesis might contribute to memory consolidation. C1 NICHD, Sect Neural Dev & Plast, Lab Cellular & Synapt Neurophysiol, Bethesda, MD 20892 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Lu, B (reprint author), NICHD, Sect Neural Dev & Plast, Lab Cellular & Synapt Neurophysiol, Bldg 35,Room ICI004,35 Lincoln Dr, Bethesda, MD 20892 USA. EM bailu@mail.NIH.gov RI Lu, Bai/A-4018-2012; deng, chuxia/N-6713-2016 FU Intramural NIH HHS NR 59 TC 84 Z9 90 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2007 VL 62 IS 5 BP 381 EP 390 DI 10.1016/j.biopsych.2006.10.019 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 204KP UT WOS:000249042800003 PM 17239352 ER PT J AU Savitz, J van der Merwe, L Stein, DJ Solms, M Ramesar, R AF Savitz, Jonathan van der Merwe, Lize Stein, Dan J. Solms, Mark Ramesar, Rajkumar TI Genotype and childhood sexual trauma moderate neurocognitive performance: A possible role for brain-derived neurotrophic factor and apolipoprotein E variants SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ApoE; BDNF; cognitive; endophenotype; gene-environment interaction; memory; sexual abuse; trauma ID POSTTRAUMATIC-STRESS-DISORDER; BIPOLAR AFFECTIVE-DISORDER; SMALLER HIPPOCAMPAL VOLUME; BECK DEPRESSION INVENTORY; SHORT-TERM-MEMORY; VAL(66)MET POLYMORPHISM; MALTREATED CHILDREN; ALZHEIMERS-DISEASE; SUICIDAL-BEHAVIOR; APOE GENOTYPE AB Background: Limited success in the identification of genetic variants underpinning psychiatric illness has prompted attempts to elucidate gene-environment interactions and illness-associated endophenotypes. Here we measured childhood sexual abuse, a potential environmental risk factor, and verbal and visual recall and recognition memory, a possible illness-associated endophenotype in a cohort of bipolar disorder (BPD) subjects and their relatives. We predicted that memory would be affected by sexual trauma and that a number of functional polymorphisms previously implicated in BPD and cognition would moderate the effect of psychological trauma on memory. Methods: A cohort of 350 individuals from 47 BPD families was recruited, tested with a neuropsychological battery, and given the Childhood Trauma Questionnaire (CTQ). Eleven different genetic variants previously found to be relevant to BPD or memory dysfunction were typed. Results: As predicted, scores on the sexual abuse scale of the CTQ were negatively associated with memory performance. Furthermore, the low-activity Met allele of the brain-derived neurotrophic factor (BDNF) gene and the epsilon 4 allele of the apolipoprotein E gene interacted with sexual abuse scores to result in reduced memory test performance. Conclusions: Apolipoprotein E and BDNF exert a neurotrophic effect in response to cellular injury. Their possible moderation of the association between sexual abuse and memory performance might indicate that there is some degree of overlap in the pathophysiological mechanisms by which psychological and physical trauma impact brain function. The finding of an environmental effect on memory performance and a gene-environment interaction on this hypothetical endophenotype of BPD illustrates the difficulty of identifying genetically and phenotypically simple intermediate traits for molecular genetic studies. C1 MRC, UCT Human Genet Res Unit, Inst Infect Dis & Mol Med, London W1N 4AL, England. Univ Cape Town, Dept Psychol, ZA-7700 Rondebosch, South Africa. Univ Cape Town, Dept Neurol, ZA-7700 Rondebosch, South Africa. MRC S Africa, Biostat Unit, Cape Town, South Africa. RP Savitz, J (reprint author), NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, 15 K N Dr,Room 200, Bethesda, MD 20892 USA. EM savitzj@mail.nih.gov RI Savitz, Jonathan/C-3088-2009; Ramesar, Raj/I-6941-2015; Stein, Dan/A-1752-2008 OI Savitz, Jonathan/0000-0001-8143-182X; Ramesar, Raj/0000-0001-5688-1634; Stein, Dan/0000-0001-7218-7810 NR 78 TC 39 Z9 39 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2007 VL 62 IS 5 BP 391 EP 399 DI 10.1016/j.biopsych.2006.10.017 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 204KP UT WOS:000249042800004 PM 17210134 ER PT J AU Grillon, C Cornwell, B AF Grillon, Christian Cornwell, Brian TI Comments on fearful and sexual pictures not consciously seen modulate the startle reflex in human beings SO BIOLOGICAL PSYCHIATRY LA English DT Letter C1 NIMH, Bethesda, MD 20892 USA. RP Grillon, C (reprint author), NIMH, 15K N Dr,Room 113,MSC 2670, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 MH002798-06] NR 2 TC 3 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2007 VL 62 IS 5 BP 541 EP 541 DI 10.1016/j.biopsych.2006.12.026 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 204KP UT WOS:000249042800023 PM 17531204 ER PT J AU Mol, N Baas, JMP Grillon, C van Ooijen, L Kenemans, JL AF Mol, Nisan Baas, Johanna M. P. Grillon, Christian van Ooijen, Linda Kenemans, J. Leon TI Startle potentiation in rapidly alternating conditions of high and low predictability of threat SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE startle; anxiety; fear ID ACOUSTIC STARTLE; BLINK STARTLE; ATTENTIONAL MODULATION; STIMULUS MODALITY; BED NUCLEUS; BASE-LINE; FEAR; ANXIETY; AMYGDALA; HUMANS AB Effects of predictability of threat on potentiation of the startle reflex were investigated by presenting participants with predictable and unpredictable electric shocks. Shocks were presented either paired with a visual cue (paired condition) or unrelated to the presentation of the visual cues (unpaired condition). In contrast to previous slower-paced studies, conditions alternated at a rapid rate: each context lasted 8.5 s and within these contexts the visual cues had a duration of 1.5 s. Results replicated previous findings: in the predictable condition, startle responses were augmented by a threat-signaling stimulus, and startle responses in the unpredictable condition were larger than in a neutral condition in which no shocks were presented. In all three conditions, visual stimuli that did not carry information about when a shock could be presented augmented startle reactivity. A control experiment showed that the effects of threat on the startle response could not be ascribed to attention and that the effects of the lead stimuli that did not signal threat are likely to be unrelated to the effects of threat. These results show that the fear system is modulated dynamically as a function of rapidly changing information about threat and emphasize the role of predictability of an aversive stimulus in the distinction between cue-specific and contextual fear. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Utrecht, Dept Psychon, NL-3584 CS Utrecht, Netherlands. Natl Inst Mental Hlth Mood & Anxiety Disorder Pro, Bethesda, MD 20892 USA. RP Mol, N (reprint author), Univ Utrecht, Dept Psychon, Heidelberglaan 2, NL-3584 CS Utrecht, Netherlands. EM N.Mol1@uu.nl OI Baas, Johanna/0000-0001-6267-8712 NR 32 TC 15 Z9 15 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD SEP PY 2007 VL 76 IS 1-2 BP 43 EP 51 DI 10.1016/j.biopsycho.2007.05.005 PG 9 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 213MI UT WOS:000249671300005 PM 17644240 ER PT J AU Lissek, S Orme, K Mcdowell, DJ Johnson, LL Luckenbaugh, DA Baas, JM Cornwell, BR Grillon, C AF Lissek, Shmuel Orme, Kaebah Mcdowell, Dana J. Johnson, Linda L. Luckenbaugh, David A. Baas, Johanna M. Cornwell, Brian R. Grillon, Christian TI Emotion regulation and potentiated startle across affective picture and threat-of-shock paradigms SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE emotion regulation; startle; psychophysiology; anxiety; fear ID POSTTRAUMATIC-STRESS-DISORDER; ACOUSTIC STARTLE; COVARIATION BIAS; FEAR; REFLEX; HUMANS; MODULATION; ANXIETY; ALPRAZOLAM; INTENSITY AB Past studies beginning with Jackson et al. [Jackson, D.C., Malmstadt, J.R., Larson, C.L., Davidson, R.J., 2000. Suppression and enhancement of emotional responses to unpleasant pictures. Psychophysiology 37 (4), 515-522.] document increases and decreases in emotionally-potentiated startle by way of instructing participants to enhance or suppress their emotional responses to symbolic sources of threat (unpleasant pictures). The present study extends this line of work to a threat-of-shock paradigm to assess whether startle potentiation elicited by threat of actual danger or pain is subject to emotion regulation. Results point to successful volitional modulation for both Affective-Picture and Threat-of-Shock experiments with startle magnitudes from largest to smallest occurring in the enhance, maintain, and suppress conditions. Successful regulation of startle potentiation to the threat of shock found by the current study supports the external validity of the Jackson paradigm for assessment of regulation processes akin to those occurring in the day-to-day context in response to real elicitors of emotion. Published by Elsevier B.V. C1 NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, Bethesda, MD 20892 USA. Univ Utrecht, Dept Psychon, NL-3508 TB Utrecht, Netherlands. RP Lissek, S (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, 15K North Dr,Bldg 15K,MSC 2670, Bethesda, MD 20892 USA. EM lisseks@intra.nimh.nih.gov RI Lissek, Shmuel/B-6577-2008; OI Baas, Johanna/0000-0001-6267-8712 FU Intramural NIH HHS [Z01 MH002798-06] NR 38 TC 26 Z9 26 U1 4 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD SEP PY 2007 VL 76 IS 1-2 BP 124 EP 133 DI 10.1016/j.biopsycho.2007.07.002 PG 10 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 213MI UT WOS:000249671300014 PM 17692453 ER PT J AU Hardy, NM Hakim, F Steinberg, SM Krumlauf, M Cvitkovic, R Babb, R Odom, F Fowler, DH Gress, RE Bishop, MR AF Hardy, Nancy M. Hakim, Frances Steinberg, Seth M. Krumlauf, Michael Cvitkovic, Romana Babb, Rebecca Odom, Feanne Fowler, Daniel H. Gress, Ronald E. Bishop, Michael R. TI Host T cells affect donor T cell engraftment and graft-versus-host disease after reduced-intensity hematopoietic stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE reduced-intensity stem cell transplantation; graft-versus-host disease; T cells ID BONE-MARROW-TRANSPLANTATION; HEMATOLOGIC MALIGNANCIES; LYMPHOCYTE DEPLETION; LEUKOCYTE INFUSIONS; SIBLING DONORS; ADD-BACK; CHIMERISM; LEUKEMIA; RECONSTITUTION; CHEMOTHERAPY AB Mixed chimerism in the T cell compartment (MC,) after reduced-intensity stem cell transplantation (RIST) may influence immune repopulation with alloreactive donor T cells. We examined effects of host T cell numbers on donor T cell engraftment and recovery and on acute graft-versus-host disease (aGVHD) in a relatively homogeneous patient population with respect to residual host T cells through quantified immune depletion prior to RIST and to donor T cells by setting the allograft T cell dose of 1 x 10(5) CD3(+) cells/kg. In this setting, 2 patterns of early donor T cell engraftment could be distinguished by day +42: (1) early and complete donor chimerism in the T cell compartment (FDCT) and (2) persistent MCT. FDCT was associated with lower residual host CD8(+) T cell counts prior to transplant and aGVHD. With persistent MCTI subsequent development of aGVHD could be predicted by the direction of change in T cell donor chimerism after donor lymphocyte infusion, and no aGVHD occurred until FDCT was established. MCT did not affect recovery of donor T cell counts. These observations suggest that the relative number and alloreactivity of donor and host T cells are more important than the absolute allograft T cell dose in determining donor engraftment and aGVHD after RIST. (c) 2007 American Society for Blood and Marrow Transplantation C1 NIH, NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. Brigham Young Univ, Provo, UT 84602 USA. RP Bishop, MR (reprint author), NIH, NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, 10 Ctr Dr CRC 3E-3330, Bethesda, MD 20892 USA. EM mbishop@mail.nih.gov FU Intramural NIH HHS [Z01 BC010698-03] NR 29 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2007 VL 13 IS 9 BP 1022 EP 1030 DI 10.1016/j.bbmt.2007.05.008 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 205YX UT WOS:000249152200004 PM 17697964 ER PT J AU Shih, JH Lu, SE AF Shih, Joanna H. Lu, Shou-En TI Analysis of failure time data with multilevel clustering, with application to the child vitamin a intervention trial in Nepal SO BIOMETRICS LA English DT Article DE frailty; multilevel clustered failure time data; within-cluster resampling ID SURVIVAL-DATA; COX MODEL; PARAMETER; CHECKING AB We consider the problem of estimating covariate effects in the marginal Cox proportional hazard model and multilevel associations for child mortality data collected from a vitamin A supplementation trial in Nepal, where the data are clustered within households and villages. For this purpose, a class of multivariate survival models that can be represented by a functional of marginal survival functions and accounts for hierarchical structure of clustering is exploited. Based on this class of models, an estimation strategy involving a within-cluster resampling procedure is proposed, and a model assessment approach is presented. The asymptotic theory for the proposed estimators and lack-of-fit test is established. The simulation study shows that the estimates are approximately unbiased, and the proposed test statistic is conservative under extremely heavy censoring but approaches the size otherwise. The analysis of the Nepal study data shows that the association of mortality is much greater within households than within villages. C1 NCI, Div Canc Treatment & Diagnosis, Biomet Res Branch, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Dept Biostat, Piscataway, NJ 08854 USA. RP Shih, JH (reprint author), NCI, Div Canc Treatment & Diagnosis, Biomet Res Branch, Bethesda, MD 20892 USA. EM jshih@mail.nih.gov NR 18 TC 4 Z9 5 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2007 VL 63 IS 3 BP 673 EP 680 DI 10.1111/j.1541-0420.2007.00756.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 203AJ UT WOS:000248947200007 PM 17825001 ER PT J AU Kinney, SK Dunson, DB AF Kinney, Satkartar K. Dunson, David B. TI Fixed and random effects selection in linear and logistic models SO BIOMETRICS LA English DT Article DE Bayesian model selection; logistic regression; mixed effects model; model averaging; parameterexpansion; random effects; variance components test; variable selection ID BAYESIAN VARIABLE SELECTION; MIXED MODELS; VARIANCE COMPONENT; PARAMETER EXPANSION; LONGITUDINAL DATA; SCORE TESTS; REGRESSION; INFERENCE AB We address the problem of selecting which variables should be included in the fixed and random components of logistic mixed effects models for correlated data. A fully Bayesian variable selection is implemented using a stochastic search Gibbs sampler to estimate the exact model-averaged posterior distribution. This approach automatically identifies subsets of predictors having nonzero fixed effect coefficients or nonzero random effects variance, while allowing uncertainty in the model selection process. Default priors are proposed for the variance components and an efficient parameter expansion Gibbs sampler is developed for posterior computation. The approach is illustrated using simulated data and an epidemiologic example. C1 Duke Univ, Inst Stat & Decis Sci, Durham, NC 27705 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Kinney, SK (reprint author), Duke Univ, Inst Stat & Decis Sci, Box 90251, Durham, NC 27705 USA. EM saki@stat.duke.edu FU Intramural NIH HHS NR 42 TC 43 Z9 44 U1 1 U2 15 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2007 VL 63 IS 3 BP 690 EP 698 DI 10.1111/j.1541-0420.2007.00771.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 203AJ UT WOS:000248947200009 PM 17403104 ER PT J AU Bigelow, JL Dunson, DB AF Bigelow, Jamie L. Dunson, David B. TI Bayesian adaptive regression splines for hierarchical data SO BIOMETRICS LA English DT Article DE adaptive regression splines; hormones; longitudinal data; menstrual cycle; mixed model; random effects; reversible jump MCMC ID CONCEPTION; WOMEN; PREGNANCY; PROFILES; MODELS; CYCLES AB This article considers methodology for hierarchical functional data analysis, motivated by studies of reproductive hormone profiles in the menstrual cycle. Current methods standardize the cycle lengths and ignore the timing of ovulation within the cycle, both of which are biologically informative. Methods are needed that avoid standardization, while flexibly incorporating information on covariates and the timing of reference events, such as ovulation and onset of menses. In addition, it is necessary to account for within-woman dependency when data are collected for multiple cycles. We propose an approach based on a hierarchical generalization of Bayesian multivariate adaptive regression splines. Our formulation allows for an unknown set of basis functions characterizing the population-averaged and woman-specific trajectories in relation to covariates. A reversible jump Markov chain Monte Carlo algorithm is developed for posterior computation. Applying the methods to data from the North Carolina Early Pregnancy Study, we investigate differences in urinary progesterone profiles between conception and nonconception cycles. C1 Duke Univ, Inst Stat & Decis Sci, Durham, NC 27708 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Bigelow, JL (reprint author), Duke Univ, Inst Stat & Decis Sci, Durham, NC 27708 USA. EM jbigelow@stat.duke.edu FU Intramural NIH HHS NR 18 TC 15 Z9 15 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2007 VL 63 IS 3 BP 724 EP 732 DI 10.1111/j.1541-0420.2007.00761.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 203AJ UT WOS:000248947200013 PM 17403106 ER PT J AU Albert, PS AF Albert, Paul S. TI Imputation approaches for estimating diagnostic accuracy for multiple tests from partially verified designs SO BIOMETRICS LA English DT Article DE diagnostic accuracy; gold standard evaluation; latent class models; mean imputation; multiple tests; partial verification; prevalence; semilatent class models; sensitivity; specificity; verification bias. ID ESTIMATING DISEASE PREVALENCE; VERIFICATION BIAS; SPECIFICITY; SENSITIVITY; NONRESPONSE; 2-PHASE; 2-STAGE; MODELS AB Interest often focuses on estimating sensitivity and specificity of a group of raters or a set of new diagnostic tests in situations in which gold standard evaluation is expensive or invasive. Various authors have proposed semilatent class modeling approaches for estimating diagnostic accuracy in this situation. This article presents imputation approaches for this problem. I show how imputation provides a simpler way of performing diagnostic accuracy and prevalence estimation than the use of semilatent modeling. Furthermore, the imputation approach is more robust to modeling assumptions and, in general, there is only a moderate efficiency loss relative to a correctly specified semilatent class model. I apply imputation to a study designed to estimate the diagnostic accuracy of digital radiography for gastric cancer. The feasibility and robustness of imputation is illustrated with analysis, asymptotic results, and simulations. C1 NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. EM albertp@mail.nih.gov NR 23 TC 7 Z9 7 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2007 VL 63 IS 3 BP 947 EP 957 DI 10.1111/j.1541-0420.2006.00734.x PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 203AJ UT WOS:000248947200039 PM 17825024 ER PT J AU Chatterjee, N Kalayliouglu, Z Shih, JH Gail, M AF Chatterjee, Nilanjan Kalayliouglu, Zeynep Shih, Joanna H. Gail, Mitchell TI Letter to the editor of biometrics - Reply SO BIOMETRICS LA English DT Letter C1 Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. Informat Management Syst, Rockville, MD 20852 USA. Natl Canc Inst, Div Canc Treatment & Diag, NIH, DHHS, Rockville, MD 20852 USA. RP Chatterjee, N (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2007 VL 63 IS 3 BP 965 EP 966 DI 10.1111/j.1541-0420.2007.00854_2.x PG 2 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 203AJ UT WOS:000248947200043 ER PT J AU Le, SY Maizel, JV AF Le, Shu-Yun Maizel, J. V., Jr. TI Data mining of imperfect double-stranded RNA in 3 ' untranslated regions of eukaryotic mRNAs SO BIOMOLECULAR ENGINEERING LA English DT Article; Proceedings Paper CT Conference on Computational Biology and Genome Informatics CY JUL 21-26, 2005 CL Salt Lake City, UT DE double-stranded RNA; well-ordered stem-loop; 3 ' UTR; RNA-based regulation ID SECONDARY STRUCTURES; LOCALIZATION; RECOGNITION; SEQUENCES; MICRORNAS; PROTEIN AB Recent developments in the study of RNA silencing indicate that double-stranded RNA (dsRNA) can be used in eukaryotes to block expression of a corresponding cellular gene. There is also a large class of small non-coding RNAs having potential to form a distinct, stable stem-loop in numbers of eukaryotic genomes. We had reported that a large imperfect dsRNA structure with hundreds of base-pairs (bp) in the 3' untranslated region (3'UTR) of cytotoxic ribonuclease was correlated with the translation suppression. In this study, we search for such dsRNAs in a 3'UTR database. The occurrence rate of large dsRNA in 3'UTRs ranges from 0.01% in plant to 0.30% in vertebrate mRNAs. However, small imperfect dsRNAs of similar to 30 bp are much more prevalent than large ones. The small dsRNAs are statistically very significant and uniquely well-ordered. Most of them have the conserved structural features of pre-miRNAs. Our data mining of the dsRNAs in the 3'UTR database can be used to explore RNA-based regulation of gene expression. (C) 2007 Elsevier B.V. All rights reserved. C1 Natl Canc Inst, Ctr Canc Res Nanobiol Program, CCR, NIH, Frederick, MD 21702 USA. RP Le, SY (reprint author), Natl Canc Inst, Ctr Canc Res Nanobiol Program, CCR, NIH, Bldg 469,Room 151, Frederick, MD 21702 USA. EM shuyun@ncifcrf.gov FU Intramural NIH HHS NR 26 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-0344 J9 BIOMOL ENG JI Biomol. Eng. PD SEP PY 2007 VL 24 IS 3 BP 351 EP 359 DI 10.1016/j.bioeng.2007.02.006 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 220WG UT WOS:000250187400011 PM 17482872 ER PT J AU Jha, A Mukheriee, C Prasad, AK Parmar, VS De Clercq, E Balzarini, J Stables, JP Manavathu, EK Shrivastav, A Sharma, RK Nienaber, KH Zello, GA Dimmock, JR AF Jha, Amitabh Mukheriee, Chandrani Prasad, Ashok K. Parmar, Virinder S. De Clercq, Erik Balzarini, Jan Stables, James P. Manavathu, Elias K. Shrivastav, Anuraag Sharma, Rajendra K. Nienaber, Kurt H. Zello, Gordon A. Dimmock, Jonathan R. TI E,E,E-1-(4-Arylamino-4-oxo-2-btitenoyl)-3,5-bis(arylidene)-4piperidones: A topographical study of some novel potent cytotoxins SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE 3,5-bis(arylidene)-4-piperidones; cytostatic activity; molecular modeling; human N-myristoyltransferase; murine toxicity ID STYRYL KETONES; MANNICH-BASES; TRANSFERASE; ANTICANCER; ANTITUMOR; CANCER; AGENTS; DRUGS AB A series of E,E,E-3,5-bis(arylidene)-1-(4-arylamino-4-oxo-2-butenoyl)-4-piperidones 4 (phenylidene) and 5 (4-nitrophenylidene) were prepared in order to explore the structural features of the N-acyl group which affects the cytotoxic potency. Evaluation toward human Molt 4/C8 and CEM T-lymphocytes revealed that many of the IC(50) figures were submicromolar and lower than melphalan. Marked inhibitory potencies toward murine leukemia L1210 cells were also noted. When evaluated against a panel of human tumor cell lines, three representative compounds in series 4 displayed selective toxicity to leukemia and colon cancer cell lines and were significantly more potent than the reference drug melphalan. Molecular modeling of representative compounds in both series 4 and the analogs, in which the configuration of the olefinic double bond was changed from E to Z (series 3), revealed that the torsion angles of the arylidene aryl rings and locations of the terminal arylaminocarbonyl groups may have contributed to the greater cytotoxic properties displayed in 3. Compounds 4c (3,4-dichlorophenylamino), d (4-methylphenylamino) and 5c (3,4-dichlorophenylamino), d (4-methylphenylamino) inhibited the activity of human N-myristoyltransferase by approximately 50% at concentrations of 50-100 mu M. The compounds in series 4 and 5 were well tolerated in a short-term toxicity study in mice. (c) 2007 Elsevier Ltd. All rights reserved. C1 Acadia Univ, Dept Chem, Wolfville, NS B4P 2R6, Canada. Univ Delhi, Dept Chem, Delhi 110007, India. Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. Natl Inst Neurol Disorders & Stroke, Rockville, MD 20852 USA. Wayne State Univ, Dept Med, Detroit, MI 48201 USA. Univ Saskatchewan, Coll Med, Dept Pathol, Saskatoon, SK S7N 4H4, Canada. Saskatoon Canc Ctr, Canc Res Unit, Saskatoon, SK S7N 4H4, Canada. Univ Saskatchewan, Coll Med, Dept Biochem, Saskatoon, SK S7N 5E5, Canada. Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. RP Jha, A (reprint author), Acadia Univ, Dept Chem, Wolfville, NS B4P 2R6, Canada. EM ajha@acadiau.ca RI Jha, Amitabh/B-5452-2010 OI Jha, Amitabh/0000-0002-6305-0721 NR 29 TC 27 Z9 27 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD SEP 1 PY 2007 VL 15 IS 17 BP 5854 EP 5865 DI 10.1016/j.bmc.2007.05.065 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 200QX UT WOS:000248779000017 PM 17562365 ER PT J AU Kipper, MJ Kleinman, HK Wang, FW AF Kipper, Matt J. Kleinman, Hynda K. Wang, Francis W. TI New method for Modeling connective-tissue cell migration: Improved accuracy on motility parameters SO BIOPHYSICAL JOURNAL LA English DT Article ID LAMININ ALPHA-1 CHAIN; HUMAN-NEUTROPHILS; STOCHASTIC-MODEL; CHEMOTAXIS; FIBRONECTIN; PEPTIDES; IDENTIFICATION; GRADIENTS; MOVEMENT; TRACKING AB Mathematical models of cell migration based on persistent random walks have been successfully applied to describe the motility of several cell types. However, the migration of slowly moving connective-tissue cells, such as fibroblasts, is difficult to observe experimentally and difficult to describe theoretically. We identify two primary sources of this difficulty. First, cells such as fibroblasts tend to migrate slowly and change shape during migration. This makes accurate determination of cell position difficult. Second, the cell population is considerably heterogeneous with respect to cell speed. Here we develop a method for fitting connective-tissue cell migration data to persistent random walk models, which accounts for these two significant sources of error and enables accurate determination of the cell motility parameters. We demonstrate the usefulness of this method for modeling both isotropic cell motility and biased cell motility, where the migration of a population of cells is influenced by a gradient in a surface-bound adhesive peptide. This method can discern differences in the motility of populations of cells at different points along the peptide gradient and can therefore be used as a tool to quantify the effects of peptide concentration and gradient magnitude on cell migration. C1 Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. Natl Inst Stand & Technol, Natl Inst Dental & Craniofacial Res, Gaithersburg, MD USA. RP Wang, FW (reprint author), Natl Inst Stand & Technol, 100 Bureau Dr, Gaithersburg, MD 20899 USA. EM francis.wang@nist.gov RI Kipper, Matt/B-6941-2013 OI Kipper, Matt/0000-0002-8818-745X NR 27 TC 14 Z9 14 U1 0 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2007 VL 93 IS 5 BP 1797 EP 1808 DI 10.1529/biophysj.106.096800 PG 12 WC Biophysics SC Biophysics GA 199VB UT WOS:000248722200035 PM 17483177 ER PT J AU Fang, J Iwasa, KH AF Fang, Jie Iwasa, K. H. TI Effects of chlorpromazine and trinitrophenol on the membrane motor of outer hair cells SO BIOPHYSICAL JOURNAL LA English DT Article ID FORCE GENERATION; SHAPE CHANGES; BIOLOGICAL-MEMBRANES; COCHLEAR AMPLIFIER; BILAYER-MEMBRANES; PLASMA-MEMBRANE; GATING CHARGE; ION CHANNELS; PRESTIN; PROTEIN AB The motile activity of outer hair cells' cell body is associated with large nonlinear capacitance due to a membrane motor that couples electric displacement with changes in the membrane area, analogous to piezoelectricity. This motor is based on prestin, a member of the SLC26 family of anion transporters and utilizes the electric energy available at the plasma membrane associated with the sensory function of these cells. To understand detailed mechanism of this motile activity, we examined the effect of amphipathic ions, cationic chlorpromazine and anionic trinitrophenol, which are thought to change the curvature of the membrane in opposite directions. We found that both chemicals reduced cell length at the holding potential of -75 mV and induced positive shifts in the cells' voltage dependence. The shift observed was similar to 10 mV for 500 mM trinitrophenol and 20 mV for 100 mu M cationic chlorpromazine. Length reduction at the holding potential and voltage shifts of the motile activity were well correlated. The voltage shifts of nonlinear capacitance were not diminished by eliminating the cells' turgor pressure or by digesting the cortical cytoskeleton. These observations suggest that the membrane motor undergoes conformational transitions that involve changes not only in membrane area but also in bending stiffness. C1 NIH, Bethesda, MD 20892 USA. Natl Tech Inst Deaf, Cell Biol Lab, Sect Biophys, Bethesda, MD USA. RP Iwasa, KH (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM iwasa@nih.gov OI Iwasa, Kuni/0000-0002-9397-7704 FU Intramural NIH HHS NR 54 TC 12 Z9 12 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2007 VL 93 IS 5 BP 1809 EP 1817 DI 10.1529/biophysj.106.100834 PG 9 WC Biophysics SC Biophysics GA 199VB UT WOS:000248722200036 PM 17483184 ER PT J AU Coppey, M Berezhkovskii, AM Sealfon, SC Shvartsman, SY AF Coppey, Mathieu Berezhkovskii, Alexander M. Sealfon, Stuart C. Shvartsman, Stanislav Y. TI Time and length scales of autocrine signals in three dimensions SO BIOPHYSICAL JOURNAL LA English DT Article ID GROWTH-FACTOR RECEPTOR; EPITHELIAL LAYERS; LIGAND-BINDING; CELL-CULTURES; MODEL; ACTIVATION; PARACRINE; RANGE AB A model of autocrine signaling in cultures of suspended cells is developed on the basis of the effective medium approximation. The fraction of autocrine ligands, the mean and distribution of distances traveled by paracrine ligands before binding, as well as the mean and distribution of the ligand lifetime are derived. Interferon signaling by dendritic immune cells is considered as an illustration. C1 Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA. Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Natl Inst Hlth, Bethesda, MD USA. CUNY Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Ctr Translat Syst Biol, New York, NY 10029 USA. RP Shvartsman, SY (reprint author), Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. EM stas@princeton.edu FU Intramural NIH HHS; NIAID NIH HHS [N01AI50021, N01 AI 50021] NR 31 TC 12 Z9 12 U1 0 U2 4 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2007 VL 93 IS 6 BP 1917 EP 1922 DI 10.1529/biophysj.107.109736 PG 6 WC Biophysics SC Biophysics GA 203ZZ UT WOS:000249013900010 PM 17720734 ER PT J AU Jang, H Zheng, J Nussinov, R AF Jang, Hyunbum Zheng, Jie Nussinov, Ruth TI Models of beta-amyloid ion channels in the membrane suggest that channel formation in the bilayer is a dynamic process SO BIOPHYSICAL JOURNAL LA English DT Article ID RAPID CELLULAR DEGENERATION; PROTEIN MISFOLDING DISEASES; INDIVIDUAL ALPHA-HELICES; SOLID-STATE NMR; MOLECULAR-DYNAMICS; LIPID-BILAYERS; ALZHEIMERS-DISEASE; ZN2+-SENSITIVE CHANNEL; CALCIUM-CHANNELS; CORTICAL-NEURONS AB Here we model the Alzheimer beta-peptide ion channel with the goal of obtaining insight into the mechanism of amyloid toxicity. The models are built based on NMR data of the oligomers, with the universal U-shaped (strand-turn-strand) motif. After 30-ns simulations in the bilayer, the channel dimensions, shapes and subunit organization are in good agreement with atomic force microscopy (AFM). The models use the A beta(17-42) pentamer NMR-based coordinates. Extension and bending of the straight oligomers lead to two channel topologies, depending on the direction of the curvature: 1), the polar/charged N-terminal beta-strand of A beta(17-42) faces the water-filled pore, and the hydrophobic C-terminal beta-strand faces the bilayer (CNpNC; p for pore); and 2), the C-terminal beta-strand faces the solvated pore (NCpCN). In the atomistic simulations in a fully solvated DOPC lipid bilayer, the first (CNpNC) channel preserves the pore and conducts solvent; by contrast, hydrophobic collapse blocks the NCpCN channel. AFM demonstrated open pores and collapsed complexes. The final averaged CNpNC pore dimensions (outer diameter 8 nm; inner diameter; similar to 2.5 nm) are in the AFM range (8-12 nm; similar to 2 nm, respectively). Further, in agreement with high-resolution AFM images, during the simulations, the channels spontaneously break into ordered subunits in the bilayer; however, we also observe that the subunits are loosely connected by partially disordered inner beta-sheet, suggesting subunit mobility in the bilayer. The cationic channel has strong selective affinity for Ca2+, supporting experimental calcium-selective beta-amyloid channels. Membrane permeability and consequent disruption of calcium homeostasis were implicated in cellular degeneration. Consequently, the CNpNC channel topology can sign cell death, offering insight into amyloid toxicity via an ion ''trap-release'' transport mechanism. The observed loosely connected subunit organization suggests that amyloid channel formation in the bilayer is a dynamic, fluid process involving subunit association, dissociation, and channel rearrangements. C1 NCI, SAIC Frederick, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, SAIC Frederick, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Zheng, Jie/B-5057-2013 OI Zheng, Jie/0000-0003-1547-3612 FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, R01 CO 12400] NR 54 TC 106 Z9 107 U1 2 U2 28 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2007 VL 93 IS 6 BP 1938 EP 1949 DI 10.1529/biophysj.107.110148 PG 12 WC Biophysics SC Biophysics GA 203ZZ UT WOS:000249013900012 PM 17526580 ER PT J AU Stuelten, CH Kamaraju, K Wakefield, LM Roberts, AB AF Stuelten, Christina H. Kamaraju, K. Wakefield, Lalage M. Roberts, Anita B. TI Lentiviral reporter constructs for fluorescence tracking of the temporospatial pattern of Smad3 signaling SO BIOTECHNIQUES LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; TUMOR-SUPPRESSOR; CANCER; FIBROBLASTS; METASTASIS; RESPONSES AB Canonical TGF-beta is involved in cell differentiation, tissue maintenance, and wound healing, bill also plays a central role in the pathogenesis of diseases such as cancer Here we describe a lentivirus-based reporter vector system expressing green fluorescent protein (GFP) or red fluorescent protein (RFP) under the control of a Smad3-responshe element (CAGA)(12) that allows observation of the temporospatial pattern of endogeneous Smad3-mediated signaling on I cellular level. Use of this method v-ill be valuable to identify cells with active Smad3 signaling and investigate the role of endogelious Smad3 signaling in complex systems such as co-cultures in vitro, or in tuinors during tumor cell invasion and metastasis ill vivo. C1 NCI, NIH, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. RP Stuelten, CH (reprint author), NCI, NIH, Cell & Canc Biol Branch, 37 Convent Dr Room 1042, Bethesda, MD 20892 USA. EM chrisstu@mail.nih.gov NR 13 TC 3 Z9 4 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 2007 VL 43 IS 3 BP 289 EP + DI 10.2144/000112549 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 211GD UT WOS:000249511400011 PM 17907571 ER PT J AU Giannone, RJ McDonald, WH Hurst, GB Huang, Y Wu, J Liu, Y Wang, YS AF Giannone, Richard J. McDonald, W. Hayes Hurst, Gregory B. Huang, Ying Wu, Jun Liu, Yie Wang, Yisong TI Dual-tagging system for the affinity purification of mammalian protein complexes SO BIOTECHNIQUES LA English DT Article ID CELLS; PROTEOMICS; TELOMERES AB Although affinity purification coupled with mass spectrometry (MS)provides a powerful tool to study protein-protein interactions, this strategy has encountered numerous difficulties when adapted to mammalian cells. Here we describe a Gateway (R)-compatible dual-tag affinity purification system that integrates regulatable expression, tetracysteine motifs, and mrious combinations ofa ini facilitate the cloning, detection, and purification of bait proteins and their interacting partners. Utilizing the human telomere binding protein TRF2 as a benchmark, we demonstrate bait protein recoveries upwards of approxiniately 16%from as little as 1-7 x 10(7) cells and successfully identify known TRF2 interacting proteins, suggesting that our dual-tag affinity purification approach is a capable new toolfor expanding the capacity, to explore mammalian proteomic networks. C1 Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA. Univ Tennessee, Knoxville, TN USA. NIA, Baltimore, MD 21224 USA. RP Wang, YS (reprint author), Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA. EM liuyie@grc.nia.nih.gov; ywa@ornl.gov RI McDonald, W. Hayes/B-4109-2016 OI McDonald, W. Hayes/0000-0002-3510-426X FU Intramural NIH HHS NR 15 TC 19 Z9 21 U1 0 U2 3 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 2007 VL 43 IS 3 BP 296 EP + DI 10.2144/000112550 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 211GD UT WOS:000249511400012 PM 17907572 ER PT J AU Zarate, CA Singh, JB Carlson, PJ Quiroz, J Jolkovsky, L Luckenbaugh, DA Manji, HK AF Zarate, Carlos A., Jr. Singh, Jaskaran B. Carlson, Paul J. Quiroz, Jorge Jolkovsky, Libby Luckenbaugh, David A. Manji, Husseini K. TI Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study SO BIPOLAR DISORDERS LA English DT Article DE antimanic; mania; protein kinase C; tamoxifen ID BIPOLAR AFFECTIVE-DISORDER; HIGH-DOSE TAMOXIFEN; BREAST-CANCER; DOPAMINE TRANSPORT; IN-VITRO; LITHIUM; AMPHETAMINE; INJECTION; ALPHA; TRANSDUCTION AB Objectives: Considerable preclinical biochemical and behavioral data suggest that protein kinase C inhibition would bring about antimanic effects. Notably, the structurally highly dissimilar antimanic agents lithium and valproate, when administered in therapeutically relevant paradigms, attenuate protein kinase C inhibition function. There is currently only one relatively selective protein kinase C inhibitor that crosses the blood-brain barrier available for human use - tamoxifen. Our group recently conducted a single-blind study with tamoxifen in acute mania and found that it significantly decreased manic symptoms within a short period of time (3-7 days). In this study, we investigated whether antimanic effects can be achieved with a protein kinase C inhibitor in subjects with mania. Methods: In a double-blind, placebo-controlled study, 16 subjects with bipolar disorder, manic or mixed, with or without psychotic features, were randomly assigned to receive tamoxifen (20-140 mg/day; n = 8) or placebo (n = 8) for three weeks. Primary efficacy was assessed by the Young Mania Rating Scale. Results: Subjects on tamoxifen showed significant improvement in mania compared to placebo as early as five days, an effect that remained significant throughout the three-week trial. The effect size for the drug difference was very large (d = 1.08, 95% confidence interval 0.45-1.71) after three weeks (p = 0.001). At study endpoint, response rates were 63% for tamoxifen and 13% for placebo (p = 0.12). Conclusions: Antimanic effects resulted from a protein kinase C inhibitor; onset occurred within five days. Large, controlled studies with selective protein kinase C inhibitors in acute mania are warranted. C1 NIMH, Lab Mol Pathophysiol & Expt Therapeut, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), 10 Ctr Dr,CRC,Unit 7 SE,Room 7-3445, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov FU Intramural NIH HHS NR 45 TC 107 Z9 110 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD SEP PY 2007 VL 9 IS 6 BP 561 EP 570 DI 10.1111/j.1399-5618.2007.00530.x PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 207TY UT WOS:000249275200002 PM 17845270 ER PT J AU Consoli, A Soultanian, C Tanguy, ML Laurent, C Perisse, D Luque, R Berrios, GE Cohen, D AF Consoli, Angele Soultanian, Charlotte Tanguy, Marie-Laure Laurent, Claudine Perisse, Didier Luque, Rogelio Berrios, German E. Cohen, David TI Cotard's syndrome in adolescents and young adults is associated with an increased risk of bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE adolescence; age at onset; bipolar disorder; Cotard's syndrome; mood stabilizer ID MAJOR DEPRESSIVE DISORDER; ELECTROCONVULSIVE-THERAPY; FOLLOW-UP; PATIENT; ONSET; ECT; AGE AB Objectives: To assess the effect of age at onset on the phenomenology of Cotard's syndrome (CS) as a recent study reported a high rate of occurrence of bipolar disorder (BD) in adolescents and young adults with CS followed up for >= 2 years. Methods: We reviewed all cases of CS reported since it was first described. A statistical analysis was carried out to determine the effect of age at onset on CS phenomenology. Results: We found 138 cases including 21 cases aged 25 years or younger. In these younger CS patients, BD was more frequent, and the risk of associated BD was increased nine times (p < 0.0001). Within the BD sub-group (n = 27), admixture analysis identified two sub-groups with mean ages at onset of 18.7 years [standard deviation (SD) = 3.2] and 50.5 years (SD = 11.7). Conclusions: Young people with CS should be monitored carefully for the onset of BD, and families should be educated about this risk. Treatment with mood stabilizers can be helpful for those who develop BD. Within BD associated with CS, early versus late onset should be distinguished. C1 Univ Paris 06, Hop La Pitie Salpetriere, Dept Child & Adolescent Psychiat Comportement & C, APHP, F-75252 Paris 05, France. Hop St Antoine, Dept Psychiat, APHP, Paris, France. Hop La Pitie Salpetriere, Dept Biostat, APHP, Paris, France. NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. Univ Cordoba, Hosp Univ Reina Sofia, Cordoba, Spain. Univ Cambridge, Dept Psychiat, Addenbrookes Hosp, Cambridge, England. RP Cohen, D (reprint author), Grp Hosp La Pitie Salpetriere, Serv Psychiat Enfant & Adolescent, 47 Bd Hop, F-75651 Paris 13, France. EM david.cohen@psl.ap-hop-paris.fr NR 40 TC 7 Z9 7 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD SEP PY 2007 VL 9 IS 6 BP 665 EP 668 DI 10.1111/j.1399-5618.2007.00420.x PG 4 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 207TY UT WOS:000249275200015 PM 17845283 ER PT J AU Alter, BP Baerlocher, GM Savage, SA Chanock, SJ Weksler, BB Willner, JP Peters, JA Giri, N Lansdorp, PM AF Alter, Blanche P. Baerlocher, Gabriela M. Savage, Sharon A. Chanock, Stephen J. Weksler, Babette B. Willner, Judith P. Peters, June A. Giri, Neelarn Lansdorp, Peter M. TI Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita SO BLOOD LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol ID SHWACHMAN-DIAMOND-SYNDROME; APLASTIC-ANEMIA; REVERSE-TRANSCRIPTASE; FANCONI-ANEMIA; MUTATIONS; COMPONENT; DISEASE; GENE; TRANSPLANTATION; ANTICIPATION AB Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome in which the known susceptibility genes (DKC1, TERC, and TERT) belong to the telomere maintenance pathway; patients with DC have very short telomeres. We used multicolor flow fluorescence in situ hybridization analysis of median telomere length in total blood leukocytes, granulocytes, lymphocytes, and several lymphocyte subsets to confirm the diagnosis of DC, distinguish patients with DC from unaffected family members, identify clinically silent DC carriers, and discriminate between patients with DC and those with other bone marrow failure disorders. We defined "very short" telomeres as below the first percentile measured among 400 healthy control subjects over the entire age range. Diagnostic sensitivity and specificity of very short telomeres for DC were more than 90% for total lymphocytes, CD45RA+/CD20- naive T cells, and CD20+ B cells. Granulocyte and total leukocyte assays were not specific; CD45RA- memory T cells and CD57+ NK/NKT were not sensitive. We observed very short telomeres in a clinically normal family member who subsequently developed DC. We propose adding leukocyte subset flow fluorescence in situ hybridization telomere length measurement to the evaluation of patients and families suspected to have DC, because the correct diagnosis will substantially affect patient management. C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Hosp Bern, CH-3010 Bern, Switzerland. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Weill Med Coll, Dept Med, New York, NY USA. Mt Sinai Sch Med, Dept Genet, New York, NY USA. British Columbia Canc Res Ctr, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. RP Alter, BP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM alterb@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU Intramural NIH HHS; NCI NIH HHS [N02CP11019]; NIAID NIH HHS [AI29524, R01 AI029524, R21 AI029524] NR 35 TC 161 Z9 166 U1 1 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2007 VL 110 IS 5 BP 1439 EP 1447 DI 10.1182/blood-2007-02-075598 PG 9 WC Hematology SC Hematology GA 205YT UT WOS:000249151800016 PM 17468339 ER PT J AU Phipps, S Lam, CE Mahalingam, S Newhouse, M Ramirez, R Rosenberg, HF Foster, PS Matthaei, KI AF Phipps, Simon Lam, Chuan En Mahalingam, Suresh Newhouse, Matthew Ramirez, Ruben Rosenberg, Helene F. Foster, Paul S. Matthaei, Klaus I. TI Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus SO BLOOD LA English DT Article ID INTERFERON REGULATORY FACTOR; TOLL-LIKE RECEPTOR-4; NITRIC-OXIDE; AIRWAY HYPERRESPONSIVENESS; EPITHELIAL-CELLS; GENE-EXPRESSION; STRANDED-RNA; INFECTION; ASTHMA; RECOGNITION AB Eosinophils are recruited to the lungs in response to respiratory syncytial virus (RSV) infection; however, their role in promoting antiviral host defense remains unclear. Here, we demonstrate that eosinophils express TLRs that recognize viral nucleic acids, are activated and degranulate after single-stranded RNA (ssRNA) stimulation of the TLR-7-MyD88 pathway, and provide host defense against RSV that is MyD88 dependent. In contrast to wild-type mice, virus clearance from lung tissue was more rapid in hypereosinophilic (interleukin-5 trans-genic) mice. Transfer of wild-type but not MyD88-deficient eosinophils to the lungs of RSV-infected wild-type mice accelerated virus clearance and inhibited the development of airways hyperreactivity. Similar responses were observed when infected recipient mice were MyD88 deficient. Eosinophils isolated from infected hypereosinophilic MyD88-sufficient but not MyD88-deficient mice expressed greater amounts of IFN regulatory factor (IRF)-7 and eosinophil-associated ribonucleases EAR-1 and EAR-2. Hypereosinophilia in the airways of infected mice also correlated with increased expression of IRF-7, IFN-beta, and NOS-2, and inhibition of NO production with the NOS-2 inhibitor L-NMA partially reversed the accelerated virus clearance promoted by eosinophils. Collectively, our results demonstrate that eosinophils can protect against RSV in vivo, as they promote virus clearance and may thus limit virus-induced lung dysfunction. C1 Univ Newcastle, Sch Biomed Sci, Ctr Asthma & Rep Dis, Newcastle, NSW 2300, Australia. Hunter Med Res Inst, Vaccines Immun Viruses & Asthma Grp, Newcastle, NSW, Australia. Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2600, Australia. Univ Canberra, Sch Hlth Sci, Ctr Virus Res, Belconnen, ACT 2616, Australia. NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Foster, PS (reprint author), Univ Newcastle, Sch Biomed Sci, Ctr Asthma & Rep Dis, David Maddison Clin Sci Bldg,Watt St, Newcastle, NSW 2300, Australia. EM paul.foster@newcastle.edu.au RI Klaus, Matthaei/D-8691-2011; Phipps, Simon/F-9170-2010; Foster, Paul/G-5057-2013 OI Phipps, Simon/0000-0002-7388-3612; NR 57 TC 110 Z9 114 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2007 VL 110 IS 5 BP 1578 EP 1586 DI 10.1182/blood-2007-01-071340 PG 9 WC Hematology SC Hematology GA 205YT UT WOS:000249151800033 PM 17495130 ER PT J AU Solomou, EE Rezvani, K Mielke, S Malide, D Keyvanfar, K Visconte, V Kajigaya, S Barrett, AJ Young, NS AF Solomou, Elena E. Rezvani, Katayoun Mielke, Stephan Malide, Daniela Keyvanfar, Keyvan Visconte, Valeria Kajigaya, Sachiko Barrett, A. John Young, Neal S. TI Deficient CD4(+) CD25(+) FOXP3(+) T regulatory cells in acquired aplastic anemia SO BLOOD LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRANSCRIPTION; AUTOIMMUNITY; LYMPHOCYTES; MUTATIONS; TOLERANCE; PROMOTER; NFAT AB Regulatory T cells are believed to control the development and progression of autoimmunity by suppressing autoreactive T cells. Decreased numbers of CD4(+)CD25(+) FOXP3(+) T cells (Tregs) are associated with impaired immune homeostasis and development of autoimmune diseases. The transcription factors FOXP3 and NFAT1 have key roles in regulatory T-cell development and function. We show that Tregs are decreased at presentation in almost all patients with aplastic anemia; FOXP3 protein and mRNA levels also are significantly lower in patients with aplastic anemia and NFAT1 protein levels are decreased or absent. Transfection of FOXP3-deficlent CD4(+)CD25(+) T cells from patients with a plasmid encoding wild-type NFAT1 resulted in increased FOXP3 expression in these cells. By NFAT1 knockdown in CD4(+)CD25(+) T cells, FOXP3 expression was decreased when NFAT1 expression was decreased. Our findings indicate that decreased NFAT1 could explain low FOXP3 expression and diminished Treg frequency in aplastic anemia. Treg defects are now implicated in autoimmune marrow failure. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Light Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. RP Solomou, EE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC,Room 3E5216,10 Ctr Dr, Bethesda, MD 20892 USA. EM solomoue@nhlbi.nih.gov FU Intramural NIH HHS NR 22 TC 81 Z9 113 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2007 VL 110 IS 5 BP 1603 EP 1606 DI 10.1182/blood-2007-01-066258 PG 4 WC Hematology SC Hematology GA 205YT UT WOS:000249151800036 PM 17463169 ER PT J AU Mielke, S Rezvani, K Savani, BN Nunes, R Yong, ASM Schindler, J Kurlander, R Ghetie, V Read, EJ Solomon, SR Vitetta, ES Barrett, AJ AF Mielke, Stephan Rezvani, Katayoun Savani, Bipin N. Nunes, Raquel Yong, Agnes S. M. Schindler, John Kurlander, Roger Ghetie, Victor Read, Elizabeth J. Solomon, Scott R. Vitetta, Ellen S. Barrett, A. John TI Reconstitution of FOXP3(+) regulatory T cells (T-regs) after CD25-depleted allotransplantion in elderly patients and association with acute graft-versus-host disease SO BLOOD LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol ID BONE-MARROW-TRANSPLANTATION; SELECTIVE DEPLETION; ANTI-CD25 IMMUNOTOXIN; IMMUNE RECONSTITUTION; DONOR LYMPHOCYTES; SELF-TOLERANCE; VIVO BLOCKADE; PREVENTION; EXPRESSION; GVHD AB Selective depletion (SID) of host-reactive donor T cells from allogeneic stem-cell transplants (SCTs) using an anti-CD25 immunotoxin (IT) is a strategy to prevent acute graft-versus-host disease (aGvHD). There is concern that concurrent removal of regulatory T cells (T-regs) with incomplete removal of alloactivated CD25(+) T cells could increase the risk of aGvHD. We therefore measured T,g, in the blood of 16 patients receiving a T-cell-depleted allograft together with anti-CD25-IT-treated SD lymphocytes, in 13 of their HLA-Identical donors, and in 10 SD products. T-regs were characterized by intracellular staining for forkhead box protein 3 (FOXP3) and by quantitative reversetranscription-polymerase chain reaction (qRT-PCR) for FOXP3 gene in CD4(+) cells. Patients received a median of 1.0 x 10(8)/kg SD T cells and a stem cell product containing a median of 0.25 x 10(4)/kg residual T cells. Tregs reconstituted promptly after SCT and underwent further expansion. Of the CD4(+) T cells in SD products, 1.5% to 4.8% were CD25(-) T-regs. Acute GvHD (>= grade II) was restricted to 5 patients whose donors had significantly (P = .019) fewer Tregs compared with those without clinically significant aGvHD. These results suggest that rapid T-reg reconstitution can occur following SD allografts, either from CD25(-) T-regs escaping depletion, or from residual CD25(-) and CD25(+) T-regs contained in the stem-cell product that expand after transplantation and may confer additional protection against GvHD. C1 NHLBI, Stem Cell Allogene Transplant Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Canc Immunobiol Ctr, Dallas, TX 75216 USA. NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NIH, Cell Proc Sect, Dept Transfus Med, Bethesda, MD 20892 USA. RP Mielke, S (reprint author), NHLBI, Stem Cell Allogene Transplant Sect, Hematol Branch, NIH, Bldg 10 CRC Rm 3-5288,10 Ctr Dr,MSC 1202, Bethesda, MD 20892 USA. EM mielkes@nhlbi.nih.gov NR 48 TC 56 Z9 61 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2007 VL 110 IS 5 BP 1689 EP 1697 DI 10.1182/blood-2007-03-079160 PG 9 WC Hematology SC Hematology GA 205YT UT WOS:000249151800047 PM 17478639 ER PT J AU Soule, BP Simone, NL Savani, BN Ning, H Albert, PS Barrett, AJ Singh, AK AF Soule, B. P. Simone, N. L. Savani, B. N. Ning, H. Albert, P. S. Barrett, A. J. Singh, A. K. TI Pulmonary function following total body irradiation (with or without lung shielding) and allogeneic peripheral blood stem cell transplant SO BONE MARROW TRANSPLANTATION LA English DT Article DE pulmonary function; total body radiation; stem-cell transplant; lung shielding ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; LONG-TERM SURVIVORS; FUNCTION TESTS; HEMATOLOGIC MALIGNANCIES; INTERSTITIAL PNEUMONITIS; RANDOMIZED-TRIAL; BREAST-CANCER; COMPLICATIONS; REGIMENS AB Our purpose was to determine if total body irradiation (TBI) with lung dose reduction protects against subsequent radiation-induced deterioration in pulmonary function. Between July 1997 and August 2004, 181 consecutive patients with hematologic malignancies received fractionated TBI before allogeneic peripheral blood stem cell transplant. The first 89 patients were treated to a total dose of 13.6 Gy. Thereafter, total body dose was decreased to 12 Gy with lung dose reduction to 9 or 6 Gy. All patients underwent pulmonary function test evaluation before treatment, 90 days post-treatment, then annually. Median follow- up was 24.0 months. Eighty-nine patients were treated with lung shielding, and 92 without. At 1-year post transplant, there was a small but significant difference in lung volume measurements between patients with lung shielding and those without. This was not observed at the 2-year time point. When stratified by good (> 100% predicted) or poor (<= 100% predicted) baseline lung function, patients with poor function demonstrated protection at 1 year with lung shielding, while those with good initial lung function did not. TBI with or without lung dose reduction has a small but statistically significant effect on pulmonary function measured at 1 year but not 2 years post irradiation. C1 NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. RP Singh, AK (reprint author), NCI, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10-CRC,Room B2-3500 MSC 1642, Bethesda, MD 20892 USA. EM singan@mail.nih.gov FU Intramural NIH HHS NR 45 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD SEP PY 2007 VL 40 IS 6 BP 573 EP 578 DI 10.1038/sj.bmt.1705771 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 207UU UT WOS:000249277400011 PM 17637691 ER PT J AU Abrahamson, PE Tworoger, SS Aiello, EJ Bernstein, L Ulrich, CM Gilliland, FD Stanczyk, FZ Baumgartner, R Baumgartner, K Sorensen, B Ballard-Barbash, R McTiernan, A AF Abrahamson, Page E. Tworoger, Shelley S. Aiello, Erin J. Bernstein, Leslie Ulrich, Cornelia M. Gilliland, Frank D. Stanczyk, Frank Z. Baumgartner, Richard Baumgartner, Kathy Sorensen, Bess Ballard-Barbash, Rachel McTiernan, Anne TI Associations between the CYP17, CYPIB1, COMT and SHBG polymorphisms and serum sex hormones in post-menopausal breast cancer survivors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; COMT; CYP17; CYP1B1; estrogen; SHBG; testosterone ID CATECHOL-O-METHYLTRANSFERASE; BINDING GLOBULIN SHBG; GENETIC POLYMORPHISMS; PREMENOPAUSAL WOMEN; CYTOCHROME-P450 1B1; RISK; VARIANT; ESTRADIOL; ESTROGENS; CARCINOGENESIS AB Several polymorphisms have been identified in genes that code for enzymes involved with estrogen biosynthesis and metabolism. Little is known about the functional relevance of these polymorphisms on sex hormones in vivo. We examined the association between CYP17, CYP1B1, COMT or SHBG genotypes and serum concentrations of estrone, estradiol, free estradiol, sex hormone-binding globulin (SHBG), testosterone, free testosterone and dehyroepiandrosterone in 366 post-menopausal breast cancer survivors in New Mexico, California and Washington. Hormone levels were determined by high performance liquid chromatography and radioimmunoassay in blood drawn approximately 2 years post-diagnosis. We used generalized linear regression to calculate mean hormone levels by genotype, adjusting for age, race/ethnicity, stage, study site, tamoxifen use, number of remaining ovaries, hormone therapy use, marital status and BMI. No associations were observed between any of the genotypes and sex hormones when analyzing the main effects. In subgroup analyses, androgen levels of Hispanic women with the variant (A2) CYP17 genotype were 46-87% higher than those of women with the wild-type; androgen levels were 13-20% lower in non-Hispanic whites with the variant genotype; no difference by genotype was observed for African-American women. Current tamoxifen users with the variant asn(327) SHBG genotype had 81% higher serum SHBG and 39% lower free testosterone concentrations than women with the wild-type genotype. Non-tamoxifen users with the variant SHBG allele had elevated free estradiol levels. These results provide little evidence that the CYP17, CYP1B1, and COMT polymorphisms are associated with different sex hormone levels in post-menopausal breast cancer survivors. C1 Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Grp Hlth Ctr Hlth Studies, Seattle, WA USA. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Dept Obstet & Gynecol, Keck Sch Med, Los Angeles, CA 90089 USA. Univ Louisville, Dept Epidemiol & Clin Invest Sci, Louisville, KY 40292 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM amctiern@fhcrc.org RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Tworoger, Shelley/0000-0002-6986-7046 FU NCI NIH HHS [N01 PC035138-22, N01 CN005228, N01 PC067010, N01-CN-05228, N01-CN-75036-20, R25 CA094880, R25 CA94880] NR 42 TC 7 Z9 7 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 2007 VL 105 IS 1 BP 45 EP 54 DI 10.1007/s10549-006-9426-2 PG 10 WC Oncology SC Oncology GA 201SV UT WOS:000248853800006 PM 17077994 ER PT J AU Breslow, RA Falk, DE Fein, SB Grummer-Strawn, LM AF Breslow, Rosalind A. Falk, Daniel E. Fein, Sara B. Grummer-Strawn, Laurence M. TI Alcohol Consumption Among Breastfeeding Women SO BREASTFEEDING MEDICINE LA English DT Article AB Purpose: To determine the prevalence of alcohol consumption among breastfeeding and non-breastfeeding women at 3 months postpartum. Methods: We analyzed the most recent data available, which were from the 1993-1994 Food and Drug Administration Infant Feeding Practices Study I, a longitudinal panel study of infant-mother pairs. Self-reported data on alcohol consumption were analyzed for 772 breastfeeding women and 776 non-breastfeeding women age >= 14 years. Results: At 3 months postpartum, 36% of breastfeeding women and 40% of non-breastfeeding women consumed alcohol (p = 0.09). In multinomial regression models adjusted for age, race, education, income, marital status, region, smoking, and alcohol consumption before and during pregnancy, breastfeeding women were significantly less likely than non-breastfeeding women to consume two drinks per week (p < 0.01), or equal to or more than three drinks per week (p < 0.01), but equally likely to consume one drink (p = 0.23). Conclusions: A substantial percentage of breastfeeding women consumed alcohol. Their infants may or may not have been exposed, as some women may have used alcohol avoidance strategies. Nationally representative data are needed on alcohol consumption and infant feeding practices among breastfeeding women. C1 [Breslow, Rosalind A.] NIAAA, Div Epidemiol & Prevent Res, NIH, Bethesda, MD 20892 USA. [Falk, Daniel E.] CSR Inc, Arlington, VA USA. [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Grummer-Strawn, Laurence M.] Ctr Dis Control & Prevent, Div Nutr & Phys Act, Atlanta, GA USA. RP Breslow, RA (reprint author), NIAAA, Div Epidemiol & Prevent Res, NIH, 5635 Fishers Lane,Room 2860, Bethesda, MD 20892 USA. EM rbreslow@mail.nih.gov NR 12 TC 11 Z9 12 U1 1 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1556-8253 J9 BREASTFEED MED JI Breastfeed. Med. PD SEP PY 2007 VL 2 IS 3 BP 152 EP 157 DI 10.1089/bfm.2007.0012 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA V11LU UT WOS:000207533900005 PM 17903101 ER PT J AU Kann, MG AF Kann, Maricel G. TI Protein interactions and disease: computational approaches to uncover the etiology of diseases SO BRIEFINGS IN BIOINFORMATICS LA English DT Review DE computational biology; diseases; genes; phenotype; proteins; protein interactions ID HUMAN GENETIC-DISEASE; SIMPLE MENDELIAN DISORDERS; CO-EVOLUTIONARY ANALYSIS; FANCONI-ANEMIA PROTEINS; CYSTIC-FIBROSIS GENE; SACCHAROMYCES-CEREVISIAE; INTERACTION NETWORKS; HUNTINGTONS-DISEASE; FUNCTIONAL-ORGANIZATION; POLYGLUTAMINE TOXICITY AB The genomic era has been characterised by vast amounts of data from diverse sources, creating a need for new tools to extract biologically meaningful information. Bioinformatics is, for the most part, responding to that need. The sparseness of the genomic data associated with diseases, however, creates a new challenge. Understanding the complex interplay between genes and proteins requires integration of data from a wide variety of sources, i.e. gene expression, genetic linkage, protein interaction, and protein structure among others. Thus, computational tools have become critical for the integration, representation and visualization of heterogeneous biomedical data. Furthermore, several bioinformatics methods have been developed to formulate predictions about the functional role of genes and proteins, including their role in diseases. After an introduction to the complex interplay between proteins and genetic diseases, this review explores recent approaches to the understanding of the mechanisms of disease at the molecular level. Finally, because most known mechanisms leading to disease involve some form of protein interaction, this review focuses on the recent methodologies for understanding diseases through their underlying protein interactions. Recent contributions from genetics, protein structure and protein interaction network analyses to the understanding of diseases are discussed here. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. RP Kann, MG (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. EM kann@mail.nih.gov RI Kann, Maricel/E-5701-2012 FU Intramural NIH HHS NR 133 TC 93 Z9 94 U1 3 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD SEP PY 2007 VL 8 IS 5 BP 333 EP 346 DI 10.1093/bib/bbm031 PG 14 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 232QR UT WOS:000251034700006 PM 17638813 ER PT J AU Kim, KT Baird, K Davis, S Piloto, O Levis, M Li, L Chen, P Meltzer, P Small, D AF Kim, Kyu-Tae Baird, Kristin Davis, Sean Piloto, Obdulio Levis, Mark Li, Li Chen, Peili Meltzer, Paul Small, Donald TI Constitutive Fms-like tyrosine kinase 3 activation results in specific changes in gene expression in myeloid leukaemic cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Fms-like tyrosine kinase 3; Fms-like tyrosine kinase 3; internal tandem duplication; acute myeloid leukaemia; gene expression profile ID INTERNAL TANDEM DUPLICATION; TYROSINE KINASE INHIBITOR; ACUTE MYELOGENOUS LEUKEMIA; FLT3 GENE; CLINICAL RESISTANCE; SIGNALING PATHWAYS; 32D CELLS; IN-VITRO; MUTATION; TRANSFORMATION AB Constitutively activating internal tandem duplication (ITD) mutations of the receptor tyrosine kinase FLT3 (Fms-like tyrosine kinase 3) play an important role in leukaemogenesis. We have examined, by cDNA microarray analysis, the changes in gene expression induced by FLT3/ITD or constitutively activated wild type FLT3 signalling. A limited set of genes was consistently affected by FLT3 inhibition. In confirmation of their FLT3 dependence, these genes returned toward pretreatment levels of expression after reversal of FLT3 inhibition. Several of the most significantly affected genes are involved in the RAS/mitogen-activated protein kinase, Janus kinase/signal transducer and activator of transcription and phosphatidylinositol 3 kinase (PI3K)/AKT pathways. These data suggest that constitutively activated FLT3 works through multiple signal transduction pathways. PIM1, MYC and CCND3 were chosen from this gene set to explore their biological roles. Knock-down of these genes by small interfering RNA showed that these genes play important roles in constitutively activated FLT3 expressing cells. The alterations of the gene expression profiles in these cells help to further elucidate the mechanisms of FLT3-mediated leukaemogenesis. C1 Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21218 USA. NIH, NCI, Canc Res Ctr, Genet Branch, Bethesda, MD 20892 USA. RP Small, D (reprint author), CRB 251,1650 Orleans St, Baltimore, MD 21231 USA. EM donsmall@jhmi.edu OI Davis, Sean/0000-0002-8991-6458 FU NCI NIH HHS [CA100632, CA70970, CA90668] NR 44 TC 21 Z9 21 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2007 VL 138 IS 5 BP 603 EP 615 DI 10.1111/j.1365-2141.2007.06696.x PG 13 WC Hematology SC Hematology GA 197XS UT WOS:000248591100005 PM 17686054 ER PT J AU Giri, N Pitel, PA Green, D Alter, BP AF Giri, Neelam Pitel, Paul A. Green, David Alter, Blanche P. TI Splenic peliosis and rupture in patients with dyskeratosis congenita on androgens and granulocyte colony-stimulating factor SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE splenic peliosis; splenic rupture; anabolic steroids; haematopoietic growth factors; dyskeratosis congenita ID MULTIPLE-MYELOMA; PEGFILGRASTIM C1 NCI, NIH, Dept Hlth, Div Canc Epidemiol & Genet,Clin Genet Branch, Rockville, MD USA. NCI, NIH, Human Serv, Rockville, MD USA. Nemours Childrens Clin, Div Haematol Oncol, Jacksonville, FL USA. Feinberg Sch Med NW Univ, Div Haematol Oncol, Chicago, IL USA. RP Giri, N (reprint author), NCI, NIH, Dept Hlth, Div Canc Epidemiol & Genet,Clin Genet Branch, Rockville, MD USA. EM girin@mail.nih.gov NR 10 TC 15 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2007 VL 138 IS 6 BP 815 EP 817 DI 10.1111/j.1365-2141.2007.06718.x PG 3 WC Hematology SC Hematology GA 203EQ UT WOS:000248958300018 PM 17760812 ER PT J AU Waters, EA Weinstein, ND Colditz, GA Emmons, KM AF Waters, Erika A. Weinstein, Neil D. Colditz, Graham A. Emmons, Karen M. TI Aversion to side effects in preventive medical treatment decisions SO BRITISH JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article ID RISK COMMUNICATION; BREAST-CANCER; GRAPHICAL DISPLAYS; FREQUENCY FORMATS; INFORMATION; PROBABILITY; UNCERTAINTY; INSTRUCTION; NUMERACY; INTERNET AB Objectives. Individuals may be overly sensitive to the side effects of treatments aimed at preventing illness, in part because they have difficulty in evaluating situations with several possible outcomes that differ in probability. This study tested willingness to undergo a hypothetical preventive treatment and accuracy in determining the probability of harm from the treatment as a function of the presence of a side effect, the initial probability of harm, the format in which probabilities were presented (percentages or frequencies), and the presence or absence of a graphic. Design. The study was a factorial experiment involving 5,251 participants. Methods. Participants recruited from a health-oriented internet site read about a hypothetical cancer prevention treatment situation and were asked to indicate their willingness to accept this treatment and whether it would increase or decrease their overall risk of cancer. The net benefit of the treatment was the same in all conditions, whether or not it was associated with a small side effect. Results. The presence of information about a side effect dramatically decreased willingness to undergo preventive treatment and accuracy in evaluating the treatment's effects. Willingness and accuracy were not influenced by the initial probability of harm, whether the risk probability information was presented as frequencies (N in 100) or as percentages, or whether the initial risk was presented with a bar graph or an array of asterisks or stick figures. Conclusions. Individuals are highly averse to preventive treatments with even small side effects and have difficulty combining the likelihood of positive and negative outcomes to determine the treatment's overall benefits. C1 Rutgers State Univ, Dept Psychol, Piscataway, NJ 08855 USA. Rutgers State Univ, Dept Human Ecol, Piscataway, NJ 08855 USA. Harvard Univ, Brigham & Womens Hosp, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Waters, EA (reprint author), Canc Prevent Fellowship Program, Natl Canc Inst, 6130 Execut Blvd,EPN Ste 321, Rockville, MD 20852 USA. EM erika.a.waters@gmail.com RI Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Waters, Erika/0000-0001-7402-0133 NR 35 TC 9 Z9 9 U1 4 U2 7 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND SN 1359-107X J9 BRIT J HEALTH PSYCH JI Br. J. Health Psychol. PD SEP PY 2007 VL 12 BP 383 EP 401 DI 10.1348/135910706X115209 PN 3 PG 19 WC Psychology, Clinical SC Psychology GA 196TT UT WOS:000248505800005 PM 17640453 ER PT J AU Garland, M Hallahan, B Hibbein, JR Davis, JM AF Garland, M. Hallahan, B. Hibbein, J. R. Davis, J. M. TI Omega-3 fatty acid for recurrent self-harm: unanswered questions - Reply SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Letter C1 St Itas Hosp, Dublin, Ireland. Beaumont Hosp, Dept Psychiat, Beaumont, TX USA. Royal Coll Surgeons Ireland, Dublin 2, Ireland. NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. Univ Chicago, Inst Psychiat, Chicago, IL 60637 USA. RP Garland, M (reprint author), St Itas Hosp, Dublin, Ireland. EM mgarland@ireland.com NR 0 TC 0 Z9 0 U1 0 U2 2 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD SEP PY 2007 VL 191 BP 264 EP 264 DI 10.1192/bjp.191.3.264a PG 1 WC Psychiatry SC Psychiatry GA 209BB UT WOS:000249362000018 ER PT J AU Thomas, MB Chadha, R Glover, K Wang, XM Morris, J Brown, T Rashid, A Dancey, J Abbruzzese, JL AF Thomas, Melanie B. Chadha, Romil Glover, Katrina Wang, Xuemei Morris, Jeffrey Brown, Thomas Rashid, Asif Dancey, Janet Abbruzzese, James L. TI Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma SO CANCER LA English DT Article DE EGFR; hepatoma; HCC; signal transduction; chemotherapy; hepatocellular; erlotinib ID HEPATOCYTE GROWTH-FACTOR; CELL LUNG-CANCER; II TRIAL; HEPATIC RESECTION; CLINICAL-TRIALS; FACTOR RECEPTOR; LIVER GROWTH; GEMCITABINE; DOXORUBICIN; EXPRESSION AB BACKGROUND. Growth factor overexpression, including epidermal growth factor receptor (EGFR) expression, is common in hepatocellular cancers. Erlotimb is a receptor tyrosine kinase inhibitor with specificity for EGFR. The primary objective of this study was to determine the proportion of hepatocellular carcinoma (HCC) patients treated with erlotimb who were alive and progression-free (PFS) at 16 weeks of continuous treatment. METHODS. Patients with unresectable FICC, no prior systemic therapy, performance status (PS) of 0, 1, or 2, and Childs-Pugh (CP) cirrhosis A or B received oral erlotinib 150 mg daily for 28-day cycles. Tumor response was assessed every 2 cycles by using Response Evaluation Criteria in Solid Tumors (RECIST; National Cancer Institute Cancer Therapy Evaluation Program, Bethesda, Md) criteria. Patients accrued to either "low" or "high" EGFR expression cohorts; each colhort had stopping rules applied when there was a lack of efficacy. RESULTS. Forty FICC patients were enrolled. Median age was 64 years (range, 3383 years), sex distribution was 32 males and 8 females, performance scores were 40% PS 0, 55% PS 1, Childs-Pugh distribution was 75% A and 20% B. There were no complete or partial responses; however, 17 of 40 patients achieved stable disease at 16 weeks of continuous therapy. The PFS at 16 weeks was 43%, and the median overall survival (OS) was 43 weeks (10.75 months). No patients required dose reductions of eflotinib. No correlation between EGFR expression and outcome was found. CONCLUSIONS. Results of this study indicated that single-agent erlotimb is well tolerated and has modest disease-control benefit in HCC, manifested as modestly prolonged PFS and OS when compared with historical controls. Cancer 2007;110:1059-67. Published 2007American Cancer Society. C1 Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Unit 426, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. NCI, Canc Therapeut Evaluat Program, Bethesda, MD 20892 USA. RP Thomas, MB (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Unit 426, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM methomas@mdanderson.org FU NCI NIH HHS [N01 CM17003] NR 66 TC 202 Z9 213 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2007 VL 110 IS 5 BP 1059 EP 1067 DI 10.1002/cncr.22886 PG 9 WC Oncology SC Oncology GA 206NV UT WOS:000249191100017 PM 17623837 ER PT J AU Koyfman, SA Agrawal, M Garreft-Mayer, E Krohmal, B Wolf, E Emanuel, EJ Gross, CR AF Koyfman, Shlomo A. Agrawal, Manish Garreft-Mayer, Elizabeth Krohmal, Benjamin Wolf, Elizabeth Emanuel, Ezekiel J. Gross, Cary P. TI Risks and benefits associated with novel phase 1 oncology trial designs SO CANCER LA English DT Article DE phase 1; trial design; cancer; ethics ID I CLINICAL-TRIALS; CONTINUAL REASSESSMENT METHOD; INFORMED CONSENT; NONCYTOTOXIC AGENTS; ANTICANCER AGENTS; DRUG DEVELOPMENT; CANCER TRIALS; END-POINTS; ETHICS; CHEMOTHERAPY AB BACKGROUND. Although aggressive dose escalation strategies were designed to improve the risk-benefit profile of phase I oncology trials, they have not been adequately studied. The prevalence of several novel trial designs and their asso ciation with a variety of clinical endpoints was evaluated. METHODS. A review of the literature was performed to identify phase I oncology studies of cytotoxic agents published from 2002 through 2004. RESULTS. Of 955 phase I oncology articles initially identified, 149 Studies, comprising 4532 patients, were analyzed. Only 34% of studies utilized aggressive dose Department of Radiation Oncology, Cleveland escalation schemes, 22% permitted intrapatient dose escalation, and only 28% Clinic. Cleveland, Ohio. enrolled fewer than 3 patients to any dose level. Studies that allowed intrapatient 2 Department of Clinical Bioethics, Warren G. dose escalation or used fewer than 3 patients per dose were not associated with different rates of response or toxicity, nor did they increase the number of Institute, National Institutes of Health, Bethesda, patients who received the recommended phase 2 dose. However, aggressive dose Maryland. escalations were associated with increased rates of both hematologic (17% vs 10%) and nonhematologic (17% vs 13%) toxicity with similar response rates. Only Studies that used conservative dose escalation designs and those that studied U.S. Food and Drug Administration (FDA)-approved agents required fewer patients to complete a trial. Trials of FDA-approved agents were also associated 5 Department of General Internal Medicine, Yale with higher response rates than trials of non-FDA-approved agents (10% vs 2%), without all increased risk of toxicity. CONCLUSIONS. Several novel aggressive design strategies intended to improve the risk-benefit profile of phase I oncology trials are not associated with improved clinical outcome, and may be harmful in certain instances. Cancer 2007;110:1115-24. Published 2007American Cancer Society C1 Yale Univ, Sch Med, Primary Care Ctr, New Haven, CT 06520 USA. Cleveland Clin, Dept Radiat Oncol, Cleveland, OH 44106 USA. Warren G Maguson Clin Ctr, Dept Clin Bioeth, Bethesda, MD USA. NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. Johns Hopkins Univ, Dept Biostat, Baltimore, MD USA. Yale Univ, Sch Med, Dept Gen Internal Med, New Haven, CT USA. RP Gross, CR (reprint author), Yale Univ, Sch Med, Primary Care Ctr, 333 Cedar St,Box 208025, New Haven, CT 06520 USA. EM cary.gross@yale.edu FU NCI NIH HHS [1 K07 CA90402]; NIA NIH HHS [P30 AG21342] NR 37 TC 26 Z9 27 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2007 VL 110 IS 5 BP 1115 EP 1124 DI 10.1002/cncr.22878 PG 10 WC Oncology SC Oncology GA 206NV UT WOS:000249191100023 PM 17628485 ER PT J AU Sharifi, N Figg, WD AF Sharifi, Nima Figg, William D. TI Androgen receptor modulation - Lessons learned from beyond the prostate SO CANCER BIOLOGY & THERAPY LA English DT Article DE androgen receptor; trinucleotide repeat; prostate cancer; spinal and bulbar muscular atrophy; steroid receptor; hormonal therapy; testosterone ID BULBAR MUSCULAR-ATROPHY; CANCER AB Androgen receptor (AR) is an important transcription factor in prostatic diseases, such as prostate cancer and benign prostatic hyperplasia (BPH). AR regulates the growth and survival of both benign and cancerous prostate epithelial cells. Therefore, modulation of AR function is an important means of treating prostatic diseases. Modern pharmacotherapy for these diseases includes, for example, medical castration and AR antagonists for prostate cancer and 5-alpha-reductase inhibitors for BPH. However, these treatments have limitations and are illustrated by AR reactivation after medical castration for prostate cancer, commonly termed castrate-resistant prostate cancer. A novel method of AR modulation has been demonstrated in spinal and bulbar muscular atrophy, a disease defined by a polyglutamine repeat expansion which leads to gain-of-function changes in AR and neuromuscular pathology. Here, we examine recent findings from the description of a compound that degrades AR and induces dissociation of AR from an AR coactivator. The biochemistry of this compound may have implications for prostate cancer. C1 [Sharifi, Nima; Figg, William D.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Sharifi, N (reprint author), NCI, Med Oncol Branch, Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM nima.sharifi@nih.gov; wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS NR 12 TC 1 Z9 1 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD SEP PY 2007 VL 6 IS 9 BP 1358 EP 1359 PG 2 WC Oncology SC Oncology GA 252GL UT WOS:000252434900014 PM 17881894 ER PT J AU Cho, SY Fox, E McCully, C Bauch, J Marsh, K Balis, FM AF Cho, Steve Y. Fox, Elizabeth McCully, Cynthia Bauch, Joy Marsh, Kennan Balis, Frank M. TI Plasma and cerebrospinal fluid pharmacokinetics of intravenously administered ABT-751 in non-human primates SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE ABT-751; cerebrospinal fluid; non-human primate; pharmacokinetics; tubulin; microtubule ID PENETRATION; SULFONAMIDE; INHIBITION; AGENT; E7010 AB Purpose ABT-751 is an orally bioavailable sulfonamide that binds to the colchicine binding site on beta-tubulin and inhibits microtubule polymerization. The plasma and cerebrospinal fluid (CSF) pharmacokinetics of ABT-751, after a short intravenous infusion, were evaluated in a non-human primate (Macaca mulatta) model that is highly predictive of the CSF penetration of drugs in humans. Materials and methods Plasma and CSF samples were collected over 24 h after 7.5 mg/kg (150 mg/m(2)) ABT-751 infused over 0.25-0.70 h, and ABT-751 concentrations in plasma and CSF were quantified using a validated HPLC-MS/MS assay. Pharmacokinetic parameters in plasma and CSF were derived using non-compartmental methods. Results and conclusion Plasma disappearance was bi-exponential with a terminal half-life of 13 h. The mean +/- SD clearance was 100 +/- 18 ml/min m(2), the mean +/- SD volume of distribution at steady state was 1.3 +/- 0.5 l/kg, and the mean +/- SD mean residence time was 4.6 +/- 1.8 h. The mean +/- SD peak ABT-751 concentration in CSF was 0.26 +/- 0.08 mu M, and the mean +/- SD CSF half-life of 1.3 +/- 0.3 h. CSF penetration was limited (mean +/- SD AUC(CSF):AUC(plasma), 1.1 +/- 0.3%) relative to total (protein-bound + free) plasma drug concentrations, but the CSF concentrations approximated the estimated free drug concentrations in plasma. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Abbott Labs, Abbott Pk, IL 60064 USA. RP Balis, FM (reprint author), NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. EM balisf@nih.gov FU Intramural NIH HHS NR 14 TC 2 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 2007 VL 60 IS 4 BP 563 EP 567 DI 10.1007/s00280-006-0402-7 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 191MG UT WOS:000248134700012 PM 17187251 ER PT J AU Brinton, LA Lacey, JV AF Brinton, Louise A. Lacey, James V., Jr. TI Hormones and breast cancer: What's the story? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID PROGESTIN-REPLACEMENT THERAPY; ESTROGEN PLUS PROGESTIN; HEALTHY POSTMENOPAUSAL WOMEN; RANDOMIZED CONTROLLED-TRIAL; UNITED-STATES; DIFFERENT REGIMENS; RISK-FACTORS; HYSTERECTOMY; MAMMOGRAPHY; MENOPAUSE C1 NCI, NIH, DCEG, Hormonal & Reprod Epidemiol Branch, Rockville, MD 20852 USA. RP Brinton, LA (reprint author), NCI, NIH, DCEG, Hormonal & Reprod Epidemiol Branch, 6120 Execut Blvd,EPS 5018,MSC 7234, Rockville, MD 20852 USA. EM brinton@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 31 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2007 VL 16 IS 9 BP 1697 EP 1699 DI 10.1158/1055-9965.EPI-07-0700 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 213CN UT WOS:000249643600001 PM 17855684 ER PT J AU Troisi, R Potischman, N Hoover, RN AF Troisi, Rebecca Potischman, Nancy Hoover, Robert N. TI Exploring the underlying hormonal mechanisms of prenatal risk factors for breast cancer: A review and commentary SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID GROWTH-FACTOR-I; UMBILICAL-CORD SERUM; ASIAN-AMERICAN WOMEN; HUMAN CHORIONIC-GONADOTROPIN; HUMAN PLACENTAL-LACTOGEN; FACTOR-BINDING PROTEIN-1; BODY-MASS INDEX; CIRCULATING ANGIOGENIC FACTORS; MATERNAL PLASMA-CONCENTRATIONS; URINARY ESTRIOL EXCRETION AB Prenatal factors have been hypothesized to influence subsequent breast cancer development. Directly evaluating the associations of in utero exposures with risk, however, presents several methodologic and theoretical challenges, including the long induction period between exposure and disease and the lack of certainty regarding the critical timing of exposure. Indirect evaluation of these associations has been achieved by use of proxies such as gestational and neonatal characteristics. Evidence suggests that pre-eclampsia is associated with a reduced breast cancer risk, whereas high birth weight and dizygotic twinning seem associated with an increased risk. Asians born in Asia have substantially lower breast cancer risks than women born in the West. Although data thus far are few, what exists is not consistent with a unifying hypothesis for a particular biological exposure (such as estrogens or androgens) during pregnancy as mediating the observed associations between pregnancy factors and breast cancer risk. This suggests that additional studies of prenatal factors should seek to broaden the range of hormones, growth, and other endocrine factors that are evaluated in utero. Once candidate biomarkers are identified, assessing them with respect to breast cancer and with intermediate end points in carcinogenesis should be a priority. In addition, investigations should explore the possibility that in utero exposures may not act directly on the breast, but may alter other physiologic pathways such as hormone metabolism that have their effect on risk later in life. C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH USA. RP Troisi, R (reprint author), Dartmouth Hitchcock Med Ctr, Room 854,7297 Rubin Bldg,1 Med Ctr Dr, Lebanon, NH 03756 USA. EM troisir@mail.nih.gov NR 199 TC 31 Z9 32 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2007 VL 16 IS 9 BP 1700 EP 1712 DI 10.1158/1055-9965.EPI-07-0073 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 213CN UT WOS:000249643600002 PM 17855685 ER PT J AU Faupel-Badger, JM Hsieh, CC Troisi, R Lagiou, P Potischman, N AF Faupel-Badger, Jessica M. Hsieh, Chung-Cheng Troisi, Rebecca Lagiou, Pagona Potischman, Nancy TI Plasma volume expansion in pregnancy: Implications for biomarkers in population studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID BREAST-CANCER RISK; HORMONAL CHANGES; BLOOD-VOLUME; WHITE WOMEN; PREECLAMPSIA; CHINESE; WEIGHT; SHANGHAI; ESTROGEN; ANEMIA AB There is a growing body of literature focused on endogenous hormone exposures during pregnancy and subsequent cancer risk for both mother and offspring. Examples of these studies include those focused on the biological mechanism for the association of pre-eclampsia with reduced risk of breast cancer for mother and female offspring or studies that have examined hormone concentrations during pregnancy between different ethnic groups who vary in their rates of breast cancer incidence. Although these studies seem relatively straightforward in conception and analysis, measurement of the concentration of hormones and other biomarkers in pregnant subjects is influenced by plasma volume expansion (PVE). During pregnancy, the maternal plasma volume expands 45% on average to provide for the greater circulatory needs of the maternal organs. Consequently, serum protein and hormone concentrations are greatly altered when comparing the pregnant with nonpregnant state. Assessing PVE also is complicated by the vast individual variation in PVE, ranging from minimal to a 2-fold increase. We propose that PVE needs to be evaluated when comparing biomarker concentrations during pregnancy in two populations that may differ with respect to PVE. Small body size is associated with lower PVE compared with higher body size. Therefore, we hypothesize that variation in PVE will influence the interpretation of differences in biomarker concentrations across population groups with respect to the etiologic significance of the biomarker to the disease under study (e.g., breast cancer). It is possible that some observations may be due only to differences in dilution between the two groups. We present PVE as a topic for consideration in population-based studies, examples of the types of studies where PVE may be relevant, and our own analysis of one such study in the text below. C1 NCI, Mamary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Univ Athens, Sch Med, Dept Hyg & Epidemiol, GR-11527 Athens, Greece. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Faupel-Badger, JM (reprint author), NCI, Mamary Biol & Tumorigenesis Lab, Ctr Canc Res, MSC 4254,37 Convent Dr, Bethesda, MD 20892 USA. EM badger@mail.nih.gov NR 38 TC 34 Z9 34 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2007 VL 16 IS 9 BP 1720 EP 1723 DI 10.1158/1055-9965.EPI-07-0311 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 213CN UT WOS:000249643600004 PM 17855687 ER PT J AU McBride, CM Brody, LC AF McBride, Colleen M. Brody, Lawrence C. TI Point: Genetic risk feedback for common disease - Time to test the waters SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY; SMOKING; SMOKERS; CANCER; LOCI C1 NIH, NHGRI, Bethesda, MD 20892 USA. RP McBride, CM (reprint author), NIH, NHGRI, 31 Ctr Dr,Bldg 31,Room B2B37, Bethesda, MD 20892 USA. EM cmcbride@mail.nih.gov NR 12 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2007 VL 16 IS 9 BP 1724 EP 1726 DI 10.1158/1055-9965.EPI-07-0102 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 213CN UT WOS:000249643600005 PM 17855688 ER PT J AU Lanza, E Yu, BB Murphy, G Albert, PS Caan, B Marshall, JR Lance, P Paskett, ED Weissfeld, J Slattery, M Burt, R Iber, F Shike, M Kikendall, JW Brewer, BK Schatzkin, A AF Lanza, Elaine Yu, Binbing Murphy, Gwen Albert, Paul S. Caan, Bette Marshall, James R. Lance, Peter Paskett, Electra D. Weissfeld, Joel Slattery, Marty Burt, Randall Iber, Frank Shike, Moshe Kikendall, James W. Brewer, Brenda K. Schatzkin, Arthur CA Polyp Prevention Trial Study Grp TI The polyp prevention trial-continued follow-up study: No effect of a low-fat, high-fiber, high-fruit, and -vegetable diet on adenoma recurrence eight years after randomization SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SURROGATE END-POINTS; COLORECTAL-CANCER; CARCINOMA SEQUENCE; LIFE-STYLE; RISK; TUMORIGENESIS; QUESTIONNAIRE; INTERVENTION; POLYPECTOMY; NUTRITION AB The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial to evaluate the effects of a high-fiber (18 g/1,000 kcal), high-fruit and -vegetable (3.5 servings/1,000 kcal), and low-fat (20% of total energy) diet on the recurrence of adenomatous polyps in the large bowel over a period of 4 years. Although intervention participants reported a significantly reduced intake of dietary fat, and increased fiber, fruit, and vegetable intakes, their risk of recurrent adenomas was not significantly different from that of the controls. Since the PPT intervention lasted only 4 years, it is possible that participants need to be followed for a longer period of time before treatment differences in adenoma recurrence emerge, particularly if diet affects early events in the neoplastic process. The PPT Continued Follow-up Study (PPT-CFS) was a post-intervention observation of PPT participants for an additional 4 years from the completion of the trial. Of the 1,905 PPT participants, 1,192 consented to participate in the PPT-CFS and confirmed colonoscopy reports were obtained on 801 participants. The mean time between the main trial end point colonoscopy and the first colonoscopy in the PPT-CFS was 3.94 years (intervention group) and 3.87 years (control group). The baseline characteristics of 405 intervention participants and 396 control participants in the PPT-CFS were quite similar. Even though the intervention group participants increased their fat intake and decreased their intakes of fiber, fruits, and vegetables during the PPT-CFS, they did not go back to their prerandomization baseline diet (P < 0.001 from paired t tests) and intake for each of the three dietary goals was still significantly different from that in the controls during the PPT-CFS (P < 0.001 from t tests). As the CFS participants are a subset of the people in the PPT study, the nonparticipants might not be missing completely at random. Therefore, a multiple imputation method was used to adjust for potential selection bias. The relative risk (95% confidence intervals) of recurrent adenoma in the intervention group compared with the control group was 0.98 (0.88-1.09). There were no significant intervention-control group differences in the relative risk for recurrence of an advanced adenoma (1.06; 0.81-1.39) or multiple adenomas (0.92; 0.77-1.10). We also used a multiple imputation method to examine the cumulative recurrence of adenomas through the end of the PPT-CFS: the intervention-control relative risk (95% confidence intervals) for any adenoma recurrence was 1.04 (0.98-1.09). This study failed to show any effect of a low-fat, high-fiber, high-fruit and -vegetable eating pattern on adenoma recurrence even with 8 years of follow-up. C1 NCI, Ctr Canc Res, Lab Can Prevent, Bethesda, MD 20892 USA. Informat Management Serv Inc, Rockville, MD USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. Kaiser Fdn Res Inst, Oakland, CA USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Utah, Salt Lake City, UT USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Vet Affairs Med Ctr, Hines, IL 60141 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Westat Corp, Rockville, MD 20850 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Murphy, G (reprint author), NCI, Ctr Canc Res, Lab Can Prevent, 6116 Execut Blvd,Room 7206, Bethesda, MD 20892 USA. EM murphygw@mail.nih.gov RI Murphy, Gwen/G-7443-2015 NR 40 TC 48 Z9 49 U1 5 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2007 VL 16 IS 9 BP 1745 EP 1752 DI 10.1158/1055-9965.EPI-07-0127 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 213CN UT WOS:000249643600009 PM 17855692 ER PT J AU Hong, CC Ambrosone, CB Ahn, JY Choi, JY McCullough, ML Stevens, VL Rodriguez, C Thun, MJ Calle, EE AF Hong, Chi-Chen Ambrosone, Christine B. Ahn, Jiyoung Choi, Ji-Yeob McCullough, Marjorie L. Stevens, Victoria L. Rodriguez, Carmen Thun, Michael J. Calle, Eugenia E. TI Genetic variability in iron-related oxidative stress pathways (Nrf2, NQ01, NOS3, and HO-1), iron intake, and risk of postmenopausal breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID NITRIC-OXIDE SYNTHASE; HUMAN-SKIN FIBROBLASTS; HEME OXYGENASE SYSTEM; II NUTRITION COHORT; DIETARY IRON; MICROSATELLITE POLYMORPHISM; SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; VEGETABLE CONSUMPTION; CIGARETTE-SMOKING AB Oxidative stress resulting from excess reactive oxygen species and/or deficiencies in antioxidant capabilities may play a role in breast cancer etiology. In a nested case-control study of postmenopausal women (505 cases and 502 controls) from the American Cancer Society Prevention 11 Nutrition Cohort, we examined relationships between breast cancer risk and genetic polymorphisms of enzymes involved in the generation and removal of iron-mediated reactive oxygen species. Using unconditional logistic regression, genetic variations in Nrf2 (11108C>T), NQ01 (609C>T), NOS3 (894G>T), and HO-1 [(GT)(n) dinucleotide length polymorphism] were not associated with breast cancer risk in a multivariate model. A significant dose trend (P trend = 0.04), however, was observed for total number of putative "at-risk" alleles (Nrf T, NQO1 T, NOS T, and HO-1 LL and LM genotypes), with those carrying three or more at-risk alleles having an odds ratio (OR) of 1.56 [95% confidence interval (95% CI), 0.97-2.51] compared with those having none. When examined in relation to iron, carriage of three or more high-risk alleles in the highest tertile of iron intake (OR, 2.27; 95% CI, 0.97-5.29; P trend = 0.02; P interaction = 0.30) or among users of supplemental iron (OR, 2.39; 95% CI, 1.09-5.26; P trend = 0.02; P interaction = 0.11) resulted in a greater than 2-fold increased risk compared with women with no high-risk alleles. Increased risk was also observed among supplement users with the HO-1 LL or LM genotypes (OR, 1.56; 95% CI, 1.01-2.41; P interaction = 0.32) compared with S allele carriers; and MM genotypes combined. These results indicate that women with genotypes resulting in potentially higher levels of iron-generated oxidative stress may be at increased risk of breast cancer and that this association may be most relevant among women with high iron intake. C1 Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. RP Hong, CC (reprint author), Roswell Pk Canc Inst, Dept Canc Prevent & Control, Elm & Carlton St, Buffalo, NY 14263 USA. EM Chi-Chen.Hong@roswellpark.org RI Choi, Ji-Yeob/J-2796-2012 NR 106 TC 61 Z9 63 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2007 VL 16 IS 9 BP 1784 EP 1794 DI 10.1158/1055-9965.EPI-07-0247 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 213CN UT WOS:000249643600014 PM 17726138 ER PT J AU Trivers, KF Gammon, MD Abrahamson, PE Lund, MJ Flagg, EW Moorman, PG Kaufman, JS Cai, JW Porter, PL Brinton, LA Eley, JW Coates, RJ AF Trivers, Katrina F. Gammon, Marilie D. Abrahamson, Page E. Lund, Mary Jo Flagg, Elaine W. Moorman, Patricia G. Kaufman, Jay S. Cai, Jianwen Porter, Peggy L. Brinton, Louise A. Eley, J. William Coates, Ralph J. TI Oral contraceptives and survival in breast cancer patients aged 20 to 54 years SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID YOUNGER WOMEN; RISK-FACTORS; BODY SIZE; PROGNOSIS; RECURRENCE; CARCINOMA; DIAGNOSIS; MORTALITY; STEROIDS; POTENCY AB Recent oral contraceptive (00 use is associated with modestly higher breast cancer incidence among younger women, but its impact on survival is unclear. This study examined the relationship between OC use before breast cancer diagnosis and survival. A population-based sample of 1,264 women aged 20 to 54 years with a first primary invasive breast cancer during 1990 to 1992 were followed up for 8 to 10 years. OC and covariate data were obtained by interviews conducted shortly after diagnosis and from medial records. All cause mortality was ascertained through the National Death Index (n = 292 deaths). Age- and income-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox regression methods. All-cause mortality was not associated with ever use of OCs or duration of use. Compared with nonusers, mortality estimates were elevated among women who were using OCs at diagnosis or stopped use in the previous year (HR, 1.57; 95% CI, 0.95-2.61). The HR for use of high-dose estrogen pills within 5 years before diagnosis was double that of nonusers (HR, 2.39; 95% CI, 1.29-4.41) or, if the most recent pill included the progestin levonorgestrel, compared with nonusers (HR, 2.01; 95% CI, 1.03-3.91). Because subgroup estimates were based on small numbers of OC users, these results should be cautiously interpreted. Overall, most aspects of OC use did not seem to influence survival, although there is limited evidence that OC use just before diagnosis, particularly use of some pill types, may negatively impact survival in breast cancer patients aged 20 to 54 years. C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Div Human Biol, Seattle, WA 98104 USA. Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Div Global Migrat, Surveillance & Epidemiol Branch, Atlanta, GA USA. Div Quarantine, Surveillance & Epidemiol Branch, Atlanta, GA USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Emory Univ, Sch Med, Winship Canc Ctr, Atlanta, GA 30322 USA. Duke Univ, Med Ctr, Dept Community & Family Med, Canc Prevent & Control Res Program, Durham, NC 27710 USA. NIH, Div Canc Epidemiol & Genet, NCI, Bethesda, MD 20892 USA. NIH, Dept Hlth, Bethesda, MD 20892 USA. NIH, Human Serv, Bethesda, MD 20892 USA. RP Trivers, KF (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, 4770 Buford Highway,NE,MS K-52, Atlanta, GA 30341 USA. EM ktrivers@cdc.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [R25 CA57726, T32 CA09330]; NIEHS NIH HHS [P30ES10126] NR 39 TC 11 Z9 11 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2007 VL 16 IS 9 BP 1822 EP 1827 DI 10.1158/1055-9965.EPI-07-0053 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 213CN UT WOS:000249643600018 PM 17855700 ER PT J AU Kaae, J Wohlfahrt, J Boyd, HA Wulf, HC Biggar, RJ Melbye, M AF Kaae, Jeanette Wohlfahrt, Jan Boyd, Heather A. Wulf, Hans Christian Biggar, Robert J. Melbye, Mads TI The impact of autoimmune diseases on the incidence and prognosis of cutaneous malignant melanoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DOSE INTERFERON-ALPHA-2B; RHEUMATOID-ARTHRITIS; THYROID-DYSFUNCTION; RENAL-CARCINOMA; INTERLEUKIN-2; HYPOTHYROIDISM; IMMUNOTHERAPY; RISK; THERAPY AB Background: Persons being treated with IFN alpha-2b for advanced cutaneous malignant melanoma (CMM) have been reported to have a greatly improved prognosis if they develop autoantibodies or clinical signs of autoimmunity during therapy. Consequently, we examined whether autoimmune diseases might also be associated with lower CMM incidence and better prognosis. Methods: We established a study cohort based on the entire Danish population, obtaining information on CMM and autoimmune diseases from the Danish national registers. Using log-linear regression models adjusting for age, period, and sex, we compared CMM incidence and CMM-specific mortality rates in persons with and without a history of autoimmune disease. Results: Between 1977 and 2003, 20,482 cases of CMM were registered in the Danish Cancer Register. Previously diagnosed autoimmune diseases did not affect the incidence of CMM (incidence rate ratio, 1.0; 95% confidence interval, 0.9-1.1). In the first 5 years after CMM diagnosis, we observed 8,957 deaths in individuals with CMM (5,181 expected). CMM-specific mortality rates 1 to 5 years after diagnosis were similar in CMM patients with and without autoimmune diseases (mortality rate ratio, 0.9; 95% confidence interval, 0.7-1.2). Conclusions: Autoimmune conditions were not associated with CMM incidence or prognosis. The better CMM prognosis previously observed when autoantibodies or clinical signs of autoimmunity developed during IFN alpha-2b therapy may have been related to variation in individual responses to this therapy, with individuals sensitive to treatment exhibiting more signs of autoimmunity but also (independently) experiencing greater antitumor responses as a result of treatment. C1 Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen S, Denmark. Bispebjerg Hosp, Dept Dermatol, DK-2400 Copenhagen, Denmark. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Kaae, J (reprint author), Statens Serum Inst, Dept Epidemiol Res, Artillerivej 5, DK-2300 Copenhagen S, Denmark. EM jtk@ssi.dk NR 21 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2007 VL 16 IS 9 BP 1840 EP 1844 DI 10.1158/1055-9965.EPI-07-0459 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 213CN UT WOS:000249643600021 PM 17855703 ER PT J AU Lubin, JH Caporaso, N Hatsukami, DK Joseph, AM Hecht, SS AF Lubin, Jay H. Caporaso, Neil Hatsukami, Dorothy K. Joseph, Anne M. Hecht, Stephen S. TI The association of a tobacco-specific biomarker and cigarette consumption and its dependence on host characteristics SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FAGERSTROM TOLERANCE QUESTIONNAIRE; DOSE-RESPONSE RELATIONSHIP; MODELING TOTAL EXPOSURE; URINARY METABOLITES; LUNG CARCINOGEN; NICOTINE DEPENDENCE; COTININE LEVELS; BLADDER-CANCER; SMOKING STATUS; WHITE SMOKERS AB The tobacco-specific nitrosamine 4-(methylnitrosamino)1-(3-pyridyl)-1-butanone (NNK) is a potent carcinogen, which can be characterized by urinary concentrations of the metabolite 4-(methylnitrosamino)-1-(3-pyridyl)butanol (NNAL) and its glucuronide. Using baseline data in current smokers from four clinical trials, we examine the associations of urinary cotinine with CPD and of total NNAL with cotinine and the modification of these associations by several host factors. There was a linear relationship between ln(cotinine) and ln(CPD) within categories of the Fagerstrom Test of Nicotine Dependence and of age. The increasing trend was significantly smaller for subjects with high and very high nicotine addiction and for older subjects and larger in females than males. The regression of In(total NNAL/cotinine) on In(cotinine) declined linearly, suggesting reduced NNK uptake per unit cotinine with increasing cotinine. The decline in trend was greater in subjects with increased CPD, with greater nicotine addiction, and at older ages and was smaller in females, although gender differences were small. Variations in the ratio with host characteristics were generally similar to a recent epidemiologic analysis of effect modification of the association between lung cancer and cigarette smoking. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Minnesota, Transdisciplinary Tobacco Res Ctr, Minneapolis, MN USA. Ctr Canc, Minneapolis, MN USA. RP Lubin, JH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA. EM lubinj@mail.nih.gov OI Hecht, Stephen/0000-0001-7228-1356 FU Intramural NIH HHS; NIDA NIH HHS [P50 DA013333] NR 31 TC 20 Z9 20 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2007 VL 16 IS 9 BP 1852 EP 1857 DI 10.1158/1055-9965.EPI-07-0018 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 213CN UT WOS:000249643600023 PM 17855705 ER PT J AU Abnet, CC Chen, W Dawsey, SM Wei, WQ Roth, MJ Liu, B Lu, N Taylor, PR Qiao, YL AF Abnet, Christian C. Chen, Wen Dawsey, Sanford M. Wei, Wen-Qiang Roth, Mark J. Liu, Bing Lu, Ning Taylor, Philip R. Qiao, You-Lin TI Serum 25(OH)-Vitamin D concentration and risk of esophageal squamous dysplasia SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID VITAMIN-D STATUS; GASTRIC CANCERS; CELL CARCINOMA; CHINA; LINXIAN; MORTALITY; AREA AB Background: Squamous dysplasia is the precursor lesion for esophageal squamous cell carcinoma, and nutritional factors play an important role in the etiology of this cancer. Previous studies using a variety of measures for vitamin D exposure have reached different conclusions about the association between vitamin D and the risk of developing esophageal cancer. Methods: We measured serum 25-hydroxyvitamin D [25(OH)D] concentrations in a cross-sectional analysis of 720 subjects from Linxian, China, a population at high risk for developing esophageal squamous cell carcinoma. All subjects underwent endoscopy and biopsy and were categorized by the presence or absence of histologic squamous dysplasia. We used crude and multivariate-adjusted generalized linear models to estimate the relative risks (RR) and 95% confidence intervals (95% CI) for the association between squamous dysplasia and sex-specific quartiles of serum 25(OH)D concentration. Results: Two-hundred and thirty of 720 subjects (32%) had squamous dysplasia. Subjects with dysplasia had significantly higher median serum 25(OH)D concentrations than subjects without dysplasia, 36.5 and 31.5 nmol/L, respectively (Wilcoxon two-sample test, P = 0.0004). In multivariate-adjusted models, subjects in the highest compared with the lowest quartiles were at a significantly increased risk of squamous dysplasia (1111, 1.86; 95% CI, 1.35-2.62). Increased risks were similar when examined in men and women separately: men (RR, 1.74; 95% CI, 1.08-2.93); women (RR, 1.96; 95% CI, 1.28-3.18). Conclusions: Higher serum 25(OH)D concentrations were associated with significantly increased risk of squamous dysplasia. No obvious source of measured or unmeasured confounding explains this finding. C1 Div Canc Epidemiol & Genet, Nutrit Epidemiol Branch, Rockville, MD 20852 USA. Chinese Acad Med Sci, Inst Canc, Dept Canc Epidemiol, Beijing 100021, Peoples R China. Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. Chinese Acad Med Sci, Canc Inst Hosp, Beijing 100037, Peoples R China. RP Abnet, CC (reprint author), Div Canc Epidemiol & Genet, Nutrit Epidemiol Branch, 6120 Execut Blvd,EPS-320,MSC 7232, Rockville, MD 20852 USA. EM abnetc@mail.nih.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 FU Intramural NIH HHS [ZIA CP000185-05] NR 22 TC 37 Z9 37 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2007 VL 16 IS 9 BP 1889 EP 1893 DI 10.1158/1055-9965.EPI-07-0461 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 213CN UT WOS:000249643600028 PM 17855710 ER PT J AU Chakraborty, M Schlom, J Hodge, JW AF Chakraborty, Mala Schlom, Jeffrey Hodge, James W. TI The combined activation of positive costimulatory signals with modulation of a negative costimulatory signal for the enhancement of vaccine-mediated T-cell responses SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE CTLA-4; costimulation; vaccine ID COLONY-STIMULATING FACTOR; CARCINOEMBRYONIC ANTIGEN GENE; CTLA-4 BLOCKADE; METASTATIC MELANOMA; SELF-ANTIGEN; COMBINATION IMMUNOTHERAPY; ANTITUMOR RESPONSES; IMMUNE-RESPONSES; TUMOR; CANCER AB Blockade of CTLA-4 by monoclonal antibodies (mAb) can mediate regression of tumors and increase the efficacy of tumor antigen specific vaccines. Blockade of CTLA-4 has also been shown to significantly increase the avidity of antigen-specific T cells after immunization with live recombinant viral vector based vaccine. Here, we demonstrate a biological synergy between CTLA-4 blockade and active vaccine therapy consisting of recombinant vaccinia and avipox viruses expressing carcinoembryonic antigen (CEA) and three T cell costimulatory molecules to enhance antitumor effects. However, this synergy was very much dependent on the temporal relationship of scheduling of the two agents. We evaluated the strategies in both a foreign antigen model using beta-galactosidase as immunogen, and in a "self" antigen model using CEA as immunogen. For antitumor activity the model used consisted of mice transgenic for human CEA and a murine carcinoma cell line transfected with CEA. The enhanced antitumor activity after vaccine and CTLA-4 blockade did not result in any signs of autoimmunity. These studies form a rational basis for the use of vector-based vaccines with anti-CTLA-4 and demonstrate that both enhancement of positive costimulatory signals and inhibition of negative costimulatory signals can be simultaneously exploited. These studies also underscore the importance of "drug" scheduling in vaccine combination therapies. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr Room 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 FU Intramural NIH HHS NR 49 TC 20 Z9 21 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD SEP PY 2007 VL 56 IS 9 BP 1471 EP 1484 DI 10.1007/s00262-007-0291-6 PG 14 WC Oncology; Immunology SC Oncology; Immunology GA 186MU UT WOS:000247783600013 PM 17318654 ER PT J AU Jarboe, JS Johnson, KR Choi, Y Lonser, RR Park, JK AF Jarboe, John S. Johnson, Kory R. Choi, Yong Lonser, Russell R. Park, John K. TI Expression of interleukin-13 receptor alpha 2 in glioblastoma multiforme: Implications for targeted therapies SO CANCER RESEARCH LA English DT Article ID HUMAN GLIOMA-CELLS; RESTRICTIVE RECEPTOR; MALIGNANT GLIOMAS; BRAIN; PROTEIN; CANCER; TUMORS AB Glioblastoma multiforme is the most common primary malignant brain tumor and despite treatment with surgery, radiation, and chemotherapy, the median survival of patients with glioblastoma multiforme is similar to I year. Glioblastoma multiforme explants and cell lines have been reported to overexpress the interleukin-13 receptor alpha 2 subunit (ILI3R alpha 2) relative to nonneoplastic brain. Based on this finding, a recombinant cytotoxin composed of IL13 ligand and a truncated form of Pseudomonas aeraginosa exotoxin A (IL-PE38QQR) was developed for the targeted treatment of glioblastoma multiforme tumors. In a recently completed phase III clinical trial, however, IL13-PE38QQR was found to be no more effective than an existing therapy in prolonging survival. To determine possible explanations for this result, we analyzed the relative expression levels of IL13R alpha 2 in glioblastoma multiforme and nonneoplastic brain specimens using publicly available oligonucleotide microarray databases, quantitative real-time reverse transcription PCR, and inummohistochemical staining. Increased expression of the IL13R alpha 2 gene relative to nonneoplastic brain was observed in 36 of 81 (44%) and 8 of 17 (47%) tumor specimens by microarray and quantitative real-time reverse transcription PCR analyses, respectively. Inummohistochemical staining of tumor specimens showed highly variable expression of IL13R alpha 2 protein both within and across specimens. These data indicate that prescreening of subjects may he of benefit in future trials of IL13R alpha 2 targeting therapies. C1 NINDS, Surg & Mol Neurooncol Unit, NIH, Bethesda, MD 20892 USA. NINDS, Bioinformat Grp, Intranural Informat Technol Program, Div Intramural Res,NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Park, JK (reprint author), NINDS, Surg & Mol Neurooncol Unit, NIH, Room 2B-1002,35 Convent Dr,MSC 3706, Bethesda, MD 20892 USA. EM parkjk@ninds.nih.gov FU Intramural NIH HHS NR 19 TC 53 Z9 53 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2007 VL 67 IS 17 BP 7983 EP 7986 DI 10.1158/0008-5472.CAN-07-1493 PG 4 WC Oncology SC Oncology GA 209RW UT WOS:000249406700010 PM 17804706 ER PT J AU Caudell, D Zhang, ZH Chung, YJ Aplan, PD AF Caudell, David Zhang, Zhenhua Chung, Yang Jo Aplan, Peter D. TI Expression of a CALM-AF10 fusion gene leads to Hoxa cluster overexpression and acute leukemia in transgenic mice SO CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHROMOSOMAL TRANSLOCATION; T-ALL; MOLECULAR CHARACTERIZATION; BETHESDA PROPOSALS; CALM/AF10 FUSION; LEUCINE-ZIPPER; BONE-MARROW; STEM-CELL AB To assess the role of the CALM-AF10 fusion gene in leukemic transformation in vivo, we generated transgenic mice that expressed a CALM-AF10 fusion gene. Depending on the transgenic line, at least 40% to 50% of the F, generation mice developed acute leukemia at a median age of 12 months. Leukemic mice typically had enlarged spleens, invasion of parenchymal organs with malignant cells, and tumors with myeloid markers such as myeloperoxidase, Macl, and Gr1. Although most leukemias were acute myeloid leukemia, many showed lymphoid features, such as CD3 staining, or clonal Tcrb or Igh gene rearrangements. Mice were clinically healthy for the first 9 months of life and had normal peripheral blood hemograms but showed impaired thymocyte differentiation, manifested by decreased CD4(+)/CDS+ cells and increased immature CD4(-)/CD8(-) cells in the thymus. Hematopoietic tissues from both clinically healthy and leukemic CALM-AF10 mice showed up-regulation of Hoxa cluster genes, suggesting a potential mechanism for the impaired differentiation. The long latency period and incomplete penetrance suggest that additional genetic events are needed to complement the CALM-AF10 transgene and complete the process of leukemic transformation. C1 Natl Canc Inst, NIH, Genet Branch, Bethesda, MD USA. Natl Canc Inst, NIH, Comparat Mol Pathol Unit, Bethesda, MD USA. Univ Maryland, Dept Vet Med Sci, College Pk, MD USA. RP Aplan, PD (reprint author), Navy 8, Room 5101, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM aplanp@mail.nih.gov RI Aplan, Peter/K-9064-2016 FU Intramural NIH HHS [Z01 SC010378-06] NR 42 TC 38 Z9 39 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2007 VL 67 IS 17 BP 8022 EP 8031 DI 10.1158/0008-5472.CAN-06-3749 PG 10 WC Oncology SC Oncology GA 209RW UT WOS:000249406700017 PM 17804713 ER PT J AU Deeb, KK Michalowska, AM Yoon, CY Krummey, SM Hoenerhoff, MJ Kavanaugh, C Li, MC Demayo, FJ Linnoila, I Deng, CX Lee, EYHP Medina, D Shih, JH Green, JE AF Deeb, Kristin K. Michalowska, Aleksandra M. Yoon, Cheol-yong Krummey, Scott M. Hoenerhoff, Mark J. Kavanaugh, Claudine Li, Ming-chung Demayo, Francesco J. Linnoila, Ilona Deng, Chu-xia Lee, Eva Y. -H. P. Medina, Daniel Shih, Joanna H. Green, Jeffrey E. TI Identification of an integrated SV40 T/t-antigen cancer signature in aggressive human breast, prostate, and lung carcinomas with poor prognosis SO CANCER RESEARCH LA English DT Article ID LARGE T-ANTIGEN; GENE-EXPRESSION PATTERNS; MAMMARY EPITHELIAL-CELLS; TRANSGENIC MICE; CELLULAR-TRANSFORMATION; MICROARRAY ANALYSIS; METASTATIC-DISEASE; FUSION GENE; TUMORS; MOUSE AB Understanding the genetic architecture of cancer pathways that distinguishes subsets of human cancer is critical to developing new therapies that better target tumors based on their molecular expression profiles. In this study, we identify an integrated gene signature from multiple transgenic models of epithelial cancers intrinsic to the functions of the Simian virus 40 T/t-antigens that is associated with the biological behavior and Prognosis for several human epithelial tumors. This genetic signature, composed primarily of genes regulating cell replication, proliferation, DNA repair, and apoptosis, is not a general cancer signature. Rather, it is uniquely activated primarily in tumors with aberrant p53, Rb, or BRCA1 expression but not in tumors initiated through the overexpression of myc, ras, her2/neu, or polyoma middle T oncogenes. Importantly, human breast, lung, and prostate tumors expressing this set of genes represent subsets of tumors with the most aggressive phenotype and with poor prognosis. The T/t-antigen signature is highly predictive of human breast cancer prognosis. Because this class of epithelial tumors is generally intractable to currentiv existing standard therapies, this genetic signature identifies potential targets for novel therapies directed against these lethal forms of cancer. Because these genetic targets have been discovered using mammary, prostate, and lung T/t-antigen mouse cancer models, these models are rationale candidates for use in preclinical testing of therapies focused on these biologically important targets. C1 Roswell Park Canc Inst, Buffalo, NY USA. SUNY Stony Brook, Dept Biol, Stony Brook, NY USA. US FDA, College Pk, MD USA. NIH, NIDDK, Lab Cell Regulation & Carcinogenes, Bethesda, MD USA. NIH, NIDDK, Cell & Canc Biol Branch, Bethesda, MD USA. NIH, NIDDK, Ctr Canc Res, Natl Canc Inst,Biometrics Res Branch, Bethesda, MD USA. NIH, NIDDK, Ctr Canc Res, Genet Dev & Dis Branch, Bethesda, MD USA. EMMES Corp, Rockville, MD USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Univ, Ctr Canc, Houston, TX USA. Univ Calif Irvine, Irvine, CA USA. RP Green, JE (reprint author), NCI, Transgenic Oncogenes & Genomics Sect, Canc Biol Lab & Genet, Room 4054,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA. EM JEGreen@nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS NR 49 TC 74 Z9 75 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2007 VL 67 IS 17 BP 8065 EP 8080 DI 10.1158/0008-5472.CAN-07-1515 PG 16 WC Oncology SC Oncology GA 209RW UT WOS:000249406700022 PM 17804718 ER PT J AU Liao, MJ Zhang, CC Zhou, B ZimonjiC, DB Mani', SA Kaba, M Gifford, A Reinhardt, F Popescu, NC Guo, W Eaton, EN Lodish, HF Weinberg, RA AF Liao, Mai-Jing Zhang, Cheng Cheng Zhou, Beiyan ZimonjiC, Drazen B. Mani', Sendurai A. Kaba, Megan Gifford, Ann Reinhardt, Ferenc Popescu, Nicholas C. Guo, Wenjun Eaton, Elinor Nor Lodish, Harvey F. Weinberg, Robert A. TI Enrichment of a population of mammary gland cells that form mammospheres and have in vivo repopulating activity SO CANCER RESEARCH LA English DT Article ID HEMATOPOIETIC STEM-CELLS; BREAST-CANCER; SELF-RENEWAL; PHENOTYPE; DEFINES; VITRO AB The identification of mammary gland stem cells (MGSC) or progenitors is important for the study of normal breast development and tumorigenesis. Based on their immunophenotype, we have isolated a population of mouse mammary gland cells that are capable of forming "mammospheres" in vitro. Importantly, mammospheres are enriched for cells that regenerate an entire mammary gland on implantation into a mammary fat pad. We also undertook cytogenetic analyses of mammosphere-forming cells after prolonged culture, which provided preliminary insight into the genomic stability of these cells. Our identification of new cell surface markers for enriching mammosphere-initiating cells, including endoglin and prion protein, will facilitate the elucidation of the cell biology of MGSC. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA USA. Natl Canc Inst, Sect Cytogenet Mol, Expt Carcinogenesis Lab, Bethesda, MD USA. Texas So Univ, Ctr Med, Dept Physiol & Dev Biol, Dallas, TX USA. RP Weinberg, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM weinberg@wi.mit.edu RI Mani, Sendurai/A-7244-2009 OI Mani, Sendurai/0000-0002-5918-4276 FU Intramural NIH HHS; NCI NIH HHS [K01 CA120099-01]; NIDDK NIH HHS [R01 DK067356] NR 21 TC 110 Z9 114 U1 3 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2007 VL 67 IS 17 BP 8131 EP 8138 DI 10.1158/0008-5472.CAN-06-4493 PG 8 WC Oncology SC Oncology GA 209RW UT WOS:000249406700029 PM 17804725 ER PT J AU Hudson, TS Hartle, DK Hursting, SD Nunez, NP Wang, TTY Young, HA Arany, P Green, JE AF Hudson, Tamaro S. Hartle, Diane K. Hursting, Stephen D. Nunez, Nomeli P. Wang, Thomas T. Y. Young, Heather A. Arany, Praveen Green, Jeffrey E. TI Inhibition of prostate cancer growth by muscadine grape skin extract and resveratrol through distinct mechanisms SO CANCER RESEARCH LA English DT Article ID RAT MAMMARY TUMORIGENESIS; CARCINOMA DU145 CELLS; ENDOTHELIAL FUNCTION; CYCLE ARREST; IN-VIVO; APOPTOSIS; JUICE; INDUCTION; LINES; IDENTIFICATION AB The phytochemical resveratrol contained in red grapes has been shown to inhibit prostate cancer cell growth, in part, through its antioxidant activity. Muscadine grapes contain unique phytochemical constituents compared with other grapes and are potentially a source for novel compounds with antitumor activities. We compared the antitumor activities of muscadine grape skin extract (MSKE), which we show contains no resveratrol, with that of resveratrol using primary cultures of normal prostate epithelial cells (PrEC) and the prostate cancer cell lines RWPE-1, WPE1-NA22, WPE1-NB14, and WPE1-NB26, representing different stages of prostate cancer progression. MSKE significantly inhibite tumor cell growth in all transformed prostate cancer cell lines but not PrEC cells. Prostate tumor cell lines, but not PrEC cells, exhibited high rates of apoptosis in response to MSKE through targeting of the phosphatidylinositol 3-kinase-Akt and mitogen-activated protein kinase survival pathways. The reduction in Akt activity by MSKE is mediated through a reduction in Akt transcription, enhanced proteosome degradation of Akt, and altered levels of DJ-I, a known regulator of PTEN. In contrast to MSKE, resveratrol did not induce apoptosis in this model but arrested cells at the G(1)-S phase transition of the cell cycle associated with increased expression of p21 and decreased expression of cyclin D1 and cyclin-dependent kinase 4 proteins. These results show that MSKE and resveratrol target distinct pathways to inhibit prostate cancer cell growth in this system and that the unique properties of MSKE suggest that it may be an important source for further development of chemopreventive or therapeutic agents against prostate cancer. C1 NCI, Lab Cellular Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Univ Georgia, Coll Pharm, Dept Pharmaceut & Biomed Sci, Athens, GA USA. Univ Texas, Div Nutr Sci, Austin, TX 78712 USA. USDA, Beltsville Human Nutr Res Ctr, Phytonutr Lab, Beltsville, MD 20705 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. RP Green, JE (reprint author), NCI, Lab Cellular Regulat & Carcinogenesis, NIH, Bldg 41,Room C619, Bethesda, MD 20892 USA. EM jegreen@mail.nih.gov FU Intramural NIH HHS NR 37 TC 74 Z9 81 U1 1 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2007 VL 67 IS 17 BP 8396 EP 8405 DI 10.1158/0008-5472.CAN-06-4069 PG 10 WC Oncology SC Oncology GA 209RW UT WOS:000249406700060 PM 17804756 ER PT J AU Endo, Y Rubin, JS AF Endo, Yoshimi Rubin, Jeffrey S. TI Wnt signaling and neurite outgrowth: Insights and questions SO CANCER SCIENCE LA English DT Review ID MICROTUBULE-ASSOCIATED PROTEINS; GLYCOGEN-SYNTHASE KINASE-3; N-TERMINAL KINASE; BETA-CATENIN; NEURONAL POLARITY; CELL POLARITY; AXON GUIDANCE; DIRECTED CELL; C-ELEGANS; RECEPTOR AB Wnt signaling consists of a highly conserved set of biochemical pathways that have a multitude of functions during embryonic development and in the adult. The Wnt proteins are extracellular agents that often act as gradient morphogens, indicating that their distribution in tissues is tightly controlled. This attribute is also characteristic of factors that regulate neurite outgrowth and guide axons precisely to their specific destinations. Several studies in various species now have established that Wnts and their receptors have an important role in axonal guidance. Different ligand/receptor combinations have been identified that mediate this activity in many of the experimental models. Clues about downstream effector molecules have come from in vitro systems. In this article, the authors review the results from many of these models, evaluate what is known about the associated signaling pathways and speculate about the direction of future research. C1 NCI, Bethesda, MD 20892 USA. RP Rubin, JS (reprint author), NCI, 37 Convent Dr, Bethesda, MD 20892 USA. EM rubinj@mail.nih.gov FU Intramural NIH HHS NR 79 TC 28 Z9 29 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD SEP PY 2007 VL 98 IS 9 BP 1311 EP 1317 DI 10.1111/j.1349-7006.2007.00536.x PG 7 WC Oncology SC Oncology GA 203IO UT WOS:000248968500005 PM 17627619 ER PT J AU Shi, Z Jain, S Kim, IW Peng, XX Abraham, I Youssef, DTA Fu, LW El Sayed, K Ambudkar, SV Chen, ZS AF Shi, Zhi Jain, Sandeep Kim, In-Wha Peng, Xing-Xiang Abraham, Ioana Youssef, Diaa T. A. Fu, Li-Wu El Sayed, Khalid Ambudkar, Suresh V. Chen, Zhe-Sheng TI Sipholenol A, a marine-derived sipholane triterpene, potently reverses P-glycoprotein (ABCB1)-mediated multidrug resistance in cancer cells SO CANCER SCIENCE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; IN-VITRO; AGOSTEROL-A; DRUG-RESISTANCE; CATALYTIC CYCLE; ATP HYDROLYSIS; KB CELLS; BINDING; INHIBITOR; PROTEIN AB Through extensive screening of marine sponge compounds, the authors have found that sipholenol A, a sipholane triterpene isolated from the Red Sea sponge, Callyspongia siphonella, potently reversed multidrug resistance (MDR) in cancer cells that overexpressed P-glycoprotein (P-gp). In experiments, sipholenol A potentiated the cytotoxicity of several P-gp substrate anticancer drugs, including colchicine, vinblastine, and paclitaxel, but not the non-P-gp substrate cisplatin, and significantly reversed the MDR of cancer cells KB-C2 and KB-V1 in a concentration-dependent manner. Furthermore, sipholenol A had no effect on the response to cytotoxic agents in cells lacking P-gp expression or expressing MDR protein 1 or breast cancer resistance protein. Sipholenol A (IC50 > 50 mu M) is not toxic to all the cell lines that were used, regardless of their membrane transporter status. Accumulation and efflux studies with the P-gp substrate [H-3]-paclitaxel demonstrated that sipholenol A time-dependently increased the intracellular accumulation of [H-3]-paclitaxel by directly inhibiting P-gp-mediated drug efflux. In addition, sipholenol A did not alter the expression of P-gp after treating KB-C2 and KB-V1 cells for 36 h and 72 h. However, it efficaciously stimulated the activity of ATPase of P-gp and inhibited the photolabeling of this transporter with its transport substrate [I-125]-iodoarylazidoprazosin. Overall, the present results indicate that sipholenol A efficiently inhibits the function of P-gp through direct interactions, and sipholane triterpenes are a new class of potential reversing agents for treatment of MDR in P-gp-overexpressing tumors. C1 Sun Yat Sen Univ, State Key Lab Oncol S China, Ctr Canc, Guangzhou 510060, Peoples R China. St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. NE Louisiana Univ, Coll Pharm, Dept Basic Pharmaceut Sci, Monroe, LA 71209 USA. NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. Suez Canal Univ, Fac Pharm, Dept Pharmacognosy, Ismailia 41522, Egypt. RP Fu, LW (reprint author), Sun Yat Sen Univ, State Key Lab Oncol S China, Ctr Canc, Guangzhou 510060, Peoples R China. EM fulw@mail.sysu.edu.cn; chenz@stjohns.edu RI Youssef, Diaa/H-9813-2012 FU Intramural NIH HHS NR 37 TC 35 Z9 37 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD SEP PY 2007 VL 98 IS 9 BP 1373 EP 1380 DI 10.1111/j.1349-7006.2007.00554.x PG 8 WC Oncology SC Oncology GA 203IO UT WOS:000248968500014 PM 17640301 ER PT J AU Lea, IA Jackson, MA Li, X Bailey, S Peddada, SD Dunnick, JK AF Lea, I. A. Jackson, M. A. Li, X. Bailey, S. Peddada, S. D. Dunnick, J. K. TI Genetic pathways and mutation profiles of human cancers: site- and exposure-specific patterns SO CARCINOGENESIS LA English DT Review ID MOUSE LUNG-TUMORS; K-RAS MUTATIONS; STRAIN A/J MICE; TOBACCO-SMOKE; MOLECULAR EPIDEMIOLOGY; ENVIRONMENT INTERACTIONS; MUTAGENIC SIGNATURE; ONCOGENE MUTATIONS; CIGARETTE-SMOKING; MULTISTAGE THEORY AB Cancer is a complex disease that involves the accumulation of both genetic and epigenetic alterations of numerous genes. Data in the Genetic Alterations in Cancer database for gene mutations and allelic loss [loss of heterozygosity (LOH)] in human tumors (e.g. lung, oral, esophagus, stomach and colon/rectum) were reviewed. Results for the genes and pathways implicated in tumor development at these sites are presented. Mutation incidence, spectra and codon specificity are described for lung, larynx and oral tumors. LOH occurred more frequently than gene mutations in tumors from all sites examined. The cell cycle gene, TP53 (all sites), and cell signaling gene, APC (colorectal and gastric cancers), were the only genes with similar incidences of LOH and mutation. Alterations of one or more cell cycle and cell signaling genes were reported for tumors from each site. Site-specific activation was apparent in the cell signaling mitogen-activated protein kinase oncogenes (KRAS in lung, HRAS in oral cancers and BRAF in esophageal and colorectal cancers). Analysis of genetic changes in lung tumors showed that the incidence of mutations in the TP53 and KRAS genes and the incidence of LOH in the FHIT gene were significantly greater in smokers versus non-smokers (P < 0.01). In lung and oral cancers, the TP53 GC -> TA transversion frequency increased with tobacco smoke exposure (P < 0.05). Furthermore, the TP53 mutational hot spots for lung and laryngeal cancers from smokers included codons 157, 245 and 273, whereas for oral tumors included codons 280 and 281. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. RP Dunnick, JK (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. EM ilea@ils-inc.com; dunnickj@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 FU Intramural NIH HHS [Z99 ES999999]; NIEHS NIH HHS [N43ES15477] NR 53 TC 67 Z9 73 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2007 VL 28 IS 9 BP 1851 EP 1858 DI 10.1093/carcin/bgm176 PG 8 WC Oncology SC Oncology GA 227RU UT WOS:000250676300001 PM 17693665 ER PT J AU Moore, LE Brennan, P Karami, S Hung, RJ Hsu, C Boffetta, P Toro, J Zaridze, D Janout, V Bencko, V Navratilova, M Szeszenia-Dabrowska, N Mates, D Mukeria, A Holcatova, I Welch, R Chanock, S Rothman, N Chow, WH AF Moore, L. E. Brennan, P. Karami, S. Hung, R. J. Hsu, C. Boffetta, P. Toro, J. Zaridze, D. Janout, V. Bencko, V. Navratilova, M. Szeszenia-Dabrowska, N. Mates, D. Mukeria, A. Holcatova, I. Welch, R. Chanock, S. Rothman, N. Chow, W. -H. TI Glutathione S-transferase polymorphisms, cruciferous vegetable intake and cancer risk in the Central and Eastern European kidney cancer study SO CARCINOGENESIS LA English DT Article ID LUNG-CANCER; ISOTHIOCYANATES; SINGAPORE; BRASSICA; SHANGHAI; GENOTYPE; CHINESE AB High consumption of cruciferous vegetables has been associated with reduced kidney cancer risk in many studies. Isothiocyanates, thought to be responsible for the chemopreventive properties of this food group, are conjugated to glutathione by glutathione S-transferases (GSTs) before urinary excretion. Modification of this relationship by host genetic factors is unknown. We investigated cruciferous vegetable intake in 1097 cases and 1555 controls enrolled in a multicentric case-control study from the Czech Republic, Poland, Romania and Russia. To assess possible gene-diet interactions, genotyped cases (N = 925) and controls (N = 1247) for selected functional or non-synonymous polymorphisms including the GSTM1 deletion, GSTM3 3 bp deletion (IVS6 + 22-AGG) and V224I G > A substitution, GSTT1 deletion and the GSTP1 I105V A > G substitution. The odds ratio (OR) for low (less than once per month) versus high (at least once per week) intake of cruciferous vegetables was 1.29 [95% confidence interval (CI): 1.02-1.62; P-trend = 0.03]. When low intake of cruciferous vegetables (less than once per month) was stratified by GST genotype, higher kidney cancer risks were observed among individuals with the GSTT1 null (OR = 1.86; 95% CI: 1.07-3.23; P-interaction = 0.05) or with both GSTM1/T1 null genotypes (OR = 2.49; 95% CI: 1.08-5.77; P-interaction = 0.05). These data provide additional evidence for the role of cruciferous vegetables in cancer prevention among individuals with common, functional genetic polymorphisms. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Int Agcy Res Canc, F-69008 Lyon, France. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow 115478, Russia. Palacky Univ, Fac Med, Dept Prevent Med, Olomouc 77515, Czech Republic. Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague 12800, Czech Republic. Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno 65200, Czech Republic. Inst Occupat Med, Dept Epidemiol, PL-90950 Lodz, Poland. Inst Publ Hlth, Bucharest 76256, Romania. NCI, Core Genotyping Facil, Ctr Adv Technol, NIH,Dept Hlth & Human Serv, Gaithersburg, MD 20877 USA. RP Moore, LE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM moorele@mail.nih.gov RI Hung, Rayjean/A-7439-2013; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; OI mates, dana/0000-0002-6219-9807 NR 19 TC 37 Z9 38 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2007 VL 28 IS 9 BP 1960 EP 1964 DI 10.1093/carcin/bgm151 PG 5 WC Oncology SC Oncology GA 227RU UT WOS:000250676300015 PM 17617661 ER PT J AU Berndt, SI Huang, WY Chatterjee, N Yeager, M Welch, R Chanock, SJ Weissfeld, JL Schoen, RE Hayes, RB AF Berndt, Sonja I. Huang, Wen-Yi Chatterjee, Nilanjan Yeager, Meredith Welch, Robert Chanock, Stephen J. Weissfeld, Joel L. Schoen, Robert E. Hayes, Richard B. TI Transforming growth factor beta 1 (TGFB1) gene polymorphisms and risk of advanced colorectal adenoma SO CARCINOGENESIS LA English DT Article ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1 GENE; BONE-MINERAL DENSITY; COLON-CANCER CELLS; MICROSATELLITE INSTABILITY; MYOCARDIAL-INFARCTION; DISEASE PROGRESSION; RAS PROTOONCOGENE; EPITHELIAL-CELLS; BREAST-CANCER AB Transforming growth factor beta 1 (TGFB1) is a multifunctional cytokine that has been implicated in the pathogenesis of colorectal neoplasia. To investigate the association between genetic variants in TGFB1 and the risk of colorectal adenoma, we conducted a case-control study of 754 advanced adenoma cases and 769 controls from the baseline screening exam of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Cases included participants diagnosed with advanced left-sided adenoma (>= 1 cm, high-grade dysplasia or villous characteristics), and controls were subjects without evidence of a left-sided polyp by sigmoidoscopy. DNA was extracted from blood specimens, and five single-nucleotide polymorphisms in TGFB1 of known or suggested functional significance (-800G > A, -509C > T, Leu10Pro, Arg25Pro and Thr263Ile) were genotyped. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between each polymorphism and adenoma. The high TGFB1 producer genotypes, -509TT and 10Pro/Pro, were associated with an increased risk of colorectal adenoma compared with other genotypes (OR = 1.51, 95% CI: 1.04-2.20 and OR = 1.37, 95% CI: 1.02-1.86, respectively). These increased risks, particularly for -509TT, were greater for persons with multiple adenomas (OR = 1.89, 95% CI: 1.16-3.09, P = 0.01) and individuals with rectal adenoma (OR = 2.95, 95% CI: 1.66-5.26, P = 0.0002). Haplotype analysis revealed similar findings under a recessive model. No associations were observed for polymorphisms at codons 25 and 263. In conclusion, variants that enhance TGFB1 production may be associated with an increased risk of advanced colorectal adenoma. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 20877 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. RP Berndt, SI (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM berndts@mail.nih.gov OI Hayes, Richard/0000-0002-0918-661X FU Intramural NIH HHS NR 55 TC 28 Z9 33 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2007 VL 28 IS 9 BP 1965 EP 1970 DI 10.1093/carcin/bgm155 PG 6 WC Oncology SC Oncology GA 227RU UT WOS:000250676300016 PM 17615257 ER PT J AU Martinez, ME Jacobs, ET Ashbeck, EL Sinha, R Lance, P Alberts, DS Thompson, PA AF Martinez, Maria Elena Jacobs, Elizabeth T. Ashbeck, Erin L. Sinha, Rashmi Lance, Peter Alberts, David S. Thompson, Patricia A. TI Meat intake, preparation methods, mutagens and colorectal adenoma recurrence SO CARCINOGENESIS LA English DT Article ID HETEROCYCLIC AROMATIC-AMINES; DONE RED MEAT; COLON-CANCER; WELL-DONE; VARYING DEGREES; COOKED MEATS; RISK; CONSUMPTION; FOOD; METABOLISM AB Red meat intake has been shown to be associated with higher risk of colorectal cancer. Though the exact mechanisms responsible for this association remain unknown, several tumorigenic properties of meat have been proposed. One well-supported biologic mechanism is elevated exposure to the genotoxic formation of heterocyclic amines (HCAs), which occur when meat is cooked at high temperatures for a long period of time. We prospectively assessed the relation between type of meat, meat preparation method, doneness, a metric of HCAs and other mutagens and colorectal adenoma recurrence among 869 participants in a chemoprevention trial of ursodeoxycholic acid. Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and associated 95% confidence intervals (CIs). Most meat variables assessed were positively but weakly associated with recurrence of any adenoma. In contrast, recurrence of advanced or multiple adenomas was more strongly associated with a number of the meat exposure variables evaluated. For recurrence of advanced lesions, significant associations were detected among individuals in the highest when compared with the lowest tertile of intake for pan-fried red meat (OR = 1.85; 95% CI = 1.10-3.13) and well/very well done red meat (OR = 1.71; 95% CI = 1.02-2.86). Significant positive associations were shown for recurrence of multiple adenomas and the following variables: processed meat (OR = 1.83; 95% CI = 1.10-3.04), pan-fried red meat (OR = 1.63; 95% CI = 1.01-2.61), well/very well done red meat (OR = 1.68; 95% CI = 1.03-2.74), 2-amino-3,4,8-trimethylimidazo[4,5,-f]quinoxaline (OR = 1.74; 95% CI = 1.07-2.82) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (OR = 1.68; 95% CI = 1.03-2.75). Our results support a meat mutagen exposure hypothesis as a potential mechanism for recurrence of clinically significant adenomatous polyps. C1 Univ Arizona, Arizona Canc Ctr, Coll Agr & Life Sci, Tucson, AZ 85721 USA. Univ Arizona, Mel & Enid Zuckerman Arizona Coll Publ Hlth, Coll Agr & Life Sci, Tucson, AZ USA. Univ Arizona, Dept Nutr Sci, Coll Agr & Life Sci, Tucson, AZ USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Univ Arizona, Dept Med, Tucson, AZ 85724 USA. Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA. RP Martinez, ME (reprint author), Univ Arizona, Arizona Canc Ctr, Coll Agr & Life Sci, Tucson, AZ 85721 USA. EM emartinez@azcc.arizona.edu RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [CA-41108, CA-23074, CA106269, CA95060] NR 53 TC 28 Z9 28 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2007 VL 28 IS 9 BP 2019 EP 2027 DI 10.1093/carcin/bgm179 PG 9 WC Oncology SC Oncology GA 227RU UT WOS:000250676300025 PM 17690112 ER PT J AU Pacher, P Szabo, C AF Pacher, Pal Szabo, Csaba TI Role of Poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: The therapeutic potential of PARP inhibitors SO CARDIOVASCULAR DRUG REVIEWS LA English DT Review DE angiogenesis; apoptosis; cardiomyopathy; diabetes; DNA repair; heart failure; inflammation; necrosis; nitric oxide; peroxynitrite; poly(ADP-ribose) polymerase; vascular remodeling ID ADP-RIBOSE SYNTHETASE; APOPTOSIS-INDUCING FACTOR; ISCHEMIA-REPERFUSION INJURY; NITRIC-OXIDE SYNTHASE; KAPPA-B ACTIVATION; POLY(ADENOSINE DIPHOSPHATE-RIBOSE) POLYMERASE; DIABETIC ENDOTHELIAL DYSFUNCTION; MYOFIBRILLAR CREATINE-KINASE; INDUCED HEART-FAILURE; MYOCYTE CELL-DEATH AB Accumulating evidence suggests that the reactive oxygen and nitrogen species are generated in cardiomyocytes and endothelial cells during myocardial ischemia/reperfusion injury, various forms of heart failure or cardiomyopathies, circulatory shock, cardiovascular aging, diabetic complications, myocardial hypertrophy, atherosclerosis, and vascular remodeling following injury. These reactive species induce oxidative DNA damage and consequent activation of the nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP-1), the most abundant isoform of the PARP enzyme family. PARP overactivation, on the one hand, depletes its substrate, NAD(+), slowing the rate of glycolysis, electron transport, and ATP formation, eventually leading to the functional impairment or death of the endothelial cells and cardiomyocytes. On the other hand, PARP activation modulates important inflammatory pathways, and PARP-1 activity can also be modulated by several endogenous factors such as various kinases, purines, vitamin D, thyroid hormones, polyamines, and estrogens, just to mention a few. Recent studies have demonstrated that pharmacological inhibition of PARP provides significant benefits in animal models of cardiovascular disorders, and novel PARP inhibitors have entered clinical development for various cardiovascular indications. Because PARP inhibitors can enhance the effect of anticancer drugs and decrease angiogenesis, their therapeutic potential is also being explored for cancer treatment. This review discusses the therapeutic effects of PARP inhibitors in myocardial ischemia/reperfusion injury, various forms of heart failure, cardiomyopathies, circulatory shock, cardiovascular aging, diabetic cardiovascular complications, myocardial hypertrophy, atherosclerosis, vascular remodeling following injury, angiogenesis, and also summarizes our knowledge obtained from the use of PARP-1 knockout mice in the various preclinical models of cardiovascular diseases. C1 NIAAA, NIH, Lab Physiol Studies, Sect Oxidat Stress & Tissue Injury, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Sch Med, Dept Surg, Newark, NJ 07103 USA. RP Pacher, P (reprint author), NIAAA, NIH, Lab Physiol Studies, Sect Oxidat Stress & Tissue Injury, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z01 AA000375-02]; NIGMS NIH HHS [R01 GM060915, R01 GM060915-01] NR 163 TC 137 Z9 146 U1 0 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0897-5957 J9 CARDIOVASC DRUG REV JI Cardiovasc. Drug Rev. PD FAL PY 2007 VL 25 IS 3 BP 235 EP 260 DI 10.1111/j.1527-3466.2007.00018.x PG 26 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 217ND UT WOS:000249953700004 PM 17919258 ER PT J AU Zhou, Y Bianco, K Huang, L Nien, JK McMaster, M Romero, R Fisher, SJ AF Zhou, Yan Bianco, Katherine Huang, Ling Nien, Jyh K. McMaster, Michael Romero, Roberto Fisher, Susan J. TI Comparative analysis of maternal-fetal interface in preeclampsia and preterm labor SO CELL AND TISSUE RESEARCH LA English DT Article DE pregnancy; preeclampsia; preterm birth; placenta; trophoblast; human ID UTERINE ARTERY DOPPLER; PLACENTAL BED; G EXPRESSION; CYTOTROPHOBLASTS; PATHOGENESIS; WOMEN; RISK; DIFFERENTIATION; HYPERTENSION; PREVENTION AB The maternal-fetal interface, a chimeric structure, is formed when fetal cytotrophoblasts (CTBs) from the placenta invade the uterine wall and its resident vasculature. In preeclampsia (PE), interstitial and endovascular invasion are often shallow, and fewer spiral arterioles are breached in toto. Our previous work has shown that faulty CTB differentiation to an invasive phenotype is a contributing factor. Here, we have tested the hypothesis that the constellation of morphological and molecular defects that are associated with PE are unique to this condition. Specifically, we have compared the histology of the maternal-fetal interface and CTB expression of stage-specific antigens in PE and in preterm labor (PTL) with or without inflammation. In the absence of inflammation, biopsies obtained after PTL were near normal at histological and molecular levels. In accord with previously published data, PE had severe negative effects on the endpoints analyzed. Biopsies obtained after PTL with inflammation had an intermediate phenotype. Our results suggest that the maternal-fetal interface from cases of PTL without inflammation can be used for comparative purposes, e.g., as age-matched controls, in studies of the effects of PE on cells in this region. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. NICHHD, NIH, Perinatol Res Branch, Dept Hlth & Human Serv, Detroit, MI USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. RP Fisher, SJ (reprint author), Univ Calif San Francisco, 513 Parnassus Ave,HSE 1619, San Francisco, CA 94143 USA. EM sfisher@cgl.ucsf.edu FU Intramural NIH HHS; NICHD NIH HHS [HD 30367] NR 40 TC 11 Z9 13 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD SEP PY 2007 VL 329 IS 3 BP 559 EP 569 DI 10.1007/s00441-007-0428-0 PG 11 WC Cell Biology SC Cell Biology GA 205PZ UT WOS:000249128400013 PM 17549520 ER PT J AU Nemeth, MJ Bodine, DM AF Nemeth, Michael J. Bodine, David M. TI Regulation of hematopoiesis and the hematopoietic stem cell niche by Wnt signaling pathways SO CELL RESEARCH LA English DT Review DE hematopoiesis; hematopoietic stem cell; Writ proteins; osteoblast ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTOID LEUKEMIA; INTERNAL TANDEM DUPLICATION; RECEPTOR-RELATED PROTEIN-5; BETA-CATENIN DEGRADATION; IMMUNE-DEFICIENT MICE; DUAL-KINASE MECHANISM; MOUSE BONE-MARROW; SELF-RENEWAL; PROGENITOR CELLS AB Hematopoietic stem cells (HSCs) are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal (in which the ability to function as HSCs is retained) and initiation of hematopoietic differentiation. Multiple signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Writ family of ligands. Writ signaling pathways play a crucial role during embryogenesis and deregulation of these pathways has been implicated in the formation of solid tumors. Wnt signaling also plays a role in the regulation of stem cells from multiple tissues, such as embryonic, epidermal, and intestinal stem cells. However, the function of Writ signaling in HSC biology is still controversial. In this review, we will discuss the basic characteristics of the adult HSC and its regulatory microenvironment, the "niche", focusing on the regulation of the HSC and its niche by the Wnt signaling pathways. C1 NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Nemeth, MJ (reprint author), NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, Bldg 49,Room 3A18,49 Convent Dr,MSC 4442, Bethesda, MD 20892 USA. EM mnemeth@nhgri.nih.gov FU Intramural NIH HHS NR 157 TC 44 Z9 50 U1 0 U2 7 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD SEP PY 2007 VL 17 IS 9 BP 746 EP 758 DI 10.1038/cr.2007.69 PG 13 WC Cell Biology SC Cell Biology GA 224NX UT WOS:000250454800003 PM 17768401 ER PT J AU Sharov, AA Ko, MSH AF Sharov, Alexei A. Ko, Minoru S. H. TI Human ES cell profiling broadens the reach of bivalent domains SO CELL STEM CELL LA English DT Editorial Material ID EMBRYONIC STEM-CELLS; CHROMATIN; PLURIPOTENT; GENOME AB In this issue of Cell Stem Cell, Pan et al. (2007) and Zhao et al. (2007) report genome-wide histone H3 trimethylations at lysines 4 and 27 in human embryonic stem (ES) cells. Similar gene sets arise via different experimental systems, advancing our understanding of stem cell epigenetics. C1 NIA, Dev Genom & Aging Sect, Genet Lab, Baltimore, MD 21224 USA. RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, Baltimore, MD 21224 USA. EM kom@mail.nih.gov RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU Intramural NIH HHS NR 10 TC 24 Z9 24 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD SEP PY 2007 VL 1 IS 3 BP 237 EP 238 DI 10.1016/j.stem.2007.08.015 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 232XT UT WOS:000251055200001 PM 18371354 ER PT J AU Hillefors, M Gioio, AE Mameza, MG Kaplan, BB AF Hillefors, Mi Gioio, Anthony E. Mameza, Marie G. Kaplan, Barry B. TI Axon viability and mitochondrial function are dependent on local protein synthesis in sympathetic neurons SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE Superior cervical ganglia; Axon; Local protein synthesis; Mitochondrial membrane potential; ATP levels ID LONG-TERM FACILITATION; SQUID GIANT-AXON; MESSENGER-RNAS; BETA-TUBULIN; GROWTH CONES; SYNAPSE; TRANSLATION; TRANSPORT; NERVE; APLYSIA AB (1) Axons contain numerous mRNAs and a local protein synthetic system that can be regulated independently of the cell body. (2) In this study, cultured primary sympathetic neurons were employed, to assess the effect of local protein synthesis blockade on axon viability and mitochondrial function. (3) Inhibition of local protein synthesis reduced newly synthesized axonal proteins by 65% and resulted in axon retraction after 6 h. Acute inhibition of local protein synthesis also resulted in a significant decrease in the membrane potential of axonal mitochondria. Likewise, blockade of local protein transport into the mitochondria by transfection of the axons with Hsp90 C-terminal domain decreased the mitochondrial membrane potential by 65%. Moreover, inhibition of the local protein synthetic system also reduced the ability of mitochondria to restore axonal levels of ATP after KCl-induced depolarization. (4) Taken together, these results indicate that the local protein synthetic system plays an important role in mitochondrial function and the maintenance of the axon. C1 NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kaplan, BB (reprint author), NIMH, Mol Biol Lab, NIH, Bldg 10,Room 4N222, Bethesda, MD 20892 USA. EM barry.kaplan@nih.gov NR 40 TC 41 Z9 42 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD SEP PY 2007 VL 27 IS 6 BP 701 EP 716 DI 10.1007/s10571-007-9148-y PG 16 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 213DN UT WOS:000249646400003 PM 17619140 ER PT J AU Ortaldo, JR Mason, A Willette-Brown, J Ruscetti, FW Wine, J Back, T Stull, T Bere, EW Feigenbaum, L Winklet-Pickett, R Young, HA AF Ortaldo, John R. Mason, Anna Willette-Brown, Jami Ruscetti, Frank W. Wine, John Back, Timothy Stull, Terri Bere, E. William Feigenbaum, Lionel Winklet-Pickett, Robin Young, Howard A. TI Modulation of lymphocyte function with inhibitory CD2: Loss of NK and NKT cells SO CELLULAR IMMUNOLOGY LA English DT Article DE NK; NKT; CD2; transgene; ITIM ID NATURAL-KILLER-CELLS; MONOCLONAL-ANTIBODY; CUTTING EDGE; T-CELLS; IN-VIVO; RECEPTORS; ACTIVATION; MICE; GENE; DIFFERENTIATION AB Analysis of the NK cell developmental pathway suggests that CD2 expression may be important in regulating NK maturation. To test this hypothesis, we developed mice containing only an inhibitory CD2 molecule by linking the extracellular domain of CD2 to an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM) motif. Mice containing the CD2 Tg(ITIM) transgene, introduced into a CD2 KO background, have no morphologically detectable lymph nodes, although development of the thymus appears normal. In addition, these mice had major loss of both NK and NKT subsets in peripheral organs, while T and B cell frequencies were intact. Expression of CD2 was low on T cells and lacking on B cells and functional defects were observed in these populations. NKT cells expressing CD4 were absent, while the CD8(+) and double negative NKT cells were retained. Small subsets of NK cells were detected but expression of CD2 on these cells was very low or absent, and their maturation was impaired. Based on the phenotype described here, we believe that these mice represent a unique model to study lymphoid organ and lymphocyte development. (c) 2007 Published by Elsevier Inc. C1 [Ortaldo, John R.; Mason, Anna; Willette-Brown, Jami; Ruscetti, Frank W.; Wine, John; Back, Timothy; Winklet-Pickett, Robin; Young, Howard A.] NCI CCR, Canc Inflammat Program, Expt Immunol Lab, Frederick, MD 21702 USA. [Stull, Terri; Bere, E. William; Feigenbaum, Lionel] SAIC Frederick, Basic Res Labs, LASP, Frederick, MD 21702 USA. RP Young, HA (reprint author), NCI CCR, Canc Inflammat Program, Expt Immunol Lab, 560-31-93, Frederick, MD 21702 USA. EM YoungHow@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 33 TC 2 Z9 2 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD SEP PY 2007 VL 249 IS 1 BP 8 EP 19 DI 10.1016/j.cellimm.2007.10.001 PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 258AU UT WOS:000252841600002 PM 18039542 ER PT J AU Carabeo, RA Dooley, CA Grieshaber, SS Hackstadt, T AF Carabeo, Rey A. Dooley, Cheryl A. Grieshaber, Scott S. Hackstadt, Ted TI Rac interacts with Abi-1 and WAVE2 to promote an Arp2/3-dependent actin recruitment during chlamydial invasion SO CELLULAR MICROBIOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASE; SYNDROME PROTEIN WASP; ARP2/3 COMPLEX; HOST-CELLS; SALMONELLA-TYPHIMURIUM; N-WASP; EPITHELIAL-CELLS; HELA-CELLS; DEPOLYMERIZING PROTEIN; RICKETTSIA-RICKETTSII AB Chlamydiae are Gram-negative obligate intracellular pathogens to which access to an intracellular environment is fundamental to their development. Chlamydial attachment to host cells induces the activation of the Rac GTPase, which is required for the localization of WAVE2 at the sites of chlamydial entry. Co-immunoprecipitation experiments demonstrated that Chlamydia trachomatis infection promoted the interaction of Rac with WAVE2 and Abi-1, but not with IRSp53. siRNA depletion of WAVE2 and Abi-1 abrogated chlamydia-induced actin recruitment and significantly reduced the uptake of the pathogen by the depleted cells. Chlamydia invasion also requires the Arp2/3 complex as demonstrated by its localization to the sites of chlamydial attachment and the reduced efficiency of chlamydial invasion in cells overexpressing the VCA domain of the neural Wiskott-Aldrich syndrome protein. Thus, C. trachomatis activates Rac and promotes its interaction with WAVE2 and Abi-1 to activate the Arp2/3 complex resulting in the induction of actin cytoskeletal rearrangements that are required for invasion. C1 Univ Louisville, Sch Med, Dept Microbiol & Immunol, Louisville, KY 40292 USA. NIH, NIAID, Rocky Mt Labs, Lab Intracellular Parasites,Host Parasite Interac, Hamilton, MT USA. RP Hackstadt, T (reprint author), Univ Louisville, Sch Med, Dept Microbiol & Immunol, Louisville, KY 40292 USA. EM Ted_Hackstadt@NIH.gov FU Intramural NIH HHS; NIAID NIH HHS [R01 AI065545-01, R01 AI065545, K22 AI052252-02, AI065545, K22 AI052252] NR 63 TC 29 Z9 31 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD SEP PY 2007 VL 9 IS 9 BP 2278 EP 2288 DI 10.1111/j.1462-5822.2007.00958.x PG 11 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 198ZS UT WOS:000248666600016 PM 17501982 ER PT J AU Nelson, DE Taylor, LD Shannon, JG Whitmire, WM Crane, DD McClarty, G Su, H Kari, L Caldwell, HD AF Nelson, David E. Taylor, Lacey D. Shannon, Jeffrey G. Whitmire, William M. Crane, Deborah D. McClarty, Grant Su, Hua Kari, Laszlo Caldwell, Harlan D. TI Phenotypic rescue of Chlamydia trachomatis growth in IFN-gamma treated mouse cells by irradiated Chlamydia muridarum SO CELLULAR MICROBIOLOGY LA English DT Article ID FIBROBLASTS L-CELLS; TRYPTOPHAN SYNTHASE; INFECTION TROPISM; PROTEOME ANALYSIS; MEMBRANE-PROTEIN; GENOME SEQUENCE; IMMUNE EVASION; IN-VITRO; PNEUMONIAE; PSITTACI AB Chlamydia trachomatis and C. muridarum, human and mouse pathogens, respectively, share more than 99% of open reading frames (ORFs) but differ in a cytotoxin locus. Presence or absence of cytotoxin gene(s) in these strains correlates with their ability to grow in IFN-gamma treated mouse cells. Growth of toxin-positive C. muridarum is not affected in IFN-gamma treated cells, whereas growth of toxin-negative C. trachomatis is inhibited. We previously reported that this difference in IFN-gamma sensitivity is important to the in vivo infection tropism of these pathogens. Here we describe a phenotypic rescue assay that utilizes C. muridarum gamma irradiated killed elementary bodies (iEB) to rescue C. trachomatis infectivity in IFN-gamma treated mouse cells. Rescue by iEB was temporal, maximal early post infection, directly related to multiplicity of iEB infection, and was independent of de novo chlamydial transcription. Lastly, C. muridarum iEB vacuoles and C. trachomatis inclusions were not fusogenic, suggesting the factor(s) responsible for rescue was secreted or exposed to the cytosol where it inactivated IFN-gamma induced effectors. Chlamydial phenotypic rescue may have broader utility for the study of other EB associated virulence factors that function early in the interaction of chlamydiae with host cells. C1 Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. NIH, NIAID, Rocky Mt Labs, Lab Intracellular Parasites, Hamilton, MT 59840 USA. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3T 2N2, Canada. RP Nelson, DE (reprint author), Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. EM nelsonde@indiana.edu RI Shannon, Jeffrey/A-5735-2009 OI Shannon, Jeffrey/0000-0003-4211-4308 FU Intramural NIH HHS NR 39 TC 13 Z9 13 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD SEP PY 2007 VL 9 IS 9 BP 2289 EP 2298 DI 10.1111/j.1462-5822.2007.00959.x PG 10 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 198ZS UT WOS:000248666600017 PM 17501981 ER PT J AU Tan, HY Callicott, JH Weinberger, DR AF Tan, Hao-Yang Callicott, Joseph H. Weinberger, Daniel R. TI Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia SO CEREBRAL CORTEX LA English DT Article; Proceedings Paper CT Kavli Symposium on Dynamic Landscape of the Frontal Lobe held in Honour of Patricia Goldman-Rakic CY MAY 04-05, 2006 CL Yale Univ, New Haven, CT HO Yale Univ DE dopannine; fMRI; genetics; glutamate; psychosis; working memory ID CATECHOL-O-METHYLTRANSFERASE; WORKING-MEMORY PERFORMANCE; ALTERED EFFECTIVE CONNECTIVITY; VAL(108/158) MET GENOTYPE; DENDRITIC SPINE DENSITY; DOPAMINE D1 RECEPTORS; CEREBRAL BLOOD-FLOW; CARD SORTING TEST; FUNCTIONAL POLYMORPHISM; CORTEX DYSFUNCTION AB Cognitive deficits are critical determinants of schizophrenia morbidity. In this review, we offer a mechanistic perspective regarding schizophrenia-related changes observed in prefrontal cortical networks engaged in working memory. A body of earlier work converges on aberrations in putative macrocircuit stability and functional efficiency as the underlying pathophysiology of the cognitive deficits in schizophrenia. In parsing the dysfunctional prefrontal cortical dynamics of schizophrenia, recent functional magnetic resonance imaging and electoencephalography works suggest that in the context of reduced capacity for executive aspects of working memory, patients engage a larger network of cortical regions consistent with an interplay between reduced signal-to-noise components and the recruitment of compensatory networks. The genetic programming underlying these systems-level cortical interactions has been examined under the lens of certain schizophrenia susceptibility genes, especially catechol-o-methyltransferase (COMT) and GRM3. Variation in COMT, which presumably impacts on cortical dopamine signaling, translates into variable neural strategies for working memory and altering patterns of intracortical functional correlations. GRM3, which impacts on synaptic glutamate, interacts with COMT and exaggerates the genetic dissection of cortical processing strategies. These findings reveal novel insights into the modulation and parcellation of working memory processing in cortical assemblies and provide a mechanistic link between susceptibility genes and cortical pathophysiology related to schizophrenia. C1 NIMH, NIH, Cognit & Psychosis Program, IRP, Bethesda, MD 20892 USA. RP Tan, HY (reprint author), NIMH, NIH, Cognit & Psychosis Program, IRP, Rm 4S-235,10 Ctr Dr, Bethesda, MD 20892 USA. RI Callicott, Joseph/C-9102-2009 OI Callicott, Joseph/0000-0003-1298-3334 FU Intramural NIH HHS NR 161 TC 76 Z9 77 U1 5 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2007 VL 17 SU 1 BP I171 EP I181 DI 10.1093/cercor/hhm069 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 225HN UT WOS:000250507800019 PM 17726000 ER PT J AU Pabst, G Danner, S Podgornik, R Katsaras, J AF Pabst, Georg Danner, Sabine Podgornik, Rudi Katsaras, John TI Entropy-driven softening of fluid lipid bilayers by alamethicin SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Meeting Abstract CT 48th International Conference on the Bioscience of Lipids CY SEP 04-08, 2007 CL Turku, FINLAND C1 Austrian Acad Sci, Inst Biophys & Nanosyst Res, A-1010 Vienna, Austria. NIH, Lab Phys & Struct Biol, Bethesda, MD USA. Univ Ljubljana, Fac Math & Phys, Ljubljana 61000, Slovenia. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD SEP PY 2007 VL 149 SU S BP S12 EP S12 DI 10.1016/j.chemphyslip.2007.06.026 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 207HA UT WOS:000249241000025 ER PT J AU Gray, J Mao, JT Szabo, E Kelley, M Kurie, J Bepler, G AF Gray, Jhanelle Mao, Jenny T. Szabo, Eva Kelley, Michael Kurie, Jonathan Bepler, Gerold TI Lung cancer chemoprevention - ACCP evidence-based clinical practice guidelines (2nd edition) SO CHEST LA English DT Review DE acetyl sacylic acid; apoptosis; biomarkers; chemoprevention; cyclooxygenase-2 inbitors; lung cancer; proliferation; protein kinase C; selenium; signal transduction pathways; tyrosine kinase inhibitors; vitamin A; vitamin E ID RANDOMIZED CONTROLLED-TRIAL; SUSTAINED-RELEASE BUPROPION; BRONCHIAL SQUAMOUS METAPLASIA; LONG-TERM SUPPLEMENTATION; RECEPTOR PARTIAL AGONIST; PROTEIN-KINASE-C; PHASE IIB TRIAL; SMOKING-CESSATION; CARDIOVASCULAR-DISEASE; CELL-PROLIFERATION AB Background: Lung cancer is the most common cause of cancer death in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk for lung cancer compared with lifetime never-smokers. Chemoprevention is the use of specific agents to reverse, suppress, or prevent the process of carcinogenesis. This article reviews the major agents that have been studied for chemoprevention. Methods: Articles of primary, secondary, and tertiary prevention trials were reviewed and summarized to obtain recommendations. Results: None of the phase III trials with the agents beta carotene, retinol, 13-cis-retinoic acid, alpha-tocopherol, N-acetylcysteine, or acetylsalicylic acid has demonstrated beneficial, reproducible results. For facilitating the evaluation of promising agents and for lessening the need for a large sample size, extensive time commitment, and expense, focus is now turning toward the assessment of surrogate end point biomarkers for lung carcinogenesis. With the understanding of important cellular signaling pathways, various inhibitors that may prevent or reverse lung carcinogenesis are being developed. Conclusions: By integrating biological knowledge, more trials can be performed in a reasonable time frame. The future of lung cancer chemoprevention should entail the evaluation of single agents or combinations that target various pathways while working toward identification and validation of intermediate end points. C1 Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Div Thorac Oncol, Tampa, FL 33612 USA. Program Thorac Oncol, Tampa, FL 33612 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. NCI, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Bepler, G (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Div Thorac Oncol, 12902 Magnolia Dr,MRC-4W,Room 4046, Tampa, FL 33612 USA. EM gerold.bepler@moffitt.org OI Kelley, Michael/0000-0001-9523-6080 NR 121 TC 15 Z9 15 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2007 VL 132 IS 3 SU S BP 56S EP 68S DI 10.1378/chest.07-1348 PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 216OZ UT WOS:000249889400005 PM 17873160 ER PT J AU Stewart, DR Cogan, JD Kramer, MR Miller, WT Christiansen, LE Pauciulo, MW Messiaen, LM Tu, GS Thompson, WH Pyertiz, RE Ryu, JH Nicholas, WC Kodama, M Meyrick, BO Ross, DJ AF Stewart, Douglas R. Cogan, Joy D. Kramer, Mordechai R. Miller, Wallace T. Christiansen, Lief E. Pauciulo, Michael W. Messiaen, Ludwine M. Tu, George S. Thompson, William H. Pyertiz, Reed E. Ryu, Jay H. Nicholas, William C. Kodama, Makoto Meyrick, Barbara O. Ross, David J. TI Is pulmonary arterial hypertension in neurofibromatosis type 1 secondary to a plexogenic arteriopathy? SO CHEST LA English DT Article DE bone morphogenic protein 2; mosaic perfusion pattern of lung attenuation; neurofibromatosis type 1; plexiform arteriopathy; vasculopathy ID VON-RECKLINGHAUSEN-DISEASE; MAST-CELLS; LUNG ATTENUATION; MOSAIC PATTERN; HIGH-FREQUENCY; CT SCANS; VASCULOPATHIES; PATHOGENESIS; MUTATIONS; FIBROSIS AB Background: Neurofibromatosis type I (NF1) is a common disorder of dysregulated tissue growth secondary to mutations in the tumor suppressor gene NF1. Pulmonary arterial hypertension (PAH) in patients with NF1 is hypothesized to be secondary to an underlying vasculopathy. Methods: We describe the entity we term NF1-associated PAH (NF1-PAH) in four new patients and update the data on four previously published reports of patients with PAH and NF1. We performed genetic testing of the bone morphogenic protein receptor 2 (BMPR2) gene, which mutated in 70% of patients with familial PAH and approximately 25% of patients with idiopathic PAH. We report, for the first time, pathologic findings in the autopsy-obtained lung of one patient with NF1-PAH. Results: Patients with NF1-PAH have a generally poor long-term prognosis. In four patients, we observed the mosaic pattern of lung attenuation on a CT scan of the chest, a radiographic finding that can be consistent with an underlying vasculopathy. No mutations or rearrangements in the BMPR2 gene were found. We observed complex plexiform lesions in the one available autopsy specimen. Similar lesions are a hallmark of plexogenic pulmonary arteriopathy and are associated with several severe types of PAH. (Plexiform lesions should not be confused with plexiform neurofibromas, which are distinctive tumors seen in NF1.) Conclusions: Our findings suggest that NF1 should be considered as being "associated with PAH as outlined in the Revised Clinical Classification of Pulmonary Hypertension. Understanding the mechanism of PAH in NF1 may inform the pathogenesis of PAH, NF1-PAH itself, and other NF1-associated vasculopathies. The pulmonary vasculature should now be included among the arterial beds affected by NF1 vasculopathy. C1 NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN USA. Rabin Med Ctr, Inst Pulm Med, Petah Tiqwa, Israel. Univ Penn, Sch Med, Dept Radiol, Philadelphia, PA USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA USA. St Josephs Hosp, Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. Lung Ctr Nevada, Las Vegas, NV USA. Univ Washington, Div Pulm & Crit Care Med, Seattle, WA USA. Mayo Clin, Div Pulm & Crit Care Med, Rochester, MN USA. Niigata Univ, Sch Med, Dept Internal Med 1, Niigata, Japan. Vanderbilt Univ, Med Ctr, Dept Pathol & Med, Nashville, TN USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pulm & Crit Care Med & Hosp, Los Angeles, CA USA. RP Stewart, DR (reprint author), NIH, Natl Human Genome Res Inst, 49 Convent Dr,Bldg 49,Rm 4A62, Bethesda, MD 20892 USA. EM drstewart@mail.nih.gov OI Miller, Wallace/0000-0001-7403-9969 FU Intramural NIH HHS; NHLBI NIH HHS [P01 HL072058] NR 29 TC 24 Z9 26 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2007 VL 132 IS 3 BP 798 EP 808 DI 10.1378/chest.06-3017 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 214MN UT WOS:000249742100016 PM 17573495 ER PT J AU Lauer, MS AF Lauer, Michael S. TI Screening for coronary heart disease: Has the time for universal imaging arrived? SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ABDOMINAL AORTIC-ANEURYSM; SERVICES-TASK-FORCE; TREATMENT PANEL-III; COMPUTED-TOMOGRAPHY; RISK-ASSESSMENT; PREVENTION; CALCIUM; CHOLESTEROL; PREDICTION AB The Screening for Heart Attack Prevention and Education (SHAPE) Task Force has recommended a strategy of screening for coronary heart disease in which nearly all middle-aged and older adults would undergo an imaging test. However, this approach is not supported by evidence and is not endorsed by professional societies or the US Preventive Services Task Force. Physicians should follow established guidelines such as those of the third Adult Treatment Panel of the National Cholesterol Education Program. C1 NHLBI, Div Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Lauer, MS (reprint author), NHLBI, Div Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA. RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 FU NHLBI NIH HHS [R01 HL-66004] NR 34 TC 8 Z9 8 U1 0 U2 1 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD SEP PY 2007 VL 74 IS 9 BP 645 EP + PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 207XS UT WOS:000249285000005 PM 17879518 ER PT J AU Levy, D AF Levy, Daniel TI Hypertension from Framingham to ALLHAT: Translating clinical trials into practice SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Article ID ISOLATED SYSTOLIC HYPERTENSION; BLOOD-PRESSURE; RISK; POPULATION AB Despite decades of observational and clinical data about the effectiveness of treating hypertension, most Americans are still not being adequately treated. it makes little sense that much of our efforts are directed toward performing large trials to find out whether newer, more expensive agents are superior to conventional therapy, especially when little evidence shows any benefit to the newer drugs. Rather, our priority should be to treat more patients and to treat them more aggressively. C1 NHLBI, Framingham Heart Dis Epidemiol Study, Ctr Populat Studies, Framingham, MA 01702 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Dis Epidemiol Study, Ctr Populat Studies, 5 Thurber St, Framingham, MA 01702 USA. EM levyd@nih.gov NR 17 TC 0 Z9 0 U1 0 U2 0 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD SEP PY 2007 VL 74 IS 9 BP 672 EP 678 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 207XS UT WOS:000249285000008 PM 17879521 ER PT J AU Klauschen, F Angermann, BR Meier-Schellersheim, M AF Klauschen, F. Angermann, B. R. Meier-Schellersheim, M. TI Understanding diseases by mouse click: the promise and potential of computational approaches in Systems Biology SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Review DE computational modelling; data integration; Systems Biology ID TRANSLATIONAL MINIREVIEW SERIES; SIGNAL-TRANSDUCTION; T-BET; CELL; NETWORKS; DIFFERENTIATION; PATHWAYS; STANDARDS; DYNAMICS; PLATFORM AB Computational modelling approaches can nowadays build large-scale simulations of cellular behaviour based on data describing detailed molecular level interactions, thus performing the space- and time-scale integrations that would be impossible just by intuition. Recent progress in the development of both experimental methods and computational tools has provided the means to generate the necessary quantitative data and has made computational methods accessible even to non-theorists, thereby removing a major hurdle that has in the past made many experimentalists hesitate to invest serious effort in formulating quantitative models. We describe how computational biology differs from classical bioinformatics, how it emerged from mathematical biology and elucidate the role it plays for the integration of traditionally separated areas of biomedical research within the larger framework of Systems Biology. C1 NIAID, Program Syst Immunol & Infect Dis Modelling, NIH, DHHS, Bethesda, MD 20892 USA. Univ Montreal, Fac Med, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada. RP Meier-Schellersheim, M (reprint author), NIAID, Program Syst Immunol & Infect Dis Modelling, NIH, DHHS, Bldg 10,Room 11 N311,10 Ctr Dr MSC-1892, Bethesda, MD 20892 USA. EM mms@niaid.nih.gov RI Klauschen, Frederick/C-5637-2015 FU Intramural NIH HHS NR 45 TC 10 Z9 10 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD SEP PY 2007 VL 149 IS 3 BP 424 EP 429 DI 10.1111/j.1365-2249.2007.03472.x PG 6 WC Immunology SC Immunology GA 203MH UT WOS:000248978200003 PM 17666096 ER PT J AU Van Waes, C Yu, M Nottingham, L Karin, M AF Van Waes, Carter Yu, Ming Nottingham, Liesl Karin, Michael TI Inhibitor-kappa B kinase in tumor promotion and suppression during progression of squamous cell carcinoma SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID PROINFLAMMATORY CYTOKINE EXPRESSION; NECROSIS-FACTOR-ALPHA; HUMAN HEAD; IKK-ALPHA; CONSTITUTIVE ACTIVATION; GROWTH; SKIN; PHOSPHORYLATION; CARCINOGENESIS; MORPHOGENESIS C1 Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Pharmacol & Canc Ctr, Sch Med, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. RP Van Waes, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Room 4-2732,CRC Bldg,10 Ctr Dr, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov FU NIDCD NIH HHS [Z01-DC-00016] NR 31 TC 21 Z9 21 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 2007 VL 13 IS 17 BP 4956 EP 4959 DI 10.1158/1078-0432.CCR-07-1287 PG 4 WC Oncology SC Oncology GA 207YT UT WOS:000249287700004 PM 17785544 ER PT J AU Molinolo, AA Hewitt, SM Amornphimoltham, P Keelawat, S Rangdaeng, S Garcia, AM Raimondi, AR Jufe, R Itoiz, M Gao, Y Saranath, D Kaleebi, GS Yoo, GH Leak, L Myers, EM Shintan, S Wong, D Massey, HD Yeudall, WA Lonardo, F Ensley, J Gutkind, JS AF Molinolo, Alfredo A. Hewitt, Stephen M. Amornphimoltham, Panomwat Keelawat, Somboon Rangdaeng, Samraeung Garcia, Abelardo Meneses Raimondi, Ana R. Jufe, Rafael Itoiz, Maria Gao, Yan Saranath, Dhananjaya Kaleebi, George S. Yoo, George H. Leak, Lee Myers, Ernest M. Shintan, Satoru Wong, David Massey, H. Davis Yeudall, W. Andrew Lonardo, Fulvio Ensley, John Gutkind, J. Silvio TI Dissecting the Akt/Mammalian target of rapamycin signaling network: Emerging results from the head and neck cancer tissue array initiative SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; IN-SITU HYBRIDIZATION; THERAPEUTIC TARGET; CIGARETTE-SMOKING; MOLECULAR TARGET; PROGNOSTIC VALUE; P53 MUTATIONS; TONGUE CANCER; ORAL-CANCER AB Purpose: As an approach to evaluate the expression pattern and status of activation of signaling pathways in clinical specimens from head and neck squamous cell carcinoma (HNSCC) patients, we established the Head and Neck Cancer Tissue Array Initiative, an international consortium aimed at developing a high-density HNSCC tissue microarray, with a high representation of oral squamous cell carcinoma. Experimental Design: These tissue arrays were constructed by acquiring cylindrical biopsies from multiple individual tumor tissues and transferring them into tissue microarray blocks. From a total of 1,300 cases, 547 cores, including controls, were selected and used to build the array. Results: Emerging information by the use of phosphospecific antibodies detecting the activated state of signaling molecules indicates that the Akt-mammalian target of rapamycin (mTOR) pathway is frequently activated in HNSCC, but independently from the activation of epidermal growth factor receptor or the detection of mutant p53. Indeed, we identified a large group of tissue samples displaying active Akt and mTOR in the absence of epidermal growth factor receptor activation. Furthermore, we have also identified a small subgroup of patients in which the mTOR pathway is activated but not Akt, suggesting the existence of an Akt-independent signaling route stimulating mTOR. Conclusions: These findings provide important information about the nature of the dysregulated signaling networks in HNSCC and may also provide the rationale for the future development of novel mechanism-based therapies for HNSCC patients. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Chulalongkorn Univ, Fac Med, Dept Pathol, Bangkok 10330, Thailand. Chiang Mai Univ, Fac Med, Dept Pathol, Chieng Mai, Thailand. Inst Nacl Cancerol, Mexico City, DF, Mexico. Univ Buenos Aires, Sch Dent, Lab Patol, Buenos Aires, DF, Argentina. Univ Buenos Aires, Sch Dent, Dept Pathol, Buenos Aires, DF, Argentina. Peking Univ, Sch Stomatol, Dept Oral Pathol, Beijing 100871, Peoples R China. Reliance Ind Ltd, Bombay, Maharashtra, India. MEDUNSA, Limpopo, South Africa. Wayne State Univ, Dept Otolaryngol Head & Neck Surg & Oncol, Detroit, MI USA. Howard Univ, Coll Med, Washington, DC 20059 USA. Ehime Univ, Sch Med, Matsuyama, Ehime 790, Japan. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. Virginia Commonwealth Univ, Phillips Inst Oral & Cranofacial Mol Biol, Richmond, VA USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; OI Hewitt, Stephen/0000-0001-8283-1788 FU Intramural NIH HHS; NIDCR NIH HHS [R01-DE15970] NR 69 TC 136 Z9 136 U1 0 U2 8 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 2007 VL 13 IS 17 BP 4964 EP 4973 DI 10.1158/1078-0432.CCR-07-1041 PG 10 WC Oncology SC Oncology GA 207YT UT WOS:000249287700006 PM 17785546 ER PT J AU McMaster, ML Csako, G Giambarresi, TR Vascluez, L Berg, M Saddlemire, S Hulleyl, B Tucker, MA AF McMaster, Mary L. Csako, Gyorgy Giambarresi, Therese R. Vascluez, Linda Berg, Melissa Saddlemire, Stephanie Hulleyl, Benjamin Tucker, Margaret A. TI Long-term evaluation of three multiple-case Waldenstrom macroglobulinemia families SO CLINICAL CANCER RESEARCH LA English DT Article ID IGM MONOCLONAL GAMMOPATHY; POPULATION-BASED REGISTRY; NON-HODGKIN-LYMPHOMA; UNDETERMINED SIGNIFICANCE; IMMUNOFIXATION ELECTROPHORESIS; FOLLOW-UP; HIGH-RISK; IMMUNOGLOBULIN; AGGREGATION; IMMUNOELECTROPHORESIS AB Purpose: Because the clinical significance of immunoglobulin abnormalities reported in relatives of familial Waldenstrom macroglobulinemia (WM) patients is unknown, we initiated a follow-up study of three WM families originally evaluated 27 years previously. Experimental Design: Of 29 eligible first-degree relatives of WM patients, 27 (93%) had originally participated in clinical and electrophoretic evaluations. We re-contacted all participants for prospective follow-up electrophoretic analysis and other studies. Results: Initially, five relatives had IgM monoclonal gammopathy (IgM MG), and four had IgM polyclonal gammopathy (PG). Twenty-two relatives (81 %) were re-evaluated. Median follow-up was 17years (range,7-27). At re-contact, all IgM MG persisted or progressed, including three that evolved to WM. Among the four with PG, two new IgM MG cases developed. Overall, seven relatives (26 %) had IgM MG, and five (18 %) had IgM PG. Conclusions: Although based on small numbers, this study provides the longest comprehensive follow-up of WM families to date. IgM MG seems to be a phenotypic marker of WM susceptibility in some families and may have a high risk of progression to WM. IgM PG may also be important in WM families. These observations require validation in larger studies and, if confirmed, may be used to identify a cohort (relatives with IgM MG) for future prevention strategies. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Ctr Clin, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. WESTAT Corp, Rockville, MD 20850 USA. Commissioned Corps, US Publ Hlth Serv, Dept Hlth & Human Serv, Washington, DC USA. RP McMaster, ML (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,MSC 7236, Bethesda, MD 20892 USA. EM mcmastem@mail.nih.gov RI Tucker, Margaret/B-4297-2015 FU Intramural NIH HHS NR 34 TC 21 Z9 21 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 2007 VL 13 IS 17 BP 5063 EP 5069 DI 10.1158/1078-0432.CCR-07-0299 PG 7 WC Oncology SC Oncology GA 207YT UT WOS:000249287700018 PM 17785558 ER PT J AU Hassan, R Bullock, S Premkumar, A Kreitman, RJ Kindler, H Willingham, MC Pastan, I AF Hassan, Raffit Bullock, Susie Premkumar, Ahalya Kreitman, Robert J. Kindler, Hedy Willingham, Mark C. Pastan, Ira TI Phase I study of SS1P a recombinant anti-mesothelin immunotoxin given as a bolus IV infusion to patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancers SO CLINICAL CANCER RESEARCH LA English DT Article ID ADVANCED SOLID TUMORS; ANTITUMOR-ACTIVITY; PSEUDOMONAS EXOTOXIN; MONOCLONAL-ANTIBODY; HIGH-AFFINITY; TRIAL; ADENOCARCINOMAS; SS1(DSFV)PE38; MALIGNANCIES; DIAGNOSIS AB Purpose: To determine the toxicities, maximum tolerated dose (MTD) and pharmacokinetics of the recombinant immunotoxin SS1P (anti-mesothelin dsFv-PE38) in patients with mesothelin-expressing cancers. Experimental Design: SS1P given as a 30-min i.v. infusion every other day (QOD) for six or three doses was administered to 34 patients with advanced mesothelioma (n = 20), ovarian (n = 12), and pancreatic (n = 2) cancer. Results: The initial cohort of 17 patients received SS1P QOD x 6 doses and the MTD was 18 mu g/ kg/dose. Dose-limiting toxicities (DLT) included grade 3 uticaria (one patient) and grade 3 vascular leak syndrome (two patients). To allow further SS1P dose escalation, 17 patients were treated on the QOD x 3 schedule and the MTD was 45 mu g/kg/dose. The DLT was grade 3 pleuritis and was seen in two of two patients treated at a dose of 60 mu g/kg and in one of nine patients treated at a dose of 45 mu g/kg. At the MTD of 45 mu g/kg, the mean C-max Of SS1P was 483 ng/mL and half-life was 466 min. Of the 33 evaluable patients treated, 4 had minor responses, 19 had stable disease (including 2 with resolution of ascites), and 10 had progressive disease. Conclusions: SS1P is well tolerated with pleuritis as the DLT at the highest dose level. Evidence of clinical activity was noted in a group of heavily pretreated patients. Phase 11 clinical trials of SS1P are being planned for malignant mesothelioma and other mesothelin-expressing malignancies. C1 NCI, Mol Biol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27109 USA. RP Hassan, R (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, Room 5116,37 Convent Dr, Bethesda, MD 20892 USA. EM hassanr@mail.nih.gov FU Intramural NIH HHS NR 28 TC 211 Z9 213 U1 0 U2 8 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 2007 VL 13 IS 17 BP 5144 EP 5149 DI 10.1158/1078-0432.CCR-07-0869 PG 6 WC Oncology SC Oncology GA 207YT UT WOS:000249287700029 PM 17785569 ER PT J AU Gills, J Lo Piccolo, J Tsurutani, J Shoemaker, RH Best, CJM Abu-Asab, MS Borojerdi, J Warfel, NA Gardner, ER Danish, M Hollander, MC Kawabata, S Tsokos, M Figga, WD Steeg, PS Dennis, PA AF Gills, JoellJ. Lo Piccolo, Jaclyn Tsurutani, Junji Shoemaker, Robert H. Best, Carolyn J. M. Abu-Asab, Mones S. Borojerdi, Jennifer Warfel, Noel A. Gardner, Erin R. Danish, Matthew Hollander, M. Christine Kawabata, Shigeru Tsokos, Maria Figga, William D. Steeg, Patricia S. Dennis, Phillip A. TI Nelfinavir, a lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo SO CLINICAL CANCER RESEARCH LA English DT Article ID VIRUS (HIV)-1 PROTEASE; CANCER-CELLS; MULTIPLE-MYELOMA; BREAST-CANCER; GROWTH ARREST; DRUG SCREEN; INSULIN; RECEPTOR; ACTIVATION; RESISTANCE AB Purpose: The development of new cancer drugs is slow and costly. HIV protease inhibitors are Food and Drug Administration approved for HIV patients. Because these drugs cause toxicities that can be associated with inhibition of Akt, an emerging target in cancer, we assessed the potential of HIV protease inhibitors as anticancer agents. Experimental Design: HIV protease inhibitors were screened in vitro using assays that measure cellular proliferation, apoptotic and nonapoptotic cell death, endoplasmic reticulum (ER) stress, autophagy, and activation of Akt. Nelfinavir was tested in non-small cell lung carcinoma (NSCLC) xenografts with biomarker assessment. Results: Three of six HIV protease inhibitors, nelfinavir, ritonavir, and sacluinavir, inhibited proliferation of NSCLC cells, as well as every cell line in the NCI60 cell line panel. Nelfinavir was most potent with a mean 50% growth inhibition of 5.2 mu mol/L, a concentration achievable in HIV patients. Nelfinavir caused two types of cell death, caspase-dependent apoptosis and caspase-independent death that was characterized by induction of ER stress and autophagy. Autophagy was protective because an inhibitor of autophagy increased nelfinavir-induced death. Akt was variably inhibited by HIV protease inhibitors, but nelfinavir caused the greatest inhibition of endogenous and growth factor-induced Akt activation. Nelfinavir decreased the viability of a panel of drug-resistant breast cancer cell lines and inhibited the growth of NSCLC xenografts that was associated with induction of ER stress, autophagy, and apoptosis. Conclusions: Nelfinavir is a lead HIV protease inhibitor with pleioitropic effects in cancer cells. Given its wide spectrum of activity, oral availability, and familiarity of administration, nelfinavir is a Food and Drug Administration-approved drug that could be repositioned as a cancer therapeutic. C1 NCI, Canc Res Ctr, Med Oncol Branch, Bethesda, MD 20889 USA. NCI, Canc Res Ctr, Mol Therapeut Program, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Pathol Lab, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Clin Pharmacol Program, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Frederick, MD 21701 USA. NCI, Clin Pharmacol Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. RP Dennis, PA (reprint author), NCI, Canc Res Ctr, Med Oncol Branch, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov RI Figg Sr, William/M-2411-2016; OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [, NIH0011335962]; NCI NIH HHS [N01-CO-12400]; PHS HHS [NIH0011335962] NR 49 TC 174 Z9 177 U1 1 U2 19 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 2007 VL 13 IS 17 BP 5183 EP 5194 DI 10.1158/1078-0432.CCR-07-0161 PG 12 WC Oncology SC Oncology GA 207YT UT WOS:000249287700035 PM 17785575 ER PT J AU Yang, D Din, NL Browning, DD Abrams, SI Liu, K AF Yang, Dafeng Din, Najam Lid Browning, Darren D. Abrams, Scott I. Liu, Kebin TI Targeting lymphotoxin beta receptor with tumor-specific T lymphocytes for tumor regression SO CLINICAL CANCER RESEARCH LA English DT Article ID CTL ADOPTIVE IMMUNOTHERAPY; SECONDARY LYMPHOID-TISSUES; PERFORIN-DEFICIENT MICE; FAS-MEDIATED APOPTOSIS; COLON-CARCINOMA CELLS; IN-VIVO; IMMUNE SURVEILLANCE; IFN-GAMMA; PULMONARY METASTASES; ABNORMAL-DEVELOPMENT AB Purpose: One of the impediments of immunotherapy against cancer is the suppression of tumor-specific CTLs in the tumor microenvironment, partly due to the selective inhibition of the perforin pathway and the emergence of Fas-resistant tumors. Therefore, we sought to identify perforinand Fas-independent cytotoxic pathways and explored the potential of targeting LT beta R with tumor-specific CTLs to induce tumor rejection in vivo. Experimental Design: Fas-resistant tumors were examined for their susceptibility to perforin-deficient (pfp) CTLs via CTL adoptive transfer in mouse models of experimental lung metastasis. The specificity of LT beta R, a cell surface death receptor, in causing tumor rejection by CTLs was analyzed by LT beta R-specific neutralizing monoclonal antibody in vitro. The specificity and efficacy of LT beta R in the suppression of established tumors was further investigated by silencing LT R in tumor cells in vivo. Results: pfp CTLs exhibited significant cytotoxicity against Fas-resistant tumors in vivo. The perforin-and Fas-independent cytotoxicity was directly mediated, at least in part, by the adoptively transferred CTLs. It was observed that LT R was expressed on the tumor cell surface, and LT alpha, LT beta, and LIGHT, all of which are ligands for LT R, were either constitutively expressed or activated in the tumor-specific CTLs and primary CD8(+) Tcells. Blocking LT beta R with LT beta R-specific neutralizing monoclonal antibody decreased CTL cytotoxicity in vitro. Silencing LT beta R using LT beta R-specific short hairpin RNA reduced the ability of pfp CTLs to induce tumor rejection in vivo. Conclusion: LT beta R directly mediates CTL-directed tumor rejection in vivo. Targeting LT beta R with tumor-specific CTLs is a potential therapeutic approach. C1 Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Liu, K (reprint author), Med Coll Georgia, Dept Biochem & Mol Biol, 1459 Laney Walker Blvd, Augusta, GA 30912 USA. EM Kliu@mcg.edu OI Liu, Kebin/0000-0003-1965-7240 FU Intramural NIH HHS NR 54 TC 8 Z9 8 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 2007 VL 13 IS 17 BP 5202 EP 5210 DI 10.1158/1078-0432.CCR-07-1161 PG 9 WC Oncology SC Oncology GA 207YT UT WOS:000249287700037 PM 17785576 ER PT J AU Price, CP Kricka, LJ AF Price, Christopher P. Kricka, Larry J. TI Improving healthcare accessibility through point-of-care technologies SO CLINICAL CHEMISTRY LA English DT Article ID CONGESTIVE-HEART-FAILURE; MICROSPHERES; SYSTEMS; ARRAY AB Background: The NIH is committed to improving healthcare quality in the US and has set up initiatives to address problems such as the fragmented nature of healthcare provision. A hypothesis has been developed that testing closer to the point at which care is delivered may reduce fragmentation of care and improve outcomes. Methods: The National Institute of Biomedical Imaging and Bioengineering (NIBIB), the NIH's National Heart, Lung, and Blood Institute and the National Science Foundation sponsored a workshop, "Improving Health Care Accessibility through Poini-of-Care Technologies," in April 2006. The workshop assessed the clinical needs and opportunities for point-of-care (POC) technologies in primary care, the home, and emergency medical services and reviewed minimally invasive and noninvasive testing, including imaging, and conventional testing based on sensor and lab-on-a-chip technologies. Emerging needs of informatics and telehealth and healthcare systems engineering were considered in the POC testing context. Additionally, implications of evidence-based decision-making were reviewed, particularly as it related to the challenges in producing reliable evidence, undertaking regulation, implementing evidence responsibly, and integrating evidence into health policy. Results: Many testing procedures were considered to be valuable in the clinical settings discussed. Technological solutions were proposed to meet these needs, as well as the practical requirements around clinical process change and regulation. From these considerations, a series of recommendations was formulated for development of POC technologies based on input from the symposium attendees. Conclusion: NIBIB has developed a funding initiative to establish a Point-of-Care Technologies Research Network that will work to bridge the technology/clinical gap and provide the partnerships necessary for the application of technologies to pressing clinical needs in POC testing. (c) 2007 American Association for Clinical Chemistry C1 Hosp Univ Penn, Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Med Ctr, Lab Med, Philadelphia, PA 19104 USA. Natl Sci Fdn, NHLBI, NIBIB, Workship Fac, Arlington, VA 22230 USA. Univ Oxford, John Radcliffe Hosp, Dept Clin Biochem, Oxford OX3 9DU, England. Natl Inst Biomed Imaging & Bioengn, NIH, Dept Hlth & Human Serv, Div Discovery Sci & Technol, Bethesda, MD USA. RP Kricka, LJ (reprint author), Hosp Univ Penn, Med Ctr, Dept Pathol, 7-103 Founders Pavil,3400 Spruce St, Philadelphia, PA 19104 USA. EM kricka@mail.med.upenn.edu RI McDevitt, John/P-4108-2014 OI McDevitt, John/0000-0001-8789-9351 NR 41 TC 45 Z9 47 U1 6 U2 16 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2007 VL 53 IS 9 BP 1665 EP 1675 DI 10.1373/clinchem.2006.084707 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 206OP UT WOS:000249193100016 ER PT J AU Gulley, JL Wu, S Arlen, PM Dahut, WL AF Gulley, James L. Wu, Shenhong Arlen, Philip M. Dahut, William L. TI Persistent hypocalcemia induced by zoledronic acid in a patient with androgen-independent prostate cancer and extensive bone metastases SO CLINICAL GENITOURINARY CANCER LA English DT Article DE calcium; secondary hyperparathyroidism; vitamin D ID PLACEBO-CONTROLLED TRIAL; VITAMIN-D DEFICIENCY; SKELETAL COMPLICATIONS AB Zoledronic acid is a highly potent bisphosphonate that has been shown. to reduce skeletal-related events in patients with androgen-independent prostate cancer metastatic to bone. We report a patient with androgen-independent prostate cancer and extensive bone metastases. After receiving a single dose of zoledronic acid, the patient developed hypocalcemia that persisted for approximately 60 days despite intravenous and oral calcium supplementation, likely because of excess unopposed osteoblastic activity. This case underscores the need for calcium and vitamin D monitoring and supplementation to avoid bisphosphonate-induced secondary hyperparathyroidism and highlights the possibility that extensive osteoblastic metastasis alone might lead to hypocalcemia. C1 Ctr Canc Res, NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), Ctr Canc Res, NCI, Tumor Immunol & Biol Lab, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM gullcyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS NR 12 TC 9 Z9 9 U1 0 U2 4 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD SEP PY 2007 VL 5 IS 6 BP 403 EP 405 DI 10.3816/CGC.2007.n.025 PG 3 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 216GW UT WOS:000249867500008 PM 17956715 ER PT J AU Mishra, MV Singh, AK AF Mishra, Mark V. Singh, Anurag K. TI A second transient prostate-specific antigen elevation after external-beam radiation therapy and fractionated magnetic resonance imaging-guided high-dose rate brachytherapy boost SO CLINICAL GENITOURINARY CANCER LA English DT Article DE androgen deprivation therapy; biochemical failure; disease progression ID BIOCHEMICAL RELAPSE DEFINITION; ANDROGEN DEPRIVATION; PSA BOUNCE; CANCER; RADIOTHERAPY; FAILURE; MEN; EJACULATION; NEOADJUVANT; KINETICS AB A 63-year-old man with a T1c adenocarcinoma of the prostate, Gleason score of 7 (4 + 3), and a pretreatment prostate-specific antigen (PSA) level of 9.5 ng/mL was treated with external-beam radiation therapy (45 Gy) and 2 magnetic resonance imaging-guided high-dose rate brachytherapy boosts (10 Gy each.) The patient also received neoadjuvant, concurrent, and adjuvant hormonal treatment with leuprolide for 7 months total. Without any further intervention the patient had 2 separate and prolonged PSA increases and decreases 12-35 months after therapy. His PSA nadir was < 0.2 ng/mL and rose slowly over several months to 4.2 ng/mL, resolved, and then rose 2.3 ng/mL before again slowly resolving. After prostate irradiation, many patients experience a transient rise in serum PSA levels and a subsequent decline without any treatment. This is known as a PSA "bounce" or "bump." Some patients experience a second transient rise in PSA levels after irradiation. To our knowledge, this case report is the first documentation of a second PSA bump in a patient treated with external-beam radiation therapy and high-dose rate boost therapy and provides context to address concerns and therapeutic decisions confronting physicians and patients. C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Singh, AK (reprint author), NCI, Radiat Oncol Branch, 10 Ctr Dr,Bldg 10,CRC Room B2-3561, Bethesda, MD 20892 USA. EM anurag.singh@rosewellpark.org FU Intramural NIH HHS NR 23 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD SEP PY 2007 VL 5 IS 6 BP 406 EP 408 DI 10.3816/CGC.2007.n.026 PG 3 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 216GW UT WOS:000249867500009 PM 17956716 ER PT J AU Johnston, CP Qiu, HM Ticehurst, JR Dickson, C Rosenbaum, P Lawson, P Stokes, AB Lowenstein, CJ Kaminsky, M Cosgrove, SE Green, KY Perl, TM AF Johnston, Cecilia P. Qiu, Haoming Ticehurst, John R. Dickson, Conan Rosenbaum, Patricia Lawson, Patricia Stokes, Amy B. Lowenstein, Charles J. Kaminsky, Michael Cosgrove, Sara E. Green, Kim Y. Perl, Trish M. TI Outbreak management and implications of a nosocomial norovirus outbreak SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID NORWALK-LIKE VIRUSES; UNITED-STATES; ACUTE GASTROENTERITIS; FELINE CALICIVIRUS; CONTAMINATION; EPIDEMIOLOGY; INACTIVATION; SURROGATE; VARIANT; TRENDS AB Background. Noroviruses are enterically transmitted and are a frequent cause of gastroenteritis, affecting 23 million people annually in the United States. We describe a norovirus outbreak and its control in a tertiary care hospital during February-May 2004. Methods. Patients and health care workers met the case definition if they had new onset of vomiting and/ or diarrhea during the outbreak period. Selected stool samples were tested for norovirus RNA. We also determined outbreak costs, including the estimated lost revenue associated with unit closures, sick leave, and cleaning expenses. Results. We identified 355 cases that affected 90 patients and 265 health care workers and that were clustered in the coronary care unit and psychiatry units. Attack rates were 5.3% ( 7 of 133) for patients and 29.9% ( 29 of 97) for health care workers in the coronary care unit and 16.7% ( 39 of 233) for patients and 38.0% ( 76 of 200) for health care workers in the psychiatry units. Thirteen affected health care workers (4.9%) required emergency department visits or hospitalization. Detected noroviruses had 98%-99% sequence identity with representatives of a new genogroup II.4 variant that emerged during 2002-2004 in the United States ( e. g., Farmington Hills and other strains) and Europe. Aggressive infection-control measures, including closure of units and thorough disinfection using sodium hypochlorite, were required to terminate the outbreak. Costs associated with this outbreak were estimated to be $657,644. Conclusions. The significant disruption of patient care and cost of this single nosocomial outbreak support aggressive efforts to prevent transmission of noroviruses in health care settings. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Cardiol, Div Infect Dis, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Hosp Epidemiol & Infect Control, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21218 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Ctr Innovat Qual Patient Care, Baltimore, MD USA. RP Johnston, CP (reprint author), 4940 Eastern Ave,B-3 N, Baltimore, MD 21224 USA. EM cpark@jhmi.edu RI Ticehurst, John/I-7532-2012 NR 27 TC 98 Z9 104 U1 0 U2 22 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2007 VL 45 IS 5 BP 534 EP 540 DI 10.1086/520666 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 197LM UT WOS:000248557000011 PM 17682985 ER PT J AU Walsh, TJ Perfect, JR AF Walsh, Thomas J. Perfect, John R. TI Posaconazole for invasive aspergillosis? - Reply to Baden and Marty SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID FUNGAL-INFECTIONS; AMPHOTERICIN-B; PULMONARY ASPERGILLOSIS; ANTIFUNGAL THERAPY; EFFICACY; ITRACONAZOLE; VORICONAZOLE; INTOLERANT; SCH-56592; SAFETY C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Div Infect Dis, Durham, NC 27706 USA. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, NIH, CRC 1-5750,10 Str Dr, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 13 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2007 VL 45 IS 5 BP 665 EP 666 DI 10.1086/521971 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 197LM UT WOS:000248557000033 ER PT J AU Powers, JH AF Powers, John H. TI Increasing the efficiency of clinical trials of antimicrobials: The scientific basis of substantial evidence of effectiveness of drugs SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Conference on Antimicrobial Resistance of the National-Foundation-for-Infectious-Diseases CY JUN 26-28, 2006 CL Bethesda, MD SP Natl Fdn Infect Dis ID SURROGATE END-POINTS; ACUTE OTITIS-MEDIA; SALVAGE THERAPY; DISEASE; METAANALYSIS; ANTIBIOTICS; ASSOCIATION AB In the United States, drug sponsors must obtain approval from the US Food and Drug Administration before licensure and widespread clinical use of drugs. In this article, I discuss the definition and history of the regulatory requirement for "substantial evidence" of effectiveness from "adequate and well-controlled" clinical trials of drugs. These requirements apply to antimicrobials as they do to other therapeutic drug classes, and they may be even more important in their application to antimicrobials, given issues of antimicrobial resistance. I will discuss the evidence requirements, using examples from clinical trials in diseases such as acute otitis media, acute bacterial sinusitis, and acute exacerbations of chronic bronchitis. Examination of the principles of substantial evidence also points to opportunities to improve the efficiency of confirmatory clinical trials of antimicrobials to obtain more clinically relevant and useful information without increasing the uncertainty regarding the safety and efficacy of these drugs. C1 NIAID, NIH, Sci Applicat Int Corp, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. RP Powers, JH (reprint author), 6700B Rockledge Dr,Rm 1123, Bethesda, MD 20892 USA. EM powersjohn@mail.nih.gov NR 33 TC 18 Z9 18 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2007 VL 45 SU 2 BP S153 EP S162 DI 10.1086/519253 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 198VG UT WOS:000248655000008 PM 17683020 ER PT J AU Cho, ME Smith, DC Branton, MH Penzak, SR Kopp, JB AF Cho, Monique E. Smith, David C. Branton, Mary H. Penzak, Scott R. Kopp, Jeffrey B. TI Pirfenidone slows renal function decline in patients with focal segmental glomerulosclerosis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GROWTH-FACTOR-BETA; PULMONARY-FIBROSIS; MULTIPLE-SCLEROSIS; CONTROLLED TRIAL; KIDNEY FIBROSIS; DOUBLE-BLIND; OPEN-LABEL; RATS; NEPHROPATHY; PROGRESSION AB Background and Objectives: Pirfenidone is an orally available antifibrotic agent that has shown benefit in animal models of pulmonary and renal fibrosis and in clinical trials of pulmonary fibrosis, multiple sclerosis, and hepatic cirrhosis. Our objective was to determine whether pirfenidone slows the loss of renal function in focal segmental glonterulosclerosis. Design, Setting, Participants, & Measurements: An open-label trial was performed to evaluate the safety and efficacy of pirfenidone in patients with idiopathic and postadaptive focal segmental glomerulosclerosis. The monthly change in estimated GFR, expressed as ml/min per 1.73 m(2), was compared between the baseline period and the treatment period. During both periods, patients received angiotensin antagonist therapy if tolerated. Twenty-one patients were enrolled, and 18 patients completed a median of 13 mo of pirfenidone treatment. Results: The monthly change in GFR improved from a median of -0.61 mli/min per 1.73 M2 Unterquartile range -1.31 to -0.41 during the baseline period to -0.45 ml/min per 1.73 M2 (interquartile range -0.78 to -0.16) with pirfertidone therapy. This change represents a median of 25% improvement in the rate of decline W < 0.01). Pirfenidone had no effect on BP or proteinuria. Adverse events attributed to therapy included dyspepsia, sedation, and photosensitive dermatitis. Conclusions: It is concluded that pirfenidone is an attractive candidate for placebo-controlled trials in patients with progressive chronic kidney disease. C1 NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. NIH, Clin Pharmacokinet Res Lab, Clin Ctr Pharm Dept, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIDDK, Kidney Dis Sect, NIH, 10-2N116, Bethesda, MD 20892 USA. EM jbkopp@nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X FU Intramural NIH HHS NR 37 TC 90 Z9 92 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2007 VL 2 IS 5 BP 906 EP 913 DI 10.2215/CJN.01050207 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 204JJ UT WOS:000249039500008 PM 17702727 ER PT J AU Katz, LH Zelazny, A Scharf, S Hourvitz, A Asor, N Arbeli, Y Yust-Katz, S Smollan-Fredman, G Gdalevich, M AF Katz, L. H. Zelazny, A. Scharf, S. Hourvitz, A. Asor, N. Arbeli, Y. Yust-Katz, S. Smollan-Fredman, G. Gdalevich, M. TI Mass antibiotic treatment to stop an outbreak of meningococcal disease: a molecular analysis SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE carriage; children; meningococci; Neisseria meningitidis; prophylaxis; REP-PCR ID POLYMERASE-CHAIN-REACTION; SEQUENCE-BASED PCR; NEISSERIA-MENINGITIDIS; REP-PCR; CHEMOPROPHYLAXIS; CARRIAGE; STRAINS; POPULATION; COMMUNITY; RIFAMPIN AB The occurrence of three cases of meningococcal disease among children in a small community, two of whom attended the same day-care centre, prompted a programme of mass antibiotic prophylaxis. Nasopharyngeal and throat swabs were obtained on three occasions from all children registered at the day-care centre. Serogroup B Neisseria meningitidis was isolated from 13 of 61 children before prophylaxis, from three children after 2 weeks, and from 19 children after 3 months. Repetitive extragenic palindromic PCR analysis identified several meningococcal strains before treatment, one of which became predominant after 3 months. Mass antibiotic prophylaxis initially suppressed meningococcal carriage, but the carriage rate subsequently rebounded. C1 Israel Def Forces Med Corps, Rabin Med Ctr, Dept Internal Med D, IL-49100 Petah Tiqwa, Israel. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. Natl Ctr Meningococci, Chaim Sheba Med Ctr, Tel Hashomer, Israel. NIH, Bethesda, MD 20892 USA. Barzilai Govt Hosp, Ashkelon Dis Hlth Off, Israel Minist Hlth, Ashqelon, Israel. Tel Aviv Univ, Sackler Fac Med, Rabin Med Ctr, Dept Neurol, IL-69978 Tel Aviv, Israel. RP Katz, LH (reprint author), Israel Def Forces Med Corps, Rabin Med Ctr, Dept Internal Med D, Beilinson Campus, IL-49100 Petah Tiqwa, Israel. EM liorshlomit@yahoo.com NR 20 TC 3 Z9 3 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD SEP PY 2007 VL 13 IS 9 BP 943 EP 946 DI 10.1111/j.1469-0691.2007.01767.x PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 197YW UT WOS:000248594300016 PM 17635531 ER PT J AU Lomarev, MP Kim, DY Richardson, SP Voller, B Hallett, M AF Lomarev, M. P. Kim, D. Y. Richardson, S. Pirio Voller, B. Hallett, M. TI Safety study of high-frequency transcranial magnetic stimulation in patients with chronic stroke SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE TMS; rTMS; EMG; stroke; rehabilitation; safety ID MOTOR CORTEX; EXCITABILITY AB Objective: Repetitive transcranial magnetic stimulation (rTMS) is a potential therapeutic tool to rehabilitate chronic stroke patients. In this study, the safety of high-frequency rTMS in stroke was investigated (Phase 1). Methods: The safety of 20 and 25 Hz rTMS over the motor cortex (MC) of the affected hemisphere, with intensities of 110-130% of the motor threshold (MT), was evaluated using surface electromyography (EMG) of hand and arm muscles. Results: Brief EMG bursts, possibly representing peripheral manifestations of after discharges, and spread of excitation to proximal muscles are considered to be associated with a high risk of seizure occurrence. These events were recorded after the rTMS trains. Neither increased MC excitability nor improved pinch force dynamometry was found after rTMS. Conclusions: Stimulation parameters for rTMS, which are safe for healthy volunteers, may lead to a higher risk for seizure occurrence in chronic stroke patients. Significance: rTMS at rates of 20 and 25 Hz using above threshold stimulation potentially increases the risk of seizures in patients with chronic stroke. (C) 2007 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Natl Inst Hlth, NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. Yonsei Univ, Coll Med, Res Inst Rehabilil Med, Dept Rehabil Med, Seoul, South Korea. Med Univ Vienna, Dept Neurol, Div Neurorehabilil, Vienna, Austria. RP Lomarev, MP (reprint author), Natl Inst Hlth, NINDS, Human Motor Control Sect, NIH Bldg 10,Rm 5N240,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. EM Lomarevm@ninds.nih.gov OI Voller, Bernhard/0000-0001-5809-874X NR 8 TC 31 Z9 36 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD SEP PY 2007 VL 118 IS 9 BP 2072 EP 2075 DI 10.1016/j.clinph.2007.06.016 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 209BW UT WOS:000249364200022 PM 17652018 ER PT J AU Gotsch, F Romero, R Kusanovic, JP Mazaki-Tovi, S Pineles, BL Erez, O Espinoza, J Hassan, SS AF Gotsch, Francesca Romero, Roberto Kusanovic, Juan Pedro Mazaki-Tovi, Shali Pineles, Beth L. Erez, Offer Espinoza, Jimmy Hassan, Sonia S. TI The fetal inflammatory response syndrome SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Review DE preterm labor; premature birth; prematurity; funisitis; chorioammionitis; intrauterine infection; PROM ID TUMOR-NECROSIS-FACTOR; BIRTH-WEIGHT INFANTS; TOLL-LIKE RECEPTORS; PRETERM PREMATURE RUPTURE; WHITE-MATTER INJURY; MEDICINE CONSENSUS CONFERENCE; RESPIRATORY-DISTRESS-SYNDROME; ANTAGONIST GENE POLYMORPHISM; MIGRATION INHIBITORY FACTOR; PLATELET-ACTIVATING-FACTOR AB The fetal inflammatory response syndrome (FIRS) is a condition characterized by systemic inflammation and an elevation of fetal plasma interleukin-6. This syndrome has been observed in fetuses with preterm labor with intact membranes, preterm prelabor rupture of the membranes, and also fetal viral infections such as cytomegalovirus. FIRS is a risk factor for short-term perinatal morbidity and mortality after adjustment for gestational age at delivery and also for the development of long-term sequelae such as bronchopulmonary dysplasia and brain injury. Multiorgan involvement in FIRS has been demonstrated in the hematopoietic system, thymus, adrenal glands, skin, kidneys, heart, lung, and brain. This article reviews the fetal systemic inflammatory response as a mechanism of disease. Potential interventions to control an exaggerated inflammatory response in utero are also described. C1 NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS,Hutzel Womens Hosp, Bethesda, MD USA. NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS,Hutzel Womens Hosp, Box 4,3990 John R, Detroit, MI 48201 USA. EM nivhdprbchiefdtaff@mail.nih.gov FU Intramural NIH HHS NR 273 TC 228 Z9 239 U1 2 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD SEP PY 2007 VL 50 IS 3 BP 652 EP 683 DI 10.1097/GRF.0b013e31811ebef6 PG 32 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 198ON UT WOS:000248637500009 PM 17762416 ER PT J AU Skarlatos, S AF Skarlatos, S. I. TI New programs for gene- and cell-based therapies at NHLBI SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID LENTIVIRAL VECTORS; MONKEYS; FETAL AB The development of new and novel clinical therapies depends on our ability to translate basic research findings into meaningful clinical applications. These "translational studies'' are expensive and complex but necessary if we are to develop new treatments that prevent or treat heart, lung, and blood diseases. This study describes newly created programs at NHLBI ( National Heart, Lung, and Blood Institute), which support academic research efforts to translate gene- and cell-based therapies into viable clinical applications. C1 NHLBI, Div Cardiovasc Dis, NIH, Bethesda, MD 20892 USA. RP Skarlatos, S (reprint author), NHLBI, Div Cardiovasc Dis, NIH, Bldg 10, Bethesda, MD 20892 USA. EM skarlats@nhlbi.nih.gov NR 5 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2007 VL 82 IS 3 BP 334 EP 336 DI 10.1038/sj.clpt.6100289 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 204RS UT WOS:000249062300018 PM 17625516 ER PT J AU Mahnke, YD Roederer, M AF Mahnke, Yolanda D. Roederer, Mario TI Optimizing a multicolor immunophenotyping assay SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID POLYCHROMATIC FLOW-CYTOMETRY; CELLS; LIVE AB Multicolor experiments can be frustratingly difficult to implement and optimize; however, it is important to spend as much time as possible trying out variations and understanding in detail the impact of every reagent (and every labeling step) on the distribution of fluorescences in the final experiment. The resulting data sets will be far more interpretable and provide a rich source of information regarding the experimental conditions. Although panel development still largely is empiric, we hope that heuristic approaches and experience soon will translate into algorithms that can be used to assist in the development of such panels. C1 NIAID, NIH, ImmunoTechnol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Roederer, M (reprint author), NIAID, NIH, ImmunoTechnol Sect, Vaccine Res Ctr, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA. EM roederer@nih.gov RI Roederer, Mario/G-1887-2011 FU Intramural NIH HHS [Z01 AI005020-06, Z99 AI999999] NR 13 TC 77 Z9 81 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 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD SEP PY 2007 VL 27 IS 3 BP 469 EP + DI 10.1016/j.cII.2007.05.002 PG 19 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 207DK UT WOS:000249231600003 PM 17658403 ER PT J AU Wang, P AF Wang, Philip TI Pharmacoepidemiology: Examples of databases and studies SO CNS SPECTRUMS LA English DT Editorial Material ID COMORBIDITY SURVEY REPLICATION; SCHIZOPHRENIA; MEDICATIONS; DISORDERS C1 [Wang, Philip] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wang, Philip] NIMH, Div Serv Intervent Res, Bethesda, MD 20892 USA. RP Wang, P (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD SEP PY 2007 VL 12 IS 9 SU 16 BP 8 EP 10 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 256BP UT WOS:000252703000003 ER PT J AU Tucker, CM Herman, KC Ferdinand, LA Bailey, TR Lopez, MT Beato, C Adams, D Cooper, LL AF Tucker, Carolyn M. Herman, Keith C. Ferdinand, Lisa A. Bailey, Tamika R. Lopez, Manuel Thomas Beato, Cristina Adams, Diane Cooper, Leslie L. TI Providing patient-centered culturally sensitive health care: A formative model SO COUNSELING PSYCHOLOGIST LA English DT Article ID AFRICAN-AMERICANS; COMMUNICATIVE STYLES; DIABETIC-PATIENTS; METABOLIC CONTROL; SATISFACTION; PHYSICIAN; INTERVENTION; OUTCOMES; CONSULTATIONS; PERSPECTIVES AB This article describes the literature-based, testable, formative Patient-Centered Culturally Sensitive Health Care Model that explains the associations between patient-centered culturally sensitive health care, health-promoting treatment behaviors, and health outcomes and statuses. An intervention program based on the model and its foundational research are also described. In addition, the article summarizes research concerning the ongoing evaluation of the model and the intervention program as well as the development of pilot inventories to assess patient-centered culturally sensitive health care in community-based primary care clinics. C1 Univ Florida, Gainesville, FL 32611 USA. Univ Missouri, Columbia, MO 65211 USA. US Dept HHS, Washington, DC USA. Natl Canc Inst, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Tucker, CM (reprint author), Univ Florida, Gainesville, FL 32611 USA. EM cmtucker@ufl.edu NR 46 TC 21 Z9 22 U1 2 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0011-0000 J9 COUNS PSYCHOL JI Couns. Psychol. PD SEP PY 2007 VL 35 IS 5 BP 679 EP 705 DI 10.1177/0011000007301689 PG 27 WC Psychology, Applied SC Psychology GA 204AR UT WOS:000249015700003 ER PT J AU LoPiccolo, J Ballas, MS Dennis, PA AF LoPiccolo, Jaclyn Ballas, Marc S. Dennis, Phillip A. TI PTEN hamartomatous tumor syndromes (PHTS): Rare syndromes with great relevance to common cancers and targeted drug development SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE PHTS; Cowden syndrome; PTEN; mTOR ID LHERMITTE-DUCLOS-DISEASE; RILEY-RUVALCABA-SYNDROME; PHOSPHATIDYLINOSITOL 3-KINASE/AKT PATHWAY; CELECOXIB INDUCES APOPTOSIS; CASPASE-MEDIATED APOPTOSIS; BANNAYAN-ZONANA-SYNDROME; RENAL-CELL CARCINOMA; PROSTATE-CANCER; COWDEN-DISEASE; BREAST-CANCER AB Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor gene located on chromosome 10q22-23 that negatively regulates the pro-survival PI3K/Akt/mTOR pathway by functioning as a lipid phosphatase. Signaling through this pathway promotes cellular transformation and survival as well as resistance to chemotherapy and radiation. Loss of PTEN function is commonly observed in human cancers through somatic mutation, hypermethylation, and/or enhanced degradation. PTEN hamartomatous tumor syndromes (PHTS) are a collection of rare clinical syndromes marked by germline PTEN loss. Compared to the general population, PHTS patients have an increased risk of developing certain cancers and can develop benign tumors in virtually any organ. These patients provide a unique opportunity to examine the role of PTEN in human tumorigenesis, as well as study genotype-phenotype relationships. Because these patients are at higher risk of developing malignancies and have no established medical therapies, early screening, surveillance, and preventive care are important issues. Inhibitors of the PI3K/Akt/mTOR pathway that are being developed as cancer therapeutics could provide new therapeutic options for these rare patients, and could be credentialed as pathway inhibitors prior to testing in the general oncology population. Published by Elsevier Ireland Ltd. C1 NCI, Canc Res Ctr, Med Oncol Branch, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), NCI, Canc Res Ctr, Med Oncol Branch, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov NR 123 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD SEP PY 2007 VL 63 IS 3 BP 203 EP 214 DI 10.1016/j.critrevonc.2007.06.002 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 208AL UT WOS:000249292100002 PM 17643312 ER PT J AU Greig, NH Giacobini, E Lahiri, DK AF Greig, Nigel H. Giacobini, Ezio Lahiri, Debomoy K. TI Advances in Alzheimer therapy and development of innovative new strategies SO CURRENT ALZHEIMER RESEARCH LA English DT Editorial Material C1 NIA, Drug Design & Dev Sect, Neurosci Lab, NIH, Baltimore, MD 21224 USA. Univ Hosp Geneva, Univ Geneva Med Sch, Dept Geriatr, CH-1226 Thonex Geneva, Switzerland. Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM greign@grc.nia.nih.gov NR 0 TC 9 Z9 10 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD SEP PY 2007 VL 4 IS 4 BP 336 EP 339 DI 10.2174/156720507781788819 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 225CM UT WOS:000250494700001 PM 17908034 ER PT J AU Sugaya, K Kwak, YD Ohmitsu, O Marutle, A Greig, NH Choumrina, E AF Sugaya, K. Kwak, Y. D. Ohmitsu, O. Marutle, A. Greig, N. H. Choumrina, E. TI Practical issues in stem cell therapy for Alzheimer's disease SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE stem cell; beta-amyloid; amyloid precursor protein; neural differentiation; neurogenesis; gliosis; (+)-phenserine ID AMYLOID PRECURSOR PROTEIN; ADULT SUBVENTRICULAR ZONE; FIBRILLARY ACIDIC PROTEIN; EMBRYONAL CARCINOMA-CELLS; BINDING PROTEIN; NERVOUS-SYSTEM; HUMAN NEURONS; MOUSE-BRAIN; IN-VITRO; DIFFERENTIATION AB We have demonstrated that aged animals show significant improvements in cognitive function and neurogenesis after brain transplantation of human neural stem cells or of human adult mesenchymal stem cells that have been dedifferentiated by transfection of the embryonic stem cell gene. We have also demonstrated that peripheral administration of a pyrimidine derivative increased cognition, endogenous brain stem cell proliferation and neurogenesis. These results indicate a bright future for stem cell therapies in Alzheimer's disease (AD). Before this is realized, however, we need to consider the affect of AD pathology on stem cell biology to establish an effective stem cell therapy for this disease. Although amyloid-beta (A beta) deposition is a hallmark of AD, an absence of a phenotype in the beta-amyloid precursor protein (APP) knockout mouse, might lead one to underestimate the potential physiological functions of APP and suggest that it is unessential or can be compensated for. We have found, however, that APP is needed for differentiation of neural stem cells (NSCs) in vitro, and that NSCs transplanted into a APP-knockout mouse did not migrate or differentiate - indicating that APP plays an important role in differentiation or migration process of NSCs in the brain. Then again, treatment with high a concentration of APP or its over-expression increased glial differentiation of NSCs. Human NSCs transplanted into APP-transgenic mouse brain exhibited less neurogenesis and active gliosis around the plaque like fort-nations. Treatment of such animals with the compound, (+)-phenserine, that is known to reduce APP protein levels, increased neurogenesis and suppressed gliosis. These results suggest APP levels can regulate NSC biology in the adult brain, that altered APP metabolism in Down syndrome or AD may have implications for the pathophysiology of these diseases, and that a combination of stem cell therapy and regulation of APP levels could provide a treatment strategy for these disorders. C1 Univ Cent Florida, Burnett Coll Biomed Sci, Orlando, FL 32816 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Sugaya, K (reprint author), Univ Cent Florida, Biomol Sci Ctr, 4000 Cent Florida Blvd,BMS Bldg,Room 223, Orlando, FL 32816 USA. EM ksugaya@mail.ucf.du FU NIA NIH HHS [R01 AG23472] NR 72 TC 25 Z9 31 U1 1 U2 22 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD SEP PY 2007 VL 4 IS 4 BP 370 EP 377 DI 10.2174/156720507781788936 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 225CM UT WOS:000250494700006 PM 17908039 ER PT J AU Tweedie, D Sambamurti, K Greig, NH AF Tweedie, David Sambamurti, Kumar Greig, Nigel H. TI TNF-alpha inhibition as a treatment strategy for neurodegenerative disorders: New drug candidates and targets SO CURRENT ALZHEIMER RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; AMYOTROPHIC-LATERAL-SCLEROSIS; CREUTZFELDT-JAKOB-DISEASE; INFLUENZA-ASSOCIATED ENCEPHALOPATHY; AMYLOID PRECURSOR PROTEIN; TRANSGENIC MOUSE MODEL; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; MESSENGER-RNA AB As the average ages of North Americans and Europeans continue to rise; similarly the incidence of "old age" associated illnesses likewise increases. Most notably among these ailments are conditions linked to dementia-related neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and stroke. While in the early stages, these conditions are associated with cellular dysfunction in distinctly different brain regions, thus affecting different neuronal cell types; it is most likely that the final stages share similar cellular and molecular processes leading to neuronal death and ultimately overt clinical symptoms. In this regard, different environmental and genetic triggers ranging from head trauma to protein mutations and toxicological exposure may instigate a cascade of intracellular events that ultimately lead to neuronal death. One strong candidate trigger protein, and thus a potential target for therapeutic manipulation is the potent pro-inflammatory / pro-apoptotic cytokine, tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is secreted by the brain resident marcophage (the microglial cell) in response to various stimuli. It has been demonstrated to play a major role in central nervous system (CNS) neuroinflammation-mediated cell death in AD, PD and amyotrophic lateral sclerosis (ALS) as well as several other CNS complications. Recently, agents that modulate the levels of circulating peripheral TNF-alpha protein have been shown to be worthwhile therapeutic agents with the use. of Enbrel (Etanercept) and Remicade (Infliximab), both of which display beneficial properties against rheumatoid arthritis and other peripheral inflammatory diseases. Unfortunately, these agents are largely unable to penetrate the blood-brain barrier, which severely limits their use in the setting of neuroinflammation in the CNS. However, thalidomide, a small molecule drug, can inhibit TNF-alpha protein synthesis and, unlike larger molecules, is readily capable of crossing the blood-brain barrier. Thus thalidomide and its analogs are excellent candidate agents for use in determining the potential value of anti-TNF-alpha therapies in a variety of diseases underpinned by inflammation within the nervous system. Consequently, we have chosen to discuss the relevance of unregulated TNF-a expression in illnesses of the CNS and, to an extent, the peripheral nervous system. Additionally, we consider the utilization of thalidomide-derived agents as anti-TNF-alpha therapeutics in the setting of neuroinflammation. C1 NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. Med Univ S Carolina, Dept Neurosci, Charleston, SC 29464 USA. RP Tweedie, D (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Tweedieda@grc.nia.nih.gov FU Intramural NIH HHS; NIA NIH HHS [R01 AG023055, R01 AG023055-01A1, R01 AG023055-02, R01 AG023055-03, R01 AG023055-04, R01 AG023055-05] NR 92 TC 101 Z9 106 U1 0 U2 17 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD SEP PY 2007 VL 4 IS 4 BP 378 EP 385 DI 10.2174/156720507781788873 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 225CM UT WOS:000250494700007 PM 17908040 ER PT J AU Kapogiannis, BG Lee, SS AF Kapogiannis, Bill G. Lee, Sonia S. TI Rolling up our sleeves now to reap the benefits later: preparing the community for an adolescent HIV vaccine SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE adolescent HIV vaccine; community preparedness AB Purpose of review The staggering global incidence of HIV among youth and recent advances in the vaccine research pipeline have prompted a dialogue between investigators and the community whose adolescents are potential trial participants. We update progress on relevant efforts to prepare communities for HIV vaccine trials in youth and explore crucial next steps that may ensure willingness of communities to participate when such trials are offered. Recent findings Scientists hope that an effective HIV vaccine will confer highly reliable primary prevention; however, for optimal effectiveness in this vulnerable population, it must be administered before sexual debut. In addition to general participant concerns about HIV vaccine research, adolescent-focused researchers are challenged with caregiver and provider attitudes, ethical considerations (autonomy, consent, and confidentiality), and regulatory constraints. Several ongoing community HIV vaccine research preparation initiatives are addressing these challenges. Throughout the USA, a youth-oriented HIV research infrastructure was established by Connect-to-Protect (a program conducted by the National Institute of Child Health and Human Development-supported Adolescent Medicine Trials Network for HIV/AIDS Interventions) to mobilize communities, monitor intervention impact, provide HIV vaccine education, and effect structural change to decrease HIV among youths. Summary The inclusion of youth in plans for HIV vaccine research is timely and must be ensured. Communities want decision-making capacity, educational opportunities, and multifaceted HIV prevention contributions from researchers. C1 [Kapogiannis, Bill G.; Lee, Sonia S.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Kapogiannis, BG (reprint author), NICHHD, NICHD, CRMC, Pediat Adolescent & Maternal AIDS PAMA Branch, 6100 Execut Blvd,Room 4B11J, Bethesda, MD 20892 USA. EM Kapogiannisb@mail.nih.gov NR 57 TC 5 Z9 5 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD SEP PY 2007 VL 2 IS 5 BP 375 EP 384 DI 10.1097/COH.0b013e3282cecf0a PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NV UT WOS:000208418000003 PM 19372915 ER PT J AU Sampaio, J Brites, C Araujo, I Bacchi, CE Dittmer, DP Tanaka, PY Harrington, W Netto, EM AF Sampaio, Julio Brites, Carlos Araujo, Iguaracyra Bacchi, Carlos E. Dittmer, Dirk P. Tanaka, Paula Y. Harrington, William, Jr. Netto, Eduardo M. TI AIDS related malignancies in Brazil SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE Brazil; HAART; HIV; HTLV-I; Kaposi's sarcoma; lymphoma ID HUMAN-IMMUNODEFICIENCY-VIRUS; SARCOMA-ASSOCIATED HERPESVIRUS; NON-HODGKIN-LYMPHOMA; EPSTEIN-BARR-VIRUS; KAPOSIS-SARCOMA; NORTHEASTERN BRAZIL; HEPATITIS-C; HUMAN-HERPESVIRUS-8; SEROPREVALENCE; AMERINDIANS AB Purpose of review There have been relatively few studies,of HIV-related malignancies in Brazil. Universal,access to antiretroviral drugs in Brazil has changed both the mortality and morbidity rates of AIDS. Nevertheless, there is also extreme poverty in both urban and rural areas and complications of prolonged immune suppression such as mycobacterial and malignant diseases have put a significant strain on the country's healthcare system. This brief review outlines the existing data regarding AIDS related malignancies in the largest Latin American country. Recent findings Currently, there are almost 600000 people infected with HIV in Brazil and 170 000 patients are receiving highly active antiretroviral therapy. In the studies done of HIV malignancies in Brazil, it appears that these tumors are histologically similar to those that occur in other equatorial countries and differ somewhat from those seen in Europe and the US. Another unique distinction is the high association with oncogenic herpes viruses. Summary The existence of federally sponsored highly active antiretroviral therapy, clinicians and healthcare providers experienced in the care of HIV patients and high incidence of malignancies associated with oncogenic viruses make Brazil an important site for clinical and basic research in AIDS and immunodeficiency related malignancies. C1 Univ Miami, Miller Sch Med, Div Hematol Oncol,Sylvester Comprehens Canc Ctr, Dept Med,Fogarty Int Ctr,AIDS & TB Program, Miami, FL 33136 USA. Univ Fed Bahia, Edgard Santos Univ Hosp, Salvador, BA, Brazil. Univ N Carolina, Chapel Hill, NC USA. Emilio Ribas Infectol Inst, Sect Hematol, Sao Paulo, Brazil. RP Harrington, W (reprint author), Univ Miami, Miller Sch Med, Div Hematol Oncol,Sylvester Comprehens Canc Ctr, Dept Med,Fogarty Int Ctr,AIDS & TB Program, Room 3400 D8-4, Miami, FL 33136 USA. EM wharring@med.miami.edu RI Netto, Eduardo/D-1432-2013 OI Netto, Eduardo/0000-0003-1691-6761 FU FIC NIH HHS [D43 TW000017, 5D43 TW00017-18]; NCI NIH HHS [U01 CA070058, CA70058, R01 CA109232-03S1, R01 CA109232-05, R01 CA109232-01, R01 CA163217, R01 CA109232-04, R01 CA109232-02, R01 CA109232-03, R01 CA109232]; NIDCR NIH HHS [R01 DE018304-03, R01 DE018304-01, R01 DE018304-02, R01 DE018304] NR 22 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD SEP PY 2007 VL 19 IS 5 BP 476 EP 478 DI 10.1097/CCO.0b013e3282c8c8eb PG 3 WC Oncology SC Oncology GA 201NA UT WOS:000248837400010 PM 17762574 ER PT J AU Mohamed, MA Cunningham-Rundles, S Dean, CR Hammad, TA Nesin, M AF Mohamed, Mohamed A. Cunningham-Rundles, Susanne Dean, Charles R. Hammad, Tarek A. Nesin, Mirjana TI Levels of pro-inflammatory cytokines produced from cord blood in-vitro are pathogen dependent and increased in comparison to adult controls SO CYTOKINE LA English DT Article DE interleukin-6; inteleukin-8; interleukin-1 beta; tumor necrosis factor-alpha; group B streptococcus; e. coli; staphylococcus epidermidis; immunemetric; assay ID TUMOR-NECROSIS-FACTOR; GROUP-B STREPTOCOCCI; EARLY-ONSET SEPSIS; NEONATAL RESEARCH NETWORK; BIRTH-WEIGHT INFANTS; PRETERM INFANTS; PLASMA-LEVELS; DEFECTIVE PRODUCTION; FACTOR-ALPHA; INTERLEUKIN-6 AB Background: Overproduction of pro-inflammatory cytokines may play a role in increased morbidity and mortality from neonatal sepsis. Objective of this study was to compare secretion of pro-inflammatory cytokines by the cord blood cells of healthy term neonates to the venous blood cells of healthy adults in vitro after stimulation with common neonatal pathogens. Method: Blood samples were cultured in the presence of heat-killed group B beta-hemolytic streptococci (GBS), Escherichia coli (E. coli) and Staphylococcus epidermidis (S. epi). Concentrations of secreted cytokines (interleukine-6, IL-6, tumor necrosis factor-alpha, TNF-alpha, interleukine-1 beta, IL-1 beta and interleukine-8, IL-8) were measured after 0, 1, 2 and 4 h of incubation using chemiluminescent immunometric automated assay. Results: Blood samples from 22 neonates and 16 adults were compared. After stimulation by GBS and E. coli, cord blood cells secreted significantly higher levels of IL-6 and IL-8 than blood cells of healthy adults. In cord blood, E. coli induced secretion of higher concentration of IL-6, TNF-alpha, IL- 1 beta and IL-8 than S. epi, and more IL-6 than GBS; GBS induced more IL-1 beta than S. epi. Conclusions: Response of cord blood to microbial activators is different from that of adult controls. Each isolate of heat-killed bacteria induced different amount of pro-inflammatory cytokines in vitro. This may represent a useful in vitro virulence test. (c) 2007 Elsevier Ltd. All rights reserved. C1 NIAID, NIH, DMID OCRA, Bethesda, MD 20892 USA. George Washington Univ Hosp, Newborn Serv Dept, Washington, DC 20037 USA. Cornell Univ, Weill Med Coll, Dept Pediat, New York, NY 11021 USA. BioMed Res Inc, Infect Dis Novartis Inst, Cambridge, MA 02139 USA. RP Nesin, M (reprint author), NIAID, NIH, DMID OCRA, 6610 Rockledge Dr,Room 6049, Bethesda, MD 20892 USA. EM mmohamed@mfa.gwu.edu; scrundle@med.cornell.edu; charlesR.dean@pharma.novartis.com; nesinm@niaid.nih.gov NR 41 TC 21 Z9 22 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 2007 VL 39 IS 3 BP 171 EP 177 DI 10.1016/j.cyto.2007.07.004 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 234HI UT WOS:000251151000003 PM 17884557 ER PT J AU Roederer, M AF Roederer, Mario TI The impact of flow cytometry on hiv vaccine development SO CYTOMETRY PART A LA English DT Meeting Abstract CT 17th Annual Meeting of the German-Society-of-Cytometry (DGfZ) CY OCT 10-13, 2007 CL Univ Hosp, Regensburg, Regensburg, GERMANY SP Regensburger Univ Hans Vielberth, STIF NG, Partec GmbH HO Univ Hosp, Regensburg C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD SEP PY 2007 VL 71A IS 9 MA 5 BP 744 EP 744 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 206MO UT WOS:000249187800021 ER PT J AU Roederer, M AF Roederer, Mario TI Designing, implementing and analyzing multicolor flow experiments SO CYTOMETRY PART A LA English DT Meeting Abstract CT 17th Annual Meeting of the German-Society-of-Cytometry (DGfZ) CY OCT 10-13, 2007 CL Univ Hosp, Regensburg, Regensburg, GERMANY SP Regensburger Univ Hans Vielberth, STIF NG, Partec GmbH HO Univ Hosp, Regensburg C1 NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD SEP PY 2007 VL 71A IS 9 MA 19 BP 750 EP 750 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 206MO UT WOS:000249187800035 ER PT J AU Ried, T AF Ried, Thomas TI Multiparametric fluorescence-in-situ-hybridization (fish) and spectral karyotyping (sky) in diagnosis of human malignancies SO CYTOMETRY PART A LA English DT Meeting Abstract CT 17th Annual Meeting of the German-Society-of-Cytometry (DGfZ) CY OCT 10-13, 2007 CL Univ Hosp, Regensburg, Regensburg, GERMANY SP Regensburger Univ Hans Vielberth, STIF NG, Partec GmbH HO Univ Hosp, Regensburg C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD SEP PY 2007 VL 71A IS 9 MA 22 BP 751 EP 751 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 206MO UT WOS:000249187800038 ER PT J AU Spinelli, S Schwandt, ML Lindell, SG Newman, TK Heilig, M Suomi, SJ Higley, JD Goldman, D Barr, CS AF Spinelli, Simona Schwandt, Melanie L. Lindell, Stephen G. Newman, Timothy K. Heilig, Markus Suomi, Stephen J. Higley, J. Dee Goldman, David Barr, Christina S. TI Association between the recombinant human serotonin transporter linked promoter region polymorphism and behavior in rhesus macaques during a separation paradigm SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; PITUITARY-ADRENAL AXIS; REARING CONDITION; GENE VARIATION; STEREOTYPIC BEHAVIOR; SOCIAL SEPARATION; LIFE STRESS; DRUG-ABUSE; PRIMATE; MONKEYS AB Human studies have suggested an association between a variable length polymorphism in the serotonin transporter gene promoter region and vulnerability to anxiety and depression. Relative to the long (l) allele, the short (s) allele increases the risk of developing depression in individuals exposed to stressful life events. An orthologue of the human variant is present in rhesus macaques and allows for studies in animals exposed to stress. Here, we used an established model of early life stress exposure, in which rhesus macaques are raised without adults in a group of peers (peer-only reared [PR]), or with their mothers. At 6 months of age, animals were subjected to 4-day long social separations for 4 consecutive weeks, with 3 days of reunion in between. Data were collected during both the acute (Day 1) and chronic phases (Days 2-4) of separation. Behavioral factors were separately extracted for each phase of separation. For acute separation, the behavioral factors generated were despair and behavioral pathology and, for the chronic phase despair, agitation, and behavioral pathology. During both phases of social separation, PR l/s animals were more likely to exhibit pathological behaviors, whereas PR l/l monkeys show higher levels of despair compared to the other three groups. These findings indicate that early stress affects the behavioral response to separation differently as a function of recombinant human serotonin transporter linked polymorphic repeat genotype and suggest that carriers of the s allele are not only more anxious but may also be more vulnerable to developing behavioral pathology in the face of chronic adversity. C1 NIAAA, Lab Clin & Translat Studies, Primate Sect, NIH,Anim Ctr, Poolesville, MD 20837 USA. Brigham Young Univ, Provo, UT 84602 USA. RP Barr, CS (reprint author), NIAAA, Lab Clin & Translat Studies, Primate Sect, NIH,Anim Ctr, POB 529, Poolesville, MD 20837 USA. EM cbarr@mail.nih.gov RI Goldman, David/F-9772-2010; Schwandt, Melanie/L-9866-2016; OI Goldman, David/0000-0002-1724-5405; Heilig, Markus/0000-0003-2706-2482 FU Intramural NIH HHS NR 37 TC 47 Z9 47 U1 2 U2 10 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 2007 VL 19 IS 4 BP 977 EP 987 DI 10.1017/S095457940700048X PG 11 WC Psychology, Developmental SC Psychology GA 223VJ UT WOS:000250400300003 PM 17931429 ER PT J AU Lau, JYF Gregory, AM Goldwin, MA Pine, DS Eley, TC AF Lau, Jennifer Y. F. Gregory, Alice M. Goldwin, Michelle A. Pine, Daniel S. Eley, Thalia C. TI Assessing gene-environment interactions on anxiety symptom subtypes across childhood and adolescence SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID SEPARATION ANXIETY; PANIC DISORDER; DEPRESSIVE-DISORDERS; MANIFEST ANXIETY; CARBON-DIOXIDE; MENTAL-HEALTH; CHILDREN; RISK; TWIN; SCREEN AB Consistent evidence shows both genetic and stress-related risks on child and adolescent anxiety, yet few studies have considered the degree to which genetic effects are moderate(] by stress (gene-environment interaction). We used longitudinal data from both a child and adolescent sample of twins to examine three novel issues on the presence of gene-environment interaction on anxiety symptoms. First, we assessed moderation of genetic risks on anxiety symptoms by negative life events in each age group. Second, by distinguishing between "stable" and "age-specific" genetic factors, we explored the continuity of gene-environment interaction across time and/or its emergence at specific ages. Third, we compared the presence of gene-environment interaction across different symptom types (general, panic, social, and separation). Genetic effects on separation anxiety symptoms in childhood (mean age = 8 years, 6 months) and panic anxiety symptoms in adolescence (mean age = 15 years) increased across independent negative life events. Shared environmental effects on separation anxiety symptoms and nonshared environmental effects on general anxiety symptoms in adolescence were also moderated by negative life events. We interpret these preliminary findings tentatively in the context of gene-environment interaction on anxiety in general, and on early separation and later panic anxiety in particular. C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Lau, JYF (reprint author), NIMH, NIH, 15K,N Dr, Bethesda, MD 20892 USA. EM lauj@mail.nih.gov RI Eley, Thalia/D-4811-2011 FU Intramural NIH HHS; Medical Research Council [G120/635] NR 51 TC 39 Z9 40 U1 3 U2 13 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 2007 VL 19 IS 4 BP 1129 EP 1146 DI 10.1017/S0954579407000582 PG 18 WC Psychology, Developmental SC Psychology GA 223VJ UT WOS:000250400300013 PM 17931439 ER PT J AU Mammarella, S Creati, B Staniscia, T Verginelli, F Manzoli, L Di Valerio, A Aceto, G Romano, F Cama, G Capani, F Consoli, A Vitacolonna, E Esposito-Del Puente, A Battista, P Della Loggia, F Mariani-Costantini, R Quon, MJ Cama, A AF Mammarella, S. Creati, B. Staniscia, T. Verginelli, F. Manzoli, L. Di Valerio, A. Aceto, G. Romano, F. Cama, G. Capani, F. Consoli, A. Vitacolonna, E. Esposito-Del Puente, A. Battista, P. Della Loggia, F. Mariani-Costantini, R. Quon, M. J. Cama, A. TI Obesity modifies the effects of the Asp905Tyr variant of PPP1R3A on risk of type 2 diabetes and insulin sensitivity SO DIABETES OBESITY & METABOLISM LA English DT Letter ID RESISTANCE; POLYMORPHISMS; MELLITUS; SUBUNIT; GENE C1 Univ Chieti Gabriele Annunzio, Dept Oncol & Neurosci, Sect Mol Pathol, I-66013 Chieti, Italy. G Annunzio Univ Fdn, Ctr Excellence Aging, Chieti, Italy. G Annunzio Univ Fdn, Dept Med Aging, Chieti, Italy. Univ Roma La Sapienza, Dept Expt Med & Pathol, Rome, Italy. Hosp Casoria S Maria Pieta, Dept Pediat, Naples, Italy. Ctr Study Diabetes, Chieti, Italy. NCCAM, Diabet Unit, Bethesda, MD USA. RP Cama, A (reprint author), Univ Chieti Gabriele Annunzio, Dept Oncol & Neurosci, Sect Mol Pathol, Edificio C Livello 4,Via VEstini, I-66013 Chieti, Italy. EM cama@unich.it RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; VITACOLONNA, Ester/0000-0003-1756-661X; Manzoli, Lamberto/0000-0002-8129-9344; Quon , Michael /0000-0002-5289-3707 NR 8 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD SEP PY 2007 VL 9 IS 5 BP 759 EP 761 DI 10.1111/j.1463-1326.2006.00699.x PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 203HO UT WOS:000248965900018 PM 17697067 ER PT J AU Jamieson, HA Cogger, VC Twigg, SM McLennan, SV Warren, A Cheluvappa, R Hilmer, SN Fraser, R de Cabo, R Le Couteur, DG AF Jamieson, H. A. Cogger, V. C. Twigg, S. M. McLennan, S. V. Warren, A. Cheluvappa, R. Hilmer, S. N. Fraser, R. de Cabo, R. Le Couteur, D. G. TI Alterations in liver sinusoidal endothelium in a baboon model of type 1 diabetes SO DIABETOLOGIA LA English DT Article DE diabetes mellitus; electron microscopy; fenestrations; liver sinusoidal endothelial cell; LSEC; papio hamadryas; stellate cells ID PAPIO-HAMADRYAS MODEL; PERISINUSOIDAL FIBROSIS; OXIDATIVE STRESS; RAT-LIVER; PSEUDOCAPILLARIZATION; CIRRHOSIS; DISEASE; SIEVE; ATHEROSCLEROSIS; LIPOPROTEINS AB Aims/hypothesis Diabetes mellitus is associated with extensive vascular pathology, yet little is known about its long-term effects on liver sinusoidal endothelial cells (LSECs). Potential diabetic changes in LSECs are important because of the role played by fenestrations in the LSECs in hepatic disposition of lipoproteins. Materials and methods Surgical liver biopsies for electron microscopy and immunohistochemistry were obtained from baboons with long-standing streptozotocin-induced, insulin-treated diabetes mellitus and compared with those from age-matched control animals. Results There was an increase in the thickness of LSECs (170 +/- 17 vs 123 +/- 10 nm, p < 0.01). Fenestrations in LSECs, as determined by overall porosity, were markedly reduced (1.4 +/- 0.1% vs 2.6 +/- 0.2%, p < 0.01). Increased numbers of stellate cells were seen on electron microscopy, and this finding was corroborated by increased smooth muscle actin expression. Diabetes mellitus was also associated with increased endothelial production of von Willebrand factor and caveolin-1. Conclusions/interpretation Diabetes mellitus in the non-human primate is associated with marked changes in LSECs, including a reduction in fenestrations. Such changes provide an additional and novel mechanism for impaired hepatic lipoprotein clearance and post-prandial hyperlipidaemia in diabetes mellitus. C1 Concord RG Hosp, ANZAC Res Inst, Concord, NSW 2139, Australia. Univ Sydney, Concord, NSW 2139, Australia. NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. Royal Prince Alfred Hosp, Dept Endocrinol, Camperdown, NSW 2050, Australia. Univ Sydney, Camperdown, NSW, Australia. Royal N Shore Hosp, Dept Aged Care, St Leonards, NSW 2065, Australia. Royal N Shore Hosp, Dept Clin Pharmacol, St Leonards, NSW 2065, Australia. Univ Otago, Christchurch Sch Med, Dept Pathol, Christchurch, New Zealand. RP Jamieson, HA (reprint author), Concord RG Hosp, ANZAC Res Inst, Concord, NSW 2139, Australia. EM hjamieson@med.usyd.edu.au RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Hilmer, Sarah/0000-0002-5970-1501; , rafael/0000-0003-2830-5693 NR 35 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 IS 9 BP 1969 EP 1976 DI 10.1007/s00125-007-0739-4 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 200OD UT WOS:000248771800022 PM 17604976 ER PT J AU Mabley, JG Nemeth, ZH Bleich, D Csoka, B Pacher, P Vizi, S Deitch, EA Szabo, C Cronstein, BN Hasko, G AF Mabley, J. G. Nemeth, Z. H. Bleich, D. Csoka, B. Pacher, P. Vizi, S. Deitch, E. A. Szabo, C. Cronstein, B. N. Hasko, G. TI Activation of adenosine receptors protects against type 1 diabetes SO DIABETOLOGIA LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 18-21, 2007 CL Amsterdam, NETHERLANDS SP European Assco Study Diabet C1 Univ Brighton, Sch Pharm & Biomol Sci, Brighton, E Sussex, England. Univ Med & Dent New Jersey, Dept Surg, Newark, NJ 07103 USA. NIH, Lab Physiol Studies, Bethesda, MD 20892 USA. Hungarian Acad Sci, Inst Expt Med, Budapest, Hungary. NYU, Sch Med, Div Clin Pharmacol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 SU 1 MA 0446 BP S190 EP S190 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 209NP UT WOS:000249395600447 ER PT J AU Prokopenko, I Zeggini, E Rayner, NW Groves, CJ Hanson, RL Mitchell, BD Vaxillaire, M Hunt, SE Cardon, LR Froguel, P Elbein, SC Shuldiner, AR Deloukas, P McCarthy, MI AF Prokopenko, I. Zeggini, E. Rayner, N. W. Groves, C. J. Hanson, R. L. Mitchell, B. D. Vaxillaire, M. Hunt, S. E. Cardon, L. R. Froguel, P. Elbein, S. C. Shuldiner, A. R. Deloukas, P. McCarthy, M. I. TI High-density association mapping and comprehensive tagging of the type 2 diabetes linkage region on chromosome 1q in 4 European populations SO DIABETOLOGIA LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 18-21, 2007 CL Amsterdam, NETHERLANDS SP European Assco Study Diabet C1 Univ Oxford, WTCHG, Oxford, England. NIDDK, NIH, Phoenix, AZ USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Inst Pasteur, Inst Biol Lille Genom Physiol Mol Malad Metab, F-59019 Lille, France. Wellcome Trust Sanger Inst, Hinxton, England. Univ London Imperial Coll Sci & Technol, Div Med, London, England. Univ Arkansas, Div Endocrinol & Metab, Little Rock, AR 72204 USA. RI Deloukas, Panos/B-2922-2013; Hanson, Robert/O-3238-2015 OI Deloukas, Panos/0000-0001-9251-070X; Hanson, Robert/0000-0002-4252-7068 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 SU 1 MA 0169 BP S75 EP S75 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 209NP UT WOS:000249395600170 ER PT J AU Cummings, JR Jamison, GR Boudreaux, JW Howles, MJ Walsh, TJ Hayden, RT AF Cummings, Jessica R. Jamison, Ginger R. Boudreaux, Jan W. Howles, Merry J. Walsh, Thomas J. Hayden, Randall T. TI Cross-reactivity of non-Aspergillus fungal species in the Aspergillus galactomannan enzyme immunoassay SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE aspergillus; galactomannan; antigen ID LINKED-IMMUNOSORBENT-ASSAY; INVASIVE ASPERGILLOSIS; TRANSPLANT RECIPIENTS; IN-VIVO; DIAGNOSIS; ANTIGEN AB The Aspergillus galactomannan enzyme-linked immunosorbant assay (EIA) has been demonstrated to facilitate rapid and sensitive detection of invasive aspergillosis. However, test specificity has not been fully evaluated in non-Aspergillus fungal species. Of 53 fungal isolates, cross-reactivity was observed with 5 non-Aspergillus spp.: Blastomyces dermatitidis, Nigrospora oryzae, Paecilomyces lilacinus, Penicillium chrysogenum, and Trichothecium roseum. (c) 2007 Elsevier Inc. All rights reserved. C1 St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38103 USA. NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. RP Hayden, RT (reprint author), St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38103 USA. EM randall.hayden@stjude.org FU Intramural NIH HHS; NCI NIH HHS [R25 CA023944] NR 19 TC 55 Z9 58 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD SEP PY 2007 VL 59 IS 1 BP 113 EP 115 DI 10.1016/j.diagmicrobio.2007.04.022 PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 217WH UT WOS:000249977500019 PM 17662550 ER PT J AU Garcia-Diaz, M Bebenek, K Krahn, JM Pedersen, LC Kunkel, TA AF Garcia-Diaz, Miguel Bebenek, Katarzyna Krahn, Joseph M. Pedersen, Lars C. Kunkel, Thomas A. TI Role of the catalytic metal during polymerization by DNA polymerase lambda SO DNA REPAIR LA English DT Article DE DNA polymerase lambda; DNA repair; nucleotidyl transfer; phosphoryl transfer; X-ray crystallography; crystal structure; divalent metal; catalysis; manganese; non-hydrolyzable nucleotide ID BASE EXCISION-REPAIR; ESCHERICHIA-COLI; MECHANISM; FIBROBLASTS; DEPENDENCE; FIDELITY; SYSTEM; BETA AB The incorporation of dNMPs into DNA by polymerases involves a phosphoryl transfer reaction hypothesized to require two divalent metal ions. Here we investigate this hypothesis using as a model human DNA polymerase lambda (Pol lambda), an enzyme suggested to be activated in vivo by manganese. We report the crystal structures of four complexes of human Pol X. In a 1.9 angstrom structure of Pol lambda containing a 3'-OH and the non-hydrolyzable analog dUpnpp, a non-catalytic Na+ ion occupies the site for metal A and the ribose of the primer-terminal nucleotide is found in a conformation that positions the acceptor 3'-OH out of line with the a-phosphate and the bridging oxygen of the pyrophosphate leaving group. Soaking this crystal in MnCl2 yielded a 2.0 angstrom structure with Mn2+ occupying the site for metal A. In the presence of Mn2+, the conformation of the ribose is C3'-endo and the 3'-oxygen is in line with the leaving oxygen, at a distance from the phosphorus atom of the alpha-phosphate (3.69 angstrom) consistent with and supporting a catalytic mechanism involving two divalent metal ions. Finally, soaking with MnCl2 converted a pre-catalytic Pol lambda/Na+ complex with unreacted dCTP in the active site into a product complex via catalysis in the crystal. These data provide pre- and post-transition state information and outline in a single crystal the pathway for the phosphoryl transfer reaction carried out by DNA polymerases. Published by Elsevier B.V. C1 [Garcia-Diaz, Miguel; Bebenek, Katarzyna; Krahn, Joseph M.; Pedersen, Lars C.; Kunkel, Thomas A.] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Garcia-Diaz, Miguel; Bebenek, Katarzyna; Kunkel, Thomas A.] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU Intramural NIH HHS [Z01 ES065070-17] NR 34 TC 37 Z9 37 U1 1 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 2007 VL 6 IS 9 BP 1333 EP 1340 DI 10.1016/j.dnarep.2007.03.005 PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 208PR UT WOS:000249332200011 PM 17475573 ER PT J AU Oh, KS Imoto, K Boyle, J Khan, SG Kraemer, KH AF Oh, Kyu-Seon Imoto, Kyoko Boyle, Jennifer Khan, Sikandar G. Kraemer, Kenneth H. TI Influence of XPB helicase on recruitment and redistribution of nucleotide excision repair proteins at sites of UV-induced DNA damage SO DNA REPAIR LA English DT Article DE xeroderma pigmentosum; Confocal microscopy; helicase; TFIIH ID REPAIR/TRANSCRIPTION FACTOR TFIIH; RNA-POLYMERASE-II; GROUP-C PROTEIN; XERODERMA-PIGMENTOSUM; COCKAYNE-SYNDROME; IRRADIATED DNA; CELL-NUCLEI; GENE ERCC3; IN-VIVO; TRANSCRIPTION AB The XPB DNA helicase, a subunit of the basal transcription factor TFIIH, is also involved in nucleotide excision repair (NER). We examined recruitment of NER proteins in XP-B cells from patients with mild or severe xeroderma. pigmentosum (XP) having different XPB mutations using local UV-irradiation through filters with 5 mu m pores combined with fluorescent antibody labeling. XPC was rapidly recruited to UV damage sites containing DNA photoproducts (cyclobutane pyrimidine dimers, CPD) in all the XP-B and normal cells, thus reflecting its role in damage recognition prior to the function of XPB. Cells from the mild XP-B patients, with a missense mutation, showed delayed recruitment of all NER proteins except XPC to UV damage sites, demonstrating that this mutation impaired localization of these proteins. Surprisingly, in cells from severely affected patients, with a C-terminal XPB mutation, XPG and XPA proteins were normally recruited to UV damage sites demonstrating that this mutation permits recruitment of XPG and XPA. In marked contrast, in all the XP-B cells recruitment of XPF was absent immediately after UV and was delayed by 0.5 and 3 h in cells from the mild and severely affected XP patients, respectively. Redistribution of NER proteins was nearly complete in normal cells by 3 h but by 24 h redistribution was only partially present in cells from mild patients and virtually absent in cells from the severely affected patients. ineffectual repair of UV-induced photoproducts resulting from delayed recruitment and impaired redistribution of NER proteins may contribute to the markedly increased frequency of skin cancer in XP patients. Published by Elsevier B.V. C1 [Oh, Kyu-Seon; Imoto, Kyoko; Boyle, Jennifer; Khan, Sikandar G.; Kraemer, Kenneth H.] NCI, Ctr Canc Res, DNA Repair Sect, Basic Res Lab, Bethesda, MD 20892 USA. RP Kraemer, KH (reprint author), NCI, Ctr Canc Res, DNA Repair Sect, Basic Res Lab, Bldg 37,Room 4002,MSC 4258, Bethesda, MD 20892 USA. EM kraemerk@nih.gov FU Intramural NIH HHS [Z01 BC004517-31] NR 45 TC 21 Z9 22 U1 1 U2 4 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 2007 VL 6 IS 9 BP 1359 EP 1370 DI 10.1016/j.dnarep.2007.03.025 PG 12 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 208PR UT WOS:000249332200013 PM 17509950 ER PT J AU Thomas, YF Schnur, P Iguchi, MY AF Thomas, Yonette F. Schnur, Paul Iguchi, Martin Y. TI Behavioral and economic perspectives in drug abuse research SO DRUG AND ALCOHOL DEPENDENCE LA English DT Editorial Material DE economics C1 Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD 20852 USA. NIH, Div Basic Neurosci & Behav Res, Dept Hlth & Human Serv, Bethesda, MD 20852 USA. RAND Corp, Drug Policy Res Ctr, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90005 USA. RP Thomas, YF (reprint author), Natl Inst Drug Abuse, Epidemiol Res Branch, Div Epidemiol Serv & Prevent Res, 6001 Execut Blvd,Room 5185,MSC 9589, Bethesda, MD 20892 USA. EM yt38e@nih.gov RI Iguchi, Martin/A-7848-2009 NR 12 TC 1 Z9 1 U1 2 U2 3 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 PY 2007 VL 90 SU 1 BP S1 EP S3 DI 10.1016/j.drugalcdep.2007.05.002 PG 3 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 193LO UT WOS:000248275700001 PM 17553636 ER PT J AU Dhamoon, AS Kohn, EC Azad, NS AF Dhamoon, Amit S. Kohn, Elise C. Azad, Nilofer S. TI The ongoing evolution of proteomics in malignancy SO DRUG DISCOVERY TODAY LA English DT Review ID GROWTH-FACTOR RECEPTOR; LASER CAPTURE MICRODISSECTION; FLIGHT MASS-SPECTROMETRY; IDENTIFY OVARIAN-CANCER; HUMAN PLASMA PROTEOME; CELL LUNG-CANCER; PROSTATE-CANCER; BREAST-CANCER; COPY-NUMBER; 2-DIMENSIONAL ELECTROPHORESIS AB The complementary fields of genomics and proteomics offer insights into the molecular mechanisms of diseases. While genomics seeks to define our genetic substrate, proteomics explores the structure and function of proteins, which are the end effectors of our genes. Proteomics has been revolutionized in the past decade by the application of techniques such as protein arrays, two-dimensional gel electrophoresis, and mass spectrometry. These techniques have tremendous potential for biomarker development, target validation, diagnosis, prognosis, and optimization of treatment in medical care, especially in the field of clinical oncology. We will discuss innovations in proteomic technologies and highlight their prospective applications to patient care. C1 NIH, NCI, Canc Res Ctr, Med Oncol Branch, Bethesda, MD 20892 USA. RP Dhamoon, AS (reprint author), NIH, NCI, Canc Res Ctr, Med Oncol Branch, 10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. EM azadn@mail.nih.gov FU Intramural NIH HHS NR 72 TC 14 Z9 14 U1 0 U2 0 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 2007 VL 12 IS 17-18 BP 700 EP 708 DI 10.1016/j.drudis.2007.07.015 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 216LF UT WOS:000249878800003 PM 17826682 ER PT J AU Mansky, P Hoffman, K Gerber, L Chrousos, G Steinberg, S Mackall, C AF Mansky, P. Hoffman, K. Gerber, L. Chrousos, G. Steinberg, S. Mackall, C. TI Long-term cancer survivorship issues: Is there a role for CAM? SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Mansky, P.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Hoffman, K.; Steinberg, S.; Mackall, C.] NIH, Natl Canc Inst, Bethesda, MD USA. [Gerber, L.] George Mason Univ, Ctr Chron Illness & Disability, Fairfax, VA 22030 USA. [Chrousos, G.] NIH, NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 54 BP 18 EP 18 DI 10.1016/S1359-6349(07)70168-4 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000053 ER PT J AU Giaccone, G AF Giaccone, G. TI How to exploit the apoptic machinery SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Giaccone, G.] Natl Canc Inst, Med Oncol Branch, Bethesda, MD 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 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 74 BP 22 EP 22 DI 10.1016/S1359-6349(07)70188-X PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000067 ER PT J AU Ambros, PF Ambros, IM Brodeur, GM Haber, M Khan, J Nakagawara, A Schleiermacher, G Speleman, F Spitz, R Maris, JM AF Ambros, P. F. Ambros, I. M. Brodeur, G. M. Haber, M. Khan, J. Nakagawara, A. Schleiermacher, G. Speleman, F. Spitz, R. Maris, J. M. TI International consensus for neuroblastoma molecular diagnostics: report from the international neuroblastoma risk grouping (INRG) biology committee SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Ambros, P. F.; Ambros, I. M.] Anna Kinderkrebsforsch Tumorcytogenet, CCRI, Vienna, Austria. [Brodeur, G. M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Haber, M.] Childrens Canc Inst Australia, Randwick, NSW, Australia. [Khan, J.] NCI, Oncogenom Sect, Bethesda, MD 20892 USA. [Nakagawara, A.] Chiba Canc Ctr, Res Inst, Div Biochem, Chiba, Japan. [Schleiermacher, G.] Inst Curie, Dept Pediat Oncol, Paris, France. [Speleman, F.] State Univ Ghent Hosp, Ctr Genet Med, Ghent, Belgium. [Spitz, R.] Univ Cologne, Dept Pediat Oncol & Hematol, Cologne, Germany. [Maris, J. M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 181 BP 48 EP 48 DI 10.1016/S1359-6349(07)70295-1 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000154 ER PT J AU Pastwa, E Neumann, RD Winters, T AF Pastwa, E. Neumann, R. D. Winters, Ta. TI Influence of wortmannin on non-homologous DNA end joining in human normal and cancer cells SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Pastwa, E.] Med Univ Lodz, Dept Mol Genet, Lodz, Poland. [Neumann, R. D.; Winters, Ta.] NIH, Dept Nucl Med, 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 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 BP 82 EP 82 DI 10.1016/S1359-6349(07)70410-X PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000261 ER PT J AU Kil, WJ Cerna, D Burgan, WE Beam, K Carter, D Tofilon, P Ohta, S Camphausen, K AF Kil, W. J. Cerna, D. Burgan, W. E. Beam, K. Carter, D. Tofilon, P. Ohta, S. Camphausen, K. TI Enhancement of glioma cell line radiosensitivity by the DNA methylating agent Temozolomide SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Kil, W. J.; Cerna, D.; Burgan, W. E.; Beam, K.; Carter, D.; Ohta, S.; Camphausen, K.] Natl Canc Inst, Natl Inst Hlth, Bethesda, MD USA. [Tofilon, P.] Drug Discovery Program, H Lee Moffitt Canc Ctr, Tampa, FL 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 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 915 BP 123 EP 123 DI 10.1016/S1359-6349(07)70554-2 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000405 ER PT J AU Giaccone, G Melosky, B Reck, M AF Giaccone, G. Melosky, B. Reck, M. TI Epidermal Ggrowth Factor Receptor Inhibitor (EGFRI)-associated rash: a suggested novel management paradigm. A consensus position from the EGFRI Dermatologic Toxicity Forum SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Giaccone, G.] Natl Canc Inst, CCR, Med Oncol Branch, Bethesda, MD USA. [Melosky, B.] British Columbia Canc Agcy, Vancouver, BC, Canada. [Reck, M.] Hosp Grosshansdorf, Grosshansdorf, Germany. 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 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 1115 BP 146 EP 146 DI 10.1016/S1359-6349(07)70634-1 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000485 ER PT J AU Mencoboni, M Serra, M Tunesi, G Gianola, M Rebella, L Galbusera, V Filiberti, R Puntoni, R Paganuzzi, M Bergaglio, M AF Mencoboni, M. Serra, M. Tunesi, G. Gianola, M. Rebella, L. Galbusera, V. Filiberti, R. Puntoni, R. Paganuzzi, M. Bergaglio, M. TI Clinical and potential prognostic significance of serum mesothelin and osteopontin in chemotherapy treated patients affected by malignant pleural mesothelioma SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Mencoboni, M.; Serra, M.; Tunesi, G.; Gianola, M.; Rebella, L.; Galbusera, V.; Bergaglio, M.] Scassi Hosp, Genoa, Italy. [Filiberti, R.; Puntoni, R.; Paganuzzi, M.] Natl Canc Inst, Genoa, Italy. 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 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 6523 BP 364 EP 364 DI 10.1016/S1359-6349(07)71351-4 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204001202 ER PT J AU Vladimirtsev, VA Nikitina, RS Renwick, N Ivanova, AA Danilova, AP Platonov, FA Krivoshapkin, VG McLean, CA Masters, CL Gajdusek, C Goldfarb, LG AF Vladimirtsev, Vsevolod A. Nikitina, Raisa S. Renwick, Neil Ivanova, Anastasia A. Danilova, Al'bina P. Platonov, Fyodor A. Krivoshapkin, Vadim G. McLean, Catriona A. Masters, Colin L. Gajdusek, Carleton Goldfarb, Lev G. TI Family clustering of viliuisk encephalomyelitis in traditional and new geographic regions SO EMERGING INFECTIOUS DISEASES LA English DT Article AB Viliuisk encephalomyelitis is an acute, often fatal, meningoencephalitis that tends to develop into a prolonged chronically progressive panencephalitis. Clinical, neuropathologic, and epidemiologic data argue for an infectious cause, although multiple attempts at pathogen isolation have been unsuccessful. To assess mechanisms of disease transmission and spread, we studied 6 multiplex families. Secondary cases occurred among genetically related and unrelated persons in a setting of prolonged intrahousehold contact with a patient manifesting the disease. Transmission to unrelated persons was documented in a densely populated region around the city of Yakutsk in which Viliuisk encephalomyelitis had not been previously known. Initially identified in a small Yakut-Evenk population on the Viliui River of eastern Siberia, the disease subsequently spread through human contacts to new geographic areas, thus characterizing Viliuisk encephalomyelitis as an emerging infectious disease. C1 Inst Hlth Sakha, Yakutsk, Russia. Columbia Univ, Ctr Med, New York, NY USA. Univ Melbourne, Parkville, Vic 3052, Australia. Inst Alfred Fessard, Gif Sur Yvette, France. NIH, Bethesda, MD USA. RP Goldfarb, LG (reprint author), Natl Inst Hlth, Rm 4S06,5625 Fishers Lane,MSC 9404, Bethesda, MD 20892 USA. EM goldfarbl@ninds.nih.gov FU Intramural NIH HHS NR 12 TC 8 Z9 8 U1 0 U2 4 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD SEP PY 2007 VL 13 IS 9 BP 1321 EP 1326 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 205XM UT WOS:000249148500007 PM 18252102 ER PT J AU Lubensky, IA Zhuang, ZP AF Lubensky, Irina A. Zhuang, Zhengping TI Molecular genetic events in gastrointestinal and pancreatic neuroendocrine tumors SO ENDOCRINE PATHOLOGY LA English DT Article DE neuroendocrine tumor; carcinoid; gastrointestinal; pancreatic; foregut; midgut; hindgut; genetics ID COMPARATIVE GENOMIC HYBRIDIZATION; DIFFERENTIATED ENDOCRINE CARCINOMAS; NEOPLASIA TYPE-I; SUPPRESSOR GENE; SPORADIC GASTRINOMAS; PROGNOSTIC IMPLICATIONS; ALLELIC DELETIONS; LINDAU-DISEASE; P53 GENE; K-RAS AB Gastrointestinal and pancreatic neuroendocrine tumors originate from the cells of the diffuse endocrine system. Their molecular genetic mechanism of development and progression is complex and remains largely unknown, and they are different in genetic composition from the gastrointestinal epithelial tumors. The current literature suggests that multiple genes are involved in their tumorigenesis with significant differences for tumors of different embryological derivatives: foregut, midgut and hindgut. The MEN1 gene is involved in initiation of 33% of foregut gastrointestinal neuroendocrine tumors. 18q defects are present almost exclusively in mid/hindgut neuroendocrine tumors. X-chromosome markers are associated with malignant behavior in foregut tumors only. Analysis of poorly differentiated neuroendocrine carcinomas of any site demonstrates high chromosomal instability and frequent p53 alterations similar to other poorly differentiated carcinomas. Several factors played a limiting role in the molecular studies published to date: the tumors are rare and heterogeneous, it is difficult to predict their behavior and prognosis, and several different tumor classifications are used by the investigators in the studies. Future studies need to evaluate molecular genetic composition of large series of gastrointestinal and pancreatic neuroendocrine tumors of each specific tumor type. Understanding of specific genetic alterations characteristic for gastrointestinal and pancreatic neuroendocrine tumors might lead to their improved diagnosis, morphologic and molecular characterization and treatment. C1 [Lubensky, Irina A.] NCI, Canc Diag Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Zhuang, Zhengping] NINCDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Lubensky, IA (reprint author), NCI, Canc Diag Program, Div Canc Treatment & Diag, NIH, 6130 Execut Blvd,EPN 6032, Bethesda, MD 20892 USA. EM lubenskyi@mail.nih.gov NR 66 TC 15 Z9 15 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD FAL PY 2007 VL 18 IS 3 BP 156 EP 162 DI 10.1007/s12022-007-9007-x PG 7 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA 245DJ UT WOS:000251914700005 PM 18041590 ER PT J AU Ilias, L Sahdev, A Reznek, RH Grossman, AB Pacak, K AF Ilias, Loannis Sahdev, Anju Reznek, Rodney H. Grossman, Ashley B. Pacak, Karel TI The optimal imaging of adrenal tumours: A comparison of different methods SO ENDOCRINE-RELATED CANCER LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; OF-THE-ART; COMPUTED-TOMOGRAPHY; METASTATIC PHEOCHROMOCYTOMA; MALIGNANT PHEOCHROMOCYTOMA; ENHANCED CT; MASSES; PET; MR; METAIODOBENZYLGUANIDINE AB Computed tomography (CT; unenhanced, followed by contrast-enhanced examinations) is the cornerstone of imaging of adrenal tumours. Attenuation values of <10 Hounsfield units on an unenhanced CT are practically diagnostic for adenomas. When lesions cannot be characterised adequately with CT, magnetic resonance imaging (MRI) evaluation (with T1- and T2-weighted sequences and chemical shift and fat-suppression refinements) is sought. Functional nuclear medicine imaging is useful for adrenal lesions that are not adequately characterised with CT and MRI. Scintigraphy with [131 I]-6-iodomethyl norchhlesterol (a labelled cholesterol analogue) can differentiate adrenal cortical adenomas from carcinomas. Phaeochromocytomas appear as areas of abnormal and/or increased uptake of [I-123](-) and [I-131]-meta-iodobenzylguanidine (a labelled noradrenaline analogue). The specific and useful roles of adrenal imaging include the characterisation of tumours, assessment of true tumour size, differentiation of adenomas from carcinomas and metastases, and differentiation of hyperfunctioning from non-functioning lesions. Adrenal imaging complements and assists the clinical and hormonal evaluation of adrenal tumours. C1 Elena Venizelou Hosp, Dept Endocrinol, GR-11521 Athens, Greece. St Bartholomews Hosp, Dept Radiol, London EC1A 7BE, England. St Bartholomews Hosp, Dept Endocrinol, London EC1A 7BE, England. NICHHD, Sect Med Neuroendocrinol, Med Branch, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), Elena Venizelou Hosp, Dept Endocrinol, GR-11521 Athens, Greece. EM karel@mail.nih.gov NR 61 TC 29 Z9 32 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD SEP PY 2007 VL 14 IS 3 BP 587 EP 599 DI 10.1677/ERC-07-0045 PG 13 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 224XX UT WOS:000250482800004 PM 17914090 ER PT J AU Hoshi, N Kusakabe, T Taylor, BJ Kimura, S AF Hoshi, Nobuo Kusakabe, Takashi Taylor, Barbara J. Kimura, Shioko TI Side population cells in the mouse thyroid exhibit stem/progenitor cell-like characteristics SO ENDOCRINOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; ADULT HUMAN LIVER; IN-VITRO; FUNCTIONAL-PROPERTIES; FOLLICULAR CELLS; SKELETAL-MUSCLE; DIFFERENTIATION; EXPRESSION; GLAND; PHENOTYPE AB Side population (SP) cells are characterized by their ability to efflux the vital dye Hoechst 33342 (Sigma-Aldrich, St. Louis, MO) due to expression of the ATP binding cassette (ABC)dependent transporter ABCG2, and are highly enriched for stem/progenitor cell activity. In this study we identified SP cells in murine thyroid, which are composed of two populations of cells: CD45( -)/c-kit(-)/Sca1( +) and CD45( -)/c-kit( -)/Sca1( -) cells. Quantitative RT-PCR analysis revealed that SP cells highly express ABCG2 and the stem cell marker genes encoding nucleostemin and Oct4, whereas the expression of genes encoding the thyroid differentiation markers, thyroid peroxidase, thyroglobulin ( TG), and TSH receptor, and two transcription factors, thyroid transcription factor 1 ( TITF1) and paired PAX8, critical for thyroid specific gene expression, are low in SP cells as compared with the main population cells. In situ hybridization and double immunofluorescence demonstrated that cells expressing Abcg2 gene reside in the interfollicular space of the thyroid gland. Approximately half and a small percentage of the ABCG2-positive cells were also positive for vimentin and calcitonin, respectively. After 9 wk under three-dimensional thyroid primary culture conditions, main population cells formed an epithelial arrangement and follicle-like structures that are immunoreactive for TITF1 and TG. In contrast, SP cells demonstrated very few morphological changes without any epithelial or follicle-like structure and negative immunostaining for TITF1 and TG. These results demonstrate that thyroid possesses SP cells that may represent stem/ progenitor cells. C1 NCI, Met Lab, NIH, Bethesda, MD 20892 USA. NCI, FACS Core Fac, NIH, Bethesda, MD 20892 USA. Fukushima Med Univ, Dept Pathol, Fukushima, Japan. RP Kimura, S (reprint author), NCI, Met Lab, NIH, Bldg 37,Room 3112B, Bethesda, MD 20892 USA. EM Shioko@helix.nih.gov FU Intramural NIH HHS [Z01 BC005522-20, Z99 CA999999] NR 37 TC 42 Z9 49 U1 0 U2 5 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 2007 VL 148 IS 9 BP 4251 EP 4258 DI 10.1210/en.2006-0490 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 200UX UT WOS:000248789400018 PM 17584961 ER PT J AU Martin, B Pearson, M Kebejian, L Golden, E Keselman, A Bender, M Carlson, O Egan, J Ladenheim, B Cadet, JL Becker, KG Wood, W Duffy, K Vinayakumar, P Maudsley, S Mattson, MP AF Martin, Bronwen Pearson, Michele Kebejian, Lisa Golden, Erin Keselman, Alex Bender, Meredith Carlson, Olga Egan, Josephine Ladenheim, Bruce Cadet, Jean-Lud Becker, Kevin G. Wood, William Duffy, Kara Vinayakumar, Prabhu Maudsley, Stuart Mattson, Mark P. TI Sex-dependent metabolic, neuroendocrine, and cognitive responses to dietary energy restriction and excess SO ENDOCRINOLOGY LA English DT Article ID CALORIC RESTRICTION; ANOREXIA-NERVOSA; GROWTH-HORMONE; NEUROTROPHIC FACTOR; INSULIN-RESISTANCE; ANTICIPATORY ACTIVITY; GLUCOSE-METABOLISM; DAILY RHYTHMS; FEMALE RATS; LIFE-SPAN AB Females and males typically play different roles in survival of the species and would be expected to respond differently to food scarcity or excess. To elucidate the physiological basis of sex differences in responses to energy intake, we maintained groups of male and female rats for 6 months on diets with usual, reduced [ 20% and 40% caloric restriction ( CR), and intermittent fasting ( IF)], or elevated ( high-fat/high-glucose) energy levels and measured multiple physiological variables related to reproduction, energy metabolism, and behavior. In response to 40% CR, females became emaciated, ceased cycling, underwent endocrine masculinization, exhibited a heightened stress response, increased their spontaneous activity, improved their learning and memory, and maintained elevated levels of circulating brain-derived neurotrophic factor. In contrast, males on 40% CR maintained a higher body weight than the 40% CR females and did not change their activity levels as significantly as the 40% CR females. Additionally, there was no significant change in the cognitive ability of the males on the 40% CR diet. Males and females exhibited similar responses of circulating lipids ( cholesterols/triglycerides) and energy-regulating hormones ( insulin, leptin, adiponectin, ghrelin) to energy restriction, with the changes being quantitatively greater in males. The high-fat/high-glucose diet had no significant effects on most variables measured but adversely affected the reproductive cycle in females. Heightened cognition and motor activity, combined with reproductive shutdown, in females may maximize the probability of their survival during periods of energy scarcity and may be an evolutionary basis for the vulnerability of women to anorexia nervosa. C1 Natl Inst Drug Abuse, Clin Invest Lab, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Gene Express & Genom Unit, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Lab Expt Gerontol, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, NIA, Intramural Res Program, Mol Neuropsychiat Branch, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Harbor Hosp, MedStar Res Inst, Baltimore, MD 21225 USA. Natl Inst Drug Abuse, Neurosci Lab, Baltimore, MD 21224 USA. RP Martin, B (reprint author), NIA, 5600 Nathan Shock dr, Baltimore, MD 21224 USA. EM martinbro@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; OI Becker, Kevin/0000-0002-6794-6656 FU Intramural NIH HHS [Z01 AG000318-01] NR 66 TC 108 Z9 110 U1 2 U2 19 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 2007 VL 148 IS 9 BP 4318 EP 4333 DI 10.1210/en.2007-0161 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 200UX UT WOS:000248789400026 PM 17569758 ER PT J AU Gohlke, JM Portier, CJ AF Gohlke, Julia M. Portier, Christopher J. TI The forest for the trees: A systems approach to human health research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE public health; risk assessment; systems biology ID CLIMATE-CHANGE; UNITED-STATES; SCIENCE; EPIDEMIOLOGY; DISEASE; BIOLOGY; MODELS; IMPACT; FUTURE; FISH AB We explore the relationship between current research directions in human health and environmental and public health policy. Specifically; we suggest there is a link between the continuing emphasis in biomedical research on individualized, therapeutic solutions to human disease and the increased reliance on individual choice in response to environmental and/or public health threats. We suggest that continued research emphasis on these traditional approaches to the exclusion of other approaches will impede the discovery of important breakthroughs in human health research necessary to understand the emerging diseases of today. We recommend redirecting research programs to interdisciplinary and population-focused research that would support a systems approach to fully identifying the environmental factors that contribute to disease burden. Such an approach would be able to address the interactions between the social, ecological, and physical aspects of our environment and explicitly include these in the evaluation and management of health risks from environmental exposures. C1 NIEHS, NIH, Mol Toxicol Lab, Environm Syst Biol Grp,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Portier, CJ (reprint author), NIEHS, NIH, Mol Toxicol Lab, Environm Syst Biol Grp,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM portier@niehs.nih.gov RI Portier, Christopher/A-3160-2010; OI Portier, Christopher/0000-0002-0954-0279; Gohlke, Julia/0000-0002-6984-2893 FU Intramural NIH HHS NR 42 TC 13 Z9 14 U1 1 U2 9 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 2007 VL 115 IS 9 BP 1261 EP 1263 DI 10.1289/ehp.10373 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 206RM UT WOS:000249200600019 PM 17805413 ER PT J AU Wise, LA Palmer, JR Hatch, EE Troisi, R Titus-Ernstoff, L Herbst, AL Kautman, R Noller, KL Hoover, RN AF Wise, Lauren A. Palmer, Julie R. Hatch, Elizabeth E. Troisi, Rebecca Titus-Ernstoff, Linda Herbst, Arthur L. Kautman, Raymond Noller, Kenneth L. Hoover, Robert N. TI Secondary sex ratio among women exposed to diethylstilbestrol in utero SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE diethylstilbestrol; estrogens; endocrine-disrupting chemicals; females; sex ratios ID FOLLOW-UP; POLYCHLORINATED-BIPHENYLS; ENDOCRINE DISRUPTION; BISPHENOL-A; PREGNANCY; DIOXIN; BIRTH; MOTHERS; STILBESTROL; INFERTILITY AB BACKGROUND: Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the mid-1900s, is a potent endocrine disruptor. Previous studies have suggested an association between endocrine-disrupting compounds and secondary sex ratio. METHODS: Data were provided by women participating in the National Cancer Institute (NCI) DES Combined Cohort Study. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (Cls) for the relation of in utero DES exposure to sex ratio (proportion of male births). Models were adjusted for maternal age, child's birth year, parity, and Cohort, and accounted for clustering among women with multiple pregnancies. RESULTS: The OR for having a male birth comparing DES-exposed to unexposed women was 1.05 (95% Cl, 0.95-1.17). For exposed women with complete data on cumulative DES dose and timing (33%), those first exposed to DES earlier in gestation and to higher doses had the highest odds of having a male birth. The ORs were 0.91 (95% C, 0.65-1.27) for first exposure at a 13 weeks gestation to < 5 g DES; 0.95 (95% Cl, 0.71-1.27) for first exposure at a 13 weeks to 2: 5 g; 1. 16 (95% CI, 0.96-1.41) for first exposure at < 13 weeks to < 5 g; and 1.24 (95% Cl, 1.04-1.48) for first exposure at >= 13 weeks to >= 5 g compared with no exposure. Results did not. vary appreciably by maternal age, parity, cohort, or infertility history. CONCLUSIONS, Overall, no association was observed between in utero DES exposure and secondary sex ratio, but a significant increase in the proportion of male births was found among women first exposed to DES earlier in gestation and to a higher cumulative dose. C1 Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. RP Wise, LA (reprint author), Boston Univ, Slone Epidemiol Ctr, 1010 Commonwealth Ave,4th Floor, Boston, MA 02215 USA. EM twise@slone.bu.edu OI Palmer, Julie/0000-0002-6534-335X; Hatch, Elizabeth/0000-0001-7901-3928; Wise, Lauren/0000-0003-2138-3752 NR 45 TC 11 Z9 13 U1 2 U2 11 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 2007 VL 115 IS 9 BP 1314 EP 1319 DI 10.1289/ehp.10246 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 206RM UT WOS:000249200600027 PM 17805421 ER PT J AU Bloom, MS Louis, GMB Schisterman, EF Liu, A Kostyniak, PJ AF Bloom, Michael S. Louis, Germaine M. Buck Schisterman, Enrique F. Liu, Aiyi Kostyniak, Paul J. TI Maternal serum polychlorinated biphenyl concentrations across critical windows of human develooment SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE critical windows; infertility; periconception; persistent organic pollutants; polychlorinated biphenyls (PCBs); pregnancy loss ID FISH CONSUMPTION; CHILDRENS HEALTH; BLOOD-PLASMA; LAKE-ONTARIO; SPORT FISH; EXPOSURE; PREGNANCY; TIME; ORGANOCHLORINES; LACTATION AB BACKGROUND: Few data are available on polychlorinated biphenyl (PCB) concentrations over critical windows of human reproduction and development inclusive of the periconception window. OBJECTIVES: Our goal was to measure changes in PCB concentrations from preconception to pregnancy, through pregnancy, or after a year without becoming pregnant. METHODS- Seventy-nine women planning pregnancies were prospectively enrolled and followed for up to 12 menstrual cycles of attempting pregnancy. Blood specimens were obtained from participating women preconceptionally (n = 79), after a positive pregnancy test leading to a live birth (n = 54) or pregnancy loss (n = 10), at approximately 6 weeks postpartum (n = 53), and after 12 unsuccessful cycles (n = 9) for toxicologic analysis of 76 PCB congeners. We estimated overall and daily rate of change in PCB concentration (nanograms per gram serum) adjusting for relevant covariates, serum lipids, and baseline PCB concentration. RESULTS: Significant (p < 0.0001) decreases in the mean overall and daily rate of change in PCB concentrations were observed between the preconception and First pregnancy samples for total (-1.012 and -0-034, respectively), estrogenic (-0.444 and -0.016, respectively), and antiestrogenic (-0. 106 and -0.004, respectively) PCBs among women with live births. Similar significant decreases in total (-1.452 and -0.085), estrogenic (-0.647 and -0.040), and antiestrogenic (-0.093 and -0.004) PCB concentrations were seen for women with pregnancy losses. No significant changes were observed for PCB congener 153. CONCLUSIONS: These data suggest that PCB concentrations may change during the periconception interval, questioning the stability of persistent compounds during this critical window. C1 NICHHD, Stat & Prevent Res, Div Epidemiol, Epidemiol Branch, Bethesda, MD 20892 USA. NICHHD, Stat & Prevent Res, Div Epidemiol, Biometry & Math Stat Branch, Bethesda, MD 20892 USA. SUNY Buffalo, Dept Biotech, Buffalo, NY USA. SUNY Buffalo, Clin Sci Lab, Sch Med & Biomed Sci, Buffalo, NY USA. RP Louis, GMB (reprint author), 6100 Execut Blvd,Rm 7B03, Rockville, MD 20852 USA. EM louisg@mail.nih.gov OI Bloom, Michael/0000-0002-0028-5494 NR 28 TC 28 Z9 28 U1 0 U2 3 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 2007 VL 115 IS 9 BP 1320 EP 1324 DI 10.1289/ehp.10086 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 206RM UT WOS:000249200600028 PM 17805422 ER PT J AU Thayer, KA Foster, PM AF Thayer, Kristina A. Foster, Paul M. TI Workgroup report: National toxicology program workshop on Hormonally Induced Reproductive Tumors - Relevance of Rodent Bioassays SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID COMPARATIVE CARCINOGENICITY; PERINATAL EXPOSURE; RATS; MICE; PREDICTION AB The National Toxicology Program (NTP) is currently reviewing its research portfolio as part of its efforts to implement the NTP Roadmap to achieve the NTP Vision for the 21st century. This review includes a recent Workshop, "Hormonally Induced Reproductive Tumors-Relevance of Rodent Bioassays," held 22-24 May 2006, that was organized to determine the adequacy and relevance to human disease outcome of rodent models currently used in the 2-year bioassay for four types of hormonally induced reproductive tumors (ovary, mammary gland, prostate, and testis). In brief, none of the workshop's breakout groups felt the currently used models are sufficient. For some types of tumors such as prostate, no adequate animal models exist, and for others such as ovary, the predominant tumors in humans are of different cellular origins than those induced by chemicals in rodents. This inadequacy of current models also applies to the testis, although our more complete understanding of the responses of Leydig cells to hormonal changes in rats may prove predictive for effects in humans other than cancer. All breakout groups recommended that the NTP consider modifying its testing protocols (i.e., age at exposure, additional end points, etc.) and/or using alternative models (i.e., genetically engineered models, in vitro systems, etc.) to improve sensitivity. In this article we briefly review the workshop's outcome and outline some next steps forward in pursuing the workshop's recommendations. Breakout group reports and additional information on the workshop, including participants, presentations, public comments and background materials, are posted on the NTP website. C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Foster, PM (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, EC-34,POB 12233, Res Triangle Pk, NC 27709 USA. EM foster2@nichs.nih.gov FU Intramural NIH HHS NR 25 TC 10 Z9 10 U1 0 U2 3 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 2007 VL 115 IS 9 BP 1351 EP 1356 DI 10.1289/ehp.10135 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 206RM UT WOS:000249200600033 PM 17805427 ER PT J AU Stevens, RG Blask, DE Brainard, GC Hansen, J Lockley, SW Provencio, I Rea, MS Reinlib, L AF Stevens, Richard G. Blask, David E. Brainard, George C. Hansen, Johnni Lockley, Steven W. Provencio, Ignacio Rea, Mark S. Reinlib, Leslie TI Meeting report: The role of environmental lighting and circadian disruption in cancer and other diseases SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID SHORT-WAVELENGTH SENSITIVITY; CHRONIC JET-LAG; BREAST-CANCER; ENDOCRINE SYSTEMS; MAMMALIAN RETINA; ACTION SPECTRUM; GANGLION-CELLS; ELECTRIC-POWER; BLIND MICE; MELATONIN AB Light, including artificial light, has a range of effects on human physiology and behavior and can therefore alter human physiology when inappropriately timed. One example of potential light-induced disruption is the effect of light on circadian organization, including the production of several hormone rhythms. Changes in light-dark exposure (e.g., by nonday occupation or transmeridian travel) shift the timing of the circadian system such that internal rhythms can become desynchronized from both the external environment and internally with each other, impairing our ability to sleep and wake at the appropriate times and compromising physiologic and metabolic processes. Light can also have direct acute effects on neuroendocrine systems, for example, in suppressing melatonin synthesis or elevating cortisol production that may have untoward long-term consequences. For these reasons, the National Institute of Environmental Health Sciences convened a workshop of a diverse group of scientists to consider how best to conduct research on possible connections between lighting and health. According to the participants in the workshop, there are three broad areas of research effort that need to be addressed. First are the basic biophysical and molecular genetic mechanisms for phototransduction for circadian, neuroendocrine, and neurobehavioral regulation. Second are the possible physiologic consequences of disrupting these circadian regulatory processes such as on hormone production, particularly melatonin, and normal and neoplastic tissue growth dynamics. Third are effects of light-induced physiologic disruption on disease occurrence and prognosis, and how prevention and treatment could be improved by application of this knowledge. C1 Univ Connecticut, Ctr Hlth, Dept Community Med, Farmington, CT 06030 USA. Bassett Res Inst, Cooperstown, NY USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Danish Canc Soc, Copenhagen, Denmark. Harvard Univ, Sch Med, Boston, MA USA. Univ Virginia, Dept Biol, Charlottesville, VA USA. Rensselaer Polytech Inst, Lighting Res Ctr, Troy, NY USA. Natl Inst Environm Hlth Sci, Div Extramural Res & Traning, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Stevens, RG (reprint author), Univ Connecticut, Ctr Hlth, Dept Community Med, 263 Farmington Ave, Farmington, CT 06030 USA. EM bugs@uchc.edu FU NIEHS NIH HHS [ES11659, R21 ES011659] NR 60 TC 142 Z9 145 U1 4 U2 17 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 2007 VL 115 IS 9 BP 1357 EP 1362 DI 10.1289/ehp.10200 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 206RM UT WOS:000249200600034 PM 17805428 ER PT J AU Howards, PP Schisterman, EF Heagerty, PJ AF Howards, Penelope P. Schisterman, Enrique F. Heagerty, Patrick J. TI Potential confounding by exposure history and prior outcomes - An example from perinatal epidemiology SO EPIDEMIOLOGY LA English DT Article ID MARGINAL STRUCTURAL MODELS; LOW-BIRTH-WEIGHT; CLEARER DEFINITION; PREGNANCY OUTCOMES; CAUSAL INFERENCE; RISK; DEFECTS; TIME; BIAS AB Prior pregnancy outcomes, such as spontaneous abortion and preterm birth, are often predictive of future pregnancy outcomes. Therefore, many researchers adjust for reproductive history. Although this adjustment may be appropriate for a predictive model, it is not necessarily appropriate when the goal is to obtain an unbiased estimate of the effect of exposure on disease. Reproductive history may seem to meet the conventional criteria for confounding because it is unlikely to be on the causal pathway between exposure and current outcome, is often associated with current outcome, and may be associated with exposure as well. However, whether reproductive history is a confounder or not depends on the underlying reason for its associations with exposure and current outcome. Thus, conventional methods for assessing confounding are often inadequate. Directed acyclic graphs (DAGs) can be used to evaluate complex scenarios for confounding when the research question is clearly defined with respect to the exposure, the outcome, and the effect estimate of interest. Special care is required when reproductive history affects future exposure. We use 5 DAGs to illustrate possible relations between reproductive history and current outcome. We assess each DAG for confounding, and identify the appropriate analytic technique. We provide a numeric example using data from the Collaborative Perinatal Project. There is no single answer as to whether reproductive history should be included in the model; the decision depends on the research question and the underlying DAG. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Howards, PP (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03C, Bethesda, MD 20892 USA. EM howardsp@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS NR 33 TC 29 Z9 29 U1 2 U2 11 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 2007 VL 18 IS 5 BP 544 EP 551 DI 10.1097/EDE.0b013e31812001e6 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 203UW UT WOS:000249000500004 PM 17879426 ER PT J AU Weinberg, CR AF Weinberg, Clarice R. TI Can DAGs clarify effect modification? SO EPIDEMIOLOGY LA English DT Editorial Material AB The system proposed by VanderWeele and Robins for categorization of effect modifiers that are causal nodes in a directed acyclic graph (DAG) was not intended to empower DAGs to fully represent complex interactions among causes. However, once one has algebraically identified effect modifiers, the DAG implies a role for them. The limitations of epidemiologic definitions of "effect modification" are discussed, along with the implications of scale dependency for assessing interactions, where the scale can be either absolute risk, relative risk, or odds. My view is that probabilistic independence leads to the log-complement as a natural scale for interaction, but even that scale does not necessarily admit unambiguous inference. Any 2 direct causes of D are effect modifiers for each other on at least 2 scales, which can make a reasonable person question the utility of the concept. Still, etiologic models for joint effects are important, because most diseases arise through pathways involving multiple factors. I suggest an enhancement in construction of DAGs in epidemiology that includes arrow-on-arrow representations for effect modification. Examples are given, some of which depend on scale and some of which do not. An example illustrates possible biologic implications for such an effect modification DAG. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Weinberg, CR (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM Weinber2@niehs.nih.gov FU Intramural NIH HHS [Z01 ES040006-11] NR 7 TC 13 Z9 14 U1 2 U2 12 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 2007 VL 18 IS 5 BP 569 EP 572 DI 10.1097/EDE.0b013e318126c11d PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 203UW UT WOS:000249000500007 PM 17700243 ER PT J AU Chen, A Basso, O AF Chen, Aimin Basso, Olga TI Does low maternal blood pressure during pregnancy increase the risk of perinatal death? SO EPIDEMIOLOGY LA English DT Article ID HYPOTENSION; HYPERTENSION AB Background: A recent report described an association between low maximum diastolic blood pressure (DBP) during pregnancy and perinatal death (stillbirth and death in the first week combined). The authors did not account for gestational length, a strong predictor of perinatal death. Methods: We studied 41,089 singleton pregnancies from the U.S. Collaborative Perinatal Project (1959-1966). Results: We observed an association between low maximum DBP and elevated risk of perinatal death. However, this association disappeared after accounting for reverse causation related to gestational length. At any given gestational week, women whose offspring ultimately experienced perinatal death did not have significantly lower maximum DBP than women whose offspring survived the perinatal period. When accounting for the trend of increasing DBP during late pregnancy through gestational-age-specific DBP standardized score, we saw no association between low diastolic blood pressure and perinatal death. Conclusions: Low maximum maternal DBP during pregnancy is a post hoc correlate of perinatal death, not a true risk factor. C1 Creighton Univ, Sch Med, Dept Prevent Med & Pub Hlth, Omaha, NE 68178 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Chen, A (reprint author), Creighton Univ, Sch Med, Dept Prevent Med & Pub Hlth, 2500 Calif Plaza, Omaha, NE 68178 USA. EM aiminchen@creighton.edu RI Basso, Olga/E-5384-2010 OI Basso, Olga/0000-0001-9298-4921 FU Intramural NIH HHS [Z99 ES999999] NR 15 TC 3 Z9 3 U1 0 U2 2 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 2007 VL 18 IS 5 BP 619 EP 622 DI 10.1097/EDE.0b013e31812713e6 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 203UW UT WOS:000249000500016 PM 17879438 ER PT J AU Lubin, JH Caporaso, N Wichmann, HE Schaffrath-Rosario, A Alavanja, MCR AF Lubin, Jay H. Caporaso, Neil Wichmann, H. Erich Schaffrath-Rosario, Angelika Alavanja, Michael C. R. TI Cigarette smoking and lung cancer - Modeling effect modification of total exposure and intensity SO EPIDEMIOLOGY LA English DT Article ID DNA-REPAIR CAPACITY; RESIDENTIAL RADON; HISTOLOGIC TYPE; FEMALE SMOKERS; HIGHER RISK; CARCINOGEN 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; EXCISION-REPAIR; NICOTINE INTAKE; COTININE LEVELS; BLADDER-CANCER AB Background: A recent analysis indicates that the excess odds ratio for lung cancer by smoking is described by a function that is linear in pack-years and exponential in the logarithm of smoking intensity and its square (Cancer Epidemiol Biomarkers Prev. 2006;15:517i, s i, 52 he model suggests that below 15-20 cigarettes per day there a direct exposure rate" effect, ie, the excess odds ratio per pack-year for higher intensity (and shorter duration) smokers is greater than for lower-intensity (and longer duration) smokers. Above 20 cigarettes per day, there is an "inverse-exposure-rate" effect, ie, the excess odds ratio per pack-year for higher intensity smokers is smaller than for lower-intensity smokers. Methods: Using pooled data from 2 large case-control studies of lung cancer (the European Smoking and Health Study and the German Radon Study), we evaluated effect modification of the association between smoking and lung cancer. Results: Interaction effects are very specific. Variations in risk of lung cancer with years since cessation of smoking, age, method of inhalation, and type of cigarette result from interactions with smoking intensity, and not total pack-years. In contrast, risk variations by sex result from the interaction with total pack-years, while intensity effects are homogeneous. Risk variations by age at which smoking started result from interactions with both total pack-years and intensity. All intensity interactions are homogeneous across studies. Conclusions: The specificity of the interactions may provide clues for the molecular basis of the smoking and lung cancer relationship. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. GSF, Natl Res Ctr Environm & Hlth, Neuherberg, Germany. Abt Epidemiol & Gesundheitsberichterstattung, Robert Koch Inst, Berlin, Germany. NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Rockville, MD USA. RP Lubin, JH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA. EM lubinj@mail.nih.gov FU Intramural NIH HHS NR 49 TC 45 Z9 47 U1 0 U2 4 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 2007 VL 18 IS 5 BP 639 EP 648 DI 10.1097/EDE.0b013e31812717fe PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 203UW UT WOS:000249000500019 PM 17700253 ER PT J AU Bonner, M Williams, B Rusiecki, J Blair, A Freeman, LB Hoppin, J AF Bonner, M. Williams, B. Rusiecki, J. Blair, A. Beane Freeman, L. Hoppin, J. TI Occupational exposure to terbufos and the incidence of cancer in the agricultural health study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 19th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 05-09, 2007 CL Mexico City, MEXICO SP Int Soc Environm Epidemiol C1 SUNY Buffalo, Buffalo, NY USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NCI, Bethesda, MD 20892 USA. RI Beane Freeman, Laura/C-4468-2015 OI Beane Freeman, Laura/0000-0003-1294-4124 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2007 VL 18 IS 5 SU S BP S148 EP S149 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 204BQ UT WOS:000249018300488 ER PT J AU Handal, AJ Lynch, CD Jackson, WL Kostyniak, JP Louis, MGB AF Handal, A. J. Lynch, C. D. Jackson, W. L. Kostyniak, J. P. Buck Louis, M. G. TI Exposure to organochlorine pesticides and neurobehavioral development in toddlers SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 19th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 05-09, 2007 CL Mexico City, MEXICO SP Int Soc Environm Epidemiol C1 NICHHD, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Bethesda, MD USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. SUNY Buffalo, Toxicol Res Ctr, Dept Biotech & Clin Lab Serv, Buffalo, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2007 VL 18 IS 5 SU S BP S157 EP S157 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 204BQ UT WOS:000249018300516 ER PT J AU Moore, L Brennan, P Karami, S Hung, R Hsu, C Boffetta, P AF Moore, L. Brennan, P. Karami, S. Hung, R. Hsu, C. Boffetta, P. TI Glutathione S-transferase polymorphisms, cruciferous vegetable intake, and kidney cancer risk in central and eastern Europe SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 19th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 05-09, 2007 CL Mexico City, MEXICO SP Int Soc Environm Epidemiol C1 NCI, NIH, OEEB, DCEG,DHHS, Bethesda, MD 20892 USA. NCI, NIH, OEEB, DCEG, Bethesda, MD 20892 USA. RI Hung, Rayjean/A-7439-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2007 VL 18 IS 5 SU S BP S197 EP S197 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 204BQ UT WOS:000249018300649 ER PT J AU Rusiecki, J Baccarelli, A Bollati, V Moore, L Bonefeld-Jorgensen, E AF Rusiecki, J. Baccarelli, A. Bollati, V Moore, L. Bonefeld-Jorgensen, E. TI DNA methylation among Greenlandic Inuit with varying levels of exposures to specific persistent organic pollutants SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 19th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 05-09, 2007 CL Mexico City, MEXICO SP Int Soc Environm Epidemiol C1 Univ Milan, I-20122 Milan, Italy. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Milan, I-20122 Milan, Italy. NCI, Bethesda, MD 20892 USA. Univ Aarhus, DK-8000 Aarhus C, Denmark. RI Bonefeld-Jorgensen, Eva Cecilie/A-1682-2015 NR 0 TC 1 Z9 1 U1 0 U2 1 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 2007 VL 18 IS 5 SU S BP S151 EP S152 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 204BQ UT WOS:000249018300498 ER PT J AU Ward, MH Weyer, P Wang, A Cerhan, JR AF Ward, M. H. Weyer, P. Wang, A. Cerhan, J. R. TI Nitrate from drinking water and diet and thyroid disorders and thyroid cancer among women SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 19th Annual Conference of the International-Society-for-Environmental-Epidemiology CY SEP 05-09, 2007 CL Mexico City, MEXICO SP Int Soc Environm Epidemiol C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Iowa, Ctr Hlth Effects Environm Contaminants, Iowa City, IA 52242 USA. Mayo Clin, Coll Med, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 2007 VL 18 IS 5 SU S BP S169 EP S169 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 204BQ UT WOS:000249018300553 ER PT J AU Eamranond, PP Patel, KV Legedza, ATR Marcantonto, ER Leveille, SG AF Eamranond, Pracha P. Patel, Kushang V. Legedza, Anna T. R. Marcantonto, Edward R. Leveille, Suzanne G. TI The association of language with prevalence of undiagnosed hypertension among older Mexican Americans SO ETHNICITY & DISEASE LA English DT Article DE language; Spanish; cardiovascular; risk factor; hypertension; Mexican American; Hispanic ID SPANISH-SPEAKING PATIENTS; UNITED-STATES; ACCULTURATION; HEALTH; CARE; BEHAVIORS; AWARENESS; ETHNICITY; ADULTS AB Objective: Language barriers have been shown to negatively impact health care for immigrants. We evaluated the association between language use and the diagnosis of hypertension among elderly Mexican Americans. Study population: We studied subjects from the Hispanic Established Populations for Epidemiologic Studies of the Elderly, a cohort of 3050 Mexican American subjects age >= 65. Predictors: Measures of language included Spanish and/or English language read/spoken, language used in social situations, and language of mass media use. Outcome measure: Undiagnosed hypertension on physical exam was defined as systolic blood pressure >= 140 mm Hg and/or diastolic blood pressure >= 90 mm Hg in persons who did not report previous hypertension diagnosis or were not current users of anti-hypertensive medications. Results: The age- and sex-adjusted prevalence of diagnosed hypertension and undiagnosed hypertension were 50.5% and 19.3%, respectively. Among 1347 older adults without previous diagnosis of hypertension that were included in the primary analysis, the mean age was 72 years and 43% were immigrants. After adjusting for age, gender, and education, Spanish use more often than English use in mass media was significantly associated with undiagnosed hypertension (adjusted OR 2.2 [1.3-3.6]). Other measures of acculturation were not independently associated with undiagnosed hypertension. In analyses restricted to persons with hypertension, similar language factors distinguished those who had been diagnosed from those whose hypertension was undiagnosed. Conclusions: Mexican American elders who reported using Spanish more often than English use in mass media were more likely to have undiagnosed hypertension compared to those using English language in mass media. Further studies are needed to elucidate the role of mass media language in hypertension awareness and management among Hispanic elders. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. NIA, NIH, Washington, DC USA. RP Eamranond, PP (reprint author), Beth Israel Deaconess Med Ctr, 1309 Beacon St, Brookline, MA 02246 USA. EM peamrano@bidmc.harvard.edu FU Intramural NIH HHS; PHS HHS [T32 HP11001] NR 28 TC 10 Z9 10 U1 0 U2 1 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2007 VL 17 IS 4 BP 699 EP 706 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 233UK UT WOS:000251115600017 PM 18072382 ER PT J AU Venner, R Robinson, D Krebs, JE AF Venner, Rhondel Robinson, David Krebs, Jocelyn E. TI Generation of a cDNA library for a high-copy suppressor screen to identify genes that code for proteins that interact with histone H2A during DNA repair SO ETHNICITY & DISEASE LA English DT Article AB The purpose of this project was to identify genes that rescue the growth sensitivity of a serine-to-alanine mutant (S122A) of histone H2A in the presence of a double-strand break (DSB) inducing agent. Histones are proteins that DNA wraps around to form nucleosomes, the basic unit of chromatin. Chromatin is important because it is the compacted form of DNA that allows it to fit in the nucleus of a cell. Histones are globular proteins with flexible tail regions, which contain residues that can be covalently modified. Covalent modifications act as signals for enzymes involved in different cellular processes, such as DNA repair.(1) Previous research in this lab has shown that S122 of H2A is important for the repair of DNA DSBs, possibly via phosphorylation of this residue. DSBs are dangerous because of potential loss of genetic information. To identify genes that interact with H2A 5122 during DNA repair, we initiated a high-copy suppressor screen using the S122A mutant. We made a cDNA library from mRNAs isolated from both untreated cells and from cells exposed to MMS (methyl methanesulfonate), a DNA damaging agent, to create a library enriched for DNA repair factors. The cDNA library was constructed and will be screened with a plating assay. Due to time constraints, we were not able to get to this part of the project. S122A cells will be transformed with the libraries, and genes of interest will be identified by colonies that grow more robustly than the S122A control when plated on MMS-containing media. C1 [Venner, Rhondel] NIDDK, NIH, Drew High Sch, Res Program, Anchorage, AK USA. RP Venner, R (reprint author), NIDDK, NIH, Drew High Sch, Res Program, Anchorage, AK USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2007 VL 17 IS 4 SU 5 BP S37 EP S38 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 256BO UT WOS:000252702900019 ER PT J AU Sugui, JA Pardo, J Chang, YC Muellbacher, A Zarember, KA Galvez, EM Brinster, L Zerfas, P Gallin, JI Simon, MM Kwon-Chung, KJ AF Sugui, Janyce A. Pardo, Julian Chang, Yun C. Muellbacher, Arno Zarember, Kol A. Galvez, Eva M. Brinster, Lauren Zerfas, Patricia Gallin, John I. Simon, Markus M. Kwon-Chung, Kyung J. TI Role of laeA in the Regulation of alb1, gliP, conidial morphology, and virulence in Aspergillus fumigatus SO EUKARYOTIC CELL LA English DT Article ID DETECTED IN-VITRO; GLIOTOXIN PRODUCTION; GENE-CLUSTER; POLYMORPHONUCLEAR LEUKOCYTES; PULMONARY ASPERGILLOSIS; PIGMENT BIOSYNTHESIS; NADPH OXIDASE; NEUTROPHILS; DAMAGE; VIVO AB The alb1 (pksP) gene has been reported as a virulence factor controlling the pigmentation and morphology of conidia in Aspergillus fumigatus. A recent report suggested that laeA regulates alb1 expression and conidial morphology but not pigmentation in the A. fumigatus strain AF293. laeA has also been reported to regulate the synthesis of secondary metabolites, such as gliotoxin. We compared the role of laeA in the regulation of conidial morphology and the expression of alb] and gliP in strains B-5233 and AF293, which differ in colony morphology and nutritional requirements. Deletion of laeA did not affect conidial morphology or pigmentation in these strains, suggesting that laeA is not involved in alb1 regulation during conidial morphogenesis. Deletion of laeA, however, caused down-regulation of alb1 during mycelial growth in a liquid medium. Transcription of gliP, involved in the synthesis of gliotoxin, was drastically reduced in B-52331aeA Delta, and the gliotoxin level found in the culture filtrates was 20% of wild-type concentrations. While up-regulation of gliP in AF293 was comparable to that in B-5233, the relative mRNA level in AF293laeA Delta was about fourfold lower than that in B-52331aeA Delta. Strain B-52331aeA Delta caused slower onset of fatal infection in mice relative to that with B-5233. Histopathology of sections from lungs of infected mice corroborated the survival data. Culture filtrates from B-52331aeA Delta caused reduced death in thymoma cells and were less inhibitory to a respiratory burst of neutrophils than culture filtrates from B-5233. Our results suggest that while laeA is not involved in the regulation of alb1 function in conidial morphology, it regulates the synthesis of gliotoxin and the virulence of A. fumigatus. C1 NIH, NIAID, Lab Clin Infect Dis, Mol Microbiol Sect, Bethesda, MD 20892 USA. NIH, Host Def Lab, Bethesda, MD 20892 USA. NIH, Off Res Serv, Bethesda, MD 20892 USA. Univ Freiburg, Inst Phys Chem, D-7800 Freiburg, Germany. Univ Freiburg, Max Planck Inst Immunol, Freiburg, Germany. Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia. RP Kwon-Chung, KJ (reprint author), NIH, NIAID, Lab Clin Infect Dis, Mol Microbiol Sect, Bldg 10, Bethesda, MD 20892 USA. EM June_kwon-chung@nih.gov RI Galvez, Eva/K-6751-2014; Pardo, Julian/K-6764-2014 OI Galvez, Eva/0000-0001-6928-5516; Pardo, Julian/0000-0003-0154-0730 FU Intramural NIH HHS NR 44 TC 60 Z9 69 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD SEP PY 2007 VL 6 IS 9 BP 1552 EP 1561 DI 10.1128/EC.00140-07 PG 10 WC Microbiology; Mycology SC Microbiology; Mycology GA 210SZ UT WOS:000249477200005 PM 17630330 ER PT J AU Sugui, JA Pardo, J Chang, YC Zarember, KA Nardone, G Galvez, EM Muellbacher, A Gallin, JI Simon, MM Kwon-Chung, KJ AF Sugui, Janyce A. Pardo, Julian Chang, Yun C. Zarember, Kol A. Nardone, Glenn Galvez, Eva M. Muellbacher, Arno Gallin, John I. Simon, Markus M. Kwon-Chung, Kyung J. TI Gliotoxin is a virulence factor of Aspergillus fumigatus: gliP deletion attenuates virulence in mice Immunosuppressed with hydrocortisone SO EUKARYOTIC CELL LA English DT Article ID INVASIVE PULMONARY ASPERGILLOSIS; FUNGAL METABOLITE; CONIDIAL MORPHOLOGY; NADPH OXIDASE; IN-VITRO; GENE; APOPTOSIS; DISRUPTION; ACTIVATION; MODEL AB Gliotoxin is an immunosuppressive mycotoxin long suspected to be a potential virulence factor of Aspergillus fumigatus. Recent studies using mutants lacking gliotoxin production, however, suggested that the mycotoxin is not important for pathogenesis of A. fumigatus in neutropenic mice resulting from treatment with cyclophosphomide and hydrocortisone. In this study, we report on the pathobiological role of gliotoxin in two different mouse strains, 129/Sv and BALB/c, that were immunosuppressed by hydrocortisone alone to avoid neutropenia. These strains of mice were infected using the isogenic set of a wild type strain (B-5233) and its mutant strain (gliP Delta) and the the glip reconstituted strain (gliP(R)). The gliP gene encodes a nonribosomal peptide synthase that catalyzes the first step in gliotoxin biosynthesis. The gliP Delta strain was significantly less virulent than strain B-5233 or gliPR in both mouse models. In vitro assays with culture filtrates (CFs) of B-5233, gliP Delta, and gliPR strains showed the following: (i) deletion of gliP abrogated gliotoxin production, as determined by high-performance liquid chromatography analysis; (ii) unlike the CFs from strains B-5233 and gliPR, gliP Delta CFs failed to induce proapoptotic processes in EL4 thymoma cells, as tested by Bak conformational change, mitochondrial-membrane potential disruption, superoxide production, caspase 3 activation, and phosphatidylserine translocation. Furthermore, superoxide production in human neutrophils was strongly inhibited by CFs from strain B-5233 and the gliPR strain, but not the gliP Delta strain. Our study confirms that gliotoxin is an important virulence determinant of A. fumigatus and that the type of immunosuppression regimen used is important to reveal the pathogenic potential of gliotoxin. C1 NIH, NIAID, Lab Clin Infect Dis, Mol Microbiol Sect, Bethesda, MD 20892 USA. NIH, Host Def Lab, Bethesda, MD 20892 USA. NIH, Res Technol Branch, Bethesda, MD 20892 USA. Max Planck Inst Immunobiol, D-7800 Freiburg, Germany. Univ Freiburg, Inst Phys Chem, D-7800 Freiburg, Germany. Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia. RP Kwon-Chung, KJ (reprint author), NIH, NIAID, Lab Clin Infect Dis, Mol Microbiol Sect, Bldg 10, Bethesda, MD 20892 USA. EM June_kwon-chung@nih.gov RI Galvez, Eva/K-6751-2014; Pardo, Julian/K-6764-2014 OI Galvez, Eva/0000-0001-6928-5516; Pardo, Julian/0000-0003-0154-0730 FU Intramural NIH HHS NR 43 TC 100 Z9 107 U1 2 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 EI 1535-9786 J9 EUKARYOT CELL JI Eukaryot. Cell PD SEP PY 2007 VL 6 IS 9 BP 1562 EP 1569 DI 10.1128/EC.00141-07 PG 8 WC Microbiology; Mycology SC Microbiology; Mycology GA 210SZ UT WOS:000249477200006 PM 17601876 ER PT J AU Leosdottir, M Willenheimer, R Plehn, J Harris, TB Borgquist, R Gudmundsson, P Launer, LJ Bjornsdottir, H Nilsson, P Gudnason, V AF Leosdottir, M. Willenheimer, R. Plehn, J. Harris, T. B. Borgquist, R. Gudmundsson, P. Launer, L. J. Bjornsdottir, H. Nilsson, P. Gudnason, V. TI Myocardial function and structure by echocardiography/Doppler and tissue Doppler in pre-diabetic and diabetic elderly subjects in two population-based cohorts SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Leosdottir, M.; Willenheimer, R.] Malmo Univ Hosp, Dept Cardiol, Malmo, Sweden. [Plehn, J.; Borgquist, R.; Gudmundsson, P.; Gudnason, V.] George Washington Univ, Dept Med, Washington, DC USA. [Harris, T. B.; Launer, L. J.; Nilsson, P.] NIA, Bethesda, MD 20892 USA. [Bjornsdottir, H.] 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 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 2007 VL 28 SU 1 BP 87 EP 87 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702200339 ER PT J AU Gori, AM Giusti, B Corsi, AM Sestini, I Saracini, C Lauretani, F Bandinelli, S Ferrucci, L Gensini, GF Abbate, R AF Gori, A. M. Giusti, B. Corsi, A. M. Sestini, I. Saracini, C. Lauretani, F. Bandinelli, S. Ferrucci, L. Gensini, G. F. Abbate, R. TI Association between methylenetetrahydrofolate reductase and inflammatory markers in the inCHIANTI study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Gori, A. M.; Giusti, B.; Corsi, A. M.; Sestini, I.; Saracini, C.] Univ Florence, Dept Med, Florence, Italy. [Gori, A. M.; Giusti, B.; Corsi, A. M.; Sestini, I.; Saracini, C.] Surg Crit Area, Florence, Italy. [Lauretani, F.] Tuscany Reg Hlth Agcy, Florence, Italy. [Bandinelli, S.] Azienda Sanit Firenze, Geriatr Rehabil, Florence, Italy. [Ferrucci, L.; Gensini, G. F.; Abbate, R.] NIA, Gerontol Res Ctr, Baltimore, MD 21224 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 2007 VL 28 SU 1 BP 96 EP 96 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702200376 ER PT J AU Bystrup, A Adler, E Briley-Saebo, K Mani, V Giovanonne, S Frank, J Keller, G Weinmann, H Fuster, V Fayad, ZA AF Bystrup, A. Adler, E. Briley-Saebo, K. Mani, V. Giovanonne, S. Frank, J. Keller, G. Weinmann, H. Fuster, V. Fayad, Z. A. TI Magnetic resonance imaging of gadofluorine M-labeled embryonic stem cells transplanted into infarcted mouse heart SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Bystrup, A.; Adler, E.; Briley-Saebo, K.; Mani, V.; Giovanonne, S.; Keller, G.; Fuster, V.; Fayad, Z. A.] Mt Sinai Sch Med, New York, NY USA. [Frank, J.] NIH, Bethesda, MD 20892 USA. [Weinmann, H.] Schering AG, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 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 2007 VL 28 SU 1 BP 278 EP 279 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702201332 ER PT J AU Mccarthy, J Opie, LH Sack, MN Essop, MF AF Mccarthy, J. Opie, L. H. Sack, M. N. Essop, M. F. TI Activated PKCepsilon overexpression confers cardioprotection by metabolic modulation SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Mccarthy, J.] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Opie, L. H.] UCT, Hatter Inst Heart Res, Cape Town, South Africa. [Sack, M. N.] NHLBI, NIH, Washington, DC USA. [Essop, M. F.] Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa. NR 0 TC 0 Z9 0 U1 0 U2 2 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 2007 VL 28 SU 1 BP 363 EP 363 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702202010 ER PT J AU Sonmez, A Sung, K Yee, G Deng, A Mullen, S Mclaughlin, T Cushman, S Reaven, G Tsao, P AF Sonmez, A. Sung, K. Yee, G. Deng, A. Mullen, S. Mclaughlin, T. Cushman, S. Reaven, G. Tsao, P. TI Small adipocytes: implications for inflammation and insulin resistance SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Sonmez, A.] Gulhane Mil Med Acad, Ankara, Turkey. [Sung, K.; Yee, G.; Deng, A.; Cushman, S.] Stanford Univ, Sch Med, Falk Cardiovasc Res Inst, Stanford, CA 94305 USA. [Mullen, S.; Mclaughlin, T.; Reaven, G.; Tsao, P.] NIH, Bethesta, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 2007 VL 28 SU 1 BP 619 EP 619 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702203225 ER PT J AU Koh, K Quon, M Chung, W Zeon, S Shin, E AF Koh, K. Quon, M. Chung, W. Zeon, S. Shin, E. TI Efonidipine simultaneously improves blood pressure, endothelial function, and metabolic parameters in patients with hypertension SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Koh, K.] Gil Heart Ctr, Gachon Med Sch, Div Cardiol, Inchon, South Korea. [Quon, M.; Chung, W.; Zeon, S.; Shin, E.] 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 2007 VL 28 SU 1 BP 865 EP 865 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702204542 ER PT J AU Kiyatkin, EA AF Kiyatkin, Eugene A. TI Brain temperature fluctuations during physiological and pathological conditions SO EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY LA English DT Review DE brain metabolism; neural activity; hyperthermia; addictive drugs; brain edema; neurotoxicity ID LOCALIZED THERMAL-CHANGES; CEREBRAL-BLOOD-FLOW; IN-VITRO; BODY-TEMPERATURE; MDMA ECSTASY; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; SOMATOSENSORY STIMULATION; HYPOTHALAMIC TEMPERATURE; SUPRACHIASMATIC NUCLEUS; HUMAN THERMOREGULATION AB This review discusses brain temperature as a physiological parameter, which is determined primarily by neural metabolism, regulated by cerebral blood flow, and affected by various environmental factors and drugs. First, we consider normal fluctuations in brain temperature that are induced by salient environmental stimuli and occur during motivated behavior at stable normothermic conditions. Second, we analyze changes in brain temperature induced by various drugs that affect brain and body metabolism and heat dissipation. Third, we consider how these physiological and drug-induced changes in brain temperature are modulated by environmental conditions that diminish heat dissipation. Our focus is psychomotor stimulant drugs and brain hyperthermia as a factor inducing or potentiating neurotoxicity. Finally, we discuss how brain temperature is regulated, what changes in brain temperature reflect, and how these changes may affect neural functions under normal and pathological conditions. Although most discussed data were obtained in animals and several important aspects of brain temperature regulation in humans remain unknown, our focus is on the relevance of these data for human physiology and pathology. C1 Natl Inst Drug Abuse, Natl Inst Hlth, Behav Neurosci Branch, Intramural Res Program,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Natl Inst Hlth, Behav Neurosci Branch, Intramural Res Program,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov FU Intramural NIH HHS NR 120 TC 42 Z9 42 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1439-6319 J9 EUR J APPL PHYSIOL JI Eur. J. Appl. Physiol. PD SEP PY 2007 VL 101 IS 1 BP 3 EP 17 DI 10.1007/s00421-007-0450-7 PG 15 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 205FS UT WOS:000249100000002 PM 17429680 ER PT J AU Siggeirsdottir, K Aspelund, T Sigurdsson, G Mogensen, B Chang, M Jonsdottir, B Eiriksdottir, G Launer, LJ Harris, TB Jonsson, BY Gudnason, V AF Siggeirsdottir, Kristin Aspelund, Thor Sigurdsson, Gunnar Mogensen, Brynjolfur Chang, Milan Jonsdottir, Birna Eiriksdottir, Gudny Launer, Lenore J. Harris, Tamara B. Jonsson, Brynjolfur Y. Gudnason, Vilmundur TI Inaccuracy in self-report of fractures may underestimate association with health outcomes when compared with medical record based fracture registry SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE questionnaire; self-report; fracture; function; registry; AGES-Reykjavik study ID HIP FRACTURE; RISK-FACTORS; OSTEOPOROTIC FRACTURES; ELDERLY-WOMEN; VALIDITY; ACCURACY; MEN; MORTALITY; DISEASE; INFORMATION AB Introduction and objective Misreporting fractures in questionnaires is known. However, the effect of misreporting on the association of fractures with subsequent health outcomes has not been examined. Methods Data from a fracture registry (FR) developed from an extensive review of radiographic and medical records were related to self-report of fracture for 2,255 participants from the AGES Reykjavik Study. This data was used to determine false negative and false positive rates of self-reported fractures, correlates of misreporting, and the potential effect of the misreporting on estimates of health outcomes following fractures. Results In women, the false positive rate decreased with age as the false negative rate increased with no clear trend with age in men. Kappa values for agreement between FR and self-report were generally higher in women than men with the best agreement for forearm fracture (men 0.64 and women 0.82) and the least for rib (men 0.28 and women 0.25). Impaired cognition was a major factor associated with discordant answers between FR and self-report, OR 1.7 (95% CI: 1.3-2.1) (P < 0.0001). We estimated the effect of misreporting on health after fracture by comparison of the association of the self-report of fracture and fracture from the FR, adjusting for those factors associated with discordance. The weighted attenuation factor measured by mobility and muscle strength was 11% (95% CI: 0-24%) when adjusted for age and sex but reduced to 6% (95% CI: -10-22%) when adjusted for cognitive impairment. Conclusion Studies of hip fractures should include an independent ascertainment of fracture but for other fractures this study supports the use of self-report. C1 Icelandic Heart Assoc, IS-201 Kopavogur, Iceland. Landspitalinn Univ Hosp, Reykjavik, Iceland. NIA, Bethesda, MD 20892 USA. Univ Hosp, Malmo, Sweden. Univ Iceland, Reykjavik, Iceland. RP Siggeirsdottir, K (reprint author), Icelandic Heart Assoc, Holtasmari 1, IS-201 Kopavogur, Iceland. EM kristin@hjarta.is RI Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011 OI Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433; FU Intramural NIH HHS; NIA NIH HHS [N01 AG-12100] NR 33 TC 31 Z9 31 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD SEP PY 2007 VL 22 IS 9 BP 631 EP 639 DI 10.1007/s10654-007-9163-9 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 210GM UT WOS:000249444700008 PM 17653601 ER PT J AU Frahm, N Yusim, K Suscovich, TJ Adams, S Sidney, J Hraber, P Hewitt, HS Linde, CH Kavanagh, DG Woodberry, T Henry, LM Faircloth, K Listgarten, J Kadie, C Jojic, N Sango, K Brown, NV Pae, E Zaman, MT Bihl, F Khatri, A John, M Mallal, S Marincola, FM Walker, BD Sette, A Heckerman, D Korber, BT Brander, C AF Frahm, Nicole Yusim, Karina Suscovich, Todd J. Adams, Sharon Sidney, John Hraber, Peter Hewitt, Hannah S. Linde, Caitlyn H. Kavanagh, Daniel G. Woodberry, Tonia Henry, Leah M. Faircloth, Kellie Listgarten, Jennifer Kadie, Carl Jojic, Nebojsa Sango, Kaori Brown, Nancy V. Pae, Eunice Zaman, M. Tauheed Bihl, Florian Khatri, Ashok John, Mina Mallal, Simon Marincola, Francesco M. Walker, Bruce D. Sette, Alessandro Heckerman, David Korber, Bette T. Brander, Christian TI Extensive HLA class I allele promiscuity among viral CTL epitopes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE antigen; bioinformatics; CD8 T cells; HIV; immune responses ID T-CELL EPITOPES; HUMAN-IMMUNODEFICIENCY-VIRUS; LYMPHOCYTE EPITOPES; BIOINFORMATICS APPROACH; HIV POLYMORPHISMS; PEPTIDE BINDING; HEPATITIS-C; IDENTIFICATION; RECOGNITION; MOLECULES AB Promiscuous binding of T helper epitopes to MHC class 11 molecules has been well established, but few examples of promiscuous class I-restricted epitopes exist. To address the extent of promiscuity of HLA class I peptides, responses to 242 well-defined viral epitopes were tested in 100 subjects regardless of the individuals' HLA type. Surprisingly, half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Functional assays confirmed the frequent recognition of HLA class I-restricted T cell epitopes on several alternative alleles across HLA class I supertypes and encoded on different class I loci. These data have significant implications for the understanding of MHC class I-restricted antigen presentation and vaccine development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Los Alamos Natl Lab, Los Alamos, NM USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. La Jolla Inst Allergy & Immunol, La Jolla, CA USA. Microsoft Res, Redmond, WA USA. Fenway Community Hlth Ctr, Boston, MA USA. Lemuel Shattuck Hosp, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia. Murdoch Univ, Perth, WA, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. Santa Fe Inst, Santa Fe, NM 87501 USA. RP Brander, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, 149 13th St,Room 5239, Charlestown, MA 02129 USA. EM cbrander@partners.org OI Brander, Christian/0000-0002-0548-5778; Korber, Bette/0000-0002-2026-5757; Hraber, Peter/0000-0002-2920-4897 FU NIAID NIH HHS [F32 AI058457, R01 AI067077-01, R01 AI067077-02, R01 AI067077-03, R21 AI055421, R21-AI-055421-01-A1]; PHS HHS [N01-AL-15422, R01-A1-067077] NR 58 TC 77 Z9 78 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2007 VL 37 IS 9 BP 2419 EP 2433 DI 10.1002/eji.200737365 PG 15 WC Immunology SC Immunology GA 214MV UT WOS:000249743200012 PM 17705138 ER PT J AU Wen, HT Hogaboam, CM Lukacs, NW Cook, DN Lira, SA Kunkel, SL AF Wen, Haitao Hogaboam, Cory M. Lukacs, Nicholas W. Cook, Donald N. Lira, Sergio A. Kunkel, Steven L. TI The chemokine receptor CCR6 is an important component of the innate immune response SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE chemokine; macrophage; sepsis ID INFLAMMATORY PROTEIN 3-ALPHA; DENDRITIC CELLS; BONE-MARROW; CCR6-DEFICIENT MICE; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; HUMAN MONOCYTES; UNITED-STATES; SEVERE SEPSIS; HOST-DEFENSE AB In our initial studies we found that naive CCR6-deficient (CCR6(-/-)) C57BL/6 mice possessed significantly lower number of both F4/80(+) macrophages and dendritic cells (DC), but higher number of B cells in the peritoneal cavity, as compared to naive wild type (WT) controls. Furthermore, peritoneal macrophages isolated from CCR6-/- mice expressed significantly lower levels of inflammatory cytokines and nitric oxide following lipopolysaccharide (LPS) stimulation, as compared to WT macrophages. In a severe experimental peritonitis model induced by cecal ligation and puncture (CLP), CCR6-/- mice were protected when compared with WT controls. At 24 h following the induction of peritonitis, CCR6-/- mice exhibited significantly lower levels of inflammatory cytokines/chemokines in both the peritoneal cavity and blood. Interestingly, DC recruitment into the peritoneal cavity was impaired in CCR6(-/-) mice during the evolution of CLP-induced peritonitis. Peritoneal macrophages isolated from surviving CCR6-/- mice 3 days after CLP-induced peritonitis exhibited an enhanced LPS response compared with similarly treated WT peritoneal macrophages. These data illustrate that CCR6 deficiency alters the innate response via attenuating the hyperactive local and systemic inflammatory response during CLP-induced peritonitis. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. CUNY Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA. RP Kunkel, SL (reprint author), Univ Michigan, Sch Med, Dept Pathol, 4071 BSRB,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM slkunkel@umich.edu RI hogaboam, cory /M-3578-2014 FU NHLBI NIH HHS [HL74024, HL31237, HL31963] NR 54 TC 15 Z9 16 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2007 VL 37 IS 9 BP 2487 EP 2498 DI 10.1002/eji.200737370 PG 12 WC Immunology SC Immunology GA 214MV UT WOS:000249743200018 PM 17694574 ER PT J AU Kiyatkin, EA Brown, PL Sharma, HS AF Kiyatkin, Eugene A. Brown, P. Leon Sharma, Hari S. TI Brain edema and breakdown of the blood-brain barrier during methamphetamine intoxication: critical role of brain hyperthermia SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE albumin leakage; astrocytic activation and damage; ions; neurotoxicity; rats; brain water ID SPINAL CORD BARRIER; FIBRILLARY ACIDIC PROTEIN; NORMOTENSIVE YOUNG-RATS; CENTRAL-NERVOUS-SYSTEM; DOPAMINERGIC NEUROTOXICITY; ENVIRONMENTAL-TEMPERATURE; SUBSTITUTED AMPHETAMINES; C57BL/6J MOUSE; HEAT-STRESS; INJURY AB To clarify the role of brain temperature in permeability of the blood-brain barrier (BBB), rats were injected with methamphetamine (METH 9 mg/kg) at normal (23 degrees C) and warm (29 degrees C) environmental conditions and internal temperatures were monitored both centrally (nucleus accumbens, NAcc) and peripherally (skin and nonlocomotor muscle). Once NAcc temperatures peaked or reached 41.5 degrees C (a level suggesting possible lethality), animals were administered Evans blue dye (protein tracer that does not normally cross the BBB), rapidly anaesthetized, perfused and had their brains removed. All METH-treated animals showed brain and body hyperthermia associated with relative skin hypothermia, suggesting metabolic activation coupled with peripheral vasoconstriction. While METH-induced NAcc temperature elevation varied from 37.60 to 42.46 degrees C (or 1.2-5.1 degrees C above baseline), it was stronger at 29 degrees C (+4.13 degrees C) than 23 degrees C (+2.31 degrees C). Relative to control, METH-treated animals had significantly higher brain levels of water, Na+, K+ and Cl-, suggesting brain edema, and intense immunostaining for albumin, indicating breakdown of the BBB. METH-treated animals also showed strong immunoreactivity for glial fibrillary acidic protein (GFAP), possibly suggesting acute abnormality or damage of astrocytes. METH-induced changes in brain water, albumin and GFAP correlated linearly with NAcc temperature (r = 0.93, 0.98 and 0.98, respectively), suggesting a key role of brain hyperthermia in BBB permeability, development of brain edema and subsequent functional and structural neural abnormalities. Therefore, along with a direct destructive action on neural cells and functions, brain hyperthermia, via breakdown of the BBB, may be crucial for both decompensation of brain functions and cell injury following acute METH intoxication, possibly contributing to neurodegeneration resulting from chronic drug use. C1 Natl Inst Drug Abuse, Intramural Res Program, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA. Uppsala Univ, Univ Hosp, Dept Surg Sci Anaesthesiol & Intens Care Med, Lab Cerebrovasc Res, SE-75185 Uppsala, Sweden. RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Behav Neurosci Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov RI Sharma, Hari/G-4508-2016 FU Intramural NIH HHS NR 66 TC 68 Z9 70 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD SEP PY 2007 VL 26 IS 5 BP 1242 EP 1253 DI 10.1111/j.1460-9568.2007.05741.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 205QT UT WOS:000249130400016 PM 17767502 ER PT J AU Vann, SD Saunders, RC Aggleton, JP AF Vann, Seralynne D. Saunders, Richard C. Aggleton, John P. TI Distinct, parallel pathways link the medial mammillary bodies to the anterior thalamus in macaque monkeys SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE amnesia; anterior thalamic nuclei; hippocampus; mammillary bodies; mammillothalamic tract; memory ID MAMILLARY-BODY LESIONS; SUPRAMAMMILLARY NUCLEUS; MAMMILLOTHALAMIC TRACT; POSTERIOR HYPOTHALAMUS; MACACA-FASCICULARIS; HIPPOCAMPAL THETA; PREFRONTAL CORTEX; RHESUS-MONKEY; MEMORY; PROJECTIONS AB Mammillary body neurons projecting to the thalamus were identified by injecting retrograde tracers into the medial thalamus of macaque monkeys. The source of the thalamic projections from the medial mammillary nucleus showed strikingly different patterns of organization depending on the site of the injection within the two anterior thalamic nuclei, anterior medialis and anterior ventralis. These data reveal at least two distinct modes by which the primate medial mammillary bodies can regulate anterior thalamic function. Projections to the thalamic nucleus anterior medialis arise mainly from the pars lateralis of the medial mammillary nucleus. A particularly dense source is the dorsal cap in the posterior half of the pars lateralis, a subregion that has not previously been distinguished. In contrast, neurons spread evenly across the medial mammillary nucleus gave rise to projections more laterally in the anterior thalamic nuclei. A third pattern of medial mammillary neurons appeared to provide the source of projections to the rostral midline thalamic nuclei. In contrast, the labeled cells in the lateral mammillary nucleus were evenly spread across that nucleus, irrespective of injection site. In addition to the established projection to anterior dorsalis, the lateral mammillary nucleus appears to project lightly to a number of other thalamic nuclei, including lateralis dorsalis, anterior medialis, anterior ventralis, and the rostral midline nuclei, e.g. nucleus reuniens. These anatomical findings not only reveal novel ways of grouping the neurons within the medial mammillary nucleus, but also indicate that the mammillothalamic connections support cognition in multiple ways. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Cardiff Univ, Sch Psychol, Cardiff CF10 3AT, Wales. RP Saunders, RC (reprint author), NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. EM richardsaunders@mail.nih.gov RI Vann, Seralynne/A-1601-2010; OI Vann, Seralynne/0000-0002-6709-8773; Aggleton, John/0000-0002-5573-1308 NR 52 TC 24 Z9 24 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD SEP PY 2007 VL 26 IS 6 BP 1575 EP 1586 DI 10.1111/j.1460-9568.2007.05773.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 210WE UT WOS:000249485500017 PM 17880392 ER PT J AU Ruttens, B Saksena, R Kovac, P AF Ruttens, Bart Saksena, Rina Kovac, Pavol TI Synthesis of phosphorylated, conjugation-ready di-, tri- and tetrasaccharide fragments of the O-speciflic polysaccharide of V-cholerae O139 SO EUROPEAN JOURNAL OF ORGANIC CHEMISTRY LA English DT Article DE carbohydrates; regioselective phosphorylation; glycosylation; oligosaccharides; conjugate vaccine ID VIBRIO-CHOLERAE O139; CARBOHYDRATE-BASED VACCINES; 4,6-O-BENZYLIDENE ACETALS; CAPSULAR POLYSACCHARIDE; STRUCTURAL-ANALYSIS; LIPOPOLYSACCHARIDE; DERIVATIVES; 1,3,2-DIOXAPHOSPHORINAN-2-ONES; OLIGOSACCHARIDES; STEREOCHEMISTRY AB The fragments described contain a galactose residue with cyclic 4,6-phosphate and are equipped with an amino-functionalized spacer, allowing further derivatization or direct conjugation to suitable carriers. The core Gal-(1-->3,3)-GlcNAc disaccharide was obtained by condensation of 8-azido-3,6-dioxaoctyl 2-acetamido-4,6-0-benzylidene-2-deoxy-alpha-D-glUcopyranoside with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide under Helferich conditions. Reductive opening of the benzylidene acetal, followed by deacetylation and selective benzylation gave 8-azido-3,6-dioxaoctyl 2-acetamido6-O-benzyl-3-0-(3-0-benzyl-beta-D-galactopyranosyl)-2-deoxy-beta-D-glucopyranoside, which was regioselectively phosphorylated to give two isomeric 4,6-cyclic 2,2,2-trichloroethyl phosphates. The (R)-phosphate was subjected to catalytic hydrogenation/hydrogenolysis to give the fully deprotected title disaccharide fragment. Glycosylation of the (S) -phosphate diol with 2,4-di-O-benzyl-3,6-dideoxy-alpha-L-xylo-hexopyranosyl bromide under halide-assisted conditions yielded a mixture of the tetrasaccharide and a trisaccharide, which were readily separable by chromatography. Their hydrogenation/hydrogenolysis effected global deprotection as well as reduction of the azide, to furnish the deprotected title tri- and tetrasaccharide. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007). C1 NIDDK, NIH, Sect Carbohydrates, LBC, Bethesda, MD 20892 USA. RP Ruttens, B (reprint author), NIDDK, NIH, Sect Carbohydrates, LBC, Bldg 10, Bethesda, MD 20892 USA. EM kpn@helix.nih.gov NR 52 TC 12 Z9 12 U1 2 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1434-193X J9 EUR J ORG CHEM JI Eur. J. Org. Chem. PD SEP PY 2007 IS 26 BP 4366 EP 4375 PG 10 WC Chemistry, Organic SC Chemistry GA 215GV UT WOS:000249797200013 ER PT J AU Ward, CM Jyonouchi, H Kotenko, SV Smirnov, SV Patel, R Aguila, H McSherry, G Dashefsky, B Holland, SM AF Ward, Carla M. Jyonouchi, Harumi Kotenko, Sergei V. Smirnov, Sergey V. Patel, Rakesh Aguila, Helen McSherry, George Dashefsky, Barry Holland, Steven M. TI Adjunctive treatment of disseminated Mycobacterium avium complex infection with interferon alpha-2b in a patient with complete interferon-gamma receptor R1 deficiency SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE complete IFNGR1 defect; disseminated Mycobacterium avium complex infection; interferon-alpha 2b ID GAMMA RECEPTOR-1 DEFICIENCY; STEM-CELL TRANSPLANTATION; CALMETTE-GUERIN INFECTION; SMALL DELETION HOTSPOT; IFN-GAMMA; TARGETED DISRUPTION; VIRAL DISEASE; CHILD; SUSCEPTIBILITY; GENE AB We report adjunct treatment of (interferon) IFN-alpha 2b (Intron-A) in a patient with complete interferon-gamma receptor R1 (IFNGR1) deficiency suffering from disseminated infection with Mycobacterium avium complex (MAC) resistant to multiple anti-mycobacterial agents. A low dose of IFN-alpha 2b (3 x 106 units/m(2) three times weekly subcutaneously) successfully attenuated progressive hepatosplenomegaly and abdominal/retroperitoneal/pelvic lymphadenopathy, although the patient continued to be mycobacteremic. This is the first report of a complete IFNGR1 deficiency treated with adjuvant IFN-alpha 2b for disseminated MAC infection. C1 Univ Med & Dent New Jersey, Div Pulmonol Allergy & Immunol & Infect Dis, Dept Pediat, New Jersey Med Sch, Newark, NJ 07101 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07101 USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Jyonouchi, H (reprint author), Univ Med & Dent New Jersey, Div Pulmonol Allergy & Immunol & Infect Dis, Dept Pediat, New Jersey Med Sch, 185 S Orange Ave,F570A,MSB, Newark, NJ 07101 USA. EM jyanouha@umdnj.edu NR 33 TC 16 Z9 16 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD SEP PY 2007 VL 166 IS 9 BP 981 EP 985 DI 10.1007/s00431-006-0339-1 PG 5 WC Pediatrics SC Pediatrics GA 192FV UT WOS:000248187100018 PM 17120031 ER PT J AU Cheng, WH Muftuoglu, M Bohr, VA AF Cheng, Wen-Hsing Muftuoglu, Meltem Bohr, Vilhelm A. TI Werner syndrome protein: Functions in the response to DNA damage and replication stress in S-phase SO EXPERIMENTAL GERONTOLOGY LA English DT Article; Proceedings Paper CT European Conference on Aging (ECONAG 2006) CY NOV 27-30, 2006 CL Innsbruck, AUSTRIA DE aging; Werner syndrome; DNA repair; replication; telomere; base excision repair; recombination ID BLOOM-SYNDROME PROTEINS; SYNDROME GENE-PRODUCT; WRN HELICASE ACTIVITY; DOUBLE-STRAND BREAKS; SYNDROME CELLS; ATM ACTIVATION; POLY(ADP-RIBOSE) POLYMERASE-1; MRE11-RAD50-NBS1 COMPLEX; MRE11 COMPLEX; CROSS-LINKS AB Werner syndrome (WS) is an excellent model system for the study of human aging. WRN, a nuclear protein mutated in WS, plays multiple roles in DNA metabolism. Our understanding about the metabolic regulation and function of this RecQ helicase has advanced greatly during the past decade, largely due to the availability of purified WRN protein, WRN knockdown cells, and WRN knockout mice. Recent biochemical and genetic studies indicate that WRN plays significant roles in DNA replication, DNA repair, and telomere maintenance. Interestingly, many WRN functions require handling of DNA ends during S-phase, and evidence suggests that WRN plays both upstream and downstream roles in the response to DNA damage. Future research should focus on the mechanism(s) of WRN in the regulation of the various DNA metabolism pathways and development of therapeutic approaches to treat premature aging syndromes such as WS. Published by Elsevier Inc. C1 Natl Inst Hlth, NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), Natl Inst Hlth, NIA, Lab Mol Gerontol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov FU Intramural NIH HHS NR 86 TC 22 Z9 22 U1 0 U2 1 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 2007 VL 42 IS 9 SI SI BP 871 EP 878 DI 10.1016/j.exger.2007.04.011 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 213OZ UT WOS:000249678300005 PM 17587522 ER PT J AU Donahue, RE An, D Kamata, M Bonifacino, A Metzger, ME Krouse, A Baltimore, D Chen, ISY AF Donahue, R. E. An, D. Kamata, M. Bonifacino, A. Metzger, M. E. Krouse, A. Baltimore, D. Chen, I. S. Y. TI Successful CCR5 downregulation using RNA interference in non-human primates following CD34+hematopoietic stem/progenitor cell transplantation SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 28-30, 2007 CL Hamburg, GERMANY SP Int Soc Expt Hematol C1 NHLBI, Hematol Branch, Rockville, MD USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Hematol & Oncol, Los Angeles, CA USA. Univ Calif Los Angeles, AIDS Inst, Dept Microbiol Immunol & Mol Genet & Med, Los Angeles, CA USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2007 VL 35 IS 9 SU 2 BP 23 EP 24 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 211PH UT WOS:000249535200055 ER PT J AU Rosu-Myles, M Markus, J Wolff, L AF Rosu-Myles, M. Markus, J. Wolff, L. TI The tumor suppressor INK4B regulates erythroid-myeloid lineage choice by common myeloid progenitors through a cell cycle independent mechanism SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 28-30, 2007 CL Hamburg, GERMANY SP Int Soc Expt Hematol C1 Natl Canc Inst, Cellular Oncol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2007 VL 35 IS 9 SU 2 BP 29 EP 29 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 211PH UT WOS:000249535200071 ER PT J AU Rosu-Myles, M Markus, J Wolff, L AF Rosu-Myles, M. Markus, J. Wolff, L. TI The tumor suppressor INK4b regulates erythroid-myeloid lineage choice by common myeloid progenitors through a cell cycle independent mechanism SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 28-30, 2007 CL Hamburg, GERMANY SP Int Soc Expt Hematol C1 NCI, Lab Cellular Oncol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2007 VL 35 IS 9 SU 2 BP 95 EP 95 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 211PH UT WOS:000249535200264 ER PT J AU Cokic, VP Beleslin-Cokic, BB Noguchi, CT Schechter, AN AF Cokic, V. P. Beleslin-Cokic, B. B. Noguchi, C. T. Schechter, A. N. TI Hydroxyurea nitrosylates and activates soluble guanylyl cyclase in human erythroid cells SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 28-30, 2007 CL Hamburg, GERMANY SP Int Soc Expt Hematol C1 Inst Med Res, Lab Expt Hematol, Belgrade, Serbia. Univ Clin Ctr, Sch Med, Inst Endocrinol Diabet & Dis Metab, Belgrade, Serbia. NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2007 VL 35 IS 9 SU 2 BP 106 EP 106 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 211PH UT WOS:000249535200296 ER PT J AU Hsieh, MM Langemeijer, S Wynter, A Phang, OA Kang, EM Tisdale, JF AF Hsieh, Matthew M. Langemeijer, Saskia Wynter, Aisha Phang, Oswald A. Kang, Elizabeth M. Tisdale, John F. TI Low-dose parenteral busulfan provides an extended window for the infusion of hematopoietic stem cells in murine hosts SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID LEUKOCYTE ADHESION DEFICIENCY; CHRONIC GRANULOMATOUS-DISEASE; BONE-MARROW TRANSPLANTATION; GENE-THERAPY; INTRAVENOUS BUSULFAN; PROGENITOR CELLS; PHARMACOKINETICS; ENGRAFTMENT; MODEL; IRRADIATION AB Objective. Myeloablative total body irradiation (TBI) in the setting of autologous transplantation of genetically modified hematopoietic stem cells (HSC) is associated with substantial toxicity. Nonmyeloablative doses of TBI are less toxic, but result in low-level engraftment of genetically modified HSCs. As an alternative to TBI, escalating doses of parenteral busulfan were tested for their hematologic toxicity, their ability to promote donor leukocyte engraftment, and the time window for such engraftment. Materials and Methods. Hematologic toxicity of busulfan was assessed in C57BL6 mice after single nonmyeloablative doses of intraperitoneal busulfan ranging from 1 to 40 mg/kg by serial complete blood counts monitored up to 40 days. The level of donor engraftment attainable after nonmyeloablative busulfan was determined by infusion of 20 million congenic murine bone marrow nucleated cells (BMNC) following 5 to 40 mg/kg of busulfan. To determine the effects of delayed HSC infusions, BMNCs were infused 1, 10, 15, and 20 days after a single dose of 10 mg/kg of busulfan. Results. Busulfan doses from I to 40 mg/kg produced hematologic toxicity that was most pronounced in the 2nd to 3rd week. In transplantation experiments, dose-dependent donor leukocyte engraftment was attained with levels > 70% after only 20 mg/kg of busulfan. Similar levels of engraftment were achieved even when infusion of BMNCs was delayed up to 20 days after busulfan injection. Conclusion. Nonmyeloablative parenteral busulfan produced transient myelosuppressive effects, clinically relevant levels of engraftment, and an extended time window for HSC infusion in murine hosts. (c) 2007 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. RP Tisdale, JF (reprint author), NIDDK, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N 116,9000 Rockville Pike, Bethesda, MD 20892 USA. EM johntis@mail.nih.gov FU Intramural NIH HHS [Z01 DK027010-04] NR 35 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2007 VL 35 IS 9 BP 1415 EP 1420 DI 10.1016/j.exphem.2007.05.009 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 210SI UT WOS:000249475500011 PM 17618036 ER PT J AU Dorner, T Lipsky, PE AF Doerner, Thomas Lipsky, Peter E. TI B-cell targeting: a novel approach to immune intervention today and tomorrow SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE autoimmunity; B cells; biologics; rheumatoid arthritis; systemic lupus erythematosus; targeted therapy ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; ANTI-CD20 MONOCLONAL-ANTIBODY; PLASMACYTOID DENDRITIC CELLS; RHEUMATOID-ARTHRITIS; LYMPHOCYTE DEPLETION; MULTIPLE-SCLEROSIS; MARGINAL-ZONE; MURINE LUPUS; SUSTAINED IMPROVEMENT AB B cells and their products, antibodies, play an important role in the diagnosis and, in some instances, in the pathogenesis of many autoimmune diseases. Specific B-cell directed therapies are of recent interest as their impact on B-cell activity can influence a variety of autoimmune diseases. The development and introduction of rituximab, a depleting antibody targeting CD20(+) B cells, and previously CD52-directed treatment with Campath-1h for the treatment of B-cell malignancies as well as rheumatoid arthritis have pioneered this therapeutic field. Other non-depleting strategies employ CD22 or B-cell activating factor/B lymphocyte stimulator and apoptosis-inducing ligand as targets and are under clinical investigation at present. Abnormalities of B-cell subsets have been identified by a number of independent groups which often represent characteristic patterns of disturbances of the human B-cell repertoire. However, the clinical value of specific B-cell subset targeting/depletion has not been addressed extensively. As such an approach may afford the possibility to avoid unnecessary adverse events related to depletion of non-pathogenic B-cell populations, B-cell subset targeting may have the capacity to enhance the benefit/risk ratio of B-cell immune intervention. C1 Charite Univ Med Berlin, D-10098 Berlin, Germany. Deutsch Rheumaforschungszentrum, D-10098 Berlin, Germany. NIAMS, NIH, Bethesda, MD USA. RP Dorner, T (reprint author), Charite Univ Med Berlin, Charitepl 01, D-10098 Berlin, Germany. EM thomas.doerner@charite.de NR 112 TC 22 Z9 23 U1 0 U2 1 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 2007 VL 7 IS 9 BP 1287 EP 1299 DI 10.1517/14712598.7.9.1287 PG 13 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 212MZ UT WOS:000249601900002 PM 17727320 ER PT J AU Gao, ZG Jacobson, KA AF Gao, Zhan-Guo Jacobson, Kenneth A. TI Emerging adenosine receptor agonists SO EXPERT OPINION ON EMERGING DRUGS LA English DT Review DE adenosine receptor; agonist; cardiac arrhythmia; cardiac perfusion imaging; colon cancer; G protein-coupled receptor; inflammation; nucleoside; pain; rheumatoid arthritis ID COLON-CARCINOMA GROWTH; HUMAN-MELANOMA CELLS; NF-KAPPA-B; CL-IB-MECA; A(1) RECEPTOR; MICE LACKING; SUPRAVENTRICULAR ARRHYTHMIAS; ALLOSTERIC MODULATION; RHEUMATOID-ARTHRITIS; ATRIAL-FIBRILLATION AB Adenosine receptors (ARs) are a four-member subfamily of G protein-coupled receptors and are major targets of caffeine and theophylline. There are four subtypes of ARs, designated as A(1), A(2A), A(2B) and A(3). Selective agonists are now available for all four subtypes. Over a dozen of these selective agonists are now in clinical trials for various conditions, although none has received regulatory approval except for the endogenous AR agonist adenosine itself. A(1)AR agonists are in clinical trials for cardiac arrhythmias and neuropathic pain. A(2A)AR agonists are now in trials for myocardial perfusion imaging and as anti-inflammatory agents. A(2B)AR agonists are under preclinical scrutiny for potential treatment of cardiac ischemia. A(3)AR agonists are in clinical trials for the treatment of rheumatoid arthritis and colorectal cancer. The present review will mainly cover the agonists that are presently in clinical trials for various conditions and only a brief introduction will be given to major chemical classes of AR agonists presently under investigation. C1 NIDDK, NIH, Mol Recognit Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Gao, ZG (reprint author), NIDDK, NIH, Mol Recognit Sect, Bioorgan Chem Lab, Bldg 8A,Room B1A-23,9000 Rockville Pike, Bethesda, MD 20892 USA. EM zg21o@nih.gov; kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 108 TC 68 Z9 73 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8214 J9 EXPERT OPIN EMERG DR JI Expert Opin Emerg. Drugs PD SEP PY 2007 VL 12 IS 3 BP 479 EP 492 DI 10.1517/14728214.12.3.479 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 217QW UT WOS:000249963400011 PM 17874974 ER PT J AU Johann, DJ Blondert, J AF Johann, Donald J., Jr. Blondert, Josip TI Biomarker discovery: tissues versus fluids versus both SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Editorial Material ID PROTEOMIC ANALYSIS C1 Natl Canc Inst, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21170 USA. Natl Inst Hlth, Natl Canc Inst, Med Oncol Branch, Bethesda, MD 20892 USA. RP Blondert, J (reprint author), Natl Canc Inst, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21170 USA. EM blonder@ncifcrf.gov FU NCI NIH HHS [N01-CO12400] NR 9 TC 8 Z9 9 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD SEP PY 2007 VL 7 IS 5 BP 473 EP 475 DI 10.1586/14737159.7.5.473 PG 3 WC Pathology SC Pathology GA 222TY UT WOS:000250321400003 PM 17892354 ER PT J AU Yu, LR Veenstra, TD AF Yu, Li-Rong Veenstra, Timothy D. TI AACR-FDA-NCI cancer biomarkers collaborative SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Article AB The past few years have seen a frantic effort in an attempt to discover and validate novel biomarkers for the diagnosis and treatment of diseases such as cancer. Unfortunately, the rate at which biomarkers are being used in actual patient treatment is not increasing accordingly. There are a number of reasons for this discrepancy; one is the failure to recognize and appreciate which validated biomarkers have the greatest chance of being used in a clinical setting. In addition, there is a general lack of understanding within the basic research community of the intricacies involved in the regulatory process required to produce a clinically useful biomarker. Fortunately, a collaboration involving the American Association for Cancer Research, the National Cancer Institute and the US FDA hopes to expedite the process of bringing validated biomarkers to the point where they can have an impact on the diagnosis and treatment of disease. C1 Natl Canc Inst, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), Natl Canc Inst, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. EM lyu@ncifcrf.gov; veenstra@ncifcrf.gov NR 0 TC 3 Z9 3 U1 0 U2 1 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD SEP PY 2007 VL 7 IS 5 BP 507 EP 509 DI 10.1586/14737159.7.5.507 PG 3 WC Pathology SC Pathology GA 222TY UT WOS:000250321400007 PM 17892359 ER PT J AU Lin, DC Dimitriadis, EK Horkay, F AF Lin, D. C. Dimitriadis, E. K. Horkay, F. TI Elasticity of rubber-like materials measured by AFM nanoindentation SO EXPRESS POLYMER LETTERS LA English DT Article DE mechanical properties; atomic force microscopy; polymer gels; indentation AB We exploit the force spectroscopy capabilities of the atomic force microscope in characterizing the local elasticity of rubber-like materials. Extraction of elastic properties from force curves usually relies on the linear theory pioneered by Hertz. While the Hertzian force-indentation relationships have been shown to be accurate in modeling the contact mechanics at sufficiently shallow indentation depths, the linear deformation regime of the probed material is exceeded in many practical applications of nanoindentation. In this article, a simple, nonlinear force-indentation equation based on the Mooney-Rivlin model is derived and used to fit data from the indentation of lightly crosslinked poly(vinyl alcohol) gels in equilibrium with water. The extracted values of Young's modulus show good agreement with those obtained by both macroscopic compression testing and by fitting truncated portions of the force curves with the Hertz equation. C1 [Lin, D. C.; Horkay, F.] NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. [Dimitriadis, E. K.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Lin, DC (reprint author), NIH, Lab Integrat & Med Biophys, 9 Mem Dr,Bldg 9,Rm 1E118, Bethesda, MD 20892 USA. EM lindavid@mail.nih.gov; horkay@helix.nih.gov FU National Institutes of Health/National Institute of Child Health and Human Development FX This work was supported by the Intramural Research Program of the National Institutes of Health/National Institute of Child Health and Human Development. NR 31 TC 36 Z9 36 U1 1 U2 30 PU BUDAPEST UNIV TECHNOL & ECON PI BUDAPEST PA DEPT POLYMER ENG, MUEGYETEM RKP 3, BUDAPEST, H-1111, HUNGARY SN 1788-618X J9 EXPRESS POLYM LETT JI Express Polym. Lett. PD SEP PY 2007 VL 1 IS 9 BP 576 EP 584 DI 10.3144/expresspolymlett.2007.79 PG 9 WC Polymer Science SC Polymer Science GA V91OQ UT WOS:000206189600003 ER PT J AU Siegmund, SV Qian, T de Minicis, S Harvey-White, J Kunos, G Vinod, KY Hungund, B Schwabe, RF AF Siegmund, Soeren V. Qian, Ting de Minicis, Samuele Harvey-White, Judith Kunos, George Vinod, K. Y. Hungund, Basalingappa Schwabe, Robert F. TI The endocannabinoid 2-arachidonoyl glycerol induces death of hepatic stellate cells via mitochondrial reactive oxygen species SO FASEB JOURNAL LA English DT Article DE ROS; 2-AG; HSC; hepatocyte; fibrosis ID RAT-LIVER FIBROSIS; N-TERMINAL KINASE; CANNABINOID-RECEPTOR; PERMEABILITY TRANSITION; KAPPA-B; NADPH OXIDASE; ANANDAMIDE; APOPTOSIS; PROLIFERATION; ACTIVATION AB The endocannabinoid system is an important regulator of hepatic fibrogenesis. In this study, we determined the effects of 2- arachidonoyl glycerol ( 2- AG) on hepatic stellate cells ( HSCs), the main fibrogenic cell type in the liver. Culture- activated HSCs were highly susceptible to 2- AG- induced cell death with > 50% cell death at 10 mu M after 18 h of treatment. 2- AG- induced HSC death showed typical features of apoptosis such as PARP- and caspase 3- cleavage and depended on reactive oxygen species ( ROS) formation. Confocal microscopy revealed mitochondria as primary site of ROS production and demonstrated mitochondrial depolarization and increased mitochondrial permeability after 2- AG treatment. 2- AG- induced cell death was independent of cannabinoid receptors but required the presence of membrane cholesterol. Primary hepatocytes were resistant to 2- AG- induced ROS induction and cell death but became susceptible after GSH depletion suggesting antioxidant defenses as a critical determinant of 2- AG sensitivity. Hepatic levels of 2- AG were significantly elevated in two models of experimental fibrogenesis and reached concentrations that are sufficient to induce death in HSCs. These findings suggest that 2- AG may act as an antifibrogenic mediator in the liver by inducing cell death in activated HSCs but not hepatocytes. C1 Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Univ Heidelberg, Med Fac Mannheim, Dept Med 2, D-6800 Mannheim, Germany. Univ Texas, Med Branch, Dept Cell Biol & Neurosci, Galveston, TX 77550 USA. NIAAA, NIH, Bethesda, MD USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. RP Schwabe, RF (reprint author), Columbia Univ, Coll Phys & Surg, Dept Med, Russ Berrie Pavill,Rm 415,1150 St Nicholas Ave, New York, NY 10032 USA. EM rfs2102@columbia.edu NR 53 TC 71 Z9 79 U1 0 U2 1 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 2007 VL 21 IS 11 BP 2798 EP 2806 DI 10.1096/fj.06-7717com PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 207FR UT WOS:000249237500021 PM 17440119 ER PT J AU Watterson, KR Berg, KM Kapitonov, D Payne, SG Miner, AS Bittman, R Milstien, S Ratz, PH Spiegel, S AF Watterson, Kenneth R. Berg, Krystina M. Kapitonov, Dmitri Payne, Shawn G. Miner, Amy S. Bittman, Robert Milstien, Sheldon Ratz, Paul H. Spiegel, Sarah TI Sphingosine-1-phosphate and the immunosuppressant, FTY720-phosphate, regulate detrusor muscle tone SO FASEB JOURNAL LA English DT Article DE sphingolipid metabolite; calcium channels ID 2-AMINOETHOXYDIPHENYL BORATE 2-APB; CAPACITATIVE CALCIUM-ENTRY; VASCULAR SMOOTH-MUSCLE; SPHINGOSINE 1-PHOSPHATE; DEPENDENT REGULATION; SIGNAL-TRANSDUCTION; ENDOTHELIAL-CELLS; CHANNEL CA(V)1.2; CA2+ RELEASE; RECEPTOR AB Overactive bladder syndrome ( OBS) results from disturbances of bladder function. Bladder smooth muscle ( detrusor) exhibits spontaneous rhythmic activity ( tone) independent of neurogenic control, which is enhanced in patients with OBS. We have now uncovered a prominent role for the bioactive sphingolipid metabolite, sphingosine- 1- phosphate ( S1P), in regulating rabbit detrusor smooth muscle tone and contraction. S1P- induced contraction of detrusor muscle was dependent on stretch and intracellular calcium. Although detrusor expresses the S1P receptors S1P1 and S1P2, only S1P2 appeared to be involved in S1Pinduced contraction, since SEW2871 ( S1P1 agonist) and dihydro- S1P ( potent agonist for all S1P receptors except S1P2) were poor contractile agents. In agreement, the S1P2 antagonist JTE013 inhibited S1P- induced contraction. The fast, transient muscle contraction ( phasic) mediated by S1P was dependent on phospholipase C ( PLC) whereas the slower, sustained contraction ( tonic) was not. Surprisingly, the immunosuppressant FTY720phosphate, an agonist for all S1P receptors except S1P2, had distinct contractile properties and also induced slow, sustained contraction. Thus, FTY720- phosphate and/ or S1P may regulate calcium channels in an S1P receptor- independent manner. Collectively, our results demonstrate that S1P may regulate detrusor smooth muscle tone and suggest that dysregulation of complex S1P signaling might contribute to OBS. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. NIMH, NIH, Bethesda, MD 20892 USA. CUNY, Queens Coll, Dept Chem & Biochem, Flushing, NY USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, 1101 E Marshall St,2011 Sanger Hall, Richmond, VA 23298 USA. EM sspiegel@vcu.edu FU Intramural NIH HHS; NIDDK NIH HHS [R01DK059620]; NIGMS NIH HHS [R37 GM043880] NR 54 TC 10 Z9 10 U1 0 U2 2 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 2007 VL 21 IS 11 BP 2818 EP 2828 DI 10.1096/fj.06-7326com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 207FR UT WOS:000249237500023 PM 17449719 ER PT J AU Mechsner, S Schwarz, J Thode, J Loddenkemper, C Salomon, DS Ebert, AD AF Mechsner, Sylvia Schwarz, Jessica Thode, Johanna Loddenkemper, Christoph Salomon, David S. Ebert, Andreas D. TI Growth-associated protein 43-positive sensory nerve fibers accompanied by immature vessels are located in or near peritoneal endometriotic lesions SO FERTILITY AND STERILITY LA English DT Article DE endometriosis; sensory nerve fibers; pelvic pain; neurotrophism; vascularization; GAP-43; angiogenesis; neurogenesis ID PELVIC PAIN; MORPHOLOGICAL APPEARANCE; PROSTAGLANDIN-F; ANGIOGENESIS; EXPRESSION; STAGE; CLASSIFICATION; LOCALIZATION; REGENERATION; DYSMENORRHEA AB Objective: To investigate the topographical relationship between nerve fibers and peritoneal endometriotic lesions and to determine the origin of endometriosis-associated nerve fibers: Design: Retrospective nonrandomized study. Setting: University hospital endometriosis research center. Patient(s): Premenopausal women with histologically confirmed endometriosis were selected (n = 73). Peritoneal endometriotic lesions (n = 106) and unaffected peritoneal biopsies from patients without endometriosis (n = 9) were obtained. Intervention(s): Immunohistochemistry was used to study the expression of neurofilament, substance P, smooth muscle actin, von Willebrand factor, growth-associated protein 43, nerve growth factor, and neutrophin-3 in peritoneal endometriotic lesion samples from women with symptomatic endometriosis and in peritoneal samples from women without endometriosis: Result(s): Pain-conducting substance-P-positive nerve fibers were found to be directly colocalized with human peritoneal endometriotic lesions in 74.5% of all cases. The endometriosis-associated nerve fibers are accompanied by immature blood vessels within the stroma. Nerve growth factor and neutrophin-3 are expressed by endometriotic cells. Growth-associated protein 43, a marker of neural outgrowth and regeneration, is expressed in endometriosis-associated nerve fibers but not in existing peritoneal nerves. Conclusion(s): The data provide the first evidence of direct contact between sensory nerve fibers and peritoneal endometriotic lesions. This implies that the fibers play an important role in the etiology of endometriosis-associated pelvic pain. Moreover, emerging evidence suggests that peritoneal endometriotic cells exhibit neurotrophic properties. C1 Vivantes Humboldt Klinikum, Dept Obstet & Gynecol, Endometriosis Ctr Berlin Level 3, D-13509 Berlin, Germany. NCI, Mammary Biol & Tumorifeneis Lab, NIH, Bethesda, MD USA. Inst Pathol Consultat & Reference Ctr Lymph Node, Charite, Berlin, Germany. Endometriosis Res Ctr Berlin, Dept Gynecol, Berlin, Germany. RP Ebert, AD (reprint author), Vivantes Humboldt Klinikum, Dept Obstet & Gynecol, Endometriosis Ctr Berlin Level 3, Nordgraben 2, D-13509 Berlin, Germany. EM andreas.ebert@vivantes.de NR 43 TC 57 Z9 63 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 IS 3 BP 581 EP 587 DI 10.1016/j.fertnstert.2006.12.087 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 214PZ UT WOS:000249751900007 PM 17412328 ER PT J AU Bloom, MS Schisterman, EF Hediger, ML AF Bloom, Michael S. Schisterman, Enrique F. Hediger, Mary L. TI The use and misuse of matching in case-control studies: the example of polycystic ovary syndrome SO FERTILITY AND STERILITY LA English DT Editorial Material ID DESIGN EFFICIENCY; SELECTION; WOMEN; PCOS AB Matching control selection strategies are often used in polycystic ovary syndrome case-control studies; however, they are infrequently used in an appropriate fashion. When properly applied, matching may offer improved study precision, but this is highly contingent on the causal pathway under consideration, strength of the associations between the matching variable and both the risk factor of interest and polycystic ovary syndrome, and the use of an appropriate stratified data analysis. C1 NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Schisterman, EF (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,US Dept Hlth & Human Serv, 6100 Execut Blvd,Rm 7B03,MSC 7510, Bethesda, MD 20892 USA. EM SchisteE@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X; Bloom, Michael/0000-0002-0028-5494 FU Intramural NIH HHS [Z99 HD999999] NR 23 TC 14 Z9 14 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 IS 3 BP 707 EP 710 DI 10.1016/j.fertnstert.2006.11.125 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 214PZ UT WOS:000249751900028 PM 17433314 ER PT J AU Levens, ED AF Levens, Eric D. TI Variables affecting the decision for numbers of embryos transferred SO FERTILITY AND STERILITY LA English DT Letter C1 NIH, NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. RP Levens, ED (reprint author), NIH, NICHHD, Reprod Biol & Med Branch, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 IS 3 BP 760 EP 761 DI 10.1016/j.fertnstert.2007.07.007 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 214PZ UT WOS:000249751900055 PM 17681294 ER PT J AU Blocker, WK Armstrong, AY Levens, E Nieman, L AF Blocker, W. K. Armstrong, A. Y. Levens, E. Nieman, L. TI Strategies for recruitment of minority women for clinical research trials. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S11 EP S11 DI 10.1016/j.fertnstert.2007.07.057 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800031 ER PT J AU Brennan, KM Levens, E Huang, A Richter, K Hill, D Kipersztok, S AF Brennan, K. M. Levens, E. Huang, A. Richter, K. Hill, D. Kipersztok, S. TI Recipient age, not paternal age, reduces pregnancy rate in oocyte donation cycles. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Univ Calif Los Angeles, Los Angeles, CA USA. So Calif Reprod Ctr Med Grp, Beverly Hills, CA USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S262 EP S262 DI 10.1016/j.fertnstert.2007.07.892 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800746 ER PT J AU Britten, JL Malik, M Payson, M Norian, J Joseph, D Catherino, WH AF Britten, J. L. Malik, M. Payson, M. Norian, J. Joseph, D. Catherino, W. H. TI All-trans retinoic acid regulates collagen synthesis in human uterine leiomyomas. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S218 EP S218 DI 10.1016/j.fertnstert.2007.07.743 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800611 ER PT J AU Browne, H James, A Hoover, D Payson, M Segars, J AF Browne, H. James, A. Hoover, D. Payson, M. Segars, J. TI Couples' choices when faced with the 'unexpected' failure of surgical retrieval of sperm. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. Walter Reed Army Med Ctr, Dept OB GYN, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S389 EP S389 DI 10.1016/j.fertnstert.2007.07.496 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889801125 ER PT J AU Browne, H Armstrong, A Babb, R Illei, G Segars, J Pavletic, S AF Browne, H. Armstrong, A. Babb, R. Illei, G. Segars, J. Pavletic, S. TI Do anti-mullerian hormone levels predict ovarian reserve in SLE patients presenting for hematopoietic stem cell transplant? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S280 EP S281 DI 10.1016/j.fertnstert.2007.07.950 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800799 ER PT J AU Browne, H Stegmann, BJ Larsen, FW James, A Payson, M Segars, J AF Browne, H. Stegmann, B. J. Larsen, F. W. James, A. Payson, M. Segars, J. TI A study of 92 patient cycles using the ganirelix salvage protocol in women at risk of OHSS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHD, NIH, Reprod Biol & Med Branch, Bethesda, MD USA. Walter Reed Army Med Ctr, ART Program, Washington, DC USA. ART Inst Washington Inc, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S34 EP S35 DI 10.1016/j.fertnstert.2007.07.125 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800090 ER PT J AU Closshey, WB Browne, RW Huddleston, HG Sandler, JR Schisterman, EF Fujimoto, VY AF Closshey, W. B. Browne, R. W. Huddleston, H. G. Sandler, J. R. Schisterman, E. F. Fujimoto, V. Y. TI High activity of paraoxonase 3 (PON3), a known potent antioxidant, identified in follicular fluid. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. Univ Buffalo, Dept Biotech, Buffalo, NY USA. Univ Buffalo, Clin Lab Sci, Buffalo, NY USA. NICHD, NIH, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S304 EP S305 DI 10.1016/j.fertnstert.2007.07.1023 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800868 ER PT J AU Davis, MC Wieners, MA Ventura, JL Covington, SN Koziol, DE Nelson, LM AF Davis, M. C. Wieners, M. A. Ventura, J. L. Covington, S. N. Koziol, D. E. Nelson, L. M. TI Goal flexibility and emotional well-being in women with spontaneous 46,XX primary ovarian insufficiency (premature ovarian failure). SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Arizona State Univ, Dept Psychol, Tempe, AZ USA. NICHD, NIH, Reprod Biol & Med Branch, Bethesda, MD USA. CC, NIH, Biostat & Clin Epidemiol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S84 EP S85 DI 10.1016/j.fertnstert.2007.07.281 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800224 ER PT J AU Levens, ED Wei, Q Nieman, LK AF Levens, E. D. Wei, Q. Nieman, L. K. TI Indian hedgehog and its associated down-stream targets are altered in response to in vivo CDB-2914 administration. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. USN, Med Ctr, Combined Fed Fellowship Reprod Endocrinol & Infer, NIH,Walter Reed Army Med Ctr, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S196 EP S196 DI 10.1016/j.fertnstert.2007.07.673 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800546 ER PT J AU Levens, ED Whitcomb, BW Kort, JD Materia-Hoover, D Feinberg, EC Larsen, FW AF Levens, E. D. Whitcomb, B. W. Kort, J. D. Materia-Hoover, D. Feinberg, E. C. Larsen, F. W. TI A retrospective comparison of microdose follicular phase and luteal phase gonadotropin releasing hormone agonist (GnRH-a) suppression for in vitro fertilization in patients 30 years old and younger. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Walter Reed Army Med Ctr, ART Program, Washington, DC 20307 USA. USN, Med Ctr, Combined Fed Fellowship Reprod Endocrinol & Infer, NIH,Walter Reed Army Med Ctr, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. ART Inst Washington Inc, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S139 EP S140 DI 10.1016/j.fertnstert.2007.07.447 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800377 ER PT J AU Levens, ED Payson, MD Larsen, FW AF Levens, E. D. Payson, M. D. Larsen, F. W. TI A prospective, randomized comparison trial of ovarian follicular re-aspiration at oocyte retrieval among patients with reduced ovarian response undergoing art. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Walter Reed Army Med Ctr, ART Program, Washington, DC USA. USN, Med Ctr, Combined Fellowship Reprod Endocrinol & Infertil, NIH,Walter Reed Army Med Ctr, Bethesda, MD 20084 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S126 EP S126 DI 10.1016/j.fertnstert.2007.07.404 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800336 ER PT J AU Li, L Baibakov, B Gauthier, L Dean, J AF Li, L. Baibakov, B. Gauthier, L. Dean, J. TI Novel maternal effect gene essential for progression beyond the early cleavage stage of mouse embryogenesis. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NIDDK, Cellular & Dev Biol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S70 EP S70 DI 10.1016/j.fertnstert.2007.07.236 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800185 ER PT J AU Malik, M Britten, J Driggers, P Payson, M Segars, JH Catherino, WH AF Malik, M. Britten, J. Driggers, P. Payson, M. Segars, J. H. Catherino, W. H. TI Curcumin, a nutritional supplement with antineoplastic activity, selectively inhibits leiomyoma growth. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S217 EP S217 DI 10.1016/j.fertnstert.2007.07.740 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800608 ER PT J AU Manipalviram, S Stratton, P Ballweg, ML Sinai, N AF Manipalviram, S. Stratton, P. Ballweg, M. L. Sinai, N. TI Does the duration of pelvic symptoms play a role in the prevalence of infertility in women with endometriosis? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Int Headquarters, Endometriosis Assoc, Milwaukee, WI USA. NIH, Ctr Clin, Biostat & Clin Epidemiol Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S212 EP S212 DI 10.1016/j.fertnstert.2007.07.723 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800593 ER PT J AU McCarthy-Keith, D Blocker, W Levens, E Nieman, L Armstrong, A AF McCarthy-Keith, D. Blocker, W. Levens, E. Nieman, L. Armstrong, A. TI Recruitment and retention of subjects for clinical leiomyoma trials. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Natl Naval Med Ctr, Walter Reed Army Med Ctr, NIH, Combined Fed Fellowship Reprod Endocrinol & Infer, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S219 EP S219 DI 10.1016/j.fertnstert.2007.07.747 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800615 ER PT J AU Norian, J Christman, G Korecki, C Iatridis, J Chen, F Segars, J AF Norian, J. Christman, G. Korecki, C. Iatridis, J. Chen, F. Segars, J. TI Stiffness matters: Mechanical,properties of human leiomyomas and their extracellular matrix composition. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Univ Vermont, Sch Engn, Burlington, VT USA. NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S218 EP S219 DI 10.1016/j.fertnstert.2007.07.745 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800613 ER PT J AU Norian, J Malik, M Joseph, D Payson, M Segars, J Catherino, W AF Norian, J. Malik, M. Joseph, D. Payson, M. Segars, J. Catherino, W. TI Glycosaminoglycan expression in versican variants is tightly regulated by TGF-beta 3 in leiomyoma cells. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHD, NIH, Reprod Biol Med Branch, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S106 EP S106 DI 10.1016/j.fertnstert.2007.07.342 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800278 ER PT J AU Popat, VB Kalantardou, S Reynolds, JC Calis, K Troendle, J Nelson, LM AF Popat, V. B. Kalantardou, S. Reynolds, J. C. Calis, K. Troendle, J. Nelson, L. M. TI Physiologic transdermal estradiol replacement therapy restores femoral neck bone density in women with spontaneous 46,XX primary ovarian insufficiency: 3 year randomized controlled clinical trial. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHHD, NIH, Bethesda, MD 20892 USA. NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S48 EP S48 DI 10.1016/j.fertnstert.2007.07.168 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800127 ER PT J AU Sarajari, S Manipalviram, S Surrey, MW Danzer, HC Briton-Jones, C Hill, DL AF Sarajari, S. Manipalviram, S. Surrey, M. W. Danzer, H. C. Briton-Jones, C. Hill, D. L. TI Post-thaw survival and resumption of meiosis of immature oocytes using slow-freeze vs. vitrification methods of cryopreservation. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Univ Calif Los Angeles, Los Angeles, CA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. So Calif Reprod Ctr, Beverly Hills, CA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S354 EP S355 DI 10.1016/j.fertnstert.2007.07.1191 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889801017 ER PT J AU Sproul, K Huang, A Landay, M Trivax, B Wu, J DeCherney, A AF Sproul, K. Huang, A. Landay, M. Trivax, B. Wu, J. DeCherney, A. TI Predictors of a spontaneous luteinizing hormone surge in controlled ovarian hyperstimulation cycles. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Univ Calif Los Angeles, Div REI, Los Angeles, CA USA. NIH, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Div REI, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S176 EP S177 DI 10.1016/j.fertnstert.2007.07.609 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800489 ER PT J AU Stegmann, BJ Gemmill, JA Segars, J Chrousos, G Stratton, P AF Stegmann, B. J. Gemmill, J. A. Segars, J. Chrousos, G. Stratton, P. TI An abnormal response to CRH stimulation in chronic pelvic pain patients is not explained by anxiety or depression. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHD, NIH, Repro Biol & Med Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S210 EP S211 DI 10.1016/j.fertnstert.2007.07.718 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800588 ER PT J AU Stegmann, BJ Larsen, FW DeCherney, A Segars, J AF Stegmann, B. J. Larsen, F. W. DeCherney, A. Segars, J. TI Presence of blood in the transfer catheter does not affect implantation or clinical pregnancy rates when using the 'afterload' method of ET. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Walter Reed Army Med Ctr, ART Program, Washington, DC 20307 USA. NICHD, NIH, Reprod Biol & Med Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S117 EP S117 DI 10.1016/j.fertnstert.2007.07.377 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800310 ER PT J AU Stegmann, BJ Payson, M DeCherney, A Segars, J AF Stegmann, B. J. Payson, M. DeCherney, A. Segars, J. TI The 'afterload' method of embryo transfer corrects for provider-dependent effects at et. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. Walter Reed Army Med Ctr, ART Program, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S103 EP S104 DI 10.1016/j.fertnstert.2007.07.335 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800272 ER PT J AU Vanderhoof, V Ventura, J Covington, S Popat, V Koziol, D Nelson, LM AF Vanderhoof, V. Ventura, J. Covington, S. Popat, V. Koziol, D. Nelson, L. M. TI The ABC's of emotional health: Nursing assessment of women with spontaneous 46,XX primary ovarian insufficiency (premature ovarian failure). SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHD, Reprod Biol & Med Branch, Bethesda, MD USA. NICHD, Biostat & Clin Epidemiol Serv, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S9 EP S9 DI 10.1016/j.fertnstert.2007.07.051 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800025 ER PT J AU Vanderhoof, VH Prodanov, T Jenkins, JF Ventura, JL Calis, KA Nelson, LM AF Vanderhoof, V. H. Prodanov, T. Jenkins, J. F. Ventura, J. L. Calis, K. A. Nelson, L. M. TI "My Family Health Portrait": Nursing application of a web-based tool to evaluate women with primary ovarian insufficiency (premature ovarian failure). SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. NIH, Natl Human Genome Res Inst, Dept Pharm, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S11 EP S12 DI 10.1016/j.fertnstert.2007.07.058 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800032 ER PT J AU Ventura, JL Davis, MC Covington, SN Vanderhoof, VH Koziol, DE Nelson, LM AF Ventura, J. L. Davis, M. C. Covington, S. N. Vanderhoof, V. H. Koziol, D. E. Nelson, L. M. TI Illness uncertainty and stigma: Factors positively associated with symptoms of depression and anxiety in women with spontaneous 46,XX primary ovarian insufficiency (premature ovarian failure). SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHD, NIH, Reprod Biol & Med Branch, Bethesda, MD USA. Arizona State Univ, Tempe, AZ USA. CC, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S82 EP S83 DI 10.1016/j.fertnstert.2007.07.275 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800218 ER PT J AU Wei, Q Levens, ED Nieman, LK AF Wei, Q. Levens, E. D. Nieman, L. K. TI CDB-2914, a novel selective progesterone receptor modulator, differentially regulates endometrial gene expression in the proliferative phase of the menstrual cycle. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. USN, Med Ctr, Combined Fed Fellowship Reprod Endocrinol & Infer, NIH,Walter Reed Army Med Ctr, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S194 EP S194 DI 10.1016/j.fertnstert.2007.07.667 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800540 ER PT J AU Wittenberger, MD Rochman, M Furusawa, T Feigenbaum, L Bustin, M AF Wittenberger, M. D. Rochman, M. Furusawa, T. Feigenbaum, L. Bustin, M. TI The nucleosomal binding protein 1 (NSBP1) facilitates early embryonic development and parallels differentiation leading to embryo implantation. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NCI, Cryopreservat & Assisted Reprod Lab, Frederick, MD 21701 USA. RI Bustin, Michael/G-6155-2015 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S308 EP S309 DI 10.1016/j.fertnstert.2007.07.1038 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800881 ER PT J AU Yauger, BJ Chason, RJ Payson, MD AF Yauger, B. J. Chason, R. J. Payson, M. D. TI Cesarean section scars detrimentally affect embryo transfer. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Walter Reed Army Med Ctr, Washington, DC 20307 USA. NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S334 EP S334 DI 10.1016/j.fertnstert.2007.07.1115 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800955 ER PT J AU Yauger, BJ Whitcomb, BW Levens, ED Hennessy, S Larsen, EW AF Yauger, B. J. Whitcomb, B. W. Levens, E. D. Hennessy, S. Larsen, E. W. TI The impact of the duration of estradiol supplementation and peak serum estradiol on frozen blastocyst-embryo transfer outcome. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Walter Reed Army Med Ctr, ART Program, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Natl Naval Med Ctr, NIH, Combined Fed Fellowship Reprod Endocrinol & Infer, Bethesda, MD USA. NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. NICHHD, NIH, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. Inst Washington Inc, ART, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S149 EP S149 DI 10.1016/j.fertnstert.2007.07.475 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800405 ER PT J AU Sharp, HJ Wansley, EK Garnett, CT Chakraborty, M Camphausen, K Schlom, J Hodge, JW AF Sharp, Hadley J. Wansley, Elizabeth K. Garnett, Charlie T. Chakraborty, Mala Camphausen, Kevin Schlom, Jeffrey Hodge, James W. TI Synergistic antitumor activity of immune strategies combined with radiation SO FRONTIERS IN BIOSCIENCE LA English DT Article DE radiation; radionuclide; brachytherapy; immunotherapy; vaccine; review ID RELATIVE BIOLOGICAL EFFECTIVENESS; RECOMBINANT VACCINIA VIRUS; ENCAPSULATED I-125 SOURCES; INDUCED LEUKOCYTE ADHESION; CYTOTOXIC T-LYMPHOCYTES; LOCAL TUMOR-IRRADIATION; DOSE-RATE BRACHYTHERAPY; IONIZING-RADIATION; BONE METASTASES; PHASE-I AB Since its discovery more than a hundred years ago, radiation has been used to treat cancer. In recent decades, advances in radiation technology have expanded the role and value of radiation in imaging and treating many forms of cancer. Currently, there is a growing interest in combining radiation with other modalities, such as immunotherapy, to treat a broad range of malignancies. This article reviews the use of standard and novel combinations of radiation therapy and immunotherapy to eradicate tumor cells. The combination of radiation therapy and immunotherapy holds particular promise as a strategy for cancer therapeutics for a variety of reasons. First, there is evidence that immunotherapy is most beneficial when employed early in the disease process and in combination with standard therapies. In addition, radiation may act synergistically with immunotherapy to enhance immune responses, inhibit immunosuppression, and/or alter the phenotype of tumor cells, thus rendering them more susceptible to immune-mediated killing. Finally, as monotherapies, both immunotherapy and radiation may be insufficient to eliminate tumor masses. However, following immunization with a cancer vaccine, the destruction of even a small percentage of tumor cells by radiation could result in cross-priming and presentation of tumor antigens to the immune system, thereby potentiating antitumor responses. C1 [Sharp, Hadley J.; Wansley, Elizabeth K.; Garnett, Charlie T.; Chakraborty, Mala; Camphausen, Kevin; Schlom, Jeffrey; Hodge, James W.] NCI, Recombinant Vaccine Grp, Tumor Immunol & Biol Lab, Natl Inst Hlth, Bethesda, MD 20879 USA. RP Hodge, JW (reprint author), NCI, Recombinant Vaccine Grp, Tumor Immunol & Biol Lab, Natl Inst Hlth, Bldg 10,Rm 8B13,9000 Rockville Pike, Bethesda, MD 20879 USA. EM hodgej@mail.nih.gov RI Hodge, James/D-5518-2015; OI Hodge, James/0000-0001-5282-3154; Wansley, Elizabeth/0000-0002-0110-7550 NR 98 TC 13 Z9 14 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2007 VL 12 BP 4900 EP 4910 DI 10.2741/2436 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 273PJ UT WOS:000253943900010 PM 17569618 ER PT J AU Aragon-Ching, JB Williams, KM Gulley, JL AF Aragon-Ching, Jeanny B. Williams, Kirsten M. Gulley, James L. TI Impact of androgen-deprivation therapy on the immune system: implications for combination therapy of prostate cancer SO FRONTIERS IN BIOSCIENCE LA English DT Review DE immune modulation; immunopotentiation; combination therapy; thymic stimulation; Review ID IMMUNOLOGICAL SELF-TOLERANCE; RECOMBINANT VACCINIA VIRUS; ANTIGEN-PRESENTING CELLS; REGULATORY T-CELLS; NORMAL-MALE MICE; RADICAL PROSTATECTOMY; APOPTOTIC CELLS; LYMPHOCYTE POPULATIONS; THYMOCYTE DEVELOPMENT; ANTITUMOR IMMUNITY AB Prostate cancer is the most common non-cutaneous malignancy in American men. Standard therapeutic strategies for systemic disease include androgen-deprivation therapy (ADT) and chemotherapy, both of which are palliative. However, there is a growing interest in the use of immunotherapy for prostate cancer. Evidence suggests that ADT may 1) enhance lymphopoiesis and thus potentially improve immune responses to vaccine, 2) renew thymopoiesis and thus reverse age-induced thymic involution, 3) augment B-cell development, and 4) mitigate tolerance to prostate cancer antigens. Although no vaccines are currently approved for prostate cancer, there are many promising agents under investigation. This review focuses on recent findings on immune regulation by androgens and immune-system regeneration with ADT, with emphasis on the rationale for the combination of ADT and vaccines in the clinical treatment of prostate cancer. C1 [Aragon-Ching, Jeanny B.] NCI, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Williams, Kirsten M.] NCI, Expt Transplantat & Immunol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Aragon-Ching, Jeanny B.] NCI, Med Oncol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, Ctr Canc Res, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016; OI Gulley, James/0000-0002-6569-2912; Aragon-Ching, Jeanny/0000-0002-6714-141X FU Intramural NIH HHS NR 104 TC 76 Z9 76 U1 0 U2 2 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2007 VL 12 BP 4957 EP 4971 DI 10.2741/2441 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 273PJ UT WOS:000253943900015 PM 17569623 ER PT J AU Bugge, TH List, K Szabo, R AF Bugge, Thomas H. List, Karin Szabo, Roman TI Matriptase-dependent cell surface proteolysis in epithelial development and pathogenesis SO FRONTIERS IN BIOSCIENCE LA English DT Article DE matriptase; cell surface proteolysis; epithelial development; review ID HEPATOCYTE GROWTH-FACTOR; TRANSMEMBRANE SERINE-PROTEASE; FACTOR ACTIVATOR INHIBITOR-1; EPIDERMAL BARRIER FUNCTION; FACTOR SCATTER FACTOR; HUMAN BREAST-CANCER; ICHTHYOSIS VULGARIS; EXPRESSION ANALYSIS; NETHERTON-SYNDROME; STRATUM-CORNEUM AB Matriptase is an epithelial type II transmembrane serine protease with a complex modular structure and sophisticated activation mechanism. Reduced matriptase activity in mice or humans is associated with incomplete terminal differentiation of epidermis, epidermal appendages, oral epithelium, and, likely, other epithelial structures. Preliminary evidence indicates that matriptase is part of a serine protease zymogen activation cascade that regulates epithelial cell proliferation and fate. Matriptase activity must be tightly controlled in epithelial tissues by transcriptional and posttranslational mechanisms, as matriptase dysregulation can cause embryonic demise as well as malignant transformation. C1 [Bugge, Thomas H.; List, Karin; Szabo, Roman] Natl Inst Dental & Craniofacial Res, Natl Inst Hlth, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. RP Bugge, TH (reprint author), Natl Inst Dental & Craniofacial Res, Natl Inst Hlth, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, 30 Convent Dr,Room 211, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov FU Intramural NIH HHS NR 83 TC 48 Z9 48 U1 1 U2 8 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2007 VL 12 BP 5060 EP 5070 DI 10.2741/2448 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 273PJ UT WOS:000253943900022 PM 17569630 ER PT J AU Qu, YX Adler, V Izotova, L Pestka, S Bowne, W Michl, J Boutjdir, M Friedman, FK Pincus, MR AF Qu, Yongxia Adler, Victor Izotova, Lara Pestka, Sidney Bowne, Wilbur Michl, Josef Boutjdir, Mohamed Friedman, Fred K. Pincus, Matthew R. TI The dual-specificity kinases, TOPK and DYRK1A, are critical for oocyte maturation induced by wild-type but not by oncogenic-ras-p21 protein SO FRONTIERS IN BIOSCIENCE LA English DT Article DE oncogenic ras-p21; wild-type ras-p21; oocyte maturation; dual-specificity kinases; TOPK; DYRK1A; signal transduction ID N-TERMINAL KINASE; RAS-P21 PROTEIN; XENOPUS-LAEVIS; JUN PROTEINS; INSULIN; RAF; JNK; ACTIVATION; EXPRESSION; INDUCTION AB We have previously found that oncogenic ras-p21 and insulin, which activates wild-type ras-21 protein, both induce Xenopus laevis oocyte maturation that is dependent on activation of raf. However, oncogenic ras-p21 utilizes raf-dependent activation of the two classic raf targets, MEK and MAP kinase (MAPK or ERK) while insulin-activated wild-type ras-p21 does not depend on activation of these two kinases. Utilizing a microarray containing the entire Xenopus genome, we discovered two dual specificity kinases, T-Cell Origin Protein Kinase (TOPK), known to bind to raf and the nuclear kinase, DYRK1A, that are expressed at much higher levels in insulin-matured oocytes. Using SiRNA's directed against expression of both of these proteins, we now show that each inhibits insulin-but not oncogenic ras-p21-induced oocyte maturation. Control siRNA's have no effect on either agent in induction of maturation. We find that each SiRNA "knocks down" expression of its target protein while not affecting expression of the other protein. These results suggest that both proteins are required for maturation induced by wild-type, but not oncogenic, ras-p21. They also suggest that oncogenic and wild-type ras-p21 utilize pathways that become divergent downstream of raf. On the basis of these findings, we propose a model for two signal transduction pathways by oncogenic and activated wild-type ras-p21 showing points of overlap and divergence. C1 [Qu, Yongxia; Adler, Victor; Bowne, Wilbur; Boutjdir, Mohamed; Pincus, Matthew R.] New York Harbor VA Med Ctr, Dept Pathol & Lab Med 113, Res & Dev Serv, Brooklyn, NY 11209 USA. [Adler, Victor; Pincus, Matthew R.] New York Harbor VA Med Ctr, Program Mol Cardiol, Brooklyn, NY 11209 USA. [Adler, Victor; Michl, Josef; Pincus, Matthew R.] Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA. [Izotova, Lara; Pestka, Sidney] Univ Med & Dent New Jersey, Dept Microbiol & Human Genet, Robert Wood Johnson Med Ctr, Piscataway, NJ 08854 USA. [Izotova, Lara; Pestka, Sidney] Canc Inst New Jersey, New Brunswick, NJ 08901 USA. [Bowne, Wilbur] Suny Downstate Med Ctr, Dept Surg, Brooklyn, NY 11203 USA. [Michl, Josef] Suny Downstate Med Ctr, Dept Microbiol, Brooklyn, NY 11203 USA. [Michl, Josef] Suny Downstate Med Ctr, Dept Anat & Cell Biol, Brooklyn, NY 11203 USA. [Friedman, Fred K.] NCI, Lab Expt & Comp Biol, Bethesda, MD 20892 USA. RP Pincus, MR (reprint author), New York Harbor VA Med Ctr, Dept Pathol & Lab Med 113, Res & Dev Serv, 800 Poly Pl, Brooklyn, NY 11209 USA. EM Matthew.Pincus2@med.va.gov RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [R01-CA46465]; NIAID NIH HHS [R01-AI36450, R01-AI43369] NR 19 TC 3 Z9 3 U1 1 U2 3 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2007 VL 12 BP 5089 EP 5097 DI 10.2741/2550 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 273PJ UT WOS:000253943900024 PM 17569632 ER PT J AU Hance, KW Rogers, CJ Hursting, SD Greiner, JW AF Hance, Kenneth W. Rogers, Connie J. Hursting, Stephen D. Greiner, John W. TI Combination of physical activity, nutrition, or other metabolic factors and vaccine response SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Review DE exercise; calorie restriction; obesity prevention; Vitamin A; Vitamin; E; arachidonic acid; arginine; tryptophan; glucose; immunotherapy; cancer vaccine; review ID BODY-MASS INDEX; RANDOMIZED CONTROLLED-TRIAL; ALPHA-TOCOPHERYL SUCCINATE; BREAST-CANCER PATIENTS; KILLER-CELL-ACTIVITY; VITAMIN-E SUPPLEMENTATION; RESPIRATORY-TRACT INFECTIONS; ESTROGEN-RECEPTOR MODULATOR; COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA AB A number of lifestyle factors that reduce cancer risk in the primary prevention setting may be potential new targets for use in combination with cancer vaccines. This review discusses the modulation of energy balance (physical activity, calorie restriction, and obesity prevention), and the supplementation with natural and synthetic analogs of vitamins A and E, as potential interventions for use in combination with cancer vaccines. Additionally, the pharmacologic manipulation of nutrient metabolism in the tumor microenvironment (e. g., arachidonic acid, arginine, tryptophan, and glucose metabolism) is discussed. This review includes a brief overview of the role of each agent in primary cancer prevention; outlines the effects of these agents on immune function, specifically adaptive and/or anti-tumor immune mechanisms, when known; and discusses the potential use of these interventions in combination with therapeutic cancer vaccines. Modulation of energy balance through exercise and strategies targeting nutrient metabolism in the tumor microenvironment represent the most promising interventions to partner with therapeutic cancer vaccines. Additionally, the use of vitamin E succinate and the retinoid X receptor-directed rexinoids in combination with cancer vaccines offer promise. In summary, a number of energy balance- and nutrition-related interventions are viable candidates for further study in combination with cancer vaccines. C1 [Hance, Kenneth W.; Rogers, Connie J.; Greiner, John W.] NCI, Natl Canc Inst Hlth, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. [Hursting, Stephen D.] Univ Texas Austin, Div Nutr Sci, Austin, TX 78712 USA. [Hursting, Stephen D.] Univ Texas Dallas, Dept Carcinogenesis, Smithville, TX 78957 USA. [Hursting, Stephen D.] MD Anderson Canc Ctr, Smithville, TX 78957 USA. RP Hance, KW (reprint author), NCI, Natl Canc Inst Hlth, Tumor Immunol & Biol Lab, 10 Ctr Dr,Bldg 10,Room 8B04,MDC 1750, Bethesda, MD 20892 USA. EM hancek@mail.nih.gov FU Intramural NIH HHS [NIH0011268250]; PHS HHS [NIH0011268250] NR 359 TC 8 Z9 8 U1 0 U2 6 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD SEP 1 PY 2007 VL 12 BP 4997 EP 5029 DI 10.2741/2444 PG 33 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 273PJ UT WOS:000253943900018 PM 17569626 ER PT J AU Auclair, BA Benoit, YD Rivard, N Mishina, Y Perreault, N AF Auclair, Benoit A. Benoit, Yannick D. Rivard, Nathalie Mishina, Yuji Perreault, Nathalie TI Bone morphogenetic protein signaling is essential for terminal differentiation of the intestinal secretory cell lineage SO GASTROENTEROLOGY LA English DT Article ID CRYPT-VILLUS AXIS; ENTEROENDOCRINE CELLS; GENE-EXPRESSION; SUPPRESSION; COLON; REQUIREMENT; PATHWAY; CANCER; MICE AB Background & Aims: Bone morphogenetic proteins (Bmps) are morphogens known to play key roles in gastrointestinal development and pathology. Most Bmps are produced primarily by the mesenchymal compartment and activate their signaling pathways following a paracrine or autocrine route. The aim of this study was to investigate the role of epithelial Bmp signaling in intestinal morphogenesis and maintenance of adult epithelial cell functions. Methods: With the use of tissue-specific gene ablation, we generated mice lacking the Bmp receptor type IA (Bmprla) exclusively in the intestinal epithelium. Bmprla mutant and control mice were sacrificed for histology, immunofluorescence, Western blot analysis, electron microscopy, and quantitative polymerase chain reaction. Results: As well as showing increased proliferation and altered intestinal epithelial morphology, Bmpr1a mutant mice revealed that epithelial Bmp signaling is associated with impaired terminal differentiation of cells from the secretory lineage but not with the determination of cell fate. Loss of Bmp signaling exclusively in the epithelial compartment is not sufficient for the initiation of the de novo crypt phenomenon associated with juvenile polyposis syndrome. Conclusions: Epithelial Bmp signaling plays an important role in the terminal differentiation of the intestinal secretory cell lineage but not in de novo crypt formation. These findings emphasize the importance of delineating the contribution of the stroma vs the epithelium in gastrointestinal physiology and pathology. C1 Univ Sherbrooke, Fac Med Sci, Canadian Inst Hlth Res Team Digest Epithelium, Dept Anat & Biol Cellulaire, Sherbrooke, PQ J1K 2R1, Canada. Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Dev Biol Sect, Res Triangle Pk, NC USA. RP Perreault, N (reprint author), Univ Sherbrooke, Fac Med Sci, Dept Anat & Biol Cellulaire, 3001 12E Ave Nord, Sherbrooke, PQ J1H 5N4, Canada. EM Nathalie.Perreault@USherbrooke.ca FU Intramural NIH HHS NR 30 TC 80 Z9 83 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2007 VL 133 IS 3 BP 887 EP 896 DI 10.1053/j.gastro.2007.06.066 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 208NQ UT WOS:000249326900022 PM 17678919 ER PT J AU Mayhew, CN Carter, SL Fox, SR Sexton, CR Reed, CA Srinivasaw, SV Liu, XD Wikenheiser-Brokamp, K Boivin, GP Lee, JS Aronow, BJ Thorgersson, SS Knudsen, ES AF Mayhew, Christopher N. Carter, Scott L. Fox, Sejal R. Sexton, Charlene R. Reed, Christopher A. Srinivasaw, Seetha V. Liu, Xiangdong Wikenheiser-Brokamp, Kathryn Boivin, Gregory P. Lee, Ju-Seog Aronow, Bruce J. Thorgersson, Snorri S. Knudsen, Erik S. TI RB loss abrogates cell cycle control and genome integrity to promote liver tumorigenesis SO GASTROENTEROLOGY LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; RETINOBLASTOMA TUMOR-SUPPRESSOR; CHROMOSOMAL INSTABILITY; SIGNALING PATHWAYS; DNA-REPLICATION; EXPRESSION; GENES; CANCER; MECHANISMS; STABILITY AB Background & Aims: The retinoblastoma (RB) tumor suppressor is functionally inactivated in most hepatocellular carcinomas (HCC), although the mechanisms by which RB suppresses liver tumorigenesis are poorly defined. We investigated th e impact of RB loss on carcinogen-induced liver tumorigenesis. Methods: Mice harboring liver-specific RB ablation and normal littermates were exposed to the hepatocarcinogen diethylnitrosamine (DEN). The influence of RB loss on liver tumorigenesis was assessed by evaluating tumor multiplicity, proliferation, and genome integrity within tumors arising in RB-deficient and wild-type livers. In silico analyses were used to probe the association between gene expression signatures for RB loss and chromosomal instability and the ability of genes up-regulated by RB loss to predict the survival of human HCC patients. Results: RB deficiency significantly increased tumor multiplicity in fivers exposed to DEN. Although hepatocytes in nontumor regions of DEN-exposed livers were quiescent regardless of RB status, tumors arising in RB-deficient fivers were significantly more proliferative than those in normal fivers and expressed high levels of RB/E2F target genes. Analysis of genes up-regulated by RB loss demonstrated significant overlap with a gene expression signature associated with chromosomal instability. Correspondingly, tumors arising in RB-deficient livers were significantly more likely to harbor hepatocytes exhibiting altered ploidy. Finally, gene expression analysis of human HCCs demonstrated that elevated expression of RB-regulated genes independently predicts poor survival. Conclusions: RB deletion in the mouse liver enhances DEN-induced tumorigenesis, associated with increased hepatocyte proliferation and compromised genome integrity. Evaluation of RB status may be a useful prognostic factor in human HCC. C1 Univ Cincinnati, Dept Cell & Canc Biol, Cincinnati, OH 45221 USA. Childrens Hosp, Harvard Med Sch, Informat Program, Boston, MA 02115 USA. Childrens Hosp, Med Ctr, Div Pathol & Lab Med, Cincinnati, OH 45229 USA. Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH 45221 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX 77030 USA. NIH, NCI, Lab Expt Carcinogenesis, Bethesda, MD 20892 USA. RP Knudsen, ES (reprint author), Univ Cincinnati, Vontz Ctr Mol Studies, Dept Cell & Canc Biol, 3125 Eden Ave, Cincinnati, OH 45267 USA. EM erik.knudsen@uc.edu RI Aronow, Bruce/F-8438-2012 FU NCI NIH HHS [CA106471, R01 CA106471, T32 CA117846]; NIEHS NIH HHS [U01 ES011038, U01 ES11038-02]; PHS HHS [T32 59268] NR 37 TC 53 Z9 54 U1 0 U2 3 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 2007 VL 133 IS 3 BP 976 EP 984 DI 10.1053/j.gastro.2007.06.025 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 208NQ UT WOS:000249326900031 PM 17854601 ER PT J AU Hwang, SK Jin, H Kwon, JT Chang, SH Kim, TH Cho, CS Lee, KH Young, MR Colburn, NH Beck, GR Yang, HS Cho, MH AF Hwang, S.-K. Jin, H. Kwon, J. T. Chang, S.-H. Kim, T. H. Cho, C.-S. Lee, K. H. Young, M. R. Colburn, N. H. Beck, G. R., Jr. Yang, H.-S. Cho, M.-H. TI Aerosol-delivered programmed cell death 4 enhanced apoptosis, controlled cell cycle and suppressed AP-1 activity in the lungs of AP-1 luciferase reporter mice SO GENE THERAPY LA English DT Article DE programmed cell death 4; apoptosis; cell cycle; activator protein-1; non-invasive aerosol gene delivery ID INITIATION-FACTOR 4A; RAS NULL MICE; MOLECULAR TARGETS; CANCER CELLS; PDCD4; TRANSLATION; TRANSACTIVATION; TRANSFORMATION; ANGIOGENESIS; INVOLVEMENT AB The long-term survival of lung cancer patients treated with conventional therapies remains poor and therefore the need for novel approaches remains high. This has led to the reemergence of aerosol delivery as a therapeutic intervention. In this study, glucosylated polyethylenimine (GPEI) was used as carrier to investigate programmed cell death 4 (PDCD4) and PDCD4 mutant (D418A), an eIF4A-binding mutant, on PDCD4-related signaling and activator protein-1 (AP-1) activity in the lungs of AP-1 luciferase reporter mice. After confirming the efficiency of GPEI as a carrier in lungs, the effects of aerosol-delivered PDCD4 were investigated in AP-1 luciferase reporter mice. Aerosol delivery of GPEI/PDCD4 through a nose-only inhalation facilitated the apoptosis of lungs whereas aerosol PDCD4 mutant did not. Also, such aerosol delivery regulated proteins relevant to cell-cycle control and suppressed AP-1 activity. Results obtained by western blot analysis, immunohistochemistry, luciferase assay and deoxynucleotidyl-transferase-mediated nick end labeling study suggest that combined actions such as facilitating apoptosis, controlling cell cycle and suppression of AP-1 activity by PDCD4 may provide useful tool for designing lung tumor prevention and treatment by which PDCD4 functions as a transformation suppressor in the future. C1 Seoul Natl Univ, Coll Vet Med, Toxicol Lab, Seoul 151742, South Korea. Seoul Natl Univ, Sch Agr Biotechnol, Lab Biomed Polymer & Tissue Engn, Seoul, South Korea. Korea Inst Radiol & Med Sci, Mol Oncol Lab, Seoul, South Korea. NCI, Lab Canc Prevent, Frederick, MD 21701 USA. Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA 30322 USA. Univ Kentucky, Coll Med, Grad Ctr Toxicol, Markey Canc Ctr, Lexington, KY USA. RP Cho, MH (reprint author), Seoul Natl Univ, Coll Vet Med, Toxicol Lab, Sillim Dong, Seoul 151742, South Korea. EM mchotox@snu.ac.kr RI Yang, Hsin-Sheng/A-6419-2008; CHO, Myung-Haing/B-7362-2014 FU NCI NIH HHS [CA84573] NR 22 TC 31 Z9 33 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD SEP PY 2007 VL 14 IS 18 BP 1353 EP 1361 DI 10.1038/sj.gt.3302983 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 207GP UT WOS:000249239900005 PM 17611588 ER PT J AU Yong-Gonzalez, V Wang, BD Butylin, P Ouspenski, I Strunnikov, A AF Yong-Gonzalez, Vladimir Wang, Bi-Dar Butylin, Pavel Ouspenski, Ilia Strunnikov, Alexander TI Condensin function at centromere chromatin facilitates proper kinetochore tension and ensures correct mitotic segregation of sister chromatids SO GENES TO CELLS LA English DT Article ID HISTONE H3 VARIANT; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; CHROMOSOME CONDENSATION; SPINDLE CHECKPOINT; CELL-CYCLE; DNA-REPLICATION; FISSION YEAST; MICROTUBULE ATTACHMENT; PRECOCIOUS SEPARATION AB The condensin complex is essential for sister chromatid segregation in eukaryotic mitosis. Nevertheless, in budding yeast, condensin mutations result in massive mis-segregation of chromosomes containing the nucleolar organizer, while other chromosomes, which also contain condensin binding sites, remain genetically stable. To investigate this phenomenon we analyzed the mechanism of the cell-cycle arrest elicited by condensin mutations. Under restrictive conditions, the majority of condensin-deficient cells arrest in metaphase. This metaphase arrest is mediated by the spindle checkpoint, particularly by the spindle-kinetochore tension-controlling pathway. Inactivation of the spindle checkpoint in condensin mutants resulted in frequent chromosome non-disjunction, eliminating the bias in chromosome mis-segregation towards rDNA-containing chromosomes. The spindle tension defect in condensin-impaired cells is likely mediated by structural defects in centromere chromatin reflected by the partial loss of the centromere histone Cse4p. These findings show that, in addition to its essential role in rDNA segregation, condensin mediates segregation of the whole genome by maintaining the centromere structure in Saccharomyces cerevisiae. C1 NICHD, NIH, LGRD, Bethesda, MD 20892 USA. RP Strunnikov, A (reprint author), NICHD, NIH, LGRD, Bethesda, MD 20892 USA. EM strunnik@mail.nih.gov OI Strunnikov, Alexander/0000-0002-9058-2256 FU Intramural NIH HHS [Z01 HD001903-11, Z99 AI999999] NR 69 TC 29 Z9 29 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1356-9597 J9 GENES CELLS JI Genes Cells PD SEP PY 2007 VL 12 IS 9 BP 1075 EP 1090 DI 10.1111/j.1365-2443.2007.01109.x PG 16 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 207AC UT WOS:000249223000008 PM 17825050 ER PT J AU Kaneko, KJ Kohn, MJ Liu, C DePamphilis, ML AF Kaneko, Kotaro J. Kohn, Matthew J. Liu, Chengyu DePamphilis, Melvin L. TI Transcription factor TEAD2 is involved in neural tube closure SO GENESIS LA English DT Article DE exencephaly; anencephaly; TEAD; PAX3; fetal brain ID ENHANCER FACTOR-I; M-CAT MOTIF; GENE-EXPRESSION; MOUSE DEVELOPMENT; DEFECTS; PROTEIN; FAMILY; TEF-1; EMBRYOS; DOMAIN AB TEAD2, one of the first transcription factors expressed at the beginning of mammalian development, appears to be required during neural development. For example, Tead2 expression is greatest in the dorsal neural crest where it appears to regulate expression of Pax3, a gene essential for brain development. Consistent with this hypothesis, we found that inactivation of the Tead2 gene in mice significantly increased the risk of exencephaly (a defect in neural tube closure). However, none of the embryos exhibited spina bifida, the major phenotype of Pax3 nullizygous embryos, and expression of Pax3 in E11.5 Tead2 nullizygous embryos was normal. Thus, Tead2 plays a role in neural tube closure that is independent of its putative role in Pax3 regulation. In addition, the risk of exencephaly was greatest with Tead2 nullizygous females, and could be suppressed either by folic acid or pifithrin-alpha. These results reveal a maternal genetic contribution to neural tube closure, and suggest that Tead2-deficient mice provide a model for anencephaly, a common human birth defect that can be prevented by folic acid. C1 NICHHD, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Genet & Dev Biol Ctr, Bethesda, MD 20892 USA. RP DePamphilis, ML (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM depamphm@mail.nih.gov FU Intramural NIH HHS [Z01 HD000507-12] NR 41 TC 36 Z9 36 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD SEP PY 2007 VL 45 IS 9 BP 577 EP 587 DI 10.1002/dvg.20330 PG 11 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 223JG UT WOS:000250365600006 PM 17868131 ER PT J AU Boehringer, S Pfeiffer, R AF Boehringer, Stefan Pfeiffer, Ruth TI Estimating association parameters in family-based association studies SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 07-10, 2007 CL York, ENGLAND SP Int Genet Epidemiol Soc C1 Univ Klinikum Essen, Inst Humangenet, Essen, Germany. NCI, Biostat Branch, DCEG, Bethesda, MD 20892 USA. RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD SEP PY 2007 VL 31 IS 6 MA 44 BP 618 EP 618 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 210SP UT WOS:000249476200052 ER PT J AU Duggal, P Gillanders, EM Holmes, T Bailey-Wilson, JE AF Duggal, P. Gillanders, E. M. Holmes, T. N. Bailey-Wilson, J. E. TI Establishing an adjusted p-value threshold to control the family-wide Type 1 error in genome-wide association studies SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 07-10, 2007 CL York, ENGLAND SP Int Genet Epidemiol Soc C1 NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD SEP PY 2007 VL 31 IS 6 MA 68 BP 624 EP 624 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 210SP UT WOS:000249476200076 ER PT J AU Franceschini, N MacCluer, JW Goring, HHH Diego, VP Cole, SA Laston, S Best, LG Fabsitz, RR Lee, ET Russell, M North, KE AF Franceschini, N. MacCluer, J. W. Goring, H. H. H. Diego, V. P. Cole, S. A. Laston, S. Best, L. G. Fabsitz, R. R. Lee, E. T. Russell, M. North, K. E. TI Genotype-by-smoking interaction on blood pressure traits: The Strong Heart Family Study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 07-10, 2007 CL York, ENGLAND SP Int Genet Epidemiol Soc C1 UNC, Chapel Hill, NC USA. SFBR, San Antonio, TX USA. NHLBI, Bethesda, MD 20892 USA. Univ Oklahoma, Oklahoma City, OK USA. MedStar, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD SEP PY 2007 VL 31 IS 6 MA 74 BP 626 EP 626 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 210SP UT WOS:000249476200082 ER PT J AU Ibay, G Wojciechowski, R Ciner, E Stambolian, D Bailey-Wilson, JE AF Ibay, G. Wojciechowski, R. Ciner, E. Stambolian, D. Bailey-Wilson, J. E. TI Genomewide scan of African American and caucasian populations for linkage to myopia SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 07-10, 2007 CL York, ENGLAND SP Int Genet Epidemiol Soc C1 NHGRI, NIH, Baltimore, MD USA. Penn Coll Optometry, Philadelphia, PA 19141 USA. Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD SEP PY 2007 VL 31 IS 6 MA 93 BP 631 EP 632 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 210SP UT WOS:000249476200101 ER PT J AU Mathias, RA Deepa, M Raj, D Wilson, AF Mohan, V AF Mathias, R. A. Deepa, M. Raj, D. Wilson, A. F. Mohan, V. TI Heritability of quantitative traits associated with type 2 diabetes in families from South India SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 07-10, 2007 CL York, ENGLAND SP Int Genet Epidemiol Soc C1 NIH, NHGRI, Baltimore, MD USA. Madras Diabet Res Fdn, Dr Mohans Diabet Special Ctr Gopalapuram, Madras, Tamil Nadu, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD SEP PY 2007 VL 31 IS 6 MA 114 BP 638 EP 638 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 210SP UT WOS:000249476200122 ER PT J AU Mathias, RA Grant, A Wilson, AF Beaty, T Barnes, K AF Mathias, R. A. Grant, A. Wilson, A. F. Beaty, T. Barnes, K. TI Genome-wide association study of asthma-related quantitative traits in populations of African descent SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 07-10, 2007 CL York, ENGLAND SP Int Genet Epidemiol Soc C1 NIH, NHGRI, Bethesda, MD USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RI Beaty, Terri/A-6032-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD SEP PY 2007 VL 31 IS 6 MA 115 BP 638 EP 638 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 210SP UT WOS:000249476200123 ER PT J AU Sung, H Sorant, AJM Wilson, AF AF Sung, H. Sorant, A. J. M. Wilson, A. F. TI A comparison of the distribution of extreme p-values under alternative genetic models SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 07-10, 2007 CL York, ENGLAND SP Int Genet Epidemiol Soc C1 NIH, NHGRI, Genometr Sect, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD SEP PY 2007 VL 31 IS 6 MA 139 BP 645 EP 645 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 210SP UT WOS:000249476200147 ER PT J AU Turley-Stoulig, TN Sorant, AJM Bailey-Wilson, JE Mandal, DM AF Turley-Stoulig, T. N. Sorant, A. J. M. Bailey-Wilson, J. E. Mandal, D. M. TI Investigation of type I error in linkage analysis of complex qualitative traits with common disease alleles and quantitative covariates SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 07-10, 2007 CL York, ENGLAND SP Int Genet Epidemiol Soc C1 SE Louisiana Univ, Hammond, LA USA. NHGRI, NIH, Baltimore, MD USA. LSUHSC, New Orleans, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD SEP PY 2007 VL 31 IS 6 MA 149 BP 648 EP 648 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 210SP UT WOS:000249476200157 ER PT J AU Yang, XR Tucker, MA Goldstein, AM AF Yang, X. R. Tucker, M. A. Goldstein, A. M. TI Linkage analysis may not be effective for detecting a modifier locus: example using melanoma, CDKN2A and MC1R SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 07-10, 2007 CL York, ENGLAND SP Int Genet Epidemiol Soc C1 NIH, NCI, DHHS, DCEG,Genet Epidemiol Branch, Bethesda, MD USA. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD SEP PY 2007 VL 31 IS 6 MA 159 BP 651 EP 651 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 210SP UT WOS:000249476200167 ER PT J AU Olschwang, S Blanche, H De Moncuit, C Thomas, G AF Olschwang, Sylviane Blanche, Helene De Moncuit, Celine Thomas, Gilles TI Similar colorectal cancer risk in patients with monoallelic and biallelic mutations in the MYH gene identified in a population with adenomatous polyposis SO GENETIC TESTING LA English DT Article ID SOMATIC G-C->T-A MUTATIONS; GERMLINE MUTATIONS; FAMILY; COLI AB A large proportion of non-FAP non-HNPCC patients with multiple colorectal adenomas have been reported to carry germline mutations on the MYH gene. Although the number of adenomas appears to be dependent on the number of mutated MYH alleles present in a patient, little is known on the relation of this number with cancer risk. Four hundred fifty-three APC-negative patients with more than five colorectal adenomas were screened for mutations on the entire coding sequence of the MYH gene. Pathogenic mutations were initially found in 74 patients without extradigestive tumors (22.5%) and subsequently in 75 at-risk relatives. Polyposis was more severe in cases with biallelic mutations. However, mutation copy number was correlated neither with the age at diagnosis of adenomas or adenocarcinomas, nor with the presence of a family history of colorectal tumors. Heterozygous and homozygous MYH mutation carriers were both at high risk for synchronous cancers (24% in colorectum and 16% in the upper gastrointestinal tract), but did not demonstrate an increased risk for extradigestive tumors. MYH-associated polyposis is a frequent inherited colorectal cancer predisposition with a strong dominance component. From age 25-30, MYH mutation carriers should be proposed an early screening program, which includes endoscopies of the upper digestive tract and the colorectum every 2 years. C1 Inst J Paoli I Calmettes, F-13009 Marseille, France. Ctr Rech Cancerol Marseille, INSERM, U599, F-13009 Marseille, France. Univ Aix Marseille 2, F-13007 Marseille, France. Fdn Jean Dausset, Paris, France. Hop St Antoine, Assistance Publ Hop Paris, F-75571 Paris, France. NCI, NIH, Div Canc Epidemiol & Genet, Gaithersburg, MD USA. RP Olschwang, S (reprint author), Inst J Paoli I Calmettes, 232 Blvd Sainte Marguerite, F-13009 Marseille, France. RI Olschwang, Sylviane/G-2716-2013 NR 20 TC 21 Z9 23 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD FAL PY 2007 VL 11 IS 3 BP 315 EP 320 DI 10.1089/gte.2007.9995 PG 6 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 224KD UT WOS:000250445000016 PM 17949294 ER PT J AU Wei, DS Rong, YS AF Wei, Debbie S. Rong, Yikang S. TI A genetic screen for DNA double-strand break repair mutations in Drosophila SO GENETICS LA English DT Article ID SITE-SPECIFIC ENDONUCLEASE; MUTAGEN-SENSITIVE MUTANTS; SACCHAROMYCES-CEREVISIAE; HOMOLOGOUS RECOMBINATION; ANNEALING PATHWAY; MAMMALIAN-CELLS; MELANOGASTER; YEAST; EXCISION; PROTEIN AB The study of DNA double-strand break (DSB) repair has been greatly facilitated by the use of rarecutting endonucleases, which induce a break precisely at their cut sites that can be strategically placed in the genome. We previously established such a system in Drosophila and showed that the yeast I-SceI enzyme cuts efficiently in Drosophila cells and those breaks are effectively repaired by conserved mechanisms. In this study, we determined the genetic requirements for the repair of this I-SceI-induced DSB in the germline. We show that Drosophila Rad51 and Rad54 are both required for homologous repair by gene conversion, but are dispensable for single-strand annealing repair. We provided evidence suggesting that Rad51 is more stringently required than Rad54 for intersister gene conversion. We uncovered a significant role of DNA ligase W in nonhomologous end joining. We conducted a screen for candidate mutations affecting DSB repair and discovered novel mutations in genes that include mutagen sensitive 206, single-strand annealing reducer, and others. In addition, we demonstrated an intricate balance among different repair pathways in which the cell differentially utilizes repair mechanisms in response to both changes in the genomic environment surrounding the break and deficiencies in one or the other repair pathways. C1 NIH, NCI, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA. RP Rong, YS (reprint author), NIH, NCI, Biochem & Mol Biol Lab, Room 6056,37 Convent Dr, Bethesda, MD 20892 USA. EM rongy@mail.nih.gov RI rong, yikang/G-6179-2011 FU Intramural NIH HHS NR 66 TC 22 Z9 23 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 2007 VL 177 IS 1 BP 63 EP 77 DI 10.1534/genetics.107.077693 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 218XM UT WOS:000250049300006 PM 17660539 ER PT J AU Missirlis, F Kosmidis, S Brody, T Mavrakis, M Holmberg, S Odenwald, WF Skoulakis, EMC Rouault, TA AF Missirlis, Fanis Kosmidis, Stylianos Brody, Tom Mavrakis, Manos Holmberg, Sara Odenwald, Ward F. Skoulakis, Efthimios M. C. Rouault, Tracey A. TI Homeostatic mechanisms for iron storage revealed by genetic manipulations and live imaging of Drosophila ferritin SO GENETICS LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; ACID-SECRETING CELLS; REGULATORY PROTEIN-2; IN-VIVO; MELANOGASTER FERRITIN; TARGETED DELETION; INSECT FERRITIN; MESSENGER-RNA; H-CHAIN; METABOLISM AB Ferritin is a symmetric, 24-subunit iron-storage complex assembled of H and L chains. It is found in bacteria, plants, and animals and in two classes of mutations in the human L-chain gene, resulting in hereditary hyperferritinemia cataract syndrome or in neuroferritinopathy. Here, we examined systemic and cellular ferritin regulation and trafficking in the model organism Drosophila melanogaster. We showed that ferritin H and L transcripts are coexpressed during embryogenesis and that both subunits are essential for embryonic development. Ferritin overexpression impaired the survival of iron-deprived flies. In vivo expression of GFP-tagged holoferritin confirmed that iron-loaded ferritin molecules traffic through the Golgi organelle and are secreted into hemolymph. A constant ratio of ferritin H and L subunits, secured via tight post-transcriptional regulation, is characteristic of the secreted ferritin in flies. Differential cellular expression, conserved post-transcriptional regulation via the iron regulatory element, and distinct subcellular localization of the ferritin subunits prior to the assembly of holoferritin are all important steps mediating iron homeostasis. Our study revealed both conserved features and insect-specific adaptations of ferritin nanocages and provides novel imaging possibilities for their in vivo characterization. C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Inst Mol Biol & Genet BSRC Alexander Fleming, GR-16672 Vari, Greece. NINDS, Neural Cell Fate Determinants Sect, Bethesda, MD 20892 USA. RP Missirlis, F (reprint author), NIH, Bldg 18T,Room 101,900 Rockville Pike, Bethesda, MD 20892 USA. EM missirlf@mail.nih.gov RI Missirlis, Fanis/C-1137-2011 OI Missirlis, Fanis/0000-0003-0467-8444 FU Intramural NIH HHS NR 64 TC 59 Z9 63 U1 2 U2 7 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 2007 VL 177 IS 1 BP 89 EP 100 DI 10.1534/genetics.107.075150 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 218XM UT WOS:000250049300008 PM 17603097 ER PT J AU Yamada-Inagawa, T Klar, AJS Dalgaard, JZ AF Yamada-Inagawa, Tomoko Klar, Amar J. S. Dalgaard, Jacob Z. TI Schizosaccharomyces pombe switches mating type by the synthesis-dependent strand-annealing mechanism SO GENETICS LA English DT Article ID HOMOTHALLIC FISSION YEAST; DNA MISMATCH REPAIR; S-POMBE; SACCHAROMYCES-CEREVISIAE; RECOMBINATIONAL REPAIR; DAUGHTER CELLS; GENE; REPLICATION; INTERCONVERSION; IMPRINT AB Schizosaccharomyces pombe cells can switch between two mating types, plus (P) and minus (M). The change in cell type occurs due to a replication-coupled recombination event that transfers genetic information from one of the silent-donor loci, mat2P or mat3M, into the expressed mating-type determining mail locus. The mail locus can as a consequence contain DNA encoding either Por Minformation. A molecular mechanism, known as synthesis-dependent strand annealing, has been proposed for the underlying recombination event. A key feature of this model is that only one DNA strand of the donor locus provides the information that is copied into the mat1. Here we test the model by constructing strains that switch using two different mutant P cassettes introduced at the donor loci, mat2 and mat3. We show that in such strains wild-type P-cassette DNA is efficiently generated at mail through heteroduplex DNA formation and repair. The present data provide an in vivo genetic test of the proposed molecular recombination mechanism. C1 Marie Curie Res Inst, DNA Replicat lab, Surrey RH8 0TL, England. NCI, Canc Res Ctr, Bethesda, MD 21702 USA. RP Dalgaard, JZ (reprint author), Marie Curie Res Inst, DNA Replicat lab, The Chart,Oxted, Surrey RH8 0TL, England. EM j.dalgaard@mcri.ac.uk OI Dalgaard, Jacob/0000-0001-9545-7254 FU Intramural NIH HHS NR 54 TC 12 Z9 14 U1 0 U2 1 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 2007 VL 177 IS 1 BP 255 EP 265 DI 10.1534/genetics.107.076315 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 218XM UT WOS:000250049300021 PM 17660548 ER PT J AU Hims, MM Shetty, RS Pickel, J Mull, J Leyne, M Liu, LJ Gusella, JF Slaugenhaupt, SA AF Hims, Matthew M. Shetty, Ranjit S. Pickel, James Mull, James Leyne, Maire Liu, Lijuan Gusella, James F. Slaugenhaupt, Susan A. TI A humanized IKBKAP transgenic mouse models a tissue-specific human splicing defect SO GENOMICS LA English DT Article DE familial dysautonomia; mRNA splicing; transgenic model ID FAMILIAL DYSAUTONOMIA; MESSENGER-RNA; ARTIFICIAL CHROMOSOMES; HUMAN-DISEASE; MUTATION; ISRAEL; CELLS; GENE AB Familial dysautonomia (FD) is a severe hereditary sensory and autonomic neuropathy, and all patients with FD have a splice mutation in the IKBKAP gene. The FD splice mutation results in variable, tissue-specific skipping of exon 20 in IKBKAP rnRNA, which leads to reduced IKAP protein levels. The development of therapies for FD will require suitable mouse models for preclinical studies. In this study, we report the generation and characterization of a mouse model carrying the complete human IKBKAP locus with the FD IVS20+6T -> C splice mutation. We show that the mutant IKBKAP transgene is misspliced in this model in a tissue-specific manner that replicates the pattern seen in FD patient tissues. Creation of this humanized mouse is the first step toward development of a complex phenotypic model of FD. These transgenic mice are an ideal model system for testing the effectiveness of therapeutic agents that target the missplicing defect. Last, these mice will permit direct studies of tissue-specific splicing and the identification of regulatory factors that play a role in complex gene expression. (c) 2007 Elsevier Inc. All rights reserved. C1 Natl Inst Hlth, NIMH, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Slaugenhaupt, SA (reprint author), Natl Inst Hlth, NIMH, Boston, MA 02114 USA. EM slaugenhaupt@chgr.mgh.harvard.edu FU Intramural NIH HHS; NINDS NIH HHS [R01 NS036326, R01 NS036326-07A1, R01 NS036326-08, R01 NS036326-09, R01 NS036326-10] NR 26 TC 22 Z9 23 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 2007 VL 90 IS 3 BP 389 EP 396 DI 10.1016/j.ygeno.2007.05.012 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 199SQ UT WOS:000248715900012 PM 17644305 ER PT J AU Einstein, MH Kadish, AS Burk, RD Kim, MY Wadler, S Strelcher, H Goldberg, GL Runowicz, CD AF Einstein, Mark H. Kadish, Anna S. Burk, Robert D. Kim, Mimi Y. Wadler, Scott Strelcher, Howard Goldberg, Gary L. Runowicz, Carolyn D. TI Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III SO GYNECOLOGIC ONCOLOGY LA English DT Article DE HPV; immunotherapy; heat shock protein; HPV e7 protein ID HUMAN-PAPILLOMAVIRUS INFECTION; HPV INFECTION; CANCER; REGRESSION; VACCINES; HSP70; E7; METAANALYSIS; COLPOSCOPY; PREVENTION AB Objectives. SGN-00101 (HspE7, Nventa, San Diego, CA) is a novel therapeutic vaccine consisting of a fusion protein containing an M bovis BCG heat shock protein (Hsp65) covalently linked to the entire sequence of HPV 16 ET This trial was designed to evaluate the efficacy and toxicities of HspE7 in women with CIN III. Methods. HIV (-) women with biopsy-proven CIN III were eligible. Two cohorts were accrued; one cohort to establish efficacy and a second cohort with a longer follow-up period to improve the precision of the trial to estimate response rates. Each patient underwent 3 monthly subcutaneous vaccinations with 500 mu g of HspE7 followed by monthly colposcopic follow-up for I month in cohort I and an extended observation period (2 months) in cohort 2. All patients then underwent a LEEP or cone biopsy of the cervix. A complete pathologic response (pCR) was defined as no evidence of CIN or CIN I (only HPV changes). A partial response (PR) was defined as colposcopic lesion regression of > 50% in size. Cervicovaginal lavage samples were obtained at each visit for HPV typing using MY09/MY11 HPV PCR. Results. Seventy-two patients were registered and screened, of whom 64 were eligible. Fifty-eight patients completed the trial and were evaluable (31 in cohort 1, 27 in cohort 2). There were no significant epidemiologic or HPV type differences between the 2 cohorts so responses were combined for analysis. Of the 58 evaluable patients, 13 (22.5%) had a pCR; 32 (55%) had a PR and 11 (19%) had stable disease. Two (3.5%) patients in cohort 2 had microinvasive disease and were defined as progressive disease. Thirty-three of 58 (57%) of the patients were infected with HPV 16 prior to vaccination or in subsequent visits. There was no significant difference in regression in women infected with HPV 16 compared to those without HPV 16 infection (88% vs. 70%; p=0.12). Women who had a previous LEEP or ablation for CIN were 2.7 times more likely to have a complete response compared to patients without previous treatment, although the difference was not statistically significant (95% Cl for rate ratio: 0.95-6.19, p=0.10). At a cellular level, there was a significant association between local inflammation and response; lower grade of lesional inflammation correlated with a response to HspE7 (p=0.04 using Wilcoxon rank sum test). Conclusions. HspE7 appeared to demonstrate activity in women with CIN III and met a priori assumptions for efficacy; however, it is unclear whether this response was due to natural regression rather than treatment effect. HspE7, which targets the HPV 16 E7 oncoprotein, had efficacy in patients infected with HPV types other than 16, suggesting cross-reactivity. A larger randomized, controlled trial is needed to better define efficacy and to identify subsets of women most likely to benefit from immunotherapy. (c) 2007 Elsevier Inc. All rights reserved. C1 Montefiore Med Ctr, Dept Obstet & Gynecol & Womens Hlth, Div Gynecol Oncol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Albert Einstein Canc Ctr, Bronx, NY USA. Cornell Med Ctr, New York, NY USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Univ Connecticut, Sch Med, Neag Comprehens Canc Ctr, Farmington, CT USA. RP Einstein, MH (reprint author), Montefiore Med Ctr, Dept Obstet & Gynecol & Womens Hlth, Div Gynecol Oncol, 1695 Eastchester Rd,Suite 601, Bronx, NY 10461 USA. EM meinstei@montefiore.org FU NCI NIH HHS [N01 CM017103, U01 CA063422-04S4, L30 CA110417-01, L30 CA110417, R01 CA148966, U01 CA063422-04]; NCRR NIH HHS [K12 RR017672, K12 RR017672-01]; NIAID NIH HHS [P30 AI051519-01A1, P30 AI051519-03, P30 AI051519, AI-51519, P30 AI051519-01A19001] NR 39 TC 58 Z9 62 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2007 VL 106 IS 3 BP 453 EP 460 DI 10.1016/j.ygyno.2007.04.038 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 209AS UT WOS:000249361100004 PM 17586030 ER PT J AU Shen, M Purdue, MR Kricker, A Lan, Q Grulich, AE Vajdic, CM Turner, J Whitby, D Chanock, S Rothman, N Armstrong, BK AF Shen, Min Purdue, Mark R. Kricker, Anne Lan, Qing Grulich, Andrew E. Vajdic, Claire M. Turner, Jennifer Whitby, Denise Chanock, Stephen Rothman, Nathaniel Armstrong, Bruce K. TI Polymorphisms in DNA repair genes and risk of non-Hodgkin's lymphoma in New South Wales, Australia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article ID O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; CANCER-RISK; MGMT; SENSITIVITY; CELLS; XRCC1; O-6-ALKYLGUANINE; RNA AB Background and Objectives A number of occupational and environmental exposures that can directly or indirectly cause DNA damage have been proposed as risk factors for non-Hodgkin's lymphoma (NHL). The human DNA damage repair system can recognize and repair such damage and maintain genomic stability. We investigated whether putatively functional single-nucleotide polymorphisms (SNIP) in DNA repair genes influence susceptibility to NHL in a population-based case-control study conducted in Australia. Design A total of 561 cases and 506 controls were included in the analysis. Twenty-two SNIP in 14 DNA repair genes were genotyped by a TaqMan-based assay. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, sex, residence, and ethnicity. Results Two SNIP in MGMT (lle143Val and Lys178Arg) were in complete linkage disequilibrium and associated with increased risk of NHL (lle143Val, Ile/Val vs. lle/lle, OR: 1.26; 95% CI: 0.93-1.70; Val/Val vs. lle/lle, OR: 2.55; 95% CI: 0.98-6.63; p trend: 0.024). These SNP were associated with increased risk of several NHL subtypes. In addition, the XRCC1 Arg194Trp polymorphism was associated with decreased NHL risk (Arg/Trp vs. Arg/Arg, OR: 0.72; 95% CI: 0.49-1.07; Trp/Trp vs. Arg/Arg, OR: 0.45; 95% CI: 0.10-1.99; p trend: 0.059), mainly in diffuse large B-cell lymphoma. Interpretation and Conclusions The association of genetic variants in MGMT with increased risk of NHL suggests that alkyl adducts may contribute to lymphomagenesis, and points to environmental and enclogenous alkylating agents as possible risk factors for NHL. However, given that these results were based on a small number of variant carriers and the possibility that these results may have arisen due to chance, replication in other studies is needed. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Sydney, Sydney, NSW 2006, Australia. Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. St Vincents Hosp, Sydney, NSW 2010, Australia. NCI, Frederick, MD 21701 USA. NCI, Core Genotyping Facil, Gaithersburg, MD USA. RP Shen, M (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8012,MSC 7240, Bethesda, MD 20892 USA. EM shenmi@mail.nih.gov RI Armstrong, Bruce/K-9464-2015; OI Armstrong, Bruce/0000-0001-8940-7525; Vajdic, Claire/0000-0002-3612-8298 NR 24 TC 45 Z9 50 U1 1 U2 4 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD SEP PY 2007 VL 92 IS 9 BP 1180 EP 1185 DI 10.3324/haematol.11324 PG 6 WC Hematology SC Hematology GA 209QC UT WOS:000249402100005 PM 17666372 ER PT J AU Pomykacz, B Mao, M Weiss, RD Teter, CJ AF Pomykacz, Brian Mao, Melissa Weiss, Roger D. Teter, Christian J. TI A review of brief medication-adherence instruments used in patients with schizophrenia and bipolar disorder SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID SCALE; VALIDITY; HOSPITALIZATION; QUESTIONNAIRE; NONCOMPLIANCE; NONADHERENCE; RELIABILITY; BELIEFS C1 Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. RP Teter, CJ (reprint author), McLean Hosp, PharmD Alcohol & Drug Abuse Treatment Program, 115 Mill St, Belmont, MA 02478 USA. EM cteter@mclean.harvard.edu FU NIDA NIH HHS [K24 DA022288, R01 DA15968] NR 21 TC 6 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 2007 VL 15 IS 5 BP 259 EP 263 DI 10.1080/10673220701650383 PG 5 WC Psychiatry SC Psychiatry GA 229KZ UT WOS:000250803200006 PM 17924260 ER PT J AU Resnik, DB AF Resnik, David B. TI Embryonic stem cell patents and human dignity SO HEALTH CARE ANALYSIS LA English DT Article DE human embryonic stem cell patents; human dignity; morality; human embryo; European patent office; Wisconsin Alumni Research Foundation ID INTELLECTUAL PROPERTY; SCIENCE; BIOTECHNOLOGY; RESPECT AB This article examines the assertion that human embryonic stem cells patents are immoral because they violate human dignity. After analyzing the concept of human dignity and its role in bioethics debates, this article argues that patents on human embryos or totipotent embryonic stem cells violate human dignity, but that patents on pluripotent or multipotent stem cells do not. Since patents on pluripotent or multipotent stem cells may still threaten human dignity by encouraging people to treat embryos as property, patent agencies should carefully monitor and control these patents to ensure that patents are not inadvertently awarded on embryos or totipotent stem cells. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,Mail Drop NH06,Res Triangle Pk, Res Triangle Pk, NC 27709 USA. EM resnikd@nichs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 46 TC 5 Z9 5 U1 1 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1065-3058 J9 HEALTH CARE ANAL JI Health Care Anal. PD SEP PY 2007 VL 15 IS 3 BP 211 EP 222 DI 10.1007/s10728-007-0045-9 PG 12 WC Ethics; Health Policy & Services; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Biomedical Social Sciences GA 211KP UT WOS:000249523000005 PM 17922198 ER PT J AU Danis, M Goold, SD Parise, C Ginsburg, M AF Danis, Marion Goold, Susan Dorr Parise, Carol Ginsburg, Marjorie TI Enhancing employee capacity to prioritize health insurance benefits SO HEALTH EXPECTATIONS LA English DT Article DE consumer preferences; decision aids; employees; employment; health insurance; insurance benefits ID COVERAGE AB Objective To demonstrate that employees can gain understanding of the financial constraints involved in designing health insurance benefits. Background While employees who receive their health insurance through the workplace have much at stake as the cost of health insurance rises, they are not necessarily prepared to constructively participate in prioritizing their health insurance benefits in order to limit cost. Design Structured group exercises. Setting and paticipants Employees of 41 public and private organizations in Northern California. Intervention Administration of the CHAT (Choosing Healthplans All Together) exercise in which participants engage in deliberation to design health insurance benefits under financial constraints. Main outcome measures Change in priorities and attitudes about the need to exercise insurance cost constraints. Results Participants (N = 744) became significantly more cognizant of the need to limit insurance benefits for the sake of affordability and capable of prioritizing benefit options. Those agreeing that it is reasonable to limit health insurance coverage given the cost increased from 47% to 72%. Conclusion It is both possible and valuable to involve employees in priority setting regarding health insurance benefits through the use of structured decision tools. C1 NIH, Sect Eth & Hlth Policy, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Bioeth Program, Ann Arbor, MI 48109 USA. Sutter Inst Med Res, Rancho Cordova, CA USA. Sacramento Healthcare Decis, Rancho Cordova, CA USA. RP Danis, M (reprint author), NIH, Sect Eth & Hlth Policy, Bldg 10 Rm 1C118, Bethesda, MD 20892 USA. EM mdanis@nih.gov OI Goold, Susan Dorr/0000-0002-0258-9774 NR 14 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1369-6513 J9 HEALTH EXPECT JI Health Expect. PD SEP PY 2007 VL 10 IS 3 BP 236 EP 247 DI 10.1111/j.1369-7625.2007.00442.x PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 203TI UT WOS:000248996500004 PM 17678512 ER PT J AU Modi, AA Hoofnagle, JH AF Modi, Apurva A. Hoofnagle, Jay H. TI New therapies for hepatitis C SO HEPATOLOGY LA English DT Editorial Material ID VALOPICITABINE NM283; PROTEASE INHIBITOR; HCV-1 INFECTION; SERINE-PROTEASE; PLUS RIBAVIRIN; NAIVE PATIENTS; VIRAL-RNA; VIRUS; PEGINTERFERON; INTERFERON C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDK, Liver Dis Branch, NIH, Bldg 31,Room 9A27,31 Ctr Dr, Bethesda, MD 20892 USA. EM hoofnaglej@extra.niddk.nib.gov FU Intramural NIH HHS NR 22 TC 22 Z9 23 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 2007 VL 46 IS 3 BP 615 EP 617 DI 10.1002/hep.21892 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 206OA UT WOS:000249191600002 PM 17879364 ER PT J AU Tseng, FC O'Brien, TR Zhang, M Kral, AH Ortiz-Conde, BA Lorvick, J Busch, MP Edlin, BR AF Tseng, Fan-Chen O'Brien, Thomas R. Zhang, Mingdong Kral, Alex H. Ortiz-Conde, Betty A. Lorvick, Jennifer Busch, Michael P. Edlin, Brian R. TI Seroprevalence of hepatitis C virus and hepatitis B virus among San Francisco injection drug users, 1998 to 2000 SO HEPATOLOGY LA English DT Article ID HEPATOCELLULAR-CARCINOMA; HUMAN-IMMUNODEFICIENCY; NEEDLE EXCHANGE; RISK-FACTORS; PREVALENCE; INFECTION; PREVENTION; ASSOCIATION; SYRINGE; HIV AB Previous studies suggest that most injection drug users (IDUs) become infected with hepatitis C virus (HCV) and hepatitis B virus (HBV) soon after initiating drug use. The Urban Health Study (UHS) recruited serial cross-sections of IDUs in the San Francisco Bay area from 1986 to 2005. In the current study, we determined the prevalence of antibody to HCV and HBV (core) among UHS participants during 1998 to 2000. To examine whether the time from onset of injection to acquisition of viral hepatitis has increased, we also compared the findings among recent (< 10 years) initiates to drug use who participated during 19982000 with those who participated in 1987. Of 2,296 IDUs who participated during 19982000, 91.1% had antibody to HCV and 80.5% to HBV. The number of years a person had injected drugs strongly predicted infection with either virus (P-trend < 0.0001). HCV seroprevalence among recent initiates in 1998-2000, by years of injection drug use, was: :52, 46.8%; 3 to 5, 72.4%; 6 to 9, 71.3%. By comparison, HCV seroprevalence among 1987 participants was: :52 years, 75.9%; 3 to 5, 85.7%; 6 to 9, 91.1% (P < 0.0001). A consistent pattern was observed for HBV (P < 0.0001), and these findings were not explained by demographic differences between 1987 and 1998-2000 participants. During 1987, however, 58.7% of recent initiates had shared syringes within the past 30 days compared with 33.6% during 1998-2000 (P < 0.0001). Conclusion: HCV and HBV seroprevalence among newer initiates to injection drug use in the San Francisco Bay area decreased markedly between 1987 and 1998-2000. This decrease coincided with the implementation of prevention activities among this population. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Univ Hong Kong, Ctr Emerging Infect Dis, Hong Kong, Hong Kong, Peoples R China. Univ Calif San Francisco, San Francisco, CA 94143 USA. Sci Applicat Int Corp, AIDS Vaccine Program, Viral Epidemiol Sect, Frederick, MD USA. NCI, Frederick, MD 21701 USA. Blood Syst Res Inst, San Francisco, CA USA. Cornell Univ, Weill Med Coll, New York, NY USA. RP O'Brien, TR (reprint author), Ctr Adv Technol, Room 225A,MSC 4605,8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM obrient@mail.nib.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 [N02-CP-91027, N01CO12400, N01-CO-12400]; NIDA NIH HHS [R01-DA13245, R01 DA013245, R01 DA009532-08, R01-DA16159, R01 DA021550, R01 DA016159-04, R01 DA016159, R01 DA009532] NR 25 TC 36 Z9 36 U1 1 U2 3 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 2007 VL 46 IS 3 BP 666 EP 671 DI 10.1002/hep.21765 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 206OA UT WOS:000249191600009 PM 17657818 ER PT J AU Winterer, G Carver, FW Musso, F Mattay, V Weinberger, DR Coppola, R AF Winterer, Georg Carver, Frederick W. Musso, Francesco Mattay, Venkata Weinberger, Daniel R. Coppola, Richard TI Complex relationship between BOLD signal and synchronization/desynchronization of human brain MEG oscillations SO HUMAN BRAIN MAPPING LA English DT Article DE MEG; BOLD; synchronization; desynchronization ID EVENT-RELATED DESYNCHRONIZATION; RAT CEREBELLAR CORTEX; SINGLE CORTICAL CELLS; GAMMA-OSCILLATIONS; VISUAL-CORTEX; SENSORIMOTOR INTEGRATION; THETA OSCILLATIONS; EVOKED-POTENTIALS; FIELD POTENTIALS; SIMULTANEOUS EEG AB Functional magnetic resonance imaging (fMRI) depends on the coupling of cerebral blood flow, energy demand, and neural activity. The precise nature of this interaction, however, is poorly understood. A positive correlation between BOLD-response and cortically generated local field potentials, which reflect the weighted average of synchronized dentrosomatic components of pyramidal synaptic signals, has been demonstrated. Likewise, positive BOLD-responses have been reported in conjunction with scalp-recorded synchronized electromagnetic activity by a number of groups. However, it is not yet clear how the opposite electromagnetic pattern, i.e. cortical clesynchronization, is related to the BOLD signal. To address this question, we conducted a combined event-related fMRl and 275 sensor whole-head MEG study during identical visual two-choice reaction time task conditions in 10 human subjects. We found complex sequences of MEG-synchronization and desynchronization across a wide frequency range in the visual and motor area in close correspondence with "locales" of positive BOLD-responses. These results indicate that a correspondence of positive BOLD-responses is not exclusively found for cortical synchronization but also for desynchronization, suggesting that the relationship between BOLD signals and electromagnetic activity might be more complex than previously thought. (c) 2006 Wiley-Liss, Inc. C1 Univ Dusseldorf, Dept Psychiat, D-40629 Dusseldorf, Germany. NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. NIMH, MEG Core Facil, NIH, Bethesda, MD 20892 USA. RP Winterer, G (reprint author), Univ Dusseldorf, Dept Psychiat, Berg Landstr 2, D-40629 Dusseldorf, Germany. EM georg.winterer@uni-duesseldorf.de NR 68 TC 41 Z9 41 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2007 VL 28 IS 9 BP 805 EP 816 DI 10.1002/hbm.20322 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 209XC UT WOS:000249420300001 PM 17133396 ER PT J AU Osada, R Horiuchi, A Kikuchi, N Yoshida, J Hayashi, A Ota, M Katsuyama, Y Melilo, G Konishi, I AF Osada, Ryosuke Horiuchi, Akiko Kikuchi, Norihiko Yoshida, Junko Hayashi, Akiko Ota, Masao Katsuyama, Yoshihiko Melilo, Giovanni Konishi, Ikuo TI Expression of hypoxia-inducible factor 1 alpha, hypoxia-inducible factor 2 alpha, and von Hippel-Lindau protein in epitheLiaL ovarian neoplasms and allelic loss of von Hippel-Lindau gene: nuclear expression of hypoxia-inducible factor 1 alpha is an independent prognostic factor in ovarian carcinoma SO HUMAN PATHOLOGY LA English DT Article DE HIF-1 alpha; HIF-2 alpha; VHL; ovarian carcinoma; prognosis ID ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1; FACTOR (HIF)-1-ALPHA; FACTORS HIF-1-ALPHA; TUMOR ANGIOGENESIS; CANCER PATIENTS; NECK-CANCER; HIF-2-ALPHA; THERAPY; CELLS AB The hypoxia-inducible factor (HIF) is a transcriptional factor with important roles in tumor biology. To clarify the possible involvement of the HIF-alpha subunit and von Hippel-Lindau (VHL) protein in the development and progression of ovarian carcinoma, we analyzed the immunohistochemical expressions of HIF-1 alpha, HIF-2 alpha, and VHL in 107 cases of epithelial ovarian tumors. In addition, we examined loss of heterozygosity (LOH) at VHL gene loci. The frequency of the cytoplasmic expression of HIF-2 alpha in carcinomas was higher than that in benign and borderline tumors (P < .0001). Furthermore, the nuclear expression of HIF-1 alpha and the cytoplasmic expression of HIF-2a were significantly higher in tumors of FIGO (International Federation of Gynecology and Obstetrics) stages III and IV than in those of stages I and II. On the other hand, the cytoplasmic expression of HIF-1 alpha did not show differences among histological malignancies. There was a positive correlation between nuclear HIF-1 alpha expression and vascular endothelial growth factor (p = 0.320, P < .001). Although LOH at the VHL gene locus was frequent in ovarian carcinomas (24%), there is no significant correlation between LOH and loss of VHL expression. In 22 clear cell carcinomas, VHL expression showed a significantly negative correlation with the nuclear expression of HIF-1 alpha (rho = -0.529, P = .0153). The log-rank test showed that nuclear positive immunostaining for HIF-1 alpha (P = .002) and cytoplasmic positive immunostaining for HIF-2 alpha (P = .0112) in tumor cells are associated with poor prognosis of patients with ovarian carcinoma. Multivariate analysis also showed that the nuclear expression of HIF-1 alpha is an independent prognostic factor. These results show that the HIF-alpha subunit represents an important biomarker in the evaluation of the prognosis of patients with ovarian carcinoma. (c) 2007 Elsevier Inc. All rights reserved. C1 Shinshu Univ, Sch Med, Dept Obstet & Gynecol, Matsumoto, Nagano 3908621, Japan. Shinshu Univ, Sch Med, Dept Legal Med, Matsumoto, Nagano 3908621, Japan. Shinshu Univ Hosp, Div Pharma, Matsumoto, Nagano 3908621, Japan. NCI, Sci Applicat Int Corp Fredrick Inc, Dev Therapeut Program, Tumor Hypoxia Lab, Frederick, MD 21702 USA. RP Horiuchi, A (reprint author), Shinshu Univ, Sch Med, Dept Obstet & Gynecol, Matsumoto, Nagano 3908621, Japan. EM aki9hori@hsp.md.shinshu-u.ac.jp NR 38 TC 67 Z9 75 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 2007 VL 38 IS 9 BP 1310 EP 1320 DI 10.1006/j.humpath.2007.02.010 PG 11 WC Pathology SC Pathology GA 205PW UT WOS:000249128100003 PM 17555795 ER PT J AU Begnami, MD Palau, M Rushing, EI Santi, M Quezado, M AF Begnami, Maria D. Palau, Mauricio Rushing, Elisabeth I. Santi, Mariarita Quezado, Martha TI Evaluation of NF2 gene deletion in sporadic schwannomas, meningiomas, and ependymomas by chromogenic in situ hybridization SO HUMAN PATHOLOGY LA English DT Article DE CISH; ependymomas; meningiomas; NF2; Schwannomas ID NEUROFIBROMATOSIS TYPE-2 GENE; VESTIBULAR SCHWANNOMAS; CHROMOSOME 22Q; MUTATIONS; MERLIN; IMMUNOHISTOCHEMISTRY; HETEROZYGOSITY; AMPLIFICATION; MICROARRAY; CISH(TM) AB Fluorescence in situ hybridization, loss of heterozygosity testing, and comparative genomic hybridization have been used to detect NF2 gene alterations in both sporadic and neurofibromatosis type 2 (NF2)-associated central nervous system tumors. In this study, we performed chromogenic in situ hybridization (CISH) and immunohistochemistry to evaluate for NF2 gene deletion in a group of sporadic meningiomas, schwannomas, and ependymomas. Twenty-two sporadic tumors, including 9 ependymomas, 10 meningiomas, and 3 schwannomas, were studied. CISH and immunohistochemistry were performed using the NF2 gene deletion probe and NF2 polyclonal antibody. Deletion of the NF2 gene was identified in 11 (50%) tumors, including 60% (6/10) of meningiomas, 33% (3/9) of ependymomas, and 67% (2/3) of schwannomas. The remaining 11 (50%) cases were diploid. Overall, immunoexpression of NF2 protein was observed in 50% (11/22) tumors, and concordance between CISH and immunohistochemistry was observed in 73% of cases. Our results support previous observations that schwannomas and meningiomas, and to a lesser degree, ependymomas, express a high incidence of NF2 gene deletion, which supports the hypothesis that NF2 gene plays an important role in their tumorigenesis. In addition, we have validated CISH as an efficient, economic, and reliable method for routinely assessing NF2 gene deletion in these tumors. (c) 2007 Elsevier Inc. All rights reserved. C1 NCI, NIH, Pathol Lab, Surg Pathol Sect, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Neuropathol & Ophthalm Pathol, Washington, DC 20306 USA. Childrens Hosp, Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA. RP Begnami, MD (reprint author), NCI, NIH, Pathol Lab, Surg Pathol Sect, Bethesda, MD 20892 USA. EM mariadirlei@gmail.com RI Begnami, Maria/D-9663-2012 OI Begnami, Maria/0000-0003-0848-7813 FU Intramural NIH HHS [Z99 CA999999] NR 35 TC 15 Z9 15 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 2007 VL 38 IS 9 BP 1345 EP 1350 DI 10.1016/j.humpath.2007.01.027 PG 6 WC Pathology SC Pathology GA 205PW UT WOS:000249128100007 PM 17509660 ER PT J AU Nguyen, RHN Wilcox, AJ Skjaerven, R Baird, DD AF Nguyen, Ruby H. N. Wilcox, Allen J. Skjaerven, Rolv Baird, Donna D. TI Men's body mass index and infertility SO HUMAN REPRODUCTION LA English DT Article DE body mass index; infertility; time to pregnancy; body weight ID DELAYED CONCEPTION; OBESITY; PREGNANCY; TIME; WEIGHT; COHORT; WOMEN; MORTALITY; AGE; DYSFUNCTION AB BACKGROUND: In men, excess weight may be linked with altered testosterone, estradiol levels, poor semen quality and infertility. We investigated whether higher BMI among men is associated with infertility and if so, to what extent that effect might be mediated by altered sexual function. METHODS: A retrospective cohort study of pregnancies from 1999 through 2005 based within the Norwegian Mother and Child Cohort Study (MoBa). Questionnaires assessed mother's and father's height and weight and time to pregnancy. Our sample comprises 26 303 planned pregnancies. Couples were considered infertile if they took >= 12 months to achieve pregnancy or received infertility treatment. RESULTS: After adjusting for the woman's BMI, coital frequency and the ages and smoking habits of both partners, the odds ratio for infertility was 1.20 for overweight men [BMI 25-29.9; 95% confidence interval (CI) = 1.04-1.38] and 1.36 for obese men (BMI 30-34.9; 95% CI = 1.13-1.63) relative to men with low-normal BMI (20.0-22.4). When BMI was divided into eight categories, there was a trend of increased infertility with increased male BMI. The effect of men's BMI was nearly identical when coital frequency was not included indicating that the effect is not mediated by sexual dysfunction in heavier men. CONCLUSIONS: This study adds further support that men with excess body weight are at increased risk of infertility. Values may be underestimated because the most severe cases, couples who do not conceive, are not included in this birth cohort. Research is needed to see if weight loss improves fertility for these men. C1 NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Univ Bergen, Sect Epidemiol & Med Stat, Bergen, Norway. Norwegian Inst Publ Hlth, Med Birth Registry, Bergen, Norway. RP Nguyen, RHN (reprint author), 111 TW Alexander Dr,POB 12233,Mail Stop A3-05, Res Triangle Pk, NC 27709 USA. EM nguyen5@niehs.nih.gov RI Baird, Donna/D-5214-2017; OI Baird, Donna/0000-0002-5544-2653; Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS NR 39 TC 105 Z9 111 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD SEP PY 2007 VL 22 IS 9 BP 2488 EP 2493 DI 10.1093/humrep/dem139 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 218IL UT WOS:000250009100020 PM 17636282 ER PT J AU Jimenez, GS Planchon, R Wei, Q Rusalov, D Geall, A Enas, J Lalor, P Leamy, V Vahlel, R Luke, CJ Rolland, A Kaslow, DC Smith, LR AF Jimenez, Gretchen S. Planchon, Rodrick Wei, Qun Rusalov, Denis Geall, Andrew Enas, Joel Lalor, Peggy Leamy, Vicky Vahle, Ruth Luke, Catherine J. Rolland, Alain Kaslow, David C. Smith, Larry R. TI Vaxfectin (TM)-formulated influenza DNA vaccines encoding NP and M2 viral proteins protect mice against lethal viral challenge SO HUMAN VACCINES LA English DT Article DE DNA vaccine; influenza virus; Vaxfectin (TM) ID A/DUCK/SINGAPORE/97 H5N3 VACCINE; MF59-ADJUVANTED INFLUENZA; EXTRACELLULAR DOMAIN; IMMUNE-RESPONSES; RANDOMIZED-TRIAL; AVIAN INFLUENZA; PLASMID; VIRUS; IMMUNOGENICITY; ANTIBODY AB Next generation influenza vaccines containing conserved antigens may enhance immunity against seasonal or pandemic influenza virus strains. Using a plasmid DNA (pDNA)-based vaccine approach, we systematically tested combinations of NP, M1 and M2 antigens derived from consensus sequences for protection against lethal influenza challenge and compared formulations for adjuvanting low pDNA vaccine doses. The highest level of protection at the lowest pDNA doses was provided by Vaxfectin p (TM)-formulated NP + M2. Vaxfectin (TM) adjuvanticity was confirmed with a low dose of HA pDNA. These promising proof-of-concept data support the clinical development of Vaxfectin (TM)-formulated pDNA encoding NP + M2 consensus proteins. C1 Vical Inc, San Diego, CA 92121 USA. Natl Inst Hlth, Infect Dis Lab, Bethesda, MD USA. Marck Res Lab, N Wales, PA USA. RP Smith, LR (reprint author), Vical Inc, 10390 Pacific Ctr Court, San Diego, CA 92121 USA. EM lsmith@vical.com FU NIAID NIH HHS [1R43AI065016-01] NR 30 TC 64 Z9 71 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1554-8619 J9 HUM VACCINES JI Hum. Vaccines PD SEP-OCT PY 2007 VL 3 IS 5 BP 157 EP 164 PG 8 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 221MZ UT WOS:000250233300004 PM 17637571 ER PT J AU Abd-Elmoniem, KZ Sampath, S Osman, NF Prince, JL AF Abd-Elmoniem, Khaled Z. Sampath, Smita Osman, Nael F. Prince, Jerry L. TI Real-time monitoring of cardiac regional function using FastHARP MRI and region-of-interest reconstruction SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE cardiac motion; FastHARP (HARP-MRI); harmonic phase (HARP); magnetic resonance (MR) tagging; myocardial strain; real-time imaging ID HARP-MRI; MOTION; HEART AB Cardiovascular stress test imaging assists in the diagnosis and monitoring of cardiovascular disease. The procedure can be carried out in a magnetic resonance (MR) scanner using pharmacological agents that mimic the effects of natural exercise. In order to provide real time indication of ischemia, thereby assisting in diagnosis and helping to assure patient safety, it is desirable to have real time monitoring of the myocardial regional function. This paper presents an algorithm for the real time myocardium region-of-interest reconstruction and myocardial strain computation using data acquired from a real time pulse sequence that has been previously reported. The chirp Fourier transform is used for efficient computation, enabling a real-time continuous strain map at a rate of 25 frames/s. Coupled with a real time data path from the scanner to a laptop computer, this algorithm enables real time continuous monitoring of cardiac strain and is targeted for use in the early detection and quantification of ischemia during MR stress tests. C1 Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Elect & Comp Engn, Image Anal & Commun Lab, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21205 USA. RP Abd-Elmoniem, KZ (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. EM khlaed@jhu.edu RI Abd-Elmoniem, Khaled/B-9289-2008; Prince, Jerry/A-3281-2010 OI Abd-Elmoniem, Khaled/0000-0002-1001-1702; Prince, Jerry/0000-0002-6553-0876 FU NHLBI NIH HHS [R01 HL47405] NR 14 TC 6 Z9 6 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD SEP PY 2007 VL 54 IS 9 BP 1650 EP 1656 DI 10.1109/TBME.2007.891946 PG 7 WC Engineering, Biomedical SC Engineering GA 204TW UT WOS:000249067900012 PM 17867357 ER PT J AU Chang, JH Yen, JT Shung, KK AF Chang, Jin Ho Yen, Jesse T. Shung, K. Kirk TI A novel envelope detector for high-frame rate, high-frequency ultrasound imaging SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID SYSTEM; ARRAY; BEAMFORMER; ALGORITHMS; PROCESSOR; FILTERS; FIR AB This paper proposes a novel design of envelope detectors capable of supporting a small animal cardiac imaging system requiring a temporal resolution of more than 150 frames per second. The proposed envelope de tector adopts the quadrature demodulation and the look-up table (LUT) method to compute the magnitude of the complex baseband components of received echo signals. Because the direct use of the LUT method for a square root function is not feasible due to a large memory size, this paper presents a new LUT strategy dramatically reducing its size by using binary logarithmic number system (BLNS). Due to the nature of BLNS, the proposed design does not require an individual LOG-compression functional block. In the implementation using a field programmable gate array (FPGA), a total of 166.56 Kbytes memories were used for computing the magnitude of 16-bit in-phase and quadrature components instead of 4 Gbytes in the case of the direct use of the LUT method. The experimental results show that the proposed envelope detector is capable of generating LOG-compressed envelope data at every clock cycle after 32 clock cycle latency, and its maximum error is less than 0.5 (i.e., within the rounding error), compared with the arithmetic results of square root function and LOG compression. C1 Ctr Med Ultrasonic Transducer Technol, NIH Transducer Resource, Dept Biomed Engn, Los Angeles, CA USA. RP Chang, JH (reprint author), Ctr Med Ultrasonic Transducer Technol, NIH Transducer Resource, Dept Biomed Engn, Los Angeles, CA USA. EM jhchang@ieee.org FU NHLBI NIH HHS [R01-HL079976] NR 24 TC 18 Z9 18 U1 0 U2 1 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 2007 VL 54 IS 9 BP 1792 EP 1801 DI 10.1109/TUFFC.2007.463 PG 10 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 211EY UT WOS:000249508300010 PM 17941385 ER PT J AU Stephens, GL Shevach, EM AF Stephens, Geoffrey L. Shevach, Ethan M. TI Foxp3(+) regulatory T cells: Selfishness under scrutiny SO IMMUNITY LA English DT Editorial Material ID SELF; REPERTOIRES AB The Foxp3(+) T cell lineage is thought to arise from self-specific precursors during development. By using a unique mouse model, Pacholczyk et al. (2007) present compelling evidence that self-specific cells are exceedingly rare among Foxp3(-) and, surprisingly, Foxp3(+) subsets. C1 NIAID, NIH, Cellular Immunol Sect, Immunol Lab, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, NIH, Cellular Immunol Sect, Immunol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov NR 9 TC 25 Z9 33 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2007 VL 27 IS 3 BP 417 EP 419 DI 10.1016/j.immuni.2007.08.008 PG 3 WC Immunology SC Immunology GA 215XX UT WOS:000249843400007 PM 17892850 ER PT J AU Zhang, XR Wang, HS Claudio, E Brown, K Siebenlist, U AF Zhang, Xiaoren Wang, Hongshan Claudio, Estefania Brown, Keith Siebenlist, Ulrich TI A role for the I kappa B family member bcl-3 in the control of central immunologic tolerance SO IMMUNITY LA English DT Article ID REGULATORY T-CELLS; LYMPHOTOXIN BETA-RECEPTOR; GERMINAL CENTER REACTIONS; THYMIC EPITHELIAL-CELLS; SELF-TOLERANCE; SPLENIC MICROARCHITECTURE; SIGNALING PATHWAY; ONCOPROTEIN BCL-3; MICE DEFICIENT; P50 HOMODIMERS AB Bcl-3 is a member of the family of I kappa B inhibitors. Unlike the classical, cytoplasmic I kappa Bs, Bcl-3 does not inhibit ReIA- or c-Rel-containing NF-kappa B transcription factor dimers. Instead, Bcl-3 can enter the nucleus and modulate NF-kappa B activity, although the underlying mechanism and physiologic function remain largely unknown. Here we identified Bcl-3 as a regulator of immunologic tolerance to self. In parallel with NF-kappa B2, Bcl-3 functions within stroma to generate medullary thymic epithelial cells, which are essential for negative selection of autoreactive T cells. Loss of both NF-kappa B2 and Bcl-3, but not either one alone, led to a profound breakdown in central tolerance resulting in rapid and fatal multiorgan inflammation. These data reveal extensive utilization of the NF-kappa B system to promote central tolerance in the thymus, in apparent contrast with the well-known roles of NF-kappa B to promote inflammation and autoimmunity in the periphery. C1 NIAID, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Siebenlist, U (reprint author), NIAID, NIH, Immunoregulat Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM us3n@nih.gov OI Zhang, Xiaoren/0000-0002-0649-8183 FU Intramural NIH HHS [Z01 AI000723-13, Z01 AI000722-13] NR 54 TC 38 Z9 42 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2007 VL 27 IS 3 BP 438 EP 452 DI 10.1016/j.immuni.2007.07.017 PG 15 WC Immunology SC Immunology GA 215XX UT WOS:000249843400011 PM 17869136 ER PT J AU Jin, B Wang, RY Qiu, Q Sugauchi, F Grandinetti, T Alter, HJ Shih, JWK AF Jin, Bo Wang, Richard Y. Qiu, Qi Sugauchi, Fuminaka Grandinetti, Teresa Alter, Harvey J. Shih, J. Wai-Kuo TI Induction of potent cellular immune response in mice by hepatitis C virus NS3 protein with double-stranded RNA SO IMMUNOLOGY LA English DT Article DE ELISA/ELSIPOT; hepatitis C virus; intracellular cytokine staining; vaccine ID TOLL-LIKE RECEPTOR-3; HUMAN MONOCLONAL-ANTIBODIES; DOMAIN-CONTAINING ADAPTER; NF-KAPPA-B; DNA IMMUNIZATION; CPG OLIGODEOXYNUCLEOTIDES; NONSTRUCTURAL PROTEIN-3; PLASMODIUM-FALCIPARUM; INTERFERON-GAMMA; CELLS AB Double-stranded RNA is produced during virus replication and, together with the viral antigen, is responsible for inducing host antivirus immunity. The hepatitis C virus (HCV) non-structural protein-3 (NS3) has been implicated in the immune evasion of HCV, and is one of the prime targets for inducing immunity against HCV infection. Mice were immunized with recombinant NS3 protein (rNS3) and poly (I:C) emulsified in Montanide ISA 720 (M720). Cytokine production was assayed by enzyme-linked immunospot assay, and CD4(+) IFN-gamma(+) T helper (Th) cells or CD8(+) IFN-gamma(+) cytotoxic T lymphocytes were detected by flow cytometry. Anti-NS3 titre and immunoglobulin G2a (IgG2a) and IgG1 levels were monitored by enzyme-linked immunosorbent assay. Administration of rNS3 formulated in poly (I:C) and M720 induced anti-NS3 titres with a predominantly IgG2a isotype comparable to those induced by rNS3 in CpG-ODN and M720. The cytokine profiles showed that this formulation induced a Th1-biased immune response with several-fold more interferon-gamma (IFN-gamma)-producing cells than interleukin-4-producing cells. In contrast, rNS3 in M720 induced a Th2-biased immune response. The frequency of IFN-gamma-producing CD4(+) and CD8(+) cells induced by rNS3 in poly (I:C) and M720 was significantly higher than that induced by rNS3, rNS3 in M720, or rNS3 in poly (I:C), and was comparable to that induced by rNS3 in CpG-ODN with M720. The antigen-specific CD8(+) T-cell immune response persisted for up to 7 months after immunization. In conclusion, poly (I:C) with rNS3 in M720 can elicit a strong and persistent Th1-biased immune response and a cytotoxic T-lymphocyte response through cross-priming in mice. This study highlighted a promising formulation for inducing an efficient cellular immune response against HCV that has potential for HCV vaccine development. C1 Warren G Magnuson Clin Ctr, NIH, Dept Transfus Med, Infect Dis Sect, Bethesda, MD USA. RP Jin, B (reprint author), Naval Gen Hosp, Dept Digest Dis, 6 Fucheng Rd, Beijing 100037, Peoples R China. EM bjbo.jin@gmail.com; jwshih@xmu.edu.cn NR 53 TC 18 Z9 18 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2007 VL 122 IS 1 BP 15 EP 27 DI 10.1111/j.1365-2567.2007.02607.x PG 13 WC Immunology SC Immunology GA 204JU UT WOS:000249040700002 PM 17451465 ER PT J AU Fan, H Williams, DL Zingarelli, B Breuel, KF Teti, G Tempel, GE Spicher, K Boulay, G Birnbaumer, L Halushka, PV Cook, JA AF Fan, Hongkuan Williams, David L. Zingarelli, Basilia Breuel, Kevin F. Teti, Giuseppe Tempel, George E. Spicher, Karsten Boulay, Guylain Birnbaumer, Lutz Halushka, Perry V. Cook, James A. TI Differential regulation of lipopolysaccharide and Gram-positive bacteria induced cytokine and chemokine production in macrophages by G alpha(i) proteins SO IMMUNOLOGY LA English DT Article DE endotoxin; G(i) protein-deficient mice; group B streptococci; Staphylococcus aureus; toll-like receptor signalling ID SIGNAL-TRANSDUCTION EVENTS; NITRIC-OXIDE PRODUCTION; TUMOR-NECROSIS-FACTOR; GROUP-B STREPTOCOCCI; STAPHYLOCOCCUS-AUREUS; MURINE MACROPHAGES; TYROSINE KINASE; CUTTING EDGE; RECEPTOR; ACTIVATION AB Heterotrimeric G(i) proteins play a role in signalling activated by lipopolysaccharide (LPS), Staphylococcus aureus (SA) and group B streptococci (GBS), leading to production of inflammatory mediators. We hypothesized that genetic deletion of G(i) proteins would alter cytokine and chemokine production induced by LPS, SA and GBS stimulation. LPS-induced, heat-killed SA-induced and heat-killed GBS-induced cytokine and chemokine production in peritoneal macrophages from wild-type (WT), G alpha(-/-)(i2) or G alpha(-/-)(i1/3) mice were investigated. LPS induced production of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10 and interferon-gamma-inducible protein-10 (IP-10); SA induced TNF-alpha, and IL-1 beta production; and GBS induced TNF-alpha, IL-6, IL-1 beta, macrophage inflammatory protein-1 alpha (MIP-1 alpha) and keratinocyte chemoattract (KC) production were all decreased (P < 0.05) in G alpha(-/-)(i2) or G alpha(-/-)(i1/3) mice compared with WT mice. In contrast to the role of G(i) proteins as a positive regulator of mediators, LPS-induced production of MIP-1 alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in macrophages from G alpha(-/-)(i1/3) mice, and SA-induced MIP-1 alpha production was increased in both groups of G alpha(i) protein-depleted mice. LPS-induced production of KC and IL-1 beta, SA-induced production of GM-CSF, KC and IP-10, and GBS-induced production of IL-10, GM-CSF and IP-10 were unchanged in macrophages from G alpha(-/-)(i2) or G alpha(-/-)(i1/3) mice compared with WT mice. These data suggest that G(i2) and G(i1/3) proteins are both involved and differentially regulate murine inflammatory cytokine and chemokine production in response to both LPS and Gram-positive microbial stimuli. C1 Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med & Pharmacol, Charleston, SC 29425 USA. E Tennessee State Univ, James H Quillen Coll Med, Dept Surg, Johnson City, TN 37614 USA. Cincinnati Childrens Hosp, Med Ctr, Div Crit Care Med, Cincinnati, OH USA. E Tennessee State Univ, James H Quillen Coll Med, Dept Obstet & Gynecol, Johnson City, TN 37614 USA. Med Univ Messina, Dept Expt Pathol & Microbiol, Messina, Italy. Univ Dusseldorf, Sch Med, Inst Biochem & Mol Biol, D-4000 Dusseldorf, Germany. Univ Sherbrooke, Sch Med, Dept Pharmacol, Sherbrooke, PQ J1H 5N4, Canada. Natl Inst Environm Hlth Sci, Lab Signal Transduct, Transmembrane Signaling Grp, Res Triangle Pk, NC USA. RP Cook, JA (reprint author), Med Univ S Carolina, Dept Neurosci, 173 Ashley Ave,BSB Room 403, Charleston, SC 29425 USA. EM cookja@musc.edu FU Intramural NIH HHS; NIDDK NIH HHS [DK19318]; NIGMS NIH HHS [GM27673, R01 GM027673, R01 GM067202, R01 GM053522, GM67202, GM53522] NR 39 TC 17 Z9 20 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2007 VL 122 IS 1 BP 116 EP 123 DI 10.1111/j.1365-2567.2007.02619.x PG 8 WC Immunology SC Immunology GA 204JU UT WOS:000249040700013 PM 17484771 ER PT J AU Zhu, Y Weiss, EC Otto, M Fey, PD Smeltzer, MS Somerville, GA AF Zhu, Yefei Weiss, Elizabeth C. Otto, Michael Fey, Paul D. Smeltzer, Mark S. Somerville, Greg A. TI Staphylococcus aureus Biofilm metabolism and the influence of arginine on polysaccharide intercellular adhesin synthesis, 14 Biofilm formation, and pathogenesis SO INFECTION AND IMMUNITY LA English DT Article ID GENE-EXPRESSION; IN-VIVO; STREPTOCOCCUS-LACTIS; GEL-ELECTROPHORESIS; DEIMINASE PATHWAY; EPIDERMIDIS; ACID; RESISTANT; INFECTIONS; SURVIVAL AB Staphylococcus aureus and Staphylococcus epidermidis are the leading causes of nosocomial infections in the United States and often are associated with biofilms attached to indwelling medical devices. Despite the importance of biofilms, there is very little consensus about the metabolic requirements of S. aureus during biofilm growth. To assess the metabolic requirements of S. aureus growing in a biofilm, we grew USA200 and USA300 clonal types in biofilm How cells and measured the extraction and accumulation of metabolites. In spite of the genetic differences, both clonal types extracted glucose and accumulated lactate, acetate, formate, and acetoin, suggesting that glucose was catabolized to pyruvate that was then catabolized via the lactate dehydrogenase, pyruvate formate-lyase, and butanediol pathways. Additionally, both clonal types selectively extracted the same six amino acids (serine, proline, arginine, glutamine, glycine, and threonine) from the culture medium. These data and recent speculation about the importance of arginine in biofilm growth and the function of arginine deiminase in USA300 clones led us to genetically inactivate the sole copy of the arginine deiminase operon by deleting the arginine/ornithine antiporter gene (arcD) in the USA200 clonal type and to assess the effect on biofilm development and pathogenesis. Although inactivation of arcD did completely inhibit arginine transport and did reduce polysaccharide intercellular adhesin accumulation, arcD mutants formed biofilms and achieved cell densities in catheter infection studies that were equivalent to those for isogenic wild-type strains. C1 Univ Nebraska, Dept Vet Biomed Sci, Lincoln, NE 68583 USA. Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. NIH, NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Lab, Hamilton, MT USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. RP Somerville, GA (reprint author), Univ Nebraska, Dept Vet Biomed Sci, 155 VBS E Campus Loop, Lincoln, NE 68583 USA. EM gsomerville3@unl.edu RI Somerville, Greg/B-1326-2013; Zhu, Yefei/F-8940-2013 OI Somerville, Greg/0000-0002-0991-8737; FU Intramural NIH HHS; NIAID NIH HHS [AI43356, R01 AI043356]; NIGMS NIH HHS [GM076585, R21 GM076585] NR 60 TC 62 Z9 65 U1 0 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2007 VL 75 IS 9 BP 4219 EP 4226 DI 10.1128/IAI.00509-07 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 205RG UT WOS:000249131700004 PM 17576756 ER PT J AU Voth, DE Howe, D Heinzen, RA AF Voth, Daniel E. Howe, Dale Heinzen, Robert A. TI Coxiella burnetii inhibits apoptosis in human THP-1 cells and monkey primary alveolar macrophages SO INFECTION AND IMMUNITY LA English DT Article ID NF-KAPPA-B; TRACHOMATIS-INFECTED CELLS; IV SECRETION SYSTEMS; Q-FEVER; LEGIONELLA-PNEUMOPHILA; CHLAMYDIA-TRACHOMATIS; BH3-ONLY PROTEINS; PHASE-I; PROAPOPTOTIC PROTEINS; LYSOSOMAL RESPONSE AB Coxiella burnetii, the cause of human Q fever, is an aerosol-borne, obligate intracellular bacterium that targets host alveolar mononuclear phagocytic cells during infection. In all cell types examined, C burnetii establishes a replicative niche in a lysosome-like parasitophorous vacuole where it carries out a lengthy infectious cycle with minimal cytopathic effects. The persistent and mild nature of C. burnetii infection in vitro suggests that the pathogen modulates apoptosis to sustain the host cell. In the current study, we examined the ability of C. burnetii to inhibit apoptotic cell death during infection of human THP-1 monocyte-derived macrophages and primary monkey alveolar macrophages. C. burnetti-infected cells demonstrated significant protection from death relative to uninfected cells following treatment with staurosporine, a potent inducer of intrinsic apoptosis. This protection correlated with reduced cleavage of caspase-9, caspase-3, and poly(ADPribose) polymerase (PARP), all proteolytic events that occur during apoptosis. Reduced PARP cleavage was also observed in cells treated with tumor necrosis factor alpha to induce extrinsic apoptosis. Apoptosis inhibition was a C. burnetii-driven process as infected cells treated with rifampin or chloramphenicol, inhibitors of bacterial RNA and protein synthesis, respectively, showed significantly reduced protection against staurosporine-induced apoptosis. C. burnetii infection affected the expression of multiple apoptosis-related genes and resulted in increased synthesis of the antiapoptotic proteins AI/Bfl-I and c-IAP2. Collectively, these data suggest that C. burnetii modulates apoptotic pathways to inhibit host cell death, thus providing a stable, intracellular niche for the course of the pathogen's infectious cycle. C1 NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Heinzen, RA (reprint author), NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov NR 63 TC 70 Z9 72 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 2007 VL 75 IS 9 BP 4263 EP 4271 DI 10.1128/IAI.00594-07 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 205RG UT WOS:000249131700009 PM 17606599 ER PT J AU Hisatsune, J Yamasaki, E Nakayama, M Shirasaka, D Kurazono, H Katagata, Y Inoue, H Han, J Sap, J Yahiro, K Moss, J Hirayama, T AF Hisatsune, Junzo Yamasaki, Eiki Nakayama, Masaaki Shirasaka, Daisuke Kurazono, Hisao Katagata, Yohtaro Inoue, Hiroyasu Han, Jiahuai Sap, Jan Yahiro, Kinnosuke Moss, Joel Hirayama, Toshiya TI Helicobacter pylori VacA enhances prostaglandin E-2 production through induction of cyclooxygenase 2 expression via a p38 mitogen-activated protein Kinase/Activating transcription factor 2 cascade in AZ-521 cells SO INFECTION AND IMMUNITY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; CYTOCHROME-C RELEASE; VASCULAR ENDOTHELIAL-CELLS; EPIDERMAL-GROWTH-FACTOR; VACUOLATING TOXIN VACA; HUMAN GASTRIC CELLS; NUCLEAR-FACTOR; T-CELLS; GENE-EXPRESSION; PHORBOL ESTER AB Treatment of AZ-521 cells with Helicobacter pylori VacA increased cyclooxygenase 2 (COX-2) mRNA in a time- and dose-dependent manner. A p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, blocked elevation of COX-2 mRNA levels, whereas PD98059, which blocks the Erk1/2 cascade, partially suppressed the increase. Consistent with involvement of p38 MAPK,, VacA-induced accumulation of COX-2 mRNA was reduced in AZ-521 cells overexpressing a dominant-negative p38 MAPK (DN-p38). Phosphatidylinositol-specific phospholipase C, which inhibits VacA-induced p38 MAPK activation, blocked VacA-induced COX-2 expression. In parallel with COX-2 expression, VacA increased prostaglandin E-2 (PGE(2)) production, which was inhibited by SB203580 and NS-398, a COX-2 inhibitor. VacA-induced PGE2 Production was markedly attenuated in AZ-521 cells stably expressing DN-p38. VacA increased transcription of a COX-2 promoter reporter gene and activated a COX-2 promoter containing mutated NF-kappa B or NF-interieukin-6 sites but not a mutated cis-acting replication element (CRE) site, suggesting direct involvement of the activating transcription factor 2 (ATF-2)/CREB-binding region in VacA-induced COX-2 promoter activation. The reduction of ATF-2 expression in AZ-521 cells transformed with ATF-2-small interfering RNA duplexes resulted in suppression of COX-2 expression. Thus, VacA enhances PGE2 production by AZ-521 cells through induction of COX-2 expression via the p38 MAPK/ATF-2 cascade, leading to activation of the CRE site in the COX-2 promoter. C1 Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. Kobe Univ, Grad Sch Med, Div Digest Dis, Kobe, Hyogo 6500017, Japan. Osaka Prefecture Univ, Grad Sch Life Sci & Environm Sci, Lab Vet Publ Hlth, Osaka 5998531, Japan. Hirosaki Univ, Hirosaki, Aomori 0368561, Japan. Nara Womens Univ, Dept Food & Nutr, Nara 6308506, Japan. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Univ Copenhagen, Dept Mol Pathol, DK-2100 Copenhagen, Denmark. NHLBI, Pulm & Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Hirayama, T (reprint author), Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. EM hirayama@net.nagasaki-u.ac.jp RI Han, J/G-4671-2010 FU Intramural NIH HHS NR 60 TC 21 Z9 24 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 2007 VL 75 IS 9 BP 4472 EP 4481 DI 10.1128/IAI.00500-07 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 205RG UT WOS:000249131700033 PM 17591797 ER PT J AU Francischetti, IMB Lopes, AH Dias, FA Pham, VM Ribeiro, JMC AF Francischetti, Ivo M. B. Lopes, Angela H. Dias, Felipe A. Pham, Van M. Ribeiro, Jose M. C. TI An insight into the sialotranscriptome of the seed-feeding bug, Oncopeltus fasciatus SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE feeding; phytophagy; salivary glands; sialotranscriptome ID SALIVARY-GLAND TRANSCRIPTS; ADULT FEMALE MOSQUITO; RHODNIUS-PROLIXUS; HIGH-AFFINITY; PLATELET-AGGREGATION; ANNOTATED CATALOG; ANOPHELES-GAMBIAE; HISTAMINE-BINDING; MOLECULAR-CLONING; LYGUS-LINEOLARIS AB The salivary transcriptome of the seed-feeding hemipteran, Oncopeltus fasciatus (milkweed bug), is described following assembly of 1025 expressed sequence tags (ESTs) into 305 clusters of related sequences. Inspection of these sequences reveals abundance of low complexity, putative secreted products rich in the amino acids (aa) glycine, serine or threonine, which might function as silk or mucins and assist food canal lubrication and sealing of the feeding site around the mouthparts. Several protease inhibitors were found, including abundant expression of cystatin transcripts that may inhibit cysteine proteases common in seeds that might injure the insect or induce plant apoptosis. Serine proteases and lipases are described that might assist digestion and liquefaction of seed proteins and oils. Finally, several novel putative proteins are described with no known function that might affect plant physiology or act as antimicrobials. Published by Elsevier Ltd. C1 NIH, NIAID, Lab Malaria & Vector Res, Sect Vector Biol, Rockville, MD 20852 USA. Univ Fed Rio de Janeiro, Inst Microbiol, BR-21941902 Rio De Janeiro, Brazil. RP Ribeiro, JMC (reprint author), NIH, NIAID, Lab Malaria & Vector Res, Sect Vector Biol, 12735 Twinbrook Pkwy,Room 2E32D, Rockville, MD 20852 USA. EM jribeiro@niaid.nih.gov RI Dias, Felipe/L-7390-2013; OI Dias, Felipe/0000-0003-2074-1052; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS [Z01 AI000810-11, Z99 AI999999] NR 48 TC 15 Z9 15 U1 0 U2 8 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 2007 VL 37 IS 9 BP 903 EP 910 DI 10.1016/j.ibmb.2007.04.007 PG 8 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 205TI UT WOS:000249137100002 PM 17681229 ER PT J AU Xu, L Lao, LX Ge, A Yu, S Li, J Mansky, PJ AF Xu, Ling Lao, Li Xing Ge, Adeline Yu, Shan Li, Jie Mansky, Patrick J. TI Chinese herbal medicine for cancer pain SO INTEGRATIVE CANCER THERAPIES LA English DT Review DE Chinese herbal medicine; cancer Pain ID ANTIINFLAMMATORY ACTIVITY; MANAGEMENT; ARTHRITIS; DRUG AB Aim: The purpose of this review is to summarize and evaluate the current status of clinical research on the use of Chinese herbal medicine in treating cancer pain, with emphasis on the efficacy and safety of the applications. Method: A search of the clinical research published between 1986 and 2006 on the effects and applications of Chinese herbal medicine in cancer pain management was conducted using databases of CBM, CMCC, Wanfang, and Weipu (available since 1989) in Chinese and PubMed and EMBASE in English. We included only reports of original publications on cancer-induced pain, resulting in a total of 115 articles. We evaluated the methodological quality of the articles following the guidelines set forth as "Levels of Evidence of Human Studies of Cancer in Complementary and Alternative Medicine" by the National Cancer Institute. Results: Various methods of traditional Chinese medicine herbal treatment for cancer pain management have been reported. These methods include external application, oral administration, intravenous infusion, and other applications such as inhalation and clysmata. Forty-one of the 115 studies reviewed were randomized controlled clinical trials, most comparing the effects of Chinese herbal medicine to conventional analgesics and the others using placebo controls. These trials suggest that (1) Chinese medicine may be effective for cancer pain, and its effects are similar to those of Western analgesics; (2) Chinese medicine may reduce the side effects of conventional analgesics, thus enhancing cancer patients' quality of life; and (3) the various methods of application-topical, oral, and intravenous-are suitable to treat a range of pain conditions found in cancer patients. However, trials were of varying quality with respect to control group selection, dosing and side effect information, and outcome measures. Conclusion: The studies reviewed in this article suggest that Chinese herbal medicine may be useful for managing cancer pain, at least for short-term application. The products evaluated appear relatively safe, with no serious adverse effects reported. However, the quality of the published reports is variable. More research using rigorously controlled clinical trial design is warranted. C1 NIH, Natl Ctr Complementary & Alternat Med, Div Intramural Res, DHHS, Bethesda, MD 20892 USA. Second Mil Med Univ, Shanghai Changzheng Hosp, Shanghai, Peoples R China. Univ Maryland, Ctr Integrat Med, Baltimore, MD 21201 USA. NIH, Ctr Clin, Dept Rehabil Med, Bethesda, MD 20892 USA. Shanghai Univ Tradit Chinese Med, Shanghai, Peoples R China. RP Mansky, PJ (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Div Intramural Res, DHHS, 10 Ctr Dr,CRC,Room 41741,MSC 1302, Bethesda, MD 20892 USA. EM manskyp@mail.nih.gov NR 189 TC 28 Z9 32 U1 5 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1534-7354 EI 1552-695X J9 INTEGR CANCER THER JI Integr. Cancer Ther. PD SEP PY 2007 VL 6 IS 3 BP 208 EP 234 DI 10.1177/1534735407305705 PG 27 WC Oncology; Integrative & Complementary Medicine SC Oncology; Integrative & Complementary Medicine GA 204XY UT WOS:000249078500002 PM 17761635 ER PT J AU Kitazawa, H Yonezawa, K Tohno, M Shimosato, T Kawai, Y Saito, T Wang, JM AF Kitazawa, Haruki Yonezawa, Kumiko Tohno, Masanori Shimosato, Takeshi Kawai, Yasushi Saito, Tadao Wang, Ji Ming TI Enzymatic digestion of the milk protein beta-casein releases potent chemotactic peptide(s) for monocytes and macrophages SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE beta-casein; monocyte; macrophage; chemotaxis; peptide; beta-casochemotide ID LACTIC-ACID BACTERIA; PLATELET FACTOR-IV; RECEPTOR-LIKE 1; CHEMOKINES; CELLS; OLIGODEOXYNUCLEOTIDE; PHOSPHOPEPTIDE; IDENTIFICATION; PROLIFERATION; TRANSFECTANT AB Proteins in the milk release biologically active peptides upon enzymatic digestion. in the present study, we report the identification of novel monocyte/macrophage chemotactic peptides derived from enzymatically digested bovine beta-casein, a casein family member that is a major constituent of milk. beta-casein fragments generated by actinase E showed potent chemotactic activity for human and mouse monocytes/macrophages, but not neutrophils, T lymphocytes or dendritic cells. The fragment-induced migration of human monocytes was inhibited by pertussis toxin and was not desensitized by a variety of known chemoattractants, suggesting that the digests activate a unique G protein-coupled receptor(s). The digests were further fractionated and purified to yield 3 small peptides. One peptide Q I designated as ''beta-casochemotide-l '' with the amino acid sequence of YPVEP (f114-118 of beta-casein) induced high levels of macrophage chemotaxis. It also promoted calcium mobilization in macrophages, another indication of cell activation. Our study suggests that biologically active peptides released by actinase-digested milk beta-casein may promote innate host immune responses by inducing macrophage migration and activation. (c) 2007 Elsevier B.V. All rights reserved. C1 Tohoku Univ, Grad Sch Agr Sci, Lab Anim Prod Chem, Aoba Ku, Sendai, Miyagi, Japan. NCI, NIH, Canc Res Ctr, Mol Immunoregulat Lab,Canc & Inflammat Program, Frederick, MD 21701 USA. RP Kitazawa, H (reprint author), Tohoku Univ, Grad Sch Agr Sci, Lab Anim Prod Chem, Aoba Ku, Sendai, Miyagi, Japan. EM haruki@bios.tohoku.ac.jp; wangji@ncifcrf.gov RI Kitazawa, Haruki/C-1256-2011 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 46 TC 12 Z9 14 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD SEP PY 2007 VL 7 IS 9 BP 1150 EP 1159 DI 10.1016/j.intimp.2007.04.008 PG 10 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 199CG UT WOS:000248673200003 PM 17630193 ER PT J AU Sherman, ME Rimm, DL Yang, XHR Chatterjee, N Brinton, LA Lissowska, J Peplonska, B Szeszenia-Dbrowska, N Zatonski, W Cartun, R Mandich, D Rymkiewicz, G Ligaj, M Lukaszek, S Kordek, R Kalaylioglu, Z Harigopal, M Charrette, L Falk, RT Richesson, D Anderson, WF Hewitt, SM Garcia-Closas, M AF Sherman, Mark E. Rimm, David L. Yang, Xiaohong R. Chatterjee, Nilanjan Brinton, Louise A. Lissowska, Jolanta Peplonska, Beata Szeszenia-Dbrowska, Neonila Zatonski, Witold Cartun, Richard Mandich, Daniza Rymkiewicz, Grzegorz Ligaj, Marcin Lukaszek, Stanislaw Kordek, Radzislaw Kalaylioglu, Zynep Harigopal, Malini Charrette, Lori Falk, Roni T. Richesson, Douglas Anderson, William F. Hewitt, Stephen M. Garcia-Closas, Montserrat TI Variation in breast cancer hormone receptor and HER2 levels by etiologic factors: A population-based analysis SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE breast; etiology; hormones; epidemiology ID TISSUE MICROARRAYS; POSTMENOPAUSAL WOMEN; ENDOGENOUS ESTROGEN; PROTEIN EXPRESSION; RISK; TUMORS; ANTIGENICITY; ESTRADIOL AB Evidence suggests that breast cancer hormone receptor status varies by etiologic factors, but studies have been inconsistent. In a population-based case-control study in Poland that included 2,386 cases and 2,502 controls, we assessed ER-a and PR status of tumors based on clinical records according to etiologic exposure data collected via interview. For 842 cancers, we evaluated ER-a, ER-P, PR and HER2 levels by semiquantitative microscopic scoring of immumostained tissue microarrays and a quantitative immunofluorescence method, automated quantitative analysis (AQUA(TM)). We related marker levels in tumors to etiologic factors, using standard regression models and novel statistical methods, permitting adjustment for both correlated tumor features and exposures. Results obtained with different assays were generally consistent. Receptor levels varied most significantly with body mass index (BMI), a factor that was inversely related to risk among premenopausal women and directly related to risk among postmenopausal women with larger tumors. After adjustment for correlated markers, exposures and pathologic characteristics, PR and HER2 AQUA levels were inversely related to BMI among premenopausal women (p-trend = 0.01, both comparisons), whereas among postmenopausal women, PR levels were! associated directly with BMI (p-trend = 0.002). Among postmenopausal women, analyses demonstrated that BMI was related to an interaction of PR and HER2: odds ratio (OR) = 0.86 (95% CI = 0.691.07) for low PR and HER2 expression vs. OR 1.78 (95% CI = 1.25-2.55) for high expression (p-heterogeneity 0.001). PR and HER2 levels in breast cancer vary by BMI, suggesting a heterogeneous etiology for tumors related to these markers. (C) 2007 Wiley-Liss, Inc. C1 Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, DHHS, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. Marie Curie Sklodowska Inst Oncol, Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland. Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. Hartford Hosp, Dept Pathol, Hartford, CT 06115 USA. Marie Curie Sklodowska Inst Oncol, Ctr Canc, Dept Pathol, Warsaw, Poland. Polish Mother Mem Hosp Res Inst, Dept Clin Pathomorphol, Lodz, Poland. Med Univ Lodz, Dept Pathol, Lodz, Poland. IMS, Silver Spring, MD USA. Ctr Canc Res, Natl Canc Inst, Natl Inst Hlth, Pathol Lab,Tissue Array Res Program, Bethesda, MD USA. RP Sherman, ME (reprint author), Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, DHHS, Bethesda, MD 20892 USA. EM shermanm@mail.nih.gov RI Peplonska, Beata/F-6004-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Szeszenia-Dabrowska, Neonila/F-7190-2010; Kordek, Radzislaw/S-9616-2016; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Hewitt, Stephen/0000-0001-8283-1788; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS NR 29 TC 36 Z9 36 U1 0 U2 6 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 2007 VL 121 IS 5 BP 1079 EP 1085 DI 10.1002/ijc.22812 PG 7 WC Oncology SC Oncology GA 192ZK UT WOS:000248242500020 PM 17487843 ER PT J AU Goedert, JJ Li, HC Gao, XJ Chatterjee, N Sonoda, S Biggar, RJ Cranston, B Kim, N Carrington, M Morgan, O Hanchard, B Hisada, M AF Goedert, James J. Li, Hong-Chuan Gao, Xiao-Jiang Chatterjee, Nilanjan Sonoda, Shunro Biggar, Robert J. Cranston, Beverley Kim, Norma Carrington, Mary Morgan, Owen Hanchard, Barrie Hisada, Michie TI Risk of human T-lymphotropic virus type I-associated diseases in Jamaica with common HLA types SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HTLV-I; CELL LEUKEMIA/LYMPHOMA; VIRAL LOAD; LYMPHOCYTES; ALLELES; TRANSMISSION; POPULATION; INFECTION; LEUKEMIA AB Human T-lymphotropic virus-I (HTLV-I) causes adult T-cell leukemia/lymphoma (ATL) and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We postulated a higher disease risk for people with common human leukocyte antigen (HLA) types, due to a narrower immune response against viral or neoplastic antigens, compared to people with uncommon types. HLA class-I (A,B) and class-II (DRBI, DQBI) allele and haplotype frequencies in 56 ATL patients, 59 HAM/TSP patients and 190 population- based, asymptomatic HTLV-I-infected carriers were compared by logistic regression overall (score test) and with odds ratios (ORs) for common types (prevalence >50% of asymptomatic carriers) and by prevalence quartile. HTLV-I proviral load between asymptomatic carriers with common versus uncommon types was compared by t-test. ATL differed from asymptomatic carriers in overall DQB1 allele and class-I haplotype frequencies (p <= 0.04). ATL risk was increased significantly with common HLA-B (OR 2.25,95% CI 1.19-4.25) and DRB1 (OR 1.11,95% CI 1.13-3.40) alleles. Higher prevalence HLA-B alleles were associated with higher ATL risk (OR 1.14 per quartiles, P-trend = 0.02). Asymptomatic carriers with common HLA-B alleles had marginally higher HTLV-I proviral load (p = 0.057). HAM/TSP risk did not differ consistently with common HLA types. Thus, ATL risk, but not HAM/TSP risk, was increased with higher prevalence HLA-B alleles. Perhaps breadth of cellular immunity affects risk of this viral leukemia/lymphoma. (C) 2007 Wiley-Liss, Inc. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Rockville, MD 20852 USA. Natl Canc Inst, SAIC Frederick, Lab Genom Divers, Frederick, MD USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD USA. Univ W Indies, Kingston 7, Jamaica. RTI Int, Rockville, MD USA. RP Goedert, JJ (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, 6120 Execut Blvd, Rockville, MD 20852 USA. EM goedertj@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CP33043-21, N01-CO-12400, N01-CP-21121, N01-CP31006, N01-CP-40548] NR 17 TC 12 Z9 13 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 2007 VL 121 IS 5 BP 1092 EP 1097 DI 10.1002/ijc.22767 PG 6 WC Oncology SC Oncology GA 192ZK UT WOS:000248242500022 PM 17437273 ER PT J AU Miller, S Tudor, C Nyima Thorsten, VR Sonam Droyoung Craig, S Le, P Wright, LL Varner, MW AF Miller, S. Tudor, C. Nyima Thorsten, V. R. Sonam Droyoung Craig, S. Le, P. Wright, L. L. Varner, M. W. TI Maternal and neonatal outcomes of hospital vaginal deliveries in Tibet SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE postpartum hemorrhage; maternal mortality; Tibet; high altitude; pre-eclampsia; gestational hypertension ID INTRAUTERINE GROWTH RESTRICTION; PREGNANCY-INDUCED HYPERTENSION; RANDOMIZED CONTROLLED-TRIAL; HIGH-ALTITUDE; BIRTH-WEIGHT; POSTPARTUM HEMORRHAGE; OXYGEN-TRANSPORT; PREECLAMPSIA; MISOPROSTOL; PROTECTION AB Introduction: To determine the outcomes of vaginal deliveries in three study hospitals in Lhasa, Tibet Autonomous Region (TAR), People's Republic of China (PRC), at high attitude (3650 m). Methods: Prospective observational study of 1121 vaginal deliveries. Results: Pre-eclampsia/ gestational hypertension (PE/GH) was the most common maternal complication 18.9% (n = 212), followed by postpartum hemorrhage (blood loss >= 500 ml) 13.4%. There were no maternal deaths. Neonatal complications included: low birth weight (10.2%), small for gestational age (13.7%), pre-term delivery (4.1 %) and tow Apgar (3.7%). There were 11 stillbirths (9.8/1000 live births) and 19 early neonatal deaths (17/1000 live births). Conclusion: This is the largest study of maternal and newborn outcomes in Tibet. It provides information on the outcomes of institutional vaginal births among women delivering infants at high attitude. There was a higher incidence of PE/GH and tow birth weight; rates of PPH were not increased compared to those at tower attitudes. (c) 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. Lhasa Municipal Hosp, Womens Div, Lhasa, Peoples R China. RTI Intl, Res Triangle Pk, NC USA. Astrol Hosp, Mentsikhang Tradit Tibetan Med, Womens Div, Lhasa, Peoples R China. Lhasa Maternal Child Hlth Hosp, Womens Div, Lhasa, Peoples R China. Dartmount Univ, Dept Anthropol, Hanover, NH USA. Harvard Univ, Sch Med, Cambridge, MA USA. Ctr Res Mothers & Childrens, Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. Univ Utah, Sch Med, Maternal Fetal Med, Salt Lake City, UT USA. RP Miller, S (reprint author), Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. EM suellenmiller@gmail.com; ctudor@globalhealth.ucsf.edu RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU NICHD NIH HHS [U01 HD040613-05, U01 HD040613, U01 HD040613-01, U01 HD040613-02, U01 HD040613-03, U01 HD040613-04, U01 HD040613-05S1] NR 31 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD SEP PY 2007 VL 98 IS 3 BP 217 EP 221 DI 10.1016/j.ijgo.2007.03.033 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 210MI UT WOS:000249459900008 PM 17481630 ER PT J AU Park, SK Cho, S Lee, IH Jeon, DS Hong, SH Smego, RA Cho, SN AF Park, Seung-Kyu Cho, Sungae Lee, In-Hee Jeon, Doo-Soo Hong, Sung-Hee Smego, Raymond A., Jr. Cho, Sang-Nae TI Subcutaneously administered interferon-gamma for the treatment of multidrug-resistant pulmonary tuberculosis SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE tuberculosis; multidrug-resistant TB; interferon-gamma; subcutaneous injection ID MYCOBACTERIUM-TUBERCULOSIS; RESPONSES; MACROPHAGES; EXPRESSION; ALPHA; IMMUNOTHERAPY; CHEMOTHERAPY; CYTOKINES; THERAPY; CELLS AB Objective: We evaluated the clinical and laboratory effects of subcutaneously administered interferon-gamma (IFN-gamma) in the treatment of chronic and advanced multidrug-resistant tuberculosis (MDR-TB). Design: Eight patients with sputum smear and culture persistently positive MDR-TB were subcutaneously administered 2 million international units of recombinant human IFN-gamma three times a week for 24 weeks (72 doses total) between December 2002 and May 2003. Subjects also received a customized drug regimen containing second- and third-time antituberculosis agents based upon drug susceptibility testing and previous treatment history. Results: Body weight remained stable or slightly decreased in all subjects during the study period, and none displayed radiographic improvement on serial chest computed tomography scanning. Sputum smears and cultures remained positive for all patients, and there was no increase in the mean time to yield a positive culture (from 16.5 +/- 6.4 to 11.8 +/- 4.9 days). There was no enhancement of cell-mediated immune responses in terms of production of IFN-gamma or IL-10, or of composition of lymphocytes among peripheral blood mononuclear cells. In four patients, therapy was discontinued because of adverse reactions. Conclusion: In patients with chronic and advanced MDR-TB, subcutaneous IFN-gamma treatment did not result in improvement in clinical, radiologic, microbiologic, or immunologic parameters. (C) 2007 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. C1 Natl Masan Tuberculosis Hosp, Dept Chest Surg, Masan, South Korea. Natl Masan Tuberculosis Hosp, Clin Res Ctr, Masan, South Korea. Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea. NIH, NIAID, Tuberculosis Res Sect, Rockville, MD USA. EM rsmego@hsc.wvu.edu NR 34 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD SEP PY 2007 VL 11 IS 5 BP 434 EP 440 DI 10.1016/j.ijid.2006.12.004 PG 7 WC Infectious Diseases SC Infectious Diseases GA 207TE UT WOS:000249273200011 PM 17321178 ER PT J AU Holup, JL Press, N Vollmer, WM Harris, EL Vogt, TM Chen, CH AF Holup, Joan L. Press, Nancy Vollmer, William M. Harris, Emily L. Vogt, Thomas M. Chen, Chuhe TI Performance of the US Office of Management and Budget's revised race and ethnicity categories in Asian populations SO INTERNATIONAL JOURNAL OF INTERCULTURAL RELATIONS LA English DT Article DE Asian; race; ethnicity; measurement; ethnic identity ID PUBLIC-HEALTH; UNITED-STATES; RISK-FACTORS; PACIFIC ISLANDERS; FAT DISTRIBUTION; RACE/ETHNICITY; SELF; AMERICANS; IDENTIFICATION; RELIABILITY AB The US Office of Management and Budget (OMB) guidelines for collecting and reporting race and ethnicity information recently divided the "Asian or Pacific Islander" category into "Asian" and "Native Hawaiian or Other Pacific Islander." The OMB's decision to disaggregate the "Asian or Pacific Islander" category was the first step toward providing these communities with information to better serve their needs. However, whether individuals who formerly made up the combined group categorize themselves as the new guidelines intend is a question analyzed in this report. A subset of adults participating in the Hemochromatosis and Iron Overload Screening Study completed both the OMB-minimum and the expanded race and ethnicity measure used in the National Health Interview Survey. We compared responses on the expanded measure contained within the OMB "Asian" definition (Filipino, Korean, Vietnamese, Japanese, Asian Indian, Chinese, and/or Other Asian) to "Asian" responses on the OMB-minimum measure. Mixed heritage Asians less often marked "Asian." Among mixed heritage Japanese, Chinese, and Filipinos, 27%, 49%, and 52% did not mark "Asian" on the OMB measure, respectively. Eleven percent of single-heritage Filipinos did not mark "Asian." Many individuals formerly making up the combined "Asian or Pacific Islander" group do not categorize themselves as the revised OMB guidelines intend. This is particularly evident among Filipinos and among Asians of mixed heritage. This research illuminates the reliability and utility of the broad "Asian" category and points to possible consequences of collapsing groups into a single category, i.e., missed information and/or erroneous generalization. (c) 2007 Elsevier Ltd. All rights reserved. C1 Kaiser Permanente NW, Ctr Hlth Res, Portland, OR 97227 USA. Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97239 USA. NHGRI, NIH, Rockville, MD 20852 USA. Kaiser Permanente Hawaii, Ctr Hlth Res, Honolulu, HI 96817 USA. RP Holup, JL (reprint author), Kaiser Permanente NW, Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR 97227 USA. EM Joan.L.Holup@kpchr.org; pressn@ohsu.edu; William.Vollmer@kpchr.org; harrisel@mail.nih.gov; Tom.M.Vogt@kp.org FU NHGRI NIH HHS [R03 HG002763-01A1, R03 HG002763]; NHLBI NIH HHS [N01 HC005189, N01 HC005192, N01HC05189] NR 45 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0147-1767 J9 INT J INTERCULT REL JI Int. J. Intercult. Relat. PD SEP PY 2007 VL 31 IS 5 BP 561 EP 573 DI 10.1016/j.ijintrel.2007.02.001 PG 13 WC Psychology, Social; Social Sciences, Interdisciplinary; Sociology SC Psychology; Social Sciences - Other Topics; Sociology GA 215HD UT WOS:000249798000003 PM 18037976 ER PT J AU Hall, KD Bain, HL Chow, CC AF Hall, K. D. Bain, H. L. Chow, C. C. TI How adaptations of substrate utilization regulate body composition SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE body composition; weight loss; weight gain; mathematical model; substrate utilization ID DE-NOVO LIPOGENESIS; ENERGY-EXPENDITURE; MACRONUTRIENT BALANCE; FAT OXIDATION; DIETARY-FAT; WEIGHT; CARBOHYDRATE; MODEL; CALORIMETRY; PREDICTION AB Objective: To elucidate the mathematical relationship between longitudinal changes of body composition and the adaptations of substrate utilization required to produce those changes. Design: We developed a simple mathematical model of macronutrient balance. By using an empirical relationship describing lean body mass as a function of fat mass, we derived a mathematical expression for how substrate utilization adapts to changes of diet, energy expenditure and body fat such that energy imbalances produced the required changes of body composition. Results: The general properties of our model implied that short-term changes of dietary fat alone had little impact on either fat or non-fat oxidation rates, in agreement with indirect calorimetry data. In contrast, changes of non-fat intake caused robust adaptations of both fat and non-fat oxidation rates. Without fitting any model parameters, the predicted body composition changes and oxidation rates agreed with experimental studies of overfeeding and underfeeding when the measured food intake, energy expenditure and initial body composition were used as model inputs. Conclusion: This is the first report to define the quantitative connection between longitudinal changes of body composition and the required relationship between substrate utilization, diet, energy expenditure and body fat mass. The mathematical model predictions are in good agreement with experimental data and provide the basis for future study of how changes of substrate utilization impact body composition regulation. C1 NIDDK, NIH, Lab Biol Modeling, Bethesda, MD USA. RP Hall, KD (reprint author), NIDDK, NIH, 12A S Dr,Room 4007, Bethesda, MD 20892 USA. EM kevinh@niddk.nih.gov RI Chow, Carson/A-7970-2009; Hall, Kevin/F-2383-2010 FU Intramural NIH HHS [Z01 DK013036-01] NR 24 TC 10 Z9 10 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 2007 VL 31 IS 9 BP 1378 EP 1383 DI 10.1038/sj.ijo.0803608 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 205CF UT WOS:000249090000006 PM 17356526 ER PT J AU Yim, JE Heshka, S Albu, J Heymsfield, S Kuznia, P Harris, T Gallagher, D AF Yim, J-E Heshka, S. Albu, J. Heymsfield, S. Kuznia, P. Harris, T. Gallagher, D. TI Intermuscular adipose tissue rivals visceral adipose tissue in independent associations with cardiovascular risk SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE muscle fat; adipose tissue; imaging; body composition; health risk ID BODY-FAT DISTRIBUTION; CORONARY-HEART-DISEASE; NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; DIABETES-MELLITUS; ABDOMINAL FAT; METABOLIC SYNDROME; THIGH MUSCLE; OBESE WOMEN; MEN AB Background: The metabolic implications of intermuscular adipose tissue (IMAT) are poorly understood compared to those of visceral adipose tissue (VAT) even though the absolute quantities of both depots are similar in many individuals. Objective: The aim was to determine the independent relationship between whole-body IMAT and cardiovascular risk factor parameters. Design: Whole body magnetic resonance imaging (MRI) was used to quantify total skeletal muscle (SM), total adipose tissue (TAT) of which IMAT, defined as the AT visible by MRI within the boundary of the muscle fascia, is a sub-component. Fasting serum measures (n=262) of glucose, total cholesterol (T-Chol), high-density lipoprotein cholesterol (HDL-Chol), triglycerides (TG),protein bound glucose (PBG, n=206) and insulin (n=119) were acquired in healthy African-American (AA, n=78) and Caucasian (Ca, n=109) women (body mass index (BMI) 26.5 +/- 5.7 kg/m(2); 44.4 +/- 16.4 years) and men (39 AA, 62 Ca; BMI 25.6 +/- 3.5 kg/m(2); 45.6 +/- 17.4 years). General linear models identified the independent effects of IMAT after covarying for SM, VAT, TAT, race, sex and two-way interactions. Results: Significant independent associations were observed for IMAT with glucose (P<0.001), PBG (P<0.001) and T-Chol (P<0.05). The association of IMAT with cholesterol differed by race in such a manner that for a unit increase in IMAT, T-Chol increased more rapidly in Ca compared to AA (P<0.05). TG, HDL-Chol and insulin had no independent association with IMAT. Conclusion: The strong independent associations of IMAT with fasting glucose and PBG suggest that IMAT may be related to glucose metabolism; however, IMAT is also associated with T-Chol in Ca. C1 Columbia Univ, St Lukes Roosevelt Hosp, Obes Res Ctr, Dept Med, New York, NY USA. NIA, Lab Epidemiol Demography & Biometry, Geriatr Epidemiol Sect, Bethesda, MD 20892 USA. Columbia Univ, Inst Human Nutr, New York, NY 10032 USA. RP Gallagher, D (reprint author), Columbia Univ, Obes Res Ctr, Dept Med, 1090 Amsterdam Ave, New York, NY 10025 USA. EM dg108@columbia.edu OI Gallagher, Dympna/0000-0003-1769-9754 FU NCRR NIH HHS [M01 RR000645, RR00645]; NIA NIH HHS [AG14715, R29 AG014715, R29 AG014715-05]; NIDDK NIH HHS [DK40414, DK42618, P01 DK042618, P01 DK042618-120006, P01 DK042618-15] NR 36 TC 58 Z9 58 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 2007 VL 31 IS 9 BP 1400 EP 1405 DI 10.1038/sj.ijo.0803621 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 205CF UT WOS:000249090000009 PM 17452994 ER PT J AU Yanoff, LB Menzie, CM Denkinger, B Sebring, NG McHugh, T Remaley, AT Yanovski, JA AF Yanoff, L. B. Menzie, C. M. Denkinger, B. Sebring, N. G. McHugh, T. Remaley, A. T. Yanovski, J. A. TI Inflammation and iron deficiency in the hypoferremia of obesity SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE iron deficiency; adiposity; ferritin; inflammation; C-reactive protein; transferrin receptor ID SOLUBLE TRANSFERRIN RECEPTOR; SERUM FERRITIN; BINDING-CAPACITY; CHRONIC DISEASE; HEPCIDIN; ADOLESCENTS; INDEXES; ANEMIA; POPULATIONS; ABSORPTION AB Context: Obesity is associated with hypoferremia, but it is unclear if this condition is caused by insufficient iron stores or diminished iron availability related to inflammation-induced iron sequestration. Objective: To examine the relationships between obesity, serum iron, measures of iron intake, iron stores and inflammation. We hypothesized that both inflammation-induced sequestration of iron and true iron deficiency were involved in the hypoferremia of obesity. Design: Cross-sectional analysis of factors anticipated to affect serum iron. Setting: Outpatient clinic visits. Patients: Convenience sample of 234 obese and 172 non-obese adults. Main outcome measures: Relationships between serum iron, adiposity, and serum transferrin receptor, C-reactive protein, ferritin, and iron intake analyzed by analysis of covariance and multiple linear regression. Results: Serum iron was lower (75.8 +/- 35.2 vs 86.5 +/- 34.2 g/dl, P=0.002), whereas transferrin receptor (22.6 +/- 7.1 vs 21.0 +/- 7.2 nmol/l, P=0.026), C-reactive protein (0.75 +/- 0.67 vs 0.34 +/- 0.67 mg/dl, P<0.0001) and ferritin (81.1 +/- 88.8 vs 57.6 +/- 88.7 mg/l, P=0.009) were higher in obese than non-obese subjects. Obese subjects had a higher prevalence of iron deficiency defined by serum iron (24.3%, confidence intervals (CI) 19.3-30.2 vs 15.7%, CI 11.0-21.9%, P=0.03) and transferrin receptor (26.9%, CI 21.6-33.0 vs 15.7%, CI 11.0-21.9%, P=0.0078) but not by ferritin (9.8%, CI 6.6-14.4 vs 9.3%, CI 5.7-14.7%, P=0.99). Transferrin receptor, ferritin and C-reactive protein contributed independently as predictors of serum iron. Conclusions: The hypoferremia of obesity appears to be explained both by true iron deficiency and by inflammatory-mediated functional iron deficiency. C1 NICHHD, Dev Endocrinol Branch, Unit Growth & Obes, Bethesda, MD 20892 USA. NIH, Hatfield Clin Res Ctr, Dept Nutr, Bethesda, MD 20892 USA. NIH, Dept Nursing, Hatfield Clin Res Ctr, DHHS, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Hatfield Clin Res Ctr, DHHS, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHHD, NIH, Hatfield Clin Res Ctr, Unit Growth & Obes,Dev Endocrinol Branch, Room 1E-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM jy15i@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [Z01 HD-00641, Z01 HD000641]; NIH HHS [Y2-OD-2067] NR 42 TC 133 Z9 140 U1 4 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 2007 VL 31 IS 9 BP 1412 EP 1419 DI 10.1038/sj.ijo.0803625 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 205CF UT WOS:000249090000011 PM 17438557 ER PT J AU Hall, K Bain, H Chow, C AF Hall, Kevin Bain, Heather Chow, Carson TI How adaptations of macronutrient metabolism regulate body composition - Abstracts SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Meeting Abstract CT 15th European Congress on Obesity CY APR 22-25, 2007 CL Budapest, HUNGARY C1 NIH, Bethesda, MD 20892 USA. RP Hall, K (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. RI Hall, Kevin/F-2383-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 2007 VL 31 IS 9 BP 1485 EP 1485 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 205CF UT WOS:000249090000027 ER PT J AU Cizza, G Smirne, N Brancati, G AF Cizza, Giovanni Smirne, Nicoletta Brancati, Giacomino TI Obesity and sleep deprivation are alarmingly high in a rural southern Italian population and BMI is inversely related with sleep time and sleep quality: Implications for increased diabetes risk SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Meeting Abstract CT 15th European Congress on Obesity CY APR 22-25, 2007 CL Budapest, HUNGARY C1 NIDDK, NIH, Inst Endocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 2007 VL 31 IS 9 BP 1487 EP 1487 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 205CF UT WOS:000249090000031 ER PT J AU Brooks, BP Larson, DM Chan, CC Kjellstrom, S Smith, RS Crawford, MA Lamoreux, L Huizing, M Hess, R Jiao, XD Hejtmancik, JF Maminishkis, A John, SWM Bush, R Pavan, WJ AF Brooks, Brian P. Larson, Denise M. Chan, Chi-Chao Kjellstrom, Sten Smith, Richard S. Crawford, Mary A. Lamoreux, Lynn Huizing, Marjan Hess, Richard Jiao, Xiaodong Hejtmancik, J. Fielding Maminishkis, Arvydas John, Simon W. M. Bush, Ronald Pavan, William J. TI Analysis of ocular Hypopigmentation in Rab38(cht/cht) mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HERMANSKY-PUDLAK-SYNDROME; LYSOSOME-RELATED ORGANELLES; OCULOCUTANEOUS ALBINISM; DBA/2J MICE; MUTATIONS; PROTEIN; RAB38; GENES; BROWN; LOCI AB PURPOSE. To characterize the ocular phenotype resulting from mutation of Rab38, a candidate gene for Hermansky-Pudlak syndrome. METHODS. Chocolate mice (cht, Rab38(cht/cht)) and control heterozygous (Rab38(cht/+)) and wild-type mice were examined clinically, histologically, ultrastructurally, and electrophysiologically. Mice homozygous for both the Rab38(cht) and the Tyrp1(b) alleles were similarly examined. RESULTS. Rab38(cht/cht) mice showed variable peripheral iris transillumination defects at 2 months of age. Patches of RPE hypopigmentation were noted clinically in 57% of Rab38(cht/cht) eyes and 6% of Rab38(cht/+) eyes. Rab38(cht/cht) mice exhibited thinning of the iris and RPE and larger b-wave amplitudes in the scotopic range when compared with the control animals. Compared with wild-type mice, Rab38(cht/cht) melanosomes were smaller and there were fewer in neuroectodermally derived retinal pigment epithelium; in neural crest-derived choroid melanocytes, they were smaller in size only. Mutation of both Rab38 and Tyrp1 produced mice with ocular and coat color pigment dilution greater than that seen with either mutation alone. Comprehensive clinical and pathologic analyses showed no other organ system or blood defects in Rab38(cht/cht) mice. CONCLUSIONS. Rab38(cht/cht) mice show ocular characteristics reminiscent of human oculocutaneous albinism, as well as iris and RPE thinning. The synergistic effects of the Rab38(cht) and Tyrp1(b) alleles suggest that TYRP1 is not the only target of RAB38 trafficking. This mouse line provides a useful model for studying melanosome biology and its role in human ocular diseases. C1 NEI, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bar Harbor, ME USA. Jackson Lab, Bar Harbor, ME 04609 USA. Texas A&M Univ, Comparat Genet Program, College Stn, TX USA. RP Brooks, BP (reprint author), NEI, NIH, Bldg 10,Room 10B16, Bethesda, MD 20892 USA. EM brooksb@mail.nih.gov FU Intramural NIH HHS; NEI NIH HHS [EY01475, EY11721, R01 EY011721, R29 EY011721] NR 38 TC 13 Z9 13 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 2007 VL 48 IS 9 BP 3905 EP 3913 DI 10.1167/iovs.06-1464 PG 9 WC Ophthalmology SC Ophthalmology GA 204RO UT WOS:000249061900001 PM 17724166 ER PT J AU Hansen, L Yao, WL Eiberg, H Kjaer, KW Baggesen, K Hejtmancik, JF Rosenberg, T AF Hansen, Lars Yao, Wenliang Eiberg, Hans Kjaer, Klaus Wilbrandt Baggesen, Kirsten Hejtmancik, J. Fielding Rosenberg, Thomas TI Genetic heterogeneity in microcornea-cataract: Five novel mutations in CRYAA, CRYGD, and GJA8 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ANTERIOR SEGMENT DYSGENESIS; HEAT-SHOCK-PROTEIN; DNA-BINDING DOMAIN; CONGENITAL CATARACT; ALPHA-CRYSTALLIN; MISSENSE MUTATION; INDIAN FAMILY; IRIS COLOBOMA; GLAUCOMA; MAF AB PURPOSE. To unravel the molecular genetic background in families with congenital cataract in association with microcornea (CCMC, OMIM 116150). METHODS. CCMC families were recruited from a national database on hereditary eye diseases; DNA was procured from a national gene bank on hereditary eye diseases and by blood sampling from one large family. Genomewide linkage analysis, fine mapping, and direct genomic DNA sequencing of nine cataract candidate genes were applied. Restriction enzyme digests confirmed identified mutations. RESULTS. Analyses of 10 Danish families with hereditary congenital cataract and microcornea revealed five novel mutations. Three of these affected the crystallin, alpha-A gene (CRYAA), including two mutations (R12C and R21W) in the crystallin domain and one mutation (R116H) in the small heat shock domain. One mutation (P189L) affected the gap junction protein alpha 8 (GJA8), and one mutation (Y134X) was detected in crystallin gamma-D (CRYGD). CONCLUSIONS. The identification of a CRYGD mutation adds another gene to those that may be mutated in CCMC and underscores the genetic heterogeneity of this condition. Three CRYAA mutations at the R116 position, in association with CCMC, suggest that R116 represents a CCMC-mutational hot-spot. The CCMC phenotype demonstrates variable expression with regard to cataract morphology and age of appearance. Clinical heterogeneity, including additional malformation of the anterior segment of the eye, confirm that dedicated cataract genes may be involved in the largely unknown developmental molecular mechanisms involved in lens-anterior segment interactions. C1 Univ Copenhagen, Panum Inst, Inst Med Biochem & Genet, Dept G, DK-2200 Copenhagen N, Denmark. Univ Copenhagen, Panum Inst, Inst Med Biochem & Genet, Wilhelm Johannsen Ctr Funct Genome Res, DK-2200 Copenhagen, Denmark. NEI, Sect Ophthalm Mol Genet, NIH, Bethesda, MD USA. NEI, Visual Funct Branch, NIH, Bethesda, MD USA. Aalborg Univ Hosp, Dept Ophthalmol, Aalborg, Denmark. Kennedy Inst, Natl Eye Clin, Gordon Norrie Ctr Genet Eye Dis, Hellerup, Denmark. RP Hansen, L (reprint author), Univ Copenhagen, Panum Inst, Inst Med Biochem & Genet, Dept G, Bldg 24-4,Blegdamsvej 3b, DK-2200 Copenhagen N, Denmark. EM larsh@imbg.ku.dk NR 43 TC 83 Z9 89 U1 0 U2 3 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 2007 VL 48 IS 9 BP 3937 EP 3944 DI 10.1167/iovs.07-0013 PG 8 WC Ophthalmology SC Ophthalmology GA 204RO UT WOS:000249061900005 PM 17724170 ER PT J AU Peet, JA Cotch, MF Wojciechowski, R Bailey-Wilson, JE Stambolian, D AF Peet, Jon A. Cotch, Mary-Frances Wojciechowski, Robert Bailey-Wilson, Joan E. Stambolian, Dwight TI Heritability and familial aggregation of refractive error in the old order amish SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HIGH MYOPIA MAPS; NEAR-WORK ACTIVITY; OCULAR REFRACTION; CHROMOSOME 18P; UNITED-STATES; POPULATION; LOCUS; LINKAGE; SCAN; ENVIRONMENT AB PURPOSE. To determine the heritability of refractive error and familial aggregation of myopia and hyperopia in an elderly Old Order Amish ( OOA) population. METHODS. Nine hundred sixty-seven siblings ( mean age, 64.2 years) in 269 families were recruited for the Amish Eye Study in the Lancaster County area of Pennsylvania. Refractive error was determined by noncycloplegic manifest refraction. Heritability of refractive error was estimated with multivariate linear regression as twice the residual sibling-sibling correlation after adjustment for age and gender. Logistic regression models were used to estimate the sibling recurrence odds ratio (ORs). Myopia and hyperopia were defined with five different thresholds. RESULTS. The age- and gender-adjusted heritability of refractive error was 70% (95% CI: 48%-92%) in the OOA. Age and gender-adjusted ORs and sibling recurrence risk (lambda(s)), with different thresholds defining myopia ranged from 3.03 ( 95% CI: 1.58-5.80) to 7.02 ( 95% CI: 3.41-14.46) and from 2.36 ( 95% CI: 1.65-3.19) to 5.61 ( 95% CI: 3.06-9.34). Age and gender-adjusted ORs and lambda(s) for different thresholds of hyperopia ranged from 2.31 ( 95% CI: 1.56-3.42) to 2.94 ( 95% CI: 2.04-4.22) and from 1.33 ( 95% CI: 1.22-1.43) to 1.85 ( 95% CI: 1.18-2.78), respectively. Women were significantly more likely than men to have hyperopia. There was no significant gender difference in the risk of myopia. CONCLUSIONS. In the OOA, refractive error is highly heritable. Hyperopia and myopia aggregate strongly in OOA families. C1 Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Stambolian, D (reprint author), 313B Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA. EM stamboli@mail.med.upenn.edu OI Cotch, Mary Frances/0000-0002-2046-4350; Bailey-Wilson, Joan/0000-0002-9153-2920; Wojciechowski, Robert/0000-0002-9593-4652 FU Intramural NIH HHS [Z01 EY000405-05, Z01 EY000405-06, Z01 HG200327-03, Z99 EY999999, Z99 HG999999, ZIA EY000405-07, ZIA EY000405-08, ZIA EY000405-09]; NEI NIH HHS [2R01 EY012226, N01-EY1-2113, R01 EY012226, R01 EY012226-05, Z01 EY000405, Z01EY000405] NR 35 TC 23 Z9 23 U1 0 U2 0 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 2007 VL 48 IS 9 BP 4002 EP 4006 DI 10.1167/iovs.06-1388 PG 5 WC Ophthalmology SC Ophthalmology GA 204RO UT WOS:000249061900014 PM 17724179 ER PT J AU Lanzieri, TM Pinto, D Prevots, DR AF Lanzieri, Tatiana Miranda Pinto, Diana Prevots, D. Rebecca TI Impact of rubella vaccination strategy on the occurrence of congenital rubella syndrome SO JORNAL DE PEDIATRIA LA English DT Article ID UNITED-STATES; SYNDROME CRS; BRAZIL; BURDEN; ELIMINATION; OUTBREAK AB Objective: Routine rubella vaccination was introduced in Paraiba, northeastern Brazil, through a catch-up campaign targeting children aged 1-11 years, in 1998. A campaign among women of childbearing age was conducted in 2001, We describe the epidemiology of rubella and congenital rubella syndrome (CRS) in the state of Paraiba between 1999 and 2005. Methods: Rubella and CRS surveillance data for the 1999-2005 period were analyzed. Suspected cases of rubella were confirmed by laboratory findings, epidemiological link, or clinical data. International standardized CRS definitions were used. Results: Of 5,924 suspected cases of rubella between 1999 and 2005, 1,266 (21%) were confirmed, 766 (61%) by laboratory findings. During a rubella epidemic in 2000 (18.8/100,000), the incidence among individuals aged 14-19 years (42/100,000) had a fourfold increase relative to children aged 1-13 years (95% confidence interval = 3.2-5.1). The overall rubella incidence was 0.9/100,000 in 2005. Of 177 suspected cases of CRS between 1999 and 2005, 167 (94%) were tested for IgM. Of 14 (8%) laboratory confirmed cases of CRS, 12 (86%) were born in 2001, with an incidence of 0.2/100,000 children aged less than 1 year. Conclusions: The 1998 rubella vaccination campaign was insufficient to prevent an outbreak among young adults in 2000, with a high CRS incidence in 2001. Between 2002 and 2005 the incidence of rubella and CRS decreased; however, high routine vaccination coverage and high-quality surveillance remain critically important to achieve CRS elimination by 2010. C1 [Lanzieri, Tatiana Miranda] SCS, Secretaria Vigilancia Saude, Minist Saude, BR-70304000 Brasilia, DF, Brazil. [Pinto, Diana] Secretaria Estado Saude Parabia, Joao Pessoa, Paraiba, Brazil. [Prevots, D. Rebecca] NIAID, NIH, Bethesda, MD 20892 USA. RP Lanzieri, TM (reprint author), SCS, Secretaria Vigilancia Saude, Minist Saude, SCS Quadra 4,Bloco A, BR-70304000 Brasilia, DF, Brazil. NR 22 TC 3 Z9 3 U1 0 U2 0 PU SOC BRASIL PEDIATRIA PI RIO DE JANEIRO, RJ PA RUA SANTA CLARA 292, RIO DE JANEIRO, RJ, CEP 22401-01, BRAZIL SN 0021-7557 J9 J PEDIAT JI J. Pediatr. PD SEP-OCT PY 2007 VL 83 IS 5 BP 415 EP 421 DI 10.2223/JPED.1692 PG 7 WC Pediatrics SC Pediatrics GA 281OG UT WOS:000254506600004 PM 17853958 ER PT J AU Shields, JJ Broome, KM Delany, PJ Fletcher, BW Flynn, PM AF Shields, Joseph J. Broome, Kirk M. Delany, Peter J. Fletcher, Bennett W. Flynn, Patrick M. TI Religion and substance abuse treatment: Individual and program effects SO JOURNAL FOR THE SCIENTIFIC STUDY OF RELIGION LA English DT Article ID FOLLOW-UP OUTCOMES; DRUG-ABUSE; TREATMENT RETENTION; MORAL-COMMUNITIES; TIME SPENT; DELINQUENCY; ALCOHOL; DATOS; HELLFIRE; INVOLVEMENT AB The relationship between personal religiousness and substance abuse treatment outcomes has emerged as an important issue in the public health arena. Using the " moral community" perspective, a conceptual framework developed by Stark, Kent, and Doyle (1982) to analyze the contextual effects of religion, we explore the degree to which religion influences two drug treatment outcome measures - critical retention and commitment to treatment. The data are derived from the Drug Abuse Treatment Outcome Studies (DATOS), a national study of 10,010 clients enrolled in 70 drug treatment programs. Three research questions were addressed: (1) What is the relationship between an individual's level of religiosity and retention in treatment and commitment to treatment? (2) How does the ecological context of treatment programs shape the individual-level relationships? (3) To what extent are program practices and characteristics directly linked to outcome level? The findings are supportive of the literature that shows a weak to moderate relationship between religiosity and treatment outcomes. However, the findings did not show strong support for the "moral community" hypothesis. Although there was a wide variation in the size of the individual-level religiosity - treatment correlations, the variation could not be conclusively attributed to the overall religious emphasis of the programs. The findings suggest that further research is needed in order to understand fully the role of religion in substance abuse treatment. C1 Catholic Univ Amer, Natl Catholic Sch Social Serv, Washington, DC 20064 USA. Texas Christian Univ, Inst Behav Res, Ft Worth, TX 76129 USA. Natl Inst Drug Abuse, Natl Inst Hlth, Bethesda, MD 20892 USA. NIAAA, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Shields, JJ (reprint author), Catholic Univ Amer, Natl Catholic Sch Social Serv, Washington, DC 20064 USA. EM Shields@cua.edu; k.broome@tcu.edu; delanyp@mail.nih.gov; Bfletche@mail.nih.gov; p.flynn@tcu.edu NR 59 TC 9 Z9 9 U1 8 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-8294 J9 J SCI STUD RELIG JI J. Sci. Stud. Relig. PD SEP PY 2007 VL 46 IS 3 BP 355 EP 371 DI 10.1111/j.1468-5906.2007.00363.x PG 17 WC Sociology; Religion SC Sociology; Religion GA 210JR UT WOS:000249453000005 ER PT J AU Levin, KH Herning, RI Better, WE Epstein, DH Cadet, JL Gorelick, DA AF Levin, Kenneth H. Herning, Ronald I. Better, Warren E. Epstein, David H. Cadet, Jean-Lud Gorelick, David A. TI EEG absolute power during extended cocaine abstinence SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE cocaine; abstinence; withdrawal; EEG; longitudinal ID QUANTITATIVE EEG; NEUROLOGICAL COMPLICATIONS; DEPRESSIVE TRAITS; DRUG-ABUSE; DEPENDENCE; WITHDRAWAL; SMOKING; USERS; FREQUENCY; AMPLITUDE AB We examined the effects of cocaine withdrawal on EEG during 3 months of abstinence. Twenty physically healthy cocaine users (80% men, 80% African American, mean (SD) age, 34.8 (4.1) years, 9 (5.4) years of cocaine use, minimal recent use of other drugs) were subject to I to 3 EEG recordings during 3 months of monitored abstinence on a closed clinical research ward. Three-minute eyes closed EEG recordings used 8 or 16 leads located at standard International 10/20 scalp sites. First EEG was recorded 16.8 (13.6) days after last cocaine use. Betal absolute power in the left temporal region and delta power in the mid right hemisphere (temporal region) increased significantly over time. Eight subjects tested during the first 2 weeks of abstinence showed trends toward decreased absolute power in all bands except beta] in the left frontal region, and toward decreased absolute delta power in the mid right hemisphere, compared with 8 nondrug-using controls. These results are not totally consistent with some previous studies, which may be the result of differences in Subject characteristics and EEG recording procedures. The findings suggest that chronic cocaine use is associated with EEG changes that may reflect persisting brain electrophysiological abnormalities during cocaine abstinence. C1 [Levin, Kenneth H.; Herning, Ronald I.; Better, Warren E.; Epstein, David H.; Cadet, Jean-Lud; Gorelick, David A.] Natl Inst Drug Abuse, NIH, Intramural Res Program, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Gorelick, DA (reprint author), Natl Inst Drug Abuse, NIH, Intramural Res Program, Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov NR 35 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD SEP PY 2007 VL 1 IS 3 BP 139 EP 144 DI 10.1097/ADM.0b013e3180f493ee PG 6 WC Substance Abuse SC Substance Abuse GA 305GL UT WOS:000256165800004 PM 21768949 ER PT J AU Spriggs, AL Iannotti, RJ Nansel, TR Haynie, DL AF Spriggs, Aubrey L. Iannotti, Ronald J. Nansel, Tonja R. Haynie, Denise L. TI Adolescent bullying involvement and perceived family, peer and school relations: Commonalities and differences across race/ethnicity SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE bullying; race/ethnicity; prevention; HBSC; family; school; peers ID AGGRESSIVE VICTIMS; DISTINCT GROUPS; VICTIMIZATION; BULLIES; INTERVENTIONS; BEHAVIOR; RISK; PREVALENCE; CHILDHOOD; EXPOSURE AB Purpose: Although bullying is recognized as a serious problem in the United States, little is known about racial/ethnic differences in bullying risk. This study examined associations between bullying and family, peer, and school relations for white, black and Hispanic adolescents. Methods: A nationally representative sample (n = 11,033) of adolescents in grades six to ten participated in the 2001 Health Behaviors in School-Aged Children survey, self-reporting bullying involvement and information on family, peer and school relations. Descriptive statistics and multinormal logistic regression analyses controlling for gender, age and affluence were stratified by race/ethnicity. Results: Nine percent of respondents were victims of bullying, 9% were bullies, and 3% were bully-victims. Black adolescents reported a significantly lower prevalence of victimization than white and Hispanic students. Multivariate results indicated modest racial/ethnic variation in associations between bullying and family, peer, and school factors. Parental communication, social isolation, and classmate relationships were similarly related to bullying across racial/ethnic groups. Living with two biological parents was protective against bullying involvement for white students only. Furthermore, although school satisfaction and performance were negatively associated with bullying involvement for white and Hispanic students, school factors were largely unrelated to bullying among black students. Conclusions: Although school attachment and performance were inconsistently related to bullying behavior across race/ethnicity, bullying behaviors are consistently related to peer relationships across black, white, and Hispanic adolescents. Negative associations between family communication and bullying behaviors for white, black, and Hispanic adolescents suggest the importance of addressing family interactions in future bullying prevention efforts. (c) 2007 Society for Adolescent Medicine. All rights reserved. C1 Univ N Carolina, Dept Maternal & Child Hlth, Chapel Hill, NC 27599 USA. Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA. NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Spriggs, AL (reprint author), Univ N Carolina, Dept Maternal & Child Hlth, CB 7445, Chapel Hill, NC 27599 USA. EM spriggs@email.unc.edu OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079 FU Intramural NIH HHS [Z99 HD999999] NR 39 TC 176 Z9 178 U1 10 U2 53 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD SEP PY 2007 VL 41 IS 3 BP 283 EP 293 DI 10.1016/j.jadohealth.2007.04.009 PG 11 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 204OS UT WOS:000249054500011 PM 17707299 ER PT J AU Foroughi, S Foster, B Kim, N Bernardino, LB Scott, LM Hamilton, RG Metcalfe, DD Mannon, PJ Prussin, C AF Foroughi, Shabnam Foster, Barbara Kim, NaYoung Bernardino, Leigh B. Scott, Linda M. Hamilton, Robert G. Metcalfe, Dean D. Mannon, Peter J. Prussin, Calman TI Anti-IgE treatment of eosinophil-associated gastrointestinal disorders SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE eosinophil; eosinophilic gostroenteritis; eosinophilic esophagitis; omalizumab; IgE; food allergy; basophil ID EPSILON-RI EXPRESSION; BASOPHIL ACTIVATION; ALLERGIC-ASTHMA; SERUM IGE; F-RI; OMALIZUMAB; ESOPHAGITIS; THERAPY; INFLAMMATION; HISTAMINE AB Background: Eosinophil-associated gastrointestinal disorders (EGIDs) are commonly associated with atopy and are being recognized with increasing frequency. Current therapy for EGIDs is inadequate. Objective: We sought to determine the efficacy of anti-IgE therapy in EGIDs and investigate the role of IgE in disease pathogenesis. Methods: Nine subjects with EGIDs received omalizumab every 2 weeks for 16 weeks while other therapy was held constant. Blood absolute eosinophil counts, tissue eosinophil counts, symptom scores, and free IgE levels were serially measured. Allergen skin testing and flow cytometry for basophil activation and Fc epsilon RI were determined at baseline and at week 16. Results: Omalizumab was associated with a decrease in absolute eosinophil count at both the week 16 (34%, P =.004) and combined weeks 12 to 16 (42%, P =.012) time points. Tissue eosinophils decreased in the duodenum (59%) and gastric antrum (69%) but did not reach statistical significance (P =.074 and .098, respectively). Esophageal eosinophil counts remained unchanged. Basophil and dendritic cell Fc epsilon RI expression and free IgE levels were all significantly decreased (P <.005). Omalizumab increased the concentration of allergen required to trigger half-maximal basophil activation by 170-fold. Allergen skin test wheal and erythema responses decreased by 78% and 82%, respectively. Symptom scores were decreased at both the midstudy (63%) and end of study (70%) time points (P <.005 for both). Conclusion: These results demonstrate that IgE-mediated processes contribute to the generation of eosinophilic inflammation in EGIDs and suggest that anti-IgE therapy might be effective in these disorders. Clinical implications: Anti-IgE might be a potential therapy for EGIDs. C1 NIH, Bethesda, MD 20892 USA. Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Lab Allerg Dis, Bethesda, MD USA. Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Host Def Lab, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Clin Immunol & Allergy, Baltimore, MD USA. RP Prussin, C (reprint author), NIH, Bldg 10,Room 11C205, Bethesda, MD 20892 USA. EM cprussin@niaid.nih.gov OI Prussin, Calman/0000-0002-3917-3326 FU Intramural NIH HHS [Z01 AI000761-10]; NIAID NIH HHS [Z01 AI000761] NR 21 TC 69 Z9 71 U1 0 U2 1 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 2007 VL 120 IS 3 BP 594 EP 601 DI 10.1016/j.jaci.2007.06.015 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 211DV UT WOS:000249505400018 PM 17765756 ER PT J AU Kattan, M Gergen, PJ Eggleston, P Visness, CM Mitchell, HE AF Kattan, Meyer Gergen, Peter J. Eggleston, Peyton Visness, Cynthia M. Mitchell, Herman E. TI Health effects of indoor nitrogen dioxide and passive smoking on urban asthmatic children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE asthma; nitrogen dioxide; tobacco smoke; pollution; passive smoking ID INNER-CITY CHILDREN; RESPIRATORY SYMPTOMS; CHILDHOOD ASTHMA; AIR-POLLUTION; RISK-FACTORS; PERSONAL EXPOSURE; PARENTAL SMOKING; LUNG-FUNCTION; ASSOCIATION; MORBIDITY AB Background: Nitrogen dioxide (NO2) and environmental tobacco smoke (ETS) have been associated with adverse respiratory effects. Objective: We sought to assess the effect of NO2 and ETS on asthma morbidity among children in inner-city environments. Methods: Asthmatic children between the ages of 4 and 9 years had exposure to NO2 and ETS measured by using Palmes tubes in the home and urinary cotinine. A baseline interview and telephone assessments at 3, 6, and 9 months evaluated health service use, asthma symptoms, and peak flow rates. Results: Gas stoves were present in 87.8% of 469 homes. The median level of indoor NO2 was 29.8 ppb compared with the US national outdoor median of 18 ppb. Of 1444 children, 48% had urinary cotinine/creatinine ratios of greater than 30 ng/mg. The median level of the cotinine/creatinine ratio was 42.4 ng/mg in smoking homes compared with 18.0 ng/mg in nonsmoking homes. The relative risk for asthma symptoms with increased NO2 exposure was 1.75 (95% CI, 1.10-2.78) in children who did not have positive skin test responses. Higher NO2 exposure resulted in lower peak flows during colder months (relative risk, 1.46; 95% CI, 1.07-1.97). Higher ETS exposure in colder months was weakly associated with lower peak flows (relative risk, 1.21; 95% CI, 0.99-1.47). There was no effect of ETS exposure on symptoms or use of health care services. Conclusion: Higher levels of indoor NO2 are associated with increased asthma symptoms in nonatopic children and decreased peak flows.Clinical implications: Interventions to reduce NO2 exposure, such as venting of gas stoves, might help reduce asthma morbidity. C1 Univ Hosp Columbia & Cornell, Childrens Hosp New York Presbyterian, Dept Pediat, New York, NY 10032 USA. Mt Sinai Sch Med, Dept Pediat, New York, NY USA. Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Div Allergy Immunol & Transplantat, Asthma Allergy & Inflammat Branch, Bethesda, MD USA. Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA. Rho Fed Syst Div Inc, Chapel Hill, NC USA. RP Kattan, M (reprint author), Univ Hosp Columbia & Cornell, Childrens Hosp New York Presbyterian, Dept Pediat, 3959 Broadway, New York, NY 10032 USA. EM meyer.kattan@mssm.edu FU PHS HHS [A1-30752, A1-30756, A1-30772, A1-30773-01, A1-30777, A1-30779, A1-30780, N01-A1-15105, UOI A1-30751] NR 41 TC 67 Z9 69 U1 1 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2007 VL 120 IS 3 BP 618 EP 624 DI 10.1016/j.jaci.2007.05.014 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 211DV UT WOS:000249505400021 PM 17582483 ER PT J AU Maric, I Robyn, J Metcalfe, DD Fay, MP Carter, M Wilson, T Fu, WM Stoddard, J Scott, L Hartsell, M Kirshenbaum, A Akin, C Nutman, TB Noel, P Klion, AD AF Maric, Irina Robyn, Jamie Metcalfe, Dean D. Fay, Michael P. Carter, Melody Wilson, Todd Fu, Weiming Stoddard, Jennifer Scott, Linda Hartsell, Marilyn Kirshenbaum, Arnold Akin, Cem Nutman, Thomas B. Noel, Pierre Klion, Amy D. TI KIT D816V-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are distinct entities SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE systemic mastocytosis; hypereosinophilic syndrome; HES; mast cell disease; eosinophilia; FIP1L1/PDGFRA; imatinib; KIT D816V mutation ID MAST-CELL DISEASE; IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; CHRONIC MYELOID DISORDERS; ELEVATED SERUM TRYPTASE; C-KIT; IMATINIB MESYLATE; MYELOPROLIFERATIVE VARIANT; FIP1L1-PDGFRA FUSION; WILD-TYPE; INHIBITOR AB Background: The broad and overlapping clinical manifestations of D816V KIT-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia (CEL), coupled with the increase in activated eosinophils and mast cells seen in both disorders, have led to confusion in the nomenclature. It is of paramount importance, however, to distinguish between these 2 groups of patients because of differences in clinical sequelae, prognoses, and selection of treatment. Objective: We thus sought to identify clinical and laboratory features that could be used to distinguish these 2 diagnoses. Methods: We compared 12 patients with D816V-positive systemic mastocytosis with eosinophilia with 17 patients with FIP1L1/PDGFRA-positive CEL. Distinguishing features were used to create a risk factor scoring system. Results: This system correctly classified 16 of 17 FIP1L1/ PDGFRA-positive patients with CEL and all 12 patients with systemic mastocytosis with eosinophilia. Thirty-four FIP1L1/ PDGFRA-positive patients described in the literature were also classified using this system, and although a complete set of data was not available for any of the historical patients, 21 were correctly classified. Conclusion: These results reinforce the hypothesis that the FIP1L1/PDGFRA gene fusion and D816V-KIT mutation cause distinct clinical syndromes. Clinical implications: This novel diagnostic approach should prove helpful in clinical practice in the evaluation of patients with increased mast cells and peripheral eosinophilia. C1 NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Div Allergy & Immunol, Ann Arbor, MI 48109 USA. RP Maric, I (reprint author), NIH, Hematol Sect, Dept Lab Med, Ctr Clin, 10 Ctr Dr,Bldg 10-Room 2C390, Bethesda, MD 20892 USA. EM marici@mail.nih.gov RI Fay, Michael/A-2974-2008; OI Klion, Amy/0000-0002-4986-5326; Fay, Michael P./0000-0002-8643-9625; Akin, Cem/0000-0001-6301-4520 FU Intramural NIH HHS NR 34 TC 58 Z9 60 U1 0 U2 1 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 2007 VL 120 IS 3 BP 680 EP 687 DI 10.1016/j.jaci.2007.05.024 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 211DV UT WOS:000249505400030 PM 17628645 ER PT J AU Lay, JC Alexis, NE Kleeberger, SR Roubey, RAS Harris, BD Bromberg, PA Hazucha, MJ Devlin, RB Peden, DB AF Lay, John C. Alexis, Neil E. Kleeberger, Steven R. Roubey, Robert A. S. Harris, Bradfrd D. Bromberg, Philip A. Hazucha, Milan J. Devlin, Robert B. Peden, David B. TI Ozone enhances markers of innate immunity and antigen presentation on airway monocytes in healthy individuals SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID IN-VIVO; EXPOSURE; ASTHMA; VOLUNTEERS C1 Univ N Carolina, Sch Med, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC 27515 USA. Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. Natl Inst Environm Hlth, Lab Res Biol, Res Triangle Pk, NC USA. US EPA, Natl Hlth Environm Effects Res Lab, Human Studies Div, Clin Res Branch, Res Triangle Pk, NC 27711 USA. RP Lay, JC (reprint author), Univ N Carolina, Sch Med, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC 27515 USA. EM jcl@med.unc.edu RI Lay, John/A-6380-2012 FU NCRR NIH HHS [M01 RR000046-461441, M01 RR000046]; NIEHS NIH HHS [R01 ES012706, R01 ES012706-03] NR 9 TC 33 Z9 33 U1 0 U2 1 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 2007 VL 120 IS 3 BP 719 EP 722 DI 10.1016/j.jaci.2007.05.005 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 211DV UT WOS:000249505400037 PM 17586033 ER PT J AU Gray, DE Messer, D Porter, A Hefner, B Logan, D Harris, RK Clark, AP Algaier, JA Overstreet, JD Smith, CS AF Gray, Dean E. Messer, Dale Porter, Andrew Hefner, Brian Logan, Dania Harris, Roger K. Clark, Alice P. Algaier, Joseph A. Overstreet, J. Diane Smith, Cynthia S. TI Analysis of flavonol aglycones and terpenelactones in Ginkgo biloba extract: A comparison of high-performance thin-layer chromatography and column high-performance liquid chromatography SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID EVAPORATIVE LIGHT-SCATTERING; HPTLC AB Advancements in automated high-performance thin-layer chromatography (HPTLC) have made it feasible to assess its use for the quantitative analysis of marker compounds in botanical preparations. We report here the findings of method comparisons for the terpenelactones and flavonol aglycones by column high-performance liquid chromatography (HPLC) with evaporative light scattering and UV detection, and HPTLC with a scanning densitometer. For the HPTLC assay of terpenelactones, total bilobalide, ginkgolide A, and ginkgolide B consistently achieved <70% of the total determined using HPLC, regardless of variations to postchromatographic derivatization time and temperature. Accuracy testing showed the possibility of a matrix interference. In contrast, a good relationship (95%) was determined between HPTLC and HPLC for determination of total flavonol glycosides (calculated from combined quercetin, kaempferol, and isorhamnetin) from an acid-hydrolyzed Ginkgo biloba L. (GBE) sample. The HPTLC flavonol aglycone method also performed well in terms of accuracy (overall average of 96% recovery for the 3 aglycones) and consecutive plate repeatability (overall percent relative standard deviation of 4.4). It is demonstrated that HPTLC can be a time-saving complement to HPLC for routine analysis of the flavonol glycosides in GBE. C1 Midwest Res Inst, Kansas City, MO 64110 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Gray, DE (reprint author), Midwest Res Inst, 425 Volker Blvd, Kansas City, MO 64110 USA. EM dgray@mriresearch.org FU NIEHS NIH HHS [N01-ES-05457] NR 19 TC 11 Z9 11 U1 1 U2 11 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2007 VL 90 IS 5 BP 1203 EP 1209 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 214QI UT WOS:000249752800001 PM 17955963 ER PT J AU Chen, HM Puhl, HL Ikeda, SR AF Chen, Huanmian Puhl, Henry L., III Ikeda, Stephen R. TI Estimating protein-protein interaction affinity in living cells using quantitative Forster resonance energy transfer measurements SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE Forster resonance energy transfer; protein-protein interaction; fluorescent proteins ID FLUORESCENT PROTEIN; FRET EFFICIENCY; LIVE CELLS; MICROSCOPY; PREASSOCIATION; VARIANT; FLIM AB We have previously demonstrated that Forster resonance energy transfer (FRET) efficiency and the relative concentration of donor and acceptor fluorophores can be determined in living cells using three-cube wide-field fluorescence microscopy. Here, we extend the methodology to estimate the effective equilibrium dissociation constant (Kd) and the intrinsic FRET efficiency (E(max)) of an interacting donor-acceptor pair. Assuming bimolecular interaction, the predicted FRET efficiency is a function of donor concentration, acceptor concentration, Kd, and Emax. We estimate Kd and Emax by minimizing the sum of the squared error (SSE) between the predicted and measured FRET efficiency. This is accomplished by examining the topology of SSE values for a matrix of hypothetical Kd and Emax values. Applying an F-test, the 95% confidence contour of Kd and E(max) is calculated. We test the method by expressing an inducible FRET fusion pair consisting of FKBP12-Cerulean and Frb-Venus in HeLa cells. As the Kd for FKBP12-rapamycin and Frb has been analytically determined, the relative Kd (in fluorescence units) could be calibrated with a value based on protein concentration. The described methodology should be useful for comparing protein-protein interaction affinities in living cells. (C) 2007 Society of Photo-Optical Instrumentation Engineers. C1 [Chen, Huanmian; Puhl, Henry L., III; Ikeda, Stephen R.] NIAAA, Lab Mol Physiol, NIH, Sect Transmitter Signaling, Bethesda, MD 20892 USA. RP Ikeda, SR (reprint author), NIAAA, Lab Mol Physiol, NIH, Sect Transmitter Signaling, 5265 Fishers Lane,Room TS11A,MSC 9411, Bethesda, MD 20892 USA. EM sikeda@mail.nih.gov OI Puhl, Henry/0000-0003-3095-7201; Ikeda, Stephen/0000-0002-4088-9508 FU Intramural NIH HHS NR 29 TC 23 Z9 24 U1 2 U2 15 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2007 VL 12 IS 5 AR 054011 DI 10.1117/1.2799171 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 239WS UT WOS:000251549600042 PM 17994899 ER PT J AU Gandjbakhche, A Vogel, A AF Gandjbakhche, Amir Vogel, Abby TI Optical diagnostic imaging from bench to bedside SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Editorial Material C1 [Gandjbakhche, Amir; Vogel, Abby] NIH, Bethesda, MD 20892 USA. RP Gandjbakhche, A (reprint author), NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2007 VL 12 IS 5 AR 051301 DI 10.1117/1.2801395 PG 1 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 239WS UT WOS:000251549600004 ER PT J AU Hama, Y Urano, Y Koyama, Y Choyke, PL Kobayashi, H AF Hama, Yukihiro Urano, Yasuteru Koyama, Yoshinori Choyke, Peter L. Kobayashi, Hisataka TI D-galactose receptor-targeted in vivo spectral fluorescence imaging of peritoneal metastasis using galactosamin-conjugated serum albumin-rhodamine green SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article; Proceedings Paper CT Conference on Water Environment-Membrane Technology CY JUN 07-10, 2004 CL Seoul, SOUTH KOREA SP IWA DE molecular imaging; ovarian cancer; clinical application; multivalency; in vivo spectral fluorescence imaging; D-galactose receptor ID ANTIBODY; AVIDIN AB The wavelength resolved spectral fluorescence imaging technique using a fluorescein-conjugated avidin has been reported to visualize submillimeter implants of ovarian cancer because of its highly targeted and quickly cleared pharmacokinetics. However, clinical application of avidin was hampered by its strong immunogenicity. As a clinically feasible alternative to avidin, which targets the same D-galactose receptor but is made from a nonimmunogenic source, with even better binding capability by multiplying binding sites but still maintaining a favorable characteristic of high isoelectric point, a serum albumin conjugated with 23 galactosamine and 2 rhodamine green molecules (GmSA-RhodG) was designed and synthesized. GmSA-RhodG showed more than 10-fold rapid and higher uptake by SHIN3 ovarian cancer cells than both avidin- and no galactosamine-conjugated albumin (bovine serum) - RhodG. Sensitivity and specificity of GmSA-RhodG to detect red fluorescence labeled peritoneal cancer foci in mouse cancer model were 100%/99% (n=566), respectively for similar to 1-mm lesions and even smaller lesions were detected in vivo. These results indicate that GmSA-RhodG is not only a clinically feasible alternative but more efficient targeting reagent for D-galactose receptors than avidin- RhodG. (c) 2007 Society of Photo-Optical Instrumentation Engineers. C1 [Hama, Yukihiro; Koyama, Yoshinori; Choyke, Peter L.; Kobayashi, Hisataka] NCI, NIH, Ctr Canc Res, Mol Imaging Program, Bethesda, MD 20892 USA. [Urano, Yasuteru] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan. RP Kobayashi, H (reprint author), NCI, NIH, Ctr Canc Res, Mol Imaging Program, Bldg 10,Rm 1B40,MSC 1088,10 Ctr Dr, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov RI Urano, Yasuteru/H-1380-2012 NR 16 TC 0 Z9 0 U1 1 U2 4 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2007 VL 12 IS 5 AR 051501 DI 10.1117/1.2779351 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 239WS UT WOS:000251549600008 ER PT J AU Nadiarnykh, O Plotnikov, S Mohler, WA Kalajzic, I Redford-Badwal, D Campagnola, PJ AF Nadiarnykh, Oleg Plotnikov, Sergey Mohler, William A. Kalajzic, Ivo Redford-Badwal, Deborah Campagnola, Paul J. TI Second harmonic generation imaging microscopy studies of osteogenesis imperfecta SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article; Proceedings Paper CT Conference on Water Environment-Membrane Technology CY JUN 07-10, 2004 CL Seoul, SOUTH KOREA SP IWA DE second harmonic generation; nonlinear optics; tissues, lasers in medicine; microscopy; scattering ID MECHANICAL-PROPERTIES; TRIPLE-HELIX; IN-VIVO; COLLAGEN; TENDON; MICE; FLUORESCENCE; RESOLUTION; COHERENT; MUTATION AB We have used quantitative second harmonic generation (SHG) imaging microscopy to investigate the collagen matrix organization in the oim mouse model for human osteogenesis imperfecta (OI). OI is a heritable disease in which the type I collagen fibrils are either abnormally organized or small, resulting in a clinical presentation of recurrent bone fractures and other pathologies related to collagen-comprised tissues. Exploiting the exquisite sensitivity of SHG to supramolecular assembly, we investigated whether this approach can be utilized to differentiate normal and oim tissues. By comparing SHG intensity, fibrillar morphology, polarization anisotropy, and signal directionality, we show that statistically different results are obtained for the wild type (WT) and disease states in bone, tendon, and skin. All these optical signatures are consistent with the collagen matrix in the oim tissues being more disordered, and these results are further consistent with the known weaker mechanical properties of the oim mouse. While the current work shows the ability of SHG to differentiate normal and diseased states in a mouse model, we suggest that our results provide a framework for using SHG as a clinical diagnostic tool for human OI. We further suggest that the SHG metrics described could be applied to other connective tissue disorders that are characterized by abnormal collagen assembly. (C) 2007 Society of Photo-Optical Instrumentation Engineers. C1 [Nadiarnykh, Oleg; Campagnola, Paul J.] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Ctr Cellular Anal & Modeling, Farmington, CT 06030 USA. [Plotnikov, Sergey] NHLBI, NIH, Lab Cell & Tissue Morphodynam, Bethesda, MD 20892 USA. [Mohler, William A.] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Ctr Cellular Anal & Modeling, Farmington, CT 06030 USA. [Kalajzic, Ivo] Univ Connecticut, Ctr Hlth, Dept Reconstruct Serv, Farmington, CT 06030 USA. [Redford-Badwal, Deborah] Univ Connecticut, Ctr Hlth, Dept Oral Rehabil, Dept Craniofacial Sci, Farmington, CT 06030 USA. RP Campagnola, PJ (reprint author), Univ Connecticut, Ctr Hlth, Dept Cell Biol, Ctr Cellular Anal & Modeling, MC-1507,263 Farmington Ave, Farmington, CT 06030 USA. EM campagno@neuron.uchc.edu RI Nadiarnykh, Oleg/D-1940-2013 FU NIBIB NIH HHS [EB-01842] NR 26 TC 43 Z9 44 U1 0 U2 9 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2007 VL 12 IS 5 AR 051805 DI 10.1117/1.2799538 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 239WS UT WOS:000251549600026 PM 17994883 ER PT J AU Shi, ZD Wu, H Ruddy, B Griffiths, GL AF Shi, Zhen-Dan Wu, Haitao Ruddy, Brian Griffiths, Gary L. TI Imaging Probe Development Center: a National Institutes of Health core synthesis resource for imaging probes SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article; Proceedings Paper CT Conference on Water Environment-Membrane Technology CY JUN 07-10, 2004 CL Seoul, SOUTH KOREA SP IWA DE chemistry; detection; fluorescence; imaging AB The Imaging Probe Development Center (IPDC) has been set up under the auspices of the National Institutes of Health (NIH) Roadmap as part of the molecular libraries and imaging initiatives. It comprises a core synthesis facility dedicated to the preparation of imaging probes, initially for intramural NIH scientists, and later, for the extramural scientific community. The facility opened fully in late 2006, in refurbished laboratories in Rockville, Maryland, and a staff of around a dozen was recruited into place by early 2007; the director was hired in late 2005. The IPDC provides a mechanism for the production of sensitive probes for use by imaging scientists who cannot obtain such probes commercially. The probes to be made will encompass all major imaging modalities including radionuclide, magnetic resonance, and optical. The operation of the IPDC is outlined, together with the results of interim achievements while the IPDC maintained a small temporary laboratory in Bethesda. As of December 2006, a total of eleven probe compositions had been made, and several of these are described with particular mention of those probes intended for use in optical applications. (c) 2007 Society of Photo-Optical Instrumentation Engineers. C1 [Shi, Zhen-Dan; Wu, Haitao; Ruddy, Brian; Griffiths, Gary L.] NHLBI, NIH, Imaging Probe Dev Ctr, Bethesda, MD 20892 USA. RP Griffiths, GL (reprint author), NHLBI, NIH, Imaging Probe Dev Ctr, 9800 Med Ctr Dr,Bldg 2B,Suite 3042, Bethesda, MD 20892 USA. EM griffithsgl@mail.nih.gov NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2007 VL 12 IS 5 AR 051502 DI 10.1117/1.2778702 PG 5 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 239WS UT WOS:000251549600009 ER PT J AU Sumner, JP Conroy, R Shapiro, EM Moreland, J Koretsky, AP AF Sumner, James P. Conroy, Richard Shapiro, Erik M. Moreland, John Koretsky, Alan P. TI Delivery of fluorescent probes using iron oxide particles as carriers enables in-vivo labeling of migrating neural precursors for magnetic resonance imaging and optical imaging SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article; Proceedings Paper CT Conference on Water Environment-Membrane Technology CY JUN 07-10, 2004 CL Seoul, SOUTH KOREA SP IWA DE magnetic resonance imaging; fluorescent probes; iron oxide particles; optical imaging ID NEURONAL PRECURSORS; CELL-MIGRATION; BRAIN; MRI; REJECTION; STROKE; LEVEL; STEM AB Iron oxide particles are becoming an important contrast agent for magnetic resonance imaging (MRI) cell tracking studies. Simultaneous delivery of fluorescence indicators with the particles to individual cells offers the possibility of correlating optical images and MRI. In this work, it is demonstrated that micron-sized iron oxide particles (MPIOs) can be used as a carrier to deliver fluorescent probes to cells in culture as well as to migrating neural progenitors in vivo. Migrating progenitors were tracked with MRI and easily identified by histology because of the fluorescent probe. These data suggest that using MPIOs to deliver fluorescent probes should make it possible to combine MRI and optical imaging for in vivo cell tracking. (c) 2007 Society of Photo-Optical Instrumentation Engineers. C1 [Sumner, James P.; Conroy, Richard; Koretsky, Alan P.] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Conroy, Richard; Moreland, John] Natl Inst Stand & Technol, Boulder, CO USA. [Shapiro, Erik M.] Yale Univ, Sch Med, Dept Radiol, New Haven, CT 06510 USA. RP Koretsky, AP (reprint author), Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,Bldg 10 RM B1D728, Bethesda, MD 20892 USA. EM koretskya@ninds.nih.gov RI Conroy, Richard/D-1979-2009; Koretsky, Alan/C-7940-2015 OI Conroy, Richard/0000-0002-8896-6090; Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS003047-01] NR 21 TC 10 Z9 13 U1 1 U2 5 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2007 VL 12 IS 5 AR 051504 DI 10.1117/1.2800294 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 239WS UT WOS:000251549600011 PM 17994868 ER PT J AU Vogel, A Chernomordik, VV Riley, JD Hassan, M Amyot, F Dasgeb, B Demos, SG Pursley, R Little, RF Yarchoan, R Tao, Y Gandjbakhche, AH AF Vogel, Abby Chernomordik, Victor V. Riley, Jason D. Hassan, Moinuddin Amyot, Franck Dasgeb, Bahar Demos, Stavros G. Pursley, Randall Little, Richard F. Yarchoan, Robert Tao, Yang Gandjbakhche, Amir H. TI Using noninvasive multispectral imaging to quantitatively assess tissue vasculature SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article; Proceedings Paper CT Conference on Water Environment-Membrane Technology CY JUN 07-10, 2004 CL Seoul, SOUTH KOREA SP IWA DE multispectral imaging; tissue oxygenation; blood volume; drug therapy monitoring; quantitative assessment; functional information ID NEAR-INFRARED SPECTROSCOPY; ENDOTHELIAL GROWTH-FACTOR; KAPOSIS-SARCOMA; PARAMETERS; THERAPY; LIGHT; SKIN; ANGIOGENESIS; HEMOGLOBIN AB This research describes a noninvasive, noncontact method used to quantitatively analyze the functional characteristics of tissue. Multispectral images collected at several near-infrared wavelengths are input into a mathematical optical skin model that considers the contributions from different analytes in the epidermis and dermis skin layers. Through a reconstruction algorithm, we can quantify the percent of blood in a given area of tissue and the fraction of that blood that is oxygenated. Imaging normal tissue confirms previously reported values for the percent of blood in tissue and the percent of blood that is oxygenated in tissue and surrounding vasculature, for the normal state and when ischemia is induced. This methodology has been applied to assess vascular Kaposi's sarcoma lesions and the surrounding tissue before and during experimental therapies. The multispectral imaging technique has been combined with laser Doppler imaging to gain additional information. Results indicate that these techniques are able to provide quantitative and functional information about tissue changes during experimental drug therapy and investigate progression of disease before changes are visibly apparent, suggesting a potential for them to be used as complementary imaging techniques to clinical assessment. (c) 2007 Society of Photo-Optical Instrumentation Engineers. C1 [Vogel, Abby; Chernomordik, Victor V.; Riley, Jason D.; Hassan, Moinuddin; Amyot, Franck; Dasgeb, Bahar; Gandjbakhche, Amir H.] NICHHD, NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. [Vogel, Abby; Tao, Yang] Univ Maryland, Fischell Dept Bioengn, Bioimaging & Machine Vis Lab, College Pk, MD 20742 USA. [Demos, Stavros G.] Lawrence Livermore Natl Lab, Livermore, CA 94551 USA. [Pursley, Randall] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. [Little, Richard F.; Yarchoan, Robert] NCI, NIH, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Gandjbakhche, AH (reprint author), NICHHD, NIH, Lab Integrat & Med Biophys, 9000 Rockville Pike,Bldg 9,Room B1E11, Bethesda, MD 20892 USA. EM amir@helix.nih.gov FU Intramural NIH HHS [Z01 CT000261-11] NR 30 TC 46 Z9 46 U1 0 U2 3 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2007 VL 12 IS 5 AR 051604 DI 10.1117/1.2801718 PG 13 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 239WS UT WOS:000251549600016 PM 17994873 ER PT J AU Samelson, EJ Cupples, LA Broe, KE Hannan, MT O'Donnell, CJ Kiel, DP AF Samelson, Elizabeth J. Cupples, L. Adrienne Broe, Kerry E. Hannan, Marian T. O'Donnell, Christopher J. Kiel, Douglas P. TI Vascular calcification in middle age and long-term risk of hip fracture: The Framingham Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE hip fracture; men; osteoporosis; population studies; vascular calcification; women ID CORONARY-HEART-DISEASE; BONE-MINERAL DENSITY; AORTIC CALCIFICATION; POSTMENOPAUSAL WOMEN; CARDIOVASCULAR-DISEASE; OSTEOPOROSIS; PROGRESSION; ATHEROSCLEROSIS; ASSOCIATION; MORTALITY AB Osteoporosis and atherosclerosis frequently occur in the same individuals and may share similar pathogenic mechanisms. This study examined the relation between severity of aortic calcification in middleage years and subsequent risk of hip fracture in women and men in the population-based Framingham Study. C1 Inst Aging Res Hebrew SeniorLife, Boston, MA 02131 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NHLBI Framingham Heart Study, Framingham, MA USA. RP Samelson, EJ (reprint author), Inst Aging Res Hebrew SeniorLife, 1200 Ctr St, Boston, MA 02131 USA. EM samelson@hrca.harvard.edu OI Cupples, L. Adrienne/0000-0003-0273-7965; Hannan, Marian/0000-0002-9586-6928; Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [N01-HC-25195, N01HC25195]; NIA NIH HHS [R01 AR/AG 41398]; NIAMS NIH HHS [K01 AR053118, K01 AR053118-03, K01AR053118-01, R01 AR041398] NR 37 TC 41 Z9 45 U1 1 U2 3 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 2007 VL 22 IS 9 BP 1449 EP 1454 DI 10.1359/JBMR.070519 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 204MW UT WOS:000249049100014 PM 17542685 ER PT J AU Hart, ES Kelly, MH Brillante, B Chen, CC Ziran, N Lee, JS Feuillan, P Leet, AI Kushner, H Robey, PG Collins, MT AF Hart, Elizabeth S. Kelly, Marilyn H. Brillante, Beth Chen, Clara C. Ziran, Navid Lee, Janice S. Feuillan, Penelope Leet, Arabella I. Kushner, Harvey Robey, Pamela G. Collins, Michael T. TI Onset, progression, and plateau of skeletal lesions in fibrous dysplasia and the relationship to functional outcome SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE fibrous dysplasia; bone; outcomes; McCune-Albright syndrome; GNAS; G(s)alpha ID MCCUNE-ALBRIGHT-SYNDROME; STIMULATORY G-PROTEIN; MARROW STROMAL CELLS; BONE-MARROW; DYSFUNCTION; GENE; ABNORMALITIES; PIGMENTATION; MUTATIONS AB Most lesions in FD and their attendant functional disability occur within the first decade; 90% of lesions are present by 15 years, and the median age when assistive devices are needed is 7 years. These findings have implications for prognosis and determining the timing and type of therapy. C1 NIDCR, SCSU, CSDB, NIH, Bethesda, MD 20892 USA. NIH, Hatfield Clin Res Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. Univ Rochester, Dept Orthoped, Rochester, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NHGRI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Orthoped, Baltimore, MD USA. Biomed Comp Res Inst, Philadelphia, PA USA. RP Collins, MT (reprint author), NIDCR, SCSU, CSDB, NIH, Bldg 30,Room 228,MSC 4320, Bethesda, MD 20892 USA. EM mc247k@nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Intramural NIH HHS NR 26 TC 42 Z9 47 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 2007 VL 22 IS 9 BP 1468 EP 1474 DI 10.1359/JBMR.070511 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 204MW UT WOS:000249049100017 PM 17501668 ER PT J AU Barsony, J Manigrasso, MB Tam, H Doshi, AH Verbalis, JG AF Barsony, J. Manigrasso, M. B. Tam, H. Doshi, A. H. Verbalis, J. G. TI Hyponatremia induces bone loss and prevents fat accumulation in aged F344 brown Norway rats SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Barsony, J.] NIDDK, NIH, Bethesda, MD USA. [Manigrasso, M. B.; Tam, H.; Doshi, A. H.; Verbalis, J. G.] Georgetown Univ, Div Endocrinol & Metab, Washington, DC 20057 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 2007 VL 22 SU 1 MA T448 BP S344 EP S344 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102014 ER PT J AU Bi, Y Kilts, TM Griffin, AC Young, MF AF Bi, Y. Kilts, T. M. Griffin, A. C. Young, M. F. TI Biglycan and fibromodulin control bone mass by regulating osteoclast differentiation through bone marrow stromal cells SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Bi, Y.; Kilts, T. M.; Griffin, A. C.; Young, M. F.] NIH, Natl Inst Dent & Craniofac Res, 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 2007 VL 22 SU 1 BP S102 EP S102 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100375 ER PT J AU Bi, Y Kilts, TM Griffin, AC Young, MF AF Bi, Y. Kilts, T. M. Griffin, A. C. Young, M. F. TI Biglycan and fibromodulin control bone mass by regulating osteoclast differentiation through bone marrow stromal cells SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Bi, Y.; Kilts, T. M.; Griffin, A. C.; Young, M. F.] NIH, Natl Inst Dent & Craniofacial Res, 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 2007 VL 22 SU 1 MA O157 BP S85 EP S85 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100307 ER PT J AU Cabral, WA Barnes, AM Porter, FD Marini, JC AF Cabral, W. A. Barnes, A. M. Porter, F. D. Marini, J. C. TI Carrier frequency of recurring mutation causing severe/lethal recessive type VIII Osteogenesis imperfecta in African-Americans SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Cabral, W. A.; Barnes, A. M.; Marini, J. C.] NIH, NICHD, Bone & Extracellular Matrix Branch, Bethesda, MD USA. [Porter, F. D.] NIH, NICHD, Heritable Disorders Branch, 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 2007 VL 22 SU 1 MA T471 BP S350 EP S350 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102037 ER PT J AU Collins, MT Mckie, JE Reynolds, JC Winer, KK AF Collins, M. T. Mckie, J. E. Reynolds, J. C. Winer, K. K. TI Bone mass in adults and children with hypoparathyroidism SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Collins, M. T.; Mckie, J. E.] NIDCR, CSDB, Skeletal Clin Studies Unit, Bethesda, MD USA. [Winer, K. K.] NIH, NICHD, 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 2007 VL 22 SU 1 BP S498 EP S498 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102613 ER PT J AU David, V Martin, A Fisher, LW Hedge, A Rowe, PSN AF David, V. Martin, A. Fisher, L. W. Hedge, A. Rowe, P. S. N. TI Abnormal bone mineralization, osteoclastogenesis & bone turnover in transgenic mice overexpressing MEPE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [David, V.; Martin, A.; Hedge, A.; Rowe, P. S. N.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Fisher, L. W.] NIDCR, NIH, Bethesda, MD 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 2007 VL 22 SU 1 MA 1226 BP S64 EP S64 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100227 ER PT J AU David, V Martin, A Laurence, J Mckee, MD Fisher, LW Hedge, A Rowe, PSN AF David, V. Martin, A. Laurence, J. Mckee, M. D. Fisher, L. W. Hedge, A. Rowe, P. S. N. TI Degradation of MEPE, DMPI & release of SIBLING ASARM-peptides (minhibins): ASARM-peptide(s) are directly responsible for defective mineralization in HYP SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [David, V.; Martin, A.; Laurence, J.; Hedge, A.; Rowe, P. S. N.] Kansas Uni Med Ctr, Kansas City, KS USA. [Mckee, M. D.] McGill Univ, Montreal, PQ, Canada. [Fisher, L. W.] NIDCR, 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 2007 VL 22 SU 1 MA 1155 BP S44 EP S44 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100156 ER PT J AU Guo, D Mishina, Y Feng, J Ray, M Scott, G Harris, M Bonewald, L AF Guo, D. Mishina, Y. Feng, J. Ray, M. Scott, G. Harris, M. Bonewald, L. TI Targeted deletion of E11/gp38 in osteocytes results in increased skeletal size and bone mineral density SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Guo, D.; Feng, J.; Bonewald, L.] Univ Missouri, Kansas City, MO 64110 USA. [Mishina, Y.; Ray, M.; Scott, G.; Harris, M.] NIEHS, Mol Dev Biol, Res Triangle Pk, NC 27709 USA. [Harris, M.] UTHSCSA, Dept Periodont, San Antonio, TX 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 2007 VL 22 SU 1 MA 1043 BP S13 EP S13 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100044 ER PT J AU Inkson, CI Kilts, TM Fisher, LW Young, MF AF Inkson, C. I. Kilts, T. M. Fisher, L. W. Young, M. F. TI WISP-1/CCN-4 a novel target for inhibiting prostate cancer growth in bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Inkson, C. I.; Kilts, T. M.; Fisher, L. W.; Young, M. F.] Natl Inst Dental & Cranofacial Res, 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 2007 VL 22 SU 1 MA 1174 BP S50 EP S50 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100175 ER PT J AU Ishijima, M Arikawa-Hirasawa, E Hozumi, K Suzuki, N Kosaki, K Matsunobu, T Yamada, Y AF Ishijima, M. Arikawa-Hirasawa, E. Hozumi, K. Suzuki, N. Kosaki, K. Matsunobu, T. Yamada, Y. TI Perlecan modulates FGF and VEGF signaling and is essential for vascularization in the development of the cartilage growth plate SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Ishijima, M.; Hozumi, K.; Suzuki, N.; Kosaki, K.; Matsunobu, T.; Yamada, Y.] NIH, Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, Bethesda, MD 20892 USA. [Arikawa-Hirasawa, E.] Juntendo Univ, Sch Med, Res Inst Dis Old Age, Tokyo 113, Japan. 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 2007 VL 22 SU 1 MA 1064 BP S18 EP S18 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100065 ER PT J AU Islam, M Jiang, X Li, H Kronenberg, MS Adams, DJ Morasso, MM Lichtler, AC AF Islam, M. Jiang, X. Li, H. Kronenberg, M. S. Adams, D. J. Morasso, M. M. Lichtler, A. C. TI Role of Dlx3 in bone: Study of inducible Cre mediated Dlx3 inactivation in mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Islam, M.; Jiang, X.; Li, H.; Kronenberg, M. S.; Adams, D. J.; Lichtler, A. C.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Morasso, M. M.] Natl Inst Hlth, NIAMS, 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 2007 VL 22 SU 1 BP S91 EP S91 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100333 ER PT J AU Jackson, WM Koehler, SM Giuliani, JR Tuan, RS Nesti, LJ AF Jackson, W. M. Koehler, S. M. Giuliani, J. R. Tuan, R. S. Nesti, L. J. TI Progenitor cells in traumatically injured muscle have characteristic similarities to bone marrow-derived stem cells SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Jackson, W. M.; Koehler, S. M.; Tuan, R. S.] NIAMSD, Cartilage Biol & Orthopaed Branch, Bethesda, MD 20892 USA. [Giuliani, J. R.; Nesti, L. J.] Walter Reed Army Med Ctr, Dept Orthopaed, Washington, DC 20307 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 2007 VL 22 SU 1 MA W039 BP S372 EP S372 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102126 ER PT J AU Kamiya, N Ye, L Kobayashi, T Mochida, Y Yamauchi, M Kronenberg, H Feng, J Mishina, Y AF Kamiya, N. Ye, L. Kobayashi, T. Mochida, Y. Yamauchi, M. Kronenberg, H. Feng, J. Mishina, Y. TI BMP signaling in osteoblasts negatively regulates canonical Wnt signaling to reduce bone mass during embryonic bone development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Kamiya, N.; Mishina, Y.] NIEHS, NIH, LRDT, Res Triangle Pk, NC 27709 USA. [Ye, L.; Feng, J.] Univ Missouri, Kansas City, MO 64110 USA. [Kobayashi, T.] Massachusetts Gen Hosp, Harvard Med Sch, Endocrine Unit, Boston, MA 02114 USA. [Mochida, Y.; Yamauchi, M.] Univ N Carolina, Dent Res Ctr, Chapel Hill, NC 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 2007 VL 22 SU 1 MA S270 BP S110 EP S110 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100409 ER PT J AU Kelly, MH Brillante, B Khosravi, A Collins, MT AF Kelly, M. H. Brillante, B. Khosravi, A. Collins, M. T. TI Lack of efficacy of octreotide in the treatment of tumor-induced osteomalacia SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Kelly, M. H.; Brillante, B.; Collins, M. T.] NIH, NIDCR, Bethesda, MD 20892 USA. [Khosravi, A.] Johns Hopkins Univ, Kennedy Krieger Inst, Neurorehabil Dept, Baltimore, MD 21218 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 2007 VL 22 SU 1 MA W424 BP S470 EP S470 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102510 ER PT J AU Lang, TF Cheng, X Li, C Koyama, A Harris, T Lu, Y AF Lang, T. F. Cheng, X. Li, C. Koyama, A. Harris, T. Lu, Y. TI Hip muscle cross-sectional area and attenuation: Association with hip fracture SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Lang, T. F.; Li, C.; Koyama, A.; Lu, Y.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cheng, X.] Beijing Ji Shui Tan Hosp, Beijing, Peoples R China. [Harris, T.] NIA, 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 2007 VL 22 SU 1 MA 1281 BP S79 EP S79 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100283 ER PT J AU Li, L Gundberg, CM Dowd, TL AF Li, L. Gundberg, C. M. Dowd, T. L. TI The three dimensional H-1 NMR structure of bovine lead ion-bound osteocalcin and implications for lead toxicity SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Li, L.] NIEHS, Res Triangle Pk, NC 27709 USA. [Gundberg, C. M.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Dowd, T. L.] CUNY Brooklyn Coll, Brooklyn, NY 11210 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 2007 VL 22 SU 1 MA M159 BP S163 EP S163 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100610 ER PT J AU Mackey, DC Harris, TB Manini, TM Ferrucci, L Hardy, SE Strotmeyer, ES Tylavsky, FA Cummings, SR AF Mackey, D. C. Harris, T. B. Manini, T. M. Ferrucci, L. Hardy, S. E. Strotmeyer, E. S. Tylavsky, F. A. Cummings, S. R. CA Hlth ABC Stud TI Gold standard measurement of physical activity energy expenditure and bone mineral density in older adults: The Health ABC Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Mackey, D. C.; Cummings, S. R.; Hlth ABC Stud] Calif Pacific Med Ctr, San Francisco Coordinat Ctr, San Francisco, CA USA. [Harris, T. B.; Ferrucci, L.] Natl Inst Aging, Baltimore, MD USA. [Manini, T. M.] Univ Florida, Gainesville, FL USA. [Hardy, S. E.; Strotmeyer, E. S.] Univ Pittsburgh, Pittsburgh, PA USA. [Tylavsky, F. A.] Univ Tennessee, Memphis, TN USA. RI Strotmeyer, Elsa/F-3015-2014 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 2007 VL 22 SU 1 MA T346 BP S317 EP S317 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101567 ER PT J AU Martin, A David, V Fisher, LW Hedge, A Rowe, PSN AF Martin, A. David, V. Fisher, L. W. Hedge, A. Rowe, P. S. N. TI Reduced kidney-stone formation and altered renal phosphate-homeostasis in mice over-expressing Murine-MEPE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Martin, A.; David, V.; Hedge, A.; Rowe, P. S. N.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Fisher, L. W.] NIH, NIDCR, 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 2007 VL 22 SU 1 MA 1118 BP S34 EP S35 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100119 ER PT J AU Oshima, Y Akiyama, T Iwasawa, M Nagase, Y Hennighausen, L Nakamura, K Tanaka, S AF Oshima, Y. Akiyama, T. Iwasawa, M. Nagase, Y. Hennighausen, L. Nakamura, K. Tanaka, S. TI Molecular interaction between Bcl-xL and Bnip3 determines the cell fate of hypertrophic chondrocytes SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Oshima, Y.; Akiyama, T.; Iwasawa, M.; Nagase, Y.; Nakamura, K.; Tanaka, S.] Univ Tokyo, Tokyo, Japan. [Hennighausen, L.] Natl Inst Hlth, Genet & Physiol Lab, 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 2007 VL 22 SU 1 MA 1181 BP S51 EP S51 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100182 ER PT J AU Oz, OK Hajibeigi, A Siyambalapitiyage, W Korach, K Kuro-O, M AF Oz, O. K. Hajibeigi, A. Siyambalapitiyage, W. Korach, K. Kuro-o, M. TI Down-regulation of klotho protein expression by estrogen SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Oz, O. K.; Hajibeigi, A.; Siyambalapitiyage, W.; Kuro-o, M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75235 USA. [Korach, K.] NIH, NIEHS, Res Triangle Pk, NC 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 2007 VL 22 SU 1 MA T192 BP S278 EP S278 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101413 ER PT J AU Ozawa, A Agarwal, K Mateo, CM Burns, AL Rice, TS Kennedy, PA Quigley, CM Simonds, WF Weinstein, LS Chandrasekharappa, SC Collins, FS Spiegel, AM Marx, SJ AF Ozawa, A. Agarwal, K. Mateo, C. M. Burns, A. L. Rice, T. S. Kennedy, P. A. Quigley, C. M. Simonds, W. F. Weinstein, L. S. Chandrasekharappa, S. C. Collins, F. S. Spiegel, A. M. Marx, S. J. TI In multiple endocrine neoplasia type 1 (MEN1) the estimated ratio of mutated p27 versus mutated MEN1 genes is below 1 : 100 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Ozawa, A.; Agarwal, K.; Mateo, C. M.; Burns, A. L.; Rice, T. S.; Kennedy, P. A.; Quigley, C. M.; Simonds, W. F.; Weinstein, L. S.; Spiegel, A. M.; Marx, S. J.] Natl Inst Hlth, NIDDK, Bethesda, MD USA. [Chandrasekharappa, S. C.; Collins, F. S.] Natl Inst Hlth, NHGRI, 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 2007 VL 22 SU 1 MA T483 BP S353 EP S353 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102049 ER PT J AU Rousche, KT Derfoul, A Helm, J Tuan, RS AF Rousche, K. T. Derfoul, A. Helm, J. Tuan, R. S. TI Activation of the non-canonical Wnt pathway during human mesenchymal stem cell osteogenesis: Microarray expression analyses to examine the effects of dexamethasone on cell differentiation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Rousche, K. T.; Derfoul, A.; Helm, J.; Tuan, R. S.] NIH, NIAMS, 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 2007 VL 22 SU 1 BP S243 EP S243 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101269 ER PT J AU Shi, J Son, M Yamada, S Szabova, L Kahan, S Chrysovergis, K Wolf, L Surmak, A Holmbeck, K AF Shi, J. Son, M. Yamada, S. Szabova, L. Kahan, S. Chrysovergis, K. Wolf, L. Surmak, A. Holmbeck, K. TI MT3-MMP is a major mesenchymal collagenase essential for skeletal development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Shi, J.; Son, M.; Yamada, S.; Szabova, L.; Kahan, S.; Chrysovergis, K.; Wolf, L.; Surmak, A.; Holmbeck, K.] NIDCR, CSDB MMPU, 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 2007 VL 22 SU 1 MA M167 BP S165 EP S165 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100615 ER PT J AU Sigeirsdottir, K Aspelund, T Sigurdsson, G Jonsson, B Mogensen, B Eiriksdottir, G Sigurdsson, S Launer, L Harris, T Lang, TF Gudnason, V AF Sigeirsdottir, K. Aspelund, T. Sigurdsson, G. Jonsson, B. Mogensen, B. Eiriksdottir, G. Sigurdsson, S. Launer, L. Harris, T. Lang, T. F. Gudnason, V. TI Bone mineral density in hip and spine by quantitative CT and previous history as predictors of incidental low trauma fractures in elderly men and women SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Sigeirsdottir, K.; Aspelund, T.; Sigurdsson, G.; Eiriksdottir, G.; Sigurdsson, S.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Jonsson, B.] Univ Hosp Malmo, Malmo, Sweden. [Mogensen, B.] Univ Iceland, IS-101 Reykjavik, Iceland. [Harris, T.] NIA, Bethesda, MD 20892 USA. [Lang, T. F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. 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 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 2007 VL 22 SU 1 MA 1278 BP S78 EP S78 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100279 ER PT J AU Szabova, L Yamada, S Holmbeck, K AF Szabova, L. Yamada, S. Holmbeck, K. TI Rescue of MT1-MMP expression in cartilage increases survival, chondrocyte proliferation and bone formation in MT1-MMP deficient mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Szabova, L.; Yamada, S.; Holmbeck, K.] NIDCR, CSDB MMPU, 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 2007 VL 22 SU 1 BP S103 EP S103 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100378 ER PT J AU Szabova, L Yamada, S Holmbeck, K AF Szabova, L. Yamada, S. Holmbeck, K. TI Rescue of MT1-MMP expression in cartilage increases survival, chondrocyte proliferation and bone formation in MT1-MMP deficient mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Szabova, L.; Yamada, S.; Holmbeck, K.] NIDCR, CSDB MMPU, 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 2007 VL 22 SU 1 MA O165 BP S85 EP S85 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100308 ER PT J AU Uveges, TE Cabral, WA Bergwitz, C Legard, F Collin-Osdoby, P Forlino, A Osdoby, P Gronowitz, GA Marini, JC AF Uveges, T. E. Cabral, W. A. Bergwitz, C. Legard, F. Collin-Osdoby, P. Forlino, A. Osdoby, P. Gronowitz, G. A. Marini, J. C. TI Bone formation rate falls after puberty in Brtl OI mouse due to cellular uncoupling SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Uveges, T. E.; Cabral, W. A.; Marini, J. C.] NIH, NICHD, BEMB, Bethesda, MD USA. [Bergwitz, C.] Massachusetts Gen Hosp, Harvard Med Sch, Endocrine Unit, Boston, MA 02114 USA. [Legard, F.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Collin-Osdoby, P.; Osdoby, P.] Washington Univ, Dept Biol Bone & Min Metab, St Louis, MO USA. [Forlino, A.] Univ Pavia, Dept Biochem, I-27100 Pavia, Italy. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 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 2007 VL 22 SU 1 MA W166 BP S403 EP S403 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102253 ER PT J AU Verdelis, K Wright, JT Haruyama, N Kulkarni, A Lukashova, L Boskey, AL AF Verdelis, K. Wright, J. T. Haruyama, N. Kulkarni, A. Lukashova, L. Boskey, A. L. TI Enamel phenotype and sexual dimorphism in dentin of dspp-null mouse molars SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Verdelis, K.; Lukashova, L.; Boskey, A. L.] Hosp Special Surg, Mineralized Tissues Lab, New York, NY USA. [Wright, J. T.] Univ N Carolina, Sch Dent, Chapel Hill, NC USA. [Haruyama, N.; Kulkarni, A.] NIH, NIDCR, Bethesda, MD USA. RI Haruyama, Naoto/D-1993-2011 OI Haruyama, Naoto/0000-0001-6225-5816 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 2007 VL 22 SU 1 MA T148 BP S266 EP S267 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101369 ER PT J AU Wang, Y ElAlieh, HZ Nakamura, E Nguyen, M Mackem, S Bikle, DD Chang, W AF Wang, Y. ElAlieh, H. Z. Nakamura, E. Nguyen, M. Mackem, S. Bikle, D. D. Chang, W. TI IGF-I signaling is required for postnatal growth plate development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Wang, Y.; ElAlieh, H. Z.; Bikle, D. D.; Chang, W.] Univ Calif San Francisco, Endocrine Unit, San Francisco, CA 94143 USA. [Nakamura, E.; Nguyen, M.; Mackem, S.] NIH, NCI, Canc Res Ctr, Pathol Lab, 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 2007 VL 22 SU 1 MA 1109 BP S32 EP S32 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100110 ER PT J AU Wu, JY Rodda, S Sims, NA Poulton, IJ Chen, M Weinstein, LS McMahon, AP Kronenberg, HM AF Wu, J. Y. Rodda, S. Sims, N. A. Poulton, I. J. Chen, M. Weinstein, L. S. McMahon, A. P. Kronenberg, H. M. TI Impaired bone formation in mice lacking the G protein subunit Gs alpha in early osteoblasts leads to marked bone fragility SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Wu, J. Y.; Kronenberg, H. M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Rodda, S.; McMahon, A. P.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Sims, N. A.; Poulton, I. J.] St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. [Chen, M.; Weinstein, L. S.] Natl Inst Diabet & Digest & Kidney Dis, Metab Dis Branch, 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 2007 VL 22 SU 1 MA 1020 BP S7 EP S7 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100021 ER PT J AU Yan, W Guo, D Gluhak, J Harris, MA Lichtler, A Kream, B Edwards, J Mundy, GR Mishina, Y Harris, SE AF Yan, W. Guo, D. Gluhak, J. Harris, M. A. Lichtler, A. Kream, B. Edwards, J. Mundy, G. R. Mishina, Y. Harris, S. E. TI Role of BMP2 in postnatal bone biology: Conditional knock-out (cKO) of BMP2 using the 3.6 collagen type IA1-Cre model SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Yan, W.; Gluhak, J.; Harris, M. A.; Harris, S. E.] UTHSCSA, San Antonio, TX USA. [Guo, D.] UMKC, Kansas City, MO USA. [Lichtler, A.; Kream, B.] UCONN Hlth Ctr, Farmington, CT USA. [Edwards, J.; Mundy, G. R.] Vanderbilt Univ, Nashville, TN USA. [Mishina, Y.] NIH, NIEHS, LRDT, Res Triangle Pk, NC 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 2007 VL 22 SU 1 MA 1106 BP S31 EP S31 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100107 ER PT J AU Yin, J Tracy, K Ward, Y Kelly, K AF Yin, J. Tracy, K. Ward, Y. Kelly, K. TI Bone metastases select for integrin alpha 2 beta 1 negative cells in prostate cancer cell line DU145 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Yin, J.; Tracy, K.; Ward, Y.; Kelly, K.] Natl Canc Inst, 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 2007 VL 22 SU 1 MA M301 BP S189 EP S189 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101069 ER EF