FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wang, E Panelli, MC Marincola, FM AF Wang, E Panelli, MC Marincola, FM TI Understanding the response to immunotherapy in humans SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article DE immunization; immunotherapy; interleukin-2; melanoma ID CD8(+) T-CELLS; COLONY-STIMULATING FACTOR; METASTATIC MELANOMA; DENDRITIC CELLS; GENE-EXPRESSION; TUMOR-ANTIGENS; IN-VIVO; ANTITUMOR IMMUNITY; PEPTIDE VACCINE; CANCER-PATIENTS AB Whether the efforts of the last decade aimed at the development of vaccines against tumor-specific antigens encountered success or failure is a matter of expectations. On the bright side, we could optimistically observe that anti-cancer-vaccines stand as an outstanding example of the successful implementation of modern biotechnology tools for the development of biologically sound therapeutics. In particular, vaccines against melanoma (the prototype model of tumor immunology in humans) can reproducibly induce cytotoxic T cell (CTL) responses exquisitely specific for cancer cells. This achievement trespasses the specificity of any other anti-cancer therapy. The skeptics, on the other end, might point out that immunization only rarely leads to cancer regression, labeling, therefore, this approach is ineffective. In our opinion this judgment stems from the naive expectation that CTL induction is sufficient for an effective immune response. Here we propose that more needs to be understood about the mechanisms required for the induction of a therapeutically relevant immune response in humans. In particular, we will discuss the variables related to cancer heterogeneity, the weight of individual patients polymorphism(s), the role of the T cell activation and differentiation and, finally, the complex relationship between immune and cancer cells within the tumor microenvironment. C1 NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM FMarincola@cc.nih.gov NR 96 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD JUN PY 2005 VL 27 IS 1 BP 105 EP 117 DI 10.1007/s00281-004-0198-7 PG 13 WC Immunology; Pathology SC Immunology; Pathology GA 937EC UT WOS:000229906400009 PM 15666150 ER PT J AU Kania, G Corbeil, D Fuchs, J Tarasov, KV Blyszczuk, P Huttner, WB Boheler, KR Wobus, AM AF Kania, G Corbeil, D Fuchs, J Tarasov, KV Blyszczuk, P Huttner, WB Boheler, KR Wobus, AM TI Somatic stem cell marker prominin-1/CD133 is expressed in embryonic stem cell-derived progenitors SO STEM CELLS LA English DT Article DE mouse; embryonic stem cells; embryonic carcinoam cells; blastocysts; prominin-1; nestin; nanog; neuronal; differentiation ID PLASMA-MEMBRANE PROTRUSIONS; INTERMEDIATE FILAMENT PROTEIN; HUMAN HEMATOPOIETIC STEM; EPITHELIAL-CELLS; IN-VITRO; SAGE IDENTIFICATION; TIGHT JUNCTION; MOUSE; DIFFERENTIATION; AC133 AB Prominin-1/CD133 is a plasma membrane marker found in several types of somatic stem cells, including hematopoietic and neural stem cells. To study its role during development and with differentiation, we analyzed its temporal and spatial expression (mRNA and protein) in preimplantation embryos, undifferentiated mouse embryonic stem (ES) cells, and differentiated ES cell progeny. In early embryos, prominin-1 was expressed in trophoblast but not in cells of the inner cell mass; however, prominin-1 transcripts were detected in undifferentiated ES cells. Both ES-derived cells committed to differentiation and early progenitor cells coexpressed prominin-1 with early lineage markers, including the cytoskeletal markers (nestin, cytokeratin 18, desmin), fibulin-1, and valosin-containing protein. After spontaneous differentiation at terminal stages, prominin-1 expression was downregulated and no coexpression with markers characteristic for neuroectodermal, mesodermal, and endodermal cells was found. Upon induction of neuronal differentiation, some prominin-I-positive cells, which coexpressed nestin and showed the typical morphology of neural progenitor cells, persisted until terminal stages of differentiation. However, no coexpression of prominin-1 with markers of differentiated neural cells was detected. In conclusion, we present the somatic stem cell marker prominin-1 as a new parameter to define ES-derived committed and early progenitor cells. C1 IPK, In Vitro Differentiat Grp, D-06466 Gatersleben, Germany. Carl Gustav Carus Univ, Med Clin & Polyclin 1, Dresden, Germany. Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Wobus, AM (reprint author), IPK, In Vitro Differentiat Grp, Corrensstr 3, D-06466 Gatersleben, Germany. EM wobusam@ipk-gatersleben.de RI Corbeil, Denis/A-6519-2010 NR 49 TC 89 Z9 96 U1 0 U2 6 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JUN-JUL PY 2005 VL 23 IS 6 BP 791 EP 804 DI 10.1634/stemcells.2004-0232 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 933JQ UT WOS:000229625100009 PM 15917475 ER PT J AU Yang, AX Mejido, J Luo, YQ Zeng, XM Schwartz, C Wu, TX Thies, RS Bhattacharya, B Han, J Freed, B Rao, M Puri, RK AF Yang, AX Mejido, J Luo, YQ Zeng, XM Schwartz, C Wu, TX Thies, RS Bhattacharya, B Han, J Freed, B Rao, M Puri, RK TI Development of a focused microarray to assess human embryonic stem cell differentiation SO STEM CELLS AND DEVELOPMENT LA English DT Article ID GENE-EXPRESSION; MOLECULAR SIGNATURE; GROWTH; LINES AB Human embryonic stem cells (hESC) must be differentiated before clinical use. In addition, the extent of contamination of undifferentiated cells and the efficiency of differentiation must also be assessed prior to clinical application. In this manuscript, we describe the development of a focused microarray that may be used to discriminate between hESC and their differentiated progeny. This array contains 755 genes including embryonic stem cell markers as well as markers of differentiation into neural, mesodermal, and endodermal phenotypes. In addition, we have included candidate genes belonging to families of cytokines, chemokines, receptors, signaling pathways, and homeodomain proteins that are likely to be important in the process of differentiation. Testing and validation of the focused array was performed using RNA from hESC, human embryoid body ( hEB) outgrowths, and a human embryonal carcinoma ( hEC) cell line. We have compared gene expression with negative background, GAPDH, beta-actin positive controls, and human universal RNA ( hURNA), showing that such an array can rapidly distinguish between undifferentiated and differentiated hESC-derived cell populations. We expect that the described array will be extremely useful in evaluating the extent of differentiation and the state of the hESC-derived population utilized for therapeutic purposes. C1 US FDA, Lab Mol & Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Cellular Neurobiol Branch, Baltimore, MD 21224 USA. Natl Inst Dent & Craniofacial Res, Biostat Core Unit, NIH, Bethesda, MD 20892 USA. Geron Corp, Menlo Pk, CA 94025 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21218 USA. RP Puri, RK (reprint author), US FDA, Lab Mol & Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 14 TC 21 Z9 22 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD JUN PY 2005 VL 14 IS 3 BP 270 EP 284 DI 10.1089/scd.2005.14.270 PG 15 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 940QI UT WOS:000230158600006 PM 15969622 ER PT J AU You, SH Jang, SH Kim, YH Hallett, M Ahn, SH Kwon, YH Kim, JH Lee, MY AF You, SH Jang, SH Kim, YH Hallett, M Ahn, SH Kwon, YH Kim, JH Lee, MY TI Virtual reality-induced cortical reorganization and associated locomotor recovery in chronic stroke - An experimenter-blind randomized study SO STROKE LA English DT Article DE gait; magnetic resonance imaging; rehabilitation ID INDUCED MOVEMENT THERAPY; CEREBRAL-PALSY; FUNCTIONAL MRI; MOTOR CORTEX; HUMAN BRAIN; GAIT; HUMANS; FMRI AB Background and Purpose-Virtual reality (VR) is a new promising computer-assisted technology to promote motor recovery in stroke patients. VR-induced neuroplasticity supporting locomotor recovery is not known. We investigated the effects of VR intervention on cortical reorganization and associated locomotor recovery in stroke patients. Methods-Ten chronic stroke patients were assigned randomly to either the control group or the VR group. VR was designed to provide interactive real-life practice environments in which practice parameters can be individualized to optimize motor relearning. Laterality index (LI) in the regions of interests (ROIs) and locomotor recovery were measured before and after VR using functional MRI ( fMRI) and standardized locomotor tests, respectively. The t test and nonparametric test were performed to compare the mean differences at P < 0.05. Results-There was a significant difference in the interval change in the LI score for the primary sensorimotor cortex (SMC) between the groups (P < 0.05), indicating that VR practice produced a greater increase in LI for the control group. However, the interval changes in the other ROIs were not significantly different (P > 0.05). Motor function was significantly improved after VR (P < 0.05). Conclusions-Our novel findings suggest that VR could induce cortical reorganization from aberrant ipsilateral to contralateral SMC activation. This enhanced cortical reorganization might play an important role in recovery of locomotor function in patients with chronic stroke. This is the first fMRI study in the literature that provides evidence for neuroplasticity and associated locomotor recovery after VR. C1 Hampton Univ, Phys Therapy Program, Hampton, VA 23668 USA. Yeungnam Univ, Coll Med, Dept Phys Med & Rehabil, Taegu, South Korea. Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Dept Phys Med & Rehabil, Seoul, South Korea. NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. RP You, SH (reprint author), Hampton Univ, Phys Therapy Program, Phoenix Hall 219B, Hampton, VA 23668 USA. EM sung.you@hamptonu.edu RI Kim, Yun Hee/F-4600-2014 NR 27 TC 151 Z9 179 U1 4 U2 31 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2005 VL 36 IS 6 BP 1166 EP 1171 DI 10.1161/01.STR.0000162715.43417.91 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 929EL UT WOS:000229324800020 PM 15890990 ER PT J AU Verma, M AF Verma, M TI Pancreatic cancer epidemiology SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article ID GENE-EXPRESSION; RISK-ASSESSMENT; ENDOCRINE NEOPLASMS; PROTEOMIC ANALYSIS; CELL-LINES; BIOMARKERS; CARCINOMA; ADENOCARCINOMA; METHYLATION; PREVENTION AB Carcinoma of the exocrine pancreas remains a challenging disease mainly due to advanced stage diagnosis, the early systemic dissemination, aggressive local tumor progression, and subsequent short patient survival. Thus, assessment of incidence markers instead of prevalence indicators is recommended because the time between diagnosis and death is usually very short. Investigations to date have led to the discovery of many rare genes and environmental factors that contribute to pancreatic cancer. However, common genes involved in genetic polymorphisms, and specific risk factors have not been identified. Furthermore, the role of gene-environment interactions on the tumorogenesis and progression of pancreatic cancer need to be further investigated. Given current therapeutic modalities, only early detection of cancer of the pancreas, followed by surgical resection, offers the possibility of lengthening survival time. C1 NCI, Analyt Epidemiol Res Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. RP Verma, M (reprint author), NCI, Analyt Epidemiol Res Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. EM vermam@mail.nih.gov NR 65 TC 9 Z9 11 U1 0 U2 5 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD JUN PY 2005 VL 4 IS 3 BP 295 EP 301 PG 7 WC Oncology SC Oncology GA 935MY UT WOS:000229787600009 PM 15896085 ER PT J AU Langer, RD Pradhan, AD Lewis, CE Manson, JE Rossouw, JE Hendrix, SL LaCroix, AZ Ridker, PM AF Langer, RD Pradhan, AD Lewis, CE Manson, JE Rossouw, JE Hendrix, SL LaCroix, AZ Ridker, PM TI Baseline associations between postmenopausal hormone therapy and inflammatory, haemostatic, and lipid biomarkers of coronary heart disease - The Women's Health Initiative Observational Study SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE postmenopausal hormone therapy; estrogens; coronary heart disease; inflammatory factors; haemostatic factors ID C-REACTIVE PROTEIN; RANDOMIZED CONTROLLED-TRIAL; ESTROGEN/PROGESTIN INTERVENTIONS PEPI; CARDIOVASCULAR RISK-FACTORS; ESTROGEN PLUS PROGESTIN; REPLACEMENT THERAPY; PLASMA HOMOCYSTEINE; LIPOPROTEIN CHOLESTEROL; ARTERY ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION AB Clinical trials of postmenopausal hormone therapy (PHT) have found an early increase in cardiovascular events, and have not demonstrated the reduction in coronary heart disease (CHID) predicted from changes in conventional risk factors or found in observational studies, suggesting that PHT may increase coronary risk through other pathways. We compared baseline levels of C-reactive protein (CRP), interleukin-6 (IL-6), sICAM-l, tissue plasminogen activator antigen (tPA-antigen), D-dimer, homocysteine, triglycerides, total-, HDL- and LDL- cholesterol in 304 cases with incident CHD and 304 controls, according to self-reported use of PHT Subjects were selected from the 75,343 participants in the WHI Observational Study without baseline cardiovascular disease or cancer. PHT was associated with higher CRP, HDL and triglycerides, and lower tPA-antigen and homocysteine. CRP was highest in users of unopposed conjugated equine estrogen. Levels of IL-6,sICAM-l, D-dimer and total cholesterol did not differ between PHT users and non-users. Transdermal estrogen users had low levels of D-dimer and CRP, Among users of estrogen plus progestin (EP), CRP, IL-6, tPA-antigen, D-dimer, total cholesterol and triglycerides were higher in women with incident coronary events than controls. Estrogen alone (E) controls shared only the tPA-antigen association, but had higher HDL and lower LDL than E cases. In non-users CRP tPA-antigen and D-dimer were associated with incident CHD. In summary, risk markers differed by PHT category. Some associations differed between women with and without incident CHD, especially for ER where inflammatory and thrombotic markers were higher in cases. These associations remain speculative pending confirmation in randomized trials. C1 Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. Brigham & Womens Hosp, Dept Cardiol, Boston, MA USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA USA. Rockledge Ctr, Natl Heart Lung & Blood Inst, Bethesda, MD USA. Wayne State Univ, Hutzel Womens Hosp, Detroit, MI USA. Fred Hutchinson Canc Res Ctr, Seattle, WA USA. RP Langer, RD (reprint author), Univ Calif San Diego, Dept Family & Prevent Med, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM rdlanger@ucsd.edu RI bashzar, salman/R-5748-2016 FU NHLBI NIH HHS [HL 07575, HL 63293]; WHI NIH HHS [N01-WH-3-2109, N01-WH-3-2120] NR 49 TC 21 Z9 22 U1 0 U2 7 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 2005 VL 93 IS 6 BP 1108 EP 1116 DI 10.1160/TH04-09-0608 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 938UL UT WOS:000230028800017 PM 15968396 ER PT J AU Ji, Y Sun, JL Du, KM Xie, JH Ji, YH Yang, JH Fu, M Sun, Y Jin, Y Liu, DZ Zhao, TM AF Ji, Y Sun, JL Du, KM Xie, JH Ji, YH Yang, JH Fu, M Sun, Y Jin, Y Liu, DZ Zhao, TM TI Identification of a novel HLA-A*0278 allele in a Chinese family SO TISSUE ANTIGENS LA English DT Article DE cloning of HLA-A*0278; HLA-A allele; PCR-SSP; SNP AB A novel human leukocyte antigen-A (HLA-A) allele, A*0278, has been identified in a Chinese family using DNA-based typing and molecular cloning methods. The alleles A*0278 differs from its closest matching HLA sequence of A*0256 by a silent substitution at 102 A > C and by two replacement substitutions, 98T > A and 292 C > G in exon 2, resulting in a change of codon 33 from Phe (TTC) to Tyr (TAC) and codon 98 from His (CAC) to Asp (GAC). Serology study revealed that A*0278 is associated with HLA-A2 broad specificity. A polymerase chain reaction-sequence-specific primers-based assay was developed to identify A*0278. Family study indicated that the propositus inhered his father's HLA haplotype A*0278, B*35, DRB1*15. No further individuals of A*0278 were found in 5000 Chinese bone marrow donor volunteers. C1 NIAID, Mol & Cellular Immunogenet Sect, NIH, Bethesda, MD 20892 USA. Shanghai Blood Ctr, Shanghai, Peoples R China. RP Zhao, TM (reprint author), NIAID, Mol & Cellular Immunogenet Sect, NIH, Bldg 50,Room 5516,50 South Dr, Bethesda, MD 20892 USA. EM tzhao@niaid.nih.gov NR 3 TC 11 Z9 12 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JUN PY 2005 VL 65 IS 6 BP 564 EP 566 DI 10.1111/j.0001-2815.2005.00405.x PG 3 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 925VC UT WOS:000229080400009 PM 15896205 ER PT J AU Foster, PMD Harris, MW AF Foster, PMD Harris, MW TI Changes in androgen-mediated reproductive development in male rat offspring following exposure to a single oral dose of flutamide at different gestational ages SO TOXICOLOGICAL SCIENCES LA English DT Article DE flutamide; gestational exposure; endocrine; disruptor; antiandiogen ID IN-UTERO; 5-ALPHA-REDUCTASE INHIBITOR; ANTIANDROGEN FLUTAMIDE; CRYPTORCHIDISM; MALFORMATIONS; TRACT; HYPOSPADIAS; FINASTERIDE; PESTICIDES; MORPHOLOGY AB Previous studies have indicated that the androgen receptor antagonist, flutamide, can produce a suite of reproductive malformations in the male rat when orally administered daily on gestation days (GD) 12-21. The objective of this study was to investigate the gestation time dependence for the induction of these malformations to establish a robust animal model for future studies of gene expression related to specific malformations. Groups of timed-pregnant Sprague-Dawley rats (GD 0 = day of mating) were administered flutamide as a single gavage dose (50 mg/kg) on GD 16, 17, 18, or 19 with 10 dams per group. Control animals (5 dams per time per group) were administered corn oil vehicle (2 ml/kg). Dams were allowed to litter, and their adult male offspring were killed at postnatal day (PND) 100 +/- 10. Anogenital distance was measured at PND 1 and 100. Areolae were scored at PND 13, and permanent nipples evaluated at PND 100. No reproductive tract malformations were found in control male offspring. In the treated groups, malformations were noted following exposure at every GD, although the incidence of specific malformations varied by GD. At GD 16, the highest incidence was noted for permanent nipples (46% pups, 60% litters), epispadias (12% pups, 30% litters), and missing epididymal components (5% pups, 20% litters). The highest incidences for hypospadias (58% pups, 80% litters), vaginal pouch (49% pups, 70% litters), cleft prepuce (29% pups, 60% litters), and missing prostate lobes (12% pups, 60% litters) were noted at GD 17. At GD 18 the highest incidence of malformations noted were epispadias (5% pups, 30% litters), reduced prostate size (32% pups, 90% litters), and abnormal kidneys (3% pups, 30% litters) and bladders (7% pups, 30% litters), while on GD 19 70% of the litters had animals with abnormal seminal vesicles. Testicular and epididymal morphological changes were noted at all GDs and were consistent with the gross observations and peaked in incidence and severity on GD17. The major discrepancy between this study and previous multiple-dose studies was in the very few numbers of animals presenting with cryptorchidism (only one each on GDs 16 and 17), suggesting that exposure over multiple days may be required to induce this malformation. Thus, a single gestational exposure of flutamide induced numerous reproductive tract malformations consistent with previously reports following multiple exposures, with the timing of the exposure producing marked tissue selectivity in the response noted in adult offspring. C1 NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Foster, PMD (reprint author), NIEHS, Mol Toxicol Lab, POB 12233 MD EC-34, Res Triangle Pk, NC 27709 USA. EM foster2@niehs.nih.gov NR 24 TC 47 Z9 49 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2005 VL 85 IS 2 BP 1024 EP 1032 DI 10.1093/toxsci/kfi159 PG 9 WC Toxicology SC Toxicology GA 928QN UT WOS:000229286900023 PM 15788718 ER PT J AU El Hadri, L Chanas, B Ghanayem, BI AF El Hadri, L Chanas, B Ghanayem, BI TI Comparative metabolism of methacrylonitrile and acrylonitrile to cyanide using cytochrome P4502E1 and microsomal epoxide hydrolase-null mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE methacrylonitrile; acrylonitrile; cytochrome P4502E1 ID URINARY METABOLITES; STEROID-METABOLISM; B6C3F1 MICE; F344 RATS; TOXICITY; CYP2E1; 2E1; CARCINOGENICITY; IDENTIFICATION; DISPOSITION AB Methacrylonitrile (MAN) and acrylonitrile (AN) are metabolized via glutathione (GSH) conjugation or epoxide formation. We have recently shown that CYP2E1 is essential for AN epoxidation and subsequent cyanide liberation. Current studies were designed to compare the enzymatic basis of MAN vs. AN metabolism to cyanide using wild-type (WT), CYP2E1-, and mEH-null mice. Mice received a single gavage dose of 0.047, 0.095, 0.19, or 0.38 mmol/kg of MAN or AN, and blood cyanide was measured at 1 or 3 h later. Blood cyanide levels in WT mice treated with AN or MAN were dose and time dependent. At equimolar doses, significantly higher levels of cyanide were detected in the blood of MAN- vs. AN-treated mice. Further, while significant reduction in blood cyanide levels occurred in MAN-treated CYP2E1-null vs. WT mice, AN metabolism to cyanide was largely abolished in CYP2E1-null mice. Pretreatment of mice with 1-aminobenzotriazole (ABT, CYP inhibitor) demonstrated that CYPs other than CYP2E1 also contribute to MAN metabolism to cyanide. Blood cyanide levels in mEH-null mice treated with aliphatic nitriles are generally lower than levels in similarly treated WT mice. Western blot analysis showed that expression of sEH was greater in male vs. female mice. The role of various epoxide hydrolases (EHs) in the production of cyanide from aliphatic nitriles is apparently structure and dose dependent. Regardless of genotype, significantly higher levels of cyanide were measured in the blood of male vs. female mice treated with MAN or AN. In conclusion, these data showed that (1) at equimiolar doses, higher blood cyanide levels were detected in mice treated with MAN vs. AN; (2) while CYP2E1 is the only enzyme responsible for AN metabolism to cyanide, other CYPs also contribute to MAN metabolism; and (3) significantly higher levels of cyanide were measured in the blood of male vs. female treated with either nitrile. Higher blood cyanide levels in male vs. female mice and in MAN- vs. AN-treated mice may explain the gender-related differences in the toxicity of these chemicals and the greater potency of MAN vs. AN. Published by Elsevier Inc. C1 NIEHS, Lab Pharmacol & Chem, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Ghanayem, BI (reprint author), NIEHS, Lab Pharmacol & Chem, Environm Toxicol Program, NIH, 111 Alexander Dr,MD B3-10, Res Triangle Pk, NC 27709 USA. EM ghanayem@niehs.nih.gov NR 52 TC 9 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUN 1 PY 2005 VL 205 IS 2 BP 116 EP 125 DI 10.1016/j.taap.2004.10.002 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 929WM UT WOS:000229377300002 PM 15893539 ER PT J AU Crosland, RD Fitch, RW Hines, HB AF Crosland, RD Fitch, RW Hines, HB TI Characterization of beta-leptinotarsin-h and the effects of calcium flux antagonists on its activity SO TOXICON LA English DT Article DE Ca2+ channel; Ca2+ uptakes; synaptosomes; Leptinotarsa haldemani ID JUVENILE-HORMONE ESTERASE; COLORADO POTATO BEETLE; CA2+ CHANNELS; FUNCTIONAL DIVERSITY; NEUROSECRETORY-CELLS; TRANSMITTER RELEASE; SENSORY NEURONS; RAT; SYNAPTOSOMES; THAPSIGARGIN AB beta-Leptinotarsin-h, purified from the hemolymph of the beetle Leptinotarsa haldemani, is a potent (similar to 1 nM) neuroactive protein that rapidly (few seconds) stimulates Ca2+ influx and neurotransmitter release. Our goals were to further characterize beta-leptinotarsin-h and to test the hypothesis that it stimulates Ca2+ influx through presynaptic Ca2+ channels. Analysis of partial amino acid sequences revealed that beta-leptinotarsin-h is a unique protein with significant similarity to only one other protein, the juvenile hormone esterase of Leptinotarsa decemlineata, commonly known as the Colorado potato beetle. We have examined the effect of beta-Ieptinotarsin-h on Ca2+ current, Ca2+ uptake, Ca2+ levels, and neurotransmitter release in synaptosomes, cell lines, and neuronal systems. We found that its preferred site of action appears to be mammalian presynaptic nerve terminals. We tested antagonists of Ca2+ flux for their effects on beta-leptinotarsin-h-stimulated Ca2+ uptake in rat brain synaptosomes. The non-selective Ca2+ channel blockers flunarizine, Ni2+, ruthenium red, high-concentration thapsigargin, and SKF 96365 inhibited beta-leptinotarsin-h's activity, but none of the tested selective blockers of voltage-operated Ca2+ channels (omega-agatoxin IVA, omega-conotoxin GVIA, omega-conotoxin MVIIC, nicardipine, nifedipine, SNX-482) was inhibitory. Selective inhibitors of ligand-operated, store-operated, and transduct ion-operated channels were also not inhibitory. beta-Leptinotarsin-h did not stimulate Na+ uptake, ruling out Na+ channels and many non-selective cation channels as targets. We conclude that beta-leptinotarsin-h stimulated Ca2+ uptake through presynaptic Ca2+ channels; which channel is yet to be determined. beta-Leptinotarsin-h may prove to be a useful tool with which to investigate calcium channels and calcium flux. Published by Elsevier Ltd. C1 NINDS, NIH, Sci Review Branch, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, Sect Pharmacodynam, NIH, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Div Toxinol, Ft Detrick, MD 21701 USA. RP Crosland, RD (reprint author), NINDS, NIH, Sci Review Branch, Room 3208,6001 Execut Blvd, Bethesda, MD 20892 USA. EM crosland@nih.gov NR 39 TC 5 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD JUN 1 PY 2005 VL 45 IS 7 BP 829 EP 841 DI 10.1016/j.toxicon.2004.12.022 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 936HQ UT WOS:000229846500003 PM 15904678 ER PT J AU Kurtzberg, J Cairo, MS Fraser, JK Baxter-Lowe, L Cohen, G Carter, SL Kernan, NA AF Kurtzberg, J Cairo, MS Fraser, JK Baxter-Lowe, L Cohen, G Carter, SL Kernan, NA TI Results of the Cord Blood Transplantation (COBLT) Study unrelated donor banking program SO TRANSFUSION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Bone-Marrow-Transplantation CY FEB, 2004 CL Orlando, FL SP Amer Soc Bone Marrow Transplantat ID VERSUS-HOST-DISEASE; PLACENTAL-BLOOD; ENGRAFTMENT; RECIPIENTS; RECONSTITUTION; OUTCOMES; CHILDREN; ADULTS AB Background: The goals of the Cord Blood Transplantation (COBLT) Study banking program initiated in 1996 were to develop standard operating procedures (SOPs) for cord blood (CB) donor recruitment and banking and to build an ethnically diverse unrelated CB bank to support a transplantation protocol. Study Design and Methods: The program included collection centers, three banks, a steering committee, and a medical coordinating center (MCC) that developed and validated SOPs and a Web-based data collection system. External oversight was performed by the National Heart, Lung, and Blood Institute and the MCC. Results: A total of 34,799 potential donors were screened and 20,710 consented. A total of 17,207 ethnically diverse units were collected between 1998 and 2001. A total of 11,077 (64%) units were cryopreserved and quarantined. Of these, 79 percent met eligibility criteria and were HLA-typed and entered into the search registry. Higher CB volumes and cell counts were obtained from cesarean sections compared to vaginal deliveries. Units from African American persons contained lower cell counts per volume compared to other ethnicities. Birth weight correlated with volume and cell content. External oversight was accomplished through custom reports generated by the data collection system and periodic site visits. During maintenance, a breach in the SOPs was detected during a site visit at one of the banks. These units were designated for future use in nonclinical research. Conclusion: The COBLT Study demonstrated that SOPs and data collection can be implemented in multiple banks coordinated by one MCC. Relationships between donor demographics and CB content may be useful in the development of other CB banking programs. C1 Duke Univ, Med Ctr, Div Pediat Blood & Marrow Transplantat, Durham, NC 27710 USA. EMMES Corp, Rockville, MD USA. Georgetown Univ, Washington, DC USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NHLBI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Kurtzberg, J (reprint author), Duke Univ, Med Ctr, Div Pediat Blood & Marrow Transplantat, Box 3350, Durham, NC 27710 USA. EM kurtz001@mc.duke.edu RI Fraser, John/I-7309-2013; OI Kernan, Nancy/0000-0003-1417-1823 FU NHLBI NIH HHS [N01-HB-67132, N01-HB-67136, N01-HB-67141, N01-HB-67142] NR 25 TC 57 Z9 59 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2005 VL 45 IS 6 BP 842 EP 855 DI 10.1111/j.1537-2995.2005.04428.x PG 14 WC Hematology SC Hematology GA 927TW UT WOS:000229224400005 PM 15934981 ER PT J AU Cairo, MS Wagner, EL Fraser, J Cohen, G van de Ven, C Carter, SL Kernan, NA Kurtzberg, J AF Cairo, MS Wagner, EL Fraser, J Cohen, G van de Ven, C Carter, SL Kernan, NA Kurtzberg, J TI Characterization of banked umbilical cord blood hematopoietic progenitor cells and lymphocyte subsets and correlation with ethnicity, birth weight, sex, and type of delivery: a Cord Blood Transplantation (COBLT) Study report SO TRANSFUSION LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 17-20, 2004 CL New Orleans, LA SP Int Soc Expt Hematol ID VERSUS-HOST-DISEASE; BONE-MARROW RECONSTITUTION; UNRELATED DONORS; STEM-CELLS; NONMALIGNANT DISEASE; MONONUCLEAR-CELLS; PLACENTAL-BLOOD; ACTIVATED CORD; ENGRAFTMENT; RECIPIENTS AB Background: The Cord Blood Transplantation (COBLT) Study banking program was initiated in 1996. The study goals were to develop standard operating procedures for cord blood (CB) donor recruitment and banking and to build an ethnically diverse unrelated CB bank to support a transplantation protocol. Study Design and Methods: The hematopoietic progenitor cell (HPC) and lymphocyte subset (LS) content of approximately 8000 CB units were characterized, and these results were correlated with donor ethnicity, birth weight, gestational age, sex, and type of delivery. Results: There was a significant correlation of CD34+ cell count with colony-forming unit (CFU)-granulocyte-macrophage (r=0.68, p < 0.001), CFU-granulocyte-erythroid-macrophage-megakaryocyte (r=0.52, p < 0.001), burst-forming unit-erythroid (BFU-E; r=0.61, p < 0.001), and total CFUs (r=0.67, p < 0.001). Nucleated red blood cell count was significantly correlated with total CD34+ (r=0.56, p < 0.001), total CFU (r=0.50, p < 0.001), BFU-E (r=0.48, p < 0.001), and counts of CD34+ subsets (p < 0.001). Caucasian ethnicity was significantly correlated with higher CD3+/CD4+, CD19+, and CD16+/CD56+ LSs. Furthermore, CD34+/CD38- and CD34+/CD61+ CB units (HPC-C) were significantly lower in African American and Asian persons compared to Caucasian and Hispanic persons. Male sex was associated with significantly fewer CD3+/CD4+, CD19+, and CD16+/CD56+ but increased CD3+/CD8+ LSs (p < 0.001). Finally, cesarean section was associated with significantly higher total CFU and CD16+/CD56+ but lower CD3+/CD4+, CD3+/CD8+, and CD19+ LSs. Conclusion: These results provide a standard and range for uniformly processed HPC-C progenitor cells and LSs. CB progenitor cells and/or LSs may in the future predict for rapidity of engraftment, incidence of graft-versus-host disease, speed and quality of immunore-constitution, graft-versus-tumor effects, and/or success of gene transfection after CB transplantation. C1 Georgetown Univ, Washington, DC USA. EMMES Corp, Rockville, MD USA. Univ Calif Los Angeles, Los Angeles, CA USA. NHLBI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Duke Univ, Med Ctr, Durham, NC USA. RP Cairo, MS (reprint author), Columbia Univ, Div Pediat Hematol & Blood & Marrow Transplantat, 180 Ft Washington Ave,HP 5-506, New York, NY 10032 USA. EM mc1310@columbia.edu RI Fraser, John/I-7309-2013 FU NHLBI NIH HHS [N01-HB-67142, N01-HB-67136, N01-HB-67141, N01-HB-67132] NR 49 TC 63 Z9 69 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2005 VL 45 IS 6 BP 856 EP 866 DI 10.1111/j.1537-2995.2005.04429.x PG 11 WC Hematology SC Hematology GA 927TW UT WOS:000229224400006 PM 15934982 ER PT J AU Haddad, S Leitman, SF Wesley, RA Cecco, S Yau, YY Starling, J Rehak, NN Bolan, CD AF Haddad, S Leitman, SF Wesley, RA Cecco, S Yau, YY Starling, J Rehak, NN Bolan, CD TI Placebo-controlled study of intravenous magnesium supplementation during large-volume leukapheresis in healthy allogeneic donors SO TRANSFUSION LA English DT Article ID IONIZED MAGNESIUM; CALCIUM; CITRATE; PLATELETPHERESIS; DEFICIENCY; SECRETION; RAT AB Background: Marked decreases in ionized magnesium (iMg) levels occur during large-volume leukapheresis (LVL); however, the effect of intravenous (IV) magnesium supplementation in this setting has not been carefully studied. Study Design and Methods: Thirty healthy allogeneic peripheral blood progenitor cell donors receiving citrate anticoagulant with IV calcium prophylaxis were randomized to receive either IV magnesium (0.2 mg Mg per mL acid citrate dextrose-A) or placebo during LVL, with a double-blind design. Results: Thirty subjects underwent 75 LVL pro- cedures, 37 with magnesium and 38 with placebo. Group characteristics were similar for sex, weight, citrate infusion rate (1.36 mg/kg/min vs. 1.37 mg/kg/min), and volume processed (16 L vs. 17 L). Serum iMg levels remained within the reference range with magnesium supplementation, but decreased 39 +/- 11 percent below baseline (p < 10(-10)) after placebo, with greater decreases after consecutive procedures. Subjects receiving magnesium had more vigorous parathyroid hormone responses and higher glucose levels and also tended to have higher serum potassium and ionized calcium levels. Mild paresthesias, coldness, and nausea occurred in 28, 20, and 7 percent of donors, respectively, with no significant differences between groups. Severe symptoms (chest tightness) occurred in only one subject receiving placebo. Conclusion: IV magnesium supplementation exerts a significant impact on serum magnesium levels, but does not reduce the frequency or severity of the relatively mild citrate-related effects observed in LVL performed with continuous IV calcium prophylaxis. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Biostat Serv, Off Director, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Silver Spring, MD USA. RP Haddad, S (reprint author), US FDA, Rockville, MD 20857 USA. EM salim.haddad@Fda.hhs.gov NR 23 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2005 VL 45 IS 6 BP 934 EP 944 DI 10.1111/j.1537-2995.2005.04312.x PG 11 WC Hematology SC Hematology GA 927TW UT WOS:000229224400016 PM 15934992 ER PT J AU Prikhod'ko, GG Vasilyeva, I Reyes, H Wong, S Brown, KE Jameson, T Busby, TF AF Prikhod'ko, GG Vasilyeva, I Reyes, H Wong, S Brown, KE Jameson, T Busby, TF TI Evaluation of a new LightCycler reverse transcription-polymerase chain reaction infectivity assay for detection of human parvovirus B19 in dry-heat inactivation studies SO TRANSFUSION LA English DT Article ID CELL-LINE; IDENTIFICATION; DNA; TRANSMISSION; REPLICATION; PROMOTER AB Background: Human parvovirus B19 (B19) is a widely distributed infectious agent, which causes a variety of illnesses including erythema infectiosum (fifth disease) especially in children, arthritis, aplastic crisis, and hydrops fetalis. B19 can be transmitted from asymptomatic blood donors to recipients of their blood components. Fifth disease has been reported in patients receiving red blood cells, platelets, solvent/detergent-treated plasma, and clotting factor concentrates. Study Design and Methods: A new B19-specific Light Cycler (LC) reverse transcription-polymerase chain reaction (RT-PCR) infectivity assay was developed for quantitative analysis of the infectivity of B19 in virus validation studies. The cycling conditions and the primers of the new assay were designed to amplify spliced RNA forms but not precursor RNA or B19 genome. One 50 percent infectious dose, determined on UT7/Epo-S1 cells of low passage, equaled 3.74 +/- 0.1 log international units of B19 DNA. Results: The efficiency of the dry-heat process (100 degrees C) on inactivation of B19 spiked and lyophilized with fibrinogen, a major component of the clotting factor concentrate and hemostatic dressing products, was investigated by use of B19-specific LC RT-PCR infectivity assay. At 1.3 to 1.7 percent residual moisture of fibrinogen, the infectivity of B19 was reduced dramatically by 3.3 to 5.1 log for 1 and 2 hours of dry-heat treatment, respectively. B19 infectivity was reduced 1.5, 2.8, and 3.8 log for 1, 2, and 3 hours of dry-heat treatment, respectively, at 0.5 to 0.7 percent residual moisture level. Conclusion: These findings suggest that level of residual moisture of lyophilized fibrinogen with B19 spike correlated with a different resistance of B19 to dry-heat treatment, and that low moisture may stabilize virus against heat. C1 Amer Red Cross, Jerome H Holland Lab Biomed Sci, Plasma Derivat Dept, Rockville, MD 20855 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Prikhod'ko, GG (reprint author), Amer Red Cross, Jerome H Holland Lab Biomed Sci, Plasma Derivat Dept, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. EM PrikhodkoG@usa.redcross.org NR 27 TC 18 Z9 22 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2005 VL 45 IS 6 BP 1011 EP 1019 DI 10.1111/j.1537-2995.2005.04393.x PG 9 WC Hematology SC Hematology GA 927TW UT WOS:000229224400025 PM 15935001 ER PT J AU Semsey, S Virnik, K Adhya, S AF Semsey, S Virnik, K Adhya, S TI A gamut of loops: meandering DNA SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID SITE-SPECIFIC RECOMBINATION; INTEGRATION HOST FACTOR; RESONANCE ENERGY-TRANSFER; LAC REPRESSOR; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; PROTEIN HU; IN-VITRO; V-MYB; NUCLEOPROTEIN STRUCTURES AB Nucleoprotein complexes comprising short DNA loops (150 base pairs or less) are involved in a wide variety of DNA transactions (e.g. transcription regulation, replication and recombination) in both prokaryotes and eukaryotes, and also can be useful in designing nanostructures. In these higher-order nucleoprotein complexes, proteins bound to spatially separated sites on a DNA interact with each other by looping out the relatively stiff intervening DNA. Recent technological developments have enabled determination of DNA trajectories in a few DNA-loop-containing regulatory complexes. Results show that, in a given system, a specific DNA trajectory is preferred over others. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM adhyas@mail.nih.gov RI Semsey, Szabolcs/L-6329-2013; OI Semsey, Szabolcs/0000-0002-4522-5495 NR 70 TC 60 Z9 62 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUN PY 2005 VL 30 IS 6 BP 334 EP 341 DI 10.1016/j.tibs.2005.04.009 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 939TS UT WOS:000230095900014 PM 15950878 ER PT J AU Waugh, DS AF Waugh, DS TI Making the most of affinity tags SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID MALTOSE-BINDING-PROTEIN; SOLUBLE RECOMBINANT PROTEINS; GLUTATHIONE-S-TRANSFERASE; ETCH VIRUS PROTEASE; ESCHERICHIA-COLI; FUSION PROTEINS; MAMMALIAN PROTEINS; PURIFICATION; EXPRESSION; PEPTIDE AB Proteins do not naturally lend themselves to high-throughput analysis because of their diverse physiochemical properties. Consequently, affinity tags have become indispensable tools for structural and functional proteomics initiatives. Although originally developed to facilitate the detection and purification of recombinant proteins, in recent years it has become clear that affinity tags can have a positive impact on the yield, solubility and even the folding of their fusion partners. However, no single affinity tag is optimal with respect to all of these parameters; each has its strengths and weaknesses. Therefore, combinatorial tagging might be the only way to harness the full potential of affinity tags in a high-throughput setting. C1 NCI, Prot Engn Sect, Macromol Crystallog Lab, Canc Res Ctr, Frederick, MD 21701 USA. RP Waugh, DS (reprint author), NCI, Prot Engn Sect, Macromol Crystallog Lab, Canc Res Ctr, POB B, Frederick, MD 21701 USA. EM waughd@ncifcrf.gov NR 42 TC 293 Z9 324 U1 8 U2 63 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD JUN PY 2005 VL 23 IS 6 BP 316 EP 320 DI 10.1016/j.tibtech.2005.03.012 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 936WQ UT WOS:000229886500008 PM 15922084 ER PT J AU Haeryfar, SMM AF Haeryfar, SMM TI The importance of being a pDC in antiviral immunity: the IFN mission versus Ag presentation? SO TRENDS IN IMMUNOLOGY LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; INTERFERON-PRODUCING CELLS; CD8(+) T-CELLS; IN-VIVO; ANTIGEN PRESENTATION; INFLUENZA-VIRUS; TRANSCRIPTION FACTORS; MONOCLONAL-ANTIBODY; ADAPTIVE IMMUNITY; ALPHA PRODUCTION AB Plasmacytoid pre-dendritic cells (pDCs) comprise a pivotal element of antiviral immune responses. They recognize viral components, leading to type I interferon (IFN) production, and affect adaptive defense strategies designed to eliminate viral pathogens. These strategies include the ability of pDCs to modulate virus-specific CD8(+) T-cell responses. Although a great deal has been learned recently about pDCs, our knowledge of whether, how and why pDCs might function as antigen-presenting cells is extremely limited, and now is a prime time for exploring the unknowns of this area. This Opinion will focus on the IFN production and T-cell priming capacity of pDCs, and will argue that IFN production (and not T-cell priming) is the main function of pDCs during viral infection. C1 NIAID, Cellular Biol Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Viral Immunol Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Haeryfar, SMM (reprint author), NIAID, Cellular Biol Sect, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mhaeryfar@niaid.nih.gov NR 54 TC 25 Z9 27 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD JUN PY 2005 VL 26 IS 6 BP 311 EP 317 DI 10.1016/j.it.2005.04.002 PG 7 WC Immunology SC Immunology GA 936WD UT WOS:000229885200007 PM 15922947 ER PT J AU Le Foll, B Goldberg, SR AF Le Foll, B Goldberg, SR TI Control of the reinforcing effects of nicotine by associated environmental stimuli in animals and humans SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID DOPAMINE D-3 RECEPTOR; CONDITIONED PLACE PREFERENCES; COCAINE-SEEKING BEHAVIOR; ADMINISTER PURE NICOTINE; UNLIMITED ACCESS; RAT-BRAIN; RIMONABANT SR141716; SMOKING CESSATION; CIGARETTE SMOKERS; NUCLEUS-ACCUMBENS AB Tobacco dependence through cigarette smoking is the leading preventable cause of death in the world and kills nearly 4 million people annually. Nicotine, a psychoactive component of tobacco, is thought to have a major role in tobacco dependence by acting directly as a reinforcer of drug-seeking and drug-taking behavior. However, recent findings obtained with two procedures that are used widely to assess reinforcing effects of drugs in experimental animals, intravenous drug self-administration and conditioned place-preference procedures, demonstrate that environmental factors have a major influence on the reinforcing effects of nicotine. Under some experimental conditions, nicotine is also self-administered reliably by humans. Environmental stimuli that have been associated previously with the self-administration of nicotine can reinstate extinguished drug-seeking behavior in animals and precipitate relapse to smoking behavior in ex-smokers. Innovative medications that target cannabinoid CB1 and dopamine D-3 receptors and might block specifically the influence of such conditioned environmental stimuli in smokers are in development. C1 NIDA, Behav Neurosci Res Branch, Preclin Pharmacol Sect, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. RP Le Foll, B (reprint author), NIDA, Behav Neurosci Res Branch, Preclin Pharmacol Sect, Dept Hlth & Human Serv,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM blefoll@intra.nida.nih.gov RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 NR 81 TC 59 Z9 60 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JUN PY 2005 VL 26 IS 6 BP 287 EP 293 DI 10.1016/j.tips.2005.04.005 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 936TY UT WOS:000229879500002 PM 15925703 ER PT J AU Pacher, P Schulz, R Liaudet, L Szabo, C AF Pacher, P Schulz, R Liaudet, L Szabo, C TI Nitrosative stress and pharmacological modulation of heart failure SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; NITRIC-OXIDE SYNTHASE; ISCHEMIA-REPERFUSION INJURY; PEROXYNITRITE DECOMPOSITION CATALYST; MATRIX-METALLOPROTEINASE INHIBITION; MYOFIBRILLAR CREATINE-KINASE; APOPTOSIS-INDUCING FACTOR; ENDOTHELIAL DYSFUNCTION; MYOCARDIAL-ISCHEMIA; CONTRACTILE DYSFUNCTION AB Dysregulation of nitric oxide (NO) and increased oxidative and nitrosative stress are implicated in the pathogenesis of heart failure. Peroxynitrite is a reactive oxidant that is produced from the reaction of nitric oxide with superoxide anion and impairs cardiovascular function through multiple mechanisms, including activation of matrix metalloproteinases (MMPs) and nuclear enzyme poly(ADP-ribose) polymerase (PARP). Recent studies suggest that the neutralization of peroxynitrite or pharmacological inhibition of MMPs and PARP are promising new approaches in the experimental therapy of various forms of myocardial injury. In this article, the role of nitrosative stress and downstream mechanisms, including activation of MMPs and PARP, in various forms of heart failure are discussed and novel emerging therapeutic strategies offered by neutralization of peroxynitrite and inhibition of MMPs and PARP in these pathophysiological conditions are reviewed. C1 NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. Univ Alberta, Dept Pharmacol, Cardiovasc Res Grp, Edmonton, AB, Canada. Univ Alberta, Dept Pediat, Cardiovasc Res Grp, Edmonton, AB, Canada. Univ Lausanne Hosp, Dept Internal Med, Div Crit Care, Lausanne, Switzerland. Univ Med & Dent New Jersey, Sch Med, Dept Surg, Newark, NJ 07103 USA. Semmelweis Univ, Sch Med, Dept Human Physiol & Clin Expt Res, Budapest, Hungary. Inotek Pharmaceut, Beverly, MA 01915 USA. RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413,Room 2S25, Bethesda, MD 20892 USA. EM ppacher@lycos.com RI Schulz, Richard/A-8739-2012; Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017 OI Schulz, Richard/0000-0002-5045-3193; Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural NIH HHS [Z01 AA000375-02] NR 80 TC 161 Z9 168 U1 0 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JUN PY 2005 VL 26 IS 6 BP 302 EP 310 DI 10.1016/j.tips.2005.04.003 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 936TY UT WOS:000229879500004 PM 15925705 ER PT J AU Ikeda, K Ide, S Han, WH Hayashida, M Uhl, GR Sora, I AF Ikeda, K Ide, S Han, WH Hayashida, M Uhl, GR Sora, I TI How individual sensitivity to opiates can be predicted by gene analyses SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID MU-OPIOID RECEPTOR; SINGLE-NUCLEOTIDE POLYMORPHISM; KNOCKOUT MICE; LINKAGE DISEQUILIBRIUM; MOLECULAR-MECHANISMS; SUBSTANCE DEPENDENCE; UNTRANSLATED REGION; CANDIDATE GENE; DEFICIENT MICE; MESSENGER-RNA AB Opiate analgesics are widely used and abused drugs. Individual differences in opiate sensitivity can hamper effective pain treatments and increase risks of drug abuse. Although genetic factors might affect individual differences in opiate sensitivity, scientific evidence for specific genetic mechanisms that underlie these differences has been sparse. Recent studies using inbred and knockout mice have revealed that the mu opioid peptide (MOP) receptor encoded by the Oprm1 gene has a mandatory role in the analgesic and addictive properties of opiate drugs. Increasing evidence suggests that differences in Oprm1 gene sequences affect the amount of Oprm1 mRNA and sensitivity to opiates, and > 100 polymorphisms have been identified in the human OPRM1 gene, some of which are related to vulnerability to drug dependence in some populations. Rapid advances in this research field are leading to improved understanding of the relationships between gene polymorphisms and opiate sensitivities that will enable more-accurate prediction of the opiate sensitivity and opiate requirements in individual patients. C1 Tokyo Inst Psychiat, Dept Mol Psychiat, Setagaya Ku, Tokyo 1568585, Japan. Hiroshima Int Univ, Dept Pharmaceut Sci, Neuropharmacol Lab, Kure, Hiroshima 7370112, Japan. Univ Tokyo, Inst Med Sci, Surg Ctr, Res Hosp,Minato Ku, Tokyo, Japan. NIDA, Baltimore, MD 21224 USA. Tohoku Univ, Grad Sch Med, Dept Neurosci, Div Psychobiol, Sendai, Miyagi 9808574, Japan. RP Ikeda, K (reprint author), Tokyo Inst Psychiat, Dept Mol Psychiat, Setagaya Ku, 2-1-8 Kamikitazawa, Tokyo 1568585, Japan. EM ikedak@prit.go.jp RI Ikeda, Kazutaka/I-4694-2013 OI Ikeda, Kazutaka/0000-0001-8342-0278 NR 57 TC 94 Z9 97 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JUN PY 2005 VL 26 IS 6 BP 311 EP 317 DI 10.1016/j.tips.2005.04.001 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 936TY UT WOS:000229879500005 PM 15925706 ER PT J AU Chen, C Kong, ANT AF Chen, C Kong, ANT TI Dietary cancer-chemopreventive compounds: from signaling and gene expression to pharmacological effects SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID ANTIOXIDANT-RESPONSE ELEMENT; DRUG-METABOLIZING-ENZYMES; ACTIVATED PROTEIN-KINASE; GLUTATHIONE-S-TRANSFERASE; COLON ADENOCARCINOMA CELLS; YA-SUBUNIT GENE; OXIDATIVE STRESS; NITRIC-OXIDE; (-)-EPIGALLOCATECHIN GALLATE; TRANSCRIPTIONAL ACTIVATION AB The process of cancer development (carcinogenesis leading to advanced metastasized cancers) in humans generally takes many years through initiation, promotion and progression. Because advanced metastasized cancers are almost impossible to treat, cancer chemoprevention for the control and containment of early cancer development is highly desirable. Recent studies have provided strong evidence that many daily-consumed dietary compounds possess cancer-protective properties that might interrupt the carcinogenesis process. These properties include the induction of cellular defense detoxifying and antioxidant enzymes, which can protect against cellular damage caused by environmental carcinogens or endogenously generated reactive oxygen species. These compounds can also affect cell-death signaling pathways, which could prevent the proliferation of tumor cells. In this review, we will summarize current knowledge on dietary cancer-chemopreventive compounds and their induction of detoxifying enzymes and anti-proliferative effects, and discuss the challenges in translating these signaling and gene-expression events to pharmacological effects. C1 Rutgers State Univ, Dept Pharmaceut, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USA. RP Kong, ANT (reprint author), NCI, Lab Metab, Bethesda, MD 20892 USA. EM kongt@rci.rutgers.edu RI Chen, Chi/B-4618-2008 FU NCI NIH HHS [R01 CA 092515, R01 CA 073674, R01 CA 094828] NR 79 TC 149 Z9 157 U1 0 U2 8 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JUN PY 2005 VL 26 IS 6 BP 318 EP 326 DI 10.1016/j.tips.2005.04.004 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 936TY UT WOS:000229879500006 PM 15925707 ER PT J AU Hediger, ML Luke, B van de Ven, C Nugent, C AF Hediger, ML Luke, B van de Ven, C Nugent, C TI Midupper arm circumference (MUAC) changes in late pregnancy predict fetal growth in twins SO TWIN RESEARCH AND HUMAN GENETICS LA English DT Article ID BIRTH-WEIGHT; INTRAUTERINE GROWTH; SEVERE ADULT; FAMINE; MALNUTRITION; WOMEN; GAIN AB The objective of the study was to test the hypothesis that changes in arm anthropometry can be used to determine the risk of faltering growth in twin gestations. Serial data on midupper arm circumference (MUAC) and maternal weight gain were collected from a sample of 156 mothers. Changes in MUAC were monitored from 20 to 34 weeks. Women with a large loss of MUAC (greater than 1.5 cm), particularly when it occurred within two to four weeks of delivery, were significantly heavier, had higher pregravid Body Mass Indexes (BMIs), but gained less weight than mothers with no change in MUAC. In analysis of covariance models adjusting for length of gestation, black ethnicity, males per twin pair, monochorionicity, and baseline MUAC at 20 weeks, a large loss of MUAC was associated with significantly lower birthweight (2263 g vs. 2499 g) and birthweight z-score (-0.92 SDU vs. -0.39 SDU). Changes in MUAC from 20 to 34 weeks, and especially near delivery, are significantly associated with fetal growth in twin pregnancies. A positive change may indicate that the mother has adequate dietary intake or nutrient stores to continue to accrue lean body mass and support fetal growth, while a loss of MUAC indicates that dietary intake or nutrient stores may be inadequate. This simple, relatively precise, measure of change in maternal body composition during pregnancy may be useful in identifying twin pregnancies at risk for faltering intrauterine growth, particularly among overweight or obese women. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Miami, Sch Nursing & Hlth Studies, Coral Gables, FL 33124 USA. Sch Med, Dept Obstet & Gynecol, Miami, FL USA. Univ Michigan, Sch Med, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. RP Hediger, ML (reprint author), DESPR, Epidemiol Branch, Bldg 6100,Room 7B03,MSC 7510,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hedigerm@exchange.nih.gov NR 18 TC 1 Z9 1 U1 0 U2 2 PU AUSTRALIAN ACAD PRESS PI BOWEN HILLS PA 32 JEAYS ST, BOWEN HILLS, QLD 4006, AUSTRALIA SN 1832-4274 J9 TWIN RES HUM GENET JI Twin Res. Hum. Genet. PD JUN PY 2005 VL 8 IS 3 BP 267 EP 270 PG 4 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 939AM UT WOS:000230044500011 PM 15989755 ER PT J AU Fogdell-Hahn, A Soldan, SS Shue, S Akhyani, N Refai, H Ahlqvist, J Jacobson, S AF Fogdell-Hahn, A Soldan, SS Shue, S Akhyani, N Refai, H Ahlqvist, J Jacobson, S TI Co-purification of soluble membrane cofactor protein (CD46) and human herpesvirus 6 variant A genome in serum from multiple sclerosis patients SO VIRUS RESEARCH LA English DT Article DE human herpesvirus 6; CD46; membrane cofactor protein; MCP; multiple sclerosis ID HUMAN-HERPESVIRUS 6; COMPLEMENT CONTROL PROTEINS; MEASLES-VIRUS; CELLULAR RECEPTOR; ELEVATED SERUM; HHV-6 DNA; IN-VITRO; INFECTION; PLASMA; FORMS AB The association of human herpesvirus 6 (HHV-6) and multiple sclerosis (MS) has been supported by several immunological and molecular studies. Recently, membrane cofactor protein (CD46) has been identified as the cellular receptor for the A and B variants of HHV-6. Elevated levels of soluble CD46 (sCD46) have been reported in the serum and CSF of MS patients. The aim of this study was to investigate a possible correlation between elevated levels of soluble CD46 and the presence of serum HHV-6 DNA in MS patients. An immunoaffinity column comprised of immobilized monoclonal antibodies to CD46 was developed to isolate sCD46 from cell free body fluids of MS patients and controls. After immunoaffinity purification, DNA was extracted from anti-CD46 column eluates and subjected to PCR amplification. Of the 42 MS samples tested, 4 serum samples were HHV-6 positive, 3 of which were typed as HHV-6A. The co-purification of sCD46 and HHV-6 DNA from MS sera indicates that HHV-6 is tightly connected to its receptor, CD46, in the serum of MS patients. Published by Elsevier B.V. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Inst Biomed Sci, Dept Genet, Washington, DC 20037 USA. Karolinska Hosp, Karolinska Inst, Neurol Sect, S-10401 Stockholm, Sweden. RP Jacobson, S (reprint author), NINDS, Neuroimmunol Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 5B-16, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 40 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD JUN PY 2005 VL 110 IS 1-2 BP 57 EP 63 DI 10.1016/j.virusres.2005.01.005 PG 7 WC Virology SC Virology GA 928JG UT WOS:000229267100006 PM 15845255 ER PT J AU Mahaney, JE Albers, RW Waggoner, JR Kutchai, HC Froehlich, JP AF Mahaney, JE Albers, RW Waggoner, JR Kutchai, HC Froehlich, JP TI Intermolecular conformational coupling and free energy exchange enhance the catalytic efficiency of cardiac muscle SERCA2a following the relief of phospholamban inhibition SO BIOCHEMISTRY LA English DT Article ID SARCOPLASMIC-RETICULUM MEMBRANES; 3'-5'-MONOPHOSPHATE-DEPENDENT PROTEIN-KINASE; ATPASE POLYPEPTIDE-CHAINS; CA-ATPASE; CALCIUM-PUMP; ADENOSINE-TRIPHOSPHATASE; ROTATIONAL-DYNAMICS; SKELETAL-MUSCLE; CROSS-LINKING; STATE AB Activation of cardiac muscle sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) by beta(1)-agonists involves cAMP- and PKA-dependent phosphorylation of phospholamban (PLB), which relieves the inhibitory effects of PLB on SERCA2a. To investigate the mechanism of SERCA2a activation, we compared the kinetic properties of SERCA2a expressed with (+) and without (-) PLB in High Five insect cell microsomes to those of SERCA1 and SERCA2a in native skeletal and cardiac muscle SR. Both native SERCA1 and expressed SERCA2a without PLB exhibited high-affinity (10-50 mu M) activation of pre-steady-state catalytic site dephosphorylation by ATP, steady-state accumulation of the ADP-sensitive phosphoenzyme (E1P), and a rapid phase of EGTA-induced phosphoenzyme (E2P) hydrolysis. In contrast, SERCA2a in native cardiac SR vesicles and expressed SERCA2a with PLB lacked the high-affinity activation by ATP and the rapid phase of E2P hydrolysis, and exhibited low steady-state levels of EIP. The results indicate that the kinetic differences in Ca2+ transport between skeletal and cardiac SR are due to the presence of phospholamban in cardiac SR, and not due to isoform-dependent differences between SERCA1 and SERCA2a. Therefore, the results are discussed in terms of a model in which PLB interferes with SERCA2a oligomeric interactions, which are important for the mechanism of Ca2+ transport in skeletal muscle SERCA1 [Mahaney, J. E., Thomas, D. D., and Froehlich, J. P. (2004) Biochemistry 43, 4400-4416]. We propose that intermolecular coupling of SERCA2a molecules during catalytic cycling is obligatory for the changes in Ca2+ transport activity that accompany the relief of PLB inhibition of the cardiac SR Ca2+-ATPase. C1 Univ Maryland, Dept Biochem & Mol Biol, Sch Med, Baltimore, MD 21201 USA. Edward Via Virginia Coll Osteopath Med, Biomed Sci Div, Blacksburg, VA 24060 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45267 USA. Univ Virginia, Dept Mol Physiol & Biophys, Charlottesville, VA 22908 USA. RP Froehlich, JP (reprint author), Univ Maryland, Dept Biochem & Mol Biol, Sch Med, 108 N Greene St, Baltimore, MD 21201 USA. EM froehlichj@grc.nia.nih.gov NR 48 TC 15 Z9 16 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 MAY 31 PY 2005 VL 44 IS 21 BP 7713 EP 7724 DI 10.1021/bi048011i PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930BD UT WOS:000229389900012 PM 15909986 ER PT J AU Phillips, RS Miles, EW Holtermann, G Goody, RS AF Phillips, RS Miles, EW Holtermann, G Goody, RS TI Hydrostatic pressure affects the conformational equilibrium of Salmonella typhimurium tryptophan synthase SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; ALPHA(2)BETA(2) COMPLEX; BIENZYME COMPLEX; MONOVALENT CATIONS; INTERSUBUNIT COMMUNICATION; L-SERINE; ALLOSTERIC REGULATION; CRYSTAL-STRUCTURES; ALPHA-SUBUNITS; BETA-SUBUNITS AB The effect of hydrostatic pressure on the tryptophan (Trp) synthase alpha(2)beta(2) complex from Salmonella typhimurium has been investigated. Trp synthase has been shown previously to exhibit low-activity (open) and high-activity (closed) conformations. The equilibrium between the open and closed conformations of Trp synthase has been found to be affected by a wide range of variables, including a-subunit ligands, monovalent cations, organic solvents, pH, and temperature. The absorption spectrum of the Trp synthase-L-Ser complex shows an increase in absorption of the 423 nm band of the external aldimine, which is a characteristic of the open conformation, as hydrostatic pressure is increased from I to 2000 bar. The Delta V-o and K-o for the equilibrium between the closed and open conformations of the Trp synthase-L-Ser complex are - 126 mL/mol and 0.12 for the Na+ form and - 171 mL/mol and 2.3 x 10(-4) for the NH4+ form. When the Trp synthase-L-Ser complex is subjected to pressure jumps of 100-400 bar, relaxations are observed, exhibiting an increase in fluorescence emission at wavelengths greater than 455 nm, with 405 nm excitation. The relaxation to the new equilibrium position requires two exponentials to fit the data in the presence of 0.1 M Na+ and three exponentials to obtain a reasonable fit in the absence of cations and with 0.1 M NH4+. Fluorescence emission at 325 nm, with excitation at 280 nm, also increases when the Trp synthase-L-Ser complex is subjected to pressure jump. These data demonstrate that the open conformation of Trp synthase is favored by higher pressure. Thus, the open conformation has a smaller apparent net system volume than the closed conformation. We estimate that there are 3547 more waters in the solvation shell of the open conformation than in that of the closed conformation. C1 Univ Georgia, Dept Chem, Athens, GA 30602 USA. Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. Univ Georgia, Ctr Metalloenzyme Studies, Athens, GA 30602 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Max Planck Inst Mol Physiol, D-44227 Dortmund, Germany. RP Phillips, RS (reprint author), Univ Georgia, Dept Chem, Athens, GA 30602 USA. EM rsphillips@chem.uga.edu RI Goody, Roger/J-8845-2014; OI Goody, Roger/0000-0002-0772-0444; Phillips, Robert/0000-0001-8710-562X FU NIGMS NIH HHS [GM-45288] NR 48 TC 18 Z9 18 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 31 PY 2005 VL 44 IS 21 BP 7921 EP 7928 DI 10.1021/bi050056b PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930BD UT WOS:000229389900033 PM 15910007 ER PT J AU Lepore, AC Bakshi, A Swanger, SA Rao, MS Fischer, I AF Lepore, AC Bakshi, A Swanger, SA Rao, MS Fischer, I TI Neural precursor cells can be delivered into the injured cervical spinal cord by intrathecal injection at the lumbar cord SO BRAIN RESEARCH LA English DT Article DE neural stem cell; spinal cord injury; neuron; glial cell; transplantation; neural progenitor ID NEUROEPITHELIAL STEM-CELLS; PROGENITOR CELLS; CEREBROSPINAL-FLUID; ADULT BRAIN; RESTRICTED PRECURSORS; CHEMOKINE RECEPTORS; FUNCTIONAL RECOVERY; WHITE-MATTER; RAT MODEL; TRANSPLANTATION AB Neural precursor cells (NPCs) are promising grafts for treatment of traumatic CNS injury and neurodegenerative disorders because of their potential to differentiate into neurons and glial cells. When designing clinical protocols for NPC transplantation, it is important to develop alternatives to direct parenchymal injection, particularly at the injury site. We reasoned that since it is minimally invasive, intrathecal delivery of NPCs at lumbar spinal cord (lumbar puncture) represents an important and clinically applicable strategy. We tested this proposition by examining whether NPCs can be delivered to the injured cervical spinal cord via lumbar puncture using a mixed population of neuronal-restricted precursors (NRPs) and glial-restricted precursors (GRPs). For reliable tracking, the NPCs were derived from the embryonic spinal cord of transgenic donor rats that express the marker gene, human placental alkaline phosphatase, under the control of the ubiquitous Rosa 26 promoter. We found that mixed NRP/GRP grafts can be efficiently delivered to a cervical hemisection injury site by intrathecal delivery at the lumbar cord. Similar to direct parenchymal injections, transplanted NRP/GRP cells survive at the injury cavity for at least 5 weeks post-engraftment, migrate into intact spinal cord along white matter tracts and differentiate into all three mature CNS cell types, neurons, astrocytes, and oligodendrocytes. Furthermore, very few graft-derived cells localize to areas outside the injury site, including intact spinal cord and brain. These results demonstrate the potential of delivering lineage-restricted NPCs using the minimally invasive lumbar puncture method for the treatment of spinal cord injury. (C) 2005 Elsevier B.V. All rights reserved. C1 Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Fischer, I (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, 2900 Queen Lane, Philadelphia, PA 19129 USA. EM Itzhak.fischer@drexel.edu RI Fischer, Itzhak/D-1080-2012; OI Fischer, Itzhak/0000-0003-3187-8740; Swanger, Sharon/0000-0003-0615-6244 FU NINDS NIH HHS [NS 37515, NS24707] NR 43 TC 69 Z9 77 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 31 PY 2005 VL 1045 IS 1-2 BP 206 EP 216 DI 10.1016/j.brainres.2005.03.050 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 932BX UT WOS:000229530300024 PM 15910779 ER PT J AU Helm, RH Leclercq, C Faris, OP Ozturk, C McVeigh, E Lardo, AC Kass, DA AF Helm, RH Leclercq, C Faris, OP Ozturk, C McVeigh, E Lardo, AC Kass, DA TI Cardiac dyssynchrony analysis using circumferential versus longitudinal strain - Implications for assessing cardiac resynchronization SO CIRCULATION LA English DT Article DE resynchronization therapy; heart failure; bundle-branch block; pacing ID CHRONIC HEART-FAILURE; BUNDLE-BRANCH BLOCK; TAGGED MR-IMAGES; DILATED CARDIOMYOPATHY; ECHOCARDIOGRAPHIC EVALUATION; VENTRICULAR ASYNCHRONY; FAILING HEART; QRS DURATION; IN-VIVO; THERAPY AB Background - QRS duration is commonly used to select heart failure patients for cardiac resynchronization therapy (CRT). However, not all patients respond to CRT, and recent data suggest that direct assessments of mechanical dyssynchrony may better predict chronic response. Echo-Doppler methods are being used increasingly, but these principally rely on longitudinal motion (epsilon(II)). It is unknown whether this analysis yields qualitative and/or quantitative results similar to those based on motion in the predominant muscle-fiber orientation (circumferential; epsilon(cc)). Methods and Results - Both epsilon(II) and epsilon(cc) strains were calculated throughout the left ventricle from 3D MR-tagged images for the full cardiac cycle in dogs with cardiac failure and a left bundle conduction delay. Dyssynchrony was assessed from both temporal and regional strain variance analysis. CRT implemented by either biventricular (BiV) or left ventricular - only (LV) pacing enhanced systolic function similarly and correlated with improved dyssynchrony based on epsilon(cc)-based metrics. In contrast, longitudinal-based analyses revealed significant resynchronization with BiV but not LV for the overall cycle and correlated poorly with global functional benefit. Furthermore, unlike circumferential analysis, epsilon(II)-based indexes indicated resynchronization in diastole but much less in systole and had a lower dynamic range and higher intrasubject variance. Conclusions - Dyssynchrony assessed by longitudinal motion is less sensitive to dyssynchrony, follows different time courses than those from circumferential motion, and may manifest CRT benefit during specific cardiac phases depending on pacing mode. These results highlight potential limitations to epsilon(II)-based analyses and support further efforts to develop noninvasive synchrony measures based on circumferential deformation. C1 Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. Univ Rennes, Dept Cardiol, Rennes, France. NIH, Cardiac Energet Lab, Bethesda, MD 20892 USA. RP Kass, DA (reprint author), Johns Hopkins Med Inst, Dept Med, Div Cardiol, 720 Rutland Ave, Baltimore, MD 21205 USA. EM dkass@jhmi.edu RI Ozturk, Cengizhan/A-6177-2016 OI Ozturk, Cengizhan/0000-0002-6966-0774 FU Intramural NIH HHS [Z01 HL004609-08] NR 41 TC 197 Z9 214 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 MAY 31 PY 2005 VL 111 IS 21 BP 2760 EP 2767 DI 10.1161/CIRCULATIONAHA.104.508457 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 931DE UT WOS:000229465200010 PM 15911694 ER PT J AU Varnai, P Balla, A Hunyady, L Balla, T AF Varnai, P Balla, A Hunyady, L Balla, T TI Targeted expression of the inositol 1,4,5-triphosphate receptor (IP3R) ligand-binding domain releases Ca2+ via endogenous IP3R channels SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Ca2+ channel; endoplasmic reticulum; red fluorescent protein ID 1,4,5-TRISPHOSPHATE RECEPTOR; ENDOPLASMIC-RETICULUM; CALCIUM OSCILLATIONS; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; PROTEIN; TRISPHOSPHATE; INHIBITION; CELLS; LOCALIZATION AB Virtually all functions of a cell are influenced by cytoplasmic [Ca2+] increases. Inositol 1,4,5-trisphosphate receptor (IP3R) channels, located in the endoplasmic reticulum (ER), release Ca2+ in response to binding of the second messenger, IP3- IP(3)Rs thus are part of the information chain interpreting external signals and transforming them into cytoplasmic Ca2+ transients. IP(3)Rs function as tetramers, each unit comprising an N-terminal ligand-binding domain (LBD) and a C-terminal channel domain linked by a long regulatory region. It is not yet understood how the binding of IP3 to the LBD regulates the gating properties of the channel. Here, we use the expression of IP3 binding protein domains tethered to the surface of the endoplasmic reticulum (ER) to show that the all-helical domain of the IP3R LBD is capable of depleting the ER Ca2+ pools by opening the endogenous IP(3)Rs, even without IP3 binding. This effect requires the domain to be within 50 A of the ER membrane and is impaired by the presence of the N-terminal inhibitory segment on the LBD. These findings raise the possibility that the helical domain of the LBD functions as an effector module possibly interacting with the channel domain, thereby being part of the gating mechanisms by which the IP3-induced conformational change within the LBD regulates Ca2+ release. C1 NIH, Endocrinol & Reprod Res Branch, NICHHD, Bethesda, MD 20892 USA. Semmelweis Univ, Fac Med, Dept Physiol, H-1085 Budapest, Hungary. RP Balla, T (reprint author), NIH, Endocrinol & Reprod Res Branch, NICHHD, Bldg 49,Room 6A35,49 Convent Dr, Bethesda, MD 20892 USA. EM tambal@box-t.nih.gov OI Balla, Tamas/0000-0002-9077-3335; Balla, Andras/0000-0002-6450-2793 NR 32 TC 27 Z9 30 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 31 PY 2005 VL 102 IS 22 BP 7859 EP 7864 DI 10.1073/pnas.0407535102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 932CE UT WOS:000229531000016 PM 15911776 ER PT J AU McCormick, PJ Martina, JA Bonifacino, JS AF McCormick, PJ Martina, JA Bonifacino, JS TI Involvement of clathrin and AP-2 in the trafficking of MHC class II molecules to antigen-processing compartments SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE invariant chain; adaptor proteins; endosomes; antigen presentation ID MAJOR HISTOCOMPATIBILITY COMPLEX; INVARIANT CHAIN COMPLEXES; ENDOCYTIC PATHWAY; HLA-DR; INTRACELLULAR-TRANSPORT; MONOCLONAL-ANTIBODIES; MEDIATED ENDOCYTOSIS; SORTING MOTIFS; B-LYMPHOBLASTS; CELL-SURFACE AB Major histocompatibility complex class II (MHC-II) molecules are composed of two polymorphic chains, α and β, which assemble with an invariant chain, Ii, in the endoplasmic reticulum. The assembled MHC-II complexes are transported to the Golgi complex and then to late endosomes/lysosomes, where Ii is degraded and αβ climers bind peptides derived from exogenous antigens. Targeting of MHC-II molecules to these compartments is mediated by two dileucine-based signals in the cytoplasmic domain of Ii. These signals bind in vitro to two adaptor protein (AP) complexes, AP-1 and AP-2, which are components of clathrin coats involved in vesicle formation and cargo sorting. The physiological roles of these proteins in MHC-II molecule trafficking, however, remain to be addressed. Here, we report the use of RNA interference to examine the involvement of clathrin and four AP complexes (AP-1, AP-2, AP-3, and AP-4) in MHC-II molecule trafficking in vivo. We found that depletion of clathrin or AP-2 caused > 10-fold increases in Ii expression on the cell surface and a concomitant decrease in Ii localization to endosomal/lysosomal vesicles. in addition, depletion of clathrin or AP-2 delayed the degradation of Ii and reduced the surface expression of peptide-loaded αβ dinners. In contrast, depletion of AP-1, AP-3, or AP-4 had little or no effect. These findings demonstrate that clathrin and AP-2 participate in MHC-II molecule trafficking in vivo. Because AP-2 is only associated with the plasma membrane, these results also indicate that a significant pool of MHC-II molecules traffic to the endosomal-lysosomal system by means of the cell surface. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101, Bethesda, MD 20892 USA. EM bonifacinoj@mail.nih.gov RI McCormick, Peter/E-7387-2012; OI McCormick, Peter/0000-0002-2225-5181; Bonifacino, Juan S./0000-0002-5673-6370 NR 44 TC 77 Z9 78 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 31 PY 2005 VL 102 IS 22 BP 7910 EP 7915 DI 10.1073/pnas.0502206102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 932CE UT WOS:000229531000025 PM 15911768 ER PT J AU Song, KM Rabin, RL Hill, BJ De Rosa, SC Perfetto, SP Zhang, HH Foley, JF Reiner, JS Liu, J Mattapallil, JJ Douek, DC Roederer, M Farber, JM AF Song, KM Rabin, RL Hill, BJ De Rosa, SC Perfetto, SP Zhang, HH Foley, JF Reiner, JS Liu, J Mattapallil, JJ Douek, DC Roederer, M Farber, JM TI Characterization of subsets of CD4(+) memory T cells reveals early branched pathways of T cell differentiation in humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chemokines; immunologic memory; Th1/Th2 cells ID CHEMOKINE RECEPTOR EXPRESSION; CYTOKINE MESSENGER-RNA; FLOW-CYTOMETRY; L-SELECTIN; EFFECTOR; QUANTIFICATION; LYMPHOCYTES; GENERATION; DIVERSITY; IMMUNITY AB The pathways for differentiation of human CD4(+) T cells into functionally distinct subsets of memory cells in vivo are unknown. The identification of these subsets and pathways has clear implications for the design of vaccines and immune-targeted therapies. Here, we show that populations of apparently naive CD4(+) T cells express the chemokine receptors CXCR3 or CCR4 and demonstrate patterns of gene expression and functional responses characteristic of memory cells. The proliferation history and T cell receptor repertoire of these chemokine-receptor(+) cells suggest that they are very early memory CD4(+) T cells that have "rested down" before acquiring the phenotypes described for "central" or "effector" memory T cells. In addition, the chemokine-receptor(+) "naive" populations contain Th1 and Th2 cells, respectively, demonstrating that Th1/Th2 differentiation can occur very early in vivo in the absence of markers conventionally associated with memory cells. We localized ligands for CXCR3 and CCR4 to separate foci in T cell zones of tonsil, suggesting that the chemokine-receptor(+) subsets may be recruited and contribute to segregated, polarized microenvironments within lymphoid organs. Importantly, our data suggest that CD4(+) T cells do not differentiate according to a simple schema from naive CD45RO(+) noneffector/central memory &RARR; effector/effector memory cells. Rather, developmental pathways branch early on to yield effector/memory populations that are highly heterogeneous and multifunctional and have the potential to become stable resting cells. C1 NIH, Inflammat Biol Sect, Lab Mol Immunol, NIAID,Vaccine Res Ctr, Bethesda, MD 20892 USA. NIH, Sect Human Immunol, Vaccine Res Ctr, Bethesda, MD 20892 USA. NIH, Sect ImmunoTechnol, Vaccine Res Ctr, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Farber, JM (reprint author), NIH, Inflammat Biol Sect, Lab Mol Immunol, NIAID,Vaccine Res Ctr, 10 Ctr Dr,Room 11N-107, Bethesda, MD 20892 USA. EM jfarber@niaid.nih.gov RI Roederer, Mario/G-1887-2011 FU Intramural NIH HHS NR 26 TC 51 Z9 52 U1 1 U2 8 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 MAY 31 PY 2005 VL 102 IS 22 BP 7916 EP 7921 DI 10.1073/pnas.0409720102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 932CE UT WOS:000229531000026 PM 15905333 ER PT J AU Nagata, S Ise, T Onda, M Nakamura, K Ho, M Raubitschek, A Pastan, H AF Nagata, S Ise, T Onda, M Nakamura, K Ho, M Raubitschek, A Pastan, H TI Cell membrane-specific epitopes on CD30: Potentially superior targets for immunotherapy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antibody therapy; Hodgkin's lymphoma; soluble; CD30; monoclonal antibody; conformation ID IN-VITRO; MONOCLONAL-ANTIBODIES; HODGKINS-DISEASE; ANTITUMOR-ACTIVITY; KI-1 ANTIGEN; SOLUBLE CD30; RECOMBINANT IMMUNOTOXINS; ANTI-CD22 IMMUNOTOXIN; LEUKEMIA-CELLS; PHAGE DISPLAY AB Because CD30 is highly expressed on Hodgkin's lymphoma and anaplastic large cell lymphoma, it is a promising target for immunotherapy. Soluble CD30, the extracellular domain of CD30 that is shed from the cells, can reduce the effects of CD30-targeting agents by competitive binding. In this study, we identified two epitopes on membrane-associated CD30 that are missing on soluble CD30 probably because of a conformational change upon shedding. These epitopes are potentially superior targets for immunotherapy because targeting them should be free from the competitive effects of soluble CD30. We studied 27 anti-native CD30 mAbs that were assigned to 8 different topographical epitopes. Soluble CD30 was prepared from culture supernatants of L540 cells or Karpas 299 cells. In an ELISA, the mAbs to two epitopes, Ep2 (amino acids 107-153) and Ep7 (amino acids 282338), showed less than a 2% average cross-reactivity to soluble CD30 compared with a CD30-Fc fusion protein. In addition, these mAbs bound to CD30 on cells in the presence of an excess of soluble CD30. These epitopes (Ep2 and Ep7) are, therefore, more efficiently presented on cell-associated CD30 than on soluble CD30 (membrane-specific epitopes). Also, soluble CD30 in the sera of mice bearing L540 tumors did not form immune complexes with the membrane-specific mAbs analyzed by size-exclusion chromatography. In contrast, mAbs to the other epitopes reacted with both soluble CD30 and membrane CD30. Our results suggest that it may be possible to find membrane-specific epitopes on other immunotherapy target molecules. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. City Hope Med Ctr, Duarte, CA 91010 USA. RP Pastan, H (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov RI Ho, Mitchell/F-5059-2015 NR 45 TC 16 Z9 18 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 31 PY 2005 VL 102 IS 22 BP 7946 EP 7951 DI 10.1073/pnas.0502975102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 932CE UT WOS:000229531000031 PM 15905329 ER PT J AU Nishimura, Y Brown, CR Mattapallil, JJ Igarashi, T Buckler-White, A Lafont, BAP Hirsch, VM Roederer, M Martin, MA AF Nishimura, Y Brown, CR Mattapallil, JJ Igarashi, T Buckler-White, A Lafont, BAP Hirsch, VM Roederer, M Martin, MA TI Resting naive CD4(+) T cells are massively infected and eliminated by X4-tropic simian-human immunodeficiency viruses in macaques SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE acute infection; animal model; CXCR4-tropic SHIV; HIV pathogenesis ID RHESUS-MONKEYS; GASTROINTESTINAL-TRACT; VIRAL REPLICATION; CLINICAL-OUTCOMES; CORECEPTOR USAGE; HIV-1 INFECTION; SIV INFECTION; AIDS; DEPLETION; VACCINE AB Unlike HIV-1 and simian immunodeficiency virus (SIV), which induce a slow, unrelenting loss of immune function spanning several years, highly pathogenic simian-human immunodeficiency viruses (SHIVs) induce a rapid, complete, and irreversible depletion of CD4(+) T lymphocytes in rhesus monkeys within weeks of infection, leading to death from immunodeficiency. We recently reported that, because these SHIVs exclusively use the CXCR4 coreceptor for cell entry, they target naive CD4(+) T cells for depletion in infected monkeys, whereas SIVs, which use CCR5, not CXCR4, cause the selective loss of memory CD4(+) T lymphocytes in vivo. Here we show both by DNA PCR analyses and infectivity assays, using live sorted CD4(+) T lymphocyte subsets, that 30-90% of circulating naive cells were productively infected by day 10 after inoculation. This result implies that direct cell killing, not bystander apoptosis, is responsible for the massive loss of CD4(+) T cells in the X4-tropic SHIV model. Furthermore, we directly demonstrate that > 96% of virus producing cells did not express the Ki-67 proliferation marker on day 10 after inoculation using confocal microscopic analysis of lymph nodes samples. This finding is consistent with the prodigious levels of plasma viremia measured during acute X4-tropic SHIV infections of macaques being generated almost entirely by resting naive CD4(+) T cells. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. EM malm@nih.gov RI Roederer, Mario/G-1887-2011; Lafont, Bernard/B-7236-2014 NR 44 TC 70 Z9 73 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 MAY 31 PY 2005 VL 102 IS 22 BP 8000 EP 8005 DI 10.1073/pnas.0503233102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 932CE UT WOS:000229531000040 PM 15911767 ER PT J AU Pfaff, M Powaga, N Akinci, S Schutz, W Banno, Y Wiegand, S Kummer, W Wess, J Haberberger, RV AF Pfaff, M Powaga, N Akinci, S Schutz, W Banno, Y Wiegand, S Kummer, W Wess, J Haberberger, RV TI Activation of the SPHK/SIP signalling pathway is coupled to muscarinic receptor-dependent regulation of peripheral airways SO RESPIRATORY RESEARCH LA English DT Article ID SMOOTH-MUSCLE-CELLS; SPHINGOSINE KINASE; ACETYLCHOLINE-RECEPTORS; FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; PLASMA-MEMBRANE; LIGHT-CHAIN; CONTRACTION; MICE; SPHINGOSINE-1-PHOSPHATE AB Background: In peripheral airways, acetylcholine induces contraction via activation of muscarinic M2-and M3-receptor subtypes (M2R and M3R). Cholinergic hypersensitivity is associated with chronic obstructive pulmonary disease and asthma, and therefore the identification of muscarinic signaling pathways are of great therapeutic interest. A pathway that has been shown to be activated via MR and to increase [Ca2+](i) includes the activation of sphingosine kinases (SPHK) and the generation of the bioactive sphingolipid sphingosine 1-phosphate (S1P). Whether the SPHK/S1P signaling pathway is integrated in the muscarinic control of peripheral airways is not known. Methods: To address this issue, we studied precision cut lung slices derived from FVB and M2R-KO and M3R-KO mice. Results: In peripheral airways of FVB, wild-type, and MR-deficient mice, SPHK1 was mainly localized to smooth muscle. Muscarine induced a constriction in all investigated mouse strains which was reduced by inhibition of SPHK using D, L-threo-dihydrosphingosine (DHS) and N, N-dimethylsphingosine (DMS) but not by N-acetylsphingosine (N-AcS), a structurally related agent that does not affect SPHK function. The initial phase of constriction was nearly absent in peripheral airways of M3R-KO mice when SPHK was inhibited by DHS and DMS but was unaffected in M2R-KO mice. Quantitative RT-PCR revealed that the disruption of the M2R and M3R genes had no significant effect on the expression levels of the SPHK1-isoform in peripheral airways. Conclusion: These results demonstrate that the SPHK/S1P signaling pathway contributes to cholinergic constriction of murine peripheral airways. In addition, our data strongly suggest that SPHK is activated via the M2R. Given the important role of muscarinic mechanisms in pulmonary disease, these findings should be of considerable therapeutic relevance. C1 Univ Giessen, Inst Anat & Cell Biol, D-35390 Giessen, Germany. Gifu Univ, Grad Sch Med, Dept Cell Signaling, Gifu, Japan. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Haberberger, RV (reprint author), Univ Giessen, Inst Anat & Cell Biol, D-35390 Giessen, Germany. EM Mel.pfaff@gmx.de; Norbert.powaga@web.de; Sibel.akinci@web.de; Werner-schuetz@web.de; banno@cc.gifu-u.ac.jp; Silke.wiegand@anatomie.med.unigiessen.de; Wolfgang.kummer@anatomie.med.uni-giessen.de; jwess@helix.nih.gov; Rainer.v.haberberger@anatomie.med.uni-giessen.de NR 40 TC 27 Z9 27 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-9921 J9 RESP RES JI Respir. Res. PD MAY 31 PY 2005 VL 6 AR 48 DI 10.1186/1465-9921-6-48 PG 14 WC Respiratory System SC Respiratory System GA 938LK UT WOS:000230004700001 PM 15927078 ER PT J AU Hoshino, Y Jones, RW Ross, J Kapikian, AZ AF Hoshino, Y Jones, RW Ross, J Kapikian, AZ TI Porcine rotavirus strain Gottfried-based human rotavirus candidate vaccines: Construction and characterization SO VACCINE LA English DT Article DE rotavirus; rotavirus vaccine; porcine-based rotavirus vaccine ID POLYMERASE CHAIN-REACTION; RHESUS ROTAVIRUS; MONOCLONAL-ANTIBODIES; GEL-ELECTROPHORESIS; NEUTRALIZATION SPECIFICITIES; SEROTYPIC CHARACTERIZATION; REASSORTANT ROTAVIRUSES; ANIMAL ROTAVIRUSES; YOUNG-CHILDREN; PROTEIN VP4 AB Rotavirus gastroenteritis remains the leading cause of severe diarrheal disease in infants and young children worldwide, and thus, a safe and effective rotavirus vaccine is urgently needed in both developing and developed countries. Various candidate rotavirus vaccines that were developed by us and others have been or are being evaluated in different populations in various pans of the world. We have recently confirmed that a porcine rotavirus Gottfried strain bears a P (VP4) serotype (P2B[6]) closely related to human rotavirus P serotype 2A[6] which is of epidemiologic importance in some regions of the world. Based on the modified Jennerian approach to immunization, we have constructed 11 Gottfried-based single VP7 or VP4 gene substitution reassortant vaccine candidates which could provide: (i) an attenuation phenotype of a porcine rotavirus in humans; and (ii) antigenic coverage for G serotypes 1-6 and 8-10 and P serotype 1A[8], 1B[4] and 2A[6]. In addition, following immunization of guinea pigs with Gottfried VP4, we found low but consistent levels of neutralizing antibodies to VP4 with PIA[8] or P1B[4] specificity, both of which are of global epidemiologic importance. Thus, porcine-based VP7 reassortant rotavirus vaccines may provide an advantage over rhesus- or bovine-based VP7 reassortant vaccines since the VP4s of the latter vaccines do not evoke antibodies capable of neutralizing the viruses bearing PIA[8], P1B[4] or P2A[6] VP4. © 2005 Elsevier Ltd. All rights reserved. C1 NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Hoshino, Y (reprint author), NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bldg 50,Room 6308,50 S Dr,MSC 8026, Bethesda, MD 20892 USA. EM thoshino@niaid.nih.gov NR 81 TC 10 Z9 12 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 31 PY 2005 VL 23 IS 29 BP 3791 EP 3799 DI 10.1016/j.vaccine.2005.02.024 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 931YT UT WOS:000229522100005 PM 15893616 ER PT J AU Rappaport, SM Waidyanatha, S Yeowell-O'Connell, K Rothman, N Smith, MT Zhang, LP Qu, QS Shore, R Li, GL Yin, SN AF Rappaport, SM Waidyanatha, S Yeowell-O'Connell, K Rothman, N Smith, MT Zhang, LP Qu, QS Shore, R Li, GL Yin, SN TI Protein adducts as biomarkers of human benzene metabolism SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT International Symposium on Recent Advances in Benzene Toxicity CY OCT 09-12, 2004 CL Munich, GERMANY DE benzene; protein adducts; albumin; benzene oxide; benzoquinone; nonlinear kinetics ID S-PHENYLMERCAPTURIC ACID; ALBUMIN ADDUCTS; URINARY BENZENE; TRANS,TRANS-MUCONIC ACID; LIQUID-CHROMATOGRAPHY; UNEXPOSED SUBJECTS; HUMAN-LYMPHOCYTES; EXPOSURE; OXIDE; HYDROQUINONE AB We used cysteinyl adducts of serum albumin (Alb) to investigate the production of two reactive benzene metabolites, namely, benzene oxide (130) and 1,4-benzoquinone (1,4-BQ) in workers exposed to benzene. Adducts were measured in 160 benzene-exposed workers who did not use respiratory protection (based upon individual geometric mean benzene exposure levels: median = 5.27 ppm, interquartile range = 2.14-13.4 ppm, range = 0.074-328 ppm) and 101 local controls, from populations in Shanghai and Tianjin, China. After isolation of Alb, these adducts (designated as BO-Alb and 1,4-BQ-Alb) were cleaved from the protein with methanesulfonic acid and trifluoroacetic anhydride and measured by gas chromatography-mass spectrometry. Although BO-Alb and 1,4-BQ-Alb were measured in all subjects, levels of both adducts were 2.4-fold greater (median value) in exposed subjects than in controls (interquartile-fold range = 1.63-4.05 for BO-Alb and 1.64-3.69 for 1,4-BQ-Alb). Log-log plots of the individual adduct levels versus exposure were quasi-linear with straight-line slopes of about 0.3 for both BO-Alb and 1,4-BQ-Alb. Since these log-space slopes were significantly less than one, we infer that adduct production was nonlinear, i.e., less-than proportional to benzene exposure, over the indicated range. This behavior points to saturation of CYP2E1 as a critical metabolic consequence of high exposure to benzene in humans. Thus, the biologically effective dose of BO and 1,4-BQ should be proportionally greater in persons exposed to low rather than high levels of benzene. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NYU, Sch Med, Nelson Inst Environm Med, Tuxedo Pk, NY USA. Inst Occupat Med, Beijing, Peoples R China. RP Rappaport, SM (reprint author), Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. EM smr@unc.edu FU NIEHS NIH HHS [P42ES04705, P30ES10126, P42ES05948] NR 32 TC 26 Z9 29 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD MAY 30 PY 2005 VL 153 SI SI BP 103 EP 109 DI 10.1016/j.cbi.2005.03.014 PG 7 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 939IH UT WOS:000230065500012 PM 15935805 ER PT J AU Lan, Q Zhang, LP Hakim, F Shen, M Memon, S Li, GL Vermeulen, R Smith, MT Rappaport, SM Hayes, R Linet, M Yin, SN Rothman, N Rabkin, CS AF Lan, Q Zhang, LP Hakim, F Shen, M Memon, S Li, GL Vermeulen, R Smith, MT Rappaport, SM Hayes, R Linet, M Yin, SN Rothman, N Rabkin, CS TI Lymphocyte toxicity and T cell receptor excision circles in workers exposed to benzene SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT International Symposium on Recent Advances in Benzene Toxicity CY OCT 09-12, 2004 CL Munich, GERMANY DE T cell receptor excision circle (TREC); thymic function; benzene exposure; occupational hazard; T cell subsets; hematotoxicity; China; organic vapor; peripheral blood leukocytes ID HIV-INFECTION; HEMATOTOXICITY; CHINA AB We have previously reported that benzene decreases peripheral white blood cell and platelet counts and specifically lowers subsets of several blood cell types, including CD4(+)-T cells, B cells, NK cells, and granulocytes. Diminished thymus function has been implicated as a mechanism for CD4(+)-T cell loss in other conditions such as AIDS by assays of T cell receptor excision circles (TRECs), a marker of naive T cells that have recently emigrated from the thymus. To evaluate alteration of thymic function as a mechanism for benzene's effects on CD4(+)-T cell counts, we measured total TREC levels in 45 benzene-exposed workers and 45 unexposed controls. There was no significant difference in TREC levels per 106 peripheral blood leukocytes in the benzene-exposed workers compared to the controls. Although our study does not rule out counterbalancing alterations of TREC levels in specific T cell subsets, benzene's lymphotoxicity does not appear to be mediated through diminished thymus function. Published by Elsevier Ireland Ltd. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NCI, Dept Expt Transplantat & Immunol, NIH, DHHS, Bethesda, MD 20892 USA. Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. RP Lan, Q (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA. EM qingl@mail.nih.gov RI Vermeulen, Roel/F-8037-2011; OI Vermeulen, Roel/0000-0003-4082-8163; Memon, Sarfraz/0000-0002-0164-9739 FU NIEHS NIH HHS [P30ES01896, P30ES10126, P42ES04705, P42ES05948, R01ES06721] NR 12 TC 5 Z9 7 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD MAY 30 PY 2005 VL 153 SI SI BP 111 EP 115 DI 10.1016/j.cbi.2005.03.015 PG 5 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 939IH UT WOS:000230065500013 PM 15935806 ER PT J AU Zhang, LP Lan, Q Guo, WH Li, GL Yang, W Hubbard, AE Vermeulen, R Rappaport, SM Yin, SN Rothman, N Smith, MT AF Zhang, LP Lan, Q Guo, WH Li, GL Yang, W Hubbard, AE Vermeulen, R Rappaport, SM Yin, SN Rothman, N Smith, MT TI Use of OctoChrome fluorescence in situ hybridization to detect specific aneuploidy among all 24 chromosomes in benzene-exposed workers SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT International Symposium on Recent Advances in Benzene Toxicity CY OCT 09-12, 2004 CL Munich, GERMANY DE benzene; biomarkers; chromosomal aberrations; leukemia ID LONG ARM DELETION; MOLECULAR-GENETICS; HUMAN-LYMPHOCYTES; METABOLITES; LEUKEMIA; ABERRATIONS; MELPHALAN; ANEUSOMY AB Benzene is an established human leukemogen. The mechanism of benzene-induced leukemogenesis, however, remains unclear, but chromosomal damage is thought to play a critical role. We previously reported that the loss of chromosomes 5 and 7 (monosomy 5 and 7) and the gain of chromosomes 8 and 21 (trisomy 8 and 21) are significantly increased in benzene-exposed workers in comparison to matched controls. To determine if selective effects of benzene can occur, we employed three-color painting on an 8-square slide to screen numerical changes in all 24 human chromosomes (OctoChrome FISH) in a pilot study of 11 subjects (6 exposed to > 5 ppm benzene and 5 age- and sex-matched controls). The effects of benzene on each chromosome were assessed as the incidence rate ratio (IRR) from a Poisson regression model with the strongest effects being reflected by the highest IRR values. Monosomy of chromosomes 5, 6, 7 and 10 had the highest IRRs and statistical significance in this preliminary study (IRR > 2.5, p < 0.01). On the other hand, the monosomy levels of six other chromosomes (1, 4, 9, 11, 22 and Y) were unchanged in the exposed workers with IRRs close to 1.0. Similarly, selective effects were also observed on trisomy induction with chromosomes 8, 9, 17, 21 and 22 (IRR > 2.5, p < 0.01). These results suggest that benzene has the capability of producing selective effects on certain chromosomes, which is supported by our in vitro findings showing that chromosomes 5 and 7 are more sensitive to loss than other chromosomes following exposure to benzene metabolites. We are currently investigating potential mechanisms for this induction of selective aneuploidy. (c) 2005 Published by Elsevier Ireland Ltd. C1 Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Inst Occupat Hlth & Dis Control, Chinese CDC, Beijing 100050, Peoples R China. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. RP Zhang, LP (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 140 Warren Hall, Berkeley, CA 94720 USA. EM luoping@berkeley.edu RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU NIEHS NIH HHS [R01 ES006721, P42 ES04705] NR 25 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD MAY 30 PY 2005 VL 153 SI SI BP 117 EP 122 DI 10.1016/j.cbi.2005.03.016 PG 6 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 939IH UT WOS:000230065500014 PM 15935807 ER PT J AU Smith, MT Vermeulen, R Li, GL Zhang, LP Lan, Q Hubbard, AE Forrest, MS McHale, C Zhao, X Gunn, L Shen, M Rappaport, SM Yin, SN Chanock, S Rothman, N AF Smith, MT Vermeulen, R Li, GL Zhang, LP Lan, Q Hubbard, AE Forrest, MS McHale, C Zhao, X Gunn, L Shen, M Rappaport, SM Yin, SN Chanock, S Rothman, N TI Use of 'Omic' technologies to study humans exposed to benzene SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT International Symposium on Recent Advances in Benzene Toxicity CY OCT 09-12, 2004 CL Munich, GERMANY DE benzene; biomarkers; genomics; proteomics; microarray ID GENE-EXPRESSION; BONE-MARROW; HEMATOTOXICITY; MICROARRAYS; PROTEOMICS; PROFILES; GENOME; CANCER; BLOOD; NQ01 AB 'Omic' technologies include genomics, transcriptomics (gene expression profiling), proteomics and metabolomics. We are utilizing these new technologies in an effort to develop novel biomarkers of exposure, susceptibility and response to benzene. Advances in genomics allow one to study hundreds to thousands of single nucleotide polymorphisms simultaneously on small quantities of DNA using array-based technologies. We are currently utilizing these technologies to examine genetic variation in pathways relating to biotransformation, DNA repair, folate metabolism and immune response with the goal of finding biomarkers of susceptibility to benzene hematotoxicity. Transcriptomics is used to measure the full complement of activated genes, mRNAs or transcripts in a particular tissue at a particular time typically using microarray technology. We have applied microarrays to the study of global gene expression in the peripheral blood cells of benzene-exposed workers. More than 100 genes were identified as being potentially differentially expressed, with genes related to apoptosis and immune function being the most significantly affected. Initial studies employing proteomics have also shown that several proteins are altered in the serum of exposed compared to control subjects and these proteins are potential biomarkers of benzene exposure. Omic technologies therefore have significant potential in generating novel biomarkers of exposure, susceptibility and response to benzene. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. RP Smith, MT (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 140 Warren Hall, Berkeley, CA 94720 USA. EM martynts@berkeley.edu RI Vermeulen, Roel/F-8037-2011; OI Vermeulen, Roel/0000-0003-4082-8163; Forrest, Matthew/0000-0002-2141-0303 FU NIEHS NIH HHS [P30ES01896, P42ES04705, R01ES06721] NR 28 TC 24 Z9 25 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD MAY 30 PY 2005 VL 153 SI SI BP 123 EP 127 DI 10.1016/j.cbi.2005.03.017 PG 5 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 939IH UT WOS:000230065500015 PM 15935808 ER PT J AU Recio, L Bauer, A Faiola, B AF Recio, L Bauer, A Faiola, B TI Use of genetically modified mouse models to assess pathways of benzene-induced bone marrow cytotoxicity and genotoxicity SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT International Symposium on Recent Advances in Benzene Toxicity CY OCT 09-12, 2004 CL Munich, GERMANY DE benzene; hematopoietic stem cell (HSC); bone marrow; NQO1; mEH; p53 ID HEMATOPOIETIC PROGENITOR CELLS; INDUCED TOXICITY; GENE-EXPRESSION; INHALED BENZENE; MICE; METABOLISM; MECHANISM; ALTERS AB Benzene induces bone marrow cytotoxicity and chromosomal breaks as a primary mode of action for the induction of bone marrow toxicity. Our research group has used genetically modified mouse models to examine metabolic and genomic response pathways involved in benzene induced cytotoxicity and genotoxicity in bone marrow and in hematopoietic stem cells (HSC). We review our studies using NQO1-/- mice and mEH-/- mice to examine the roles of these enzymes, NAD(P)H:quinone oxidoreductase-1 (NQO1) and microsomal epoxide hydrolase (mEH) in mediating benzene-induced toxicity. NQO1 catalyzes the detoxication of benzene quinone metabolites and mEH catalyzes the hydrolysis of benzene oxide. Our studies using gene expression profiling of bone marrow and enriched HSC populations isolated from the bone marrow of benzene-exposed mice demonstrate differential gene expression responses of key genes induced by inhaled benzene. These studies show that benzene toxicity is regulated by a number of genetic pathways that affect the production of reactive metabolites and DNA damage response pathways in a target tissue. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Integrated Lab Syst Inc, Genet Toxicol Program, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. GlaxoSmithKline Res & Dev, Res Triangle Pk, NC 27709 USA. RP Recio, L (reprint author), Integrated Lab Syst Inc, Genet Toxicol Program, POB 13501, Res Triangle Pk, NC 27709 USA. EM lrecio@ils-inc.com FU NIEHS NIH HHS [N01-ES-35514] NR 13 TC 16 Z9 21 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD MAY 30 PY 2005 VL 153 SI SI BP 159 EP 164 DI 10.1016/j.cbi.2005.03.020 PG 6 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 939IH UT WOS:000230065500019 PM 15935812 ER PT J AU Matsumoto, K Okajo, A Kobayashi, T Mitchell, JB Krishna, MC Endo, K AF Matsumoto, K Okajo, A Kobayashi, T Mitchell, JB Krishna, MC Endo, K TI Estimation of free radical formation by beta-ray irradiation in rat liver SO JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS LA English DT Article DE electron paramagnetic resonance; nitroxyl radical; spin probe; spin clearance; reactive oxygen species; redox ID ELECTRON-PARAMAGNETIC-RESONANCE; WHOLE MICE; SPIN-RESONANCE; MOUSE; SPECTROSCOPY; NITROXYL; REDUCTION; RADIATION; DAMAGE; LUNG AB In vivo free radical reactions in rat liver as a result of exposure to low-dose x-radiation was evaluated with electron paramagnetic resonance (EPR) spectroscopy by monitoring the reduction of the nitroxyl spin probe after intravenous administration. The EPR signal intensity of a nitroxyl probe as a function of time in bile flow was monitored by cannulating the bile duct through the cavity of an X-band EPR spectrometer. The results show that the rate of nitroxyl signal loss was higher in rats whose livers were exposed to x-rays compared to unexposed rats. However, the rate of signal loss was lower in animals whose organs were exposed to air by opening the abdominal cavity. In vitro experiments also showed that the nitroxyl EPR signal loss was greater in an atmosphere of nitrogen than in air. Results suggest that under low levels of tissue oxygen, exposure to P-rays results in nitroxyl signal loss, which may be mediated by free radical dependent pathways. When tissue oxygen were higher, hydrogen peroxide mediated oxidation of hydroxylamine may predominate resulting in a signal loss of smaller magnitudes. This study shows possible evidence of reactive oxygen species formation by low-dose beta-ray irradiation in a living animal. (c) 2005 Elsevier B.V All rights reserved. C1 Showa Pharmaceut Univ, Dept Phys Chem, Machida, Tokyo 1948543, Japan. NCI, Radiat Biol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Endo, K (reprint author), Showa Pharmaceut Univ, Dept Phys Chem, 3-3165 Higashi Tamagawagakuen, Machida, Tokyo 1948543, Japan. EM kazutoyo@ac.shoyaku.ac.jp NR 19 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-022X J9 J BIOCHEM BIOPH METH JI J. Biochem. Biophys. Methods PD MAY 30 PY 2005 VL 63 IS 2 BP 79 EP 90 DI 10.1016/j.jbbm.2005.03.004 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 937TG UT WOS:000229947900001 PM 15896849 ER PT J AU Tessitore, A Hariri, AR Fera, F Smith, WG Das, S Weinberger, DR Mattay, VS AF Tessitore, A Hariri, AR Fera, F Smith, WG Das, S Weinberger, DR Mattay, VS TI Functional changes in the activity of brain regions underlying emotion processing in the elderly SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE aging; modulating emotions; amygdala; prefrontal cortex; BOLD-fMRI ID AGE-RELATED-CHANGES; CEREBRAL-BLOOD-FLOW; ADULT LIFE-SPAN; HUMAN AMYGDALA; HEMODYNAMIC-RESPONSE; ALZHEIMERS-DISEASE; FACE PERCEPTION; WORKING-MEMORY; NEURAL SYSTEM; ACTIVATION AB Aging is associated with a decline in both cognitive and motor abilities that reflects deterioration of underlying brain circuitry. While age-related alterations have also been described in brain regions underlying emotional behavior (e.g., the amygdala), the functional consequence of such changes is less clear. To this end, we used blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) to explore age-related changes in brain regions underlying emotion processing. Twelve young (age < 30 years) and 14 elderly subjects (age > 60 years) were studied with BOLD fMRI during a paradigm that involved perceptual processing of fearful and threatening stimuli. Consistent with previous reports, direct group comparisons revealed relatively increased BOLD fMRI responses in prefrontal cortical regions, including Broca's area, and relatively decreased responses in the amygdala and posterior fusiform gyri in elderly subjects. Importantly, additional analyses using an elderly-specific brain template for spatial normalization of the elderly BOLD fMRI data confirmed these divergent regional response patterns. While there was no difference between groups in accuracy on the task, elderly subjects were significantly slower (delayed reaction times) in performing the task. Our current data suggest that elderly subjects engage a more distributed neocortical network during the perceptual processing of emotional facial expressions. In light of recent converging data froth two other studies, our observed effects may reflect age-related compensatory responses and/or alternative strategies in processing emotions, as the elderly appear to engage cognitive/linguistic systems in the context of reduced sensory and/or limbic responses. (c) Published by Elsevier Ireland Ltd. C1 NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. Univ Naples 2, Dept Neurosci, Div Neurol 2, I-80138 Naples, Italy. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. CNR, Inst Neurol Sci, Lab Neuroimaging, I-87050 Cosenza, Italy. RP Mattay, VS (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. EM vsm@helix.nih.gov RI Hariri, Ahmad/D-5761-2011 FU Intramural NIH HHS NR 44 TC 79 Z9 82 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD MAY 30 PY 2005 VL 139 IS 1 BP 9 EP 18 DI 10.1016/j.pscychresns.2005.02.009 PG 10 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 946WI UT WOS:000230603600002 PM 15936178 ER PT J AU Ivanova, A Barrier, RC Berger, VW AF Ivanova, A Barrier, RC Berger, VW TI Adjusting for observable selection bias in block randomized trials SO STATISTICS IN MEDICINE LA English DT Article DE randomized block design; randomized clinical trials; selection bias ID CLINICAL-TRIALS AB In this paper, we propose a model-based approach to detect and adjust for observable selection bias in a randomized clinical trial with two treatments and binary outcomes. The proposed method was evaluated using simulations of a randomized block design in which the investigator favoured the experimental treatment by attempting to enrol stronger patients (with greater probability of treatment success) if the probability of the next treatment being experimental was high, and enrol weak patients (with less probability of treatment success) if the probability of the next treatment being experimental was low. The method allows not only testing for the presence of observable selection bias, but also testing for a difference in treatment effects, adjusting for possible selection bias. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. NCI, DCP, Biometry Res Grp, Bethesda, MD 20892 USA. Univ Maryland Baltimore Cty, Dept Math & Stat, Baltimore, MD 21250 USA. RP Ivanova, A (reprint author), Univ N Carolina, Dept Biostat, CB 7420, Chapel Hill, NC 27599 USA. EM aivanova@bios.unc.edu NR 13 TC 4 Z9 4 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 30 PY 2005 VL 24 IS 10 BP 1537 EP 1546 DI 10.1002/sim.2058 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 928HI UT WOS:000229261700006 PM 15723426 ER PT J AU Horwitz, B Warner, B Fitzer, J Tagamets, MA Husain, FT Long, TW AF Horwitz, B Warner, B Fitzer, J Tagamets, MA Husain, FT Long, TW TI Investigating the neural basis for functional and effective connectivity. Application to fMRI SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE brain; human; functional magnetic resonance imaging; positron emission tomography; neural modelling; object processing ID TRANSCRANIAL MAGNETIC STIMULATION; CEREBRAL-BLOOD-FLOW; DORSOLATERAL PREFRONTAL CORTEX; GLUCOSE METABOLIC RATES; WORKING-MEMORY; BRAIN-REGIONS; DYNAMIC CONNECTIVITY; GRANGER CAUSALITY; SYNAPTIC ACTIVITY; NETWORK ANALYSIS AB Viewing cognitive functions as mediated by networks has begun to play a central role in interpreting neuroscientific data, and studies evaluating interregional functional and effective connectivity have become staples of the neuroimaging literature. The neurobiological substrates of functional and effective connectivity are, however, uncertain. We have constructed neurobiologically realistic models for visual and auditory object processing with multiple interconnected brain regions that perform delayed match-to-sample (DMS) tasks. We used these models to investigate how neurobiological parameters affect the interregional functional connectivity between functional magnetic resonance imaging (fMRI) time-series. Variability is included in the models as subject-to-subject differences in the strengths of anatomical connections, scan-to-scan changes in the level of attention, and trial-to-trial interactions with non-specific neurons processing noise stimuli. We find that time-series correlations between integrated synaptic activities between the anterior temporal and the prefrontal cortex were larger during the DMS task than during a control task. These results were less clear when the integrated synaptic activity was haemodynamically convolved to generate simulated fMRI activity. As the strength of the model anatomical connectivity between temporal and frontal cortex was weakened, so too was the strength of the corresponding functional connectivity. These results provide a partial validation for using fMRI functional connectivity to assess brain interregional relations. C1 NIDOCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. Imagenet Inc, Williamsburg, VA USA. RP Horwitz, B (reprint author), NIDOCD, Brain Imaging & Modeling Sect, NIH, Bldg 10,Room 6C420,MSC 1591, Bethesda, MD 20892 USA. EM horwitz@helix.nih.gov NR 76 TC 63 Z9 66 U1 0 U2 4 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD MAY 29 PY 2005 VL 360 IS 1457 BP 1093 EP 1108 DI 10.1098/rstb.2005.1647 PG 16 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 947VZ UT WOS:000230676700020 PM 16087450 ER PT J AU Strebel, K AF Strebel, K TI APOBEC3G & HTLV-1: Inhibition without deamination SO RETROVIROLOGY LA English DT Editorial Material ID HIV-1; VIF; REPLICATION; INFECTIVITY; EXCLUSION AB APOBEC3G is a cellular cytidine deaminase that was recently identified as the Vif-sensitive antiviral host factor responsible for the restriction of vif-defective HIV-1 in primary human cells and certain non-permissive T cell lines. Inhibition of HIV-1 replication is thought to be the result of APOBEC3G-induced hypermutation of the viral genome that occurs early during reverse transcription. Against this backdrop is a new report from the Uchiyama laboratory that proposes deaminase-independent restriction of HTLV-1 by APOBEC3G ( Sasada et al. Retrovirology 2005, 2: 32). These findings combined with recent reports of deaminase-independent inhibition of Hepatitis B virus as well as HIV-1 suggest that cytidine deaminase activity and antiviral activity may be separable functional properties of APOBEC3G. C1 NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bldg 4,Room 310,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM kstrebel@niaid.nih.gov NR 15 TC 18 Z9 20 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD MAY 29 PY 2005 VL 2 AR 37 DI 10.1186/1742-4690-2-37 PG 3 WC Virology SC Virology GA 033CW UT WOS:000236825100001 PM 15921532 ER PT J AU De Angelis, C Drazen, JM Frizelle, FA Haug, C Hoey, J Horton, R Kotzin, S Laine, C Marusic, A Overbeke, AJPM Schroeder, TV Sox, HC Van der Weyden, MB AF De Angelis, C Drazen, JM Frizelle, FA Haug, C Hoey, J Horton, R Kotzin, S Laine, C Marusic, A Overbeke, AJPM Schroeder, TV Sox, HC Van der Weyden, MB TI Is this clinical trial fully registered? A statement from the International Committee of Medical Journal Editors SO LANCET LA English DT Editorial Material C1 Natl Lib Med, MEDLINE, Bethesda, MD 20894 USA. RI Marusic, Ana/E-7683-2013; OI Marusic, Ana/0000-0001-6272-0917; Schroeder, Torben/0000-0002-9827-9438 NR 2 TC 47 Z9 47 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 28 PY 2005 VL 365 IS 9474 BP 1827 EP 1829 DI 10.1016/S0140-6736(05)6658-9 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 931JK UT WOS:000229481400004 PM 15924965 ER PT J AU Akagi, T Usuda, M Matsuda, T Ko, MSH Niwa, H Asano, M Koide, H Yokota, T AF Akagi, T Usuda, M Matsuda, T Ko, MSH Niwa, H Asano, M Koide, H Yokota, T TI Identification of Zfp-57 as a downstream molecule of STAT3 and Oct-3/4 in embryonic stem cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE ES cells; STAT3; Oct-3/4; Zfp-57; self-renewal; targeted disruption; RNAi ID TRANSCRIPTION FACTOR; GENE-EXPRESSION; MOUSE EMBRYOS; SELF-RENEWAL; ES CELLS; DIFFERENTIATION; PLURIPOTENCY; ACTIVATION; PROTEIN; NANOG AB Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. Transcription factor STAT3 is essential for the self-renewal of ES cells. In this study, we searched for downstream molecules of STAT3 in ES cells. Using DNA chip analysis, we obtained zinc finger protein (Zfp)-57. The expression of Zfp-57 was restricted to undifferentiated ES cells and activation of STAT3 led to expression of Zfp-57. We also found that forced expression of a dominant-negative mutant of STAT3 or repression of Oct-3/4 expression led to down-regulation of Zfp-57. Targeted disruption of Zfp-57 resulted in no gross phenotypical defects, including expression of undifferentiated-state-specific genes. These data suggest that Zfp-57 is a downstream molecule of STAT3 and Oct-3/4 in ES cells, although dispensable for their self-renewal. © 2005 Elsevier Inc. All rights reserved. C1 Kanazawa Univ, Grad Sch Med Sci, Dept Stem Cell Biol, Kanazawa, Ishikawa 9208640, Japan. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RIKEN, Ctr Dev Biol, Lab Pluripotent Cell Studies, Kobe, Hyogo 6500047, Japan. Kanazawa Univ, Adv Res Ctr, Inst Expt Anim, Kanazawa, Ishikawa 9208640, Japan. RP Yokota, T (reprint author), Kanazawa Univ, Grad Sch Med Sci, Dept Stem Cell Biol, 13-1 Takara Machi, Kanazawa, Ishikawa 9208640, Japan. EM tyokota@med.kanazawa-u.ac.jp RI Akagi, Tadayuki/E-1078-2011; Koide, Hiroshi/E-9000-2011; Yokota, Takashi/F-6021-2011; Ko, Minoru/B-7969-2009; Yokota, Takashi/J-8483-2015; OI Ko, Minoru/0000-0002-3530-3015; Koide, Hiroshi/0000-0001-5916-3179 NR 26 TC 25 Z9 27 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 27 PY 2005 VL 331 IS 1 BP 23 EP 30 DI 10.1016/j.bbrc.2005.03.118 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 924EB UT WOS:000228960500003 PM 15845352 ER PT J AU Sonveaux, P Kaz, AM Snyder, SA Richardson, RA Cadenas-Navia, LI Braun, RD Pawloski, JR Tozer, GM Bonaventura, J McMahon, TJ Stamler, JS Dewhirst, MW AF Sonveaux, P Kaz, AM Snyder, SA Richardson, RA Cadenas-Navia, LI Braun, RD Pawloski, JR Tozer, GM Bonaventura, J McMahon, TJ Stamler, JS Dewhirst, MW TI Oxygen regulation of tumor perfusion by S-nitrosohemoglobin reveals a pressor activity of nitric oxide SO CIRCULATION RESEARCH LA English DT Article DE nitric oxide; hemoglobin; oxygen; hemodynamics; blood flow ID BLOOD-FLOW REGULATION; HEMOGLOBIN; RAT; OXIDATION; DELIVERY; NITROSOCYSTEINE; NITROSOTHIOLS; THERAPEUTICS; CELLS AB In erythrocytes, S-nitrosohemoglobin (SNO-Hb) arises from S-nitrosylation of oxygenated hemoglobin (Hb). It has been shown that SNO-Hb behaves as a nitric oxide ( NO) donor at low oxygen tensions. This property, in combination with oxygen transport capacity, suggests that SNO-Hb may have unique potential to reoxygenate hypoxic tissues. The present study was designed to test the idea that the allosteric properties of SNO-Hb could be manipulated to enhance oxygen delivery in a hypoxic tumor. Using Laser Doppler flowmetry, we showed that SNO-Hb infusion to animals breathing 21% O-2 reduced tumor perfusion without affecting blood pressure and heart rate. Raising the pO(2) (100% O-2) slowed the release of NO bioactivity from SNO-Hb (ie, prolonged the plasma half-life of the SNO in Hb), preserved tumor perfusion, and raised the blood pressure. In contrast, native Hb reduced both tumor perfusion and heart rate independently of the oxygen concentration of the inhaled gas, and did not elicit hypertensive effects. Window chamber ( to image tumor arteriolar reactivity in vivo) and hemodynamic measurements indicated that the preservation of tissue perfusion by micromolar concentrations of SNO-Hb is a composite effect created by reduced peripheral vascular resistance and direct inhibition of the baroreceptor reflex, leading to increased blood pressure. Overall, these results indicate that the properties of SNO-Hb are attributable to allosteric control of NO release by oxygen in central as well as peripheral issues. C1 Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. Duke Univ, Marine Lab, Nicholas Sch Environm & Earth Sci, Durham, NC 27710 USA. Univ Puerto Rico, NIH, COBREII Prot Res Ctr, Beaufort, NC USA. Univ Puerto Rico, NIH, COBREII Prot Res Ctr, Mayaguez, PR 00708 USA. Mt Vernon Hosp, Gray Canc Inst, Tumor Microcirculat Grp, Northwood HA6 2RN, Middx, England. RP Dewhirst, MW (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Res Dr,Box 3455,Room 201 MSRB, Durham, NC 27710 USA. EM dewhirst@radonc.duke.edu RI McMahon, Timothy/K-3986-2012; OI McMahon, Timothy/0000-0002-3404-3223; Sonveaux, Pierre/0000-0001-6484-8834 FU NCI NIH HHS [CA40355]; NCRR NIH HHS [5P20RR016439] NR 33 TC 28 Z9 29 U1 1 U2 3 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 MAY 27 PY 2005 VL 96 IS 10 BP 1119 EP 1126 DI 10.1161/01.RES.0000168740.04986.a7 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 930DR UT WOS:000229396500014 PM 15879309 ER PT J AU Rathore, D Nagarkatti, R Jani, D Chattopadhyay, R de la Vega, P Kumar, S McCutchan, TF AF Rathore, D Nagarkatti, R Jani, D Chattopadhyay, R de la Vega, P Kumar, S McCutchan, TF TI An immunologically cryptic epitope of Plasmodium falciparum circumsporozoite protein facilitates liver cell recognition and induces protective antibodies that block liver cell invasion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MALARIA; VACCINE; GENE; HEPARIN; ANTIGEN; REGION; SPOROZOITES; HEPATOCYTES; RECEPTORS; INFECTION AB Circumsporozoite, a predominant surface protein, is involved in invasion of liver cells by Plasmodium sporozoites, which leads to malaria. We have previously reported that the amino terminus region ( amino acids 27 117) of P. falciparum circumsporozoite protein plays a critical role in the invasion of liver cells by the parasite. Here we show that invasion-blocking antibodies are induced by a polypeptide encoding these 91 amino acids, only when it is presented in the absence of the rest of the protein. This suggests that when present in the whole protein, the amino terminus remains immunologically cryptic. A single reactive epitope was identified and mapped to a stretch of 21 amino acids from position 93 to 113. The epitope is configurational in nature, since its recognition was affected by deleting as little as 3 amino acids from either end of the 21-residue peptide. Lysine 104, the only known polymorphic position in the epitope, affected its recognition by the antibodies, and its conversion to leucine in the protein led to a substantial loss of binding activity of the protein to the hepatocytes. This indicated that in the protein, the epitope serves as a binding ligand and facilitates the interaction between sporozoite and hepatic cells. When considered along with the observation that in its native state this motif is immunologically unresponsive, we suggest that hiding functional moieties of the protein from the immune system is an evasion strategy to preserve liver cell binding function and may be of importance in designing anti-sporozoite vaccines. C1 Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. NIAID, Growth & Dev Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. USN, Med Res Ctr, Malaria Program, Silver Spring, MD 20910 USA. US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP McCutchan, TF (reprint author), Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. EM Tmccutchan@niaid.nih.gov NR 28 TC 32 Z9 35 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 27 PY 2005 VL 280 IS 21 BP 20524 EP 20529 DI 10.1074/jbc.M414254200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 927ZX UT WOS:000229242000046 PM 15781464 ER PT J AU Williams, DC Cao, ML Suh, JY Peterkofsky, A Clore, GM AF Williams, DC Cao, ML Suh, JY Peterkofsky, A Clore, GM TI Solution NMR structure of the 48-kDa IIA(Mannose)-HPr complex of the Escherichia coli mannose phosphotransferase system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHORYL TRANSFER COMPLEX; MACROMOLECULAR STRUCTURE DETERMINATION; PHOSPHOCARRIER PROTEIN HPR; SIGNAL-TRANSDUCING PROTEIN; N-TERMINAL DOMAIN; BACTERIAL PHOSPHOENOLPYRUVATE; CARBOHYDRATE TRANSPORTERS; STEREOCHEMICAL COURSE; STRUCTURE REFINEMENT; ANGSTROM RESOLUTION AB The solution structure of the 48-kDa IIA(Man)-HPr complex of the mannose branch of the Escherichia coli phosphotransferase system has been solved by NMR using conjoined rigid body/torsion angle-simulated annealing on the basis of intermolecular nuclear Overhauser enhancement data and residual dipolar couplings. IIA(Man) is dimeric and has two symmetrically related binding sites per dimer for HPr. A convex surface on HPr, formed primarily by helices 1 and 2, interacts with a deep groove at the interface of the two subunits of IIAMan. The interaction surface on IIAMan is predominantly helical, comprising helix 3 from the subunit that bears the active site His-10 and helices 1, 4, and 5 from the other subunit. The total buried accessible surface area at the protein-protein interface is 1450 angstrom(2). The binding sites on the two proteins are complementary in terms of shape and distribution of hydrophobic, hydrophilic, and charged residues. The active site histidines, His-10 of IIAMan and His-15 ( italics indicate HPr residues) of HPr, are in close proximity. An associative transition state involving a pentacoordinate phosphoryl group with trigonal bipyramidal geometry bonded to the N-is an element of 2 atom of His-10 and the N-delta 1 atom of His-15 can be readily formed with negligible displacement in the backbone coordinates of the residues immediately adjacent to the active site histidines. Comparing the structures of complexes of HPr with three other structurally unrelated phosphotransferase system proteins, enzymes I, IIA(glucose), and IIA(mannitol), reveals a number of common features that provide a molecular basis for understanding how HPr specifically recognizes a wide range of diverse proteins. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Labs, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Phys Chem Lab, NIH, Bldg 5,Rm B1-301, Bethesda, MD 20892 USA. EM mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU NIDDK NIH HHS [Z01 DK029023-15] NR 50 TC 46 Z9 47 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 MAY 27 PY 2005 VL 280 IS 21 BP 20775 EP 20784 DI 10.1074/jbc.M501986200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 927ZX UT WOS:000229242000075 PM 15788390 ER PT J AU Ma, YM Aisha, HA Liao, LX Aibai, S Zhang, TY Ito, Y AF Ma, YM Aisha, HA Liao, LX Aibai, S Zhang, TY Ito, Y TI Preparative isolation and purification of rupestonic acid from the Chinese medicinal plant Artemisia rupestris L. by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Artemisia rupestris L.; counter-current chromatography; rupestonic acid AB Rupestonic acid was purified for the first time by high-speed counter-current chromatography from a dichloromethane extract of the traditional Chinese medicinal plant Artemisia rupestris L. The separation was performed in two steps with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (6:4:3.5:6.5, v/v) with 0.5% acetic acid in stationary-phase, From 200 mg of the crude extract, 27.9 mg of rupestonic acid was obtained at over 98% purity as determined by HPLC analysis. and its chemical structure was confirmed by MS, H-1 and C-13 nuclear magnetic resonance. © 2005 Elsevier B.V. All rights reserved. C1 NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. CAS, Xinjiang Tech Ins Phys & Chem, Urumqi 830011, Peoples R China. Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China. Inst Xinjiang Uyghur Med, Urumqi 83001, Peoples R China. Beijing Inst New Technol Appl, Beijing 100035, Peoples R China. RP Ito, Y (reprint author), NHLBI, Ctr Biochem & Biophys, NIH, Bldg 50,Room 3334,50 S Dr,MSC 8014, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov NR 11 TC 21 Z9 22 U1 1 U2 10 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 MAY 27 PY 2005 VL 1076 IS 1-2 BP 198 EP 201 DI 10.1016/j.chroma.2005.04.040 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 932JW UT WOS:000229551000027 PM 15974089 ER PT J AU Ma, XF Wu, LH Ito, Y Tian, WX AF Ma, XF Wu, LH Ito, Y Tian, WX TI Application of preparative high-speed counter-current chromatography for separation of methyl gallate from Acer truncatum Bunge SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Acer truncation Bunge; counter-current chromatography; preparative chromatography; methyl gallate ID MONGHOLICUS BGE. HSIAO; SIMPLEX VIRUS INVITRO; PURIFICATION; INHIBITOR; ALKALOIDS; POTENT; PLANTS; HERB AB Preparative separation of methyl gallate in leaves extract of Acer truncatum Bunge was conducted using high-speed counter-current chromatography (HSCCC) with a solvent system composed of ethyl acetate-ethanol-water at volume ratios of 5:1:5 (v/v/v). In a single operation, 57.5 mg of methyl gallate was obtained from 120 mg of the extract. HPLC analyses of the counter-current chromatography (CCC) fraction revealed that the methyl gallate was having over 97% purity. Its structure was identified by H-1 NMR and C-13 NMR. © 2005 Published by Elsevier B.V. C1 Chinese Acad Sci, Grad Sch, Dept Biol, Beijing 100049, Peoples R China. Katholieke Univ Leuven, Fac Appl Biosci & Engn, B-3000 Louvain, Belgium. NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Tian, WX (reprint author), Chinese Acad Sci, Grad Sch, Dept Biol, Beijing 100049, Peoples R China. EM tianweixi@gscas.ac.cn NR 25 TC 24 Z9 28 U1 0 U2 15 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 MAY 27 PY 2005 VL 1076 IS 1-2 BP 212 EP 215 DI 10.1016/j.chroma.2005.04.077 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 932JW UT WOS:000229551000030 PM 15974092 ER PT J AU Souza, JA Yu, YK Neumeier, JJ Terashita, H Jardim, RF AF Souza, JA Yu, YK Neumeier, JJ Terashita, H Jardim, RF TI Method for analyzing second-order phase transitions: Application to the ferromagnetic transition of a polaronic system SO PHYSICAL REVIEW LETTERS LA English DT Article ID MANGANESE PEROVSKITES; HEAT AB A new method for analyzing second-order phase transitions is presented and applied to the polaronic system La0.7Ca0.3MnO3. It utilizes heat capacity and thermal expansion data simultaneously to correctly predict the critical temperature's pressure dependence. Analysis of the critical phenomena reveals second-order behavior and an unusually large heat capacity exponent. C1 Montana State Univ, Dept Phys, Bozeman, MT 59717 USA. Univ Sao Paulo, Inst Fis, BR-05315970 Sao Paulo, Brazil. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Souza, JA (reprint author), Montana State Univ, Dept Phys, POB 173840, Bozeman, MT 59717 USA. RI Souza, Jose/G-5555-2012; Jardim, Renato/J-8068-2014 OI Souza, Jose/0000-0002-6832-3581; Jardim, Renato/0000-0002-2000-0257 NR 23 TC 39 Z9 39 U1 0 U2 7 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD MAY 27 PY 2005 VL 94 IS 20 AR 207209 DI 10.1103/PhysRevLett.94.207209 PG 4 WC Physics, Multidisciplinary SC Physics GA 930EH UT WOS:000229398100059 PM 16090285 ER PT J AU Clemencet, MC Muzio, G Trombetta, A Peters, JM Gonzalez, FJ Canuto, RA Latruffe, N AF Clemencet, MC Muzio, G Trombetta, A Peters, JM Gonzalez, FJ Canuto, RA Latruffe, N TI Differences in cell proliferation in rodent and human hepatic derived cell lines exposed to ciprofibrate SO CANCER LETTERS LA English DT Article DE peroxisome proliferator-activated receptor-alpha; (PPAR alpha); c-myc; human hepatoma cells; rat hepatorna cells; proliferation; apoptosis ID ACTIVATED RECEPTOR-ALPHA; PEROXISOME-PROLIFERATOR; PPAR-ALPHA; NONGENOTOXIC HEPATOCARCINOGEN; HUMAN RELEVANCE; LIVER-TUMORS; IN-VITRO; C-MYC; APOPTOSIS; EXPRESSION AB Humans appear to be refractory to some effects of peroxisome proliferators including alterations in cell proliferation, whereas rodents are susceptible. In this study, differences between the human and rat response to peroxisome proliferators were evaluated using rat and human tumour liver cell lines. Rat 7777 cells were more responsive than human HepG2 cells to ciprofibrate as they exhibited a higher decrease in cell number than HepG2, and underwent apoptosis. Results from these studies reveal a surprising response in tumour cell lines as the typical in vivo response of increased cell proliferation and reduced apoptosis was not observed in rat tumour cell lines at concentrations greater than those used to elicit the former response. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Bourgogne, Lab Biol Mol & Cellulaire, EA 2978, GDR,CNRS 2583,Fac Sci Gabriel, F-21000 Dijon, France. Univ Turin, Dept Med & Expt Oncol, I-10125 Turin, Italy. Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Latruffe, N (reprint author), Univ Bourgogne, Lab Biol Mol & Cellulaire, EA 2978, GDR,CNRS 2583,Fac Sci Gabriel, 6 Bd Gabriel, F-21000 Dijon, France. EM norbert.latruffe@u-bourgogne.fr RI Peters, Jeffrey/D-8847-2011; trombetta, antonella/J-7879-2016 OI trombetta, antonella/0000-0002-1752-2775 NR 43 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 26 PY 2005 VL 222 IS 2 BP 217 EP 226 DI 10.1016/j.canlet.2004.09.016 PG 10 WC Oncology SC Oncology GA 929NC UT WOS:000229351800011 PM 15863271 ER PT J AU Sun, GY Nicklaus, MC Xie, RH AF Sun, GY Nicklaus, MC Xie, RH TI Structure, stability, and NMR properties of lower fullerenes C-38-C-50 and azafullerene C44N6 SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID DENSITY-FUNCTIONAL THEORY; MOLECULAR-ORBITAL METHODS; IPR ISOMERS; CHEMICAL-SHIFTS; MAJOR ISOMERS; MAGNETIC-PROPERTIES; ARC-DISCHARGE; MINOR ISOMERS; SPECTRA; C-60 AB A systematic survey of the complete set of isomers of fullerenes C-38, C-40, C-42, C-44, C-46, C-48, C-50 and azafullerene C44N6 is reported. All isomeric structures were optimized using first-principle density functional theory at the B3LYP/6-31G* level. The isomeric structures with the lowest energies are C-38:17, C-40:38, C-42:45, C-44:75, C-44:89, C-46:109, C-48:171, and C-50:270. The ground-state structure of the azafullerene C44N6 in the framework Of C-50:270 has D-3 symmetry. The C-13 NMR chemical shifts and nucleus-independent chemical shifts (NICS) for the stable isomers of each fullerene are presented. C1 NCI, Med Chem Lab, CCR, DHHS,NIH, Ft Detrick, MD 21702 USA. NIST, Gaithersburg, MD 20899 USA. RP NCI, Med Chem Lab, CCR, DHHS,NIH, 376 Boyles St, Ft Detrick, MD 21702 USA. EM mn1@helix.nih.gov RI Nicklaus, Marc/N-4183-2014; OI Nicklaus, Marc/0000-0002-4775-7030 NR 50 TC 37 Z9 43 U1 0 U2 3 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 MAY 26 PY 2005 VL 109 IS 20 BP 4617 EP 4622 DI 10.1021/jp0450181 PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 928UC UT WOS:000229296200026 PM 16833800 ER PT J AU Ghei, M Stroncek, DF Provenzano, M AF Ghei, M Stroncek, DF Provenzano, M TI Analysis of memory T lymphocyte activity following stimulation with overlapping HLA-A*2402, A*0101 and Cw*0402 restricted CMV pp65 peptides SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID ADOPTIVE IMMUNOTHERAPY; CLINICAL-SCALE; CELLS; IDENTIFICATION; GENERATION; EXPANSION; EPITOPES AB The continuous efforts aimed at the identification of new immune epitopes across the MHC system has led to the discovery that more than one peptide may be restricted to the same HLA antigen and function as an immune determinant for that association. The aim of this study was to compare the ability of two overlapping peptides, the nonamer (9-mer) cytomegalovirus (CMV) pp65(341-349) (QYDPVAALF) and the decamer (10-mer) CMV pp65(341-350) (QYDPVAALFF), and the esadecamer (16-mer) peptide containing both the 9-mer and 10-mer sequences, CMV pp65(340-355) (RQYDPVAALFFFDIDL), to stimulate and maintain over time a T cell immune reactivation by HLA-A*2402, A*0101, and Cw*0402 cells from CMV-seropositive subjects. The 9-mer, 10-mer, and 16-mer peptides effectively stimulated CTLs from HLA-A*2402, HLA-A*0101, and HLA-Cw*0402 CMV seropositive donors. This data confirms that both the 9-mer and the 10-mer peptides are promiscuous and are not restricted to a single HLA antigen. CMV pp65(341-349) and CMV pp65(341-350) have the ability to produce CMV-specific CTLs in subjects with several different HLA types, presenting a practical advantage over other peptides that are restricted only to a single HLA antigen, and thus being optimal for CMV adoptive immune therapy. Moreover, since the 16-mer peptide encompasses both the 9-mer and 10-mer peptides, it may be better than either of these peptides for CMV adoptive immune therapy. C1 NIH, Mol Immunol Sect, Dept Transfus Med, Bethesda, MD 20892 USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Basel, Inst Chirurg Forsch & Spitalmanagement, Basel, Switzerland. RP Provenzano, M (reprint author), NIH, Mol Immunol Sect, Dept Transfus Med, Bethesda, MD 20892 USA. EM gheim@msnotes.wustl.edu; dstroncek@dtm.cc.nih.gov; mprovenzano@uhbs.ch NR 15 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD MAY 26 PY 2005 VL 3 DI 10.1186/1479-5876-3-23 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 968KI UT WOS:000232161000001 ER PT J AU Fauci, AS AF Fauci, AS TI Race against time SO NATURE LA English DT Editorial Material ID VACCINE; VIRUS C1 NIAID, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, US Dept HHS, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 6 TC 30 Z9 31 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 MAY 26 PY 2005 VL 435 IS 7041 BP 423 EP 424 DI 10.1038/435423a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 929IF UT WOS:000229337800027 PM 15917781 ER PT J AU Hawk, E Viner, JL AF Hawk, E Viner, JL TI Statins and cancer - Beyond the "one drug, one disease'' model SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID REDUCTASE INHIBITORS; CLINICAL-TRIALS; RISK; PREVENTION; METAANALYSIS; PRAVASTATIN C1 NCI, Off Ctr Training & Resources, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Hawk, E (reprint author), NCI, Off Ctr Training & Resources, Bethesda, MD 20892 USA. NR 15 TC 26 Z9 27 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 MAY 26 PY 2005 VL 352 IS 21 BP 2238 EP 2239 DI 10.1056/NEJMe058074 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 929HS UT WOS:000229333300015 PM 15917390 ER PT J AU Xie, Q Gao, CF Shinomiya, N Sausville, E Hay, R Gustafson, M Shen, YH Wenkert, D Vande Woude, GF AF Xie, Q Gao, CF Shinomiya, N Sausville, E Hay, R Gustafson, M Shen, YH Wenkert, D Vande Woude, GF TI Geldanamycins exquisitely inhibit HGF/SF-mediated tumor cell invasion SO ONCOGENE LA English DT Article DE geldanamycin; HGF/SF; Met; HSP90; uPA; molecular target; urokinase-type plasminogen activator ID UROKINASE PLASMINOGEN-ACTIVATOR; SHOCK-PROTEIN 90; MOLECULAR CHAPERONES; BREAST-CANCER; IN-VIVO; GROWTH; RECEPTOR; MET; DEGRADATION; EXPRESSION AB Induction of the urokinase-type plasminogen activator (uPA) by hepatocyte growth factor/scatter factor (HGF/ SF) plays an important role in tumor cell invasion and metastasis that is mediated through the Met receptor tyrosine kinase. Geldanamycins (GA) are antitumor drugs that bind and inhibit HSP90 chaperone activity at nanomolarconcent rations (nM-GAi) by preventing proper folding and functioning of certain oncoproteins. Previously, we have shown that a subset of GA derivatives exhibit exquisite potency, inhibiting HGF/ SF-induced uPA-plasmin activation at femtomolarconcent rations (fM-GAi) in canine MDCK cells. Here, we report that ( 1) inhibition of HGF/ SF-induced uPA activity by fM-GAi is not uncommon, in that several human tumor glioblastoma cell lines (DBTRG, U373 and SNB19), as well as SK-LMS-1 human leiomyosarcoma cells are also sensitive to fM-GAi; ( 2) fM-GAi drugs only display inhibitory activity against HGF/SF-induced uPA activity ( rather than basal activity), and only when the observed magnitude of uPA activity induction by HGF/ SF is at least 1.5 times basal uPA activity; and ( 3) not only do fM-GAi derivatives strongly inhibit uPA activity but they also block MDCK cell scattering and in vitro invasion of human glioblastoma cells at similarly low drug concentrations. These effects of fM-GAi drugs on the Met-activated signaling pathway occur at concentrations well below those required to measurably affect Met expression or cell proliferation. We also examined the effect of Radicicol ( RA), a drug with higher affinity than GA for HSP90. RA displays uPA activity inhibition at nanomolar levels, but not at lower concentrations, indicating that HSP90 is not likely the fM-GAi molecular tar get. Thus, we show that certain GA drugs ( fM-GAi) in an HGF/ SF-dependent mannerblock uPA-plasmin activation in tumor cells at femtomolar levels. This inhibition can also be observed in scattering and in vitro invasion assays. Our findings also provide strong circumstantial evidence for a novel non-HSP90 molecular target that is involved in HGF/SF-mediated tumor cell invasion. C1 Van Andel Res Inst, Mol Oncol Lab, Grand Rapids, MI 49503 USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA. RP Vande Woude, GF (reprint author), Van Andel Res Inst, Mol Oncol Lab, 333 Bostwick NE, Grand Rapids, MI 49503 USA. EM michelle.reed@vai.org RI Shen, Yuehai/J-7829-2012 NR 41 TC 43 Z9 49 U1 1 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 MAY 26 PY 2005 VL 24 IS 23 BP 3697 EP 3707 DI 10.1038/sj.onc.1208499 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 929KZ UT WOS:000229346300001 PM 15782129 ER PT J AU Huang, YP Wernyj, RP Norton, DD Precht, P Seminario, MC Wange, RL AF Huang, YP Wernyj, RP Norton, DD Precht, P Seminario, MC Wange, RL TI Modulation of specific protein expression levels by PTEN: identification of AKAP121, DHFR, G3BP, Rap1, and RCC1 as potential targets of PTEN SO ONCOGENE LA English DT Article DE PTEN; RCC1; G3BP; proteomics; leukemia; tumor suppressor ID GTPASE-ACTIVATING PROTEIN; TUMOR-SUPPRESSOR GENE; JURKAT T-CELLS; PHOSPHATASE-ACTIVITY; BINDING-PROTEIN; GROWTH; RAS; DEGRADATION; INHIBITOR; MECHANISM AB The tumor suppressor PTEN is mutated in a high percentage of human cancers, and is implicated in pathways regulating cell growth, proliferation, survival, and migration. Despite significant advances, our understanding of its mechanisms of action remains incomplete. We have used a high-throughput proteomic immunoblotting approach to identify proteins whose expression levels are modulated by PTEN. Out of over 800 proteins screened, 22 proteins showed significant changes in expression. Five proteins that exhibited two-fold or greater changes in expression level were further characterized. AKAP121 and G3BP expression was reduced, while dihydrofolate reductase ( DHFR), Rap1 and RCC1 expression was elevated in response to PTEN expression in a PTEN-null T-cell leukemia line. The phosphatase activity of PTEN was required for these effects. However, direct inhibition of PI-3 Kinase could mimic PTEN in modulating expression of DHFR, G3BP, Rap1 and RCC1, but not AKAP121. Real-time PCR showed that the effects of PTEN were primarily post-transcriptional, and would not have been revealed by mRNA-based screens. We conclude from these data that PTEN can modulate the expression level of a number of different proteins. The identified proteins have the potential to serve as previously unrecognized effectors of PTEN, and suggest the existence of additional complexity in the modes by which PTEN can regulate cellular biology. C1 NIA, Cellular & Mol Biol Lab, IRP NIH DHHS, Baltimore, MD 21224 USA. RP Wange, RL (reprint author), NIA, Cellular & Mol Biol Lab, IRP NIH DHHS, 5600 Nathan Shock Dr,MSC-12, Baltimore, MD 21224 USA. EM wanger@grc.nia.nih.gov NR 43 TC 12 Z9 13 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 26 PY 2005 VL 24 IS 23 BP 3819 EP 3829 DI 10.1038/sj.onc.1208527 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 929KZ UT WOS:000229346300012 PM 15782128 ER PT J AU Petrovics, G Liu, AJ Shaheduzzaman, S Furasato, B Sun, C Chen, YM Nau, M Ravindranath, L Chen, YD Dobi, A Srikantan, V Sesterhenn, IA McLeod, DG Vahey, M Moul, JW Srivastava, S AF Petrovics, G Liu, AJ Shaheduzzaman, S Furasato, B Sun, C Chen, YM Nau, M Ravindranath, L Chen, YD Dobi, A Srikantan, V Sesterhenn, IA McLeod, DG Vahey, M Moul, JW Srivastava, S TI Frequent overexpression of ETS-related gene-1 (ERG1) in prostate cancer transcriptome SO ONCOGENE LA English DT Article DE ERG1; ETS transcription factor family; prostate cancer; proto-oncogene; overexpression ID EXPRESSION; ONCOGENE; FAMILY AB Transcription factors encoded by the ETS family of genes are central in integrating signals that regulate cell growth and differentiation, stress responses, and tumorigenesis. This study, analysing laser microdissected paired benign and malignant prostate epithelial cells from prostate cancer (CaP) patients ( n = 114; 228 specimen) by GeneChip and quantitative real-time RT-PCR, identifies ETS-related gene ( ERG), a member of the ETS transcription factor family, as the most frequently overexpressed proto-oncogene in the transcriptome of malignant prostate epithelial cells. Combined quantitative expression analysis of ERG with two other genes commonly overexpressed in CaP, AMACR and DD3, revealed overexpression of at least one of these three genes in virtually all CaP specimen ( 54 of 55). Comprehensive evaluation of quantitative ERG1 expression with clinicopathological features also suggested that ERG1 expression level in prostate tumor cells relative to benign epithelial cells is indicator of disease-free survival after radical prostatectomy. C1 Ctr Prostate Dis Res, Dept Surg, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, US Mil Canc Inst, Rockville, MD 20852 USA. Armed Forces Inst Pathol, Dept Genitourinary Pathol, Washington, DC 20306 USA. Walter Reed Army Inst Res, Lab Funct Genom, Rockville, MD 20850 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Urol Serv, Washington, DC 20307 USA. RP Srivastava, S (reprint author), Ctr Prostate Dis Res, Dept Surg, Rockville, MD 20852 USA. EM gpetrovics@cpdr.org FU NIDDK NIH HHS [R01 DK065977] NR 18 TC 212 Z9 226 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 26 PY 2005 VL 24 IS 23 BP 3847 EP 3852 DI 10.1038/sj.onc.1208518 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 929KZ UT WOS:000229346300016 PM 15750627 ER PT J AU Horkay, F Basser, PJ Hecht, AM Geissler, E AF Horkay, F Basser, PJ Hecht, AM Geissler, E TI Structural investigations of a neutralized polyelectrolyte gel and an associating neutral hydrogel SO POLYMER LA English DT Article DE hydrogel; polyelectrolyte; small angle neutron scattering ID POLYMER NETWORKS; SWOLLEN AB Small angle neutron scattering (SANS) measurements are used to differentiate the local organization of the polymer chains in two different classes of hydrogel. In neutral polyvinyl alcohol gels, hydrogen bonding gives rise to long range structural perturbations that are superimposed on the underlying chemically cross-linked network, thus producing excess scattering at small values of the scattering vector q. This secondary superstructure causes an increase in the elastic modulus. The intensity scattered by the thermal fluctuations in these gels can be described by an Ornstein-Zernike lineshape and is consistent with the osmotic modulus deduced from macroscopic osmotic and mechanical observations. Strongly charged polyacrylate hydrogels, however, display a qualitatively different scattering response. At low q a power law behavior is observed characteristic of a fractal surface. At intermediate q another component of osmotic origin is visible, which varies as q(-1), which indicates that the presence of divalent cations favors linear alignment of the network chains. Acceptable agreement is found between the estimate of the thermal fluctuations deduced from SANS and the results derived from independent osmotic observations. © 2005 Elsevier Ltd. All rights reserved. C1 NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Univ Grenoble 1, CNRS, Spectrometrie Phys Lab, UMR 5588, F-38402 St Martin Dheres, France. RP Horkay, F (reprint author), NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bldg 13,Room 3W16E,13 S Dr, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov RI Basser, Peter/H-5477-2011 NR 21 TC 19 Z9 19 U1 3 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0032-3861 J9 POLYMER JI Polymer PD MAY 26 PY 2005 VL 46 IS 12 BP 4242 EP 4247 DI 10.1016/j.polymer.2005.02.054 PG 6 WC Polymer Science SC Polymer Science GA 933BH UT WOS:000229598400030 ER PT J AU Magalhaes, AC Baron, GS Lee, KS Steele-Mortimer, O Dorward, D Prado, MAM Caughey, B AF Magalhaes, AC Baron, GS Lee, KS Steele-Mortimer, O Dorward, D Prado, MAM Caughey, B TI Uptake and neuritic transport of scrapie prion protein coincident with infection of neuronal cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE prion; trafficking; transport; neurites; endosomes; lysosomes ID VESICULAR ACETYLCHOLINE TRANSPORTER; CREUTZFELDT-JAKOB-DISEASE; PERIPHERAL NERVOUS-SYSTEM; RETROGRADE TRANSPORT; AXONAL-TRANSPORT; RESISTANT STATE; CULTURED-CELLS; MOUSE SCRAPIE; PRP; TRAFFICKING AB Invasion of the nervous system and neuronal spread of infection are critical, but poorly understood, steps in the pathogenesis of transmissible spongiform encephalopathies or prion diseases. To characterize pathways for the uptake and intraneuronal trafficking of infectious, protease-resistant prion protein (PrP-res), fluorescent-labeled PrP-res was used to infect a neuronally derived murine cell line (SN56) and adult hamster cortical neurons in primary culture. Concurrent with the establishment of persistent scrapie infection, SN56 cells internalized PrP-res aggregates into vesicles positive for markers for late endosomes and/or lysosomes but not synaptic, early endocytic, or raft-derived vesicles. Internalized PrP-res was then transported along neurites to points of contact with other cells. Similar trafficking was observed with dextran, Alzheimer's A beta 1 - 42 fibrils and noninfectious recombinant PrP fibrils, suggesting that PrP-res is internalized by a relatively nonspecific pinocytosis or transcytosis mechanism. Hamster cortical neurons were also capable of internalizing and disseminating exogenous PrP-res. Similar trafficking of exogenous PrP-res by cortical neurons cultured from the brains of PrP knock-out mice showed that uptake and neuritic transport did not require the presence of endogenous cellular PrP. These experiments visualize and characterize the initial steps associated with prion infection and transport within neuronal cells. C1 Univ Fed Minas Gerais, Dept Pharmacol, BR-31270901 Belo Horizonte, MG, Brazil. NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Microscopy Facil, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), Univ Fed Minas Gerais, Dept Pharmacol, Ave Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil. EM mprado@mono.icb.ufmg.br; bcaughey@nih.gov RI Lee, Kil/D-3678-2012; Prado, Marco/K-7638-2013 OI Prado, Marco/0000-0002-3028-5778 NR 58 TC 101 Z9 104 U1 3 U2 12 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 MAY 25 PY 2005 VL 25 IS 21 BP 5207 EP 5216 DI 10.1523/JNEUROSCI.0653-05.2005 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 930AK UT WOS:000229387900011 PM 15917460 ER PT J AU Bannister, NJ Benke, TA Mellor, J Scott, H Gurdal, E Crabtree, JW Isaac, JTR AF Bannister, NJ Benke, TA Mellor, J Scott, H Gurdal, E Crabtree, JW Isaac, JTR TI Developmental changes in AMPA and kainate receptor-mediated quantal transmission at thalamocortical synapses in the barrel cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glutamate; synaptic transmission; layer IV; neocortex; miniature EPSC; nonstationary fluctuation analysis ID CEREBELLAR GRANULE CELLS; MOSSY FIBER SYNAPSES; NONSTATIONARY FLUCTUATION ANALYSIS; SYNAPTICALLY RELEASED GLUTAMATE; HIPPOCAMPAL-NEURONS; NMDA RECEPTOR; UNITARY CONDUCTANCE; CHANNEL PROPERTIES; PYRAMIDAL NEURONS; ION CHANNELS AB During the first week of life, there is a shift from kainate to AMPA receptor-mediated thalamocortical transmission in layer IV barrel cortex. However, the mechanisms underlying this change and the differential properties of AMPA and kainate receptor-mediated transmission remain essentially unexplored. To investigate this, we studied the quantal properties of AMPA and kainate receptor-mediated transmission using strontium-evoked miniature EPSCs. AMPA and kainate receptor-mediated transmission exhibited very different quantal properties but were never coactivated by a single quantum of transmitter, indicating complete segregation to different synapses within the thalamocortical input. Nonstationary fluctuation analysis showed that synaptic AMPA receptors exhibited a range of single-channel conductance (gamma) and a strong negative correlation between gamma and functional channel number, indicating that these two parameters are reciprocally regulated at thalamocortical synapses. We obtained the first estimate of gamma for synaptic kainate receptors (<2 pS), and this primarily accounted for the small quantal size of kainate receptor-mediated transmission. Developmentally, the quantal contribution to transmission of AMPA receptors increased and that of kainate receptors decreased. No changes in AMPA or kainate quantal amplitude or in AMPA receptor gamma were observed, demonstrating that the developmental change was attributable to a decrease in the number of kainate synapses and an increase in the number of AMPA synapses contributing to transmission. Therefore, we demonstrate fundamental differences in the quantal properties for these two types of synapse. Thus, the developmental switch in transmission will dramatically alter information transfer at thalamocortical inputs to layer IV. C1 Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. Univ Bristol, Dept Anat, Med Res Council Ctr Synapt Plastic, Bristol BS8 1TD, Avon, England. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Marmara Univ, Sch Med, Dept Anat, TR-34668 Istanbul, Turkey. RP Isaac, JTR (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, 35 Convent Drive, Bethesda, MD 20892 USA. EM isaacj@ninds.nih.gov RI Scott, Helen/A-6307-2009 OI Scott, Helen/0000-0003-2656-4034 FU NINDS NIH HHS [NS 41267] NR 67 TC 28 Z9 30 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 MAY 25 PY 2005 VL 25 IS 21 BP 5259 EP 5271 DI 10.1523/JNEUROSCI.0827-05.2005 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 930AK UT WOS:000229387900017 PM 15917466 ER PT J AU Bryce, DL Grishaev, A Bax, A AF Bryce, DL Grishaev, A Bax, A TI Measurement of ribose carbon chemical shift tensors for A-form RNA by liquid crystal NMR spectroscopy SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RESIDUAL DIPOLAR COUPLINGS; CROSS-CORRELATED RELAXATION; NUCLEIC-ACID STRUCTURE; MAGNETIC-FIELD; MOLECULAR-DYNAMICS; PROTEIN-STRUCTURE; DNA DODECAMER; SUGAR PUCKERS; STEM-LOOP; ALIGNMENT AB Incomplete motional averaging of chemical shift anisotropy upon weak alignment of nucleic acids and proteins in a magnetic field results in small changes in chemical shift. Knowledge of nucleus-specific chemical shift (CS) tensor magnitudes and orientations is necessary to take full advantage of these measurements in biomolecular structure determination. We report the determination by liquid crystal NMR of the CS tensors for all ribose carbons in A-form helical RNA, using a series of novel 3D NMR pulse sequences for accurate and resolved measurement of the ribose C-13 chemical shifts. The orientation of the riboses relative to the rhombic alignment tensor of the molecule studied, a stem-loop sequence corresponding to helix-35 of 23S rRNA, is known from an extensive set of residual dipolar couplings (RDC), previously used to refine its structure. Singular-value-decomposition fits of the chemical shift changes to this structure, or alternatively to a database of helical RNA X-ray structures, provide the CS tensor for each type of carbon. Quantum chemical calculations complement the experimental results and confirm that the most shielded tensor component lies approximately along the local carbon-oxygen bond axis in all cases and that shielding anisotropy for C3' and C4' is much larger than for C1' and C2', with C5' being intermediate. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM bax@nih.gov RI Bryce, David/A-3534-2008 OI Bryce, David/0000-0001-9989-796X NR 72 TC 28 Z9 28 U1 1 U2 8 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 MAY 25 PY 2005 VL 127 IS 20 BP 7387 EP 7396 DI 10.1021/ja051039c PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 928AX UT WOS:000229244600042 PM 15898787 ER PT J AU Nardelli-Haefliger, D Lurati, F Wirthner, D Spertini, F Schiller, JT Lowy, DR Ponci, F De Grandi, P AF Nardelli-Haefliger, D Lurati, F Wirthner, D Spertini, F Schiller, JT Lowy, DR Ponci, F De Grandi, P TI Immune responses induced by lower airway mucosal immunisation with a human papillomavirus type 16 virus-like particle vaccine SO VACCINE LA English DT Article DE aerosol vaccination; virus like particles; human papillomavirus; cervical cancer ID FEMALE GENITAL-TRACT; SYSTEMIC ANTIBODY-RESPONSES; TOXIN B-SUBUNIT; INTRANASAL IMMUNIZATION; VAGINAL IMMUNIZATION; RECTAL IMMUNIZATION; ADULT VOLUNTEERS; CERVICAL-CANCER; MEASLES-VACCINE; INDUCTION AB Cervical cancer results from cervical infection by human papillomaviruses (HPV). especially HPV16. Previous studies have shown that intramuscular vaccination of women with an HPV16 virus-like particle (VLP) vaccine induced a strong IgG response and protected against genital HPV16 infection. However, an alternative route of administration that avoids parenteral injection while inducing mucosal immunity might facilitate vaccine implementation in some settings, and partially overcome the substantial variation in HPV16 antibodies at the cervix seen in ovulating women. In this study, women were vaccinated with escalating doses of HPV16LI VLPs Via nasal nebulisation, bronchial aerosolisation, or a combination of intramuscular and aerosol vaccination. The alternative routes of vaccination were well tolerated and many of the volunteers who received aerosol vaccinations exhibited serum antibody titers that were comparable to those induced by intramuscular vaccination. A mucosal immune response was induced by aerosol vaccination as demonstrated by the induction of anti-HPV16 VLP IgA secreting cells in PBMC and SIgA in secretions. Our data suggest that aerosol administration of HPV VLPs may represent a potential alternative to parenteral injection. © 2005 Elsevier Ltd. All rights reserved. C1 CHU Vaudois, Dept Gynecol, CH-1011 Lausanne, Switzerland. CHU Vaudois, Div Immunol & Allergy, CH-1011 Lausanne, Switzerland. NCI, Cellular Oncol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Nardelli-Haefliger, D (reprint author), CHU Vaudois, Dept Gynecol, CH-1011 Lausanne, Switzerland. EM dnardell@hospvd.ch OI nardelli-haefliger, denise/0000-0003-1812-9905 NR 47 TC 67 Z9 72 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 25 PY 2005 VL 23 IS 28 BP 3634 EP 3641 DI 10.1016/j.vaccine.2005.02.019 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 931KK UT WOS:000229484000003 PM 15882523 ER PT J AU Tanabe, L Xie, N Thom, LH Matten, W Wilbur, WJ AF Tanabe, L Xie, N Thom, LH Matten, W Wilbur, WJ TI GENETAG: a tagged corpus for gene/protein named entity recognition SO BMC BIOINFORMATICS LA English DT Article AB Background: Named entity recognition (NER) is an important first step for text mining the biomedical literature. Evaluating the performance of biomedical NER systems is impossible without a standardized test corpus. The annotation of such a corpus for gene/protein name NER is a difficult process due to the complexity of gene/protein names. We describe the construction and annotation of GENETAG, a corpus of 20K MEDLINE(R) sentences for gene/protein NER. 15K GENETAG sentences were used for the BioCreAtIvE Task 1A Competition. Results: To ensure heterogeneity of the corpus, MEDLINE sentences were first scored for term similarity to documents with known gene names, and 10K high- and 10K low-scoring sentences were chosen at random. The original 20K sentences were run through a gene/protein name tagger, and the results were modified manually to reflect a wide definition of gene/protein names subject to a specificity constraint, a rule that required the tagged entities to refer to specific entities. Each sentence in GENETAG was annotated with acceptable alternatives to the gene/protein names it contained, allowing for partial matching with semantic constraints. Semantic constraints are rules requiring the tagged entity to contain its true meaning in the sentence context. Application of these constraints results in a more meaningful measure of the performance of an NER system than unrestricted partial matching. Conclusion: The annotation of GENETAG required intricate manual judgments by annotators which hindered tagging consistency. The data were pre-segmented into words, to provide indices supporting comparison of system responses to the "gold standard". However, character-based indices would have been more robust than word-based indices. GENETAG Train, Test and Round1 data and ancillary programs are freely available at ftp://ftp.ncbi.nlm.nih.gov/pub/tanabe/GENETAG.tar.gz. A newer version of GENETAG-05, will be released later this year. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Consolidated Safety Serv, Fairfax, VA 22030 USA. RP Wilbur, WJ (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM tanabe@ncbi.nlm.nih.gov; natxie@ncbi.nlm.nih.gov; Meadowln@comcast.net; wmatten@consolidatedsafety.com; wilbur@ncbi.nlm.nih.gov NR 10 TC 66 Z9 69 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAY 24 PY 2005 VL 6 SU 1 AR S3 DI 10.1186/1471-2105-6-S1-S3 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 022NB UT WOS:000236061400003 PM 15960837 ER PT J AU Gray, DT Walters, S Spertus, J Brazier, J Horvath, K AF Gray, DT Walters, S Spertus, J Brazier, J Horvath, K TI Quality-adjusted survival and cost-effectiveness of transmyocardial revascularization using the CO2 laser SO CIRCULATION LA English DT Meeting Abstract CT 6th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 14-16, 2005 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdiciplinary Working Grp, Councils Cardiovasc Nursing, Councils Cardiovasc Surg & Anesthesia, Councils Clin Cardiol, Councils Epidemiol & Prevent & Stroke, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Agcy Healthcare Rsch & Qual, Rockville, MD USA. Univ Sheffield, Sheffield, S Yorkshire, England. Univ Missouri, Kansas City, MO 64110 USA. NHLBI, Bethesda, MD 20892 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 0009-7322 J9 CIRCULATION JI Circulation PD MAY 24 PY 2005 VL 111 IS 20 BP E319 EP E319 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 929AD UT WOS:000229313000068 ER PT J AU Richie, CT Golden, A AF Richie, CT Golden, A TI Chromosome segregation: Aurora B gets tousled SO CURRENT BIOLOGY LA English DT Editorial Material ID DNA-REPLICATION; KINASE-ACTIVITY; HISTONE H3; PHOSPHORYLATION; TRANSCRIPTION; CYTOKINESIS; SPINDLE; COMPLEX; INCENP; DAMAGE AB Aurora B kinases play important roles during mitosis in eukaryotic cells; new work in Caenorhabditis elegans has identified the Tousled kinase TLK-1 as a substrate activator of the model nematode's Aurora B kinase AIR-2 which acts to ensure proper chromosome segregation during cell division. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Richie, CT (reprint author), NIDDKD, Lab Biochem & Genet, NIH, 8 Ctr Dr, Bethesda, MD 20892 USA. EM andyg@intra.niddk.nih.gov NR 18 TC 4 Z9 10 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 24 PY 2005 VL 15 IS 10 BP R379 EP R382 DI 10.1016/j.cub.2005.05.009 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 930VZ UT WOS:000229446500012 PM 15916939 ER PT J AU Chiu, TK Kubelka, J Herbst-Irmer, R Eaton, WA Hofrichter, J Davies, DR AF Chiu, TK Kubelka, J Herbst-Irmer, R Eaton, WA Hofrichter, J Davies, DR TI High-resolution x-ray crystal structures of the villin headpiece subdomain, an ultrafast folding protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE kinetics; temperature jump; NMR ID 3-HELIX BUNDLE; NMR STRUCTURE; MAXIMUM RATE; SPEED LIMIT; FAST EVENTS; DYNAMICS; SIMULATIONS; KINETICS; MODEL; PATHWAYS AB The 35-residue subdomain of the villin headpiece (HP35) is a small ultrafast folding protein that is being intensely studied by experiments, theory, and simulations. We have solved the x-ray structures of HP35 and its fastest folding mutant [K24 norleucine (nL)] to atomic resolution and compared their experimentally measured folding kinetics by using laser temperature jump. The structures, which are in different space groups, are almost identical to each other but differ significantly from previously solved NMR structures. Hence, the differences between the x-ray and NMR structures are probably not caused by lattice contacts or crystal/solution differences, but reflect the higher accuracy of the x-ray structures. The x-ray structures reveal important details of packing of the hydrophobic core and some additional features, such as cross-helical H bonds. Comparison of the x-ray structures indicates that the nL substitution produces only local perturbations. Consequently, the finding that the small stabilization by the mutation is completely reflected in an increased folding rate suggests that this region of the protein is as structured in the transition state as in the folded structure. It is therefore a target for engineering to increase the folding rate of the subdomain from approximate to 0.5 mu s(-1) for the nL mutant to the estimated theoretical speed limit of approximate to 3 mu s(-1). C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Gottingen, Dept Struct Chem, D-37077 Gottingen, Germany. RP Davies, DR (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM david.davies@nih.gov NR 43 TC 133 Z9 135 U1 5 U2 19 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 MAY 24 PY 2005 VL 102 IS 21 BP 7517 EP 7522 DI 10.1073/pnas.0502495102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 930LN UT WOS:000229417500023 PM 15894611 ER PT J AU Aoki, K Kato, J Shoemaker, MT Moss, J AF Aoki, K Kato, J Shoemaker, MT Moss, J TI Genomic organization and promoter analysis of the mouse ADP-ribosylarginine hydrolase gene SO GENE LA English DT Article DE mono-ADP-ribosylation; ADP-ribosylarginine hydrolase; promoter; housekeeping genes; Sp1 ID BOX-BINDING-PROTEINS; SMOOTH-MUSCLE-CELLS; RNA-POLYMERASE-II; TURKEY ERYTHROCYTES; TRANSGENIC MICE; RECEPTOR GENE; SP1; IDENTIFICATION; EXPRESSION; CLONING AB Mono-ADP-ribosylation is a reversible modification of proteins with NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine hydrolases (ADPRH) catalyzing the opposing arms of an ADP-ribosylation cycle. The ADPRH cDNA had been cloned from human, rat, and mouse tissues and high levels of mRNA were found in brain, spleen, and testis. To begin to understand the molecular mechanisms that regulate ADPRH gene expression, we cloned the full-length cDNA, determined the genomic structure of mouse ADPRH, and investigated promoter function. Northern analysis using different regions of the ADPRH cDNA as probes identified two mRNAs of 1.7 and 3.0 kb, which resulted from the use of alternative polyadenylation signals, CATAAC and ATTAAA, beginning at positions 1501 and 2885, respectively, of the nucleotide sequence (A of ATG=1). The ADPRH gene, represented in two overlapping genomic clones, spans similar to 9 kilobases with four exons and three introns. The 5'-flanking region contains the features of a housekeeping gene; it has neither a TATA nor a CAAT box, but is, instead, highly GC-rich with multiple transcription initiation sites. Promoter analysis, assessed using transient transfection of PC12, N1341A3, NIH/3T3, and Hepa 1-6 cells with truncated constructs, revealed potent stimulatory (-119 to -89) and inhibitory (-161 to -119) elements, which were utilized similarly in the different cell lines. Further mutational analysis of the promoter and electrophoretic mobility-shift assays identified a positive GC-box element (- 107 to -95); Sp1 and Sp3, which bound to this motif, were also detected by supershift assays. In cotransfection experiments using Drosophila SL2 cells that lack endogenous Sp1, Sp1 trans-activated the ADPRH promoter in a manner dependent on the presence of an Sp1-binding motif. The promoter activity pattern and involvement of Sp transcription factors are consistent with prior observations of widespread hydrolase expression in mammalian tissues. (c) 2005 Elsevier B.V. All rights reserved. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, 10 Ctr Dr MSC 1434,Bldg 10,Room 5N307, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov NR 30 TC 1 Z9 2 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 23 PY 2005 VL 351 BP 83 EP 95 DI 10.1016/j.gene.2005.02.016 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 936SA UT WOS:000229874500009 PM 15893437 ER PT J AU Zhao, TM Hague, B Caudell, DL Simpson, RM Kindt, TJ AF Zhao, TM Hague, B Caudell, DL Simpson, RM Kindt, TJ TI Quantification of HTLV-I proviral load in experimentally infected rabbits SO RETROVIROLOGY LA English DT Article ID VIRUS TYPE-I; MYELOPATHY/TROPICAL SPASTIC PARAPARESIS; CD8(+) T-CELLS; REAL-TIME PCR; DNA LOAD; ASYMPTOMATIC CARRIERS; INTERFERON-ALPHA; MOLECULAR CLONE; HAM/TSP; TYPE-1 AB Background: Levels of proviral load in HTLV-1 infected patients correlate with clinical outcome and are reasonably prognostic. Adaptation of proviral load measurement techniques is examined here for use in an experimental rabbit model of HTLV-1 infection. Initial efforts sought to correlate proviral load with route and dose of inoculation and with clinical outcome in this model. These methods contribute to our continuing goal of using the model to test treatments that alleviate virus infection. Results: A real-time PCR assay was used to measure proviral load in blood and tissue samples from a series of rabbits infected using HTLV-1 inocula prepared as either cell-free virus particles, infected cells or blood, or by naked DNA injection. Proviral loads from asymptomatically infected rabbits showed levels corresponding to those reported for human patients with clinically silent HTLV-1 infections. Proviral load was comparably increased in 50% of experimentally infected rabbits that developed either spontaneous benign or malignant tumors while infected. Similarly elevated provirus was found in organs of rabbits with experimentally induced acute leukemia/ lymphoma-like disease. Levels of provirus in organs taken at necropsy varied widely suggesting that reservoirs of infections exist in non-lymphoid organs not traditionally thought to be targets for HTLV-1. Conclusion: Proviral load measurement is a valuable enhancement to the rabbit model for HTLV-1 infection providing a metric to monitor clinical status of the infected animals as well as a means for the testing of treatment to combat infection. In some cases proviral load in blood did not reflect organ proviral levels, revealing a limitation of this method for monitoring health status of HTLV-1 infected individuals. C1 NIAID, Mol & Cellular Immunogenet Sect, NIH, Bethesda, MD 20892 USA. NCI, Mol Pathol Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kindt, TJ (reprint author), NIAID, Mol & Cellular Immunogenet Sect, NIH, Bldg 50,Room 5515,50 South Dr, Bethesda, MD 20892 USA. EM tzhao@niaid.nih.gov; bhague@niaid.nih.gov; caudelld@mail.nih.gov; simpsoma@mail.nih.gov; tkindt@niaid.nih.gov NR 38 TC 12 Z9 13 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD MAY 23 PY 2005 VL 2 AR 34 DI 10.1186/1742-4690-2-34 PG 10 WC Virology SC Virology GA 033CR UT WOS:000236824500001 PM 15910683 ER PT J AU Podgornik, R Saslow, WM AF Podgornik, R Saslow, WM TI Long-range many-body polyelectrolyte bridging interactions SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID FORCES; ADSORPTION; SURFACES; CHAINS AB We investigate polyelectrolyte bridging interactions mediated by charged, flexible, polyelectrolyte chains between fixed cylindrical macroions of opposite charge in a two-dimensional hexagonal crystalline array. We show that in the asymptotic regime of small macroion density, the polyelectrolyte-mediated attraction is long range, falling off approximately linearly with the macroion array density. We investigate the polyelectrolyte free energy as a function of the macroion density and derive several analytic limiting laws valid in different regimes of the parameter space. C1 Univ Ljubljana, Dept Phys, Ljubljana 1000, Slovenia. Jozef Stefan Inst, Dept Theoret Phys, SL-1000 Ljubljana, Slovenia. NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Texas A&M Univ, Dept Phys, College Stn, TX 77840 USA. RP Univ Ljubljana, Dept Phys, Jadranska 19, Ljubljana 1000, Slovenia. EM rudi@helix.nih.gov RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 30 TC 12 Z9 12 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD MAY 22 PY 2005 VL 122 IS 20 AR 204902 DI 10.1063/1.1908870 PG 13 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 932HJ UT WOS:000229544500066 PM 15945772 ER PT J AU Shi, YH Song, YL Lin, DH Tan, JZ Roller, PP Li, Q Long, YQ Song, GQ AF Shi, YH Song, YL Lin, DH Tan, JZ Roller, PP Li, Q Long, YQ Song, GQ TI Binding affinity difference induced by the stereochemistry of the sulfoxide bridge of the cyclic peptide inhibitors of Grb2-SH2 domain: NMR studies for the structural origin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE solution structure; NMR; dynamics; Grb2-SH2 domain inhibitors; cyclic peptide; signal transduction; chiral sulfoxide; configuration ID SH2 DOMAIN; NONPHOSPHORYLATED INHIBITOR; CHEMICAL-SHIFTS; ANTAGONISTS; PROTEINS; REQUIREMENTS; DYNAMICS; ENERGY; CELLS AB The SAR study on a phage library-derived non-phosphorylated cyclic peptide ligand of Grb2-SH2 domain indicates that the configuration of the cyclization linkage is crucial for assuming the active binding conformation. When the thioether linkage was oxidized to the two chiral sulfoxides, the R-configured sulfoxide-cyclized peptide displayed 10-30 times more potency than the corresponding S-configured one in binding affinity to the Grb2-SH2 domain. In this paper, the solution structures of such a pair of sulfoxide-bridged cyclic peptide diastereoisomers, i.e., cyclo[CH2CO-Gla(1)-L-Y-E-N-V-G-NPG-Y-(R/S)C(O)(10)]-amide, were determined by NMR and molecular dynamics simulation. Results indicate that the consensus sequence of Y-3-E-4-N-5-V-6 in both diastereoisomers adopt a U-turn conformation; however, the R-configured peptide forms an extended structure with a circular backbone conformation, while the S-configured isomer forms a compact structure with key residues buried inside the molecule. The average root-mean-square deviations were found to be 0.756 and 0.804 angstrom, respectively. It is apparent that the chiral S -> O group played a key role in the solution structures of the sulfoxide-bridged cyclic peptides. The R-sulfoxide group forms an intramolecular hydrogen bond with the C-terminal amide, conferring a more rigid conformation with all residues protruding outside except for Leu2, in which the Gla1 and Tyr3 share an overlapping function as previous SAR studies proposed. Additionally, the extended structure endows a more hydrophilic binding surface of the R-configured peptide to facilitate its capture by its targeted protein. In comparison, the S-configured sulfoxide was embedded inside the ligand peptide leading to a compact structure, in which the essential residues of Gla1, Tyr3, and Asn5 form multiple intramolecular hydrogen bonds resulting in an unfavorable conformational change and a substantial loss of the interaction with the protein. The solution structures disclosed by our NMR and molecular dynamics simulation studies provide a molecular basis for understanding how the chirality of the cyclization linkage remarkably discriminates in terms of the binding affinity, thus advancing the rational design of potent non-phosphorylated inhibitors of Grb2-SH2 domain as antitumor agents. Published by Elsevier Inc. C1 CAS, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Dept Analyt Sci, Shanghai 201203, Peoples R China. CAS, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, State Key Lab Drug Res,Dept Synth Chem, Shanghai 201203, Peoples R China. CAS, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China. NCI, Med Chem Lab, FCRDC, NIH, Frederick, MD 21702 USA. RP Long, YQ (reprint author), CAS, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Dept Analyt Sci, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China. EM yqlong@mail.shcnc.ac.cn; gqsong@mail.shcnc.ac.cn NR 34 TC 10 Z9 11 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 20 PY 2005 VL 330 IS 4 BP 1254 EP 1261 DI 10.1016/j.bbrc.2005.03.110 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 918RW UT WOS:000228566300035 PM 15823578 ER PT J AU Cheadle, C Fan, JS Cho-Chung, YS Werner, T Ray, J Do, L Gorospe, M Becker, KG AF Cheadle, C Fan, JS Cho-Chung, YS Werner, T Ray, J Do, L Gorospe, M Becker, KG TI Control of gene expression during T cell activation: alternate regulation of mRNA transcription and mRNA stability SO BMC GENOMICS LA English DT Article ID MICROARRAY DATA; CDNA; LYMPHOCYTES; PATTERNS; ARRAYS; MYC AB Background: Microarray technology has become highly valuable for identifying complex global changes in gene expression patterns. The effective correlation of observed changes in gene expression with shared transcription regulatory elements remains difficult to demonstrate convincingly. One reason for this difficulty may result from the intricate convergence of both transcriptional and mRNA turnover events which, together, directly influence steady-state mRNA levels. Results: In order to investigate the relative contribution of gene transcription and changes in mRNA stability regulation to standard analyses of gene expression, we used two distinct microarray methods which individually measure nuclear gene transcription and changes in polyA mRNA gene expression. Gene expression profiles were obtained from both polyA mRNA (whole-cell) and nuclear run-on ( newly transcribed) RNA across a time course of one hour following the activation of human Jurkat T cells with PMA plus ionomycin. Comparative analysis revealed that regulation of mRNA stability may account for as much as 50% of all measurements of changes in polyA mRNA in this system, as inferred by the absence of any corresponding regulation of nuclear gene transcription activity for these groups of genes. Genes which displayed dramatic elevations in both mRNA and nuclear run-on RNA were shown to be inhibited by Actinomycin D (ActD) pretreatment of cells while large numbers of genes regulated only through altered mRNA turnover ( both up and down) were ActD-resistant. Consistent patterns across the time course were observed for both transcribed and stability-regulated genes. Conclusion: We propose that regulation of mRNA stability contributes significantly to the observed changes in gene expression in response to external stimuli, as measured by high throughput systems. C1 NCI, Cellular Biochem Sect, Basic Res Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Genomatix Software GmbH, D-80339 Munich, Germany. Capital Genomix, Gaithersburg, MD 20877 USA. NIA, DNA Array Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Cheadle, C (reprint author), NCI, Cellular Biochem Sect, Basic Res Lab, Ctr Canc Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM cheadlec@mail.nih.gov; fanjin@grc.nia.nih.gov; YC12b@nih.gov; werner@genomatix.de; jill.ray@capitalgenomix.com; ldo@capitalgenomix.com; gorospem@grc.nia.nih.gov; beckerk@grc.nia.nih.gov NR 27 TC 104 Z9 109 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAY 20 PY 2005 VL 6 AR 75 DI 10.1186/1471-2164-6-75 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 937HG UT WOS:000229914600001 PM 15907206 ER PT J AU Rajeevan, MS Swan, DC Nisenbaum, R Lee, DR Vernon, SD Ruffin, MT Horowitz, IR Flowers, LC Kmak, D Tadros, T Birdsong, G Husain, M Srivastava, S Unger, ER AF Rajeevan, MS Swan, DC Nisenbaum, R Lee, DR Vernon, SD Ruffin, MT Horowitz, IR Flowers, LC Kmak, D Tadros, T Birdsong, G Husain, M Srivastava, S Unger, ER TI Epidemiologic and viral factors associated with cervical neoplasia in HPV-16-positive women SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE HPV-16 E6/E7 transcripts; biomarker; cervical neoplasia; screening; exfoliated cervical cells ID POLYMERASE-CHAIN-REACTION; HUMAN-PAPILLOMAVIRUS TYPES; INTRAEPITHELIAL NEOPLASIA; TYPE-16; LOAD; PCR; INFECTION; RISK; DNA; QUANTITATION AB While infection with high-risk HPV is the most important risk factor for cervical cancer, HPV alone is insufficient. Our purpose was to identify viral and epidemiologic factors associated with cervical disease in HPV-16 DNA-positive women referred to colposcopy. We used a standardized interview to collect epidemiologic data from consenting women. Total nucleic acids from exfoliated cervical cells were used for all viral assays (HPV detection and typing using L1 consensus PCR with line probe hybridization, variant classification by sequencing, viral load and transcript copy determination by quantitative PCR and transcript pattern by nested RT-PCR). Cervical disease was based on colposcopic biopsy. Logistic regression was used to calculate ORs with 95% CIs. There were 115 HPV-16 positive women among 839 enrollees. By univariate analyses, age > 25 years (OR = 3.05, 95% CI 1.20-7.76), smoking (OR = 3.0,95% CI 1.19-7.56), high viral load (OR = 5.27, 95% CI 2.05-13.60), detection of both E6 and E6*1 transcripts (OR = 10.0, 95% CI 2.1-47.58) and high transcript copies (OR = 5.56, 95% CI 2.05-13.60) were significant risk factors for CIN III with reference to No CIN/CIN I. Less than a third of the women (31.5%) had prototype HPV-16 detected, and variants showed no association with disease, viral load or transcription. Viral DNA and transcript copies were highly correlated, and the ratio of transcript copies to DNA copies was not changed with disease status. While viral load, transcript copies and transcript pattern were statistically associated with CIN III, none of these measures effectively discriminated between HPV-16 women with disease requiring treatment and those who could be followed. Cellular proliferation and differentiation pathways affected by HPV should be investigated as biomarkers for cervical cancer screening. (c) 2005 Wiley-Liss, Inc. C1 Univ Michigan, Ann Arbor, MI 48109 USA. Emory Univ, Atlanta, GA 30322 USA. Wayne State Univ, Detroit, MI USA. NCI, Rockville, MD USA. RP Unger, ER (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd,MSG-41, Atlanta, GA 30333 USA. EM eunger@cdc.gov OI Ruffin, Mack/0000-0001-8336-478X; Unger, Elizabeth/0000-0002-2925-5635 FU NCI NIH HHS [K24 CA80846] NR 29 TC 40 Z9 41 U1 0 U2 1 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 MAY 20 PY 2005 VL 115 IS 1 BP 114 EP 120 DI 10.1002/ijc.20894 PG 7 WC Oncology SC Oncology GA 918GP UT WOS:000228530600014 PM 15688414 ER PT J AU Bao, JJ Jana, SS Adelstein, RS AF Bao, JJ Jana, SS Adelstein, RS TI Vertebrate nonmuscle myosin II Isoforms rescue small interfering RNA-induced defects in COS-7 cell cytokinesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAVY-CHAIN ISOFORMS; CONTRACTILE RING; CULTURED-CELLS; GENE; LOCALIZATION; EXPRESSION; MECHANISM; ABLATION; IDENTIFICATION; DICTYOSTELIUM AB RNA interference (RNAi) treatment of monkey COS-7 cells, a cell line that lacks nonmuscle myosin heavy chain II-A (NMHC II-A) but contains NMHC II-B and II-C, was used to investigate the participation of NMHC isoforms in cytokinesis. We specifically suppressed the expression of NMHC II-B or II-C using 21 nucleotide small interfering RNA (siRNA) duplexes. Down-regulation of NMHC II-B protein expression to 10.2 &PLUSMN; 0.7% inhibited COS-7 cell proliferation by 50% in the RNAi-treated cells compared with control cells. Moreover, whereas 8.7 &PLUSMN; 1.0% of control cells were multinucleated, 62.4 &PLUSMN; 8.8% of the NMHC II-B RNAi-treated cells were multinucleated 72 h after transfection. The RNAi-treated cells had increased surface areas and, unlike control cells, lacked actin stress fibers. Treatment of the COS-7 cells with NMHC II-C siRNA decreased NMHC II-C expression to 5.2 &PLUSMN; 0.1% compared with the endogenous content of II-C; however, down-regulation of NMHC II-C did not cause increased multinucleation. Immunoblot analysis using a pan-myosin antibody showed that the content of NMHC II-C was less than one-twentieth the amount of NMHC II-B, thereby explaining the lack of response to II-C siRNA. Introducing green fluorescent protein (GFP)-tagged NMHC II isoforms into II-B siRNA-treated cells resulted in reduction of multinucleation from 62.4 &PLUSMN; 8.8% to 17.8 &PLUSMN; 2.2% using GFP-NMHC II-B, to 29.8 &PLUSMN; 7.4% using GFP-NMHC II-A, and to 34.1 &PLUSMN; 8.6% using NMHC II-C- GFP. These studies have shown that expression of endogenous NMHC II-C in COS-7 cells is insufficient for normal cytokinesis and that exogenous NMHC II-A and NMHC II-C can, at least partially, rescue the defect in cytokinesis due to the loss of NMHC II-B. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Adelstein, RS (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Rm 8N202,10 Ctr Dr,MSC 1762, Bethesda, MD 20892 USA. EM AdelsteR@NHLBI.NationalInstitutesofHealth.GOV OI Adelstein, Robert/0000-0002-8683-2144 NR 34 TC 70 Z9 72 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 MAY 20 PY 2005 VL 280 IS 20 BP 19594 EP 19599 DI 10.1074/jbc.M501573200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 926HH UT WOS:000229113700022 PM 15774463 ER PT J AU Wei, CJ Francis, R Xu, X Lo, CW AF Wei, CJ Francis, R Xu, X Lo, CW TI Connexin43 associated with an N-cadherin-containing multiprotein complex is required for gap junction formation in NIH3T3 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CARDIAC MYOCYTES; PLASMA-MEMBRANE; INTERCELLULAR COMMUNICATION; PROTEIN CONNEXIN-43; RAT CARDIOMYOCYTES; MEDIATED ADHESION; CATENIN COMPLEXES; CHANNEL PROTEIN; PHOSPHORYLATION; EXPRESSION AB Previous studies have indicated an intimate linkage between gap junction and adherens junction formation. It was suggested this could reflect the close membrane-membrane apposition required for junction formation. In NIH3T3 cells, we observed the colocalization of connexin43 (Cx43α 1) gap junction protein with N-cadherin, p120, and other N-cadherin-associated proteins at regions of cell-cell contact. We also found that Cx43α 1, N-cadherin, and N-cadherin-associated proteins were coimmunoprecipitated by antibodies to either Cx43α 1, N-cadherin, or various N-cadherin-associated proteins. These findings suggest that Cx43α 1 and N-cadherin are coassembled in a multiprotein complex containing various N-cadherin-associated proteins. Studies using siRNA knockdown indicated that cell surface expression of Cx43α 1 required N-cadherin, and conversely, N-cadherin cell surface expression required Cx43α 1. Pulse-chase labeling and cell surface biotinylation experiments indicated that in the absence of N-cadherin, Cx43α 1 cell surface trafficking is blocked. Surprisingly, siRNA knockdown of p120, an N-cadherin-associated protein known to modulate cell surface turnover of N-cadherin, reduced N-cadherin cell surface expression without altering Cx43α 1 expression. These observations suggest that in contrast to the coregulated cell surface trafficking of Cx43α 1 and N-cadherin, N-cadherin turnover at the cell surface may be regulated independently of Cx43α 1. Functional studies showed gap junctional communication is reduced and cell motility inhibited with N-cadherin or Cx43α 1 knockdown, consistent with the observed loss of both gap junction and cadherin contacts with either knockdown. Overall, these studies indicate that the intracellular coassembly of connexin and cadherin is required for gap junction and adherens junction formation, a process that likely underlies the intimate association between gap junction and adherens junction formation. C1 NHLBI, Dev Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Lo, CW (reprint author), 50 South Dr,MSC 8019,Rm 4537, Bethesda, MD 20892 USA. EM loc@nhlbi.nih.gov RI Francis, Richard/P-2524-2015 FU NHLBI NIH HHS [Z01-HL005701] NR 48 TC 132 Z9 136 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 MAY 20 PY 2005 VL 280 IS 20 BP 19925 EP 19936 DI 10.1074/jbc.M412921200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 926HH UT WOS:000229113700062 PM 15741167 ER PT J AU Bebenek, K Garcia-Diaz, M Patishall, SR Kunkel, TA AF Bebenek, K Garcia-Diaz, M Patishall, SR Kunkel, TA TI Biochemical properties of Saccharomyces cerevisiae DNA polymerase IV SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASE-EXCISION-REPAIR; POL-MU; BETA; FIDELITY; LAMBDA; RIBONUCLEOTIDES; IDENTIFICATION; TRANSFERASE; HOLOENZYME; EXTRACTS AB Although mammals encode multiple family X DNA polymerases implicated in DNA repair, Saccharomyces cerevisiae has only one, DNA polymerase IV ( pol IV). To better understand the repair functions of pol IV, here we characterize its biochemical properties. Like mammalian pol β and pol λ, but not pol μ, pol IV has intrinsic 5'-2-deoxyribose-5-phosphate lyase activity. Pol IV has low processivity and can fill short gaps in DNA. Unlike the case with pol β and pol λ, the gap-filling activity of pol IV is not enhanced by a 5'-phosphate on the downstream primer but is stimulated by a 5'-terminal synthetic abasic site. Pol IV incorporates rNTPs into DNA with an unusually high efficiency relative to dNTPs, a property in common with pol β but not pol μ or pol λ. Finally, pol IV is highly inaccurate, with an unusual error specificity indicating the ability to extend primer termini with limited homology. These properties are consistent with a possible role for pol IV in base excision repair and with its known role in non-homologous end joining of double strand breaks, perhaps including those with damaged ends. C1 NIEHS, Genet Mol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Genet Mol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov NR 38 TC 41 Z9 42 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 20 PY 2005 VL 280 IS 20 BP 20051 EP 20058 DI 10.1074/jbs.M501981200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 926HH UT WOS:000229113700075 PM 15778218 ER PT J AU Yi-Brunozzi, HY Le Grice, SFJ AF Yi-Brunozzi, HY Le Grice, SFJ TI Investigating HIV-1 polypurine tract geometry via targeted insertion of abasic lesions in the (-)-DNA template and (+)-RNA primer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 REVERSE-TRANSCRIPTASE; COLI RIBONUCLEASE HI; SEQUENCE FEATURES IMPORTANT; MURINE LEUKEMIA-VIRUS; RNASE-H; DNA-TEMPLATE; RECOGNITION; SUBSTRATE; COMPLEX AB A variety of biochemical and structural studies indicate that two regions of the human immunodeficiency virus type 1 (HIV-1) polypurine tract ( PPT)-containing RNA/DNA hybrid deviate from standard Watson-Crick geometry. However, it is unclear whether and how these regions cooperate to ensure PPT primer selection by reverse transcriptase-associated ribonuclease H and subsequent removal from nascent (+)-DNA. To address these issues, we synthesized oligonucleotides containing abasic lesions in either the PPT (+)-RNA primer or (-)-DNA template to locally remove nucleobases, although retaining the sugar-phosphate backbone. KMnO4 footprinting indicates such lesions locally alter duplex structure, whereas thermal melting studies show significantly reduced stability when lesions are positioned around the scissile bond. Substituting the (-)DNA template between positions -15 and -13 altered cleavage specificity, whereas equivalent substitutions of the (+)- RNA had almost no effect. The unpaired base of the DNA template observed crystallographically (-11C) could also be removed without significant loss of cleavage specificity. With respect to the scissile -1/+1 phosphodiester bond, template nucleobases could be removed without loss of cleavage specificity, whereas equivalent lesions in the RNA primer were inhibitory. Our data suggest an interaction between the p66 thumb subdomain of HIV-1 reverse transcriptase, and the DNA template in the "unzipped" portion of the RNA/DNA hybrid could aid in positioning the ribonuclease H catalytic center at the PPT/U3 junction and also provides insights into nucleic acid geometry around the scissile bond required for hydrolysis. C1 NCI, Reverse Transcriptase Biochem Sect, Resistance Mech Lab, HIV Drug Resistance Program,NIH, Frederick, MD 21702 USA. RP Le Grice, SFJ (reprint author), NCI, Reverse Transcriptase Biochem Sect, Resistance Mech Lab, HIV Drug Resistance Program,NIH, Frederick, MD 21702 USA. EM slegrice@nciferf.gov NR 36 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 20 PY 2005 VL 280 IS 20 BP 20154 EP 20162 DI 10.1074/jbc.M411228200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 926HH UT WOS:000229113700088 PM 15778225 ER PT J AU Berg, SL Blaney, SM Devidas, M Lampkin, TA Murgo, A Bernstein, M Billett, A Kurtzberg, J Reaman, G Gaynon, P Whitlock, J Krailo, M Harris, MB AF Berg, SL Blaney, SM Devidas, M Lampkin, TA Murgo, A Bernstein, M Billett, A Kurtzberg, J Reaman, G Gaynon, P Whitlock, J Krailo, M Harris, MB TI Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-Cell malignancies: A report from the children's oncology group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NUCLEOSIDE-PHOSPHORYLASE-DEFICIENCY; ACUTE LYMPHOBLASTIC-LEUKEMIA; MITOCHONDRIAL DEOXYGUANOSINE KINASE; BONE-MARROW RELAPSE; DEOXYCYTIDINE KINASE; ARABINOSYL-GUANINE; CYTO-TOXICITY; 9-BETA-D-ARABINOFURANOSYLGUANINE; CHILDHOOD; IMMUNODEFICIENCY AB Purpose Nelarabine (compound 506U78), a water soluble prodrug of 9-b-d-arabinofuranosylguanine, is converted to ara-GTP in T lymphoblasts. We sought to define the response rate of nelarabine in children and young adults with refractory or recurrent T-cell disease. Patients and Methods We performed a phase II study with patients stratified as follows: stratum 2 >= 25 % bone marrow blasts in first relapse; stratum 2 >= 25 % bone marrow blasts in ! second relapse; stratum 3: positive CSF; stratum 4: extramedullary (non-CNS) relapse. The initial nelarabine dose was 1.2 g/m(2) daily for 5 consecutive days every 3 weeks. There were two dose de-escalations due to neurotoxicity on this or other studies. The final dose was 650 mg/m(2)/d for strata 1 and two patients and 400 mg/m(2)/d for strata 3 and four patients. Results We enrolled 121 patients (106 assessable for response) at the final dose levels. Complete plus partial response rates at the final dose levels were: 55 % in stratum 1; 27 % in stratum 2; 33 % in stratum 3; and 14 % in stratum 4. There were 31 episodes of >= grade 3 neurologic adverse events in 27 patients (18 % of patients). Conclusion Nelarabine is active as a single agent in recurrent T-cell leukemia, with a response rate more than 50 % in first bone marrow relapse. The most significant adverse events associated with nelarabine administration are neurologic. Further studies are planned to determine whether the addition of nelarabine to front-line therapy for T-cell leukemia in children will improve survival. C1 Texas Childrens Canc Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Childrens Oncol Grp, Arcadia, CA USA. Childrens Oncol Grp, Bethesda, MD USA. Childrens Oncol Grp, Gainesville, FL USA. Duke Univ, Med Ctr, Durham, NC USA. GlaxoSmithKline, Collegeville, PA USA. Hosp St Justine, Montreal, PQ, Canada. Natl Canc Inst, Bethesda, MD USA. Tomorrows Childrens Inst, Hackensack, NJ USA. Vanderbilt Childrens Hosp, Nashville, TN USA. RP Berg, SL (reprint author), Texas Childrens Canc Ctr, 6621 Fannin St,MC3-3320, Houston, TX 77030 USA. EM sberg@txccc.org NR 24 TC 128 Z9 131 U1 0 U2 3 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 MAY 20 PY 2005 VL 23 IS 15 BP 3376 EP 3382 DI 10.1200/JCO.2005.03.426 PG 7 WC Oncology SC Oncology GA 929NI UT WOS:000229352400014 PM 15908649 ER PT J AU Marcucci, G Stock, W Dai, GW Klisovic, RB Liu, SJ Klisovic, MI Blum, W Kefauver, C Sher, DA Green, M Moran, M Maharry, K Novick, S Bloomfield, CD Zwiebel, JA Larson, RA Grever, MR Chan, KK Byrd, JC AF Marcucci, G Stock, W Dai, GW Klisovic, RB Liu, SJ Klisovic, MI Blum, W Kefauver, C Sher, DA Green, M Moran, M Maharry, K Novick, S Bloomfield, CD Zwiebel, JA Larson, RA Grever, MR Chan, KK Byrd, JC TI Phase I study of oblimersen sodium, an antisense to Bcl-2, in untreated older patients with acute myeloid leukemia: Pharmacokinetics, pharmacodynamics, and clinical activity SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID REFRACTORY PROSTATE-CANCER; OLIGONUCLEOTIDE THERAPY; DRUG-RESISTANCE; G3139; APOPTOSIS; AML; PROLIFERATION; CHEMOTHERAPY; EXPRESSION; GENASENSE AB Purposes Pharmacologic downregulation of Bcl-2, an antiapoptotic protein overexpressed in cancer, might increase chemosensitivity in acute myeloid leukemia (AML). Herein, we investigated the feasibility of this approach in untreated elderly AML patients by administering oblimersen sodium (G3139), an 18-mer phosphorothioate antisense to Bcl-2, during induction and consolidation treatments. Patients and Methods Untreated patients with primary or secondary AML (stratified to cohort I or 2, respectively) who were 60 years received induction with G3139, cytarabine, and daunorubicin at one of two different dose levels (45 and 60 mg/m(2)) and, on achievement of complete remission (CR), consolidation with G3139 and high-dose cytarabine. An enzyme-linked immunosorbent assay (ELISA) -based assay was used to measure plasma and intracellular concentrations (IC) of G3139. Bcl-2 mRNA and protein levels were quantified by real-time reverse transcriptase polymerase chain reaction and ELISA, respectively, in bone marrow samples collected before induction treatment and after 72 hours of G3139 infusion, prior to initiation of chemotherapy. Results Of the 29 treated patients, 14 achieved CR. With a median follow-up of 12.6 months, seven patients had relapsed. Side effects of this combination were similar to those expected with chemotherapy alone and were not dose limiting at both dose levels. After 72-hour G3139 infusion, Bcl-2/ABL mRNA copies were decreased compared with baseline (P = .03) in CR patients and increased in nonresponders (NRs; P = .05). Changes in Bcl-2 protein showed a similar trend. Although plasma pharmacokinetics did not correlate with disease response, the median IC of the antisense was higher in the CR patients compared with NRs (17.0 v 4.4 pmol/mg protein, respectively; P = .05). Conclusion G3139 can be administered safely in combination with intensive chemotherapy, and the degree of Bcl-2 downmodulation may correlate with response to therapy. (c) 2005 by American Society of Clinical Oncology. C1 Ohio State Univ, Ctr Comprehens Canc, Div Hematol Oncol, Columbus, OH 43210 USA. Ohio State Univ, Coll Pharm, Ctr Comprehens Canc, Dept Med,Div Hematol Oncol, Columbus, OH 43210 USA. Ohio State Univ, Coll Pharm, Ctr Comprehens Canc, Div Pharmaceut, Columbus, OH 43210 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. Natl Canc Inst, Bethesda, MD USA. Genta Inc, Berkeley Hts, NJ USA. RP Marcucci, G (reprint author), Ohio State Univ, Ctr Comprehens Canc, Div Hematol Oncol, 433A Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM marcucci-1@medctr.osu.edu RI Klisovic, Rebecca/E-3401-2011; Blum, William/E-2769-2011; OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [K08-CA90469, P30-CA16058, R01-CA102031, R21-CA 094552, U01-CA76576] NR 36 TC 87 Z9 97 U1 0 U2 6 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 MAY 20 PY 2005 VL 23 IS 15 BP 3404 EP 3411 DI 10.1200/JCO.2005.09.118 PG 8 WC Oncology SC Oncology GA 929NI UT WOS:000229352400018 PM 15824414 ER PT J AU Calzone, KA Prindiville, SA Jourkiv, O Jenkins, J DeCarvalho, M Wallerstedt, DB Liewehr, DJ Steinberg, SM Soballe, PW Lipkowitz, S Klein, P Kirsch, IR AF Calzone, KA Prindiville, SA Jourkiv, O Jenkins, J DeCarvalho, M Wallerstedt, DB Liewehr, DJ Steinberg, SM Soballe, PW Lipkowitz, S Klein, P Kirsch, IR TI Randomized comparison of group versus individual genetic education and counseling for familial breast and/or ovarian cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COMPUTER-PROGRAM; CONTROLLED-TRIAL; EVENT SCALE; BRCA1; RISK; WOMEN; SUSCEPTIBILITY; PREDISPOSITION; KNOWLEDGE; ATTITUDES AB Purpose An efficient approach to education and counseling before BRCA1 and BRCA2 mutation testing is necessary for effective utilization of testing in the community. Education and counseling, when delivered individually, are limited by a shortage of trained health care providers as well as by financial and time constraints. The purpose of this study was to determine whether pretest education and counseling for breast cancer genetics in a group setting is equivalent to that provided on an individual basis. Patients and Methods One hundred forty-two patients at high risk for harboring a BRCA mutation were randomly assigned to group or individual education and counseling sessions. Group education was followed by brief individual counseling. Knowledge and Impact of Events Scales (IES) were administered at baseline and after education and counseling and at 1 week and 3, 6, and 12 months. Satisfaction with education and counseling was measured at completion of the session. Preferred method of education and counseling was solicited at 3 months. Results There was no difference in knowledge or IES scores between groups. When stratified by genetic test results, knowledge scores showed no difference. Regardless of group, post-test IES scores in patients with positive results were higher than patients with negative or uninformative results but returned to baseline by 12 months. Participants were equally satisfied with either method they were assigned. Significantly more time was spent per patient in individual sessions (1.25 hours) than in group education (0.74 hours). Conclusion Our data suggest that group education and counseling may confer similar benefits compared with traditional individual sessions. Additional investigation of this approach in larger numbers of patients is warranted. C1 Natl Canc Inst, Ctr Canc Res, Genet Branch, Gaithersburg, MD 20899 USA. Canc Res Ctr, Biostat & Data Management Sect, Bethesda, MD USA. Ctr Canc Res, Cellular & Mol Biol Lab, Bethesda, MD USA. Natl Canc Inst, Natl Inst Hlth, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD 20814 USA. Genentech Inc, San Francisco, CA 94080 USA. RP Calzone, KA (reprint author), Natl Canc Inst, Ctr Canc Res, Genet Branch, 8901 Wisconsin Ave,Bldg 8,Rm 5101, Gaithersburg, MD 20899 USA. EM calzonek@mail.nih.gov NR 37 TC 40 Z9 40 U1 4 U2 6 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 MAY 20 PY 2005 VL 23 IS 15 BP 3455 EP 3464 DI 10.1200/JCO.2005.04.050 PG 10 WC Oncology SC Oncology GA 929NI UT WOS:000229352400024 PM 15908654 ER PT J AU Pingpank, JF Libutti, SK Chang, R Wood, BJ Neeman, Z Kam, AW Figg, WD Zhai, SP Beresneva, T Seidel, GD Alexander, HR AF Pingpank, JF Libutti, SK Chang, R Wood, BJ Neeman, Z Kam, AW Figg, WD Zhai, SP Beresneva, T Seidel, GD Alexander, HR TI Phase I study of hepatic arterial melphalan infusion and hepatic venous hemofiltration using percutaneously placed catheters in patients with unresectable hepatic malignancies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID TUMOR-NECROSIS-FACTOR; COLORECTAL-CANCER; UVEAL MELANOMA; OCULAR MELANOMA; LIVER; METASTASES; PERFUSION; CHEMOEMBOLIZATION; CHEMOTHERAPY; HYPERTHERMIA AB Purpose We conducted a phase I study of a 30-minute hepatic artery infusion of melphalan via a percutaneously placed catheter and hepatic venous hemofiltration using a double balloon catheter positioned in the retrohepatic inferior vena Cava to shunt hepatic venous effluent through an activated charcoal filter and then to the systemic circulation. The purpose of the study was to demonstrate feasibility in an initial cohort and subsequently determine the maximum tolerated dose and dose-limiting toxicity of melphalan. Patients and Methods The initial cohort (n = 12) was treated with 2.0 mg/kg of melphalan before dose escalation to 3.5 mg/kg (n = 16). Total hepatic drug delivery, systemic levels, and percent filter efficiency were determined. Patients were assessed for hepatic and systemic toxicity and response. Results A total of 74 treatments were administered to 28 patients. Twelve patients with primary and metastatic hepatic tumors received 30 treatments (mean, 2.5 per patient) at an initial melphalan dose of 2.0 mg/kg. At 3.5 mg/kg, a dose-limiting toxicity (neutropenia and/or thrombocytopenia) was observed in two of six patients. Transient grade 3/4 hepatic and systemic toxicity was seen after 19 % and 66 % of treatments, respectively. An overall radiographic response rate of 30 % was observed in treated patients. In the 10 patients with ocular melanoma, a 50 % overall response rate was observed, including two complete responses. Conclusion Delivery of melphalan via this system is feasible, with limited, manageable toxicity and evidence of substantial antitumor activity; 3 mg/kg is the maximum safe tolerated dose of melphalan administered via this technique. (c) 2005 by American Society of Clinical Oncology C1 NCI, Surg Metab Sect, Surg Branch, NIH,Diagnost Radiol Dept, Bethesda, MD 20892 USA. NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, Dept Diagnost Radiol,NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH,Diagnost Radiol Dept, Bldg 10,Room 2B07, Bethesda, MD 20892 USA. EM Richard_Alexander@nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS [Z99 CL999999] NR 25 TC 46 Z9 46 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2005 VL 23 IS 15 BP 3465 EP 3474 DI 10.1200/JCO.2005.00.927 PG 10 WC Oncology SC Oncology GA 929NI UT WOS:000229352400025 PM 15908655 ER PT J AU Petricoin, EF Bichsel, VE Calvert, VS Espina, V Winters, M Young, L Belluco, C Trock, BJ Lippman, M Fishman, DA Sgroi, DC Munson, PJ Esserman, LJ Liotta, LA AF Petricoin, EF Bichsel, VE Calvert, VS Espina, V Winters, M Young, L Belluco, C Trock, BJ Lippman, M Fishman, DA Sgroi, DC Munson, PJ Esserman, LJ Liotta, LA TI Mapping molecular networks using proteomics: A vision for patient-tailored combination therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; GASTROINTESTINAL STROMAL TUMORS; PROTEIN-INTERACTION NETWORKS; ACUTE LYMPHOBLASTIC-LEUKEMIA; TYROSINE KINASE; BREAST-CANCER; ACTIVATING MUTATIONS; SIGNAL-TRANSDUCTION; MASS-SPECTROMETRY AB Mapping tumor cell protein networks in vivo will be critical for realizing the promise of patient-tailored molecular therapy. Cancer can be defined as a dysregulation or hyperactivity in the network of intracellular and extracellular signaling cascades. These protein signaling circuits are the ultimate targets of molecular therapy. Each patient's tumor may be driven by a distinct series of molecular pathogenic defects. Thus, for any single molecular targeted therapy, only a subset of cancer patients may respond. Individualization of therapy, which tailors a therapeutic regimen to a tumor molecular portrait, may be the solution to this dilemma. Until recently, the field lacked the technology for molecular profiling at the genomic and proteomic level. Emerging proteomic technology, used concomitantly with genomic analysis, promises to meet this need and bring to reality the clinical adoption of molecular stratification. The activation state of kinase-driven signal networks contains important information relative to cancer pathogenesis and therapeutic target selection. Proteomic technology offers a means to quantify the state of kinase pathways, and provides post-translational phosphorylation data not obtainable by gene arrays. Case studies using clinical research specimens are provided to show the feasibility of generating the critical information needed to individualize therapy. Such technology can reveal potential new pathway interconnections, including differences between primary and metastatic lesions. We provide a vision for individualized combinatorial therapy based on proteomic mapping of phosphorylation end points in clinical tissue material. (c) 2005 by American Society of Clinical Oncology. C1 NCI, US FDA, Clin Prote Program, Off Cellular & Gene Therapy,CBER, Bethesda, MD 20892 USA. NCI, US FDA, Clin Prote Program, Pathol Lab,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NIH, Biostat Sect, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Urol, Baltimore, MD USA. Univ Padua, Dept Oncol & Surg Sci, Padua, Italy. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Petricoin, EF (reprint author), George Mason Univ, Ctr Appl Prote & Mol Med, 10900 Univ Blvd,MS 4E3, Manassas, VA 20110 USA. EM epetrico@gmu.edu OI belluco, claudio/0000-0001-5972-9574; Espina, Virginia/0000-0001-5080-5972 NR 59 TC 116 Z9 124 U1 1 U2 4 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 MAY 20 PY 2005 VL 23 IS 15 BP 3614 EP 3621 DI 10.1200/JCO.2005.02.509 PG 8 WC Oncology SC Oncology GA 929NI UT WOS:000229352400043 PM 15908672 ER PT J AU Kanevsky, I Chaminade, F Ficheux, D Moumen, A Gorelick, R Negroni, M Darlix, JL Fosse, P AF Kanevsky, I Chaminade, F Ficheux, D Moumen, A Gorelick, R Negroni, M Darlix, JL Fosse, P TI Specific interactions between HIV-1 nucleocapsid protein and the TAR element SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE nucleocapsid protein; HIV-1; RNA; TAR; cDNA strand transfer ID IMMUNODEFICIENCY-VIRUS TYPE-1; BASE-PAIRING INTERACTION; PRIMER BINDING-SITE; DNA STRAND TRANSFER; STRONG-STOP DNA; REVERSE TRANSCRIPTION; PACKAGING SIGNAL; GENOMIC RNA; VIRAL-DNA; IN-VITRO AB During retroviral reverse transcription, the minus-strand strong-stop DNA (ss-cDNA) is transferred to the 3' end of the genomic RNA and this requires the repeat (R) sequences present at both ends of the genome. In vitro, the human immunodeficiency virus type 1 (HIV-1) R sequence can promote DNA strand transfer when present in ectopic internal positions. Using, HIV-1 model systems, the R sequences and nucleocapsid protein (NC) were found to be key determinants of ss-cDNA transfer. To gain insights into specific interactions between HIV-1 NC and RNA and the influence of NC on R folding, we investigated the secondary structures of R in two natural contexts, namely at the 5' or 3' end of RNAs representing the terminal regions of the genome, and in two ectopic internal positions that also support efficient minus-strand transfer. To investigate the roles of NC zinc fingers and flanking basic domains in the NC/RNA interactions, we used NC mutants. Analyses of the viral RNA/NC complexes by chemical and enzymatic probings, and gel retardation assays were performed under conditions allowing ss-cDNA transfer by reverse transcriptase. We report that NC binds the TAR apical loop specifically in the four genetic contexts without changing the folding of the TAR hairpin and R region significantly; and this requires the NC zinc fingers. In addition, we show that efficient annealing of cTAR DNA to the 3' R relies on sequence complementarities between TAR and cTAR terminal loops. These findings suggest that the TAR apical loop in the acceptor RNA is the initiation site for the annealing reaction that is chaperoned by NC during the minus-strand transfer. © 2005 Elsevier Ltd. All rights reserved. C1 Ecole Normale Super, CNRS, UMR 8113, LBPA Alembert, F-94235 Cachan, France. Inst Biol & Chim Prot, CNRS, UMR 5086, F-69367 Lyon, France. Inst Pasteur, URA 1960, CNRS, F-75270 Paris, France. NCI, SAIC Frederick Inc, AIDS Vaccine Program, Frederick, MD 21702 USA. Ecole Normale Super Lyon, Unite Virol Humaine, INSERM, U 412, F-69364 Lyon, France. RP Fosse, P (reprint author), Ecole Normale Super, CNRS, UMR 8113, LBPA Alembert, F-94235 Cachan, France. EM fosse@lbpa.ens-cachan.fr FU NCI NIH HHS [N01-CO-12400] NR 71 TC 33 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 20 PY 2005 VL 348 IS 5 BP 1059 EP 1077 DI 10.1016/j.jmb.2005.03.046 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 925LK UT WOS:000229054400002 PM 15854644 ER PT J AU Beltz, H Clauss, C Piemont, E Ficheux, D Gorelick, RJ Roques, B Gabus, C Darlix, JL de Rocquigny, H Mely, Y AF Beltz, H Clauss, C Piemont, E Ficheux, D Gorelick, RJ Roques, B Gabus, C Darlix, JL de Rocquigny, H Mely, Y TI Structural determinants of HIV-1 nucleocapsid protein for cTAR DNA binding and destabilization, and correlation with inhibition of self-primed DNA synthesis SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE nucleocapsid protein; fluorescence; nucleic acid chaperone; HIV; TAR ID IMMUNODEFICIENCY-VIRUS TYPE-1; NUCLEIC-ACID-CHAPERONE; TIME-RESOLVED FLUORESCENCE; ZINC-FINGER STRUCTURES; MINUS-STRAND TRANSFER; RNA PACKAGING SIGNAL; STRONG-STOP DNA; REVERSE TRANSCRIPTION; VIRAL-DNA; POSTTRANSLATIONAL MODIFICATIONS AB The nucleocapsid protein (NC) of human immunodeficiency virus type 1 (HIV-1) is formed of two highly conserved CCHC zinc fingers flanked by small basic domains. NC is required for the two obligatory strand transfers in viral DNA synthesis through its nucleic acid chaperoning properties. The first DNA strand transfer relies on NC's ability to bind and destabilize the secondary structure of complementary transactivation response region (cTAR) DNA, to inhibit self-priming, and to promote the annealing of cTAR to TAR RNA. To further investigate NC chaperone properties, our aim was to identify by fluorescence spectroscopy and gel electrophoresis, the NC structural determinants for cTAR binding and destabilization, and for the inhibition of self-primed DNA synthesis on a model system using a series of NC mutants and HIV-1 reverse transcriptase. NC destabilization and self-priming inhibition properties were found to be supported by the two fingers in their proper context and the basic (29)RAPRKKG(35) linker. The strict requirement of the native proximal finger suggests that its hydrophobic platform (Val13, Phe16, Thr24 and Ala25) is crucial for binding, destabilization and inhibition of self-priming. In contrast, only partial folding of the distal finger is required, probably for presenting the Trp37 residue in an appropriate orientation. Also, Trp37 and the hydrophobic residues of the proximal finger appear to be essential for the propagation of the melting from the cTAR ends up to the middle of the stem. Finally, both N-terminal and C-terminal basic domains contribute to cTAR binding but not to its destabilization. © 2005 Elsevier Ltd. All rights reserved. C1 Univ Louis Pasteur Strasbourg 1, Lab Phamacol & Physiochim Interact Cellulaires &, UMR 7034, CNRS,Fac Pharm, F-67401 Illkirch Graffenstaden, France. IBCP, F-69367 Lyon, France. NCI, SAIC Frederick Inc, AIDS Vaccine Program, Frederick, MD 21702 USA. Fac Pharm, INSERM, Dept Pharmacochim Mol & Struct, U 266, F-75270 Paris, France. Ecole Normale Super Lyon, INSERM, Unite Virol Humaine, LabRetro, F-69364 Lyon, France. RP Mely, Y (reprint author), Univ Louis Pasteur Strasbourg 1, Lab Phamacol & Physiochim Interact Cellulaires &, UMR 7034, CNRS,Fac Pharm, 74,Route Rhin, F-67401 Illkirch Graffenstaden, France. EM mely@pharma.u-strasbg.fr FU NCI NIH HHS [N01-CO-12400] NR 71 TC 66 Z9 67 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 20 PY 2005 VL 348 IS 5 BP 1113 EP 1126 DI 10.1016/j.jmb.2005.02.042 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 925LK UT WOS:000229054400006 PM 15854648 ER PT J AU Yan, J Feng, JN Craddock, N Jones, IR Cook, EH Goldman, D Heston, LL Chen, JS Burkhart, P Li, WY Shibayama, A Sommer, SS AF Yan, J Feng, JN Craddock, N Jones, IR Cook, EH Goldman, D Heston, LL Chen, JS Burkhart, P Li, WY Shibayama, A Sommer, SS TI Vitamin D receptor variants in 192 patients with schizophrenia and other psychiatric diseases SO NEUROSCIENCE LETTERS LA English DT Article DE vitamin D receptor; schizophrenia; psychiatric diseases; DOVAM-S; mutation detection ID PREGNANT-WOMEN; DOVAM-S; GENE; DISORDER; ASSOCIATION; ASIANS AB Intriguing parallels have been noted previously between the biology of Vitamin D and the epidemiology of schizophrenia. We have scanned the Vitamin D receptor (VDR) gene by DOVAM-S (Detection of Virtually All Mutations-SSCP), a robotically enhanced multiplexed scanning method. In total, 100 patients with schizophrenia (86 Caucasians and 14 African-Americans) were scanned. In addition, pilot experiments were performed in patients with bipolar disorder (BPD) (24), autism (24), attention deficit hyperactivity disorder (ADHD) (24), and alcoholism (20). A total of 762 kb of the VDR genomic sequence was scanned. R208N and V339I were each found in one African-American patient, while absent in 35 African-American controls without schizophrenia (2/14 versus 0/35, P = 0.08). Within the power of the study (&GE; 1.6-fold relative risk), the common M1T variant is not associated with schizophrenia. In the 92 scanned patients with other psychiatric diseases, R173S was found in a single patient with bipolar disorder. In conclusion, we describe three novel structural variants of the Vitamin D receptor. Further study is required to clarify their role, if any, in psychiatric disease. © 2005 Elsevier Ireland Ltd. All rights reserved. C1 City Hope Natl Med Ctr, Dept Mol Genet & Mol Diag, Duarte, CA 91010 USA. Univ Wales Coll Med, Dept Psychol Med, Cardiff CF4 4XN, S Glam, Wales. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. NIAAA, Dept Psychiat, NIH, Bethesda, MD USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. RP Sommer, SS (reprint author), City Hope Natl Med Ctr, Dept Mol Genet & Mol Diag, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM sommerlab@coh.org RI Jones, Ian/B-4925-2009; turton, miranda/F-4682-2011; Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Cook, Edwin/0000-0002-5848-5114 NR 24 TC 18 Z9 20 U1 4 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 20 PY 2005 VL 380 IS 1-2 BP 37 EP 41 DI 10.1016/j.neulet.2005.01.018 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 924DI UT WOS:000228958600008 PM 15854747 ER PT J AU Fritzsch, B Piatigorsky, J AF Fritzsch, B Piatigorsky, J TI Ancestry of photic and mechanic sensation? SO SCIENCE LA English DT Letter ID PAX GENES; JELLYFISH; EVOLUTION; EYES C1 Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. NEI, LMDB, NIH, Bethesda, MD 20892 USA. RP Fritzsch, B (reprint author), Creighton Univ, Dept Biomed Sci, 2500 Calif Plaza, Omaha, NE 68178 USA. OI Fritzsch, Bernd/0000-0002-4882-8398 NR 17 TC 19 Z9 19 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 MAY 20 PY 2005 VL 308 IS 5725 BP 1113 EP 1114 DI 10.1126/science.308.5725.1113 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 928TA UT WOS:000229293400019 PM 15912599 ER PT J AU Cheng, J Kapranov, P Drenkow, J Dike, S Brubaker, S Patel, S Long, J Stern, D Tammana, H Helt, G Sementchenko, V Piccolboni, A Bekiranov, S Bailey, DK Ganesh, M Ghosh, S Bell, I Gerhard, DS Gingeras, TR AF Cheng, J Kapranov, P Drenkow, J Dike, S Brubaker, S Patel, S Long, J Stern, D Tammana, H Helt, G Sementchenko, V Piccolboni, A Bekiranov, S Bailey, DK Ganesh, M Ghosh, S Bell, I Gerhard, DS Gingeras, TR TI Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution SO SCIENCE LA English DT Article ID TRANS-ACTING SIRNAS; HUMAN GENOME; MESSENGER-RNAS; BINDING SITES; ASCITES-CELLS; CDNA; ARABIDOPSIS; ANNOTATION; HUMAN-CHROMOSOME-21; SEQUENCE AB Sites of transcription of polyadenylated and nonpolyadenylated RNAs for 10 human chromosomes were mapped at 5-base pair resolution in eight cell lines. Unannotated, nonpotyadenylated transcripts comprise the major proportion of the transcriptional output of the human genome. Of all transcribed sequences, 19.4, 43.7, and 36.9% were observed to be polyadenytated, nonpolyadenylated, and bimorphic, respectively. Half of all transcribed sequences are found only in the nucleus and for the most part are unannotated. Overall, the transcribed portions of the human genome are predominantly composed of interlaced networks of both poly A+ and poly A- annotated transcripts and unannotated transcripts of unknown function. This organization has important implications for interpreting genotype-phenotype associations, regulation of gene expression, and the definition of a gene. C1 Affymetrix Inc, Santa Clara, CA 95051 USA. NCI, Off Canc Genom, Bethesda, MD 20892 USA. RP Gingeras, TR (reprint author), Affymetrix Inc, Santa Clara, CA 95051 USA. EM tom_gingeras@affymetrix.com OI Gingeras, Thomas/0000-0001-9106-3573 NR 35 TC 727 Z9 776 U1 7 U2 42 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 MAY 20 PY 2005 VL 308 IS 5725 BP 1149 EP 1154 DI 10.1126/science.1108625 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 928TA UT WOS:000229293400038 PM 15790807 ER PT J AU Pinto, LA Castle, PE Roden, RB Harro, CD Lowy, DR Schiller, JT Wallace, D Williams, M Kopp, W Frazer, IH Berzofsky, JA Hildesheim, A AF Pinto, LA Castle, PE Roden, RB Harro, CD Lowy, DR Schiller, JT Wallace, D Williams, M Kopp, W Frazer, IH Berzofsky, JA Hildesheim, A TI HPV-16 L1 VLP vaccine elicits a broad-spectrum of cytokine responses in whole blood SO VACCINE LA English DT Article DE HPV-16 L1 VLP vaccine; cytokines; whole blood ID VIRUS-LIKE PARTICLES; CELLULAR IMMUNE-RESPONSES; IFN-GAMMA; ADULT VOLUNTEERS; T-CELLS; IMMUNIZATION; ACTIVATION; PROTEIN; MODULATION; INFECTION AB Here, we evaluated innate and adaptive immune system cytokine responses induced by HPV-16 L1 VLP in whole blood (WB) cultures from individuals receiving the vaccine (n = 20) or placebo (n = 4) before and after vaccination. 11 cytokines were measured: IL- 1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, 1L- 10, IL- 12, IFN-gamma, TNF-alpha, and GM-CSF using multiplex bead arrays. Cytokine profiles from WB samples clearly discriminated between vaccine and placebo recipients and between pre and post-vaccination responses. Significant increases in Th1, Th2 and inflammatory cytokines were observed in WB assays following vaccination. Results from WB assays were compared against parallel PBMC-based assays in a subset of patients. Differences between whole blood assay and PBMC were observed, with the highest levels of induction found for WB for several cytokines. Our results indicate that multiplex assays for cytokine profiling in WB are an efficient toot for assessing broad spectrum, innate and adaptive immune responses to vaccines and identifying immunologic correlates of protection in efficacy studies. (c) 2005 Elsevier Ltd. All rights reserved. C1 SAIC Frederick Inc, NCI Frederick, Frederick, MD 21702 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Queensland, Ctr Immunol & Canc Res, St Lucia, Qld 4067, Australia. RP Pinto, LA (reprint author), SAIC Frederick Inc, NCI Frederick, Room 120,Bldg 469, Frederick, MD 21702 USA. EM lpinto@ncifcrf.gov OI Frazer, Ian/0000-0002-8002-4680 FU NCI NIH HHS [CA098252, N01-CO-12400]; NIAID NIH HHS [AI48203] NR 37 TC 44 Z9 47 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 20 PY 2005 VL 23 IS 27 BP 3555 EP 3564 DI 10.1016/j.vaccine.2005.01.146 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 928JV UT WOS:000229268700008 PM 15855014 ER PT J AU Ghosh, AK Swanson, LM Cho, HN Leshchenko, S Hussain, KA Kay, S Walters, DE Koh, Y Mitsuya, H AF Ghosh, AK Swanson, LM Cho, HN Leshchenko, S Hussain, KA Kay, S Walters, DE Koh, Y Mitsuya, H TI Structure-based design: Synthesis and biological evaluation of a series of novel cycloamide-derived HIV-1 protease inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HIGH-AFFINITY P-2-LIGANDS; POTENT; RESOLUTION; ACIDS AB The structure-based design and synthesis of a series of novel nonpeptide HIV protease inhibitors are described. The inhibitors were designed based upon the X-ray crystal structure of inhibitor I (UIC-94017)-bound HIV-1 protease. The inhibitors incorporated 3-hydroxysalicyclic acid-derived acyclic and cyclic P2 ligand into the (R)-(hydroxyethylamino)sulfonamide isostere. The inhibitors contain only two chiral centers and are readily synthesized in optically active form utilizing Sharpless asymmetric epoxidation, regioselective epoxide opening, and ring-closing olefin metathesis using Grubbs' catalyst as the key steps. We have synthesized 13-15-membered cycloamides and evaluated their HIV-1 protease enzyme inhibitory and antiviral activities in MT-2 cells. Interestingly, all cycloamide-derived inhibitors are noticeably more potent than the corresponding acyclic compounds. The ring size and substituent effects were investigated. It turned out that the 14-membered saturated ring is preferred by the S-1-S-2 active sites of HIV-1 protease. Macrocycle 26 showed excellent enzyme inhibitory potency with a K-i value of 0.7 nM and an antiviral IC50 value of 0.3 μ M. In view of their structural simplicity and preliminary interesting results, further optimization of these inhibitors is underway. C1 Univ Illinois, Dept Chem, Chicago, IL 60607 USA. Rosalind Franklin Univ Med & Sci, Dept Biol Chem, N Chicago, IL 60064 USA. Kumamoto Univ, Sch Med, Dept Hematol & Infect Dis, Kumamoto 8608556, Japan. NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Ghosh, AK (reprint author), Univ Illinois, Dept Chem, 845 W Taylor St, Chicago, IL 60607 USA. EM arunghos@uic.edu RI Walters, D. Eric/C-9626-2010 OI Walters, D. Eric/0000-0002-1513-3522 FU NIGMS NIH HHS [GM 53386] NR 26 TC 30 Z9 30 U1 0 U2 9 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 MAY 19 PY 2005 VL 48 IS 10 BP 3576 EP 3585 DI 10.1021/jm050019i PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 926NK UT WOS:000229129700015 PM 15887965 ER PT J AU Choi, MH Lee, IK Kim, GW Kim, BU Han, YH Yu, DY Park, HS Kim, KY Lee, JS Choi, CH Bae, YS Lee, BI Rhee, SG Kang, SW AF Choi, MH Lee, IK Kim, GW Kim, BU Han, YH Yu, DY Park, HS Kim, KY Lee, JS Choi, CH Bae, YS Lee, BI Rhee, SG Kang, SW TI Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II SO NATURE LA English DT Article ID CYSTEINE-SULFINIC ACID; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; MAMMALIAN PEROXIREDOXIN; SITE CYSTEINE; ACTIVATION; MECHANISM; REQUIRES; RECEPTOR AB Platelet-derived growth factor ( PDGF) is a potent mitogenic and migratory factor that regulates the tyrosine phosphorylation of a variety of signalling proteins via intracellular production of H2O2 (refs 1 - 3). Mammalian 2-Cys peroxiredoxin type II ( Prx II; gene symbol Prdx2) is a cellular peroxidase that eliminates endogenous H2O2 produced in response to growth factors such as PDGF and epidermal growth factor(4); however, its involvement in growth factor signalling is largely unknown. Here we show that Prx II is a negative regulator of PDGF signalling. Prx II deficiency results in increased production of H2O2, enhanced activation of PDGF receptor ( PDGFR) and phospholipase Cγ 1, and subsequently increased cell proliferation and migration in response to PDGF. These responses are suppressed by expression of wild-type Prx II, but not an inactive mutant. Notably, Prx II is recruited to PDGFR upon PDGF stimulation, and suppresses protein tyrosine phosphatase inactivation. Prx II also leads to the suppression of PDGFR activation in primary culture and a murine restenosis model, including PDGF-dependent neointimal thickening of vascular smooth muscle cells. These results demonstrate a localized role for endogenous H2O2 in PDGF signalling, and indicate a biological function of Prx II in cardiovascular disease. C1 Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea. Yonsei Univ, Coll Med, Dept Neurol, Seoul 120752, South Korea. Korea Res Inst Biosci & Biotechnol, Lab Human Genom, Taejon 305333, South Korea. Labfrontier Co Ltd, Inst Life Sci, Suwon 442766, Kyunggi Do, South Korea. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Korea Adv Inst Sci & Technol, Dept Biosyst, Taejon 305701, South Korea. RP Rhee, SG (reprint author), Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. EM sgrhee@nih.gov RI Choi, Chulhee/C-1642-2011 OI Choi, Chulhee/0000-0001-5542-9136 NR 23 TC 235 Z9 245 U1 1 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 19 PY 2005 VL 435 IS 7040 BP 347 EP 353 DI 10.1038/nature03587 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 927HM UT WOS:000229185000046 PM 15902258 ER PT J AU Youngren, KK Coveney, D Peng, XN Bhattacharya, C Schmidt, LS Nickerson, ML Lamb, BT Deng, JM Behringer, RR Capel, B Rubin, EM Nadeau, JH Matin, A AF Youngren, KK Coveney, D Peng, XN Bhattacharya, C Schmidt, LS Nickerson, ML Lamb, BT Deng, JM Behringer, RR Capel, B Rubin, EM Nadeau, JH Matin, A TI The Ter mutation in the dead end gene causes germ cell loss and testicular germ cell tumours SO NATURE LA English DT Article ID RNA-BINDING PROTEIN; MESSENGER-RNA; STEM-CELLS; MOUSE CHROMOSOME-18; MICE; TERATOMAS; DEFICIENCY; CYCLOOXYGENASE-2; TRANSCRIPTION; EXPRESSION AB In mice, the Ter mutation causes primordial germ cell (PGC) loss in all genetic backgrounds(1). Ter is also a potent modifier of spontaneous testicular germ cell tumour (TGCT) susceptibility in the 129 family of inbred strains, and markedly increases TGCT incidence in 129-Ter/Termales(2-4). In 129-Ter/Ter mice, some of the remaining PGCs transform into undifferentiated pluripotent embryonal carcinoma cells(2-6), and after birth differentiate into various cells and tissues that compose TGCTs. Here, we report the positional cloning of Ter, revealing a point mutation that introduces a termination codon in the mouse orthologue (Dnd1) of the zebrafish dead end (dnd) gene. PGC deficiency is corrected both with bacterial artificial chromosomes that contain Dnd1 and with a Dnd1-encoding transgene. Dnd1 is expressed in fetal gonads during the critical period when TGCTs originate. DND1 has an RNA recognition motif and is most similar to the apobec complementation factor, a component of the cytidine to uridine RNA-editing complex. These results suggest that Ter may adversely affect essential aspects of RNA biology during PGC development. DND1 is the first protein known to have an RNA recognition motif directly implicated as a heritable cause of spontaneous tumorigenesis. TGCT development in the 129-Ter mouse strain models paediatric TGCT in humans. This work will have important implications for our understanding of the genetic control of TGCT pathogenesis and PGC biology. C1 Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. Duke Univ, Dept Cell Biol, Durham, NC 27710 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. NCI, Immunobiol Lab, Frederick, MD 21702 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Genome Sci Dept, Berkeley, CA 94720 USA. RP Nadeau, JH (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. EM jhn4@case.edu; amatin@mdanderson.org FU NCI NIH HHS [P30 CA016672, R01 CA075056, R01 CA093754]; NHLBI NIH HHS [R01 HL063054] NR 30 TC 199 Z9 212 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 19 PY 2005 VL 435 IS 7040 BP 360 EP 364 DI 10.1038/nature03595 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 927HM UT WOS:000229185000048 PM 15902260 ER PT J AU Xu, JH Wu, LG AF Xu, JH Wu, LG TI The decrease in the presynaptic calcium current is a major cause of short-term depression at a calyx-type synapse SO NEURON LA English DT Article ID PAIRED-PULSE DEPRESSION; READILY RELEASABLE POOL; SQUID GIANT SYNAPSE; AUDITORY BRAIN-STEM; TRANSMITTER RELEASE; CLIMBING FIBER; VESICLE POOLS; NEUROTRANSMITTER RELEASE; POSTSYNAPTIC MECHANISMS; HIPPOCAMPAL SYNAPSES AB Repetitive nerve firings cause short-term depression (STD) of release at many synapses. Its underlying mechanism is largely attributed to depletion of a readily releasable vesicle pool (RRP) and a decreased probability of releasing a readily releasable vesicle during an action potential. Which of these two mechanisms is dominant and the mechanism that decreases the release probability remain debated. Here, we report that a decreased release probability is caused by a calcium-induced inhibition of presynaptic calcium channels, particularly P/Q-type channels at the calyx of Held in rat brainstem. This mechanism was the dominant cause of STD in a wide range of stimulation conditions, such as during 2 to 20 action potential-equivalent stimuli (AP-e) at 0.2-30 Hz and after 2 to 20 AP-e at 0.2-100 Hz. Only during 100 Hz AP-e was depletion the dominant mechanism. C1 NINDS, Bethesda, MD 20892 USA. RP Wu, LG (reprint author), NINDS, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov OI Xu, Jianhua/0000-0003-0084-8856 FU Intramural NIH HHS NR 60 TC 143 Z9 144 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY 19 PY 2005 VL 46 IS 4 BP 633 EP 645 DI 10.1016/j.neuron.2005.03.024 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 928TJ UT WOS:000229294300014 PM 15944131 ER PT J AU Schoenfeld, P Cash, B Flood, A Dobhan, R Eastone, J Coyle, W Kikendall, JW Kim, HM Weiss, DG Emory, T Schatzkin, A Lieberman, D AF Schoenfeld, P Cash, B Flood, A Dobhan, R Eastone, J Coyle, W Kikendall, JW Kim, HM Weiss, DG Emory, T Schatzkin, A Lieberman, D CA CONCeRN Study Investigators TI Colonoscopic screening of average-risk women for colorectal neoplasia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FLEXIBLE SIGMOIDOSCOPY; ADENOMATOUS POLYPS; COST-EFFECTIVENESS; CANCER; DESIGN; SIZE AB BACKGROUND: Veterans Affairs (VA) Cooperative Study 380 showed that some advanced colorectal neoplasias (i.e., adenomas at least 1 cm in diameter, villous adenomas, adenomas with high-grade dysplasia, or cancer) in men would be missed with the use of flexible sigmoidoscopy but detected by colonoscopy. In a tandem study, we examined the yield of screening colonoscopy in women. METHODS: To determine the prevalence and location of advanced neoplasia, we offered colonoscopy to consecutive asymptomatic women referred for colon-cancer screening. The diagnostic yield of flexible sigmoidoscopy was calculated by estimating the proportion of patients with advanced neoplasia whose lesions would have been identified if they had undergone flexible sigmoidoscopy alone. Lesions were considered detectable by flexible sigmoidoscopy if they were in the distal colon or if they were in the proximal colon in patients who had concurrent small adenomas in the distal colon, a finding that would have led to colonoscopy. The results were compared with the results from VA Cooperative Study 380 for age-matched men and women with negative fecal occult-blood tests and no family history of colon cancer. RESULTS: Colonoscopy was complete in 1463 women, 230 of whom (15.7 percent) had a family history of colon cancer. Colonoscopy revealed advanced neoplasia in 72 women (4.9 percent). If flexible sigmoidoscopy alone had been performed, advanced neoplasia would have been detected in 1.7 percent of these women (25 of 1463) and missed in 3.2 percent (47 of 1463). Only 35.2 percent of women with advanced neoplasia would have had their lesions identified if they had undergone flexible sigmoidoscopy alone, as compared with 66.3 percent of matched men from VA Cooperative Study 380 (P<0.001). CONCLUSIONS: Colonoscopy may be the preferred method of screening for colorectal cancer in women. C1 VAMC, Vet Affairs Ctr Excellence Hlth Serv Res, Ann Arbor, MI 48105 USA. Univ Michigan, Sch Med, Div Gastroenterol, Ann Arbor, MI USA. Uniformed Serv Univ Hlth Sci, Div Gastroenterol, Bethesda, MD 20814 USA. Natl Naval Med Ctr, Div Gastroenterol, Bethesda, MD 20889 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Natl Naval Med Ctr, Div Gastroenterol, San Diego, CA USA. Natl Naval Med Ctr, Div Gastroenterol, Portsmouth, VA USA. Walter Reed Army Med Ctr, Div Gastroenterol, Washington, DC 20307 USA. Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Vet Affairs Med Ctr, Dept Biostat, Perry Point, MD USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97201 USA. Vet Affairs Med Ctr, Portland, OR USA. RP Schoenfeld, P (reprint author), VAMC, Vet Affairs Ctr Excellence Hlth Serv Res, 111-D,2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM pschoenf@umich.edu FU NIDDK NIH HHS [K23-DK-60040] NR 25 TC 309 Z9 321 U1 0 U2 1 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 MAY 19 PY 2005 VL 352 IS 20 BP 2061 EP 2068 DI 10.1056/NEJMoa042990 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 927GJ UT WOS:000229180100004 PM 15901859 ER PT J AU Janz, S AF Janz, S TI Uncovering MYC's full oncogenic potential in the hematopoietic system SO ONCOGENE LA English DT Editorial Material DE transgenic mice; hematopoietic stem and early progenitor cells; T-cell lymphomas; Vav promoter ID TRANSGENIC MICE; COMPARTMENT; VAV AB MYC is an important oncogene in hematopoietic neoplasms in humans, yet the mechanism by which MYC induces the malignant transformation of blood cells has remained elusive. Postulating that mouse models of deregulated MYC expression may be helpful for advancing our understanding of MYC-induced hematopoietic malignancies, Suzanne Cory and her associates took advantage of the Vav promoter to express MYC throughout the hematopoietic system in transgenic mice. In this issue of Oncogene, they report ( Smith et al.) that the newly developed strain, referred to as VavP-MYC17, is prone to mature T-cell lymphomas ( for which few good mouse models exist). They further show that VavP-MYC17 mice that are devoid of mature T cells ( and B cells) because of genetic deficiency in Rag1 recombinase develop neoplasms of three distinct blood cell lineages: pre-T cells, pro-B cells, and macrophages. These findings establish that VavP-driven MYC has broad oncogenic potential in the hematopoietic compartment and prompts new views of the cellular assaults of deregulated MYC on hematopoietic stem and early progenitor cells. C1 NCI, Ctr Canc Res, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Janz, S (reprint author), NCI, Ctr Canc Res, Genet Lab, NIH, Bldg 37,Room 3140A, Bethesda, MD 20892 USA. EM sj4s@nih.gov NR 5 TC 7 Z9 7 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 19 PY 2005 VL 24 IS 22 BP 3541 EP 3543 DI 10.1038/sj.onc.1208473 PG 3 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 927SW UT WOS:000229221800001 PM 15782131 ER PT J AU Jones, LP Li, ML Halama, ED Ma, YX Lubet, R Grubbs, CJ Deng, CX Rosen, EM Furth, PA AF Jones, LP Li, ML Halama, ED Ma, YX Lubet, R Grubbs, CJ Deng, CX Rosen, EM Furth, PA TI Promotion of mammary cancer development by tamoxifen in a mouse model of Brca1-mutation-related breast cancer SO ONCOGENE LA English DT Article DE Brca1; tamoxifen; mammary gland; transgenic mice ID ESTROGEN-RECEPTOR MODULATORS; BRCA2 MUTATION CARRIERS; TRANSGENIC MICE; TUMOR; WOMEN; GLAND; PREVENTION; INHIBITION; ALPHA; RISK AB Loss of full-length Brca1 in mammary epithelial cells of the mouse mammary tumor virus (MMTV)-Cre Brca1 conditional exon 11 deletion mouse model results in the development of mammary adenocarcinomas with similar genetic changes to those found in human BRCA1-mutation-related breast cancers. We used this experimental model to evaluate the chemopreventive effect of tamoxifen on the development of mammary preneoplasia and adenocarcinoma. No protective effects of tamoxifen administration on mammary cancer development were found. Instead, tamoxifen treatment significantly increased rates of mammary epithelial cell proliferation and the prevalence of mammary hyperplasia at 6 months of age. Tamoxifen-exposed mice developed adenocarcinomas at younger ages than control mice and a higher percentage of mice developed adenocarcinomas by 12 months of age. Both whole mouse and tissue culture cell models were used to test if loss of full-length Brca1 was associated with a relative increase in the agonist activity of tamoxifen. Tamoxifen induced increased ductal growth in MMTV-Cre Brca1 conditional mice compared to wild type. Estrogen receptor alpha (ER alpha) expression was downregulated in the tamoxifen-induced hyperplasias. Reducing BRCA1 levels in MCF-7 cells using siRNA resulted in a relative increase in the agonist activity of tamoxifen. Results suggest a model of mammary cancer progression in which loss of full-length Brca1 altered the agonist/antagonist activity of tamoxifen, resulting in tamoxifen-induced mammary epithelial cell proliferation with subsequent loss of ERalpha expression and development of ER alpha-negative hyperplasias and adenocarcinomas. C1 Georgetown Univ, Lombardi Canc Ctr, Dept Oncol, Washington, DC 20057 USA. NCI, Div Chemoprevent, Bethesda, MD 20892 USA. Univ Alabama, Chemoprevent Ctr, Birmingham, AL USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Furth, PA (reprint author), Georgetown Univ, Lombardi Canc Ctr, Dept Oncol, Res Bldg Room E520A,3970 Reservoir Rd, Washington, DC 20057 USA. EM paf3@georgetown.edu RI deng, chuxia/N-6713-2016 FU NCI NIH HHS [2T32CA09-686-08, N01-CN-05024] NR 55 TC 40 Z9 44 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 19 PY 2005 VL 24 IS 22 BP 3554 EP 3562 DI 10.1038/sj.onc.1208426 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 927SW UT WOS:000229221800003 PM 15750629 ER PT J AU Lal, A Kawai, T Yang, XL Mazan-Mamczarz, K Gorospe, M AF Lal, A Kawai, T Yang, XL Mazan-Mamczarz, K Gorospe, M TI Antiapoptotic function of RNA-binding protein HuR effected through prothymosin alpha SO EMBO JOURNAL LA English DT Article DE ELAV; post-transcriptional gene expression; ProT alpha; stress response; translational regulation ID COMPARATIVE GENOMIC HYBRIDIZATION; FACTOR MESSENGER-RNA; RICH ELEMENT; POSTTRANSCRIPTIONAL REGULATION; CYCLOOXYGENASE-2 EXPRESSION; STABILITY FACTOR; GENE-EXPRESSION; HL-60 CELLS; CANCER; TRANSLATION AB We report the antiapoptotic effect of RNA-binding protein HuR, a critical regulator of the post-transcriptional fate of target transcripts. Among the most prominent mRNAs complexing with HuR is that encoding prothymosin a (ProT alpha), an inhibitor of the apoptosome. In HeLa cells, treatment with the apoptotic stimulus ultraviolet light (UVC) triggered the mobilization of ProT alpha mRNA to the cytoplasm and onto heavier polysomes, where its association with HuR increased dramatically. Analysis of a chimeric ProT alpha mRNA directly implicated HuR in regulating ProT alpha production: ProT alpha translation and cytoplasmic concentration increased in HuR-overexpressing cells and declined in cells in which HuR levels were lowered by RNA interference. Importantly, the antiapoptotic influence engendered by HuR was vitally dependent on ProT alpha expression, since use of oligomers that blocked ProT alpha translation abrogated the protective effect of HuR. Together, our data support a regulatory scheme whereby HuR binds the ProT alpha mRNA, elevates its cytoplasmic abundance and translation, and thereby elicits an antiapoptotic program. C1 NIA, LCMB, IRP, NIH, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, LCMB, IRP, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov FU NIA NIH HHS [Z01 AG000511-08] NR 69 TC 122 Z9 123 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 18 PY 2005 VL 24 IS 10 BP 1852 EP 1862 DI 10.1038/sj.emboj.7600661 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 932XG UT WOS:000229587500009 PM 15861128 ER PT J AU Wu, CJ Conze, DB Li, XM Ying, SX Hanover, JA Ashwell, JD AF Wu, CJ Conze, DB Li, XM Ying, SX Hanover, JA Ashwell, JD TI TNF-alpha induced c-IAP1/TRAF2 complex translocation to a Ubc6-containing compartment and TRAF2 ubiquitination SO EMBO JOURNAL LA English DT Article DE c-IAP1; intracellular translocation; TNFR; TRAF2; ubiquitination ID TUMOR-NECROSIS-FACTOR; ENDOPLASMIC-RETICULUM STRESS; RECEPTOR-ASSOCIATED FACTOR-2; NF-KAPPA-B; MEDIATED PROTEIN-DEGRADATION; GROWTH-FACTOR RECEPTOR; CELL-DEATH; (ER)-ASSOCIATED DEGRADATION; APOPTOSIS PROTEINS; ER AB Signaling through tumor necrosis factor receptor 2 (TNF-R2) results in ubiquitination of TRAF2 by the E3 c-IAP1. In this report, we confirm that TRAF2 translocates to a Triton X-100 (TX)-insoluble compartment upon TNF-R2 engagement. Moreover, TRAF2 ubiquitination occurs in this compartment, from which TRAF2 is degraded in a proteasome-dependant manner. Confocal microscopy demonstrated that the TX-insoluble compartment is perinuclear and co-localizes with endoplasmic reticulum (ER) markers. The ER transmembrane Ubc6 bound to c-IAP1 and served as a cognate E2 for c-IAP1's E3 activity in vitro. Furthermore, Ubc6 co-localized with translocated TRAF2/c-IAP1 in the ER-associated compartment in vivo, and a catalytically inactive Ubc6 mutant inhibited TNF-alpha-induced, TNF-R2-dependent TRAF2 degradation. These results indicate that upon TNF-R2 signaling, translocation of TRAF2 and c-IAP1 to an ER-associated, Ubc6-containing perinuclear compartment is required for the ubiquitination of TRAF2 by c-IAP1. Therefore, the ER plays a key role in the TNF-R-mediated signal transduction cascade by acting as a site of assembly for E2/E3/substrate complexes. C1 NIDDKD, Lab Immune Cell Biol, NCI, NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NIDDKD, Lab Immune Cell Biol, NCI, NIH, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov NR 55 TC 62 Z9 66 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 18 PY 2005 VL 24 IS 10 BP 1886 EP 1898 DI 10.1038/sj.emboj.7600649 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 932XG UT WOS:000229587500012 PM 15861135 ER PT J AU Chefer, VI Czyzyk, T Bolan, EA Moron, J Pintar, JE Shippenberg, TS AF Chefer, VI Czyzyk, T Bolan, EA Moron, J Pintar, JE Shippenberg, TS TI Endogenous kappa-opioid receptor systems regulate mesoaccumbal dopamine dynamics and vulnerability to cocaine SO JOURNAL OF NEUROSCIENCE LA English DT Article DE kappa-opioid receptor; nucleus accumbens; dopamine; microdialysis; cocaine; nor-binaltorphimine ID RAT NUCLEUS-ACCUMBENS; EARLY GENE-EXPRESSION; MESSENGER-RNA; BEHAVIORAL SENSITIZATION; EXTRACELLULAR DOPAMINE; MICRODIALYSIS; PRODYNORPHIN; INHIBITION; ADDICTION; ABSTINENCE AB Genetic and pharmacological approaches were used to examine kappa-opioid receptor ( KOR-1) regulation of dopamine ( DA) dynamics in the nucleus accumbens and vulnerability to cocaine. Microdialysis revealed that basal DA release and DA extraction fraction ( E-d), an indirect measure of DA uptake, are enhanced in KOR-1 knock-out mice. Analysis of DA uptake revealed a decreased Km but unchanged V-max in knock-outs. Knock-out mice exhibited an augmented locomotor response to cocaine, which did not differ from that of wild-types administered a behavioral sensitizing cocaine treatment. The ability of cocaine to increase DA was enhanced in knock-outs, whereas c-fos induction was decreased. Although repeated cocaine administration to wild types produced behavioral sensitization, knock-outs exhibited no additional enhancement of behavior. Administration of the long-acting KOR antagonist nor-binaltorphimine to wild-type mice increased DA dynamics. However, the effects varied with the duration of KOR-1 blockade. Basal DA release was increased whereas Ed was unaltered after 1 h blockade. After 24 h, release and Ed were increased. The behavioral and neurochemical effects of cocaine were enhanced at both time points. These data demonstrate the existence of an endogenous KOR-1 system that tonically inhibits mesoaccumbal DA neurotransmission. Its loss induces neuroadaptations characteristic of " cocaine- sensitized" animals, indicating a critical role of KOR-1 in attenuating responsiveness to cocaine. The increased DA uptake after pharmacological inactivation or gene deletion highlights the plasticity of mesoaccumbal DA neurons and suggests that loss of KOR-1 and the resultant disinhibition of DA neurons trigger short- and long-term DA transporter adaptations that maintain normal DA levels, despite enhanced release. C1 NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Ctr Adv Biotechnol & Med, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. RP Chefer, VI (reprint author), NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vchefer@intra.nida.nih.gov RI Moron, Jose/F-3236-2012 FU NIA NIH HHS [T32 AG-19957]; NIAAA NIH HHS [AA-01-002]; NIDA NIH HHS [DA-09040, Z01 DA000398-10]; NIMH NIH HHS [T32 MH-19957, T32 MH019957] NR 37 TC 94 Z9 99 U1 1 U2 4 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 MAY 18 PY 2005 VL 25 IS 20 BP 5029 EP 5037 DI 10.1523/JNEUROSCI.0854-05.2005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 927OQ UT WOS:000229203600015 PM 15901784 ER PT J AU Blasi, G Mattay, VS Bertolino, A Elvevag, B Callicott, JH Das, S Kolachana, BS Egan, MF Goldberg, TE Weinberger, DR AF Blasi, G Mattay, VS Bertolino, A Elvevag, B Callicott, JH Das, S Kolachana, BS Egan, MF Goldberg, TE Weinberger, DR TI Effect of catechol-O-methyltransferase val(158)met genotype on attentional control SO JOURNAL OF NEUROSCIENCE LA English DT Article DE attention; cognitive control; catechol-O-methyltransferase; genetics; dopamine; dorsal cingulate; fMRI; variable attentional control task ID ANTERIOR CINGULATE CORTEX; OBSESSIVE-COMPULSIVE DISORDER; VAL(108/158) MET GENOTYPE; RAT PREFRONTAL CORTEX; EVENT-RELATED FMRI; WORKING-MEMORY; DOPAMINE MODULATION; FUNCTIONAL POLYMORPHISM; GENETIC-VARIATION; VISUAL-ATTENTION AB The cingulate cortex is richly innervated by dopaminergic projections and plays a critical role in attentional control ( AC). Evidence indicates that dopamine enhances the neurophysiological signal-to-noise ratio and that dopaminergic tone in the frontal cortex is critically dependent on catechol-O-methyltransferase ( COMT). A functional polymorphism ( val(158)met) in the COMT gene accounts for some of the individual variability in executive function mediated by the dorsolateral prefrontal cortex. We explored the effect of this genetic polymorphism on cingulate engagement during a novel AC task. We found that the COMT val(158)met polymorphism also affects the function of the cingulate during AC. Individuals homozygous for the high-activity valine ("val") allele show greater activity and poorer performance than val/methionine ("met") heterozygotes, who in turn show greater activity and poorer performance than individuals homozygous for the low-activity met allele, and these effects are most evident at the highest demand for AC. These results indicate that met allele load and presumably enhanced dopaminergic tone improve the "efficiency" of local circuit processing within the cingulate cortex and thereby its function during AC. C1 NIMH, Clin Brain Disorders Branch, NIH, Dept Hlth & Human Serv,Gene Cognit & Psychosis Pr, Bethesda, MD 20892 USA. Univ Bari, Dept Neurol & Psychiat Sci, Neurosci Psychiat Grp, I-70124 Bari, Italy. Ist Ricovero & Cura Carattere Sci Casa Sollievo S, Dept Neuroradiol, I-71013 San Giovanni Rotondo, Italy. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Dept Hlth & Human Serv,Gene Cognit & Psychosis Pr, Bldg 10,Ctr Dr,Room 4S-235, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Callicott, Joseph/C-9102-2009; Bertolino, Alessandro/O-6352-2016 OI Callicott, Joseph/0000-0003-1298-3334; Bertolino, Alessandro/0000-0002-1251-1380 NR 55 TC 211 Z9 215 U1 1 U2 8 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 MAY 18 PY 2005 VL 25 IS 20 BP 5038 EP 5045 DI 10.1523/JNEUROSCI.0476-05.2005 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 927OQ UT WOS:000229203600016 PM 15901785 ER PT J AU Ikemoto, S Qin, M Liu, ZH AF Ikemoto, S Qin, M Liu, ZH TI The functional divide for primary reinforcement of D-mphetamine lies between the medial and lateral ventral striatum: Is the division of the accumbens core, shell, and olfactory tubercle valid? SO JOURNAL OF NEUROSCIENCE LA English DT Article DE reward; intracranial self-administration; psychomotor stimulants; nucleus accumbens; olfactory tubercle; reinforcing ID NUCLEUS-ACCUMBENS; TEGMENTAL AREA; TOPOGRAPHICAL ORGANIZATION; EFFERENT CONNECTIONS; BASAL FOREBRAIN; D-AMPHETAMINE; RAT; PROJECTIONS; REWARD; DOPAMINE AB When projection analyses placed the nucleus accumbens and olfactory tubercle in the striatal system, functional links between these sites began to emerge. The accumbens has been implicated in the rewarding effects of psychomotor stimulants, whereas recent work suggests that the medial accumbens shell and medial olfactory tubercle mediate the rewarding effects of cocaine. Interestingly, anatomical evidence suggests that medial portions of the shell and tubercle receive afferents from common zones in a number of regions. Here, we report results suggesting that the current division of the ventral striatum into the accumbens core and shell and the olfactory tubercle does not reflect the functional organization for amphetamine reward. Rats quickly learned to self-administer D-amphetamine into the medial shell or medial tubercle, whereas they failed to learn to do so into the accumbens core, ventral shell, or lateral tubercle. Our results suggest that primary reinforcement of amphetamine is mediated via the medial portion of the ventral striatum. Thus, the medial shell and medial tubercle are more functionally related than the medial and ventral shell or the medial and lateral tubercle. The current core - shell tubercle scheme should be reconsidered in light of recent anatomical data and these functional findings. C1 NIDA, Behav Neurosci Branch, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Branch, NIH, Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sikemoto@intra.nida.nih.gov OI Ikemoto, Satoshi/0000-0002-0732-7386 FU NIDA NIH HHS [Z01 DA000439-06] NR 39 TC 73 Z9 73 U1 0 U2 6 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 MAY 18 PY 2005 VL 25 IS 20 BP 5061 EP 5065 DI 10.1523/JNEUROSCI.0892-05.2005 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 927OQ UT WOS:000229203600019 PM 15901788 ER PT J AU Qin, M Kang, J Burlin, TV Jiang, CH Smith, CB AF Qin, M Kang, J Burlin, TV Jiang, CH Smith, CB TI Postadolescent changes in regional cerebral protein synthesis: An in vivo study in the Fmr1 null mouse SO JOURNAL OF NEUROSCIENCE LA English DT Article DE fragile X; age; synaptic pruning; synaptic plasticity; FMRP; protein synthesis ID X MENTAL-RETARDATION; METABOTROPIC GLUTAMATE RECEPTORS; TISSUE AMINO-ACIDS; FRAGILE-X; MESSENGER-RNA; KNOCKOUT MICE; IMMOBILIZATION STRESS; PRECURSOR POOL; LATE-PHASE; BRAIN AB Methylation-induced transcriptional silencing of the fragile X mental retardation-1 ( Fmr1) gene leads to absence of the gene product, fragile X mental retardation protein ( FMRP), and consequently fragile X syndrome ( FrX), an X-linked inherited form of mental retardation. Absence of FMRP in Fmr1 null mice imparts some characteristics of the FrX phenotype, but the precise role of FMRP in neuronal function remains unknown. FMRP is an RNA-binding protein that has been shown to suppress translation of certain mRNAs in vitro. We applied the quantitative autoradiographic L-[1-C-14] leucine method to the in vivo determination of regional rates of cerebral protein synthesis ( rCPS) in adult wild-type ( WT) and Fmr1 null mice at 4 and 6 months of age. Our results show a substantial decrease in rCPS in all brain regions examined between the ages of 4 and 6 months in both WT and Fmr1 null mice. Superimposed on the age-dependent decline in rCPS, we demonstrate a regionally selective elevation in rCPS in Fmr1 null mice. Our results suggest that the process of synaptic pruning during young adulthood may be reflected in decreased rCPS. Our findings support the hypothesis that FMRP is a suppressor of translation in brain in vivo. C1 NIMH, Unit Neuroadapt & Prot Metab, Cerebral Metab Lab, US Publ Hlth,Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Smith, CB (reprint author), NIMH, Unit Neuroadapt & Prot Metab, Cerebral Metab Lab, US Publ Hlth,Dept Hlth & Human Serv,NIH, Bldg 36,Room 1A07,36 Convent Dr, Bethesda, MD 20892 USA. EM beebec@intra.nimh.nih.gov NR 53 TC 121 Z9 125 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 18 PY 2005 VL 25 IS 20 BP 5087 EP 5095 DI 10.1523/JNEUROSCI.0093-05.2005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 927OQ UT WOS:000229203600022 PM 15901791 ER PT J AU Narazaki, M Tosato, G AF Narazaki, M Tosato, G TI Targeting coagulation to the tumor microvasculature: Perspectives and therapeutic implications from preclinical studies SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID UNRESECTABLE HEPATOCELLULAR-CARCINOMA; RANDOMIZED CONTROLLED TRIAL; ANGIOGENESIS INHIBITORS; BLOOD-VESSELS; SOLID TUMORS; IN-VIVO; CANCER; CHEMOEMBOLIZATION; NEOVASCULATURE; VASCULATURE C1 NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), Bldg 10,12C205,10 Ctr Dr, Bethesda, MD 20892 USA. EM tosatog@mail.nih.gov OI narazaki, masashi/0000-0002-5613-4409 NR 32 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 18 PY 2005 VL 97 IS 10 BP 705 EP 707 PG 3 WC Oncology SC Oncology GA 936LC UT WOS:000229856500002 PM 15900035 ER PT J AU Freedman, AN Seminara, D Gail, MH Hartge, P Colditz, GA Ballard-Barbash, R Pfeiffer, RM AF Freedman, AN Seminara, D Gail, MH Hartge, P Colditz, GA Ballard-Barbash, R Pfeiffer, RM TI Cancer risk prediction models: A workshop on development, evaluation, and application SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID FAMILIAL BREAST-CANCER; CORONARY-HEART-DISEASE; OVARIAN-CANCER; BRCA2 MUTATIONS; COLORECTAL-CANCER; SUSCEPTIBILITY GENES; SEQUENCE-ANALYSIS; PROSTATE-CANCER; NURSES HEALTH; HISTORY AB Cancer researchers, clinicians, and the public are increasingly interested in statistical models designed to predict the occurrence of cancer. As the number and sophistication of cancer risk prediction models have grown, so too has interest in ensuring that they are appropriately applied, correctly developed, and rigorously evaluated. On May 20-21, 2004, the National Cancer Institute sponsored a workshop in which experts identified strengths and limitations of cancer and genetic susceptibility prediction models that were currently in use and under development and explored methodologic issues related to their development, evaluation, and validation. Participants also identified research priorities and resources in the areas of 1) revising existing breast cancer risk assessment models and developing new models, 2) encouraging the development of new risk models, 3) obtaining data to develop more accurate risk models, 4) supporting validation mechanisms and resources, 5) strengthening model development efforts and encouraging coordination, and 6) promoting effective cancer risk communication and decision-making. C1 NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Freedman, AN (reprint author), NCI, Div Canc Control & Populat Sci, NIH, EPN 4005 MSC 7344,6130 Execut Blvd, Bethesda, MD 20892 USA. EM Andrew_Freedman@nih.gov RI Pfeiffer, Ruth /F-4748-2011; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 53 TC 139 Z9 143 U1 2 U2 20 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 18 PY 2005 VL 97 IS 10 BP 715 EP 723 PG 9 WC Oncology SC Oncology GA 936LC UT WOS:000229856500010 PM 15900041 ER PT J AU Cardis, E Kesminiene, A Ivanov, V Malakhova, I Shibata, Y Khrouch, V Drozdovitch, V Maceika, E Zvonova, I Vlassov, O Bouville, A Goulko, G Hoshi, M Abrosimov, A Anoshko, J Astakhova, L Chekin, S Demidchik, E Galanti, R Ito, M Korobova, E Lushnikov, E Maksioutov, MA Masyakin, V Nerovnia, A Parshin, V Parshkov, E Piliptsevich, N Pinchera, A Polyakov, S Shabeka, N Suonio, E Tenet, V Tsyb, A Yamashita, S Williams, D AF Cardis, E Kesminiene, A Ivanov, V Malakhova, I Shibata, Y Khrouch, V Drozdovitch, V Maceika, E Zvonova, I Vlassov, O Bouville, A Goulko, G Hoshi, M Abrosimov, A Anoshko, J Astakhova, L Chekin, S Demidchik, E Galanti, R Ito, M Korobova, E Lushnikov, E Maksioutov, MA Masyakin, V Nerovnia, A Parshin, V Parshkov, E Piliptsevich, N Pinchera, A Polyakov, S Shabeka, N Suonio, E Tenet, V Tsyb, A Yamashita, S Williams, D TI Risk of thyroid cancer after exposure to (131)I in childhood SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID POWER-STATION ACCIDENT; CHERNOBYL ACCIDENT; IODINE DEFICIENCY; BRYANSK-OBLAST; RADIATION; BYELARUS; CHILDREN; RUSSIA; IRRADIATION; MORTALITY AB Background. After the Chernobyl nuclear power plant accident in April 1986, a large increase in the incidence of childhood thyroid cancer was reported in contaminated areas. Most of the radiation exposure to the thyroid was from iodine isotopes, especially (131)I. We carried out a population-based case-control study of thyroid cancer in Belarus and the Russian Federation to evaluate the risk of thyroid cancer after exposure to radioactive iodine in childhood and to investigate environmental and host factors that may modify this risk. Methods: We studied 276 case patients with thyroid cancer through 1998 and 1300 matched control subjects, all aged younger than 15 years at the time of the accident. Individual doses were estimated for each subject based on their whereabouts and dietary habits at the time of the accident and in following days, weeks, and years; their likely stable iodine status at the time of the accident was also evaluated. Data were analyzed by conditional logistic regression using several different models. All statistical tests were two-sided. Results: A strong dose-response relationship was observed between radiation dose to the thyroid received in childhood and thyroid cancer risk (P <.001). For a dose of 1 Gy, the estimated odds ratio of thyroid cancer varied from 5.5 (95% confidence interval [CI] = 3.1 to 9.5) to 8.4 (95% CI =4.1 to 17.3), depending on the risk model. A linear dose-response relationship was observed up to 1.5-2 Gy. The risk of radiation-related thyroid cancer was three times higher in iodine-deficient areas (relative risk [RR]= 3.2, 95% CI = 1.9 to 5.5) than elsewhere. Administration of potassium iodide as a dietary supplement reduced this risk of radiation-related thyroid cancer by a factor of 3 (RR = 0.34, 95% CI = 0.1 to 0.9, for consumption of potassium iodide versus no consumption). Conclusion: Exposure to 1311 in childhood is associated with an increased risk of thyroid cancer. Both iodine deficiency and iodine supplementation appear to modify this risk. These results have important public health implications: stable iodine supplementation in iodine-deficient populations may substantially reduce the risk of thyroid cancer related to radioactive iodines in case of exposure to radioactive iodines in childhood that may occur after radiation accidents or during medical diagnostic and therapeutic procedures. C1 Int Agcy Res Canc, Lyon, France. Med Radiol Res Ctr RAMS, Obninsk, Russia. Adm & Management Hlth, Belarusian Ctr Med Technol, Comp Syst, Minsk, Byelarus. Nagasaki Univ, Nagasaki 852, Japan. State Res Ctr, Inst Biophys, Moscow, Russia. Inst Phys, Vilnius, Lithuania. Res Inst Radiat Hyg, St Petersburg, Russia. NCI, Bethesda, MD 20892 USA. Univ Wurzburg, Clin & Policlin Nucl Med, Wurzburg, Germany. Hiroshima Univ, Res Inst Radiat Biol & Med, Hiroshima, Japan. Natl Acad Sci Belarus, Inst Geol Sci, Minsk, Byelarus. Ctr Laser Med, Childhood Polyclin 8, Minsk, Byelarus. Belarussian State Med Univ, Minsk, Byelarus. Stockholm Ctr Publ Hlth, Ctr Tobacco Prevent, Stockholm, Sweden. Karolinska Univ Hosp, Clin Epidemiol Unit, Stockholm, Sweden. Natl Nagasaki Med Ctr, Nagasaki, Japan. Russian Acad Sci, Vernadsky Inst Geochem Analyt Chem, Moscow, Russia. Republican Res Ctr Radiat Med & Human Ecol, Gomel, Byelarus. Univ Pisa, Dept Endocrinol & Metab, Pisa, Italy. Turku Univ Hosp, Clin Oncol, FIN-20520 Turku, Finland. Strangeways Res Lab, Cambridge CB1 4RN, England. RP Cardis, E (reprint author), Int Agcy Res Canc, Lyon, France. EM cardis@iarc.fr RI Ivanov, Victor/R-9385-2016; Abrosimov, A/H-3382-2015; Cardis, Elisabeth/C-3904-2017; OI Ivanov, Victor/0000-0003-1372-0018; Abrosimov, A/0000-0001-8284-9996; Maceika, Evaldas/0000-0002-9251-6789; Yamashita, Shunichi/0000-0001-6399-6261; Korobova, Elena/0000-0002-1512-9291 NR 36 TC 271 Z9 285 U1 5 U2 41 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 18 PY 2005 VL 97 IS 10 BP 724 EP 732 PG 9 WC Oncology SC Oncology GA 936LC UT WOS:000229856500011 PM 15900042 ER PT J AU Zhou, CS Arslan, F Wee, S Krishnan, S Ivanov, AR Oliva, A Leatherwood, J Wolf, DA AF Zhou, CS Arslan, F Wee, S Krishnan, S Ivanov, AR Oliva, A Leatherwood, J Wolf, DA TI PCI proteins eIF3e and eIF3m define distinct translation initiation factor 3 complexes SO BMC BIOLOGY LA English DT Article ID COP9 SIGNALOSOME INTERACTS; FISSION YEAST HOMOLOG; UBIQUITIN-LIGASE; SCHIZOSACCHAROMYCES-POMBE; 26S PROTEASOME; COP9/SIGNALOSOME SUBUNITS; RIBONUCLEOTIDE REDUCTASE; SACCHAROMYCES-CEREVISIAE; STRESS-RESPONSE; CORE COMPLEX AB Background: PCI/MPN domain protein complexes comprise the 19S proteasome lid, the COP9 signalosome (CSN), and eukaryotic translation initiation factor 3 (eIF3). The eIF3 complex is thought to be composed of essential core subunits required for global protein synthesis and nonessential subunits that may modulate mRNA specificity. Interactions of unclear significance were reported between eIF3 subunits and PCI proteins contained in the CSN. Results: Here, we report the unexpected finding that fission yeast has two distinct eIF3 complexes sharing common core subunits, but distinguished by the PCI proteins eIF3e and the novel eIF3m, which was previously annotated as a putative CSN subunit. Whereas neither eIF3e nor eIF3m contribute to the non-essential activities of CSN in cullin-RING ubiquitin ligase control, eif3m, unlike eif3e, is an essential gene required for global cellular protein synthesis and polysome formation. Using a ribonomic approach, this phenotypic distinction was correlated with a different set of mRNAs associated with the eIF3e and eIF3m complexes. Whereas the eIF3m complex appears to associate with the bulk of cellular mRNAs, the eIF3e complex associates with a far more restricted set. The microarray findings were independently corroborated for a random set of 14 mRNAs by RT-PCR analysis. Conclusion: We propose that the PCI proteins eIF3e and eIF3m define distinct eIF3 complexes that may assist in the translation of different sets of mRNAs. C1 Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Appl Biosyst Inc, Framingham, MA USA. Harvard Univ, Sch Publ Hlth, NIEHS, Ctr Prote Facil, Boston, MA 02115 USA. SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wolf, DA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM czhou@rics.bwh.harvard.edu; lion_fatih@yahoo.com; swee@hsph.harvard.edu; krishnsc@appliedbiosystems.com; aivanov@hsph.harvard.edu; anoliva@ms.cc.sunysb.edu; Janet.Leatherwood@sunysb.edu; dwolf@hsph.harvard.edu FU NCRR NIH HHS [P40 RR016320, P40 RR16320]; NIEHS NIH HHS [ES-00002, ES07155, P30 ES000002, T32 ES007155]; NIGMS NIH HHS [GM59780, R01 GM059780] NR 65 TC 88 Z9 104 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1741-7007 J9 BMC BIOL JI BMC Biol. PD MAY 17 PY 2005 VL 3 AR 14 DI 10.1186/1741-7007-3-14 PG 16 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 026UN UT WOS:000236368100001 PM 15904532 ER PT J AU Koh, KK Quon, MJ Han, SH Chung, WJ Ahn, JY Seo, YH Choi, IS Shin, EK AF Koh, KK Quon, MJ Han, SH Chung, WJ Ahn, JY Seo, YH Choi, IS Shin, EK TI Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID VASCULAR ENDOTHELIAL-CELLS; INSULIN SENSITIVITY; NITRIC-OXIDE; SIMVASTATIN; GEMFIBROZIL; CHOLESTEROL; PRAVASTATIN; DISEASE; EVENTS; RISK AB OBJECTIVES We compared vascular and metabolic responses (and adverse responses) to statin and fibrate therapies alone or in combination in patients with combined hyperlipidemia. BACKGROUND The mechanisms of action for statins and fibrates are distinct. METHODS Fifty-six patients were given atorvastatin 10 mg and placebo, atorvastatin 10 mg and fenofibrate 200 mg, or fenofibrate 200 mg and placebo daily during each two-month treatment period of a randomized, double-blind, placebo-controlled crossover trial with two washout periods of two months' each. RESULTS Lipoproteins were changed to a greater extent with combined therapy when compared with atorvastatin or fenofibrate alone. Flow-mediated dilator response to hyperemia and plasma high-sensitivity C-reactive protein and fibrinogen levels were changed to a greater extent with combined therapy when compared with atorvastatin or fenofibrate alone (p < 0.001, p = 0.182, and p = 0.015 by analysis of variance [ANOVA], respectively). The effects of combined therapy or fenofibrate alone on plasma adiponectin levels and insulin sensitivity (determined by the Quantitative Insulin-Sensitivity Check Index [QUICKI]) were significantly greater than those of atorvastatin alone (p = 0.022 for adiponectin and p = 0.049 for QUICKI by ANOVA). No patients were withdrawn from the study as the result of serious adverse effects. CONCLUSIONS Combination therapy is safe and has beneficial additive effects on endothelial function in patients with combined hyperlipidemia. © 2005 by the American College of Cardiology Foundation. C1 Gachon Med Sch, Gil Heart Ctr, Dept Cardiol, Vasc Med & Atherosclerosis Unit, Inchon 405760, South Korea. Gachon Med Sch, Dept Lab Med, Inchon 405760, South Korea. Natl Ctr Complementary & Alternat Med, Diabet Unit, NIH, Bethesda, MD USA. RP Koh, KK (reprint author), Gachon Med Sch, Gil Heart Ctr, Dept Cardiol, Vasc Med & Atherosclerosis Unit, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@ghil.com RI Quon, Michael/B-1970-2008; OI Chung, Wook-Jin/0000-0002-9767-7098; Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 16 TC 140 Z9 148 U1 0 U2 10 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 MAY 17 PY 2005 VL 45 IS 10 BP 1649 EP 1653 DI 10.1016/j.jacc.2005.02.052 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 926KB UT WOS:000229121000016 PM 15893182 ER PT J AU Wang, LH Chmelik, R Tang, D Nirenberg, M AF Wang, LH Chmelik, R Tang, D Nirenberg, M TI Identification and analysis of vnd/NK-2 homeodomain binding sites in genomic DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE homeobox; neurobiology; Drosophila ID CONGENITAL HEART-DISEASE; GENE-EXPRESSION; HOMEOBOX GENE; DROSOPHILA EMBRYO; TARGET GENES; 3-DIMENSIONAL STRUCTURE; PATTERN-FORMATION; NK-2 HOMEODOMAIN; NERVOUS-SYSTEM; REGULATORY DNA AB Vnd/NK-2 homeodomain affinity column chromatography was used to purify Drosophila DNA fragments bound by the vnd/NK-2 homeodomain. Sequencing the selected genomic DNA fragments led to the identification of 77 Drosophila DNA fragments that were grouped into 42 vnd/NK-2 homeodomain-binding loci. Most loci were within upstream or intronic regions, especially first introns. Nineteen of the Drosophila DNA fragments cloned correspond to one locus, termed Clone A, which is 312 bp in length and contains five vnd/NK-2 homeodomain core consensus binding sites, 5'-AAGTG, and is part of the first intron of the Beadex gene. We further analyzed the interactions between Clone A and vnd/NK-2 homeodomain protein by mobility-shift assay, DNase I footprinting, methylation interference, and ethylation interference. The DNase I footprinting analysis of Clone A with vnd/NK-2 homeodomain protein revealed three strong binding sites and one weak binding site between 15 and 130 bp of Clone A. We also analyzed binding of the vnd/NK-2 homeodomain to the 5'-flanking sequence of vnd/NK-2 genomic DNA. The DNase I footprinting result showed that there are two strong binding sites and five weak binding sites in the fragment between -385 and -675 bp from the transcription start site of the vnd/NK-2 gene. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Nirenberg, M (reprint author), NHLBI, Lab Biochem Genet, NIH, Bldg 10, Bethesda, MD 20892 USA. EM mnirenberg@nih.gov NR 44 TC 6 Z9 7 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 17 PY 2005 VL 102 IS 20 BP 7097 EP 7102 DI 10.1073/pnas.0502261102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 928SO UT WOS:000229292200010 PM 15870192 ER PT J AU Ihee, H Rajagopal, S Srajer, V Pahl, R Anderson, S Schmidt, M Schotte, F Anfinrud, PA Wulff, M Moffat, K AF Ihee, H Rajagopal, S Srajer, V Pahl, R Anderson, S Schmidt, M Schotte, F Anfinrud, PA Wulff, M Moffat, K TI Visualizing reaction pathways in photoactive yellow protein from nanoseconds to seconds SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE intermediates; mechanism; signal transduction; time-resolved crystallography; singular value decomposition ID P-COUMARIC ACID; ECTOTHIORHODOSPIRA-HALOPHILA; PHOTORECEPTOR PROTEIN; PHOTOCYCLE INTERMEDIATE; PHOTOTROPHIC BACTERIUM; ANGSTROM RESOLUTION; STRUCTURAL-CHANGES; E46Q MUTANT; CHROMOPHORE; KINETICS AB Determining 3D intermediate structures during the biological action of proteins in real time under ambient conditions is essential for understanding how proteins function. Here we use timer-esolved Laue crystallography to extract short-lived intermediate structures and thereby unveil signal transduction in the blue light photoreceptor photoactive yellow protein (PYP) from Halorhodospira halophila. By analyzing a comprehensive set of Laue data during the PYP photocycle (forty-seven time points from one nanosecond to one second), we track all atoms in PYP during its photocycle and directly observe how absorption of a blue light photon by its p-coumaric acid chromophore triggers a reversible photocycle. We identify a complex chemical mechanism characterized by five distinct structural intermediates. Structural changes at the chromophore in the early, red-shifted intermediates are transduced to the exterior of the protein in the late, blue-shifted intermediates through an initial "volume-conserving" isomerization of the chromophore and the progressive disruption of hydrogen bonds between the chromophore and its surrounding binding pocket. These results yield a comprehensive view of the PYP photocycle when seen in the light of previous biophysical studies on the system. C1 Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South Korea. Korea Adv Inst Sci & Technol, Sch Mol Sci, Taejon 305701, South Korea. Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. Univ Chicago, Ctr Adv Radiat Sources, Chicago, IL 60637 USA. Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA. Tech Univ Munich, Phys Dept E17, D-85747 Garching, Germany. NIH, Bethesda, MD 20982 USA. European Synchrotron Radiat Facil, F-38043 Grenoble, France. RP Ihee, H (reprint author), Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South Korea. EM hyotcherl.ihee@kaist.ac.kr RI Ihee, Hyotcherl/C-1614-2011; Rajagopal, Sudarshan/G-8975-2013; Schmidt, Marius/A-1537-2014 OI Rajagopal, Sudarshan/0000-0002-3443-5040; Schmidt, Marius/0000-0002-0962-9468 FU NCRR NIH HHS [RR07707, P41 RR007707]; NIGMS NIH HHS [GM36452, R01 GM036452, R37 GM036452] NR 47 TC 158 Z9 164 U1 2 U2 39 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 MAY 17 PY 2005 VL 102 IS 20 BP 7145 EP 7150 DI 10.1073/pnas.0409035102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 928SO UT WOS:000229292200018 PM 15870207 ER PT J AU Fokine, A Leiman, PG Shneider, MM Ahvazi, B Boeshans, KM Steven, AC Black, LW Mesyanzhinov, VV Rossmann, MG AF Fokine, A Leiman, PG Shneider, MM Ahvazi, B Boeshans, KM Steven, AC Black, LW Mesyanzhinov, VV Rossmann, MG TI Structural and functional similarities between the capsid proteins of bacteriophages T4 and HK97 point to a common ancestry SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE evolution; gene product 24; major capsid protein ID SCAFFOLDING PROTEIN; GENETIC-CONTROL; MOLECULAR ARCHITECTURE; ANGSTROM RESOLUTION; COAT PROTEIN; BINDING; EVOLUTION; DOMAIN; LENGTH; VIRUS AB Gene product (gp) 24 of bacteriophage T4 forms the pentameric vertices of the capsid. Using x-ray crystallography, we found the principal domain of gp24 to have a polypeptide fold similar to that of the HK97 phage capsid protein plus an additional insertion domain. Fitting gp24 monomers into a cryo-EM density map of the mature T4 capsid suggests that the insertion domain interacts with a neighboring subunit, effecting a stabilization analogous to the covalent crosslinking in the HK97 capsid. Sequence alignment and genetic data show that the folds of gp24 and the hexamer-forming capsid protein, gp23*, are similar. Accordingly, models of gp24* pentamers, gp23* hexamers, and the whole capsid were built, based on a cryo-EM image reconstruction of the capsid. Mutations in gene 23 that affect capsid shape map to the capsomer's periphery, whereas mutations that allow gp23 to substitute for gp24 at the vertices modify the interactions between monomers within capsomers. Structural data show that capsid proteins of most tailed phages, and some eukaryotic viruses, may have evolved from a common ancestor. C1 Purdue Univ, Dept Sci Biol, W Lafayette, IN 47907 USA. Shemyakin Ovchinnikov Inst Bioorgan Chem, Lab Mol Bioengn, Moscow 117997, Russia. NIAMSD, Xray Crystallog Facil, Off Sci & Technol, Bethesda, MD 20892 USA. NIAMSD, Lab Struct Biol, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. RP Rossmann, MG (reprint author), Purdue Univ, Dept Sci Biol, 915 W State St, W Lafayette, IN 47907 USA. EM mr@purdue.edu RI Fokin, Andrey/A-1330-2013; Leiman, Petr/E-5120-2010 OI Leiman, Petr/0000-0002-9091-0918 NR 48 TC 130 Z9 131 U1 0 U2 13 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 MAY 17 PY 2005 VL 102 IS 20 BP 7163 EP 7168 DI 10.1073/pnas.0502164102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 928SO UT WOS:000229292200021 PM 15878991 ER PT J AU Hageman, GS Anderson, DH Johnson, LV Hancox, LS Taiber, AJ Hardisty, LI Hageman, JL Stockman, HA Borchardt, JD Gehrs, KM Smith, RJH Silvestri, G Russell, SR Klaver, CCW Barbazetto, I Chang, S Yannuzzi, LA Barile, GR Merriam, JC Smith, RT Olsh, AK Bergeron, J Zernant, J Merriam, JE Gold, B Dean, M Allikmets, R AF Hageman, GS Anderson, DH Johnson, LV Hancox, LS Taiber, AJ Hardisty, LI Hageman, JL Stockman, HA Borchardt, JD Gehrs, KM Smith, RJH Silvestri, G Russell, SR Klaver, CCW Barbazetto, I Chang, S Yannuzzi, LA Barile, GR Merriam, JC Smith, RT Olsh, AK Bergeron, J Zernant, J Merriam, JE Gold, B Dean, M Allikmets, R TI A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; CHOROIDAL NEOVASCULARIZATION; SUSCEPTIBILITY LOCI; APOLIPOPROTEIN-E; DRUSEN FORMATION; LARGE FAMILY; DISEASE; MACULOPATHY; ACTIVATION AB Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly in developed countries. Our previous studies implicated activation of complement in the formation of drusen, the hallmark lesion of AMD. Here, we show that factor H (HF1), the major inhibitor of the alternative complement pathway, accumulates within drusen and is synthesized by the retinal pigmented epithelium. Because previous linkage analyses identified chromosome 1q25-32, which harbors the factor H gene (HF1/CFH), as an AMD susceptibility locus, we analyzed HF1 for genetic variation in two independent cohorts comprised of approximate to 900 AMD cases and 400 matched controls. We found association of eight common HF1 SNPs with AMD; two common missense variants exhibit highly significant associations (162V, chi(2) = 26.1 and P = 3.2 x 10(-7) and Y402H, chi(2) = 54.4 and P = 1.6 x 10(-13)). Haplotype analysis reveals that multiple HF1 variants confer elevated or reduced risk of AMD. One common at-risk haplotype is present at a frequency of 50% in AMD cases and 29% in controls [odds ratio (OR) = 2.46, 95% confidence interval (1.95-3.11)]. Homozygotes for this haplotype account for 24% of cases and 8% of controls [OR = 3.51, 95% confidence interval (2.13-5.78)]. Several protective haplotypes are also identified (OR = 0.44-0.55), further implicating HF1 function in the pathogenetic mechanisms underlying AMD. We propose that genetic variation in a regulator of the alternative complement pathway, when combined with a triggering event, such as infection, underlie a major proportion of AMD in the human population. C1 Univ Iowa, Dept Ophthalmol & Visual Sci, Cell Biol & Funct Genom Lab, Iowa City, IA 52240 USA. Univ Calif Santa Barbara, Ctr Study Macular Degenerat, Santa Barbara, CA 93106 USA. Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA. Queens Univ Belfast, Interdept Nutr Genet, Belfast BT7 1NN, Antrim, North Ireland. Queens Univ Belfast, Dept Otolaryngol Head & Neck Surg, Belfast BT7 1NN, Antrim, North Ireland. Queens Univ Belfast, Dept Ophthalmol, Div Surg & Perioperat Care, Belfast BT7 1NN, Antrim, North Ireland. Erasmus Univ, Dept Ophthalmol, NL-3000 DR Rotterdam, Netherlands. Erasmus Univ, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands. Netherlands Ophthalm Res Inst, NL-3000 DR Rotterdam, Netherlands. NCI, Lab Genom Divers, Frederick, MD 21702 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21702 USA. Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10027 USA. RP Allikmets, R (reprint author), Univ Iowa, Dept Ophthalmol & Visual Sci, Cell Biol & Funct Genom Lab, 11190E PFP,200 Hawkins Dr, Iowa City, IA 52240 USA. EM ria22@columbia.edu RI Dean, Michael/G-8172-2012; Klaver, Caroline/A-2013-2016; OI Dean, Michael/0000-0003-2234-0631; smith, theodore/0000-0002-1693-943X FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NEI NIH HHS [EY11521, EY11515, EY11527, EY13435, R01 EY011515, R01 EY011521, R01 EY011527, R01 EY013435] NR 56 TC 1201 Z9 1233 U1 9 U2 48 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 MAY 17 PY 2005 VL 102 IS 20 BP 7227 EP 7232 DI 10.1073/pnas.0501536102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 928SO UT WOS:000229292200032 PM 15870199 ER PT J AU Mentis, GZ Alvarez, FJ Bonnot, A Richards, DS Gonzalez-Forero, D Zerda, R O'Donovan, MJ AF Mentis, GZ Alvarez, FJ Bonnot, A Richards, DS Gonzalez-Forero, D Zerda, R O'Donovan, MJ TI Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VESICULAR GLUTAMATE TRANSPORTERS; DORSAL-ROOT GANGLIA; MOTOR-NEURONS; NEUROMUSCULAR-JUNCTION; MOLECULAR-CLONING; RENSHAW CELLS; L-ASPARTATE; RAT; EXPRESSION; MOUSE AB Mammalian spinal motoneurons are considered to be output elements of the spinal cord that generate exclusively cholinergic actions on Renshaw cells, their intraspinal synaptic targets. Here, we show that antidromic stimulation of motor axons evokes depolarizing monosynaptic potentials in Renshaw cells that are depressed, but not abolished, by cholinergic antagonists. This residual potential was abolished by 2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione. In the presence of cholinergic antagonists, motor axon stimulation triggered locomotor-like activity that was blocked by 2-amino-5-phosphonovaleric acid. Some cholinergic motoneuronal terminals on both Renshaw cells and motoneurons were enriched in glutamate, but none expressed vesicular glutamate transporters. Our results raise the possibility that motoneurons release an excitatory amino acid in addition to acetylcholine and that they may be more directly involved in the genesis of mammalian locomotion than previously believed. C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. Wright State Univ, Dept Anat & Physiol, Dayton, OH 45435 USA. RP Mentis, GZ (reprint author), NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. EM mentisg@ninds.nih.gov RI o'donovan, michael/A-2357-2015; Alvarez, Francisco/H-4929-2011; OI o'donovan, michael/0000-0003-2487-7547; Gonzalez Forero, David/0000-0001-5748-9546 FU Intramural NIH HHS; NINDS NIH HHS [NS047357, R01 NS047357, R01 NS047357-02, R01 NS047357-03, R01 NS047357-04, R56 NS047357] NR 45 TC 85 Z9 86 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 17 PY 2005 VL 102 IS 20 BP 7344 EP 7349 DI 10.1073/pnas.0502788102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 928SO UT WOS:000229292200052 PM 15883359 ER PT J AU Chen, M Gavrilova, O Liu, J Xie, T Deng, CX Nguyen, AT Nackers, LM Lorenzo, J Shen, L Weinstein, LS AF Chen, M Gavrilova, O Liu, J Xie, T Deng, CX Nguyen, AT Nackers, LM Lorenzo, J Shen, L Weinstein, LS TI Alternative Gnas gene products have opposite effects on glucose and lipid metabolism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE G protein; genomic imprinting; pseudohypoparathyroidism ID PROTEIN ALPHA-SUBUNIT; INCREASED INSULIN SENSITIVITY; G(S)ALPHA KNOCKOUT MICE; MOUSE-CHROMOSOME 2; CONTROL REGION; TISSUE; IDENTIFICATION; TRANSCRIPTS; MUTATIONS; NESP55 AB Gnas is an imprinted gene with multiple gene products resulting from alternative splicing of different first exons onto a common exon 2. These products include stimulatory G protein alpha-subunit (G(s)alpha), the G protein required for receptor-stimulated cAMP production; extralarge G(s)alpha (XL alpha s), a paternally expressed G(s alpha) isoform; and neuroendocrine-specific protein (NESP55), a maternally expressed chromogranin-like protein. G(s)alpha undergoes tissue-specific imprinting, being expressed primarily from the maternal allele in certain tissues. Heterozygous mutation of exon 2 on the maternal (E2(m-/+)) or paternal (E2(+/p-)) allele results in opposite effects on energy metabolism. E2(m-/+) mice are obese and hypometabolic, whereas E2(+/p-) mice are lean and hypermetabolic. We now studied the effects of G(s)alpha deficiency without disrupting other Gnas gene products by deleting G(s)alpha exon 1 (El). E1(+/p-) mice lacked the E2(+/p-) phenotype and developed obesity and insulin resistance. The lean, hypermetabolic, and insulin-sensitive E2(+/p-) phenotype appears to result from XL alpha s deficiency, whereas loss of paternal-specific G(s)alpha expression in E1(+/p-) mice leads to an opposite metabolic phenotype. Thus, alternative Gnas gene products have opposing effects on glucose and lipid metabolism. Like E2(m-/+) mice, E1(m-/+) mice had s.c. edema at birth, presumably due to loss of maternal G(s)alpha expression. However, E1(m-/+) mice differed from E2(m-/+) mice in other respects, raising the possibility for the presence of other maternal-specific gene products. E1(m-/+) mice had more severe obesity and insulin resistance and lower metabolic rate relative to E1(+/p-) mice. Differences between E1(m-/+) and E1(+/p-) mice presumably result from differential effects on G(s)alpha expression in tissues where G(s)alpha is normally imprinted. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov RI deng, chuxia/N-6713-2016; OI Weinstein, Lee/0000-0002-1899-5152 NR 30 TC 110 Z9 113 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 17 PY 2005 VL 102 IS 20 BP 7386 EP 7391 DI 10.1073/pnas.0408268102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 928SO UT WOS:000229292200059 PM 15883378 ER PT J AU Lin, HH Faunce, DE Stacey, M Terajewicz, A Nakamura, T Zhang-Hoover, J Kerley, M Mucenski, ML Gordon, S Stein-Streilein, J AF Lin, HH Faunce, DE Stacey, M Terajewicz, A Nakamura, T Zhang-Hoover, J Kerley, M Mucenski, ML Gordon, S Stein-Streilein, J TI The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNE DEVIATION ACAID; ACTIVATED MOUSE MACROPHAGES; GROWTH-FACTOR-BETA; ANTERIOR-CHAMBER; DENDRITIC CELLS; PRIVILEGED SITE; ORAL TOLERANCE; MANNOSE RECEPTOR; CELLULAR LIGAND; EGF-TM7 FAMILY AB We show that the mouse macrophage-restricted F4/80 protein is not required for the development and distribution of tissue macrophages but is involved in the generation of antigen-specific efferent regulatory T (T reg) cells that suppress antigen-specific immunity. In the in vivo anterior chamber (a.c.)-associated immune deviation (ACAID) model of peripheral tolerance, a.c. inoculation of antigen into F4/80(-)/(-) mice was unable to induce efferent T reg cells and suppress delayed-type hypersensitivity (DTH) responses. Moreover, the use of anti-F4/80 mAb and F4/80(-)/(-) APCs in an in vitro ACAID model showed that all APC cells in the culture must be able to express F4/80 protein if efferent T reg cells were to be generated. In a low-dose oral tolerance model, WT but not F4/80(-)/(-) mice generated an efferent CD8(+) T reg cell population that suppressed an antigen-specific DTH response. Peripheral tolerance was restored in F4/80(-)/(-) mice by adoptive transfer of F4/80(+) APCs in both peripheral tolerance models, indicating a central role for the F4/80 molecule in the generation of efferent CD8(+) T reg cells. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. NEI, Training Program Mol Bases Eye Dis, Bethesda, MD 20892 USA. Chang Gung Univ, Dept Microbiol & Immunol, Taoyuan 333, Taiwan. Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN 37831 USA. Childrens Hosp, Div Pulm Biol, Cincinnati, OH 45229 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Pulm & Crit Care Div, Boston, MA 02115 USA. RP Gordon, S (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. EM christine.holt@path.ox.ac.uk; jstein@vision.eri.harvard.edu FU NEI NIH HHS [EY 11983, EY 13066, R01 EY011983, R01 EY013066]; Wellcome Trust NR 56 TC 170 Z9 177 U1 2 U2 19 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 MAY 16 PY 2005 VL 201 IS 10 BP 1615 EP 1625 DI 10.1084/jem.20042307 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 931HJ UT WOS:000229476100009 PM 15883173 ER PT J AU El-Asady, R Yuan, RW Liu, KC Wang, DH Gress, RE Lucas, PJ Drachenberg, CB Hadley, GA AF El-Asady, R Yuan, RW Liu, KC Wang, DH Gress, RE Lucas, PJ Drachenberg, CB Hadley, GA TI TGF-beta-dependent CD103 expression by CD8(+) T cells promotes selective destruction of the host intestinal epithelium during graft-versus-host disease SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID GROWTH-FACTOR-BETA; IMMUNOLOGICALLY MEDIATED ENTEROPATHY; BONE-MARROW-TRANSPLANTATION; LYMPHOCYTES-T; E-CADHERIN; ADHESION MOLECULES; VIRAL-INFECTION; PEYERS PATCH; MICE; TISSUE AB Destruction of the host intestinal epithelium by donor effector T cell populations is a hallmark of graft-versus-host disease (GVHD), but the underlying mechanisms remain obscure. We demonstrate that CD8(+) T cells expressing CD103, an integrin conferring specificity for the epithelial ligand E-cadherin, play a critical role in this process. A TCR transgenic GVHD model was used to demonstrate that CD103 is selectively expressed by host-specific CD8(+) T cell effector populations (CD8 effectors) that accumulate in the host intestinal epithelium during GVHD. Although host-specific CD8 effectors infiltrated a wide range of host compartments, only those infiltrating the intestinal epithelium expressed CD103. Host-specific CD8 effectors expressing a TGF-beta dominant negative type II receptor were defective in CD103 expression on entry into the intestinal epithelium, which indicates local TGF-beta activity as a critical regulating factor. Host-specific CD8 effectors deficient in CD103 expression successfully migrated into the host intestinal epithelium but were retained at this site much less efficiently than wild-type host-specific CD8 effectors. The relevance of these events to GVHD pathogenesis is supported by the finding that CD103-deficient CD8 (+) T cells were strikingly defective in transferring intestinal GVHD pathology and mortality. Collectively, these data document a pivotal role for TGF-beta-dependent CD103 expression in dictating the gut tropism, and hence the destructive potential, of CD8(+) T cells during GVHD pathogenesis. C1 Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Hadley, GA (reprint author), Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. EM ghadley@smail.umaryland.edu FU NIAID NIH HHS [AI36532, R01 AI036532, R21 AI036532, R56 AI036532] NR 57 TC 115 Z9 119 U1 0 U2 0 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 MAY 16 PY 2005 VL 201 IS 10 BP 1647 EP 1657 DI 10.1084/jem.20041044 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 931HJ UT WOS:000229476100012 PM 15897278 ER PT J AU Rossouw, JE AF Rossouw, JE TI Coronary heart disease in menopausal women: Implications of primary and secondary prevention trials of hormones SO MATURITAS LA English DT Article; Proceedings Paper CT 3rd International Symposium of the Portugese-Menopause-Society CY OCT 23, 2004 CL Oporto, PORTUGAL SP Portugese Menopause Soc DE hormone therapy; menopause; cardioprotection; Women's Health Initiative; primary prevention; secondary prevention ID ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; HEALTHY POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; MYOCARDIAL-INFARCTION; ARTERY ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; RISK; EVENTS; CANCER AB In direct contrast to the observational studies, both primary and secondary prevention trials of female reproductive hormones have found no benefit for coronary heart disease (CHD). Basic science studies have elucidated several mechanisms by which estrogen may improve coronary arterial physiology and prevent pathology, but have also found mechanisms by which estrogen might increase coagulation or inflammation, or might trigger coronary events in advanced lesions. Animal studies suggest that hormones may retard early atherosclerosis, while both animal studies and human angiographic trials are conclusive that hormones do not retard progression of raised lesions. Hormone use in the primary prevention observational studies would mostly have started at the age of menopause, in women whose arteries on average would be closer to normal than those of women in the clinical trials. One hypothesis worthy of further study is that estrogen may have a beneficial effect in normal or near-normal arteries, but the opposite effect in the presence of established atherosclerosis. However, at the average age of menopause, a substantial proportion of women has raised lesions, and a smaller proportion already has advanced lesions. Also, the apparent benefit of hormone use was found in secondary prevention observational studies, i.e., in women with compromised arteries. It is likely that uncorrected biases in the observational studies lead to an overestimation of any benefit of hormone use. On the other hand, endogenous estradiol may be responsible for the later onset of coronary disease in women compared to men; if so, then the appropriate test of the estrogen hypothesis would employ transdermal estradiol in a young population of menopausal women. Hormones are not indicated for the prevention of CHD, particularly in the light of the increased risk for stroke and venous thrombosis. Their use for other indications (menopausal symptoms, osteoporosis) needs to be tempered by the risk for cardiovascular disease (CVD). © 2005 Elsevier Ireland Ltd. All rights reserved. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Rossouw, JE (reprint author), NHLBI, NIH, Bethesda, MD 20892 USA. EM rossouwj@nih.gov NR 43 TC 19 Z9 20 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-5122 J9 MATURITAS JI Maturitas PD MAY 16 PY 2005 VL 51 IS 1 BP 51 EP 63 DI 10.1016/j.maturitas.2005.02.015 PG 13 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA 931PE UT WOS:000229496500010 PM 15883110 ER PT J AU Chakrabarti, BK Ling, X Yang, ZY Montefiori, DC Panet, A Kong, WP Welcher, B Louder, MK Mascola, JR Nabel, GJ AF Chakrabarti, BK Ling, X Yang, ZY Montefiori, DC Panet, A Kong, WP Welcher, B Louder, MK Mascola, JR Nabel, GJ TI Expanded breadth of virus neutralization after immunization with a multiclade envelope HIV vaccine candidate SO VACCINE LA English DT Article DE HIV-1 neutralizing antibodies; multiclade vaccine; AIDS vaccines ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; HIV-1/SIV CHIMERIC VIRUS; 2ND HYPERVARIABLE REGION; PBL-SCID MICE; PASSIVE-IMMUNIZATION; TYPE-1 INFECTION; PARTIAL DELETION; GLYCOPROTEIN 120; EPITOPE AB Although the V3 loop of the human immunodeficiency virus type I (HIV- 1) envelope (Env) effectively elicits potent neutralizing antibodyAlthough the V3 loop of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) effectively elicits potent neutralizing antibody responses, the specificity of the antibody response is often restricted to T cell line adapted (TCLA) strains and a small subset of primary isolates, limiting its utility for an AIDS vaccine. In this study, we have compared Env immunogens with substituted V3 regions to combinations of strains from different clades and evaluated their ability to expand the breadth of the neutralizing antibody response. When the V3 region from HIV BaL was substituted for HIV HXB2, an effective neutralizing antibody response against several clade B primary isolates was elicited, but it remained restricted to neutralization of most clade B isolates. In an attempt to expand this response further, a linear epitope recognized by the broadly neutralizing 2F5 antibody was inserted into V3. A V3 2F5 epitope was identified that bound to 2F5 and elicited a potent 2F5 antibody response as an immunogen, but the antisera neutralized only a tab-adapted strain and not primary isolates. In contrast, combinations of Envs from clades A, B, and C, elicited neutralizing antibodies to a more diverse group of primary HIV- I isolates. These studies suggest that combinations of Env immunogens, despite the limited reactivity of the V3 from each component, can be used to expand the breadth of the neutralizing antibody response. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Virol, Hadassah Hosp, IL-91120 Jerusalem, Israel. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC 3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov NR 53 TC 47 Z9 47 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 16 PY 2005 VL 23 IS 26 BP 3434 EP 3445 DI 10.1016/j.vaccine.2005.01.099 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 927LX UT WOS:000229196500008 PM 15837367 ER PT J AU Biesecker, LG AF Biesecker, LG TI SOX2 anophthalmia syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Editorial Material ID KLIPPEL-TRENAUNAY-SYNDROME C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, NIH, Bldg 49,Room 4A80, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov NR 6 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 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY 15 PY 2005 VL 135A IS 1 BP 8 EP 8 DI 10.1002/ajmg.a.30641 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 921JA UT WOS:000228759200002 ER PT J AU Vadaparampil, ST Wideroff, L Olson, L Viswanath, K Freedman, AN AF Vadaparampil, ST Wideroff, L Olson, L Viswanath, K Freedman, AN TI Physician exposure to and attitudes toward advertisements for gene-tic tests for inherited cancer susceptibility SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE genetic testing; hereditary cancer; advertising; physician survey; physician specialty ID BREAST-OVARIAN CANCER; OF-CLINICAL-ONCOLOGY; SOCIETY; INFORMATION; STATEMENT; KNOWLEDGE AB Commercial marketing materials may serve as a source of information for physicians about genetic testing for inherited cancer susceptibility (GTICS) in addition to medical guidelines, continuing education, and journal articles. The primary purposes of this study were to: (1) determine the percentage of physicians who received advertisements for GTICS early in the diffusion of commercial GTICS (1999-2000); (2) assess associated characteristics; and (3) measure the perceived importance of commercial advertisements and promotions in physicians' decisions to recommend testing to patients. A nationally representative, stratified random sample of 1,251 physicians from the American Medical Association (AMA) Physician Masterfile completed a 15-20 min mixed mode questionnaire that assessed specialty, previous use of genetic tests, practice characteristics, age, and receipt of advertising materials (response rate=71%). Overall, 27.4% (n = 426) had received advertisements. In multivariate analysis, factors associated with receipt of advertisements included: specialties in obstetrics/gynecology, oncology, or gastroenterology; past GTICS use, and age 50+. One of four felt that advertisements would be important in their decision to recommend GTICS. Study results indicate that physicians, particularly in oncology, obstetrics/gynecology, and gastroenterology, began receiving GTICS advertisements commensurate with the early diffusion of commercially available tests into clinical practice. At that time, one-quarter of the physicians considered advertisements to play an important role in their clinical decision making, suggesting attention to (other sources of information and additional factors. Published 2005 Wiley-Liss, Inc(dagger) C1 H Lee Moffit Canc Ctr & Res Inst, Hlth Outcomes & Behav Program, Tampa, FL USA. NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. Abt Associates Inc, Chicago, IL USA. Harvard Univ, Sch Publ Hlth, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA USA. RP Vadaparampil, ST (reprint author), 12902 Magnolia Dr,LCS,FOW, Tampa, FL 33612 USA. EM vadapast@moffitt.usf.edu RI Hernandez, Jessica/G-6527-2011 NR 31 TC 15 Z9 15 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY 15 PY 2005 VL 135A IS 1 BP 41 EP 46 DI 10.1002/ajmg.a.30681 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 921JA UT WOS:000228759200008 PM 15810000 ER PT J AU Beckett, WS Chalupa, DF Pauly-Brown, A Speers, DM Stewart, JC Frampton, MW Utell, MJ Huang, LS Cox, C Zareba, W Oberdorster, G AF Beckett, WS Chalupa, DF Pauly-Brown, A Speers, DM Stewart, JC Frampton, MW Utell, MJ Huang, LS Cox, C Zareba, W Oberdorster, G TI Comparing inhaled ultrafine versus fine zinc oxide particles in healthy adults - A human inhalation study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE air pollution; metal fume fever; particulate matter; ultrafine; zinc ID METAL FUME FEVER; PULMONARY RESPONSES; EXPOSURE; INFLAMMATION; CIRCULATION; AEROSOLS; PASSAGE; INJURY; MODEL AB Rationale: Zinc oxide is a common, biologically active constituent of particulate air pollution as well as a workplace toxin. Ultrafine particles (< 0.1 μ m diameter) are believed to be more potent than an equal mass of inhaled accumulation mode particles (0.1-1.0 μ m diameter). Objectives: We compared exposure-response relationships for respiratory, hematologic, and cardiovascular endpoints between ultrafine and accumulation mode zinc oxide particles. Methods: In a human inhalation study, 12 healthy adults inhaled 500 μ g/m(3) of ultrafine zinc oxide, the same mass of fine zinc oxide, and filtered air while at rest for 2 hours. Measurements and Main Results: Preexposure and follow-up studies of symptoms, leukocyte surface markers, hemostasis, and cardiac electrophysiology were conducted to 24 hours post-exposure. Induced sputum was sampled 24 hours after exposure. No differences were detected between any of the three exposure conditions at this level of exposure. Conclusions: Freshly generated zinc oxide in the fine or ultrafine fractions inhaled by healthy subjects at rest at a concentration of 500 μ g/m(3) for 2 hours is below the threshold for acute systemic effects as detected by these endpoints. C1 Univ Rochester, Med Ctr, Sch Med & Dent, Dept Environm Med, Rochester, NY 14642 USA. Univ Rochester, Med Ctr, Sch Med & Dent, Dept Med, Rochester, NY 14642 USA. Univ Rochester, Med Ctr, Sch Med & Dent, Dept Biostat, Rochester, NY 14642 USA. NICHHD, Div Epidemiol Stat & Prevent, NIH, Bethesda, MD 20892 USA. RP Beckett, WS (reprint author), Univ Rochester, Med Ctr, Sch Med & Dent, Dept Environm Med, 601 Elmwood Ave,Box EHSC, Rochester, NY 14642 USA. EM bill_beckett@urmc.rochester.edu FU EAPO CDC HHS [EPA R-827354]; NCRR NIH HHS [5 M01 RR00044]; NHLBI NIH HHS [HL65208-03]; NIEHS NIH HHS [P30 ES01247] NR 32 TC 74 Z9 79 U1 0 U2 6 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 MAY 15 PY 2005 VL 171 IS 10 BP 1129 EP 1135 DI 10.1164/rccm.200406-837OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 924AL UT WOS:000228950700013 PM 15735058 ER PT J AU Rishi, V Potter, T Laudeman, J Reinhart, R Silvers, T Selby, M Stevenson, T Krosky, P Stephen, AG Acharya, A Moll, J Oh, WJ Scudiero, D Shoemaker, RH Vinson, C AF Rishi, V Potter, T Laudeman, J Reinhart, R Silvers, T Selby, M Stevenson, T Krosky, P Stephen, AG Acharya, A Moll, J Oh, WJ Scudiero, D Shoemaker, RH Vinson, C TI A high-throughput fluorescence-anisotropy screen that identifies small molecule inhibitors of the DNA binding of B-ZIP transcription factors SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE high-throughput screen; B-ZIP protein; fluorescence anisotropy/fluorescence polarization; small molecules; CREB; VBP; C/EBP; AP-1 ID BASIC REGION; COILED-COIL; POLARIZATION; ALPHA; ACTIVATION; ASSAYS; TUMORIGENESIS; IMMUNOASSAY; MEDIATOR; PATHWAY AB We have developed a high-throughput fluorescence anisotropy screen, using a 384-well format, to identify small molecules that disrupt the DNA binding of B-ZIP proteins. Binding of a B-ZIP dimer to fluorescently labeled DNA can be monitored by fluorescence anisotropy. We screened the National Cancer Institute diversity, set of 1990 compounds to identify small molecules that disrupt the B-ZIP vertical bar DNA coniplex of CREB, C/EBP beta, VBP, and AP-1 (FOS vertical bar JUND) bound to their cognate DNA sequence. We identified 21 compounds that inhibited the DNA binding of at least one B-ZIP Protein, and 12 representative compounds were grouped depending on whether they displaced ethidium bromide from DNA. Of the 6 compounds that did not displace ethidium bromide. 2 also inhibited B-ZIP binding to DNA in a secondary electrophoretic niobility shift assay screen with some specificity. Thermal stability monitored by circular dichroism spectroscopy demonstrated that both compounds bound the basic region of the B-ZIP motif. NSC13778 preferentially binds C/EBP alpha of 1000-fold better than it binds C/EBP beta. Chimeric proteins combining C/EBP alpha. and C/EBP beta mapped the binding of NSC13778 to three amino acids immediately N terminal of the leucine zipper of C/EBP alpha.. These experiments suggest that the DNA binding of B-ZIP transcription factors is a potential target for clinical intervention. Published by Elsevier Inc. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. SAIC, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Frederick, MD 21702 USA. RP Vinson, C (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. EM vinsonc@dc37a.nci.nih.gov NR 30 TC 38 Z9 39 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAY 15 PY 2005 VL 340 IS 2 BP 259 EP 271 DI 10.1016/j.ab.2005.02.012 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 921QH UT WOS:000228779000010 PM 15840499 ER PT J AU Dobbin, KK Kawasaki, ES Petersen, DW Simon, RM AF Dobbin, KK Kawasaki, ES Petersen, DW Simon, RM TI Characterizing dye bias in microarray experiments SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION MEASUREMENTS; DNA; NORMALIZATION; DESIGNS; MODELS AB Motivation: Spot intensity serves as a proxy for gene expression in dual-label microarray experiments. Dye bias is defined as an intensity difference between samples labeled with different dyes attributable to the dyes instead of the gene expression in the samples. Dye bias that is not removed by array normalization can introduce bias into comparisons between samples of interest. But if the bias is consistent across samples for the same gene, it can be corrected by proper experimental design and analysis. If the dye bias is not consistent across samples for the same gene, but is different for different samples, then removing the bias becomes more problematic, perhaps indicating a technical limitation to the ability of fluorescent signals to accurately represent gene expression. Thus, it is important to characterize dye bias to determine: (1) whether it will be removed for all genes by array normalization, (2) whether it will not be removed by normalization but can be removed by proper experimental design and analysis and (3) whether dye bias correction is more problematic than either of these and is not easily removable. Results: We analyzed two large (each > 27 arrays) tissue culture experiments with extensive dye swap arrays to better characterize dye bias. Indirect, amino-allyl labeling was used in both experiments. We found that post-normalization dye bias that is consistent across samples does appear to exist for many genes, and that controlling and correcting for this type of dye bias in design and analysis is advisable. The extent of this type of dye bias remained unchanged under a wide range of normalization methods (median-centering, various loess normalizations) and statistical analysis techniques (parametric, rank based, permutation based, etc.). We also found dye bias related to the individual samples for a much smaller subset of genes. But these sample-specific dye biases appeared to have minimal impact on estimated gene-expression differences between the cell lines. C1 NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, NIH, Bethesda, MD 20892 USA. RP Dobbin, KK (reprint author), NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. EM dobbinke@mail.nih.gov NR 22 TC 50 Z9 52 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 15 PY 2005 VL 21 IS 10 BP 2430 EP 2437 DI 10.1093/bioinformatics/bti378 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 928QA UT WOS:000229285600037 PM 15774555 ER PT J AU Sharov, AA Dudekula, DB Ko, MSH AF Sharov, AA Dudekula, DB Ko, MSH TI A web-based tool for principal component and significance analysis of microarray data SO BIOINFORMATICS LA English DT Article ID FALSE DISCOVERY RATE; EXPRESSION AB We have developed a program for microarray data analysis, which features the false discovery rate for testing statistical significance and the principal component analysis using the singular value decomposition method for detecting the global trends of gene-expression patterns. Additional features include analysis of variance with multiple methods for error variance adjustment, correction of cross-channel correlation for two-color microarrays, identification of genes specific to each cluster of tissue samples, biplot of tissues and corresponding tissue-specific genes, clustering of genes that are correlated with each principal component (PC), three-dimensional graphics based on virtual reality modeling language and sharing of PC between different experiments. The software also supports parameter adjustment, gene search and graphical output of results. The software is implemented as a web tool and thus the speed of analysis does not depend on the power of a client computer. C1 NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. EM kom@mail.nih.gov RI Ko, Minoru/B-7969-2009; OI Ko, Minoru/0000-0002-3530-3015; Dudekula, Dawood/0000-0002-4054-1827 NR 11 TC 164 Z9 168 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 15 PY 2005 VL 21 IS 10 BP 2548 EP 2549 DI 10.1093/bioinformatics/bti343 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 928QA UT WOS:000229285600061 PM 15734774 ER PT J AU Friedman, MJ Wang, S Jalowiec, JE McHugo, GJ McDonagh-Coyle, A AF Friedman, MJ Wang, S Jalowiec, JE McHugo, GJ McDonagh-Coyle, A TI Thyroid hormone alterations among women with posttraumatic stress disorder due to childhood sexual abuse SO BIOLOGICAL PSYCHIATRY LA English DT Article DE PTSD; triiodothyronine; thyroid stimulating hormone; childhood sexual abuse; depression; clinician administered PTSD scale (CAPS) ID ADMINISTERED PTSD SCALE; COMBAT VETERANS; ELEVATION; TRIIODOTHYRONINE; DEPRESSION; SYMPTOMS AB Background: Research on thyroid activity among male combat veterans with, positraumatic stress disorder (PTSD) has consistently shown elevations in total triiodothyronine (TT3) and inconsistent elevations of other thyroid variables. This study is the first large scale investigation of thyroid,function in women with PTSD. Methods: Thyroid function was measured in 63 women with PTSD due to childhood sexual abuse (PTSD-CSA) in comparison with a community sample of 42 women without current PTSD-CSA. Clinical measures included the Clinician Administered PTSD Scale (CAPS), the Evaluation of Lifetime Stressors, the Trauma Assessment for Adults and the Beck Depression Inventory. Results: Women with PTSD-CSA showed significant elevations in Total T-3 and the TT3/free thyroxine (TT3/FT4) ratio, the FT3/TT3 ratio, and modest reductions in thyroid stimulating hormone relative to our community sample. These findings could not be explained by the influence of prior trauma, lifetime PTSD or depressive symptoms. Conclusions: Altered thyroid activity especially elevated Total T-3 levels, was found in women with PTSD associated with childhood sexual abuse. C1 VA Med Ctr, Natl Ctr PTSD, White River Jct, VT 05009 USA. NH Dartmouth Psychiat Res Ctr, Lebanon, NH USA. Dartmouth Coll Sch Med, Dept Psychiat, Hanover, NH USA. NIA, Lab Personal & Cognit, Emot & Quantitat Psychophysiol Sect, Baltimore, MD 21224 USA. RP Friedman, MJ (reprint author), VA Med Ctr, Natl Ctr PTSD, 215 N Main St, White River Jct, VT 05009 USA. EM Matthew.Friedman@Dartmouth.Edu FU NIMH NIH HHS [R01-MH52787] NR 29 TC 14 Z9 15 U1 3 U2 6 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 MAY 15 PY 2005 VL 57 IS 10 BP 1186 EP 1192 DI 10.1016/j.biopsych.2005.01.019 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 923MT UT WOS:000228914700014 PM 15866559 ER PT J AU Papakrivos, J Wellems, TE AF Papakrivos, J Wellems, TE TI Designer transport of malaria proteins in erythrocytes SO BLOOD LA English DT Editorial Material ID CYTOADHERENCE; PFEMP1 C1 NIAID, Bethesda, MD 20892 USA. RP Papakrivos, J (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 2005 VL 105 IS 10 BP 3757 EP 3758 DI 10.1182/blood-2005-02-0837 PG 2 WC Hematology SC Hematology GA 924VO UT WOS:000229009000001 ER PT J AU Willemze, R Jaffe, ES Burg, G Cerroni, L Berti, E Swerdlow, SH Ralfkiaer, E Chimenti, S Diaz-Perez, JL Duncan, LM Grange, F Harris, NL Kempf, W Kerl, H Kurrer, M Knobler, R Pimpinelli, N Sander, C Santucci, M Sterry, W Vermeer, MH Wechsler, J Whittaker, S Meijer, CJLM AF Willemze, R Jaffe, ES Burg, G Cerroni, L Berti, E Swerdlow, SH Ralfkiaer, E Chimenti, S Diaz-Perez, JL Duncan, LM Grange, F Harris, NL Kempf, W Kerl, H Kurrer, M Knobler, R Pimpinelli, N Sander, C Santucci, M Sterry, W Vermeer, MH Wechsler, J Whittaker, S Meijer, CJLM TI WHO-EORTC classification for cutaneous lymphomas SO BLOOD LA English DT Review ID T-CELL LYMPHOMA; TREATMENT-OF-CANCER; MYCOSIS FUNGOIDES/SEZARY-SYNDROME; GRANULOMATOUS SLACK SKIN; BCL-2 PROTEIN EXPRESSION; CD30-POSITIVE LYMPHOPROLIFERATIVE DISORDERS; COMPARATIVE GENOMIC HYBRIDIZATION; DISSEMINATED PAGETOID RETICULOSIS; MOLECULAR CYTOGENETIC ANALYSIS; WORINGER-KOLOPP-DISEASE AB Primary cutaneous lymphomas are currently classified by the European Organization for Research and Treatment of Cancer (EORTC) classification or the World Health Organization (WHO) classification, but both systems have shortcomings. In particular, differences in the classification of cutaneous T-cell lymphomas other than mycosis fungoides, Sezary syndrome, and the group of primary cutaneous CD30+ lymphoproliferative disorders and the classification and terminology of different types of cutaneous B-cell lymphomas have resulted in considerable debate and confusion. During recent consensus meetings representatives of both systems reached agreement on a new classification, which is now called the WHO-EORTC classification. In this paper we describe the characteristic features of the different primary cutaneous lymphomas and other hematologic neoplasms frequently presenting in the skin, and discuss differences with the previous classification schemes. In addition, the relative frequency and survival data of 1905 patients with primary cutaneous lymphomas derived from Dutch and Austrian registries for primary cutaneous lymphomas are presented to illustrate the clinical significance of this new classification. 2005 by The American Society of Hematology. C1 Leiden Univ Ctr, Med Ctr, Dept Dermatol, NL-2300 RC Leiden, Netherlands. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. Graz Univ, Dept Dermatol, Graz, Austria. Univ Milan Biococca, Dept Dermatol, Milan, Italy. Osped Maggiore, Milan, Italy. Univ Pittsburgh, Sch Med, Dept Pathol, Div Hematopahtol, Pittsburgh, PA USA. Univ Copenhagen, Dept Pathol, Copenhagen, Denmark. Univ Rome, Dept Dermatol, Rome, Italy. Cruces Hosp, Dept Dermatol, Bilbao, Spain. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Hop Louis Pasteur, Dept Dermatol, Colmar, France. Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland. Univ Vienna, Dept Dermatol, Vienna, Austria. Univ Florence, Dept Dermatol Sci, Florence, Italy. Allgemeines Krankenhaus St Georg, Dept Dermatol, Hamburg, Germany. Univ Florence, Dept Human Pathol & Oncol, I-50121 Florence, Italy. Humboldt Univ, Dept Dermatol, Berlin, Germany. Hop Henri Mondor, Dept Pathol, F-94010 Creteil, France. St Thomas Hosp, St Johns Inst Dermatol, Skin Tumour Unit, London, England. Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands. RP Willemze, R (reprint author), Leiden Univ Ctr, Med Ctr, Dept Dermatol, B1-Q-93,POB 9600, NL-2300 RC Leiden, Netherlands. EM rein.willemze@planet.nl RI Berti, Emilio/F-5256-2012 NR 180 TC 1809 Z9 1948 U1 10 U2 58 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 15 PY 2005 VL 105 IS 10 BP 3768 EP 3785 DI 10.1182/blood-2004-09-3502 PG 18 WC Hematology SC Hematology GA 924VO UT WOS:000229009000013 PM 15692063 ER PT J AU Kortesidis, A Zannettino, A Isenmann, S Shi, ST Lapidot, T Gronthos, S AF Kortesidis, A Zannettino, A Isenmann, S Shi, ST Lapidot, T Gronthos, S TI Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells SO BLOOD LA English DT Article ID ADULT HUMAN BONE; CHEMOKINE RECEPTORS; MOLECULAR-CLONING; PROGENITOR CELLS; TELOMERASE EXPRESSION; CANCER METASTASIS; NOD/SCID MICE; SDF-1; MIGRATION; CXCR4 AB The maintenance of bone marrow stromal stem cells (BMSSCs) is tightly controlled by the local microenvironment and by autocrine regulatory factors secreted by BMSSCs. To identify such factors, a cDNA subtraction library was generated from purified BMSSCs, based on their high expression of the STRO-1 antigen. Stromal-derived factor-1 (SDF-1) was one differentially expressed gene highly expressed by purified BMSSCs prior to culture. In vitro, immature preosteogenic cells expressed greater levels of SDF-1 when compared with mature cell types representative of osteoblasts and osteocytes/bone lining cells. Furthermore, SDF-1 expression was rapidly down-regulated when BMSSCs were cultured under osteoinductive conditions. BMSSCs were also shown to express functional cell surface SDF-1 receptors (CXCR4). Transduced BMSSC lines, secreting high SDF-1 levels, displayed an enhanced ability to form ectopic bone in vivo, in comparison with control BMSSC lines. Moreover, high SDF-1-expressing BMSSCs displayed an increased capacity for cellular growth and protection against interieukin-4-induced apoptosis. Similarly, fibroblast colony-forming units (CFU-Fs) also displayed increased growth and resistance to alpha-interferon-2a-induced apoptosis, in synergy with platelet-derived growth factor BB (PDGF-BB) and SDF-1 in vitro. These studies indicate that the chemokine, SDF-1, may play a role in the maintenance, survival, and osteogenic capacity of immature BMSSC populations. (c) 2005 by The American Society of Hematology. C1 Hanson Inst, Inst Med & Vet Sci, Mesenchymal Stem Cell Grp, Div Hematol, Adelaide, SA 5000, Australia. Hanson Inst, Inst Med & Vet Sci, Div Haematol, Myeloma & Mesenchymal Res Grp,Matthew Roberts Fdn, Adelaide, SA, Australia. NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. RP Gronthos, S (reprint author), Hanson Inst, Inst Med & Vet Sci, Mesenchymal Stem Cell Grp, Div Hematol, Frome Rd, Adelaide, SA 5000, Australia. EM stan.gronthos@imvs.sa.gov.au RI Lapidot, Tsvee/A-1812-2010 NR 67 TC 241 Z9 265 U1 0 U2 15 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 2005 VL 105 IS 10 BP 3793 EP 3801 DI 10.1182/blood-2004-11-4349 PG 9 WC Hematology SC Hematology GA 924VO UT WOS:000229009000016 PM 15677562 ER PT J AU Curtis, RE Metayer, C Rizzo, JD Socie, G Sobocinski, KA Flowers, MED Travis, WD Travis, LB Horowitz, MM Deeg, HJ AF Curtis, RE Metayer, C Rizzo, JD Socie, G Sobocinski, KA Flowers, MED Travis, WD Travis, LB Horowitz, MM Deeg, HJ TI Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; SEVERE APLASTIC-ANEMIA; ORGAN-TRANSPLANTATION; HUMAN-PAPILLOMAVIRUS; MALIGNANT-TUMORS; FANCONI-ANEMIA; SOLID CANCERS; HOST DISEASE; SKIN-CANCER; RISK AB Previous studies of recipients of hematopoietic stem-cell transplants suggest that graft-versus-host disease (GVHD) and its therapy may increase the risk for solid cancers, particularly squamous-cell carcinomas (SCCs) of the buccal cavity and skin. However, the importance and magnitude of these associations are not well characterized. We conducted a case-control study of 183 patients with post-transplantation solid cancers (58 SCCs, 125 non-SCCs) and 501 matched control patients within a cohort of 24 011 patients who underwent hematopoietic stem-cell transplantation (HSCT) at 215 centers worldwide. Our results showed that chronic GVHD and its therapy were strongly related to the risk for SCC, whereas no increase in risk was found for non-SCCs. Major risk factors for the development of SCC were long duration of chronic GVHD therapy (P <.001); use of azathioprine, particularly when combined with cyclosporine and steroids (P <.001); and severe chronic GVHD (P =.004). Given that most patients who received prolonged immunosuppressive therapy and those with severe chronic GVHD were also treated with azathioprine, the independent effects of these factors could not be evaluated. Additional analyses determined that prolonged immunosuppressive therapy and azathioprine use were also significant risk factors for SCC of the skin and of the oral mucosa. These data provide further encouragement for strategies to prevent chronic GVHD and for the development of more effective and less carcinogenic treatment regimens for patients with moderate or severe chronic GVHD. Our results also suggest that clinical screening for SCC is appropriate among patients exposed to persistent chronic GVHD, prolonged immunosuppressive therapy, or both. (c) 2005 by The American Society of Hematology. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Hop St Louis, Hematol Greffe de Moelle, Paris, France. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Curtis, RE (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Execut Plaza S,Suite 7042,6120 Execut Blvd, Bethesda, MD 20892 USA. EM rcurtis@mail.nih.gov FU NCI NIH HHS [CP-51027, CP-51028, K23 CA82350, P01-CA15704, P01-CA18029, U24-CA76518]; NHLBI NIH HHS [P01-HL36444] NR 42 TC 121 Z9 124 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 15 PY 2005 VL 105 IS 10 BP 3802 EP 3811 DI 10.1182/blood-2004-09-3411 PG 10 WC Hematology SC Hematology GA 924VO UT WOS:000229009000017 PM 15687239 ER PT J AU Sohn, RH Deming, CB Johns, DC Champion, HC Bian, C Gardner, K Rade, JJ AF Sohn, RH Deming, CB Johns, DC Champion, HC Bian, C Gardner, K Rade, JJ TI Regulation of endothelial thrombomodulin expression by inflammatory cytokines is mediated by activation of nuclear factor-kappa B SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; ELEMENT-BINDING PROTEIN; FACTOR-ALPHA; TISSUE FACTOR; TRANSCRIPTIONAL ACTIVATION; RETINOIC ACID; SESQUITERPENE LACTONES; RESPONSIVE ELEMENT; GENE-TRANSCRIPTION; MONOCYTIC CELLS AB Inflammation and thrombosis are increasingly recognized as interrelated biologic processes. Endothelial cell expression of thrombomodulin (TM), a key component of the anticoagulant protein C pathway, is potently inhibited by inflammatory cytokines. Because the mechanism underlying this effect is largely unknown, we investigated a potential role for the inflammatory transcription factor nuclear factor-kappa B (NF-kappa B). Blocking NF-kappa B activation effectively prevented cytokine-induced down-regulation of TM, both in vitro and in a mouse model of tumor necrosis factor-alpha (TNF-alpha)-mediated lung injury. Although the TM promoter lacks a classic NF-kappa B consensus site, it does contain tandem Ets transcription factor binding sites previously shown to be important for both constitutive TM gene expression and cytokine-induced repression. Using electrophoretic mobility shift assay and chromatin immunoprecipitation, we found that multiple Ets species bind to the TNF-alpha response element within the TM promoter. Although cytokine exposure did not alter Ets factor binding, it did reduce binding of p300, a coactivator required by Ets for full transcriptional activity. Overexpression of p300 also prevented TM repression by cytokines. We conclude that NF-kappa B is a critical mediator of TM repression by cytokines. Further evidence suggests a mechanism involving competition by NF-kappa B for limited pools of the transcriptional coactivator p300 necessary for TM gene expression. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA. Natl Canc Inst, Lab Receptor Biol & Gene Express, Bethesda, MD USA. RP Rade, JJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Carnegie 568,600 N Wolfe St, Baltimore, MD 21287 USA. EM jjrade@jhmi.edu NR 57 TC 67 Z9 69 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 2005 VL 105 IS 10 BP 3910 EP 3917 DI 10.1182/blood-2004-03-0928 PG 8 WC Hematology SC Hematology GA 924VO UT WOS:000229009000032 PM 15677570 ER PT J AU Lelievre, E Bourbon, PM Duan, LJ Nussbaum, RL Fong, GH AF Lelievre, E Bourbon, PM Duan, LJ Nussbaum, RL Fong, GH TI Deficiency in the p110 alpha subunit of PI3K results in diminished Tie2 expression and Tie2(-/-) - like vascular defects in mice SO BLOOD LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; SIGNAL-TRANSDUCTION PATHWAY; CELL-SURVIVAL; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE 3-KINASE; ANGIOGENESIS; ANGIOPOIETIN-1; RECEPTOR; ACTIVATION; GENE AB Phosphoinositide 3-kinase (PI3K) is activated by transmembrane tyrosine kinases such as vascular endothelial growth factor (VEGF) receptors and Tie2 (tunica intima endothelial kinase 2), both of which are key regulators of vascular development. However, the in vivo role of PI3K during developmental vascularization remains to be defined. Here we demonstrate that mice deficient in the p110 alpha catalytic subunit of PI3K display multiple vascular defects, including dilated vessels in the head, reduced branching morphogenesis in the endocardium, lack of hierarchical order of large and small branches in the yolk sac, and impaired development of anterior cardinal veins. These vascular defects are strikingly similar to those in mice defective in the Tie2 signaling pathway. Indeed, Tie2 protein levels were significantly lower in p110 alpha-deficient mice. Furthermore, RNA interference of p110 alpha, in cultured endothelial cells significantly reduced Tie2 protein levels. These findings raise the possibility that PI3K may function as an upstream regulator of Tie2 expression during mouse development. C1 Univ Connecticut, Ctr Hlth, Ctr Vasc Biol, Dept Cell Biol, Farmington, CT 06030 USA. Univ Connecticut, Ctr Hlth, Ctr Vasc Biol, Dept Genet & Dev Biol, Farmington, CT 06030 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Fong, GH (reprint author), Univ Connecticut, Ctr Hlth, Ctr Vasc Biol, Dept Cell Biol, 263 Farmington Ave, Farmington, CT 06030 USA. EM fong@nso2.uchc.edu FU NHLBI NIH HHS [5R01HL68168, 5PO1HL70694] NR 27 TC 29 Z9 31 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 2005 VL 105 IS 10 BP 3935 EP 3938 DI 10.1182/blood-2004-10-3955 PG 4 WC Hematology SC Hematology GA 924VO UT WOS:000229009000035 PM 15687236 ER PT J AU Jiao, W Lin, HN Timmons, J Nagaich, AK Ng, SW Misteli, T Rane, SG AF Jiao, W Lin, HN Timmons, J Nagaich, AK Ng, SW Misteli, T Rane, SG TI E2F-dependent repression of topoisomerase II regulates heterochromatin formation and apoptosis in cells with melanoma-prone mutation SO CANCER RESEARCH LA English DT Article ID DNA TOPOISOMERASES; E2F FAMILY; E2F1-INDUCED APOPTOSIS; CELLULAR SENESCENCE; MALIGNANT-MELANOMA; BINDING DOMAIN; CANCER; MICE; ROLES; CDK4 AB RB pathway mutations, especially at the CDK4 and INK4A loci, are hallmarks of melanomagenesis. It is presently unclear what advantages these alterations confer during melanoma progression and how they influence melanoma therapy. Topoisomerase II inhibitors are widely used to treat human malignancies, including melanoma, although their variable success is attributable to a poor understanding of their mechanism of action. Using mouse and human cells harboring the melanoma-prone p16(Ink4a)-insensitive CDK4(R24C) mutation, we show here that topoisomerase II proteins are direct targets of E2F-mediated repression. Drug-treated cells fail to load repressor E2Fs on topoisomerase II promoters leading to elevated topoisomerase II levels and an enhanced sensitivity of cells to apoptosis. This is associated with the increased formation of heterochromatin domains enriched in structural heterochromatin proteins, methylated histones H3/H4, and topoisomerase II. We refer to these preapoptotic heterochromatin domains as apoptosis-associated heterochromatic foci. We suggest that cellular apoptosis is preceded by an intermediary chromatin remodeling state that involves alterations of DNA topology by topoisomerase II enzymes and gene silencing via formation of heterochromatin. These observations provide novel insight into the mechanism of drug action that influence treatment outcome: drug sensitivity or drug resistance. C1 NCI, Lab Cell Regulat & Carcinogenesis, Cell Cycle & Human Dis Grp, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Dept OB GYN & Reprod Biol, Boston, MA 02115 USA. RP Rane, SG (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Cell Cycle & Human Dis Grp, NIH, Bethesda, MD 20892 USA. EM sushil_rane@nih.gov NR 48 TC 7 Z9 7 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 MAY 15 PY 2005 VL 65 IS 10 BP 4067 EP 4077 DI 10.1158/0008-5472.CAN-04-3999 PG 11 WC Oncology SC Oncology GA 925OI UT WOS:000229062000013 PM 15899796 ER PT J AU Avis, I Martinez, A Tauler, J Zudaire, E Mayburd, A Abu-Ghazaleh, R Ondrey, F Mulshine, JL AF Avis, I Martinez, A Tauler, J Zudaire, E Mayburd, A Abu-Ghazaleh, R Ondrey, F Mulshine, JL TI Inhibitors of the arachidonic acid pathway and peroxisome proliferator-activated receptor ligands have superadditive effects on lung cancer growth inhibition SO CANCER RESEARCH LA English DT Article ID PPAR-GAMMA AGONISTS; CELL-LINES; IN-VITRO; 5-LIPOXYGENASE-ACTIVATING PROTEIN; ADJUVANT CHEMOTHERAPY; COLORECTAL-CANCER; RETINOIC ACID; APOPTOSIS; EXPRESSION; DRUGS AB Arachidonic acid (AA) metabolizing enzymes and peroxisome proliferator-activated receptors (PPARs) have been shown to regulate the growth of epithelial cells. We have previously reported that exposure to the 5-lipoxygenase activating protein-directed inhibitor MK886 but not the cyclooxygenase inhibitor, indomethacin, reduced growth, increased apoptosis, and up-regulated PPARα and γ expression in breast cancer cell lines. In the present study, we explore approaches to maximizing the proapoptotic effects of PPARγ on lung cancer cell lines. Non-small-cell cancer cell line A549 revealed dose-dependent PPARγ reporter activity after treatment with MK886. The addition of indomethacin in combination with MK886 further increases reporter activity. We also show increased growth inhibition and up-regulation of apoptosis after exposure to MK886 alone, or in combination with indomethacin and the PPAR ligand, 15-deoxy-&UDelta;(12,14)-prostaglandin J(2) compared with single drug exposures on the adenocarcinoma cell line A549 and small-cell cancer cell lines H345, N417, and H510. Real-time PCR analyses showed increased PPAR mRNA and retinoid X receptor (RXR)α mRNA expression after exposure to MK886 and indomethacin in a time-dependent fashion. The results suggest that the principal proapoptotic effect of these drugs may be mediated through the known antiproliferative effects of the PPARγ-RXR interaction. We therefore explored a three-drug approach to attempt to maximize this effect. The combination of low-dose MK886, ciglitazone, and 13-cis-retinoic acid interacted at least in a superadditive fashion to inhibit the growth of lung cancer cell lines A549 and H1299, suggesting that targeting PPARγ and AA action is a promising approach to lung cancer growth with a favorable therapeutic index. C1 NCI, Intervent Sect, Cell & Canc Biol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. CSIC, Inst Cajal, Dept Cell Biol & Neuroanat, E-28002 Madrid, Spain. Univ Minnesota, Dept Otolaryngol, Mol Oncol Program, Minneapolis, MN USA. RP Mulshine, JL (reprint author), NCI, Intervent Sect, Cell & Canc Biol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM mulshinj@mail.nih.gov RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 52 TC 65 Z9 69 U1 1 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 MAY 15 PY 2005 VL 65 IS 10 BP 4181 EP 4190 DI 10.1158/0008-5472.CAN-04-3441 PG 10 WC Oncology SC Oncology GA 925OI UT WOS:000229062000026 PM 15899809 ER PT J AU Liu, KB Caldwell, SA Abrams, SI AF Liu, KB Caldwell, SA Abrams, SI TI Immune selection and emergence of aggressive tumor variants as negative consequences of Fas-mediated cytotoxicity and altered IFN-gamma-regulated gene expression SO CANCER RESEARCH LA English DT Article ID CTL ADOPTIVE IMMUNOTHERAPY; PERFORIN-DEFICIENT MICE; COLON-CARCINOMA CELLS; RENAL-CANCER CELLS; T-CELLS; IN-VIVO; INFILTRATING LYMPHOCYTES; LIGAND INTERACTIONS; INDUCED SARCOMAS; LUNG-CANCER AB Antitumor responses can be induced in patients via active or adoptive immunotherapy, yet complete tumor eradication occurs infrequently. This paradox in tumor immunology led us to address two questions: (a) Does an antitumor response, which is intended to destroy the aberrant target population, also at the same time select for aggressive tumor variants (ATV) in vivo? (b) If this process does occur, what is the contribution of the perforin- or Fas-mediated effector mechanism in the immune selection of such ATV? Here, in an experimental mouse lung metastasis model, we showed that ATV generated either naturally in vivo or in vitro by anti-Fas selection resembled each other biologically and genetically as judged by enhanced tumor growth and genome-scale gene expression profiling, respectively. Furthermore, ATV that survived CTL adoptive immunotherapy displayed an even more profound loss of Fas expression and function as well as enhanced malignant proficiency in vivo. ATV, however, retained sensitivity to perforin-mediated lysis in vitro. Lastly, such ATV displayed a diminished responsiveness in their expression of IFN-γ-regulated genes, including those mechanistically linked to Fas-mediated death (i.e., Fas and caspase-1). Overall, we showed that (a) immune selection did occur in vivo and played an important role in the emergence of ATV, (b) ATV bearing a Fas-resistant phenotype was a chief consequence of immune Selection, and (c) an overall diminished responsiveness of IFN-γ-regulated gene expression was characteristic of ATV. Thus, in this model, Fas-mediated cytotoxicity, in concert with IFN-γ-regulated gene expression, mechanistically constituted significant determinants of immune selection of ATV in vivo. C1 NCI, Ctr Canc Res, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA. RP Abrams, SI (reprint author), NCI, Ctr Canc Res, Lab Tumor Immunol & Biol, NIH, Bldg 10,Room 5B46,10 Ctr Dr, Bethesda, MD 20892 USA. EM sa47z@nih.gov OI Liu, Kebin/0000-0003-1965-7240 NR 51 TC 27 Z9 28 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 MAY 15 PY 2005 VL 65 IS 10 BP 4376 EP 4388 DI 10.1158/0008-5472.CAN-04-4269 PG 13 WC Oncology SC Oncology GA 925OI UT WOS:000229062000047 PM 15899830 ER PT J AU Panelli, MC Wang, E Marincola, FM AF Panelli, MC Wang, E Marincola, FM TI The pathway to biomarker discovery: Carbonic anhydrase IX and the prediction of immune responsiveness SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID RENAL-CELL CARCINOMA; HIGH-DOSE INTERLEUKIN-2; METASTATIC MELANOMA; IMMUNIZATION; ACTIVATION; IMIQUIMOD; CANCER C1 NIH, Dept Transfus Med, Immunogenet Sect, Ctr Clin, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Dept Transfus Med, Immunogenet Sect, Ctr Clin, Bldg 10,Room 1C-711,10 Ctr Dr MSC 1502, Bethesda, MD 20892 USA. EM FMarincola@mail.cc.nih.gov NR 27 TC 10 Z9 11 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2005 VL 11 IS 10 BP 3601 EP 3603 DI 10.1158/1078-0432.CCR-05-0475 PG 3 WC Oncology SC Oncology GA 925XJ UT WOS:000229086600001 PM 15897553 ER PT J AU Vogel, TW Zhuang, ZP Li, J Okamoto, H Furuta, M Lee, YS Zeng, WF Oldfield, EH Vortmeyer, AO Weil, RJ AF Vogel, TW Zhuang, ZP Li, J Okamoto, H Furuta, M Lee, YS Zeng, WF Oldfield, EH Vortmeyer, AO Weil, RJ TI Proteins and protein pattern differences between glioma cell lines and glioblastoma multiforme SO CLINICAL CANCER RESEARCH LA English DT Article ID DIFFERENTIALLY EXPRESSED GENES; FIBRILLARY ACIDIC PROTEIN; IN-VITRO; MOLECULAR SUBTYPES; MALIGNANT GLIOMAS; DNA; IDENTIFICATION; TUMORS; CLASSIFICATION; MICROARRAY AB Introduction: Research into the pathogenesis, molecular signaling, and treatment of glioblastoma multiforme (GBM) has traditionally been conducted using cell lines derived from malignant gliomas. We compared protein expression patterns between solid primary GBMs and GBM cell lines to identify proteins whose expression may be altered in cell culture. Methods: We cultured cell lines U87, U118, U251, and A172 and used tissue-selective microdissection of eight primary GBMs to obtain pure populations of tumor cells, which we studied using two-dimensional gel electrophoresis (2DGE) and examined using differential expression software. Select protein targets expressed differentially between GBM tumors and GBM cell lines were sequenced using tandem mass spectrometry. Results: Analysis of the primary GBM tumor samples (n = 8) and the GBM cell lines revealed reproducibly similar proteomic patterns for each group, which distinguished tumors from the cell lines. Gels contained up to 500 proteins that were consistently identified in the pH 4 to 7 range. Comparison of proteins identified in the GBM tumors and in the cell lines showed similar to 160 proteins that were gained and 60 proteins that were lost on culture. Using normalized intensity patterns from the 2DGE images, ANOVA tests were done and statistically significant spots were identified. Seven proteins found in the cell lines were significantly increased when compared with the GBM tumors (P < 0.05), whereas 10 proteins were significantly decreased from cell lines compared with the GBM tumors. Proteins identified included transcription factors, tumor suppressor genes, cytoskeletal proteins, and cellular metabolic proteins. Conclusion: Global protein and proteomic differences were identified between primary GBM tumor samples and GBM cell lines. The proteins identified by 2DGE analysis elucidate some of the selection pressures of in vitro culture, help accentuate the advantages and limitations of cell culture, and may aid comprehension of gliomagenesis and enhance development of new therapeutics. C1 Cleveland Clin Fdn, Brain Tumor Inst, Cleveland, OH 44195 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Saga Med Sch, Dept Neurosurg, Saga, Japan. Catholic Univ, Dept Pathol, Seoul, South Korea. Sun Yat Sen Univ, Zhongshan Med Coll, Dept Pathol, Guangzhou, Guangdong, Peoples R China. RP Weil, RJ (reprint author), Cleveland Clin Fdn, Brain Tumor Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM weilr@ccf.org NR 46 TC 46 Z9 47 U1 1 U2 9 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 MAY 15 PY 2005 VL 11 IS 10 BP 3624 EP 3632 DI 10.1158/1078-0432.CCR-04-2115 PG 9 WC Oncology SC Oncology GA 925XJ UT WOS:000229086600005 PM 15897557 ER PT J AU Ho, M Hassan, R Zhang, JL Wang, QC Onda, M Bera, T Pastan, I AF Ho, M Hassan, R Zhang, JL Wang, QC Onda, M Bera, T Pastan, I TI Humoral immune response to mesothelin in mesothelioma and ovarian cancer patients SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN TUMOR-ANTIGENS; ANTIBODY-RESPONSE; T-LYMPHOCYTES; DIFFERENTIATION; EXPRESSION; GENERATION; CELLS AB Purpose: Mesothelin is a glycosyl-phosphaticlylinositol - anchored glycoprotein present on the cell surface. Mesothelin is a differentiation antigen that is highly expressed on mesothelioma, ovarian cancer, and pancreatic cancer. The existence of a spontaneous humoral immune response to mesothelin in humans has not been fully studied. Here we addressed the issue of whether mesothelin elicits a humoral immune response in patients with mesothelioma and ovarian cancer. Experimental Design: Using an ELISA, we analyzed immunoglobulin G antibodies specific for mesothelin in sera from patients with mesothelioma and epithelial ovarian cancer. Tumor specimens were examined by immunohistochemistry for mesothelin protein expression. Results: Elevated levels of mesothelin-specific antibodies were detected in the sera of 39.1% of patients with mesothelioma (27 of 69 patients) and 41.7% with epithelial ovarian cancer (10 of 24 patients) when compared with a normal control population (44 blood donors; P < 0.01 for both mesothblioma and ovarian cancer). We also found that 53% to 56% of patients with mesothelin immunostaining-positive mesothelioma and ovarian cancer had antibodies specific for mesothelin, whereas only 0% to 8% of patients with negative mesothelin immunostaining had detectable mesothelin-specific antibodies (X-2 test: P < 0.01 for mesothelioma and P = 0.025 for ovarian cancer). Conclusions: Our findings indicate that mesothelin is a new tumor antigen in patients with mesotheliom and ovarian cancer and the immunogenicity of mesothelin is associated with its high expression on the tumor cells. Mesothelin represents an excellent target for immunebased therapies. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov RI Ho, Mitchell/F-5059-2015 NR 20 TC 100 Z9 101 U1 2 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 MAY 15 PY 2005 VL 11 IS 10 BP 3814 EP 3820 DI 10.1158/1078-0432.CCR-04-2304 PG 7 WC Oncology SC Oncology GA 925XJ UT WOS:000229086600029 PM 15897581 ER PT J AU Holleran, JL Parise, RA Joseph, E Eiseman, JL Covey, JM Glaze, ER Lyubimov, AV Chen, YF D'Argenio, D Egorin, MJ AF Holleran, JL Parise, RA Joseph, E Eiseman, JL Covey, JM Glaze, ER Lyubimov, AV Chen, YF D'Argenio, D Egorin, MJ TI Plasma pharmacokinetics, oral bioavailability, and interspecies scaling of the DNA methyltransferase inhibitor, zebularine SO CLINICAL CANCER RESEARCH LA English DT Article ID CANCER; METHYLATION AB Purpose: Zebularine is a DNA methyltransferase inhibitor proposed for clinical evaluation. Experimental Design: We developed a liquid chromatography/mass spectrometry assay and did i.v. and oral studies in mice, rats, and rhesus monkeys. Results: In mice, plasma zebularine concentrations declined with terminal half-lives (t(1/2)) of 40 and 91 minutes after 100 mg/kg i.v. and 1,000 mg/kg given orally, respectively. Zebularine plasma concentration versus time curves (area under the curve) after 100 mg/kg i.v. and 1,000 mg/kg given orally were 7,323 and 4,935 μ g/mL min, respectively, corresponding to a total body clearance (CLtb) of 13.65 mL/min/kg, apparent total body clearance (CLapp) of 203 mL/min/kg, and oral bioavailability of 6.7%. In rats, plasma zebularine concentrations declined with t(1/2) of 363, 110, and 126 minutes after 50 mg/kg i.v., 250 mg/kg given orally, and 500 mg/kg given orally, respectively. Zebularine areas under the curve after 50 mg/kg i.v., 250 mg/kg given orally, and 500 mg/kg given orally were 12,526,1,969, and 7,612 μ g/mL min, respectively, corresponding to a CLtb of 3.99 mL/min/kg for 50 mg/kg i.v. and CL,pp of 127 and 66 mL/min/kg for 250 and 500 mg/kg given orally, respectively. Bioavailabilities of 3.1% and 6.1% were calculated for the 250 and 500 mg/kg oral doses, respectively. In monkeys, zebularine t(1/2) was 70 and 150 minutes, CLtb was 3.55 and 10.85 mL/min/kg after i.v. administration, and CLapp was 886 and 39,572 mL/min/kg after oral administration of 500 and 1,000 mg/kg, respectively. Zebularine oral bioavailability was < 1 % in monkeys. Interspecies scaling produced the following relationship: CLtb = 6.46(weight(0.9)). Conclusions: Zebularine has limited oral bioavailability. Interspecies scaling projects a CLtb Of 296 mL/min in humans. C1 Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Univ Illinois, Dept Pharmacol, Toxicol Res Lab, Chicago, IL USA. Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. RP Egorin, MJ (reprint author), Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Room G27E,Hillman Res Pavil 5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM egorinmj@upmc.edu FU NCI NIH HHS [P30CA47904, N01-CM-07106, N01-CM-87103]; NIBIB NIH HHS [P41-EB001978] NR 15 TC 58 Z9 60 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 MAY 15 PY 2005 VL 11 IS 10 BP 3862 EP 3868 DI 10.1158/1078-0432.CCR-04-2406 PG 7 WC Oncology SC Oncology GA 925XJ UT WOS:000229086600035 PM 15897587 ER PT J AU Li, K Thomasson, D Ketai, L Contag, C Pomper, M Wright, M Bray, M AF Li, K Thomasson, D Ketai, L Contag, C Pomper, M Wright, M Bray, M TI Potential applications of conventional and molecular imaging to biodefense research SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PUBLIC-HEALTH MANAGEMENT; EBOLA HEMORRHAGIC-FEVER; IN-VIVO; INHALATIONAL ANTHRAX; BIOLOGICAL WEAPON; CONTRAST AGENTS; BIOTERRORISM EXPOSURE; CYNOMOLGUS MACAQUES; DENDRITIC CELLS; VIRUS-INFECTION AB Imaging methods that visualize the structure and function of the living body are widely used in patient care and biomedical research, but their full potential has not yet been applied to the study and treatment of the severe illnesses caused by pathogens of biodefense concern. "Conventional" imaging techniques (e.g., radiography, computed tomography, ultrasound, or magnetic resonance imaging) delineate anatomic changes in tissues, whereas "molecular" methods employ magnetic resonance, positron emission tomography, single-photon emission computed tomography, or optical (fluorescence or bioluminescence) imaging to detect biochemical reactions that accompany pathogen replication or host responses. We review the basic principles of these methods, describe the diseases caused by 6 pathogens classified as category A or B bioterror agents (anthrax, plague, tularemia, filoviral hemorrhagic fever, smallpox, and aerosolized equine encephalitis virus infection), and discuss how imaging could be used to study their pathogenesis in laboratory animals and to diagnose and monitor infection in humans. C1 NIAID, Biodef Clin Res Branch, Off Clin Res, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. Univ New Mexico, Dept Radiol, Albuquerque, NM 87131 USA. Stanford Univ, Dept Pediat, BioX Program, Stanford, CA 94305 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. RP Bray, M (reprint author), NIAID, Biodef Clin Res Branch, Off Clin Res, NIH, 6700A Rockledge Dr, Bethesda, MD 20892 USA. EM mbray@niaid.nih.gov NR 54 TC 8 Z9 8 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2005 VL 40 IS 10 BP 1471 EP 1480 DI 10.1086/429723 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 917MG UT WOS:000228465500014 PM 15844070 ER PT J AU Sun, YX Zhou, J Liao, XD Lu, YX Deng, CX Huang, PT Chen, Q Yang, X AF Sun, YX Zhou, J Liao, XD Lu, YX Deng, CX Huang, PT Chen, Q Yang, X TI Disruption of Smad5 gene induces mitochondria-dependent apoptosis in cardiomyocytes SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE smad5; cardiomyocytes; mitochondria; apoptosis ID CYTOCHROME-C RELEASE; SMAD3-DEPENDENT MECHANISM; CASPASE ACTIVATION; HEPATOMA-CELLS; P53; GROWTH; BETA; LOCALIZATION; DEATH; MICE AB Our previous studies have shown that SMAD5, an important intracellular mediator of transforming growth factor β (TGF-β) family, is required for normal development of the cardiovascular system in vivo. In the current study, we reported that the lack of the Smad5 gene resulted in apoptosis of cardiac myocytes in vivo. To further investigate the mechanism of the Smad5 gene in cardiomyocyte apoptosis, the embryonic stern (ES) cell differentiation system was employed. We found that the myotubes that differentiated from the homozygous Smad5(ex6/cx6) mutant ES cells underwent collapse and degeneration during the late stages of in vitro differentiation, mimicking the in vivo observation. By electron microscopy, abnormal swollen mitochondria were observed in cardiomyocytes both from Smad5-deficient embryos and from ES-differentiated cells. There was also a significant reduction in mitochondrial membrane potential (&UDelta;ψ(m)) and a leakage of cytochrome c from mitochondria into the cytosol of myocytes differentiated from Smad5 mutant ES cells. The expression of p53 and p21 was found to be elevated in the differentiated Smad5 mutant myocytes, and this was accompanied by an up-regulation in caspase 3 expression. These results suggest that the Smad5-mediated TGF-β signals may protect cardiomyocytes from apoptosis by maintaining the integrity of the mitochondria, probably through suppression of p53 mediated pathways. © 2005 Elsevier Inc. All rights reserved. C1 Inst Biotechnol, Genet Lab Dev & Dis, Beijing 100071, Peoples R China. Chinese Acad Sci, Inst Zool, Natl Key Lab Bio Membrane & Membrane Engn, Beijing 100080, Peoples R China. NIDDKD, Bethesda, MD 20892 USA. RP Yang, X (reprint author), Inst Biotechnol, Genet Lab Dev & Dis, 20 Dongdajie, Beijing 100071, Peoples R China. EM yangx@nic.bmi.ac.cn RI deng, chuxia/N-6713-2016; OI Chen, Quan/0000-0001-7539-8728 NR 32 TC 11 Z9 11 U1 0 U2 7 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 15 PY 2005 VL 306 IS 1 BP 85 EP 93 DI 10.1016/j.yexcr.2005.02.012 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 926PF UT WOS:000229134400009 PM 15878335 ER PT J AU Dougherty, GW Chopp, T Qi, S Cutler, ML AF Dougherty, GW Chopp, T Qi, S Cutler, ML TI The Ras suppressor Rsu-1 binds to the LIM 5 domain of the adaptor protein PINCH1 and participates in adhesion-related functions SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Rsu-1; leucine rich repeat; PINCH; LIM domain; Ras; Jun kinase ID INTEGRIN-LINKED KINASE; FOCAL ADHESION; CELL-ADHESION; 2-HYBRID SYSTEM; ACTIVATED RAS; CANCER CELLS; MAP KINASE; GROWTH; NCK; IDENTIFICATION AB Rsu-1 is a highly conserved leucine rich repeat (LRR) protein that is expressed ubiquitously in mammalian cells. Rsu-1 was identified based on its ability to inhibit transformation by Ras, and previous studies demonstrated that ectopic expression of Rsu-1 inhibited anchorage-independent growth of Ras-transformed cells and human tumor cell lines. Using GAL4-based yeast two-hybrid screening, the LIM domain protein, PINCH1, was identified as the binding partner of Rsu-1. PINCH1 is an adaptor protein that localizes to focal adhesions and it has been implicated in the regulation of adhesion functions. Subdomain mapping in yeast revealed that Rsu-1 binds to the LIM 5 domain of PINCH 1, a region not previously identified as a specific binding domain for any other protein. Additional testing demonstrated that PINCH2, which is highly homologous to PINCH1, exceptintheLIM 5 domain, does not interact with Rsu-1. Glutathione transferase fusion protein binding studies determined that the LRR region of Rsu-1 interacts with PINCH1. Transient expression studies using epitope-tagged Rsu-I and PINCH1 revealed that Rsu-1 co-immunoprecipitated with PINCH1 and colocalized with vinculin at sites of focal adhesions in mammalian cells. In addition, endogenousP33 Rsu-1 from 293T cells co-immunoprecipitated with transiently expressed myc-tagged PINCH 1. Furthermore, RNA-induced reduction in Rsu-I RNA and protein inhibited cell attachment, and while previous studies demonstrated that ectopic expression of Rsu1 inhibited Jun kinase activation, the depletion of Rsu-1 resulted inactivation of Jun and p38 stress kinases. These studies demonstrate that Rsu1 interacts with PINCH] in mammalian cells and functions, in part, by altering cell adhesion. Published by Elsevier Inc. C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. NIDCD, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. RP Cutler, ML (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, 4301 Jones Bridge Rd,B3122, Bethesda, MD 20814 USA. EM mcutler@usuhs.mil NR 51 TC 47 Z9 50 U1 0 U2 3 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 15 PY 2005 VL 306 IS 1 BP 168 EP 179 DI 10.1016/j.yexcr.2005.01.025 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 926PF UT WOS:000229134400016 PM 15878342 ER PT J AU Ridnour, LA Sim, JE Choi, J Dickinson, DA Forman, HJ Ahmad, IM Coleman, MC Hunt, CR Goswami, PC Spitz, DR AF Ridnour, LA Sim, JE Choi, J Dickinson, DA Forman, HJ Ahmad, IM Coleman, MC Hunt, CR Goswami, PC Spitz, DR TI Nitric oxide-induced resistance to hydrogen peroxide stress is a glutamate cysteine ligase activity-dependent process SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE nitric oxide; stress response; hydrogen peroxide; glutamate cysteine ligase; glutathione; thiols; free radicals ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; PERFORMANCE LIQUID-CHROMATOGRAPHY; CHINESE-HAMSTER FIBROBLASTS; INDUCED OXIDATIVE STRESS; GLUTATHIONE SYNTHESIS; ESCHERICHIA-COLI; RAT HEPATOCYTES; INDUCED CYTOTOXICITY; CELLULAR-RESISTANCE; ENDOTHELIAL-CELLS AB Nitric oxide ((NO)-N-&BULL;) is a reactive nitrogen species known to be involved in cytotoxic processes. Cells respond to cytotoxic injury by stress response induction leading to the development of cellular resistance. This report describes an (NO)-N-&BULL;-induced stress response in Chinese hamster fibroblasts (HA1), which leads to glutathione synthesis-dependent resistance to H2O2-mediated oxidative stress. The development of resistance to H2O2 was completely abolished by the inhibition of glutamate cysteine ligase (GCL) during the first 8 h of recovery after (NO)-N-&BULL; exposure. Altered thiol metabolism was observed immediately after (NO)-N-&BULL; exposure as demonstrated by up to 75% decrease in intracellular thiol pools (glutathione, γ-glutamylcysteine, and cysteine), which then reaccumulated during the (NO)-N-&BULL;-mediated development of resistance. Immunoreactive protein and activity associated with GCL decreased immediately after exposure to (NO)-N-&BULL; and then reaccumulated during the development of resistance to H2O2 challenge. Moreover, compared to N-2 controls the activity levels of GCL in (NO)-N-&BULL;-exposed cells increased approximately twofold 24 h after H2O2 challenge. These results demonstrate that (NO)-N-&BULL; exposure is capable of inducing an adaptive response to H2O2-mediated oxidative stress in mammalian cells, which involves alterations in thiol metabolism and is dependent upon glutathione synthesis and increased GCL activity. © 2005 Elsevier Inc. All rights reserved. C1 Washington Univ, Sch Med, Div Radiat & Canc Biol, Dept Radiat Oncol, St Louis, MO 63108 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. Univ Calif Merced, Sch Nat Sci, Merced, CA 95344 USA. Univ Alabama, Sch Publ Hlth, Dept Environm Hlth Sci, Birmingham, AL 35294 USA. Univ Iowa, Free Rad & Radiat Biol Program, Dept Radiat Oncol, Holden Comprehens Canc Ctr,Med Labs B180, Iowa City, IA 52242 USA. RP Ridnour, LA (reprint author), Washington Univ, Sch Med, Div Radiat & Canc Biol, Dept Radiat Oncol, 4511 Forest Pk Blvd,Room 411, St Louis, MO 63108 USA. EM ridnourl@mail.nih.gov OI Forman, Henry Jay/0000-0001-5838-2791 FU NCI NIH HHS [R29CAG9593]; NHLBI NIH HHS [2R01HL51469]; NIEHS NIH HHS [ES05511, F32ES05781] NR 59 TC 22 Z9 23 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY 15 PY 2005 VL 38 IS 10 BP 1361 EP 1371 DI 10.1016/j.freeradbiomed.2005.01.023 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 924ND UT WOS:000228984600009 PM 15855054 ER PT J AU Lin, ZC Walther, D Yu, XY Li, SX Drgon, T Uhl, GR AF Lin, ZC Walther, D Yu, XY Li, SX Drgon, T Uhl, GR TI SLC18A2 promoter haplotypes and identification of a novel protective factor against alcoholism SO HUMAN MOLECULAR GENETICS LA English DT Article ID VESICULAR MONOAMINE TRANSPORTER-2; SINGLE-NUCLEOTIDE POLYMORPHISMS; DOPAMINE TRANSPORTER; MOLECULAR-CLONING; SEQUENCE VARIANTS; GENE-EXPRESSION; CANDIDATE GENES; KNOCKOUT MICE; VMAT2; AMPHETAMINE AB The vesicular monoamine transporter 2 (VMAT2, SLC18A2) takes up cytosolic monoamines into intracellular secretory vesicles, preventing their neurotoxicity in the cytosol and discharging them into extracellular space by exocytosis. It has been shown that one-copy deletion of the VMAT2 gene increases locomotion activity significantly in response to drug treatments and dopamine neuron death rate in response to neurotoxin treatments in knockout mice. Little is known about promoter polymorphisms and their influence on SLC18A2 promoter activity. We have re-sequenced a 17.4 kb DNA in the SLC18A2 promoter region for Caucasians and revealed 47 polymorphisms that confer 13 haplotypes. One of the haplotypes reaches a frequency as high as 65%, likely due to positive selection. In vitro analysis showed a 20% difference in promoter activity between two frequent haplotypes and identified some of the polymorphisms that influence promoter activity. Four haplotype-defining single nucleotide polymorphisms (hdSNPs) can define the frequent haplotypes and by genotyping these hdSNPs, we find that haplotypes with -14234G and -2504C of SLC18A2 promoter region represent a protective factor against alcoholism (P = 0.0038 by Fisher's exact tests). Therefore, SLC18A2 promoter haplotypes defined here create a foundation for transcriptional characterization of individuality and for association study on monoamine-related human diseases. C1 NIDA, Mol Neurobiol Branch, NIH, IRP,DHHS, Baltimore, MD 21224 USA. RP Lin, ZC (reprint author), NIDA, Mol Neurobiol Branch, NIH, IRP,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM zlin@intra.nida.nih.gov NR 40 TC 34 Z9 34 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 MAY 15 PY 2005 VL 14 IS 10 BP 1393 EP 1404 DI 10.1093/hmg/ddi148 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 931HR UT WOS:000229476900015 PM 15829504 ER PT J AU Zhou, QF Shung, KK Zhang, QQ Djuth, FT AF Zhou, QF Shung, KK Zhang, QQ Djuth, FT TI Structure and electrical properties of sol-gel-derived (001)-oriented Pb[Yb1/2Nb1/2]O-3-PbTiO3 thin films grown on LaNbO3/Si(001) substrates SO JOURNAL OF APPLIED PHYSICS LA English DT Article ID TRANSVERSE PIEZOELECTRIC PROPERTIES; SINGLE-CRYSTALS; PB(YB1/2NB1/2)O-3-PBTIO3; DEPOSITION; BEHAVIOR AB (1 -x)Pb[Yb1/2Nb1/2]O-3-xPbTiO(3) (PYbN-PT, x=0.5) oriented thin films were deposited onto LaNiO3 (LNO)/Si substrates by sol-gel processing. Highly (001)-oriented LNO thin films were prepared by a simple metal-organic decomposition technique when sample annealed at 650 degrees C using a rapid thermal annealing. The room -temperature resistivity of LNO thin films was 0.65 m Omega cm. X-ray diffraction analysis revealed that the films of PYbN-PT were highly (001) oriented along LNO/Si substrates. No pyrochlore phase was observed by X-ray diffraction and films had a uniform grain size of about 80-120 nm. At 1 kHz, the dielectric permittivity was 920 and dielectric loss is about 0.035. The ferroelectric films displayed good P-E hysteresis characteristic and better temperature stabilization compared with the films that have low Curie temperature. (c) 2005 American Institute of Physics. C1 Univ So Calif, NIH, Transducer Resource Ctr, Los Angeles, CA 90089 USA. Univ So Calif, NIH, Dept Biomed Engn, Los Angeles, CA 90089 USA. Geospace Res Inc, El Segundo, CA 90245 USA. RP Zhou, QF (reprint author), Univ So Calif, NIH, Transducer Resource Ctr, Los Angeles, CA 90089 USA. EM qifazhou@usc.edu NR 19 TC 5 Z9 5 U1 1 U2 8 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-8979 EI 1089-7550 J9 J APPL PHYS JI J. Appl. Phys. PD MAY 15 PY 2005 VL 97 IS 10 AR 104103 DI 10.1063/1.1894582 PN 1 PG 4 WC Physics, Applied SC Physics GA 940TO UT WOS:000230168100102 ER PT J AU Balla, T AF Balla, T TI Inositol-lipid binding motifs: signal integrators through protein-lipid and protein-protein interactions SO JOURNAL OF CELL SCIENCE LA English DT Review DE phosphoinositide; pleckstrin homology domain; intracellular signaling; inositol lipid kinase; inositol lipid phosphatase; phosphorylation ID PLECKSTRIN HOMOLOGY DOMAINS; HETEROTRIMERIC G-PROTEINS; CLATHRIN-COATED PITS; BETA-GAMMA-SUBUNITS; CRYSTAL-STRUCTURE; PHOSPHOINOSITIDE-BINDING; STRUCTURAL BASIS; FERM DOMAIN; PX DOMAIN; PH DOMAIN AB Inositol lipids have emerged as universal lipid regulators of protein signaling complexes in defined membrane compartments. The number of protein modules that are known to recognise these membrane lipids is rapidly increasing. Pleckstrin homology domains, FYVE domains, PX domains, ENTH domains, CALM domains, PDZ domains, PTB domains and FERM domains are all inositide-recognition modules. The latest additions to this list are members of the clathrin adaptor protein and arrestin families. Initially, inositol lipids were believed to recruit signaling molecules to specific membrane compartments, but many of the domains clearly do not possess high enough affinity to act alone as localisation signals. Another important notion is that some (and probably most) of these protein modules also have protein binding partners, and their protein- and lipid-binding activities might influence one another through allosteric mechanisms. Comparison of the structural features of these domains not only reveals a high degree of conservation of their lipid interaction sites but also highlights their evolutionary link to protein modules known for protein-protein interactions. Protein-protein interactions involving lipid-binding domains could serve as the basis for phosphoinositide-induced conformational regulation of target proteins at biological membranes. Therefore, these modules function as crucially important signal integrators, which explains their involvement in a broad range of regulatory functions in eukaryotic cells. C1 NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Balla, T (reprint author), NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. EM ballat@mail.nih.gov OI Balla, Tamas/0000-0002-9077-3335 NR 131 TC 162 Z9 167 U1 4 U2 26 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 MAY 15 PY 2005 VL 118 IS 10 BP 2093 EP 2104 DI 10.1242/jcs.02387 PG 12 WC Cell Biology SC Cell Biology GA 937TW UT WOS:000229949600004 PM 15890985 ER PT J AU Stuelten, CH Byfield, SD Arany, PR Karpova, TS Stetler-Stevenson, WG Roberts, AB AF Stuelten, CH Byfield, SD Arany, PR Karpova, TS Stetler-Stevenson, WG Roberts, AB TI Breast cancer cells induce stromal fibroblasts to express MMP-9 via secretion of TNF-alpha and TGF-beta SO JOURNAL OF CELL SCIENCE LA English DT Article DE breast cancer; coculture; MMP-9; TGF-beta; TNF-alpha ID GROWTH-FACTOR-BETA; NECROSIS-FACTOR-ALPHA; MATRIX METALLOPROTEINASES; IV COLLAGENASE; EXTRACELLULAR-MATRIX; RECEPTOR TRANSACTIVATION; 72-KDA GELATINASE; TISSUE INHIBITOR; EPITHELIAL-CELLS; TUMOR INVASION AB We used 2D-cocultures employing fibroblasts of different genetic backgrounds and MCF10A-derived human breast epithelial cells of increasingly malignant potential to investigate tumor-stroma interactions in breast cancer and to identify possible signaling pathways involved. Tumor cells induced expression of matrix-metalloproteinase 9 (MMP-9) in fibroblasts in a pattern dependent on the degree of their malignancy. In-situ zymography localized the main gelatinolytic activity around stromal cells in cocultures and xenografted tumors. Use of Smad3 knockout fibroblasts, small molecule inhibitors, and neutralizing antibodies showed that MMP-9 expression was induced by tumor cell-derived TNF-alpha and TGF-beta, dependent on Smad-, Ras-, and PI3-kinase-signaling, and likewise modulated by subsequent HGF- and EGF-signaling. Together, our results indicate that MMP-9 levels in tumor fibroblasts are regulated by a complex tumor-stroma cross-talk, involving multiple ligands and cellular signaling pathways. C1 NCI, Lab Cell Regulat & Carcinogenesis, CCR, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Genet Express, CCR, NIH, Bethesda, MD 20892 USA. NCI, Canc & Cell Biol Branch, CCR, NIH, Bethesda, MD 20892 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, CCR, NIH, Bethesda, MD 20892 USA. EM robertsa@dce41.nci.nih.gov RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 66 TC 116 Z9 130 U1 2 U2 15 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 MAY 15 PY 2005 VL 118 IS 10 BP 2143 EP 2153 DI 10.1242/jcs.02334 PG 11 WC Cell Biology SC Cell Biology GA 937TW UT WOS:000229949600008 PM 15855236 ER PT J AU Gomez, G Ramirez, CD Rivera, J Patel, M Norozian, F Wright, HV Kashyap, MV Barnstein, BO Fischer-Stenger, K Schwartz, LB Kepley, CL Ryan, JJ AF Gomez, G Ramirez, CD Rivera, J Patel, M Norozian, F Wright, HV Kashyap, MV Barnstein, BO Fischer-Stenger, K Schwartz, LB Kepley, CL Ryan, JJ TI TGF-beta 1 inhibits mast cell Fc epsilon RI expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; IGE; SUBUNIT; RELEASE; DISEASE; PROLIFERATION; MECHANISMS; RECEPTORS; MIGRATION AB Mast cell activation through the high affinity IgE receptor (Fc epsilon RI) is a critical component of atopic inflammation. The cytokine TGF-beta 1 has been shown to inhibit IgE-dependent mast cell activation, possibly serving to dampen mast cell-mediated inflammatory responses. We present proof that TGF-beta 1 inhibits mast cell Fc epsilon RI expression through a reversible pathway that diminishes protein, but not mRNA, expression of the Fc epsilon RI subunit proteins alpha, beta, and gamma. The stability of the expressed proteins and the assembled cell surface complex was unaltered by TGF-beta 1 treatment. However, TGF-beta 1 decreased the rate of Fc epsilon RI beta-chain synthesis, arguing that this inhibitory cytokine exerts its effects at the level of mRNA translation. TGF-beta 1 consistently diminished Fc epsilon RI expression on cultured human or mouse mast cells as well as freshly isolated peritoneal mast cells. The related cytokines, TGF-beta 2 and TGF-beta 3, had similar effects. We propose that TGF-beta 1 acts as a negative regulator of mast cell function, in part by decreasing Fc epsilon RI expression. C1 Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA. Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23284 USA. NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. Univ Richmond, Dept Biol, Richmond, VA 23173 USA. RP Ryan, JJ (reprint author), Virginia Commonwealth Univ, Dept Biol, Box 842012, Richmond, VA 23284 USA. EM jjryan@saturn.vcu.edu FU NCI NIH HHS [1R01CA91839, R01 CA091839]; NIAID NIH HHS [1R01AI43433, R01 AI020487, R01 AI027517] NR 34 TC 52 Z9 53 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2005 VL 174 IS 10 BP 5987 EP 5993 PG 7 WC Immunology SC Immunology GA 924DL UT WOS:000228958900012 PM 15879091 ER PT J AU Hodge, JW Chakraborty, M Kudo-Saito, C Garnett, CT Schlom, J AF Hodge, JW Chakraborty, M Kudo-Saito, C Garnett, CT Schlom, J TI Multiple costimulatory modalities enhance CTL avidity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; CARCINOEMBRYONIC ANTIGEN GENE; CYTOTOXIC T-LYMPHOCYTES; REGIONAL LYMPH-NODES; DENDRITIC CELLS; FUNCTIONAL AVIDITY; ANTITUMOR-ACTIVITY; TRANSGENIC MICE; TUMOR-ANTIGEN; SELF-ANTIGEN AB Recent studies in both animal models and clinical trials have demonstrated that the avidity of T cells is a major determinant of antitumor and antiviral immunity. In this study, we evaluated several different vaccine strategies for their ability to enhance both the quantity and avidity of CTL responses. CD8(+) T cell quantity was measured by tetramer binding precursor frequency, and avidity was measured by both tetramer dissociation and quantitative cytolytic function. We have evaluated a peptide, a viral vector expressing the Ag transgene alone, with one costimulatory molecule (B7-1), and with three costimulatory molecules (B7-1, ICAM-1, and LFA-3), with anti-CTLA-4 mAb, with GM-CSF, and combinations of the above. We have evaluated these strategies in both a foreign Ag model using P-galactosidase as immunogen, and in a "self" Ag model, using carcinoembryonic Ag as immunogen in carcinoembryonic Ag transgenic mice. The combined use of several of these strategies was shown to enhance not only the quantity, but, to a greater magnitude, the avidity of T cells generated; a combination strategy is also shown to enhance antitumor effects. The results reported in this study thus demonstrate multiple strategies that can be used in both antitumor and antiviral vaccine settings to generate higher avidity host T cell responses. 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,Bldg 10,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM jsl141c@nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 FU NCI NIH HHS [Z01 BC010426-06] NR 64 TC 85 Z9 87 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2005 VL 174 IS 10 BP 5994 EP 6004 PG 11 WC Immunology SC Immunology GA 924DL UT WOS:000228958900013 PM 15879092 ER PT J AU Min, B Yamane, H Hu-Li, J Paul, WE AF Min, B Yamane, H Hu-Li, J Paul, WE TI Spontaneous and homeostatic proliferation of CD4 T cells are regulated by different mechanisms SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NAIVE T-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; CUTTING EDGE; IN-VIVO; MEMORY CELLS; IL-7; COMPETITION; LYMPHOPENIA; EXPANSION; SURVIVAL AB Transfer of naive CD4 T cells into lymphopenic mice initiates a proliferative response of the transferred cells, often referred to as homeostatic proliferation. Careful analysis reveals that some of the transferred cells proliferate rapidly and undergo robust differentiation to memory cells, a process we have designated spontaneous proliferation, and other cells proliferate relatively slowly and show more limited evidence of differentiation. In this study we report that spontaneous proliferation is IL-7 independent, whereas the slow proliferation (referred to as homeostatic proliferation) is IL-7 dependent. Administration of IL-7 induces homeostatic proliferation of naive CD4 T cells even within wild-type recipients. Moreover, the activation/differentiation pattern of the two responses are clearly distinguishable, indicating that different activation mechanisms may be involved. Our results reveal the complexity and heterogeneity of lymphopenia-driven T cell proliferation and suggest that they may have fundamentally distinct roles in the maintenance of CD4 T cell homeostasis. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Min, B (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM minb@ccf.org NR 32 TC 113 Z9 116 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 MAY 15 PY 2005 VL 174 IS 10 BP 6039 EP 6044 PG 6 WC Immunology SC Immunology GA 924DL UT WOS:000228958900018 PM 15879097 ER PT J AU Pitcher, LA Mathis, MA Subramanian, S Young, JA Wakeland, EK Love, PE van Oers, NSC AF Pitcher, LA Mathis, MA Subramanian, S Young, JA Wakeland, EK Love, PE van Oers, NSC TI Selective expression of the 21-kilodalton tyrosine-phosphorylated form of TCR promotes the emergence of T cells with autoreactive potential SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ALTERED PEPTIDE LIGANDS; THYMOCYTE SELECTION; LYMPHOPROLIFERATIVE DISORDERS; INTRACELLULAR SIGNALS; NEGATIVE SELECTION; SURFACE EXPRESSION; ZAP-70 ACTIVATION; SELF-RECOGNITION; FOREIGN ANTIGEN; TRANSGENIC MICE AB T cells undergo negative selection in the thymus to eliminate potentially autoreactive cells. The signals generated through the alpha beta TCR following receptor interactions with peptide/MHC complexes in the thymus control these selection processes. Following receptor ligation, a fraction of the TCR zeta subunit appears as two distinct tyrosine-phosphorylated forms of 21 and 23 kDa (p21 and p23). Previous data have reported elevated levels of p21 in some murine models of autoimmunity. We have examined the contributions of both the p21 and p23 to T cell negative selection in the HY TCR-transgenic system using ITAM-substituted TCR zeta and CD3 epsilon transgenic mice. Expression of just p21, in the absence of p23, partially impairs negative selection of self-reactive HY-specific T cells. This results in the emergence of potentially autoreactive peripheral T cells and an elevated population of CD11b(+)B220(+) B cells in the spleen. These data clearly identify a specific and unique role for p21 during negative selection. C1 Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Microbiol, Dallas, TX 75390 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP van Oers, NSC (reprint author), Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75390 USA. EM nicolai.vanoers@utsouthwestern.edu NR 42 TC 13 Z9 13 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 MAY 15 PY 2005 VL 174 IS 10 BP 6071 EP 6079 PG 9 WC Immunology SC Immunology GA 924DL UT WOS:000228958900022 PM 15879101 ER PT J AU Kurosaka, K Chen, Q Yarovinsky, F Oppenheim, JJ Yang, D AF Kurosaka, K Chen, Q Yarovinsky, F Oppenheim, JJ Yang, D TI Mouse cathelin-related antimicrobial peptide chemoattracts leukocytes using formyl peptide receptor-like 1/mouse formyl peptide receptor-like 2 as the receptor and acts as immune adjuvant SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EOSINOPHIL-DERIVED NEUROTOXIN; DENDRITIC CELL MATURATION; N-FORMYLPEPTIDE RECEPTOR; TRANSFER-RNA SYNTHETASE; ANTIBACTERIAL PEPTIDE; ANTIBIOTIC LL-37/HCAP-18; DIFFERENTIAL REGULATION; HUMAN NEUTROPHILS; INNATE IMMUNITY; A(4) RECEPTORS AB Mammalian antimicrobial proteins, such as defensins and cathelicidin, have stimulating effects on host leukocytes. Cathelin-related antimicrobial peptide (CRAMP), the orthologue of human cathelicidin/LL-37, is the sole identified murine cathelicidin. CRAMP has been shown to have both antimicrobial and angiogenic activities. However, whether CRAMP, like human cathelicidin/LL-37, also exhibits a direct effect on the migration and function of leukocytes is not known. We have observed that CRAMP, like LL-37, was chemotactic for human monocytes, neutrophils, macrophages, and mouse peripheral blood leukocytes. CRAMP also induced calcium mobilization and the activation of MAPK in monocytes. CRAMP-induced calcium flux in monocytes was desensitized by MMK-1, an agonistic ligand specific for formyl peptide receptor-like-1 (FPRL1), and vice versa, suggesting the use of FPRL1 by CRAMP as a receptor. Furthermore, CRAMP induced the chemotaxis of human embryonic kidney 293 cells transfected with either FPRL1 or mouse formyl peptide receptor-2, the mouse homologue of FPRL1, but not by untransfected parental human embryonic kidney 293 cells, confirming the use of FPRL1/mouse formyl peptide receptor-2 by CRAMP. Injection of CRAMP into mouse air pouches resulted in the recruitment predominantly of neutrophils and monocytes, indicating that CRAMP acts as a chemotactic factor in vivo. Finally, simultaneous administration of OVA with CRAMP to mice promoted both Immoral and cellular Ag-specific immune responses. Thus, CRAMP functions as both a chemoattractant for phagocytic leukocytes and an enhancer of adaptive immune response. C1 Sci Applicat Int Corp, Basic Res Program, Ctr Canc Res, Lab Mol Immunoregulat, Frederick, MD 21702 USA. Sci Applicat Int Corp, Basic Res Program, NCI, NIH, Frederick, MD 21702 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Kurosaka, K (reprint author), Sci Applicat Int Corp, Basic Res Program, Ctr Canc Res, Lab Mol Immunoregulat, Bldg 560,Room 31-19, Frederick, MD 21702 USA. EM dyang@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 73 TC 122 Z9 127 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2005 VL 174 IS 10 BP 6257 EP 6265 PG 9 WC Immunology SC Immunology GA 924DL UT WOS:000228958900045 PM 15879124 ER PT J AU Silva, EM Guillermo, LVC Ribeiro-Gomes, FL De Meis, J Pereira, RMS Wu, ZQ Calegari-Silva, TC Seabra, SH Lopes, UG Siegel, RM DosReis, GA Lopes, MF AF Silva, EM Guillermo, LVC Ribeiro-Gomes, FL De Meis, J Pereira, RMS Wu, ZQ Calegari-Silva, TC Seabra, SH Lopes, UG Siegel, RM DosReis, GA Lopes, MF TI Caspase-8 activity prevents type 2 cytokine responses and is required for protective T cell-mediated immunity against Trypanosoma cruzi infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; LYMPHOPROLIFERATIVE SYNDROME; INCREASED SUSCEPTIBILITY; FAS LIGAND; DEATH; ACTIVATION; MICE; APOPTOSIS; FLIP; PROLIFERATION AB During Trypanosoma cruzi infection, T cells up-regulate caspase-8 activity. To assess the role of caspase-8 in T cell-mediated immunity, we investigated, the effects of caspase-8 inhibition on T cells in viral FLIP (v-FLIP) transgenic mice. Compared with wild-type controls, increased parasitemia was observed in v-FLIP mice infected with T. cruzi. There was a profound decrease in expansion of both CD4 and CD8 T cell subsets in the spleens of infected v-FLIP mice. We did not find differences in activation ratios of T cells from transgenic or wild-type infected mice. However, the numbers of memory/activated CD4 and CD8 T cells were markedly reduced in v-FLIP mice, possibly due to defective survival. We also found decreased production of IL-2 and increased secretion of type 2 cytokines, IL-4 and IL-10, which could enhance susceptibility to infection. Similar, but less pronounced, alterations were observed in mice treated with the caspase-8 inhibitor, zIETD. Furthermore, blockade of caspase-8 by zIETD in vitro mimicked the effects observed on T. cruzi infection in vivo, affecting the generation of activated/memory T cells and T cell cytokine production. Caspase-8 is also required for NF-kappa B signaling upon T cell activation. Blockade of caspase-8 by either v-FLIP expression or treatment with zIETD peptide decreased NF-kappa B responses to TCR:CD3 engagement in T cell cultures. These results suggest a critical role for caspase-8 in the establishment of T cell memory, cell signaling, and regulation of cytokine responses during protozoan infection. C1 Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Ctr Ciencias Saude, Ilha Fundao, BR-21944970 Rio De Janeiro, Brazil. NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Lopes, MF (reprint author), Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Ctr Ciencias Saude, Ilha Fundao, Bloco G, BR-21944970 Rio De Janeiro, Brazil. EM marcela1@biof.ufrj.br RI Siegel, Richard/C-7592-2009; lopes, marcela/E-2201-2012; Meis, Juliana/B-2211-2013; Ribeiro-Gomes, Flavia/F-7609-2015 OI Siegel, Richard/0000-0001-5953-9893; lopes, marcela/0000-0002-4508-0505; NR 55 TC 28 Z9 29 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 MAY 15 PY 2005 VL 174 IS 10 BP 6314 EP 6321 PG 8 WC Immunology SC Immunology GA 924DL UT WOS:000228958900052 PM 15879131 ER PT J AU Borjesson, DL Kobayashi, SD Whitney, AR Voyich, JM Argue, CM DeLeo, FR AF Borjesson, DL Kobayashi, SD Whitney, AR Voyich, JM Argue, CM DeLeo, FR TI Insights into pathogen immune evasion mechanisms: Anaplasma phagocytophilum fails to induce an apoptosis differentiation program in human neutrophils SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN GRANULOCYTIC EHRLICHIOSIS; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; BACTERIAL PATHOGENS; GENE-EXPRESSION; HL-60 CELLS; AGENT; INFECTION; CHAFFEENSIS; DISEASE AB Polymorphonuclear leukocytes (PMNs or neutrophils) are essential to human innate host defense. However, some bacterial pathogens circumvent destruction by PMNs and thereby cause disease. Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, survives within PMNs in part by altering normal host cell processes, such as production of reactive oxygen species (ROS) and apoptosis. To investigate the molecular basis of A. phagocytophilum survival within neutrophils, we used Affymetrix microarrays to measure global changes in human PMN gene expression following infection with A. phagocytophilum. Notably, A. phagocytophilum uptake induced fewer perturbations in host cell gene regulation compared with phagocytosis of Staphylococcus aureus. Although ingestion of A. phagocytophilum did not elicit significant PMN ROS, proinflammatory genes were gradually up-regulated, indicating delayed PMN activation rather than loss of proinflammatory capacity normally observed during phagocytosis-induced apoptosis. Importantly, ingestion of A. phagocytophilum failed to trigger the neutrophil apoptosis differentiation program that typically follows phagocytosis and ROS production. Heat-killed A. phagocytophilum caused some similar initial alterations in neutrophil gene expression and function, which included delaying normal PMN apoptosis and blocking Fas-induced programmed cell death. However, at 24 h, down-regulation of PMN gene transcription may be more reliant on active infection. Taken together, these findings suggest two separate antiapoptotic processes may work concomitantly to promote bacterial survival: 1) uptake of A. phagocytophilum fails to trigger the apoptosis differentiation program usually induced by bacteria, and 2) a protein or molecule on the pathogen surface can mediate an early delay in spontaneous neutrophil apoptosis. C1 Univ Minnesota, Coll Vet Med, Dept Vet Populat Med, St Paul, MN 55108 USA. NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. RP Borjesson, DL (reprint author), Univ Minnesota, Coll Vet Med, Dept Vet Populat Med, 1365 Gortner Ave, St Paul, MN 55108 USA. EM borje002@umn.edu OI DeLeo, Frank/0000-0003-3150-2516 FU NIAID NIH HHS [AI-51529] NR 29 TC 87 Z9 90 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2005 VL 174 IS 10 BP 6364 EP 6372 PG 9 WC Immunology SC Immunology GA 924DL UT WOS:000228958900058 PM 15879137 ER PT J AU Duray, PH Yin, SR Ito, Y Bezrukov, L Cox, C Cho, MS Fitzgerald, W Dorward, D Zimmerberg, J Margolis, L AF Duray, PH Yin, SR Ito, Y Bezrukov, L Cox, C Cho, MS Fitzgerald, W Dorward, D Zimmerberg, J Margolis, L TI Invasion of human tissue ex vivo by Borrelia burgdorferi SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN LYMPHOID-TISSUE; ROTATING-WALL VESSEL; LYME-DISEASE; SIMULATED MICROGRAVITY; GENETIC DIVERSITY; SENSU-STRICTO; HIV-INFECTION; OSPC; PHENOTYPE; DIFFERENTIATION AB Borrelia burgdorferi sensu stricto is an etiological agent of Lyme disease. The lack of an adequate ex vivo system for human tissue infection is an obstacle to fully understanding the molecular mechanisms of invasion of tissue by B. burgdorferi and its adaptation within the human host. Here, we report on the development of such a system. We inoculated blocks of human tonsillar tissue with B. burgdorferi spirochetes, cultured them in a low-shear rotating wall vessel (RWV) bioreactor, and analyzed them using light and electron microscopy, nested polymerase chain reaction (PCR), and quantitative real-time PCR. Also, we evaluated the expression of the outer surface proteins (Osps) OspA and OspC by use of quantitative Western blotting. Light and electron microscopic analysis revealed multiple spirochetes localized extracellularly within the tissue, and their identity was confirmed by PCR. Quantification of spirochetes inside the RWV-cultured tonsillar tissue demonstrated that the number of B. burgdorferi exceeded the initial inoculum by an order of magnitude, indicating that spirochetes replicated in the tissue. Electron microscopic analysis showed that some spirochetes were arranged in cystic structures and that invading spirochetes differentially expressed surface proteins; both of these features have been described for infected tissues in vivo. The system we have developed can be used to study B. burgdorferi pathogenesis under controlled conditions ex vivo, in particular to explore the gene activation responsible for the adaptation of B. burgdorferi to human tissue that leads to Lyme disease. C1 NICHHD, NASA,NAtl Inst Hlth Ctr Dimens Tissue Culture 3, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NICHHD, Dept Pathol, NIH, Bethesda, MD 20892 USA. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Duray, PH (reprint author), NICHHD, NASA,NAtl Inst Hlth Ctr Dimens Tissue Culture 3, Lab Cellular & Mol Biophys, NIH, 10 Ctr Dr,Bldg 10,Room 9D58, Bethesda, MD 20892 USA. EM paul.duray@med.va.gov; margolis@helix.nih.gov FU Intramural NIH HHS NR 36 TC 15 Z9 15 U1 0 U2 3 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 MAY 15 PY 2005 VL 191 IS 10 BP 1747 EP 1754 DI 10.1086/429632 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 917MB UT WOS:000228465000022 PM 15838803 ER PT J AU Hisada, M Biggar, RJ Li, HC Hanchard, B AF Hisada, M Biggar, RJ Li, HC Hanchard, B TI Comments on the brief report "Provirus load in breast milk and risk of mother-to-child transmission of human T lymphotropic virus type I" - Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID CELL LEUKEMIA/LYMPHOMA C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Rockville, MD USA. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. RP Biggar, RJ (reprint author), NCI, Div Canc Epidemiol, 6120 Execut Blvd,Rm 8014, Bethesda, MD 20814 USA. EM biggarb@mail.nih.gov NR 7 TC 1 Z9 1 U1 0 U2 0 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 MAY 15 PY 2005 VL 191 IS 10 BP 1781 EP 1781 DI 10.1086/429753 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 917MB UT WOS:000228465000029 ER PT J AU Masuda, R Monahan, JW Kashiwaya, Y AF Masuda, R Monahan, JW Kashiwaya, Y TI D-beta-hydroxybutyrate is neuroprotective against hypoxia in serum-free hippocampal primary cultures SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE ketone body; D-beta-hydroxybutyrate; hypoxia; hippocampal neurons; necrosis; apoptosis ID FOCAL CEREBRAL-ISCHEMIA; TRANSIENT FOREBRAIN ISCHEMIA; OXYGEN-GLUCOSE DEPRIVATION; CYTOCHROME-C; KETONE-BODIES; RAT-BRAIN; MITOCHONDRIAL RESPIRATION; PULMONARY APOPTOSIS; DNA FRAGMENTATION; RADICAL SCAVENGER AB Hypoxia decreased survival of cultured rat primary hippocampal neurons in a time dependent mariner. Addition of 4 mM Na D-beta-hydroxybutyrate (bHB), a ketone body, protected the cells for 2 hr and maintained the increase in survival compared to that of controls for up to 6 hr. Trypan blue exclusion indicated that acute cell death was reduced markedly after 2-hr exposure to hypoxia in the bHB-treated group. The presence of bHB also decreased the number of neurons exhibiting condensed nuclei visualized by propidium iodide, indicative of apoptosis. The mitochondrial transmembrane potential (E-m/c) was maintained for up to 2 hr exposure to hypoxia in the bHB-treated group, whereas the potential in the control group was decreased. Furthermore, cytochrome C release, caspase-3 activation, and poly (ADP-ribose) polymerase (PARP) cleavage were decreased in the bHB-treated group for the first 2 hr of exposure. These findings indicate that ketone bodies may be a candidate for widening the therapeutic window before thrombolytic therapy and at the same time decreasing apoptotic damage in the ischemic penumbra. (c) 2005 Wiley-Liss, Inc.*. C1 NIAAA, Lab Metabol Control, NIH, DHHS, Bethesda, MD 20892 USA. RP Kashiwaya, Y (reprint author), NIAAA, Lab Metabol Control, NIH, DHHS, 5625 Fishers Lane,Rm 2S28, Bethesda, MD 20892 USA. EM kashi@mail.nih.gov NR 64 TC 48 Z9 49 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAY 15 PY 2005 VL 80 IS 4 BP 501 EP 509 DI 10.1002/jnr.20464 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 922YO UT WOS:000228876000007 PM 15825191 ER PT J AU Covell, DG Wallqvist, A Huang, RL Thanki, N Rabow, AA Lu, XJ AF Covell, DG Wallqvist, A Huang, RL Thanki, N Rabow, AA Lu, XJ TI Linking tumor cell cytotoxicity to mechanism of drug action: An integrated analysis of gene expression, small-molecule screening and structural databases SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Review DE system biology; anticancer agents; drug resistance; stress response ID DEPENDENT QUERCETIN 2,3-DIOXYGENASE; FACTOR-KAPPA-B; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; INHIBITS GLYCOGEN-PHOSPHORYLASE; PROTEINASE-ACTIVATED RECEPTORS; DIRECT THROMBIN INHIBITORS; GROWTH-FACTOR EXPRESSION; IN-VITRO; RIBONUCLEOTIDE REDUCTASE; FUNCTIONAL-ANALYSIS AB An integrated, bioinformatic analysis of three databases comprising tumor-cell-based small molecule screening data, gene expression measurements, and PDB (Protein Data Bank) ligand-target structures has been developed for probing mechanism of drug action (MOA). Clustering analysis of GI(50) profiles for the NCI's database of compounds screened across a panel of tumor cells (NCI60) was used to select a subset of unique cytotoxic responses for about 4000 small molecules. Drug-gene-PDB relationships for this test set were examined by correlative analysis of cytotoxic response and differential gene expression profiles within the NCI60 and structural comparisons with known ligand-target crystallographic complexes. A survey of molecular features within these compounds finds thirteen conserved Compound Classes, each class exhibiting chemical features important for interactions with a variety of biological targets. Protein targets for an additional twelve Compound Classes could be directly assigned using drug-protein interactions observed in the crystallographic database. Results from the analysis of constitutive gene expressions established a clear connection between chemo-resistance and overexpression of gene families associated with the extracellular matrix, cytoskeletal organization, and xenobiotic metabolism. Conversely, chemo-sensitivity implicated overexpression of gene families involved in homeostatic functions of nucleic acid repair, aryl hydrocarbon metabolism, heat shock response, proteasome degradation and apoptosis. Correlations between chemo-responsiveness and differential gene expressions identified chemotypes with nonselective (i.e., many) molecular targets from those likely to have selective (i.e., few) molecular targets. Applications of data mining strategies that jointly utilize tumor cell screening, genomic, and structural data are presented for hypotheses generation and identifying novel anticancer candidates. Published 2005 Wiley-Liss, Inc.* C1 NCI, Dev Therapeut Program, Screening Technol Branch, Lab Computat Technol, Frederick, MD 21702 USA. NCI, Sci Applicat Int Corp, NIH, Frederick, MD 21702 USA. Astra Zeneca Corp, Macclesfield, Cheshire, England. RP Covell, DG (reprint author), NCI, Dev Therapeut Program, Screening Technol Branch, Lab Computat Technol, Frederick, MD 21702 USA. EM covell@ncifcrf.gov OI wallqvist, anders/0000-0002-9775-7469 FU NCI NIH HHS [N01-CO-12400] NR 218 TC 27 Z9 31 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD MAY 15 PY 2005 VL 59 IS 3 BP 403 EP 433 DI 10.1002/prot.20392 PG 31 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 921QJ UT WOS:000228779200002 PM 15778971 ER PT J AU Dostalova, L Kopsky, V Duskova, J Papezova, H Pacak, K Nedvidkova, J AF Dostalova, L Kopsky, V Duskova, J Papezova, H Pacak, K Nedvidkova, J TI Leptin concentrations in the abdominal subcutaneous adipose tissue of patients with anorexia nervosa assessed by in vivo microdialysis SO REGULATORY PEPTIDES LA English DT Article DE microdialysis; anorexia nervosa; leptin; adipose tissue ID SERUM LEPTIN; EATING-DISORDERS; BULIMIA-NERVOSA; BOUND LEPTIN; WEIGHT-LOSS; RECEPTOR; EXPRESSION; HUMANS; INDEX; PLACENTA AB Objective: The adipocyte-derived hormone leptin is involved in energy metabolism and body weight regulation. Plasma leptin concentrations are significantly reduced in patients with anorexia nervosa (AN) and with severe malnutrition. Whether reduced plasma leptin is reflected by its decreased production by the adipose tissue is unknown. Methods: In the present study we measured leptin concentrations locally in the abdominal subcutaneous adipose tissue of 9 female AN patients and 11 healthy controls by in vivo microdialysis. Results: Adipose tissue free leptin levels were not different in patients with AN compared to controls (2.59 +/- 1.99 vs 2.36 +/- 0.25 ng/ml, P > 0.05). Plasma leptin soluble receptor (sOb-R) levels were significantly higher in patients with AN than in healthy subjects (58.05 +/- 38.69 vs 12.79 +/- 5.08 U/ml, P < 0.01). The area of adipocyte in AN was considerably smaller than in the controls (183 +/- 104.01 mu m(2) compared to 2145.8 +/- 1003.41). Conclusions: We conclude that decreased plasma leptin levels in patients with AN are not directly related to dialysate leptin levels in the abdominal subcutaneous adipose tissue. (c) 2004 Published by Elsevier B.V. C1 Inst Endocrinol, Lab Clin & Expt Neuroendocrinol, Prague 1, Czech Republic. Charles Univ, Fac Sci, Prague 12800, Czech Republic. Charles Univ, Fac Med 1, Inst Pathol, Prague 12800 2, Czech Republic. Charles Univ, Fac Med 1, Psychiat Clin, Prague 12000 2, Czech Republic. NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Nedvidkova, J (reprint author), Inst Endocrinol, Lab Clin & Expt Neuroendocrinol, Narodni 8,Z116 94, Prague 1, Czech Republic. EM jnedvidkova@endo.cz NR 38 TC 3 Z9 3 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD MAY 15 PY 2005 VL 128 IS 1 BP 63 EP 68 DI 10.1016/j.regpep.2004.12.029 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 908XN UT WOS:000227823600009 ER PT J AU Miller, NH Justice, CM Marosy, B Doheny, KF Pugh, E Zhang, J Dietz, HC Wilson, AF AF Miller, NH Justice, CM Marosy, B Doheny, KF Pugh, E Zhang, J Dietz, HC Wilson, AF TI Identification of candidate regions for familial idiopathic scoliosis SO SPINE LA English DT Article DE idiopathic scoliosis; model-independent linkage analysis; stratification; autosomal dominant ID LINKAGE ANALYSIS; PREVALENCE; INFERENCE; GENETICS; LOCUS; TWINS AB Study Design. A genomic screen and statistical linkage analysis of 202 families with at least two individuals with idiopathic scoliosis was performed. Objectives. To identify candidate regions or the autosomal loci that may be involved in the expression of familial idiopathic scoliosis. Summary of Background Data. A large sample of families with individuals having idiopathic scoliosis (202 families; 1,198 individuals) was ascertained; diagnoses were based on physical examination and radiographic criteria. Methods. Model-independent linkage analysis of qualitative and quantitative traits (degree of lateral curvature) related to scoliosis was used to screen genotyping data from 391 markers in the 202 families. Subsets of families were determined before genotyping based on the most likely mode of inheritance for each family (autosomal dominant vs. X-linked dominant). Fine mapping results corroborated linkage in the primary candidate regions. Results. Candidate regions on chromosomes 6, 9, 16, and 17 were considered to have the strongest evidence for linkage across all subsets considered. Conclusion. Linkage analyses have identified several candidate regions, a significant step in defining the genetic etiology of this disorder. C1 Johns Hopkins Univ, Baltimore, MD USA. NHGRI, Genometr Sect, IDRB, NIH, Baltimore, MD USA. JHU, IGM, Ctr Inherited Dis Res, SOM, Baltimore, MD USA. RP Miller, NH (reprint author), 601 N Caroline St, Baltimore, MD 21287 USA. EM nmillerb@jhmi.edu RI Wilson, Alexander/C-2320-2009 FU NCRR NIH HHS [1 P41 RR03655]; NHGRI NIH HHS [N01-HG-65403] NR 33 TC 69 Z9 89 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAY 15 PY 2005 VL 30 IS 10 BP 1181 EP 1187 DI 10.1097/01.brs.0000162282.46160.0a PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 927QB UT WOS:000229209100012 PM 15897833 ER PT J AU Kowara, R Karaczyn, A Cheng, RYS Salnikow, K Kasprzak, KS AF Kowara, R Karaczyn, A Cheng, RYS Salnikow, K Kasprzak, KS TI Microarray analysis of altered gene expression in murine fibroblasts transformed by nickel(II) to nickel(II)-resistant malignant phenotype SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE nickel; nickel(II)-transformed cells; nickel(II)-resistant cells; gene expression; glutathione metabolism ID GROWTH-FACTOR-I; HISTONE DEACETYLASE INHIBITOR; CELL-LINES; MOLECULAR-MECHANISMS; LIPID-PEROXIDATION; OXIDATIVE STRESS; BETA-CATENIN; C-MYC; CYCLOOXYGENASE-2 EXPRESSION; TRANSCRIPTION FACTORS AB B200 cells are Ni(II)-transformed mouse BALB/c-3T3 fibroblasts displaying a malignant phenotype and increased resistance to Ni(II) toxicity. In an attempt to find genes whose expression has been altered by the transformation, the Atlas Mouse Stress/Toxicology cDNA Expression Array (Clontech Laboratories, Inc., Palo Alto, CA) was used to analyze the levels of gene expression in both parental and Ni(II)transformed cells. Comparison of the results revealed a significant up- or downregulation of the expression of 62 of the 588 genes present in the array (approximately 10.5%) in B200 cells. These genes were assigned to different functional groups, including transcription factors and oncogenes (9/14; fractions in parentheses denote the number of up-regulated versus the total number of genes assigned to this group), stress and DNA damage response genes (11/12), growth factors and hormone receptors (6/9), metabolism (7/7), cell adhesion (2/7), cell cycle (3/6), apoptosis (3/4), and cell proliferation (2/3). Among those genes, overexpression of beta-catenin and its downstream targets c-myc and cyclin D1, together with upregulated cyclin G, points at the malignant character of B200 cells. While the increased expression of glutathione (GSH) synthetase, glutathione-S-transferase A4 (GSTA4), and glutathione-S-transferase theta (GSTT), together with high level of several genes responding to oxidative stress, suggests the enforcement of antioxidant defenses in Ni-transformed cells. Published by Elsevier Inc. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Kowara, R (reprint author), Natl Res Council Canada, Inst Biol Sci, M-54,1200 Montreal Rd, Ottawa, ON K1A 0R6, Canada. EM Rcnata.Kowara@nrc-cnrc.gc.ca OI Cheng, Robert/0000-0003-0287-6439 NR 68 TC 16 Z9 16 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY 15 PY 2005 VL 205 IS 1 BP 1 EP 10 DI 10.1016/j.taap.2004.10.006 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 928CJ UT WOS:000229248400001 PM 15885260 ER PT J AU Lambert, LC AF Lambert, LC TI Lifeline SO LANCET LA English DT Editorial Material C1 NIAID, Resp Dis Branch, Div Microbiol & Infect Dis, US Natl Inst Hlth, Bethesda, MD 20205 USA. RP Lambert, LC (reprint author), NIAID, Resp Dis Branch, Div Microbiol & Infect Dis, US Natl Inst Hlth, Bethesda, MD 20205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 14 PY 2005 VL 365 IS 9472 BP 1681 EP 1681 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 925VV UT WOS:000229082300013 ER PT J AU Abe, O Abe, R Enomoto, K Kikuchi, K Koyama, H Masuda, H Nomura, Y Sakai, K Sugimachi, K Tominaga, T Uchino, J Yoshida, M Haybittle, JL Davies, C Harvey, VJ Holdaway, TM Kay, RG Mason, BH Forbes, JF Wilcken, N Gnant, M Jakesz, R Ploner, M Yosef, HMA Focan, C Lobelle, JP Peek, U Oates, GD Powell, J Durand, M Mauriac, L Di Leo, A Dolci, S Piccart, MJ Masood, MB Parker, D Price, JJ Hupperets, PSGJ Jackson, S Ragaz, J Berry, D Broadwater, G Cirrincione, C Muss, H Norton, L Weiss, RB Abu-Zahra, HT Portnoj, SM Baum, M Cuzick, J Houghton, J Riley, D Gordon, NH Davis, HL Beatrice, A Mihura, J Naja, A Lehingue, Y Romestaing, P Dubois, JB Delozier, T Mace-Lesec'h, J Rambert, P Andrysek, O Barkmanova, J Owen, JR Meier, P Howell, A Ribeiro, GC Swindell, R Alison, R Boreham, J Clarke, M Collins, R Darby, S Davies, C Elphinstone, P Evans, V Godwin, J Gray, R Harwood, C Hicks, C James, S MacKinnon, E McGale, P McHugh, T Mead, G Peto, R Wang, Y Albano, J de Oliveira, CF Gervasio, H Gordilho, J Johansen, H Mouridsen, HT Gelman, RS Harris, JR Henderson, IC Shapiro, CL Andersen, KW Axelsson, CK Blichert-Toft, M Moller, S Mouridsen, HT Overgaard, J Overgaard, M Rose, C Cartensen, B Palshof, T Trampisch, HJ Dalesio, O de Vries, EGE Rodenhuis, S van Tinteren, H Comis, RL Davidson, NE Gray, R Robert, N Sledge, G Tormey, DC Wood, W Cameron, D Chetty, U Forrest, P Jack, W Rossbach, J Klijn, JGM Treurniet-Donker, AD van Putten, WLJ Costa, A Veronesi, U Bartelink, H Duchateau, L Legrand, C Sylvester, R van der Hage, JA van de Velde, CJH Cunningham, MP Catalano, R Creech, RH Bonneterre, J Fargeot, P Fumoleau, P Kerbrat, P Namer, M Jonat, W Kaufmann, M Schumacher, M von Minckwitz, G Bastert, G Rauschecker, H Sauer, R Sauerbrei, W Schauer, A Schumacher, M de Schryver, A Vakaet, L Belfiglio, M Nicolucci, A Pellegrini, F Sacco, M Valentini, M McArdle, CS Smith, DC Galligioni, E Boccardo, F Rubagotti, A Dent, DM Gudgeon, CA Hacking, A Erazo, A Medina, JY Izuo, M Morishita, Y Takei, H Fentiman, IS Hayward, JL Rubens, RD Skilton, D Graeff, H Janicke, F Meisner, C Scheurlen, H Kaufmann, M von Fournier, D Dafni, U Fountzilas, G Klefstrom, P Blomqvist, C Saarto, T Margreiter, R Asselain, B Salmon, RJ Vilcoq, JR Arriagada, R Hill, C Laplanche, A Le, MG Spielmann, M Bruzzi, P Montanaro, E Rosso, R Sertoli, MR Venturini, M Amadori, D Benraadt, J Kooi, M van de Velde, AO van Dongen, JA Vermorken, JB Castiglione, M Cavalli, F Coates, A Collins, J Forbes, J Gelber, RD Goldhirsch, A Lindtner, J Price, KN Rudenstam, CM Senn, HJ Bliss, JM Chilvers, CED Coombes, RC Hall, E Marty, M Borovik, R Brufman, G Hayat, H Robinson, E Wigler, N Bonadonna, G Camerini, T De Palo, G Del Vecchio, M Formelli, F Valagussa, P Martoni, A Pannuti, F Cocconi, G Colozza, A Camisa, R Aogi, K Takashima, S Abe, O Ikeda, T Inokuchi, K Kikuchi, K Sawa, K Sonoo, H Korzeniowski, S Skolyszewski, J Ogawa, M Yamashita, J Bonte, J Christiaens, R Paridaens, R Van den Boegart, W Martin, P Romain, S Hakes, T Hudis, CA Norton, L Wittes, R Giokas, G Kondylis, D Lissaios, B de la Huerta, R Sainz, MG Altemus, R Cowan, K Danforth, D Lichter, A Lippman, M O'Shaughnessy, J Pierce, LJ Steinberg, S Venzon, D Zujewski, J Paradiso, A De Lena, M Schittulli, F Myles, JD Pater, JL Pritchard, KI Nomura, Y Anderson, S Bass, G Brown, A Bryant, J Costantino, J Dignam, J Fisher, B Redmond, C Wieand, S Wolmark, N Baum, M Jackson, IM Palmer, MK Ingle, JN Suman, VJ Bengtsson, NO Jonsson, H Larsson, LG Lythgoe, JP Swindell, R Kissin, M Erikstein, B Hannisdal, E Jacobsen, AB Varhaug, JE Erikstein, B Gundersen, S Hauer-Jensen, M Host, H Jacobsen, AB Nissen-Meyer, R Blamey, RW Mitchell, AK Morgan, DAL Robertson, JFR Di Palma, M Mathe, G Misset, JL Clark, RM Levine, M Morimoto, K Sawa, K Takatsuka, Y Crossley, E Harris, A Talbot, D Taylor, M Cocconi, G di Blasio, B Ivanov, V Semiglazov, V Brockschmidt, J Cooper, MR Ueo, H Falkson, CI A'Hern, R Ashley, S Powles, TJ Smith, IE Yarnold, JR Gazet, JC Cocoran, N Deshpande, N di Martino, L Douglas, P Hacking, A Host, H Lindtner, A Notter, G Bryant, AJS Ewing, GH Firth, LA Krushen-Kosloski, JL Nissen-Meyer, R Foster, L George, WD Stewart, HJ Stroner, P Malmstrom, P Moller, TR Ryden, S Tengrup, I Tennvall-Nittby, L Carstenssen, J Dufmats, M Hatschek, T Nordenskjold, B Soderberg, M Carpenter, JT Albain, K Crowley, J Green, S Martino, S Osborne, CK Ravdin, PM Glas, U Johansson, U Rutqvist, LE Singnomklao, T Wallgren, A Castiglione, M Goldhirsch, A Maibach, R Senn, HJ Thurlimann, B Brenner, H Hercbergs, A Yoshimoto, M DeBoer, G Paterson, AHG Pritchard, KI Meakin, JW Panzarella, T Pritchard, KI Shan, Y Shao, YF Wang, X Zhao, DB Boreham, J Chen, ZM Pan, HC Peto, R Bahi, J Reid, M Spittle, M Deutsch, GP Senanayake, F Kwong, DLW Bianco, AR Carlomagno, C De Laurentiis, M De Placido, S Buzdar, AU Smith, T Bergh, J Holmberg, L Liljegren, G Nilsson, J Seifert, M Sevelda, P Zielinsky, CC Buchanan, RB Cross, M Royle, GT Dunn, JA Hills, RK Lee, M Morrison, JM Spooner, D Litton, A Chlebowski, RT Caffier, H AF Abe, O Abe, R Enomoto, K Kikuchi, K Koyama, H Masuda, H Nomura, Y Sakai, K Sugimachi, K Tominaga, T Uchino, J Yoshida, M Haybittle, JL Davies, C Harvey, VJ Holdaway, TM Kay, RG Mason, BH Forbes, JF Wilcken, N Gnant, M Jakesz, R Ploner, M Yosef, HMA Focan, C Lobelle, JP Peek, U Oates, GD Powell, J Durand, M Mauriac, L Di Leo, A Dolci, S Piccart, MJ Masood, MB Parker, D Price, JJ Hupperets, PSGJ Jackson, S Ragaz, J Berry, D Broadwater, G Cirrincione, C Muss, H Norton, L Weiss, RB Abu-Zahra, HT Portnoj, SM Baum, M Cuzick, J Houghton, J Riley, D Gordon, NH Davis, HL Beatrice, A Mihura, J Naja, A Lehingue, Y Romestaing, P Dubois, JB Delozier, T Mace-Lesec'h, J Rambert, P Andrysek, O Barkmanova, J Owen, JR Meier, P Howell, A Ribeiro, GC Swindell, R Alison, R Boreham, J Clarke, M Collins, R Darby, S Davies, C Elphinstone, P Evans, V Godwin, J Gray, R Harwood, C Hicks, C James, S MacKinnon, E McGale, P McHugh, T Mead, G Peto, R Wang, Y Albano, J de Oliveira, CF Gervasio, H Gordilho, J Johansen, H Mouridsen, HT Gelman, RS Harris, JR Henderson, IC Shapiro, CL Andersen, KW Axelsson, CK Blichert-Toft, M Moller, S Mouridsen, HT Overgaard, J Overgaard, M Rose, C Cartensen, B Palshof, T Trampisch, HJ Dalesio, O de Vries, EGE Rodenhuis, S van Tinteren, H Comis, RL Davidson, NE Gray, R Robert, N Sledge, G Tormey, DC Wood, W Cameron, D Chetty, U Forrest, P Jack, W Rossbach, J Klijn, JGM Treurniet-Donker, AD van Putten, WLJ Costa, A Veronesi, U Bartelink, H Duchateau, L Legrand, C Sylvester, R van der Hage, JA van de Velde, CJH Cunningham, MP Catalano, R Creech, RH Bonneterre, J Fargeot, P Fumoleau, P Kerbrat, P Namer, M Jonat, W Kaufmann, M Schumacher, M von Minckwitz, G Bastert, G Rauschecker, H Sauer, R Sauerbrei, W Schauer, A Schumacher, M de Schryver, A Vakaet, L Belfiglio, M Nicolucci, A Pellegrini, F Sacco, M Valentini, M McArdle, CS Smith, DC Galligioni, E Boccardo, F Rubagotti, A Dent, DM Gudgeon, CA Hacking, A Erazo, A Medina, JY Izuo, M Morishita, Y Takei, H Fentiman, IS Hayward, JL Rubens, RD Skilton, D Graeff, H Janicke, F Meisner, C Scheurlen, H Kaufmann, M von Fournier, D Dafni, U Fountzilas, G Klefstrom, P Blomqvist, C Saarto, T Margreiter, R Asselain, B Salmon, RJ Vilcoq, JR Arriagada, R Hill, C Laplanche, A Le, MG Spielmann, M Bruzzi, P Montanaro, E Rosso, R Sertoli, MR Venturini, M Amadori, D Benraadt, J Kooi, M van de Velde, AO van Dongen, JA Vermorken, JB Castiglione, M Cavalli, F Coates, A Collins, J Forbes, J Gelber, RD Goldhirsch, A Lindtner, J Price, KN Rudenstam, CM Senn, HJ Bliss, JM Chilvers, CED Coombes, RC Hall, E Marty, M Borovik, R Brufman, G Hayat, H Robinson, E Wigler, N Bonadonna, G Camerini, T De Palo, G Del Vecchio, M Formelli, F Valagussa, P Martoni, A Pannuti, F Cocconi, G Colozza, A Camisa, R Aogi, K Takashima, S Abe, O Ikeda, T Inokuchi, K Kikuchi, K Sawa, K Sonoo, H Korzeniowski, S Skolyszewski, J Ogawa, M Yamashita, J Bonte, J Christiaens, R Paridaens, R Van den Boegart, W Martin, P Romain, S Hakes, T Hudis, CA Norton, L Wittes, R Giokas, G Kondylis, D Lissaios, B de la Huerta, R Sainz, MG Altemus, R Cowan, K Danforth, D Lichter, A Lippman, M O'Shaughnessy, J Pierce, LJ Steinberg, S Venzon, D Zujewski, J Paradiso, A De Lena, M Schittulli, F Myles, JD Pater, JL Pritchard, KI Nomura, Y Anderson, S Bass, G Brown, A Bryant, J Costantino, J Dignam, J Fisher, B Redmond, C Wieand, S Wolmark, N Baum, M Jackson, IM Palmer, MK Ingle, JN Suman, VJ Bengtsson, NO Jonsson, H Larsson, LG Lythgoe, JP Swindell, R Kissin, M Erikstein, B Hannisdal, E Jacobsen, AB Varhaug, JE Erikstein, B Gundersen, S Hauer-Jensen, M Host, H Jacobsen, AB Nissen-Meyer, R Blamey, RW Mitchell, AK Morgan, DAL Robertson, JFR Di Palma, M Mathe, G Misset, JL Clark, RM Levine, M Morimoto, K Sawa, K Takatsuka, Y Crossley, E Harris, A Talbot, D Taylor, M Cocconi, G di Blasio, B Ivanov, V Semiglazov, V Brockschmidt, J Cooper, MR Ueo, H Falkson, CI A'Hern, R Ashley, S Powles, TJ Smith, IE Yarnold, JR Gazet, JC Cocoran, N Deshpande, N di Martino, L Douglas, P Hacking, A Host, H Lindtner, A Notter, G Bryant, AJS Ewing, GH Firth, LA Krushen-Kosloski, JL Nissen-Meyer, R Foster, L George, WD Stewart, HJ Stroner, P Malmstrom, P Moller, TR Ryden, S Tengrup, I Tennvall-Nittby, L Carstenssen, J Dufmats, M Hatschek, T Nordenskjold, B Soderberg, M Carpenter, JT Albain, K Crowley, J Green, S Martino, S Osborne, CK Ravdin, PM Glas, U Johansson, U Rutqvist, LE Singnomklao, T Wallgren, A Castiglione, M Goldhirsch, A Maibach, R Senn, HJ Thurlimann, B Brenner, H Hercbergs, A Yoshimoto, M DeBoer, G Paterson, AHG Pritchard, KI Meakin, JW Panzarella, T Pritchard, KI Shan, Y Shao, YF Wang, X Zhao, DB Boreham, J Chen, ZM Pan, HC Peto, R Bahi, J Reid, M Spittle, M Deutsch, GP Senanayake, F Kwong, DLW Bianco, AR Carlomagno, C De Laurentiis, M De Placido, S Buzdar, AU Smith, T Bergh, J Holmberg, L Liljegren, G Nilsson, J Seifert, M Sevelda, P Zielinsky, CC Buchanan, RB Cross, M Royle, GT Dunn, JA Hills, RK Lee, M Morrison, JM Spooner, D Litton, A Chlebowski, RT Caffier, H CA EBCTCG TI Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials SO LANCET LA English DT Article ID TAMOXIFEN; DEATHS AB Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, >= 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs. 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EM bc.overview@ctsu.ox.ac.uk RI Vakaet, Luc/A-6467-2010; Jonat, Walter/E-3024-2010; Barkmanova, Jaroslava/A-1411-2017 OI Barkmanova, Jaroslava/0000-0003-1406-7292 NR 22 TC 3679 Z9 3735 U1 69 U2 542 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAY 14 PY 2005 VL 365 IS 9472 BP 1687 EP 1717 PG 31 WC Medicine, General & Internal SC General & Internal Medicine GA 925VV UT WOS:000229082300022 ER PT J AU Pastan, I AF Pastan, I TI An NIH career: from bedside to basic research and back SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECOMBINANT IMMUNOTOXIN; ESCHERICHIA-COLI; PSEUDOMONAS EXOTOXIN; ANTIBODY; HORMONE; CELLS; FIBROBLASTS; SEQUENCE; DOMAINS; BINDING C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov NR 18 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 13 PY 2005 VL 280 IS 19 BP 18553 EP 18557 DI 10.1074/jbc.X500002200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 923TN UT WOS:000228932300001 PM 15797860 ER PT J AU Neutzner, A Youle, RJ AF Neutzner, A Youle, RJ TI Instability of the mitofusin Fzo1 regulates mitochondrial morphology during the mating response of the yeast Saccharomyces cerevisiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DYNAMIN-RELATED GTPASE; FUSION-COMPETENT MITOCHONDRIA; PROGRAMMED CELL-DEATH; SHUTTLE VECTORS; FISSION; PROTEIN; APOPTOSIS; EXPRESSION; MAINTENANCE; SPORULATION AB Mitochondria form a highly dynamic network that is shaped by continuous fission and fusion of these organelles. In the yeast Saccharomyces cerevisiae two machineries are involved in this process, one of which includes the mitochondrial fusion promoting GTPase Fzo1. Although a role for the F-box protein Mdm30 in regulating the stability of Fzo1 has been proposed, the molecular basis for the regulation of the fission to fusion ratio of mitochondria remains unknown. To discern the mechanism of the regulation of mitochondrial morphology, we arrested cells at different stages of the cell cycle and examined mitochondrial morphology as well as the stability of mitochondrial fission and fusion proteins. In response to a G(1) arrest evoked by the mating pheromone α factor the mitochondrial network fragmented into small pieces, which was accompanied by dramatic down-regulation of Fzo1. Mating pheromone also triggered the degradation of Fzo1 produced under the control of a constitutive promoter, and Fzo1 was stabilized upon proteasome inhibition, indicating a role for the proteasome system in the degradation of Fzo1. However, deletion of MDM30 did not stabilize Fzo1 after mating pheromone treatment, showing a different mechanism from the previously reported process of steady state Fzo1 regulation. We show an example for a regulated change of the mitochondrial fission to fusion ratio during the life cycle of budding yeast. Proteasomal degradation of Fzo1 in response to the mating pheromone is proposed to mediate the remodeling of the mitochondrial network during the process of mating. C1 NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov OI Neutzner, Albert/0000-0001-9254-5558 NR 35 TC 67 Z9 69 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 13 PY 2005 VL 280 IS 19 BP 18598 EP 18603 DI 10.1074/jbc.M500807200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 923TN UT WOS:000228932300008 PM 15760898 ER PT J AU Shim, M Eling, TE AF Shim, M Eling, TE TI Protein kinase C-dependent regulation of NAG-1/placental bone morphogenic protein/MIC-1 expression in LNCaP prostate carcinoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TGF-BETA SUPERFAMILY; NF-KAPPA-B; MACROPHAGE INHIBITORY CYTOKINE; ACTIVATED GENE NAG-1; GROWTH-FACTOR-BETA; CANCER CELLS; 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED APOPTOSIS; T-LYMPHOCYTES; FAS-LIGAND; MEMBER AB NAG-1 (nonsteroidal anti-inflammatory drug-activated gene), a member of the transforming growth factor β superfamily, is involved in cellular processes such as inflammation, apoptosis/survival, and tumorigenesis and is regulated by p53, Sp1, and Egr-1. In the current study, the regulation of NAG-1 expression in LNCaP human prostate carcinoma cells by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was examined. TPA treatment increased NAG-1 protein and mRNA levels in a time- and concentration-dependent manner as well as NF-κ B binding/transcriptional activity in LNCaP cells. Pretreatment with protein kinase C (PKC) inhibitor blocked the TPA-induced increase in NAG-1 protein levels and NF-κ B binding/transcriptional activity, whereas an inhibition of p38, JNK, MEK activity had no effect on TPA-induced NAG-1 levels and NF-κ B transcriptional activity. Expression of constitutively active PKCs induced an increase in NF-κ B transcriptional activity and NAG-1 protein levels in LNCaP cells. The expression of NF-κ B p65 induced NAG-1 promoter activity, and chromatin immunoprecipitation assay for p65 showed that NF-κ B binds the NAG-1 promoter in LNCaP cells. Inhibition of TPA-induced NAG-1 expression by NAG-1 short interfering RNA blocked TPA-induced apoptosis in LNCaP cells, suggesting induction of NAG-1 negatively affects LNCaP cell survival. These results demonstrate that NAG-1 expression is up-regulated by TPA in LNCaP cells through a PKC-dependent pathway involving the activation of NF-κ B. C1 NIEHS, Eicosanoids Biochem Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Eling, TE (reprint author), NIEHS, Eicosanoids Biochem Sect, Mol Carcinogenesis Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM eling@niehs.nih.gov NR 40 TC 62 Z9 64 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 MAY 13 PY 2005 VL 280 IS 19 BP 18636 EP 18642 DI 10.1074/jbc.M414613200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 923TN UT WOS:000228932300013 PM 15757899 ER PT J AU Tanos, T Marinissen, MJ Leskow, FC Hochbaum, D Martinetto, H Gutkind, JS Coso, OA AF Tanos, T Marinissen, MJ Leskow, FC Hochbaum, D Martinetto, H Gutkind, JS Coso, OA TI Phosphorylation of c-fos by members of the p38 MAPK family - Role in the AP-1 response to UV light SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; IMMEDIATE-EARLY GENE; N-TERMINAL KINASE; GROWTH-FACTOR; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; COUPLED RECEPTORS; JUN PROMOTER; CELLULAR-TRANSFORMATION; MESSENGER-RNA AB Exposure to sources of UV radiation, such as sunlight, induces a number of cellular alterations that are highly dependent on its ability to affect gene expression. Among them, the rapid activation of genes coding for two subfamilies of proto-oncoproteins, Fos and Jun, which constitute the AP-1 transcription factor, plays a key role in the subsequent regulation of expression of genes involved in DNA repair, cell proliferation, cell cycle arrest, death by apoptosis, and tissue and extracellular matrix remodeling proteases. Besides being regulated at the transcriptional level, Jun and Fos transcriptional activities are also regulated by phosphorylation as a result of the activation of intracellular signaling cascades. In this regard, the phosphorylation of c-Jun by UV-induced JNK has been readily documented, whereas a role for Fos proteins in UV-mediated responses and the identification of Fos-activating kinases has remained elusive. Here we identify p38 MAPKs as proteins that can associate with c-Fos and phosphorylate its transactivation domain both in vitro and in vivo. This phosphorylation is transduced into changes in its transcriptional ability as p38-activated c-Fos enhances AP1-driven gene expression. Our findings indicate that as a consequence of the activation of stress pathways induced by UV light, endogenous c-Fos becomes a substrate of p38 MAPKs and, for the first time, provide evidence that support a critical role for p38 MAPKs in mediating stress-induced c-Fos phosphorylation and gene transcription activation. Using a specific pharmacological inhibitor for p38α and -β, we found that most likely these two isoforms mediate UV-induced c-Fos phosphorylation in vivo. Thus, these newly described pathways act concomitantly with the activation of c-Jun by JNK/MAPKs, thereby contributing to the complexity of AP1-driven gene transcription regulation. C1 Univ Buenos Aires, Fac Ciencias Exactas & Nat, Lab Fisiol & Biol Mol, Ifibyne Conicet, RA-1428 Buenos Aires, DF, Argentina. Univ Buenos Aires, Inst Invest & Ingn Genet, Ingebi Conicet, RA-1428 Buenos Aires, DF, Argentina. NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Coso, OA (reprint author), Univ Buenos Aires, Fac Ciencias Exactas & Nat, Lab Fisiol & Biol Mol, Ifibyne Conicet, RA-1428 Buenos Aires, DF, Argentina. EM ocoso@fbmc.fcen.uba.ar RI Gutkind, J. Silvio/A-1053-2009 NR 64 TC 115 Z9 121 U1 1 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 MAY 13 PY 2005 VL 280 IS 19 BP 18842 EP 18852 DI 10.1074/jbc.M500620200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 923TN UT WOS:000228932300036 PM 15708845 ER PT J AU Tamamura, Y Otani, T Kanatani, N Koyama, E Kitagaki, J Komori, T Yamada, Y Costantini, F Wakisaka, S Pacifici, M Iwamoto, M Enomoto-Iwamoto, M AF Tamamura, Y Otani, T Kanatani, N Koyama, E Kitagaki, J Komori, T Yamada, Y Costantini, F Wakisaka, S Pacifici, M Iwamoto, M Enomoto-Iwamoto, M TI Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHICK LIMB BUD; SYNOVIAL JOINT FORMATION; LONG-BONE DEVELOPMENT; BETA-CATENIN; CHONDROCYTE DIFFERENTIATION; ARTICULAR-CARTILAGE; NEGATIVE REGULATOR; PATTERN-FORMATION; WNT; EXPRESSION AB Studies have suggested that continuous Wnt/β-catenin signaling in nascent cartilaginous skeletal elements blocks chondrocyte hypertrophy and endochondral ossification, whereas signaling starting at later stages stimulates hypertrophy and ossification, indicating that Wnt/β-catenin roles are developmentally regulated. To test this conclusion further, we created transgenic mice expressing a fusion mutant protein of β-catenin and LEF (CA-LEF) in nascent chondrocytes. Transgenic mice had severe skeletal defects, particularly in limbs. Growth plates were totally disorganized, lacked maturing chondrocytes expressing Indian hedgehog and collagen X, and failed to undergo endochondral ossification. Interestingly, the transgenic cartilaginous elements were ill defined, intermingled with surrounding connective and vascular tissues, and even displayed abnormal joints. However, when activated β-catenin mutant (&UDelta;-β-catenin) was expressed in chondrocytes already engaged in maturation such as those present in chick limbs, chondrocyte maturation and bone formation were greatly enhanced. Differential responses to Wnt/β-catenin signaling were confirmed in cultured chondrocytes. Activation in immature cells blocked maturation and actually de-stabilized their phenotype, as revealed by reduced expression of chondrocyte markers, abnormal cytoarchitecture, and loss of proteoglycan matrix. Activation in mature cells instead stimulated hypertrophy, matrix mineralization, and expression of terminal markers such as metalloprotease (MMP)-13 and vascular endothelial growth factor. Because proteoglycans are crucial for cartilage function, we tested possible mechanisms for matrix loss. &UDelta;-β-Catenin expression markedly increased expression of MMP-2, MMP-3, MMP-7, MMP-9, MT3-MMP, and ADAMTS5. In conclusion, Wnt/β-catenin signaling regulates chondrocyte phenotype, maturation, and function in a developmentally regulated manner, and regulated action by this pathway is critical for growth plate organization, cartilage boundary definition, and endochondral ossification. C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. Nagasaki Univ, Sch Dent, Dept Oral Cytol & Cell Biol, Nagasaki 8528501, Japan. Osaka Univ, Fac Dent, Suita, Osaka 5650871, Japan. NIDCR, Mol Biol Sect, NIH, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA. RP Iwamoto, M (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Orthoped Surg, 1015 Walnut St,Curtis Bldg,Suite 501, Philadelphia, PA 19107 USA. EM Motomi.Iwamoto@jefferson.edu FU NIAMS NIH HHS [AR050507, AR46000, AR47543] NR 62 TC 186 Z9 196 U1 1 U2 12 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 MAY 13 PY 2005 VL 280 IS 19 BP 19185 EP 19195 DI 10.1074/jbc.M414275200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 923TN UT WOS:000228932300075 PM 15760903 ER PT J AU Cabral, WA Makareeva, E Colige, A Letocha, AD Ty, JM Yeowell, HN Pals, G Leikin, S Marini, JC AF Cabral, WA Makareeva, E Colige, A Letocha, AD Ty, JM Yeowell, HN Pals, G Leikin, S Marini, JC TI Mutations near amino end of alpha 1(I) collagen cause combined osteogenesis imperfecta/Ehlers-Danlos syndrome by interference with N-propeptide processing SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNDROME TYPE-VII; SPLICE ACCEPTOR SITE; I PROCOLLAGEN; PRO-ALPHA-1(I) CHAIN; COL1A2 GENE; CLINICAL-FEATURES; BASE SUBSTITUTION; THERMAL-STABILITY; ALPHA-2(I) CHAIN; PROTEINASE AB Patients with OI/EDS form a distinct subset of osteogenesis imperfecta (OI) patients. In addition to skeletal fragility, they have characteristics of Ehlers-Danlos syndrome (EDS). We identified 7 children with types III or IV OI, plus severe large and small joint laxity and early progressive scoliosis. In each child with OI/EDS, we identified a mutation in the first 90 residues of the helical region of α 1(I) collagen. These mutations prevent or delay removal of the procollagen N-propeptide by purified N-proteinase (ADAMTS-2) in vitro and in pericellular assays. The mutant pN-collagen which results is efficiently incorporated into matrix by cultured fibroblasts and osteoblasts and is prominently present in newly incorporated and immaturely cross-linked collagen. Dermal collagen fibrils have significantly reduced cross-sectional diameters, corroborating incorporation of pN-collagen into fibrils in vivo. Differential scanning calorimetry revealed that these mutant collagens are less stable than the corresponding procollagens, which is not seen with other type I collagen helical mutations. These mutations disrupt a distinct folding region of high thermal stability in the first 90 residues at the amino end of type I collagen and alter the secondary structure of the adjacent N-proteinase cleavage site. Thus, these OI/EDS collagen mutations are directly responsible for the bone fragility of OI and indirectly responsible for EDS symptoms, by interference with N-propeptide removal. C1 NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. NICHD, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA. Univ Liege, Lab Connect Tissue Biol, B-4000 Liege, Belgium. Duke Univ, Med Ctr, Div Dermatol, Durham, NC 27710 USA. VU Med Ctr, NL-1007 MB Amsterdam, Netherlands. RP Marini, JC (reprint author), NICHD, Bone & Extracellular Matrix Branch, NIH, Bldg 10,Rm 9s239,9000 Rockville Pike, Bethesda, MD 20892 USA. EM oidoc@helix.nih.gov RI Leikin, Sergey/A-5518-2008; Makareeva, Elena/F-5183-2011 OI Leikin, Sergey/0000-0001-7095-0739; NR 49 TC 61 Z9 65 U1 3 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 MAY 13 PY 2005 VL 280 IS 19 BP 19259 EP 19269 DI 10.1074/jbc.M414698200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 923TN UT WOS:000228932300083 PM 15728585 ER PT J AU Du, QZ Jerz, G He, YC Li, L Xu, YJ Zhang, Q Zheng, QX Winterhalter, P Ito, Y AF Du, QZ Jerz, G He, YC Li, L Xu, YJ Zhang, Q Zheng, QX Winterhalter, P Ito, Y TI Semi-industrial isolation of salicin and amygdalin from plant extracts using slow rotary counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE salicin; Salix alba; amygdalin; Semen armeniacae; slow rotary counter-current chromatograph; industrial isolation AB Salicin in the bark extract of Salix alba and amygdalin in the fruit extract of Semen armeniacae were each separated by slow rotary counter-current chromatography (SRCCC). The apparatus was equipped with a 40-L column made of 17 mm i.d. convoluted Teflon tubing. A 500 g amount of crude extract containing salicin at 13.5% was separated yielding 63.5 g of salicin at 95.3% purity in 20 h using methyl tert-butyl ether-l-butanol (1:3) saturated by methanol-water (1:5) as a stationary phase and methanol-water (1:5) saturated by methyl tertbutyl ether-l-butanol (1:3) as a mobile phase. A 400 g amount of crude extract containing amygdalin at 55.3% was isolated to yield 221.2 g of amygdalin at 94.1% purity in 19h using ethyl acetate-1-butanol (1:2) saturated by water as a stationary phase and water saturated by ethyl acetate-1-butanol (1:2) as a mobile phase. The flow rate of the mobile phase was 50 ml/min. The results show that industrial SRCCC separation of salicin and amygdalin is feasible using a larger column at a higher flow rate of the mobile phase. (c) 2005 Elsevier B.V. All rights reserved. C1 Hangzhou Univ Commerce, Inst Food & Biol Engn, Zhejiang 310035, Peoples R China. Tech Univ Carolo Wilhelmina Braunschweig, Inst Food Chem, DE-38106 Braunschweig, Germany. NHLBI, NIH, Bethesda, MD 20792 USA. RP Du, QZ (reprint author), Hangzhou Univ Commerce, Inst Food & Biol Engn, 149 Jiaogong Rd, Zhejiang 310035, Peoples R China. EM qizhendu@mail.zjgsu.edu.cn NR 9 TC 25 Z9 29 U1 0 U2 14 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 MAY 13 PY 2005 VL 1074 IS 1-2 BP 43 EP 46 DI 10.1016/j.chroma.2005.03.064 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 927KJ UT WOS:000229192500006 PM 15941037 ER PT J AU Le Menach, A McKenzie, FE Flahault, A Smith, DL AF Le Menach, A McKenzie, FE Flahault, A Smith, DL TI The unexpected importance of mosquito oviposition behaviour for malaria: non-productive larval habitats can be sources for malaria transmission SO MALARIA JOURNAL LA English DT Article ID ANOPHELES-GAMBIAE COMPLEX; VECTOR BREEDING SITES; ENVIRONMENTAL-MANAGEMENT; PASSIVE ZOOPROPHYLAXIS; WESTERN KENYA; AFRICA; RISK; DISPERSAL; DISEASE; DIPTERA AB Background: Mosquitoes commute between blood-meal hosts and water. Thus, heterogeneity in human biting reflects underlying spatial heterogeneity in the distribution and suitability of larval habitat as well as inherent differences in the attractiveness, suitability and distribution of blood-meal hosts. One of the possible strategies of malaria control is to identify local vector species and then attack water bodies that contain their larvae. Methods: Biting and host seeking, not oviposition, have been the focus of most previous studies of mosquitoes and malaria transmission. This study presents a mathematical model that incorporates mosquito oviposition behaviour. Results: The model demonstrates that oviposition is one potential factor explaining heterogeneous biting and vector distribution in a landscape with a heterogeneous distribution of larval habitat. Adult female mosquitoes tend to aggregate around places where they oviposit, thereby increasing the risk of malaria, regardless of the suitability of the habitat for larval development. Thus, a water body may be unsuitable for adult mosquito emergence, but simultaneously, be a source for human malaria. Conclusion: Larval density may be a misleading indicator of a habitat's importance for malaria control. Even if mosquitoes could be lured to oviposit in sprayed larval habitats, this would not necessarily mitigate - and might aggravate - the risk of malaria transmission. Forcing mosquitoes to fly away from humans in search of larval habitat may be a more efficient way to reduce the risk of malaria than killing larvae. Thus, draining, fouling, or filling standing water where mosquitoes oviposit can be more effective than applying larvicide. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Univ Paris 06, INSERM, U707, F-75012 Paris, France. RP Le Menach, A (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM lemenach@u707.jussieu.fr; mckenzel@mail.nih.gov; flahault@u707.jussieu.fr; smitdave@helix.nih.gov RI Smith, David/L-8850-2013; Barley, Kamal/F-9579-2011 OI Smith, David/0000-0003-4367-3849; Barley, Kamal/0000-0003-1874-9813 FU Intramural NIH HHS [Z99 TW999999] NR 58 TC 45 Z9 47 U1 1 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD MAY 13 PY 2005 VL 4 AR 23 DI 10.1186/1475-2875-4-23 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 940MM UT WOS:000230148600001 PM 15892886 ER PT J AU Chik, J Mizrahi, S Chi, SL Parsegian, VA Rau, DC AF Chik, J Mizrahi, S Chi, SL Parsegian, VA Rau, DC TI Hydration forces underlie the exclusion of salts and of neutral polar solutes from hydroxypropylcellulose SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID DNA DOUBLE HELICES; OSMOTIC-STRESS; PREFERENTIAL HYDRATION; INTERMOLECULAR FORCES; UNCHARGED SOLUTES; HOFMEISTER SERIES; PROTEIN STABILITY; WATER; FLUCTUATIONS; EQUILIBRIA AB The distance dependence for the preferential exclusion of several salts and neutral solutes from hydroxypropyl cellulose (HPC) has been measured via the effect of these small molecules on the thermodynamic forces between HPC polymers in ordered arrays. The concentration of salts and neutral solutes decreases exponentially as the spacing between apposing nonpolar HPC surfaces decreases. For all solutes, the spatial decay lengths of this exclusion are remarkably similar to those observed between many macromolecules at close spacings where intermolecular forces have been ascribed to the energetics of water structuring. Exclusion magnitudes depend strongly on the nature and size of the particular salt or solute; for the three potassium salts studied, exclusion follows the anionic Hofmeister series. The change in the number of excess waters associated with HPC polymers is independent of solute concentration suggesting that the dominating interactions are between solutes and the hydrated polymer. These findings further confirm the importance of solvation interactions and reveal an unexpected unity of Hofmeister effects, preferential hydration, and hydration forces. C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Rau, DC (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bldg 9,Rm 1E114, Bethesda, MD 20892 USA. EM raud@mail.nih.gov NR 36 TC 30 Z9 31 U1 0 U2 5 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 MAY 12 PY 2005 VL 109 IS 18 BP 9111 EP 9118 DI 10.1021/jp046999k PG 8 WC Chemistry, Physical SC Chemistry GA 924MM UT WOS:000228982900081 PM 16852084 ER PT J AU Lin, L Ozaki, T Takada, Y Kageyama, H Nakamura, Y Hata, A Zhang, JH Simonds, WF Nakagawara, A Koseki, H AF Lin, L Ozaki, T Takada, Y Kageyama, H Nakamura, Y Hata, A Zhang, JH Simonds, WF Nakagawara, A Koseki, H TI topors, a p53 and topoisomerase I-binding RING finger protein, is a coactivator of p53 in growth suppression induced by DNA damage SO ONCOGENE LA English DT Article DE topors; p53; tumor suppressor; DNA damage; cell cycle; apoptosis ID TUMOR-SUPPRESSOR; SUMO-1 MODIFICATION; NUCLEAR-BODIES; GENE; EXPRESSION; SUMOYLATION; INTERACTS; LIGASE; CANCER; DEATH AB The RING family zinc-finger protein topors (topoisomerase I-binding protein) binds not only topoisomerase I, but also p53 and the AAV-2 Rep78/68 proteins. topors maps to human chromosome 9p21, which contains candidate tumor suppressor genes implicated in small cell lung cancers. In this study, we isolated the murine counterpart of topors and investigated its impact on p53 function. The deduced amino-acid sequence of mouse topors exhibits extensive similarity to human topors. Overexpressed myc-tagged topors associates with and stabilizes p53, and enhances the p53-dependent transcriptional activities of p21(Waf1), MDM2 and Bax promoters and elevates endogenous p21(Waf1) mRNA levels. Overexpression of topors consequently results in the suppression of cell growth by cell cycle arrest and/or by the induction of apoptosis. Taken together, these studies identify topors as a positive regulator of p53. The expression of topors is induced by exposure to the genotoxic reagents cisplatin and camptothecin, a DNA topoisomerase I inhibitor. We therefore postulate that topors mediates p53-dependent cellular responses induced by DNA damage, suggesting its physiological role as a tumor suppressor. C1 RIKEN Yokohama Inst, RIKEN Res Ctr Allergy & Immunol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. Chiba Univ, Grad Sch Med, Dept Mol Embryol, Chuo Ku, Chiba 2608670, Japan. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Chiba Canc Ctr Res Inst, Div Biochem, Chuoh Ku, Chiba 2608717, Japan. Chiba Univ, Grad Sch Med, Dept Publ Hlth, Chuo Ku, Chiba 2608670, Japan. RP Koseki, H (reprint author), RIKEN Yokohama Inst, RIKEN Res Ctr Allergy & Immunol, Tsurumi Ku, 1-7-22 Suehiro, Yokohama, Kanagawa 2300045, Japan. EM koseki@rcai.riken.jp RI Koseki, Haruhiko/I-3825-2014 OI Koseki, Haruhiko/0000-0001-8424-5854 NR 33 TC 26 Z9 30 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 12 PY 2005 VL 24 IS 21 BP 3385 EP 3396 DI 10.1038/sj.onc.1208554 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 925FT UT WOS:000229038800001 PM 15735665 ER PT J AU O'Donnell, CJ AF O'Donnell, CJ TI Translating the human genome project into prevention of myocardial infarction and stroke-getting close? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; LINKAGE ANALYSIS; SUSCEPTIBILITY LOCUS; RISK; METAANALYSIS; ASSOCIATION; PREDICTION C1 NHLBI, Framingham Heart Study, Div Cardiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP O'Donnell, CJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave 2, Framingham, MA 01702 USA. EM codonnell@nih.gov NR 20 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 11 PY 2005 VL 293 IS 18 BP 2277 EP 2279 DI 10.1001/jama.293.18.2277 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 924LU UT WOS:000228981100031 PM 15886385 ER PT J AU House, RL Cassady, JP Eisen, EJ Eling, TE Collins, JB Grissom, SF Odle, J AF House, RL Cassady, JP Eisen, EJ Eling, TE Collins, JB Grissom, SF Odle, J TI Functional genomic characterization of delipidation elicited by trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) in a polygenic obese line of mice SO PHYSIOLOGICAL GENOMICS LA English DT Article DE apoptosis; cell biology; gene expression; lipid metabolism; obesity ID ADIPOSE-SPECIFIC PROTEIN; BODY-COMPOSITION; 3T3-L1 PREADIPOCYTES; GENE-EXPRESSION; FATTY-ACID; INHIBITS DIFFERENTIATION; INSULIN SENSITIVITY; ENERGY-EXPENDITURE; APOPTOSIS; TISSUE AB Gene expression was measured during t10c12-CLA-induced body fat reduction in a polygenic obese line of mice. Adult mice (n = 185) were allotted to a 2 x 2 factorial experiment consisting of either nonobese (ICR-control) or obese (M16-selected) mice fed a 7% fat, purified diet containing either 1% linoleic acid (LA) or 1% t10c12-CLA. Body weight (BW) by day 14 was 12% lower in CLA-compared with LA-fed mice ( P < 0.0001). By day 14, t10c12-CLA reduced weights of epididymal, mesenteric, and brown adipose tissues, as a percentage of BW, in both lines by 30, 27, and 58%, respectively, and increased liver weight/BW by 34% ( P < 0.0001). Total RNA was isolated and pooled (4 pools per tissue per day) from epididymal adipose (days 5 and 14) of the obese mice to analyze gene expression profiles using Agilent mouse oligo microarray slides representing > 20,000 genes. Numbers of genes differentially expressed by greater than or equal to twofold in epididymal adipose (days 5 and 14) were 29 and 125, respectively. It was concluded that, in adipose tissue, CLA increased expression of uncoupling proteins (1 and 2), carnitine palmitoyltransferase system, tumor necrosis factor-α (P < 0.05), and caspase-3 but decreased expression of peroxisome proliferator-activated receptor-γ, glucose transporter-4, perilipin, caveolin-1, adiponectin, resistin, and Bcl-2 (P < 0.01). In conclusion, this experiment has revealed candidate genes that will be useful in elucidating mechanisms of adipose delipidation. C1 N Carolina State Univ, Dept Anim Sci, Raleigh, NC 27695 USA. Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA. RP Cassady, JP (reprint author), N Carolina State Univ, Dept Anim Sci, Raleigh, NC 27695 USA. EM joe_cassady@ncsu.edu OI Odle, Jack/0000-0003-4965-2096 NR 67 TC 46 Z9 46 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD MAY 11 PY 2005 VL 21 IS 3 BP 351 EP 361 DI 10.1152/physiolgenomics.00244.2004 PG 11 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 924ZQ UT WOS:000229021500008 PM 15888570 ER PT J AU Karlsson, G Liu, YC Larsson, J Goumans, MJ Lee, JS Thorgeirsson, SS Ringner, M Karlsson, S AF Karlsson, G Liu, YC Larsson, J Goumans, MJ Lee, JS Thorgeirsson, SS Ringner, M Karlsson, S TI Gene expression profiling demonstrates that TGF-beta 1 signals exclusively through receptor complexes involving Alk5 and identifies targets of TGF-beta signaling SO PHYSIOLOGICAL GENOMICS LA English DT Article DE signal transduction; Smad; microarrays ID GROWTH-FACTOR-BETA; EPITHELIAL-CELLS; DEFICIENT MICE; KINASE; ANGIOGENESIS; REPRESSION; RESOURCE; DATABASE AB Transforming growth factor-β 1 (TGF-β) regulates cellular functions like proliferation, differentiation, and apoptosis. On the cell surface, TGF-β binds to receptor complexes consisting of TGF-β receptor type II (Tβ RII) and activin-like kinase receptor-5 (Alk5), and the downstream signaling is transduced by Smad and MAPK proteins. Recent data have shown that alternative receptor combinations aside from the classical pairing of Tβ RII/Alk5 can be relevant for TGF-β signaling. We have screened for alternative receptors for TGF-β and also for gene targets of TGF-β signaling, by performing functional assays and microarray analysis in murine embryonic fibroblast (MEF) cell lines lacking Alk5. Data from TGF-β-stimulated Alk5(-/-) cells show them to be completely unaffected by TGF-β. Additionally, 465 downstream targets of Alk5 signaling were identified when comparing Alk5(-/-) or TGF-β-stimulated Alk5(+/+) MEFs with unstimulated Alk5(+/+) cells. Our results demonstrate that, in MEFs, TGF-β signals exclusively through complexes involving Alk5, and give insight to its downstream effector genes. C1 Lund Univ, Dept Theoret Phys, Complex Syst Div, S-22362 Lund, Sweden. Univ Lund Hosp, Inst Lab Med, Lab Mol Med & Gene Therapy, S-22185 Lund, Sweden. Univ Lund Hosp, Lund Strateg Res Ctr Stem Cell Biol & Cell Therap, S-22185 Lund, Sweden. Heart Lung Ctr, Dept Cardiol, Utrecht, Netherlands. Natl Canc Inst, Expt Carcinogenesis Lab, Bethesda, MD USA. RP Ringner, M (reprint author), Lund Univ, Dept Theoret Phys, Complex Syst Div, Solvegatan 14A, S-22362 Lund, Sweden. EM markus@thep.lu.se RI Ringner, Markus/G-3641-2011; OI Ringner, Markus/0000-0001-5469-8940; Karlsson, Goran/0000-0001-8197-754X NR 24 TC 23 Z9 23 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD MAY 11 PY 2005 VL 21 IS 3 BP 396 EP 403 DI 10.1152/physiolgenomics.00303.2004 PG 8 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 924ZQ UT WOS:000229021500013 PM 15769904 ER PT J AU Lodowski, DT Barnhill, JF Pyskadlo, RM Ghirlando, R Sterne-Marr, R Tesmer, JJG AF Lodowski, DT Barnhill, JF Pyskadlo, RM Ghirlando, R Sterne-Marr, R Tesmer, JJG TI The role of g beta gamma and domain interfaces in the activation of G protein-coupled receptor kinase 2 SO BIOCHEMISTRY LA English DT Article ID ADRENERGIC-RECEPTOR KINASE; PLECKSTRIN HOMOLOGY DOMAIN; MUSCARINIC ACETYLCHOLINE-RECEPTORS; HETEROTRIMERIC G-PROTEINS; DEPENDENT PHOSPHORYLATION; G(BETA-GAMMA) SUBUNITS; CATALYTIC SUBUNIT; RHODOPSIN KINASE; BINDING-SITE; FAMILY AB In response to extracellular signals, G protein-coupled receptors (GPCRs) catalyze guanine nucleotide exchange on Gα subunits, enabling both activated Gα and Gβγ subunits to target downstream effector enzymes. One target of Gβγ is G protein-coupled receptor kinase 2 (GRK2), an enzyme that initiates homologous desensitization by phosphorylating activated GPCRs. GRK2 consists of three distinct domains: an RGS homology (RH) domain, a protein kinase domain, and a pleckstrin homology (PH) domain, through which it binds Gβγ. The crystal structure of the GRK2-Gβγ complex revealed that the domains of GRK2 are intimately associated and left open the possibility for allosteric regulation by Gβγ. In this paper, we report the 4.5 &ANGS; structure of GRK2, which shows that the binding of Gβγ does not induce large domain rearrangements in GRK2, although small rotations of the RH and PH domains relative to the kinase domain are evident. Mutation of residues within the larger domain interfaces of GRK2 generally leads to diminished expression and activity, suggesting that these interfaces are important for stability and remain intact upon activation of GRK2. Geranylgeranylated Gβγ, but not a soluble mutant of Gβγ, protects GRK2 from clostripain digestion at a site within its kinase domain that is 80 A away from the Gβγ binding site. Equilibrium ultracentrifugation experiments indicate that neither abnormally large detergent micelles nor protein oligornerization can account for the observed protection. The Gβγ/mediated binding of GRK2 to CHAPS micelles or lipid bilayers therefore appears to rigidify the kinase domain, perhaps by encouraging stable contacts between the RH and kinase domains. C1 Univ Texas, Dept Chem & Biochem, Inst Cellular & Mol Biol, Austin, TX 78712 USA. NIDDKD, Mol Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Siena Coll, Dept Biol, Loudonville, NY 12211 USA. RP Tesmer, JJG (reprint author), Univ Texas, Dept Chem & Biochem, Inst Cellular & Mol Biol, 1 Univ Stn A5300, Austin, TX 78712 USA. EM tesmer@mail.utexas.edu RI Ghirlando, Rodolfo/A-8880-2009 FU NHLBI NIH HHS [HL071818] NR 68 TC 32 Z9 33 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 10 PY 2005 VL 44 IS 18 BP 6958 EP 6970 DI 10.1021/boi050119q PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 924EU UT WOS:000228962500025 PM 15865441 ER PT J AU Sanbe, A James, J Tuzcu, V Nas, S Martin, L Gulick, J Osinska, H Sakthivel, S Klevitsky, R Ginsburg, KS Bers, DM Zinman, B Lakatta, EG Robbins, J AF Sanbe, A James, J Tuzcu, V Nas, S Martin, L Gulick, J Osinska, H Sakthivel, S Klevitsky, R Ginsburg, KS Bers, DM Zinman, B Lakatta, EG Robbins, J TI Transgenic rabbit model for human troponin I - Based hypertrophic cardiomyopathy SO CIRCULATION LA English DT Article DE cardiovascular diseases; heart diseases; hypertrophy ID HEAVY-CHAIN PROMOTER; GAP-JUNCTION; CLINICAL MANIFESTATIONS; REGULATORY PROPERTIES; CARDIAC-DISEASE; MYOSIN; MUSCLE; PATHOPHYSIOLOGY; CONTRACTION; HEART AB Background-Transgenic and gene-targeted models have focused on the mouse. Fundamental differences between the mouse and human exist in Ca2+ handling during contraction/relaxation and in alterations in Ca2+ flux during heart failure, with the rabbit more accurately reflecting the human system. Methods and Results-Cardiac troponin I (cTnI) mutations can cause familial hypertrophic cardiomyopathy. An inhibitory domain mutation, arginine146 &RARR; glycine (cTnI(146Gly)), was modeled with the use of transgenic expression in the rabbit ventricle. cTnI146Gly levels > 40% of total cTnI were perinatally lethal, whereas replacement levels of 15% to 25% were well tolerated. cTnI(146Gly) expression led to a leftward shift in the force-pCa(2+) curves with cardiomyocyte disarray, fibrosis, and altered connexin43 organization. In isolated cTnI(146Gly) myocytes, twitch relaxation amplitudes were smaller than in normal cells, but [Ca](i) transients and sarcoplasmic reticulum Ca2+ load were not different. Detrended fluctuation analysis of the QT(max) intervals was used to evaluate the cardiac repolarization phase and showed a significantly higher scaling exponent in the transgenic animals. Conclusions-Expression of modest amounts of cTnI(146Gly) led to subtle defects without severely affecting cardiac function. Aberrant connexin organization, subtle morphological deficits, and an altered fractal pattern of the repolarization phase of transgenic rabbits, in the absence of entropy or other ECG abnormalities, may indicate an early developing pathology before the onset of more obvious repolarization abnormalities or major alterations in cardiac mechanics. C1 Childrens Hosp Res Fdn, Div Mol Cardiovasc Biol, Cincinnati, OH 45229 USA. Childrens Hosp Res Fdn, Div Pediat Cardiol, Cincinnati, OH 45229 USA. Loyola Univ, Dept Physiol, Maywood, IL 60153 USA. Loyola Univ, Cardiovasc Inst, Maywood, IL 60153 USA. NIA, Intramural Res Program, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Robbins, J (reprint author), Childrens Hosp Res Fdn, Div Mol Cardiovasc Biol, Cincinnati, OH 45229 USA. EM jeff.robbins@cchmc.org RI Bers, Donald/C-4507-2012; OI Bers, Donald/0000-0002-2237-9483 FU NHLBI NIH HHS [R01 HL056370, P01 HL069779, P50 HL052318, P50 HL074728] NR 38 TC 44 Z9 45 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 10 PY 2005 VL 111 IS 18 BP 2330 EP 2338 DI 10.1161/01.CIR.0000164234.24957.75 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 924QT UT WOS:000228995700010 PM 15867176 ER PT J AU Gonzalez-Moreno, O Calvo, A Joshi, BH Abasolo, I Leland, P Wang, Z Montuenga, L Puri, RK Green, JE AF Gonzalez-Moreno, O Calvo, A Joshi, BH Abasolo, I Leland, P Wang, Z Montuenga, L Puri, RK Green, JE TI Gene expression profiling identifies IL-13 receptor alpha 2 chain as a therapeutic target in prostate tumor cells overexpressing adrenomedullin SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cDNA microarrays; prostate cancer; adrenomedullin; IL-13R alpha 2; gene expression profiling ID PSEUDOMONAS EXOTOXIN; IN-VIVO; INTERLEUKIN-13 RECEPTOR; SIGNAL-TRANSDUCTION; AUTOCRINE GROWTH; MUTATED FORM; CANCER; LINES; PEPTIDE; CARCINOMA AB Human adrenomedullin (AM) is a 52 amino acid peptide, which shares homology with the calcitonin gene-related peptide. Overexpression of AM in the prostate carcinoma cell line PC-3 results in growth inhibition with a 20% (for human AM) and 35% (for rat AM) increase in doubling time compared to parental or mock-transfected cells. We demonstrate by gene expression profiling that AM overexpression results in the dysregulation of approximately 100 genes. Examples of such genes include many involved in the formation of the cytoskeleton, cell adhesion and the extracellular matrix, as well as regulators of the cell cycle and apoptosis, cytokines and transcription factors. Several genes related to cell growth arrest, such as GADD45, IGF-BP6 and RUNX-3, are upregulated by AM. Interestingly, interleukin-13 receptor alpha 2 (IL-13R alpha 2) transcripts were significantly increased in clones overexpressing AM, which was confirmed by semiquantitative RT-PCR analysis. In addition, PC-3 cells treated with AM showed an overexpression of IL-13R alpha 2, which was abolished when cells were preincubated with an anti-AM blocking antibody. When PC-3 cells overexpressing AM and the IL-13R alpha 2 were treated with the highly specific IL13-PE38 cytotoxin, which binds to this receptor, a concentration-dependent inhibition of protein synthesis was observed. The IC50 (concentration of cytotoxin inhibiting protein synthesis by 50%) ranged from 1 to 4 ng/ml. This cytotoxicity was specific as it was neutralized by the excess of IL-13 and confirmed by clonogenic assays. This study describes a novel AM-induced mechanism of tumor sensitization through the upregulation of functional IL-13R alpha 2 chain, an ideal target for the highly specific recombinant chimeric cytotoxin IL13-PE38. (c) 2004 Wiley-Liss, Inc. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Univ Navarra, Dept Histol & Pathol, E-31080 Pamplona, Spain. Food & Drug Adm, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD USA. Northwestern Univ, Sch Med, Robert H Lurie Comprehens Canc Ctr, Dept Urol, Chicago, IL 60611 USA. RP Green, JE (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bldg 41,Room C629,41 Lib Dr, Bethesda, MD 20892 USA. EM jegreen@nih.gov RI Abasolo, Ibane/H-7741-2012 OI Abasolo, Ibane/0000-0001-5970-6276 NR 43 TC 16 Z9 16 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 MAY 10 PY 2005 VL 114 IS 6 BP 870 EP 878 DI 10.1002/ijc.20789 PG 9 WC Oncology SC Oncology GA 915VF UT WOS:000228338700004 PM 15609296 ER PT J AU Mulshine, JL AF Mulshine, JL TI New developments in lung cancer screening SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID HELICAL COMPUTED-TOMOGRAPHY; IMAGE DATABASE CONSORTIUM; SMALL PULMONARY NODULES; AIDED DIAGNOSIS; COST-EFFECTIVENESS; SPIRAL CT; SMOKERS; EXPERIENCE; PERFORMANCE; MORTALITY AB Lung cancer is the most lethal cancer in our society. Late diagnosis of this disease is a major problem and so recent favorable reports with spiral computed tomography screening of high-risk populations have rekindled interest in improving early lung cancer detections. The process of lung cancer screening is a complicated process that involves many component activities. Interest to date has heavily focused on the initial case identification, but more recent reports have suggested that the issues with case work-up and surgical management also bear closer consideration. Given the dynamic nature of spiral computed tomography scan development and the remarkable improvements in imaging resolution over the last decade, there is an urgent need for research to establish optimal clinical management of early lung cancer detected in a screening setting. C1 NIH, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. RP Mulshine, JL (reprint author), NIH, Cell & Canc Biol Branch, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM mulshinej@bprb.nci.nih.gov NR 48 TC 9 Z9 10 U1 0 U2 7 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 MAY 10 PY 2005 VL 23 IS 14 BP 3198 EP 3202 DI 10.1200/JCO.2005.12.344 PG 5 WC Oncology SC Oncology GA 925ZX UT WOS:000229093500004 PM 15886306 ER PT J AU Shankar, LK Sullivan, DC AF Shankar, LK Sullivan, DC TI Functional imaging in lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; SOLITARY PULMONARY NODULES; MEDIASTINAL LYMPH-NODES; FDG-PET; PROGNOSTIC VALUE; F-18 FLUOROMISONIDAZOLE; INDUCTION CHEMOTHERAPY; INITIAL EXPERIENCE; COST-EFFECTIVENESS; IN-VIVO AB Accurate detection of the presence and extent of disease is vital in the management of non-small-cell lung cancer. While computed tomography and magnetic resonance imaging tend to be the routine diagnostic modalities used in the management of lung cancer, there have been significant advances in the field of functional and molecular imaging. In this article, we review the performance of the functional imaging techniques that are currently available for the evaluation of non-small-cell lung cancer. The techniques range from evaluation of glucose metabolism in tumors with fluorodeoxyglucose, to evaluation of proliferation with fluorothymidine and evaluation of tumor hypoxia with agents such as fluoromisonidazole. Magnetic resonance imaging with an emphasis on dynamic contrast enhancement of tumors as well as detecting of malignant lymph nodes with targeted contrast agents is discussed. Emerging technologies such as lung imaging fluorescence endoscopy are considered. The role of functional imaging in planning, predicting response to, and evaluating effects of, various therapies is explored. C1 NCI, Canc Imaging Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Shankar, LK (reprint author), 6130 Execut Blvd,Room 6048, Bethesda, MD 20892 USA. EM shankarl@mail.nih.gov NR 74 TC 24 Z9 25 U1 2 U2 3 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 MAY 10 PY 2005 VL 23 IS 14 BP 3203 EP 3211 DI 10.1200/JCO.2005.08.854 PG 9 WC Oncology SC Oncology GA 925ZX UT WOS:000229093500005 PM 15886307 ER PT J AU Best, RB Hummer, G AF Best, RB Hummer, G TI Reaction coordinates and rates from transition paths SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE carbon nanotubes; chemical kinetics; protein folding; transition-state theory; Grotthuss mechanism ID ISOMERIZATION DYNAMICS; CARBON NANOTUBES; FOLDING FUNNELS; FREE-ENERGY; WATER; MOLECULES; PROTEINS; KINETICS; STATES; CONDUCTION AB The molecular mechanism of a reaction in solution is reflected in its transition-state ensemble and transition paths. We use a Bayesian formula relating the equilibrium and transition-path ensembles to identify transition states, rank reaction coordinates, and estimate rate coefficients. We also introduce a variational procedure to optimize reaction coordinates. The theory is illustrated with applications to protein folding and the dipole reorientation of an ordered water chain inside a carbon nanotube. To describe the folding of a simple model of a three-helix bundle protein, we variationally optimize the weights of a projection onto the matrix of native and nonnative amino acid contacts. The resulting one-dimensional reaction coordinate captures the folding transition state, with formation and packing of helix 2 and 3 constituting the bottleneck for folding. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDKD, Phys Chem Lab, NIH, Bldg 5,Room 132, Bethesda, MD 20892 USA. EM hummer@helix.nih.gov RI Hummer, Gerhard/A-2546-2013; Best, Robert/H-7588-2016 OI Hummer, Gerhard/0000-0001-7768-746X; Best, Robert/0000-0002-7893-3543 NR 41 TC 259 Z9 260 U1 7 U2 60 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 MAY 10 PY 2005 VL 102 IS 19 BP 6732 EP 6737 DI 10.1073/pnas.0408098102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 925JD UT WOS:000229048500018 PM 15814618 ER PT J AU Giovannucci, EL Liu, Y Leitzmann, MF Stampfer, MJ Willett, WC AF Giovannucci, EL Liu, Y Leitzmann, MF Stampfer, MJ Willett, WC TI A prospective study of physical activity and incident and fatal prostate cancer SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MALE HEALTH-PROFESSIONALS; NATIONAL-HEALTH; SEX-HORMONES; IN-VITRO; RISK; INSULIN; EXERCISE; LEPTIN; TESTOSTERONE; POPULATION AB Background: Whether physical activity has benefits against prostate cancer incidence or progression is unclear. Therefore, we assessed physical activity in relation to prostate cancer incidence, mortality, and Gleason histologic grade. Methods: We used data from the Health Professionals Follow-up Study, a prospective cohort study, to determine the number of cases of incident, advanced (seminal vesicle invasion, metastasis, or fatal), fatal, and high-grade prostate cancer in a cohort of 47 620 US male health professionals, followed up from February 1, 1986, to January 31, 2000. Results: During 14 years of follow-up, we documented 2892 new cases of prostate cancer, including 482 advanced cases (280 of which were fatal). For total prostate cancer, no association was observed for total, vigorous, and nonvigorous physical activity. In men 65 years or older, we observed a lower risk in the highest category of vigorous activity for advanced (multivariable relativ risk, 0.33; 95% confidence interval, 0.17-0.62, for more than 29 vs 0 metabolic equivalent hours) and for fatal (relative risk, 0.26; 95% confidence interval, 0.110.66) prostate cancer. No associations were observed in younger men. Differential screening by prostate-specific antigen or a reduction in physical activity due to undiagnosed prostate cancer did not appear to account for the results. Among cases, men with high levels of physical activity were less likely to be diagnosed with poorly differentiated cancers (Gleason grade 7). Conclusion: Although the mechanisms are not yet understood, these findings suggest that regular vigorous activity could slow the progression of prostate cancer and might be recommended to reduce mortality from prostate cancer, particularly given the many other documented benefits of exercise. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. NCI, Nutr Epidemiol Branch, Rockville, MD USA. RP Giovannucci, EL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM edward.giovannucci@channing.harvard.edu FU NCI NIH HHS [CA 55075] NR 42 TC 89 Z9 93 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 9 PY 2005 VL 165 IS 9 BP 1005 EP 1010 DI 10.1001/archinte.165.9.1005 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 924ST UT WOS:000229001400005 PM 15883238 ER PT J AU Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL AF Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL TI Long-term intake of trans-fatty acids and risk of gallstone disease in men SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID LIPOPROTEIN CHOLESTEROL LEVELS; FOOD FREQUENCY QUESTIONNAIRE; CORONARY-HEART-DISEASE; HEALTHY-SUBJECTS; PLASMA-LIPIDS; STEARIC-ACID; SERUM; DIET; HUMANS; WOMEN AB Background: The consumption of trans-fatty acids adversely affects blood lipid levels. The relationship with the incidence of gallstone disease is unknown. Methods: We prospectively studied consumption of trans-fatty acids in relation to the risk of gallstone disease in a cohort of 45 912 men. trans-Fatty acid consumption was assessed using a validated semiquantitative food frequency questionnaire. Newly diagnosed gallstone disease, by radiology or cholecystectomy, was ascertained biennially. Results: During 14 years of follow-up, we documented 2356 new cases of symptomatic gallstones. After adjusting for age and other potential risk factors, we found that compared with men in the lowest quintile of dietary intake of trans-fatty acids, the relative risk (RR) of gallstone disease for those in the highest quintile was 1.23 (95% confidence interval [CI], 1.04-1.44; P for trend, .03). Among individual trans-fatty acids, the RR for trans-oleic fatty acid, when extreme quintiles were compared, was 1.24 (95% CI, 1.06-1.45; P for trend, .02). Intakes of trans-palmitoleic fatty acid (RR, 1.09; 95% CI, 0.90-1.31), trans,trans 18:2 fatty acid (RR, 1.14; 95% CI, 0.96-1.34), and cis-trans 18:2 fatty acid (RR, 1.00; 95% CI, 0.86-1.16) were not significantly associated with the risk. Conclusions: Our results suggest that a higher intake of trans-fatty acids modestly increases risk of gallstone disease. This adds to the concern that partial hydrogenation of vegetable oils to form shortening and margarine can lead to adverse health effects. C1 Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY 40536 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. RP Tsai, CJ (reprint author), Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, 800 Rose St, Lexington, KY 40536 USA. EM hpcjt@channing.harvard.edu FU NCI NIH HHS [CA55075]; NIDDK NIH HHS [DK46200] NR 35 TC 17 Z9 18 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 9 PY 2005 VL 165 IS 9 BP 1011 EP 1015 DI 10.1001/archinte.165.9.1011 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 924ST UT WOS:000229001400006 PM 15883239 ER PT J AU Cohen, JI AF Cohen, JI TI HMG CoA reductase inhibitors (statins) to treat Epstein-Barr virus-driven lymphoma SO BRITISH JOURNAL OF CANCER LA English DT Review DE statin; Epstein-Barr virus; apoptosis; NF-kappa B; lymphoma ID NF-KAPPA-B; LATENT GENE-EXPRESSION; MEMBRANE-PROTEIN 1; IN-VITRO; MEVALONATE PATHWAY; CELL-SURVIVAL; LIPID RAFTS; SIMVASTATIN; INFECTION; DISEASE AB While statins have been highly effective for lowering serum cholesterol and reducing the incidence of coronary events, they have multiple other effects. Certain statins block the interaction of adhesion molecules that are important for cell-cell interactions including those between EBV-transformed B cells. These same statins inhibit NF-κ B activation in the cells and induce apoptosis of transformed B cells. Studies in severe combined immunodeficiency mice show that simvastatin delays the development of EBV-lymphomas in these animals. These statins might be considered for the treatment of EBV-lymphomas in selected patients. C1 NIAID, Lab Clin Infect Dis, Med Virol Sect, NIH, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Lab Clin Infect Dis, Med Virol Sect, NIH, Bldg 10,Rm 11N228,10 Ctr Dr,MSC 1888, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov NR 45 TC 14 Z9 17 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 MAY 9 PY 2005 VL 92 IS 9 BP 1593 EP 1598 DI 10.1038/sj.bjc.6602561 PG 6 WC Oncology SC Oncology GA 922UE UT WOS:000228863500002 PM 15856040 ER PT J AU Zhang, Y Graubard, BI Klebanoff, MA Ronckers, C Stanczyk, FZ Longnecker, MP McGlynn, KA AF Zhang, Y Graubard, BI Klebanoff, MA Ronckers, C Stanczyk, FZ Longnecker, MP McGlynn, KA TI Maternal hormone levels among populations at high and low risk of testicular germ cell cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE maternal hormone levels; testicular germ cell cancer; ethnic differences; undescended testes ID SERUM-ALPHA-FETOPROTEIN; UNITED-STATES; INDUCED CRYPTORCHIDISM; UNCONJUGATED ESTRIOL; BREAST-CANCER; BIRTH-WEIGHT; ESTROGEN; PREGNANCY; RACE; TESTOSTERONE AB Ethnic differences in maternal oestrogen levels have been suggested as explaining the significantly higher risk of testicular germ cell tumours (TGCT) of white men than black men in the United States. We therefore examined levels of maternal oestrogens, as well as testosterone and alphafetoprotein (AFP), in 150 black and 150 white mothers in the Collaborative Perinatal Project. Serum levels of estradiol ( total, free and bioavailable), estriol, testosterone ( total, free and bioavailable), sex hormone binding globulin ( SHBG), and AFP were examined during first and third trimesters. We found that the black mothers, rather than the white mothers, had significantly higher estradiol levels in first trimester ( P = 0.05). Black mothers also had significantly higher levels of all testosterone (P<0.001) and AFP (P<0.001) in both trimesters. In addition, the ratios of sex hormones ( estradiol/ testosterone) were significantly lower among black mothers. These findings provide little support to the oestrogen hypothesis, but are consistent with higher levels of testosterones and/or AFP being associated with reduced risk of TGCT; alternatively, lower oestrogen/androgen ratios may be associated with reduced risk. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. NICHHD, NIH, DHHS, Rockville, MD USA. Univ So Calif, Keck Sch Med, Reprod Endocrine Res Lab, Los Angeles, CA USA. NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP McGlynn, KA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS-7060, Rockville, MD 20852 USA. EM mcglynnk@mail.nih.gov RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Longnecker, Matthew/0000-0001-6073-5322 NR 35 TC 27 Z9 28 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 MAY 9 PY 2005 VL 92 IS 9 BP 1787 EP 1793 DI 10.1038/sj.bjc.6602545 PG 7 WC Oncology SC Oncology GA 922UE UT WOS:000228863500030 PM 15841083 ER PT J AU Handa, V Goldwater, D Stiles, D Cam, M Poy, G Kumari, D Usdin, K AF Handa, V Goldwater, D Stiles, D Cam, M Poy, G Kumari, D Usdin, K TI Long CGG-repeat tracts are toxic to human cells: Implications for carriers of Fragile X premutation alleles SO FEBS LETTERS LA English DT Article DE fragile X syndrome; CGG-repeat; premutation; POF; fragile X tremor and ataxia syndrome ID PREMATURE OVARIAN FAILURE; HUNTINGTONS-DISEASE; INTERMEDIATE ALLELES; GENE-EXPRESSION; NEURODEGENERATION; DROSOPHILA; RNA; TRANSCRIPTION; EXPANSION; PROTEIN AB People with 59-200 CGG (.) CCG-repeats in the 5' UTR of one of their FMR1 genes are at risk for Fragile X tremor and ataxia syndrome. Females are also at risk for premature ovarian failure. These symptoms are thought to be due to the presence of the repeats at the DNA and/or RNA level. We show here that long transcribed but untranslated CGG-repeat tracts are toxic to human cells and alter the expression of a wide variety of different genes including caspase-8, CYFIP, Neurotensin and UBE3A. © 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Microarray Core Facil, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, 8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. EM ku@helix.nih.gov NR 32 TC 36 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 9 PY 2005 VL 579 IS 12 BP 2702 EP 2708 DI 10.1016/j.febslet.2005.04.004 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 925KI UT WOS:000229051600026 PM 15862312 ER PT J AU Putney, JW AF Putney, JW TI Capacitative calcium entry: sensing the calcium stores SO JOURNAL OF CELL BIOLOGY LA English DT Editorial Material ID INFLUX; MECHANISM; CELLS AB A long-standing mystery in the cell biology of calcium channel regulation is the nature of the signal linking intracellular calcium stores to plasma membrane capacitative calcium entry channels. An RNAi-based screen of selected Drosophila genes has revealed that a calcium-binding protein, stromal interaction molecule ( STIM), plays an essential role in the activation of these channels and may be the long sought sensor of calcium store content. C1 NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov NR 11 TC 107 Z9 108 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 9 PY 2005 VL 169 IS 3 BP 381 EP 382 DI 10.1083/jcb.200503161 PG 2 WC Cell Biology SC Cell Biology GA 924QU UT WOS:000228995800003 PM 15866892 ER PT J AU Lizunov, VA Matsumoto, H Zimmerberg, J Cushman, SW Frolov, VA AF Lizunov, VA Matsumoto, H Zimmerberg, J Cushman, SW Frolov, VA TI Insulin stimulates the halting, tethering, and fusion of mobile GLUT4 vesicles in rat adipose cells SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GLUCOSE-TRANSPORTER GLUT4; PLASMA-MEMBRANE; SUBCELLULAR TRAFFICKING; INFLUENZA HEMAGGLUTININ; REGULATED TRANSPORT; 3T3-L1 ADIPOCYTES; STORAGE-VESICLES; TRANSLOCATION; COMPARTMENTS; EXOCYTOSIS AB Glucose transport in adipose cells is regulated by changing the distribution of glucose transporter 4 ( GLUT4) between the cell interior and the plasma membrane (PM). Insulin shifts this distribution by augmenting the rate of exocytosis of specialized GLUT4 vesicles. We applied time-lapse total internal reflection fluorescence microscopy to dissect intermediates of this GLUT4 translocation in rat adipose cells in primary culture. Without insulin, GLUT4 vesicles rapidly moved along a microtubule network covering the entire PM, periodically stopping, most often just briefly, by loosely tethering to the PM. Insulin halted this traffic by tightly tethering vesicles to the PM where they formed clusters and slowly fused to the PM. This slow release of GLUT4 determined the overall increase of the PM GLUT4. Thus, insulin initially recruits GLUT4 sequestered in mobile vesicles near the PM. It is likely that the primary mechanism of insulin action in GLUT4 translocation is to stimulate tethering and fusion of trafficking vesicles to specific fusion sites in the PM. C1 NIDDKD, Diabet Branch, Lab Cellular & Mol Biophys, NICHHD,NIH, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, Expt Diabet Metab & Nutr Sect, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, AN Frumkin Electrochem Inst, Moscow 119071, Russia. RP Zimmerberg, J (reprint author), NIDDKD, Diabet Branch, Lab Cellular & Mol Biophys, NICHHD,NIH, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov RI Lizunov, Vladimir/B-5468-2009; OI Frolov, Vadim/0000-0002-0653-5669 NR 42 TC 115 Z9 120 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 9 PY 2005 VL 169 IS 3 BP 481 EP 489 DI 10.1083/jcb.200412069 PG 9 WC Cell Biology SC Cell Biology GA 924QU UT WOS:000228995800014 PM 15866888 ER PT J AU Carter, CRD Dagg, BM Whitmore, KM Keeble, JR Asokanathan, C Rodgers, A Watanabe, M Xing, D Walker, KB AF Carter, CRD Dagg, BM Whitmore, KM Keeble, JR Asokanathan, C Rodgers, A Watanabe, M Xing, D Walker, KB TI Treatment of mice with IL-12 DNA constructs leads to augmented NK activity in lungs but low IFN-gamma release - Implications for Bordetella pertussis infections following aerosol challenge SO CYTOKINE LA English DT Article DE DNA constructs; interleukin-12; Bordetella pertussis; cell mediated responses; aerosol challenge ID CELL-MEDIATED-IMMUNITY; MYCOBACTERIUM-TUBERCULOSIS; IN-VIVO; MURINE INTERLEUKIN-12; RESPIRATORY-INFECTION; TH1 CELLS; NAKED DNA; VACCINATION; MODEL; GENE AB Interleukin-12 protein has been widely used experimentally in therapeutic and adjuvant settings in the treatment of different diseases including intra-cellular bacterial infections. The in vivo clearance of Bordetella pertussis infections in naive mice and in animals vaccinated with whole cell vaccine is considered to be a Th-1 dependent mechanism. Furthermore, the addition of IL-12 protein to an acellular pertussis vaccine increases the efficacy of this vaccine. Whilst the use of IL-12 protein is often beneficial, a number of problems there are associated with this cytokine including toxicities and down regulation of normal immune functions. The use of DNA constructs encoding this cytokine may be a way of achieving maximum therapeutic benefit with minimum toxicity. The aims of this study were to optimise the effects of two IL-12 DNA constructs, especially with respect to augmenting pulmonary immune responsiveness and to compare the effect of IL-12 DNA and IL-12 protein on bacterial colonisation of lungs following aerosol challenge with B. pertussis. We found that IL-12 DNA constructs augmented the activity of pulmonary NK cells but had little effect on the course of B. pertussis infections in mice. In contrast to IL-12 protein, the DNA constructs had no immuno suppressive effects on splenic lymphocyte mitogen responses. (c) 2005 Elsevier Ltd. All rights reserved. C1 Natl Inst Biol Stand & Controls, Div Immunol, Potters Bar EN6 3QG, Herts, England. Natl Inst Biol Stand & Controls, Div Bacteriol, Potters Bar EN6 3QG, Herts, England. NCI, Expt Immunol Lab, Frederick, MD 21702 USA. RP Walker, KB (reprint author), Natl Inst Biol Stand & Controls, Div Immunol, Blanche Lane,S Mimms, Potters Bar EN6 3QG, Herts, England. EM kbwalker@nibsc.ac.uk NR 34 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAY 7 PY 2005 VL 30 IS 3 BP 100 EP 108 DI 10.1016/j.cyto.2004.12.003 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 921JR UT WOS:000228760900002 PM 15826816 ER PT J AU Leopold, DA Rhodes, G Muller, KM Jeffery, L AF Leopold, DA Rhodes, G Muller, KM Jeffery, L TI The dynamics of visual adaptation to faces SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE visual perception; face recognition; adaptation ID INSPECTION DURATION; TILTED LINES; MOTION; PERCEPTION; SIZE; ORIENTATION; CONTRAST; DECAY; DISTINCTIVENESS; MECHANISMS AB Several recent demonstrations using visual adaptation have revealed high-level aftereffects for complex patterns including faces. While traditional aftereffects involve perceptual distortion of simple attributes such as orientation or colour that are processed early in the visual cortical hierarchy, face adaptation affects perceived identity and expression, which are thought to be products of higher-order processing. And, unlike most simple aftereffects, those involving faces are robust to changes in scale, position and orientation between the adapting and test stimuli. These differences raise the question of how closely related face aftereffects are to traditional ones. Little is known about the build-up and decay of the face aftereffect, and the similarity of these dynamic processes to traditional aftereffects might provide insight into this relationship. We examined the effect of varying the duration of both the adapting and test stimuli on the magnitude of perceived distortions in face identity. We found that, just as with traditional aftereffects, the identity aftereffect grew logarithmically stronger as a function of adaptation time and exponentially weaker as a function of test duration. Even the subtle aspects of these dynamics, such as the power-law relationship between the adapting and test durations, closely resembled that of other aftereffects. These results were obtained with two different sets of face stimuli that differed greatly in their low-level properties. We postulate that the mechanisms governing these shared dynamics may be dissociable from the responses of feature-selective neurons in the early visual cortex. C1 Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. Univ Western Australia, Sch Psychol, Perth, WA 6907, Australia. RP Leopold, DA (reprint author), NIH, Unit Cognit Neurophysiol & Imaging, MSC 4400,49 Convent Dr,Bldg 49,Room B2J-45, Bethesda, MD 20892 USA. EM leopoldd@mail.nih.gov RI Jeffery, Linda/H-5127-2014; OI Jeffery, Linda/0000-0002-3980-5864; Leopold, David/0000-0002-1345-6360 NR 49 TC 151 Z9 153 U1 12 U2 40 PU ROYAL SOCIETY PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 J9 P ROY SOC B-BIOL SCI JI Proc. R. Soc. Lond. Ser. B-Biol. Sci. PD MAY 7 PY 2005 VL 272 IS 1566 BP 897 EP 904 DI 10.1098/rspb.2004.3022 PG 8 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA 937MU UT WOS:000229929300003 PM 16024343 ER PT J AU Li, WM Pi, RB Chan, HHN Fu, HJ Lee, NTK Tsang, HW Pu, YM Chang, DC Li, CY Luo, JL Xiong, KM Li, ZW Xue, H Carlier, PR Pang, YP Tsim, KWK Li, MT Han, YF AF Li, WM Pi, RB Chan, HHN Fu, HJ Lee, NTK Tsang, HW Pu, YM Chang, DC Li, CY Luo, JL Xiong, KM Li, ZW Xue, H Carlier, PR Pang, YP Tsim, KWK Li, MT Han, YF TI Novel dimeric acetylcholinesterase inhibitor bis(7)-tacrine, but not donepezil, prevents glutamate-induced neuronal apoptosis by blocking N-methyl-D-aspartate receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CEREBELLAR GRANULE NEURONS; ANTI-ALZHEIMERS AGENT; RAT CORTICAL-NEURONS; CEREBRAL-CORTEX; IN-VITRO; DISEASE; ACTIVATION; CELLS; P38; EXCITOTOXICITY AB The neuroprotective properties of bis(7)-tacrine, a novel dimeric acetylcholinesterase (AChE) inhibitor, on glutamate-induced excitotoxicity were investigated in primary cultured cerebellar granule neurons (CGNs). Exposure of CGNs to 75 mu M glutamate resulted in neuronal apoptosis as demonstrated by Hoechst staining, TUNEL, and DNA fragmentation assays. The bis(7)-tacrine treatment ( 0.01 - 1 mu M) on CGNs markedly reduced glutamate-induced apoptosis in dose-and time-dependent manners. However, donepezil and other AChE inhibitors, even at concentrations of inhibiting AChE to the similar extents as 1 mu M bis( 7)- tacrine, failed to prevent glutamate-induced excitotoxicity in CGNs; moreover, both atropine and dihydro-beta-erythroidine, the cholinoreceptor antagonists, did not affect the anti-apoptotic properties of bis( 7)- tacrine, suggesting that the neuroprotection of bis( 7)- tacrine appears to be independent of inhibiting AChE and cholinergic transmission. In addition, ERK1/2 and p38 pathways, downstream signals of N-methyl-D-aspartate ( NMDA) receptors, were rapidly activated after the exposure of glutamate to CGNs. Bis(7)-tacrine inhibited the apoptosis and the activation of these two signals with the same efficacy as the coapplication of PD98059 and SB203580. Furthermore, using fluorescence Ca(2+) imaging, patch clamp, and receptor-ligand binding techniques, bis( 7)- tacrine was found effectively to buffer the intracellular Ca(2+) increase triggered by glutamate, to reduce NMDA-activated currents and to compete with [(3)H] MK-801 with an IC(50) value of 0.763 mu M in rat cerebellar cortex membranes. These findings strongly suggest that bis( 7)- tacrine prevents glutamate-induced neuronal apoptosis through directly blocking NMDA receptors at the MK-801-binding site, which offers a new and clinically significant modality as to how the agent exerts neuroprotective effects. C1 Hong Kong Univ Sci & Technol, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. Hong Kong Univ Sci & Technol, Dept Biol, Hong Kong, Hong Kong, Peoples R China. Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Mol & Cellular Neurobiol, Wuhan 430030, Peoples R China. NIAAA, Mol & Cellular Neurobiol Lab, Bethesda, MD 20892 USA. Virginia Tech, Dept Chem, Blacksburg, VA 24061 USA. Mayo Fdn Med Educ & Res, Rochester, MN 55905 USA. Sun Yat Sen Univ, Dept Pharmacol, Guangzhou 510080, Peoples R China. RP Han, YF (reprint author), Hong Kong Univ Sci & Technol, Dept Biochem, Clear Water Bay, Hong Kong, Hong Kong, Peoples R China. EM bcyfhan@ust.hk RI FU, HONGJUN/H-4498-2011; OI Han, Yifan/0000-0002-5833-069X; Pang, Yuan-Ping/0000-0003-0838-2560; Xue, Hong/0000-0002-8133-9828; Carlier, Paul/0000-0002-6683-285X NR 49 TC 79 Z9 90 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 2005 VL 280 IS 18 BP 18179 EP 18188 DI 10.1074/jbc.M411085200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 922AH UT WOS:000228807200076 PM 15710623 ER PT J AU Braithwaite, EK Prasad, R Shock, DD Hou, EW Beard, WA Wilson, SH AF Braithwaite, EK Prasad, R Shock, DD Hou, EW Beard, WA Wilson, SH TI DNA polymerase lambda mediates a back-up base excision repair activity in extracts of mouse embryonic fibroblasts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL NUCLEAR ANTIGEN; MAMMALIAN-CELLS; LYASE ACTIVITY; SITE REPAIR; BETA; IDENTIFICATION; ENZYME; PATHWAY; CYTOTOXICITY; GLYCOSYLASE AB Mammalian DNA polymerase (pol) lambda is a member of the X-family of DNA polymerases and has striking enzymatic and structural similarities to mammalian DNA pol beta. Because pol beta provides two important enzymatic activities for base excision repair (BER), we examined whether pol lambda might also contribute to BER. We used extracts from mouse embryonic fibroblasts representing wild-type and null genotypes for pol beta and pol lambda. In combination with neutralizing antibodies against pol beta and pol lambda, our results show a BER deficiency in the pol lambda -/- cell extract compared with extract from isogenic wild-type cells. In addition, the pol lambda antibody strongly reduced in vitro BER in the pol beta -/- cell extract. These data indicate that pol lambda is able to contribute to BER in mouse fibroblast cell extract. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov NR 40 TC 90 Z9 94 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 2005 VL 280 IS 18 BP 18469 EP 18475 DI 10.1074/jbc.M411864200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 922AH UT WOS:000228807200110 PM 15749700 ER PT J AU Rodriguez-Rosasa, ME Medrano, JG Epstein, DH Moolchan, ET Preston, KL Wainer, IW AF Rodriguez-Rosasa, ME Medrano, JG Epstein, DH Moolchan, ET Preston, KL Wainer, IW TI Determination of total and free concentrations of the enantiomers of methadone and its metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine) in human plasma by enantioselective liquid chromatography with mass spectrometric detection SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 28th International Symposium and Exhibition on High Performance Liquid-Phase Sepatations and Related Techniques CY JUN 12-18, 2004 CL Philadelphia, PA DE (S)methadone; (R)-methadone; chiral chromatography; AGP-chiral stationary phase ID SOLID-PHASE EXTRACTION; STEREOSELECTIVE DETERMINATION; MAIN METABOLITE; ALPHA-1-ACID GLYCOPROTEIN; PROTEIN BINDING; SERUM; MAINTENANCE; PHARMACOKINETICS; URINE; PHARMACODYNAMICS AB A sensitive enantioselective liquid chromatographic assay with mass spectrometric detection (LC-MS) has been validated for the determination of total and free plasma concentrations of (R)- and (S)-methadone (Met) and (R)- and (S)-2-ethylidene-1,5-dimethyl-3,3diphenylpyrrolidine (EDDP the primary metabolite of Met), using their respective deuterium-labeled compounds as internal standards [(R,S)d(3) -Met and (R,S)-d3-EDDP]. For total drug determinations, 1 ml human plasma was extracted, using a cation-exchange solid-phase extraction cartridge: the eluate was evaporated, reconstituted in the mobile phase, and injected into the LC-MS system. The free fractions of Met and EDDP were determined, using 500 μ l of plasma, which were placed in an ultrafiltration device and centrifuged at 2000 x g until 250 111 of filtrate was collected. The filtrate was extracted as described above and analyzed. Enantioselective separations were achieved using an α(1)-acid glycoprotein chiral stationary phase, a mobile phase composed of acetonitrile-ammoniurn acetate buffer [10mM, pH 7.0] (18:82, v/v), a flow rate of 0.9 ml/min at 25 &DEG; C. Under these conditions, enantioselective separations were observed for Met (α = 1.30) and EDDP (α = 1. 17) within 15 min. Met, EDDP, [H-2(3)]-Met and [H-2(3)]-EDDP were detected using selected ion monitoring at m/z 310.30, 278.20, 313.30, and 281.20. respectively. Linear relationships between peak height ratio and drug-enantiomer concentrations were obtained for Met in the range 1.0--300.0 ng/ml, and for EDDP from 0.1 to 25.0 ng/ml with correlation coefficients greater than 0.999, where the lower limit of quantification (LLOQ) was I ng/ml for Met and 0.1 ng/ml for EDDP. The relative standard deviation (R.S.D.)expressed as R.S.D. for the intra- and inter-day precision of the method were < 5.3% and the R.S.D. for accuracy was < 5.0%. The method was used to analyze plasma samples obtained from patients enrolled in a Met-maintenance program. © 2004 Elsevier B.V. All rights reserved. C1 NIA, Gerontol Res Ctr, Bioanalyt & Drug Discovery Unit, NIH, Baltimore, MD 21224 USA. NIDA, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Wainer, IW (reprint author), NIA, Gerontol Res Ctr, Bioanalyt & Drug Discovery Unit, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wainerir@grc.nia.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 49 TC 26 Z9 27 U1 0 U2 5 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 MAY 6 PY 2005 VL 1073 IS 1-2 BP 237 EP 248 DI 10.1016/j.chroma.2004.08.153 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 922YI UT WOS:000228875400028 PM 15909525 ER PT J AU Louis, JM Byeon, IJL Baxal, U Gronenborn, AM AF Louis, JM Byeon, IJL Baxal, U Gronenborn, AM TI The GB1 amyloid fibril: Recruitment of the peripheral beta-strands of the domain swapped dimer into the polymeric interface SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE immunoglobulin binding domain B1; amyloid; fibril; crosslinking; domain-swapping ID IMMUNOGLOBULIN-BINDING DOMAIN; STREPTOCOCCAL PROTEIN-G; INTRINSICALLY UNSTRUCTURED PROTEINS; HIV-INACTIVATING PROTEIN; CYANOVIRIN-N; X-RAY; UNFOLDED PROTEINS; CRYSTAL-STRUCTURE; CORE MUTATIONS; PRION PROTEIN AB Three-dimensional domain swapping has been evoked as a mechanism for oligomerization of proteins. Here, we show for the immunoglobulin-binding domain 131 of streptococcal protein G (GB1) that fibril formation is observed readily for variants that exist as domain-swapped dimers. No fibril was formed by a revertant that exhibits the stable wild-type GB1 fold or a mutant comprising a highly destabilized, fluctuating ensemble of conformers. Structural features of the GB1 amyloid fibril were characterized by cysteine disulfide cross-linking. Residues in the outer edge beta-strands of the domain-swapped dimer readily form intermolecular disulfide bonds prior to and during fibril formation. On the basis of these data, a structural model for the assembly of domain-swapped dimers into a polymeric structure of the GB1 fibril is proposed. Published by Elsevier Ltd. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. RP Gronenborn, AM (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM gronenborn@nih.gov OI Gronenborn, Angela M/0000-0001-9072-3525 NR 58 TC 27 Z9 27 U1 0 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 MAY 6 PY 2005 VL 348 IS 3 BP 687 EP 698 DI 10.1016/j.jmb.2005.02.071 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 920ST UT WOS:000228711100016 PM 15826664 ER PT J AU Toth, A Wang, Y Kedei, N Tran, R Pearce, LV Kang, SU Jin, MK Choi, HK Lee, J Blumberg, PM AF Toth, A Wang, Y Kedei, N Tran, R Pearce, LV Kang, SU Jin, MK Choi, HK Lee, J Blumberg, PM TI Different vanilloid agonists cause different patterns of calcium response in CHO cells heterologously expressing rat TRPV1 SO LIFE SCIENCES LA English DT Article DE vanilloid receptor 1 (TRPV1 or VR1) pharmacology; agonist; intracellular calcium imaging; kinetics ID CAPSAICIN RECEPTOR; ANALGESIC AGENTS; INTRAVESICAL RESINIFERATOXIN; NEUROPATHIC PAIN; ANALOGS; VR1; ANANDAMIDE; DESENSITIZATION; NEURONS; BLADDER AB The vanilloid receptor subtype 1 (TRPV1 or VR1) is expressed in nociceptive primary afferents of the C-fiber 'pain' pathway and has attracted considerable attention as a therapeutic target. Here, using rat TRPV1 heterologously expressed in Chinese hamster ovary cells, we show that different agonists show different patterns of modulation of the intracellular Ca2+ concentration, monitored in individual cells by fura-2 Ca2+ imaging. We identified 5 parameters (potency, maximal response, latency of response, variability of latency of response among individual cells, and desensitization) which behaved differently for different compounds. The potencies of the compounds examined ranged from EC50 values of 80 pM to 9 mu M. Peak levels of induced [Ca2+](i) were observed either higher (RTX) or lower (anandamide) than for capsaicin. Significant latencies of response were observed for some (e.g. RTX) but not other derivatives, with great variation among individual cells in this latency. Marked desensitization after stimulation was detected in some cases (e.g. anandamide, capsaicin); for others, no desensitization was observed. We conclude that structurally diverse vanilloid agonists induce marked diversity in the patterns of Ca2+ response. This diversity of response may provide opportunities for pharmacological exploitation. Published by Elsevier Inc. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul, South Korea. RP Blumberg, PM (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37,Room 4048,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM blumberp@dc37a.nci.nih.gov RI Toth, Attila/F-4859-2010 OI Toth, Attila/0000-0001-6503-3653 NR 42 TC 37 Z9 38 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD MAY 6 PY 2005 VL 76 IS 25 BP 2921 EP 2932 DI 10.1016/j.lfs.2004.10.056 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 919BQ UT WOS:000228593700004 PM 15820503 ER PT J AU Buetow, KH AF Buetow, KH TI Cyberinfrastructure: Empowering a "third way" in biomedical research SO SCIENCE LA English DT Article ID SCIENCE AB Biomedicine has experienced explosive growth, fueled in parts by the substantial increase of government support, continued development of the biotechnology industry, and the increasing adoption of molecutar-based medicine. At its core, it is composed of fiercely independent, innovative, entrepreneurial individuals, organizations, and institutions. The field has developed unprecedented capacity to characterize biologic systems at their most fundamental levels with the use of toots and technologies almost unimaginable a generation ago. Biomedicine is at the precipice of unlocking the very essence of biologic life and enabling a new generation of medicine. Development and deployment of cyberinfrastructure may prove to be on the critical path to obtaining these goals. C1 NCI, Ctr Bioinformat, NIH, Bethesda, MD 20892 USA. RP Buetow, KH (reprint author), NCI, Ctr Bioinformat, NIH, Bethesda, MD 20892 USA. EM buetowk@nih.gov RI Wright, Dawn/A-4518-2011; Hoek, Carien/K-9106-2013 OI Wright, Dawn/0000-0002-2997-7611; NR 5 TC 86 Z9 90 U1 3 U2 7 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 MAY 6 PY 2005 VL 308 IS 5723 BP 821 EP 824 DI 10.1126/science.1112120 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 924NW UT WOS:000228986500039 PM 15879210 ER PT J AU Holmans, P Hamshere, M Hollingworth, P Rice, F Tunstall, N Jones, S Moore, P DeVrieze, FW Myers, A Crook, R Compton, D Marshall, H Meyer, D Shears, S Booth, J Ramic, D Williams, N Norton, N Abraham, R Kehoe, P Williams, H Rudrasingham, V O'Donovan, M Jones, L Hardy, J Goate, A Lovestone, S Owen, M Williams, J AF Holmans, P Hamshere, M Hollingworth, P Rice, F Tunstall, N Jones, S Moore, P DeVrieze, FW Myers, A Crook, R Compton, D Marshall, H Meyer, D Shears, S Booth, J Ramic, D Williams, N Norton, N Abraham, R Kehoe, P Williams, H Rudrasingham, V O'Donovan, M Jones, L Hardy, J Goate, A Lovestone, S Owen, M Williams, J TI Genome screen for loci influencing age at onset and rate of decline in late onset Alzheimer's disease SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE Alzheimer's Disease; age at onset; rate of decline; genome screen; linkage ID MISSENSE MUTATIONS; VASCULAR DEMENTIA; OF-ONSET; LINKAGE; SCALE; GENE; METAANALYSIS; ASSOCIATION; DIAGNOSIS AB We performed an affected sib-pair (ASP) linkage analysis to test for the effects of age at onset (AAO), rate of decline (ROD), and Apolipoprotein E (APOE) genotype on linkage to late-onset Alzheimer's disease (AD) in a sample comprising 428 sib-pairs. We observed linkage of mean AAO to chromosome 21 in the whole sample (max LOD = 2.57). This came entirely from the NIMH sample (max LOD=3.62), and was strongest in pairs with high mean AAO (> 80). A similar effect was observed on chromosome 2q in the NIMH sample (max LOD=2.73); this region was not typed in the IADC/UK sample. Suggestive evidence was observed in the combined sample of linkage of AAO difference to chromosome 19q (max LOD=2.33) in the vicinity of APOE and 12p (max LOD=2.22), with linkage strongest in sib-pairs with similar AAO. Mean ROD showed suggestive evidence of linkage to chromosome 9q in the whole sample (max LOD=2.29), with the effect strongest in the NIMH sample (max LOD=3.58), and in pairs with high mean ROD. Additional suggestive evidence was also observed in the NIMH sample with AAO difference on chromosome 6p (max LOD=2.44) and 15p (max LOD=1.87), with linkage strongest in pairs with similar AAO, and in the UK sample with mean ROD on chromosome 1p (max LOD=2.73, linkage strongest in pairs with high mean ROD). We also observed suggestive evidence of increased identical by descent (IBD) in APOE EA homozygotes on chromosome 1 (max LOD=3.08) and chromosome 9 (max LOD=3.34). The previously reported genome-wide linkage of AD to chromosome 10 was not influenced by any of the covariates studied. (c) 2005 Wiley-Liss, Inc. C1 Univ Wales Coll Med, Biostat & Bioinformat Unit, Cardiff CF14 4XN, S Glam, Wales. Univ Wales Coll Cardiff, Coll Med, Dept Psychol Med, Cardiff CF1 3NS, S Glam, Wales. Inst Psychiat, London, England. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Mayo Clin Jacksonville, Neurogenet Lab, Jacksonville, FL 32224 USA. RP Holmans, P (reprint author), Univ Wales Coll Med, Biostat & Bioinformat Unit, Heath Pk, Cardiff CF14 4XN, S Glam, Wales. EM holmanspa@cardiff.ac.uk RI Lovestone, Simon/E-8725-2010; Myers, Amanda/B-1796-2010; turton, miranda/F-4682-2011; Hardy, John/C-2451-2009; Holmans, Peter/F-4518-2015; OI Myers, Amanda/0000-0002-3100-9396; Holmans, Peter/0000-0003-0870-9412; O'Donovan, Michael/0000-0001-7073-2379 FU NIA NIH HHS [U24 AG021886]; NIMH NIH HHS [U01 MH46281, U01 MH46290, U01 MH46373] NR 38 TC 56 Z9 56 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAY 5 PY 2005 VL 135B IS 1 BP 24 EP 32 DI 10.1002/ajmg.b.30114 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 921JD UT WOS:000228759500006 PM 15729734 ER PT J AU Petersen, D Chandramouli, GVR Geoghegan, J Hilburn, J Paarlberg, J Kim, CH Munroe, D Gangi, L Han, J Puri, R Staudt, L Weinstein, J Barrett, JC Green, J Kawasaki, ES AF Petersen, D Chandramouli, GVR Geoghegan, J Hilburn, J Paarlberg, J Kim, CH Munroe, D Gangi, L Han, J Puri, R Staudt, L Weinstein, J Barrett, JC Green, J Kawasaki, ES TI Three microarray platforms: an analysis of their concordance in profiling gene expression SO BMC GENOMICS LA English DT Article ID DENSITY OLIGONUCLEOTIDE ARRAYS; DNA MICROARRAYS; CELL-LINES; MOLECULAR PHARMACOLOGY; PROSTATE-CANCER; CDNA; METAANALYSIS; PATTERNS; CLASSIFICATION; HYBRIDIZATION AB Background: Microarrays for the analysis of gene expression are of three different types: short oligonucleotide (25-30 base), long oligonucleotide (50-80 base), and cDNA ( highly variable in length). The short oligonucleotide and cDNA arrays have been the mainstay of expression analysis to date, but long oligonucleotide platforms are gaining in popularity and will probably replace cDNA arrays. As part of a validation study for the long oligonucleotide arrays, we compared and contrasted expression profiles from the three formats, testing RNA from six different cell lines against a universal reference standard. Results: The three platforms had 6430 genes in common. In general, correlation of gene expression levels across the platforms was good when defined by concordance in the direction of expression difference (upregulation or downregulation), scatter plot analysis, principal component analysis, cell line correlation or quantitative RT-PCR. The overall correlations (r values) between platforms were in the range 0.7 to 0.8, as determined by analysis of scatter plots. When concordance was measured for expression ratios significant at p-values of < 0.05 and at expression threshold levels of 1.5 and 2-fold, the agreement among the platforms was very high, ranging from 93% to 100%. Conclusion: Our results indicate that the long oligonucleotide platform is highly suitable for expression analysis and compares favorably with the cDNA and short oligonucleotide varieties. All three platforms can give similar and reproducible results if the criterion is the direction of change in gene expression and minimal emphasis is placed on the magnitude of change. C1 NCI, Ctr Adv Technol, Canc Res Ctr, Gaithersburg, MD 20877 USA. SAIC Frederick, Lab Mol Technol, Frederick, MD 21701 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. RP Kawasaki, ES (reprint author), NCI, Ctr Adv Technol, Canc Res Ctr, Gaithersburg, MD 20877 USA. EM petersed@mail.nih.gov; chandrag@mail.nih.gov; geoghej@mail.nih.gov; hilburnj@mail.nih.gov; paarlbej@mail.nih.gov; kimcha@mail.nih.gov; dmunroe@ncifcrf.gov; gangil@mail.nih.gov; hanj@cber.fda.gov; puri@cber.fda.gov; lstaudt@mail.nih.gov; jw4i@nih.gov; barrett@mail.nih.gov; jegreen@nih.gov; kawasake@mail.nih.gov NR 57 TC 67 Z9 74 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAY 5 PY 2005 VL 6 AR 63 DI 10.1186/1471-2164-6-63 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 929XJ UT WOS:000229379600001 PM 15876355 ER PT J AU Caputo, E Lombardi, ML Luongo, V Moharram, R Tornatore, P Pirozzi, G Guardiola, J Martin, BA AF Caputo, E Lombardi, ML Luongo, V Moharram, R Tornatore, P Pirozzi, G Guardiola, J Martin, BA TI Peptide profiling in epithelial tumor plasma by the emerging proteomic techniques SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE melanoma; breast cancer; plasma peptide component; SELDI-TOF MS ID TRYPSIN INHIBITOR FAMILY; FLIGHT-MASS-SPECTROMETRY; MALIGNANT-MELANOMA; FIBRINOGEN; GLYCOPROTEIN; CONSEQUENCES; CANCER; CDNA; TIME AB The plasma peptide component (PPC) from ten melanoma (Mel), breast cancer (BC) and healthy individuals was examined by a combination of RP-HPLC, surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOFMS) and tandem mass spectrometry. A three peak pattern (2023, 2039, 2053.5 m/z) was primarily observed in melanoma. Two peaks (2236.1 and of 2356.3 m/z) were found only in BC samples. Fibrinogen alpha and inter-alpha-trypsin inhibitor heavy chain H4 fragments were absent in both tumor samples. (c) 2005 Elsevier B.V. All rights reserved. C1 CNR, A Buzzati Traverso, IGB, I-80125 Naples, Italy. NIMH, Unit Mol Struct, Bethesda, MD 20892 USA. Immunol Ist Nazl Tumori Fdn G Pascale, I-80131 Naples, Italy. Ciphergen Biosyst, Fremont, CA USA. RP Caputo, E (reprint author), CNR, A Buzzati Traverso, IGB, Via G Marconi 10, I-80125 Naples, Italy. EM caputo@igb.cnr.it OI CAPUTO, EMILIA/0000-0002-6485-8802 NR 20 TC 20 Z9 20 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAY 5 PY 2005 VL 819 IS 1 BP 59 EP 66 DI 10.1016/j.jchromb.2005.01.022 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 914DT UT WOS:000228206000008 PM 15797521 ER PT J AU Jozwiak, K Moaddel, R Yamaguchi, R Ravichandran, S Collins, JR Wainer, IW AF Jozwiak, K Moaddel, R Yamaguchi, R Ravichandran, S Collins, JR Wainer, IW TI Qualitative assessment Of IC50 values of inhibitors of the neuronal nicotinic acetylcholine receptor using a single chromatographic experiment and multivariate cluster analysis SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE affinity chromatography; immobilized receptors; nicotinic acetylcholine receptor stationary phase; drug discovery ID AFFINITY-CHROMATOGRAPHY; NONCOMPETITIVE INHIBITORS; BINDING CONSTANTS; STATIONARY-PHASE; ALPHA-3-BETA-4; DRUG; DEXTROMETHORPHAN; ALPHA-4-BETA-2; SUBTYPES AB It has been widely demonstrated that affinity chromatography can be used to derive binding affinities, and that these affinities can be correlated to data obtained using standard techniques such as membrane binding, ultrafiltration and equilibrium dialysis. The purpose of this study is to evaluate the use of immobilized nicotinic acetylcholine receptor stationary phase in chromatographic experiments to assess the functional activity of series of noncompetitive inhibitors (NCIs) as reflected in their IC50 values. Chromatographically determined retention values and computer generated molecular descriptors were obtained for 29 compounds and the data were analyzed by cluster analysis. The approach qualitatively ranked the test compounds as efficient NCIs (low IC50 values) or poor NCIs (high IC50 values). The data obtained with the 29 compounds used in this study demonstrate that the experimental approach had been able to place 25 of these compounds in the correct IC50 clusters. To our knowledge, this is the first relationship established between chromatographic retention and IC50 for membrane-bound receptors. These results suggest that the chromatographic approach may be useful in development of lead drug candidates including the determination of off-target binding. (c) 2005 Elsevier B.V. All rights reserved. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Med Univ Lublin, Dept Chem, PL-20081 Lublin, Poland. Natl Canc Ctr, Frederick SAIC, Adv Biomed Comp Ctr, Ft Detrick, MD 21702 USA. RP Jozwiak, K (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM krzysztof.jozwiak@am.lublin.pl NR 24 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAY 5 PY 2005 VL 819 IS 1 BP 169 EP 174 DI 10.1016/j.jchromb.2005.01.043 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 914DT UT WOS:000228206000022 PM 15797535 ER PT J AU Xiao, XS Antony, S Pommier, Y Cushman, M AF Xiao, XS Antony, S Pommier, Y Cushman, M TI On the binding of indeno[1,2-c]isoquinolines in the DNA-topoisomerase I cleavage complex SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BIOLOGICAL EVALUATION; BASE-PAIRS; CURRENT PERSPECTIVES; CLINICAL-EXPERIENCE; ANTICANCER ACTIVITY; CAMPTOTHECIN; INHIBITORS; INDENOISOQUINOLINE; DESIGN; BREAKS AB An ab initio quantum mechanics calculation is reported which predicts the orientation of indenoisoquinoline 4 in the ternary cleavage complex formed from DNA and topoisomerase I (top1). The results of this calculation are consistent with the hypothetical structures previously proposed for the indenoisoquinoline-DNA-top1 ternary complexes based on molecular modeling, the crystal structure of a recently reported ternary complex, and the biological results obtained with a pair of diaminoalkyl-substituted indenoisoquinoline enantiomers. The results of these studies indicate that the π-π stacking interactions between the indenoisoquinolines and the neighboring DNA base pairs play a major role in determining binding orientation. The calculation of the electrostatic potential surface maps of the indenoisoquinolines and the adjacent DNA base pairs shows electrostatic complementarity in the observed binding orientation, leading to the conclusion that electrostatic attraction between the intercalators and the base pairs in the cleavage complex plays a major stabilizing role. On the other hand, the calculation of LUMO and HOMO energies of indenoisoquinoline 13b and neighboring DNA base pairs in conjunction with NBO analysis indicates that charge transfer complex formation plays a relatively minor role in stabilizing the ternary complexes derived from indenoisoquinolines, DNA, and top1. The results of these studies are important in understanding the existing structure-activity relationships for the indenoisoquinolines as top1 inhibitors and as anticancer agents, and they will be important in the future design of indenoisoquinoline-based top1 inhibitors. C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, Sch Pharm & Pharmaceut Sci, W Lafayette, IN 47907 USA. NCI, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Cushman, M (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu FU NCI NIH HHS [UO1 CA89566]; NCRR NIH HHS [C06-RR14499] NR 40 TC 58 Z9 59 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 MAY 5 PY 2005 VL 48 IS 9 BP 3231 EP 3238 DI 10.1021/jm050017y PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 922WX UT WOS:000228871700020 PM 15857129 ER PT J AU Bazhenov, M Stopfer, M Sejnowski, TJ Laurent, G AF Bazhenov, M Stopfer, M Sejnowski, TJ Laurent, G TI Fast odor learning improves reliability of odor responses in the locust antennal lobe SO NEURON LA English DT Article ID ENCODING NEURAL ASSEMBLIES; ZEBRAFISH OLFACTORY-BULB; SYNAPTIC DEPRESSION; REPRESENTATIONS; DISCRIMINATION; OSCILLATIONS; NEURONS; SYNCHRONIZATION; INFORMATION; MECHANISMS AB Recordings in the locust antennal lobe (AL) reveal activity-dependent, stimulus-specific changes in projection neuron (PN) and local neuron response patterns over repeated odor trials. During the first few trials, PN response intensity decreases, while spike time precision increases, and coherent oscillations, absent at first, quickly emerge. We examined this "fast odor learning" with a realistic computational model of the AL. Activity-dependent facilitation of AL inhibitory synapses was sufficient to simulate physiological recordings of fast learning. In addition, in experiment:; with noisy inputs, a network including synaptic facilitation of both inhibition and excitation responded with reliable spatiotemporal patterns from trial to trial despite the noise. A network lacking fast plasticity, however, responded with patterns that varied across trials, reflecting the input variability. Thus, our study suggests that fast olfactory learning results from stimulus-specific, activity-dependent synaptic facilitation and may improve the signal-to-noise ratio for repeatedly encountered odor stimuli. C1 Salk Inst Biol Studies, Computat Neurobiol Lab, La Jolla, CA 92037 USA. NICHD, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. CALTECH, Pasadena, CA 91125 USA. RP Bazhenov, M (reprint author), Salk Inst Biol Studies, Computat Neurobiol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM bazhenov@salk.edu RI Laurent, Gilles/A-4583-2012 FU Howard Hughes Medical Institute NR 38 TC 44 Z9 45 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY 5 PY 2005 VL 46 IS 3 BP 483 EP 492 DI 10.1016/j.neuron.2005.03.022 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 924WL UT WOS:000229011400019 PM 15882647 ER PT J AU Lauri, SE Segerstrale, M Vesikansa, A Maingret, F Mulle, C Collingridge, GL Isaac, JTR Taira, T AF Lauri, SE Segerstrale, M Vesikansa, A Maingret, F Mulle, C Collingridge, GL Isaac, JTR Taira, T TI Endogenous activation of kainate receptors regulates glutamate release and network activity in the developing hippocampus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE development; interneuron; presynaptic; plasticity; pyramidal cell; synaptic transmission ID MOSSY FIBER SYNAPSES; EXCITATORY SYNAPTIC-TRANSMISSION; LONG-TERM POTENTIATION; RAT HIPPOCAMPUS; IN-VIVO; NEONATAL HIPPOCAMPUS; PYRAMIDAL CELLS; INTERNEURONS; PLASTICITY; GLUR5 AB Kainate receptors (KARs) are highly expressed throughout the neonatal brain, but their function during development is unclear. Here, we show that the maturation of the hippocampus is associated with a switch in the functional role of presynaptic KARs. In a developmental period restricted to the first postnatal week, endogenous L-glutamate tonically activates KARs at CA3 glutamatergic synapses to regulate release in an action potential-independent manner. At synapses onto pyramidal cells, KARs inhibit glutamate release via a G-protein and PKC-dependent mechanism. In contrast, at glutamatergic terminals onto CA3 interneurons, presynaptic KARs can facilitate release in a G-protein-independent mechanism. In both cell types, however, KAR activation strongly upregulates inhibitory transmission. We show that, through the interplay of these novel diverse mechanisms, KARs strongly regulate the characteristic synchronous network activity observed in the neonatal hippocampus. By virtue of this, KARsare likely to play a central role in the development of hippocampal synaptic circuits. C1 Univ Helsinki, Ctr Neurosci, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Biol & Environm Sci, FIN-00014 Helsinki, Finland. Univ Bristol, Sch Med, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. Univ Bordeaux 2, Inst Francois Magendie, CNRS,Unite Mixte Rech 5091, Lab Physiol Cellulaire Synapse, F-33076 Bordeaux, France. NINDS, NIH, Bethesda, MD 20892 USA. RP Taira, T (reprint author), Univ Helsinki, Ctr Neurosci, FIN-00014 Helsinki, Finland. EM tomi.taira@helsinki.fi RI Collingridge, Graham/C-4605-2015; OI Collingridge, Graham/0000-0002-9572-5359; Lauri, Sari/0000-0002-5895-1357; Mulle, Christophe/0000-0003-2709-6615 FU Medical Research Council [G9532377] NR 63 TC 64 Z9 68 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 4 PY 2005 VL 25 IS 18 BP 4473 EP 4484 DI 10.1523/JNEUROSCI.4050-04.2005 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 923FN UT WOS:000228895200005 PM 15872094 ER PT J AU Zhou, R Gray, NA Yuan, PX Li, XX Chen, JS Chen, G Damschroder-Williams, P Du, J Zhang, L Manji, HK AF Zhou, R Gray, NA Yuan, PX Li, XX Chen, JS Chen, G Damschroder-Williams, P Du, J Zhang, L Manji, HK TI The anti-apoptotic, glucocorticoid receptor cochaperone protein BAG-1 is a long-term target for the actions of mood stabilizers SO JOURNAL OF NEUROSCIENCE LA English DT Article DE lithium; valproate; bipolar disorder; BAG-1; glucocorticoid; neuroplasticity ID ALTERNATIVE TRANSLATION INITIATION; LITHIUM AUGMENTATION INCREASES; UNIPOLAR MAJOR DEPRESSION; BIPOLAR DISORDER; VALPROIC ACID; HORMONE TEST; HUMAN BRAIN; IN-VIVO; EXPRESSION; AGENTS AB Increasing data suggest that impairments of cellular plasticity/resilience underlie the pathophysiology of bipolar disorder. A series of microarray studies with validating criteria have recently revealed a common, novel target for the long-term actions of the structurally highly dissimilar mood stabilizers lithium and valproate: BAG-1 [BCL-2 (B-cell CLL/lymphoma 2)-associated athanogene]. Because BAG-1 attenuates glucocorticoid receptor (GR) nuclear translocation, activates ERK (extracellular signal-regulated kinase) MAP (mitogen-activated protein) kinases, and potentiates anti-apoptotic functions of BCL-2, extensive additional studies were undertaken. Chronic administration of both agents at therapeutic doses increased the expression of BAG-1 in rat hippocampus. Furthermore, these findings were validated at the protein level, and the effects were seen in a time frame consistent with therapeutic effects and were specific for mood stabilizers. Functional studies showed that either lithium or valproate, at therapeutically relevant levels, inhibited dexamethasone-induced GR nuclear translocation and inhibited GR transcriptional activity. Furthermore, small interfering RNA studies showed that these inhibitory effects on GR activity were mediated, at least in part, through BAG-1. The observation that BAG-1 inhibits glucocorticoid activation suggests that mood stabilizers may counteract the deleterious effects of hypercortisolemia seen in bipolar disorder by upregulating BAG-1. Additionally, these studies suggest that regulation of GR-mediated plasticity may play a role in the treatment of bipolar disorder and raise the possibility that agents affecting BAG-1 more directly may represent novel therapies for this devastating illness. C1 NIMH, Mol Pathophysiol Lab, Rockville, MD 20852 USA. NIMH, Clin Brain Disorders Branch, Rockville, MD 20852 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, Porter Neurosci Res Ctr, Bldg 35,Room 1C-917,35 Convent Dr, Bethesda, MD 20892 USA. EM manji@nih.gov RI Chen, Guang/A-2570-2017 NR 39 TC 70 Z9 71 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 4 PY 2005 VL 25 IS 18 BP 4493 EP 4502 DI 10.1523/JNEUROSCI.4530-04.2005 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 923FN UT WOS:000228895200007 PM 15872096 ER PT J AU Winter, S Brunk, I Walther, DJ Holtje, M Jiang, M Peter, JU Takamori, S Jahn, R Birnbaumer, L Ahnert-Hilger, G AF Winter, S Brunk, I Walther, DJ Holtje, M Jiang, M Peter, JU Takamori, S Jahn, R Birnbaumer, L Ahnert-Hilger, G TI G alpha(o2) regulates vesicular glutamate transporter activity by changing its chloride dependence SO JOURNAL OF NEUROSCIENCE LA English DT Article DE G alpha(o2); VGLUT; regulation; vesicular transmitter transporter; presynaptic; plasticity; chloride dependence ID FROG NEUROMUSCULAR-JUNCTION; G-PROTEIN HETEROTRIMERS; SYNAPTIC VESICLES; PHOSPHATE TRANSPORTER; TRANSMITTER UPTAKE; MOLECULAR-CLONING; LIGHT RESPONSE; QUANTAL SIZE; EXPRESSION; NEURONS AB Classical neurotransmitters, including monoamines, acetylcholine, glutamate, GABA, and glycine, are loaded into synaptic vesicles by means of specific transporters. Vesicular monoamine transporters are under negative regulation by α subunits of trimeric G-proteins, including Gα(o2) and Gα(q). Furthermore, glutamate uptake, mediated by vesicular glutamate transporters (VGLUTs), is decreased by the nonhydrolysable GTP-analog guanylylimidodiphosphate. Using mutant mice lacking various Gα subunits, including Gα(o1), Gα(o2), Gα(q), and Gα(11), and a Gα(o2)-specific monoclonal antibody, we now show that VGLUTs are exclusively regulated by Gα(o2). G-protein activation does not affect the electrochemical proton gradient serving as driving force for neurotransmitter uptake; rather, Gα(o2) exerts its action by specifically affecting the chloride dependence of VGLUTs. All VGLUTs show maximal activity at &SIM; 5 mM chloride. Activated Gα(o2) shifts this maximum to lower chloride concentrations. In contrast, glutamate uptake by vesicles isolated from Gα(-/-)(o2) mice have completely lost chloride activation. Thus, Gα(o2) acts on a putative regulatory chloride binding domain that appears to modulate transport activity of vesicular glutamate transporters. C1 Charite Hochsch Med Berlin, Ctr Anat, AG Funct Zellbiol, D-10115 Berlin, Germany. Max Planck Inst Mol Genet, D-14195 Berlin, Germany. NIEHS, Res Triangle Pk, NC 27709 USA. Max Planck Inst Biophys Chem, D-37707 Gottingen, Germany. RP Ahnert-Hilger, G (reprint author), Charite Hochsch Med Berlin, Ctr Anat, AG Funct Zellbiol, Philippstr 12, D-10115 Berlin, Germany. EM JM@ucla.edu OI Jahn, Reinhard/0000-0003-1542-3498 NR 58 TC 21 Z9 23 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 4 PY 2005 VL 25 IS 18 BP 4672 EP 4680 DI 10.1523/JNEUROSCI.0549-05.2005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 923FN UT WOS:000228895200026 PM 15872115 ER PT J AU Myers, MC Wang, J Iera, JA Bang, JK Hara, T Saito, S Zambetti, GP Appella, DH AF Myers, MC Wang, J Iera, JA Bang, JK Hara, T Saito, S Zambetti, GP Appella, DH TI A new family of small molecules to probe the reactivation of mutant p53 SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CORE DOMAIN; APOPTOSIS; RESCUE; GENE; CONFORMATION; RESTORATION; ACTIVATION; EXPRESSION; CANCER C1 NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. Northwestern Univ, Evanston, IL 60208 USA. St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Appella, DH (reprint author), NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM appellad@niddk.nih.gov FU NCI NIH HHS [CA21765, CA63230, CA71907] NR 25 TC 26 Z9 27 U1 1 U2 5 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 MAY 4 PY 2005 VL 127 IS 17 BP 6152 EP 6153 DI 10.1021/ja045752y PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 921HQ UT WOS:000228755300008 PM 15853303 ER PT J AU Kaye, FJ AF Kaye, FJ TI A curious link between epidermal growth factor receptor amplification and survival: Effect of "Allele dilution" on gefitinib sensitivity? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CELL LUNG-CANCER; KINASE DOMAIN; TYROSINE KINASE; GENE-MUTATIONS; EXPRESSION; ADENOCARCINOMAS; RESISTANCE; ERLOTINIB; TUMORS; DUPLICATION C1 NCI, Canc Res Ctr, Genet Branch, Bethesda, MD 20889 USA. RP Kaye, FJ (reprint author), NCI, Canc Res Ctr, Genet Branch, Bethesda, MD 20889 USA. EM fkaye@helix.nih.gov RI kaye, frederic/E-2437-2011 NR 34 TC 15 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 4 PY 2005 VL 97 IS 9 BP 621 EP 623 DI 10.1093/jnci/dji127 PG 3 WC Oncology SC Oncology GA 936LB UT WOS:000229856400002 PM 15870427 ER PT J AU Palmieri, D Halverson, DO Ouatas, T Horak, CE Salerno, M Johnson, J Figg, WD Hollingshead, M Hursting, S Berrigan, D Steinberg, SM Merino, MJ Steeg, PS AF Palmieri, D Halverson, DO Ouatas, T Horak, CE Salerno, M Johnson, J Figg, WD Hollingshead, M Hursting, S Berrigan, D Steinberg, SM Merino, MJ Steeg, PS TI Medroxyprogesterone acetate elevation of Nm23-H1 metastasis suppressor expression in hormone receptor-negative breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID KINASE ALPHA-ISOFORM; CARCINOMA CELL-LINES; GENE-EXPRESSION; PROGESTERONE-RECEPTOR; DIPHOSPHATE KINASE; GROWTH-FACTOR; GLUCOCORTICOID ACTIVITY; ADENOCARCINOMA CELLS; RANDOMIZED TRIAL; MELANOMA-CELLS AB Background. Reestablishment of metastasis suppressor gene expression may constitute a therapeutic strategy for high-risk breast cancer patients. We previously showed that medroxyprogesterone acetate (MPA), a progestin that has been tested as treatment for advanced breast cancer, elevates expression of the Nm23-H1 metastasis suppressor gene in hormone receptor-negative metastatic human breast carcinoma cell lines in vitro via a glucocorticoid receptor-based mechanism. Here, we tested whether MPA treatment inhibits metastatic colonization of a hormone receptor-negative breast cancer cell line in vivo. Methods: We tested the soft-agar colony-forming efficiency of untransfected MDA-MB-231T human breast carcinoma cells and MDA-MB-231T cells transfected with antisense Nm23-H1 in the presence and absence of MPA. Pharmacokinetic studies were used to establish dose and injection schedules that led to MPA serum levels in mice similar to those achievable in humans. For in vivo studies, nude mice were injected intravenously with MDA-MB-231T cells. After 4 weeks, mice were randomized to control or MPA arms. Endpoints included incidence, number, and size of gross pulmonary metastases; Nm23-H1 protein expression in gross metastases; and side effects. All statistical tests were two-sided. Results: MPA reduced colony formation of MDA-MB-231T cells by 40%-50% but had no effect on colony formation of Nm23-H1 antisense transfectants. Metastases developed in 100% (95% confidence interval [CI] = 78% to 100% and 77% to 100%, respectively) of control mice injected with MDA-MB-231T cells. In two independent experiments, only 73% (95% CI = 45% to 92%) and 64% (95% CI = 35% to 87%) of mice injected with 2 mg of MPA developed metastases. Mice injected with 2 mg of MPA showed reductions in the mean numbers, per mouse, of all metastases and of large (> 3 mm) metastases (P =.04 and .013, respectively). Nm23-H1 was expressed at high levels in 43% of pulmonary metastases in MPA-treated mice but only 13% of metastases in untreated mice. Mice receiving at least 1-mg doses of MPA gained more weight than control-treated mice but exhibited no bone density alterations or abnormal mammary fat pad histology. Conclusion: Our preclinical results show that MPA appears to elevate Nm23-H1 metastasis suppressor gene expression, thereby reducing metastatic colonization. The data suggest a new use for an old agent in a molecularly defined subset of breast cancer patients. C1 NCI, Womens Canc Sect, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. Lab Anim Sci Program, Frederick, MD USA. NCI, Canc Therapeut Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. NCI, Lab Biosyst & Canc, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Surg Pathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Steeg, PS (reprint author), NIH, Bldg 10,Rm 2A33, Bethesda, MD 20892 USA. EM steegp@mail.nih.gov RI Palmieri, Diane/B-4258-2015; Figg Sr, William/M-2411-2016 NR 70 TC 83 Z9 87 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 4 PY 2005 VL 97 IS 9 BP 632 EP 642 PG 11 WC Oncology SC Oncology GA 936LB UT WOS:000229856400008 PM 15870434 ER PT J AU Robin, G DeBonis, S Dornier, A Cappello, G Ebel, C Wade, RH Thierry-Mieg, D Kozielski, F AF Robin, G DeBonis, S Dornier, A Cappello, G Ebel, C Wade, RH Thierry-Mieg, D Kozielski, F TI Essential kinesins: Characterization of Caenorhabditis elegans KLP-15 SO BIOCHEMISTRY LA English DT Article ID MICROTUBULE MOTOR PROTEIN; PREDICTING COILED COILS; C-ELEGANS; ESCHERICHIA-COLI; AMINO-ACID; SEDIMENTATION ANALYSIS; LAMM EQUATION; SENSORY CILIA; DOMAIN; MOTILITY AB Kinesins form a superfamily of molecular motors involved in cell division and intracellular transport. Twenty kinesins have been found in the Caenorhabditis elegans genome, and four of these belong to the kinesin-14 subfamily, i.e., kinesins with C-terminal motor domains. Three of these kinesin-14s, KLP-15, KLP-16, and KLP-17, form a distinct subgroup in which KLP-15 and KLP-16 are more than 90% identical and appear to be related by a relatively recent gene duplication. They are essential for meiotic spindle organization and chromosome segregation, and are mostly expressed in the germline. With 587 amino acids each, they are among the smallest kinesins known. Using bacterially expressed KLP-15 constructs with different length extensions preceding the motor domain, we have determined in vitro the following characteristic properties: ATPase activity, microtubule binding, oligomeric state, microtubule gliding activity, and direction of movement. The constructs exhibit a monomer-dimer equilibrium that depends on the length of the predicted alpha-helical coiled-coil region preceding the motor domain. The longest construct with the complete coiled-coil domain is a stable dimer, and the shortest construct with only seven amino acids preceding the motor domain is a monomer. In microtubule gliding assays, the monomer is immobile whereas the fully dimeric KLP-15 construct supports gliding at 2.3 mu m/min and moves toward microtubule minus ends, like other members of the kinesin-14 subfamily studied to date. C1 CEA, Inst Biol Struct, UJF, CNRS UMR 5075, F-38027 Grenoble, France. Inst Curie, Lab Physicochim, CNRS, UMR 168, F-75231 Paris, France. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP CEA, Inst Biol Struct, UJF, CNRS UMR 5075, 41 Rue Jules Horowitz, F-38027 Grenoble, France. EM wade@ibs.fr; Frank.Kozielski@ibs.fr NR 51 TC 2 Z9 5 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 3 PY 2005 VL 44 IS 17 BP 6526 EP 6536 DI 10.1021/bi048157h PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 920YP UT WOS:000228731700015 PM 15850386 ER PT J AU Basu, NK Kovarova, M Garza, A Kubota, S Saha, T Mitra, PS Banerjee, R Rivera, J Owens, IS AF Basu, NK Kovarova, M Garza, A Kubota, S Saha, T Mitra, PS Banerjee, R Rivera, J Owens, IS TI Phosphorylation of a UDP-glucuronosyltransferase regulates substrate specificity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PKC; PKC inhibitors; detoxifying enzymes; UDP-glucuronosyltransferase mutants; immunofluorescence ID PROTEIN-KINASE-C; I PATIENT; BILIRUBIN; EPSILON; CELLS; ALPHA; BETA; DEFICIENCY; REDUCTASE; CURCUMIN AB UDP-glucuronosyltransferase (UGT) isozymes catalyze detoxification of numerous chemical toxins present in our daily diet and environment by conjugation to glucuronic acid. The special properties and enzymatic mechanism(s) that enable endoplasmic reticulum-bound UGT isozymes to convert innumerable structurally diverse lipophiles to excretable glucuronides are unknown. Inhibition of cellular UGT1A7 and UGT1A10 activities and of [P-33]orthophosphate incorporation into immunoprecipitable proteins after exposure to curcumin or calphostin-C indicated that the isozymes are phosphorylated. Furthermore, inhibition of UGT phosphorylation and activity by treatment with PKCε-specific inhibitor peptide supported PKC involvement. Coimmunoprecipitation, colocalization by means of immunofluorescence, and cross-linking studies of PKCε and UGT1A7His revealed that the proteins reside within 11.4 &ANGS; of each other. Moreover, mutation of three PKC sites in each UGT isozyme demonstrated that T73A/G and T202A/G caused null activity, whereas S432G-UGT1A7 caused a major shift of its pH-8.5 optimum to 6.4 with new substrate selections, including 17β-estradiol. S432G-UGT1A10 exhibited a minor pH shift without substrate alterations. PKCε involvement was confirmed by the demonstration that PKCε overexpression enhanced activity of UGT1A7 but not of its S432 mutant and the conversion of 17β-[C-14]estradiol by S432G-UGT1A7 but not by UGT1A7. Consistent with these observations, treatment of UGT1A7-transfected cells with PKCε-specific inhibitor peptide or general PKC inhibitors increased 17β-estradiol catalysis between 5- and 11-fold, with parallel decreases in phosphoserine-432. Here, we report a mechanism involving PKC-mediated phosphorylation of UGT such that phosphoserine/threonine regulates substrate specificity in response to chemical exposures, which possibly confers survival benefit. C1 NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Mol Inflammat Sect, NIH, Bethesda, MD 20892 USA. RP Owens, IS (reprint author), NICHHD, Heritable Disorders Branch, NIH, Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. EM owensi@mail.nih.gov NR 27 TC 38 Z9 38 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 MAY 3 PY 2005 VL 102 IS 18 BP 6285 EP 6290 DI 10.1073/pnas.0407872102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 923OE UT WOS:000228918400010 PM 15845768 ER PT J AU Bedell, VM Yeo, SY Park, KW Chung, J Seth, P Shivalingappa, V Zhao, JH Obara, T Sukhatme, VP Drummond, IA Li, DY Ramchandran, R AF Bedell, VM Yeo, SY Park, KW Chung, J Seth, P Shivalingappa, V Zhao, JH Obara, T Sukhatme, VP Drummond, IA Li, DY Ramchandran, R TI roundabout4 is essential for angiogenesis in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE axon guidance; endothelial cell; zebrafish ID AXON GUIDANCE; CELL-MIGRATION; SLIT PROTEINS; ZEBRAFISH; RECEPTORS; MIDLINE; GROWTH; ROBO2; INHIBITION; EXPRESSION AB Stereotypical patterns of vascular and neuronal networks suggest that specific genetic programs tightly control path determination and, consequently, angiogenesis and axon-guidance mechanisms. Our study focuses on one member of the roundabout family of receptors, which traditionally mediate repulsion from the midline. Here, we characterize a fourth member of this family, roundabout4 (robo4), which is the predominant roundabout (robo) that is expressed in embryonic zebrafish vasculature. Gene knockdown and overexpression approaches show that robo4 is essential for coordinated symmetric and directed sprouting of intersomitic vessels and provide mechanistic insights into this process. Also, human robo4 gene functionally compensates for loss of robo4 gene function, suggesting evolutionary conservation. This article reports an endothelial-specific function for a robo gene in vertebrates in vivo. C1 NCI, Pathol Lab, NIH, Rockville, MD 20850 USA. NICHHD, Mol Genet Lab, Unit Vertebrate Neural Dev, NIH, Bethesda, MD 20892 USA. Univ Utah, Div Cardiol, Salt Lake City, UT 84132 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Study Tumor Microenvironm, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. RP Ramchandran, R (reprint author), NCI, Pathol Lab, NIH, 9610 Med Ctr Dr,Suite 320, Rockville, MD 20850 USA. EM ramchanr@mail.nih.gov RI Xiao, Yang/B-5668-2012 FU NCI NIH HHS [K22 CA095325, K22 CA095325-01, K22 CA095325-02]; NHLBI NIH HHS [R01 HL068873, R01 HL077671, R01 HL077671-03]; NIDDK NIH HHS [R01 DK078209, R21 DK069604] NR 33 TC 124 Z9 135 U1 2 U2 12 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 MAY 3 PY 2005 VL 102 IS 18 BP 6373 EP 6378 DI 10.1073/pnas.0408318102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 923OE UT WOS:000228918400025 PM 15849270 ER PT J AU Schmidt, TR Wildman, DE Uddin, M Opazo, JC Goodman, M Grossman, LI AF Schmidt, TR Wildman, DE Uddin, M Opazo, JC Goodman, M Grossman, LI TI Rapid electrostatic evolution at the binding site for cytochrome c on cytochrome c oxidase in anthropoid primates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mitochondria; electron transport chain; molecular coevolution ID MOLECULAR EVOLUTION; SUBUNIT-II; PARACOCCUS-DENITRIFICANS; SIMIAN PRIMATES; CHEMICAL MODIFICATION; POSITIVE SELECTION; ADAPTIVE EVOLUTION; INTERACTION DOMAIN; GENE FAMILY; MITOCHONDRIAL AB Cytochrome c (CYC) oxidase (COX), a multisubunit enzyme that functions in mitochondrial aerobic energy production, catalyzes the transfer of electrons from CYC to oxygen and participates in creating the electrochemical gradient used for ATP synthesis. Modeling three-dimensional structural data on COX and CYC reveals that 57 of the >1,500 COX residues can be implicated in binding CYC. Because of the functional importance of the transfer of electrons to oxygen, it might be expected that natural selection would drastically constrain amino acid replacement rates of CYC and COX. Instead, in anthropoid primates, although not in other mammals, CYC and COX show markedly accelerated amino acid replacement rates, with the COX acceleration being much greater at the positions that bind CYC than at those that do not. Specifically, in the anthropoid lineage descending from the last common ancestor of haplorhines (tarsiers and anthropoids) to that of anthropoids (New World monkeys and catarrhines) and that of catarrhines (Old World monkeys and apes, including humans), a minimum of 27 of the 57 COX amino acid residues that bind CYC were replaced, most frequently from electrostatically charged to noncharged residues. Of the COX charge-bearing residues involved in binding CYC, half (11 of 22) have been replaced with uncharged residues. CYC residues that interact with COX residues also frequently changed, but only two of the CYC changes altered charge. We suggest that reducing the electrostatic interaction between COX and CYC was part of the adaptive evolution underlying the emergence of anthropoid primates. C1 Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. NICHHD, Perinatol Res Branch, NIH, Detroit, MI 48201 USA. RP Grossman, LI (reprint author), Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. EM l.grossman@wayne.edu RI Opazo, Juan/A-9363-2009; OI Opazo, Juan/0000-0001-7938-4083 FU NIGMS NIH HHS [R24 GM065580, GM65580] NR 53 TC 48 Z9 60 U1 0 U2 7 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 MAY 3 PY 2005 VL 102 IS 18 BP 6379 EP 6384 DI 10.1073/pnas.0409714102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 923OE UT WOS:000228918400026 PM 15851671 ER PT J AU Tomso, DJ Inga, A Menendez, D Pittman, GS Campbell, MR Storici, F Bell, DA Resnick, MA AF Tomso, DJ Inga, A Menendez, D Pittman, GS Campbell, MR Storici, F Bell, DA Resnick, MA TI Functionally distinct polymorphic sequences in the human genome that are targets for p53 transactivation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bioinformatics; single nucleotide polymorphism; yeast; regulatory sequences; gene expression ID SINGLE NUCLEOTIDE POLYMORPHISM; P53-REGULATED GENE-EXPRESSION; TRANSCRIPTION FACTOR; BREAST-CANCER; BINDING SITES; DNA; RECRUITMENT; PROTEIN AB The p53 tumor suppressor protein is a master regulatory transcription factor that coordinates cellular responses to DNA damage and cellular stress. Besides mutations in p53, or in proteins involved in the p53 response pathway, genetic variation in promoter response elements (REs) of p53 target genes is expected to alter biological responses to stress. To identify SNPs in p53 REs that may modify p53-controlled gene expression, we developed an approach that combines a custom bioinformatics search to identify candidate SNPs with functional yeast and mammalian cell assays to assess their effect on p53 transactivation. Among &AP; 2 million human SNPs, we identified >200 that seem to disrupt functional p53 REs. Eight of these SNPs were evaluated in functional assays to determine both the activity of the putative RE and the impact of the candidate SNPs on transactivation. All eight candidate REs were functional, and in every case the SNP pair exhibited differential transactivation capacities. Additionally, six of the eight genes adjacent to these SNPs are induced by genotoxic stress or are activated directly by transfection with p53 cDNA. Thus, this strategy efficiently identifies SNPs that may differentially affect gene expression responses in the p53 regulatory pathway. C1 NIEHS, Mol Genet Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Bell, DA (reprint author), NIEHS, Mol Genet Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. EM bell1@niehs.nih.gov; resnick@niehs.nih.gov NR 37 TC 57 Z9 58 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 3 PY 2005 VL 102 IS 18 BP 6431 EP 6436 DI 10.1073/pnas.0501721102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 923OE UT WOS:000228918400035 PM 15843459 ER PT J AU Smith, S Gupta, A Kolodner, RD Myung, K AF Smith, S Gupta, A Kolodner, RD Myung, K TI Suppression of gross chromosomal rearrangements by the multiple functions of the Mre11-Rad50-Xrs2 complex in Saccharomyces cerevisiae SO DNA REPAIR LA English DT Article DE gross chromosomal rearrangements; Mre11-Rad50-Xrs2 complex; cancer ID DOUBLE-STRAND BREAKS; TELANGIECTASIA-LIKE DISORDER; DEPENDENT DNA-BINDING; GENOME INSTABILITY; CELL-CYCLE; MEIOTIC RECOMBINATION; TELOMERE MAINTENANCE; LENGTH MAINTENANCE; MRE11 COMPLEX; CROSSING-OVER AB The Mre11-Rad50-Xrs2 complex in Saccharomyces cerevisiae has roles in the intra-S checkpoint, homologous recombination, non-homologous end joining, meiotic recombination, telomere maintenance and the suppression of gross chromosomal rearrangements (GCRs). The discovery of mutations in the genes encoding the human homologues of two MRX subunits that underlie the chromosome fragility syndromes, Ataxia telangiectasia-like disorder and Nijmegen breakage syndrome suggest that the MRX complex also functions in suppression of GCRs in human cells. Previously, we demonstrated that the deletion mutations in each of the MRX genes increased the rate of GCRs up to 1000-fold compared to wild-type rates. However, it has not been clear which molecular function of the MRX complex is important for suppression of GCRs. Here, we present evidence that at least three different activities of the MRX complex are important for suppression of GCRs. These include the nuclease activity of Mre11, an activity related to MRX complex formation and another activity that has a close link with the telomere maintenance function of the MRX complex. An activity related to MRX complex formation is especially important for the suppression of translocation type of GCRs. However, the non-homologous end joining function of MRX complex does not appear to participate in the suppression of GCRs. Published by Elsevier B.V. C1 NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. RP Myung, K (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. EM kmyung@nhgri.nih.gov FU NIGMS NIH HHS [GM26017] NR 77 TC 21 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD MAY 2 PY 2005 VL 4 IS 5 BP 606 EP 617 DI 10.1016/j.dnarep.2005.01.004 PG 12 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 918IJ UT WOS:000228535200008 PM 15811632 ER PT J AU Decker, JM Bibollet-Ruche, F Wei, XP Wang, SY Levy, DN Wang, WQ Delaporte, E Peeters, M Derdeyn, CA Allen, S Hunter, E Saag, MS Hoxie, JA Hahn, BH Kwong, PD Robinson, JE Shaw, GM AF Decker, JM Bibollet-Ruche, F Wei, XP Wang, SY Levy, DN Wang, WQ Delaporte, E Peeters, M Derdeyn, CA Allen, S Hunter, E Saag, MS Hoxie, JA Hahn, BH Kwong, PD Robinson, JE Shaw, GM TI Antigenic conservation and immunogenicity of the HIV coreceptor binding site SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GP120 ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODY-RESPONSE; RHESUS MONOCLONAL-ANTIBODIES; RECEPTOR-BINDING; HETEROSEXUAL TRANSMISSION; TYROSINE SULFATION; VARIABLE LOOPS; SOLUBLE CD4; INFECTION AB Immunogenic, broadly reactive epitopes of the HIV-1 envelope glycoprotein could serve as important targets of the adaptive humoral immune response in natural infection and, potentially, as components of an acquired immune deficiency syndrome vaccine. However, variability in exposed epitopes and a combination of highly effective envelope-cloaking strategies have made the identification of such epitopes problematic. Here, we show that the chemokine coreceptor binding site of HIV-1 from clade A, B, C, D, F, G, and H and circulating recombinant form (CRF)01, CRF02, and CRF11, elicits high titers of CD4-induced (CD4i) antibody during natural human infection and that these antibodies bind and neutralize viruses as divergent as HIV-2 in the presence of soluble CD4 (sCD4). 178 out of 189 (94%) HIV-1-infected patients had CD4i antibodies that neutralized sCD4-pretreated HIV-2 in titers (50% inhibitory concentration) as high as 1:143,000. CD4i monoclonal antibodies elicited by HIV-1 infection also neutralized HIV-2 pretreated with sCD4, and polyclonal antibodies from HIV-1-infected humans competed specifically with such monoclonal antibodies for binding. In vivo, variants of HIV-1 with spontaneously exposed coreceptor binding surfaces were detected in human plasma; these viruses were neutralized directly by CD4i antibodies. Despite remarkable evolutionary diversity among primate lentiviruses, functional constraints on receptor binding create opportunities for broad humoral immune recognition, which in turn serves to constrain the viral quasispecies. C1 Univ Alabama Birmingham, Howard Hughes Med Inst, Birmingham, AL 35294 USA. Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama Birmingham, Sect Biostat, Birmingham, AL 35294 USA. Univ Montpellier, Inst Rech Dev, Montpellier 5, France. Emory Univ, Dept Pathol, Atlanta, GA 30329 USA. Emory Univ, Dept Lab Med, Atlanta, GA 30329 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA 70112 USA. RP Shaw, GM (reprint author), Univ Alabama Birmingham, Howard Hughes Med Inst, Birmingham, AL 35294 USA. EM gshaw@uab.edu FU NIAID NIH HHS [R01 AI024030, AI24030, AI27767, AI35467, AI41530, P30 AI027767, R01 AI058876, R37 AI035467, U01 AI041530] NR 79 TC 195 Z9 198 U1 2 U2 9 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 MAY 2 PY 2005 VL 201 IS 9 BP 1407 EP 1419 DI 10.1084/jem.20042510 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 924QV UT WOS:000228995900013 PM 15867093 ER PT J AU Hoffler, U Dixon, D Peddada, S Ghanayem, BI AF Hoffler, U Dixon, D Peddada, S Ghanayem, BI TI Inhibition of urethane-induced genotoxicity and cell proliferation in CYP2E1-null mice SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE urethane; CYP2E1-null mice; micronuclei; Ki-67 ID ETHYL CARBAMATE; VINYL CARBAMATE; NUCLEAR ANTIGEN; LUNG-TUMORS; IN-VIVO; CARCINOGENICITY; METABOLISM; EXPRESSION; INDUCTION; NEOPLASMS AB Urethane is a multi-site animal carcinogen and was classified as "reasonably anticipated to be a human carcinogen." Urethane is a fermentation by-product and found at appreciable levels in alcoholic beverages and foods such as bread and cheese. Recent work in this laboratory demonstrated for the first time that CYP2E1 is the principal enzyme responsible for urethane metabolism. The current studies were undertaken to assess the relationships between CYP2E1 -mediated metabolism and urethane- induced genotoxicity and cell proliferation as determined by induction of micronucleated erythrocytes (MN) and expression of Ki-67, respectively, using CYP2E1 -null and wild-type mice. Urethane was administered at 0 (vehicle), 1, 10, or 100 me/kg/day (p.o.), 5 days/week for 6 weeks. A significant dose-dependent increase in MN was observed in wild-type mice; however, a slight increase was measured in the MN-polychromatic erythrocytes in CYP2E1 -null mice treated with 100mg/kg. A significant increase in the expression of Ki-67 was detected in the livers and the lungs (terminal bronchioles, alveoli, and bronchi) of wild-type mice administered 100 mg urethane/kg in comparison to controls. In contrast, CYP2E1 -null mice administered this dose exhibited negligible alterations in Ki-67 expression in the livers and lungs compared to controls. Interestingly, while Ki-67 expression in the forestomach decreased in wild-type mice, it increased in CYP2E1 -null mice. Subsequent comparative metabolism studies demonstrated that total urethane-derived radioactivity in the plasma, liver, and lung was significantly higher in CYP2E1 -null versus wild-type mice and un-metabolized urethane constituted greater than 83% of the radioactivity in CYP2E1 -null mice. Unmetabolized urethane was not detectable in the plasma, liver, and lung of wild-type mice. In conclusion, these data demonstrated C1 Meharry Med Coll, Dept Pharmacol, Nashville, TN 37208 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Ghanayem, BI (reprint author), Meharry Med Coll, Dept Pharmacol, Nashville, TN 37208 USA. EM ghanayem@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 NR 32 TC 19 Z9 19 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 2 PY 2005 VL 572 IS 1-2 BP 58 EP 72 DI 10.1016/j.mrfmmm.2004.12.005 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 915ZU UT WOS:000228351500005 PM 15790490 ER PT J AU Malkin, EM Durbin, AP Diemert, DJ Sattabongkot, J Wu, YM Miura, K Long, CA Lambert, L Miles, AP Wang, J Stowers, A Miller, LH Saul, A AF Malkin, EM Durbin, AP Diemert, DJ Sattabongkot, J Wu, YM Miura, K Long, CA Lambert, L Miles, AP Wang, J Stowers, A Miller, LH Saul, A TI Phase 1 vaccine trial of Pvs25H: a transmission blocking vaccine for Plasmodium vivax malaria SO VACCINE LA English DT Article DE clinical trial; Plasmodium vivax; transmission blocking vaccine ID CANDIDATES PVS25; MOSQUITOS; BIOSYNTHESIS; POLYMORPHISM; COMPLEMENT; PROTEIN; BERGHEI AB Plasmodium vivax is responsible for the majority of malaria cases outside of Africa, and results in substantial morbidity. Transmission blocking vaccines are a potentially powerful component of a multi-faceted public health approach to controlling or eliminating malaria. We report the first phase 1 clinical trial of a P. vivax transmission blocking vaccine in humans. The Pvs25H vaccine is a recombinant protein derived from the Pvs25 surface antigen of P. vivax ookinetes. The protein was expressed in Saccharomyces cerevisiae, purified, and adsorbed onto Alhydrogel. Ten volunteers in each of three dose groups (5, 20, or 80 p,g) were vaccinated by intramuscular injection in an open-label study at 0, 28 and 180 days. No vaccine-related serious adverse events were observed. The majority of adverse events causally related to vaccination were mild or moderate in severity. Injection site tenderness was the most commonly observed adverse event. Anti-Pvs25H antibody levels measured by ELISA peaked after the third vaccination. Vaccine-induced antibody is functionally active as evidenced by significant transmission blocking activity in the membrane feeding assay. Correlation between antibody concentration and degree of inhibition was observed. Pvs25H generates transmission blocking immunity in humans against P. vivax demonstrating the potential of this antigen as a component of a transmission blocking vaccine. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD USA. AFRIMS, USA Med Component, Dept Entomol, Bangkok, Thailand. RP Malkin, EM (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, 5640 Fishers Lane,Twinbrook 1,Room 1123, Rockville, MD 20852 USA. EM emalkin@niaid.nih.gov RI Saul, Allan/I-6968-2013; OI Saul, Allan/0000-0003-0665-4091; Diemert, David/0000-0002-2789-0512 NR 15 TC 131 Z9 140 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 2 PY 2005 VL 23 IS 24 BP 3131 EP 3138 DI 10.1016/j.vaccine.2004.12.019 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 922WP UT WOS:000228870900007 PM 15837212 ER PT J AU Zhou, YH Purcell, RH Emerson, SU AF Zhou, YH Purcell, RH Emerson, SU TI A truncated ORF2 protein contains the most immunogenic site on ORF2: antibody responses to non-vaccine sequences following challenge of vaccinated and non-vaccinated macaques with hepatitis E virus SO VACCINE LA English DT Article DE hepatitis E virus; vaccine; immune responses ID PAKISTAN; GENOTYPE-4; EPIDEMIC; DISEASE; HEV AB A candidate hepatitis E vaccine is composed of amino acids (aa) 112-607 of the 660-aa protein encoded by open reading frame 2 (ORF2) of hepatitis E virus (HEV). We have studied the antibody response to vaccine-associated epitopes and to epitopes excluded from the vaccine to determine if important epitopes were omitted from the vaccine and if antibody responses to these regions could be used to differentiate between infection and vaccination. ELISAs were developed based on genotype 1 ORF2 peptides, containing as 112-607 (vaccine), 458-607 (minimum neutralization site), 1-111 (N-terminus) and 607-660 (C-terminus), as well as on ORF3 peptides, containing as 1-123 (complete) and 91-123 (C-terminus). All naive macaques infected with HEV genotype 1, 2, 3 or 4 produced antibodies to all ORF2 peptides. Anti-ORF3 was detected in both monkeys infected with genotype 1 virus and in one of two infected with genotype 2 virus. These antibody responses were considerably weaker than those directed against the neutralization site. In contrast, vaccinated animals that were challenged with HEV had a diminished or absent immune response to the peptides not included in the vaccine. Thus, only minor epitopes were excluded from the vaccine; they had limited utility for distinguishing between vaccination and infection. Published by Elsevier Ltd. C1 NIAID, Infect Dis Lab, Sect Hepatitis Viruses & Mol Hepatitis, NIH, Bethesda, MD 20892 USA. RP Zhou, YH (reprint author), NIAID, Infect Dis Lab, Sect Hepatitis Viruses & Mol Hepatitis, NIH, 50 S Dr MSC-8009, Bethesda, MD 20892 USA. EM vzhou@niaid.nih.gov NR 22 TC 29 Z9 35 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 2 PY 2005 VL 23 IS 24 BP 3157 EP 3165 DI 10.1016/j.vaccine.2004.12.020 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 922WP UT WOS:000228870900010 PM 15837215 ER PT J AU Hartos, JL Simons-Morton, BG Beck, KH Leaf, WA AF Hartos, JL Simons-Morton, BG Beck, KH Leaf, WA TI Parent-imposed limits on high-risk adolescent driving: are they stricter with graduated driver licensing? SO ACCIDENT ANALYSIS AND PREVENTION LA English DT Article DE graduated driver licensing; young drivers; parent restriction; parenting; adolescent driving risk; driving restrictions ID EXPERIENCE; TEENAGERS; PROGRAM; VIEWS AB The purpose of this study was to determine whether parent-imposed limits on 16-year-old high-risk driving are stricter in Maryland (MD), a state with graduated driver licensing (GDL) than in Connecticut (CT), a non-GDL state. In both states, parents and adolescents completed telephone surveys about the restrictions that parents placed on their adolescents' driving at night, with adolescent passengers, and at high speeds. In Maryland, surveys took place 1 month (294 parent-adolescent pairs) and 4 months (292 parent-adolescent pairs) after provisional licensure. In Connecticut, surveys took place the first month (132 pairs) and the third month (108 pairs) after adolescent licensure. The findings indicated that after controlling for demographic characteristics, Maryland parents and adolescents reported stricter parent-imposed limits for adolescent passengers, high-speed roads, weekend night driving, and overall limits. Parents in GDL states appear better able to establish and enforce adolescent driving restrictions when the licensing state stipulates, favors, and supports regulated adolescent driving. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ N Carolina, Coll Hlth & Human Serv, Interdisciplinary Hlth Studies, Dept Hlth Behav & Adm, Charlotte, NC 28223 USA. NICHD, DESPR, Prevent Res Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Publ & Community Hlth, College Pk, MD 20742 USA. Preusser Res Grp Inc, Trumbull, CT 06611 USA. RP Hartos, JL (reprint author), Univ N Carolina, Coll Hlth & Human Serv, Interdisciplinary Hlth Studies, Dept Hlth Behav & Adm, 9201 Univ Blvd, Charlotte, NC 28223 USA. EM jessica_hartos@nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 FU NICHD NIH HHS [HD-8-3285] NR 15 TC 17 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0001-4575 J9 ACCIDENT ANAL PREV JI Accid. Anal. Prev. PD MAY PY 2005 VL 37 IS 3 BP 557 EP 562 DI 10.1016/j.aap.2005.01.008 PG 6 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA 915ND UT WOS:000228310000020 PM 15784210 ER PT J AU Cohen, GH Silverton, EW Padlan, EA Dyda, F Wibbenmeyer, JA Willson, RC Davies, DR AF Cohen, GH Silverton, EW Padlan, EA Dyda, F Wibbenmeyer, JA Willson, RC Davies, DR TI Water molecules in the antibody-antigen interface of the structure of the Fab HyHEL-5-lysozyme complex at 1.7 angstrom resolution: comparison with results from isothermal titration calorimetry SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID EGG-WHITE LYSOZYME; BOBWHITE QUAIL LYSOZYME; ELECTRON-DENSITY MAPS; CRYSTAL-STRUCTURES; 3-DIMENSIONAL STRUCTURE; PHASING-POWER; CYTOCHROME-C; HYHEL-5; ASSOCIATION; BINDING AB The structure of the complex between hen egg-white lysozyme and the Fab HyHEL-5 at 2.7 angstrom resolution has previously been reported [Cohen et al. ( 1996), Acta Cryst. D52, 315 - 326]. With the availability of recombinant Fab, the X-ray structure of the complex has been re-evaluated at 1.7 angstrom resolution. The refined structure has yielded a detailed picture of the Fab lysozyme interface, showing the high complementarity of the protein surfaces as well as several water molecules within the interface that complete the good fit. The model of the full complex has improved significantly, yielding an R-work of 19.5%. With this model, the structural results can be compared with the results of isothermal titration calorimetry. An attempt has been made to estimate the changes in bound waters that accompany complex formation and the difficulties inherent in using the crystal structures to provide the information necessary to make this calculation are discussed. C1 NIH, Bethesda, MD 20892 USA. Univ Houston, Dept Chem Engn, Houston, TX 77004 USA. Univ Houston, Dept Biol & Chem, Houston, TX 77004 USA. RP Cohen, GH (reprint author), NIH, 5 Ctr Dr,MSC 0560, Bethesda, MD 20892 USA. EM gerson.cohen@nih.gov NR 44 TC 29 Z9 29 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD MAY PY 2005 VL 61 BP 628 EP 633 DI 10.1107/S0907444905007870 PN 5 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 918LQ UT WOS:000228543700017 PM 15858274 ER PT J AU Tovanabutra, S Brodine, SK Mascola, JR Sankale, JL Sanders-Buell, E Kim, B Birx, DL McCutchan, FE AF Tovanabutra, S Brodine, SK Mascola, JR Sankale, JL Sanders-Buell, E Kim, B Birx, DL McCutchan, FE TI Characterization of complete HIV type 1 genomes from non-B subtype infections in U.S. military personnel SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DEFICIENCY SYNDROME AIDS; GENETIC SUBTYPES; UNITED-STATES; RECOMBINANT; SEROCONVERSION; BREAKPOINTS; ORIGIN; RISK AB Infections with non-B HIV-1 subtypes are rare in the United States, but comprise a significant percentage of infections among U. S. military personnel. Risk behavior while on overseas deployment correlates with non-B infection in this population. Extensive genetic characterization will be required to define HIV-1 diversity, and to effectively evaluate requirements for HIV-1 vaccines and other prevention strategies in this group. From 1997 to 2000, 520 recent seroconverters, identified through routine HIV-1 testing in the U. S. active military force, volunteered for a prospective study. V3 loop serology or partial genome sequencing identified 28 non-B subtype infections; 14 were studied by full genome sequencing and phylogenetic analysis. Five strains were CRF01_AE. Four of these clustered with CM240 from Thailand, and one clustered with African CRF01_AE. Four strains were CRF02_AG, prevalent in West and West Central Africa. Two strains were subtype C. One strain was a unique recombinant between CRF01_AE and subtype B, and another was a complex unique recombinant between subtype A and D. The final strain was a member of a complex circulating recombinant first identified in Senegal, CRF09_cpx, incorporating subtypes A, F, G, and an unclassified genome. This diversity of non-B subtype HIV-1 strains, encompassing three globally prevalent non-B strains and including rare or even possibly unique strains, illustrates the breadth of U. S. military exposure while deployed and sets the bar higher for breadth of cross-subtype protection to be afforded by an HIV-1 vaccine. C1 San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. Naval Hlth Res Ctr, San Diego, CA 92186 USA. Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA. Henry M Jackson Fdn, US Mil HIV Res Program, Rockville, MD 20850 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard AIDS Inst, Boston, MA 02115 USA. RP McCutchan, FE (reprint author), Henry M Jackson Fdn Advancement Mil Med, Global Mol Epidemiol Program, 16000 Ease Gude Dr, Rockville, MD 20850 USA. EM fmccutchan@hivresearch.org NR 26 TC 16 Z9 17 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 BP 424 EP 429 DI 10.1089/aid.2005.21.424 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700013 PM 15929707 ER PT J AU Biggar, RJ Ng, J Kim, N Hisada, M Cranston, B Hanchard, B Maloney, E AF Biggar, RJ Ng, J Kim, N Hisada, M Cranston, B Hanchard, B Maloney, E TI Mother-child HLA concordance as a risk factor for Htlv-I transmission SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Georgetown Univ, Sch Med, Washington, DC 20057 USA. NIH, Viral Epidemiol Branch, Rockville, MD USA. Univ W Indies, Fac Med Sci, Kingston 7, Jamaica. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O5 BP 441 EP 442 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700019 ER PT J AU Jeang, KJ Haller, K Peloponese, J AF Jeang, KJ Haller, K Peloponese, J TI Htlv-1 Tax interacts with the Ran-Gtp network and induces centrosome amplification in primary cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIAID, NIH, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O10 BP 443 EP 443 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700024 ER PT J AU Waldmann, TA Patel, H Zhang, M AF Waldmann, TA Patel, H Zhang, M TI The introduction of Hu-Mik-Beta-1 that blocks Il-15 action in the therapy of autoimmune diseases including HTLV-I associated Ham/Tsp SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O14 BP 444 EP 444 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700027 ER PT J AU Morris, JC O'Mahony, D Lee, CC O'Hagan, D Wendy, G Waldmann, TA Janik, JE AF Morris, JC O'Mahony, D Lee, CC O'Hagan, D Wendy, G Waldmann, TA Janik, JE TI A phase Ii study of the efficacy and toxicity of Campath-1H (anti-Cd52) for the therapy of adult T cell leukemia (Atl): Early results. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NCI, Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O22 BP 446 EP 446 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700035 ER PT J AU Fukumoto, R Dundr, M Nicot, CP Samelson, L Franchini, G AF Fukumoto, R Dundr, M Nicot, CP Samelson, L Franchini, G TI Htlv-1 P12I is recruited to the immunological synapse, binds to Lat, and inhibits downstream Tcr signaling SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. Univ Kansas, Kansas City, KS USA. NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O25 BP 447 EP 447 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700038 ER PT J AU Thete, J Sibon, D Delfau-Larue, M Barbeau, B Rabaaoui, S Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mesnard, J Mortreux, F Wattel, E AF Thete, J Sibon, D Delfau-Larue, M Barbeau, B Rabaaoui, S Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mesnard, J Mortreux, F Wattel, E TI Cloned Htlv-1 positive cells from Tsp/Ham frequently express Hbz SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Hop Edouard Herriot, Ctr Leon Berard, Lyon, Rhone, France. CNRS, Montpellier, Herault, France. NIH, Bethesda, MD 20892 USA. Fdn Adolphe De Rothschild, Paris, Ile De France, France. Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, Paris, Ile De France, France. CHU Angers, Hematol Lab, Angers, Maine Et Loire, France. Int Agcy Res Canc, Unit Infect & Canc, F-69372 Lyon, Rhone, France. Univ Laval, CHUL, Res Ctr, Ste Foy, PQ G1K 7P4, Canada. CHU Henri Mondor, Immunol Lab, F-94010 Creteil, Val De Maine, France. Ctr Leon Berard, F-69373 Lyon, Rhone, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O24 BP 447 EP 447 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700037 ER PT J AU Jacobson, S AF Jacobson, S TI Immunopathogenesis of Htlv-I associated neurologic disease: Role of Htlv-I infected Cd4+ Cd25+ T cells. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O39 BP 451 EP 451 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700052 ER PT J AU Azimi, NA Groh, V Tanaka, Y Jacobson, S Spies, T AF Azimi, NA Groh, V Tanaka, Y Jacobson, S Spies, T TI Dysregulation of the Nk receptor Nkg2D and its ligand Mic contributes to the disease progression in Ham. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Bethesda, MD 20892 USA. Univ Ryukyus, Nishihara, Okinawa 90301, Japan. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O45 BP 452 EP 453 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700058 ER PT J AU Gagnon, SJG Damirjian, M Turner, RV Biddison, WE AF Gagnon, SJG Damirjian, M Turner, RV Biddison, WE TI T cell receptor cross-reactivity between Hltv-1 Tax 11-19 and a hapten-modified peptide SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Neuroimmunol Branch, Mol Immunol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O43 BP 452 EP 452 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700056 ER PT J AU Cazares, L Qi, L Ward, M Hisada, M Trosset, M Jacobson, S Semmes, J AF Cazares, L Qi, L Ward, M Hisada, M Trosset, M Jacobson, S Semmes, J TI Discrete serum protein signatures discriminate between human retrovirus associated hematologic and neurologic disease SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Bethesda, MD 20892 USA. Coll William & Mary, Williamsburg, VA USA. NIH, Viral Epidemiol Branch, Rockville, MD USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O50 BP 454 EP 454 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700063 ER PT J AU Kaumaya, PT Lynch, MP Jacobson, S AF Kaumaya, PT Lynch, MP Jacobson, S TI Vaccine design and peptide therapeutic strategies for Htlv-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Ohio State Univ, Columbus, OH 43210 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O56 BP 456 EP 456 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700069 ER PT J AU Lynch, MP Carbin, DM Rawale, SV Lieblein, JC Jacobson, S Kaumaya, PT AF Lynch, MP Carbin, DM Rawale, SV Lieblein, JC Jacobson, S Kaumaya, PT TI Heteroclitic analogues derived from Htlv-1 Gag and Tax antigens increase cytolytic and Ifn-responses in Hla-A*0201 transgenic mice SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O55 BP 456 EP 456 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700068 ER PT J AU Puccioni-Soler, M Yamano, Y Rios, M Goncalves, RR Domingues, RC Carvalho, S Papaiz-Alvarenga, R Jacobson, S AF Puccioni-Soler, M Yamano, Y Rios, M Goncalves, RR Domingues, RC Carvalho, S Papaiz-Alvarenga, R Jacobson, S TI Htlv-i proviral load in Pbmnc and Csf of Ham/Tsp, Htlv-i positive patients with multiple sclerosis-like manifestations, other neurological diseases and asymptomatic carriers SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Bethesda, MD 20892 USA. Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. Inst Estadual Hematol Arthur de S Cavalcanti, HEMORIO, Rio De Janeiro, Brazil. MR Muti Imagem, Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, DMD Clin Pathol, HUCFF UFRJ, Neurolife Lab, Rio De Janeiro, Brazil. US FDA, Bethesda, MD 20014 USA. Kagoshima Univ, Kagoshima 890, Japan. HUGG UNIRIO, HUCFF UFRJ, Rio De Janeiro, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O57 BP 456 EP 457 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700070 ER PT J AU Derse, DD Heidecker, G Mazurov, D Mitchell, M Hill, S Lloyd, PA Princler, G AF Derse, DD Heidecker, G Mazurov, D Mitchell, M Hill, S Lloyd, PA Princler, G TI Molecular mechanisms of Htlv-1 infection and replication SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 SAIC Frederick, Frederick, MD USA. NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O67 BP 459 EP 459 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700080 ER PT J AU Jones, KS Petrow-Sadowski, C Huang, Y Bertolette, D Fugo, K Takenouchi, N Grant, CW Yao, K Jacobson, S Ruscetti, FW AF Jones, KS Petrow-Sadowski, C Huang, Y Bertolette, D Fugo, K Takenouchi, N Grant, CW Yao, K Jacobson, S Ruscetti, FW TI Heparan sulfate proteoglycans are critical for efficient attachment and entry of HTLV-I into Cd4+ T cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. SAIC Frederick, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O65 BP 459 EP 459 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700078 ER PT J AU Mueller, N Okayama, A Stuver, S Cranston, B Hanchard, B Birmann, B Hisada, M AF Mueller, N Okayama, A Stuver, S Cranston, B Hanchard, B Birmann, B Hisada, M TI The epidemiology of Htlv-i infection: Where do we go from here? SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Viral Epidemiol Branch, Rockville, MD USA. Univ W Indies, Fac Med Sci, Kingston 7, Jamaica. Boston Univ, Boston, MA 02215 USA. Miyazaki Med Coll, Miyazaki, Japan. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA O68 BP 459 EP 460 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700081 ER PT J AU Levy-Clarke, GA Janik, J Smith, J Morris, J Buggage, R Chan, C Nussenblatt, R Waldmann, T AF Levy-Clarke, GA Janik, J Smith, J Morris, J Buggage, R Chan, C Nussenblatt, R Waldmann, T TI A decade of ocular findings in human T-cell lymphotrophic virus type-1 (Htlv-1) infected patients at the National Eye Institute (Nei) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Immunol Lab, Bethesda, MD USA. NIH, Immunol Lab, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIH, Div Clin Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P1 BP 463 EP 463 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700082 ER PT J AU O'Hagan, D Janik, J O'Mahony, D Gao, W Wharfe, GF Cranston, B Waldmann, TA Morris, J AF O'Hagan, D Janik, J O'Mahony, D Gao, W Wharfe, GF Cranston, B Waldmann, TA Morris, J TI Diffuse synovial involvement with Htlv-1-associated adult T cell lymphoma (Atl) presenting as Htlv-1-associated arthropathy (Haa) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Univ W Indies, Dept Pathol, Kingston 7, Jamaica. Univ W Indies, Fac Med Sci, Kingston 7, Jamaica. NIH, Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P10 BP 465 EP 465 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700091 ER PT J AU O'Mahony, D Janik, J Morris, J O'Hagan, D Gao, W Waldmann, TA Raffeld, M AF O'Mahony, D Janik, J Morris, J O'Hagan, D Gao, W Waldmann, TA Raffeld, M TI Emergence of a second leukemic T cell population in a patient with Htlv1 associated adult T cell leukemia (Atl) following treatment with Campath-1H (antiCd52). SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Pathol Lab, Bethesda, MD 20892 USA. NIH, Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P12 BP 466 EP 466 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700093 ER PT J AU Sonoda, J Kozako, T Li, H Yamada, H Kawahira, K Arima, N Sonoda, S AF Sonoda, J Kozako, T Li, H Yamada, H Kawahira, K Arima, N Sonoda, S TI Green tea polyphenols reduce Htlv-1 provirus load in peripheral blood mononuclear cells of Htlv-1 carriers SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Kagoshima Univ, Ctr Res & Dev, Kagoshima 890, Japan. Kagoshima Univ, Grad Sch Med & Dent Sci, Div Host Response, Ctr Chron Viral Dis, Kagoshima 890, Japan. Kagoshima Univ, Kagoshima Univ Hosp, Kirishima Rehabil Ctr, Kagoshima 890, Japan. NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P15 BP 466 EP 467 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700096 ER PT J AU Janik, J O'Mahony, D Morris, J Stetler-Stevenson, M Gao, W O'Hagan, D Moses, L Taylor, M McEwen, C Hammershaimb, L Waldmann, T AF Janik, J O'Mahony, D Morris, J Stetler-Stevenson, M Gao, W O'Hagan, D Moses, L Taylor, M McEwen, C Hammershaimb, L Waldmann, T TI Phase I trial of siplizumab in Cd2-positive lymphoproliferative disease SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 MedImmune, Gaithersburg, MD USA. NCI, Lab Path, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P25 BP 470 EP 470 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700106 ER PT J AU Brown, B Brown, E Yeager, M Welch, R Cranston, B Hanchard, B Hisada, M AF Brown, B Brown, E Yeager, M Welch, R Cranston, B Hanchard, B Hisada, M TI Common genetic variants in cytokine genes and risk of human T-Cell lymphotropic virus type I infection in Jamaican children SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NIH, Core Genotyping Facil, Bethesda, MD USA. Natl Inst Hlth, Kingston, Jamaica. Univ W Indies, Fac Med Sci, Kingston 7, Jamaica. NIH, Viral Epidemiol Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P30 BP 471 EP 471 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700111 ER PT J AU Vanveldhuisen, PC Sawada, T Miley, W Levine, PH Hanchard, B Cranston, B Hisada, M AF Vanveldhuisen, PC Sawada, T Miley, W Levine, PH Hanchard, B Cranston, B Hisada, M TI Evaluation of predictive markers of HTLV-I-associated disease in Jamaica SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 George Washington Univ, Washington, DC 20052 USA. EMMES Corp, Rockville, MD USA. Eisai & Co Ltd, Tsukuba, Ibaraki, Japan. NIH, Viral Epidemiol Sect, SAIC, Bethesda, MD USA. Univ W Indies, Fac Med Sci, Kingston 7, Jamaica. NIH, Viral Epidemiol Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P34 BP 472 EP 472 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700115 ER PT J AU Maloney, E Yamano, Y Vanveldhuisen, P Sawada, T Kim, N Cranston, B Hanchard, B Jacobson, S Hisada, M AF Maloney, E Yamano, Y Vanveldhuisen, P Sawada, T Kim, N Cranston, B Hanchard, B Jacobson, S Hisada, M TI Follow-up study of HTLV-I viral markers in children in Jamaica SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Ctr Dis Control & Prevent, Atlanta, GA USA. NIH, Neuroimmunol Branch, Bethesda, MD USA. EMMES Corp, Rockville, MD USA. Eisai & Co Ltd, Tsukuba, Ibaraki, Japan. Univ W Indies, Fac Med Sci, Kingston 7, Jamaica. NIH, Viral Epidemiol Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P37 BP 473 EP 473 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700118 ER PT J AU Birmann, B Mueller, N Breen, EC Stuver, S Okayama, A Martinez-Maza, O Raker, CA Aziz, N Li, H Cranston, B Hanchard, B Hisada, M AF Birmann, B Mueller, N Breen, EC Stuver, S Okayama, A Martinez-Maza, O Raker, CA Aziz, N Li, H Cranston, B Hanchard, B Hisada, M TI HTLV-I infection is associated with elevated plasma biomarkers of immune activation in Jamaican but not in Japanese carriers. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Miyazaki Med Coll, Dept Lab Med, Miyazaki 88916, Japan. NIH, Viral Epidemiol Branch, Rockville, MD USA. Univ W Indies, Fac Med Sci, Kingston, Jamaica. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P44 BP 475 EP 475 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700125 ER PT J AU Li, H Walters, M Carrington, M Headley, C Amarasinghe, A Goedert, J Cranston, B Hanchard, B Hisada, M AF Li, H Walters, M Carrington, M Headley, C Amarasinghe, A Goedert, J Cranston, B Hanchard, B Hisada, M TI Serologic and molecular characteristics of atypical HTLV Western blot banding patterns in Jamaican blood donors SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 SAIC Frederick, Viral Epidemiol Sect, Frederick, MD USA. NCI, SAIC Frederick, Lab Genom Divers, Frederick, MD 21701 USA. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. Res Triangle Inst, Washington, DC USA. NCI, Viral Epidemiol Branch, NIH, DHHS, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P56 BP 479 EP 479 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700137 ER PT J AU Porto, A Braga, S Muniz, A Rodrigues, W Jacobson, S Carvalho, E AF Porto, A Braga, S Muniz, A Rodrigues, W Jacobson, S Carvalho, E TI Helminthic infections down regulate immunological response in HTLV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 UFBA, Serv Imunol, Salvador, BA, Brazil. NINDS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P70 BP 483 EP 483 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700151 ER PT J AU Puccioni-Sohler, M Jacobson, S AF Puccioni-Sohler, M Jacobson, S TI Higher proviral load in lumbar than in cisternal CSF cells of HAM/TSP SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Univ Fed Rio de Janeiro, HUCFF, HUGG, Rio De Janeiro, Brazil. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P72 BP 484 EP 484 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700153 ER PT J AU Yao, K Hisada, M Maloney, E Yamano, Y Hanchard, B Wilks, RJ Rios, M Jacobson, S AF Yao, K Hisada, M Maloney, E Yamano, Y Hanchard, B Wilks, RJ Rios, M Jacobson, S TI HTLV-I/II Western blot seroindeterminate status and its association with exposure to prototype HTLV-I. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Bethesda, MD 20892 USA. NIH, Viral Epidemiol Branch, Rockville, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Kagoshima Univ, Kagoshima 890, Japan. Univ W Indies, Fac Med Sci, Kingston 7, Jamaica. Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P74 BP 484 EP 484 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700155 ER PT J AU Sibon, D Thete, J Delfau-Larue, M Rabaaoui, S Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E AF Sibon, D Thete, J Delfau-Larue, M Rabaaoui, S Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E TI Uninfected cloned T cells from Tsp/Ham resist apoptosis. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Ctr Leon Berard, F-69373 Lyon, Rhone, France. CHU Henri Mondor, Immunol Lab, F-94010 Creteil, Val De Marne, France. Int Agcy Res Canc, Unit Infect & Canc, F-69372 Lyon, Rhone, France. CHU Angers, Hematol Lab, Angers, Maine Loire, France. Inst Pasteur, Unite epidemiol & Physiopathol Virus Oncogenes, Paris, France. Fdn Adolphe De Rothschild, Neurol, Paris, France. NIH, Bethesda, MD 20892 USA. Ctr Leon Berard, Hop Edouard Herriot, F-69373 Lyon, Rhone, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P82 BP 487 EP 487 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700163 ER PT J AU Satou, YS Wu, X Doi, K Yasunaga, J Taniguchi, Y Matsuoka, M AF Satou, YS Wu, X Doi, K Yasunaga, J Taniguchi, Y Matsuoka, M TI Different preference of HTLV-I provirus integration SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Kyoto Univ, Inst Virus Res, Kyoto 606, Japan. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P91 BP 489 EP 489 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700172 ER PT J AU Iha, H Peloponese, J Yedavalli, VR Jeang, K AF Iha, H Peloponese, J Yedavalli, VR Jeang, K TI Distinct role of Tax-binding protein, TXBP151, on Tax-mediated or interleukine-1beta (Il-1B) triggered NF-kB signaling SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P93 BP 490 EP 490 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700174 ER PT J AU Lu, H Zhou, M Park, H Brady, J AF Lu, H Zhou, M Park, H Brady, J TI Functional interaction between Tax and the cyclin dependent kinase CDK9 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P98 BP 491 EP 491 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700179 ER PT J AU Franchini, G AF Franchini, G TI HTLV leukemogenesis SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P102 BP 492 EP 493 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700183 ER PT J AU Sibon, D Thete, J Delfau-Larue, M Rabaaoui, S Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E AF Sibon, D Thete, J Delfau-Larue, M Rabaaoui, S Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E TI HTLV-1 infected and uninfected T cell clones from Tsp/Ham display the same altered bcl2, Bax, Mad, p53, and Glut-1 expression. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Ctr Leon Berard, F-69373 Lyon, Rhone, France. CHU Henri Mondor, Immunol Lab, F-94010 Creteil, Val De Marne, France. Int Agcy Res Canc, Univ Infect & Canc, F-69372 Lyon, Rhone, France. CHU Angers, Hematol Lab, Angers, Maine Loire, France. Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, Paris, Ile De France, France. Fdn Adolphe De Rothschild, Neurol, Paris, Ile De France, France. NIH, Bethesda, MD 20892 USA. Hop Edouard Herriot, Ctr Leon Berard, Lyon, Rhone, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P104 BP 493 EP 493 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700185 ER PT J AU Thete, J Sibon, D Delfau-Larue, M Rabaaoui, S Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E AF Thete, J Sibon, D Delfau-Larue, M Rabaaoui, S Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E TI HTLV-1 5 ' LTR methylation is influenced by integration position SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Ctr Leon Berard, F-69373 Lyon, Rhone, France. CHU Henri Mondor, Immunol Lab, Creteil, Val De Marne, France. Int Agcy Res Canc, Unit Infect & Canc, F-69372 Lyon, Rhone, France. CHU Angers, Hematol Lab, Angers, Maine Loire, France. Inst Pasteur, Unite Epidemiol & Physiopathol Viruis Oncogenes, Paris, Ile De France, France. Fdn Adolphe De Rothschild, Neurol, Paris, Ile De France, France. NIH, Bethesda, MD 20892 USA. Hop Edouard Herriot, Ctr Leon Berard, Lyon, Rhone, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P103 BP 493 EP 493 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700184 ER PT J AU De la Fuente, C Kehn, K Strouss, KM Berro, R Jiang, H Brady, J Mahieux, R Pumfery, A Bottazzi, M Kashanchi, F AF De la Fuente, C Kehn, K Strouss, KM Berro, R Jiang, H Brady, J Mahieux, R Pumfery, A Bottazzi, M Kashanchi, F TI The HTLV-I Tax oncoprotein targets the Retinoblastoma (Rb) protein for proteasomal degradation SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 George Washington Univ, Washington, DC USA. NIH, Bethesda, MD 20892 USA. Inst Pasteur, Paris 15, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P137 BP 502 EP 502 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700218 ER PT J AU Heidecker, GH Lloyd, P Nagashima, K Derse, D AF Heidecker, GH Lloyd, P Nagashima, K Derse, D TI The role of ubiquitination in HTLV-1 budding SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. SAIC Frederick, Basic Res Program, Frederick, MD USA. SAIC Frederick, Image Anal Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P141 BP 503 EP 503 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700222 ER PT J AU Jeong, S Radonovich, M Brady, J Pise-Masison, C AF Jeong, S Radonovich, M Brady, J Pise-Masison, C TI The role of HTLV-1-Tax mediated IKK2 activation in the inhibition of the tumor suppressor p53 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P140 BP 503 EP 503 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700221 ER PT J AU Lynch, MP Rawale, SV Jacobson, S Kaumaya, PT AF Lynch, MP Rawale, SV Jacobson, S Kaumaya, PT TI Novel retro-inverso envelope peptide mimetic fusion inhibitors as a potential therapy for HTLV-1 infected individuals SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Ohio State Univ, Dept Microbiol, Columbus, OH USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH USA. NIH, hnq2242, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P146 BP 505 EP 505 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700227 ER PT J AU Fugo, K Takenouchi, N Yao, K Lisinski, I Cushman, SW Ruscetti, FW Jones, K Jacobson, S AF Fugo, K Takenouchi, N Yao, K Lisinski, I Cushman, SW Ruscetti, FW Jones, K Jacobson, S TI Cell surface GLUT-1 overexpression enhances cell-cell transmission of HTLV-I virions SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. NIH, Diabet Branch, Bethesda, MD 20892 USA. SAIC Frederick, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P150 BP 506 EP 506 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700231 ER PT J AU Sibon, D Thete, J Delfau-Larue, M Rabaaoui, S Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E AF Sibon, D Thete, J Delfau-Larue, M Rabaaoui, S Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E TI Cloned CD4+ HTLV-1 naturally infected cells proliferate while their CD8+ counterparts accumulate SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Hop Edouard Herriot, Ctr Leon Berard, Lyon, Rhone, France. CHU Henri Mondor, Immunol Lab, F-94010 Creteil, Val De Marne, France. Int Agcy Res Canc, Unit Infect & Canc, F-69372 Lyon, Rhone, France. CHU Angers, Hematol Lab, Angers, Maine Et Loire, France. Inst Pasteur, Unite Epidemiol & Physiopatholie Virus Oncogenes, Paris, Ile De France, France. Fdn Adolphe De Rothschild, Paris, Ile De France, France. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P151 BP 506 EP 506 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700232 ER PT J AU Sibon, D Thete, J Delfau-Larue, M Rabaaoui, S Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E AF Sibon, D Thete, J Delfau-Larue, M Rabaaoui, S Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E TI Fully dependent, partially dependent and Tax-independent cellular alterations in T cells cloned from HTLV-1 carriers without malignancy. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol Myers-Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Hop Edouard Herriot, Ctr Leon Berard, Lyon, Rhone, France. CHU Henri Mondor, Immunol Lab, F-94010 Creteil, Val De Marne, France. Int Agcy Res Canc, Unit Infect & Canc, F-69372 Lyon, Rhone, France. CHU Angers, Hematol Lab, Angers, Maine Et Loire, France. Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, Paris, Ile De France, France. Fdn Adolphe De Rothschild, Paris, Ile De France, France. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P158 BP 508 EP 508 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700239 ER PT J AU Sibon, D Rabaaoui, S Delfau-Larue, M Thete, J Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E AF Sibon, D Rabaaoui, S Delfau-Larue, M Thete, J Gabet, A Zandecki, M Pinatel, C Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E TI Frequent superinfection in Htlv-1 cloned T cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol Myers-Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Hop Edouard Herriot, Ctr Leon Berard, Lyon, Rhone, France. CHU Henri Mondor, Immunol Lab, F-94010 Creteil, Val De Marne, France. Int Agcy Res Canc, Unit Infect & Canc, F-69372 Lyon, Rhone, France. CHU Angers, Hematol Lab, Angers, Maine Et Loire, France. Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, Paris, Ile De France, France. Fdn Adolphe De Rothschild, Paris, Ile De France, France. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P157 BP 508 EP 508 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700238 ER PT J AU Takenouchi, N Fugo, K Yao, K Lisinski, I Cushman, SW Ruscetti, FW Jones, K Jacobson, S AF Takenouchi, N Fugo, K Yao, K Lisinski, I Cushman, SW Ruscetti, FW Jones, K Jacobson, S TI HTLV SU binding is not increased on GLUT-1 over-expressing cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Viral Immunol Branch, Bethesda, MD 20892 USA. NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. NIH, Diabet Branch, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. SAIC Frederick, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P159 BP 509 EP 509 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700240 ER PT J AU Oh, U Yamano, Y Mora, C Akhyani, N Griffith, C Nagai, M Takenuochi, N Yao, K Jacobson, S AF Oh, U Yamano, Y Mora, C Akhyani, N Griffith, C Nagai, M Takenuochi, N Yao, K Jacobson, S TI Interferon-beta1a therapy for HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) reduces HTLV-I-specific CD8+ T cells: Analysis of HAM/TSP biomarkers.) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. Kagoshima Univ, Fac Med, Dept Internal Med 3, Kagoshima 890, Japan. Georgetown Univ, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P169 BP 511 EP 512 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700250 ER PT J AU Chevalier, SC Meertens, L Pise-Masison, C Brady, J Gessain, A Mahieux, R AF Chevalier, SC Meertens, L Pise-Masison, C Brady, J Gessain, A Mahieux, R TI Molecular characterization of the Tax protein from the highly divergent simian T-cell lymphotropic virus type 3 strain SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, Paris, France. NIH, Bethesda, MD 20892 USA. RI Meertens, Laurent/E-8043-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P174 BP 513 EP 513 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700255 ER PT J AU Grant, CW Oh, U Yamano, Y Fugo, K Griffith, C Takenouchi, N Yao, K Maric, D Jacobson, S AF Grant, CW Oh, U Yamano, Y Fugo, K Griffith, C Takenouchi, N Yao, K Maric, D Jacobson, S TI Mechanism of the regulatory T cell-specific protein Foxp3: Overexpression of Foxp3 is associated with enhanced NF-kB activation SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Kagoshima Univ, Kagoshima 890, Japan. NIH, Neurophysiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P173 BP 513 EP 513 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700254 ER PT J AU Rauch, DR Weilgosz, M Choudhary, G Jones, K Ruscetti, F Ratner, L AF Rauch, DR Weilgosz, M Choudhary, G Jones, K Ruscetti, F Ratner, L TI Rafts, Glut-1, and HTLV SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol Myers-Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource C1 Washington Univ, St Louis, MO USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NCI, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2005 VL 21 IS 5 MA P176 BP 513 EP 514 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 936AV UT WOS:000229825700257 ER PT J AU Barr, CS Newman, TK Lindell, BG Schwandt, ML Chen, SA Goldman, D Higley, JD AF Barr, CS Newman, TK Lindell, BG Schwandt, ML Chen, SA Goldman, D Higley, JD TI A functional polymorphism in the MU opiod receptor gene (MORC77G) is associated with increased alcohol consumption in rhesus macaques SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIMH, NIAAA, NIH, Lab Clin & Translat Studies, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 9A EP 9A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900016 ER PT J AU Newman, T Barr, CS Champoux, M Suomi, SJ Goldman, D Higley, JD AF Newman, T Barr, CS Champoux, M Suomi, SJ Goldman, D Higley, JD TI DRD1 gene variation interacts with sex and rearing experience to influence ethanol consumption in rhesus macaques. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 9A EP 9A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900015 ER PT J AU Thanos, PPK Katana, JM Volkow, ND AF Thanos, PPK Katana, JM Volkow, ND TI Ethanol self-administration is markedly reduced in ethanol preferring (P) rat: Treated with the CB1 antagonist SR 141716 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 Brookhaven Natl Lab, Behav Neuropharmacol Lab, Dept Med, Upton, NY 11973 USA. NIAAA, Lab Neuroimaging, Bethesda, MD 20892 USA. NIDA, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 12A EP 12A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900035 ER PT J AU Chiapella, AP Willenbring, ML AF Chiapella, AP Willenbring, ML TI Symptom clustering in time: Relationships with alcohol diagnoses and treatment as seen in the national epidemiological survey on alcohol and related conditions (NESARC) SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 31A EP 31A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900146 ER PT J AU Chen, C Yi, H Yahn, H AF Chen, C Yi, H Yahn, H TI Patterns of polydrug use in drinkers with DSM-IV alcohol abuse and dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Alcohol Epidemiol Data Syst, NIH, CSR Inc, Arlington, VA 22201 USA. NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 34A EP 34A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900168 ER PT J AU Stinson, FS Grant, BF Dawson, DA AF Stinson, FS Grant, BF Dawson, DA TI Homotypic comorbidity between DSM-IV alcohol and specific drug use disorders in the United States SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 34A EP 34A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900169 ER PT J AU Falk, DE Yi, H Hitton, ME AF Falk, DE Yi, H Hitton, ME TI Temporal sequencing of lifetime DSM-IV alcohol use disorders relative to comorbid mood, anxiety, and antisocial personality disorders in NESARC SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Alcohol Epidemiol Data Syst, NIH, CSR Inc, Arlington, VA 22201 USA. NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 35A EP 35A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900171 ER PT J AU Huang, B Dawson, DA Grant, BF Stinson, FF Chou, P Saha, T Ruan, WJ Pickering, R AF Huang, B Dawson, DA Grant, BF Stinson, FF Chou, P Saha, T Ruan, WJ Pickering, R TI Ethnicity and alcohol related psychiatric comorbidity: United States, 2001-2002 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 35A EP 35A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900173 ER PT J AU Smith, SM Dawson, DA Grant, BF Stinson, FS Chou, SP AF Smith, SM Dawson, DA Grant, BF Stinson, FS Chou, SP TI DSM IV alcohol dependence and selected chronic conditions SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 37A EP 37A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900182 ER PT J AU Goldstein, RB Grant, BF Stinson, FS Hasin, DS Dawson, DA Chou, SP Ruan, WJ Huang, B AF Goldstein, RB Grant, BF Stinson, FS Hasin, DS Dawson, DA Chou, SP Ruan, WJ Huang, B TI Prevalence, correlates, and comorbidity of bipolar I, axis 1, mid axis II disorders: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Epidemiol & Biomety, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 38A EP 38A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900193 ER PT J AU Yoon, YH Yi, H Breslow, RA AF Yoon, YH Yi, H Breslow, RA TI Unintentional alcohol poisoning and co-occurring causes of death in the United States, 1999-2002: A multiple cause analysis. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Alcohol Epidemiol Data Syst, NIH, CSR Inc, Arlington, VA 22201 USA. NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 38A EP 38A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900188 ER PT J AU Lakins, NE Yi, H Hilton, ME AF Lakins, NE Yi, H Hilton, ME TI Self-medication of psychological symptoms with alcohol among individuals diagnosed with psychological disorders SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Alcohol Epidemiol Data Syst, NIH, CSR Inc, Arlington, VA 22201 USA. NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 39A EP 39A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900198 ER PT J AU Pickering, RP Grant, BF Dawson, DA Chou, P AF Pickering, RP Grant, BF Dawson, DA Chou, P TI Differences among drinkers with alcohol disorders entering and not entering alcohol treatment. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 40A EP 40A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900200 ER PT J AU Stark, KD Pawlosky, RJ Beblo, S Murthy, M Flanagan, VP Janisse, J Buda-Abela, M Rockett, H Whitty, JE Sokol, RJ Hannigan, JH Salem, N AF Stark, KD Pawlosky, RJ Beblo, S Murthy, M Flanagan, VP Janisse, J Buda-Abela, M Rockett, H Whitty, JE Sokol, RJ Hannigan, JH Salem, N TI Status of plasma folate after folic acid fortification of food in pregnant black women and the influences of diet, smoking. and alcohol consumption SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 Natl Inst Alcohol Abuse & Alcoholism, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RI Stark, Ken/I-1347-2016 OI Stark, Ken/0000-0001-7828-4072 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 44A EP 44A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900227 ER PT J AU Stark, KD Beblo, S Murthy, M Whitty, JE Buda-Abela, M Janisse, J Rockett, H Martier, SS Sokol, RJ Hannigan, JH Salem, N AF Stark, KD Beblo, S Murthy, M Whitty, JE Buda-Abela, M Janisse, J Rockett, H Martier, SS Sokol, RJ Hannigan, JH Salem, N TI Alcohol consumption in pregnant, black women is associated with decreased docosahexaenoic acid status SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RI Stark, Ken/I-1347-2016 OI Stark, Ken/0000-0001-7828-4072 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 44A EP 44A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900228 ER PT J AU Lovinger, DM Shannon, EE Grant, KA AF Lovinger, DM Shannon, EE Grant, KA TI The NMDA receptor NR2A subunit is a strong determinant of the discriminative stimulus properties of ethanol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27157 USA. NIAAA, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 48A EP 48A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900253 ER PT J AU Mennella, JA Pepino, MY Teff, KL AF Mennella, JA Pepino, MY Teff, KL TI Short-term effects of alcohol consumption on the hormonal milieu and mood states of nulliparous women SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. Natl Inst Diabet Digest & Kidney Dis, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 55A EP 55A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900291 ER PT J AU Boyce-Rustay, JM Wiedhotz, LM Holmes, A AF Boyce-Rustay, JM Wiedhotz, LM Holmes, A TI Stress increases sensitivity to the intoxicating effects of ethanol in mice. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 59A EP 59A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900316 ER PT J AU Ramchandani, VA Hoefer, ME Edenberg, EF Walker, JT Hommer, DW AF Ramchandani, VA Hoefer, ME Edenberg, EF Walker, JT Hommer, DW TI A pharmacokinetic-pharmacodynamic model of acute tolerance to the subjective effects of alcohol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 66A EP 66A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900356 ER PT J AU Willenbring, ML Dieperink, E Hait, S Durfee, JM McCarthy, KM Thuras, P Ho, SB AF Willenbring, ML Dieperink, E Hait, S Durfee, JM McCarthy, KM Thuras, P Ho, SB TI Response to a brief intervention fir heavy drinkers in a hepatitis C clinic SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 Univ Minnesota, Minneapolis VA Med Ctr, Minneapolis, MN 55417 USA. NIAAA, NIH, Bethesda, MD 20891 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 75A EP 75A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900414 ER PT J AU Arroyo, JA Chen, CM Yi, H AF Arroyo, JA Chen, CM Yi, H TI Raclal/ethnic and gender differences among Whites, Blacks, and Hispanics in the initiation of drinking and association with alcohol dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, NIH, Bethesda, MD 20892 USA. NIAAA, AEDS, CSR, NIH, Arlington, VA 22201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 80A EP 80A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900444 ER PT J AU La Luz, WA AF La Luz, WA TI Successful pregnancy outcomes: Evidence of the epidemiological paradox in Latinas SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 Univ New Mexico, Dept Sociol, NIAAA, Albuquerque, NM 87131 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 83A EP 83A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900458 ER PT J AU Newes-Adeyi, G Yi, H Scott, MS AF Newes-Adeyi, G Yi, H Scott, MS TI Family structure, family alcohol history, and underage drinking among young adults ages 18-20 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, CSR, NIH, Arlington, VA 22201 USA. NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 83A EP 83A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900460 ER PT J AU Daws, LC Mottafiez, S Munn, JL Owens, WA Calderon, AC Boyca-Rusztay, J Holmes, A Toney, GM AF Daws, LC Mottafiez, S Munn, JL Owens, WA Calderon, AC Boyca-Rusztay, J Holmes, A Toney, GM TI Neuronal and behavioral responses to ethanol vary with serotonin transporter genotype: Studies using KO mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol & Physiol, San Antonio, TX 78229 USA. NIAAA, Sect Behav Sci & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 92A EP 92A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900511 ER PT J AU Bennett, AJ Szeliga, KT Pierre, PJ Suomi, SJ Friedman, DP Grant, KA AF Bennett, AJ Szeliga, KT Pierre, PJ Suomi, SJ Friedman, DP Grant, KA TI Preliminary data on long-term ethanol consumption patterns in early stressed monkeys (Macaca mulatta). SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 Wake Forest Univ, Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Dept Pediat, Winston Salem, NC 27157 USA. NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 97A EP 97A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900544 ER PT J AU Chen, SA Schwandt, ML Lindell, SG Barr, CS Newman, TK Suomi, SJ Higley, JD AF Chen, SA Schwandt, ML Lindell, SG Barr, CS Newman, TK Suomi, SJ Higley, JD TI Prior intravenous ethanol leads to increased intake of oral ethanol in rhesus macaques SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, NIH, Sect Primate Models Psychopathol, LCTS, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 97A EP 97A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375900545 ER PT J AU Faden, VB Powell, P AF Faden, VB Powell, P TI Trends in initiation of alcohol use in the United States, 1975-2003. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 Natl Inst Alochol Abuse & Alcoholism, NIH, Bethesda, MD 20802 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 118A EP 118A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901084 ER PT J AU Kim, BJ Aragon, RA Moon, KH Song, BJ AF Kim, BJ Aragon, RA Moon, KH Song, BJ TI Identification of oxidized cytosolic proteins in alcohol-exposed human hepatoma cells and mouse liver. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, LMBB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 124A EP 124A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901118 ER PT J AU Belfer, L Hipp, H McKnight, C Scully, K Buzas, B Bollettino, A Schwartz, LS Max, MB Goldman, D Enoch, MA AF Belfer, L Hipp, H McKnight, C Scully, K Buzas, B Bollettino, A Schwartz, LS Max, MB Goldman, D Enoch, MA TI Linkage of galanin haplotypes to alcoholism in two independent populations; Possible mediation by anxiety SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 132A EP 132A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901165 ER PT J AU Enoch, MA Schwartz, LS White, KV Albaugh, B Goldman, D AF Enoch, MA Schwartz, LS White, KV Albaugh, B Goldman, D TI Linkage of GABRB1 to alcoholism and low voltage ALPHA EEG in two independent populations SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 132A EP 132A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901166 ER PT J AU Hu, XZ Zhou, ZF Lipsky, RH Goldman, D AF Hu, XZ Zhou, ZF Lipsky, RH Goldman, D TI Association of serotonin transporter gene with multiple phenotypes in Caucasians SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 132A EP 132A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901168 ER PT J AU Zhou, Z Lipsky, R Thomas, C Kuchipudi, K Goldman, D AF Zhou, Z Lipsky, R Thomas, C Kuchipudi, K Goldman, D TI Linkage and resquencing analysis of TPH2 in major depression and suicide SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 132A EP 132A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901164 ER PT J AU Anderson, T Neyer, K Lamparella, N Zhou, Z Jenkins, G Lipsky, RH AF Anderson, T Neyer, K Lamparella, N Zhou, Z Jenkins, G Lipsky, RH TI Nucleotide sequence variation in the human tyrosine kinase B neurotrophin receptor gene (NTRK2) SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NIAAA, Sect Human Genet, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 133A EP 133A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901171 ER PT J AU Oroszi, G Enoch, MA Chun, J Virkkunen, M Goldman, D AF Oroszi, G Enoch, MA Chun, J Virkkunen, M Goldman, D TI Thr105Ile, a functional polymorphism of histamine N-methyltransferase (HNMT), is associated with alcoholism in two independent populations SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 134A EP 134A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901176 ER PT J AU Xu, K Terry, J Roy, A Lichtermann, D Maier, W Virkkunen, M Goldman, D AF Xu, K Terry, J Roy, A Lichtermann, D Maier, W Virkkunen, M Goldman, D TI Sequence variant discovery and haplotype linkage of Mu opioid receptor gene with substance dependence in four populations SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 135A EP 135A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901185 ER PT J AU Caycedo, D Zhu, G Mash, DC Lipsky, RH AF Caycedo, D Zhu, G Mash, DC Lipsky, RH TI Increased levels of full-length and T-SHC isoform neurotrophin tyrosine kinase receptor type 2 (NTRK2) mRNAs in postmortem cerebellum of cocaine addicts SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Sect Human Genet, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NIAAA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Univ Miami, Dept Neurol, Miami, FL 33136 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 136A EP 136A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901191 ER PT J AU Ramchandani, VA Flury, L Plawecki, M Foroud, T O'Connor, S AF Ramchandani, VA Flury, L Plawecki, M Foroud, T O'Connor, S TI Heritability of alcohol elimination kinetics in sibling pairs. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. Indiana Univ, Sch Med, Indianapolis, IN USA. VAMC, RLR, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 137A EP 137A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901194 ER PT J AU Davis, MI Stancik, EK Ohrtman, JD Lovinger, DM AF Davis, MI Stancik, EK Ohrtman, JD Lovinger, DM TI Inhibition of BDNF-stimulated ERK activation by ethanol in cerebellar granule cells SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. RI Davis, Margaret/F-4165-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 138A EP 138A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901199 ER PT J AU Honse, Y Lovinger, DM AF Honse, Y Lovinger, DM TI Ethanol inhibition of synaptic and non-synaptic NMDA receptors in autaptic hippocampal neurons. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, LIN, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 141A EP 141A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901219 ER PT J AU Hu, XQ Machu, T Lovinger, D AF Hu, XQ Machu, T Lovinger, D TI Modulation of 5-HT3A receptors by alcohols: Role of leucine 293. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 Univ N Texas, Texas Coll Osteopath Med, Ft Worth, TX 76107 USA. Natl Inst Alochol Abuse & Alcoholism, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 143A EP 143A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901232 ER PT J AU Miko, A Hosoi, M Zhang, L AF Miko, A Hosoi, M Zhang, L TI Differential sensitivity of recombinant human and mouse 5-HT3A receptors to ethanol. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 143A EP 143A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901230 ER PT J AU Sun, H Niu, SL Lovinger, DM Zhang, L AF Sun, H Niu, SL Lovinger, DM Zhang, L TI The effect of chronic alcohol consumption on the expression and posttranslational modification of 5-HT3A receptors in transgenic mice overexpressing the receptor. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. NIAAA, Lipid Biochem & Biophys, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 143A EP 143A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901229 ER PT J AU Schwandt, ML Suomi, SJ Higley, JD AF Schwandt, ML Suomi, SJ Higley, JD TI Age-dependent variation in behavior following acute ethanol administration in adolescent rhesus macaques SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Clin & Translat Studies, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 144A EP 144A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901239 ER PT J AU Ducci, F Shen, PH Vikkunen, M Albaugh, B Enoch, MA Goldman, D AF Ducci, F Shen, PH Vikkunen, M Albaugh, B Enoch, MA Goldman, D TI Temperament traits in antisocial and non-antisocial alcoholics SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 149A EP 149A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901267 ER PT J AU Ruan, WJ Grant, BF Dawson, DA AF Ruan, WJ Grant, BF Dawson, DA TI Stressful life events, alcohol consumption and alcohol use disorders. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 150A EP 150A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901271 ER PT J AU Sinha, R Garcia, M Kemp, K Krystal, JH O'Malley, SS AF Sinha, R Garcia, M Kemp, K Krystal, JH O'Malley, SS TI Alcohol craving and subjective emotional state during stress and alcohol cue exposure in alcoholics and socal drinkers SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 Yale Univ, Sch Med, Dept Psychiat, NIAAA,Ctr Translat Neurosci Alcoholism, New Haven, CT 06519 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 150A EP 150A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901274 ER PT J AU Krupitsky, EM Neznanova, ON Masalov, DV Burakov, AM Didenko, TY Romanova, TN Tsoy, MV Bespalov, AY Slavina, TY Grinenko, AY Zvartau, EE Krystal, JH AF Krupitsky, EM Neznanova, ON Masalov, DV Burakov, AM Didenko, TY Romanova, TN Tsoy, MV Bespalov, AY Slavina, TY Grinenko, AY Zvartau, EE Krystal, JH TI The NMDA receptor antagonist, memantine, reduces alcohol cue-induced craving even though it has mild ethanol-like effects in alcohol dependent patients SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 St Petersburg State Pavlov Med Univ, St Petersburg, Russia. Yale Univ, Sch Med, NIAAA, Ctr Translat Neurosci Alcoholism,Dept Psychiat, New Haven, CT 06520 USA. RI Bespalov, Anton/R-6506-2016 NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 161A EP 161A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901338 ER PT J AU Moss, HB Hardie, TL AF Moss, HB Hardie, TL TI Risk and protective factors associated with adolescent binge drinking frequency SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 166A EP 166A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901371 ER PT J AU Zapata, A Chefer, V Gonzales, R Shippenberg, TS AF Zapata, A Chefer, V Gonzales, R Shippenberg, TS TI Kappa opioid receptor modulation of the neurochemical effects of ethanol in the nucleus accumbens and central amygdala SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIDA, Integrat Neurosci Sect, IRP, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 181A EP 181A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901457 ER PT J AU Zhu, PJ Lovinger, DM AF Zhu, PJ Lovinger, DM TI Ethanol directly increases GABA release from GABAergic presynaptic terminals in basolateral amygdala SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Integrat Neurosci, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 187A EP 187A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901492 ER PT J AU Heilig, M AF Heilig, M TI Targeting the NPY system in alcohol dependence. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 188A EP 188A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901496 ER PT J AU Chou, SP Grant, BF AF Chou, SP Grant, BF TI The 12-month prevalence and changes of drinking and driving United States, 1991-1992 and 2001-2002. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 190A EP 190A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901507 ER PT J AU Dawson, DA Grant, BF Stinson, FS AF Dawson, DA Grant, BF Stinson, FS TI Survival model estimates of rates and predictors of remission from alcohol dependence. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 190A EP 190A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901508 ER PT J AU Saha, TD Grant, BF Dawson, DA AF Saha, TD Grant, BF Dawson, DA TI Assessing alcohol problems continuum using item response theory models. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 190A EP 190A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901509 ER PT J AU Machu, TK Lovinger, DM Hayrapetyan, V Hu, XQ AF Machu, TK Lovinger, DM Hayrapetyan, V Hu, XQ TI Investigation of putative alcohol binding domains in the 5-HT3A receptor SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA. NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 199A EP 199A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901561 ER PT J AU Zhang, L Sun, H Hu, XQ AF Zhang, L Sun, H Hu, XQ TI Investigation into the regulation of 5-HT3 receptor function and the receptors sensitivity to alcohol by intracallular signaling pathways SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 25-30, 2005 CL Santa Barbara, CA SP Res Soc Alcoholism C1 NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 SU S BP 199A EP 199A PG 1 WC Substance Abuse SC Substance Abuse GA 929VY UT WOS:000229375901562 ER PT J AU Mottagui-Tabar, S Prince, JA Wahlestedt, C Zhu, GS Goldman, D Heilig, M AF Mottagui-Tabar, S Prince, JA Wahlestedt, C Zhu, GS Goldman, D Heilig, M TI A novel single nucleotide polymorphism of the neuropeptide Y (NPY) gene associated with alcohol dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE neuropeptide Y polymorphisms; alcohol dependence; promoter; genetic association studies ID NATIONAL-COMORBIDITY-SURVEY; SIGNAL PEPTIDE; UNITED-STATES; HAPLOTYPE RECONSTRUCTION; PSYCHIATRIC-DISORDERS; 12-MONTH PREVALENCE; MALE TWINS; RAT LINES; ABUSE; CONSUMPTION AB Background: Neuropepticle Y (NPY) is a major endogenous regulator of anxiety-related behaviors and emotionality. Transgenic work with NPY and null-mutant mice have implicated NPY in the control of alcohol consumption, suggesting that genetic variation of the prepro-NPY gene may also contribute to the heritability of alcoholism. The aim of this study was to examine whether polymorphic variants of the NPY gene are associated with the diagnosis of alcohol dependence. Methods: We compared allele frequencies of 5 NPY polymorphisms (-883-ins/del, -602, -399, -84, and + 1128) in a Nordic population of alcohol-dependent individuals (n = 428 mates; n = 149 females) and ethnically matched controls (n = 84 males; n = 93 females) for whom alcohol dependence or any diagnosis of substance disorder was excluded. Patients were further subtyped into type I (late-onset) and type 11 (early-onset) alcoholics. Results: The -602 marker showed a significant association with alcohol dependence (p = 0,0035; OR, 2.3; 95% Cl, 1.3-4.0); a trend level association was further observed for the -399 marker (p = 0.058; OR, 1.3; 95% CI, 0.99-1.7) and the + 1128 marker (p = 0.053; OR, 1.8; 95% CI, 0.99-3.1). The association for the -602 marker remained and was strengthened when analyzed in type I subjects only, although this association was not seen in type 11 patients, and there also was a significant association in the female subjects but not in males. The -602 single nucleotide polymorphism was in strong linkage dysequilibrium (r(2) = 0.7;p < 0.0001) with the + 1128 single nucleoticle polymorphism, which has previously been reported to be associated with a diagnosis of alcoholism. Haplotype-based association confirmed these results. Conclusions: We report a novel polymorphism at position -602 in the 5' region of the NPY gene that is significantly associated with alcohol dependence. We also describe the haplotype frequencies and linkage dysequilibrium pattern of four variations in that region. C1 NIAAA, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Ctr Genom & Bioinformat, Stockholm, Sweden. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Scripps Res Inst, Jupiter, FL USA. RP Heilig, M (reprint author), NIAAA, NIH, 10 Ctr Dr,10-1E-5334, Bethesda, MD 20892 USA. EM markus.heilig@mail.nih.gov RI Wahlestedt, Claes/A-7039-2009; Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Heilig, Markus/0000-0003-2706-2482 NR 41 TC 45 Z9 46 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 BP 702 EP 707 DI 10.1097/01.ALC.0000164365.04961.B1 PG 6 WC Substance Abuse SC Substance Abuse GA 927TU UT WOS:000229224200002 PM 15897713 ER PT J AU Harford, TC Grant, BF Yi, HY Chen, CM AF Harford, TC Grant, BF Yi, HY Chen, CM TI Patterns of DSM-IV alcohol abuse and dependence criteria among adolescents and adults: Results from the 2001 National Household Survey on Drug Abuse SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE adolescents; adults; alcohol abuse and dependence; DSM-IV ID USE DISORDERS; DIAGNOSTIC ORPHANS; UNITED-STATES; NO DIAGNOSIS; 12-MONTH PREVALENCE; LONGITUDINAL DATA; FAMILY-HISTORY; RISK-FACTORS; SYMPTOMS; SAMPLE AB Background: Studies of the prevalence of DSM-IV alcohol use disorders (AUDs) in general population samples of adolescents and adults are rare. Comparisons of the prevalence of alcohol abuse and dependence in adolescent surveys with the prevalence in adult general population surveys are confounded by differences in survey design and measurement, thereby reducing their validity. The purpose of the present study was to examine the effects of age, sex, race/ethnicity, and drinking status on the prevalence of DSM-IV alcohol abuse and dependence (including diagnostic orphans) and associated diagnostic criteria among adolescents and adults aged 12-65 years in a single representative sample of the US population. Methods: This study was based on data from the 2001 National Household Survey on Drug Abuse public use file. Of the 55,561 subjects in the survey, 33,576 (60.5%) reported alcohol use in the past year and provided information on DSM-IV AUD criteria. DSM-IV AUD criteria were assessed by questions related to specific symptoms occurring during the past 12 months. Results: Overall, the most prevalent criteria of DSM-IV alcohol dependence were '' tolerance '' and '' time spent obtaining alcohol, drinking, or getting over its effects.'' The most prevalent criterion of DSM-IV alcohol abuse was '' hazardous use.'' The prevalence of alcohol abuse only and of dependence with and without abuse was highest among respondents aged 18-23 years, followed by respondents aged 12-17 years, and lowest among respondents aged 50 years and older. Among subgroups of current and heavier drinkers, differences between adolescents and young adults were less pronounced, especially among females. For each age group, the prevalence of alcohol abuse only was greater than the prevalence of dependence (with or without abuse). The abuse-to-dependence ratios also were generally consistent across age groups and slightly higher among males (2.1:1.0) than females (1.6:1.0). Conclusions: The higher prevalence for some dependence criteria among adolescents and young adults as measured in the present study may blur the distinction between symptom reports associated with the normative development of drinking patterns and clinically relevant aspects of DSM-IV alcohol dependence. C1 NIAAA, Alcohol Epidemiol Data Syst, NIH, CSR Inc, Arlington, VA 22201 USA. RP Yi, HY (reprint author), NIAAA, Alcohol Epidemiol Data Syst, NIH, CSR Inc, 2107 Wilson Blvd,Suite 1000, Arlington, VA 22201 USA. EM hyi@csrincorporated.com FU NIAAA NIH HHS [N0AA32007, N01AA82014] NR 44 TC 112 Z9 112 U1 4 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 BP 810 EP 828 DI 10.1097/01.ALC.0000164381.67723.76 PG 19 WC Substance Abuse SC Substance Abuse GA 927TU UT WOS:000229224200016 PM 15897727 ER PT J AU Dawson, DA Grant, BF Stinson, FS Zhou, Y AF Dawson, DA Grant, BF Stinson, FS Zhou, Y TI Effectiveness of the derived Alcohol Use Disorders Identification Test (AUDIT-C) in screening for alcohol use disorders and risk drinking in the US general population SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE AUDIT-C screening; alcohol use disorders; risk drinking ID CAGE; CONSUMPTION; DEPENDENCE; QUESTIONS; PERFORMANCE; ETHNICITY; VALIDITY; GENDER; ABUSE; IV AB Background: The three consumption questions from the Alcohol Use Disorders Identification Test (AUDIT-C) are increasingly used as a screener for alcohol use disorders (AUDs) and risk drinking, Methods: In a representative sample of US adults 18 years of age and older, AUDIT-C scores (derived from consumption questions embedded in a large national survey) were used to estimate sensitivity, specificity, and areas under receiver operator characteristic curves (AUROCs) for alcohol dependence, any AUD, and risk drinking. AUDs were defined according to DSM-IV criteria. For men, risk drinking was defined as consuming > 14 drinks per week or > 4 drinks in a single day at least once a month; for women, the weekly and daily limits were > 7 drinks and > 3 drinks, respectively. The derived AUDIT-C was evaluated among past-year drinkers (n = 26,946), within the total population (n = 43,093), in groups defined by age, sex. and race/ethnicity, and among pregnant women, persons attending an emergency room, and college students. Results: For past-year drinkers, the AUROCs for the derived AUDIT-C were 0.887 for alcohol dependence, 0.860 for any AUD, and 0.966 for risk drinking. Scores were higher in the total population, 0.931, 0.917, and 0.981, respectively. The derived AUDIT-C performed slightly better in screening for dependence among women than men. Screening for risk drinking was better among men, probably because the third AUDIT-C question directly mirrors one of the definitions of risk drinking for men but not for women. Performance in pregnant women, past-year emergency room patients, and college students was on a par with performance in the general population. Conclusions: The derived AUDIT-C performs well in screening for AUDs and risk drinking. The use of variable cut points for men and women improves its sensitivity and specificity. Validation in a realistic screening situation, in which the AUDIT-C questions are asked as stand-alone and not embedded items, is a critical future step. C1 NIAAA, LEB, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, LEB, Div Intramural Clin & Biol Res, NIH, Room 3093,5635 Fishers Lane,MSC 9304, Bethesda, MD 20892 USA. EM ddawson@mail.nih.gov NR 32 TC 266 Z9 268 U1 6 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 BP 844 EP 854 DI 10.1097/01.ALC.0000164374.32229.A2 PG 11 WC Substance Abuse SC Substance Abuse GA 927TU UT WOS:000229224200019 PM 15897730 ER PT J AU Dawson, DA Grant, BF Li, TK AF Dawson, DA Grant, BF Li, TK TI Quantifying the risks associated with exceeding recommended drinking limits SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol use disorders; drinking guidelines; maximum drinks ID IV ALCOHOL-ABUSE; UNITED-STATES; BINGE DRINKING; DEPENDENCE; POPULATION; CONSUMPTION; PREVALENCE; GUIDELINES; SAMPLE AB Background: Although daily and weekly drinking limits demonstrate strong sensitivity and specificity in identifying alcohol use disorders (AUDs), there are no descriptive data that present the risks associated with exceeding these limits in a format suitable for presentation to patients, students. and the general public. Methods: Data collected in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions were used to estimate the risks of past-year DSM-IV alcohol abuse and dependence associated with various frequencies of exceeding daily drinking limits (no more than 4 drinks for men no more than 3 drinks for women) in a nationally representative sample of 26,946 US drinkers 18 years of age and older, These risks were further categorized by whether weekly drinking limits (no more than 14 drinks for men; no more than 7 drinks for women) were exceeded and by maximum number of drinks consumed in the past year. Results: The prevalence of alcohol dependence with abuse increased in a fairly linear fashion with frequency of exceeding daily drinking limits. The prevalence of dependence alone (no abuse) and abuse alone (no dependence) peaked among persons who exceeded the daily limits twice a week and then leveled off, because individuals became increasingly likely to have both disorders at higher frequencies. Exceeding the weekly limits generally increased the risks of both disorders after accounting for frequency of exceeding the daily limits, but not always to a significant extent. Likewise, maximum quantity of drinks consumed was positively associated with the risks of AUDs even after accounting for frequency of risk drinking. There were few gender differences in the risk of dependence after adjusting for frequency of exceeding daily drinking limits, but the risk of alcohol abuse remained greater among men. Conclusions: These data provide a useful tool for illustrating the broad range of risk of AUDs associated with exceeding recommended drinking limits, and they support the utility of the daily and weekly drinking limits in predicting AUDs. C1 NIAAA, LEB, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, LEB, Div Intramural Clin & Biol Res, NIH, Room 3093,5635 Fishers Lane,MSC 9304, Bethesda, MD 20892 USA. EM ddawson@mail.nih.gov NR 26 TC 128 Z9 130 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2005 VL 29 IS 5 BP 902 EP 908 DI 10.1097/01.ALC.0000164544.45746.A7 PG 7 WC Substance Abuse SC Substance Abuse GA 927TU UT WOS:000229224200026 PM 15897737 ER PT J AU Chegini, S Metcalfe, DD AF Chegini, S Metcalfe, DD TI Contemporary issues in food allergy: Seafood toxin-induced disease in the differential diagnosis of allergic reactions SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article; Proceedings Paper CT Eastern Allergy Conference CY MAY 06-07, 2004 CL Key Biscayne, FL ID UNITED-STATES; FISH; TETRODOTOXIN; OUTBREAK; INFECTIONS; MANAGEMENT; MADAGASCAR AB Seafood, including fish, shrimp, lobster, crab, crayfish, mussel, and clam are among the most frequent causes of food allergy. Seafood poisoning, including reactions to natural toxins, frequently masquerades as all allergic reaction oil presentation. Ingestion of contaminated shellfish results in a wide variety of symptoms, depending oil the toxins present, their concentrations ill the shellfish, and the amount of contaminated shellfish consumed. Five types of shellfish poisoning have been identified clearly including paralytic, neurotoxic, diarrhetic, amnestic, and azaspiracid shellfish poisonings. Based oil the presence or absence of the toxin at the time of capture, fish poisoning call be considered conceptually in two categories. In ciguatera and puffer fish poisoning soiling, the toxin is present in live fish, whereas in scombroid, it is produced only after capture, in the fish flesh, by contaminating bacteria because of improper refrigeration. Most shellfish-associated illness is infectious in nature (bacterial or viral), with the Norwalk virus accounting for most cases of gastroenteritis. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Allina Med Clin, Dept Med, Cokato, MN USA. Allina Med Clin, Dept Pediat, Cokato, MN USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205,10 Ctr Dr, Bethesda, MD 20892 USA. NR 29 TC 10 Z9 10 U1 0 U2 7 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAY-JUN PY 2005 VL 26 IS 3 BP 183 EP 190 PG 8 WC Allergy SC Allergy GA 942EK UT WOS:000230265500004 PM 16119031 ER PT J AU Miller, FG Brody, H AF Miller, FG Brody, H TI Enhancement technologies and professional integrity SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID INTERNAL MORALITY; MEDICINE C1 NIH, Bethesda, MD 20892 USA. Michigan State Univ, E Lansing, MI 48824 USA. RP Miller, FG (reprint author), NIH, Bethesda, MD 20892 USA. NR 8 TC 10 Z9 11 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD MAY-JUN PY 2005 VL 5 IS 3 BP 15 EP 17 DI 10.1080/15265160561002719 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 952QA UT WOS:000231019400004 PM 16006375 ER PT J AU Martin, AM Peerzada, J AF Martin, AM Peerzada, J TI The expressive meaning of enhancement SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Martin, AM (reprint author), NIH, Bethesda, MD 20892 USA. NR 8 TC 5 Z9 5 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD MAY-JUN PY 2005 VL 5 IS 3 BP 25 EP 27 DI 10.1080/15265160591002700 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 952QA UT WOS:000231019400009 PM 16006366 ER PT J AU Litton, P AF Litton, P TI ADHD, values, and the self SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Litton, P (reprint author), NIH, Bethesda, MD 20892 USA. NR 9 TC 4 Z9 4 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD MAY-JUN PY 2005 VL 5 IS 3 BP 65 EP 67 DI 10.1080/15265160591002854 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 952QA UT WOS:000231019400024 PM 16006360 ER PT J AU Schoeller, DA Tylavsky, FA Baer, DJ Chumlea, WC Earthman, CP Fuerst, T Harris, TB Heymsfield, SB Horlick, M Lohman, TG Lukaski, HC Shepherd, J Siervogel, RM Borrud, LG AF Schoeller, DA Tylavsky, FA Baer, DJ Chumlea, WC Earthman, CP Fuerst, T Harris, TB Heymsfield, SB Horlick, M Lohman, TG Lukaski, HC Shepherd, J Siervogel, RM Borrud, LG TI QDR 4500A dual-energy X-ray absorptiometer underestimates fat mass in comparison with criterion methods in adults SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE body composition; hydration; total body water ID BODY-COMPOSITION MEASUREMENTS; 4-COMPARTMENT MODEL; SINGAPOREAN CHINESE; ETHNIC-GROUPS; PENCIL-BEAM; HYDRATION; WOMEN; BONE; AGE; CHILDREN AB Background: Dual-energy X-ray absorptiometry (DXA) has become one of the most frequently used methods for estimating human body composition. Although the DXA technique has been validated for the measurement of fat-free mass and fat mass, differences in calibration between instruments produced by different manufacturers, as well as between different models produced by the same manufacturer, have been reported. Objective: The objective was to compare the calibration of the QDR 4500A against criterion methods in a large heterogeneous population. Design: DXA-derived body-composition data were obtained from 7 studies: 6 data sets were provided by the investigators, one of which was published. The data included fat mass and fat-free mass measured with a QDR 4500A and criteria measurements of body composition from total body water by dilution at 4 centers, densitometry from 1 center, and four-compartment analysis at 2 centers. Results: In the cohort of 1195 subjects, 602 men and 593 women aged 19-82 y with a body mass index (in kg/m(2)) of 16-44, the fan-beam DXA overestimated fat-free mass (P < 0.05). A significant difference was observed in all 7 data sets, and the mean ( SE) was 5 &PLUSMN; 1%. Conclusions: It is recommended that the lean soft tissue mass estimate with the fan-beam QDR 4500A be reduced by 5% and that for fat mass be increased by that same mass. This finding is particularly important because the National Health and Nutrition Examination Survey is using the QDR 4500A to assess body composition in a nationally representative sample of. persons in the United States. C1 Univ Wisconsin, Madison, WI 53706 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Wright State Univ, Sch Med, Lifespan Hlth Res Ctr, Dept Community Hlth, Kettering, OH USA. Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIA, NIH, Bethesda, MD 20892 USA. St Lukes Roosevelt Hosp, Obes Res Ctr, New York, NY 10025 USA. Univ Arizona, Tucson, AZ USA. USDA, Grand Forks Human Nutr Res Ctr, Grand Forks, ND USA. RP Schoeller, DA (reprint author), Univ Wisconsin, 1415 Linden Dr, Madison, WI 53706 USA. EM dschoell@nutrisci.wisc.edu FU NIA NIH HHS [N01-AG-2106, N01-AG-6-2102, N01-AG-6-2103] NR 49 TC 120 Z9 120 U1 0 U2 5 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 MAY PY 2005 VL 81 IS 5 BP 1018 EP 1025 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 925IH UT WOS:000229046300012 PM 15883424 ER PT J AU Tseng, M Breslow, RA Graubard, BI Ziegler, RG AF Tseng, M Breslow, RA Graubard, BI Ziegler, RG TI Dairy, calcium, and vitamin D intakes and prostate cancer risk in the national health and nutrition examination epidemiologic follow-up study cohort SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE dairy; diet; calcium; vitamin D; prostatic neoplasms ID GROWTH-FACTOR-I; ULTRAVIOLET-RADIATION; DIETARY PATTERNS; FORTIFIED MILK; UNITED-STATES; PRODUCTS; PHOSPHORUS; HYPOTHESIS; MORTALITY; ENERGY AB Background: Dairy intake may increase prostate cancer risk, but whether this is due to calcium's suppression of circulating vitamin D remains unclear. Findings on calcium and vitamin D intake and prostate cancer are inconsistent. Objective: We examined the association of dairy, calcium, and vitamin D intake with prostate cancer. Design: In a prospective study of 3612 men followed from 19821984 to 1992 for the first National Health and Nutrition Examination Epidemiologic Follow-up Study, 131 prostate cancer cases were identified. Dietary intake was estimated from questionnaires completed in 1982-1984. Relative risk (RR) and 95% CIs were estimated by using Cox proportional hazards models adjusted for age, race, and other covariates. Results: Compared with men in the lowest tertile for dairy food intake, men in the highest tertile had a relative risk (RR) of 2.2 (95% CI: 1.2, 3.9; trend P = 0.05). Low-fat milk was associated with increased risk (RR = 1.5; 95% CL 1.1, 2.2; third compared with first tertile; trend P = 0.02), but whole milk was not (RR = 0.8; 95% CI: 0.5, 1.3; third compared with first tertile; trend P = 0.35). Dietary calcium was also strongly associated with increased risk (RR = 2.2; 95% CI: 1.4, 3.5; third compared with first tertile; trend P = 0.001). After adjustment for calcium intake, neither vitamin D nor phosphorus was clearly associated with risk. Conclusions: Dairy consumption may increase prostate cancer risk through a calcium-related pathway. Calcium and low-fat milk have been promoted to reduce risk of osteoporosis and colon cancer. Therefore, the mechanisms by which dairy and calcium might increase prostate cancer risk should be clarified and confirmed. C1 Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. NIAAA, NIH, Bethesda, MD USA. NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Tseng, M (reprint author), Fox Chase Canc Ctr, Div Populat Sci, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM m_tseng@fccc.edu RI Tseng, Marilyn/B-9334-2016 OI Tseng, Marilyn/0000-0002-9969-9055 FU NCI NIH HHS [CA-06927] NR 55 TC 94 Z9 95 U1 3 U2 17 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 MAY PY 2005 VL 81 IS 5 BP 1147 EP 1154 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 925IH UT WOS:000229046300029 PM 15883441 ER PT J AU Mahnel, R Kalt, A Ring, S Stallmach, A Strober, W Marth, T AF Mahnel, R Kalt, A Ring, S Stallmach, A Strober, W Marth, T TI Immunosuppressive therapy in Whipple's disease patients is associated with the appearance of gastrointestinal manifestations SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID TROPHERYMA-WHIPPELII; AIDS; INFECTION; BACILLUS; DEFECTS; SYSTEM AB OBJECTIVES: Whipple's disease is a rare chronic disorder, which is caused by systemic infection with Tropheryma whipplei. The first symptom of Whipple's disease usually is a nondestructive polyarthritis resembling in many aspects seronegative rheumatoid arthritis. This polyarticular inflammatory arthropathy preceding the diagnosis of Whipple's disease for several years frequently is treated with nonsteroidal antiinflammatory drugs (NSAIDs) and with immunosuppressive therapy. There is evidence that altered immune functions play a role in the manifestation of the disease and that Whipple's disease is associated with opportunistic infections. We therefore asked whether immunosuppressive treatment for arthropathy may alter the course of Whipple's disease. PATIENTS AND METHODS: In a series of 27 patients with Whipple's disease clinical data were documented and the patients were followed for 3-4 yr. The patients were classified into three groups according to their medication: (i) patients with immunosuppressive therapy preceding the diagnosis, (ii) patients with NSAIDs before diagnosis, and (iii) patients without such therapies. RESULTS: Arthropathies occurred in the mean 8 yr before diagnosis and were the first symptom in 63% of the patients. Gastrointestinal involvement usually became evident later on and frequently led to the diagnosis of Whipple's disease. In patients with immunosuppressive treatment, diarrhea occurred in the median 4 months after the initiation of such therapy and diagnosis of Whipple's disease was made after another 2 months. In contrast, other medical treatments were not closely followed by the onset of diarrhea. CONCLUSIONS: These results indicate an association between immunosuppressive therapy and the onset of diarrhea in Whipple's disease and thus support the concept that immunologic factors play a role in disease pathogenesis. Further investigation on the interaction of the immune system and Tropheryma whipplei infection are required to understand the factors contributing to the clinical manifestation of this rare disorder and possibly to introduce preventive interventions. C1 St Josef Hosp, Div Internal Med, D-56856 Zell, Germany. Stiftung Deutsch Klin Diagnost, Div Gastroenterol, Wiesbaden, Germany. NIAID, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. Univ Clin Saarland, Homburg, Germany. RP Marth, T (reprint author), St Josef Hosp, Div Internal Med, Barlstr 7, D-56856 Zell, Germany. NR 36 TC 67 Z9 69 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2005 VL 100 IS 5 BP 1167 EP 1173 DI 10.1111/j.1572-0241.2005.40128.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 917SQ UT WOS:000228489900028 PM 15842595 ER PT J AU Leenen, F Nwachuku, C Cushman, W Black, H Simpson, L Davis, B AF Leenen, F Nwachuku, C Cushman, W Black, H Simpson, L Davis, B TI Outcomes in high risk hypertensives randomized to CCB vs ACE inhibitor in ALLHAT SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 20th Annual Meeting of the American-Society-of-Hypertension CY MAY 14-18, 2005 CL San Francisco, CA SP Amer Soc Hypertension DE ACE inhibitors; calcium channel blockers; cardiovascular; outcomes C1 Univ Ottawa, Inst Heart, ALLHAT Collaborat Res Grp, Hypertens Unit, Ottawa, ON, Canada. NHLBI, DECA, CAPP OD, Bethesda, MD 20892 USA. VAMC, Memphis, TN USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Texas, Sch Publ Hlth, Houston, TX 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2005 VL 18 IS 5 SU S BP 7A EP 7A DI 10.1016/j.amjhyper.2005.03.016 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 927VW UT WOS:000229229600017 ER PT J AU Piller, L Ford, C Davis, B Nwachuku, C Black, H Oparil, S Gappy, S Retta, T Probstfield, J AF Piller, L Ford, C Davis, B Nwachuku, C Black, H Oparil, S Gappy, S Retta, T Probstfield, J TI Angioedema in the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 20th Annual Meeting of the American-Society-of-Hypertension CY MAY 14-18, 2005 CL San Francisco, CA SP Amer Soc Hypertension DE ALLHAT; angioedema; angiotensin converting enzyme inhibitor C1 Univ Texas, Sch Publ Hlth, Coordinating Ctr Clin Trials, Houston, TX USA. NHLBI, Deca, CAPP, OD, Bethesda, MD 20892 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Alabama, CVD Dis, Birmingham, AL USA. VAMC, HTN Endocrine Res Clin, Detroit, MI USA. Howard Univ, HTN Lipid Clin, Washington, DC 20059 USA. Univ Washington, Clin Trials Serv, Seattle, WA 98195 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2005 VL 18 IS 5 SU S BP 92A EP 92A DI 10.1016/j.amjhyper.2005.03.257 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 927VW UT WOS:000229229600257 ER PT J AU Velasquez, MT Bhathena, SJ Ali, AA Hansen, CT AF Velasquez, MT Bhathena, SJ Ali, AA Hansen, CT TI Long-term effects of a reduced fixed-dose combination of benazepril and amlodipine on blood pressure, metabolic control, renal function, and the heart in an animal model of type 2 diabetes mellitus and hypertension SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 20th Annual Meeting of the American-Society-of-Hypertension CY MAY 14-18, 2005 CL San Francisco, CA SP Amer Soc Hypertension C1 George Washington Univ, Washington, DC USA. USDA, Beltsville Human Nutr Res Ctr, Phytonutrients Lab, Beltsville, MD 20705 USA. NIH, Anim Genet Resource, Bethesda, MD 20892 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2005 VL 18 IS 5 SU S BP 136A EP 136A DI 10.1016/j.amjhyper.2005.03.378 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 927VW UT WOS:000229229600378 ER PT J AU Wang, XV Armando, I Mangrum, A Knepper, MA Jose, PA AF Wang, XV Armando, I Mangrum, A Knepper, MA Jose, PA TI Protein abundance of renal Na transporters in femal mice lacking type1A angiotensin II receptor SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 20th Annual Meeting of the American-Society-of-Hypertension CY MAY 14-18, 2005 CL San Francisco, CA SP Amer Soc Hypertension DE AT1A knockout mice; kidney; Na transporters C1 Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Univ Virginia, Div Nephrol, Charlottesville, VA USA. NHLBI, NIH, LKEM, 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2005 VL 18 IS 5 SU S BP 137A EP 137A DI 10.1016/j.amjhyper.2005.03.381 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 927VW UT WOS:000229229600381 ER PT J AU Yang, ZW Asico, LD Yu, PY Wang, Z Jones, JE Felder, RA Sibley, DR Jose, PA AF Yang, ZW Asico, LD Yu, PY Wang, Z Jones, JE Felder, RA Sibley, DR Jose, PA TI Hypertension and PLD2 regulation by D-5 dopamine receptor SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 20th Annual Meeting of the American-Society-of-Hypertension CY MAY 14-18, 2005 CL San Francisco, CA SP Amer Soc Hypertension DE dopamine D5 receptor; hypertension; phospholipase C1 Georgetown Univ, Med Ctr, Dept Physiol & Biophys & Pediat, Washington, DC 20007 USA. Univ Virginia, Ctr Hlth Sci, Dept Pathol, Charlottesville, VA USA. NINDS, NIH, Bethesda, MD 20892 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2005 VL 18 IS 5 SU S BP 165A EP 165A DI 10.1016/j.amjhyper.2005.03.457 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 927VW UT WOS:000229229600457 ER PT J AU Sharabi, Y Avni, I Kamari, Y Oron-Herman, M Peleg, E Grossman, E AF Sharabi, Y Avni, I Kamari, Y Oron-Herman, M Peleg, E Grossman, E TI Effect of PPAR-F agonist - rosiglitazone-on adiponectin level in the metabolic syndrome SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 20th Annual Meeting of the American-Society-of-Hypertension CY MAY 14-18, 2005 CL San Francisco, CA SP Amer Soc Hypertension DE adiponectin; metabolic syndrome; thiazolidinediones (TZDs) C1 Chaim Sheba Med Ctr, Hypertens Unit, IL-52621 Tel Hashomer, Israel. Natl Inst Hlth, 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2005 VL 18 IS 5 SU S BP 204A EP 204A DI 10.1016/j.amjhyper.2005.03.560 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 927VW UT WOS:000229229600560 ER PT J AU Kathiresan, S Larson, MG Benjamin, EJ Corey, D Murabito, JM Fox, CS Wilson, PWF Rifai, N Meigs, JB Ricken, G Lifton, RP Levy, D Vasan, RS AF Kathiresan, S Larson, MG Benjamin, EJ Corey, D Murabito, JM Fox, CS Wilson, PWF Rifai, N Meigs, JB Ricken, G Lifton, RP Levy, D Vasan, RS TI Clinical and genetic correlates of serum aldosterone in the community: The Framingham Heart Study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE aldosterone; sodium; genetics; diuretics; risk factors ID TRAIT LINKAGE ANALYSIS; PLASMA-RENIN ACTIVITY; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; SYNTHASE GENE; SEXUAL-DIMORPHISM; ANGIOTENSIN-II; URINARY SODIUM; SYSTEM; AGE AB Background: We investigated the environmental and genetic sources of interindividual variability in serum aldosterone level in a large, community-based sample. Methods: We examined the relation of serum aldosterone to vascular risk factors, urine sodium, and candidate single nucleotide polymorphisms in 2891 Framingham Offspring Study participants (53.2% women, mean age 59 years) using multivariable linear regression. Multivariable logistic regression was used to identify predictors of high (top quartile) and low (lowest quartile) serum aldosterone values. We estimated heritability of serum aldosterone via variance-component methods and evaluated linkage via a 10-cM-density genome scan. Results: Clinical variables related to higher serum aldosterone level included female sex, diuretic treatment, and a higher total/high density lipoprotein cholesterol ratio. A high urinary sodium excretion, postmenopausal status (without hormone replacement therapy), increased pulse pressure, and prevalent cardiovascular disease were related to lower serum aldosterone values. Urinary sodium was the strongest correlate of serum aldosterone (R-2 = 10%). Serum aldosterone levels did not differ by genotype in the aldosterone synthase (CYP11B2c. 1-344C> T) and the mineralocorticoid receptor (NR3C2c.754A> G) genes. The estimated heritability of serum aldosterone was 0.10. No chromosomal region attained a log-of-the-odds score > 1 in multipoint linkage analysis. Conclusions: We observed a complex relation between serum aldosterone and vascular risk factors. The genetic contribution to serum aldosterone level was modest. © 2005 American Journal of Hypertension, Ltd. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Endocrine Diabet & Hypertens, Boston, MA USA. Med Univ S Carolina, Dept Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,LeDucq Ctr Cardiovasc Res, Boston, MA 02115 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Genet & Med, New Haven, CT 06510 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02215 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Larson, Martin/0000-0002-9631-1254; Murabito, Joanne/0000-0002-0192-7516; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1RO1HL67288, 2K24 HL04334, N01-HC-25195] NR 52 TC 40 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2005 VL 18 IS 5 BP 657 EP 665 DI 10.1016/j.amjhyper.2004.12.005 PN 1 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 925YW UT WOS:000229090600012 PM 15882548 ER PT J AU Nam, JM Rice, C Gail, MH AF Nam, JM Rice, C Gail, MH TI Comparison of asbestos exposure assessments by next-of-kin respondents, by an occupational hygienist, and by a job-exposure matrix from the national occupational hazard survey SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE occupational exposure assessment; next-of-kin interviews; occupational hygienist assessment; job-exposure matrix; asbestos exposure; mesothelioma risk ID SURROGATE RESPONDENTS; INFORMATION; HISTORIES; AGREEMENT; VALIDITY; SPOUSE AB Background Assessments of occupational exposures in case-control studies of rapidly fatal illnesses often rely on data from next-of-kin respondents, which may be inaccurate. Methods Three methods for assessing exposure to asbestos from case-control data on mesothelioma, including next-of-kin assessment, expert assessment, and use of a generic job-exposure matrix (JEM). Interview data [Spirtas et al. (1994): Occup Environ Med 51:804-811] were reviewed to determine exposure status by an occupational hygienist (C.R.) who was unaware of disease status. Exposure odds ratios were calculated using standard methods, and measures of agreement included the kappa statistic and conditional and marginal odds ratios. Results Expert assessment detected higher proportions of exposed subjects than the next-of-kin respondents or JEM methods. The disease-exposure odds ratios were highest for respondents, perhaps because of recall bias, and lowest for the JEM method. The agreement was highest between the respondent and expert assessments. A combination of respondent&PRIME; s assessment and JEM assessment led to the best prediction of the expert&PRIME; s assessment. Results for spouse respondents were similar to those for other "next-of-kin" respondents. Conclusions Expert assessments were the most plausible, but the data indicate that disease associations could also be detected with the other exposure assessment methods. Using some combination of the proxy respondent's assessment and the JEM assessment, one can predict the expert's assessment. A strategy that relied on the respondent's assessment when it was positive and otherwise obtained an expert assessment could reduce costs with little error compared to expert assessment on all subjects. Published 2005 Wiley-Liss, Inc. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA. RP Nam, JM (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Execut Plaza S,Room B028,6120 Execut Blvd,MSC 724, Bethesda, MD 20892 USA. EM namj@mail.nih.gov NR 26 TC 16 Z9 16 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAY PY 2005 VL 47 IS 5 BP 443 EP 450 DI 10.1002/ajim.20168 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 923JQ UT WOS:000228906600008 PM 15828074 ER PT J AU Brown, LM Osato, M You, WC El-Zimaity, H Li, JY Zhang, LA Gail, MH AF Brown, LM Osato, M You, WC El-Zimaity, H Li, JY Zhang, LA Gail, MH TI Disinfection of endoscopes from Helicobacter pylori-positive subjects: Evaluation of the effectiveness of the Chinese Calijing disinfection kit SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article ID TRANSMISSION; INFECTION; RISK; ELIMINATION AB Background: The aim of this study was to evaluate the effectiveness of the Calijing disinfection kit (an endoscope disinfection method used in Chinese hospitals) in eradicating Helicobacter pylori and assess whether use of the kit in 1994 during endoscopies in the Shandong Intervention Trial (SIT), Shandong, China, could have resulted in iatrogenic transmission of H pylori. Methods: Bacterial Culture studies at the Veterans Affairs Medical Center, Houston, Texas, using endoscopes and forceps from 49 H pylori-positive patients were performed on contaminated endoscopes before and after disinfection with the Calijing kit. Results: At least 1 endoscope culture site was H pylori positive in 39 of 49 (79.6%) specimens predisinfection, whereas H pylori was not isolated from any endoscopic culture site postdisinfection. Non-H pylori bacteria and fungi were recovered from 22.6% of the postdisinfection cultures. Conclusion: Although no viable H pylori were recovered following the disinfection procedures, levels of H pylori below the detection threshold of the bacteriologic assay may have contributed to an increase in H pylori seroprevalence noted in the SIT. In addition. the kit was unable to provide disinfection against non-H pylori organisms, suggesting the need to adhere to internationally accepted disinfection procedures for endoscope reprocessing. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Baylor Coll Med, Vet Affairs Med Ctr, Houston, TX 77030 USA. Peking Univ Oncol, Beijing, Peoples R China. Beijing Inst Canc Res, Beijing, Peoples R China. RP Brown, LM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,MSC 7244, Bethesda, MD 20892 USA. EM brownl@mail.nih.gov NR 19 TC 1 Z9 1 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD MAY PY 2005 VL 33 IS 4 BP 197 EP 201 DI 10.1016/j.ajic.2004.11.002 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 927UC UT WOS:000229225000001 PM 15877013 ER PT J AU Hortin, G AF Hortin, G TI Overestimation of urinary peptide excretion SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Letter ID PROTEIN-FRAGMENTS; ACID C1 NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Hortin, G (reprint author), NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2005 VL 45 IS 5 BP 961 EP 961 DI 10.1053/j.ajkd.2004.12.026 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 922US UT WOS:000228866000023 PM 15861366 ER PT J AU Ng, D Stavrou, T Liu, L Taylor, MD Gold, B Dean, M Kelley, MJ Dubovsky, EC Vezina, G Nicholson, HS Byrne, J Rutka, JT Hogg, D Reaman, GH Goldstein, AM AF Ng, D Stavrou, T Liu, L Taylor, MD Gold, B Dean, M Kelley, MJ Dubovsky, EC Vezina, G Nicholson, HS Byrne, J Rutka, JT Hogg, D Reaman, GH Goldstein, AM TI Retrospective family study of childhood medulloblastoma SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE medulloblastoma; PTCH1; SUFU; GLI3 ID CELL CARCINOMA SYNDROME; SPINA-BIFIDA OCCULTA; NORMAL ADULTS; HEIGHT; SURVIVORS AB Medulloblastoma. is the most common malignant central nervous system tumor of childhood and can occur sporadically or in association with inherited cancer susceptibility syndromes such as the nevoid basal cell carcinoma syndrome (NBCCS). To determine whether an association existed between the risk of developing medulloblastoma and undiagnosed syndromes, we retrospectively reviewed clinical data on 33 patients with medulloblastoma from a single institution and compared them with their unaffected relatives (n = 46). Six patients had tumors showing desmoplastic histology. Two of the six met diagnostic criteria for NBCCS. One NBCCS patient had a missense mutation of patched-1 (PTCH1); the other had no identifiable PTCH1 mutation. Two patients with isolated desmoplastic medulloblastoma. had an insertion and splice site mutation, respectively, in suppressor of fused (SUFU). All patients with nondesmoplastic medulloblastoma histology received molecular testing for SUFU. None of these patients had an identifiable mutation in PTCH1 or SUFU. We performed a clinical evaluation for Greig cephalopolysyndactyly syndrome (GCPS) in four medulloblastoma families, who exhibited macrocephaly as the only finding consistent with the diagnosis of GCPS. Molecular analysis of GLI3 in these four families was negative. There was a paucity of clinical findings among the majority of medulloblastoma patients in this study group to suggest a definable cancer genetic syndrome. We conclude that clinically recognizable syndromes are uncommon among patients with medulloblastoma, however, PTCH1 and SUFU mutations are present at a low but significant frequency. Published 2005 Wiley-Liss, Inc.(dagger) C1 NCI, DCEG, DHHS, Genet Epidemiol Branch,NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. Univ Toronto, Div Med & Med Biophys, Toronto, ON, Canada. Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 1X8, Canada. NCI, CRC, NIH, DHHS,Lab Genom Divers, Frederick, MD 21701 USA. Duke Univ, Dept Med, Durham, NC USA. Childrens Natl Med Ctr, Dept Diagnost Imaging & Radiol, Washington, DC 20010 USA. RP Ng, D (reprint author), NCI, NIH, 6120 Executive Pl,Room 7005, Rockville, MD 20852 USA. EM davidng@mail.nih.gov RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Kelley, Michael/0000-0001-9523-6080 NR 13 TC 20 Z9 20 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY 1 PY 2005 VL 134A IS 4 BP 399 EP 403 DI 10.1002/ajmg.a.30653 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 921IT UT WOS:000228758400009 PM 15759260 ER PT J AU Lindgren, VA Ames, NJ AF Lindgren, VA Ames, NJ TI Caring for patients on mechanical ventilation SO AMERICAN JOURNAL OF NURSING LA English DT Article ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; CLINICAL-PRACTICE GUIDELINES; NOSOCOMIAL PNEUMONIA; SLEEP DISRUPTION; ICU PATIENTS; TRACHEOSTOMY; SEDATION; IMPLEMENTATION; CHLORHEXIDINE C1 Inova Fairfax Hosp, Falls Church, VA 22042 USA. Ctr Clin, NIH, Alexandria, VA USA. RP Lindgren, VA (reprint author), Inova Fairfax Hosp, 3300 Gallows Rd, Falls Church, VA 22042 USA. EM vicki.lindgren@inova.com NR 60 TC 13 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD MAY PY 2005 VL 105 IS 5 BP 50 EP 60 PG 11 WC Nursing SC Nursing GA 921AB UT WOS:000228735500027 PM 15867534 ER PT J AU Grady, PA AF Grady, PA TI National institute of nursing research working group on "Optimizing pregnancy outcomes in minority populations" SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE biomedical research; national institutes of health roadmap; pregnancy outcome; minority population AB The growing complexity of biomedical research requires new methods of discovery; scientists must use an interdisciplinary approach and explore new models of team science, as underscored in the Roadmap,of the National Institutes of Health. In March 2003, the National Institute of Nursing Research convened a working group of scientists and clinicians with a wide range of backgrounds to address "Optimizing Pregnancy Outcomes in Minority Populations." The 2-day meeting included a variety of presentations on the current state of research on pregnancy in minority populations. Many participants provided specific insights regarding biobehavioral issues in human-environment interaction, stress and health status relationships to risk, maternal-fetal interactions, and the complications of pregnancy. This supplement presents articles from several participants at this interdisciplinary meeting. The National Institute of Nursing Research looks forward to further collaborations across the National Institutes of Health and other agencies to achieve the vital aims of this working group. (c) 2005 Elsevier Inc. All rights reserved. C1 NINR, NIH, Bethesda, MD 20892 USA. RP Grady, PA (reprint author), NINR, NIH, 31 Ctr Dr,Room 5B-10, Bethesda, MD 20892 USA. EM info@ninr.nih.gov NR 3 TC 1 Z9 1 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2005 VL 192 IS 5 SU S BP S1 EP S2 DI 10.1016/j.ajog.2005.01.070 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 931KE UT WOS:000229483400001 PM 15891706 ER PT J AU Patrick, TE Bryan, Y AF Patrick, TE Bryan, Y TI Research strategies for optimizing pregnancy outcomes in minority populations SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE health disparity; reproductive health; pregnancy outcome ID PRETERM LABOR; BIRTH-WEIGHT; STRESS; MORTALITY AB The elimination of disparities in pregnancy outcomes is a common goal of clinicians and scientists and requires the collaboration of many disciplines to address the complexities of this still-increasing perinatal health concern. This commentary synthesizes the presentations and dialogue from a multidisciplinary workgroup meeting that was sponsored by the National Institute of Nursing Research in 2003. Concepts that are central to our understanding of the development and expression of such disparities are summarized, and approaches that are recognized as important in multiple disciplines that include basic, clinical, and social sciences are presented. Research strategies to foster a multidisciplinary research agenda are presented as a basis for future endeavors to improve pregnancy outcomes. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Sch Nursing, Magee Womens Res Inst, Pittsburgh, PA 15261 USA. Magee Womens Hosp, Patient Care Serv Res, Pittsburgh, PA USA. NINR, Off Extramural Programs, NIH, Bethesda, MD 20892 USA. RP Patrick, TE (reprint author), Univ Pittsburgh, Sch Nursing, Magee Womens Res Inst, 440 Victoria Bldg,3500 Victoria St, Pittsburgh, PA 15261 USA. EM patrickt@pitt.edu RI Patrick, Thelma/D-1423-2013 NR 17 TC 14 Z9 14 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2005 VL 192 IS 5 SU S BP S64 EP S70 DI 10.1016/j.ajog.2005.01.075 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 931KE UT WOS:000229483400009 PM 15891714 ER PT J AU Kurup, SK Coleman, H Chan, CC AF Kurup, SK Coleman, H Chan, CC TI Corneal pseudomembrane from acute inflammatory response and fibrin formation to acute myeloid leukemic infiltrate SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To describe an unusual ocular manifestation of a patient with acute myeloid leukemia (AML). DESIGN: Observational case report. METHODS: A 59-year-old woman with a history of preleukemic myelodysplastic syndrome (MDS) and status post bone marrow transplant (BMT) complained of a sudden onset of poor vision associated with a corneal pseudomembrane. Ocular graft vs host disease was suspected, and the pseudomembrane was excised for histopathologic examination. RESULTS: The pseudomembrane showed myeloblasts ad, mixed with an acute inflammatory response suggestive of the development of AML, a complication of MDS. Bone marrow examination confirmed the diagnosis of relapsing AML. CONCLUSIONS: Acute myeloid leukemia could present as a pseudomembrane; thus, examination of relevant ocular tissue is recommended. © 2005 by Elsevier Inc. All rights reserved. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Kurup, SK (reprint author), NEI, NIH, Bldg 10,Room 10N112, Bethesda, MD 20892 USA. EM kurups@nei.nih.gov NR 5 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 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAY PY 2005 VL 139 IS 5 BP 921 EP 923 DI 10.1016/j.ajo.2004.10.049 PG 3 WC Ophthalmology SC Ophthalmology GA 924AJ UT WOS:000228950500028 PM 15860306 ER PT J AU Steeg, PS AF Steeg, PS TI New insights into the tumor metastatic process revealed by gene expression profiling SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material ID PROTEIN-COUPLED RECEPTOR; CHROMOSOME CONDENSATION; BINDING PROTEIN; BREAST-TUMORS; CANCER; CELLS; IDENTIFICATION; KISS-1; PROLIFERATION; HOMOLOG C1 NCI, Womens Canc Sect, Pathol Lab, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. RP Steeg, PS (reprint author), NCI, Womens Canc Sect, Pathol Lab, Canc Res Ctr,NIH, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. EM steegp@mail.nih.gov NR 28 TC 15 Z9 18 U1 0 U2 0 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 MAY PY 2005 VL 166 IS 5 BP 1291 EP 1294 DI 10.1016/S0002-9440(10)62348-6 PG 4 WC Pathology SC Pathology GA 920AE UT WOS:000228658500002 PM 15855631 ER PT J AU Saika, S Miyamoto, T Yamanaka, O Kato, T Ohnishi, Y Flanders, KC Ikeda, K Nakajima, Y Kao, WWY Sato, M Muragaki, Y Ooshima, A AF Saika, S Miyamoto, T Yamanaka, O Kato, T Ohnishi, Y Flanders, KC Ikeda, K Nakajima, Y Kao, WWY Sato, M Muragaki, Y Ooshima, A TI Therapeutic effect of topical administration of SN50, an inhibitor of nuclear factor-kappa B, in treatment of corneal alkali burns in mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; AMNIOTIC MEMBRANE TRANSPLANTATION; EPITHELIAL BASEMENT-MEMBRANE; ALPHA-INDUCED APOPTOSIS; N-TERMINAL KINASE; TNF-ALPHA; CYCLIN D1; C-JUN; TRANSFORMING GROWTH-FACTOR-BETA-1; MYOFIBROBLAST DIFFERENTIATION AB We evaluated the therapeutic efficacy of topical administration of SN50, an inhibitor of nuclear factor-kappa B, in a corneal alkali burn model in mice. An alkali burn was produced with 1 N NaOH in the cornea of C57BL/6 mice under general anesthesia. SN50 (10 mu g/ mu 1) or vehicle was topically administered daily for up to 12 days. The eyes were processed for histological or immunohistochemical examination after bromodeoxyuridine labeling or for semiquantification of cytokine mRNA- Topical SN50 suppressed nuclear factor-kappa B activation in local cells and reduced the incidence of epithelial defects/ulceration in healing corneas. Myofibroblast generation, macrophage invasion, activity of matrix inetalloproteinases, basement membrane destruction, and expression of cytokines were all decreased in treated corneas compared with controls. To elucidate the role of tumor necrosis factor (TNF)-alpha' in epithelial cell proliferation, we performed organ culture of mouse eyes with TNF-alpha, SN50, or an inhibitor of c-Jun N-terminal kinase (JNK) and examined cell proliferation in healing corneal epithelium in TNF-alpha(-/-) mice treated with SN50. An acceleration of epithelial cell proliferation by SN50 treatment was found to depend on TNF-alpha/JNK signaling. in conclusion, topical application of SN50 is effective in treating corneal alkali burns in mice. C1 Wakayama Med Univ, Dept Ophthalmol, Wakayama 6410012, Japan. Wakayama Med Univ, Dept Pathol, Wakayama 6410012, Japan. Osaka City Univ, Dept Anat, Grad Sch Med, Osaka 558, Japan. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Med Ctr, Dept Ophthalmol, Cincinnati, OH 45267 USA. RP Saika, S (reprint author), Wakayama Med Univ, Dept Ophthalmol, 811-1 Kimiidera, Wakayama 6410012, Japan. EM shizuya@wakayama-med.ac.jp FU NEI NIH HHS [EY 13755, R01 EY013755] NR 59 TC 65 Z9 70 U1 0 U2 1 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 MAY PY 2005 VL 166 IS 5 BP 1393 EP 1403 DI 10.1016/S0002-9440(10)62357-7 PG 11 WC Pathology SC Pathology GA 920AE UT WOS:000228658500011 PM 15855640 ER PT J AU Saika, S Ikeda, K Yamanaka, O Miyamoto, T Ohnishi, Y Sato, M Muragaki, Y Ooshima, A Nakajima, Y Kao, WWY Flanders, KC Roberts, AB AF Saika, S Ikeda, K Yamanaka, O Miyamoto, T Ohnishi, Y Sato, M Muragaki, Y Ooshima, A Nakajima, Y Kao, WWY Flanders, KC Roberts, AB TI Expression of Smad7 in mouse eyes accelerates healing of corneal tissue after exposure to alkali SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; NF-KAPPA-B; AMNIOTIC MEMBRANE TRANSPLANTATION; EPITHELIAL-MESENCHYMAL TRANSITION; MICE LACKING SMAD3; TGF-BETA; MATRIX METALLOPROTEINASES; GENE-TRANSFER; UP-REGULATION; TRANSFORMING GROWTH-FACTOR-BETA-1 AB Damage to the cornea from chemical burns is a serious clinical problem that often leads to permanent visual impairment. Because transforming growth factor (TGF)-beta has been implicated in the response to corneal injury, we evaluated the effects of altered TGF-beta signaling in a corneal alkali burn model using mice treated topically with an adenovirus (Ad) expressing inhibitory Smad7 and mice with a targeted deletion of the TGF-beta/activin signaling mediator Smad3. Expression of exogenous Smad7 in burned corneal tissue resulted in reduced activation of Smad signaling and nuclear factor-kappa B signaling via RelA/p65. Resurfacing of the burned cornea by conjunctival epithelium and its differentiation to cornea-fike epithelium were both accelerated in Smad7-Ad-treated corneas with suppressed stromal ulceration, opacification, and neovascularization 20 days after injury. Introduction of the Smad7 gene suppressed invasion of monocytes/macrophages and expression of monocyte/macrophage chemotactic protein-1, TGF-beta 1, TGF-beta 2, vascular endothelial growth factor, matrix metalloproteinase-9, and tissue inhibitors of metalloproteinase-2 and abolished the generation of myofibroblasts. Although acceleration of healing of the burned cornea was also observed in mice lacking Smad3, the effects on epithelial and stromal healing were less pronounced than those in corneas treated with Smad7. Together these data suggest that overexpression of Smad7 may have effects beyond those of simply blocking Smad3/TGF-beta signaling and may represent an effective new strategy for treatment of ocular burns. C1 Wakayama Med Univ, Dept Ophthalmol, Wakayama 6410012, Japan. Wakayama Med Univ, Dept Pathol, Wakayama 6410012, Japan. Osaka City Univ, Grad Sch Med, Dept Anat, Osaka 558, Japan. Univ Cincinnati, Med Ctr, Dept Ophthalmol, Cincinnati, OH 45267 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD USA. RP Saika, S (reprint author), Wakayama Med Univ, Dept Ophthalmol, 811-1 Kimiidera, Wakayama 6410012, Japan. EM shizuya@wakayama-med.ac.jp FU NEI NIH HHS [R01 EY013755, EY 13755] NR 73 TC 73 Z9 82 U1 0 U2 1 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 MAY PY 2005 VL 166 IS 5 BP 1405 EP 1418 DI 10.1016/S0002-9440(10)62358-9 PG 14 WC Pathology SC Pathology GA 920AE UT WOS:000228658500012 PM 15855641 ER PT J AU Mansur, DS Kroon, EG Nogueira, ML Arantes, RME Rodrigues, SCO Akira, S Gazzinelli, RT Campos, MA AF Mansur, DS Kroon, EG Nogueira, ML Arantes, RME Rodrigues, SCO Akira, S Gazzinelli, RT Campos, MA TI Lethal encephalitis in myeloid differentiation factor 88-deficient mice infected with herpes simplex virus 1 SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SIMPLEX-VIRUS TYPE-1; TOLL-LIKE RECEPTOR-2; GAMMA-INTERFERON; VACCINIA VIRUS; RECOGNITION; DNA; CELLS; TLR4; LIPOPOLYSACCHARIDE; REPLICATION AB Herpes simplex virus 1 (HSV-1), a large DNA virus from the Herpesviridae family, is the major cause of sporadic lethal encephalitis and blindness in humans. Recent studies have shown the importance of Toll-like receptors (TLRs) in the immune response to HSV-1 infection. Myeloid differentiation factor 88 (MyD88) is a critical adaptor protein that is downstream to mediated TLR activation and is essential for the production of inflammatory cytokines. Here, we studied the relationship between MyD88 and HSV-1 using a purified HSV-1 isolated from a natural oral recurrent human infection. We observed the activation of TLR-2 by HSV-1 in vitro using Chinese hamster ovary cells stably transfected with a reporter gene. Interestingly, we found that only peritoneal macrophages from MyD88(-/-) mice, but not macrophages from TRL2(-/-) or from wild-type mice, were unable to produce tumor necrosis factor-a in response to HSV-1 exposure. Additionally, although TLR2(-/-) mice showed no enhanced susceptibility to intranasal infection with HSV-1, MyD88(-/-) mice were highly susceptible to infection and displayed viral migration to the brain, severe neuropathological signs of encephalitis, and 100% mortality by day 10 after infection. Together, our results suggest that innate resistance to HSV-1 is mediated by MyD88 and may rely on activation of multiple TLRs. C1 Fiocruz MS, Ctr Pesquisas Rene Rachou, Immunopathol Lab, BR-30190002 Belo Horizonte, MG, Brazil. Univ Fed Minas Gerais, Dept Microbiol, Belo Horizonte, MG, Brazil. Univ Fed Minas Gerais, Dept Patol, Belo Horizonte, MG, Brazil. Univ Fed Minas Gerais, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Osaka Univ, Dept Host Def, Microbial Dis Res Inst, Osaka, Japan. RP Campos, MA (reprint author), Fiocruz MS, Ctr Pesquisas Rene Rachou, Immunopathol Lab, Av Augusto Lima 1715, BR-30190002 Belo Horizonte, MG, Brazil. EM marcoasc@cpqrr.fiocruz.br RI Akira, Shizuo/C-3134-2009; Nogueira, Mauricio/B-7599-2012; Campos, Marco /C-4000-2013; Arantes, Rosa /C-5749-2013 OI Nogueira, Mauricio/0000-0003-1102-2419; Campos, Marco /0000-0003-4683-0176; Arantes, Rosa /0000-0003-1428-9717 NR 32 TC 57 Z9 58 U1 0 U2 4 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 MAY PY 2005 VL 166 IS 5 BP 1419 EP 1426 DI 10.1016/S0002-9440(10)62359-0 PG 8 WC Pathology SC Pathology GA 920AE UT WOS:000228658500013 PM 15855642 ER PT J AU Sebbane, F Gardner, D Long, D Gowen, BB Hinnebusch, BJ AF Sebbane, F Gardner, D Long, D Gowen, BB Hinnebusch, BJ TI Kinetics of disease progression and host response in a rat model of bubonic plague SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; YERSINIA-PESTIS; V-ANTIGEN; PASTEURELLA PESTIS; FUSION PEPTIDE; CELL-DEATH; PROTEIN; MACROPHAGES; INHIBITION; APOPTOSIS AB Plague, caused by the gram-negative bacterium Yersinia pestis, primarily affects rodents but is also an important zoonotic disease of humans. Bubonic plague in humans follows transmission by infected fleas and is characterized by an acute, necrotizing lymphadenitis in the regional lymph nodes that drain the intradermal flea bite site. Septicemia rapidly follows with spread to spleen, liver, and other organs. We developed a model of bubonic plague using the inbred Brown Norway strain of Rattus norvegicus to characterize the progression and kinetics of infection and the host immune response after intradermal inoculation of Y. pestis. The clinical signs and pathology in the rat closely resembled descriptions of human bubonic plague. The bacteriology; histopathology; host cellular response in infected lymph nodes, blood, and spleen; and serum cytokine levels were analyzed at various times after infection to determine the kinetics and route of disease progression and to evaluate hypothesized Y. pestis pathogenic mechanisms. Understanding disease progression in this rat infection model should facilitate further investigations into the molecular pathogenesis of bubonic plague and the immune response to Y. pestis at different stages of the disease. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Hinnebusch, BJ (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM jhinnebusch@niaid.nih.gov RI Sebbane, Florent/D-4213-2009 NR 47 TC 115 Z9 120 U1 4 U2 19 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 MAY PY 2005 VL 166 IS 5 BP 1427 EP 1439 DI 10.1016/S0002-9440(10)62360-7 PG 13 WC Pathology SC Pathology GA 920AE UT WOS:000228658500014 PM 15855643 ER PT J AU Howden, R Hanlon, PR Petranka, JG Kleeberger, S Bucher, J Dunnick, J Nyska, A Murphy, E AF Howden, R Hanlon, PR Petranka, JG Kleeberger, S Bucher, J Dunnick, J Nyska, A Murphy, E TI Ephedrine plus caffeine causes age-dependent cardiovascular responses in Fischer 344 rats SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE heart rate; cardiac toxicity; ECG; hyperthermia ID GLUCOSE-UPTAKE; WEIGHT-LOSS; MA-HUANG; ADENOSINE; VASOSPASM; MECHANISM; ISCHEMIA; EFFICACY; SAFETY; TRIAL AB Human consumption of ephedrine and caffeine in dietary supplements has been associated with a number of adverse effects including changes in the ECG, myocardial infarction, hyperthermia, and, in rare instances, death. The purpose of this study was to investigate the potential mechanisms associated with the cardiotoxicity of combined ephedrine and caffeine ingestion. Seven- and fourteen-week-old Fischer 344 rats treated with ephedrine in combination with caffeine exhibited increases in heart rate (HR), temperature, and corrected QT interval. Of the 14-wk-old rats treated with 25 mg/kg ephedrine plus 30 mg/kg caffeine, 57% died within 3-5 h of treatment, whereas none of the similarly treated 7-wk-old rats nor any of the rats treated with vehicle died. One hour after treatment with this dose of ephedrine plus caffeine, 14-wk-old rats exhibited a larger increase in HR (as % increase over baseline) than 7-wk-old rats. Furthermore, the 14-wk-old rats that died had a higher HR and temperature than the 14-wk-old rats that lived. Histopathological studies suggested interstitial hemorrhage and myofiber necrosis in the 14-wk-old rats treated with the highest concentration of ephedrine and caffeine. This study showed enhanced susceptibility to ephedrine plus caffeine in 14-wk-old rats compared with 7-wk-old rats. The greater mortality in the 14-wk-old rats was associated with increases in body temperature, HR, and myocardial necrosis. C1 Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Toxicol Operat Branch, NIH, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Hanlon, PR (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, 111 TW Alexander Dr,Bldg 101,MD F2-07, Res Triangle Pk, NC 27709 USA. EM murphy1@niehs.nih.gov NR 18 TC 10 Z9 10 U1 1 U2 6 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 MAY PY 2005 VL 288 IS 5 BP H2219 EP H2224 DI 10.1152/jpheart.01164.2004 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 918DU UT WOS:000228520400026 PM 15653753 ER PT J AU Gladwin, MT AF Gladwin, MT TI Hemoglobin as a nitrite reductase regulating red cell-dependent hypoxic vasodilation SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Editorial Material ID BLOOD-FLOW; S-NITROSOHEMOGLOBIN; XANTHINE OXIDOREDUCTASE; GUANYLATE-CYCLASE; VASCULAR CONTROL; OXYGEN-BINDING; OXIDE; DEOXYHEMOGLOBIN; MICROVESSELS; CIRCULATION C1 NIH, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 37 TC 28 Z9 30 U1 2 U2 5 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 MAY PY 2005 VL 32 IS 5 BP 363 EP 366 DI 10.1165/rcmb.F294 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 922DM UT WOS:000228816200003 PM 15837723 ER PT J AU Asiedu, C Bernardet, SLB Hutchings, A Goodwin, K Neville, D Thomas, J AF Asiedu, C Bernardet, SLB Hutchings, A Goodwin, K Neville, D Thomas, J TI T cell recovery after profound depletion with anti-CD3 immunotoxin in juvenile macaques involves homeostatic expansion of memory cells and thymopoiesis. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Univ Alabama, Birmingham, AL USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 277 BP 226 EP 226 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231600278 ER PT J AU Bruno, DA Cheng, O Hale, DA Dhanireddy, K Kirk, AD Major, EO Mannon, RB AF Bruno, DA Cheng, O Hale, DA Dhanireddy, K Kirk, AD Major, EO Mannon, RB TI Limiting overimmunosuppression post-transplant: The role of BK polyoma viral monitoring. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Georgetown Med Ctr, Washington, DC USA. NIDDK, Transplant Branch, NIH, Bethesda, MD USA. NINDS, NIH, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 386 BP 254 EP 254 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231600387 ER PT J AU Benatuil, L Donahue, R Bonifacino, A Dunbar, CE Iacomini, J AF Benatuil, L Donahue, R Bonifacino, A Dunbar, CE Iacomini, J TI Induction of molecular chimerism in rhesus macaques following retroviral transduction of autologous CD34(+) hematopoietic progenitors. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA USA. NHBLI, Hematol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 454 BP 271 EP 271 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231600455 ER PT J AU Bohl, DL Ryschkewitsch, C Major, EO Storch, GA Brennan, DC AF Bohl, DL Ryschkewitsch, C Major, EO Storch, GA Brennan, DC TI BK virus antibody titers markedly increase with viremia. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Washington Univ, St Louis, MO USA. NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. Washington Univ, St Louis, MO USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 463 BP 273 EP 273 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231600464 ER PT J AU Anam, K Kampen, RL Hale, DA AF Anam, K Kampen, RL Hale, DA TI T cell regulation does not contribute to the maintenance of tolerance in a mixed chimerism model. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, Transplantat Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 491 BP 280 EP 281 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231600492 ER PT J AU Mannon, RB Hoffmann, S Cheng, O Kampen, R Kleiner, D Becker, B Kirk, AD AF Mannon, RB Hoffmann, S Cheng, O Kampen, R Kleiner, D Becker, B Kirk, AD TI The molecular signature of calcineurin inhibitor (CNI) toxicity: Death to the graft! SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, Transplantat Branch, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 669 BP 327 EP 327 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231601088 ER PT J AU Benfield, MR Munoz, R Warshaw, BL Bartosh, SM Stablein, DM McIntosh, MJ Bridges, ND Harmon, WE AF Benfield, MR Munoz, R Warshaw, BL Bartosh, SM Stablein, DM McIntosh, MJ Bridges, ND Harmon, WE TI A randomized controlled double-blind trial of steroid withdrawal in pediatric renal transplantation: A study of the cooperative clinical trials in pediatric transplantation (CCTPT) SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 UAB, Birmingham, AL USA. Emory Univ, Atlanta, GA 30322 USA. Univ Wisconsin, Madison, WI USA. EMMES Corp, Rockville, MD USA. NIAID, Bethesda, MD 20892 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 966 BP 402 EP 402 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231601384 ER PT J AU Caroline, KL Christensen, LL Magee, JC Ojo, AO Bridges, ND AF Caroline, KL Christensen, LL Magee, JC Ojo, AO Bridges, ND TI Chronic renal failure in pediatric heart and liver recipients: Risk factors and impact on survival. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. NIAID, NIH, Bethesda, MD 20892 USA. SRTR URREA, Ann Arbor, MI USA. Univ Michigan, SRTR, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 983 BP 406 EP 407 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231601401 ER PT J AU McDonald, RA McIntosh, M Stablein, D Grimm, P Wyatt, R Arar, M Lirenman, D Bridges, N Harmon, W AF McDonald, RA McIntosh, M Stablein, D Grimm, P Wyatt, R Arar, M Lirenman, D Bridges, N Harmon, W TI Increased incidence of PTLD in pediatric renal transplant recipients enrolled in a randomized controlled trial of steroid withdrawal: A study of the CCTPT. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Univ Calif San Diego, La Jolla, CA 92093 USA. NIH, Bethesda, MD USA. Boston Childrens, Boston, MA USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 1028 BP 418 EP 418 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231601446 ER PT J AU Dhanireddy, KK Xu, H Bruno, DA Zhang, X Leopardi, FV Johnson, LB Hale, DA Kirk, AD AF Dhanireddy, KK Xu, H Bruno, DA Zhang, X Leopardi, FV Johnson, LB Hale, DA Kirk, AD TI Pretransplant portal venous donor specific transfusion in conjunction with sirolimus prolongs renal allograft survival in non-human primates. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, Transplantat Branch, NIH, Bethesda, MD USA. Georgetown Univ, Transplant Inst, Dept Surg, Washington, DC USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 1035 BP 420 EP 420 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231601453 ER PT J AU Deans, KJ Minneci, PC Hergen, AE Hoehn, G Suffredini, AF Solomon, MA AF Deans, KJ Minneci, PC Hergen, AE Hoehn, G Suffredini, AF Solomon, MA TI Serum protein expression of acute cellular rejection in a rat heart transplant model. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NHLBI, Cardiovasv Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 1268 BP 479 EP 479 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231602083 ER PT J AU Minneci, PC Deans, KJ Yu, EA Chen, H Hergen, AE Aponte, AM Logun, C Sittler, KJ Barb, JJ Munson, PJ Danner, RL Solomon, MA AF Minneci, PC Deans, KJ Yu, EA Chen, H Hergen, AE Aponte, AM Logun, C Sittler, KJ Barb, JJ Munson, PJ Danner, RL Solomon, MA TI Correlation of protein and gene expression profiles in a rat heart transplant model of acute celluar rejection. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NHLBI, Proteom Core Facil, NIH, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 1271 BP 480 EP 480 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231602086 ER PT J AU Friedman, AL Macrae, J Friedman, EA Eggers, P AF Friedman, AL Macrae, J Friedman, EA Eggers, P TI Obesity imperils survival of renal transplant recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Yale Sch Med, New Haven, CT USA. Downstate Med Ctr, Brooklyn, NY USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 1486 BP 534 EP 534 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231602301 ER PT J AU Close, NC Hering, BJ Eggerman, TL AF Close, NC Hering, BJ Eggerman, TL CA EMMES Corp TI Results from the inaugural report of the collaborative islet transplant registry (CITR). SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 EMMES Corp, Rockville, MD USA. Univ Minnesota, Diabet Inst Immunol & Transplantat, Minneapolis, MN USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 1601 BP 563 EP 563 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231602416 ER PT J AU Schneeberger, S Steinmassl, O Gundringer, P Wahl, SM Ward, PA Obrist, P Brandacher, G Mark, W Werner, ER Amberger, A Margreiter, R AF Schneeberger, S Steinmassl, O Gundringer, P Wahl, SM Ward, PA Obrist, P Brandacher, G Mark, W Werner, ER Amberger, A Margreiter, R TI SLPI essentially contributes to initial organ function and limits inflammation and myocyte damage in response to cold ischemia and cardiac transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Med Univ, Dept Gen & Transplant Surg, D Swarovski Res Lab, Innsbruck, Austria. NIH, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Wagner Jauregg Hosp, Dept Pathol, Linz, Austria. Med Univ, Dept Med Chem & Biochem, Innsbruck, Austria. RI Brandacher, Gerald/L-7540-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 1599 BP 563 EP 563 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231602414 ER PT J AU Elster, EA Chamberlin, C Mannon, RB Swanson, SJ Kirk, AD Hale, DA AF Elster, EA Chamberlin, C Mannon, RB Swanson, SJ Kirk, AD Hale, DA TI Three-year experiernce with alemtuzumab induction. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 6th American Transplant Congress CY MAY 21-25, 2005 CL Seattle, WA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, Transplantat Branch, NIH, Bethesda, MD USA. USN, Med Res Ctr, Silver Spring, MD 20903 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 SU 11 MA 1623 BP 569 EP 569 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 927WQ UT WOS:000229231602438 ER PT J AU Preston, EH Xu, H Dhanireddy, KK Pearl, JP Leopardi, FV Starost, MF Hale, DA Kirk, AD AF Preston, EH Xu, H Dhanireddy, KK Pearl, JP Leopardi, FV Starost, MF Hale, DA Kirk, AD TI IDEC-131 (anti-CD154), sirolimus and donor-specific transfusion facilitate operational tolerance in non-human primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE CD154; donor-specific transfusion; sirolimus; transplantation; tolerance ID CELL COSTIMULATORY PATHWAYS; RENAL-ALLOGRAFT REJECTION; LONG-TERM SURVIVAL; CD4(+) T-CELLS; MONOCLONAL-ANTIBODY; CD40 LIGAND; TRANSPLANTATION TOLERANCE; ISLET ALLOGRAFTS; BLOOD-TRANSFUSION; SKIN ALLOGRAFTS AB CD154- specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances antiCD154 ' s efficacy. We performed renal transplants in major histocompatibility complex-(MHC) mismatched rhesus monkeys and treated recipients with combinations of the CD154- specific antibody IDEC- 131, and/ or sirolimus, and/ or a pre- transplant donor- specific transfusion (DST). Therapy was withdrawn after 3 months. Triple therapy prevented rejection during therapy in all animals and led to operational tolerance in three of five animals including donor- specific skin graft acceptance in the two animals tested. IDEC- 131, sirolimus and DST are highly effective in preventing renal allograft rejection in primates. This apparently clinically applicable regimen is promising for human renal transplant trials. C1 NIH, Dept Hlth & Human Serv, Natl Inst Diabet Digest & Kidney Dis, Transplantat Branch, Bethesda, MD USA. Georgetown Univ Hosp, Dept Surg, Washington, DC USA. NIH, Div Vet Resources, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Kirk, AD (reprint author), NIH, Dept Hlth & Human Serv, Natl Inst Diabet Digest & Kidney Dis, Transplantat Branch, Bethesda, MD USA. EM allank@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012 NR 47 TC 58 Z9 60 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2005 VL 5 IS 5 BP 1032 EP 1041 DI 10.1111/j.1600-6143.2005.00796.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 913EQ UT WOS:000228134800010 PM 15816883 ER PT J AU Ravi, V King, TP Andersen, JF Nutman, TB Neva, FA AF Ravi, V King, TP Andersen, JF Nutman, TB Neva, FA TI Strongyloides stercoralis recombinant NIE antigen shares epitope with recombinant Ves v 5 and Pol a 5 allergens of insects SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID PATHOGENESIS-RELATED PROTEINS; VENOM ALLERGEN; CROSS-REACTIVITY; TMV INFECTION; SEQUENCE; LARVAE; GENE AB A new recombinant protein (NIE) for immunodiagnosis Of human Strongyloides infection has 13% to 18% amino acid identify with antigen 5 insect venom allergen. but the C-terminal segment of NIE showed highest identify with Ves v 5 (yellow jacket) and Pol a 5 (paper wasp). A rabbit polyclonal anti-NIE antibody identified a single band of NIE antigen as well as hands of Pol a 5 and Ves v 5 antigens, and mouse anti-Pol a 5 and anti-Ves v 5 sera reacted with recombinant NIE antigen by Western blot. A cyanogen bromide-digested C-terminal fragment of NIE was reactive with mouse anti-Ves v 5 and Pol a 5 antibodies as well as with rabbit anti-NIE serum. Although IgE and IgG antibodies from pooled sera from Strongyloides-infected patients reacted with Pol a 5 and Ves v 5 recombinant antigens on immunoblots, neither antigen inhibited human IgG reaction with NIE antigen in a competitive enzyme-linked immunosorbent assay. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, New York, NY 10021 USA. RP Neva, FA (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. EM rvaratharajalu@niaid.nih.gov; kingtp@mail.rockefeller.edu; jandersen@niaid.nih.gov; tnutman@niaid.nih.gov; fneva@niaid.nih.gov OI Varatharajalu, Ravi/0000-0001-6773-1922 NR 13 TC 5 Z9 5 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 MAY PY 2005 VL 72 IS 5 BP 549 EP 553 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 924UX UT WOS:000229007200011 PM 15891128 ER PT J AU Molina-Cruz, A Gupta, L Richardson, J Bennett, KF Black, W Barillas-Mury, C AF Molina-Cruz, A Gupta, L Richardson, J Bennett, KF Black, W Barillas-Mury, C TI Effect of mosquito midgut trypsin activity on dengue-2 virus infection and dissemination in Aedes aegypti SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID REVERSE-TRANSCRIPTION-PCR; BORNE ENCEPHALITIS-VIRUS; YELLOW-FEVER VIRUS; REPLICATIVE INTERMEDIATE; MONOCLONAL-ANTIBODIES; VECTOR COMPETENCE; BLUETONGUE VIRUS; ORAL INFECTION; BLOOD; CELLS AB The effect of mosquito midgut trypsins in dengue serotype 2 flavivirus (DENV-2) infectivity to Aedes aegypti was studied. Addition of soybean trypsin inhibitor (STI) in a DENV-2 infectious blood meal resulted in a 91-97% decrease in midgut DENV-2 RNA copies (qRT-PCR analysis). STI treatment also resulted in slower DENV-2 replica:ion in the midgut, less DENV-2 E protein expression, and decreased dissemination to the thorax and the head. A second uninfected blood meal, 7 days after the STI-treated infectious meal, significantly increased DENV-2 replication in the midgut and recovered oogenesis, suggesting that the lower viral infection caused by STI was in part due to a nutritional effect. Mosquitoes fed DENV-2 digested in vitro with bovine trypsin (before STI addition) exhibited a transient increase in midgut DENV-2 4 days postinfection. Blood digestion and possibly DENV-2 proteolytic processing, mediated by midgut trypsins, influence the rate of DENV-2 infection, replication, and dissemination in Ae. aegypti. C1 Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. Colorado State Univ, Anthropod Borne & Infect Dis Lab, Ft Collins, CO 80523 USA. NIAID, Lab Malaria & Vector Res, Med Entomol Sect, NIH, Rockville, MD USA. RP Molina-Cruz, A (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. EM amolina-cruz@niaid.nih.gov; lgupta@niaid.nih.gov; wcb4@colostate.edu; cbarillas@niaid.nih.gov NR 48 TC 42 Z9 43 U1 0 U2 3 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 MAY PY 2005 VL 72 IS 5 BP 631 EP 637 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 924UX UT WOS:000229007200024 PM 15891140 ER PT J AU Herbeck, DM Fitek, DJ Svikis, DS Montoya, ID Marcus, SC West, JC AF Herbeck, DM Fitek, DJ Svikis, DS Montoya, ID Marcus, SC West, JC TI Treatment compliance in patients with comorbid psychiatric and substance use disorders SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 16-21, 2001 CL SCOTTSDALE, AZ SP Coll Problems Drug Dependence ID OUTPATIENT TREATMENT; TREATMENT RETENTION; ABUSE TREATMENT; SCHIZOPHRENIA; PREDICTORS; PROGRAM; INCENTIVES; ADHERENCE; ALCOHOL; WOMEN AB This study examines clinical and non-clinical factors associated with treatment compliance problems in 342 patients with substance use disorders (SUD) seen in routine psychiatric practice. Weighted Wald-X-2 and multivariate logistic regression assessed sociodemographic, clinical, treatment, and health plan characteristics associated with treatment compliance problems. Among patients with SUD, 40.5% were reported to currently have treatment compliance problems. Patients with treatment compliance problems were significantly more likely to have personality disorders, lower global assessment of functioning scores, and medication side effects than those without treatment compliance problems. Patients seen by psychiatrists who were reimbursed by discounted rather than undiscounted fee-for-service were five times more likely to be reported to have treatment compliance problems. Both clinical and non-clinical factors appear to be associated with treatment compliance problems. Understanding these factors and targeting treatment interventions may improve treatment compliance and patient outcomes. C1 Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90025 USA. George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. NIDA, Div Treatment Res & Dev, Bethesda, MD 20892 USA. Univ Penn, Sch Social Work, Philadelphia, PA 19104 USA. Amer Psychiat Inst Res & Educ, Practice Res Network, Washington, DC USA. RP Herbeck, DM (reprint author), Univ Calif Los Angeles, Integrated Subst Abuse Programs, 1640 S Sepulveda Blvd,Suite 200, Los Angeles, CA 90025 USA. EM dherbeck@ucla.edu FU Intramural NIH HHS [Z99 DA999999] NR 32 TC 10 Z9 10 U1 0 U2 0 PU ROUTLEDGE TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2005 VL 14 IS 3 BP 195 EP 207 DI 10.1080/10550490590949488 PG 13 WC Substance Abuse SC Substance Abuse GA 940EP UT WOS:000230126800001 PM 16019970 ER PT J AU Smothers, BA Yahr, HT AF Smothers, BA Yahr, HT TI Alcohol use disorder and illicit drug use in admissions to general hospitals in the United States SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID HEALTH-SERVICES UTILIZATION; INTERVIEW SCHEDULE AUDADIS; RELIABILITY; ABUSE; CARE; CONSUMPTION; PREVALENCE; MODULES; SAMPLE; COST AB This study estimated the prevalence and explored the management of illicit drug use, illicit drug use associated with alcohol use disorder (AUD), and AUD without reported illicit drug use in a national sample of 2040 admissions to general hospitals in the United States. Surveyed in 1994, admissions were diagnosed with past 12-month DSM-IV AUD according to the Alcohol Use Disorders and Associated Disabilities Interview Schedule. Information about drug use was also included in the interview. Entries in hospital records were used to operationalize management. Prevalence of chronic drug use in hospital admissions was 5%, 14% in 18-44-year-old admissions, and 31% in admissions with an AUD. In admissions with an AUD, 45% reported no drug use. Detection rates were 82% for admissions with comorbid AUD and chronic drug use (where detection of either problem was assessed); detection rates hovered around 50% in admissions with one or the other condition. Low rates of treatment and referral (33% and 42%, respectively) were observed in the comorbid group; rates were 13-17% in admissions with AUD alone or illicit drug use alone. Findings indicate the need for increased attention to drug use and to AUD with and without other drug use among general hospital admissions. C1 NIAAA, Div Epidemiol & Prevent Res, NIH, Bethesda, MD USA. RP Smothers, BA (reprint author), NINR, NIH, DEA, 6701 Democracy Blvd,Suite 710, Bethesda, MD 20892 USA. EM bs86h@nih.gov NR 38 TC 13 Z9 14 U1 0 U2 3 PU ROUTLEDGE TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2005 VL 14 IS 3 BP 256 EP 267 DI 10.1080/10550490590949433 PG 12 WC Substance Abuse SC Substance Abuse GA 940EP UT WOS:000230126800007 PM 16019976 ER PT J AU Kolobow, T Berra, L Bassi, GL Curto, F AF Kolobow, T Berra, L Bassi, GL Curto, F TI Novel system for complete removal of secretions within the endotracheal tube - The mucus shaver SO ANESTHESIOLOGY LA English DT Article C1 NHLBI, Dept Hlth & Human Serv, Pulm & Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Sect Pulm & Cardiac Assist Devices, NIH, Bethesda, MD 20892 USA. RP Kolobow, T (reprint author), NHLBI, Dept Hlth & Human Serv, Pulm & Crit Care Med Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 5D-07, Bethesda, MD 20892 USA. EM kolobowt@nhlbi.nih.gov NR 6 TC 40 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2005 VL 102 IS 5 BP 1063 EP 1065 DI 10.1097/00000542-200505000-00028 PG 3 WC Anesthesiology SC Anesthesiology GA 920EU UT WOS:000228673000027 PM 15851896 ER PT J AU Li, Z Gastwirth, JL Gail, MH AF Li, Z Gastwirth, JL Gail, MH TI Power and related statistical properties of conditional likelihood score tests for association studies in nuclear families with parental genotypes SO ANNALS OF HUMAN GENETICS LA English DT Article ID TRANSMISSION DISEQUILIBRIUM TEST; CANDIDATE-GENE ASSOCIATION; COMPLEX HUMAN-DISEASES; ROBUST LINKAGE TESTS; CASE-CONTROL DESIGNS; TRANSMISSION/DISEQUILIBRIUM TEST; AFFECTED SIBS; ALLELES; RISKS; SUBDIVISION AB Both population based and family based case control studies are used to test whether particular genotypes are associated with disease. While population based studies have more power, cryptic population stratification can produce false-positive results. Family-based methods have been introduced to control for this problem. This paper presents the full likelihood function for family-based association studies for nuclear families ascertained on the basis of their number of affected and unaffected children. The likelihood of a family factors into the probability of parental mating type, conditional on offspring phenotypes, times the probability of offspring genotypes given their phenotypes and the parental mating type. The first factor can be influenced by population stratification, whereas the latter factor, called the conditional likelihood, is not. The conditional likelihood is used to obtain score tests with proper size in the presence of population stratification (see also Clayton (1999) and Whittemore & Tu (2000)). Under either the additive or multiplicative model, the TDT is known to be the optimal score test when the family has only one affected child. Thus, the class of score tests explored can be considered as a general family of TDT-like procedures. The relative informativeness of the various mating types is assessed using the Fisher information, which depends on the number of affected and unaffected offspring and the penetrances. When the additive model is true, families with parental mating type Aa x Aa are most informative. Under the dominant (recessive) model, however, a family with mating type Aa x a a (AA x Aa) is more informative than a family with doubly heterozygous (Aa x Aa) parents. Because we derive explicit formulae for all components of the likelihood, we are able to present tables giving required sample sizes for dominant, additive and recessive inheritance models. C1 George Washington Univ, Dept Stat, Washington, DC 20052 USA. NCI, DHHS, Biostat Branch, Div Canc Epidemiol & Genet,NIH, Bethesda, MD 20892 USA. RP Li, Z (reprint author), George Washington Univ, Dept Stat, 315 Funger Hall, Washington, DC 20052 USA. EM zli@gwu.edu FU NCI NIH HHS [CA 64363]; NEI NIH HHS [EY14478] NR 45 TC 12 Z9 12 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAY PY 2005 VL 69 BP 296 EP 314 DI 10.1046/j.1529-8817.2005.00169.x PN 3 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA 924AO UT WOS:000228951000007 PM 15845034 ER PT J AU Puls, I Oh, SJ Sumner, CJ Wallace, KE Floeter, MK Mann, EA Kennedy, WR Wendelschafer-Crabb, G Vortmeyer, A Powers, R Finnegan, M Holzbaurl, ELF Fischbeck, KH Ludlow, CL AF Puls, I Oh, SJ Sumner, CJ Wallace, KE Floeter, MK Mann, EA Kennedy, WR Wendelschafer-Crabb, G Vortmeyer, A Powers, R Finnegan, M Holzbaurl, ELF Fischbeck, KH Ludlow, CL TI Distal spinal and bulbar muscular atrophy caused by dynactin mutation SO ANNALS OF NEUROLOGY LA English DT Article ID VOCAL CORD PARALYSIS; DIFFERENTIATION-ASSOCIATED PROTEIN-1; LARYNGEAL-ABDUCTOR PARALYSIS; MARIE-TOOTH-DISEASE; AXONAL-TRANSPORT; HEREDITARY MOTOR; RETROGRADE TRANSPORT; SENSORY NEUROPATHY; TRANSGENIC MICE; GENE AB Impaired axonal transport has been postulated to play a role in the pathophysiology of multiple neurodegenerative disorders. In this report, we describe the results of clinical and neuropathological studies in a family with an inherited form of motor neuron disease caused by mutation in the p150(Glued) subunit of dynactin, a microtubule motor protein essential for retrograde axonal transport. Affected family members had a distinct clinical phenotype characterized by early bilateral vocal fold paralysis affecting the adductor and abductor laryngeal muscles. They later experienced weakness and atrophy in the face, hands, and distal legs. The extremity involvement was greater in the hands than in the legs, and it had a particular predilection for the thenar muscles. No clinical or electrophysiological sensory abnormality existed; however, skin biopsy results showed morphological abnormalities of epidermal nerve fibers. An autopsy study of one patient showed motor neuron degeneration and axonal loss in the ventral horn of the spinal cord and hypoglossal nucleus of the medulla. Immunohistochemistry showed abnormal inclusions of dynactin and dynein in motor neurons. This mutation of dynactin, a ubiquitously expressed protein, causes a unique pattern of motor neuron degeneration that is associated with the accumulation of dynein and dynactin in neuronal inclusions. C1 NINDS, Clin Neurosci Program, Bethesda, MD 20892 USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Med Ctr, Dept Neurol, Minneapolis, MN 55455 USA. NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), NINDS, Clin Neurosci Program, Bldg 10 Room 5D 38,10 Ctr Dr,MSC 1416, Bethesda, MD 20892 USA. EM ludlowc@ninds.nih.gov OI Ludlow, Christy/0000-0002-2015-6171 FU NIGMS NIH HHS [GM48661, R01 GM048661]; NINDS NIH HHS [Z01 NS002980, Z01 NS02980] NR 40 TC 129 Z9 133 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2005 VL 57 IS 5 BP 687 EP 694 DI 10.1002/ana.20468 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923VK UT WOS:000228937300010 PM 15852399 ER PT J AU Liang, GSL de Miguel, M Gomez-Hernandez, JM Glass, JD Scherer, SS Mintz, M Barrio, LC Fischbeck, KH AF Liang, GSL de Miguel, M Gomez-Hernandez, JM Glass, JD Scherer, SS Mintz, M Barrio, LC Fischbeck, KH TI Severe neuropathy with leaky connexin32 hemichannels SO ANNALS OF NEUROLOGY LA English DT Article ID MARIE-TOOTH-DISEASE; GAP-JUNCTION CHANNELS; X-CHROMOSOME; PLASMA-MEMBRANE; MUTATIONS; GENE; INACTIVATION; METHYLATION; PROTEIN; REPEAT AB X-linked Charcot-Ma-ric-Tooth disease is one of a set of diseases caused by mutations in gap junction proteins called connexins. We identified a connexin32 missense mutation (F235C) in a girl with unusually severe neuropathy. The localization and trafficking of the mutant protein in cell culture was normal, but electrophysiological studies showed that the mutation caused abnormal hemichannel opening, with excessive permeability of the plasma membrane and decreased cell survival. Abnormal leakiness of connexin hemichannels is likely a mechanism of cellular toxicity in this and perhaps other diseases caused by connexin mutations. C1 Univ Penn, Ctr Med, Penn Neurol Inst,Parkinsons Dis & Movement Disord, Dept Neurol, Philadelphia, PA 19107 USA. Hosp Madrid, Dept Res, Unit Expt Neurol, Madrid, Spain. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Bancroft Neurosci Inst, Cherry Hill, NJ USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Liang, GSL (reprint author), Univ Penn, Ctr Med, Penn Neurol Inst,Parkinsons Dis & Movement Disord, Dept Neurol, 330 S 9th St, Philadelphia, PA 19107 USA. EM liangg@pahosp.com FU NINDS NIH HHS [R01 NS08075] NR 20 TC 55 Z9 59 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2005 VL 57 IS 5 BP 749 EP 754 DI 10.1002/ana.20459 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923VK UT WOS:000228937300019 PM 15852376 ER PT J AU Liu, D Wu, LJ Breyer, R Mattson, MP Andreasson, K AF Liu, D Wu, LJ Breyer, R Mattson, MP Andreasson, K TI Neuroprotection by the PGE(2) EP2 receptor in permanent focal cerebral ischemia SO ANNALS OF NEUROLOGY LA English DT Article ID PROSTANOID RECEPTORS; PROSTAGLANDIN E-2; MOTOR-NEURONS; CYCLOOXYGENASE-2; MODEL; SUBTYPES; RELEASE; DAMAGE; DEATH; MICE AB Recent studies suggest a neuroprotective function of the PGE(2) EP2 receptor in excitotoxic neuronal injury. The function of the EP2 receptor was examined at time points after excitotoxicity in an organotypic hippocampal model of N-methyl-D-aspartate (NMDA) challenge and in a permanent model of focal forebrain ischemia. Activation of EP2 led to significant neuroprotection in hippocampal slices up to 3 hours after a toxic NMDA stimulus. Genetic deletion of EP2 resulted in a marked increase in stroke volume in the permanent middle cerebral artery occlusion model. These findings support further investigation into therapeutic strategies targeting the EP2 receptor in stroke. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Vanderbilt Univ, Sch Med, Dept Med, Div Nephrol, Nashville, TN 37212 USA. RP Andreasson, K (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, 600 N Wolfe St,Meyer 5-119B, Baltimore, MD 21205 USA. EM kandreas@jhmi.edu RI Mattson, Mark/F-6038-2012 FU NINDS NIH HHS [R01 NS045727] NR 20 TC 87 Z9 89 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2005 VL 57 IS 5 BP 758 EP 761 DI 10.1002/ana.20461 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923VK UT WOS:000228937300021 PM 15852374 ER PT J AU Marsh, VA Young, WO Dunaway, KK Kissling, GE Carlos, RQ Jones, SM Shockley, DH Weaver, NL Ransom, JL Gal, P AF Marsh, VA Young, WO Dunaway, KK Kissling, GE Carlos, RQ Jones, SM Shockley, DH Weaver, NL Ransom, JL Gal, P TI Efficacy of topical anesthetics to reduce pain in premature infants during eye examinations for retinopathy of prematurity SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE proparacaine; retinopathy of prematurity ID STRESS; MANAGEMENT; PREVENTION; VALIDATION; PROFILE AB BACKGROUND: Eye examinations for retinopathy of prematurity (ROP) are stressful and probably painful, but many ophthalmologists do not apply topical anesthetics because their efficacy in reducing pain has not been established. OBJECTIVE: To evaluate the potential benefits of topical anesthetic eye drops in reducing pain during neonatal eye examination for ROP. METHODS: Neonates born at <= 30 weeks' gestation and expected to have at least 2 examinations for ROP were included. Patients were randomly assigned to receive either proparacaine HCl ophthalmic solution 0.5% or NaCl 0.9% (saline) eye drops prior to an eye examination. In a subsequent examination, each patient received the alternate treatment. Eye drops were prepared in the pharmacy in identical tuberculin syringes, and physicians, nurses, and pharmacists were blinded to the treatment given. Pain was measured using a scoring system with both physical and physiologic measures of pain (Premature Infant Pain Profile [PIPP], possible range 1-21), which has been validated in preterm infants. PIPP scoring was performed simultaneously by 2 nurses: 1 and 5 minutes before and after the eye examination and during initial placement of the eye speculum. The same ophthalmologist performed all examinations. RESULTS: Twenty-two patients were studied, with 11 infants receiving proparacaine and 11 receiving saline as the first treatment. Crossover was performed with a median of 17.5 days between treatments. Patients experienced significantly less pain at speculum insertion with proparacaine than with saline (paired difference -2.5 +/- 3.4; p = 0.001). CONCLUSIONS: Topical anesthetic pretreatment reduces the pain response to eye examination for ROP and should become routine practice. Because this is not effective in all infants, additional measures to reduce pain should be taken. C1 Greensboro AHEC, Div Pharm, Greensboro, NC 27401 USA. Womens Hosp Med Ctr, Dept Nursing, Neonatal Intens Care Unit, Greensboro, NC USA. Pediat Ophthalmol Associates, Greensboro, NC USA. Womens Hosp Med Ctr, Dept Pharm, Greensboro, NC USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. Womens Hosp Med Ctr, Dept Neonatol, Greensboro, NC USA. RP Gal, P (reprint author), Greensboro AHEC, Div Pharm, Ste 100,200 E Northwood St, Greensboro, NC 27401 USA. EM peter.gal@mosescone.com NR 13 TC 29 Z9 31 U1 0 U2 4 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAY PY 2005 VL 39 IS 5 BP 829 EP 833 DI 10.1345/aph.1E476 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 920EL UT WOS:000228672100006 PM 15797982 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI The emergence of modern cancer immunotherapy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID METASTATIC MELANOMA; RECOMBINANT INTERLEUKIN-2; AUTOIMMUNITY; LYMPHOCYTES; REGRESSION; RESPONSES C1 NCI, Surg Branch, NIH, CRC, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, CRC, Room 3W-3-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM sar@nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 13 TC 7 Z9 8 U1 0 U2 0 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 MAY PY 2005 VL 12 IS 5 BP 344 EP 346 DI 10.1245/ASO.2005.01.904 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA 922YD UT WOS:000228874900003 PM 15843873 ER PT J AU Rosen, JE Costouros, NG Lorang, D Burns, AL Alexander, HR Skarulis, MC Cochran, C Pingpank, JF Marx, SJ Spiegel, AM Libutti, SK AF Rosen, JE Costouros, NG Lorang, D Burns, AL Alexander, HR Skarulis, MC Cochran, C Pingpank, JF Marx, SJ Spiegel, AM Libutti, SK TI Gland size is associated with changes in gene expression profiles in sporadic parathyrold adenomas SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE parathyroid adenoma; gene expression profile; microarray analysis; primary hyperparathyroidism ID MESSENGER-RNA AMPLIFICATION; PRIMARY HYPERPARATHYROIDISM; MICROARRAY ANALYSIS; C-FOS; TISSUE; BONE; CLASSIFICATION; GROWTH; CANCER; S100A6 AB Background: Sporadic parathyroid adenomas (SPAs) are benign neoplasms responsible for most cases of primary hyperparathyroidism (pHPT). The molecular pathways responsible for the variations in clinical severity of pHPT are unknown. We studied gene expression profiles in patients with SPAs and pHPT to determine associations between these changes and clinical parameters. Methods: We selected 10 patients with solitary SPAs and nonfamilial, non-MEN1 pHPT treated with surgery from 2001 to 2003. Pathologic and clinical data were reviewed. At operation, tissues from SPAs were frozen in liquid nitrogen; total RNA was obtained from sections, and the diagnosis was confirmed with hematoxylin and eosin staining. Control normal parathyroid RNA was age- and sex-matched. RNA was amplified, labeled, and hybridized to a microarray of 22,272 human oligonucleotides. Cluster analysis of gene expression, analysis of expression ratios, and comparison of clinical parameters were performed. Results: All patients were cured; all specimens were consistent with SPAs. K means clustering divided the 10 patients into 2 distinct 5-patient gene expression groups by using uncentered correlation based on gene subgrouping. Of the clinical parameters, only the mean gland volume was significantly different between group 1 (390 &PLUSMN; 160 mm(3)) and group 2 (1080 &PLUSMN; 615 mm(3); P = .032 by Mann-Whitney test). Seventy-five genes were significantly upregulated or downregulated (with a ratio of <.33 or >3) compared with controls. These genes included the v-fos viral oncogene homolog and six calcium ion-binding signaling proteins. Conclusions: Differential expression of a few critical genes may contribute to differences in galnd volume in SPAs. A better understanding gland volume in SPAs. A better understanding of these pathways may help to define the pathophysiology of pHPT. C1 NCI, Surg Branch, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, Bldg 10,Room 4W-5940,10 Ctr Dr, Bethesda, MD 20892 USA. EM steven_libutti@nih.gov NR 23 TC 10 Z9 10 U1 0 U2 0 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 MAY PY 2005 VL 12 IS 5 BP 412 EP 416 DI 10.1245/ASO.2005.03.103 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 922YD UT WOS:000228874900012 PM 15915376 ER PT J AU Goldbach-Mansky, R Suson, S Wesley, R Hack, CE El-Gabalawy, HS Tak, PP AF Goldbach-Mansky, R Suson, S Wesley, R Hack, CE El-Gabalawy, HS Tak, PP TI Raised granzyme B levels are associated with erosions in patients with early rheumatoid factor positive rheumatoid arthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID NATURAL-KILLER-CELLS; SYNOVIAL TISSUE; RADIOGRAPHIC DAMAGE; T-CELLS; CYTOLYTIC MEDIATORS; PROGNOSTIC FACTORS; DNA FRAGMENTATION; CYTOTOXIC-CELLS; GENE-EXPRESSION; MESSENGER-RNA AB Background: Raised granzyme B in serum and synovium of patients with rheumatoid arthritis suggests a role for cytotoxic T cells and natural killer cells in the pathogenesis of this disease. Objective: To evaluate serum granzyme B in patients with early arthritis and correlate it with specific diagnosis and clinical indices of disease severity. Methods: 257 patients with inflammatory arthritis for less than one year (46% rheumatoid arthritis, 17% spondyloarthropathy, 37% undifferentiated arthritis) had a prospective clinical, serological, and radiographic evaluation. Granzyme B was measured in initial sera by ELISA. Patients were HLA typed for DR alleles using sequence specific primers. A logistic regression model was used to evaluate the potential prognostic value of serum granzyme B in predicting radiographic erosions after one year of follow up. Results: Granzyme B values were similar in rheumatoid arthritis, spondyloarthropathy, and undifferentiated arthritis. Concentrations were higher in rheumatoid factor (RF) positive patients than in RF negative patients ( mean (SD): 3.15 (0.92) v 2.89 (0.71) pg/ml; p< 0.05). After one year, erosions were present in 30% of patients in the overall cohort, and in 44% of patients with rheumatoid arthritis. In the entire cohort, serum granzyme B did not predict erosions independently. However, high granzyme B was an independent predictor of early erosions in patients with RF positive rheumatoid arthritis ( odds ratio = 4.83 (95% confidence interval, 1.13 to 20.59)) (p< 0.05). Conclusions: Granzyme B may be a useful prognostic marker in early rheumatoid arthritis and may provide important clues to the pathogenesis of this disease. C1 Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1100 DE Amsterdam, Netherlands. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Netherlands Red Cross, Blood Transfus Serv, Cent Lab, Sanquin Res, Amsterdam, Netherlands. Univ Manitoba, Div Rheumatol, Winnipeg, MB, Canada. RP Tak, PP (reprint author), Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, F4-218,POB 22700, NL-1100 DE Amsterdam, Netherlands. EM p.p.tak@amc.uva.nl NR 56 TC 39 Z9 42 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAY PY 2005 VL 64 IS 5 BP 715 EP 721 DI 10.1136/ard.2003.007039 PG 7 WC Rheumatology SC Rheumatology GA 917GM UT WOS:000228444500011 PM 15471892 ER PT J AU Jeschke, U Bischof, A Speer, R Briese, V Richter, DU Bergemann, C Mylonas, I Shabani, N Friese, K Karsten, U AF Jeschke, U Bischof, A Speer, R Briese, V Richter, DU Bergemann, C Mylonas, I Shabani, N Friese, K Karsten, U TI Development of monoclonal and polyclonal antibodies and an ELISA for the determination of glycodelin in human serum, amniotic fluid and cystic fluid of benign and malignant ovarian tumors SO ANTICANCER RESEARCH LA English DT Article; Proceedings Paper CT 12th International Hamburg Symposium on Tumor Markers CY NOV 30-DEC 02, 2003 CL Hamburg, GERMANY DE glycodelin; monoclonal antibodies; ELISA; ovarian cancer ID HUMAN PLACENTAL PROTEIN-14; ENDOMETRIAL PROTEIN; STEROID-RECEPTORS; BREAST-CANCER; MESSENGER-RNA; CELLS; EXPRESSION; PP14; GLYCOPROTEIN; STIMULATION AB Objective: The role of glycodelin in human reproduction and gynecological malignancies has been investigated in a large number of studies in recent years. Three dominant functions of this glycoprotein were identified. Glycodelin is immunosuppressive, a morphological marker of differentiation and a contraceptive. Glycodelin is a glycoprotein with a molecular weight of 28 kDa and a carbohydrate content of 17.5%. Unusual LacdiNAc structures were identified on glycodelin A, isolated from amniotic fluid. Because no kit for glycodelin quantification is commercially available, we developed all reagents and a functional ELISA. Materials and Methods: Glycodelin A was purified from amniotic fluid by chromatographic methods. The purity of the isolated protein was checked with SDS-PAGE. Polyclonal antibodies against glycodelin were generated in rabbits. Monoclonal antibodies against glycodelin were generated from immunized BALB/c mice. Positive hybridomas were cloned and cultured. Monoclonal antibodies were isolated by immunoadsorption chromatography from culture supernatants. The glycodelin ELISA was developed in two formats, namely coating with polyclonal antibodies and the use of monoclonal antibodies. Results: The factors of variance for the ELISA were 7% (intra-assay variance) and 15% (inter-assay variance). The glycodelin ELISA was used to determine the glycodelin A concentration in sera of fertile women during the proliferative and secretory phases of the endometrium. The glycodelin A concentration was insignificantly elevated in the secretory phase compared to the proliferative phase. Significantly higher levels of glycodelin A were found in women using oral contraceptives compared to women who were not (p < 0.001). This is probably due to progesterone, which stimulates glycodelin production. We also found significantly increased glycodelin concentrations in the fluids of malignant ovarian cysts compared to benign ovarian tumors (p < 0.001). Furthermore, we tested the monoclonal and polyclonal antibodies successfully in Western blot analysis and immunoadsorption chromatography. Conclusion: We consider the described ELISA for the quantification of glycodelin as a useful tool for the determination of glycodelin in amniotic fluid, serum and cystic fluids. Its most promising application is expected in the diagnosis of ovarian cancer. The antibodies generated are applicable to multiple techniques. C1 Univ Munich, Dept Obstet & Gynecol 1, D-80337 Munich, Germany. Univ Rostock, Dept Obstet & Gynecol, Fac Med, D-18055 Rostock, Germany. NCI FDA, Clin Proteom Program, NIH, Bethesda, MD 20892 USA. Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. RP Jeschke, U (reprint author), Univ Munich, Dept Obstet & Gynecol 1, Maistr 11, D-80337 Munich, Germany. EM udo.jeschke@med.uni-muenchen.de NR 24 TC 9 Z9 9 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 2005 VL 25 IS 3A BP 1581 EP 1589 PG 9 WC Oncology SC Oncology GA 939UF UT WOS:000230097200017 PM 16033064 ER PT J AU Papadopoulou, MV Bloomer, WD Hollingshead, MG AF Papadopoulou, MV Bloomer, WD Hollingshead, MG TI NLCQ-1 (NSC 709257) in combination with radiation against human glioma U251 xenografts SO ANTICANCER RESEARCH LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the American-Association-for-Cancer-Research CY JUL 11-14, 2003 CL WASHINGTON, DC SP Amer Assoc Canc Res DE NLCQ-1; radiation; human gliomas; hypoxia ID CELL LUNG-CANCER; HYDROCHLORIDE NLCQ-1; BIOREDUCTIVE AGENT; EXPLOITING HYPOXIA; TUMOR HYPOXIA; SOLID TUMORS; PHASE-II; TIRAPAZAMINE; THERAPY; DRUGS AB Background: The efficacy of the weak DNA-intercalative hypoxia-selective cytotoxin NLCQ-1 (NSC 709257) was investigated in combination with single or fractionated doses of radiation against human glioma U251 xenografts. Two "advanced stage" experiments were performed in female athymic nude mice. Materials and Methods: Tumor-bearing mice were allocated in groups of 8-10 (treated) or 10-20 (control) and irradiated in the presence or absence of NLCQ-1. Fractionated radiation was administered either qd x 4 or qd x 2, followed by a 9-day rest and repeated dosing. NLCQ-1 was administered i.p. 45 min before each radiation dose. Results: NLCQ-1 alone did not show antitumor activity or toxicity. Radiation at the highest single dose used (5.0 Gy) showed antitumor activity without weight loss (optimal T/C = -45). Lower single radiation doses (2.0 or 3.0 Gy) were marginally effective (optimal T/C of 34 and 40, respectively). The addition of NLCQ-1 to the treatment with each single radiation dose provided better optimal T/C values (e.g., -64 with 5.0 Gy). Fractionated radiation at 1.0 Gy qd x 4 showed minimal effectiveness (T/C = 27) but, in combination with NLCQ-1, the T/C value was improved to 19. Radiation alone, given on a 3.0 Gy qd x 2, 9-day rest and repeat schedule was very effective (T/C = -57) without toxicity and resulted in 5 out of 10 complete regressions up to 42 days. When NLCQ-1 was added to the above protocol an optimal T/C value of -100 and 9 out of 10 complete regressions were obtained with a follow-up of 52 days. Conclusion: The above results suggest a significant advantage in combining radiation with NLCQ-1 against glioma tumors. C1 Evanston Northwestern Healthcare, Dept Radiat Med, Evanston, IL 60201 USA. NCI, Biol Testing Branch, DTP, DCTD,Fairview Ctr, Frederick, MD 21702 USA. RP Papadopoulou, MV (reprint author), Evanston Northwestern Healthcare, Dept Radiat Med, 2650 Ridge Ave, Evanston, IL 60201 USA. EM m-papadopoulou@northwestern.edu FU NCI NIH HHS [N01-CM-12400] NR 24 TC 7 Z9 7 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 2005 VL 25 IS 3B BP 1865 EP 1869 PG 5 WC Oncology SC Oncology GA 939UH UT WOS:000230097400003 PM 16158918 ER PT J AU Reveneau, N Crane, DD Fischer, E Caldwell, HD AF Reveneau, N Crane, DD Fischer, E Caldwell, HD TI Bactericidal activity of first-choice antibiotics against gamma interferon-induced persistent infection of human epithelial cells by Chlamydia trachomatis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO; AZITHROMYCIN; URETHRITIS; DISEASE; CULTURE; PATHOGENESIS; REACTIVATION; DOXYCYCLINE; PENICILLIN; MECHANISM AB Chlamydia trachomatis is responsible for clinically important chronic inflammatory diseases of humans, including trachoma and pelvic inflammatory disease. Persistent infection of mucosal sites may contribute to the development of these chronic inflammatory diseases. Standard clinical therapy results in satisfactory cure rates of acute infections; however, chronic infection associated with persistence has been suggested to be less responsive to antibiotic therapy. We report the efficiency of two first-line chlamydial antibiotics, azithromycin and doxycycline, under conditions of eradication of C. trachomatis persistent infection using the in vitro model of gamma interferon (IFN-γ)-mediated persistence and reactivation from persistence. Doxycycline was superior in eradicating acute (minimal bactericidal concentration [MBC](100) = 2.5 to 5.0 μ g/ml) compared to persistent (MBC100 = 10 to 50 μ g/ml) infection. In contrast, azithromycin was significantly more effective in eradicating persistent infection (MBC100 = 2.5 to 5.0 μ g/ml) than acute infection (MBC100 = 10 to 50 μ g/ml). The superior bactericidal effect of azithromycin against persistent infection was found to correlate with the enhanced uptake of the drug by IFN-γ-treated infected epithelial cells. Based on these findings, we hypothesize that azithromycin should be a particularly efficacious anti-infective agent for the eradication of IFN-γ-induced chlamydial persistent infection in vivo. C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. RP Caldwell, HD (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM hcaldwell@niaid.nih.gov NR 33 TC 32 Z9 33 U1 0 U2 0 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 MAY PY 2005 VL 49 IS 5 BP 1787 EP 1793 DI 10.1128/AAC.49.5.1787-1793.2005 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 924MJ UT WOS:000228982600018 PM 15855497 ER PT J AU Petraitiene, R Petraitis, V Kelaher, AM Sarafandi, AA Mickiene, D Groll, AH Sein, T Bacher, J Walsh, TJ AF Petraitiene, R Petraitis, V Kelaher, AM Sarafandi, AA Mickiene, D Groll, AH Sein, T Bacher, J Walsh, TJ TI Efficacy, plasma pharmacokinetics, and safety of icofungipen, an inhibitor of Candida isoleucyl-tRNA synthetase, in treatment of experimental disseminated candidiasis in persistently neutropenic rabbits SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ACID BAY 10-8888; INVASIVE CANDIDIASIS; FUNGAL-INFECTIONS; AMPHOTERICIN-B; UNITED-STATES; RISK-FACTORS; ANTIFUNGAL; EPIDEMIOLOGY; ALBICANS; CASPOFUNGIN AB Icofungipen (formerly PLD-118) is a synthetic derivative of the naturally occurring P-amino acid cispentacin that blocks isoleucyl-tRNA synthetase, resulting in the inhibition of protein synthesis and growth of fungal cells. We investigated the efficacy, plasma pharmacokinetics, and safety of icofungipen in escalating dosages for the treatment of experimental subacute disseminated candidiasis in persistently neutropenic rabbits. Icofungipen was administered for 10 days starting 24 h after the intravenous inoculation of 10(3) Candida albicans blastoconidia. Study groups consisted of rabbits treated with icofungipen at 4 (ICO-4), 10 (ICO-10), and 25 (ICO-25) mg/kg of body weight/day in two divided dosages, rabbits treated with fluconazole at 10 mg/kg/day, rabbits treated with amphotericin B at I mg/kg/day, and untreated controls. Levels of icofungipen in plasma were derivatized by phthaldialdehyde and quantified by high-performance liquid chromatography with fluorescence detection. Rabbits treated with ICO-10 (P < 0.01) and ICO-25 (P < 0.001) showed significant dosage-dependent tissue clearance of C. albicans from the liver, spleen, kidney, brain, vitreous, vena cava, and lung in comparison to untreated controls. ICO-25 cleared C. albicans from all tissues and had activity comparable to that of amphotericin B versus untreated controls (P < 0.001). Pharmacokinetics of icofungipen in plasma approximated a dose-dependent relationship of the maximum concentration of drug in serum and the area under the concentration-time curve. There was no significant elevation of the levels of hepatic transaminases, alkaline phosphatase, bilirubin, urea nitrogen, or creatinine in icofungipen-treated rabbits. Icofungipen followed dose-dependent pharmacokinetics and was effective in the treatment of experimental disseminated candidiasis, including central nervous system infection, in persistently neutropenic rabbits. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, Frederick, MD USA. NIH, Off Res Serv, Vet Resources Program, Bethesda, MD USA. Univ Chicago Hosp, Dept Pediat Hematol Oncol, Munster, Germany. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, Bldg 10,CRC,Rm 1W-5740,10 Ctr Dr,MSC 1100, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 39 TC 17 Z9 21 U1 1 U2 4 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 MAY PY 2005 VL 49 IS 5 BP 2084 EP 2092 DI 10.1128/AAC.49.5.2084-2092.2005 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 924MJ UT WOS:000228982600055 PM 15855534 ER PT J AU Rhee, SG Yang, KS Kang, SW Woo, HA Chang, TS AF Rhee, SG Yang, KS Kang, SW Woo, HA Chang, TS TI Controlled elimination of intracellular H2O2: Regulation of peroxiredoxin, catalase, and glutathione peroxidase via post-translational modification SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID THIOL-SPECIFIC ANTIOXIDANT; CYSTEINE-SULFINIC ACID; ALKYL HYDROPEROXIDE REDUCTASE; OXIDATIVE STRESS-RESPONSE; TYROSINE-PHOSPHATASE 1B; HYDROGEN-PEROXIDE; C-ABL; MAMMALIAN PEROXIREDOXIN; REACTIVE OXYGEN; GROWTH-FACTOR AB The predominant enzymes responsible for elimination of hydrogen peroxide (H2O2) in cells are peroxiredoxins (Prxs), catalase, and glutathione peroxidases (GPxs). Evidence suggests that catalytic activities of certain isoforms of these H2O2-eliminating enzymes are extensively regulated via posttranslational modification. Prx I and Prx 11 become inactivated when phosphorylated on Thr(90) by cyclin B-dependent kinase Cdc2. In addition, the active-site cysteine of Prx I-IV undergoes a reversible sulfinylation (oxidation to cysteine sulfinic acid) in cells. Desulfinylation (reduction to cysteine) is achieved by a novel enzyme named sulfiredoxin. c-Abl and Arg nonreceptor protein tyrosine kinases associate with catalase in cells treated with H2O2 by mechanisms involving the SH3 domains of the kinases and the Pro(293)PheAsnPro motif of catalase and activate catalase by phosphorylating it on Tyr(231) and Try(086). Similarily, GPx1 is activated by c-Abl- and Arg-mediated phosphorylation. The tyrosine phosphorylation is critical for ubiquitination-dependent degradation of catalase. C1 NHLBI, Lab Cell Signaling, Bethesda, MD 20892 USA. Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea. RP Bldg 50,Room 3523,South Dr,MSC 8015, Bethesda, MD 20892 USA. EM sgrhee@nih.pv NR 58 TC 207 Z9 210 U1 2 U2 24 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 MAY-JUN PY 2005 VL 7 IS 5-6 BP 619 EP 626 DI 10.1089/ars.2005.7.619 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 919BY UT WOS:000228594500009 PM 15890005 ER PT J AU Wu, XF Block, ML Zhang, W Qin, L Wilson, B Zhang, WQ Veronesi, B Hong, JS AF Wu, XF Block, ML Zhang, W Qin, L Wilson, B Zhang, WQ Veronesi, B Hong, JS TI The role of microglia in paraquat-induced dopaminergic neurotoxicity SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID ENVIRONMENTAL RISK-FACTORS; LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; ROTENONE-INDUCED DEGENERATION; PARKINSONS-DISEASE; RAT-BRAIN; NEURODEGENERATIVE DISEASES; ACTIVATED MICROGLIA; LIPID-PEROXIDATION; HERBICIDE PARAQUAT; TETRAZOLIUM SALT AB The herbicide paraquat (PQ) has been implicated as a potential risk factor for the development of Parkinson's disease. In this study, PQ (0.5-1 mu M) was shown to be selectively toxic to dopaminergic (DA) neurons through the activation of microglial NADPH oxidase and the generation of superoxide. Neuron-glia cultures exposed to PQ exhibited a decrease in DA uptake and a decline in the number of tyrosine hydroxylase-immunoreactive cells. The selectivity of PQ for DA neurons was confirmed when PQ failed to alter gamma-aminobutyric acid uptake in neuron-glia cultures. Microglia-depleted cultures exposed to I mu M PQ failed to demonstrate a reduction in DA uptake, identifying microglia as the critical cell type mediating PQ neurotoxicity. Neuron-glia cultures treated with PQ failed to generate tumor necrosis factor-alpha and nitric oxide. However, microglia-enriched cultures exposed to PQ produced extracellular superoxide, supporting the notion that microglia are a source of PQ-derived oxidative stress. Neuron-glia cultures from NADPH oxidase-deficient (PHOX-/-) mice, which lack the functional catalytic subunit of NADPH oxidase and are unable to produce the respiratory burst, failed to show neurotoxicity in response to PQ, in contrast to PHOX+/+ mice. Here we report a novel mechanism of PQ-induced oxidative stress, where at lower doses, the indirect insult generated from microglial NADPH oxidase is the essential factor mediating DA neurotoxicity. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Dalian Med Univ, Dept Physiol, Dalian, Peoples R China. Dalian Med Univ, Clin Hosp 1, Dept Neurol, Dalian, Peoples R China. US EPA, Natl Hlth & Environm Effects Univ, Off Res & Dev, Div Neurotoxicol, Res Triangle Pk, NC 27711 USA. RP NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, MD F1-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM hong3@niehs.nih.gov NR 47 TC 92 Z9 95 U1 0 U2 5 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 MAY-JUN PY 2005 VL 7 IS 5-6 BP 654 EP 661 DI 10.1089/ars.2005.7.654 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 919BY UT WOS:000228594500014 PM 15890010 ER PT J AU Rothstein, EC Lucchesi, PA AF Rothstein, EC Lucchesi, PA TI Redox control of the cell cycle: A radical encounter SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Editorial Material ID HYDROGEN-PEROXIDE; OXIDATIVE STRESS; DNA-DAMAGE; ARREST; CHECKPOINT; GROWTH; MECHANISM; P21(CIP1); KINASES C1 Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol & Expt Therapeut, New Orleans, LA 70112 USA. NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA. RP Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol, 1901 Perdido St,P7-1, New Orleans, LA 70112 USA. EM plucch@lsuhsc.edu NR 34 TC 9 Z9 13 U1 0 U2 0 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 MAY-JUN PY 2005 VL 7 IS 5-6 BP 701 EP 703 DI 10.1089/ars.2005.7.701 PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 919BY UT WOS:000228594500019 PM 15890015 ER PT J AU Oh, CK Son, HS Kwon, YW Jang, HS Kwon, KS AF Oh, CK Son, HS Kwon, YW Jang, HS Kwon, KS TI Intralesional fluorouracil injection in infantile digital fibromatosis SO ARCHIVES OF DERMATOLOGY LA English DT Article ID FIBROUS TUMORS; 5-FLUOROURACIL; CHILDHOOD; FIBROBLASTS; SURGERY; SCARS C1 Pusan Natl Univ, Dept Dermatol, Coll Med, Pusan 602739, South Korea. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Oh, CK (reprint author), Pusan Natl Univ, Dept Dermatol, Coll Med, 1-10 Ami Dong, Pusan 602739, South Korea. EM ckoh@pusan.ac.kr NR 16 TC 15 Z9 15 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAY PY 2005 VL 141 IS 5 BP 549 EP 550 DI 10.1001/archderm.141.5.549 PG 2 WC Dermatology SC Dermatology GA 925IC UT WOS:000229045800002 PM 15897374 ER PT J AU Katz, KA Yan, AC Turner, ML AF Katz, KA Yan, AC Turner, ML TI Aquagenic wrinkling of the palms in patients with cystic fibrosis homozygous for the Delta F508 CFTR mutation SO ARCHIVES OF DERMATOLOGY LA English DT Article ID REACTIVE PAPULOTRANSLUCENT ACROKERATODERMA; SYRINGEAL ACROKERATODERMA; SKIN; KERATODERMA; ROFECOXIB AB Background: Aquagenic wrinkling of the palms (AWP) is a rare condition characterized by the rapid and transient formation of edematous whitish plaques on the palms on exposure to water (the so-called hand-in-the-bucket sign). The changes may be asymptomatic or accompanied by pruritic or burning sensations. First described in 1974 in patients with cystic fibrosis-and still primarily reported in these patients-this condition has been previously described only in females. Specific mutations in CFTR, the gene responsible for cystic fibrosis, have not been reported previously in patients with AWP. Observations: We describe 2 patients with AWP, both of whom are homozygous for the &UDelta; F508 mutation in CFTR: a 17-year-old boy-the first male reported to have this condition-who has had AWP for 3 years and a 13-year-old girl who has had AWP for 6 months. Conclusions: Cystic fibrosis should be considered in patients with AWP, and patients with cystic fibrosis should be asked about symptoms of this condition. Although the etiology of AWP is unknown, the association with cystic fibrosis, and with marasmus and cyclooxygenase-2 inhibitors, suggests that exposure of the skin to abnormally high concentrations of salt may play a role in its pathogenesis. C1 Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Pediat & Dermatol, Sect Pediat Dermatol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Katz, KA (reprint author), Univ Penn, Dept Dermatol, 3600 Spruce St,2 Maloney, Philadelphia, PA 19104 USA. EM Kenneth.katz@uphs.upenn.edu NR 25 TC 39 Z9 41 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAY PY 2005 VL 141 IS 5 BP 621 EP 624 DI 10.1001/archderm.141.5.621 PG 4 WC Dermatology SC Dermatology GA 925IC UT WOS:000229045800013 PM 15897385 ER PT J AU Talamini, LM Meeter, M Elvevag, B Murre, JMJ Goldberg, TE AF Talamini, LM Meeter, M Elvevag, B Murre, JMJ Goldberg, TE TI Reduced parahippocampal connectivity produces schizophrenia-like memory deficits in simulated neural circuits with reduced parahippocampal connectivity SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID HIPPOCAMPAL-FORMATION; RECOGNITION MEMORY; SYNAPTIC CONNECTIVITY; ASSOCIATIVE MEMORY; ENTORHINAL CORTEX; EPISODIC MEMORY; IMPAIRMENT; RECALL; PATTERNS; DISORDER AB Context: Episodic memory impairments are well char acterized in schizophrenia, but their neural origin is unclear. Objective: To determine whether the episodic memory impairments in schizophrenia may originate from reduced parahippocampal connectivity. Design: Experimental in silico model. Setting: Department of Psychology, University of Amsterdam, Amsterdam, the Netherlands. Interventions: A new, in silico medial temporal lobe model that simulates normal performance on a variety of episodic memory tasks was devised. The effects of reducing parahippocampal connectivity in the model (from perirhinal and parahippocampal cortex to entorhinal cortex and from entorhinal cortex to hippocampus) were evaluated and compared with findings in schizophrenic patients. Alternative in silico neuropathologies, increased noise and loss of hippocampal neurons, were also evaluated. Results: In the model, parahippocampal processing subserves integration of different cortical inputs to the hippocampus and feature extraction during recall. Reduced connectivity in this area resulted in a pattern of deficits that closely mimicked the impairments in schizophrenia, including a mild recognition impairment and a more severe impairment in free recall. Furthermore, the schizophrenic model was not differentially sensitive to interference, also consistent with behavioral data. Notably, neither increased noise levels nor a reduction of hippocampal nodes in the model reproduced this characteristic memory profile. Conclusions: Taken together, these findings highlight the importance of parahippocampal neuropathology in schizophrenia, demonstrating that reduced connectivity in this region may underlie episodic memory problems associated with the disorder. C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Univ Amsterdam, Dept Psychol, Amsterdam, Netherlands. Johnson & Johnson PR&D, Div CNS Psychiat 1, Beerse, Belgium. RP Goldberg, TE (reprint author), NIMH, Clin Brain Disorders Branch, 10 Ctr Dr,MSC 1379, Bethesda, MD 20892 USA. EM GoldberT@INTRA.NIMH.nih.gov RI Meeter, Martijn/A-2926-2009; OI Meeter, Martijn/0000-0002-5112-6717; Murre, Jaap/0000-0003-4447-9482 NR 52 TC 42 Z9 42 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 2005 VL 62 IS 5 BP 485 EP 493 DI 10.1001/archpsyc.62.5.485 PG 9 WC Psychiatry SC Psychiatry GA 923JG UT WOS:000228905600003 PM 15867101 ER PT J AU Sparks, DL Sabbagh, MN Connor, DJ Lopez, J Launer, LJ Browne, P Wasser, D Johnson-Traver, S Lochhead, J Ziolwolski, C AF Sparks, DL Sabbagh, MN Connor, DJ Lopez, J Launer, LJ Browne, P Wasser, D Johnson-Traver, S Lochhead, J Ziolwolski, C TI Atorvastatin for the treatment of mild to moderate Alzheimer disease - Preliminary results SO ARCHIVES OF NEUROLOGY LA English DT Article ID BETA-AMYLOID IMMUNOREACTIVITY; DIAGNOSIS; DEMENTIA; SCALE; RISK; CHOLESTEROL; PROGRESSION; INVENTORY AB Background: Laboratory evidence of cholesterol-induced production of amyloid β as a putative neurotoxin precipitating Alzheimer disease, along with epidemiological evidence, suggests that cholesterol-lowering statin drugs may favorably influence the progression of the disorder. Objective: To determine if treatment with atorvastatin calcium affects the cognitive and/or behavioral decline in patients with mild to moderate Alzheimer disease. Design: Pilot intention-to-treat, proof-of-concept, double-blind, placebo-controlled, randomized (1: 1) trial with a 1-year exposure to once-daily atorvastatin calcium (80 mg; two 40-mg tablets) or placebo using last observation carried forward analysis of covariance as the primary method of statistical assessment. Participants: Individuals with mild to moderate Alzheimer disease (Mini-Mental State Examination score of 12-28) were recruited. Of the 98 participants providing informed consent, 71 were eligible for randomization, 67 were randomized, and 63 subjects completed the 3-month visit and were considered evaluable. Main Outcome Measures: The primary outcome measures were change in Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Global Impression of Change Scale scores. The secondary outcome measures included scores on the Mini-Mental State Examination, Geriatric Depression Scale, the Neuropsychiatric Inventory Scale, and the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. The tertiary outcome measures included total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels. Results: Atorvastatin reduced circulating cholesterol levels and produced a positive signal on each of the clinical outcome measures compared with placebo. This beneficial effect reached significance for the Geriatric Depression Scale and the Alzheimer's Disease Assessment Scale-cognitive subscale at 6 months and was significant at the level of a trend for the Alzheimer's Disease Assessment Scale-cognitive subscale, Clinical Global Impression of Change Scale, and Neuropsychiatric Inventory Scale at 12 months assessed by analysis of covariance with last observation carried forward. Conclusion: Atorvastatin treatment may be of some clinical benefit and could be established as an effective therapy for Alzheimer disease if the current findings are substantiated by a much larger multicenter trial. C1 Sun Hlth Res Inst, Sun City, AZ 85351 USA. NIA, Bethesda, MD USA. Walter O Boswell Hosp, Dept Cardiol, Sun City, AZ USA. Walter O Boswell Hosp, Dept Pharm, Sun City, AZ USA. RP Sparks, DL (reprint author), Sun Hlth Res Inst, 10515 W Santa Fe Dr, Sun City, AZ 85351 USA. EM larry.sparks@sunhealth.org NR 22 TC 273 Z9 291 U1 2 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2005 VL 62 IS 5 BP 753 EP 757 DI 10.1001/archneur.62.5.753 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 925IV UT WOS:000229047700007 PM 15883262 ER PT J AU Pryor, SP Demmler, G Madeo, AC Yang, Y Zalewski, CK Brewer, CC Butman, JA Fowler, KB Griffith, AJ AF Pryor, SP Demmler, G Madeo, AC Yang, Y Zalewski, CK Brewer, CC Butman, JA Fowler, KB Griffith, AJ TI Investigation of the role of congenital cytomegalovirus infection in the etiology of enlarged vestibular aqueducts SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID SENSORINEURAL HEARING-LOSS; PENDRED-SYNDROME; INNER-EAR; GENE PDS; CHILDREN; POPULATION; MUTATIONS; DEAFNESS; INFANTS; DISEASE AB Objective: To determine whether congenital cytomegalovirus (CMV) infection is an etiologic factor in the pathogenesis of enlarged vestibular aqueducts (EVA). Design: Two different cohort studies. Subjects: The study population comprised 19 subjects with a history of congenital CMV infection and sensorineural hearing loss (cohort 1); 39 subjects with nonsyndromic EVA and their unaffected mothers (cohort 2); and 16 control subjects with EVA associated with Pendred syndrome and bi-allelic mutations of the SLC26A4 gene and their unaffected mothers. Results: In cohort 1, we detected EVA in 0 of 19 subjects with congenital CMV infection and sensorineural hearing loss. In cohort 2, anti-CMV serologic profiles were consistent with possible congenital CMV infection in 10 (26%) of 39 subjects with nonsyndromic EVA and 6 (38%) of 16 control subjects with Pendred syndrome (P=.52). These seroprevalence rates are similar to those expected in the general population (40%). Conclusion: In spite of their auditory phenotypic similarities, congenital CMV infection is not a significant factor in the etiology of EVA. C1 NIH, Sect Gene Struct & Funct, Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA. NIH, Off Clin Director, Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. NIH, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Maternal & Child Hlth, Birmingham, AL 35294 USA. RP Griffith, AJ (reprint author), NIH, Sect Gene Struct & Funct, Natl Inst Deafness & Other Commun Disorders, 5 Res Ct,Room 2A-01, Rockville, MD 20850 USA. EM griffita@nided.nih.gov RI Butman, John/A-2694-2008; Madeo, Anne/K-2880-2012; OI Butman, John/0000-0002-1547-9195 FU NCRR NIH HHS [5MO1 RR00188-33]; NICHD NIH HHS [2 P30 HD24064-11, HD97003, P01 HD010699, P01 HD10699]; NIDCD NIH HHS [R01 DC002139]; PHS HHS [N01-A1-15113] NR 25 TC 10 Z9 11 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD MAY PY 2005 VL 131 IS 5 BP 388 EP 392 DI 10.1001/archotol.131.5.388 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 924SX UT WOS:000229001800003 PM 15897416 ER PT J AU Rubinow, DR AF Rubinow, DR TI Reproductive steroids in context SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Editorial Material DE sex; steroids; context; estradiol; progesterone; mood disorders ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; PREMENSTRUAL-SYNDROME; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; GONADAL-STEROIDS; TESTOSTERONE; EXPRESSION; RECEPTORS; BRAIN AB The effects of reproductive steroids on the brain are highly context-dependent, a concept necessary to understand disorders of mood related to the reproductive endocrine system. C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. RP Rubinow, DR (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10,CRC Room 6-5340,10 Ctr Dr MSC 1276, Bethesda, MD 20892 USA. EM rubinowd@intra.nimh.nih.gov NR 21 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD MAY PY 2005 VL 8 IS 1 BP 1 EP 5 DI 10.1007/s00737-005-0065-0 PG 5 WC Psychiatry SC Psychiatry GA 015LC UT WOS:000235551900001 PM 15868393 ER PT J AU Kim, JA Koh, KK Quon, MJ AF Kim, JA Koh, KK Quon, MJ TI The union of vascular and metabolic actions of insulin in sickness and in health SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Editorial Material ID NITRIC-OXIDE SYNTHASE; MUSCLE GLUCOSE-UPTAKE; UPTAKE IN-VIVO; RECEPTOR SUBSTRATE-1; ENDOTHELIAL-CELLS; MICE LACKING; MICROVASCULAR RECRUITMENT; STIMULATED PRODUCTION; RESISTANCE; HYPERTENSION C1 NIH, Diabet Unit, NCCAM, Bethesda, MD 20892 USA. Gachon Med Sch, Gil Heart Ctr, Vasc Med & Atherosclerosis Unit, Inchon, South Korea. RP Quon, MJ (reprint author), NIH, Diabet Unit, NCCAM, 10 Ctr Dr,Bldg 10,Room 6C-205, Bethesda, MD 20892 USA. EM quonm@nih.gov RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 30 TC 51 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2005 VL 25 IS 5 BP 889 EP 891 DI 10.1161/01.ATV.0000164044.42910.6b PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 922AE UT WOS:000228806900361 PM 15863720 ER PT J AU Zieman, SJ Melenovsky, V Kass, DA AF Zieman, SJ Melenovsky, V Kass, DA TI Mechanisms, pathophysiology, and therapy of arterial stiffness SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE arterial stiffness; isolated systolic hypertension; mechanisms; therapeutics; pathophysiology ID ISOLATED SYSTOLIC HYPERTENSION; GLYCATION END-PRODUCTS; SMOOTH-MUSCLE-CELLS; NITRIC-OXIDE SYNTHASE; PULSE-WAVE VELOCITY; AGE-RELATED-CHANGES; CARDIOVASCULAR-DISEASE ENTERPRISES; ANGIOTENSIN-CONVERTING ENZYME; DEPENDENT DIABETES-MELLITUS; DIASTOLIC BLOOD-PRESSURE AB Arterial stiffness is a growing epidemic associated with increased risk of cardiovascular events, dementia, and death. Decreased compliance of the central vasculature alters arterial pressure and flow dynamics and impacts cardiac performance and coronary perfusion. This article reviews the structural, cellular, and genetic contributors to arterial stiffness, including the roles of the scaffolding proteins, extracellular matrix, inflammatory molecules, endothelial cell function, and reactive oxidant species. Additional influences of atherosclerosis, glucose regulation, chronic renal disease, salt, and changes in neurohormonal regulation are discussed. A review of the hemodynamic impact of arterial stiffness follows. A number of lifestyle changes and therapies that reduce arterial stiffness are presented, including weight loss, exercise, salt reduction, alcohol consumption, and neuroendocrine-directed therapies, such as those targeting the renin-angiotensin aldosterone system, natriuretic peptides, insulin modulators, as well as novel therapies that target advanced glycation end products. C1 Johns Hopkins Univ Hosp, Div Cardiol, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, NIA, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, NIA, Gerontol Res Ctr, Div Cardiol, Baltimore, MD 21205 USA. RP Zieman, SJ (reprint author), Johns Hopkins Univ Hosp, Div Cardiol, Carnegie 568,600 N Wolfe St, Baltimore, MD 21287 USA. EM szieman@jhmi.edu OI Melenovsky, Vojtech/0000-0001-8921-7078 FU NHLBI NIH HHS [1K23HL73059]; NIA NIH HHS [AG-18324] NR 219 TC 628 Z9 669 U1 5 U2 61 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2005 VL 25 IS 5 BP 932 EP 943 DI 10.1161/01.ATV.0000160548.78317.29 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 922AE UT WOS:000228806900367 PM 15731494 ER PT J AU Neufeld, EB O'Brien, KG Stonik, JA Demosky, SJ Sabol, S Remaley, AT Santamarina-Fojo, S Brewer, HB AF Neufeld, EB O'Brien, KG Stonik, JA Demosky, SJ Sabol, S Remaley, AT Santamarina-Fojo, S Brewer, HB TI Cellular localization, trafficking, and function of the human ABCG1 transporter SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 6th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 28-30, 2005 CL Washington, DC C1 NHLBI, NIH, Bethesda, MD 20892 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2005 VL 25 IS 5 BP E71 EP E71 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 922AE UT WOS:000228806900156 ER PT J AU Nofer, JR Feuerborn, R Engel, T Remaley, AT Assmann, G AF Nofer, JR Feuerborn, R Engel, T Remaley, AT Assmann, G TI Apolipoprotein A-I activates cellular Cdc42 signaling through the ABCA1 transporter SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 6th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 28-30, 2005 CL Washington, DC C1 Inst Clin Chem, Munster, Germany. Univ Munster, Inst Arteriosclerosis Res, D-4400 Munster, Germany. NIH, Bethesda, MD 20892 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2005 VL 25 IS 5 BP E71 EP E71 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 922AE UT WOS:000228806900157 ER PT J AU Wagner, EM Basso, F Amar, MJ Vaisman, B Freeman, L Brewer, HB Santamarina-Fojo, S AF Wagner, EM Basso, F Amar, MJ Vaisman, B Freeman, L Brewer, HB Santamarina-Fojo, S TI Modulation of sterol transport in ABCG1 x ABCG5/G8 transgenic mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 6th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 28-30, 2005 CL Washington, DC C1 NIH, Bethesda, MD 20892 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2005 VL 25 IS 5 BP E89 EP E89 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 922AE UT WOS:000228806900259 ER PT J AU Phillips, SJ Phillips, RS AF Phillips, SJ Phillips, RS TI Devices and the food and drug administration SO ARTIFICIAL ORGANS LA English DT Editorial Material C1 Iowa Heart Ctr, Des Moines, IA USA. Natl Lib Med, NIH, Bethesda, MD USA. American Univ, Washington, DC 20016 USA. EM SP226@aol.com NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD MAY PY 2005 VL 29 IS 5 BP 363 EP 365 DI 10.1111/j.1525-1594.2005.01080.x PG 3 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 918PQ UT WOS:000228560500001 PM 15854210 ER PT J AU Huang, BX Dass, C Kim, HY AF Huang, BX Dass, C Kim, HY TI Probing conformational changes of human serum albumin due to unsaturated fatty acid binding by chemical cross-linking and mass spectrometry SO BIOCHEMICAL JOURNAL LA English DT Article DE arachidonic acid; conformational change; docosahexaenoic acid; MS; oleic acid; serum albumin ID 3-DIMENSIONAL STRUCTURE; PROTEIN-INTERACTION; CRYSTAL-STRUCTURE; LINKED PEPTIDES; SITES; IDENTIFICATION; REAGENTS; COMPLEXES; REVEALS AB Mass spectrometry with chemical cross-linking was used to probe the conformational changes of HSA (human serum albumin) in solution on interaction with monounsaturated OA (oleic acid) or polyunsaturated AA (arachidonic acid) or DHA (docosahexaenoic acid). Fatty acid-free or -bound HSA was modified with lysine-specific cross-linkers and digested with trypsin. Cross-linked peptides were analysed by nano-electrospray ionization MS to localize the sites of cross-linking. Our data indicated that a local conformational change involving movement of the side chains of Lys-402 of subdomain IIIA or Lys-541 of subdomain IIIB occurred upon binding of all three fatty acids. Our data also indicated that the side chains of Lys-205 (IIA) and Lys-466 (IIIA) moved closer towards each other upon binding AA or DHA, but not OA, suggesting that the conformations of HSA when bound to mono- and poly-unsaturated fatty acids are distinctively different. While these observations agreed with previous X-ray crystallographic studies, the distances between ε-amino groups of most cross-linked lysine pairs were shorter than-the crystal structure predicted, possibly reflecting a discrepancy between the solution and crystal structures. This method can serve as a useful complement to X-ray crystallography, particularly in probing the structure of a protein in solution. C1 NIAAA, Sect Mass Spectrometry, Lab Membrane Biophys & Biochem, NIH, Bethesda, MD 20892 USA. Univ Memphis, Dept Chem, Memphis, TN 38152 USA. RP Kim, HY (reprint author), NIAAA, Sect Mass Spectrometry, Lab Membrane Biophys & Biochem, NIH, Bethesda, MD 20892 USA. EM hykim@nih.gov FU NIAAA NIH HHS [Z01 AA000284-16] NR 32 TC 49 Z9 51 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 2005 VL 387 BP 695 EP 702 DI 10.1042/BJ20041624 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 926PR UT WOS:000229135600015 PM 15588254 ER PT J AU Monteiro, RQ Rezaie, AR Ribeiro, JMC Francischetti, IMB AF Monteiro, RQ Rezaie, AR Ribeiro, JMC Francischetti, IMB TI Ixolaris: a factor Xa heparin-binding exosite inhibitor SO BIOCHEMICAL JOURNAL LA English DT Article DE blood feeding; Factor Xa; heparin-binding exosite; prothrombin; tick saliva ID HUMAN ALPHA-THROMBIN; FACTOR PATHWAY INHIBITOR; BLOOD-COAGULATION FACTOR; FACTOR-VA; PROTHROMBINASE COMPLEX; TISSUE FACTOR; SUBSTRATE RECOGNITION; PROTEIN-C; CRYSTAL-STRUCTURE; BASIC RESIDUES AB Ixolaris is a two-Kunitz TFPI (tissue factor pathway inhibitor) from the tick salivary gland. In contrast with human TFPI, Ixolaris binds tightly to the zymogen FX (Factor X) and to dansyl-Glu-Gly-Arg-chloromethyl ketone-treated FXa (DEGR-FXa; active-site-blocked FXa), indicating that exosites are involved in the FX(a)-Ixolaris interaction. Here we provide evidence that Ixolaris binds specifically to the FXa HBE (heparin-binding exosite), since (i) it markedly decreases the inhibition of FXa by the antithrombin-heparin but not the antithrombin-pentasaccharide complex, (ii) it impairs FXa binding to Sepharose-immobilized heparin, and (iii) it allosterically modulates the catalytic activity of FXa for small chromogenic substrates (S-2765). By using a series of recombinant FXa mutants in which the HBE is mutated, we have identified the importance of amino acids involved in the enzyme-inhibitor interaction as being in the following order: Arg-93 &MGT; Arg-165 &GE; Lys-169 > Lys-236 > Lys-96 > Arg-240 > Arg-125. Ixolaris at appropriate concentrations also inhibits thrombin formation in vitro by the assembled prothrombinase complex, a process that is critically dependent on the FXa HBE. Ixolaris is the first inhibitor characterized to date that binds specifically to the FXa HBE. C1 NIAID, LMVR, NIH, Sect Med Entomol, Bethesda, MD 20892 USA. Univ Fed Rio de Janeiro, Inst Bioquim Med, Programa Biol Estructural, BR-21941590 Rio De Janeiro, Brazil. St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA. RP Francischetti, IMB (reprint author), NIAID, LMVR, NIH, Sect Med Entomol, 12735 Twinbrook Pkwy,Twinbrook 3 Bldg,Room 2E-28, Bethesda, MD 20892 USA. EM ifrancischetti@niaid.nih.gov RI Monteiro, Robson/B-8007-2014; OI Ribeiro, Jose/0000-0002-9107-0818 FU NHLBI NIH HHS [R01 HL062565, HL 62565] NR 38 TC 41 Z9 42 U1 0 U2 3 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 2005 VL 387 BP 871 EP 877 DI 10.1042/BJ20041738 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 926PR UT WOS:000229135600036 PM 15617517 ER PT J AU Ozbun, LL Martinez, A Jakowlew, SB AF Ozbun, LL Martinez, A Jakowlew, SB TI Differentially expressed nucleolar TGF-beta 1 target (DENTT) shows tissue-specific nuclear and cytoplasmic localization and increases TGF-beta 1-responsive transcription in primates SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE differentially expressed nucleolar TGF-beta 1target; TSPY/TSPY-like/SET/NAP-1; monkey; immunochemistry; nucleus; transcription ID TRANSFORMING-GROWTH-FACTOR; HUMAN Y-CHROMOSOME; TESTIS-SPECIFIC PROTEIN; BRAIN-SPECIFIC GENE; RETINOIC ACID; FACTOR-BETA; TGF-BETA; MOLECULAR-CLONING; MESSENGER-RNAS; LUNG-CARCINOMA AB Differentially Expressed Nucleolar TGF-beta 1 Target (DENTT) is a new member of the TSPY/TSPY-like/SET/NAP-1 (TTSN) superfamily whose mRNA is induced by TGF-beta 1 in TGF-beta 1-responsive human lung cancer cells. Monkey DENTT mRNA contains a 2085-bp open reading frame that encodes a predicted polypeptide of 695 amino acids with five nuclear localization signals, two coiled-coil regions, and a domain that shows significant identity to a region that defines the TTSN superfamily. RT-PCR amplification and Western blot analyses showed DENTT mRNA and protein in adult monkey tissues, including the adrenal gland, cerebral cortex, and ovary. Immunohistochemical staining showed that numerous neurons were intensely immunoreactive for DENTT, as were anterior pituitary secretory cells, thyroid follicular cells, and smooth muscle cells of arteries and lung bronchial walls. DENTT expression was also prominent in monkey bronchiolar-alveolar adenomas and cell lines. While the addition of TGF-beta 1 or retinoic acid to monkey normal lung bronchial 12MBr6 cells and human lung cancer NCI-H727 cells increased DENTT protein production, TGF-beta 1 together with retinoic acid resulted in a more sustained increase in DENTT production than with TGF-beta 1 or retinoic acid alone. Transient transfection studies showed that ectopic DENTT expression significantly increased TGF-beta 1-responsive 3TP-Lux and CAGA12-Lux reporter transcription in 12MBr6 and NCI-H727 cells with TGF-beta 1 addition, while ectopic DENTT expression had no significant effect on the transcription of a retinoic acid-responsive element reporter in the presence of retinoic acid or TGF-beta 1. These findings suggest new possibilities for DENTT as a TGF-beta 1-regulated, but not a retinoic acid-regulated member of the TTSN superfamily in primate physiology. (c) 2005 Elsevier B.V. All rights reserved. C1 Natl Canc Inst, Cell & Canc Biol Branch, Rockville, MD 20850 USA. RP Natl Canc Inst, Cell & Canc Biol Branch, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM jakowles@mail.nih.gov RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 51 TC 12 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD MAY 1 PY 2005 VL 1728 IS 3 BP 163 EP 180 DI 10.1016/j.bbaexp.2005.02.010 PG 18 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 924GJ UT WOS:000228966700007 PM 15823505 ER PT J AU Geho, D Lahar, N Gurnani, P Huebschman, M Herrmann, P Espina, V Shi, A Wulfkuhle, J Garner, H Petricoin, E Liotta, LA Rosenblatt, KP AF Geho, D Lahar, N Gurnani, P Huebschman, M Herrmann, P Espina, V Shi, A Wulfkuhle, J Garner, H Petricoin, E Liotta, LA Rosenblatt, KP TI Pegylated, steptavidin-conjugated quantum dots are effective detection elements for reverse-phase protein microarrays SO BIOCONJUGATE CHEMISTRY LA English DT Article ID BIOLOGICAL DETECTION; ACTIVATION; CANCER; NANOCRYSTALS; SPECIMENS; CELLS AB Protein microarray technologies provide a means of investigating the proteomic content of clinical biopsy specimens in order to determine the relative activity of key nodes within cellular signaling pathways. A particular kind of protein microarray, the reverse-phase microarray, is being evaluated in clinical trials because of its potential to utilize limited amounts of cellular material obtained through biopsy. Using this approach, cellular lysates are arrayed in dilution curves on nitrocellulose substrates for subsequent probing with antibodies. To improve the sensitivity and utility of reverse-phase microarrays, we tested whether a new reporter technology as well as a new detection instrument could enhance microarray performance. We describe the use of an inorganic fluorescent nanoparticle conjugated to streptavidin, Qdot 655 Sav, in a reverse-phase protein microarray format for signal pathway profiling. Moreover, a pegylated form of this bioconjugate, Qdot 655 Sav, is found to have superior detection characteristics in assays performed on cellular protein extracts over the nonpegylated form of the bioconjugate. Hyperspectral imaging of the quantum dot microarray enabled unamplified detection of signaling proteins within defined cellular lysates, which indicates that this approach may be amenable to multiplexed, high-throughput reverse-phase protein microarrays; in which numerous analytes are measured in parallel within a single spot. C1 SW Texas State Univ, Div Translat Pathol, Dept Pathol, Dallas, TX 75390 USA. NCI, Pathol Lab, NIH, FDA Clin Proteom Program, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Off Cellular & Gene Therapy, Bethesda, MD 20892 USA. RP Rosenblatt, KP (reprint author), SW Texas State Univ, Div Translat Pathol, Dept Pathol, Dallas, TX 75390 USA. EM kevin.rosenblatt@utsouthwestern.edu OI Espina, Virginia/0000-0001-5080-5972 NR 26 TC 100 Z9 103 U1 1 U2 7 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 MAY-JUN PY 2005 VL 16 IS 3 BP 559 EP 566 DI 10.1021/bc0479113 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 928MC UT WOS:000229274800012 PM 15898722 ER PT J AU Lever, JR Zou, MF Parnas, ML Duval, RA Wirtz, SE Justice, JB Vaughan, RA Newman, AH AF Lever, JR Zou, MF Parnas, ML Duval, RA Wirtz, SE Justice, JB Vaughan, RA Newman, AH TI Radioiodinated azide and isothiocyanate derivatives of cocaine for irreversible labeling of dopamine transporters: Synthesis and covalent binding studies SO BIOCONJUGATE CHEMISTRY LA English DT Article ID PHOTOAFFINITY LIGANDS; ANALOGS; BENZTROPINE; DOMAINS; RADIOSYNTHESIS AB Two novel N-substituted-3 beta-phenyltropane alkaloids have been labeled with iodine-125 for use as irreversible probes of dopamine transporter (DAT) binding sites. One contains an iodoaryl azide moiety for photolabeling, while the other bears an iodoaryl isothiocyanate for direct conjugation. Both radioligands were prepared in a one-flask procedure by electrophilic radioiodination of the corresponding aniline under no-carrier-added conditions, followed either by diazotization and treatment with sodium azide, or by addition of thiophosgene under basic conditions. Specifically, (-)-N-[4-(3-[I-125]iodo-4-azidophenyl)butyl]-2 beta-carbomethoxy-3-(4-chlorophenyl)tropane ([I-125]MFZ-2-24) and (-)N-[4-(3-[I-125]iodo-4-isothiocyanophenyl)butyl]-2 beta-carbomethoxy-3-(4-chlorophenyl)tropane ([I-125] MFZ 3-37) were synthesized. Isolation by reversed-phase HPLC and solid-phase extraction gave good average yields of [I-125] MFZ-2-24 (67%, n = 5) and [I-125]MFZ-3-37 (45%, n = 3) with high radiochemical purities (96-99%) and specific radioactivities (> 2000 mCi/mu mol). The utility of the radioligands was demonstrated by their covalent linkage to rat striatal membranes, and immunoprecipitation of a single radiolabeled band at 80 kDa corresponding to the full-length DAT. C1 Univ Missouri, Dept Radiol, Columbia, MO 65212 USA. Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO 65212 USA. Harry S Truman Mem Vet Hosp, Res Serv, Columbia, MO 65201 USA. Natl Inst Drug Abuse, Intramural Res Program, Med Chem Sect, Baltimore, MD 21224 USA. Univ N Dakota, Dept Biochem & Mol Biol, Grand Forks, ND 58203 USA. Emory Univ, Dept Chem, Atlanta, GA 30322 USA. RP Lever, JR (reprint author), Univ Missouri, Dept Radiol, M292 Med Sci Bldg,1 Hosp Dr, Columbia, MO 65212 USA. EM leverj@health.missouri.edu RI Duval, Romain/K-2299-2016 OI Duval, Romain/0000-0002-0125-506X FU NIDA NIH HHS [DA15175, DA11176] NR 27 TC 13 Z9 13 U1 0 U2 3 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 MAY-JUN PY 2005 VL 16 IS 3 BP 644 EP 649 DI 10.1021/bc0497214 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 928MC UT WOS:000229274800023 PM 15898733 ER PT J AU Misteli, T AF Misteli, T TI Concepts in nuclear architecture SO BIOESSAYS LA English DT Review ID GREEN FLUORESCENT PROTEIN; MAMMALIAN-CELL NUCLEUS; GENE-EXPRESSION; GLUCOCORTICOID-RECEPTOR; SPLICING FACTOR; COILED BODIES; CAJAL BODIES; LIVING CELLS; HUMAN GENOME; CHROMOSOME TERRITORIES AB Genomes are defined by their primary sequence. The functional properties of genomes, however, are determined by far more complex mechanisms and depend on multiple layers of regulatory control processes. A key emerging contributor to genome function is the architectural organization of the cell nucleus. The spatial and temporal behavior of genomes and their regulatory proteins are now being recognized as important, yet still poorly understood, control mechanisms in genome function. Combined cell biological, molecular and computational analysis of architectural aspects of genome function has added a further dimension to the investigation of some of the most fundamental cellular processes including transcription and maintenance of genome integrity. The complete elucidation of the contribution that nuclear architecture makes to gene expression will be required to fully understand physiological processes such as differentiation, development and disease at the cellular level. Here I give an overview of some of the emerging concepts in the study of in vivo genome organization and function. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov NR 100 TC 167 Z9 173 U1 2 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD MAY PY 2005 VL 27 IS 5 BP 477 EP 487 DI 10.1002/bies.20226 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 921VV UT WOS:000228794500004 PM 15832379 ER PT J AU Ogurtsov, AY AF Ogurtsov, AY TI A protocol of automatic alignment of genome sequences using the program OWEN SO BIOFIZIKA LA Russian DT Article DE alignment of DNA sequences; intergenic region ID INTERGENIC REGIONS; COLLINEAR REGIONS AB A protocol of automatic hierarchical alignment of long DNA sequences using the program OWEN is described. The protocol is based on the command line regime of the program OWEN. The protocol makes it possible to align a large number of pairs of moderately similar sequences automatically. We used this protocol to align 8623 orthologous pairs of intergenic regions in human and murine genomes. C1 Russian Acad Sci, Inst Theoret & Expt Biophys, Pushchino 142292, Moscow Region, Russia. NIH, NCBI, Bethesda, MD 20892 USA. RP Ogurtsov, AY (reprint author), Russian Acad Sci, Inst Theoret & Expt Biophys, Pushchino 142292, Moscow Region, Russia. NR 9 TC 1 Z9 1 U1 0 U2 0 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0006-3029 J9 BIOFIZIKA+ JI Biofizika PD MAY-JUN PY 2005 VL 50 IS 3 BP 475 EP 479 PG 5 WC Biophysics SC Biophysics GA 935VH UT WOS:000229811000013 PM 15977838 ER PT J AU Grillon, C Warner, V Hille, J Merikangas, KR Bruder, GE Tenke, CE Nomura, Y Leite, P Weissman, MM AF Grillon, C Warner, V Hille, J Merikangas, KR Bruder, GE Tenke, CE Nomura, Y Leite, P Weissman, MM TI Families at high and low risk for depression: A three-generation startle study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE high risk; major depressive disorder; anxiety; startle; psychophysiology ID FEAR-POTENTIATED STARTLE; POSTTRAUMATIC-STRESS-DISORDER; UNIPOLAR DEPRESSION; PREPULSE INHIBITION; ANXIETY DISORDERS; VIETNAM VETERANS; ACOUSTIC STARTLE; EARLY-ONSET; PARENTS; ADOLESCENTS AB Background: Anxiety symptoms might be a vulnerability factor for the development of major depressive disorder (MDD), Because elevated startle magnitude in threatening contexts is a marker for anxiety disorder, the present study investigated the hypothesis that enhanced startle reactivity would also be found in children and grandchildren of individuals with MDD. Methods: The magnitude of startle was investigated in two tests (anticipation of an unpleasant blast of air and during darkness) in children (second generation) and grandchildren (third generation) of probands with (high risk) or without (low risk) MDD (first generation), Results: Startle discriminated between the low- and high-risk groups, In the probands' children, the high-risk group showed increased startle magnitude throughout the fear-potentiated startle test. In the probands' grandchildren, a gender-specific abnormality was found in the high-risk group with high-risk girls, but not boys, exhibiting elevated startle magnitude throughout the procedure. Conclusions: Increased startle reactivity in threatening contexts, previously found inpatients with anxiety disorder and in children of parents with an anxiety disorder, might also constitute a vulnerability marker for MDD, These findings suggest that there might be common biologic diatheses underlying depression and anxiety. C1 NIMH, NIH, DHHS, MAP,Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, Div Biopsychol, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, Div Clin & Genet Epidemiol, New York, NY 10032 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Grillon, C (reprint author), NIMH, NIH, DHHS, MAP,Mood & Anxiety Disorder Program, 15K N Dr,Bldg 15K,Room 113,MSC 2670, Bethesda, MD 20892 USA. EM Christian.Grillon@nih.gov OI Tenke, Craig/0000-0002-0924-4314; Weissman, Myrna/0000-0003-3490-3075 FU NIMH NIH HHS [MH36197, MH36295] NR 38 TC 74 Z9 75 U1 2 U2 8 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 MAY 1 PY 2005 VL 57 IS 9 BP 953 EP 960 DI 10.1016/j.biopsych.2005.01.045 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 919IO UT WOS:000228611900001 PM 15860334 ER PT J AU Milham, MP Nugent, AC Drevets, WC Dickstein, DP Leibenluft, E Ernst, M Charney, D Pine, DS AF Milham, MP Nugent, AC Drevets, WC Dickstein, DP Leibenluft, E Ernst, M Charney, D Pine, DS TI Selective reduction in amygdala volume in pediatric anxiety disorders: A voxel-based morphometry investigation SO BIOLOGICAL PSYCHIATRY LA English DT Article DE pediatric anxiety; major depressive disorder; amygdala; voxel-based morphometry ID TEMPORAL GYRUS VOLUMES; MALTREATED CHILDREN; ADOLESCENTS; IMAGES; FMRI; FLUVOXAMINE; THREAT; SCALE AB Background Significant controversy has emerged concerning pediatric anxiety disorders. Some researchers question the justification for diagnosing and treating pediatric anxiety disorders, owing to concerns about the inappropriate medicalization of social problems. Others note the importance of diagnosis and treatment, given that pediatric anxiety disorders represent a strong risk factor for serious adult mental disorders. We examine the neural correlates of pediatric anxiety disorders, to consider the validity of the categorization scheme used in recent treatment studies. Methods: Using inclusion criteria derived from recent treatment trials, we compared gray matter volume throughout the brain in children with and without anxiety. Morphometric analyses used optimized voxel-based morphometry, an automated method for examining structural changes throughout the brain. Results: Reductions in left amygdala gray matter volume were noted for patients with anxiety disorders relative to comparison subjects. Conclusions: We discuss implications of these findings for current controversies. C1 NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Illinois, Beckman Inst, Urbana, IL 61801 USA. RP Milham, MP (reprint author), NYU, Sch Med, 150 E 30th St,Apt 5A, New York, NY 10016 USA. EM milham01@med.nyu.edu OI Nugent, Allison/0000-0003-2569-2480 NR 36 TC 86 Z9 87 U1 6 U2 13 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 MAY 1 PY 2005 VL 57 IS 9 BP 961 EP 966 DI 10.1016/j.biopsych.2005.01.0383 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 919IO UT WOS:000228611900002 PM 15860335 ER PT J AU Asbahr, FR Garvey, MA Snider, LA Zanetta, DM Elkis, H Swedo, SE AF Asbahr, FR Garvey, MA Snider, LA Zanetta, DM Elkis, H Swedo, SE TI Obsessive-compulsive symptoms among patients with sydenham chorea SO BIOLOGICAL PSYCHIATRY LA English DT Article DE sydenham chorea; rheumatic fever; obsessive-compulsive symptoms; obsessive-compulsive disorder; tic disorders; factor analysis ID AUTOIMMUNE NEUROPSYCHIATRIC DISORDERS; TOURETTES-SYNDROME; TIC DISORDERS; ADOLESCENTS; CHILDREN; RELIABILITY; DIMENSIONS; SAMPLE; CHILDHOOD; INTERVIEW AB Background. Among patients with tic disorders, a distinctive clinical profile of obsessive-compulsive symptomatology has been described. The present investigation was designed to document the phenomenology of obsessive-compulsive symptoms (OCS) among patients with Sydenham chorea (SC) the neurologic variant of rheumatic fever. We hypothesized that OCS occurring in association with SC would be similar to those among patients with tic disorders. Methods. The authors studied the presence of OCS in 73 patients with SC by using the Yale-Brown Obsessive-Compulsive Scale at the Pediatric Clinics of the University of Sao Paulo Medical Center in Sao Paulo, Brazil (n = 45) and at the National institute of Mental Health in Bethesda, Maryland (n = 28). Results: The most frequent symptoms observed among subjects with comorbid SC and OCS were aggressive, contamination, and somatic obsessions and checking, cleaning, and repeating compulsions, A principal component factor analysis yielded a five-factor solution (accountingfor 64.5% of the total variance), with contamination and symmetry obsessions and cleaning compulsions loading highly. Conclusions. The symptoms observed among the SC patients were different from those reported by patients with tic disorders but were similar to those previously noted among samples of pediatric patients with primary obsessive-compulsive disorder. C1 Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Lab Med Invest LIM 23, Sao Paulo, Brazil. Sch Med Sao Jose do Rio Preto, Dept Epidemiol & Publ Hlth, Sao Paulo, Brazil. NINDS, Med Neurol Branch, Bethesda, MD 20892 USA. NIMH, Pediat & Dev Neuropsychiat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Asbahr, FR (reprint author), FMUSP, Dept Psiquiatria, Rua Dr Ovidio Pires Campos,785,Caixa Postal 8091, BR-05403010 Sao Paulo, Brazil. EM frasbahr@usp.br RI Zanetta, Dirce/G-4950-2013; Asbahr, Fernando/G-8469-2015 NR 38 TC 28 Z9 29 U1 5 U2 7 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 MAY 1 PY 2005 VL 57 IS 9 BP 1073 EP 1076 DI 10.1016/j.biopsych.2005.01.037 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 919IO UT WOS:000228611900016 PM 15860349 ER PT J AU Shapiro, JA von Sternberg, R AF Shapiro, JA von Sternberg, R TI Why repetitive DNA is essential to genome function SO BIOLOGICAL REVIEWS LA English DT Review DE transposable element; non-coding DNA; satellite DNA; junk DNA; transcriptional regulation; chromatin domains; evolution; biocomputing; systems biology; data storage ID POSITION-EFFECT VARIEGATION; OUTER-MEMBRANE PROTEIN; CLASS-SWITCH RECOMBINATION; MATRIX-ATTACHMENT REGIONS; X-CHROMOSOME INACTIVATION; TRANSCRIPTION FACTOR YY1; ALPHA-SATELLITE DNA; TRANSPOSABLE ELEMENTS; NEISSERIA-MENINGITIDIS; DROSOPHILA-MELANOGASTER AB There are clear theoretical reasons and many well-documented examples which show that repetitive DNA is essential for genome function. Generic repeated signals in the DNA are necessary to format expression of unique coding sequence files and to organise additional functions essential for genome replication and accurate transmission to progeny cells. Repetitive DNA sequence elements are also fundamental to the cooperative molecular interactions forming nucleoprotein complexes. Here, we review the surprising abundance of repetitive DNA in many genomes, describe its structural diversity, and discuss dozens of cases where the functional importance of repetitive elements has been studied in molecular detail. In particular, the fact that repeat elements serve either as initiators or boundaries for heterochromatin domains and provide a significant fraction of scaffolding/matrix attachment regions (S/MARs) suggests that the repetitive component of the genome plays a major architectonic role in higher order physical structuring. Employing an information science model, the 'functionalist' perspective on repetitive DNA leads to new ways of thinking about the systemic organisation of cellular genomes and provides several novel possibilities involving repeat elements in evolutionarily significant genome reorganisation. These ideas may facilitate the interpretation of comparisons between sequenced genomes, where the repetitive DNA component is often greater than the coding sequence component. C1 Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Natl Museum Nat Hist, Smithsonian Inst, Dept Syst Biol, Washington, DC 20013 USA. RP Shapiro, JA (reprint author), Univ Chicago, Dept Biochem & Mol Biol, 920 E 58th St, Chicago, IL 60637 USA. EM jsha@uchicago.edu; sternber@ncbi.nlm.nih.gov NR 246 TC 74 Z9 77 U1 3 U2 38 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-7931 EI 1469-185X J9 BIOL REV JI Biol. Rev. PD MAY PY 2005 VL 80 IS 2 BP 227 EP 250 DI 10.1017/S1464793104006657 PG 24 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 928NT UT WOS:000229279300003 PM 15921050 ER PT J AU Grandjean-Laquerriere, A Laquerriere, P Guenounou, M Laurent-Maquin, D Phillips, TM AF Grandjean-Laquerriere, A Laquerriere, P Guenounou, M Laurent-Maquin, D Phillips, TM TI Importance of the surface area ratio on cytokines production by human monocytes in vitro induced by various hydroxyapatite particles SO BIOMATERIALS LA English DT Article DE hydroxyapatite; cytokines; inflammation; physical characteristics ID SINTERING TEMPERATURE; ACETABULAR COMPONENTS; DIFFERENT FORMS; SIZE; BONE; RESORPTION AB A possible complication associated with the implantation of hydroxyapatite (HA)-based prosthesis is the release of particles. Those particles can be phagocyted by monocytes that are among the first cells to colonize the inflammatory site. The activated monocytes produce inflammatory mediators, such as cytokines, which cause osteoclasts activation. It has previously been demonstrated using a surface area ratio (ratio of the total surface of the given particles to the surface area of cells) of 1 to 1 that there was a correlation between the expression and production of cytokines induced by HA. The present work studies the effect of)physical characteristics of HA particles on the production of various inflammatory cytokines (tumour necrosis factor-alpha, interleukin (IL)-6, and IL-8) and anti-inflammatory cytokine (IL-10). However, the experiments were performed using a surface area ratio of 10 to 1. Our data demonstrate that all the particles, whatever their characteristics, induced a high expression of cytokines but. he production was different, meaning that there was a post-transcriptional regulation. The size and sintering temperature seemed to be a characteristics that were less important compared to the shape; the needle particles appeared to induce the most important production of all the cytokines studied. (C) 2004 Elsevier Ltd. All rights reserved. C1 NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. UFR Pharm, Lab Immunol & Biotechnol, EA2070, IFR 53, F-51096 Reims, France. INSERM, ERM 0203, IFR 53, F-51096 Reims, France. RP Laquerriere, P (reprint author), INSERM, ERM 0203, 21 Rue Clement Ader,BP 138, F-51685 Reims, France. EM patrice.laquerriere@univ-reims.fr RI Laquerriere, Patrice/P-1025-2016 OI Laquerriere, Patrice/0000-0001-7637-9094 NR 23 TC 55 Z9 57 U1 2 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD MAY PY 2005 VL 26 IS 15 BP 2361 EP 2369 DI 10.1016/j.biomaterials.2004.07.036 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 893DB UT WOS:000226698400019 PM 15585239 ER PT J AU Zheng, WJ Brooks, BR AF Zheng, WJ Brooks, BR TI Normal-modes-based prediction of protein conformational changes guided by distance constraints SO BIOPHYSICAL JOURNAL LA English DT Article ID ELASTIC-NETWORK MODEL; MOTIONS; TRANSITIONS; RESTRAINTS; DYNAMICS; DOMAIN AB Based on the elastic network model, we develop a novel method that predicts the conformational change of a protein complex given its initial-state crystal structure together with a small set of pairwise distance constraints for the end state. The predicted conformational change, which is a linear combination of multiple low-frequency normal modes that are solved from the elastic network model, is computed as a response displacement induced by a perturbation to the system Hamiltonian that incorporates the given distance constraints. For a list of test cases, we find that the computed response displacement overlaps significantly with the measured conformational changes, when only a handful of pairwise constraints are used (<= 10). The performance of this method is also shown to be robust against different choices of pairwise distance constraints and errors in their values. This method, if supplied with the experimentally derived distance constraints ( for example, from NMR or other spectroscopic measurements), can be applied to the analysis of protein conformational changes toward transient states. C1 NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Zheng, WJ (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM zhengwj@helix.nih.gov OI Zheng, Wenjun/0000-0002-6236-9765 NR 17 TC 57 Z9 58 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 2005 VL 88 IS 5 BP 3109 EP 3117 DI 10.1529/biophysj.104.058453 PG 9 WC Biophysics SC Biophysics GA 920KW UT WOS:000228688800009 PM 15722427 ER PT J AU Dudko, OK Weiss, GH AF Dudko, OK Weiss, GH TI Estimation of anisotropic optical parameters of tissue in a slab geometry SO BIOPHYSICAL JOURNAL LA English DT Article ID LIGHT-PROPAGATION; PHOTON MIGRATION; ALIGNMENT MAPS AB The scattering and absorption coefficients of many homogeneous biological tissues such as muscle, skin, white matter in the brain, and dentin are often anisotropically oriented with respect to their bounding interface. In consequence the curves of equal intensity of re-emitted light on the surface of the slab will no longer be circular. We here consider the problem of determining the parameters allowing one to estimate the angles de. ning anisotropy, directional bias of diffusive spreading, and scattering and absorbing coefficients from data obtained from time-gated measurements of light intensity transmitted through a slab of the tissue. Our model can be solved exactly and leads to accurate approximations in which measured values of the surface intensity are shown to be elliptical. The parameters of the ellipses suffice to estimate the anisotropy of the tissue interior. A summary of the parameter estimates with the observables from which they are found is given in a table. Our analysis is based on a diffusion model. C1 NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Dudko, OK (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. EM dudko@mail.nih.gov NR 18 TC 11 Z9 11 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 2005 VL 88 IS 5 BP 3205 EP 3211 DI 10.1529/biophysj.104.058305 PG 7 WC Biophysics SC Biophysics GA 920KW UT WOS:000228688800017 PM 15731380 ER PT J AU Kobrinsky, E Mager, DE Bentil, SA Murata, SI Abernethy, DR Soldatov, NM AF Kobrinsky, E Mager, DE Bentil, SA Murata, SI Abernethy, DR Soldatov, NM TI Identification of plasma membrane macro- and microdomains from wavelet analysis of FRET microscopy SO BIOPHYSICAL JOURNAL LA English DT Article ID RESONANCE ENERGY-TRANSFER; PROTEIN-KINASE-C; IMAGES; DNA AB In this study, we sought to characterize functional signaling domains by applying the multiresolution properties of the continuous wavelet transform to fluorescence resonance energy transfer ( FRET) microscopic images of plasma membranes. A genetically encoded FRET reporter of protein kinase C (PKC)-dependent phosphorylation was expressed in COS1 cells. Differences between wavelet coefficient matrices revealed several heterogeneous domains ( typically ranging from 1 to 5 mu m), reflecting the dynamic balance between PKC and phosphatase activity during stimulation with phorbol-12,13-dibutyrate or acetylcholine. The balance in these domains was not necessarily reflected in the overall plasma membrane changes, and observed heterogeneity was absent when cells were exposed to a phosphatase or PKC inhibitor. Prolonged exposure to phorbol-12,13-dibutyrate and acetylcholine yielded more homogeneous FRET distribution in plasma membranes. The proposed wavelet-based image analysis provides, for the first time, a basis and a means of detecting and quantifying dynamic changes in functional signaling domains, and may find broader application in studying. ne aspects of cellular signaling by various imaging reporters. C1 NIA, NIH, Baltimore, MD 21224 USA. Univ Yamanashi, Interdisciplinary Grad Sch Med & Engn, Dept Pathol, Yamanashi, Japan. RP Soldatov, NM (reprint author), NIA, NIH, Baltimore, MD 21224 USA. EM soldatovn@grc.nia.nih.gov NR 24 TC 5 Z9 5 U1 1 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 MAY PY 2005 VL 88 IS 5 BP 3625 EP 3634 DI 10.1529/biophysj.104.054056 PG 10 WC Biophysics SC Biophysics GA 920KW UT WOS:000228688800056 PM 15722423 ER PT J AU Rosenberg, HF AF Rosenberg, HF TI Chemokines and chemokine receptors: here, there, and everywhere - Comment SO BLOOD LA English DT Editorial Material C1 NIAID, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2005 VL 105 IS 9 BP 3388 EP 3388 DI 10.1182/blood-2005-02-0614 PG 1 WC Hematology SC Hematology GA 921WX UT WOS:000228797400002 ER PT J AU Jaffe, ES AF Jaffe, ES TI Cutaneous lymphomas: it's location, location, location - Comment SO BLOOD LA English DT Editorial Material ID B-CELL LYMPHOMA; HODGKIN LYMPHOMA; SURVIVAL; FEATURES C1 NCI, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 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 MAY 1 PY 2005 VL 105 IS 9 BP 3394 EP 3395 DI 10.1182/blood-2005-02-0611 PG 2 WC Hematology SC Hematology GA 921WX UT WOS:000228797400009 ER PT J AU Barth, H Ulsenheimer, A Pape, GR Diepolder, HM Hoffmann, M Neumann-Haefelin, C Thimme, R Henneke, P Klein, R Paranhos-Baccala, G Depla, E Liang, TJ Blum, HE Baumert, TF AF Barth, H Ulsenheimer, A Pape, GR Diepolder, HM Hoffmann, M Neumann-Haefelin, C Thimme, R Henneke, P Klein, R Paranhos-Baccala, G Depla, E Liang, TJ Blum, HE Baumert, TF TI Uptake and presentation of hepatitis C virus-like particles by human dendritic cells SO BLOOD LA English DT Article ID CD8(+) T-CELLS; ENVELOPE GLYCOPROTEIN E2; DC-SIGN; NONSTRUCTURAL PROTEIN-3; LYMPHOCYTE RESPONSE; CROSS-PRESENTATION; IMMUNE-RESPONSES; MANNOSE RECEPTOR; VIRAL CLEARANCE; INSECT CELLS AB Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. Interaction of dendritic cells (DCs) with viral particles may play an important role in the immunopathogenesis of HCV infection. Since the synthesis or purification of infectious virions is limited, we used HCV-like particles (HCV-LPs) to study the interaction of HCV with human DCs. Immature DCs exhibited an envelope-specific and saturable binding of HCV-LPs, indicating receptor-mediated DC-HCV-LP interaction. Confocal microscopy revealed that HCV-LPs were rapidly taken up by DCs in a temperature-dependent manner. Competition experiments demonstrated that C-type lectins such as mannose receptor or DC-SIGN (DC-specific intercellular adhesion molecule 3-grabbing nonintegrin) were not sufficient for mediating HCV-LP binding. HCV-LP uptake was followed by DC activation. DCs pulsed with HCV-LPs stimulated HCV core-specific CD4(+) T cells, indicating that uptake of HCV-LPs by DCs leads to antigen processing and presentation on major histocompatibility complex (MHC) class II molecules. Finally, HCV-LP-derived antigens were efficiently cross-presented to HCV core-specific CD8(+) T cells. These findings demonstrate that HCV-LPs represent a novel model system to study HCV-DC interaction allowing definition of the molecular mechanisms of HCV uptake, DC activation, and antigen presentation to T cells. Furthermore, HCV-LP-mediated DC activation and efficient antigen presentation may explain the marked immunogenicity of HCV-LPs in vivo. C1 Univ Freiburg, Dept Med 2, D-79106 Freiburg, Germany. Univ Munich, Dept Med 2, Klinikum Grosshadern, Munich, Germany. Univ Freiburg, Childrens Hosp, Freiburg, Germany. Univ Tubingen, Dept Med 2, Tubingen, Germany. CNRS, CERVI, IFR 128, Lyon, France. Innogenet NV, Ghent, Belgium. NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. RP Baumert, TF (reprint author), Univ Freiburg, Dept Med 2, Hugstetter Str 55, D-79106 Freiburg, Germany. EM thomas.baumert@uniklinik-freiburg.de RI Neumann-Haefelin, Christoph/E-5550-2011 NR 72 TC 64 Z9 72 U1 0 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2005 VL 105 IS 9 BP 3605 EP 3614 DI 10.1182/blood-2004-05-1952 PG 10 WC Hematology SC Hematology GA 921WX UT WOS:000228797400040 PM 15657184 ER PT J AU Lappe, J Lypaczewski, G Horlick, M Gilsanz, V Kalkwarf, H Zemel, B Mahboubi, S Shepherd, J Frederick, M Winer, K AF Lappe, J Lypaczewski, G Horlick, M Gilsanz, V Kalkwarf, H Zemel, B Mahboubi, S Shepherd, J Frederick, M Winer, K TI Defining the healthy American child: Characteristics of children in the bone mineral density in childhood study SO BONE LA English DT Meeting Abstract CT 3rd International Conference on Childrens Bone Health CY MAY 11-14, 2005 CL Sorrento, ITALY C1 Creighton Univ, Osteoporosis Res Ctr, Omaha, NE 68178 USA. Columbia Univ, New York, NY USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. C TASC, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. RI Zemel, Babette/D-1117-2009 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 8756-3282 J9 BONE JI Bone PD MAY PY 2005 VL 36 SU 1 BP S70 EP S70 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 928CS UT WOS:000229249300157 ER PT J AU Taylor, ED Tanofsky-Kraff, M Ghorbani, S Theim, K Brady, S Mirch, M Yanovski, J AF Taylor, ED Tanofsky-Kraff, M Ghorbani, S Theim, K Brady, S Mirch, M Yanovski, J TI Prevalence of orthopaedic complications in overweight children and adolescents: A cross-sectional analysis SO BONE LA English DT Meeting Abstract CT 3rd International Conference on Childrens Bone Health CY MAY 11-14, 2005 CL Sorrento, ITALY C1 NICHHD, Unit Growth & Obes, 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 8756-3282 J9 BONE JI Bone PD MAY PY 2005 VL 36 SU 1 BP S94 EP S95 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 928CS UT WOS:000229249300243 ER PT J AU Pierson, DL Stowe, RP Phillips, TM Lugg, DJ Mehta, SK AF Pierson, DL Stowe, RP Phillips, TM Lugg, DJ Mehta, SK TI Epstein-Barr virus shedding by astronauts during space flight SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE antibody; DNA; viral; herpesvirus; Epstein-Barr virus; polymerase chain reaction; stress; weightlessness ID POLYMERASE-CHAIN-REACTION; CELL-MEDIATED-IMMUNITY; DURATION MISSIONS; STRESS; REACTIVATION; NEUROPEPTIDES; SPACEFLIGHT; PLASMA; RADIOIMMUNOASSAY; CYTOMEGALOVIRUS AB Patterns of Epstein-Barr virus (EBV) reactivation in 32 astronauts and 18 healthy age-matched control subjects were characterized by quantifying EBV shedding. Saliva samples were collected from astronauts before, during, and after 10 space shuttle missions of 5-14 days duration. At one time point or another, EBV was detected in saliva from each of the astronauts. Of 1398 saliva specimens from 32 astronauts, polymerase chain reaction analysis showed that 314 (23%) were positive for EBV DNA. Examination by flight phase showed that 29% of the saliva specimens collected from 28 astronauts before flight were positive for EBV DNA, as were 16% of those collected from 25 astronauts during flight and 16% of those collected after flight from 23 astronauts. The mean number of EBV copies from samples taken during the flights was 417 per mL, significantly greater (p <.05) than the number of viral copies from the preflight (40) and postflight (44) phases. In contrast, the control subjects shed EBV DNA with a frequency of 3.7% and mean number of EBV copies of 40 per mL of saliva. Ten days before flight and on landing day, titers of antibody to EBV viral capsid antigen were significantly (p <.05) greater than baseline levels. On landing day, urinary levels of cortisol and catecholamines, were greater than their preflight values. In a limited study (n = 5), plasma levels of substance P and other neuropeptides were also greater on landing day. Increases in the number of viral copies and in the amount of EBV-specific antibody were consistent with EBV reactivation before, during, and after space flight. (C) 2004 Elsevier Inc. All rights reserved. C1 Enterprise Advisory Serv Inc, Houston, TX USA. NASA, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA. Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77550 USA. NIH, Div Bioengn & Phys SCi, ORS, OD, Bethesda, MD 20892 USA. NASA Headquarters, Washington, DC USA. RP Mehta, SK (reprint author), Enterprise Advisory Serv Inc, Houston, TX USA. EM smehta@ems.jsc.nasa.gov NR 37 TC 75 Z9 77 U1 0 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD MAY PY 2005 VL 19 IS 3 BP 235 EP 242 DI 10.1016/j.bbi.2004.08.001 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 915OG UT WOS:000228313000008 PM 15797312 ER PT J AU Vucenik, I Ramakrishna, G Tantivejkul, K Anderson, LM Ramljak, D AF Vucenik, I Ramakrishna, G Tantivejkul, K Anderson, LM Ramljak, D TI Inositol hexaphosphate (IP6) blocks proliferation of human breast cancer cells through a PKC delta-dependent increase in p27(Kip1) and decrease in retinoblastoma protein (pRb) phosphorylation SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE apoptosis; breast cancer; p27(Kip1); phytic acid; PKC delta; retinoblastoma protein ID KINASE-C-DELTA; CAPILLARY ENDOTHELIAL-CELLS; RAT MAMMARY CARCINOGENESIS; CARCINOMA DU145 CELLS; INHIBITOR P27(KIP1); TYROSINE PHOSPHORYLATION; DIFFERENTIAL REGULATION; PHYTIC ACID; IN-VITRO; CYCLIN AB Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate with demonstrated anti-proliferative and anti-cancer activity in mammary cells. We hypothesized that IP6 modulates cell cycle proteins by action on cytoplasmic signaling molecules. The effects of both pharmacological (2 mM) and physiological (100 μ M) doses of IP6 on major PKC isoforms (PKCα, δ, ε, β and ζ), PI3-K/Akt and ras/Erk1/2 were evaluated. Treatment of MCF-7 human breast cancer cells with 2 mM IP6 for 24 h caused a 3.1-fold increase in the expression of anti-proliferative PKCδ. Similar results were observed with 100 μ M IP6 at only 30-60 min post-treatment. IP6 also caused an increase in PKCδ activity, shown by its translocation from cytosol to membrane. No changes in expression of PKCα, ε, β, and ζ were detected. Additionally, IP6 caused a decrease of Erk1/2 and Akt activity. Among cell cycle control proteins, IP6 resulted in increased p27(Kip1) protein levels and marked reduction of pRb phosphorylation. Specificity of the IP6 effects on p27(Kip1) and pRb in MCF-7 cells (hormone-dependent) were additionally confirmed in highly invasive hormone-independent MDA-MB 231 breast cancer cells. Use of specific pharmaclogical inhibitors of PKCδ, MEK/Erk, and PI3K/Akt pathways indicated that the IP6-mediated effects on PKCδ were responsible for up-regulation of p27(Kip), and pRb hypo-phosphorylation. In addition, IP6-induced apoptosis detected in MCF-7 cells appeared also to be PKCδ-dependent. Our data suggest potential usefulness of IP6 as a novel therapeutic modulator of PKCδ and p27(Kip1), an important prognostic factor in human breast cancers. C1 Univ Maryland, Sch Med, Dept Med & Res Technol, Baltimore, MD 21201 USA. NCI, Comparat Carcinogenesis Lab, FCRDC, Frederick, MD 21701 USA. RP Vucenik, I (reprint author), Univ Maryland, Sch Med, Dept Med & Res Technol, 100 Penn St, Baltimore, MD 21201 USA. EM ivucenik@umaryland.edu NR 50 TC 56 Z9 58 U1 0 U2 0 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 MAY PY 2005 VL 91 IS 1 BP 35 EP 45 DI 10.1007/s10549-004-6456-5 PG 11 WC Oncology SC Oncology GA 922VH UT WOS:000228867500005 PM 15868430 ER PT J AU Zhang, XN Simon, R AF Zhang, XN Simon, R TI Estimating the number of rate limiting genomic changes for human breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast mutations; genomic instability; human breast carcinogenesis; mutator phenotype ID MUTATOR PHENOTYPE; MUTATIONS; CARCINOGENESIS; INSTABILITY; GROWTH; BRCA1; RISK AB We used multistage models that incorporate the age dependent dynamics of normal breast tissue, clonal expansion of intermediate cells and mutational events to fit data for the age-specific incidence of breast cancers in the surveillance, epidemiology, and end results (SEER) registry. Our results suggest that two or three rate limiting events occurring at rates characteristic of point mutation rates for normal mammalian cells set in motion a sequence of other genomic changes that lead with high probability to breast carcinoma. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 23 TC 11 Z9 11 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAY PY 2005 VL 91 IS 2 BP 121 EP 124 DI 10.1007/s10549-004-5782-y PG 4 WC Oncology SC Oncology GA 922VI UT WOS:000228867600003 PM 15868439 ER PT J AU Machado, RF Gladwin, MT AF Machado, RF Gladwin, MT TI Chronic sickle cell lung disease: new insights into the diagnosis, pathogenesis and treatment of pulmonary hypertension SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE sickle cell disease; haemolysis; pulmonary hypertension; nitric oxide ID MICROANGIOPATHIC HEMOLYTIC-ANEMIA; BETA-THALASSEMIA MAJOR; 6-MINUTE WALK TEST; NITRIC-OXIDE BIOAVAILABILITY; HUMAN ENDOTHELIAL-CELLS; ACUTE CHEST SYNDROME; ARTERIAL-HYPERTENSION; CARDIOPULMONARY BYPASS; HEREDITARY STOMATOCYTOSIS; MANSONIC SCHISTOSOMIASIS AB Pulmonary hypertension is a common complication of sickle cell disease (SCD). In spite of the mild elevations in pulmonary artery pressures in these patients, the associated morbidity and mortality is high. In fact, in adult patients with SCD, pulmonary hypertension is emerging as the major independent risk factor for death. The aetiology of pulmonary hypertension is probably multifactorial, including haemolysis, impaired nitric oxide bioavailability, chronic hypoxaemia, thromboembolism, parenchymal and vascular injury because of sequestration of sickle erythrocytes, chronic liver disease and asplenia. Interestingly, pulmonary hypertension is emerging as a common, and probably, invariant sequella of lifelong haemolytic anaemia in other hereditary and acquired haemolytic diseases, such as thalassaemia, stomatocytosis and spherocytosis. There are currently limited specific data on the effects of any treatment modality for pulmonary hypertension in patients with SCD. It is likely that maximization of SCD therapy, in all patients, and treatment with selective pulmonary vasodilators and antiproliferative agents, in patients with severe disease, would be beneficial. A large trial evaluating the effects of therapy for pulmonary hypertension in the SCD population is clearly indicated. C1 NHLBI, Vasc Therapeut Sect, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Machado, RF (reprint author), NHLBI, Vasc Therapeut Sect, Cardiovasc Branch, NIH, 9000 Rockville Pike,Bldg 10-CRC,Room 5-5130, Bethesda, MD 20892 USA. EM robertom@nhlbi.nih.gov NR 145 TC 68 Z9 71 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2005 VL 129 IS 4 BP 449 EP 464 DI 10.1111/j.1365-2141.2005.05432.x PG 16 WC Hematology SC Hematology GA 924FW UT WOS:000228965400001 PM 15877728 ER PT J AU Rao, VK Dugan, F Dale, JK Davis, J Tretler, J Hurley, JK Fleisher, T Puck, J Straus, SE AF Rao, VK Dugan, F Dale, JK Davis, J Tretler, J Hurley, JK Fleisher, T Puck, J Straus, SE TI Use of mycophenolate mofetil for chronic, refractory immune cytopenias in children with autoimmune lymphoproliferative syndrome SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE autoimmune lymphoproliferative syndrome; mycophenolate mofetil; autoimmune neutropenia; autoimmune haemolytic anaemia; immune-mediated thrombocytopenia ID THROMBOCYTOPENIC PURPURA; LYMPHOCYTE APOPTOSIS; FAS MUTATIONS; LONG-TERM; TRANSPLANTATION; ADULTS AB Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of apoptosis associated most often with heritable FAS mutations leading to lymphadenopathy, hypersplenism and chronic refractory autoimmune cytopenias. Mycophenolate mofetil (MMF) was used to treat cytopenias in 13 ALPS patients aged 9 months to 17 years from a cohort of 118 children (aged < 18 years) and 82 adults. Twelve responded for a median follow-up of 49 weeks (range 38-240 weeks), defined by maintenance of adequate blood counts and reduction in dosage or cessation of other immunosuppressive agents. This preliminary experience suggests that MMF may spare steroid usage in patients with ALPS-associated cytopenias. C1 NIAID, LCID, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), NIAID, LCID, NIH, 10 Ctr Dr,Room 11N228, Bethesda, MD 20892 USA. EM sstraus@nih.gov NR 12 TC 65 Z9 71 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2005 VL 129 IS 4 BP 534 EP 538 DI 10.1111/j.1365-2141.2005.05496.x PG 5 WC Hematology SC Hematology GA 924FW UT WOS:000228965400009 PM 15877736 ER PT J AU Erkkila, AT Lichtenstein, AH Jacques, PF Hu, FB Wilson, PWF Booth, SL AF Erkkila, AT Lichtenstein, AH Jacques, PF Hu, FB Wilson, PWF Booth, SL TI Determinants of plasma dihydrophylloquinone in men and women SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE dihydrophylloquinone; vitamin K; trans fatty acids; biomarker ID LIPOPROTEIN CHOLESTEROL LEVELS; FOOD FREQUENCY QUESTIONNAIRE; VITAMIN-K STATUS; PHYLLOQUINONE VITAMIN-K-1; DIETARY-INTAKE; OILS; DIHYDRO-VITAMIN-K-1; REPRODUCIBILITY; VALIDITY; HEALTH AB Commercial hydrogenation results in the formation of trans fatty acids. An unintended consequence of the hydrogenation process is conversion of phylloquinone (vitamin K-1) to dihydrophylloquinone. Plasma dihydrophylloquinone concentrations have yet to be characterized in population-based studies. Dietary determinants of plasma dihydrophylloquinone were estimated using a semi-quantitative food frequency questionnaire in 803 men and 913 women in the Framingham Offspring Study. Geometric mean dihydrophylloquinone intake was 21.3 (95 % CI 20.4, 22.3) mu g/d in men and 19.4 (95 % CI 18.5, 20.2) mu g/d in women. Detectable (> 0.05 nmol/l) plasma dihydrophylloquinone concentrations were measured in 41 % and 30 % of men and women, respectively. The multivariate odds ratio (OR) of detectable plasma dihydrophylloquinone from the lowest to the highest quartile category of dihydrophylloquinone intake were 1 (referent), 1.13 (95 % CI 0.83, 1.53), 1.66 (95 % CI 1.21, 2.26) and 1.84 (95 % CI 1.31, 2.58), P for trend < 0.001, adjusted for sex, age, body mass index, triacylglycerols, season and energy intake. Higher trans fatty acid intake was associated with higher multivariate OR for detectable plasma dihydrophylloquinone (OR comparing extreme quartiles 2.41 (95 % CI 1.59, 3.64), P for trend < 0.001). There were limitations in the use of plasma dihydrophylloquinone, evident in the high proportion of the population that had non-detectable dihydrophylloquinone concentrations. Despite this caveat, higher plasma dihydrophylloquinone was associated with higher dihydrophylloquinone intake and higher trans fatty acid intake. C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Vitamin K Lab, Boston, MA 02111 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Cardiovasc Nutr Lab, Boston, MA 02111 USA. Univ Kuopio, Dept Clin Nutr, FIN-70211 Kuopio, Finland. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Program Epidemiol, Boston, MA 02111 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Channing Labs, Boston, MA 02115 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NHLBI, Framingham Heart Study, Framingham, MA 01701 USA. RP Booth, SL (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, Vitamin K Lab, 711 Washington St, Boston, MA 02111 USA. EM sarah.booth@tufts.edu FU NIA NIH HHS [AG14759] NR 26 TC 5 Z9 5 U1 0 U2 1 PU CABI PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, NOSWORTHY WAY, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD MAY PY 2005 VL 93 IS 5 BP 701 EP 708 DI 10.1079/BJN20041394 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 939OX UT WOS:000230083400017 PM 15975170 ER PT J AU Wei, XY Yang, FQ Straney, DC AF Wei, XY Yang, FQ Straney, DC TI Multiple non-ribosomal peptide synthetase genes determine peptaibol synthesis in Trichoderma virens SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE Hypocrea virens; Gliocladium virens; Trichoderma virens ID OPEN READING FRAME; MOLECULAR CHARACTERIZATION; ASPERGILLUS-NIDULANS; GLIOCLADIUM-VIRENS; SEQUENCE; CLONING; ENZYME AB Trichoderma virens, an imperfect fungus, is used as a biocontrol agent to suppress plant disease caused by soilborne fungal pathogens. Antimicrobial peptides it produces include peptaibols of 11, 14, and 18 amino acids in length. These peptaibols were previously reported to be synthesized by a non-ribosomal peptide synthetase (NRPS) encoded by the Tex1 gene in strain Tv29-8. The present study examined the Tex1 homolog in a commercially relevant T. virens strain, G20. Although the gene in G20 was 99% identical in DNA sequence to Tex1 in the 15.8 kb compared, gene disruption results indicate that it is only responsible for the production of an 18-mer peptaibol, and not 11-mer and 14-mer peptaibols. Additional NRPS adenylate domains were identified in T. virens and one was found to be part of a 5-module NRPS gene. Although the multimodule gene is not needed for peptaibol synthesis, sequence comparisons suggest that two of the individual adenylate domain clones might be part of a separate peptaibol synthesis NRPS gene. The results indicate a significant diversity of NRPS genes in T. virens that is unexpected from the literature. C1 Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Straney, DC (reprint author), Univ Maryland, Dept Cell Biol & Mol Genet, HJ Patterson Hall, College Pk, MD 20742 USA. EM straney@umd.edu NR 20 TC 18 Z9 20 U1 0 U2 6 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0008-4166 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD MAY PY 2005 VL 51 IS 5 BP 423 EP 429 DI 10.1139/W05-006 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA 955XM UT WOS:000231262800007 PM 16088338 ER PT J AU Bleyer, A Montello, M Budd, T Saxman, S AF Bleyer, A Montello, M Budd, T Saxman, S TI National survival trends of young adults with sarcoma - Lack of progress is associated with lack of clinical trial participation SO CANCER LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 03, 2003 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) DE sarcoma survival; clinical trials; young adults; adolescents ID ACUTE LYMPHOBLASTIC-LEUKEMIA; OLDER ADOLESCENTS; CANCER; DIAGNOSIS; PROTOCOLS; CHILDREN AB BACKGROUND. Young adults with cancer in the U.S. have had less improvement in Survival than either younger patients or older patients. The authors attempted to determine whether similar deficits have occurred in young adults with sarcomas and, if so, then why. METHODS. in 38,144 young adults with sarcoma who were diagnosed during 1975-1998 and were followed by the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results Program, the average annual percent change in 5-year survival was derived as a function of patient age. National sarcoma treatment trial data were obtained on 3242 patients who were entered onto NCI-sponsored trials during 1997-2002. RESULTS. 1) For patients with bone and soft-tissue sarcomas, except Kaposi sarcoma (KS), the least survival improvement occurred between age 15 years and age 45 years. For patients with KS, the pattern was reversed, with the greatest survival increase occurring among patients ages 30-44 years. 2) The lowest participation rate in NCI-sponsored sarcoma treatment trials occurred in patients ages 20-44 years. For patients with KS, the highest accrual rate occurred in patients ages 35-44 years. 3) The age-dependent survival improvement and clinical-trial accrual patterns were correlated directly (soft-tissue sarcomas, P < 0.005; bone sarcomas, P < 0.05; KS, P = 0.06), regardless of whether the accrual profile demonstrated a decline or a peak (KS) during early adulthood. CONCLUSIONS. The lack of survival prolongation in patients age 15-44 years in the U.S. with non-KS sarcomas may have been a result of their relative lack of participation in clinical trials. If this is true, then reversing the shortfall in survival among young adults with sarcomas, as was accomplished among patients with KS, should benefit from increased clinical trial availability, access, and participation. Published 2005 by the American Cancer Society.* C1 Univ Texas, MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Pediat, Houston, TX USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD USA. RP Bleyer, A (reprint author), Univ Texas, MD Anderson Canc Ctr, Div Canc Med, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM ableyer@mdanderson.org FU NCI NIH HHS [U10 CA13539, U10 CA45809] NR 24 TC 69 Z9 71 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAY 1 PY 2005 VL 103 IS 9 BP 1891 EP 1897 DI 10.1002/cncr.20995 PG 7 WC Oncology SC Oncology GA 916YQ UT WOS:000228423100018 PM 15795902 ER PT J AU Zhuang, SH Agrawal, M Edgerly, M Bakke, S Kotz, H Thambi, P Rutt, A Balis, FM Bates, S Fojo, T AF Zhuang, SH Agrawal, M Edgerly, M Bakke, S Kotz, H Thambi, P Rutt, A Balis, FM Bates, S Fojo, T TI A phase I clinical trial of ixabepilone (BMS-247550), an epothilone B analog, administered intravenously on a daily schedule for 3 days SO CANCER LA English DT Article DE microtubules; taxanes; epothilones; ixabepilone; BMS-247550 ID MICROTUBULE-STABILIZING AGENTS; SOLID TUMORS; PACLITAXEL; CANCER; TAXOL AB BACKGROUND. The epothilones are a novel class of microtubule-stabilizing agents. Ixabepilone (BMS-247550; NSC 710428) is a semisynthetic analog of the natural product epothilone B. The authors conducted a Phase I study by administering ixabepilone to patients as a 1-hour intravenous infusion daily for 3 consecutive days every 21 days. METHODS. Twenty-six patients were enrolled and received ixabepilone at a starting dose of 8 or 10 mg/m(2) per day for 3 consecutive days. RESULTS. One hundred and nineteen cycles were administered to 26 patients. The maximum-tolerated dose was 8 mg/m(2) per day of ixabepilone administered as a 1-hour intravenous infusion daily for 3 consecutive days every 21 days. The dose-limiting toxicity (DLT) was neutropenia. Other nonhematologic Grade 3 toxicities included fatigue (3 cycles), hyponatremia (1 cycle), anorexia (1 cycle), ileus (1 cycle), stornatitis (1 cycle), and emesis (1 cycle). Prolonged disease stabilization was observed in patients with mesothelioma, ovarian carcinoma, and renal cell carcinoma. CONCLUSIONS. The recommended Phase II dose of ixabepilone on the daily schedule for 3 days was 8-10 mg/m(2) per day. Neutropenia was the DLT. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting. Published 2005 by the American Cancer Society.* C1 NCI, Ctr Canc Res, Canc Therapeut Branch, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD USA. RP Fojo, T (reprint author), NCI, Ctr Canc Res, Canc Therapeut Branch, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov NR 23 TC 60 Z9 63 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAY 1 PY 2005 VL 103 IS 9 BP 1932 EP 1938 DI 10.1002/cncr.20977 PG 7 WC Oncology SC Oncology GA 916YQ UT WOS:000228423100023 PM 15800893 ER PT J AU Scripture, CD Szeheni, J Loos, WJ Figg, WD Sparreboom, A AF Scripture, CD Szeheni, J Loos, WJ Figg, WD Sparreboom, A TI Comparative in vitro properties and clinical pharmacokinetics of paclitaxel following the administration of Taxol (R) and Paxene (R) SO CANCER BIOLOGY & THERAPY LA English DT Article DE paclitaxel; Cremophor; formulation; micelles ID CREMOPHOR EL; UNBOUND PACLITAXEL; FORMULATION VEHICLES; HUMAN PLASMA; DISPOSITION; MODULATION; INFUSIONS; HUMANS; CANCER AB Purpose: Taxol(R) contains paclitaxel formulated in Cremophor EL-P (CrEL-P) and ethanol. Paxene(R) is similar to Taxol(R), except for the use of Cremophor EL (CrEL) and the addition of citric acid. Here, we investigated the physicochemical properties and clinical pharmacokinetics of the two paclitaxel formulations. Experimental Design: The size and modality of distribution of CrEL-P and CrEL micelles was determined by dynamic-light scattering. The effect of vehicle composition on the fraction unbound paclitaxel in vitro was determined by equilibrium dialysis. Paclitaxel pharmacokinetics were studied in 61 cancer patients receiving Taxol(R) and 26 patients receiving Paxene(R). Comparative pharmacokinetics of CrEL-P and CrEL were obtained in 14 and 6 patients, respectively. Results: The size of micelles present in Taxol(R) was slightly smaller (9 to 13%) than those present in Paxene(R). Surface tension and critical micellar concentration were also similar for the two formulations, with mean values of 37.0 and 38.1 mN/m and 0.0387 and 0.0307 mg/mL, respectively. The fraction unbound paclitaxel was not significantly different for Taxol(R) and Paxene(R) (p > 0.05). Over the tested dose range, the mean clearance of paclitaxel decreased from 45.1 to 16.9 L/h for Taxol(R), and from 50.7 to 16.4 L/h for Paxene(R) (p > 0.05). Concentrations of the excipient following the administration of CrEL-P or CrEL were also similar. Conclusion: The differences in formulation between Taxol(R) and Paxene(R) do not significantly affect micelle formation and/or quantitative aspects of the vehicle-paclitaxel interaction in vitro and in vivo. C1 NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Membrane Biochem, Silver Spring, MD USA. Erasmus MC Daniel den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. RP Figg, WD (reprint author), NCI, Clin Pharmacol Res Core, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 21 TC 5 Z9 6 U1 0 U2 6 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAY PY 2005 VL 4 IS 5 BP 555 EP 560 PG 6 WC Oncology SC Oncology GA 015IB UT WOS:000235544000024 PM 15917657 ER PT J AU Hodge, DR Peng, B Pompeia, C Thomas, S Cho, E Clausen, PA Marquez, VE Farrar, WL AF Hodge, DR Peng, B Pompeia, C Thomas, S Cho, E Clausen, PA Marquez, VE Farrar, WL TI Epigenetic silencing of manganese superoxide dismutase (SOD-2) in KAS 6/1 human multiple myeloma cells increases cell proliferation SO CANCER BIOLOGY & THERAPY LA English DT Article DE epigenetic silecing; hypermethylation; MnSOD; SOD-2; bisulfite sequencing; IL-6 ID NF-KAPPA-B; BREAST-CANCER CELLS; UP-REGULATION; OXIDATIVE STRESS; PHOTODYNAMIC THERAPY; TRANSFORMED-CELLS; GENE-EXPRESSION; FREE-RADICALS; ACTIVATION; GROWTH AB The generation of reactive oxygen species (ROS) by mitochondrial electron transport chain (ETC) and oxidative phosphorylation activity, has been linked to modifications of multiple molecular processes, including lipid peroxidation, signaling pathway and transcription factor modulation, and oxidative damage to DNA. Oxidative damage by endogenous ROS has been associated with the etiology of various pathological states. There are numerous reports that levels of manganese superoxide dismutase enzyme (MnSOD), an antioxidant enzyme responsible for the attenuation of ROS, are lowered in cancer cells, but the reasons for this reduction are poorly defined. Epigenetic silencing of genes involved in tumor suppression and DNA repair is known to occur in a variety of malignant cell types. Here we report that in the human multiple myeloma cell line KAS 6/1, the SOD-2 gene, encoding manganese superoxide dismutase, is epigenetically silenced as a result of promoter hypermethylation. The DNA methyltransferase inhibitor Zebularine reverses SOD-2 promoter methylation, increasing gene expression and enzyme levels. Infection of KAS 6/1 cells with a recombinant adenovirus carrying the MnSOD cDNA reduced the cell proliferation rate by approximately one-half, confirming the detrimental effects of epigenetic silencing of SOD-2 expression. C1 NCI, Mol Immunoregulat Lab, Cytogenet Mol Mech Sect, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Med Chem Lab, Frederick, MD 21702 USA. SAIC, Intramural Res Support Grp, Frederick, MD USA. SAIC, Image Anal Lab, Confocal Microscopy Lab, Frederick, MD USA. Marligen Biosci Inc, Ijamsville, MD USA. RP Hodge, DR (reprint author), NCI, Mol Immunoregulat Lab, Cytogenet Mol Mech Sect, Ctr Canc Res, Frederick, MD 21702 USA. EM hodge@mail.ncifcrl.gov NR 46 TC 28 Z9 30 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAY PY 2005 VL 4 IS 5 BP 585 EP 592 PG 8 WC Oncology SC Oncology GA 015IB UT WOS:000235544000028 PM 15908783 ER PT J AU Il'yasova, D Hertz-Picciotto, I Peters, U Berlin, JA Poole, C AF Il'yasova, D Hertz-Picciotto, I Peters, U Berlin, JA Poole, C TI Choice of exposure scores for categorical regression in meta-analysis: a case study of a common problem SO CANCER CAUSES & CONTROL LA English DT Article DE colorectal cancer; dose-response relationships; epidemiology; epidemiologic method; meta-analyses; tea ID DOSE-RESPONSE DATA; CARDIOVASCULAR-DISEASE; ALCOHOL-CONSUMPTION; TREND ESTIMATION; TEA CONSUMPTION; RISK ASSESSMENT; LUNG-CANCER; POPULATION; TOBACCO; COFFEE AB Objective: Reporting categorical relative risk estimates for a series of exposure levels versus a common reference category is a widespread practice. In meta-analysis, categorical regression estimates a dose-response trend from such results. This method requires the assignment of a single score to each exposure category. We examined how closely meta-analytical categorical regression approximates the results of analysis based on the individual-level continuous exposure. Methods: The analysis included five studies on tea intake and outcomes related to colorectal cancer. In addition, we derived categorical mean and median values from published distributions of tea consumption in similar populations to assign scores to the categories of tea intake when possible. We examined whether these derived mean and median values well approximate the individual-level results. Results: In meta-analytical categorical regression, using the midrange scores approximated the individual-level continuous analyses reasonably well, if the value assigned to the uppermost, open-ended category was at least as high as the lower bound plus the width of the second-highest category. Categorical mean values derived from the published distributions of regular tea (in the US) and green tea (in Japan) well approximated the slope obtained from individual-level analysis. Conclusion: Publication of both the categorical and the continuous estimates of effect in primary studies, with their standard errors, can enhance the quality of meta-analysis, as well as providing intrinsically valuable information on dose-response. C1 Wake Forest Univ, Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Calif Davis, Dept Epidemiol & Prevent Med, Davis, CA 95616 USA. RP Il'yasova, D (reprint author), Wake Forest Univ, Sch Med, Dept Canc Biol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM dilyasov@wfubmc.edu NR 30 TC 37 Z9 38 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2005 VL 16 IS 4 BP 383 EP 388 DI 10.1007/s10552-004-5025-x PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 935SF UT WOS:000229803000006 PM 15953980 ER PT J AU Tardon, A Lee, WJ Delgado-Rodriguez, M Dosemeci, M Albanes, D Hoover, R Blair, A AF Tardon, A Lee, WJ Delgado-Rodriguez, M Dosemeci, M Albanes, D Hoover, R Blair, A TI Leisure-time physical activity and lung cancer: a meta-analysis SO CANCER CAUSES & CONTROL LA English DT Article DE leisure physical activity; lung cancer risk; meta-analysis ID UNITED-STATES; RISK; WOMEN; EXERCISE; PREVENTION; DISEASE; SITES; BIAS; MEN AB Objective: Several studies have evaluated the relationship between physical activity and lung cancer. To summarize and review these studies, we conducted a meta-analysis of all relevant reports published from 1966 through October 2003. Method: Adjusted odds ratios (ORs) from the original studies were pooled by the inverse of their variance, and all pooled estimates were accompanied by an assessment of heterogeneity across investigations. Test for linear trend across activity categories (low, moderate, high) were applied. Results: The combined ORs were 0.87 (95 confidence interval=0.79-0.95) for moderate leisure-time physical activity (LPA) and 0.70 (0.62-0.79) for high activity (ptrend=0.00). This inverse association occurred for both sexes, although it was somewhat stronger for women. No evidence of publication bias was found. Several studies were able to adjust for smoking, but none adjusted for possible confounding from previous malignant respiratory disease. Our simulations suggest that this condition is unlikely to entirely explain the inverse association. Conclusion: The findings of this meta-analysis indicate that higher levels of LPA protect against lung cancer. The inverse association is possible remains confounded by inadequately controlled smoking patterns. However on the whole, confounding seems an unlikely explanation for the findings of individual studies on non-smokers. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Oviedo, Inst Univ Oncol, Asturias, Spain. Korea Univ, Coll Med, Dept Prevent Med, Seoul 136701, South Korea. Univ Jaen, Dept Prevent Med, Andalucia, Spain. RP Tardon, A (reprint author), Univ Oviedo, Dept Publ Hlth, Fac Med, Campus Cristo Sln Oviedo, Asturias 33006, Spain. EM atardon@uniovi.es RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [Z01 CP010120-10] NR 42 TC 92 Z9 95 U1 1 U2 15 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2005 VL 16 IS 4 BP 389 EP 397 DI 10.1007/s10552-004-5026-9 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 935SF UT WOS:000229803000007 PM 15953981 ER PT J AU El-Bastawissi, AY Aiello, EJ Buist, DSM Taplin, SH AF El-Bastawissi, AY Aiello, EJ Buist, DSM Taplin, SH TI Previous pregnancy outcome and breast density (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE breast density; fetal death; low birth weight; pre-term delivery ID MAMMOGRAPHIC PARENCHYMAL PATTERNS; CANCER RISK-FACTORS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INDUCED-ABORTION; PRETERM DELIVERY; REPLACEMENT THERAPY; TRANSIENT INCREASE; BIRTH-WEIGHT; WOMEN; AGE AB Objective: We evaluated the association of pre-term delivery (PTD), low birth weight (LBW), and fetal death with breast density by age at mammogram and years since birth. Methods: Subjects were women aged <= 55 years who had a screening mammogram between 1 June 1996 and 1 August 1997 in Seattle, Washington, and whose records were linked to their previous state birth (1 January 1968 to 1 August 1997) or fetal death (1/1/1984-8/1/1997) records. We used unconditional logistic regression, adjusting for age at mammogram, body mass index, age at first birth, and menopausal status, to calculate the odds of dense (extremely or heterogeneously dense by BI-RADS) (n=3593) versus fatty breasts (scattered fibroglandular tissue or almost entirely fat) (n=2378) for women with a prior PTD (< 34, 34-36 versus >= 37 weeks gestation), LBW (< 2500 versus >= 2500 g), or fetal death (stillborn 20 weeks gestation versus live birth). Results: The odds for denser breasts increased among women with PTD at < 34 weeks gestation who were <= 45 years at time of mammogram (odds ratio (OR) and 95 confidence interval (CI)=2.8 (1.3-6.1)) and for whom < 10 years had elapsed since pregnancy (OR=8.8 (1.7-45.8)). We observed similar increases in density among women with LBW (OR=3.3 (1.3-8.2)) when < 10 years had elapsed. Conclusions: PTD and LBW may have a transitory effect on breast density. C1 Washington State Dept Hlth, Off Epidemiol & Community Wellness & Prevent, Olympia, WA 98504 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. NCI, Appl Res Program, Bethesda, MD 20892 USA. RP El-Bastawissi, AY (reprint author), Washington State Dept Hlth, Off Epidemiol & Community Wellness & Prevent, MS 47839, Olympia, WA 98504 USA. EM Amira.el-bastawissi@doh.wa.gov FU NCI NIH HHS [T32 CA 09661, U01 CA 63731] NR 51 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2005 VL 16 IS 4 BP 407 EP 417 DI 10.1007/s10552-004-5027-8 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 935SF UT WOS:000229803000009 PM 15953983 ER PT J AU Rusiecki, JA Matthews, A Sturgeon, S Sinha, R Pellizzari, E Zheng, TZ Barisi, D AF Rusiecki, JA Matthews, A Sturgeon, S Sinha, R Pellizzari, E Zheng, TZ Barisi, D TI A correlation study of organochlorine levels in serum, breast adipose tissue, and gluteal adipose tissue among breast cancer cases in India SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NESTED CASE-CONTROL; POLYCHLORINATED-BIPHENYLS; NEW-YORK; LONG-ISLAND; PESTICIDE-RESIDUES; RISK; WOMEN; EXPOSURE; BLOOD; PLASMA AB We used data from a breast cancer pilot study carried out in Kerala, India in 1997, for which organochlorine levels were measured in three biological media, blood serum, breast adipose tissue, and gluteal adipose tissue, of 37 fasting breast cancer cases (pretreatment). Our objective was to investigate the relationships between organochlorine concentrations in different biological media. Gas-liquid chromatography determined serum, breast adipose, and gluteal adipose tissue levels of dichlorodiphenyltricholorethane, dichlorodiphenyldichloroethane, β-benzene hexachloride, and polychlorinated biphenyl (PCB) congeners, PCB-153 and PCB-180. Correlation plots were made and Spearman correlation coefficients W calculated for breast adipose tissue versus serum, gluteal adipose tissue versus serum, and breast adipose versus gluteal adipose tissue. We also examined paired ratios of all summary statistics. There were strong correlations among serum, breast adipose tissue, and gluteal adipose tissue concentrations for most organochlorines analyzed, one exception being gluteal versus serum for PCB-153. The correlations for all other comparisons ranged from r = 0.65 to 0.94. Serum (ng/g) versus adipose ratios approached 1:1 for most of the organochlorine pesticide comparisons and did not vary by summary statistic. To our knowledge, this is the first study to use three different media from fasting subjects and to comprehensively investigate the relationship between organochlorines measured across the three media for both organochlorine pesticides and PCBs. These data indicate that blood serum reflects the present body burden of a range of organochlorines to the same extent as adipose tissue, and they support the view that serum may be collected in lieu of adipose tissue to obtain similar information. However, such measurements are a combination of both recent exposures and past exposures, which have metabolized slowly and may still persist. Therefore, investigators should use caution when assigning a level as lifetime body burden. C1 NCI, Occupational & Environm Epidemiol Branch, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,NIH, Bethesda, MD 20892 USA. NCI, Nutr Epidemiol Branch, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,NIH, Bethesda, MD 20892 USA. Reg Canc Ctr, Div Epidemiol & Clin Res, Trivandrum 695011, Kerala, India. Univ Massachusetts, Sch Publ Hlth Sci, Dept Publ Hlth, Epidemiol & Biostat Program, Amherst, MA 01003 USA. Res Triangle Inst Int, Res Triangle Pk, NC USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA. RP Rusiecki, JA (reprint author), NCI, Occupational & Environm Epidemiol Branch, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,NIH, 6120 Execut Blvd,EPS 8111, Bethesda, MD 20892 USA. EM rusieckj@mail.nih.gov RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 61 TC 41 Z9 41 U1 2 U2 11 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 MAY PY 2005 VL 14 IS 5 BP 1113 EP 1124 DI 10.1158/1055-9965.EPI-04-0356 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 925DP UT WOS:000229032000013 PM 15894661 ER PT J AU Coughlin, SS Breslau, ES Thompson, T Benard, VB AF Coughlin, SS Breslau, ES Thompson, T Benard, VB TI Physician recommendation for Papanicolaou testing among US women, 2000 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CLINICAL PREVENTIVE SERVICES; CERVICAL-CANCER; OLDER WOMEN; SCREENING MAMMOGRAPHY; AMERICAN WOMEN; PRIMARY-CARE; SOCIOECONOMIC-STATUS; FAMILY PHYSICIANS; BEHAVIORAL-MODEL; SYSTEMS-MODEL AB Objective: Many women in the U.S. undergo routine cervical cancer screening, but some women have rarely or never had a Papanicolaou (Pap) test. Studies of other cancer screening tests (for example, mammograms) have shown that physician recommendation to get a screening test is one of the strongest predictors of cancer screening. Methods: In this study, we examined whether women in the U.S. had received a physician recommendation to get a Pap test using data from the 2000 National Health Interview Survey. Reported reasons for not receiving a Pap test were also explored. Results: Among women aged &GE; 18 years who had no history of hysterectomy, 83.3% [95% confidence interval (CI), 82.484.1%] of the 13,636 women in this sample had had a Pap test in the last 3 years. Among 2,310 women who had not had a recent Pap test, reported reasons for not receiving a Pap test included: "No reason/never thought about it" (48.0%; 95% CI, 45.5-50.7), "Doctor didn't order it" (10.3%; 95% CI, 8.7-12.0), "Didn't need it/didn't know I needed this type of test" (8.1%; 95% CI, 6.7-9.6), "Haven't had any problems" (9.0%; 95% CI, 7.6-10.5), "Put it off" (7.4%; 95% CI, 6.2-8.7), "Too expensive/no insurance" (8.7%; 95% CI, 7.3-10.2), "Too painful, unpleasant, embarrassing" (3.5%; 95% CI, 2.5-4.6), and "Don't have doctor" (1.7%; 95% CI, 1.2-2.4). Among women who had had a doctor visit in the last year but who had not had a recent Pap test, about 86.7% (95% CI, 84.5-88.6) reported that their doctor had not recommended a Pap test in the last year. African-American women were as likely as White women to have received a doctor recommendation to get a Pap test. Hispanic women were as likely as non-Hispanic women to have received a doctor recommendation to get a Pap test. In multivariate analysis, factors positively associated with doctor recommendation to get a Pap test included being aged 30 to 64 years, having been born in the U.S., and having seen a specialist or general doctor in the past year. Conclusion: These findings suggest that lack of a physician recommendation contributes to underuse of Pap screening by many eligible women. Given research that shows the effectiveness of physician recommendations in improving use, increased physician recommendations could contribute significantly to increased Pap screening use in the U.S. C1 Ctr Dis Control & Prevent, Epidemiol & Appl Res Branch, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Coughlin, SS (reprint author), Ctr Dis Control & Prevent, Epidemiol & Appl Res Branch, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway,NE K-55, Atlanta, GA 30341 USA. EM sic9@cdc.gov NR 56 TC 45 Z9 46 U1 3 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 MAY PY 2005 VL 14 IS 5 BP 1143 EP 1148 DI 10.1158/1055-9965.EPI-04-0559 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 925DP UT WOS:000229032000016 PM 15894664 ER PT J AU McIntyre-Seltman, K Castle, PE Guido, R Schiffman, M Wheeler, CM AF McIntyre-Seltman, K Castle, PE Guido, R Schiffman, M Wheeler, CM CA ALTS Grp TI Smoking is a risk factor for cervical intraepithelial neoplasia grade 3 among oncogenic human papillomavirus DNA-positive women with equivocal or mildly abnormal cytology SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MULTICENTRIC CASE-CONTROL; ATYPICAL SQUAMOUS-CELLS; ASCUS-LSIL TRIAGE; UNDETERMINED SIGNIFICANCE; RANDOMIZED-TRIAL; CANCER; MANAGEMENT; INFECTION; COFACTOR; ETIOLOGY AB Background: Smoking is a potential risk factor for cervical cancer and its immediate precursor, cervical intraepithelial neoplasia grade 3 (CIN3), but few studies have adequately taken into account the possible confounding effect of oncogenic human papillomavirus (HPV) infection. Methods: Women (n = 5,060) with minimally abnormal Papanicolaou smears were enrolled in the ASCUS and LSIL Triage Study, a clinical trial to evaluate management strategies, and were seen every 6 months for the 2-year duration of the study. Cervical specimens were tested for HPV DNA using both Hybrid Capture 2 and PGMY09/11 L1 consensus primer PCR with reverse line blot hybridization for genotyping. Multivariate logistics regression models were used to assess associations [odds ratio (OR) with 95% confidence intervals (95% CI)] between smoking behaviors and rigorously reviewed cases of cervical intraepithelial neoplasia grade 3 or cancer (&GE; CIN3) identified throughout the study (n = 506) in women with oncogenic HPV (n = 3,133). Results: Current smoking was only weakly associated with increased HPV infection. Among infected women, current smokers (OR, 1.7; 95% CI, 1.4-2.1) and past smokers (OR, 1.7; 95% CI, 1.2-2.4) were more likely to be diagnosed with &GE; CIN3 than nonsmokers. Greater smoking intensity (P-Trend < 0.0005) and duration (P-Trend < 0.0005) increased the strength of the association, with smoking &GE; 2 packs/d (OR, 3.3; 95% CI, 1.5-7.5) and smoking for 11 years (OR, 2.1; 95% CI, 1.5-2.9) most strongly associated with &GE; CIN3 as compared to nonsmokers. The effects of intensity and duration seemed additive. Conclusions: Women with oncogenic HPV and minimally abnormal Papanicolaou smears who smoke were up to three times more likely to be diagnosed with &GE; CIN3 than nonsmokers. Smoking cessation trials targeting this population might be warranted. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, Room 7074,6120 Execut Blvd,EPS MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov FU NCI NIH HHS [CN-55105, CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159] NR 28 TC 69 Z9 72 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 MAY PY 2005 VL 14 IS 5 BP 1165 EP 1170 DI 10.1158/1055-9965.EPI-04-0918 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 925DP UT WOS:000229032000019 PM 15894667 ER PT J AU Nilsson, M Chow, WH Lindblad, M Ye, WM AF Nilsson, M Chow, WH Lindblad, M Ye, WM TI No association between gastroesophageal reflux and cancers of the larynx and pharynx SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RISK-FACTOR; DISEASE; CARCINOMA; ESOPHAGEAL; PREVALENCE; POPULATION; ALCOHOL; NECK; HEAD AB Purpose: To examine the proposed relation between gastroesophageal reflux disease and cancers of the larynx and pharynx. Experimental Design: A cohort of 66,965 patients with discharge diagnoses of heartburn, hiatal hernia, or esophagitis was identified in the Swedish Inpatient Register. We observed a total of 376,622 person-years in the cohort. Identification of laryngeal and pharyngeal cancers was achieved through the Swedish Cancer Register. Standardized incidence ratios, the ratio of the observed to the expected number of cancers, derived from the general Swedish population and adjusted for sex, age, and calendar year, was used to estimate the relative risk. Results: During follow-up, 30 cases of laryngeal and 31 cases of pharyngeal cancer were detected in the cohort. Slightly increased risks of laryngeal [relative risk, 1.6; 95% confidence interval (0), 1.1-2.2] and pharyngeal carcinomas (relative risk, 1.9; 95% CI, 1.3-2.8) were observed in the total reflux cohort. After stratification to exclude cohort members with a diagnosis of alcoholism, no significant increase in the risk of laryngeal (relative risk, 1.3; 95% CI, 0.8-2.0) or pharyngeal carcinomas (relative risk, 1.0; 95% CI, 0.5-1.6) was found compared with the general population. Furthermore, there were no dose-response patterns of the risk for laryngeal and pharyngeal cancers with years of cohort follow-up, indicators of reflux severity, or specificity of reflux diagnosis. Conclusion: This study provides no evidence in support of the proposed association between gastroesophageal reflux disease and cancers of the larynx or pharynx. C1 Karolinska Hosp, Dept Surg P9 03, SE-17176 Stockholm, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Nilsson, M (reprint author), Karolinska Hosp, Dept Surg P9 03, SE-17176 Stockholm, Sweden. EM magnus.nilsson@meb.ki.se RI Ye, Weimin/A-5939-2008 NR 24 TC 12 Z9 12 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 MAY PY 2005 VL 14 IS 5 BP 1194 EP 1197 DI 10.1158/1055-9965.EPI-04-0697 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 925DP UT WOS:000229032000023 PM 15894671 ER PT J AU Woodson, K Weisenberger, DJ Campan, M Laird, PW Tangrea, J Johnson, LL Schatzkin, A Lanza, E AF Woodson, K Weisenberger, DJ Campan, M Laird, PW Tangrea, J Johnson, LL Schatzkin, A Lanza, E TI Gene-specific methylation and subsequent risk of colorectal adenomas among participants of the polyp prevention trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CPG ISLAND METHYLATION; MICROSATELLITE INSTABILITY; ABERRANT METHYLATION; HUMAN COLON; ER-ALPHA; CANCER; ESTROGEN; HYPERMETHYLATION; NEOPLASIA; PHENOTYPE AB Hypermethylation of tumor suppressor and other regulatory genes is thought to play an important role in colorectal neoplasia and tumorigenesis. This study examined the association between gene methylation status in baseline adenomas and subsequent adenoma recurrence in a randomized dietary intervention study, the Polyp Prevention Trial. The methylation status of four genes [CDKN2A (p16), PTGS2 (COX2), ESR1 (ER-α), and PGR(PR)] was determined by MethyLight in 284 baseline adenomas from 196 trial participants. The association of gene methylation with recurrence was determined using logistic regression models. Gene methylation was evaluated as percent of methylated reference, a measure of methylation of each gene relative to control DNA. ESR1methylation status was inversely associated with adenoma recurrence, odds ratio = 0.36 (95% confidence interval, 0.15-0.88; P = 0.02) for the highest compared with the lowest quartile of the ESR1methylation. Further, ESR1 methylation status was inversely associated with the recurrence of multiple adenomas, advanced adenomas, and the recurrence of adenomas in the proximal but not distal bowel. No association between CDKN2A, PTGS2, or PGR methylation and adenoma recurrence was observed. These data suggest that ESR1 methylation may play a role in subsequent adenoma recurrence. C1 NCI, Canc Res Ctr, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. NCI, Basic Res Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ So Calif, Keck Sch Med, Dept Surg & Biochem & Mol Biol, Los Angeles, CA USA. RP Woodson, K (reprint author), NCI, Canc Res Ctr, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. EM kw114v@nih.gov RI Laird, Peter/G-8683-2012 FU NCI NIH HHS [R01 CA075090] NR 23 TC 15 Z9 15 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 MAY PY 2005 VL 14 IS 5 BP 1219 EP 1223 DI 10.1158/1055-9965.EPI-04-0726 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 925DP UT WOS:000229032000027 PM 15894675 ER PT J AU Daugherty, SE Pfeiffer, RM Mellemkjaer, L Hemminki, K Goldin, LR AF Daugherty, SE Pfeiffer, RM Mellemkjaer, L Hemminki, K Goldin, LR TI No evidence for anticipation in lymphoproliferative tumors in population-based samples SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; FAMILY-CANCER DATABASE; AT-ONSET ANTICIPATION; GENETIC ANTICIPATION; TIME TRENDS; DISEASE; AGGREGATION; RISK AB Genetic anticipation in familial non-Hodgkin's lymphoma, Hodgkin's lymphoma, and chronic lymphocytic leukemia (CLL) has been consistently reported in the literature. However, most of these findings were based on data from families ascertained for genetic studies. Fecundity bias, right censoring bias, and secular trends can lead to erroneous conclusions regarding the presence of anticipation. Our report investigates anticipation in four lymphoproliferative cancers, non-Hodgkin's lymphoma, Hodgkin's lymphoma, CLL, and multiple myeloma, drawn from Swedish and Danish population-based registries. We used marginal survival methods to test for a relative difference in age at diagnosis between parents and offspring and to account for other risk factors, staggered entries, censored data, and correlations among relatives. Changes in incidence rates of lymphoproliferative tumors were accommodated in the models by using time-varying covariates for different periods of diagnosis. Whereas no anticipation was observed for Hodgkin's lymphoma, CLL, and multiple myeloma, our initial model, which controlled for gender and country, suggested a significant difference (hazard ratio, 0.5; 95% confidence interval, 0.33-0.75) in age at diagnosis between the parents and offspring in the non-Hodgkin's lymphoma sample. However, once we accounted for the significant change in non-Hodgkin's lymphoma incidence over time, the statistical difference between parents and offspring disappeared (hazard ratio, 0.99; 95% confidence interval, 0.56-1.76). Our results emphasize the importance of considering secular trends when evaluating the possibility of anticipation in lymphoproliferative cancers. This is the first study to consider the changes of incidence over time as a source of bias when evaluating anticipation in lymphoproliferative cancers. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. Karolinska Inst, Dept Biosci Novum, Stockholm, Sweden. German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany. RP Daugherty, SE (reprint author), NCI, Div Canc Epidemiol & Genet, EPS Room 511,6120 Execut Blvd, Bethesda, MD 20892 USA. EM daughers@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 NR 27 TC 33 Z9 33 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 MAY PY 2005 VL 14 IS 5 BP 1245 EP 1250 DI 10.1158/1055-9965.EPI-04-0783 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 925DP UT WOS:000229032000032 PM 15894680 ER PT J AU Platz, EA Leitzmann, MF Rifai, N Kantoff, PW Chen, YC Stampfer, MJ Willett, WC Giovannucci, E AF Platz, EA Leitzmann, MF Rifai, N Kantoff, PW Chen, YC Stampfer, MJ Willett, WC Giovannucci, E TI Sex steroid hormones and the androgen receptor gene CAG repeat and subsequent risk of prostate cancer in the prostate-specific antigen era SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SERUM TESTOSTERONE LEVELS; HEALTH-PROFESSIONALS; POLYMORPHIC REPEATS; ALLELIC VARIANTS; ASSOCIATION; POPULATION; LENGTH; SUSCEPTIBILITY; SURVIVAL; JAPANESE AB Objective: Sex steroid hormones are thought to contribute to the growth, differentiation, and progression of prostate cancer. We investigated plasma levels of sex steroid hormones and length of the androgen receptor gene CAG repeat in relation to incident prostate cancer diagnosed in the prostate-specific antigen (PSA) era. Methods: Using a nested case-control design, we included 460 prostate cancer cases diagnosed after providing a blood specimen in 1993 but before February 1998 among men in the Health Professionals Follow-up Study. Controls were 460 age-matched men without prostate cancer who had a screening PSA test after the date of providing a blood specimen. We measured plasma concentrations of total testosterone, free testosterone, dihydrotestosterone, androstanediol glucuronide, estradiol, and sex hormone binding globulin (SHBG) and determined the length of the androgen receptor gene CAG repeat. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer. Results: Mean concentrations of the sex steroids adjusted for SHBG, and mean CAG repeat length did not differ significantly between the prostate cancer cases and controls. No significant associations with total prostate cancer were detected for plasma total testosterone concentration (comparing highest versus lowest quartiles: OR, 0.78; 95% CI, 0.48-1.28; P-trend = 0.73) or the other sex hormones after adjusting for SHBG. However, plasma total testosterone concentration was positively associated with low-grade disease (Gleason sum < 7: OR, 1.91; 95% CI, 0.89-4.07; P-trend = 0.02) and inversely associated with high-grade disease (Gleason sum &GE; 7: OR, 0.26; 95% CI, 0.10-0.66; P-trend = 0.01). Similar patterns for grade were observed for free testosterone. Short CAG repeat length was not associated with total prostate cancer (&LE; 19 versus &GE; 24: OR, 0.84; 95% CI, 0.57-1.23; P-trend = 0.22) or grade of disease. No clear associations with regionally invasive or metastatic (&GE; T3b, N1, or M1) were found for any of the hormones or the CAG repeat, although the number of these cases was small. Conclusions: The overall lack of association of prostate cancer diagnosed in the PSA era with sex steroid hormones and the androgen receptor gene CAG repeat length is consistent with the hypothesis that these factors do not substantially contribute to the development of early prostate cancer in the PSA era. The influence of plasma total and free testosterone concentrations on prostate cancer grade merits further evaluation. C1 Johns Hopkins Med Inst, Dept Epidemiol, Bloomberg Sch Publ Hlth, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Lab Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Lank Ctr Genitourinary Oncol, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Platz, EA (reprint author), Johns Hopkins Med Inst, Dept Epidemiol, Bloomberg Sch Publ Hlth, James Buchanan Brady Urol Inst, Room E6138,615 N Wolfe St, Baltimore, MD 21205 USA. EM eplatz@jhsph.edu RI Perez , Claudio Alejandro/F-8310-2010; Chen, Yen-Ching/D-1098-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Chen, Yen-Ching/0000-0002-8159-7202 FU NCI NIH HHS [CA55075, CA72036]; NHLBI NIH HHS [HL35464] NR 36 TC 139 Z9 144 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 MAY PY 2005 VL 14 IS 5 BP 1262 EP 1269 DI 10.1158/1055-9965.EPI-04-0371 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 925DP UT WOS:000229032000035 PM 15894683 ER PT J AU Castle, PE Schiffman, M Scott, DR Sherman, ME Glass, AG Rush, BB Schussler, JE Wacholder, S Lorincz, AT AF Castle, PE Schiffman, M Scott, DR Sherman, ME Glass, AG Rush, BB Schussler, JE Wacholder, S Lorincz, AT TI Semiquantitative human papillomavirus type 16 viral load and the prospective risk of cervical precancer and cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CARCINOMA IN-SITU; INTRAEPITHELIAL NEOPLASIA; DNA; GRADE; WOMEN; PREDICTOR; INFECTION; SMEARS; WORLDWIDE; COHORT AB We examined whether higher human papillomavirus type 16 (HPV16) viral load predicted risk of cervical intra-epithelial neoplasia 3 (CIN3) or cancer (together termed &GE; CIN3) within a cohort of 20,810 women followed for 10 years with cytologic screening. Semiquantitative viral load for HPV16 was measured on baseline cervicovaginal specimens using a type-specific hybridization probe test with signal amplification. An increased risk of &GE; CIN3 associated with higher HPV16 viral load was found only among cytologically negative women in early follow-up, suggesting that these cases were related to the detection of prevalent lesions missed at baseline. Women with higher HPV16 viral load were more likely to undergo ablative treatment during follow-up than those with lower viral load (P-trend = 0.008), possibly diminishing any additional risk for &GE; CIN3 attributable to higher HPV16 viral loads. C1 Digene Corp, Gaithersburg, MD 20878 USA. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Kaiser Permanente, Portland, OR USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Lorincz, AT (reprint author), Digene Corp, 1201 Clopper Rd, Gaithersburg, MD 20878 USA. EM attila.lorincz@digene.com NR 27 TC 28 Z9 29 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 MAY PY 2005 VL 14 IS 5 BP 1311 EP 1314 DI 10.1158/1055-9965.EPI-04-0799 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 925DP UT WOS:000229032000044 PM 15894692 ER PT J AU Liu, EJ Sakoda, LC Gao, YT Rashid, A Shen, MC Wang, BS Deng, J Han, TQ Zhang, BH Fraumeni, JF Hsing, AW AF Liu, EJ Sakoda, LC Gao, YT Rashid, A Shen, MC Wang, BS Deng, J Han, TQ Zhang, BH Fraumeni, JF Hsing, AW TI Aspirin use and risk of biliary tract cancer: A population-based study in Shanghai, China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GALLSTONE DISEASE; GALLBLADDER; CYCLOOXYGENASE-2; EXPRESSION; BILE; TUMOR; CARCINOMA; WEIGHT; SITES AB The association of gallbladder and bile duct cancers with gallstones, cholecystitis, and cholangitis suggest that chronic inflammation contributes to the carcinogenic process. However, the effect of nonsteroidal anti-inflammatory drugs, such as aspirin, on biliary tract cancer has not been well studied. In a population-based case-control study conducted in Shanghai, China, we examined the relationship between aspirin use and the risk of biliary disease. A total of 627 patients with biliary tract cancer, including cancers of the gallbladder (n = 368), extrahepatic bile duct (n = 191), and ampulla of Vater (n = 68); 1,037 patients with biliary stones; and 958 healthy adults were included in the study. Self-reported data on aspirin use was collected from study participants by in-person interview. The prevalence of aspirin use was low, with 5.7% of the population controls being regular users. After controlling for age, sex, education, and biliary stone status, aspirin use was associated with a reduced risk of gallbladder cancer [odds ratio (OR), 0.37; 95% confidence interval (0), 0.17-0.88]. An inverse relationship was also observed for frequency and duration of use and with younger age when starting use. In addition, there was a nonsignificant reduction in the risk of bile duct (OR, 0.48; 95% CI, 0.19-1.19) and ampullary cancers (OR, 0.22; 95% CI, 0.03-1.65) associated with aspirin use, whereas no clear association was seen with biliary stones (OR, 0.92; 95% CI, 0.59-1.44). Further studies of biliary tract cancer in other populations are needed to confirm these results and to elucidate the mechanisms that underlie the reduced risk associated with use of aspirin and possibly other nonsteroidal anti-inflammatory drugs. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Shanghai Canc Inst, Shanghai, Peoples R China. MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA. Shanghai Tumor Hosp, Shanghai, Peoples R China. Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. Shanghai Med Univ 2, Ruijin Hosp, Dept Surg, Shanghai, Peoples R China. Shanghai Mil Univ 2, Inst Oriental Hepatobiliary Surg, Shanghai, Peoples R China. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7058, Bethesda, MD 20892 USA. EM hsinga@mail.nih.gov RI liu, enju/B-2136-2010; liu, enju/F-4062-2010 NR 20 TC 28 Z9 28 U1 1 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 MAY PY 2005 VL 14 IS 5 BP 1315 EP 1318 DI 10.1158/1055-9965.EPI-05-0032 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 925DP UT WOS:000229032000045 PM 15894693 ER PT J AU Brooks, AD Sayers, TJ AF Brooks, AD Sayers, TJ TI Reduction of the antiapoptotic protein cFLIP enhances the susceptibility of human renal cancer cells to TRAIL apoptosis SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE apoptosis; cFLIP; renal cancer; TRAIL ID LIGAND-MEDIATED APOPTOSIS; INTRACELLULAR REGULATION; TUMOR-METASTASIS; MYELOMA CELLS; DEATH; FLIP; APO2L/TRAIL; EXPRESSION; RESISTANCE; INHIBITORS AB Human renal carcinoma cells (RCCs) were sensitized to the apoptotic effects of tumor necrosis factor (TNF) - related apoptosis- inducing ligand ( TRAIL), by treatment with cycloheximide (CHX). In contrast to a previous study, a rapid and dramatic decrease in levels of cellular FLICE ( Fas-associated death domain - like IL-1beta-converting enzyme) inhibitory protein (cFLIP) following cycloheximide treatment was observed in all RCCs studied. The unambiguous detection of this decrease in cFLIP was dependent on the quality of the particular antibody preparation used to detect cFLIP. Cycloheximide treatment caused no major change in levels of pro-caspase-8 or cell surface expression of TRAIL receptors. Therefore, cycloheximide treatment resulted in an increase in the pro-caspase-8 to cFLIP ratio, which correlated with sensitization to TRAIL-mediated apoptosis. Furthermore, treatment of human RCCs with small interfering oligoribonucleotides ( siRNA) for cFLIP caused a reduction of cFLIP protein and sensitized cells to TRAIL-mediated apoptosis. We concluded that in the presence of an intact TRAIL signaling pathway, a significant reduction of cFLIP alone is sufficient to sensitize human RCCs to TRAIL apoptosis. C1 NCI, SAIC Frederick, Frederick, MD 21702 USA. RP Sayers, TJ (reprint author), NCI, SAIC Frederick, Bldg 560,Rm 31-67, Frederick, MD 21702 USA. EM Sayers@mail.ncifcrf.gov FU PHS HHS [N01-C0-12400] NR 26 TC 23 Z9 27 U1 1 U2 2 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 MAY PY 2005 VL 54 IS 5 BP 499 EP 505 DI 10.1007/s00262-004-0595-8 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA 903TX UT WOS:000227449600010 PM 15614529 ER PT J AU Zhao, YF Chaiswing, L Velez, JM Batinic-Haberle, I Colburn, NH Oberley, TD St Clair, DK AF Zhao, YF Chaiswing, L Velez, JM Batinic-Haberle, I Colburn, NH Oberley, TD St Clair, DK TI p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase SO CANCER RESEARCH LA English DT Article ID P53-DEPENDENT APOPTOSIS; P53-INDUCED APOPTOSIS; P53-TARGET GENES; IN-VIVO; ACTIVATION; CANCER; DEATH; MODEL; LOCALIZATION; PATHWAYS AB The tumor suppressor gene p53 is activated by reactive oxygen species- generating agents. After activation, p53 migrates to mitochondria and nucleus, a response that eventually leads to apoptosis, but how the two events are related is unknown. Herein, we show that p53 translocation to mitochondria precedes its translocation to nucleus in JB6 skin epidermal cells treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Translocation of p53 to mitochondria occurs within 10 minutes after TPA application. In the mitochondria, p53 interacts with the primary antioxidant enzyme, manganese superoxide dismutase (MnSOD), consistent with the reduction of its superoxide scavenging activity, and a subsequent decrease of mitochondrial membrane potential. In contrast to the immediate action on mitochondria, p53 transcriptional activity in the nucleus increases at I hour following TPA application, accompanied by an increase in the levels of its target gene bax at 15 hours following TPA treatment. Activation of p53 transcriptional activity is preventable by application of a SOD mimetic (MnTE-2-pyp(5+),). Thus, p53 translocation to mitochondria and subsequent inactivation of MnSOD explains the observed mitochondrial dysfunction, which leads to transcription-dependent mechanisms of p53-induced apoptosis. C1 Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. Univ Wisconsin, Dept Pathol, Madison, WI 53706 USA. Univ Wisconsin, Vet Affairs Med Ctr, Madison, WI 53706 USA. Duke Univ, Dept Radiat Oncol, Durham, NC 27706 USA. NCI, Gene Regulat Sect, Frederick, MD 21701 USA. RP St Clair, DK (reprint author), Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. EM dstc100@pop.uky.edu FU NCI NIH HHS [CA 49797, CA 73599] NR 27 TC 154 Z9 165 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 MAY 1 PY 2005 VL 65 IS 9 BP 3745 EP 3750 DI 10.1158/0008-5472.CAN-04-3835 PG 6 WC Oncology SC Oncology GA 919ZH UT WOS:000228656000034 PM 15867370 ER PT J AU Winters, ME Mehta, AI Petricoin, EF Kohn, EC Liotta, LA AF Winters, ME Mehta, AI Petricoin, EF Kohn, EC Liotta, LA TI Supra-additive growth inhibition by a celecoxib analogue and carboxyamido-triazole is primarily mediated through apoptosis SO CANCER RESEARCH LA English DT Article ID COLON-CANCER CELLS; NF-KAPPA-B; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FACTOR RECEPTOR TRANSACTIVATION; PROTEIN-KINASE PATHWAY; SMOOTH-MUSCLE-CELLS; EARLY GENE-PRODUCTS; BREAST-CANCER; SIGNALING PATHWAY; CYCLIN D1 AB Combination studies of celecoxib and chemotherapeutic agents suggest that combining cyclooxygenase-2 inhibitors with other agents may have supra-additive or synergistic effects on tumor growth inhibition. Carboxyamido-triazole (CAI), a voltage-independent calcium channel inhibitor, has been shown to induce growth inhibition and apoptosis in cancer cells. We found that continuous exposure to cytostatic doses of CAI and LM-1685, a celecoxib analogue, reduced the proliferation and survival of seven human cancer cell lines by at least one log (P <= 0.001) over either agent alone. To explore the mechanism of action of this combination, we further studied the effects of LM-1685/CAI on CCL-250 colorectal carcinoma cells. We found that the supra-additive antiproliferative effects occurred throughout a range of LM-1685 doses (5-25 mu mol/L) and paralleled a decrease in COX-2 activity as measured by prostaglandin E-2 production. In these cells, treatment with LM-1685/CAI suppressed the extracellular signal-regulated kinase pathway within the first hour but ultimately results in high, sustained activation of ERK over a 9-day period (P = 0.0005). Suppression of cyclin D1 and phospho-AKT, and cleavage of caspase-3 and PARP were concomitant with persistent ERK activation. Addition of PD98059, a MEK-1 inhibitor, suppressed ERK activation and significantly but incompletely reversed these signaling events and apoptosis. Flow cytometry experiments revealed that the CAI/LM-1685 combination induced a 3-fold increase in apoptosis over control (P = 0.005) in 3 days. We show that the combination of CAI and LM-1685 produces a cytotoxic effect by suppressing proliferation and triggering apoptosis. C1 NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, US FDA, Clin Proteom Program, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Off Cellular & Gene Therapy, Ctr Biol Evaluat & Res, Food & Drug Adm, Bethesda, MD USA. Howard Hughes Med Inst, Bethesda, MD USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, Ctr Canc Res, 10 Ctr Dr,Bldg 10,Room B1b41, Bethesda, MD 20892 USA. EM liottal@mail.nih.gov NR 68 TC 24 Z9 26 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 MAY 1 PY 2005 VL 65 IS 9 BP 3853 EP 3860 DI 10.1158/0008-5472.CAN-04-1989 PG 8 WC Oncology SC Oncology GA 919ZH UT WOS:000228656000048 PM 15867384 ER PT J AU Marcus, AI Zhou, J O'Brate, A Hamel, E Wong, J Nivens, N El-Naggar, A Yao, TP Khuri, FR Giannakakou, P AF Marcus, AI Zhou, J O'Brate, A Hamel, E Wong, J Nivens, N El-Naggar, A Yao, TP Khuri, FR Giannakakou, P TI The synergistic combination of the farnesyl transferase inhibitor lonafarnib and paclitaxel enhances tubulin acetylation and requires a functional tubulin deacetylase SO CANCER RESEARCH LA English DT Article ID BIPOLAR SPINDLE FORMATION; FARNESYLTRANSFERASE INHIBITOR; MEMBRANE ASSOCIATION; CANCER CELLS; IN-VITRO; RAS; PROTEIN; MICROTUBULES; GROWTH; TRANSFORMATION AB Farnesyl transferase (FT) inhibitors (FTI) are anticancer agents developed to target oncogenic Ras proteins by inhibiting Ras farnesylation. FTIs potently synergize with paclitaxel and other microtubule-stabilizing drugs; however, the mechanistic basis underlying this synergistic interaction remains elusive. Here we show that the FTI lonafarnib affects the microtubule cytoskeleton resulting in microtubule bundle formation, increased microtubule stabilization and acetylation, and suppression of microtubule dynamics. Notably, treatment with the combination of low doses of lonafarnib with paclitaxel markedly enhanced tubulin acetylation (a marker of microtubule stability) as compared with either drug alone. This synergistic effect correlated with FT inhibition and was accompanied by a synergistic increase in mitotic arrest and cell death. Mechanistically, we show that the combination of lonafarnib and paclitaxel inhibits the in vitro deacetylating activity of the only known tubulin deacetylase, historic deacetylase 6 (HDAC6). In addition, the lonafarnib/taxane combination is synergistic only in cells lines expressing the wild-type HDAC6, but not a catalytic-mutant HDAC6, revealing that functional HDAC6 is required for the synergy of lonafarnib with taxanes. Furthermore, tubacin, a specific HDAC6 inhibitor, synergistically enhanced tubulin acetylation in combination with paclitaxel, similar to the combination of lonafarnib and paclitaxel. Taken together, these data suggest a relationship between FT inhibition, HDAC6 function, and cell death, providing insight into the putative molecular basis of the lonafarnib/taxane synergistic antiproliferative combination. C1 Emory Univ, Sch Med, Paraskevi Giannakakou Winship Canc Inst, Atlanta, GA 30322 USA. NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis,NIH, Frederick, MD 21701 USA. Harvard Univ, Cambridge, MA 02138 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC USA. RP Giannakakou, P (reprint author), Emory Univ, Sch Med, Paraskevi Giannakakou Winship Canc Inst, Room D4054,1365 C Clifton Rd, Atlanta, GA 30322 USA. EM pgianna@emory.edu FU NCI NIH HHS [1R01 CA100202, R01 CA100202] NR 36 TC 72 Z9 78 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2005 VL 65 IS 9 BP 3883 EP 3893 DI 10.1158/0008-5472.CAN-04-3757 PG 11 WC Oncology SC Oncology GA 919ZH UT WOS:000228656000052 PM 15867388 ER PT J AU Bradshaw, TD Matthews, CS Cookson, J Chew, EH Shah, M Bailey, K Monks, A Harris, E Westwell, AD Wells, G Laughton, CA Stevens, MFG AF Bradshaw, TD Matthews, CS Cookson, J Chew, EH Shah, M Bailey, K Monks, A Harris, E Westwell, AD Wells, G Laughton, CA Stevens, MFG TI Elucidation of thioredoxin as a molecular target for antitumor quinols SO CANCER RESEARCH LA English DT Article ID IN-VITRO; CANCER; CELLS; APOPTOSIS; ASSOCIATION; INHIBITION; SURVIVAL; PROTEIN; SYSTEM; KINASE AB Heteroaromatic quinols 4-(benzothiazol-2-yl)-4-hydroxycyclohexa-2,5-dienone (1) and 4-(1-benzenesulfonyl-1H-indol-2-yl)-4-hydroxycyclohexa-2,5-dienone (2) exhibit potent and selective antitumor activity against colon, renal, and breast carcinoma cell lines in vitro (GI(50) < 500 nmol/L). In vivo growth inhibition of renal, colon, and breast xenografts has been observed. Profound G(2)-M Cell cycle block accompanied down-regulation of cdk1 gene transcription was corroborated by decreased CDK1 protein expression following treatment of HCT 116 cells with growth inhibitory concentrations of 1 or 2. The chemical structure of the quinol pharmacophore 4-(hydroxycyclohexa-2,5-dienone) suggested that these novel agents would readily react with nucleophiles in a double Michael (beta-carbon) addition. Indeed, COMPARE analysis within the National Cancer Institute database revealed a number of chemically related quinone derivatives that could potentially react with sulfur nucleophiles in a similar manner and suggested that thioredoxin/ thioredoxin reductase signal transduction could be a putative target. Molecular modeling predicted covalent irreversible binding between quinol analogues and cysteine residues 32 and 35 of thioredoxin, thereby inhibiting enzyme activity. Binding has been confirmed, via mass spectrometry, between reduced human thioredoxin and 1. Microarray analyses of untreated HCT 116 cells and those exposed to either 1 (1 mu mol/L) or 2 (500 nmol/L and 1 mu mol/L) determined that of >= 10,000 cancer-related genes, expression of thioredoxin reductase was up-regulated > 3-fold. Furthermore, quinols I and 2 inhibited insulin reduction, catalyzed by thioredoxin/thioredoxin reductase signaling in a dose-dependent manner (IC50 < 6 mu mol/L). Results are consistent with a mechanism of action of novel antitumor quinols involving inhibition of the small redox protein thioredoxin. C1 Univ Nottingham, Sch Pharm, Ctr Biomol Sci, Nottingham NG7 2RD, England. Sci Applicat Int Co Frederick Inc, Screening Technol Branch, Lab Funct Genom, NCI, Frederick, MD USA. RP Bradshaw, TD (reprint author), Univ Nottingham, Sch Pharm, Ctr Biomol Sci, Nottingham NG7 2RD, England. EM tracey.bradshaw@nottingham.ac.uk RI Laughton, Charles/E-5667-2010; Shah, Manish/H-6158-2011; Westwell, Andrew/M-8126-2014; Chew, Eng Hui/D-8975-2016; OI Laughton, Charles/0000-0003-4090-3960; Westwell, Andrew/0000-0002-5166-9236; Chew, Eng Hui/0000-0002-2615-8987; Wells, Geoffrey/0000-0002-0253-911X NR 25 TC 65 Z9 66 U1 0 U2 8 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 MAY 1 PY 2005 VL 65 IS 9 BP 3911 EP 3919 DI 10.1158/0008-5472.CAN-04-4141 PG 9 WC Oncology SC Oncology GA 919ZH UT WOS:000228656000055 PM 15867391 ER PT J AU Yin, YZ Russell, RG Dettin, LE Bai, R Wei, ZL Kozikowski, AP Kopleovich, L Glazer, RI AF Yin, YZ Russell, RG Dettin, LE Bai, R Wei, ZL Kozikowski, AP Kopleovich, L Glazer, RI TI Peroxisome proliferator-activated receptor delta and gamma agonists differentially alter tumor differentiation and progression during mammary carcinogenesis SO CANCER RESEARCH LA English DT Article ID HUMAN BREAST-CANCER; GROWTH-FACTOR EXPRESSION; HUMAN COLON-CANCER; PPAR-GAMMA; GENE-EXPRESSION; IN-VITRO; CELL-GROWTH; MATRIX METALLOPROTEINASES; TERMINAL DIFFERENTIATION; GLAND TUMORIGENESIS AB Peroxisome proliferator-activated receptor (PPAR) represents a ligand-dependent nuclear receptor family that regulates multiple metabolic processes associated with fatty acid beta-oxidation, glucose utilization, and cholesterol transport. These and other receptor-mediated actions pertain to their role in hypolipidemic and antidiabetic therapies and as potential targets for cancer chemopreventive agents. The present study evaluated the chemopreventive activity of two highly potent and selective PPAR gamma and PPAR delta agonists in a progestin- and carcinogen-induced mouse mammary tumorigenesis model. Animals treated with the PPAR gamma agonist GW7845 exhibited a moderate delay in tumor formation. In contrast, animals treated with the PPAR delta agonist GW501516 showed accelerated tumor formation. Significantly, tumors from GW7845-treated mice were predominantly ductal adenocarcinomas, whereas tumors from GW501516-treated animals were adenosquamous and squamous cell carcinomas. Gene expression analysis of tumors arising from GW7845- and GW501516-treated mice identified expression profiles that were distinct from each other and from untreated control tumors of the same histopathology. Only tumors from mice treated with the PPAR gamma agonist expressed estrogen receptor-alpha in luminal transit cells, suggesting increased ductal progenitor cell expansion. Tumors from mice treated with the PPAR delta agonist exhibited increased PPAR delta levels and activated 3-phosphoinositide-dependent protein kinase-1 (PDK1), which co-associated, suggesting a link between the known oncogenic activity of PDK1 in mammary epithelium and PPAR delta activation. These results indicate that PPAR delta and PPAR gamma agonists produce diverse, yet profound effects on mammary tumorigenesis that give rise to distinctive histopathologic patterns of tumor differentiation and tumor development. C1 Georgetown Univ, Sch Med, Dept Oncol, Washington, DC 20057 USA. Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL USA. NCI, Div Chemoprevent, Bethesda, MD 20892 USA. RP Glazer, RI (reprint author), Georgetown Univ, Sch Med, Dept Oncol, Room W318,Res Bldg,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM glazerr@georgetown.edu FU NCI NIH HHS [N01-CN-25101] NR 71 TC 71 Z9 72 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 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2005 VL 65 IS 9 BP 3950 EP 3957 DI 10.1158/0008-5472.CAN-04-3990 PG 8 WC Oncology SC Oncology GA 919ZH UT WOS:000228656000060 PM 15867396 ER PT J AU El-Abaseri, TB Fuhrman, J Trempus, C Shendrik, I Tennant, RW Hansen, LA AF El-Abaseri, TB Fuhrman, J Trempus, C Shendrik, I Tennant, RW Hansen, LA TI Chemoprevention of UV light-induced skin tumorigenesis by inhibition of the epidermal growth factor receptor SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; SIGNAL-REGULATED KINASE; PROTEIN-KINASE; EGF RECEPTOR; MOLECULAR MECHANISMS; TARGETED DISRUPTION; HUMAN KERATINOCYTES; ULTRAVIOLET-LIGHT; TYROSINE KINASES; HAIR FOLLICLE AB The epidermal growth factor receptor (EGFR) is activated in skin cells following UV irradiation, the primary cause of nonmelanoma skin cancer. The EGFR inhibitor AG1478 prevented the UV-induced activation of EGFR and of downstream signaling pathways through c-Jun NH2-terminal kinases, extracellular signal-regulated kinases, p38 kinase, and phosphatidylinositol 3-kinase in the skin. The extent to which the UV-induced activation of EGFR influences skin tumorigenesis was determined in genetically initiated v-ras(Ha) transgenic Tg.AC mice, which have enhanced susceptibility to skin carcinogenesis. Topical treatment or i.p. injection of AG1478 before UV exposure blocked the UV-induced activation of EGFR in the skin and decreased skin tumorigenesis in Tg.AC mice. AG1478 treatment before each of several UV exposures decreased the number of papillomas arising and the growth of these tumors by similar to 50% and 80%, respectively. Inhibition of EGFR suppressed proliferation, increased apoptotic cell death, and delayed the onset of epidermal hyperplasia following UV irradiation. Genetic ablation of Egfr similarly delayed epidermal hyperplasia in response to UV exposure. Thus, the UV-induced activation of EGFR promotes skin tumorigenesis by suppressing cell death, augmenting cell proliferation, and accelerating epidermal hyperplasia in response to UV. These results suggest that EGFR may be an appropriate target for the chemoprevention of UV-induced skin cancer. C1 Creighton Univ, Dept Biomed Sci, Sch Med, Omaha, NE 68178 USA. Creighton Univ, Dept Pathol, Omaha, NE 68178 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Hansen, LA (reprint author), Creighton Univ, Dept Biomed Sci, Sch Med, 2500 Calif Plaza, Omaha, NE 68178 USA. EM lhansen@creighton.edu FU NCRR NIH HHS [P20 RR018788, P20 RR018759, C06 RR17417-01]; NIEHS NIH HHS [ES-00365-01] NR 44 TC 58 Z9 59 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 MAY 1 PY 2005 VL 65 IS 9 BP 3958 EP 3965 DI 10.1158/0008-5472.CAN-04-2204 PG 8 WC Oncology SC Oncology GA 919ZH UT WOS:000228656000061 PM 15867397 ER PT J AU Crist, KA Zhang, ZQ You, M Gunning, WT Conran, PB Steele, VE Lubet, RA AF Crist, KA Zhang, ZQ You, M Gunning, WT Conran, PB Steele, VE Lubet, RA TI Characterization of rat ovarian adenocarcinomas developed in response to direct instillation of 7,12-dimethylbenz[a]anthracene (DMBA) coated suture SO CARCINOGENESIS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; GRANULOSA-CELL TUMORS; MONOCLONAL-ANTIBODY; GYNECOLOGIC CANCERS; INDUCTION; CARCINOMA; ANTIGEN; EXPRESSION; MICE; CARCINOGENESIS AB Human ovarian cancer is predominantly of epithelial cell origin (> 90% of malignant tumors) and most often presents at an advanced stage with poor prognosis. Most animal models of ovarian carcinoma yield thecal/granulosa cell tumors, rather than adenocarcinomas. Induction of adenocarcinoma in 10-45% of rats following an ovarian implantation of 7,12-dimethylbenz[a]anthracene (DMBA) coated silk suture has been reported. Here, DMBA of 99% purity was melted at 124 degrees C to impregnate a 1 cm length of sterile suture for direct ovarian implantation in Wistar Furth rats at 7 weeks of age. DMBA-treated ovaries showed a nearly complete loss of primary follicles and degeneration of granulosa cells at 16 weeks, consistent with the known toxic response of the ovary to direct DMBA application. No tumors were present. Untreated right ovaries and sham dimethyl sulfoxide-treated ovaries were normal. Ovarian tumors in DMBA-treated rats were first noted at 26 weeks post implantation reaching a cumulative tumor incidence of 77% (23/30) at 52 weeks. Controls showed no evidence of tumor at 52 weeks (0/31). Tumor histology was distributed as well differentiated adenocarcinoma (1/23), poorly differentiated adenocarcinoma (8/23), thecal/granulosa cell tumor (8/23), undifferentiated sarcoma (5/23) and one undifferentiated carcinoma with no adeno character. Tumors occasionally seeded to peritoneal mesentery, spleen and abdominal wall. Adenocarcinomas appeared to originate from the ovarian surface epithelium, with focal papillary extension into cystic space. Epithelial derived tumor cells positively react with antibodies to cytokeratin (8/8), epithelial cell adhesion molecule (Ep-CAM 5/5) and prostaglandin synthetase-1 (COX-1 4/4). Vimentin positive epithelial cells when present in adenocarcinomas (4/7), showed perinuclear staining, quite distinct from the uniformly stained stromal cells in thecal/granulosa cell tumors (8/8). The thecal/granulosa cell tumors were Ep-CAM negative (0/5) and weakly COX-1 positive (4/4). Thus, the DMBA suture model in rats yields epithelial derived tumors histologically similar to humans and should prove suitable for the testing of preventive or therapeutic agents. C1 Med Coll Ohio, Dept Surg, Toledo, OH 43614 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. NCI, Chemoprevent Agent Dev Grp, Rockville, MD USA. RP Crist, KA (reprint author), Med Coll Ohio, Dept Surg, Toledo, OH 43614 USA. EM kcrist@mco.edu RI Gunning, William/E-4681-2010 FU NCI NIH HHS [N01-CN-05103] NR 51 TC 22 Z9 25 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2005 VL 26 IS 5 BP 951 EP 957 DI 10.1093/carcin/bgi039 PG 7 WC Oncology SC Oncology GA 921RE UT WOS:000228781500011 PM 15695234 ER PT J AU Simeone, AM Deng, CX Kelloff, GJ Steele, VE Johnson, MM Tari, AM AF Simeone, AM Deng, CX Kelloff, GJ Steele, VE Johnson, MM Tari, AM TI N-(4-hydroxyphenyl)retinamide is more potent than other phenylretinamides in inhibiting the growth of BRCA1-mutated breast cancer cells SO CARCINOGENESIS LA English DT Article ID ESTROGEN-RECEPTOR STATUS; SYNTHETIC RETINOID FENRETINIDE; BRCA1 MUTATION CARRIERS; FAMILIAL BREAST; OVARIAN-CANCER; PROPHYLACTIC OOPHORECTOMY; TUMOR-FORMATION; MAMMARY-GLAND; WOMEN; RISK AB Women with germline mutations in the breast cancer susceptibility gene BRCA1 are at an increased risk of developing breast cancer. The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) has been shown to have a clinical chemopreventive activity in patients with premenopausal breast cancer. Since BRCA1 mutations are associated with an early-onset breast cancer, usually before menopause, we hypothesized that 4-HPR may be an effective chemopreventive agent against breast tumors exhibiting BRCA1 mutations. The objective of this study was to determine the effectiveness and mechanisms of action of 4-HPR and its phenylretinamide analogues in BRCA1-mutated breast cancer cells. At clinically relevant doses, 4-HPR induced apoptosis in human (HCC1937) and murine (W0069, W525) BRCA1-mutated breast cancer cells. Among the various phenylretinamides tested, N-(2-carboxyphenyl)retinamide (2-CPR) and 3-CPR significantly inhibited the growth of HCC1937 cells; however, they were not as potent as 4-HPR in this respect. We also determined the mechanisms by which 4-HPR induces apoptosis in BRCA1-mutated breast cancer cells. The extent to which 4-HPR induced apoptosis in BRCA1-mutated cells correlated with the increases in nitric oxide (NO) production and nitric oxide synthase (NOS) II and NOSIII expression. Use of a NOS inhibitor to block NO production suppressed the inhibitory effects of 4-HPR in all cell lines. These in vitro results suggest that 4-HPR may be an effective chemopreventive agent against breast tumors that exhibit BRCA1 mutations because of its ability to induce NO-mediated apoptosis in such tumors. C1 Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. NIDDKD, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diagnost, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Simeone, AM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM amsimeon@mdanderson.org RI deng, chuxia/N-6713-2016 NR 61 TC 22 Z9 24 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 MAY PY 2005 VL 26 IS 5 BP 1000 EP 1007 DI 10.1093/carcin/bgi038 PG 8 WC Oncology SC Oncology GA 921RE UT WOS:000228781500017 PM 15695235 ER PT J AU Pepe, S Lakatta, EG AF Pepe, S Lakatta, EG TI Aging hearts and vessels: Masters of adaptation and survival SO CARDIOVASCULAR RESEARCH LA English DT Editorial Material ID CARDIOVASCULAR-DISEASE ENTERPRISES; MAJOR SHAREHOLDERS; ARTERIAL; EXERCISE; AGE C1 Alfred Hosp, Lab Cardiac Surg Res, Melbourne, Vic 8008, Australia. Monash Univ, Baker Heart Res Inst, Dept Surg, Alfred Hosp,Lab Cardiac Surg Res,Wynn Dept Metab, Melbourne, Vic 8008, Australia. NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH,Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Pepe, S (reprint author), Alfred Hosp, Lab Cardiac Surg Res, POB 6492,St Kilda Rd Cent, Melbourne, Vic 8008, Australia. EM spepe@baker.edu.au NR 38 TC 20 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAY 1 PY 2005 VL 66 IS 2 BP 190 EP 193 DI 10.1016/j.cardiores.2005.03.004 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919GQ UT WOS:000228606800002 PM 15820187 ER PT J AU Volkova, M Garg, R Dick, S Boheler, KR AF Volkova, M Garg, R Dick, S Boheler, KR TI Aging-associated changes in cardiac gene expression SO CARDIOVASCULAR RESEARCH LA English DT Review DE aging; gene expression; gene array analysis; heart failure; statistics ID HUMAN HEART-FAILURE; OXIDATIVE STRESS; RAT-HEART; CALORIC RESTRICTION; ENDOTHELIAL-CELLS; MOUSE MODELS; AGE; MICROARRAY; SENESCENCE; THROMBOSPONDIN-4 AB Cardiovascular diseases (e.g., vascular diseases, strokes, heart failure) reach epidemic proportions in the elderly and are the primary limits to survival in man. Age-associated changes in heart structure and function represent the major risk factors in heart failure (HE) syndromes and are associated with altered patterns of gene expression that can generally be seen as relative changes in the abundance of gene transcripts. An understanding of the molecular mechanisms underlying these changes should be tantamount to defining a genetic basis for aging; however, the analysis of processes as complicated as aging requires an accounting of biological diversity. Until recently, most of the changes in transcript abundance were identified one at a time, but the advent of gene expression arrays has permitted rapid, large-scale expression profiling. This has provided information about the dynamics of total gene expression, which can be used to identify pathways and elucidate regulatory events that may be affected during senescence or in response to disease. Importantly, very large sample sizes or meta-analyses of studies of smaller sample sizes should be sufficient to account for the diversity of altered gene expression that directs alterations in specific molecular pathways, which underlie changes in cardiac structure and function in senescence and disease. (c) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 NIA, NIH, GRC, LCS, Baltimore, MD 21224 USA. RP Boheler, KR (reprint author), NIA, NIH, GRC, LCS, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bohelerk@grc.nia.nih.gov NR 76 TC 17 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAY 1 PY 2005 VL 66 IS 2 BP 194 EP 204 DI 10.1016/j.cardiores.2004.11.016 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919GQ UT WOS:000228606800003 PM 15820188 ER PT J AU Juhaszova, M Rabuel, C Zorov, DB Lakatta, EG Sollott, SJ AF Juhaszova, M Rabuel, C Zorov, DB Lakatta, EG Sollott, SJ TI Protection in the aged heart: preventing the heart-break of old age? SO CARDIOVASCULAR RESEARCH LA English DT Review DE aging; ischemia-reperfusion; preconditioning; mitochondria; ROS ID PROTEIN-KINASE-C; ACUTE MYOCARDIAL-INFARCTION; MITOCHONDRIAL PERMEABILITY TRANSITION; SENSITIVE POTASSIUM CHANNELS; NITRIC-OXIDE SYNTHASE; CARDIOVASCULAR-DISEASE ENTERPRISES; GLUCOSE-INSULIN-POTASSIUM; ISOLATED RAT-HEART; AGING HEART; CONSCIOUS RABBITS AB The aged heart has a diminished functional and adaptive reserve capacity, an increased susceptibility to incur damage (e.g., as a result of ischemia), and a limited practical ability for repair/regeneration. Thus, there has been considerable interest to harness the heart's endogenous capacity to resist such damage, known as ischemic preconditioning (IPC), as well as other cardioprotective mechanisms. However, the translation of basic research findings into clinical practice has largely been inadequate because there have been few if any successful implementations in terms of viable therapies activating cardioprotection mechanisms to limit infarct size. Here, we provide an overview of the general mechanisms of cardioprotection, changes in the structure and function of the aged heart, and the current knowledge regarding cardioprotection in aged heart. The problems and opportunities for successful bench-to-bedside translation of cardioprotection in the elderly are discussed. European Society of Cardiology. Published by Elsevier B.V. C1 NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Sollott, SJ (reprint author), NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, Intramural Res Program,NIH, 5600 Nathan Shock Dr,Box 13, Baltimore, MD 21224 USA. EM sollotts@grc.nia.nih.gov NR 126 TC 79 Z9 89 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAY 1 PY 2005 VL 66 IS 2 BP 233 EP 244 DI 10.1016/j.cardiores.2004.12.020 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919GQ UT WOS:000228606800007 PM 15820192 ER PT J AU Fields, RD Lee, PR Cohen, JE AF Fields, RD Lee, PR Cohen, JE TI Temporal integration of intracellular Ca2+ signaling networks in regulating gene expression by action potentials SO CELL CALCIUM LA English DT Article DE calcium signaling; CREB; CaMKII; microarray; plasticity; DRG; intracellular signaling ID PROTEIN-KINASE-II; FACTOR-2 TRANSCRIPTION FACTOR; RAT SENSORY NEURONS; CREB PHOSPHORYLATION; CALCIUM-CHANNELS; ENDOPLASMIC-RETICULUM; ELECTRICAL-ACTIVITY; CALMODULIN COMPLEX; NEURAL IMPULSES; MESSENGER-RNA AB Temporal aspects of intracellular calcium signaling are particularly important in activity-dependent regulation of gene expression in neurons. This review traces calcium-dependent intracellular signaling from the membrane to the nucleus in response to action-potential firing, and considers how specific genes are regulated by specific patterns of impulse firing. Modes of calcium influx, calcium-dependent protein kinases, transcription factors, individual genes, and genomic analysis are examined, with particular emphasis on the importance of temporal aspects of calcium dynamics in regulating these processes. Published by Elsevier Ltd. C1 NICHD, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHD, Nervous Syst Dev & Plast Sect, NIH, Bldg 35,Room 2A211,MSC 3713,35 Lincoln Dr, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov NR 54 TC 73 Z9 76 U1 0 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD MAY PY 2005 VL 37 IS 5 BP 433 EP 442 DI 10.1016/j.ceca.2005.01.011 PG 10 WC Cell Biology SC Cell Biology GA 920SD UT WOS:000228709500009 PM 15820391 ER PT J AU O'Donovan, MJ Bonnot, A Wenner, P Mentis, GZ AF O'Donovan, MJ Bonnot, A Wenner, P Mentis, GZ TI Calcium imaging of network function in the developing spinal cord SO CELL CALCIUM LA English DT Article DE calcium imaging; spinal cord; motoneurons ID SPONTANEOUS RHYTHMIC ACTIVITY; CHICK-EMBRYO; ACTIVITY PATTERNS; MOTOR-ACTIVITY; IN-VITRO; MOUSE; CIRCUITS; HINDLIMB; NEURONS; TRANSMISSION AB We have used calcium imaging to visualize the spatiotemporal organization of activity generated by in vitro spinal cord preparations of the developing chick embryo and the neonatal mouse. During each episode of spontaneous activity, we found that chick spinal neurons were activated rhythmically and synchronously throughout the transverse extent of the spinal cord. At the onset of a spontaneous episode, optical activity originated in the ventrolateral part of the cord. Back-labeling of spinal interneurons with calcium dyes suggested that this ventrolateral initiation was mediated by activation of a class of interneurons, located dorsomedial to the motor nucleus, that receive direct monosynaptic input from motoneurons. Studies of locomotor-like activity in the anterior lumbar segments of the neonatal mouse cord revealed the existence of a rostrocaudal wave in the oscillatory component of each cycle of rhythmic motoneuron activity. This finding raises the possibility that the activation of mammalian motoneurons during locomotion may share some of the same rostrocaudally organized mechanisms that evolved to control swimming in fishes. Published by Elsevier Ltd. C1 NINDS, Neural Control Lab, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA. RP O'Donovan, MJ (reprint author), NINDS, Neural Control Lab, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA. EM odonovm@ninds.nih.gov RI o'donovan, michael/A-2357-2015; OI o'donovan, michael/0000-0003-2487-7547; Wenner, Peter/0000-0002-7072-2194 NR 33 TC 29 Z9 30 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD MAY PY 2005 VL 37 IS 5 BP 443 EP 450 DI 10.1016/j.ceca.2005.01.012 PG 8 WC Cell Biology SC Cell Biology GA 920SD UT WOS:000228709500010 PM 15820392 ER PT J AU Roschke, AV Kirsch, IR AF Roschke, AV Kirsch, IR TI Targeting cancer cells by exploiting karyotypic complexity and chromosomal instability SO CELL CYCLE LA English DT Article DE aneuploidy; karyotypic complexity; chromosomal instability; NCI-60; anticancer drug discovery ID CLINICOPATHOLOGICAL FEATURES; MOLECULAR PHARMACOLOGY; TUMOR; ADENOCARCINOMAS; ANEUPLOIDY; PATTERN; SCREEN; AGENT; LINES AB Multiple karyotypic abnormalities and chromosomal instability are particular hallmarks of many cancers that are relatively resistant to long term control by current chemotherapeutic agents. We have asked whether these same hallmarks, karyotypic complexity and instability, can be used as determinants for the screening of potential anticancer compounds. Using a panel of well characterized cancer cell lines we have been able to identify specific groups of chemical compounds that are more cytotoxic toward the relatively more karyotypically complex and unstable panel members. Thus, we delineate an approach for the identification of "lead compounds" for anticancer drug discovery complementary to approaches that are focused at the outset on a given gene or pathway. C1 NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kirsch, IR (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM kirschi@exchange.nih.gov NR 29 TC 15 Z9 16 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY PY 2005 VL 4 IS 5 BP 679 EP 682 DI 10.4161/cc.4.5.1687 PG 4 WC Cell Biology SC Cell Biology GA 933UH UT WOS:000229657900013 PM 15846096 ER PT J AU Koonin, EV Rogozin, IB Glazko, GV AF Koonin, EV Rogozin, IB Glazko, GV TI p53 gain-of-function - Tumor biology and bioinformatics come together SO CELL CYCLE LA English DT Article DE p53; tumor suppressor; gain-of-function mutations; somatic mutations; germline mutations; Li-Fraumeni syndrome ID LI-FRAUMENI-SYNDROME; EVOLUTIONARY CONSERVATION; FUNCTION MUTATIONS; GENE; CANCER; MUTANTS; TP53 AB p53 is typically viewed as a tumor suppressor. However, many missense somatic and germline mutations in the p53 gene cause gain-of-function whereby p53 acquires novel biochemical activities, such as the ability to transactivate transcription of new genes or to mediate new regulatory protein-protein interactions. Several recent studies show that at least some gain-of-function mutations of p53 are biologically relevant leading to a change in the tumor phenotype. Independent bioinformatic analysis of somatic mutation spectra of the p53 gene yields three lines of evidence supporting the notion that gain-of-function could be the prevalent mode of p53 evolution in tumors. ( 1) The hotspots in the p53 gene show signs of intensive positive selection. ( 2) The hotspots are located primarily in functionally important motifs of the DNA-binding domain of p53 which are highly conserved in interspecies evolution. ( 3) The spectra of hotspots significantly differ among various tumor types and the germline (Li-Fraumeni syndrome); in addition to the hotspots shared by the germline and some of the tumors, many are tumor-specific. The latter observation suggests an unexpected level of complexity of p53 evolution in tumors, with distinct novel function gained in different tumors. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Stowers Inst Med Res, Kansas City, MO USA. Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, Novosibirsk 630090, Russia. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 22 TC 14 Z9 15 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY PY 2005 VL 4 IS 5 BP 686 EP 688 DI 10.4161/cc.4.5.1691 PG 3 WC Cell Biology SC Cell Biology GA 933UH UT WOS:000229657900015 PM 15846083 ER PT J AU Hollander, MC Philburn, RT Patterson, AD Wyatt, MA Fornace, AJ AF Hollander, MC Philburn, RT Patterson, AD Wyatt, MA Fornace, AJ TI Genomic instability in Gadd45a(-/-) cells is coupled with S-phase checkpoint defects SO CELL CYCLE LA English DT Article DE Gadd45a; p53; centrosome amplification; S-phase checkpoint; PALA; hydroxyurea ID CENTROSOME AMPLIFICATION; CHROMOSOME INSTABILITY; CYCLE CHECKPOINT; DNA-SYNTHESIS; P53; PATHWAY; ARREST; OVEREXPRESSION; DUPLICATION; ACTIVATION AB Gadd45a is a p53-regulated gene whose protein product, like p53, is involved in maintenance of genome stability. Specifically, deletion of Gadd45a leads to extensive aneuploidy as a consequence of centrosome amplification and subsequent abnormal segregation of chromosomes during mitosis. S-phase checkpoints were investigated in Gadd45a(-/-) cells to determine possible defects contributing to the uncoupling of centrosome duplication and DNA replication. In the presence of hydroxyurea, Gadd45a(-/-) mouse embryo fibroblasts show increased centrosome amplification coupled with loss of a sustained S-phase checkpoint. Gadd45a deletion allows another form of genomic instability, gene amplification, when p21 (Cdkn1a gene product) is deleted also. Gene amplification in Gadd45a(-/-) p21(-/-) cells correlated with loss of both G(1) and S-phase checkpoints. Multiple conditions of nutrient deprivation failed to prevent DNA synthesis in Gadd45a(-/-) cells. Gadd45a is therefore required for proper S-phase control and checkpoints under multiple conditions of nutrient deprivation. It is proposed that loss of S-phase control may account for both the uncoupling of DNA replication and centrosome duplication, and conferring gene amplification proficiency in cells lacking Gadd45a(-/-). This is of particular importance for solid tumors, which may lack sufficient nutrients yet are unable to elicit checkpoints preventing genomic instability under these conditions. C1 NCI, Canc Therapeut Branch, Bethesda, MD 20889 USA. NCI, Gene Response Sect, Bethesda, MD 20889 USA. RP Hollander, MC (reprint author), NCI, Canc Therapeut Branch, Bethesda, MD 20889 USA. EM ch96b@nih.gov RI Fornace, Albert/A-7407-2008; Patterson, Andrew/G-3852-2012 OI Fornace, Albert/0000-0001-9695-085X; Patterson, Andrew/0000-0003-2073-0070 NR 27 TC 13 Z9 16 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY PY 2005 VL 4 IS 5 BP 704 EP 709 DI 10.4161/cc.4.5.1675 PG 6 WC Cell Biology SC Cell Biology GA 933UH UT WOS:000229657900018 PM 15846075 ER PT J AU Robbins, AR Jablonski, SA Yen, TJ Yoda, K Robey, R Bates, SE Sackett, DL AF Robbins, AR Jablonski, SA Yen, TJ Yoda, K Robey, R Bates, SE Sackett, DL TI Inhibitors of histone deacetylases alter kinetochore assembly by disrupting pericentromeric heterochromatin SO CELL CYCLE LA English DT Article DE HP1-beta; aurora B; trichostatin; FR901228; CENP-E ID MITOTIC CHROMOSOME CONDENSATION; AURORA-B KINASE; CENP-E; H3 PHOSPHORYLATION; LYSINE 9; MITOSIS; SPINDLE; CELLS; ARREST; MICROTUBULES AB The kinetochore, a multi-protein complex assembled on centromeric chromatin in mitosis, is essential for sister chromosome segregation. We show here that inhibition of histone deacetylation blocks mitotic progression at prometaphase in two human tumor cell lines by interfering with kinetochore assembly. Decreased amounts of hBUB1, CENP-F and the motor protein CENP-E were present on kinetochores of treated cells. These kinetochores failed to nucleate and inefficiently captured microtubules, resulting in activation of the mitotic checkpoint. Addition of histone deacetylase inhibitors prior to the end of S-phase resulted in decreased HP1-beta on pericentromeric heterochromatin in S-phase and G(2), decreased pericentromeric targeting of Aurora B kinase, resulting in decreased premitotic phosphorylation of pericentromeric histone H3(S10) in G(2), followed by assembly of deficient kinetochores in M-phase. HP1-beta, Aurora B and the affected kinetochore proteins all were present at normal levels in treated cells; thus, effects of the inhibitors on mitotic progression do not seem to reflect changes in gene expression. In vitro kinase activity of Aurora B isolated from treated cells was unaffected. We propose that the increased presence in pericentromeric heterochromatin of histone H3 acetylated at K9 is responsible for the mitotic defects resulting from inhibition of histone deacetylation. C1 NIDDKD, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. NIDDKD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Nagoya Univ, Biosci Ctr, Chikusa Ku, Nagoya, Aichi, Japan. NCI, Med Branch, Bethesda, MD 20892 USA. RP Sackett, DL (reprint author), NIDDKD, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. EM sackettd@mail.nih.gov OI Yen, Tim/0000-0003-2159-0997 NR 46 TC 79 Z9 81 U1 0 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY PY 2005 VL 4 IS 5 BP 717 EP 726 DI 10.4161/cc.4.5.1690 PG 10 WC Cell Biology SC Cell Biology GA 933UH UT WOS:000229657900020 PM 15846093 ER PT J AU Bender, LM Morgan, MJ Thomas, LR Liu, ZG Thorburn, A AF Bender, LM Morgan, MJ Thomas, LR Liu, ZG Thorburn, A TI The adaptor protein TRADD activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE TRADD; FADD; caspase; serine protease; nuclear localization ID CYTOCHROME-C RELEASE; SERINE-PROTEASE; DEATH DOMAIN; SYMPATHETIC NEURONS; CASPASE ACTIVATION; PC12 CELLS; INHIBITOR; OMI/HTRA2; PATHWAYS; MITOCHONDRIA AB TNFR1 associated death domain protein ( TRADD) contains an N-terminal TRAF binding domain and a C-terminal death domain along with nuclear import and export sequences that cause shuttling between the cytoplasm and nucleus. The death domain of TRADD contains the nuclear import sequence and expression of the core death domain ( nuclear TRADD) results in exclusive nuclear localization and activation of a distinct apoptotic pathway. Cytoplasmic TRADD activates apoptosis through Fas-associated death domain protein ( FADD) and caspase-8 activation that was blocked by caspase inhibitors or dominant-negative FADD. These inhibitors did not inhibit death induced by nuclear TRADD, which could only be inhibited by combining caspase inhibitors and a serine protease inhibitor. The pathway activated by nuclear TRADD requires caspase-9 catalytic activity. However, apoptosis activating factor deficiency confers only partial protection from death. This pathway represents an alternate means by which TRADD can regulate cell death independently of FADD and caspase-8 that occurs from the nucleus rather than the cytoplasm. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, UCHSC Fitsimmons, Aurora, CO 80045 USA. Wake Forest Univ, Dept Canc Biol, Sch Med, Winston Salem, NC 27157 USA. NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. RP Thorburn, A (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, UCHSC Fitsimmons, L18-6100 RC1,S Tower,POB 6511,Mail Stop 8303, Aurora, CO 80045 USA. EM Andrew.Thorburn@UCHSC.edu FU NINDS NIH HHS [NS46353] NR 41 TC 33 Z9 33 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD MAY PY 2005 VL 12 IS 5 BP 473 EP 481 DI 10.1038/sj.cdd.4401578 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 918WD UT WOS:000228577400006 PM 15761471 ER PT J AU Duque, J Mazzocchio, R Dambrosia, J Murase, N Olivier, E Cohen, LG AF Duque, J Mazzocchio, R Dambrosia, J Murase, N Olivier, E Cohen, LG TI Kinematically specific interhemispheric inhibition operating in the process of generation of a voluntary movement SO CEREBRAL CORTEX LA English DT Article DE bimanual; interhemispheric inhibition; mirror movement; motor control; unimanual ID IPSILATERAL MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; HUMAN CORPUS-CALLOSUM; MIRROR MOVEMENTS; REACTION-TIME; HUMAN BRAIN; CORTICOSPINAL EXCITABILITY; TRANSCALLOSAL INHIBITION; EVOKED-POTENTIALS; PREMOTOR CORTEX AB Unilateral hand movements are accompanied by a transient decrease in corticospinal (CS) excitability of muscles in the opposite hand. However, the rules that govern this phenomenon are not completely understood. We measured the amplitude of motor evoked potentials (MEP) in the left first dorsal interosseus (FDI) elicited by transcranial magnetic stimulation (TMS) of the primary motor cortex in order to assess CS excitability changes that preceded eight possible combinations of unilateral and bilateral index finger movements with different right hand positions. Left FDI MEP amplitude (MEPLeft FDI) increased when this muscle acted as an agonist and tended to decrease when it was an antagonist. Additionally, MEPLeft FDI decreased substantially before right index finger abduction (a movement mediated by the right FDI) when both hands were lying flat (a movement mirroring left index finger abduction) but not when the right hand was turned at 90 degrees or flat with the palm up. Therefore, CS excitability of the resting FDI was differentially modulated depending on the direction of the opposite index finger movement, regardless of muscles engaged in the task. These results indicate that inhibitory interactions preceding unilateral finger movements are determined by movement kinematics possibly to counteract the default production of mirror motions. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20817 USA. Univ Louvain, Neurophysiol Lab, Brussels, Belgium. Univ Siena, Dipartimento Sci Neurol & Comportamento, Sez Neurofisiol Clin, I-53100 Siena, Italy. Univ Tokushima, Fac Med, Dept Neurol, Tokushima 770, Japan. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20817 USA. EM cohenl@ninds.nih.gov RI Mazzocchio, Riccardo/H-4223-2012 OI Mazzocchio, Riccardo/0000-0002-0628-2868 NR 49 TC 99 Z9 104 U1 0 U2 5 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 MAY PY 2005 VL 15 IS 5 BP 588 EP 593 DI 10.1093/cercor/bhh160 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 919RT UT WOS:000228636000012 PM 15342437 ER PT J AU Hummel, F Gerloff, C AF Hummel, F Gerloff, C TI Larger interregional synchrony is associated with greater behavioral success in a complex sensory integration task in humans SO CEREBRAL CORTEX LA English DT Article DE coherence; EEG; humans; interregional synchrony; visuotactile ID EVENT-RELATED COVARIANCES; BIMANUAL VISUOMOTOR TASK; VISUAL-CORTEX; HUMAN BRAIN; GAMMA-BAND; NEURONAL SYNCHRONIZATION; WORKING-MEMORY; HUMAN EEG; COHERENCE; RHYTHMS AB Successful behavior depends on effective communication between distant brain regions. Moreover, disturbance of effective communication can cause neurological symptoms like apraxia, dyslexia or object agnosia. Interregional communication can be assessed by coherence analysis of synchronized neuronal oscillations, and has been referred to as synchrony or 'binding'. The concept of synchrony as a means of information coding is attractive, but its functional relevance has been challenged. We hypothesized that if synchrony is functionally relevant in humans, then more synchrony should determine better behavioral performance. Here, we show in a visuotactile integration task that the amount of low-frequency (7-13Hz), long-range electroencephalographic coherence between visual and sensorimotor cortex is significantly correlated with the level of performance. Trials with highest coherences were the most successful ones and vice versa in the absence of differences in regional activation measured as task-related spectral power. In summary, quantitatively linking the amount of long-range synchrony with the degree of behavioral success in humans, the present data suggest that the ability to generate topographically specific synchrony of high amplitude is functionally relevant for behavioral success. They also raise the possibility that the magnitude of regional activation is less representative of the efficacy of brain functioning than interregional synchrony. C1 Univ Tubingen, Dept Neurol, Cort Physiol Res Grp, D-72076 Tubingen, Germany. Univ Tubingen, Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany. Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Univ Tubingen, Dept Neurol, Cort Physiol Res Grp, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. EM christian.gerloff@uni-tuebingen.de NR 59 TC 72 Z9 75 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD MAY PY 2005 VL 15 IS 5 BP 670 EP 678 DI 10.1093/cercor/bhh170 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 919RT UT WOS:000228636000021 PM 15342429 ER PT J AU Fukuto, JM Bartberger, MD Dutton, AS Paolocci, N Wink, DA Houk, KN AF Fukuto, JM Bartberger, MD Dutton, AS Paolocci, N Wink, DA Houk, KN TI The physiological chemistry and biological activity of nitroxyl (HNO): The neglected, misunderstood, and enigmatic nitrogen oxide SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Review ID DETERRENT AGENT CYANAMIDE; TRANSCRIPTION FACTOR ACE1; FREE NITRIC-OXIDE; NO-CENTER-DOT; SUPEROXIDE-DISMUTASE; AQUEOUS-SOLUTION; ANGELIS SALT; ALDEHYDE DEHYDROGENASE; NITROSYL HYDRIDE; S-NITROSOTHIOLS C1 Univ Calif Los Angeles, Sch Publ Hlth, Interdepartmental Program Mol Toxicol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pharmacol, Hlth Sci Ctr, Los Angeles, CA 90095 USA. Amgen Inc, Dept Mol Struct & Design, Thousand Oaks, CA 91320 USA. Univ Calif Los Angeles, Dept Biochem & Chem, Los Angeles, CA 90095 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Dept Biomed Engn, Baltimore, MD 21287 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Fukuto, JM (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Interdepartmental Program Mol Toxicol, Los Angeles, CA 90095 USA. EM jfukuto@mednet.ucla.edu; knh@chem.ucla.edu RI Liu, Peng/D-1233-2013; OI Paolocci, Nazareno/0000-0001-7011-997X NR 96 TC 103 Z9 106 U1 1 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY PY 2005 VL 18 IS 5 BP 790 EP 801 DI 10.1021/tx0496800 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 928PX UT WOS:000229285200002 PM 15892572 ER PT J AU Dubowitz, H Newton, RR Litrownik, AJ Lewis, T Briggs, EC Thompson, R English, D Lee, LC Feerick, MM AF Dubowitz, H Newton, RR Litrownik, AJ Lewis, T Briggs, EC Thompson, R English, D Lee, LC Feerick, MM TI Examination of a conceptual model of child neglect SO CHILD MALTREATMENT LA English DT Article DE child neglect; definition; conceptual model ID FAILURE-TO-THRIVE; COMMUNITY VIOLENCE; DISADVANTAGED FAMILIES; SCHOOL PERFORMANCE; HEALTH-SERVICES; PHYSICAL HEALTH; BIRTH-WEIGHT; LOW-INCOME; MALTREATMENT; ADOLESCENTS AB This study attempted to provide empirical support for conceptual definitions of child neglect. We identified 12 types of needs, conceptualizing neglect as occurring when children's basic needs are not adequately met. We examined measures administered to 377 children and caregivers at ages 4 and 6 years participating in longitudinal studies on child maltreatment to identify potential indicators of these needs. Indicators were found for latent constructs, operationalizing three of the basic needs (emotional support and/or affection, protection from family conflict and/or violence, and from community violence). These latent constructs were used in a measurement model; this supported the conceptual definitions of neglect. A structural equation model then assessed whether the latent constructs were associated with child adjustment at age 8 years. Low level of perceived support from mother was associated with internalizing and externalizing behavior problems. Exposure to family conflict was also linked to these problems, and to social difficulties. Finally, children's sense of experiencing little early affection was associated with subsequent externalizing behavior and social problems. The approach of conceptualizing neglect in terms of unmet child needs, developing a measurement model to define latent neglect constructs, and relating these constructs to subsequent adjustment can build our understanding of neglect. C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Calif State Univ Fullerton, Fullerton, CA 92634 USA. San Diego State Univ, San Diego, CA 92182 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Duke Univ, Ctr Med, Ctr Child & Family Hlth, Durham, NC 27706 USA. Univ Illinois, Chicago, IL USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. NICHHD, Bethesda, MD 20892 USA. RP Dubowitz, H (reprint author), Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RI Thompson, Richard/G-5408-2011 OI Thompson, Richard/0000-0003-0127-513X NR 90 TC 29 Z9 31 U1 3 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5595 EI 1552-6119 J9 CHILD MALTREATMENT JI Child Maltreatment PD MAY PY 2005 VL 10 IS 2 BP 173 EP 189 DI 10.1177/1077559505275014 PG 17 WC Family Studies; Social Work SC Family Studies; Social Work GA 917WI UT WOS:000228499500007 PM 15798011 ER PT J AU Lambert, JS Moye, J Plaeger, SF Stiehm, ER Bethel, J Mofenson, LM Mathieson, B Kagan, J Rosenblatt, H Paxton, H Suter, H Landay, A AF Lambert, JS Moye, J Plaeger, SF Stiehm, ER Bethel, J Mofenson, LM Mathieson, B Kagan, J Rosenblatt, H Paxton, H Suter, H Landay, A TI Association of selected phenotypic markers of lymphocyte activation and differentiation with perinatal human immunodeficiency virus transmission and infant infection SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID RECURRENT SPONTANEOUS-ABORTIONS; KAPPA-B ACTIVATION; MOTHER-TO-CHILD; DISEASE PROGRESSION; PERIPHERAL-BLOOD; RISK-FACTORS; INTRAVENOUS IMMUNOGLOBULIN; CD4(+) LYMPHOCYTES; TYPE-1 INFECTION; HEALTHY-CHILDREN AB This study of a subset of women and infants participating in National Institutes of Health Pediatric AIDS Clinical Trials Group protocol 185 evaluated lymphocyte phenotypic markers of immune activation and differentiation to determine their association with the likelihood of human immunodeficiency virus (HIV) transmission from the women to their infants and the potential for early identification and/or prognosis of infection in the infants. Lymphocytes from 215 human immunodeficiency virus type 1 (HIV)-infected women and 192 of their infants were analyzed by flow cytometry with an extended three-color panel of monoclonal antibodies. Women who did not transmit to their infants tended to have higher CD4(+) T cells. Most notably, levels of total CD8(+) T cells and CD8(+) CD38(+) cells made significant independent contributions to predicting the risk of mother-to-child transmission. Adjusting for HIV-1 RNA level at entry, a one percentage-point increase in these marker combinations was associated with a nine percent increase in the likelihood of maternal transmission. Total as well as naive CD4(+) T cells were significantly higher in uninfected than infected infants. Total CD8(+) cells, as well as CD8(+)cells positive for HLA-DR+, CD45 RA(+) HLA-DR+, and CD28(+) HLA-DR+ were elevated in infected infants. Detailed immunophenotyping may be helpful in predicting which pregnant HIV-infected women are at increased risk of transmitting HIV to their infants. Increasing differences in lymphocyte subsets between infected and uninfected infants became apparent as early as six weeks of age. Detailed immunophenotyping may be useful in supporting the diagnosis of HIV infection in infants with perinatal HIV exposure. C1 NICHHD, NIH, US Dept HHS, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. Inst Child Hlth, London, England. Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA. Westat Corp, Rockville, MD USA. DHHS, NIH, Off AIDS Res, Bethesda, MD USA. DHHS, NIH, NIAID, Div AIDS, Bethesda, MD USA. Baylor Coll Med, Houston, TX 77030 USA. Quest Diagnost Inc, Baltimore, MD USA. Rush Med Coll, Chicago, IL 60612 USA. RP Moye, J (reprint author), NICHHD, NIH, US Dept HHS, Pediat Adolescent & Maternal AIDS Branch, Bldg 6100,Room 4B11,MSC 7510,9000 Rockville Pike, Bethesda, MD 20892 USA. EM moyej@mail.nih.gov OI Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [AI-27550, AI-27565, U01 AI027550, U01 AI027565]; NICHD NIH HHS [N01 HD033162, HD-33162] NR 37 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAY PY 2005 VL 12 IS 5 BP 622 EP 631 DI 10.1128/CDLI.12.5.622-631.2005 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 955AM UT WOS:000231197000009 PM 15879023 ER PT J AU Mahesh, SP Li, ZQ Buggage, R Mor, F Cohen, IR Chew, EY Nussenblatt, RB AF Mahesh, SP Li, ZQ Buggage, R Mor, F Cohen, IR Chew, EY Nussenblatt, RB TI Alpha tropomyosin as a self-antigen in patients with Behcet's disease SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE alpha tropomyosin; autoantigen; autoantibody; Behcet's disease ID T-CELL RESPONSES; ANTIBODIES; UVEITIS; AUTOIMMUNITY; PROTEINS; MUSCLE AB We report for the first time a significant increased lymphoproliferative response to alpha tropomyosin as well as observing autoantibodies to tropomyosin observed in Behcet's disease (BD) patients with posterior uveitis. Peripheral blood mononuclear cells (PBMCs) from 18 BD patients with posterior uveitis, 18 patients with other forms of noninfectious uveitis, 9 patients with retinal damage due to photocoagulation as well as 18 healthy donors were evaluated for antigen-specific lymphoproliferative responses to alpha tropomyosin and its derivative peptides. The proliferative responses of PBMCs to these antigens were studied using H-3 thymidine incorporation assay. Serum samples were also screened by ELISA for autoantibodies against tropomyosin. Six of the 18 (33%) BD patients with posterior uveitis showed increased proliferative response to alpha tropomyosin or its derivative peptides, while none of the healthy, disease controls were positive. The mean lymphoproliferative responses to tropomyosin were significantly higher (P < 0.02) in the BD patients compared to healthy or disease controls. Higher titres of anti-tropomyosin antibodies were also seen in four of the 18 BD patients but none in the healthy or disease control groups (P < 0.002). The occurrence of these abnormalities supports a possible role for alpha tropomyosin as a self-antigen in a subset of patients with Behcet's disease. C1 NEI, Immunol Lab, Bethesda, MD 20892 USA. NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NEI Bldg 10,Room 10S219, Bethesda, MD 20892 USA. EM drbob@nei.nih.gov RI Cohen, Irun/B-3542-2009; Mor, Felix/K-1093-2012 NR 24 TC 22 Z9 23 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAY PY 2005 VL 140 IS 2 BP 368 EP 375 DI 10.1111/j.1365-2249.2005.02760.x PG 8 WC Immunology SC Immunology GA 910YU UT WOS:000227968900023 PM 15807864 ER PT J AU Ghavami, S Hashemi, M Shahriari, HA Bajestani, SN de Serres, FJ Moghaddam, EM Kazeml, M Alavian, SM Taheri, M Blanco, I Bustillo, EF AF Ghavami, S Hashemi, M Shahriari, HA Bajestani, SN de Serres, FJ Moghaddam, EM Kazeml, M Alavian, SM Taheri, M Blanco, I Bustillo, EF TI Alpha-1-antitrypsin phenotypes and HLA-B27 typing in uveitis patients in southeast Iran SO CLINICAL BIOCHEMISTRY LA English DT Article DE uveitis; alpha-1-antitrypsin deficiency; isoelectric focusing; inflammatory eye diseases; HLA-B27 ID ACUTE ANTERIOR UVEITIS; ALPHA(1)-ANTITRYPSIN DEFICIENCY; ALPHA1-ANTITRYPSIN DEFICIENCY; GENETIC EPIDEMIOLOGY; CLINICAL-FEATURES; DISEASE; SERUM; MECHANISMS; INHIBITOR; EMPHYSEMA AB Objectives: Uveitis is an eye disease that affects humans worldwide. Inflammation of the uveal tract is termed uveitis. Alpha-1-antitrypsin (AAT) deficiency is one of many factors that may be involved in abnormalities such as liver and lung disease, inflammatory joint diseases, and inflammatory eye diseases. In this study, the role of AAT in uveitis is analyzed. Design and methods: AAT phenotyping and serum-trypsin inhibitory capacity (S-TIC) experiments were performed on 103 patients who were referred to the ALZAHRA eye center in Zahedan (southeast of Iran). The same experiments were performed on 167 people who did not, suffer from any eye or systemic diseases and served as a control group. Results: The results revealed that the frequency of M(1)S, M(2)S, M(1)Z, and MV phenotypes were significantly higher in uveitis patients (P < 0.001). There was no difference in AAT phenotype frequencies between various types of uveitis (P = 0.1). Conclusion: AAT deficiency appears to be a risk factor for uveitis in southeast Iran. More investigation is needed to establish potential benefits of AAT phenotyping tests and AAT therapy in the diagnosis and treatment of uveitis cases with unclear etiology. (c) 2005 The Canadian Society of Clinical Chemists. All rights reserved. C1 Zahedan Med Univ, Sch Med, Dept Clin Biochem, Zahedan, Iran. Zahedan Med Univ, Sch Med, Dept Ophthalmol, Zahedan, Iran. Univ Florida, Dept Pathol, Gainesville, FL 32610 USA. Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Zahedan Med Univ, Sch Med, Dept Immunol & Hematol, Zahedan, Iran. Baghyat Allah Med Univ, Sch Med, Dept Internal Med, Tehran, Iran. Hosp Valle Nalon, Resp Dis Branch, Sama De Langreo 33920, Principado De A, Spain. Univ Oviedo, Hosp Cent Asturias, Biostat Unit, Oviedo 33006, Principado De A, Spain. RP Ghavami, S (reprint author), Zahedan Med Univ, Sch Med, Dept Clin Biochem, Zahedan, Iran. EM ghavami@cc.unimanitoba.ca RI Ghavami, Saeid/Q-8918-2016; taheri, mohsen/I-2567-2016; OI taheri, mohsen/0000-0002-1110-4417; Alavian., Seyed Moayed/0000-0002-4443-6602; Miri-Moghaddam, Ebrahim/0000-0001-9435-2450; hashemi, Mohammad/0000-0002-6074-7101 NR 47 TC 6 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD MAY PY 2005 VL 38 IS 5 BP 425 EP 432 DI 10.1016/j.clinbiochem.2005.02.006 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 919ID UT WOS:000228610800005 PM 15820772 ER PT J AU Buttitta, F Martella, C Barassi, F Felicioni, L Salvatore, S Rosini, S D'Antuono, T Chella, A Mucilli, F Sacco, R Mezzetti, A Cuccurullo, F Callahan, R Marchetti, A AF Buttitta, F Martella, C Barassi, F Felicioni, L Salvatore, S Rosini, S D'Antuono, T Chella, A Mucilli, F Sacco, R Mezzetti, A Cuccurullo, F Callahan, R Marchetti, A TI Int6 expression carp predict survival in early-stage non-small cell lang cancer patients SO CLINICAL CANCER RESEARCH LA English DT Article ID MAMMARY-TUMOR VIRUS; EUKARYOTIC TRANSLATION INITIATION-FACTOR-3; BREAST CARCINOMAS; CPG ISLANDS; GENE; PROTEIN; SUBUNIT; TRANSFORMATION; INTEGRATION; COMPLEXES AB Purpose: The Int6 gene was originally identified as a common insertion site for the mouse mammary tumor virus in virally induced mouse mammary tumors. Recent studies indicate that Int6 is a multifaceted protein involved in the regulation of protein translation and degradation through binding with three complexes: the eukaryotic translation initiation factor 3, the proteasome regulatory lid, and the constitutive photomorphogenesis 9 signalosome. This study aimed to investigate the prognostic role of Int6 in a large series of stage I non-small cell lung cancers (NSCLC) patients with long-term follow-up. Experimental Design: We determined the methylation status of Int6 DNA by methylation-specific PCR and the steady-state levels of Int6 RNA by quantitative real-time reverse transcription-PCR in 101 NSCLCs and matched normal lung tissues. Results: In 27% of the tumors, Int6 RNA levels were reduced relative to normal tissue. In 85% of the tumors with reduced Int6 expression, the transcription promoter and first exon were hypermethylated, whereas only 4% of the tumors with elevated Int6 RNA levels were hypermethylated (P < 0.000001). Low levels of Int6 RNA were found a significant predictor of overall and disease-free survival (P = 0.0004 and P = 0.0020, respectively). A multivariate analysis confirmed that low Int6 expression was the only independent factor to predict poor prognosis, for both overall (P = 0.0006) and disease-free (P = 0.024) survival. Conclusions: Our results suggest that Int6 expression, evaluated by quantitative real-time PCR, may represent a new prognostic factor in patients with stage I NSCLC. C1 Univ Fdn, Ctr Excellence Aging, Clin Res Ctr, Pathol Unit, I-66013 Chieti, Italy. Univ Pisa, Dept Surg, Pisa, Italy. Univ Chieti, Dept Surg, Chieti, Italy. NCI, Oncogenet Sect, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. RP Marchetti, A (reprint author), Univ Fdn, Ctr Excellence Aging, Clin Res Ctr, Pathol Unit, Via Colle DellAra, I-66013 Chieti, Italy. EM amarchetti@unich.it NR 30 TC 32 Z9 36 U1 1 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 MAY 1 PY 2005 VL 11 IS 9 BP 3198 EP 3204 DI 10.1158/1078-0432.CCR-04-2308 PG 7 WC Oncology SC Oncology GA 922OT UT WOS:000228848000008 PM 15867213 ER PT J AU Furukawa, M Raffeld, M Mateo, C Sakamoto, A Moody, TW Ito, T Venzon, DJ Serrano, J Jensen, RT AF Furukawa, M Raffeld, M Mateo, C Sakamoto, A Moody, TW Ito, T Venzon, DJ Serrano, J Jensen, RT TI Increased expression of insulin-like growth factor I and/or its receptor in gastrinomas is associated with low curability, increased growth, and development of metastases SO CLINICAL CANCER RESEARCH LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; HUMAN NEUROENDOCRINE TUMORS; FACTOR SYSTEM; IGF-I; PROGNOSTIC-FACTORS; COLORECTAL-CANCER; CARCINOID-TUMORS; TISSUE-CULTURE; BREAST-CANCER; GENE AB Purpose: Growth factors, particularly insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) in some nonendocrine and a few endocrine tumors, are thought important in recurrence, growth, and aggressiveness. Whether this is true of neuroendocrine tumors such as gastrinomas is unclear. The aim of this study was to address this question in gastrinomas. Experimental Design: IGF-I and IGF-IR expression in gastrinomas from 54 patients with Zollinger-Ellison syndrome were analyzed and correlated with clinical/tumor characteristics. IGF-I and IGF-IR mRNA levels were determined by competitive reverse transcription-PCR. IGF-IR expression, assessed by immunohistochemistry, was done on a subset. Results: IGF-IR m RNA was found in 100% and IGF-I in 89%. IGF-I m RNA expression varied by > 254-fold, IGF-IR by 2,670-fold, and the levels correlated in a given tumor. The IGF-IR level was lower in gastrinomas of patients who were rendered disease free and increased levels correlated with tumor growth, aggressiveness, extent, and with liver metastases. Increased IGF-I levels correlated with increased growth, tumor extent, and aggressiveness. Neither IGF-IR nor IGF-I levels correlated with tumor location, size, or its clinical/functional features. The IGF-IR correlated with disease-free survival. IGF-IR 13 was found in 31 of 32 tumors (97%) by immunohistochemistry. Conclusions: These results indicate that IGF-I and IGF-IR are expressed in almost all gastrinomas. Furthermore, assessment of IGF-I/IGF-IR expression in gastrinomas may be clinically useful in identifying those patients with more aggressive tumors who might benefit from more aggressive treatment. C1 NIDDK, NIH, DDB, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, NIH, DDB, Room 9C-103,Bldg 10,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov RI Venzon, David/B-3078-2008 NR 53 TC 45 Z9 55 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2005 VL 11 IS 9 BP 3233 EP 3242 DI 10.1158/1078-0432.CCR-04-1915 PG 10 WC Oncology SC Oncology GA 922OT UT WOS:000228848000013 PM 15867218 ER PT J AU Gulley, JL Arlen, PM Bastian, A Morin, S Marte, J Beetham, P Tsang, KY Yokokawa, J Hodge, JW Menard, C Camphausen, K Coleman, CN Sullivan, F Steinberg, SM Schlom, J Dahut, W AF Gulley, JL Arlen, PM Bastian, A Morin, S Marte, J Beetham, P Tsang, KY Yokokawa, J Hodge, JW Menard, C Camphausen, K Coleman, CN Sullivan, F Steinberg, SM Schlom, J Dahut, W TI Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; HUMAN CARCINOEMBRYONIC ANTIGEN; CYTOTOXIC T-LYMPHOCYTES; EXTERNAL-BEAM RADIATION; NECROSIS-FACTOR-ALPHA; RADICAL PROSTATECTOMY; PHASE-I; IMMUNE-RESPONSES; TUMOR-CELLS; DIVERSIFIED PRIME AB Purpose: Many patients with clinically localized prostate cancer develop biochemical failure despite excellent local therapy perhaps due to occult metastatic disease. One potential solution is the utilization of a well-tolerated systemic therapy (e.g., vaccine) in concert with local therapy. Experimental Design: We present a randomized phase II clinical trial designed to determine if a poxviral vaccine encoding prostate-specific antigen (PSA) can induce a PSA-specific T-cell response when combined with radiotherapy in patients with clinically localized prostate cancer. Thirty patients were randomized in a 2:1 ratio into vaccine plus radiotherapy or radiotherapy-only arms. Those patients in the combination arm received a "priming" vaccine with recombinant vaccinia (rV) PSA plus rV containing the T-cell costimulatory molecule B7.1 (rV-B7.1) followed by monthly booster vaccines with recombinant fowlpox PSA. The vaccines were given with local granulocyte-macrophage colony-stimulating factor and low-dose systemic interleukin-2. Standard external beam radiation therapy was given between the fourth and the sixth vaccinations. Results: Seventeen of 19 patients in the combination arm completed all eight vaccinations and 13 of these 17 patients had increases in PSA-specific T cells of at least 3-fold versus no detectable increases in the radiotherapy-only arm (P < 0.0005). There was also evidence of de novo generation of T cells to well-described prostate-associated antigens not found in the vaccine, providing indirect evidence of immune-mediated tumor killing. The vaccine was well tolerated. Conclusion:This vaccine regimen can be safely given in patients undergoing radiation therapy for localized prostate cancer, with the majority of patients generating a PSA-specific cellular immune response to vaccine. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Maryland Reg Canc Care, Silver Spring, MD USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Hodge, James/D-5518-2015; Gulley, James/K-4139-2016 OI Hodge, James/0000-0001-5282-3154; Gulley, James/0000-0002-6569-2912 NR 55 TC 212 Z9 220 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2005 VL 11 IS 9 BP 3353 EP 3362 DI 10.1158/1078-0432.CCR-04-2062 PG 10 WC Oncology SC Oncology GA 922OT UT WOS:000228848000030 PM 15867235 ER PT J AU Ramanathan, RK Trump, DL Eiseman, JL Belani, CP Agarwala, SS Zuhowski, EG Lan, J Potter, DM Ivy, SP Ramalingam, S Brufsky, AM Wong, MKK Tutchko, S Egorin, MJ AF Ramanathan, RK Trump, DL Eiseman, JL Belani, CP Agarwala, SS Zuhowski, EG Lan, J Potter, DM Ivy, SP Ramalingam, S Brufsky, AM Wong, MKK Tutchko, S Egorin, MJ TI Phase I pharmacokinetic-pharmacodynamic study of 17-(allylamino)-17-emethoxygeldanamycin (17AAG, NSC 330507), a novel inhibitor of heat shock protein 90, in patients with refractory advanced cancers SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID GELDANAMYCIN; HSP90; 17-(ALLYLAMINO)-17-DEMETHOXYGELDANAMYCIN; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; RECEPTOR; COMPLEX; PROTEIN; CELLS; 17-ALLYLAMINO,17-DEMETHOXYGELDANAMYCIN; DERIVATIVES AB Purpose: 17-(Allylamino)-17-demethoxygeldanamycin (17AAG), a benzoquinone antibiotic, down-regulates oncoproteins by binding specifically to heat shock protein 90 (HSP90). We did a phase I study of 17AAG to establish the dose-limiting toxicity and maximum tolerated dose and to characterize 17AAG pharmacokinetics and pharmacodynamics. Experimental Design: Escalating doses of 17AAG were given i.v. over 1 or 2 hours on a weekly x 3 schedule every 4 weeks to cohorts of three to six patients. Plasma pharmacokinetics of 17AAG and 17-(amino)-17-demethoxygeldanamycin (17AG) were assessed by high-performance liquid chromatography. Expression of HSP70 and HSP90 in peripheral blood mononuclear cells was measured by Western blot. Results: Forty-five patients were enrolled to 11 dose levels between 10 and 395 mg/m2. The maximum tolerated dose was 295 mg/m(2). Dose-limiting toxicity occurred in both patients (grade 3 pancreatitis and grade 3 fatigue) treated with 395 mg/m(2). Common drug-related toxicities (grade 1 and 2) were fatigue, anorexia, diarrhea, nausea, and vomiting. Reversible elevations of liver enzymes occurred in 29.5% of patients. Hematologic toxicity was minimal. No objective responses were observed.17AAG pharmacokinetics was linear. Peak plasma concentration and area under the curve of 17AG, the active major metabolite of 17AAG, increased with 17AAG dose, but the relationships were more variable than with 17AAG. 17AAG and 17AG in plasma were > 90% protein bound. There were no consistent changes in peripheral blood mononuclear cell HSP90 or HSP70 content. Conclusions: 17AAG doses between 10 and 295 mg/m(2) are well tolerated. 17AAG pharmacokinetics is linear. Peripheral blood mononuclear cell HSP90 and HSP70 are uninformative pharmacodynamic markers. The dose recommended for future studies is 295 mg/m2 weekly x 3, repeated every 4 weeks. C1 Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Biostat Facil, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Hematol Oncol, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Hematol Oncol, Dept Pharmacol, Pittsburgh, PA USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Ctr, Bethesda, MD 20892 USA. RP Ramanathan, RK (reprint author), UPMC Canc Pavil,562 5150 Ctr Ave, Pittsburgh, PA 15232 USA. EM ramanathanrk@upmc.edu FU NCI NIH HHS [P30CA47904, U01-CA069855, U01-CA099168]; NCRR NIH HHS [5 M01 RR 00056] NR 26 TC 161 Z9 170 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 MAY 1 PY 2005 VL 11 IS 9 BP 3385 EP 3391 DI 10.1158/1078-0432.CCR-04-2322 PG 7 WC Oncology SC Oncology GA 922OT UT WOS:000228848000034 PM 15867239 ER PT J AU Lang, JY Chen, H Zhou, J Zhang, YX Zhang, XW Li, MH Lin, LP Zhang, JS Waalkes, MP Ding, J AF Lang, JY Chen, H Zhou, J Zhang, YX Zhang, XW Li, MH Lin, LP Zhang, JS Waalkes, MP Ding, J TI Antimetastatic effect of salvicine on human breast cancer MDA-MB-435 orthotopic xenograft is closely related to Rho-dependent pathway SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-CELL INVASION; ACTIN STRESS FIBERS; BINDING PROTEIN RHO; SMALL GTPASES; LYSOPHOSPHATIDIC-ACID; ALPHA-6-BETA-4 INTEGRIN; LAMELLAE FORMATION; FOCAL ADHESIONS; FAMILY GTPASES; METASTASIS AB Purpose: Salvicine is a novel DNA topoisomerase II inhibitor with potent anticancer activity. In present study, the effect of salvicine against metastasis is evaluated using human breast carcinoma orthotopic metastasis model and its mechanism is further investigated both in animal and cellular levels. Experimental Design: The MDA-MB-435 orthotopic xenograft model was applied to detect the antimetastatic effect of salvicine. Potential target candidates were detected and analyzed by microarray technology. Candidates were verified and explored by reverse transcription-PCR and Western blot. Salvicine activities on stress fiber formation, invasion, and membrane translocation were further investigated by immunofluorescence, invasion, and ultracentrifugal assays. Results: Salvicine significantly reduced the lung metastatic foci of MDA-MB-435 orthotopic xenograft, without affecting primary tumor growth obviously. A comparison of gene expression profiles of primary tumors and lung metastatic focus between salvicine-treated and untreated groups using the CLOTECH Atlas human Cancer 1.2 cDNA microarray revealed that genes involved in tumor metastasis, particularly those closely related to cell adhesion and motility, were obviously down-regulated, including fibronectin, integrin a3, integrin beta 3, integrin beta 5, FAK, paxillin, and RhoC. Furthermore, salvicine significantly down-regulated RhoC at both mRNA and protein levels, greatly inhibited stress fiber formation and invasiveness of MDA-MB-435 cells, and markedly blocked translocation of both RhoA and RhoC from cytosol to membrane. Conclusion: The unique antimetastatic action of salvicine, particularly its specific modulation of cell motility in vivo and in vitro, is closely related to Rho-dependent signaling pathway. C1 Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China. Chinese Acad Sci, Shanghai Inst Mat Med, Div Phytochem, Shanghai 201203, Peoples R China. Chinese Acad Sci, Grad Sch, Beijing 100864, Peoples R China. NCI, Comparat Carcinogenesis Lab, NIEHS, Res Triangle Pk, NC USA. RP Ding, J (reprint author), Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China. EM jding@mail.shcnc.ac.cn RI Li, Mei-Hong/D-6941-2011; Li, Meihong/D-9922-2011; Li, Mei-Hong/B-1260-2012 NR 50 TC 19 Z9 25 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 MAY 1 PY 2005 VL 11 IS 9 BP 3455 EP 3464 DI 10.1158/1078-0432.CCR-04-2026 PG 10 WC Oncology SC Oncology GA 922OT UT WOS:000228848000043 PM 15867248 ER PT J AU Costa-Guda, J Rosen, ED Jensen, RT Chung, DC Arnold, A AF Costa-Guda, J Rosen, ED Jensen, RT Chung, DC Arnold, A TI Mutational analysis of PPARG as a candidate tumour suppressor gene in enteropancreatic endocrine tumours SO CLINICAL ENDOCRINOLOGY LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; COMPARATIVE GENOMIC HYBRIDIZATION; PANCREATIC TUMORS; NEUROENDOCRINE TUMORS; SPORADIC GASTRINOMAS; CANCER CELLS; ISLET CELLS; EXPRESSION; PATHWAYS; TUMORIGENESIS AB Objectives Loss of heterozygosity (LOH) or deletion of chromosome 3p is a frequent finding in enteropancreatic endocrine tumours (EPETs), suggesting the pathogenetic involvement of one or more tumour suppressor genes on 3p. PPARG, the gene encoding the gamma isoform of the peroxisome proliferator-activated receptor (PPAR gamma), is highly expressed in normal human pancreatic islet cells, is located at 3p25, and has been reported to sustain loss-of-function mutations in human colorectal carcinomas. Additionally, the development of islet cell hyperplasia in an islet cell-specific pparg knockout mouse has further emphasized the attractiveness of PPARG as a candidate gene important in the pathogenesis of EPETs. Therefore, we sought to examine PPARG for intragenic inactivating mutations, the evidence needed to rigorously establish it as a tumour suppressor in EPETs. Patients and design Twenty-three EPETs from 20 patients were examined for coding region mutations in PPARG and for LOH on 3p at microsatellite markers flanking PPARG. Results LOH on 3p was detected in tumours from six patients (30%), but no intragenic mutations were detected in PPARG, whether or not LOH was present. Conclusion These findings strongly suggest that PPARG does not commonly function as a classical tumour suppressor gene in the pathogenesis of EPETs. C1 Univ Connecticut, Ctr Hlth, Sch Med, Ctr Mol Med, Farmington, CT 06030 USA. Univ Connecticut, Sch Med, Div Endocrinol & Metab, Farmington, CT 06030 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Arnold, A (reprint author), Univ Connecticut, Ctr Hlth, Sch Med, Ctr Mol Med, 263 Farmington Ave, Farmington, CT 06030 USA. EM molecularmedicine@uchc.edu FU NIDCR NIH HHS [5T32-DE07302] NR 34 TC 3 Z9 3 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD MAY PY 2005 VL 62 IS 5 BP 603 EP 606 DI 10.1111/j.1365-2265.2005.02267.x PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 918PP UT WOS:000228560400015 PM 15853832 ER PT J AU Grossman, Z AF Grossman, Z TI Immune reconstitution in HIV infection: How to measure thymic function? SO CLINICAL IMMUNOLOGY LA English DT Editorial Material ID T-CELL HOMEOSTASIS; POPULATION; EMIGRANTS C1 Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Grossman, Z (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. EM Legros@post.tau.ac.il RI Grossman, Zvi/A-9643-2008 NR 11 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAY PY 2005 VL 115 IS 2 BP 115 EP 117 DI 10.1016/j.clin.2005.01.010 PG 3 WC Immunology SC Immunology GA 927DR UT WOS:000229173100001 PM 15885631 ER PT J AU Brockow, K Akin, C Huber, M Metcalfe, DD AF Brockow, K Akin, C Huber, M Metcalfe, DD TI IL-6 levels predict disease variant and extent of organ involvement in patients with mastocytosis SO CLINICAL IMMUNOLOGY LA English DT Article DE plasma interleukin-6; mastocytosis; pathology; hematologic disorders; immunoglobulin M; anemia ID SOLUBLE INTERLEUKIN-6 IL-6; BONE-MARROW PATHOLOGY; MAST-CELL DISEASE; SERUM LEVELS; MULTIPLE-MYELOMA; SYSTEMIC MASTOCYTOSIS; SYNOVIAL-FLUID; IN-VIVO; RECEPTOR; PLASMA AB Mastocytosis is often associated with organ involvement and hematological disorders. Patients may also exhibit elevated levels of plasma IL-6. To gain insight into the relevance of this observation, we correlated plasma levels of IL-6 and soluble IL-6 receptor (sIL-6R) with Multiple disease parameters in 29 patients with mastocytosis. Mean plasma IL-6 levels were elevated in patients compared to healthy controls (P < 0.0001). Disease category significantly correlated with plasma IL-6 levels, as did severity of bone marrow pathology, organomegaly, and extent of skin involvement. In plasma, there was a positive correlation of IL-6 to total tryptase, alkaline phosphatase, IgM, white blood cell count, prothrombin time, partial thromboplastin time, and neutrophil numbers. There was an inverse correlation to hemoglobin. sIL-6R levels were not elevated. These observations demonstrate that IL-6 is a useful surrogate marker of severity of hematologic disease and suggest that IL-6 contributes to pathology. Published by Elsevier Inc. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. RP Brockow, K (reprint author), Tech Univ Munich, Dept Dermatol & Allergy, Biederstein Str 29, D-80802 Munich, Germany. EM knut.brockow@lrz.tum.de OI Akin, Cem/0000-0001-6301-4520 NR 41 TC 32 Z9 32 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAY PY 2005 VL 115 IS 2 BP 216 EP 223 DI 10.1016/j.clim.2005.01.011 PG 8 WC Immunology SC Immunology GA 927DR UT WOS:000229173100016 PM 15885646 ER PT J AU Lee, HW Seo, HJ Cohen, LG Bagic, A Theodore, WH AF Lee, HW Seo, HJ Cohen, LG Bagic, A Theodore, WH TI Cortical excitability during prolonged antiepileptic drug treatment and drug withdrawal SO CLINICAL NEUROPHYSIOLOGY LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the American-Epilepsy-Society CY DEC 05-10, 2003 CL BOSTON, MA SP Amer Epilepsy Soc DE conical excitability; transcranial magnetic stimulation; plasma blood levels; antiepileptic drug treatment; drug withdrawal ID HUMAN MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; ANTICONVULSANT WITHDRAWAL; STIMULUS-INTENSITY; BRAIN-STIMULATION; LAMOTRIGINE; GABAPENTIN; CARBAMAZEPINE; SEIZURE; NEURONS AB Objective: Previous reports characterized the effects of administration of single oral doses of antiepileptic drugs (AED) on cortical excitability. However, AED effects on cortical excitability, and their relationship to plasma blood levels, during chronic drug administration at therapeutic doses are not known. The objective of the study was to determine whether plasma blood levels during chronic administration at therapeutic doses would accurately predict changes in corticomotor excitability. Methods: We used transcranial magnetic stimulation (TMS) to measure cortical excitability during 5 weeks administration of carbamazepine (CBZ) and lamotrigine (LTG), and subsequent AED withdrawal in 20 healthy volunteers. Data were analyzed using ANOVA(RM) and regression analysis. Results: Resting motor thresholds (r-MT) increased with increasing total and free CBZ and LTG levels during drug administration, but not drug withdrawal. After acute AED withdrawal, r-MT elevation persisted in most individuals with CBZ despite undetectable plasma levels, compared to a rapid normalization with LTG. In contrast, acute drug withdrawal resulted in a transient decrease in r-MT in 3/10 individuals with CBZ and 2/10 with LTG. Conclusions: Plasma levels provide information on motor cortical function during active treatment phases but not during AED withdrawal. Significance: The transient decrease in r-MT associated with acute AED withdrawal could represent a physiological substrate contributing to AED withdrawal seizures. Published by Elsevier Ireland Ltd on behalf of International Federation of Clinical Neurophysiology. C1 NINCDS, Human Cortical Physiol Sect, Med Neurol Branch, Bethesda, MD 20892 USA. NINDS, Clin Epilepsy Sect, Bethesda, MD 20892 USA. Ewha Womans Univ, Coll Med, Dept Neurol, Seoul 120750, South Korea. Ewha Med Res Inst, Seoul, South Korea. RP Cohen, LG (reprint author), NINCDS, Human Cortical Physiol Sect, Med Neurol Branch, Bldg 10,Room 5N226, Bethesda, MD 20892 USA. EM cohenl@ninds.nih.gov NR 46 TC 24 Z9 24 U1 0 U2 4 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 MAY PY 2005 VL 116 IS 5 BP 1105 EP 1112 DI 10.1016/j.clinph.2004.12.004 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923DL UT WOS:000228889200013 PM 15826851 ER PT J AU Wheaton, LA Shibasaki, H Hallett, M AF Wheaton, LA Shibasaki, H Hallett, M TI Temporal activation pattern of parietal and premotor areas related to praxis movements SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE praxis movement; ideomotor apraxia; EEG analysis; movement-related cortical potentials; event related desynchronization; parietofrontal network ID EVENT-RELATED DESYNCHRONIZATION; CORTICAL MOTOR AREAS; RHESUS-MONKEY; NEURAL REPRESENTATIONS; VOLUNTARY MOVEMENT; VISUOMOTOR CONTROL; IDEOMOTOR APRAXIA; FINGER MOVEMENT; CORTEX; POTENTIALS AB Objective: We sought to determine the cortical physiology underlying praxis movements in normal subjects using electroencephalography (EEG). Methods: Eight normal subjects were instructed to perform six types of self-paced tool-use pantomime and communicative gesture movements with the right hand. We recorded 64-channel EEG using a linked ear reference and electromyogram (EMG) from right thumb and forearm flexors. Results: Data revealed early slow wave components of the movement-related cortical potential (MRCP) beginning over the left parietal area about 3 s before movement onset, similarly for both movement types. At movement onset, maximal amplitude was present over central and bilateral sensorimotor areas. Event-related desynchronization (ERD) in the beta band was seen over the left parietal and sensorimotor cortices during preparation, later spreading to the homologous area of the right hemisphere. Alpha ERD was mainly in the left sensorimotor cortex about 1.5 s before movement onset. Beta ERD in mesial frontal areas was greater during preparation for tool use compared to communicative gesture movements. Mesial frontal beta event-related synchronization (ERS) developed more rapidly after communicative gestures than tool-use. Conclusions: The dynamics of parietal and frontal activities indicates the timing of these areas in the production of praxis. The posterior parietal cortex contributes to the early slow wave negativity of the MRCP. Significance: Planning self-paced praxis movements begins as early as 3 s before movement in the left parietal area and subsequently engages frontal cortical regions. © 2005 Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 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 60 TC 44 Z9 44 U1 1 U2 5 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 MAY PY 2005 VL 116 IS 5 BP 1201 EP 1212 DI 10.1016/j.clinph.2005.01.001 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923DL UT WOS:000228889200025 PM 15826863 ER PT J AU Bai, O Mari, Z Vorbach, S Hallett, M AF Bai, O Mari, Z Vorbach, S Hallett, M TI Asymmetric spatiotemporal patterns of event-related desynchronization preceding voluntary sequential finger movements: a high-resolution EEG study SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE handedness; dominance; hemispheric asymmetry; event-related desynchronization/synchronization (ERD/ERS) ID PRIMARY MOTOR CORTEX; CENTRAL BETA-RHYTHMS; POSITRON EMISSION TOMOGRAPHY; SELF-PACED MOVEMENT; CEREBRAL-BLOOD-FLOW; HEMISPHERIC-ASYMMETRY; OSCILLATORY ACTIVITY; HAND MOVEMENT; ACTIVATION; HUMANS AB Objective: To study spatiotemporal patterns of event-related desynchronization (ERD) preceding voluntary sequential finger movements performed with dominant right hand and nondominant left hand. Methods: Nine subjects performed self-paced movements consisting of three key strokes with either hand. Subjects randomized the laterality and timing of movements. Electroencephalogram (EEG) was recorded from 122 channels. Reference-free EEG power measurements in the beta band were calculated off-line. Results: During motor preparation (-2 to -0.5 s with respect to movement onset), contralateral preponderance of event-related desynchronization (ERD) (lateralized power) was only observed during right hand finger movements, whereas ERD during left hand finger movements was bilateral. Conclusions: For right-handers, activation on the left hemisphere during left hand movements is greater than that on the right hemisphere during right hand movements. Significance: We provide further evidence for motor dominance of the left hemisphere in early period of motor preparation for complex sequential finger movements. Published by Elsevier Ireland Ltd on behalf of International Federation of Clinical Neurophysiology. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC-1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov NR 49 TC 71 Z9 71 U1 0 U2 14 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 MAY PY 2005 VL 116 IS 5 BP 1213 EP 1221 DI 10.1016/j.clinph.2005.01.006 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923DL UT WOS:000228889200026 PM 15826864 ER PT J AU Gold, PW AF Gold, PW TI The neurobiology of stress and its relevance to psychotherapy SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE major depression; melancholic depression; atypical depression; stress; psychotherapy ID CORTICOTROPIN-RELEASING HORMONE; MAJOR DEPRESSION; BIOCHEMICAL MANIFESTATIONS; THERAPEUTIC IMPLICATIONS; TYROSINE-HYDROXYLASE; PREFRONTAL CORTEX; MOOD DISORDERS; MEMORY STORAGE; MESSENGER-RNA; UNITED-STATES AB Stress precipitates depression and significantly influences its course and severity. The neurobiology and clinical manifestation of the stress response and depression are similar, but in depression, the features persist and override the usual counter-regulating forces. Both the stress response and depression are characterized by hyperarousal, anxiety, increased expectation of harm, fixation of mood, and a bias towards well-rehearsed, relatively automatic cognitive programs. Furthermore, each is associated with preferential access to negatively charged emotional memories that emerge unconsciously, usually without identifiable cognitive content. The same stress-responsive CNS mediators that produce emotional, cognitive, and behavioral manifestations also lead to inhibition of endocrine programs for growth and reproduction to preserve energy, a catabolic state to provide glucose to the brain, and increased heart rate and blood pressure. While these phenomena are transient during stress, they may become chronic in depression, overriding their usual counter-regulatory influences. These biological phenomena constitute the basis for the now well-documented fact that depression is associated with a doubling of mortality at any age, independent of smoking, other physical risk factors, and suicide. Thus, depression is not only a state of anguish, but also the tip of the iceberg of a systemic disorder that leads to illness and significantly shortens life. Psychotherapy plays an enormously critical role in the treatment of any depression. The intersection of stressful, disturbing life experiences encoded in emotional memory, as well as genetic vulnerability provide the context for understanding how psychotherapeutic intervention can influence a disorder with biological vulnerability that is responsive to somatic treatments. Indeed, current well-controlled data indicate that pharmacological intervention is significantly more effective when combined with psychotherapy. Otherwise, unfortunate circumstances during childhood or later, persistent maladaptive behavioral patterns that increase the likelihood of stressful events, and a massive, untouched burden of aversively charged memories cam overwhelm skillful psychopharmacologic intervention. (C) 2005 Published by Elsevier B.V. on behalf of Association for Research in Nervous and Mental Disease. C1 NIMH, Clin Neuroendocrinol Branch, DIRP, Bethesda, MD USA. RP Gold, PW (reprint author), NIMH, Clin Neuroendocrinol Branch, DIRP, Bldg 10,RM 2D46,10 Denter Dr, Bethesda, MD USA. EM philipgold@mail.nih.gov NR 63 TC 6 Z9 6 U1 2 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD MAY PY 2005 VL 4 IS 5-6 BP 315 EP 324 DI 10.1016/j.cnr.2005.03.006 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 941RL UT WOS:000230231800004 ER PT J AU Shibanuma, N Sheehan, FT Stanhope, SJ AF Shibanuma, N Sheehan, FT Stanhope, SJ TI Limb positioning is critical for defining patellofemoral alignment and femoral shape SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID COMPUTED-TOMOGRAPHY; AXIAL RADIOGRAPHY; PATELLAR TRACKING; MOTION; JOINT; KNEE; REALIGNMENT; SUBLUXATION; CONGRUENCE; CHILDREN AB The source of patellofemoral pain is a common orthopaedic complaint that often is difficult to determine because of the lack of correlation between symptoms and specific clinical measurements. Excessive joint contact stresses resulting from patellofemoral malalignment and pathologic femoral shape often are associated with this pain. These measures are likely sensitive to the limb position (orientation and position relative to the imaging system with which they are quantified). Because of this sensitivity, the measures have large variations and do not show correlations with subjective symptoms. The purpose of this study was to determine if varying limb position resulted in significant changes in standard clinical measures of patellofemoral alignment and femoral shape. This dependence was investigated by simulating alterations in limb position through resectioning of three-dimensional magnetic resonance image sets (20 healthy knees) to create axial images with altered orientation (eight images) or location (four images) relative to a fixed reference. By quantifying the variability of the clinical measures across all images, it was determined that simulated alterations in limb position produced greater variability in femoral shape and patellofemoral alignment measures than the variability seen across control subjects. This indicated that a standardized method for establishing limb position relative to the imager is warranted. C1 NIH, Phys Disabil Branch, Bethesda, MD 20892 USA. Univ Maryland, Dept Phys Therapy, Baltimore, MD 21201 USA. Kobe Univ, Sch Med, Dept Orthopaed Surg, Kobe, Hyogo 657, Japan. RP Sheehan, FT (reprint author), NIH, Phys Disabil Branch, Bldg 10,Room 6s235,MSC 1604, Bethesda, MD 20892 USA. EM fsheehan@cc.nih.gov RI sheehan, frances/B-6962-2009 NR 26 TC 18 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 2005 IS 434 BP 198 EP 206 DI 10.1097/01.blo.0000155078.52475.63 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 923LF UT WOS:000228910700030 PM 15864053 ER PT J AU Deans, KJ Minneci, PC Cui, XZ Banks, SM Natanson, C Eichacker, PQ AF Deans, KJ Minneci, PC Cui, XZ Banks, SM Natanson, C Eichacker, PQ TI Mechanical ventilation in ARDS: One size does not fit all SO CRITICAL CARE MEDICINE LA English DT Editorial Material C1 NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Deans, KJ (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 7 TC 56 Z9 63 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2005 VL 33 IS 5 BP 1141 EP 1143 DI 10.1097/01.CCM.0000162384.71993.A3 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 925PO UT WOS:000229065200035 PM 15891350 ER PT J AU Masur, H Murray, P AF Masur, H Murray, P TI Tsunami disaster and infection: Beware what pathogens the transport delivers to your intensive care unit! SO CRITICAL CARE MEDICINE LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Masur, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2005 VL 33 IS 5 BP 1179 EP 1180 DI 10.1097/01.CCM.0000163271.78189.0F PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 925PO UT WOS:000229065200060 PM 15891375 ER PT J AU Normanno, N Bianco, C Strizzi, L Mancino, M Maiello, MR De Luca, A Caponigro, F Salomon, DS AF Normanno, N Bianco, C Strizzi, L Mancino, M Maiello, MR De Luca, A Caponigro, F Salomon, DS TI The ErbB receptors and their ligands in cancer: An overview SO CURRENT DRUG TARGETS LA English DT Review DE growth factors; EGF; ErbB; development; cancer; transgenic mice ID EPIDERMAL-GROWTH-FACTOR; HUMAN-BREAST-CANCER; CELL LUNG-CANCER; ALPHA TRANSGENIC MICE; MAMMARY-GLAND DEVELOPMENT; FACTOR-RELATED PEPTIDES; TGF-ALPHA; EGF-RECEPTOR; TYROSINE KINASE; SIGNALING NETWORK AB This review article provides an overview on the most recent advances on the role of ErbB receptors and growth factors of the epidermal growth factor (EGF)-family of peptides in cancer pathogenesis and progression. The ErbB tyrosine kinases and the EGF-like peptides form a complex system. In fact, the interactions occurring between receptors and ligands of these families affect the type and the duration of the intracellular signals that derive from receptor activation. Interestingly, activation of ErbB receptors is also driven by different classes of membrane receptor, suggesting that ErbB kinases can amplify growth promoting signals carried by different pathways. The importance of ErbB receptors and EGF-like peptides in development of organs and tissues has been demonstrated by using different mouse models. In vitro and in vivo studies have also shown that ErbB receptors and their ligands can act as transforming genes. However, evidence suggests that cooperation of different receptors and ligands is necessary to induce a fully transformed phenotype. Indeed, co-expression of different ErbB receptors and EGF-like growth factors is a common phenomenon in human primary carcinomas. This observation suggests that the growth and the survival of carcinoma cells is sustained by a network of receptors/ligands of the ErbB family. In this respect, the contemporary expression of different ErbB tyrosine kinases and/or EGF-like growth factors in human carcinomas might also affect tumor response to target based agents directed against the ErbB receptor/ligand system. C1 INT Fdn Pascale, Cell Biol & Preclin Models Unit, I-80131 Naples, Italy. INT Fdn Pascale, Med Oncol Unit, I-80131 Naples, Italy. NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. RP Normanno, N (reprint author), INT Fdn Pascale, Cell Biol & Preclin Models Unit, I-80131 Naples, Italy. EM nicnorm@yahoo.com RI De Luca, Antonella/J-8737-2016; ionna, Franco/K-4564-2016; OI De Luca, Antonella/0000-0001-5762-447X; ionna, Franco/0000-0002-0512-274X; Normanno, Nicola/0000-0002-7158-2605 NR 207 TC 172 Z9 188 U1 0 U2 15 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD MAY PY 2005 VL 6 IS 3 BP 243 EP 257 DI 10.2174/1389450053765879 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 922GO UT WOS:000228824900002 PM 15857286 ER PT J AU Lee, DS Vasan, RS AF Lee, DS Vasan, RS TI Novel markers for heart failure diagnosis and prognosis SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE biomarkers; brain natriuretic peptide; diagnosis; heart failure; prognosis ID BRAIN NATRIURETIC PEPTIDE; CORTICOTROPIN-RELEASING FACTOR; ACID-BINDING PROTEIN; CARDIAC TROPONIN-T; IDIOPATHIC DILATED CARDIOMYOPATHY; VENTRICULAR SYSTOLIC DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; PROCESSING ENDOPROTEASE FURIN; CARDIOVASCULAR RISK-FACTORS; AMINO-TERMINAL PROPEPTIDE AB Purpose of review This paper reviews recent advances in heart failure biomarkers for identification of disease precursors, subclinical disease, and onset or progression of overt disease. Recent findings Heart failure biomarkers can be categorized empirically as neurohormonal mediators, markers of myocyte injury and remodeling, and indicators of systemic inflammation. Brain natriuretic peptide is the most widely studied, with a potentially important but evolving role for determining prognosis and as a surrogate endpoint in clinical trials. Strong evidence exists for use of brain natriuretic peptide in the diagnosis of acute heart failure and for improved clinical outcomes with a brain natriuretic peptide-guided approach to heart failure care. The use of brain natriuretic peptide as a screening tool for asymptomatic left ventricular systolic dysfunction, or to distinguish systolic from diastolic heart failure, is not supported by current data. Markers of myocyte injury, including troponins, heart-type fatty acid binding protein, and myosin light chain-1, may further improve heart failure prognostication in conjunction with plasma brain natriuretic peptide. Biomarkers of matrix remodeling and inflammation have emerged as potential preclinical indicators to identify individuals at risk of developing clinical heart failure. A role for cellular adhesion molecules may also emerge in identifying those at risk for cardiovascular thrombotic complications, such as stroke. Summary The spectrum of heart failure biomarkers and their potential clinical applications continues to grow. Ongoing research on multimarker strategies will likely identify biomarker combinations that are optimal at various stages during the evolution of heart failure, ranging from their use for screening, diagnosis, determining prognosis, and guiding management. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02215 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu RI Lee, Douglas/J-4315-2014; OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24HL04334, 1R01HL67288, N01-HC-25195] NR 138 TC 46 Z9 48 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD MAY PY 2005 VL 20 IS 3 BP 201 EP 210 DI 10.1097/01.hco.0000161832.04952.6a PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 927XJ UT WOS:000229233500005 PM 15861008 ER PT J AU Vocci, FJ Elkashef, A AF Vocci, FJ Elkashef, A TI Pharmacotherapy and other treatments for cocaine abuse and dependence SO CURRENT OPINION IN PSYCHIATRY LA English DT Article DE behavioral therapy; clinical trials; cocaine dependence; pharmacotherapy ID PLACEBO-CONTROLLED TRIAL; DISULFIRAM TREATMENT; ALCOHOL DEPENDENCE; FUNCTIONAL POLYMORPHISM; ETHANOL INGESTION; DOUBLE-BLIND; FOLLOW-UP; NALTREXONE; MODAFINIL; COCAETHYLENE AB Purpose of review This review examines progress being made in the treatment of cocaine abuse and dependence, with a particular focus on pharmacotherapies. Medications with apparently very different mechanisms of action have been reported to reduce cocaine use in controlled clinical trials in outpatient settings. This review will summarize the latest findings in this area. Recent findings Of all the medications tested to date, disulfiram has demonstrated the most consistent effect to reduce cocaine use. Several medications have been reported to reduce cocaine use in double-blind, placebo-controlled clinical trials, namely baclofen, modafinil, tiagabine, and topiramate. All pharmacotherapy trials in cocaine-dependent patients include a behavioral therapy that is common to all participants. Consequently, these pharmacotherapy trials can be considered to evaluate whether the medication is adding to the effect of the behavioral therapy. Summary Confirmatory clinical studies are necessary to replicate the initial efficacy findings for baclofen, modafinil, tiagabine, and topiramate. More research is needed in both cocaine and cocaine-alcohol dependent populations. Once confirmatory studies have been carried out, testing of rational medication combinations with different behavioral therapies is an obvious next step to increase the ability to manage cocaine dependence. C1 NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Vocci, FJ (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Dept Hlth & Human Serv, 6001 Executive Blvd,Room 4133,MSC 9551, Bethesda, MD 20892 USA. EM fv6k@nih.gov NR 43 TC 59 Z9 61 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 2005 VL 18 IS 3 BP 265 EP 270 DI 10.1097/01.yco.0000165596.98552.02 PG 6 WC Psychiatry SC Psychiatry GA 921JO UT WOS:000228760600008 PM 16639150 ER PT J AU O'Shea, JJ Park, H Pesu, M Borie, D Changelian, P AF O'Shea, JJ Park, H Pesu, M Borie, D Changelian, P TI New strategies for immunosuppression: interfering with cytokines by targeting the Jak/Stat pathway SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE cytokines; Janus kinase 3; interleukin; protein inhibitors of activated stats; severe combined immunodeficiency; signal transducer and activator of transcription pathway; suppressors of cytokine signaling ID SEVERE COMBINED IMMUNODEFICIENCY; JAK-3 JANUS KINASE; COMMON GAMMA-CHAIN; SIGNAL-TRANSDUCTION; B10.Q/J MICE; TRANSCRIPTION FACTORS; HERITABLE DEFECT; GENE ACTIVATION; CANCER-THERAPY; IL-2 RECEPTOR AB Purpose of review Numerous immunosuppressants are available, but their adverse effects related to actions on nonlymphoid cells is problematic. Cytokines are key regulators of immune and inflammatory responses, and blocking their actions has become an important modality in treating autoimmune disorders. This review will discuss strategies to develop novel immunosuppressants that arise from advances in the understanding of cytokine signaling. Recent findings It is now recognized that large number of cytokines exert their effect by binding to receptors that activate the Janus kinase/signal transducer and activator of transcription pathway, so targeting intracellular signaling pathways is a logical strategy. A selective inhibitor of Janus kinase 3 has now been generated and is effective for transplant rejection in nonhuman primates and other models. Advances have also been made in understanding the functions of Stat family transcription factors, and approaches to interfering with the action of these DNA binding proteins are being devised. In addition, the identification of negative regulators of cytokine signaling offers additional therapeutic opportunities. Summary A selective inhibitor of Janus kinase 3 has now been generated and likely represents a new class of effective immunosuppressants. Strategies for targeting signal transducers and activators of transcription pathway are being intensively studied at present and hold potential promise. Multiple endogenous mechanisms exist for negatively regulating cytokine signaling; whether novel therapies can be devised that exploit these mechanisms remains to be determined. C1 NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Surg & Transplantat, Stanford, CA 94305 USA. Pfizer Inc, Pfizer Cent Res, Groton, CT 06340 USA. RP O'Shea, JJ (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bldg 10,Room 9N256 MSC-1820,1 Ctr Dr, Bethesda, MD 20892 USA. EM osheaj@arb.niams.nih.gov RI Pesu, marko/L-6344-2013 NR 71 TC 44 Z9 47 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAY PY 2005 VL 17 IS 3 BP 305 EP 311 DI 10.1097/01.bor.0000160781.07174.db PG 7 WC Rheumatology SC Rheumatology GA 919YT UT WOS:000228654400013 PM 15838241 ER PT J AU Lamb, LS Neuberg, R Welsh, J Best, R Stetler-Stevenson, M Sorrell, A AF Lamb, LS Neuberg, R Welsh, J Best, R Stetler-Stevenson, M Sorrell, A TI T-cell lymphoblastic leukemia/lymphoma syndrome with eosinophilia and acute myeloid leukemia SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE acute lymphoblastic leukemia; acute myeloid leukemia; hypereosinophilic syndrome; gamma/delta cells ID HYPEREOSINOPHILIC SYNDROME; MYELOPROLIFERATIVE DISORDER; LYMPHOMA; ASSOCIATION; MALIGNANCY; ENTITY AB This case represents an example of an unusual T-cell lymphoblastic leukemia/lymphoma syndrome associated with eosinophilia and myeloid malignancy in a young boy. This case is one of only five reported "leukemic" variants of the disease and demonstrates the importance of considering this poor prognostic diagnosis in pediatric acute lymphoblastic leukemia. This case also illustrates the importance of an interactive multidisciplinary approach to the laboratory evaluation of a leukemia patient. (c) 2005 Wiley-Liss, Inc. C1 Univ Alabama, Div Hematol & Oncol, Dept Med, Sch Med, Birmingham, AL 35294 USA. Univ S Carolina, Sch Med, Div Hematol & Oncol, Dept Pediat, Columbia, SC 29208 USA. Univ S Carolina, Sch Med, Dept Pathol, Columbia, SC 29208 USA. Univ S Carolina, Sch Med, Div Clin Genet, Dept Obstet & Gynecol, Columbia, SC 29208 USA. NCI, Pathol Branch, NIH, Bethesda, MD 20892 USA. RP Lamb, LS (reprint author), Univ Alabama, Div Hematol & Oncol, Dept Med, Sch Med, Tinsley Harrison Tower,Suite 541,1530 3rd Ave S, Birmingham, AL 35294 USA. EM lslamb@uambmc.edu OI Lamb, Lawrence/0000-0001-7180-0994 NR 12 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD MAY PY 2005 VL 65B IS 1 BP 37 EP 41 DI 10.1002/cyto.b.20033 PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 921NS UT WOS:000228771900006 PM 15786509 ER PT J AU Mielke, S Solomon, SR Barrett, AJ AF Mielke, S Solomon, SR Barrett, AJ TI Selective depletion strategies in allogeneic stem cell transplantation SO CYTOTHERAPY LA English DT Article DE CD25; natural regulators; photodepletion; review article; selective depletion ID GRAFT-VERSUS-HOST; ALLOREACTIVE T-CELLS; BONE-MARROW-TRANSPLANTATION; LIMITING DILUTION ANALYSIS; MINOR HISTOCOMPATIBILITY ANTIGENS; CHRONIC MYELOGENOUS LEUKEMIA; REACTIVE LYMPHOCYTES-T; REGULATORY CELLS; P-GLYCOPROTEIN; PRECURSOR FREQUENCIES AB Despite improved prophylaxis and treatment, GvHD remains a major limitation to optimal allogeneic stem cell transplantation. Ex vivo selective depletion (SD) is a strategy to prevent GvHD, in which host-reactive donor lymphocytes are selectively eliminated from a PBSC allograft while useful donor immune function is preserved. The elimination of alloreactive and thereby GvHD-mediating T cells has been shown to be feasible in both preclinical and more recently clinical studies. However, SD techniques and the translational research needed for clinical application are still under development. Here we summarize and discuss the following aspects of the SD approach: selection of an appropriate allogeneic stimulator; the responder population; the alloresponse; methods for removal of alloreacting T cells; product testing; clinical considerations. Our review highlights the diversity of possible approaches and the need to develop different techniques for specific clinical applications. C1 NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, DIR,NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, DIR,NIH, Bldg 10 CRC Room 3-5288,10 Ctr Dr MSC 1202, Bethesda, MD 20892 USA. NR 68 TC 32 Z9 32 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD MAY PY 2005 VL 7 IS 2 BP 109 EP 115 DI 10.1080/14653240510018172 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 939XQ UT WOS:000230106400003 PM 16040390 ER PT J AU Bok, JW Bronner-Fraser, M Wu, DK AF Bok, JW Bronner-Fraser, M Wu, DK TI Role of the hindbrain in dorsoventral but not anteroposterior axial specification of the inner ear SO DEVELOPMENT LA English DT Article DE inner ear; axis; axial specification; induction; hindbrain; rhombomere; sonic hedgehog; SHH; chicken ID OTIC PLACODE INDUCTION; SENSORY ORGAN GENERATION; SONIC-HEDGEHOG; FLOOR PLATE; NERVOUS-SYSTEM; CRANIAL NERVES; NEURAL-TUBE; CHICK LIMB; CELL FATE; EXPRESSION AB An early and crucial event in vertebrate inner ear development is the acquisition of axial identities that in turn dictate the positions of all subsequent inner ear components. Here, we focus on the role of the hindbrain in establishment of inner ear axes and show that axial specification occurs well after otic placode formation in chicken. Anteroposterior (AP) rotation of the hindbrain prior to specification of this axis does not affect the normal AP orientation and morphogenesis of the inner ear. By contrast, reversing the dorsoventral (DV) axis of the hindbrain results in changing the DV axial identity of the inner ear. Expression patterns of several ventrally expressed otic genes such as NeuroD, Lunatic fringe (Lfng) and Six1 are shifted dorsally, whereas the expression pattern of a normally dorsal-specific gene, Gbx2, is abolished. Removing the source of Sonic Hedgehog (SHH) by ablating the floor plate and/or notochord, or inhibiting SHH function using an antibody that blocks SHH bioactivity results in loss of ventral inner ear structures. Our results indicate that SHH, together with other signals from the hindbrain, are important for patterning the ventral axis of the inner ear. Taken together, our studies suggest that tissue(s) other than the hindbrain confer AP axial information whereas signals from the hindbrain are necessary and sufficient for the DV axial patterning of the inner ear. C1 NIDCD, Rockville, MD 20850 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. RP Wu, DK (reprint author), NIDCD, 5 Res Court, Rockville, MD 20850 USA. EM wud@nidcd.nih.gov RI Bok, Jinwoong/B-8982-2016 OI Bok, Jinwoong/0000-0003-1958-1872 FU NIDCR NIH HHS [NIH R01 DE016459] NR 65 TC 69 Z9 71 U1 0 U2 1 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 MAY PY 2005 VL 132 IS 9 BP 2115 EP 2124 DI 10.1242/dev.01796 PG 10 WC Developmental Biology SC Developmental Biology GA 933EA UT WOS:000229606100010 PM 15788455 ER PT J AU Lin, ZS Cantos, R Patente, M Wu, DK AF Lin, ZS Cantos, R Patente, M Wu, DK TI Gbx2 is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling SO DEVELOPMENT LA English DT Article DE Gbx2; Otx2; kreisler; hindbrain signaling; inner ear development; otic vesicle; mouse ID SEMICIRCULAR CANAL FORMATION; RECEPTOR TYROSINE KINASE; FINGER GENE KROX20; RETINOIC ACID; HOMEOBOX GENE; MID/HINDBRAIN ORGANIZER; TRANSCRIPTION FACTOR; TARGETED DISRUPTION; MAMMALIAN COCHLEA; MICE LACKING AB Gbx2 is a homeobox-containing transcription factor that is related to unplugged in Drosophila. In mice, Gbx2 and Otx2 negatively regulate each other to establish the midhindbrain boundary in the neural tube. Here, we show that Gbx2 is required for the development of the mouse inner ear. Absence of the endolymphatic duct and swelling of the membranous labyrinth are common features in Gbx2(-/-) inner ears. More severe mutant phenotypes include absence of the anterior and posterior semicircular canals, and a malformed saccule and cochlear duct. However, formation of the lateral semicircular canal and its ampulla is usually unaffected. These inner ear phenotypes are remarkably similar to those reported in kreisler mice, which have inner ear defects attributed to defects in the hindbrain. Based on gene expression analyses, we propose that activation of Gbx2 expression within the inner ear is an important pathway whereby signals from the hindbrain regulate inner ear development. In addition, our results suggest that Gbx2 normally promotes dorsal fates such as the endolymphatic duct and semicircular canals by positively regulating genes such as Wnt2b and D1x5. However, Gbx2 promotes ventral fates such as the saccule and cochlear duct, possibly by restricting Otx2 expression. C1 Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, NIH, Rockville, MD 20850 USA. RP Wu, DK (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, NIH, Rockville, MD 20850 USA. EM wud@nidcd.nih.gov RI Cantos Coll, Raquel /A-6318-2013 OI Cantos Coll, Raquel /0000-0002-5516-0074 NR 54 TC 57 Z9 59 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 2005 VL 132 IS 10 BP 2309 EP 2318 DI 10.1242/dev.01804 PG 10 WC Developmental Biology SC Developmental Biology GA 936YD UT WOS:000229890600006 PM 15829521 ER EF