FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Pace, C Miller, FG Danis, M AF Pace, C Miller, FG Danis, M TI Enrolling the uninsured in clinical trials: An ethical perspective SO CRITICAL CARE MEDICINE LA English DT Article DE medically uninsured; patient selection; clinical trials; informed consent; human experimentation; ethics ID PREVENTION AB Research participation by individuals who lack health insurance raises significant but seldom-discussed ethical issues for clinical investigators. Of particular concern are the possibility that their lack of options for getting care at the time of enrollment makes the uninsured susceptible to undue inducement to join trials and the possibility that their inability to access research products after trials leads to their exploitation. In tension with these concerns, however, is the right of the uninsured to fair consideration for research participation. We discuss these competing issues and make recommendations for how investigators can both protect uninsured research participants and provide the uninsured with fair access to research in their recruitment and enrollment strategies. C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Pace, C (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. NR 19 TC 38 Z9 39 U1 1 U2 3 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 MAR PY 2003 VL 31 IS 3 SU S BP S121 EP S125 DI 10.1097/01.CCM.0000054907.33928.48 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 661XL UT WOS:000181915100002 PM 12626956 ER PT J AU Reiter, CD Gladwin, MT AF Reiter, CD Gladwin, MT TI An emerging role for nitric oxide in sickle cell disease vascular homeostasis and therapy SO CURRENT OPINION IN HEMATOLOGY LA English DT Review ID ACUTE CHEST SYNDROME; LEUKOCYTE ADHESION MOLECULE; REGIONAL BLOOD-FLOW; POSTMENOPAUSAL WOMEN; RISK-FACTORS; PULMONARY-HYPERTENSION; ENDOTHELIAL-CELLS; RELAXING FACTOR; MEDIATED VASODILATION; VASOOCCLUSIVE CRISIS AB Nitric oxide participates in the compensatory response to chronic vascular injury in patients with sickle cell disease. The authors have found reductions of basal and stimulated nitric oxide production and responses to exogenous nitric oxide in male patients with sickle cell disease. Gender differences in nitric oxide bioavailability are probably caused in part by the protective effects of ovarian estrogen on nitric oxide synthase expression and activity in women. Further, in men, and likely all patients during vaso-occlusive crisis and the acute chest syndrome, nitric oxide is destroyed by increased circulating plasma hemoglobin and superoxide. The combined effects of inhaled nitric oxide gas of improving pulmonary ventilation to perfusion matching and hemodynamics, reducing alveolar and systemic inflammation, and inhibiting circulating plasma hemoglobin (and thus restoring peripheral nitric oxide bioavailability) may modulate the course of the disease, including the frequency and severity of vaso-occlusive crises and acute chest syndrome episodes. Possible effects of chronic nitric oxide-based therapies on erythrocyte density, pulmonary artery pressures, and fetal hemoglobin induction deserve study. (C) 2003 Lippincott Williams Wilkins. C1 NIDDKD, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NIDDKD, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Room 7D-43,10 Ctr Dr, Bethesda, MD 20892 USA. NR 110 TC 84 Z9 89 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAR PY 2003 VL 10 IS 2 BP 99 EP 107 DI 10.1097/00062752-200303000-00001 PG 9 WC Hematology SC Hematology GA 642YZ UT WOS:000180836100001 PM 12579034 ER PT J AU Ibrahim, HN Hostetter, TH AF Ibrahim, HN Hostetter, TH TI Aldosterone in renal disease SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE aldosterone; remnant kidney model; proteinuria ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; CONVERTING ENZYME-INHIBITION; HEART-FAILURE PATIENTS; REMNANT KIDNEY MODEL; SMOOTH-MUSCLE CELLS; GLOMERULAR INJURY; ANGIOTENSIN-II; DIABETES-MELLITUS; SALT HYPERTENSION; ACE-INHIBITION AB Purpose of review Interruption of the renin-angiotensin-aldosterone system, chiefly with angiotensin-converting enzyme inhibitors and angiotensin 11 receptor blockers, has yielded beneficial results in retarding injury and progression in numerous intrinsic renal diseases. The renoprotection offered by these agents is incomplete and far from optimal. Studying mediators of progression other than angiotensin 11 is therefore extremely important. The emerging role of aldosterone in progression of renal disease and the utility of its antagonism is discussed here. Recent findings The experimental evidence linking aldosterone to renal disease is discussed. The exciting results from clinical studies employing mineralocorticoid receptor blockers are also described. Summary Aldosterone antagonism offers additional antiproteinuric benefits to those achieved with angiotensin-converting enzyme inhibition. Long-term trials addressing effectiveness and safety, especially in regards to hyperkalemia, are greatly needed. C1 Univ Minnesota, Div Renal Dis & Hypertens, Minneapolis, MN 55455 USA. NIH, Bethesda, MD 20892 USA. RP Ibrahim, HN (reprint author), Univ Minnesota, Div Renal Dis & Hypertens, 420 Delaware St SE MMC 736, Minneapolis, MN 55455 USA. NR 65 TC 24 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAR PY 2003 VL 12 IS 2 BP 159 EP 164 DI 10.1097/01.mnh.0000058802.51455.ec PG 6 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 651EP UT WOS:000181307800006 PM 12589176 ER PT J AU Ward, MM AF Ward, MM TI Epidemiology and health services research SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Editorial Material C1 Natl Inst Musculoskeletal & Skin Dis, Intramural Res Program, NIH, Bethesda, MD USA. RP Ward, MM (reprint author), NIAMS, NIH, IRP, Bldg 10,Room 9S205,10 Ctr Dr,MSC 1828, 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 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAR PY 2003 VL 15 IS 2 BP 97 EP 98 DI 10.1097/00002281-200303000-00001 PG 2 WC Rheumatology SC Rheumatology GA 649MA UT WOS:000181211500001 ER PT J AU Ward, MM AF Ward, MM TI Clinical epidemiology: diagnostic and prognostic tests SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review ID HLA-DRB1 SHARED EPITOPE; INFLAMMATORY JOINT DISEASES; EARLY RHEUMATOID-ARTHRITIS; SYSTEMIC-SCLEROSIS; FINGER JOINTS; ANTIFILAGGRIN AUTOANTIBODIES; METACARPOPHALANGEAL JOINTS; GENE POLYMORPHISMS; ANTIBODIES; ASSOCIATION AB Recent studies of diagnostic and prognostic tests have commonly examined serological tests and new imaging techniques. Antifilaggrin antibodies have been found to be highly specific for the diagnosis of rheumatoid arthritis (RA), but uncertainty remains about the sensitivity of this test, particularly in early RA. Magnetic resonance imaging and ultrasound continue to be explored as methods to detect synovitis and erosions in RA. Several recent studies have confirmed the association between the human leukocyte antigen DRB1 shared epitope and worse radiographic outcomes in patients with RA. Interlaboratory variation in detecting autoantibodies remains a concern, as does overuse of tests for antineutrophil cytoplasmic autoantibodies. (C) 2003 Lippincott Williams Wilkins. C1 Natl Inst Musculoskeletal & Skin Dis, Intramural Res Program, NIH, Bethesda, MD USA. RP Ward, MM (reprint author), NIAMS, NIH, IRP, Bldg 10,Room 9S205,10 Ctr Dr,MSC 1828, Bethesda, MD 20892 USA. NR 53 TC 2 Z9 2 U1 0 U2 1 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 MAR PY 2003 VL 15 IS 2 BP 104 EP 109 DI 10.1097/00002281-200303000-00003 PG 6 WC Rheumatology SC Rheumatology GA 649MA UT WOS:000181211500003 PM 12598795 ER PT J AU Marti, GE Carter, P Abbasi, F Washington, GC Jain, N Zenger, VE Ishibe, N Goldin, L Fontaine, L Weissman, N Sgambati, M Fauget, G Bertin, P Vogt, RF Slade, B Noguchi, PD Stetler-Stevenson, MA Caporaso, N AF Marti, GE Carter, P Abbasi, F Washington, GC Jain, N Zenger, VE Ishibe, N Goldin, L Fontaine, L Weissman, N Sgambati, M Fauget, G Bertin, P Vogt, RF Slade, B Noguchi, PD Stetler-Stevenson, MA Caporaso, N TI B-cell monoclonal lymphocytosis and B-cell abnormalities in the setting of familial B-cell chronic lymphocytic leukemia SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE familial B-cell chronic leukemia; flow cytometry; immunophenotyping; cell cycle analysis; CD5; CD20; B-cell monoclonal lymphocytosis; kappa/lambda; absolute lymphocyte count ID FLOW CYTOMETRIC ANALYSIS; UNDETERMINED SIGNIFICANCE; LYMPHOID LEUKEMIAS; ANTICIPATION; EXPRESSION; DNA; CLL; IMMUNOGLOBULIN; GUIDELINES; RELATIVES AB Background: Among all hematologic malignancies, B-cell chronic lymphocytic leukemia (BCLL) has the highest familial clustering (three- to sevenfold increase), strongly suggesting a genetic component to its etiology. Familial BCLL can be used as a model to study the early pathogenesis of this disease. Methods: We examined nine kindreds from the National Cancer Institute's Familial BCLL Registry, consisting of 19 affected members,with BCLL and 33 clinically unaffected first-degree relatives. Flow cytometric immuno-phenotyping to detect a B-cell monoclonal lymphocytosis (BCML) was performed. Monoclonality was confirmed by polymerase chain reaction analysis of whole blood DNA. Cell cycle analysis for aneuploidy was conducted. Results: In all affected individuals, we observed the classic BCLL CD5/CD19/CD20/CD23 immunophenotypic patterns. Six of the 33 unaffected individuals (18%) had evidence of BCML. Additional individuals (13/33, 39%) showed some other abnormality, whereas 14 individuals (42%) were normal. Based on an estimated prevalence of 0.7% for BCML in the general population, the finding of six subjects (18%) with clonal abnormalities in this relatively modest sample was significantly greater than expected (i.e., 18% vs. 0.7%, P < 5.7 x 10(-9)). Conclusions: Individual components of BCML and other B-cell abnormalities were observed in almost half of the apparently unaffected individuals. Our findings suggested that BCML may be an early detectable abnormality in BCLL. The spectrum of some of these observed abnormalities suggested the involvement of different B-cell subpopulations or different pathways in clonal evolution. Population-based, longitudinal studies will be required to determine the incidence of BCML and other B-cell abnormalities and their relation to disease progression in BCLL and other closely related B-cell lymphoproliferative disorders. Published 2003 Wiley-Liss, Inc.(dagger). C1 FDA, CBER, DCGT, Lab Stem Cell Biol,Flow & Image Cytometry Sect, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, NIH, Rockville, MD USA. Med Coll Georgia, Vet Adm Med Ctr, Augusta, GA 30912 USA. Pontificia Univ Catolica Chile, Escuela Med, Lab Hematol Oncol, Santiago, Chile. Ctr Dis Control, Ctr Environm Hlth, Clin Biochem Branch, Immunol Sect, Atlanta, GA 30333 USA. Agcy Tox Substances & Dis Registry, Hlth Invest Branch, Div Hlth Studies, Atlanta, GA USA. NIH, Clin Flow Cytometry Sect, Pathol Lab, Div Clin Sci, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), FDA, CBER, DCGT, Lab Stem Cell Biol,Flow & Image Cytometry Sect, NIH Bldg,29B,Room 2NN08,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 59 TC 87 Z9 90 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD MAR PY 2003 VL 52B IS 1 BP 1 EP 12 DI 10.1002/cyto.b.10013 PG 12 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 670TY UT WOS:000182426300001 PM 12599176 ER PT J AU Solomon, KS Kudoh, T Dawid, IB Fritz, A AF Solomon, KS Kudoh, T Dawid, IB Fritz, A TI Zebrafish foxi1 mediates otic placode formation and jaw development SO DEVELOPMENT LA English DT Article DE foxi1; forkhead; zebrafish; otic placode; ear; jaw ID TREACHER-COLLINS-SYNDROME; MUTATIONS AFFECTING DEVELOPMENT; HELIX TRANSCRIPTION FACTORS; GENE-EXPRESSION SCREEN; XENOPUS-LAEVIS EMBRYOS; INNER-EAR; FORK-HEAD; CEREBRAL HEMISPHERES; TERMINATION CODON; DNA-BINDING AB The otic placode is a transient embryonic structure that gives rise to the inner ear. Although inductive signals for otic placode formation have been characterized, less is known about the molecules that respond to these signals within otic primordia. Here, we identify a mutation in zebrafish, hearsay, which disrupts the initiation of placode formation. We show that hearsay disrupts foxi1, a forkhead domain-containing gene, which is expressed in otic precursor cells before placodes become visible; foxi1 appears to be the earliest marker known for the otic anlage. We provide evidence that foxi1 regulates expression of pax8, indicating a very early role for this gene in placode formation. In addition,foxi1 is expressed in the developing branchial arches, and jaw formation is disrupted in hearsay mutant embryos. C1 Emory Univ, Dept Biol, Atlanta, GA 30322 USA. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Fritz, A (reprint author), Emory Univ, Dept Biol, Atlanta, GA 30322 USA. FU NIDCD NIH HHS [R01-DC04701]; NIGMS NIH HHS [T32 GM008490] NR 80 TC 115 Z9 116 U1 1 U2 4 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 MAR PY 2003 VL 130 IS 5 BP 929 EP 940 DI 10.1242/dev.00308 PG 12 WC Developmental Biology SC Developmental Biology GA 657UM UT WOS:000181684800009 PM 12538519 ER PT J AU Yang, YZ Topol, L Lee, H Wu, JL AF Yang, YZ Topol, L Lee, H Wu, JL TI Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation SO DEVELOPMENT LA English DT Article DE Wnt5a; Wnt5b; chondrocyte; proliferation; mouse ID PRO-ALPHA-1(II) COLLAGEN GENE; GROWTH-PLATE CHONDROCYTES; HORMONE-RELATED PEPTIDE; INDIAN HEDGEHOG; PARATHYROID-HORMONE; BONE-FORMATION; TRANSCRIPTION FACTOR; TRANSGENIC MICE; OSTEOBLAST DIFFERENTIATION; ARTICULAR-CARTILAGE AB Proper longitudinal growth of long bones relies on the regulation of specific spatial patterns of chondrocyte proliferation and differentiation. We have studied the roles of two members of the Wnt family, Wnt5a and Wnt5b in long bone development. We show that Wnt5a is required for longitudinal skeletal outgrowth and that both Wnt5a and Wnt5b regulate the transition between different chondrocyte zones independently of the Indian hedgehog (Ihh)/parathyroid hormone-related peptide (PTHrP) negative feedback loop. We find that important cell cycle regulators such as cyclin D1 and p130, a member of the retinoblastoma family, exhibit complimentary expression patterns that correlate with the distinct proliferation and differentiation states of chondrocyte zones. Furthermore, we show that Wnt5a and Wnt5b appear to coordinate chondrocyte proliferation and differentiation by differentially regulating cyclin D1 and p130 expression, as well as chondrocyte-specific Col2a1 expression. Our data indicate that Wnt5a and Wnt5b control the pace of transitions between different chondrocyte zones. C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Yang, YZ (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NR 76 TC 225 Z9 234 U1 1 U2 7 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 MAR PY 2003 VL 130 IS 5 BP 1003 EP 1015 DI 10.1242/dev.00324 PG 13 WC Developmental Biology SC Developmental Biology GA 657UM UT WOS:000181684800015 PM 12538525 ER PT J AU Granger, DA Shirtcliff, EA Zahn-Waxler, C Usher, B Klimes-Dougan, B Hastings, P AF Granger, DA Shirtcliff, EA Zahn-Waxler, C Usher, B Klimes-Dougan, B Hastings, P TI Salivary testosterone diurnal variation and psychopathology in adolescent males and females: Individual differences and developmental effects SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; VERSION DISC-R; PERSONALITY DIMENSIONS; AGGRESSIVE-BEHAVIOR; YOUNG ADOLESCENTS; SEXUAL-BEHAVIOR; CHILDREN; RELIABILITY; DEHYDROEPIANDROSTERONE; CORTISOL AB Individual differences in salivary testosterone were examined in 213 adolescents (106 boys, 107 girls; mean age 13.66 years) in relation to externalizing and internalizing psychopathology. Self- and parent-report measures of behavior problems and psychiatric symptoms were obtained. Latent anxiety-depression, disruptive behavior, and attention problem constructs were developed using multitrait, multimethod procedures. Saliva samples were collected in the morning, midday, and late afternoon on multiple days and were later assayed for testosterone. Latent constructs were derived for testosterone level and diurnal variation across the six sampling occasions. Structural equations modeled relationships between problem behavior and intra- and interindividual differences in testosterone separately by gender. For boys, lower levels of testosterone and testosterone levels that decreased more slowly across the day were related to higher levels of anxiety-depression and attention problems. These associations were not moderated by pubertal development. For girls,steep declines in testosterone production across the day related to higher levels of disruptive behavior problems, but this association was only evident after including pubertal development as a moderator in the. model. These findings raise novel questions regarding the nature and magnitude of links between testosterone and problem behavior in youth. C1 Penn State Univ, Dept Biobehav Hlth, Behav Endocrinol Lab, University Pk, PA 16802 USA. Catholic Univ Amer, Washington, DC 20064 USA. NIMH, Bethesda, MD 20892 USA. RP Granger, DA (reprint author), Penn State Univ, Dept Biobehav Hlth, Behav Endocrinol Lab, University Pk, PA 16802 USA. EM dag11@psu.edu NR 78 TC 94 Z9 94 U1 7 U2 18 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD SPR PY 2003 VL 15 IS 2 BP 431 EP 449 DI 10.1017/S0954579403000233 PG 19 WC Psychology, Developmental SC Psychology GA 695NY UT WOS:000183838200011 PM 12931836 ER PT J AU Larsen, M Hoffman, MP Sakai, T Neibaur, JC Mitchell, JM Yamada, KM AF Larsen, M Hoffman, MP Sakai, T Neibaur, JC Mitchell, JM Yamada, KM TI Role of PI 3-kinase and PIP3 in submandibular gland branching morphogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE branching morphogenesis; salivary gland; submandibular gland; organ culture; phosphatidylinositol 3-kinase; phosphatidylinositol 3,4,5-trisphosphate; akt; inhibitors; mouse; time-lapse microscopy ID EPIDERMAL GROWTH-FACTOR; PROTEIN-KINASE-C; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE 3-KINASE; FACTOR RECEPTOR; EPITHELIAL MORPHOGENESIS; GENE-EXPRESSION; ACTIVATION; SUBUNIT; INHIBITORS AB The mouse submandibular gland (SMG) epithelium undergoes extensive morphogenetic branching during embryonic development as the first step in the establishment of its glandular structure. However, the specific signaling pathways required for SMG branching morphogenesis are not well understood. Using E13 mouse SMG organ cultures, we showed that inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase), wortmannin and LY294002, substantially inhibited branching morphogenesis in SMG. Branching morphogenesis of epithelial rudiments denuded of mesenchyme was inhibited similarly, indicating that PI 3-kinase inhibitors act directly on the epithelium. Immunostaining and Western analysis demonstrated that the p85 isoform of PI 3-kinase is expressed in epithelium at levels higher than in the mesenchyme. A target of PI 3-kinase, Akt/protein kinase B (PKB), showed decreased phosphorylation at Ser(473) by Western analysis in the presence of PI 3-kinase inhibitors. The major lipid product of PI 3-kinase, phosphatidylinositol 3,4,5-trisphosphate (PIP3), was added exogenously to SMG via a membrane-transporting carrier in the presence of PI 3-kinase inhibitors and was found to stimulate cleft formation, the first step of branching morphogenesis. Together, these data indicate that PI 3-kinase plays a role in the regulation of epithelial branching morphogenesis in mouse SMG acting through a PIP3 pathway. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Yamada, KM (reprint author), NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, 30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805; Larsen, Melinda/0000-0002-5026-2012 FU Intramural NIH HHS [Z01 DE000525-15]; NIDCR NIH HHS [F32 DE014322, DE-14322, F32 DE014322-01, F32 DE014322-02, F32 DE014322-03] NR 44 TC 57 Z9 57 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR 1 PY 2003 VL 255 IS 1 BP 178 EP 191 DI 10.1016/S0012-1606(02)00047-7 PG 14 WC Developmental Biology SC Developmental Biology GA 655XF UT WOS:000181577400013 PM 12618142 ER PT J AU Randazzo, PA AF Randazzo, PA TI RhoD, Src, and hDia2C in endosome motility SO DEVELOPMENTAL CELL LA English DT Editorial Material ID PROTEINS; ACTIN AB The positioning of early endosomes is a dynamic process requiring coordinated activity of both actin and microtubules with their associated motors. A recent report from Marino Zerial and colleagues examining RhoD identifies mDia2C, a novel splice variant of mDia2, and Src as components of the regulatory machinery influencing actin-dependent endosome movement. C1 NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Randazzo, PA (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NR 10 TC 8 Z9 8 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAR PY 2003 VL 4 IS 3 BP 287 EP 288 DI 10.1016/S1534-5807(03)00067-4 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 656AV UT WOS:000181587300001 PM 12636908 ER PT J AU Ozbun, LL Martinez, A Angdisen, J Umphress, S Kang, Y Wang, M You, M Jakowlew, SB AF Ozbun, LL Martinez, A Angdisen, J Umphress, S Kang, Y Wang, M You, M Jakowlew, SB TI Differentially expressed nucleolar TGF-beta 1 target (DENTT) in mouse development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE DENTT; mouse; embryogenesis; TGF-beta 1; nucleolus ID NUCLEOSOME-ASSEMBLY PROTEIN; HUMAN Y-CHROMOSOME; F9 TERATOCARCINOMA CELLS; BRAIN-SPECIFIC GENE; MOLECULAR-CLONING; MESSENGER-RNA; RETINOIC ACID; SEQUENCE; SET; IDENTIFICATION AB Differentially expressed nucleolar TGF-beta1 target (DENTT) is a recently identified gene whose mRNA is differentially affected by TGF-beta1 in TGF-beta1-responsive human lung cancer cells and who is a new member of the TSPY/TSPY-like/SET/NAP-1 (TTSN) protein superfamily. Here, we report that mouse DENTT mRNA contains a 2031-bp open reading frame that encodes a predicted polypeptide of 677-amino acids with a relative molecular mass of 77,671 Da. The mouse and human DENTT sequences show 77% and 78% homology at the nucleotide and amino acid level, respectively. Mouse DENTT is predicted to be a nuclear protein with two nuclear localization signals (NLS), two coiled-coil regions, and a domain that shows significant identity to a region that defines the TTSN superfamily. Green fluorescent protein (GFP)-tagged full-length mouse DENTT transfected into COS-7 cells showed localization predominantly in the nucleolus. Reverse transcription-polymerase chain reaction amplification, Northern hybridization, and Western blot analyses showed expression of mouse DENTT mRNA and protein throughout mouse embryogenesis. Immunohistochemical staining analysis showed that DENTT is expressed in multiple tissues in a defined spatiotemporal pattern during mouse embryogenesis. The heart and primitive brain were the first organs of the embryo that showed immunoreactivity for the DENTT antibody by day 8 of development (E8). In the developing mouse brain, the choroid plexus was intensely stained for DENTT in all stages of development. The spinal cord and dorsal root ganglia were also positive for DENTT staining beginning in the 11-day-old embryo (E11), where homogeneous immunostaining was observed throughout the developing neurons. By day 16 of development (1216), only a small subset of the neuronal population in the spinal cord and dorsal root ganglia was positively stained for DENTT. DENTT immunoreactivity increased steadily with maturation as the differentiation of cartilage and osteoblasts proceeded and reached a maximum in the growth plate during endochondral ossification. DENTT expression was also detected in multiple rodent cell types in vitro, including mouse F9 embryonal carcinoma (EC) cells. Addition of retinoic acid or sodium butyrate to F9 EC cells showed a rapid decrease in expression of DENTT protein occurring by 1 hr that continued to decrease to almost undetectable levels after 24 hr. Cotransfection of full-length mouse DENTT expression plasmid with 3TPLux or COL7A1Luc Luciferase reporter plasmids into F9 EC cells significantly increased the level of 3TPLux reporter transcription while decreasing the level of COL7A1Luc reporter transcription, suggesting that DENTT may play multiple roles in modulating transcriptional responses. These findings suggest new roles for the TTSN superfamily during embryogenesis and differentiation. (C) 2003 Wiley-Liss, Inc. C1 NCI, Cell & Canc Biol Branch, Rockville, MD 20850 USA. Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Columbus, OH 43210 USA. RP Jakowlew, SB (reprint author), NCI, Cell & Canc Biol Branch, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 52 TC 12 Z9 16 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAR PY 2003 VL 226 IS 3 BP 491 EP 511 DI 10.1002/dvdy.10257 PG 21 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 651NL UT WOS:000181326000007 PM 12619135 ER PT J AU Limke, TL Cai, JL Miura, T Rao, MS Mattson, MP AF Limke, TL Cai, JL Miura, T Rao, MS Mattson, MP TI Distinguishing features of progenitor cells in the late embryonic and adult hippocampus SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE neural stem cells; neurogenesis; FGFR4; GFAP; nestin; PCNA; PSA-NCAM; Sox1; hippocampus; subgranular layer; telomerase ID FIBROBLAST-GROWTH-FACTOR; NEURAL STEM-CELL; RADIAL GLIAL-CELLS; SPINAL-CORD; SUBVENTRICULAR ZONE; DENTATE GYRUS; RAT-BRAIN; EXPRESSION PATTERNS; NEURONAL PRECURSORS; TELOMERASE ACTIVITY AB Adult neurogenesis occurs within the subgranular layer of the hippocampal dentate gyrus. In this study, we examined dividing cells in the late embryonic and adult rat hippocampus to identify distinguishing characteristics and potential neural stem cell population(s), as identified by the putative neural stem cell markers FGFR4 and Sox1. In embryonic hippocampal cells in primary culture, basic fibroblast factor caused cell proliferation, increased telomerase activity and upregulation of FGFR4 mRNA. In both the embryonic and adult brains, proliferating cells express Sox1, as well as markers for neuronal-and glial-restricted precursors. However, the cell markers associated with cells expressing proliferative cell nuclear antigen (PCNA) and Sox1 differed between late embryonic and adult hippocampus, suggesting that there are important differences between adult and embryonic neurogenesis. Copyright (C) 2003 S. Karger AG, Basel. C1 NIA, Neurosci Lab, Ctr Gerontol Res, Baltimore, MD 21224 USA. RP Limke, TL (reprint author), NIA, Neurosci Lab, Ctr Gerontol Res, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 58 TC 15 Z9 15 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD MAR-AUG PY 2003 VL 25 IS 2-4 BP 257 EP 272 DI 10.1159/000072273 PG 16 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 722RP UT WOS:000185390400016 PM 12966222 ER PT J AU Muller, YL Bogardus, C Pedersen, O Baier, L AF Muller, YL Bogardus, C Pedersen, O Baier, L TI A Gly482Ser missense mutation in the peroxisonte proliferator-activated receptor gamma coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; AUTOSOMAL GENOMIC SCAN; PGC-1; OBESITY; GENE; RESISTANCE; EXPRESSION; LOCUS; MASS; RATS AB Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) is a transcriptional coactivator of peroxisome proliferator-activated receptor gamma and alpha, which play important roles in adipogenesis and lipid metabolism. A single nucleotide polymorphisin within the coding region of the PGC-1 gene predicts a glycine to serine substitution at amino acid 482 and has been associated with type 2 diabetes in a Danish population. In this study, we examined whether this Gly482Ser polymorphism is associated with type 2 diabetes or obesity, or metabolic predictors of these diseases, in Pima Indians. There was no association of the Gly482Ser polymorphism with either type 2 diabetes or BMI (n = 984). However, among nondiabetic Pima Indians (n = 183-201), those with the Gly/Gly genotype had a lower mean insulin secretory response to intravenous and oral glucose and a lower mean rate of lipid oxidation (over 24 h in a respiratory chamber) despite a larger mean subcutaneous abdominal adipocyte size and a higher mean plasma free fatty acid concentration. These data indicate that the Gly482Ser missense polymorphism in PGC-1 has metabolic consequences on lipid metabolism that could influence insulin secretion. C1 NIDDK, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. Steno Diabet Ctr, DK-2820 Gentofte, Denmark. RP Baier, L (reprint author), NIDDK, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. NR 24 TC 98 Z9 109 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2003 VL 52 IS 3 BP 895 EP 898 DI 10.2337/diabetes.52.3.895 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652DF UT WOS:000181364000042 PM 12606537 ER PT J AU Meneilly, GS McIntosh, CHS Pederson, RA Habener, JF Ehlers, MRW Egan, JM Elahi, D AF Meneilly, GS McIntosh, CHS Pederson, RA Habener, JF Ehlers, MRW Egan, JM Elahi, D TI Effect of glucagon-like peptide 1 (7-36 amide) on insulin-mediated glucose uptake in patients with type 1 diabetes SO DIABETES CARE LA English DT Article ID GLYCOGEN-SYNTHASE; SKELETAL-MUSCLE; GLP-I; METABOLISM; MELLITUS; HUMANS; RATS; SENSITIVITY; HEPATOCYTES; INHIBITION AB OBJECTIVE - To examine the insulinomimetic insulin-independent effects of glucagon-like peptide (GLP)-1 on glucose uptake in type I diabetic patients. RESEARCH DESIGN AND METHODS - We used the hyperinsulinemic-euglycemic clamp (480 pmol . m(-2) . min(-1)) in paired randomized studies of six women and five men with type 1 diabetes. In the course of one of the paired studies, the subjects also received GLP-1 at a dose of 1.5 pmol . kg(-1) . min(-1). The patients were 41 +/- 3 years old with a BMI of 25 +/- 1 kg/m(2). The mean duration of diabetes was 23 - 3 years. RESULTS - Plasma glucose was allowed to fall from a fasting level of similar to11 mmol/l to 5.3 mmol/l in each study and thereafter was held stable at that level. Plasma insulin levels during both studies were similar to900 pmol/l. Plasma C-peptide levels did not change during the studies. In the GLP-1 study, plasma total GLP-1 levels were elevated from the fasting level of 31 +/- 3 to 150 +/- 17 pmol/l. Plasma glucagon levels fell from the fasting levels of similar to 14 pmol/l to 9 pmol/l during both paired studies. Hepatic glucose production was suppressed during the glucose clamps in all studies. Glucose uptake was not different between the two studies (similar to40 mumol . kg(-1) . min(-1)). CONCLUSIONS - GLP-1 does not augment insulin-mediated glucose uptake in lean type 1 diabetic patients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Geriatr Res Lab, Boston, MA 02114 USA. Univ British Columbia, Dept Med, Vancouver, BC, Canada. Univ British Columbia, Dept Physiol, Vancouver, BC, Canada. Harvard Univ, Sch Med, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02115 USA. Restoragen Inc, Dept Drug Dev, Lincoln, NE USA. NIA, NIH, Baltimore, MD 21224 USA. RP Elahi, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Geriatr Res Lab, GRB SB 0015,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-98-02] NR 29 TC 24 Z9 28 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2003 VL 26 IS 3 BP 837 EP 842 DI 10.2337/diacare.26.3.837 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UM UT WOS:000185505100046 PM 12610046 ER PT J AU Egan, JM Bulotta, A Hui, HX Perfetti, R AF Egan, JM Bulotta, A Hui, HX Perfetti, R TI GLP-1 receptor agonists are growth and differentiation factors for pancreatic istet beta cells SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Review DE GLP-1; diabetes; insulin secretion; PDX-1; pancreatic ductal cells; stem cells; islets of Langerhans; beta-cells ID GLUCAGON-LIKE PEPTIDE-1; ACTIVATED PROTEIN-KINASE; IMPROVED GLUCOSE-TOLERANCE; INSULIN-PRODUCING CELLS; TRANSCRIPTION FACTOR; GENE-EXPRESSION; RIN-1046-38 CELLS; DIABETIC RATS; ISLET GROWTH; ADULT-RATS AB Glucagon-like peptide-1 (GLP-1) is an incretin hormone that, when given exogenously, is capable of normalizing blood glucose in individuals with type 2 diabetes. Until recently most of the research on this compound had been related to its insulinotropic properties. However, GLP-1 also regulates insulin synthesis and proinsulin gene expression, as well as the components of the glucose-sensing machinery. In addition to regulating insulin release, it is involved in regulating the secretion of at least two other islet hormones - glucagon and somatostatin. Extraislet effects of GLP-1 include a role in the central nervous system stress response, hypothalamic-pituitary function, and the suppression of gastric emptying. Recent studies from our own and other laboratories show that GLP-1 can regulate islet growth and is a differentiation factor of the endocrine pancreas. This leads us to propose that GLP-1 and GLP-1 receptor agonists, in the context of long-term treatment of type 2 diabetes, will have broader biological action on the endocrine pancreas than was earlier anticipated. We propose that GLP-1 is a growth factor for pancreatic endocrine cells and can increase islet cell mass. Here we review those reports that have highlighted its role as a factor for islet cell growth and differentiation. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Cedars Sinai Med Ctr, Dept Med, Div Endocrinol & Metab, Los Angeles, CA 90048 USA. NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Perfetti, R (reprint author), Cedars Sinai Med Ctr, Dept Med, Div Endocrinol & Metab, Rm B-131,8700 Beverly Blvd, Los Angeles, CA 90048 USA. NR 62 TC 119 Z9 128 U1 4 U2 18 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD MAR-APR PY 2003 VL 19 IS 2 BP 115 EP 123 DI 10.1002/dmrr.357 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 663HC UT WOS:000181999300003 PM 12673779 ER PT J AU North, KE MacCluer, JW Williams, JT Welty, TK Best, LG Lee, ET Fabsitz, RR Howard, BV AF North, KE MacCluer, JW Williams, JT Welty, TK Best, LG Lee, ET Fabsitz, RR Howard, BV TI Evidence for distinct genetic effects on obesity and lipid-related CVD risk factors in diabetic compared to nondiabetic American Indians: the Strong Heart Family Study SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE diabetes; CVD risk factors; genetic effects; American Indians; Strong Heart Family Study ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; INSULIN-RESISTANCE SYNDROME; MULTIPOINT LINKAGE ANALYSIS; CARDIOVASCULAR-DISEASE; QUANTITATIVE TRAITS; SEXUAL DIMORPHISM; HDL CHOLESTEROL; PIMA-INDIANS; MELLITUS; PLASMA AB Background The relationship between diabetes and increased cardiovascular disease (CVD) risk is well established. Previous data from the Strong Heart Family Study (SHFS) have demonstrated significant heritabilities for CVD risk factors and implicated diabetes as an important predictor of several of the phenotypes in three large groups of American Indians in Arizona (AZ), Oklahoma (OK), and the Dakotas (DK). However, the genetic architecture of this relationship is not well understood. The purpose of the present paper is to determine whether the genetic effects on C-VD risk factors in the SHFS are different in diabetic and nondiabetic individuals. Methods Approximately 950 men and women, 18 years or older, in 32 extended families, were examined between 1997 and 1999. Interaction between genotype and diabetes status was estimated for nine CVD risk factors [body fat mass (FAT), body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), log-transformed fibrinogen, log-transformed triglycerides, log-transformed urinary albumin: creatinine ratio (LACR), plasminogen activator inhibitor 1 (PAI-1), systolic blood pressure (SBP), and waist-to-hip ratio (WHR)], using a maximum likelihood variance decomposition technique. Results We found evidence that genetic factors influencing BMI, FAT, log-transformed triglycerides, HDL-C, and WHR are differentially expressed in individuals with diabetes compared to those without diabetes. Conclusion Thus, may be distinct genetic determinants of various CVD risk factors. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Univ N Carolina, Bank Amer Ctr, Dept Epidemiol, Chapel Hill, NC 27514 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78284 USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. Missouri Breaks Ind Res Inc, Timber Lake, SD USA. Univ Oklahoma, Hlth Sci Ctr, Sch Publ Hlth, Ctr Amer Ind Hlth Res, Oklahoma City, OK USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. MedStar Res Inst, Washington, DC USA. RP North, KE (reprint author), Univ N Carolina, Bank Amer Ctr, Dept Epidemiol, 137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA. FU NHLBI NIH HHS [U01 HL41652, U01 HL65520, U01 HL41654, U01 HL41642, U01 HL65521] NR 61 TC 5 Z9 5 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD MAR-APR PY 2003 VL 19 IS 2 BP 140 EP 147 DI 10.1002/dmrr.355 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 663HC UT WOS:000181999300006 PM 12673782 ER PT J AU Klimes, I Weston, K Kovacs, P Gasperikova, D Jezova, D Kvetnansky, R Thompson, JR Sebokova, E Samani, NJ AF Klimes, I Weston, K Kovacs, P Gasperikova, D Jezova, D Kvetnansky, R Thompson, JR Sebokova, E Samani, NJ TI Mapping of genetic loci predisposing to hypertriglyceridaemia in the hereditary hypertriglyceridaemic rat: analysis of genetic association with related traits of the insulin resistance syndrome SO DIABETOLOGIA LA English DT Article DE hypertriglyceridaemia; insulin resistance syndrome; hypertension; quantitative trait loci; genetic linkage ID BLOOD-PRESSURE; HYPERTENSIVE RATS; FATTY-ACID; METABOLIC SYNDROME; FISH-OIL; MAP; DETERMINANTS; ETIOLOGY; STRAINS; TISSUE AB Aims/hypothesis. Hypertriglyceridaemia is an important risk factor for coronary heart disease, especially in the context of the insulin resistance syndrome where it often occurs with hypertension. The two phenotypes are also associated in the hereditary hypertriglyceridaemic (hHTg) rat. The aim of this study was to map quantitative trait loci that affect plasma triglyceride concentration in the hHTg rat and determine whether they co-localize with loci for blood pressure. Methods. Second filial generation progeny (n=189) from a cross of the hHTg rat with the Brown Norway rat were phenotyped for fasting plasma triglyceride, glucose and insulin concentrations, and direct unrestrained resting blood pressure. A partial genome-scan was conducted using 153 microsatellite markers that were polymorphic between the two strains. Results. A major locus (lod score 6.5) influencing plasma triglyceride concentration in a co-dominant fashion was mapped to chromosome 4 between D1Mit5 and D1Mit17. Chromosome 8 contained multiple peaks with a lod score greater than 4.0 influencing triglyceride concentration. Importantly, none of the triglyceride loci had an effect on blood pressure. The triglyceride locus on chromosome 4 co-localized with a locus for fasting plasma insulin (lod score 4.1), although the effect on insulin concentration was in the opposite direction to that on triglyceride. Conclusion/interpretation. We have mapped the major loci that affect plasma triglyceride concentration in the hHTg rat. These loci do not influence blood pressure suggesting that these commonly associated phenotypes of the insulin resistance syndrome are not be due to pleiotropic effects of the same gene(s). C1 Slovak Acad Sci, Inst Expt Endocrinol, Diabet & Nutr Res Lab, Bratislava, Slovakia. Univ Leicester, Dept Med, Div Cardiol, Leicester LE1 7RH, Leics, England. NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. Univ Leicester, Dept Epidemiol & Publ Hlth, Leicester LE1 7RH, Leics, England. RP Samani, NJ (reprint author), Univ Leicester, Glenfield Gen Hosp, Div Cardiol, Clin Sci Wing,Groby Rd, Leicester LE3 9QP, Leics, England. NR 30 TC 16 Z9 16 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAR PY 2003 VL 46 IS 3 BP 352 EP 358 DI 10.1007/s00125-003-1035-6 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 674CV UT WOS:000182620000006 PM 12687333 ER PT J AU Cervenakova, L Brown, P Soukharev, S Yakovleva, O Diringer, H Saenko, EL Drohan, WN AF Cervenakova, L Brown, P Soukharev, S Yakovleva, O Diringer, H Saenko, EL Drohan, WN TI Failure of immunocompetitive capillary electrophoresis assay to detect disease-specific prion protein in buffy coat from humans and chimpanzees with Creutzfeldt-Jakob disease SO ELECTROPHORESIS LA English DT Article DE blood screening test; immunocompetetive capillary electrophoresis prion disease; prion protein; transmissible spongiform encephalopathy; variant Creutzfeldt-Jakob disease ID FLUORESCENT-LABELED PEPTIDES; SPONGIFORM ENCEPHALOPATHY; BLOOD AB The emergence of a new environmentally caused variant of Creutzfeldt-Jakob disease (vCJD), the result of food-born infection by the causative agent of bovine spongiform encephalopathy (BSE), has stimulated research on a practical diagnostic screening test. The immunocompetitive capillary electrophoresis (ICCE) assay has been reported to detect disease-specific, proteinase-resistant prion protein (PrPres) in the blood of scrapie-infected sheep. We have applied this method to blood from CJD-infected chimpanzees and humans. The threshold of detection achieved with our ICCE was 0.6 nM of synthetic peptide corresponding to the prion protein (PrP) C-terminus, and 2 nM of recombinant human PrP at the optimized conditions. However, the test was unable to distinguish between extracts of leucocytes from healthy and CJD-infected chimpanzees, and from healthy human donors and patients affected with various forms of CJD. Thus, the ICCE assay as presently performed is not suitable for use as a screening test in human transmissible spongiform encephalopathies (TSEs). C1 Amer Red Cross, Jerome H Holland Lab Biomed Sci, Plasma Derivat Dept, Rockville, MD 20855 USA. NIH, Bethesda, MD 20892 USA. Amer Red Cross, Jerome H Holland Lab Biomed Sci, Dept Biochem, Rockville, MD 20855 USA. RP Cervenakova, L (reprint author), Amer Red Cross, Jerome H Holland Lab Biomed Sci, Plasma Derivat Dept, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. EM cervenak@usa.redcross.org NR 8 TC 28 Z9 30 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAR PY 2003 VL 24 IS 5 BP 853 EP 859 DI 10.1002/elps.200390107 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 658ZZ UT WOS:000181752800013 PM 12627447 ER PT J AU Kouprina, N Leem, SH Solomon, G Ly, A Koriabine, M Otstot, J Pak, E Dutra, A Zhao, SY Barrett, JC Larionov, V AF Kouprina, N Leem, SH Solomon, G Ly, A Koriabine, M Otstot, J Pak, E Dutra, A Zhao, SY Barrett, JC Larionov, V TI Segments missing from the draft human genome sequence can be isolated by transformation-associated recombination cloning in yeast SO EMBO REPORTS LA English DT Article ID DNA REGION; GENE; CHROMOSOME-2 AB The reported draft human genome sequence includes many contigs that are separated by gaps of unknown sequence. These gaps may be due to chromosomal regions that are not present in the Escherichia coli libraries used for DNA sequencing because they cannot be cloned efficiently, if at all, in bacteria. Using a yeast artificial chromosome (YAC)/ bacterial artificial chromosome (BAC) library generated in yeast, we found that approximately 6% of human DNA sequences tested transformed E. coli cells less efficiently than yeast cells, and were less stable in E. coli than in yeast. When the ends of several YAC/BAC isolates cloned in yeast were sequenced and compared with the reported draft sequence, major inconsistencies were found with the sequences of those YAC/BAC isolates that transformed E. coli cells inefficiently. Two human genomic fragments were re-isolated from human DNA by transformation-associated recombination (TAR) cloning. Re-sequencing of these regions showed that the errors in the draft are the results of both missassembly and loss of specific DNA sequences during cloning in E coli. These results show that TAR cloning might be a valuable method that could be widely used during the final stages of the Human Genome Project. C1 NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. Dong A Univ, Dept Biol, Pusan 604714, South Korea. NIEHS, Res Triangle Pk, NC 27709 USA. NHGRI, Bethesda, MD 20892 USA. Inst Genome Res, Rockville, MD 20850 USA. RP Kouprina, N (reprint author), NCI, Lab Biosyst & Canc, Bldg 37,Room 5031, Bethesda, MD 20892 USA. NR 20 TC 21 Z9 23 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD MAR PY 2003 VL 4 IS 3 BP 257 EP 262 DI 10.1038/sj.embor.embor766 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 665RC UT WOS:000182133700010 PM 12634842 ER PT J AU Feldman, SA Eiden, LE AF Feldman, SA Eiden, LE TI The chromogranins: Their roles in secretion from neuroendocrine cells and as markers for neuroendocrine neoplasia SO ENDOCRINE PATHOLOGY LA English DT Review DE chromogranins; secretory granules; neuroendocrine cells; pancreastatin; enterochromaffin-like cells ID BOVINE ADRENAL-MEDULLA; A-DERIVED PEPTIDE; INHIBITS INSULIN-SECRETION; PAN-NEURONAL EXPRESSION; RAT ANTERIOR-PITUITARY; CENTRAL-NERVOUS-SYSTEM; PANCREATIC BETA-CELLS; B SECRETOGRANIN-I; MESSENGER-RNA; PROTEIN-I AB Chromogranins are the major components of the secretory granules of most neuroendocrine cells. Within the secretory pathway, chromogranins are involved in granulogenesis, and in sorting and processing of secretory protein cargo prior to secretion. Once secreted, they have hormonal, autocrine, and paracrine activities. The chromogranin family includes chromogranins A (CgA) and B (CgB) and secretogranin 11 (Sgll, once called chromogranin C). The related "granins" NESP55, 7132, secretogranin III/1B 1075 (SgIII), and secretogranin IV/HISL-19 antigen (SgIV), are also sometimes included when considering the chromogranins. While it is useful to consider the granin proteins as a family with many common features, it is also necessary to examine the distinct features and properties of individual members of the granin family to understand fully their functions, employ them efficiently as tissue, serum, and urinary markers for neuroendocrine neoplasia, and develop an evolutionary-biologic perspective on their contribution to mammalian physiology. Recent advances in chromogranin research include establishing the role of CgA in granulogenesis and the role of CgB in nuclear transcription; new biologic activities for CgA-, CgB-, and SgII-derived peptides; and new marker functions for granins and their proteolytically processed products in endocrine neoplasias. C1 NIH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. NIH, Sect Mol Virol, Bethesda, MD 20892 USA. RP Eiden, LE (reprint author), NIH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, 36 Convent Dr,MSC 4090, Bethesda, MD 20892 USA. OI Eiden, Lee/0000-0001-7524-944X NR 162 TC 59 Z9 61 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD SPR PY 2003 VL 14 IS 1 BP 3 EP 23 DI 10.1385/EP:14:1:3 PG 21 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA 681FN UT WOS:000183026300002 PM 12746559 ER PT J AU Hill, GD Pace, V Persohn, E Bresser, C Haseman, JK Tischler, AS Nyska, A AF Hill, GD Pace, V Persohn, E Bresser, C Haseman, JK Tischler, AS Nyska, A TI A comparative immunohistochemical study of spontaneous and chemically induced pheochromocytomas in B6C3F1 mice SO ENDOCRINE PATHOLOGY LA English DT Article DE pheochromocytoma; spontaneous; chemically induced; immunohistochemistry; B6C3F1 mouse ID ADRENAL-MEDULLA; NEUROENDOCRINE TUMORS; PROLIFERATIVE LESIONS; RATS; CHROMOGRANIN; HYPERPLASIA; CELLS; MOUSE AB Spontaneously occurring and chemically induced pheochromocytomas are rare in mice. That the mouse pheochromocytoma is a more appropriate animal model than that of the rat for study of human medullary adrenal tumors has been suggested. The expression of phenylethanolamine-N-methyltransferase (PNMT), the enzyme responsible for production of epinephrine from norepinephrine, is common to both mouse and human pheochromocytomas. This investigation assessed the expression of the immunohistochemical markers PNMT, tyrosine hydroxylase (TH), and chromogranin A (CGA) in spontaneously occurring and chemically induced pheochromocytomas in the B6C2F1 mouse. Spontaneous tumors were derived from control animals from 10 different studies and the pheochromocytomas from treated groups from 4 different studies. All tumors were positive for maximal TH expression. A highly significant difference in PNMT expression (P < 0.01) occurred between spontaneously occurring pheochromocytomas classified as benign or "malignant" by the criteria of toxicologic pathology. Chemically induced tumors showed intermediate PNMT staining. A marked reduction in CGA expression occurred in pheochromocytomas induced by technical grade pentachlorophenol, compared to the other three chemicals and the spontaneously occurring tumors. These findings suggest that immunohistochemistry is a reliable tool in investigating the functional capabilities of pheochromocytomas in mice. PNMT expression is a tightly regulated component of the chromaffin cell phenotype and appears to be readily lost in mouse pheochromocytomas, particularly those with aggressive characteristics. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Tufts Univ New England Med Ctr, Dept Pathol, Boston, MA 02111 USA. Novartis Pharma AG, CH-4132 Muttenz, Switzerland. Dompe SpA, R&D, I-67100 Laquila, Italy. RP Hill, GD (reprint author), NIEHS, Lab Expt Pathol, POB 12233,MD B3-06, Res Triangle Pk, NC 27709 USA. NR 21 TC 10 Z9 10 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD SPR PY 2003 VL 14 IS 1 BP 81 EP 91 DI 10.1385/EP:14:1:81 PG 11 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA 681FN UT WOS:000183026300009 PM 12746566 ER PT J AU Normanno, N Bianco, C De Luca, A Maiello, MR Salomon, DS AF Normanno, N Bianco, C De Luca, A Maiello, MR Salomon, DS TI Target-based agents against ErbB receptors and their ligands: a novel approach to cancer treatment SO ENDOCRINE-RELATED CANCER LA English DT Review ID EPIDERMAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; METASTATIC BREAST-CANCER; TRANSITIONAL-CELL CARCINOMA; DIFFERENTIAL IMMUNOHISTOCHEMICAL DETECTION; C-ERBB-3 PROTEIN EXPRESSION; HUMAN PANCREATIC-CARCINOMA; MONOCLONAL-ANTIBODY C225; FACTOR-RELATED PEPTIDES; EGF-RELATED PEPTIDES AB The ErbB receptors and their cognate ligands that belong to the epidermal growth factor (EGF) family of peptides are involved in the pathogenesis of different types of carcinomas. In fact, the ErbB receptors and the EGF-like growth factors are frequently expressed in human tumors. These proteins form a complex system that regulates the proliferation and the survival of cancer cells. Therefore, ErbB receptors and their ligands might represent suitable targets for novel therapeutic approaches in human carcinomas. In this regard, different target-based agents that are directed against the ErbB receptors have been developed in the past two decades. One of these compounds, the humanized anti-ErbB-2 monoclonal antibody trastuzumab has been approved for the treatment of patients with metastatic breast cancer. The anti-EGF receptor (EGFR) antibody C225, as well as EGFR tyrosine kinase inhibitors ZD1839 and OSI-774 are currently in phase III clinical development. Several other ErbB tyrosine kinase inhibitors are in phase I/II studies. These compounds have generally been shown to have an acceptable toxicity profile and promising anti-tumor activity in heavily pretreated patients. The mechanisms of action of these compounds, as well as the potential therapeutic strategies to improve their efficacy are discussed in this review with particular regard to the combinations of anti-ErbB agents with cytotoxic drugs, or combinations of different ErbB-targeting agents. C1 INT Fdn Pascale, Div Hematol Oncol, I-80131 Naples, Italy. INT Fdn Pascale, Dept Expt Oncol, 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, Div Hematol Oncol, I-80131 Naples, Italy. RI De Luca, Antonella/J-8737-2016; OI De Luca, Antonella/0000-0001-5762-447X; Normanno, Nicola/0000-0002-7158-2605 NR 204 TC 229 Z9 244 U1 4 U2 12 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD MAR PY 2003 VL 10 IS 1 BP 1 EP 21 DI 10.1677/erc.0.0100001 PG 21 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 667PZ UT WOS:000182243100001 PM 12653668 ER PT J AU Leonessa, F Clarke, R AF Leonessa, F Clarke, R TI ATP binding cassette transporters and drug resistance in breast cancer SO ENDOCRINE-RELATED CANCER LA English DT Review ID P-GLYCOPROTEIN EXPRESSION; MDR1 GENE-EXPRESSION; CYSTEINE-SCANNING MUTAGENESIS; CHINESE-HAMSTER CELLS; POLYMERASE-CHAIN-REACTION; STRESS-INDUCED ACTIVATION; MESSENGER-RNA EXPRESSION; ACUTE MYELOID-LEUKEMIA; TUMOR-SUPPRESSOR GENE; S-PHASE FRACTION AB Resistance to chemotherapy is a critical issue in the management of breast cancer patients. The nature of clinical drug resistance is likely to be multifactorial. However, in the last decade considerable attention has been dedicated to the role played by membrane transporter proteins belonging to the ATP binding cassette protein superfamily, and in particular by the MDR1 product P-glycoprotein (Pgp) and the multidrug resistance protein (MRP1). Heterogeneity of results is a common feature Of studies evaluating the expression and prognostic role of these proteins, due to both methodological and biological factors. Nonetheless, Pgp and MRP1 are detected in a significant proportion Of untreated breast cancers (on average 40 and 50% respectively, by immunohistochemistry), without a Clear and consistent association with cancer stage. Exposure to chemotherapy increases the expression of both proteins. In vitro studies on primary cultures of breast cancer cells obtained at surgery consistently show an association between Pgp (protein) or MDR1 (mRNA) expression and resistance to chemotherapy. However, the correlation with clinical drug resistance is not as well defined. A stronger association of Pgp/MDR1 with response rates has been observed when expression or an increase in expression are detected immediately following chemotherapy. Correlations with prognosis appear more evident in studies using immunohistochemistry, in adjuvant and neoadjuvant settings. Evidence of clinical reversal of drug resistance by verapamil suggests a functional role of Pgp in drug resistance, although the significance of the evidence is generally weakened by poor trial designs. Future studies should take into account the multifactorial nature of drug resistance in breast cancer and use standardized approaches with adequate controls. Expression studies should be complemented by well-designed trials of drug-resistance reversal using target-specific chemosensitizing agents, and relating the results to the levels of expression of the target proteins. C1 Georgetown Univ, Sch Med, Dept Oncol, Washington, DC 20007 USA. NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. RP Clarke, R (reprint author), Georgetown Univ, Sch Med, Dept Oncol, Room W405A,Res Bldg,3970 Reservoir Rd NW, Washington, DC 20007 USA. RI Clarke, Robert/A-6485-2008 OI Clarke, Robert/0000-0002-9278-0854 NR 238 TC 164 Z9 178 U1 0 U2 4 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD MAR PY 2003 VL 10 IS 1 BP 43 EP 73 DI 10.1677/erc.0.0100043 PG 31 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 667PZ UT WOS:000182243100003 PM 12653670 ER PT J AU Koch, CA Brouwers, FM Rosenblatt, K Burman, KD Davis, MM Vortmeyer, AO Pacak, K AF Koch, CA Brouwers, FM Rosenblatt, K Burman, KD Davis, MM Vortmeyer, AO Pacak, K TI Adrenal ganglioneuroma in a patient presenting with severe hypertension and diarrhea SO ENDOCRINE-RELATED CANCER LA English DT Article ID NEURAL CREST TUMORS; CHROMOSOME 1P; P53 MUTATIONS; ALLELIC LOSS; RET ALLELE; NEUROBLASTOMA; PHEOCHROMOCYTOMA; BLASTOMA; METAIODOBENZYLGUANIDINE; SCINTIGRAPHY AB Ganglioneuromas (GNs) are neural crest cell-derived tumors and rarely occur in the adrenal gland. There are presently no markers that can reliably distinguish benign and malignant neuroendocrine tumors. Here we describe a 63-year-old woman who developed sudden chest pain and hypertension combined with increased stool frequency. An incidental adrenal mass 5 cm in size with a bright signal on T2-weighted magnetic resonance imaging was discovered. Biochemical evaluation and I-131-metaiodobenzylguanidine (MIBG) scintigraphy were negative. Histopathological examination revealed a mature adrenal GN. Neuroblastoma, the immature form of a GN, is known for deletions on chromosomal locus 1p36, and adrenal tumors frequently show allele loss on 17p. To further elucidate the histo- and pathogenesis of adrenal GN, we performed loss of heterozygosity studies on chromosomal loci 1p34-36 and 17p13 (the p53 gene locus) after careful microdissection of tumor and normal tissue. We did not detect allelic losses at these loci with the informative polymorphic markers used, suggesting that these loci are not involved in tumorigenesis. In addition, immunohistochemical investigation of the GN was positive for vasoactive intestinal peptide, a hormone commonly expressed in ganglion cells. We suggest that in our patient with an adrenal GN, the combination of biochemical, scintigraphic, molecular, immunohistochemical, and histopathological findings are all consistent with the benign morphology of this tumor. C1 NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. Univ Leipzig, Dept Endocrinol & Nephrol, D-04103 Leipzig, Germany. NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA. Washington Hosp Ctr, Dept Endocrinol, Washington, DC 20010 USA. NINDS, Mol Pathogenesis Unit, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Koch, CA (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, Bldg 10,Rm 9D42, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 53 TC 22 Z9 24 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD MAR PY 2003 VL 10 IS 1 BP 99 EP 107 DI 10.1677/erc.0.0100099 PG 9 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 667PZ UT WOS:000182243100006 PM 12653673 ER PT J AU Uwaifo, GI Sumner, AE Shamburek, R Sarlis, NJ AF Uwaifo, GI Sumner, AE Shamburek, R Sarlis, NJ TI A case of familial dysbetalipoproteinemia with very low serum high-density lipoprotein-cholesterol: Response to atorvastatin therapy SO ENDOCRINOLOGIST LA English DT Article; Proceedings Paper CT 82nd Annual Meeting of the Endocrine-Society CY JUN 21-24, 2000 CL TORONTO, CANADA SP Endocrine Soc ID APOLIPOPROTEIN-A-I; HORMONE REPLACEMENT THERAPY; III HYPERLIPOPROTEINEMIA; GROWTH-HORMONE; PARTICLE-CHOLESTEROL; LIPID LEVELS; HYPERLIPIDEMIA; HYPERCHOLESTEROLEMIA; ADULTS; HYPOTHYROIDISM AB The mainstays of therapy of familial dyslipoproteinemia (FDB) are diet and long-term niacin or fibrate therapy. Statins are progressively recognized as accepted alternatives for FDB. We hereby describe the case of a 32-year-old obese man with treated panhypopituitarism and FDB, whose hyperlipidemia improved significantly on atorvastatin therapy. In this patient, we also noted a marked discrepancy between the serum high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo-) AI levels, with HDL-C being disproportionately low in comparison to the corresponding apo-AI values. Although atorvastatin therapy resulted in a significant improvement of lipid metabolism parameters within 8 weeks, the aforementioned discrepancy between HDL-C and apo-AI levels persisted. This case buttresses the effectiveness of atorvastatin therapy in FDB, and highlights the occurrence of discrepancy between HDL-C and measured apo-AI levels in rare cases of dyslipidemia. We speculate that the latter phenomenon may be caused by allelic variation(s) in any of three genes: apo-AI, apo-CIII, and apo-AIV. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Sarlis, NJ (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Endo Neoplasia & Horm Dis, Unit 435, 1515 Holcombe Blvd, Houston, TX 77030 USA. RI Uwaifo, Gabriel/M-2361-2016 OI Uwaifo, Gabriel/0000-0002-6962-9304 NR 55 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD MAR-APR PY 2003 VL 13 IS 2 BP 85 EP 90 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 681GZ UT WOS:000183029600004 ER PT J AU Petering, DH Klump, V AF Petering, DH Klump, V TI Importance of the Great Lakes SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter C1 Univ Wisconsin, Dept Chem, NIEHS, Marine & Freshwater Biomed Sci Ctr, Milwaukee, WI USA. Univ Wisconsin, Great Lakes WATER Inst, Milwaukee, WI 53201 USA. RP Petering, DH (reprint author), Univ Wisconsin, Dept Chem, NIEHS, Marine & Freshwater Biomed Sci Ctr, POB 413, Milwaukee, WI USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2003 VL 111 IS 3 BP A142 EP A142 DI 10.1289/ehp.111-a142a PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 655ZJ UT WOS:000181583200002 PM 12611670 ER PT J AU Umbach, DM AF Umbach, DM TI On the determination of sample size SO EPIDEMIOLOGY LA English DT Editorial Material C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Umbach, DM (reprint author), NIEHS, Biostat Branch, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2003 VL 14 IS 2 BP 137 EP 138 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 648WQ UT WOS:000181174300003 PM 12606876 ER PT J AU Barrett, JC Davis, BJ Bennett, LM AF Barrett, JC Davis, BJ Bennett, LM TI Pregnancy and protection from hormonally associated tumor development SO EPIDEMIOLOGY LA English DT Editorial Material ID OVARIAN-CANCER; BREAST-CANCER; PROGRESSION; APOPTOSIS; SERUM; RISK; GENE C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NIEHS, Lab Womens Hlth, NIH, Res Triangle Pk, NC 27709 USA. RP Barrett, JC (reprint author), NCI, Ctr Canc Res, Bldg 31,Room 3A11,31 Ctr Dr,MSC 2440, Bethesda, MD 20892 USA. NR 15 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2003 VL 14 IS 2 BP 139 EP 140 DI 10.1097/00001648-200303000-00005 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 648WQ UT WOS:000181174300004 PM 12606877 ER PT J AU Titus-Ernstoff, L Perez, K Hatch, EE Troisi, R Palmer, JR Hartge, P Hyer, M Kaufman, R Adam, E Strohsnitter, W Noller, K Pickett, KE Hoover, R AF Titus-Ernstoff, L Perez, K Hatch, EE Troisi, R Palmer, JR Hartge, P Hyer, M Kaufman, R Adam, E Strohsnitter, W Noller, K Pickett, KE Hoover, R TI Psychosexual characteristics of men and women exposed prenatally to diethylstilbestrol SO EPIDEMIOLOGY LA English DT Article DE diethylstilbestrol; psychosexual characteristics; sexual behavior; handedness ID CANCER RISK; IN-UTERO; HANDEDNESS; DES; LATERALIZATION; ORIENTATION; HORMONES; INUTERO AB Background. Between 1939 and the 1960s, the synthetic estrogen diethylstilbestrol (DES) was given to millions of pregnant women to prevent pregnancy complications and losses. The adverse effects of prenatal exposure on the genitourinary tract in men and the reproductive tract in women are well established, but the possible effects on psychosexual characteristics remain largely unknown. Methods. We evaluated DES exposure in relation to psychosexual outcomes in a cohort of 2,684 men and 5,686 women with documented exposure status. Results. In men, DES was unrelated to the likelihood of ever having been married, age at first intercourse, number of sexual partners, and having had a same-sex sexual partner in adulthood. DES-exposed women, compared with the unexposed, were slightly more likely to have ever married (odds ratio [OR] = 1.1; confidence interval [CI] = 1.0-1.4) and less likely to report having had a same-sex sexual partner (OR = 0.7; CI = 0.5-1.0). The DES-exposed women were less likely to have had first sexual intercourse before age 17 (OR 0.7; CI = 0.6-0.9) or to have had more than one sexual partner (OR = 0.8; CI = 0.7-0.9). There was an excess of left-handedness in DES-exposed men (OR = 1.4; CI = 1.1-1.7) but not in DES-exposed women. DES exposure was unrelated to self-reported history of mental illness in women. Conclusions. Overall, our findings provide little support for the hypothesis that prenatal exposure to DES influences the psychosexual characteristics of adult men and women. C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Lebanon, NH USA. Norris Cotton Canc Ctr, Lebanon, NH USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Boston Univ, Sch Publ Hlth, Slone Epidemiol Unit, Brookline, MA USA. Informat Management Serv Inc, Rockville, MD USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. RP Titus-Ernstoff, L (reprint author), Dartmouth Hitchcock Med Ctr, HB7926,1 Med Ctr Dr, Lebanon, NH 03756 USA. FU NCI NIH HHS [CP50531-21, CP33011-21, CP01012-21] NR 33 TC 25 Z9 26 U1 4 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2003 VL 14 IS 2 BP 155 EP 160 DI 10.1097/00001648-200303000-00008 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 648WQ UT WOS:000181174300007 PM 12606880 ER PT J AU Ward, MH Cantor, KP Riley, D Merkle, S Lynch, CF AF Ward, MH Cantor, KP Riley, D Merkle, S Lynch, CF TI Nitrate in public water supplies and risk of bladder cancer SO EPIDEMIOLOGY LA English DT Article DE bladder neoplasms; water supply; water pollution; chemical; nitrates; nitrites; case-control studies ID N-NITROSO COMPOUNDS; CHLORINATION BY-PRODUCTS; DRINKING-WATER; UNITED-STATES; WELL-WATER; CONTAMINATION; NITROSAMINES; STOMACH; FARMERS; ONTARIO AB Background. Nitrate is a precursor compound in the formation of N-nitroso compounds, most of which are potent animal carcinogens. N-nitroso compounds and their precursors have not been extensively evaluated as bladder cancer risk factors. Methods. We conducted a population-based case-control study of bladder cancer in Iowa. Cases were men and women newly diagnosed with bladder cancer in 1986-1989. Nitrate data for Iowa public water supplies were sparse before the 1960s. To reduce misclassification by unknown nitrate levels, we included only those who used public supplies with nitrate data for 70% or more of their person-years since 1960 (808 cases, 1259 controls). Results. Among controls, the median average nitrate level for their Iowa residences with public water supplies was 1.3 mg/liter nitrate-nitrogen (interquartile range = 0.6-3.0). After adjustment for confounders, we found no increased risk of bladder cancer with increasing average nitrate levels in drinking water; the highest quartile odds ratio for women was 0.8 (95% confidence interval = 0.4-0.8), and for men 0.5 (0.4-0.8). We observed no association among those with high water nitrate exposure (>median) and low (100 muM db-cAMP or 10 muM Forskolin plus 100 muM IBMX in the culture medium. Neither 10-50 ng/ml GDNF nor 50 ng/ml BDNF alone significantly increased DA neuron survival in vitro. However, the combined use of GDNF and BDNF did increase DA neuron survival, and the addition of either db-cAMP or IBMX/Forskolin to media containing these neurotrophins markedly increased DA neuron survival and growth. The cAMP inhibitor Rp-cAMP, the cAMP-dependent protein kinase A inhibitor H89, and the MAP kinase (MAPK) pathway inhibitor PD98059 significantly reduced the survival of DA neurons when applied alone in the absence of added growth factors. Application of GDNF plus BDNF, or db-cAMP significantly protected the DA neurons from the deleterious effects on survival of either 20 muM H89 or 20 muM PD98059. The results suggest that BDNF, GDNF, and cAMP produce convergent signals to activate PKA and MAPK pathways which are involved in the survival of postnatal mesencephalic DA neurons in vitro. Published by Elsevier Science (USA). C1 NINDS, LNC, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, LNC, Neurochem Lab, NIH, Bldg 36,Room 4D04, Bethesda, MD 20892 USA. NR 75 TC 13 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAR PY 2003 VL 180 IS 1 BP 32 EP 45 DI 10.1016/S0014-4886(02)00028-6 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 663UR UT WOS:000182025100004 PM 12668147 ER PT J AU Chaves, CS Soares, DC Da Silva, RP Saraiva, EM AF Chaves, CS Soares, DC Da Silva, RP Saraiva, EM TI Characterization of the species- and stage-specificity of two monoclonal antibodies against Leishmania amazonensis SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Leishmania; monoclonal antibodies; diagnostic; taxonomy ID SECRETED ACID-PHOSPHATASE; CELL-SURFACE CARBOHYDRATE; PHLEBOTOMINE SAND FLIES; DONOVANI LIPOPHOSPHOGLYCAN; METACYCLIC PROMASTIGOTES; CUTANEOUS LEISHMANIASIS; VIANNIA BRAZILIENSIS; MEXICANA-AMAZONENSIS; MAJOR PROMASTIGOTES; IDENTIFICATION AB Leishmania metacyclogenesis is associated with changes in morphology, gene expression, and structural alterations of the lipophosphoglycan (LPG), the promastigote most abundant surface glycolipid. Purification of metacyclics is accomplished using lectins or monoclonal antibodies (MAbs) that exploit stage-specific differences in the LPG. Besides, LPG displays extensive interspecies polymorphisms and is synthesized by promastigotes of all species investigated to date. In this work we studied the species- and stage-specificity of two MAbs (3A1-La and LuCa-135) used to purify metacyclics of Leishmania amazonensis. Their ability to recognize different members of the Trypanosomatidae family was tested by direct agglutination, indirect immunofluorescence, and dot-blot analysis of LPG. We found that both MAbs were highly selective for L. amazonensis: 3A1-La recognized only promastigotes and LuCa-D5 labeled amastigote and promastigote stages of this species. These MAbs might be useful for Leishmania typing. (C) 2003 Elsevier Science (USA). All rights reserved. C1 UFRJ, Inst Microbiol, Dept Immunol, Rio De Janeiro, Brazil. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Saraiva, EM (reprint author), UFRJ, Inst Microbiol, Dept Immunol, Rio De Janeiro, Brazil. NR 34 TC 7 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD MAR-APR PY 2003 VL 103 IS 3-4 BP 152 EP 159 DI 10.1016/S0014-4894(03)00098-5 PG 8 WC Parasitology SC Parasitology GA 707RZ UT WOS:000184524800008 PM 12880592 ER PT J AU Freidag, BL Mendez, S Cheever, AW Kenney, RT Flynn, B Sacks, DL Seder, RA AF Freidag, BL Mendez, S Cheever, AW Kenney, RT Flynn, B Sacks, DL Seder, RA TI Immunological and pathological evaluation of rhesus macaques infected with Leishmania major SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Leishmania major; L. amazonensis; L. brasiliensis; parasitic infection; Th1 cells; cellular immunity; vaccines ID CUTANEOUS LEISHMANIASIS; CPG OLIGODEOXYNUCLEOTIDES; PROTECTIVE IMMUNITY; MACACA-MULATTA; VACCINATION; REQUIREMENTS; ADJUVANTS; PRIMATES; ANTIGENS; PATTERNS AB Cutaneous leishmaniasis, a parasitic infection causing ulcerating skin lesions, is an important disease worldwide and urgently requires a vaccine. Animal models that closely mimic human disease are essential for designing preventive vaccines against Leishmania major. We have evaluated both biologic and immunologic parameters of cutaneous L. major infection in nonhuman primates. Naive rhesus macaques or monkeys previously exposed to L. major were infected with varying doses of L. major metacyclic promastigotes, and lesion size was assessed over a 10-week period. Monkeys previously infected with L. major had much smaller lesions that resolved faster compared with those of naive monkeys in response to the two higher doses of infection. Moreover, eight of nine naive monkeys had parasites detected in their lesions during the course of the infection. In addition, the cellular infiltrate within the lesions was qualitatively and quantitatively different in naive versus previously infected monkeys. Finally, an ELIspot assay determined that the magnitude and kinetics of responses differed between previously infected and naive monkeys. Published by Elsevier Science (USA). C1 NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Biomed Res Inst, Rockville, MD 20852 USA. Iomai Corp, Gaithersburg, MD USA. RP Seder, RA (reprint author), NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 19 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD MAR-APR PY 2003 VL 103 IS 3-4 BP 160 EP 168 DI 10.1016/S0014-4894(03)00099-7 PG 9 WC Parasitology SC Parasitology GA 707RZ UT WOS:000184524800009 PM 12880593 ER PT J AU Ardekani, AM Petricoin, EF Hackett, JL AF Ardekani, AM Petricoin, EF Hackett, JL TI Molecular diagnostics: an FDA perspective SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Editorial Material DE diagnostics; FDA; microarrays ID HUMAN PROSTATE-CANCER; PROTEIN MICROARRAYS; BREAST-CANCER; DNA; PHARMACOGENETICS; PATTERNS; SURVIVAL; PROFILES; DISEASE; GENOME AB The potential medical applications of microarrays and in vitro diagnostic devices for global assessments of DNA, sequence variations, relative RNA abundance and measurements of proteins have generated much excitement, and some skepticism, within the biomedical community. It has been suggested that within the next decade these microarrays and diagnostic devices will be routinely used in the selection, assessment and quality control of the best drugs for pharmaceutical development, at the bedside for diagnostics and for clinical monitoring of both desired and adverse outcomes of therapeutic interventions. Realizing such potential will be a challenge to the entire scientific community as often breakthroughs which show great promise at the bench fall to meet the requirements of clinicians and regulatory scientists, and to make the transition into common clinical and regulatory practice. The development of a co-operative framework between regulators, product sponsors and technology experts will be essential for realizing the revolutionary promise these platforms could have on the evolution of drug development, regulatory science, the practice of medicine and public health. C1 CLIA Special Program, Div Clin Lab Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NCI, FDA, Clin Proteom Program, Proteom Unit, Bethesda, MD 20892 USA. US FDA, CBER, Dept Therapeut Prot, Bethesda, MD 20892 USA. RP Hackett, JL (reprint author), OAK8, RM375, HFZ 440 2098, Gaither Rd Rockville, Rockville, MD 20850 USA. EM Ardekani@cber.fda.gov; Petricoin@cber.fda.gov; JLH@cdrh.fda.gov NR 34 TC 8 Z9 10 U1 0 U2 5 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAR PY 2003 VL 3 IS 2 BP 129 EP 140 DI 10.1586/14737159.3.2.129 PG 12 WC Pathology SC Pathology GA 767KA UT WOS:000188437700002 PM 12647991 ER PT J AU Gold, B AF Gold, B TI Origin and utility of the reverse dot-blot SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE 5 ' mucleotidase; beta-thalassemia; cystic fibrosis; PCR; RDB; reverse dot blot; solid supports; TaqMan ID SICKLE-CELL-ANEMIA; PCR-AMPLIFIED DNA; BETA-THALASSEMIA MUTATIONS; POLYMERASE CHAIN-REACTION; PRENATAL-DIAGNOSIS; RESTRICTION ENDONUCLEASES; ENZYMATIC AMPLIFICATION; OLIGONUCLEOTIDE PROBES; POINT MUTATIONS; REGULATOR GENE AB Reverse allele specific oligonucleotide assays provide a robust method for the molecular characterization of high-mutation spectrum disorders. Commercial tests have been developed for human leukocyte antigens class I and class II regions of human chromosome 6, the cystic fibrosis transmembrane conductance regulator at 7q31 and strains of human Hepatitis B and C virus. In their most developed form, these assays rely upon highly multiplexed PCR reactions containing biotinylated primers providing a substrate for nonradioactive detection systems. Sophisticated reverse dot-blot technology involves mechanized covalent attachment of activated primary amine-conjugated oligonucleotides to carboxylated nylon membranes or bovine serum albumin. Subsequent to line or dot printing, membranes are stored or sold dry in preparation for hybridization. Circular spots or lines are visualized colorimetrically after hybridization through the use of streptavidin horseradish peroxidase incubation followed by development using tetramethylbenzidine and hydrogen peroxide, or via chemiluminescence after incubation with avidin alkaline phosphatase conjugate and a luminous substrate susceptible to enzyme activation, such as CSPD, followed by exposure to x-ray film. The entire procedure from blood specimen receipt to result usually requires less than 1 day. Because of the simplicity, speed, and generally high sensitivity and specificity, large numbers of individuals can be rapidly screened using this technology. Rapid turnaround is often required in prenatal diagnosis of cystic fibrosis, beta-thalassemia and hemoglobinopathies, giving this technology has special applicability in those genetic diseases. Commercial instruments are available which automate the hybridization and color development. In addition, scanning software can capture the probe reactivity pattern and interpret it in terms of a genotype. C1 NCI, Human Genet Sect, Lab Genom Divers, Ft Detrick, MD 21702 USA. RP Gold, B (reprint author), NCI, Human Genet Sect, Lab Genom Divers, Bldg 560,Room 11-85, Ft Detrick, MD 21702 USA. EM goldb@ncifcrf.gov NR 69 TC 17 Z9 18 U1 1 U2 9 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAR PY 2003 VL 3 IS 2 BP 143 EP 152 DI 10.1586/14737159.3.2.143 PG 10 WC Pathology SC Pathology GA 767KA UT WOS:000188437700003 PM 12647992 ER PT J AU Lee, SY Andoh, T Murphy, DL Chiueh, CC AF Lee, SY Andoh, T Murphy, DL Chiueh, CC TI 17 beta-estradiol activates ICI 182,780-sensitive estrogen receptors and cyclic GMP-dependent thioredoxin expression for neuroprotection SO FASEB JOURNAL LA English DT Article DE cognition; human SH-SY5Y neuroblastoma cell; MnSOD; NOS1/nNOS ID NITRIC-OXIDE SYNTHASE; STRESS-INDUCED APOPTOSIS; SIGNAL-REGULATED KINASE; OXIDATIVE STRESS; PROTEIN-KINASE; DOPAMINERGIC-NEURONS; CELL-DEATH; MAMMALIAN THIOREDOXIN; S-NITROSOGLUTATHIONE; NEUROTROPHIC FACTOR AB Clinical studies suggest that estrogen may improve cognition in Alzheimer's patients. Basic experiments demonstrate that 17beta-estradiol protects against neurodegeneration in both cell and animal models. In the present study, a human SH-SY5Y cell model was used to investigate molecular mechanisms underlying the receptor-mediated neuroprotection of physiological concentrations of 17beta-estradiol. 17beta-Estradiol (<10 nM) concomitantly increased neuronal nitric oxide synthase (NOS1) expression and cell viability. 17 beta-Estradiol-induced neuroprotection was blocked by the receptor antagonist ICI 182,780, also prevented by inhibitors of NOS1 (7-nitroindazole), guanylyl cyclase (LY 83,583), and cGMP-dependent protein kinase (PKG) (Rp-8-pCPT-cGMPs). In addition to the expression of NOS1 and MnSOD, 17 beta-estradiol increased the expression of the redox protein thioredoxin (Trx), which was blocked by the inhibition of either cGMP formation or PKG activity. The expression of heme oxygenase 2 and brain-derived neurotrophic factor was not altered. Estrogen receptor-enhanced cell viability against oxidative stress may be linked to Trx expression because the Trx reductase inhibitor, 5,5'-dithio-bis(2-nitrobenzoic acid) significantly reduced the cytoprotective effect of 17 beta-estradiol. Furthermore, Trx (1 mu M) inhibited lipid peroxidation, proapoptotic caspase-3, and cell death during oxidative stress caused by serum deprivation. We conclude that cGMP-dependent expression of Trx--the redox protein with potent antioxidative and antiapoptotic properties--may play a pivotal role in estrogen-induced neuroprotection. C1 NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Anat & Neurosci, Coll Med, Hershey, PA 17033 USA. Toyama Med & Pharmaceut Univ, Dept Appl Pharmacol, Fac Pharmaceut Sci, Toyama 9300194, Japan. RP Chiueh, CC (reprint author), NIMH, Clin Sci Lab, NIH, 10-3D-41, Bethesda, MD 20892 USA. EM chiueh@helix.nih.gov NR 90 TC 69 Z9 71 U1 1 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 2003 VL 17 IS 3 BP 947 EP + DI 10.1096/fj.02-0807fje PG 20 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 661LT UT WOS:000181892600021 PM 12626428 ER PT J AU Zhang, J Meikle, S Trumble, A Grainger, D AF Zhang, J Meikle, S Trumble, A Grainger, D TI Aging, twinning, and perinatal outcomes - Reply SO FERTILITY AND STERILITY LA English DT Letter C1 NICHHD, NIH, Bethesda, MD 20892 USA. Univ Kansas, Wichita, KS USA. RP Zhang, J (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAR PY 2003 VL 79 IS 3 BP 661 EP 662 DI 10.1016/S0015-0282(02)04752-0 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 656JQ UT WOS:000181605000047 ER PT J AU Boivin, GP Washington, K Yang, K Ward, JM Pretlow, TP Russell, R Besselsen, DG Godfrey, VL Doetschman, T Dove, WF Pitot, HC Halberg, RB Itzkowitz, SH Groden, J Coffey, RJ AF Boivin, GP Washington, K Yang, K Ward, JM Pretlow, TP Russell, R Besselsen, DG Godfrey, VL Doetschman, T Dove, WF Pitot, HC Halberg, RB Itzkowitz, SH Groden, J Coffey, RJ TI Pathology of mouse models of intestinal cancer: Consensus report and recommendations SO GASTROENTEROLOGY LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; ABERRANT CRYPT FOCI; DNA MISMATCH REPAIR; APC(DELTA-716) KNOCKOUT MICE; II RECEPTOR GENE; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; COLON-CANCER; BETA-CATENIN; MUTANT MICE C1 Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA. Vet Affairs Med Ctr, Cincinnati, OH 45267 USA. Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. Rockefeller Univ, Strang Canc Res Lab, New York, NY 10021 USA. NCI, Frederick, MD 21701 USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Univ Arizona, Univ Anim Care, Tucson, AZ 85721 USA. Univ N Carolina, Div Lab Anim Med, Chapel Hill, NC 27515 USA. Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45221 USA. Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA. Nashville Vet Assoc, Nashville, TN USA. Mt Sinai Sch Med, Div Gastroenterol, New York, NY USA. RP Boivin, GP (reprint author), Univ Cincinnati, Dept Pathol & Lab Med, 231 Albert Sabin Way,ML 0529, Cincinnati, OH 45267 USA. NR 92 TC 300 Z9 305 U1 1 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2003 VL 124 IS 3 BP 762 EP 777 DI 10.1053/gast.2003.50094 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 650RL UT WOS:000181277000022 PM 12612914 ER PT J AU Zhang, MD Goedert, JJ O'Brien, TR AF Zhang, MD Goedert, JJ O'Brien, TR TI High frequency of CCR5-Delta 32 homozygosity in HCV-infected, HIV-1-uninfected hemophiliacs results from resistance to HIV-1 SO GASTROENTEROLOGY LA English DT Letter ID INDIVIDUALS; GENE C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Rockville, MD USA. RP Zhang, MD (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Rockville, MD USA. NR 8 TC 30 Z9 31 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2003 VL 124 IS 3 BP 867 EP 868 DI 10.1053/gast.2003.50132 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 650RL UT WOS:000181277000034 PM 12612937 ER PT J AU Janz, S Potter, M Rabkin, CS AF Janz, S Potter, M Rabkin, CS TI Lymphoma- and leukemia-associated chromosomal translocations in healthy individuals SO GENES CHROMOSOMES & CANCER LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; POLYMERASE-CHAIN-REACTION; MINIMAL RESIDUAL DISEASE; CHRONIC MYELOGENOUS LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; IMMUNOGLOBULIN/C-MYC RECOMBINATIONS; PERIPHERAL-BLOOD CELLS; MLL FUSION TRANSCRIPTS; NON-HODGKINS-LYMPHOMA AB Chromosomal translocations (CTs) are hallmark mutations of hematopoietic malignancy that result in the deregulated expression of oncogenes or the generation of novel fusion genes. The polymerase chain reaction (PCR) can be used to detect illegitimate recombinations of genomic DNA sequences as a more sensitive assay than cytogenetics for determining the presence of CTs. Both direct DNA-PCR and reverse transcriptase-PCR were used to examine healthy individuals for lymphoma- and leukemia-associated CTs. Two oncogene-activating CTs [t(14;18)(q32;q21) and t(8;14)(q24;q32)] and one fusion-gene CT [t(2;5)(p23;q35)] from lymphomas and five fusion-gene CTs from leukemia [t(9;22)(q34;q11), t(4;11)(q21;q23), t(15;17)(q22;q11), t(12;21)(p13;q22), t(8;21)(q22;q22)] were detected in such studies. The biological implication is that CTs associated with malignant tumors may also be found in cells that are not neoplastic. CTs are characteristic attributes of neoplastic clones but are by themselves insufficient to cause malignant transformation. A better understanding of the special biology of non-neoplastic CT-bearing cells will provide insight into their putative role as tumor precursors. Prospective epidemiological studies are needed to determine whether such cells in healthy individuals may, in some instances, become clonogenic founders of lymphoma or leukemia. (C) 2003 Wiley-Liss, Inc. C1 NCI, Genet Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Janz, S (reprint author), NCI, Genet Lab, Ctr Canc Res, NIH, Bldg 37,Room 2B10, Bethesda, MD 20892 USA. NR 125 TC 85 Z9 87 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAR PY 2003 VL 36 IS 3 BP 211 EP 223 DI 10.1002/gcc.10178 PG 13 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 640QF UT WOS:000180698900001 PM 12557221 ER PT J AU Pant, V Mariano, P Kanduri, C Mattsson, A Lobanenkov, V Heuchel, R Ohlsson, R AF Pant, V Mariano, P Kanduri, C Mattsson, A Lobanenkov, V Heuchel, R Ohlsson, R TI The nucleotides responsible for the direct physical contact between the chromatin insulator protein CTCF and the H19 imprinting control region manifest parent of origin-specific long-distance insulation and methylation-free domains SO GENES & DEVELOPMENT LA English DT Article DE genomic imprinting; Igf2; chromatin insulator; CTCF; DNA methylation ID MOUSE H19; H19/IGF2 LOCUS; GENE; ASSOCIATION; EXPRESSION; 5'-FLANK; SITES; MICE AB The repression of the maternally inherited Igf2 allele has been proposed to depend on a methylation-sensitive chromatin insulator organized by the 11 zinc finger protein CTCF at the H19 imprinting control region (ICR). Here we document that point mutations of the nucleotides in physical contact with CTCF within the endogenous H19 ICR lead to loss of CTCF binding and Igf2 imprinting only when passaged through the female germline. This effect is accompanied by a significant loss of methylation protection of the maternally derived H19 ICR. Because CTCF interacts with other imprinting control regions, it emerges as a central factor responsible for interpreting and propagating gamete-derived epigenetic marks and for organizing epigenetically controlled expression domains. C1 Uppsala Univ, Dept Genet & Dev, Evolut Biol Ctr, S-75236 Uppsala, Sweden. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. Ludwig Inst Canc Res, Ctr Biomed, S-75124 Uppsala, Sweden. RP Ohlsson, R (reprint author), Uppsala Univ, Dept Genet & Dev, Evolut Biol Ctr, S-75236 Uppsala, Sweden. NR 26 TC 102 Z9 106 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 1 PY 2003 VL 17 IS 5 BP 586 EP 590 DI 10.1101/gad.254903 PG 5 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 654NE UT WOS:000181502300003 PM 12629040 ER PT J AU Wei, KC Clark, AB Wong, E Kane, MF Mazur, DJ Parris, T Kolas, NK Russell, R Hou, H Kneitz, B Yang, G Kunkel, TA Kolodner, RD Cohen, PE Edelmann, W AF Wei, KC Clark, AB Wong, E Kane, MF Mazur, DJ Parris, T Kolas, NK Russell, R Hou, H Kneitz, B Yang, G Kunkel, TA Kolodner, RD Cohen, PE Edelmann, W TI Inactivation of Exonuclease 1 in mice results in DNA mismatch repair defects, increased cancer susceptibility, and male and female sterility SO GENES & DEVELOPMENT LA English DT Article DE Exonuclease 1; MMR; lymphoma; meiosis; infertility ID NONPOLYPOSIS COLORECTAL-CANCER; SACCHAROMYCES-CEREVISIAE EXO1; MEIOTIC CROSSING-OVER; CHROMOSOME SYNAPSIS; POLYMERASE-EPSILON; MUTATION AVOIDANCE; MUTL HOMOLOGS; HELICASE-II; IN-VIVO; GENE AB Exonuclease 1 (Exol) is a 5'-3' exonuclease that interacts with MutS and MutL homologs and has been implicated in the excision step of DNA mismatch repair. To investigate the role of Exo1 in mammalian mismatch repair and assess its importance for tumorigenesis and meiosis, we generated an Exo1 mutant mouse line. Analysis of Exo1(-/-) cells for mismatch repair activity in vitro showed that Exo1 is required for the if base:base and single-base insertion/deletion mismatches in both 5' and 3' nick-directed repair. The repair defect in Exo1(-/-) cells also caused elevated microsatellite instability at a mononucleotide repeat marker and a significant increase in mutation rate at the Hprt locus. Exo1(-/-) animals displayed reduced survival and increased susceptibility to the development of lymphomas. In addition, Exo1(-/-) male and female mice were sterile because of a meiotic defect. Meiosis in Exo1(-/-) animals proceeded through prophase I; however, the chromosomes exhibited dynamic loss of chiasmata during metaphase I, resulting in meiotic failure and apoptosis. Our results show that mammalian Exo1 functions in mutation avoidance and is essential for male and female meiosis. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. NIEHS, Genet Mol Lab, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27700 USA. Ludwig Inst Canc Res, La Jolla, CA 92093 USA. RP Edelmann, W (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. FU NCI NIH HHS [CA13330, CA 76329, CA93484, P30 CA013330, R01 CA076329, R01 CA093484]; NIGMS NIH HHS [GM50006, R01 GM050006] NR 64 TC 185 Z9 188 U1 3 U2 9 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 1 PY 2003 VL 17 IS 5 BP 603 EP 614 DI 10.1101/gad.1060603 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 654NE UT WOS:000181502300006 PM 12629043 ER PT J AU Mohiddin, SA Begley, DA McLam, E Cardoso, JP Winkler, JB Sellers, JR Fananapazir, L AF Mohiddin, SA Begley, DA McLam, E Cardoso, JP Winkler, JB Sellers, JR Fananapazir, L TI Utility of genetic screening in hypertrophic cardiomyopathy: Prevalence and significance of novel and double (homozygous and heterozygous) beta-myosin mutations SO GENETIC TESTING LA English DT Article ID HEAVY-CHAIN GENE; CARDIAC MYOSIN; CLINICAL EXPRESSION; SUDDEN-DEATH; HIGH-RISK; PHENOTYPE; DISTINCT; GENOTYPE; TROPONIN; BINDING AB Genetic screening of the beta-myosin heavy chain gene (MYH7) was evaluated in 100 consecutive unrelated patients with hypertrophic cardiomyopathy (HCM) and 200 normal unrelated subjects. Seventeen beta-myosin mutations were identified in 19 patients. Notably, 13, or 76%, were novel. Mutations were detected in both alleles in two patients: homozygous for Lys(207)Gln in one, and heterozygous for Pro(211) Leu and Arg(663)His in another. No mutation was detected in the controls. MYH7-associated HCM was associated with more marked left atrial enlargement and syncope than non-MYH7-related HCM. Our findings indicate that: (1) screening methods should allow identification of novel mutations; and (2) more than one sarcomeric mutation may be present in a patient more commonly than is appreciated. Further studies are necessary to ascertain the clinical consequences of the novel and compound gene abnormalities, and to determine whether correlating functional domain to phenotype provides more useful information about the clinical significance of the molecular defects. C1 NHLBI, Inherited Heart Dis Sect, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Fananapazir, L (reprint author), NHLBI, Inherited Heart Dis Sect, Cardiol Branch, NIH, Bldg 10,Room 7B-15,10 Ctr Dr, Bethesda, MD 20892 USA. NR 21 TC 17 Z9 18 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD SPR PY 2003 VL 7 IS 1 BP 21 EP 27 DI 10.1089/109065703321560895 PG 7 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 667NE UT WOS:000182237600004 PM 12820698 ER PT J AU Mason, JM Konev, AY Biessmann, H AF Mason, JM Konev, AY Biessmann, H TI Telomeric position effect in Drosophila melanogaster reflects a telomere length control mechanism SO GENETICA LA English DT Article; Proceedings Paper CT 5th International Conference on Drosophila Heterochromatin CY JUN 18-22, 2001 CL CORTONA, ITALY DE Drosophila; heterochromatin; silencing; TAS; telomere; transcription ID HET-A; P-ELEMENT; CHROMATIN STRUCTURE; CHROMOSOME ENDS; GENE; RETROTRANSPOSON; ORGANIZATION; YEAST; DNA; HETEROCHROMATIN AB The terminal DNA arrays on chromosomes of Drosophila melanogaster are composed of two families of non-LTR retrotransposons, HeT-A and TART. Available evidence suggests that chromosome length in this species and its close relatives is maintained by targeted transposition of these elements, with attachment of the elements to the chromosome end by their 3' oligo(A) tails. However, the regulation of transposition of these elements and the control of telomere length are poorly understood. Here we present the hypothesis that the forces involved in telomere length regulation in Drosophila are the underlying forces that manifest themselves as telomeric position effect (TPE). Based on recent studies of TPE, which found that expression of a reporter gene is influenced by telomere structure in cis and trans, we propose that the subtelomeric satellite (TAS) in D. melanogaster plays an important role in controlling telomere elongation. Transcription of a HeT-A element is probably initiated at a promoter in the 3' UTR of an upstream element, and TAS may repress this transcriptional activity in cis and trans. A region of HeT-A not at the extreme 3' end of the element may act as a transcriptional enhancer that may be modulated by TAS. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Salk Inst Biol Studies, Mol Biol & Virol Lab, La Jolla, CA 92037 USA. Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. RP Mason, JM (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RI Konev, Alexander/J-4401-2015 OI Konev, Alexander/0000-0002-4497-6377 FU NIGMS NIH HHS [GM-56729] NR 31 TC 15 Z9 16 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0016-6707 J9 GENETICA JI Genetica PD MAR PY 2003 VL 117 IS 2 BP 319 EP 325 DI 10.1023/A:1022925003172 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 660WP UT WOS:000181857500022 PM 12723711 ER PT J AU Mason, JM Konev, AY Golubovsky, MD Biessmann, H AF Mason, JM Konev, AY Golubovsky, MD Biessmann, H TI Cis- and trans-acting influences on telomeric position effect in Drosophila melanogaster detected with a subterminal transgene SO GENETICS LA English DT Article ID SALIVARY-GLAND NUCLEI; EFFECT VARIEGATION; HETEROCHROMATIN PROTEIN-1; WHITE GENE; HET-A; TRANSCRIPTIONAL ENHANCERS; CHROMATIN STRUCTURE; P-ELEMENT; I FACTOR; DNA AB One model of telomeric position effect (TPE) in Drosophila melanogaster proposes that reporter genes in the vicinity of telomeres are repressed by subterminal telomere-associated sequences (TAS) and that variegation of these genes is the result of competition between the repressive effects of TAS and the stimulating effects of promoters in the terminal HeT-A transposon array. The data presented here support this model, but also suggest that TPE is more complex. Activity of a telomeric white reporter gene increases in response to deletion of some or all of the TAS on the homolog. Only transgenes next to fairly long HeT-A arrays respond to this trans-interaction. HeT-A arrays of 6-18 kb respond by increasing the number of dark spots on the eye, while longer arrays increase the background eye color or increase the number of spots sufficiently to cause them to merge. Thus, expression of a subtelomeric reporter gene is influenced by the telomere structure in cis and trans. We propose that the forces involved in telomere length regulation in Drosophila are the underlying forces that manifest themselves as TPE. In the wild-type telomere TAS may play an important role in controlling telomere elongation by repressing HeT-A promoter activity. Modulation of this repression by the homolog may thus regulate telomere elongation. C1 Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. Natl Inst Environm Hlth Sci, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. Russian Acad Sci, Inst Sci & Technol Hist, Div Evolutionary Theory, St Petersburg 199034, Russia. RP Biessmann, H (reprint author), Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. RI Konev, Alexander/J-4401-2015 OI Konev, Alexander/0000-0002-4497-6377 FU NIGMS NIH HHS [GM-56729] NR 55 TC 21 Z9 22 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAR PY 2003 VL 163 IS 3 BP 917 EP 930 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 664DR UT WOS:000182046900007 PM 12663532 ER PT J AU Liu, G Zhao, SY Bailey, JA Sahinalp, SC Alkan, C Tuzun, E Green, ED Eichler, EE AF Liu, G Zhao, SY Bailey, JA Sahinalp, SC Alkan, C Tuzun, E Green, ED Eichler, EE CA NISC Comparative Sequencing Progm TI Analysis of primate genomic variation reveals a repeat-driven expansion of the human genome SO GENOME RESEARCH LA English DT Article ID DNA-DNA HYBRIDIZATION; MOLECULAR EVOLUTION; ALU REPEATS; INTERSPERSED REPEATS; SEQUENCE; CHIMPANZEE; PHYLOGENY; ALIGNMENTS; DIVERGENCE; RETROTRANSPOSITION AB We performed a detailed analysis of both single-nucleotide and large insertion/deletion events based on large-scale comparison of 10.6 Mb of genomic sequence from lemur, baboon, and chimpanzee to human. Using a human genomic reference, optimal global alignments were constructed from large (>50-kb) genomic sequence clones. These alignments were examined for the pattern, frequency, and nature of mutational events. Whereas rates, of single-nucleotide substitution remain relatively constant (1-2 x 10-(9) substitutions/site/year), rates of retrotransposition vary radically among different primate lineages. These differences have lead to a 15%-20% expansion of human genome size over the last 50 million years of primate evolution, 90% of it due to new retroposon insertions. Orthologous comparisons with the chimpanzee suggest that the human genome continues to significantly expand due to shifts in retrotransposition activity. Assuming that the primate genome sequence we have sampled is representative, we estimate that human euchromatin has expanded 30 Mb and 550 Mb compared to the primate genomes of chimpanzee and lemur, respectively. C1 Case Western Reserve Univ, Sch Med, Ctr Human Genet, Dept Genet, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Ctr Computat Genom, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA. Inst Genome Res, Rockville, MD 20850 USA. RP Eichler, EE (reprint author), Case Western Reserve Univ, Sch Med, Ctr Human Genet, Dept Genet, Cleveland, OH 44106 USA. EM eee@po.cwru.edu RI Alkan, Can/D-2982-2009; OI Alkan, Can/0000-0002-5443-0706; Tuzun, Eray/0000-0002-5550-7816 FU NCI NIH HHS [CA094816]; NHGRI NIH HHS [HG002318, R01 HG002318]; NICHD NIH HHS [HD-07518-05, T32 HD007518]; NIGMS NIH HHS [GM58815, R01 GM058815, T32 GM007250] NR 50 TC 100 Z9 104 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAR PY 2003 VL 13 IS 3 BP 358 EP 368 DI 10.1101/gr.923303 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 653CX UT WOS:000181418600004 PM 12618366 ER PT J AU Liu, PT Jenkins, NA Copeland, NG AF Liu, PT Jenkins, NA Copeland, NG TI A highly efficient recombineering-based method for generating conditional knockout mutations SO GENOME RESEARCH LA English DT Article ID BACTERIAL ARTIFICIAL CHROMOSOMES; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; GENE REPLACEMENT; CRE RECOMBINASE; DNA; SYSTEM; HOMOLOGY; CLONING; VECTOR AB Phage-based Escherichia coli homologous recombination systems have recently been developed that now make it possible to subdone or modify DNA cloned into plasmids, BACs, or PACs without the need for restriction enzymes or DNA ligases. This new form of chromosome engineering, termed recombineering, has many different uses for functional genomic studies. Here we describe a new recombineering-based method for generating conditional mouse knockout (cko) mutations. This method uses homologous recombination mediated by the lambda phage Red proteins, to subdone DNA from BACs into high-copy plasmids by gap repair, and together with Cre or Flpe recombinases, to introduce IoxP or FRT sites into the subdoned DNA. Unlike other methods that use short 45-55-bp regions of homology for recombineering, our method uses much longer regions of homology. We also make use of several new E coli strains, in which the proteins required for recombination are expressed from a defective temperature-sensitive lambda prophage, and the Cre or Flpe recombinases from an arabinose-inducible promoter. We also describe two new Neo selection cassettes that work well in both E coli and mouse ES cells. Our method is fast, efficient, and reliable and makes it possible to generate cko-targeting vectors in less than 2 wk. This method should also facilitate the generation of knock-in mutations and transgene constructs, as well as expedite the analysis of regulatory elements and functional domains in or near genes. C1 NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Copeland, NG (reprint author), NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. NR 26 TC 625 Z9 655 U1 6 U2 41 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAR PY 2003 VL 13 IS 3 BP 476 EP 484 DI 10.1101/gr.749203 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 653CX UT WOS:000181418600016 PM 12618378 ER PT J AU Witmer, PD Doheny, KF Adams, MK Boehm, CD Dizon, JS Goldstein, JL Templeton, TM Wheaton, AM Dong, PN Pugh, EW Nussbaum, RL Hunter, K Kelmenson, JA Rowe, LB Brownstein, MJ AF Witmer, PD Doheny, KF Adams, MK Boehm, CD Dizon, JS Goldstein, JL Templeton, TM Wheaton, AM Dong, PN Pugh, EW Nussbaum, RL Hunter, K Kelmenson, JA Rowe, LB Brownstein, MJ TI The development of a highly informative mouse simple sequence length polymorphism (SSLP) marker set and construction of a mouse family tree using parsimony analysis SO GENOME RESEARCH LA English DT Article ID NONTEMPLATED NUCLEOTIDE ADDITION; INBRED STRAINS; DNA-POLYMERASE; MICE; ORIGIN AB To identify highly informative markers for a large number of commonly employed murine crosses, we selected a subset of the extant mouse simple sequence length polymorphism (SSLP) marker set for further development. Primer pairs for 314 SSLP markers were designed and typed against 54 inbred mouse strains. We designed new PCR primer sequences for the markers selected for multiplexing using the fluorescent dyes FAM, VIC, NED, and ROX. The number of informative markers for C57BL/6J x DBA/2J is 217, with an average spacing of 6.8 centiMorgans (cM). For all other pairs of strains, the mean number of informative markers per cross is 197.0 (SD 37.8) with a mean distance between markers of 6.8 cM (SD 1.1). To confirm map positions of the 224 markers in our set that are polymorphic between Mus musculus and Mus spretus, we used The Jackson Laboratory (TL) interspecific backcross mapping panel (TIL BSS); 168 (75%) of these markers had not been previously mapped in this cross by other investigators, adding new information to this community map resource. With this large data set, we sought to reconstruct a phylogenetic history of the laboratory mouse using Wagner parsimony analysis. Our results are largely congruent with the known history of inbred mouse strains. C1 Johns Hopkins Univ, Sch Med, CIDR, Baltimore, MD 21224 USA. NIMH, Genet Lab, NHGRI, NIH, Bethesda, MD 20892 USA. Appl Biosyst Inc, Foster City, CA 94404 USA. NHGRI, IDRB, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. RP Witmer, PD (reprint author), Johns Hopkins Univ, Sch Med, CIDR, Baltimore, MD 21224 USA. FU NHGRI NIH HHS [N01HG65403, HG00941] NR 18 TC 58 Z9 58 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAR PY 2003 VL 13 IS 3 BP 485 EP 491 DI 10.1101/gr.717903 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 653CX UT WOS:000181418600017 PM 12618379 ER PT J AU Pillemer, K Czaja, S Schulz, R Stahl, SM AF Pillemer, K Czaja, S Schulz, R Stahl, SM TI Finding the best ways to help: Opportunities and challenges of intervention research on aging SO GERONTOLOGIST LA English DT Editorial Material C1 Cornell Univ, Cornell Gerontol Res Inst, Ithaca, NY 14853 USA. Cornell Univ, Dept Human Dev, Ithaca, NY 14853 USA. Univ Miami, Ctr Adult Dev & Aging, Dept Psychiat & Behav Sci, Miami, FL 33152 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Social & Urban Res, Pittsburgh, PA 15260 USA. NIA, Behav & Social Res Program, NIH, Bethesda, MD 20892 USA. RP Pillemer, K (reprint author), Cornell Univ, Cornell Gerontol Res Inst, MVR G44, Ithaca, NY 14853 USA. EM kap6@cornell.edu NR 13 TC 9 Z9 9 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD MAR PY 2003 VL 43 SI 1 BP 5 EP 8 PG 4 WC Gerontology SC Geriatrics & Gerontology GA 656UX UT WOS:000181628200001 PM 12637684 ER PT J AU McCusker, ME Cote, TR Clegg, LMX Tavassoli, FJ AF McCusker, ME Cote, TR Clegg, LMX Tavassoli, FJ TI Endocrine tumors of the uterine cervix: incidence, demographics, and survival with comparison to squamous cell carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE cervix; endocrine tumors; epidemiology; incidence; neuroendocrine carcinoma; squamous cell carcinoma; SEER; survival ID NEUROENDOCRINE CARCINOMA; HUMAN-PAPILLOMAVIRUS; CANCER; EXPRESSION; THERAPY; TRENDS AB Objective. The aim was to describe the epidemiology of endocrine tumors of the cervix in comparison with invasive squamous cell carcinomas using population-based data reported to the Surveillance, Epidemiology and End-Results (SEER) program. Methods. Retrospective analysis of actively followed cases reported to SEER from 1973 to 1998. Incidence, demographic characteristics, and survival were compared for endocrine and squamous tumors. Results. There were 239 cases of endocrine tumors and 18,458 cases of invasive squamous cell carcinoma of the cervix included in the study. Mean age at diagnosis was 49 years for endocrine tumors versus 52 years for squamous cell carcinoma (P<0.01). Endocrine tumors were more likely to present at a later FIGO stage (P<0.01), and to have lymph node involvement at diagnosis (57 vs 18%, P<0.01) compared to squamous cell carcinoma. Observed median survival for women with endocrine tumors was 22 months versus 10 years for women with squamous cell carcinoma. Age and FIGO stage-adjusted hazards of death were 1.84 times greater for endocrine tumors than for squamous cell carcinoma (95% CI 1.52-2.23). At all stages of disease, survival was worse for women with endocrine tumors compared to women with squamous cell carcinomas. Conclusion. Endocrine tumors of the cervix are extremely aggressive and survival is poor regardless of stage at diagnosis. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. NCI, Div Canc Control & Populat Sci, Canc Stat Branch, Rockville, MD USA. Armed Forces Inst Pathol, Div Gynecol Pathol, Washington, DC 20306 USA. RP McCusker, ME (reprint author), Texas Dept Hlth, Bur Chron Dis & Tobacco Prevent, 1100 W 49th St,T-402, Austin, TX 78756 USA. EM zey3@cdc.gov NR 28 TC 47 Z9 53 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2003 VL 88 IS 3 BP 333 EP 339 DI 10.1016/S0090-8258(02)00150-6 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 658NB UT WOS:000181726100012 PM 12648583 ER PT J AU Backer, LC Fleming, LE Rowan, A Cheng, YS Benson, J Pierce, RH Zaias, J Bean, J Bossart, GD Johnson, D Quimbo, R Baden, DG AF Backer, LC Fleming, LE Rowan, A Cheng, YS Benson, J Pierce, RH Zaias, J Bean, J Bossart, GD Johnson, D Quimbo, R Baden, DG TI Recreational exposure to aerosolized brevetoxins during Florida red tide events SO HARMFUL ALGAE LA English DT Article DE aerosols; brevetoxins; Gymnodinium breve; Karenia brevis; red tide; bronchoconstriction ID TOXINS; BREVIS AB During two separate Karenia brevis red tide events, we measured the levels of brevetoxins in air and water samples, conducted personal interviews, and performed pulmonary function tests on people before and after they visited one of two Florida beaches. One hundred and twenty-nine people participated in the study, which we conducted during red tide events in Sarasota and Jacksonville, FL, USA. Exposure was categorized into three levels: low/no exposure, moderate exposure, and high exposure. Lower respiratory symptoms (e.g. wheezing) were reported by 8% of unexposed people, 11% of the moderately exposed people, and 28% of the highly exposed people. We performed nasal-pharyngeal swabs on people who experienced moderate or high exposure, and we found an inflammatory response in over 33% of these participants. We did not find any clinically significant changes in pulmonary function test results; however, the study population was small. In future epidemiologic studies, we plan to further investigate the human health impact of inhaled brevetoxins. Published by Elsevier Science B.V. C1 Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. Univ Miami, Sch Med, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33136 USA. Florida Dept Hlth & Rehabil Serv, Tallahassee, FL 32399 USA. Lovelace Resp Res Inst, Inhalat Toxicol Lab, Albuquerque, NM 87185 USA. Mote Marine Lab, Sarasota, FL 34236 USA. Univ Miami, Sch Med, Div Comparat Pathol, Miami, FL 33136 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Harbor Branch Oceanog Inst Inc, Ft Pierce, FL 34946 USA. Univ N Carolina, Marine Sci Res Ctr, Wilmington, NC 28409 USA. RP Backer, LC (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, 1600 Clifton Rd NE,MS E 23, Atlanta, GA 30333 USA. EM lfb9@cdc.gov NR 22 TC 83 Z9 88 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9883 J9 HARMFUL ALGAE JI Harmful Algae PD MAR PY 2003 VL 2 IS 1 BP 19 EP 28 DI 10.1016/S1568-9883(03)00005-2 PG 10 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA 812UM UT WOS:000220864400002 ER PT J AU Clauser, SB Bierman, AS AF Clauser, SB Bierman, AS TI Significance of functional status data for payment and quality SO HEALTH CARE FINANCING REVIEW LA English DT Article; Proceedings Paper CT 54th World Health Assembly Meeting CY MAY 14-22, 2001 CL Geneva, SWITZERLAND ID HEALTH MAINTENANCE ORGANIZATION; OUTPATIENT GERIATRIC EVALUATION; RANDOMIZED CLINICAL-TRIAL; ALL-INCLUSIVE CARE; LONG-TERM-CARE; RESIDENT ASSESSMENT; ELDERLY PACE; OLDER ADULTS; RUG-III; HOME AB To date, the Medicare Program has used functional status information (FSI) in patient assessment tools, performance assessment, payment mechanisms, and most recently-in quality measures to inform consumer choice. This article explores the rationale for the collection of functional status data to promote innovative models of care and examines issues related to data collection for quality improvement, performance measurement, and payment. In this issue of the Health Care Financing Review, articles focus on collection and classification of functional status for Payment and quality purposes. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Clauser, SB (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7344,EPN Room 4005, Bethesda, MD 20892 USA. EM clausers@mail.nih.gov NR 50 TC 9 Z9 9 U1 5 U2 7 PU CENTERS FOR MEDICARE & MEDICAID SERVICES PI BALTIMORE PA 7500 SECURITY BOULEVARD, BALTIMORE, MD 21244-1850 USA SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD SPR PY 2003 VL 24 IS 3 BP 1 EP 12 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 953PB UT WOS:000231089300002 PM 12894631 ER PT J AU Sanz-Ortega, J Hernandez, S Saez, MC Sierra, E Sanz-Ortega, G Torres, A Balibrea, JL Sanz-Esponera, J Merino, MJ AF Sanz-Ortega, J Hernandez, S Saez, MC Sierra, E Sanz-Ortega, G Torres, A Balibrea, JL Sanz-Esponera, J Merino, MJ TI 3p21, 5q21, 9p21 and 17p13.1 allelic deletions are potential markers of individuals with a high risk of developing adenocarcinoma in Barrett's epithelium without dysplasia SO HEPATO-GASTROENTEROLOGY LA English DT Article DE adenocarcinoma; microdissection; Barrett's esophagus; loss of heterozygosity ID APC/MCC GENE 5Q21; PRENEOPLASTIC LESIONS; FORMER SMOKERS; APC GENE; ESOPHAGUS; HETEROZYGOSITY; CARCINOMA; PROGRESSION; MUTATION; LOH AB Background/Aims: A common genetic abnormality detected in Barrett's adenocarcinoma is LOH (loss of heterozygosity) at the sites of known or putative tumor suppressor genes. Thus, some deletions have also been determined in peritumoral Barrett's epithelium. These findings suggest that a tissue field of somatic genetic alterations precede the histopathological phenotypic changes of carcinoma. We investigated 32 cases of Barrett's esophagus with no evidence of dysplasia for LOH at 5q21 (APC), 3p21, 9p21 (p16) and 17p13.1 (p53) chromosomal regions. Methodology: Two groups were randomly selected and compared: 16 cases of Barrett's epithelium adjacent to adenocarcinoma and 16 cases of Barrett's epithelium with no evidence of malignant transformation in,a 5-10 years follow-up period. In three adenocarcinomas cases several, previous endoscopic biopsies of Barrett's esophagus were available. Results: We determined frequent allelic losses in adenocarcinomas at p53 (54%), p16 (50%, 3p21 (40%) and 5q21 (33%). Identical LOH was present in most cases in the Barrett's epithelium adjacent to adenocarcinoma. LOH at these loci was unusual in Barrett's epithelium with no evidence of malignant transformation. However, in cases where sequential endoscopic biopsies were performed in advance to the adenocarcinoma diagnosis LOH was already present in the Barrett's epithelium. Conclusions: We suggest that LOH at these. loci may be present before the onset of the malignant growth and LOH studies may supplement the histopathological evaluation of Barrett's epithelium. LOH at 3p21, 5q21, 9p21 and 17p13 chromosomal regions in cells of Barrett's epithelium without dysplasia may have a role as a potential marker for individuals with a high risk of developing adenocarcinoma. C1 Hosp Clin San Carlos, Dept Anat Patol, Madrid 28040, Spain. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Sanz-Ortega, J (reprint author), Hosp Clin San Carlos, Dept Anat Patol, Martin Lagos S-N, Madrid 28040, Spain. RI Sanz, Julian/G-5276-2013 NR 22 TC 27 Z9 28 U1 0 U2 3 PU H G E UPDATE MEDICAL PUBLISHING S A PI ATHENS PA PO BOX 17257, ATHENS GR-10024, GREECE SN 0172-6390 J9 HEPATO-GASTROENTEROL JI Hepato-Gastroenterol. PD MAR-APR PY 2003 VL 50 IS 50 BP 404 EP 407 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 662ZK UT WOS:000181979800027 PM 12749233 ER PT J AU Sugimoto, K Stadanlick, J Ikeda, F Brensinger, C Furth, EE Alter, HJ Chang, KM AF Sugimoto, K Stadanlick, J Ikeda, F Brensinger, C Furth, EE Alter, HJ Chang, KM TI Influence of ethnicity in the outcome of hepatitis C virus infection and cellular immune response SO HEPATOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LIVER FIBROSIS PROGRESSION; CYTOTOXIC T-LYMPHOCYTES; QUANTITATIVE-ANALYSIS; AFRICAN-AMERICANS; NATURAL-HISTORY; VIRAL CLEARANCE; CD4(+); CELLS; INTERFERON AB This study was performed to examine the immunologic basis for the apparent ethnic difference in clinical outcome of hepatitis C virus (HCV) infection between African Americans (AA) and Caucasian Americans (CA). To this end, we recruited 99 chronically HCV-infected and 31 spontaneously HCV-cleared subjects for clinical, virologic, and immunologic analysis. In particular, CD4-proliferative T-cell response to genotype 1- derived HCV antigens (core, NS3-NS5) was examined in 82 patients chronically infected with genotype 1 (54 AA, 28 CA) and in all HCV-cleared subjects (14 AA, 17 CA). HCV-specific Th1 response also was examined in 52 chronic and 13 recovered subjects. Our results showed that HCV clearance was associated with a vigorous HCV-specific Th1 response irrespective of ethnic origin. Although the HCV-specific CD4 T-cell response dearly was weaker during chronic infection, AA ethnicity in this setting was associated with a significantly greater CD4-proliferative T-cell response to HCV, particularly to the nonstructural antigens (22% AA vs. 0% CA, P =.007) as well as better clinical parameters of liver disease. Interestingly, most HCV-specific CD4 T-cell proliferative responses in AA patients were unaccompanied by concurrent interferon gamma (IFN-gamma) production, suggesting a dysregulated virus-specific, CD4 T-cell effector function during chronic HCV infection. In conclusion, our results suggest that host ethnicity does influence the clinical outcome and antiviral T-cell response during HCV infection. AA ethnicity is associated with a more robust antiviral CD4 T-cell response than CA ethnicity, although these T cells are limited in direct virus or disease control due to their dysfunctional nature. C1 Univ Penn, Dept Med, GI Div, Div Gastroenterol, Philadelphia, PA 19104 USA. Philadelphia Vet Adm Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Chang, KM (reprint author), Univ Penn, Dept Med, GI Div, Div Gastroenterol, A212 Med Res,PVAMC,Univ & Woodland Ave, Philadelphia, PA 19104 USA. FU NCRR NIH HHS [M01-RR00040]; NIAAA NIH HHS [AA12849]; NIAID NIH HHS [AI47519]; NIDDK NIH HHS [P30DK50306] NR 49 TC 83 Z9 89 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2003 VL 37 IS 3 BP 590 EP 599 DI 10.1053/jhep.2003.50103 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 650RJ UT WOS:000181276800015 PM 12601357 ER PT J AU Kaneko, T Spande, TF Garraffo, HM Yeh, HJC Daly, JW Andriamaharavo, NR Andriantsiferana, M AF Kaneko, T Spande, TF Garraffo, HM Yeh, HJC Daly, JW Andriamaharavo, NR Andriantsiferana, M TI A structure for 261C, a novel tricyclic alkaloid from the Madagascan poison frog, Mantella betsileo SO HETEROCYCLES LA English DT Article ID DENDROBATID FROGS; INDOLIZIDINES; ANTS; 223A AB Based upon (1)H-NMR, MS and IR spectra, a perhydro 2-allyl-5-ethyl-7-n-propylpyrrolo[2,1,5-cd]indolizine structure (1) is proposed for a major tricyclic alkaloid 261C isolated from skin extracts of a Madagascan poison frog of the mantellid genus Mantella. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Antananarivo, Lab Chim Organ Prod Nat, Antananarivo 1001, Madagascar. RP Kaneko, T (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 17 TC 6 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD MAR 1 PY 2003 VL 59 IS 2 BP 745 EP 757 PG 13 WC Chemistry, Organic SC Chemistry GA 663NL UT WOS:000182011600035 ER PT J AU Kino, T Mirani, M Alesci, S Chrousos, GP AF Kino, T Mirani, M Alesci, S Chrousos, GP TI AIDS-related lipodystrophy/insulin resistance syndrome SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE adipose calls; AIDS; fat distribution; pseudo-cushing ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV PROTEASE INHIBITORS; ACTIVE ANTIRETROVIRAL THERAPY; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; REVERSE-TRANSCRIPTASE INHIBITORS; MULTIPLE SYMMETRICAL LIPOMATOSIS; NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; CELL-CYCLE; INFECTED PATIENTS AB The recent development and clinical use of three different types of highly effective anti-HIV-1 drugs, including nucleotide and non-nucleotide reverse transcriptase inhibitors (NRTIs) and non-peptidic viral protease inhibitors (Pis) and their combinations, termed highly active antiretroviral therapy (HAART), have dramatically reduced the infection-related mortality of AIDS patients in developed countries. However, the prolongation of the life expectancy of HIV-1-infected patients and/or long-term use of the above antiviral agents have generated a score of new problems and complications. Among them is the relatively common AIDS-related lipodystrophy/insulin resistance syndrome, which is associated with severe metabolic disturbances such as carbo-hydrate intolerance/diabetes mellitus and severe dyslipidemia, which influence the quality of life and threaten the life expectancies of HIV-1-infected patients by increasing the risk of atherosclerotic cardiovascular disease. The etiology of this syndrome appears to be multi-factorial; the classes of anti-viral drugs listed above, hypercytokinemia in AIDS patients, and the HIV-1 infection itself could induce the pathologic changes of this syndrome or increase the vulnerability of patients to the adverse effect of the therapeutic compounds. In this article, we review our current understanding of the pathogenesis of this severe AIDS-associated metabolic disorder. C1 NICHHD, Pediat & Reprod Endrocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Kino, T (reprint author), NICHHD, Pediat & Reprod Endrocrinol Branch, NIH, Bldg 10,Rm 9D42,10 Ctr Dr MSC 1583, Bethesda, MD 20892 USA. NR 110 TC 30 Z9 31 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD MAR PY 2003 VL 35 IS 3 BP 129 EP 136 DI 10.1055/s-2003-39072 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 680MN UT WOS:000182982100001 PM 12734771 ER PT J AU Gaillard, WD Sachs, BC Whitnah, JR Ahmad, Z Balsamo, LM Petrella, JR Braniecki, SH McKinney, CM Hunter, K Xu, B Grandin, CB AF Gaillard, WD Sachs, BC Whitnah, JR Ahmad, Z Balsamo, LM Petrella, JR Braniecki, SH McKinney, CM Hunter, K Xu, B Grandin, CB TI Developmental aspects of language processing: fMRI of verbal fluency in children and adults SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; language; verbal fluency; children; development ID FUNCTIONAL MRI; PREFRONTAL CORTEX; BRAIN ACTIVATION; WORD GENERATION; FRONTAL-CORTEX; WADA TEST; DOMINANCE; LOCALIZATION; LESIONS; TASK AB We examined developmental differences, in location and extent of fiviRI language activation maps, between adults and children while performing a semantic fluency task. We studied 29 adults and 16 children with echo planar imaging BOLD fMRI at 1.5 T using covert semantic verbal fluency (generation of words to categories compared to rest) using a block design. Post task testing was administered to assess performance. Individual data were analyzed with an a priori region of interest approach from t maps (t = 4) and asymmetry indices (AI). Group studies were analyzed using SPM 99 (Wellcome, UK; fixed effect, corrected P < 0.0001). We found no significant differences in location or laterality of activation between adults and children for a semantic verbal fluency task. Adults activated more pixels than children in left inferior frontal gyrus and left middle frontal gyrus, but AIs were the similar across ages (r(2) < 0.09). Extent or laterahty of activation was not affected by performance (r(2) < 0.15). The brain areas that process semantic verbal fluency are similar in children and adults. The laterality of activation does not change appreciably with age and appears to be strongly lateralized by age 7 years. Hum. Brain Mapping 18:176-185,2003. Published 2003 Wiley-Liss, Inc. C1 George Washington Univ, Childrens Natl Med Ctr, Dept Neurol, Sch Med, Washington, DC 20010 USA. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. Duke Med Ctr, Dept Radiol, Durham, NC USA. Catholic Univ Louvain, St Luc Univ Hosp, Dept Radiol, Brussels, Belgium. RP Gaillard, WD (reprint author), George Washington Univ, Childrens Natl Med Ctr, Dept Neurol, Sch Med, 111 Michigan Ave NW, Washington, DC 20010 USA. FU NICHD NIH HHS [1P30HD40677-01]; NINDS NIH HHS [K08-NS1663] NR 62 TC 136 Z9 140 U1 8 U2 20 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAR PY 2003 VL 18 IS 3 BP 176 EP 185 DI 10.1002/hbm.10091 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 652MA UT WOS:000181381900005 PM 12599275 ER PT J AU Rossi, GR Mautino, MR Morgan, RA AF Rossi, GR Mautino, MR Morgan, RA TI High-efficiency lentiviral vector-mediated gene transfer into murine macrophages and activated splenic B lymphocytes SO HUMAN GENE THERAPY LA English DT Article ID DENDRITIC CELLS; NITRIC-OXIDE; IN-VIVO; THERAPY; MAINTENANCE; INDUCTION; DELIVERY; CD40 AB The goal of the present report was to determine if lentiviral vectors could mediate gene transfer into murine terminally differentiated macrophages and mature B lymphocytes as a new strategy of gene delivery into professional antigen-presenting cells (APC). We demonstrated that nondividing tissue resident macrophages were efficiently transduced in vitro by lentiviral vectors. Gene transfer efficiencies of up to 90% were demonstrated using a green fluorescent protein (GFP) reporter gene-containing vector and expression was stable for the length of cell culture. Transduced macrophages were functionally competent, preserving their phagocytic activity, accessory cell function, interleukin (IL)-12 secretion, and nitric oxide (NO) production similar to control untransduced macrophages. Lentiviral vector mediated transduction of CD19(+) B cell blasts was demonstrated to be in the range of 60%-70% GFP-positive cells. These transduced cells retain the ability to upregulate CD80 and CD86 similar to control B cell cultures. In addition, we show that the human immunodeficiency virus type 1 (HIV-1) accessory proteins Nef, Vpr, Vif, and Vpu are not required for the transduction of both resident macrophages and activated B lymphoblasts. We conclude that HIV-1-based lentiviral vectors can mediate efficient gene transfer into primary murine macrophages and mature B lymphocytes. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B04,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. NR 17 TC 11 Z9 13 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR PY 2003 VL 14 IS 4 BP 385 EP 391 DI 10.1089/104303403321208989 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 662CW UT WOS:000181929500006 PM 12659679 ER PT J AU Ujhelly, O Ozvegy, C Varady, G Cervenak, J Homolya, L Grez, M Scheffer, G Roos, D Bates, SE Varadi, A Sarkadi, B Nemet, K AF Ujhelly, O Ozvegy, C Varady, G Cervenak, J Homolya, L Grez, M Scheffer, G Roos, D Bates, SE Varadi, A Sarkadi, B Nemet, K TI Application of a human multidrug transporter (ABCG2) variant as selectable marker in gene transfer to progenitor cells SO HUMAN GENE THERAPY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; CANCER RESISTANCE PROTEIN; STEM-CELLS; MULTIDRUG-RESISTANCE-1 GENE; REPOPULATING CELLS; HUMAN-NEUTROPHILS; MXR ABCG2; IN-VIVO; EXPRESSION; CHEMOPROTECTION AB Stem cell-based gene therapy is often unsuccessful because of the relatively low number of genetically modified cells with repopulating capabilities. To provide a selective advantage for the modified cells we applied the human ABCG2 protein, a resident xenobiotic transporter in stem cells, as a selectable marker. This protein is active as a homodimer, and its relatively small cDNA is an advantage in gene therapy applications. In the present study a mutant form of ABCG2 (R482G), showing drug-pumping activity with an altered substrate specificity, was coexpressed with a therapeutic gene by using a bicistronic vector and an efficient retroviral transduction protocol. Expression of the gp91(phox) protein in human gp91phox knockout hematopoietic progenitor cells corrected the loss-of-function mutation responsible for human chronic granulomatous disease, whereas the mutant ABCG2 protein selectively protected the transduced cells against clinically applicable cytotoxic agents. Overexpression of ABCG2 did not affect hematopoietic cell maturation or the restoration of granulocyte function by gp91(phox). We suggest that the mutant ABCG2 protein is an ideal candidate for human stem cell protection and for use as a selectable marker in gene therapy. C1 Hungarian Acad Sci, Inst Hematol & Immunol, Natl Med Ctr, H-1113 Budapest, Hungary. Hungarian Acad Sci, Res Grp Membrane Biol, H-1113 Budapest, Hungary. Hungarian Acad Sci, Inst Enzymol, H-1113 Budapest, Hungary. George Speyer Haus, Inst Biomed Res, D-60696 Frankfurt, Germany. Free Univ Amsterdam, NL-1081 HV Amsterdam, Netherlands. Netherlands Red Cross, Blood Transfus Serv, Cent Lab, NL-1066 CX Amsterdam, Netherlands. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Sarkadi, B (reprint author), Hungarian Acad Sci, Inst Hematol & Immunol, Natl Med Ctr, Dioszegi 64, H-1113 Budapest, Hungary. RI Varadi, Andras/A-2055-2012; Sarkadi, Balazs/I-5024-2013; Homolya, Laszlo/N-1154-2016 NR 33 TC 25 Z9 27 U1 0 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR PY 2003 VL 14 IS 4 BP 403 EP 412 DI 10.1089/104303403321209005 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 662CW UT WOS:000181929500008 PM 12659681 ER PT J AU Sun, M Zhang, GR Kong, LX Holmes, C Wang, XD Zhang, W Goldstein, DS Geller, AI AF Sun, M Zhang, GR Kong, LX Holmes, C Wang, XD Zhang, W Goldstein, DS Geller, AI TI Correction of a rat model of Parkinson's disease by coexpression of tyrosine hydroxylase and aromatic amino acid decarboxylase from a helper virus-free herpes simplex virus type 1 vector SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; GTP-CYCLOHYDROLASE-I; LONG-TERM; PLASMID VECTORS; L-DOPA; BEHAVIORAL RECOVERY; PRIMARY FIBROBLASTS; HSV-1 VECTOR; EXPRESSION; DELIVERY AB We previously reported long-term biochemical and behavioral correction of the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD) by expression of tyrosine hydroxylase (TH) in the partially denervated striatum, using a herpes simplex virus type 1 (HSV-1) vector. This study had a number of limitations, including the use of a helper virus packaging system, limited long-term expression, and expression of only TH. To address these issues, we developed a helper virus-free packaging system, a modified neurofilament gene promoter that supports long-term expression in forebrain neurons, and a vector that coexpresses TH and aromatic amino acid decarboxylase (AADC). Coexpression of TH and AADC supported high-level (80%), behavioral correction of the 6-OHDA rat model of PD for 5 weeks. Biochemical correction included increases in extracellular dopamine and DOPAC concentrations between 2 and 4 months after gene transfer. Histologic analyses demonstrated neuronal-specific coexpression of TH and AADC at 4 days to 7 months after gene transfer, and cell counts revealed 1000 to 10,000 TH positive cells per rat at 2 months after gene transfer. This improved system efficiently corrects the rat model of PD. C1 W Roxbury VA Hosp, Harvard Med Sch, Dept Neurol, W Roxbury, MA 02132 USA. NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. RP Geller, AI (reprint author), W Roxbury VA Hosp, Harvard Med Sch, Dept Neurol, Res Bldg 3,1400 VFW Pkwy, W Roxbury, MA 02132 USA. RI Geller, Alfred/C-6469-2012 FU NIA NIH HHS [K01 AG020177, R01 AG016777, R01 AG021193, AG 20177, AG 16777]; NINDS NIH HHS [NS 34025, F32 NS010805, R01 NS043107, R01 NS045855] NR 40 TC 49 Z9 53 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR PY 2003 VL 14 IS 5 BP 415 EP 424 DI 10.1089/104303403321467180 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 662CX UT WOS:000181929600001 PM 12691607 ER PT J AU Turner, C Killoran, C Thomas, NST Rosenberg, M Chuzhanova, NA Johnston, J Kemel, Y Cooper, DN Biesecker, LG AF Turner, C Killoran, C Thomas, NST Rosenberg, M Chuzhanova, NA Johnston, J Kemel, Y Cooper, DN Biesecker, LG TI Human genetic disease caused by de novo mitochondrial-nuclear DNA transfer SO HUMAN GENETICS LA English DT Article ID PALLISTER-HALL SYNDROME; DOUBLE-STRAND BREAKS; CHERNOBYL ACCIDENT; THYROID CARCINOMAS; MUTATION-RATE; HUMAN-GENOME; RADIATION; REARRANGEMENTS; INSERTION; PERSPECTIVES AB Transfer of nucleic acid from cytoplasmic organelles to the nuclear genome is a well-established mechanism of evolutionary change in eukaryotes. Such transfers have occurred throughout evolution,. but so far, none has been shown unequivocally to occur de novo to cause a heritable human disease. We have characterized a patient with a de novo nucleic acid transfer from the mitochondrial to the nuclear genome, a transfer that is responsible for a sporadic case of Pallister-Hall syndrome, a condition usually inherited in an autosomal dominant fashion. This mutation, a 72-bp insertion into exon 14 of the GLI3 gene, creates a premature stop codon and predicts a truncated protein product. Both the mechanism and the cause of the mitochondrial-nuclear transfer are unknown. Although the conception of this patient was temporally and geographically associated with, high-level radioactive contamination following the Chernobyl accident, this case cannot, on its own, be used to establish a causal relationship between radiation exposure and this rare type of mutation. Thus, for the time being, it must be considered as an intriguing coincidence. Nevertheless, these data serve to demonstrate that de novo mitochondrial-nuclear transfer of nucleic acid is a novel mechanism of human inherited disease. C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Bethesda, MD 20814 USA. Univ Wales Coll Med, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales. Univ Wales Coll Cardiff, Dept Comp Sci, Cardiff CF24 3XF, S Glam, Wales. RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov RI Cooper, David/H-4384-2011; OI Cooper, David/0000-0002-8943-8484; Chuzhanova, Nadia/0000-0002-4655-3618 NR 33 TC 58 Z9 60 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAR PY 2003 VL 112 IS 3 BP 303 EP 309 DI 10.1007/s00439-002-0892-2 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 659TA UT WOS:000181792500012 PM 12545275 ER PT J AU Staib, F Hussain, SP Hofseth, LJ Wang, XW Harris, CC AF Staib, F Hussain, SP Hofseth, LJ Wang, XW Harris, CC TI TP53 and liver carcinogenesis SO HUMAN MUTATION LA English DT Review DE cancer; carcinogenesis; hepatocellular carcinoma; p53; TP53; aflatoxin B-1; HBV; HCV; vinyl chloride; oxidative stress; nitrosative stress; tumor exposure; mutagen; risk factor ID HEPATITIS-B-VIRUS; NITRIC-OXIDE SYNTHASE; P53 TUMOR-SUPPRESSOR; HUMAN HEPATOCELLULAR-CARCINOMA; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; DIFFERENTIAL GENE-EXPRESSION; CHRONIC VIRAL-HEPATITIS; X-PROTEIN; VINYL-CHLORIDE AB Primary hepatocellular carcinoma (HCC) is one of the most common malignancies and has the fourth highest mortality rate worldwide. The major risk factors, including chronic infections with the hepatitis B or C virus, are exposure to dietary aflatoxin B-1 (AFB(1)), vinyl chloride, or alcohol consumption. Southern China and sub,Saharan Africa have the highest dietary AFB(1) exposure; making it and hepatitis B virus (HBV) the major causes of cancer mortality in these geographic areas. Recent studies have discovered genetic and epigenetic changes involved in the molecular pathogenesis of HCC, including somatic mutations in the p53 tumor suppressor gene (TP53). AFB(1) induces typical G:C to TA transversions at the third base in codon 249 of p53. Chronic active hepatitis B and C (HCV) infection, and further inflammatory and oxyradical disorders including Wilson disease (WD) or hemochromatosis, generate reactive oxygen/nitrogen species that can damage DNA and mutate the P53 gene. The X gene of HBV (HBx) is the most common open reading frame integrated into the host genome in HCC. The integrated HBx is frequently mutated and has a diminished ability to function as a transcriptional cotransactivator and to activate the NF-kappa B pathway. However, the mutant HBx proteins still retain their ability to bind to and abrogate p53-mediated apoptosis. In summary, both viruses and chemicals are implicated in the etiology and molecular pathogenesis of HCC. The resultant molecular changes in the ras and Wnt signal,transduction pathways, and the p53 and Rb tumor suppressor pathway's significantly contribute to liver carcinogenesis. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 2C05, Bethesda, MD 20892 USA. RI Wang, Xin/B-6162-2009 NR 160 TC 155 Z9 169 U1 3 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD MAR PY 2003 VL 21 IS 3 BP 201 EP 216 DI 10.1002/humu.10176 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 654CA UT WOS:000181474900005 PM 12619106 ER PT J AU Krishnan, A Murdock, C Allard, J Cisar, M Reid, E Nieman, L Segars, J AF Krishnan, A Murdock, C Allard, J Cisar, M Reid, E Nieman, L Segars, J TI Pseudo-isolated FSH deficiency caused by an inhibin B-secreting granulosa cell tumour: Case report SO HUMAN REPRODUCTION LA English DT Article DE FSH deficiency; granulosa cell tumour; hypothalamic amenorrhoea; infertility; inhibin B ID FOLLICLE-STIMULATING-HORMONE; OVARIAN-TUMORS; POSTMENOPAUSAL WOMEN; BETA-SUBUNIT; AMENORRHEA; ACTIVINS; SERUM; INFERTILITY; OVULATION; CANCER AB Isolated FSH deficiency due to a mutation in the FSHbeta subunit is characterized by an extremely low serum FSH concentration. We report a patient who presented with an FSH of 0.8 mIU/ml and infertility associated with anovulation. Endocrinological assessment and immunohistochemistry revealed that a granulosa cell tumour was secreting inhibin B and suppressing FSH; however, LH and estradiol were within their normal ranges. Upon removal of the tumour, inhibin B decreased and FSH levels rose to normal values. The patient subsequently conceived and delivered successfully. Based on this case and on those previously described in the literature, we suggest that inhibin B levels should be evaluated in anovulatory patients having a clinical presentation consistent with functional hypothalamic amenorrhoea and very low to normal values of FSH. C1 NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. RP Segars, J (reprint author), NICHD, Pediat & Reprod Endocrinol Branch, Bldg 10,Room 9D-42, Bethesda, MD 20892 USA. NR 29 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD MAR PY 2003 VL 18 IS 3 BP 502 EP 505 DI 10.1093/humrep/deg124 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 655HX UT WOS:000181546200008 PM 12615814 ER PT J AU Roberts, JM Pearson, G Cutler, J Lindheimer, M AF Roberts, JM Pearson, G Cutler, J Lindheimer, M TI Summary of the NHLBI Working Group on research on hypertension during pregnancy SO HYPERTENSION LA English DT Article DE hypertension, pregnancy; preeclampsia; pregnancy; research; oxidative stress; mortality ID OXIDATIVE STRESS; PREECLAMPTIC PREGNANCIES; ANTIHYPERTENSIVE TREATMENT; ENDOTHELIAL DYSFUNCTION; PEROXYNITRITE FORMATION; SUBSEQUENT PREGNANCY; REMOTE PROGNOSIS; LIPID PEROXIDES; DECIDUA BASALIS; ACUTE ATHEROSIS AB A Working Group on Research in Hypertension in Pregnancy was recently convened by the National Heart, Lung, and Blood Institute to determine the state of knowledge in this area and suggest appropriate directions for research. Hypertensive disorders in pregnancy, especially preeclampsia, are a leading cause of maternal death worldwide and even in developed countries increase perinatal mortality rates 5-fold. Much has been learned about preeclampsia, but gaps in the knowledge necessary to direct therapeutic strategies remain. Oxidative stress is a biologically plausible contributor to the disorder that may be amenable to intervention. Hypertension that antedates pregnancy (chronic hypertension) bears many similarities to hypertension in nonpregnant women, but the special setting of pregnancy demands information to guide evidence-based therapy. The recommendations of the Working Group are to attempt a clinical trial of antioxidant therapy to prevent preeclampsia that is be complemented by mechanistic research to increase understanding of the genetics and pathogenesis of the disorder. For chronic hypertension, clinical trials are recommended to direct choice of drugs, evaluate degree of control, and assess implications to the mother and fetus. Recommendations to increase participation in this research are also presented. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. Magee Womens Res Inst, Pittsburgh, PA USA. NHLBI, Heart Dev Funct & Failure Sci Res Grp, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Gynecol & Obstet, Div Biol Sci, Pritzker Sch Med, Chicago, IL 60637 USA. RP Roberts, JM (reprint author), 204 Craft Ave,Suite 610, Pittsburgh, PA 15213 USA. NR 74 TC 364 Z9 389 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2003 VL 41 IS 3 BP 437 EP 445 DI 10.1161/01.HYP.0000054981.03589.E9 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653QD UT WOS:000181447500010 PM 12623940 ER PT J AU Vupputuri, S He, J Muntner, P Bazzano, LA Whelton, PK Batuman, V AF Vupputuri, S He, J Muntner, P Bazzano, LA Whelton, PK Batuman, V TI Blood lead level is associated with elevated blood pressure in blacks SO HYPERTENSION LA English DT Article DE blood pressure; ethnic groups; blood lead; blacks; epidemiology ID 3RD NATIONAL-HEALTH; SURVEY NHANES-III; RENAL-FUNCTION; GENERAL-POPULATION; INDUCED HYPERTENSION; US POPULATION; UNITED-STATES; TIBIAL LEAD; EXPOSURE; NEPHROPATHY AB Chronic lead exposure has been associated with elevated blood pressure in epidemiological studies. It is not known whether the previously observed relation between blood lead and hypertension persists after significant reductions have been made in environmental lead contamination. We examined the relation between blood lead levels and blood pressure in a representative sample of 14 952 whites and blacks aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey. Blood lead was measured by atomic absorption spectrophotometry and blood pressure by standard sphygmomanometry. Mean blood lead levels were significantly higher for black men and women (5.4 and 3.4 mug/dL, respectively) compared with white men and women (4.4 and 3.0 mug/dL, respectively). After multivariate adjustment for important covariables, each standard deviation higher blood lead (3.3 mug/dL) was associated with a 0.82 (95% confidence interval [CI], 0.19 to 1.44) mm Hg and a 1.55 (95% CI, 0.47 to 2.64) mm Hg higher systolic blood pressure among black men and women, respectively. In contrast, blood lead level was not associated with blood pressure among white men or women. The multivariate-adjusted odds ratio (95% CI) of hypertension associated with a 1-SD higher level of blood lead was 1.08 (95% CI, 0.99 to 1.19) for black men and 1.39 (95% CI, 1.21 to 1.61) for black women. These findings suggest that increased levels of blood lead remain an important environmental risk factor for elevated blood pressure in blacks. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. VA Med Ctr, New Orleans, LA USA. RP He, J (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1430 Tulane Ave SL18, New Orleans, LA 70112 USA. OI Batuman, Vecihi/0000-0002-1800-9009 FU NHLBI NIH HHS [R01HL60300] NR 65 TC 66 Z9 67 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2003 VL 41 IS 3 BP 463 EP 468 DI 10.1161/01.HYP.0000055015.39788.29 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653QD UT WOS:000181447500014 PM 12623944 ER PT J AU Fedorova, OV Talan, MI Agalakova, NI Droy-Lefaix, MT Lakatta, EG Bagrov, AY AF Fedorova, OV Talan, MI Agalakova, NI Droy-Lefaix, MT Lakatta, EG Bagrov, AY TI Myocardial PKC beta 2 and the sensitivity of Na/K-ATPase to marinobufagenin are reduced by cicletanine in Dahl hypertension SO HYPERTENSION LA English DT Article DE rats; Dahl; Na/K-transporting ATPase; digitalis-like factor; bufanolides; hypertrophy; protein kinases; antihypertensive agents ID PROTEIN-KINASE-C; SODIUM-PUMP; CARDIAC-HYPERTROPHY; ENDOGENOUS LIGAND; PRESSURE-OVERLOAD; SUBUNIT ISOFORMS; MESSENGER-RNA; HEART-FAILURE; RATS; INHIBITION AB Marinobufagenin (MBG), an endogenous ligand of alpha-1 Na/K-ATPase, becomes elevated and contributes to hypertension in NaCl-loaded Dahl-S rats (DS). Protein kinase C (PKC) phosphorylates alpha-1 Na/K-ATPase and increases its MBG sensitivity. Cicletanine, an antihypertensive compound with PKC-inhibitory activity, reverses MBG-induced Na/K-ATPase inhibition and vasoconstriction. We hypothesized that increased PKC levels in sodium-loaded hypertensive DS would sensitize alpha-1 Na/K-ATPase to MBG and that PKC inhibition by cicletanine would produce an opposite effect. We studied the effects of cicletanine on systolic blood pressure, left ventricular PKC isoforms, cardiac alpha-1 Na/K-ATPase levels, and sensitivity to MBG in hypertensive DS. Seven DS received 50 mg . kg(-1) . d(-1) cicletanine, and 7 DS received vehicle during 4 weeks of an 8% NaCl diet. Vehicle-treated rats exhibited an increase in blood pressure, left ventricular mass, MBG excretion (74+/-11 vs 9+/-1 pmol/24 h, P<0.01), myocardial α-1 Na/K-ATPase protein, and PKC β2 and δ. The sensitivity of Na/K-ATPase to MBG was enhanced at the level of high-affinity binding sites (IC50, 0.8 vs 4.4 nmol/L, P<0.01). Cicletanine-treated rats exhibited a 56-mm Hg reduction in blood pressure (P<0.01) and a 30% reduction in left ventricular weight, whereas cardiac α-1 Na/K-ATPase protein and MBG levels were unchanged. In cicletanine-treated rats, PKC β2 was not increased, the sensitivity of Na/K-ATPase to MBG was decreased (IC50=20 μmol/L), and phorbol diacetate-induced α-1 Na/K-ATPase phosphorylation was reduced versus vehicle-treated rats. In vitro cicletanine treatment of sarcolemma from vehicle-treated rats also desensitized Na/K-ATPase to MBG, indicating that this effect was not solely attributable to a reduction in blood pressure. Thus, PKC-induced phosphorylation of cardiac α-1 Na/K-ATPase is a likely target for cicletanine treatment. C1 NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. IPSEN Inst, Paris, France. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 32 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2003 VL 41 IS 3 BP 505 EP 511 DI 10.1161/01.HYP.0000053446.43894.9F PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653QD UT WOS:000181447500021 PM 12623951 ER PT J AU Zhao, XY Pollock, DM Inscho, EW Zeldin, DC Imig, JD AF Zhao, XY Pollock, DM Inscho, EW Zeldin, DC Imig, JD TI Decreased renal cytochrome P4502C enzymes and impaired vasodilation are associated with angiotensin salt-sensitive hypertension SO HYPERTENSION LA English DT Article; Proceedings Paper CT 56th Annual Fall Conference and Scientific Sessions of the American-Heart-Association-Council-for-High-Blood-Pressure-Research CY SEP 25-28, 2002 CL ORLANDO, FLORIDA SP Amer Heart Assoc Council High Blood Pressure Res DE endothelium-derived factors; cytochrome P450; epoxygenase; hydroxylase; kidney; microcirculation ID ARACHIDONIC-ACID; EPOXYEICOSATRIENOIC ACIDS; EPOXYGENASE METABOLITES; 11,12-EPOXYEICOSATRIENOIC ACID; HYPERPOLARIZING FACTORS; NITRIC-OXIDE; RATS; EXPRESSION; ARTERIES; HYDROXYLASE AB Excess dietary salt intake differentially modulates the activity of cytochrome (CYP) P450 enzymes in kidney cortex. Exactly how increased angiotensin (Ang) II levels and hypertension change the regulatory effect of high salt on CYP450 enzymes remains unclear. The present study investigated the effects of combined administration of Ang II and a high-salt diet on P450 epoxygenase and hydroxylase protein levels in kidney, as well as afferent arteriolar responses to acetylcholine and sodium nitroprusside. High dietary salt administration for 14 days resulted in increased renal cortical CYP2C11 protein levels, and a significant increase of CYP2C11 and CYP2C23 protein levels in renal microvessels. Administration of Ang II in combination with a high-salt diet prevented the upregulation of renal cortical CYP2C11 protein expression observed with high dietary salt alone, and significantly downregulated expression of CYP2C11, CYP2C23, and CYP2J protein in renal microvessels. A high-salt diet alone decreased CYP4A protein in kidney cortex, and renal cortical CYP4A protein level remained at a low level in Ang II-infused rats treated with a high-salt diet. Increases in blood pressure during Ang II infusion were greater in rats fed a high-salt diet. In addition, afferent arteriolar responsiveness to acetylcholine and sodium nitroprusside was significantly attenuated in Ang II-treated rats versus controls. This decrease was significantly enhanced in Ang II-treated rats given a high-salt diet. These results support the hypothesis that an inability to upregulate CYP2C and maintain CYP2J in the rat kidney and impaired afferent arteriolar vasodilation with chronic Ang II infusion contribute to salt-induced elevation of arterial pressure. C1 Med Coll Georgia, Vasc Biol Ctr, Augusta, GA 30912 USA. Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA. Med Coll Georgia, Dept Surg, Augusta, GA 30912 USA. NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Imig, JD (reprint author), Med Coll Georgia, Vasc Biol Ctr, Augusta, GA 30912 USA. OI Imig, John/0000-0002-9668-2899 FU NHLBI NIH HHS [HL-59699, HL-64776]; NIDDK NIH HHS [DK-38226, DK-44628] NR 38 TC 63 Z9 65 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2003 VL 41 IS 3 BP 709 EP 714 DI 10.1161/01.HYP.0000047877.36743.FA PN 2 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 655YA UT WOS:000181579200017 PM 12623984 ER PT J AU Yao, L AF Yao, L TI Aplidin PharmaMar SO IDRUGS LA English DT Article ID TUMOR-CELLS; TUNICATES AB Aplidin is a cell cycle inhibitor being developed by PharmaMar SA for the potential treatment of a variety of cancers, including nonHodgkin's lymphoma (NHL), non-small-cell lung cancer (NSCLC), acute lymphoblastic leukemia (ALL), neuroendocrine, prostate, gastric and colorectal cancers [390131], [464778]. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Yao, L (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 33 TC 6 Z9 6 U1 1 U2 2 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1369-7056 J9 IDRUGS JI IDrugs PD MAR PY 2003 VL 6 IS 3 BP 246 EP 250 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 694KJ UT WOS:000183773500017 PM 12789614 ER PT J AU Fowlkes, BJ Germain, RN Leonard, WJ Paul, WE Samelson, LE AF Fowlkes, BJ Germain, RN Leonard, WJ Paul, WE Samelson, LE TI Casting a wider net SO IMMUNITY LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Fowlkes, BJ (reprint author), NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 2003 VL 18 IS 3 BP 313 EP 313 DI 10.1016/S1074-7613(03)00059-1 PG 1 WC Immunology SC Immunology GA 658GR UT WOS:000181713700001 ER PT J AU Princiotta, MF Finzi, D Qian, SB Gibbs, J Schuchmann, S Buttgereit, F Bennink, JR Yewdell, JW AF Princiotta, MF Finzi, D Qian, SB Gibbs, J Schuchmann, S Buttgereit, F Bennink, JR Yewdell, JW TI Quantitating protein synthesis, degradation, and endogenous antigen processing SO IMMUNITY LA English DT Article ID MHC CLASS-I; PROTEASOMAL DEGRADATION; PRESENTED PEPTIDES; CODON USAGE; GENERATION; MOLECULES; CELLS; LOCALIZATION; MECHANISM; COMPLEXES AB Using L929 cells, we quantitated the macroeconomics of protein synthesis and degradation and the micro-economics of producing MHC class I associated peptides from viral translation products. To maintain a content of 2.6 x 10(9) proteins, each cell's 6 x 10(6) ribosomes produce 4 x 10(6) proteins min(-1). Each of the cell's 8 x 10(5) proteasomes degrades 2.5 substrates min(-1), creating one MHC class I-peptide complex for each 500-3000 viral translation products degraded. The efficiency of complex formation is similar in dendritic cells and macrophages, which play a critical role in activating T cells in vivo. Proteasomes create antigenic peptides at different efficiencies from two distinct substrate pools: rapidly degraded newly synthesized proteins that clearly represent defective ribosomal products (DRiPs) and a less rapidly degraded pool in which DRiPs may also predominate. C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. Humboldt Univ, Dept Rheumatol & Clin Immunol, Charite Univ Hosp, D-10117 Berlin, Germany. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jyewdell@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 35 TC 309 Z9 313 U1 2 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 2003 VL 18 IS 3 BP 343 EP 354 DI 10.1016/S1074-7613(03)00051-7 PG 12 WC Immunology SC Immunology GA 658GR UT WOS:000181713700005 PM 12648452 ER PT J AU Usui, T Nishikomori, R Kitani, A Strober, W AF Usui, T Nishikomori, R Kitani, A Strober, W TI GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12R beta 2 chain or T-bet SO IMMUNITY LA English DT Article ID IFN-GAMMA PRODUCTION; TRANSCRIPTION FACTOR GATA-3; LINEAGE COMMITMENT; CYTOKINE RESPONSES; INTERFERON-GAMMA; GENE-EXPRESSION; TRANSGENIC MICE; CUTTING EDGE; CELLS; IL-4 AB To further understand the interaction among GATA-3, Stat4, and T-bet in helper T cell development, we first showed that retroviral expression of GATA-3 in developing Th1 cells suppresses Th1 development through downregulation of Stat4 rather through downregulation of the IL-12Rbeta2 chain. Correspondingly, Stat4 levels are greatly suppressed during physiological Th2 development. Then, using cells doubly infected with GFP- and YFP-expressing retroviruses, we showed that retroviral GATA-3 expression in developing Th1 cells does not block Th1 development in cells coexpressing Stat4 but does so in cells coexpressing T-bet. Finally, we showed that retroviral Stat4 expression could facilitate Th2-->Th1 conversion in cells bearing an IL-12Rbeta2 transgene, even in cells lacking T-bet. These findings reassert that Stat4 signaling is a central element of Th1/Th2 development. C1 NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov NR 35 TC 166 Z9 170 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 2003 VL 18 IS 3 BP 415 EP 428 DI 10.1016/S1074-7613(03)00057-8 PG 14 WC Immunology SC Immunology GA 658GR UT WOS:000181713700011 PM 12648458 ER PT J AU Silvestri, G Sodora, DL Koup, RA Paiardini, M O'Neil, SP McClure, HM Staprans, SI Feinberg, MB AF Silvestri, G Sodora, DL Koup, RA Paiardini, M O'Neil, SP McClure, HM Staprans, SI Feinberg, MB TI Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia SO IMMUNITY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL DEPLETION; ACTIVE ANTIRETROVIRAL THERAPY; RECENT THYMIC EMIGRANTS; HIV-1 INFECTION; PERIPHERAL-BLOOD; LYMPHOCYTE-ACTIVATION; IMMUNE ACTIVATION; TYPE-1 INFECTION; VIRAL LOAD AB HIV-infected humans and SIV-infected rhesus macaques who remain healthy despite long-term infection exhibit exceptionally low levels of virus replication and active antiviral cellular immune responses. In contrast, sooty mangabey monkeys that represent natural hosts for SIV infection do not develop AIDS despite high levels of virus replication and limited antiviral CD8(+) T cell responses. We report here that SIV-infected mangabeys; maintain preserved T lymphocyte populations and regenerative capacity and manifest far lower levels of aberrant immune activation and apoptosis than are seen in pathogenic SIV and HIV infections. These data suggest that direct consequences of virus replication alone cannot account for progressive CD4(+) T cell depletion leading to AIDS. Rather, attenuated immune activation enables SIV-infected mangabeys to avoid the bystander damage seen in pathogenic infections and protects them from developing AIDS. C1 Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA USA. Emory Univ, Sch Med, Emory Vaccine Res Ctr, Atlanta, GA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA USA. RP Feinberg, MB (reprint author), Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA. EM mbf@sph.emory.edu NR 58 TC 429 Z9 442 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 2003 VL 18 IS 3 BP 441 EP 452 DI 10.1016/S1074-7613(03)00060-8 PG 12 WC Immunology SC Immunology GA 658GR UT WOS:000181713700013 PM 12648460 ER PT J AU Cullen, M Malasky, M Harding, A Carrington, M AF Cullen, M Malasky, M Harding, A Carrington, M TI High-density map of short tandem repeats across the human major histocompatibility complex SO IMMUNOGENETICS LA English DT Article DE major histocompatibility complex; human leukocyte antigen; microsatellites; short tandem repeats; polymorphism ID POLYMORPHIC MICROSATELLITE MARKERS; HLA CLASS-II; HUMAN MHC; HUMAN GENOME; RHEUMATOID-ARTHRITIS; DINUCLEOTIDE REPEAT; DNA-SEQUENCE; MICA GENE; REGION; ASSOCIATION AB The human genome contains one short tandem repeat (STR) roughly every 2,000 base pairs. They are particularly useful markers for gene mapping and disease association studies due to their high degree of polymorphism and ubiquitous frequency throughout the genome. The major histocompatibility complex (MHC) has been the focus of many disease association studies, and the recent availability of the entire sequence of the complex has logarithmically expanded the density of potential markers for fine mapping disease loci. Here we present a complete assessment of the available STRs within a 3.8-Mb genomic segment encompassing the MHC. Of 443 potential STRs identified by computer analysis and tested for variation in a single sample containing pooled DNA from 36 individuals, 249 polymorphic STRs located throughout the complex were identified. The class of repeat (di-, tri-, etc.), precise nucleotide position, position relative to known genes, PCR conditions, and D6S numbers for the 249 polymorphic STRs are provided as a resource for selecting appropriate markers to use in future studies of MHC molecular genetics and disease association. C1 NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. George Washington Univ, GWIBS, Grad Program Genet, Washington, DC 20052 USA. RP Carrington, M (reprint author), NCI, SAIC Frederick Inc, Basic Res Program, POB B, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov FU PHS HHS [N01-C0-12400] NR 44 TC 26 Z9 26 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD MAR PY 2003 VL 54 IS 12 BP 900 EP 910 DI 10.1007/s00251-002-0535-8 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 674PD UT WOS:000182644400011 PM 12671742 ER PT J AU Winter, H Hu, HM Poehlein, CH Huntzicker, E Osterholzer, JJ Bashy, J Lashley, D Lowe, B Yamada, J Alvord, G Urba, WJ Fox, BA AF Winter, H Hu, HM Poehlein, CH Huntzicker, E Osterholzer, JJ Bashy, J Lashley, D Lowe, B Yamada, J Alvord, G Urba, WJ Fox, BA TI Tumour-induced polarization of tumour vaccine-draining lymph node T cells to a type 1 cytokine profile predicts inherent strong immunogenicity of the tumour and correlates with therapeutic efficacy in adoptive transfer studies SO IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; IFN-GAMMA; IN-VIVO; INTERFERON-GAMMA; IMMUNE-RESPONSES; DENDRITIC CELLS; ANTITUMOR IMMUNITY; MURINE TUMOR; LYMPHOCYTES; INDUCTION AB Previously we have shown that vaccination with the poorly immunogenic B16BL6-D5 melanoma (D5) elicits a dominant type 2 (T2) cytokine response that fails to protect the host from a subsequent tumour challenge. Here we investigated whether the inherent immunogenicity of a tumour can be correlated with its ability to bias the anti-tumour cytokine response towards either a type 1 (T1) or a T2 profile. The immune response to six tumours of different inherent immunogenicity was assayed. By isolating l-selectin(low) T cells from tumour vaccine draining lymph nodes (TVDLN), it was possible to detect tumour-specific cytokine responses from both immunogenic, poorly immunogenic and non-immunogenic tumours. Immunogenic tumours (MCA-304, MCA-309, MPR-4) induced a predominant tumour-specific T1 cytokine response. In contrast, weakly (MCA-310, MPR-3) and poorly/non-immunogenic tumours (MPR-5, D5) sensitized T cells with a predominant tumour-specific T2 cytokine response. A significant correlation (P < 0.025) between immunogenicity and the ratio of tumour-specific interferon-gamma : interleukin-4 (IL-4) secretion by TVDLN T cells was identified. We then documented that non-therapeutic T cells primed by the poorly immunogenic D5, recognized 'tumour-rejection' antigens and that reprogramming their cytokine response, by in vitro culture with IL-12 and anti-IL-4, to a T1 profile uncovered therapeutic efficacy. In contrast, TVDLN T cells primed by a therapeutic vaccine lose therapeutic efficacy when cultured with IL-4. These results provide insights into the development of a protective anti-tumour immune response and strengthen the hypothesis that a T1 cytokine response is critical for T-cell-mediated tumour regression. C1 Providence Portland Med Ctr, Lab Mol & Tumor Immunol, Robert W Franz Canc Res Ctr, Earle A Chiles Res Inst, Portland, OR 97213 USA. Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, OGI Sch Sci & Technol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Oregon Canc Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. NCI, Data Management Serv, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Fox, BA (reprint author), Providence Portland Med Ctr, Lab Mol & Tumor Immunol, Robert W Franz Canc Res Ctr, Earle A Chiles Res Inst, 4805 NE Glisan St, Portland, OR 97213 USA. RI Winter, Hauke/I-1394-2013 OI Winter, Hauke/0000-0001-8911-6218 FU NCI NIH HHS [R01 CA 80964, R01 CA080964] NR 54 TC 27 Z9 29 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAR PY 2003 VL 108 IS 3 BP 409 EP 419 DI 10.1046/j.1365-2567.2003.01596.x PG 11 WC Immunology SC Immunology GA 649WE UT WOS:000181230300017 PM 12603608 ER PT J AU O'Bryan, L Pinkston, P Kumaraswami, V Vijayan, V Yenokida, G Rosenberg, HF Crystal, R Ottesen, EA Nutman, TB AF O'Bryan, L Pinkston, P Kumaraswami, V Vijayan, V Yenokida, G Rosenberg, HF Crystal, R Ottesen, EA Nutman, TB TI Localized eosinophil degranulation mediates disease in tropical pulmonary eosinophilia SO INFECTION AND IMMUNITY LA English DT Article ID RESPIRATORY-TRACT INFLAMMATION; BRONCHOALVEOLAR LAVAGE; GRANULE PROTEINS; CATIONIC PROTEINS; CELLS; RELEASE; AIRWAYS; ASTHMA; FLUID; STIMULATION AB To explore the mechanisms underlying the eosinophil-mediated inflammation of tropical pulmonary eosinophilia (TPE), bronchoalveolar lavage (BAL) fluid, serum, and supernatants from pulmonary and blood leukocytes (WBC) from patients with acute TPE (n = 6) were compared with those obtained from healthy uninfected individuals (n = 4) and from patients with asthma (n = 4) or elephantiasis (n = 5). Although there were no significant differences in the levels of interleukin-4 (IL-4), IL-5, IL-13, eotaxin, granulocyte-macrophage colony-stimulating factor, RANTES, or eosinophil cationic protein, there was a marked increase in eosinophil-derived neurotoxin (EDN) both systemically and in the lungs of individuals with TPE compared to each of the control groups (P < 0.02). Moreover, there was a compartmentalization of this response, with EDN levels being higher in the BAIL fluid than in the serum (P < 0.02). Supernatants from WBC from either whole blood or BAL cells were examined for chemokines, cytokines, eosinophil degranulation products, and arachidonic acid metabolites. Of the many mediators examined-particularly those associated with eosinophil trafficking-only EDN (in BAL fluid and WBC) and MIP-1alpha (in WBC) levels were higher for TPE patients than for the non-TPE control groups (P < 0.02). These data suggest it is the eosinophilic granular protein EDN, an RNase capable of damaging the lung epithelium, that plays the most important role in the pathogenesis of TPE. C1 NIAID, LPD, NIH, Bethesda, MD 20892 USA. TB Res Ctr, Madras, Tamil Nadu, India. RP Nutman, TB (reprint author), NIAID, LPD, NIH, 4 Ctr Dr,Room 4-B1-03, Bethesda, MD 20892 USA. EM tnutman@niaid.nih.gov NR 39 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2003 VL 71 IS 3 BP 1337 EP 1342 DI 10.1128/IAI.71.3.1337-1342.2003 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 650NU UT WOS:000181270900038 PM 12595450 ER PT J AU Harlander, RS Way, M Ren, Q Howe, D Grieshaber, SS Heinzen, RA AF Harlander, RS Way, M Ren, Q Howe, D Grieshaber, SS Heinzen, RA TI Effects of ectopically expressed neuronal Wiskott-Aldrich syndrome protein domains on Rickettsia rickettsii actin-based motility SO INFECTION AND IMMUNITY LA English DT Article ID WASP-FAMILY PROTEINS; ARP2/3 COMPLEX; N-WASP; SHIGELLA-FLEXNERI; LISTERIA-MONOCYTOGENES; INTRACELLULAR MOTILITY; DEPOLYMERIZING PROTEIN; FILOPODIUM FORMATION; VACCINIA VIRUS; VERO CELLS AB Neuronal Wiskott-Aldrich syndrome protein (N-WASP) and the actin-related protein 2/3 (Arp2/3) complex have emerged as critical host proteins that regulate pathogen actin-based motility. Actin tail formation and motility in Listeria monocytogenes require the Arp2/3 complex but bypasses N-WASP signaling. Motility of Shigella flexneri and vaccinia virus requires both N-WASP and the Arp2/3 complex. Functional roles for these cytoskeletal regulatory proteins in actin-based motility of Rickettsia rickettsii have not been established. In this study, functional domains of N-WASP tagged with green fluorescent protein that have characterized effects on Shigella and vaccinia virus actin-based motility were ectopically expressed in HeLa cells infected with R. rickettsii to assess their effects on rickettsial motility. S.flexneri-infected cells were used as a control. Expressed N-WASP domains did not localize to R. rickettsii or their actin tails. Expression of N-WASP missing the VCA domain (for "verprolin homology, cofilin homology, and acidic domains"), which acts as a dominant-negative form of N-WASP, completely inhibited actin-based motility of S. flexneri while only moderately inhibiting motility of R. rickettsii. Similarly, expression of the VCA domain, which acts as a dominant-negative with respect to Arp2/3 complex function, severely inhibited actin-based motility of S. flexneri (no motility observed in the majority of expressing cells) but only moderately inhibited R. rickettsii motility. These results, taken together with the differential effects on motility observed upon expression of other N-WASP domains, suggest that actin-based motility of R. rickettsii is independent of N-WASP and the Arp2/3 complex. C1 Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA. Canc Res UK, Cell Motil Lab, London, England. RP Heinzen, RA (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Hamilton, MT 59840 USA. FU NIAID NIH HHS [AI-43502] NR 42 TC 26 Z9 26 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2003 VL 71 IS 3 BP 1551 EP 1556 DI 10.1128/IAI.71.3.1551-1556.2003 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 650NU UT WOS:000181270900063 PM 12595475 ER PT J AU Zhou, P Li, EQ Zhu, N Robertson, J Nash, T Singer, SM AF Zhou, P Li, EQ Zhu, N Robertson, J Nash, T Singer, SM TI Role of interleukin-6 in the control of acute and chronic Giardia lamblia infections in mice SO INFECTION AND IMMUNITY LA English DT Article ID SURFACE-PROTEINS; MURIS INFECTION; LYMPHOCYTES; IMMUNOGLOBULIN AB In this study, we investigated the role of interleukin-6 (IL-6) in Giardia lamblia infections in mice. Elevated IL-6 expression was found in wild-type mice 15 days postinfection. Furthermore, IL-6-deficient mice controlled infections only slowly although normal immunoglobullin A production was observed. Thus, IL-6 is necessary for early control of acute G. lamblia infections. C1 Georgetown Univ, Dept Biol, Washington, DC 20057 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Singer, SM (reprint author), Georgetown Univ, Dept Biol, Reiss Sci Bldg,Rm 307, Washington, DC 20057 USA. OI Singer, Steven/0000-0001-5719-7535 FU NIAID NIH HHS [AI-49565-01A1, R01 AI049565, R01 AI049565-01A1] NR 19 TC 46 Z9 47 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2003 VL 71 IS 3 BP 1566 EP 1568 DI 10.1128/IAI.71.3.1566-1568.2003 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 650NU UT WOS:000181270900066 PM 12595478 ER PT J AU O'Shaughnessy, EM Shea, YM Witebsky, FG AF O'Shaughnessy, EM Shea, YM Witebsky, FG TI Laboratory diagnosis of invasive mycoses SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID POLYMERASE-CHAIN-REACTION; MARROW TRANSPLANT RECIPIENTS; SEQUENCE-BASED AMPLIFICATION; STEM-CELL TRANSPLANTATION; BLOOD-STREAM INFECTIONS; HISTOPLASMA-CAPSULATUM; FUNGAL-INFECTIONS; ENZYME-IMMUNOASSAY; CIRCULATING GALACTOMANNAN; CRYPTOCOCCUS-NEOFORMANS AB Rising numbers of immunocompromised patients have led to an ever-increasing population at risk of invasive fungal disease. Much has been achieved in the laboratory diagnosis of these.; infections, such as advances in blood culture systems, and the development of new biochemical, antigen detection assays, and molecular methodologies. In an era of economic cutbacks in health care, future challenges include the development of cost-effective and technically simplified systems, which provide early detection and identification of common and emerging fungal pathogens. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Microbiol Serv, Bethesda, MD 20892 USA. RP O'Shaughnessy, EM (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Room 13N-240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 93 TC 11 Z9 12 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 2003 VL 17 IS 1 BP 135 EP + DI 10.1016/S0891-5520(02)00069-7 PG 25 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 672BK UT WOS:000182500800008 PM 12751264 ER PT J AU Groll, AH Gea-Banacloche, JC Glasmacher, A Just-Nuebling, G Maschmeyer, G Walsh, TJ AF Groll, AH Gea-Banacloche, JC Glasmacher, A Just-Nuebling, G Maschmeyer, G Walsh, TJ TI Clinical pharmacology of antifungal compounds SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID LIPOSOMAL AMPHOTERICIN-B; INVASIVE FUNGAL-INFECTIONS; ITRACONAZOLE ORAL SOLUTION; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; CANDIDA-ALBICANS; PULMONARY ASPERGILLOSIS; NEUTROPENIC PATIENTS; PRACTICE GUIDELINES; IMMUNOCOMPROMISED PATIENTS AB Prompted by the worldwide surge in fungal infections, the past decade has witnessed a considerable expansion in antifungal drug research. New compounds have entered the clinical arena, and major progress has been made in defining paradigms of antifungal therapies. This article provides an up-to-date review on the clinical pharmacology, indications, and dosage recommendations of approved and currently investigational therapeutics for treatment of invasive fungal infections in adult and pediatric patients. C1 Univ Munster, Med Ctr, Ctr Bone Marrow Transplantat, Infect Dis Res Program, D-48149 Munster, Germany. Univ Munster, Med Ctr, Dept Pediat Hematol Oncol, D-48149 Munster, Germany. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Bonn, Dept Internal Med 1, D-53121 Bonn, Germany. Univ Frankfurt, Dept Internal Med, Div Infect Dis, D-60590 Frankfurt, Germany. Univ Hosp Berlin, Charite, Dept Internal Med, Div Hematol & Oncol, D-13353 Berlin, Germany. NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. RP Groll, AH (reprint author), Univ Munster, Med Ctr, Ctr Bone Marrow Transplantat, Infect Dis Res Program, Domagkstr 9A, D-48149 Munster, Germany. NR 128 TC 79 Z9 87 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 2003 VL 17 IS 1 BP 159 EP + DI 10.1016/S0891-5520(02)00068-5 PG 34 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 672BK UT WOS:000182500800009 PM 12751265 ER PT J AU Roilides, E Lyman, CA Panagopoulou, P Chanock, S AF Roilides, E Lyman, CA Panagopoulou, P Chanock, S TI Immunomodulation of invasive fungal infections SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID COLONY-STIMULATING FACTOR; CHRONIC GRANULOMATOUS-DISEASE; BONE-MARROW TRANSPLANTATION; CANDIDA-ALBICANS INFECTION; STEM-CELL TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; PROPHYLACTIC GRANULOCYTE TRANSFUSIONS; ASPERGILLUS-FUMIGATUS HYPHAE; NEUTROPHIL-MEDIATED ACTIVITY; HEMATOPOIETIC GROWTH-FACTORS AB Genetic and acquired determinants increase the risk for invasive fungal infections. Modulation of host defenses by use mainly of hematopoietic growth factors and interferon-gamma has been supported by extensive in vitro and in vivo preclinical data. Limited clinical data suggest the use of a hematopoietic growth factor for prevention of fungal infections only in patients with very high risk for developing fungal infections. Hematopoietic growth factors, interferon-gamma, and granulocyte colony-stimulating factor-elicited granulocyte transfusions may be indicated in the management of refractory invasive fungal infections. C1 Aristotle Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, GR-54642 Thessaloniki, Greece. NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. RP Roilides, E (reprint author), Aristotle Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, Konstantinoupoleos 49, GR-54642 Thessaloniki, Greece. NR 137 TC 21 Z9 22 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 2003 VL 17 IS 1 BP 193 EP + DI 10.1016/S0891-5520(02)00070-3 PG 28 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 672BK UT WOS:000182500800010 PM 12751266 ER PT J AU Ramalho-Ortigao, JM Traub-Cseko, YM AF Ramalho-Ortigao, JM Traub-Cseko, YM TI Molecular characterization of Llchit1, a midgut chitinase cDNA from the leishmaniasis vector Lutzomyia longipalpis SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE leishmaniasis; L. longipalpis; chitinase; peritrophic matrix; RT-PCR ID PERITROPHIC MATRIX; PLASMODIUM-GALLINACEUM; PARASITE CHITINASE; MOSQUITO MIDGUT; SANDFLY VECTOR; BOMBYX-MORI; FLY; TRANSMISSION; GENE; CLONING AB During development within the midgut of the sand fly vector, Leishmania parasites after undergoing differentiation and multiplication must escape the peritrophic matrix (PM). Although Leishmania chitinase is believed to take part in promoting the escape of the parasite from the PM by inducing degradation of chitin fibers, it is conceivable that a sand fly-derived chitinase can also have a role in such an event. Here we describe the molecular cloning and partial characterization of a complete cDNA from a putative gut-specific, blood-induced chitinase from the sand fly vector Lutzomyia longipalpis. Llchit1 has an ORF of 1425 bp that encodes a predicted 51.6 kDa mature protein showing high similarity with chitinases from several different organisms. Messenger RNA expression studies indicate that Llchit1 is detected only in the blood fed midgut and it seems to reach a peak at approximately 72 h post blood meal (PBM). To date, only one midgut-specific chitinase from an insect disease vector, AgChi-1 from Anopheles gambiae, has been characterized. As with its mosquito counterpart, Llchit1] can be a target for development of a transmission blocking vaccine. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Fiocruz MS, Inst Oswaldo Cruz, Dept Bioquim & Biol Mol, Lab Biol Mol Tripanosomatideos & Flebotomineos, BR-22461900 Rio De Janeiro, Brazil. RP Ramalho-Ortigao, JM (reprint author), NIAID, Intracellular Parasite Biol Sect, Parasit Dis Lab, NIH, 4 Ctr Dr,Bldg 4,Room 126,MSC-0425, Bethesda, MD 20892 USA. RI Ramalho-Ortigao, Marcelo/E-8225-2011; Traub-Cseko, Yara/F-2723-2015 NR 28 TC 38 Z9 41 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD MAR PY 2003 VL 33 IS 3 BP 279 EP 287 DI 10.1016/S0965-1748(02)00209-6 PG 9 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 654NM UT WOS:000181503000001 PM 12609513 ER PT J AU Oredipe, OA Furbert-Harris, PM Laniyan, I Green, WR White, SL Olden, K Parish-Gause, D Vaughn, T Griffin, WM Sridhar, R AF Oredipe, OA Furbert-Harris, PM Laniyan, I Green, WR White, SL Olden, K Parish-Gause, D Vaughn, T Griffin, WM Sridhar, R TI Enhanced proliferation of functionally competent bone marrow cells in different strains of mice treated with swainsonine SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE swainsonine; immunomodulation; colony forming units-granulocyte-macrophage (CFU-GM); colony forming units-granulocyte-erythrocyte-monocyte-megakaryocyte (CFU-GEMM or CFU-Mix); erythroid-burst forming units (BFUe) ID COLONY-STIMULATING FACTOR; BREAST-CANCER; ANTIMETASTATIC IMMUNOMODULATOR; ALPHA-MANNOSIDASE; DOSE INTENSITY; CHEMOTHERAPY; MURINE; INHIBITION; TUMOR; MALIGNANCIES AB The immunomodulatory alkaloid swainsonine (8alphabeta-indolizidine-1alpha,2alpha,8beta-triol) has potential for overcoming the bone marrow suppressive effects of cancer chemotherapy and radiotherapy. An earlier study showed that multiple doses of swainsonine enhanced bone marrow cellularity in four different strains (C57BL/6; C3H-HEN; Balb/C and DBA-2 mice) of inbred mice which were not exposed to any chemotherapeutic agents or radiation. In vitro assessment of total colony formation capacity of bone marrow cells (BM CFUs) showed a 2- to 8-fold increase in swainsonine-treated mice compared to control mice that were given sham injections of physiological saline. In the current study, we have evaluated the functional competence of the bone marrow cells produced in response to swainsonine treatment of normal healthy mice. In particular, colony forming units-granulocyte-macrophage (CFU-GM), erythroid-burst forming units (BFUe) and CFU-Mix (or CFU-granulocyte-erythrocyte-monocyte-megakaryocyte (CFU-GEMM)) levels, were determined using in vitro assays. The time course of the changes in CFU-GM, BFUe and CFU-Mix (CFU-GEMM) were also followed. Our results demonstrate that swainsonine bolsters the CFU capacity of BM cells without loss of function to levels which are several folds higher than in sham-treated control mice. Swainsonine treatment caused an increase in all lineages of marrow cells without loss of function. This effect was reproduced in all four strains of inbred mice in this investigation. Examination of the peripheral blood did not reveal increase in white blood cells or changes in the hematocrit levels. The long-term effects of swainsonine treatment are not known at present. Nonetheless, swainsonine-induced increase in CFU capacity of bone marrow cells and related cells along the different differentiation paths should find clinical application in cancer treatment with chemotherapeutic agents and/or radiation. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Howard Univ, Ctr Canc, Coll Med, Dept Pharmacol, Washington, DC 20060 USA. Howard Univ, Dept Microbiol, Coll Med, Washington, DC 20060 USA. Howard Univ, Dept Pathol, Coll Med, Washington, DC 20060 USA. N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Howard Univ, Dept Radiat Oncol, Coll Med, Washington, DC 20060 USA. RP Oredipe, OA (reprint author), Howard Univ, Ctr Canc, Coll Med, Dept Pharmacol, 2041 Georgia Ave NW, Washington, DC 20060 USA. NR 37 TC 14 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD MAR PY 2003 VL 3 IS 3 BP 445 EP 455 DI 10.1016/S1567-5769(03)00042-0 PG 11 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 663YM UT WOS:000182034900018 PM 12639822 ER PT J AU Debrabant, A Lee, N Bertholet, S Duncan, R Nakhasi, HL AF Debrabant, A Lee, N Bertholet, S Duncan, R Nakhasi, HL TI Programmed cell death in trypanosomatids and other unicellular organisms SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Review DE programmed cell death; unicellular organisms; multicellular organisms; parasites; cellular growth; anti parasitic drugs ID LEISHMANIA-DONOVANI PROMASTIGOTES; YEAST SACCHAROMYCES-CEREVISIAE; CYTOCHROME-C RELEASE; APOPTOSIS-LIKE DEATH; PARASITE LEISHMANIA; DNA FRAGMENTATION; ESCHERICHIA-COLI; OXIDATIVE STRESS; MAMMALIAN-CELLS; NITRIC-OXIDE AB In multicellular organisms. cellular growth and development can be controlled by programmed cell death (PCD). which is defined by a sequence of regulated events. However, PCD is thought to have evolved not only to regulate growth and development in multicellular organisms but also to have a functional role in the biology of unicellular organisms. In protozoan parasites and in other unicellular organisms. features of PCD similar to those in multicellular organisms have been reported. suggesting some commonality in the PCD pathway between unicellular and multicellular organisms. However er. more extensive Studies are needed to fully characterise the PCD pathway and to define the factors that control PCD in the unicellular organisms. The understanding of the PCD pathway in unicellular organisms Could delineate the evolutionary origin of this pathway . Further characterisation of the PCD pathway the unicellular parasites Could provide information regarding their pathogenesis, which could be exploited to target new drugs to limit their growth and treat the disease they cause. Published by Elsevier Science Ltd. on behalf of Australian Society for Parasitology Inc. C1 US FDA, OBRR, CBER, DETTD,Lab Bacterial Parasit & Unconvent Agents, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Nakhasi, HL (reprint author), US FDA, OBRR, CBER, DETTD,Lab Bacterial Parasit & Unconvent Agents, HFM-310,Bldg 29,Room 222,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 76 TC 112 Z9 117 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD MAR PY 2003 VL 33 IS 3 BP 257 EP 267 DI 10.1016/S0020-7519(03)00008-0 PG 11 WC Parasitology SC Parasitology GA 669PF UT WOS:000182359100003 PM 12670511 ER PT J AU Tambs, K Hoffman, HJ Borchgrevink, HM Holmen, J Samuelsen, SO AF Tambs, K Hoffman, HJ Borchgrevink, HM Holmen, J Samuelsen, SO TI Hearing loss induced by noise, ear infections, and head injuries: results from the Nord-Trondelag Hearing Loss Study SO INTERNATIONAL JOURNAL OF AUDIOLOGY LA English DT Article DE hearing loss; noise; ear infections; head injury ID PERSONAL CASSETTE PLAYERS; POP MUSIC; IMPAIRMENT; ADULTS; EPIDEMIOLOGY; PREVALENCE; EXPOSURE; WORKERS; DAMAGE AB Pure-tone audiometry was administered to the adult population in Nord-Trondelag County, Norway, 1995-97. The 51975 participants also provided questionnaire information about occupational and leisure noise exposure, previous car infections, and head injury. Values averaged over both ears were calculated for low (250 and 500 Hz), middle (1 and 2 kHz) and high frequencies (3, 4, 6 and 8 kHz). The aim was to estimate the magnitude of hearing loss associated with various types of exposure by age and sex. Noise, car infections and head injury explained 1-6% of the variance in hearing loss (varying with age, sex, and frequency range), in addition to what could be explained by age alone (30-58%). Only moderate effects of noise could be detected among women. The upper tenth percentile regarding occupational noise among men older than 44 years had on average an 8-9-dB high-frequency loss, adjusted for other predictors. Exposure to impulse noise (hunting, sports shooting) caused a 7-8-dB high-frequency loss in the same group. No significant effects of frequent use of personal stereo players or regular attendance at discotheques or rock concerts could be demonstrated. There were clear effects of recurrent ear infections and head injury. C1 Norwegian Inst Publ Hlth, Div Epidemiol, N-0403 Oslo, Norway. NIDCD, NIH, Bethesda, MD USA. Natl Hosp, Oslo, Norway. Univ Technol & Sci, Community Med Res Ctr, Verdal, Norway. Univ Oslo, Dept Math, Oslo, Norway. RP Tambs, K (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, POB 4404 Nydalen, N-0403 Oslo, Norway. FU NIDCD NIH HHS [N01-DC-6-2104] NR 29 TC 35 Z9 36 U1 0 U2 10 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1499-2027 J9 INT J AUDIOL JI Int. J. Audiol. PD MAR PY 2003 VL 42 IS 2 BP 89 EP 105 DI 10.3109/14992020309078340 PG 17 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 649UW UT WOS:000181227200004 PM 12641392 ER PT J AU Tanofsky-Kraff, M Morgan, CM Yanovski, SZ Marmarosh, C Wilfley, DE Yanovski, JA AF Tanofsky-Kraff, M Morgan, CM Yanovski, SZ Marmarosh, C Wilfley, DE Yanovski, JA TI Comparison of assessments of children's eating-disordered behaviors by interview and questionnaire SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE eating-disordered pathology; binge eating; assessment; interview; questionnaires ID X-RAY ABSORPTIOMETRY; SELF-REPORT QUESTIONNAIRE; ANOREXIA-NERVOSA; BODY-COMPOSITION; BULIMIA-NERVOSA; WEIGHT PATTERNS; ATTITUDES TEST; RELIABILITY; ADOLESCENT; ACCURACY AB Objective: In adults, interview methods may detect eating-disordered behaviors more accurately than self-report methods. However, no studies have investigated the relationships between interview and self-report assessments in children. We compared results from the Eating Disorder Examination adapted for Children (ChEDE) with the Adolescent version of the Questionnaire on Eating and Weight Patterns (QEWP-A) and with the Children's Eating Attitude Test (ChEAT) in a nontreatment sample of overweight and normal weight children. Method: The ChEDE, QEWP-A, and ChEAT were administered to 46 overweight (body mass index [BMI] at or above the 85th percentile) and 42 normal weight (BMI at the 15th-85th percentile) children, 10 +/- 1.8 years, recruited from the community. Results: The ChEDE and QEWP-A were not concordant for the number or type of eating episodes that occurred in the past month. Compared with the ChEDE, the QEWP-A was reasonably specific, but it was not sensitive for the presence of objective (17% sensitivity, 91% specificity) or subjective bulimic episodes (0% sensitivity, 89% specificity) during the past month. ChEDE and ChEAT global scores were significantly related (Kendall's tau = 0.286, p < .001), but specific items assessing guilt in relation to eating and preoccupation with food were not. Discussion: Although self-report methods of eating disorder assessment in children may provide some general information regarding eating psychopathology in non-treatment-seeking children, they do not accurately reflect the results of a structured interview. Published 2003 by Wiley Periodicals, Inc. C1 NICHHD, Unit Growth & Obest, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA. Univ Fed Sao Paulo, Dept Psiquiatria, Sao Paulo, Brazil. NIDDKD, Div Digest Dis & Nutr, Bethesda, MD USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO USA. US PHS, Bethesda, MD USA. Washington Univ, Sch Med, Dept Med, St Louis, MO USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO USA. Washington Univ, Sch Med, Dept Psychol, St Louis, MO USA. RP Yanovski, JA (reprint author), NICHHD, Unit Growth & Obest, Dev Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 10N262 MSC 1862, Bethesda, MD 20892 USA. EM JY15i@NIH.GOV OI Yanovski, Jack/0000-0001-8542-1637 FU NICHD NIH HHS [Z-01-HD-04-00641] NR 37 TC 32 Z9 33 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 EI 1098-108X J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAR PY 2003 VL 33 IS 2 BP 213 EP 224 DI 10.1002/eat.10128 PG 12 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 649QF UT WOS:000181218900012 PM 12616588 ER PT J AU Norman, JE Bild, D Lewis, CE Liu, K West, DS AF Norman, JE Bild, D Lewis, CE Liu, K West, DS TI The impact of weight change on cardiovascular disease risk factors in young black and white adults: the CARDIA study SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE weight gain; cardiovascular disease risk factors; young adults ID DENSITY-LIPOPROTEIN CHOLESTEROL; BLOOD-PRESSURE; CIGARETTE-SMOKING; MORTALITY; BOGALUSA; OBESITY; LIPIDS AB OBJECTIVE: To quantify the relation between weight change and change in blood pressure, lipids and insulin levels, and determine if this relation differs by race or initial level of obesity. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: Community-based sample of 3325 black and white men and women aged 18-30y from four centers followed for 10y. Women pregnant at baseline or 10th year exam and persons without a recorded weight at both exams were excluded. Participants whose baseline BMI was greater than or equal to25 kg/m(2) were classified as overweight. Height, weight, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), fasting triglycerides, fasting insulin, and blood pressure were measured at baseline and Year 10. RESULTS: The mean (s.d.) of weight gained over 10y was 10.5 (10.0) kg (black men), 11.7 (11.0) (black women), 7.7 (8.0) (white men), and 7.2 (10.0) (white women). An increase in weight was associated with adverse changes in all factors in all race-sex groups. For example, a 9.1 kg (20-lb) weight increase in persons not overweight at baseline predicted an increase in LDL-C ranging from 0.23 mmol/l in black women to 0.28 mmol/l in black men and a decrease in HDL-C from 0.09 mmol/l (white women) to 0.11 mmol/l (white men) (all P<0.0001). The estimated change in triglycerides was greater in white than in black participants (P<0.02); no other racial differences were found. Changes in triglycerides (P<0.00001) and fasting insulin (P = 0.004) were greater in men than in women. Only for LDL-C was a weight change-associated increase significantly different (greater, P<0.001) for nonoverweight persons than for those overweight at baseline. None of these associations were highly specific. Mean levels of LDL-C, HDL-C, and systolic blood pressure improved among all those who lost or did not gain weight. CONCLUSIONS: A 10y weight gain in young adults of both races and sexes tends to confer adverse changes in their levels of LDL-C, HDL-C, triglycerides, fasting insulin, and blood pressure. This effect occurs regardless of initial weight, age, race, or gender. C1 NHLBI, Rockledge Ctr 2, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Northwestern Univ, Chicago, IL 60611 USA. RP Norman, JE (reprint author), NHLBI, Rockledge Ctr 2, Div Epidemiol & Clin Applicat, 6701 Rockledge Dr,Room 8110, Bethesda, MD 20892 USA. NR 22 TC 90 Z9 90 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAR PY 2003 VL 27 IS 3 BP 369 EP 376 DI 10.1038/sj.ijo.802243 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 655TB UT WOS:000181567800012 PM 12629565 ER PT J AU Wallis, RS Kalayjian, R Jacobson, JM Fox, L Purdue, L Shikuma, CM Arakaki, R Snyder, S Coombs, RW Bosch, RJ Spritzler, J Chernoff, M Aga, E Myers, L Schock, B Lederman, TM AF Wallis, RS Kalayjian, R Jacobson, JM Fox, L Purdue, L Shikuma, CM Arakaki, R Snyder, S Coombs, RW Bosch, RJ Spritzler, J Chernoff, M Aga, E Myers, L Schock, B Lederman, TM TI Study of the immunology, virology, and safety of prednisone in HIV-1-infected subjects with CD4 cell counts of 200 to 700 mm(-3) SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE activation; AIDS pathogenesis; clinical trial; corticosteroids; apoptosis ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR NECROSIS FACTOR; HIV-1 INFECTION; HDL-CHOLESTEROL; T-LYMPHOCYTES; TYPE-1 RNA; PLASMA; ACTIVATION; OSTEONECROSIS; APOPTOSIS AB Adult Clinical Trials Group Study 349 examined the immunology, virology, and safety of 40 mg/d prednisone as an adjunct to antiretroviral therapy in 24 HIV-infected subjects with >200 CD4(+) T cells/mm(3) in a randomized placebo-controlled trial. After 8 weeks, median lymphocyte and CD4(+) cell numbers increased >40% above baseline values (p = .08). No effect was observed on markers of cell activation or apoptosis, although the proportion of CD28(+) CD8(+) T cells increased (p = .006). Prednisone inhibited monocyte TNFalpha production without affecting T-cell responses to antigens or mitogens. Two subjects assigned to prednisone were subsequently found to have asymptomatic osteonecrosis of the hip. Many questions remain regarding the role of activation-induced sequestration and apoptosis as causes of progressive CD4(+) T-cell loss in AIDS. The potential role of corticosteroids as tools to examine this question will be limited by concerns regarding their toxicity; however, further studies of other agents to limit cellular activation in AIDS are warranted. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. Metrohlth Med Ctr, Cleveland, OH USA. Mt Sinai Hosp, New York, NY 10029 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Univ Hawaii, Honolulu, HI 96822 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Harvard Univ, Sch Publ Hlth, Stat Data & Anal Ctr, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Wallis, RS (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, 185 S Orange Ave,MSB I-503, Newark, NJ 07103 USA. RI Wallis, Robert/A-8018-2009 OI Wallis, Robert/0000-0001-6152-5183 FU NCRR NIH HHS [M01 RR00080]; NIAID NIH HHS [AI 36219, AI 25879, AI 38858, AI 30731, AI 38855, AI 27664]; PHS HHS [A1 26879] NR 30 TC 32 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR PY 2003 VL 32 IS 3 BP 281 EP 286 DI 10.1097/00126334-200303010-00006 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 655NW UT WOS:000181559800006 PM 12626887 ER PT J AU Kim, HJ Jackson, T Noben-Trauth, K AF Kim, HJ Jackson, T Noben-Trauth, K TI Genetic analyses of the mouse deafness mutations varitint-waddler (Va) and jerker (Espt(je)) SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE deafness; modifying alleles; Cdh23; Espin; jerker; varitint-waddler ID INBRED STRAINS; HEARING-LOSS; HOUSE MOUSE; MICE; MODIFIER; LINKAGE; DYSFUNCTION; MUTAGENESIS; IMPAIRMENT; LOCUS AB Genetic studies on spontaneous mouse mutants with hearing defects have provided important insights into the function of genes expressed in inner ear hair cells. Here we report on our genetic analyses of the deaf mutants varitint-waddler (Va) and jerker (Espn(je)). A high-resolution genetic map localizes Va(J) to a 0.14 +/- 0.08 cM region between D3Mit85 and D3Mit259 on distal chromosome 3. By comparative mapping, the human ortholog resides at 1p22.3 between markers D1S3449 and D1S2252. To study the effect of different genetic backgrounds on the hearing phenotype, Espn(je) and Va(J) were crossed to various inbred strains. Auditory-evoked brainstem response tests on F2 progeny demonstrate that expression, inheritance, and penetrance of the hearing phenotype are solely controlled by the mutant allele. To test for a genetic interaction between Espn(je) and Cdh23(v), auditory function was analyzed in double heterozygotes; no significant increases of thresholds of sound pressure levels were observed. The results establish the framework for cloning the Va gene and provide valuable insights into the genetics of deafness mutations in the mouse. C1 Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, Rockville, MD 20850 USA. RP Noben-Trauth, K (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, 3800 Reservoir Rd NW, Rockville, MD 20850 USA. EM nobentk@nidcd.nih.gov FU NIDCD NIH HHS [DC00056-01] NR 32 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD MAR PY 2003 VL 4 IS 1 BP 83 EP 90 DI 10.1007/s10162-002-3011-0 PG 8 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 651PM UT WOS:000181329000007 PM 12209292 ER PT J AU Stanford, PD Monte, DA Briggs, FM Flynn, PM Tanney, M Ellenberg, JH Clingan, KL Rogers, AS AF Stanford, PD Monte, DA Briggs, FM Flynn, PM Tanney, M Ellenberg, JH Clingan, KL Rogers, AS TI Recruitment and retention of adolescent participants in HIV research: Findings from the REACH (Reaching for Excellence in Adolescent Care and Health) project SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE adolescents; REACH study; recruitment; retention; longitudinal study; HIV ID AFRICAN-AMERICANS; MEDICAL-RESEARCH; CLINICAL-TRIALS; UNITED-STATES; WILLINGNESS; LEGACY; COHORT; CITY; MEN AB Purpose: To evaluate the importance of 13 items in the recruitment and retention of HIV-positive and HIV-negative adolescent participants in a longitudinal study (REACH study). Methods: A confidential, self-administered, visual analog, cross-sectional survey was offered to active participants (November 1999-August 2000) with 438 subjects (86%) participating. Sixty-six percent of the cohort were HIV-positive and 34% were HIV-negative with a mean age of 17 years, and 76% were female. Subjects were asked to recall the importance they placed on 13 items in deciding to join the REACH study (recruitment) and to remain on study (retention). Factors that might explain the judgment placed on the items were analyzed using the nonparametric Wilcoxon Rank-Sum test or the Kruskall-Wallis test. Results: The five most important factors for study recruitment were identical to those chosen for retention by participants. The factors were: (a) quality medical care, (b) caring staff, (c) health education, (d) privacy/ confidentiality, and (e) altruism. Items judged least important were social activities, compensation, transportation, and food/meals. Subject characteristics (gender, age, HIV status) were not associated with statistically different mean judgment scores at recruitment and retention, although clinical site showed significant variation. Factors that could render subjects vulnerable (health insurance, family finances) were not associated with related items. Conclusions: Adolescents found quality health care and care team characteristics critically important in considering research participation. Attention to privacy and the opportunity to be altruistic were also important. Compensation for participation was not a significant factor for recruitment and retention of this adolescent cohort. This study demonstrates that adolescents apply sound criteria in evaluating research participation and do not appear to be unduly affected by compensation. (C) Society for Adolescent Medicine, 2003. C1 Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Univ Tennessee, Memphis, TN 38163 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. WESTAT Corp, Rockville, MD 20850 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Stanford, PD (reprint author), Univ Med & Dent New Jersey, Med Sci Bldg,Pediat F-580,185 S Orange Ave, Newark, NJ 07103 USA. EM stanfopd@umdnj.edu NR 34 TC 36 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD MAR PY 2003 VL 32 IS 3 BP 192 EP 203 AR PII S1054-139X(02)00392-0 DI 10.1016/S1054-139X(02)00392-0 PG 12 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 648KH UT WOS:000181150200005 PM 12606113 ER PT J AU Blehar, MC Keita, GP AF Blehar, MC Keita, GP TI Women and depression: a millennial perspective SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Blehar, MC (reprint author), NIMH, 6001 Execut Blvd,Rm 8125,MSC 9569, Bethesda, MD 20892 USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAR PY 2003 VL 74 IS 1 BP 1 EP 4 DI 10.1016/S0165-0327(02)00425-1 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 664XZ UT WOS:000182091200001 PM 12646293 ER PT J AU Tylavsky, F Lohman, T Blunt, BA Schoeller, DA Fuerst, T Cauley, JA Nevitt, MC Visser, M Harris, TB AF Tylavsky, F Lohman, T Blunt, BA Schoeller, DA Fuerst, T Cauley, JA Nevitt, MC Visser, M Harris, TB CA Hlth ABC Study TI QDR 4500A DXA overestimates fat-free mass compared with criterion methods SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE body composition; hydration of fat-free mass; four-component model of body composition; total body water; dual-energy X-ray absorptiometer ID X-RAY ABSORPTIOMETRY; BODY-COMPOSITION; BEAM DENSITOMETERS; PENCIL-BEAM; HYDRATION AB This study evaluated the accuracy with which the dual-energy X-ray absorptiometer (Hologic QDR 4500A) measured fat-free mass (FFM), fat mass (FM), and hydration of FFM. In a study of 58 men and women (ages 70-79 yr), the QDR 4500A was found to provide a systematically higher estimate of FFM and lower estimate of FM than a four-component model of body composition. A correction factor from this study was developed and applied to two other samples (n = 13 and 37). We found mean corrected levels of FFM and FM to be equivalent to that obtained by the four-component model or total body water. In addition, the hydration of the corrected FFM was closer to the established hydration level in adult samples and that obtained from the four-component model. These findings suggest that the current calibration of the fan-beam system of the Hologic QDR 4500A provides an overestimate of FFM and underestimate of FM compared with reference methods. C1 Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38105 USA. Univ Arizona, Dept Physiol, Tucson, AZ 85721 USA. PPD Dev Inc, Austin, TX 78704 USA. Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. Synarc Inc, San Francisco, CA 94105 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94105 USA. Univ Pittsburgh, Pittsburgh, PA 15261 USA. Vrije Univ Amsterdam, Med Ctr, Inst Res Extramural Med, NL-1081 BT Amsterdam, Netherlands. NIA, NIH, Bethesda, MD 20892 USA. RP Tylavsky, F (reprint author), Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, 66 N Pauline St,Suite 633, Memphis, TN 38105 USA. EM ftylavsky@utmem.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2102, N01-AG-6-2106] NR 16 TC 49 Z9 49 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 2003 VL 94 IS 3 BP 959 EP 965 DI 10.1152/japplphysiol.00732.2002 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 642WA UT WOS:000180827400017 PM 12433854 ER PT J AU Hirai, T Heymann, JAW Maloney, PC Subramaniam, S AF Hirai, T Heymann, JAW Maloney, PC Subramaniam, S TI Structural model for 12-helix transporters belonging to the major facilitator superfamily SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LINKING IN-SITU; THIOL CROSS-LINKING; LACTOSE PERMEASE; ESCHERICHIA-COLI; TRANSMEMBRANE SEGMENT-2; CONFORMATIONAL-CHANGES; SCANNING MUTAGENESIS; HELIX PROXIMITY; PROTEINS; PROKARYOTES AB The major facilitator superfamily includes a large collection of evolutionarily related proteins that have been implicated in the transport of a variety of solutes and metabolites across the membranes of organisms ranging from bacteria to humans. We have recently reported the three-dimensional structure, at 6.5 Angstrom resolution, of the oxalate transporter, OxIT, a representative member of this superfamily. In the oxalate-bound state, 12 helices surround a central cavity to form a remarkably symmetrical structure that displays a well-defined pseudo twofold axis perpendicular to the plane of the membrane as well as two less pronounced, mutually perpendicular pseudo twofold axes in the plane of the membrane. Here, we combined this structural information with sequence information from other members of this protein family to arrive at models for the arrangement of helices in this superfamily of transport proteins. Our analysis narrows down the number of helix arrangements from about a billion starting possibilities to a single probable model for the relative spatial arrangement for the 12 helices, consistent both with our structural findings and with the majority of previous biochemical studies on members of this superfamily. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. RP Subramaniam, S (reprint author), NCI, Biochem Lab, NIH, 50 S Dr,Room 4306,MSC 8008, Bethesda, MD 20892 USA. RI Hirai, Teruhisa/G-2105-2015 OI Hirai, Teruhisa/0000-0002-2114-8149 NR 32 TC 81 Z9 83 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 2003 VL 185 IS 5 BP 1712 EP 1718 DI 10.1128/JB.185.5.1712-1718.2003 PG 7 WC Microbiology SC Microbiology GA 648KU UT WOS:000181151200028 PM 12591890 ER PT J AU Trachtenberg, S Andrews, SB Leapman, RD AF Trachtenberg, S Andrews, SB Leapman, RD TI Mass distribution and spatial organization of the linear bacterial motor of Spiroplasma citri R8A2 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID POSTCOLUMN IMAGING FILTER; CYTOSKELETON; FIBRILS; FLORICOLA; ORGANISM; BIOLOGY AB In the simple, helical, wall-less bacterial genus Spiroplasma, chemotaxis and motility are effected by a linear, contractile motor arranged as a flat cytoskeletal ribbon attached to the inner side of the membrane along the shortest helical line. With scanning transmission electron microscopy and diffraction analysis, we determined the hierarchical and spatial organization of the cytoskeleton of Spiroplasma citri R8A2. The structural unit appears to be a fibril, similar to5 nm wide, composed of dimers of a 59-kDa protein; each ribbon is assembled from seven fibril pairs. The functional unit of the intact ribbon is a pair of aligned fibrils, along which pairs of dimers form tetrameric ring-like repeats. On average, isolated and purified ribbons contain 14 fibrils or seven well-aligned fibril pairs, which are the same structures observed in the intact cell. Scanning transmission electron microscopy mass analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified cytoskeletons indicate that the 59-kDa protein is the only constituent of the ribbons. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Membrane & Ultrastruct Res, IL-91120 Jerusalem, Israel. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NIH, Off Res Serv, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. RP Trachtenberg, S (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Membrane & Ultrastruct Res, POB 12272, IL-91120 Jerusalem, Israel. NR 29 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 2003 VL 185 IS 6 BP 1987 EP 1994 DI 10.1128/JB.185.6.1987-1994.2003 PG 8 WC Microbiology SC Microbiology GA 653QR UT WOS:000181448900026 PM 12618463 ER PT J AU Traicoff, JL Periyasamy, S Brattain, MG Grady, W Casey, G AF Traicoff, JL Periyasamy, S Brattain, MG Grady, W Casey, G TI Reconstitution of TGF-beta sensitivity in the VACO-411 human colon carcinoma line by somatic cell fusion with MCF-7 SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE transforming growth factor beta; signal transduction; cell fusions; complementation; colon ID GROWTH-FACTOR-BETA; II RECEPTOR; MICROSATELLITE INSTABILITY; CANCER CELLS; GENE; TUMORIGENICITY; INHIBITION; EXPRESSION; MALIGNANCY; ONCOGENES AB We characterized the mechanism of transforming growth factor beta (TGF-beta) resistance in the VACO-411 human colon carcinoma line. VACO-411 is unique for several reasons, including having a novel mutator phenotype and wild-type p53. Like many colon tumors, VACO-411 is not growth inhibited by TGF-beta. However, VACO-411 represents a subset of colon tumors that are resistant to TGF-beta-mediated growth inhibition, despite the expression of functional TGF-beta receptors. VACO-411 expresses cell surface TGF-beta receptor types I and II, and the coding regions of these receptors are wild type. To further characterize the nature of the VACO-411 defect, we fused VACO-411 with the human breast carcinoma line MCF-7. MCF-7 is also resistant to TGF-beta-mediated growth inhibition. However, unlike VACO-411, MCF-7 lacks cell surface expression of TGF-beta receptor type II, but does contain an intact postreceptor signaling pathway, as shown by regeneration of TGF-beta sensitivity following wild-type TGF-beta receptor type II transfection. In contrast to parental VACO-411 and MCF-7, the morphologically distinct cell hybrids were growth inhibited by TGF-beta. Therefore, the TGF-beta defect in VACO-411 is a postreceptor, loss-of-function mutation which can be genetically complemented. The data suggest that the VACO-411 defect in TGF-beta signaling will be able to be further complemented by microcell-mediated chromosome transfer. Copyright (C) 2003 National Science Council, ROC and S. Karger AG, Basel. C1 Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Ireland Canc Ctr, Cleveland, OH 44106 USA. Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. Med Coll Ohio, Dept Biochem & Mol Biol, Toledo, OH 43699 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Traicoff, JL (reprint author), NIH, 6701 Rockledge Dr,Room 4152,MSC 7804, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA67409, CA72160, P01 CA51183] NR 15 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD MAR-APR PY 2003 VL 10 IS 2 BP 253 EP 259 DI 10.1159/000068706 PG 7 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 653VH UT WOS:000181457400009 PM 12595761 ER PT J AU Ishima, R Torchia, DA AF Ishima, R Torchia, DA TI Extending the range of amide proton relaxation dispersion experiments in proteins using a constant-time relaxation-compensated CPMG approach SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE chemical exchange; conformational change; NMR; CPMG; R-2 ID NMR-SPECTROSCOPY; CAVITY MUTANT; T4 LYSOZYME; CHEMICAL-EXCHANGE; CROSS-RELAXATION; SCALE DYNAMICS; SIDE-CHAINS; SENSITIVITY; PROTEASE; SEQUENCE AB Relaxation compensated constant-time Carr-Purcell-Meiboom-Gill relaxation dispersion experiments for amide protons are presented that detect mus-ms time-scale dynamics of protein backbone amide sites. Because of their ten-fold larger magnetogyric ratio, much shorter 180degrees pulses can be applied to H-1 than to N-15 spins; therefore, off-resonance effects are reduced and a wider range of effective rf fields can often be used in the case of H-1 experiments. Applications to [H-1-N-15]-ubiquitin and [H-1-N-15]-perdeuterated HIV-1 protease are discussed. In the case of ubiquitin, we present a pulse sequence that reduces artifacts that arise from homonuclear (3)J(H-N-H-alpha) coupling. In the case of the protease, we show that relaxation dispersion of both H-1 and N-15 spins provides a more comprehensive picture of slow backbone dynamics than does the relaxation dispersion of either spin alone. We also compare the relative merits of H-1 versus N-15 transverse relaxation measurements and note the benefits of using a perdeuterated protein to measure the relaxation dispersion of both spin types. C1 Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. RP Ishima, R (reprint author), Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. NR 18 TC 112 Z9 112 U1 0 U2 19 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD MAR PY 2003 VL 25 IS 3 BP 243 EP 248 DI 10.1023/A:1022851228405 PG 6 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 654PD UT WOS:000181504500006 PM 12652136 ER PT J AU de Beur, SMJ O'Connell, JR Peila, R Cho, J Deng, ZC Kam, S Levine, MA AF de Beur, SMJ O'Connell, JR Peila, R Cho, J Deng, ZC Kam, S Levine, MA TI The pseudohypoparathyroidism type 1b locus is linked to a region including GNAS1 at 20q13.3 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE pseudohypoparathyroidism; linkage analysis; GNAS1; genetic imprinting; G protein ID ALBRIGHTS HEREDITARY OSTEODYSTROPHY; PEPTIDE RECEPTOR GENE; STIMULATORY G-PROTEIN; XL-ALPHA-S; PARATHYROID-HORMONE; DEOXYRIBONUCLEIC-ACID; CHROMOSOME 20Q13.3; ADENYLYL CYCLASE; LINKAGE ANALYSIS; SUBUNIT AB Pseudohypoparathyroidism (PHP) is characterized by biochemical hypoparathyroidism with elevated parathyroid hormone levels owing to reduced target tissue responsiveness to parathyroid hormone. Patients with PHP la have somatic defects termed Albright's hereditary osteodystrophy (AHO) and exhibit resistance to additional hormones because of heterozygous mutations in the GNAS1 gene that lead to a generalized deficiency of the alpha subunit of G(s), the heterotrimeric G protein that couples receptors to adenylyl cyclase. By contrast, patients with PHP 1b lack AHO, and have selective parathyroid hormone (PTH) resistance, presumably because of an imprinting defect that impairs expression of G(s)alpha in the proximal renal tubule. Although an epigenetic defect in GNAS1 has been identified in subjects with PHP1b, the genetic defect is unknown. To define the genetic defect in PBP 1b, we performed a genome-wide linkage analysis in five multi-generational PHP 1b families. Of the 408 polymorphic microsatellite markers examined, markers located on chromosome 20q13.3, the region containing GNAS1, demonstrated linkage to PHP 1b. Fine-mapping and multipoint linkage analysis of this region demonstrated linkage to a 5.7-cM region between 907rep2 and the telomere. Haplotype analysis established that affected individuals shared a 5-cM region including part of the GNAS1 gene to the telomere. Our data confirm that PBP1b is linked to a region that includes GNAS1, and further refine the locus, although the primary genetic mutation(s) that causes defective imprinting of GNAS1 remains undefined. C1 Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Dept Med, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Ilyssa Ctr Mol & Cellular Endocrinol, Baltimore, MD USA. Univ Pittsburgh, Dept Genet, Pittsburgh, PA USA. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. RP de Beur, SMJ (reprint author), Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Dept Med, 4940 Easten Ave,B114, Baltimore, MD 21224 USA. OI Levine, Michael/0000-0003-0036-7809 NR 44 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2003 VL 18 IS 3 BP 424 EP 433 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 648YC UT WOS:000181178400006 ER PT J AU Agelli, M AF Agelli, M TI Clarification of differing requirements for two NCI R25 grant mechanisms SO JOURNAL OF CANCER EDUCATION LA English DT Editorial Material C1 NCI, Training Branch, Bethesda, MD 20892 USA. RP Agelli, M (reprint author), NCI, Training Branch, Bethesda, MD 20892 USA. EM ma215e@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2003 VL 18 IS 1 BP 4 EP 5 DI 10.1207/S15430154JCE1801_4 PG 2 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 776MR UT WOS:000189120200002 PM 12825625 ER PT J AU Canto, MT Drury, TE Horowitz, AM AF Canto, MT Drury, TE Horowitz, AM TI Oral cancer examinations among US Hispanics in 1998 SO JOURNAL OF CANCER EDUCATION LA English DT Article ID UNITED-STATES; KNOWLEDGE; NECK; HEAD; RISK AB Background. An oral cancer examination (OCE) is crucial for early detection of oral and pharyngeal cancers. The objectives of this study were: 1) to estimate the percentages of Hispanics and Hispanic subgroups who reported having an OCE in the past 12 months; 2) to compare these groups with various Non-Hispanics; and 3) to evaluate the extents to which having an OCE might be explained by age, gender, education, family income, a recent visit to a dentist, and edentulism. Methods. Descriptive and logistic regression analyses using data from the 1998 National Health Interview Survey. Results. 6.4% of Hispanics and 14.5% of non-Hispanics had had an OCE in the past 12 months. After adjusting for age, gender, education, income, a dental visit, and edentulism, Hispanics were 1.7 times less likely than non-Hispanics to have had an OCE in the past 12 months. Conclusions. Fewer Hispanics are receiving OCEs relative to Non-Hispanics. C1 NIDCR, NIH, DHHS, Div Hlth Promot & Populat Sci, Bethesda, MD 20892 USA. RP Canto, MT (reprint author), NIDCR, NIH, DHHS, Div Hlth Promot & Populat Sci, 45 Ctr Dr,Bldg 45,Room 4AS43B, Bethesda, MD 20892 USA. EM maria.canto@nih.gov NR 16 TC 5 Z9 5 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2003 VL 18 IS 1 BP 48 EP 52 DI 10.1207/S15430154JCE1801_15 PG 5 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 776MR UT WOS:000189120200011 PM 12825635 ER PT J AU Faden, AI Knoblach, SM Cernak, I Fan, L Vink, R Araldi, GL Fricke, ST Roth, BL Kozikowski, AP AF Faden, AI Knoblach, SM Cernak, I Fan, L Vink, R Araldi, GL Fricke, ST Roth, BL Kozikowski, AP TI Novel diketopiperazine enhances motor and cognitive recovery after traumatic brain injury in rats and shows neuroprotection in vitro and in vivo SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE TRH analogs; neuroprotection; traumatic brain injury; necrosis; apoptosis ID THYROTROPIN-RELEASING-HORMONE; CONTROLLED CORTICAL IMPACT; SPINAL-CORD INJURY; MAGNETIC-RESONANCE SPECTROSCOPY; NEURONAL CELL-DEATH; FREE MAGNESIUM; DOSE-RESPONSE; TRH; APOPTOSIS; MODEL AB The authors developed a novel diketopiperazine that shows neuroprotective activity in a variety of in vitro models, as well as in a clinically relevant experimental model of traumatic brain injury (TBI) in rats. Treatment with 1-ARA-35b (35b), a cyclized dipeptide derived from a modified thyrotropin-releasing hormone (TRH) analog, significantly reduced cell death associated with necrosis (maitotoxin), apoptosis (staurosporine), or mechanical injury in neuronalglial cocultures. Rats subjected to lateral fluid percussion-induced TBI and then treated with 1 mg/kg intravenous 35b thirty minutes after trauma showed significantly improved motor recovery and spatial learning compared with vehicle-treated controls. Treatment also significantly reduced lesion volumes as shown by magnetic resonance imaging, and decreased the number of TUNEL-positive neurons observed in ipsilateral hippocampus. Unlike TRH or traditional TRH analogs, 35b treatment did not change mean arterial pressure, body temperature, or thyroid- stimulating hormone release, and did not have analeptic activity. Moreover, in contrast to TRH or typical TRH analogs, 35b administration after TBI did not alter free-magnesium concentration or cellular bioenergetic state. Receptor-binding studies showed that 35b did not act with high affinity at 50 classical receptors, channels, or transporters. Thus, 35b shows none of the typical physiologic actions associated with TRH, but possesses neuroprotective actions in vivo and in vitro, and appears to attenuate both necrotic and apoptotic cell death. C1 Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. Case Western Reserve Univ, Sch Med, NIMH, Psychoact Drug Screening Program, Cleveland, OH 44109 USA. Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44109 USA. RP Faden, AI (reprint author), Georgetown Univ, Med Ctr, Dept Neurosci, 3970 Reservoir Rd NW,Room Ep-12, Washington, DC 20057 USA. RI Cernak, Ibolja/A-6399-2008; Roth, Bryan/F-3928-2010; Vink, Robert/J-7351-2012 OI Vink, Robert/0000-0002-4885-0667 FU NIMH NIH HHS [K02 MH 01366]; NINDS NIH HHS [R01 NS 41119-01] NR 55 TC 60 Z9 60 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2003 VL 23 IS 3 BP 342 EP 354 DI 10.1097/01.WCB.0000046143.31247.FD PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 652VH UT WOS:000181401200009 PM 12621309 ER PT J AU Yamakawa, H Jezova, M Ando, H Saavedra, JM AF Yamakawa, H Jezova, M Ando, H Saavedra, JM TI Normalization of endothelial and inducible nitric oxide synthase expression in brain microvessels of spontaneously hypertensive rats by angiotensin II AT(1) receptor inhibition SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE renin angiotensin system; angiotensin II receptor types; brain ischemia; cerebrovascular regulation; stroke; genetic hypertension ID SMOOTH-MUSCLE CELLS; CEREBRAL BLOOD-FLOW; ATHEROSCLEROTIC PLAQUES; TYPE-1 RECEPTOR; MESSENGER-RNA; GROWTH-FACTOR; NO SYNTHASE; ISCHEMIA; INFLAMMATION; ARTERIES AB Inhibition of angiotensin II AT(1) receptors protects against stroke, reducing the cerebral blood flow decrease in the periphery of the ischemic lesion. To clarify the mechanism, spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats were pretreated with the AT(1) receptor antagonist candesartan (0.3 mg . kg(-1) . d(-1)) for 28 days, a treatment identical to that which protected SHR from brain ischemia, and the authors studied middle cerebral artery (MCA) and common carotid morphology, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA), and protein expression in cerebral microvessels, principal arteries of the Willis polygon, and common carotid artery. The MCA and common carotid artery of SHR exhibited inward eutrophic remodeling, with decreased lumen diameter and increased media thickness when compared with WKY rats. In addition, there was decreased eNOS and increased iNOS protein and mRNA in common carotid artery, circle of Willis, and brain microvessels of SHR when compared with WKY rats. Both remodeling and alterations in eNOS and iNOS expression in SHR were completely reversed by long-term AT(1) receptor inhibition. The hemodynamic, morphologic, and biochemical alterations in hypertension associated with increased vulnerability to brain ischemia are fully reversed by AT(1) receptor blockade, indicating that AT(1) receptor activation is crucial for the maintenance of the pathologic alterations in cerebrovascular circulation during hypertension, and that their blockade may be of therapeutic advantage. C1 NIMH, DHHN, DIRP, Sect Pharmacol,Dept Hlth,NIH, Bethesda, MD 20892 USA. NIMH, DHHN, DIRP, Sect Pharmacol,Dept Human Serv,NIH, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, DHHN, DIRP, Sect Pharmacol,Dept Hlth,NIH, 10 Ctr Dr,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA. NR 47 TC 81 Z9 84 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2003 VL 23 IS 3 BP 371 EP 380 DI 10.1097/01.WCB.0000047369.05600.03 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 652VH UT WOS:000181401200012 PM 12621312 ER PT J AU Petridou, E Mantzoros, C Dessypris, N Koukoulomatis, P Addy, C Voulgaris, Z Chrousos, G Trichopoulos, D AF Petridou, E Mantzoros, C Dessypris, N Koukoulomatis, P Addy, C Voulgaris, Z Chrousos, G Trichopoulos, D TI Plasma adiponectin concentrations in relation to endometrial cancer: A case-control study in Greece SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ADIPOSE-SPECIFIC PROTEIN; POSTMENOPAUSAL WOMEN; INSULIN-RESISTANCE; DIABETES-MELLITUS; OBESITY; BINDING; RISK; CARCINOMA; HYPERINSULINEMIA AB Adiponectin is a hormone secreted exclusively by adipocytes, and obesity is an established risk factor for endometrial cancer. We have, thus, evaluated the association of adiponectin with the occurrence of endometrial cancer. Questionnaire information and blood samples were taken before treatment from 84 women with newly diagnosed, histologically confirmed endometrial cancer and 84 control women who were admitted for minor gynecologic problems, mainly pelvic prolapse. Adiponectin levels were measured by immunoassay. The results were analyzed through multiple logistic regression and controlled for known risk factors for endometrial cancer, leptin, as well as major components of the IGF system (IGF-I, IGF-II, and IGF-binding protein 3). Among control women, there was no significant association of adiponectin with age or parity. Although there was no association of adiponectin with endometrial cancer among women 65 yr or older, there was an inverse, fairly strong, and statistically significant inverse association among younger women. Among women younger than 65 yr, an increase of adiponectin by 1 SD was associated with a more than 50% reduction of the risk for endometrial cancer [odds ratio (OR) 0.44; 95% confidence interval (CI) 0.24-0.81], even after controlling for body mass index and other potential confounders. Among all women, the adjusted OR for a 1 SD increase in adiponectin was not significant (OR, 0.78; 95% Cl, 0.56-1.10) but was significant for a one quintile increase in adiponectin (OR, 0.74; 95% CI, 0.56-0.97). In women younger than 65 yr, among whom obesity represents a powerful risk factor for endometrial cancer, adiponectin is inversely and significantly related to the risk of this disease. This association is independent of possible effects of major components of the IGF system, leptin, body mass index, sociodemographic variables, and known endometrial cancer risk factors. Future studies are needed to prove causality and provide insight on both the mechanism of action of this hormone and its potential role in endometrial cancer. C1 Univ Athens, Sch Med, Dept Hyg & Epidemiol, GR-11527 Athens, Greece. Univ Athens, Sch Med, Dept Obstet & Gynecol 1, GR-11527 Athens, Greece. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol & Metab, Dept Internal Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Internal Med, Endocrinol Diabet & Hypertens Div, Boston, MA 02215 USA. NICHHD, Dept Pediat & Reprod Endocrinol, Bethesda, MD 20892 USA. Univ Athens, Sch Med, Ag Sophia Childrens Hosp, Dept Pediat 1, GR-11527 Athens, Greece. RP Petridou, E (reprint author), Univ Athens, Sch Med, Dept Hyg & Epidemiol, 75 Mikras Asias Str, GR-11527 Athens, Greece. EM epetrid@med.uoa.gr NR 32 TC 148 Z9 161 U1 0 U2 10 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2003 VL 88 IS 3 BP 993 EP 997 DI 10.1210/jc.2002-021209 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 655HR UT WOS:000181545700007 PM 12629074 ER PT J AU Gibril, F Chen, YJ Schrump, DS Vortmeyer, A Zhuang, ZP Lubensky, IA Reynolds, JC Louie, A Entsuah, LK Huang, K Asgharian, B Jensen, RT AF Gibril, F Chen, YJ Schrump, DS Vortmeyer, A Zhuang, ZP Lubensky, IA Reynolds, JC Louie, A Entsuah, LK Huang, K Asgharian, B Jensen, RT TI Prospective study of thymic carcinoids in patients with multiple endocrine neoplasia type 1 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; NEUROENDOCRINE TUMORS; METASTATIC GASTRINOMA; RADIATION-THERAPY; LONG-TERM; CLINICAL EXPRESSION; ALLELIC DELETIONS; CUSHINGS-SYNDROME; BONE METASTASES AB Little is known of the natural history of thymic careinoids in multiple endocrine neoplasia type 1 (MEN1). This is important because in 1993 they were identified as a frequent cause of death, yet only small retrospective studies and case reports exist. We report results of a prospective study of 85 patients with MEN1 evaluated for pancreatic endocrine tumors and followed over a mean of 8 yr with serial chest computed tomography, magnetic resonance imaging (MRI), chest x-ray, and, since 1994, octreoscans [somatostatin receptor scintigraphy (SRS)]. Seven patients (8%) developed thymic carcinoids. Patients with and without carcinoids did not differ in clinical, laboratory, or MEN1 tumor features, except for male gender and the presence of a gastric carcinoid. All thymic tumors were hormonally inactive. Four thymic carcinoids lacked 11q loss of heterozygosity, although it was found in three pancreatic endocrine tumors. Computed tomography and/or MRI were more sensitive than SRS or chest x-ray in detecting tumors initially or with recurrence. All patients underwent resection of the thymic carcinoid, and in all patients followed more than 1 yr, the tumor recurred. Bone metastases developed in two patients and were detected early only on MRI, not SRS. This study provides information on early thymic carcinoids and allows modifications of existing guidelines to be recommended for their diagnosis, surveillance, and treatment. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Thorac Oncol Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. NINDS, Mol Pathogenesis Unit, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov NR 98 TC 99 Z9 104 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2003 VL 88 IS 3 BP 1066 EP 1081 DI 10.1210/jc.2002-021314 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 655HR UT WOS:000181545700020 PM 12629087 ER PT J AU Zhu, WZ Wang, SQ Chakir, K Yang, DM Zhang, T Brown, JH Devic, E Kobilka, BK Cheng, HP Xiao, RP AF Zhu, WZ Wang, SQ Chakir, K Yang, DM Zhang, T Brown, JH Devic, E Kobilka, BK Cheng, HP Xiao, RP TI Linkage of beta(1)-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of Ca2+/calmodulin kinase II SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ADRENERGIC-RECEPTOR SUBTYPES; RAT VENTRICULAR MYOCYTES; MOUSE CARDIAC MYOCYTES; BETA(2)-ADRENERGIC RECEPTOR; ADENYLYL-CYCLASE; TRANSGENIC MICE; PHOSPHOLAMBAN PHOSPHORYLATION; PATHWAY; FAILURE; CALCIUM AB beta(1)-adrenergic receptor (beta(1)AR) stimulation activates the classic cAMP/protein kinase A (PKA) pathway to regulate vital cellular processes from the change of gene expression to the control of metabolism, muscle contraction, and cell apoptosis. Here we show that sustained beta(1)AR stimulation promotes cardiac myocyte apoptosis by activation of Ca2+/calmodulin kinase II (CaMKII), independently of PKA signaling. PAR-induced apoptosis is resistant to inhibition of PKA by a specific peptide inhibitor, PKI14-22, or an inactive cAMP analogue, Rp-8-CPT-cAMPS. In contrast, the beta(1)AR proapoptotic effect is associated with non-PKA-dependent increases in intracellular Ca2+ and CaMKII activity. Blocking the L-type Ca2+ channel, buffering intracellular Ca2+, or inhibiting CaMKII activity fully protects cardiac myocytes against beta(1)AR-induced apoptosis, and overexpressing a cardiac CaMKII isoform, CaMKII-deltaC, markedly exaggerates the beta(1)AR apoptotic effect. These findings indicate that CaMKII constitutes a novel PKA-independent linkage of beta(1)AR stimulation to cardiomyocyte apoptosis that has been implicated in the overall process of chronic heart failure. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. Stanford Univ, Ctr Med, Dept Med, Stanford, CA 94305 USA. Stanford Univ, Ctr Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. Peking Univ, Inst Cardiovasc Sci, Beijing, Peoples R China. RP Xiao, RP (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 50 TC 269 Z9 287 U1 1 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2003 VL 111 IS 5 BP 617 EP 625 DI 10.1172/JCI200316326 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 651XA UT WOS:000181346600010 PM 12618516 ER PT J AU Matsusue, K Haluzik, M Lambert, G Yim, SH Gavrilova, O Ward, JM Brewer, B Reitman, ML Gonzalez, FJ AF Matsusue, K Haluzik, M Lambert, G Yim, SH Gavrilova, O Ward, JM Brewer, B Reitman, ML Gonzalez, FJ TI Liver-specific disruption of PPAR gamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; GROWTH-FACTOR-I; ADIPOSE-TISSUE; GENE-EXPRESSION; INSULIN-RESISTANCE; PEROXISOME PROLIFERATORS; CHOLESTEROL EFFLUX; ACID SYNTHESIS; MOUSE-LIVER; ALPHA AB To elucidate the function of PPARgamma in leptin-deficient mouse (ob/ob) liver, a PPARgamma liver-null mouse on an ob/ob background, ob/ob-PPARgamma(fl/fl)AlbCre(+), was produced using a floxed PPARgamma allele, PPARgamma(fl/fl), and Cre recombinase under control of the albumin promoter (AlbCre). The liver of ob/ob-PPARgamma(fl/fl)AlbCre(+) mice had a deletion of exon 2 and a corresponding loss of full-length PPARgamma mRNA and protein. The PPARgamma-deficient liver in ob/ob mice was smaller and had a dramatically decreased triglyceride (TG) content compared with equivalent mice lacking the AlbCre transgene (ob/ob-PPARgamma(fl/fl)AlbCre(-)). Messenger RNA levels of the hepatic lipogenic genes, fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA desaturase-1, were reduced in ob/ob-PPARgamma(fl/fl)AlbCre(+) mice, and the levels of serum TG and FFA in ob/ob-PPARgamma(fl/fl)AlbCre(+) mice were significantly higher than in the control ob/ob-PPARgamma(fl/fl)AlbCre(-) mice. Rosiglitazone treatment exacerbated the fatty liver in ob/ob-PPARgamma(fl/fl)AlbCre(-) mice compared with livers from nonobese Cre(-) mice; there was no effect of rosiglitazone in ob/ob-PPARgamma(fl/fl)AlbCre(+) mice. The deficiency of hepatic PPARgamma further aggravated the severity of diabetes in ob/ob mice due to decreased insulin sensitivity in muscle and fat. These data indicate that hepatic PPARgamma plays a critical role in the regulation of TG content and in the homeostasis of blood glucose and insulin resistance in steatotic diabetic mice. C1 NCI, Vet & Tumor Pathol Sect, Ctr Canc Res, NIH, Frederick, MD USA. NCI, Lab Metab, NIH, Frederick, MD USA. NIDDKD, Diabet Branch, NIH, Frederick, MD USA. NHLBI, Mol Dis Branch, NIH, Frederick, MD USA. RP Gonzalez, FJ (reprint author), NIH, Bldg 37,Rm 2A19, Bethesda, MD 20892 USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 53 TC 318 Z9 332 U1 1 U2 17 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2003 VL 111 IS 5 BP 737 EP 747 DI 10.1172/JCI200317223 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 651XA UT WOS:000181346600022 PM 12618528 ER PT J AU Corbet, S Bukh, J Heinsen, A Fomsgaard, A AF Corbet, S Bukh, J Heinsen, A Fomsgaard, A TI Hepatitis C virus subtyping by a core-envelope 1-based reverse transcriptase PCR assay with sequencing and its use in determining subtype distribution among Danish patients SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CHAIN-REACTION ASSAY; NUCLEOTIDE-SEQUENCE; GENETIC GROUPS; GENOTYPES; CLASSIFICATION; VARIANTS; REGIONS; RNA; INTERFERON-ALPHA-2B; HETEROGENEITY AB A reverse transcriptase PCR (RT-PCR) assay using conserved primers deduced from the core-envelope 1 (C-E1) region of the hepatitis C virus (HCV) genome was developed for subtyping purposes. The sensitivity and specificity of this assay tested against two HCV reference panels containing genotype 1 through 5 subtypes were similar to those of an RT-PCR assay from the 5'-untranslated region (5'-UTR). The sensitivity of the RT-PCR typing assay in the more variable C-E1 region was, however, lower than that of the RT-PCR in the highly conserved 5'-UTR when testing multiple clinical samples. Thus, 71 (88%) of 81 consecutive samples from hospitalized Danish patients positive for HCV antibodies and RNA (5'-UTR) were positive also in the C-E1 RT-PCR assay. Phylogenetic analysis of the El sequences obtained by direct sequencing of HCV from two reference panels and 71 Danish patients allowed us to readily distinguish the subtypes. In contrast, phylogenetic analysis of their corresponding 5'-UTR sequences was able to predict only major genotypes. Three different genotypes and four subtypes were identified among Danish samples: 1a (43%), 1b (11%), 2b (6%), and 3a (39%). An isolate from a Somalian refugee was identified as a new HCV type related to Somalian isolates described as subtype 3h. The most common genotype in Denmark is genotype 1 (53%), which is the most difficult to treat. However, Denmark had the highest prevalence in Europe of subtype 3a, which responds more favorably to treatment. The described C-E1 RT-PCR with sequencing is suggested as an easy routine assay for definitive genotyping and subtyping of HCV. C1 Statens Serum Inst, Dept Virol, DK-2300 Copenhagen, Denmark. DAKO, Copenhagen, Denmark. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Fomsgaard, A (reprint author), Statens Serum Inst, Dept Virol, 5 Artillerivej, DK-2300 Copenhagen, Denmark. NR 43 TC 46 Z9 48 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2003 VL 41 IS 3 BP 1091 EP 1100 DI 10.1128/JCM.41.3.1091-1100.2003 PG 10 WC Microbiology SC Microbiology GA 656PQ UT WOS:000181616500027 PM 12624035 ER PT J AU Van Der Zanden, AGM Koppele-Vije, EMT Bhanu, NV Van Soolingen, D Schouls, LM AF Van Der Zanden, AGM Koppele-Vije, EMT Bhanu, NV Van Soolingen, D Schouls, LM TI Use of DNA extracts from Ziehl-Neelsen-stained slides for molecular detection of rifampin resistance and spoligotyping of Mycobacterium tuberculosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LINE PROBE ASSAY; RPOB GENE-MUTATIONS; RAPID DETECTION; ANTIMYCOBACTERIAL ACTIVITIES; STRAIN DIFFERENTIATION; ASIAN COUNTRIES; PCR; SUSCEPTIBILITY; AMPLIFICATION; POLYMORPHISM AB Multidrug resistance among new cases of tuberculosis (TB) is increasingly becoming a significant problem in countries with a high prevalence of TB and with inadequate therapies for TB. Rifampin resistance is widely used as a marker for multidrug-resistant (MDR) TB; therefore, a new approach to the retrospective measurement of rifampin resistance without the need of a viable culture has been introduced. In many developing countries culture is unavailable and diagnosis relies on clinical manifestations and the results of Ziehl-Neelsen staining of sputum smears. We determined rifampin resistance directly with DNA extracts from Ziehl-Neelsen-stained slides by identification of mutations in the rpoB gene using reverse line blot hybridization and DNA sequencing. Analysis of the rpoB gene revealed that samples containing rifampin-resistant Mycobacterium tuberculosis carried altered codons representing amino acid positions 516, 526, and 531 of the RNA polymerase. Although the sensitivities of both methods were equal (84%), sequencing of the rpoB gene was more accurate in identifying mutations in the core region of the rpoB gene. Sequence analysis of the rpoB gene in extracts from Ziehl-Neelsen-stained slides may be used to quantify more precisely the magnitude of MDR TB and, more importantly, provide information on trends in the development of resistance on a global scale. The nature of rifampin resistance and the genotype can be determined by analysis of Ziehl-Neelsen-stained slides in a laboratory equipped for sequencing and spoligotyping without the need to ship biohazardous materials. C1 Gelre Hosp, NL-7300 DS Apeldoorn, Netherlands. Res Lab Infect Dis, Mycobacteria Reference Dept, Diagnost Lab Infect Dis & Perinatal Screening, Bilthoven, Netherlands. Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. RP Van Der Zanden, AGM (reprint author), Gelre Hosp, Locat Lukas,POB 9014,Albert Schweitzerlaan 31, NL-7300 DS Apeldoorn, Netherlands. NR 53 TC 47 Z9 53 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2003 VL 41 IS 3 BP 1101 EP 1108 DI 10.1128/JCM.41.3.1101-1108.2003 PG 8 WC Microbiology SC Microbiology GA 656PQ UT WOS:000181616500028 PM 12624036 ER PT J AU Johnston, PG Benson, AB Catalano, P Rao, MS O'Dwyer, PJ Allegra, CJ AF Johnston, PG Benson, AB Catalano, P Rao, MS O'Dwyer, PJ Allegra, CJ TI Thymidylate synthase protein expression in primary colorectal cancer: Lack of correlation with outcome and response to fluorouracil in metastatic disease sites SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADVANCED COLON-CANCER; CELL-LINES; CLINICAL-RESPONSE; PRIMARY TUMOR; 5-FLUOROURACIL; LEUCOVORIN; RESISTANCE; P53; CHEMOTHERAPY; QUANTITATION AB Purpose: The aim of this study was to investigate the utility of quantitating thymidylate synthase (TS) in the primary tumor as a surrogate for metastatic disease sites to predict the likelihood of response and outcome to fluorouracil (FU) treatment in patients with metastatic colorectal cancer. Methods: TS protein expression was evaluated using the TS 106 antibody and the avidin biotin labeling immunahistochemical technique in primary tumor samples from 219 patients with metastatic colorectal cancer. The patients were a representative sample of those patients enrolled into the Eastern Cooperative Oncology Group E2290 protocol that evaluated five separate FU-containing regimens in patients with metastatic residual or recurrent colorectal carcinoma. Results: Our retrospective analysis found that the level and extent of TS protein expression in the primary tumor did not correlate with overall survival in patients with metastatic or recurrent colorectal cancer. A trend toward a direct correlation between the level of TS protein expression and response was noted in tumors that expressed high TS levels. This response advantage for patients expressing high TS levels in the primary tumor was apparent regardless of what FU-based treatment the patient received but was most apparent in the subgroup treated with leucovorin, in which the level of TS expression and response to FU and leucovorin reached statistical significance (P = .034). No significant interaction could be detected between the addition of leucovorin to FU and the level of TS expression in the primary tumor. Conclusion: This study demonstrated that measurement of TS protein levels in the primary tumor tissue does not aid in predicting outcome or response to FU in a metastatic disease site. These assays must be performed on biopsy tissue from the metastatic disease site that is used to radiologically assess response and outcome to treatment. (C) 2003 by American Society of Clinical Oncology. C1 Queens Univ Belfast, Belfast City Hosp, Dept Oncol, Canc Res Ctr, Belfast BT9 7AB, Antrim, North Ireland. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Clin Invest Program, Chicago, IL 60611 USA. Dana Farber Canc Inst, Dept Biostat Sci, Eastern Cooperat Oncol Grp, Ctr Stat, Boston, MA 02115 USA. Northwestern Mem Hosp, Chicago, IL USA. Univ Penn, Philadelphia, PA 19104 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RP Johnston, PG (reprint author), Queens Univ Belfast, Belfast City Hosp, Dept Oncol, Canc Res Ctr, Univ Floor,97 Lisburn Rd, Belfast BT9 7AB, Antrim, North Ireland. NR 21 TC 64 Z9 69 U1 0 U2 0 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 MAR 1 PY 2003 VL 21 IS 5 BP 815 EP 819 DI 10.1200/JCO.2003.07.039 PG 5 WC Oncology SC Oncology GA 652FK UT WOS:000181369000012 PM 12610179 ER PT J AU Mandelblatt, JS Edge, SB Meropol, NJ Senie, R Tsangaris, T Grey, L Peterson, BM Hwang, YT Kerner, J Weeks, J AF Mandelblatt, JS Edge, SB Meropol, NJ Senie, R Tsangaris, T Grey, L Peterson, BM Hwang, YT Kerner, J Weeks, J TI Predictors of long-term outcomes in older breast cancer survivors: Perceptions versus patterns of care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LYMPH-NODE DISSECTION; BLACK-AND-WHITE; AXILLARY DISSECTION; CLINICAL-TRIAL; ELDERLY WOMEN; CARCINOMA; STAGE; COMORBIDITY; MORBIDITY; QUALITY AB Purpose: There are few data on sequelae, of breast cancer treatments in older women. We evaluated posttreatment quality of life and satisfaction in a national population. Patients and Methods: Telephone surveys were conducted with a random cross-sectional sample of 1,812 Medicare beneficiaries 67 years of age and older who were 3, 4, and 5 years posttreatment for stage I and II breast cancer. Regression models were used to estimate the adjusted risk of decrements in physical and mental health functioning by treatment. In a subset of women (n = 732), additional data were used to examine arm problems, impact of cancer, and satisfaction, controlling for baseline health, perceptions of ageism and racism, demographic and clinical factors, region, and surgery year. Results: Use of axillary dissection was the only surgical treatment that affected outcomes, increasing the risk of arm problems four-fold (95% confidence interval, 1.56 to 10.51), controlling for other factors. Having arm problems, in turn, exerted a consistently negative independent effect on all outcomes (P less than or equal to .001). Processes of care were also associated with quality of life and satisfaction. For example, women who perceived high levels of ageism or felt that they had no choice of treatment reported significantly more bodily pain, lower mental health scores, and less general satisfaction. These some factors, as well as high perceived racism, were significantly associated with diminished satisfaction with the medical care system. Conclusion: With the exception of axillary dissection, the processes of care, and not the therapy itself, are the most important determinants of long-term quality of life in older women. (C) 2003 by American Society of Clinical Oncology. C1 Lombardi Canc Ctr, Dept Oncol, Canc Control Program, Washington, DC 20007 USA. Georgetown Univ, Dept Surg, Sch Med, Washington, DC 20057 USA. Sibley Mem Hosp, Dept Surg, Washington, DC USA. Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10027 USA. Beth Israel Med Ctr, Dept Surg, New York, NY 10003 USA. SUNY Buffalo, Roswell Pk Canc Inst, Dept Surg, Buffalo, NY 14263 USA. Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. NCI, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Mandelblatt, JS (reprint author), Lombardi Canc Ctr, Dept Oncol, Canc Control Program, 223 Wisconsin Ave,Suite 317, Washington, DC 20007 USA. OI Kerner, Jon/0000-0002-8792-3830 FU AHRQ HHS [R01 HS 08395] NR 59 TC 88 Z9 88 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2003 VL 21 IS 5 BP 855 EP 863 DI 10.1200/JCO.2003.05.007 PG 9 WC Oncology SC Oncology GA 652FK UT WOS:000181369000018 PM 12610185 ER PT J AU Hyman, JJ Reid, BC AF Hyman, JJ Reid, BC TI Epidemiologic risk factors for periodontal attachment loss among adults in the United States SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE periodontal diseases/epidemiology; etiology; periodontal attachment loss; race; smoking; models; National Health and Nutrition Examination Survey III ID ALVEOLAR BONE LOSS; DIABETES-MELLITUS; OLDER ADULTS; ORAL HEALTH; DISEASE; SMOKING; INDICATORS; PREVALENCE; POPULATION; AGE AB Objectives: The objective of this study was to identify variables related to periodontal loss of attachment (LOA). Materials and Methods: The study population consisted of a nationally representative sample of 12,325 US adults who participated in the National Health and Nutrition Examination Survey III. The analyses used survey multinomial logistic regression to account for the complex survey design. Results: The adjusted odds ratio for a mean LOA of 3 mm or more associated with current smoking was 18.55 (95% CI 9.44-36.45) among 20-49-year olds. Among those aged 50 years or more, the odds ratio for a mean LOA of 4 mm or more was 25.64 (13.04-50.40). Prior smoking, untreated decayed surfaces (on both person and site levels), and male gender were also associated with LOA. There was no excess risk observed among non-Hispanic blacks or Mexican-Americans. The adjusted population attributable fractions due to current smoking were 60% for persons aged 20-49 with the worst 10% of LOA (1.58 mm or more), and 47% for those aged 50 plus (LOA of 3.39 mm or more). Conclusion: These results support earlier findings regarding the central role of cigarette smoking in the etiology of periodontal loss of attachment, a role due in large part to the substantial relationship between smoking and severe periodontal disease. C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. Univ Maryland, Sch Dent, Dept Oral Hlth Care Delivery, Baltimore, MD 21201 USA. RP Hyman, JJ (reprint author), Natl Inst Dent & Craniofacial Res, 45 Ctr Dr, Bethesda, MD 20892 USA. NR 32 TC 73 Z9 75 U1 1 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD MAR PY 2003 VL 30 IS 3 BP 230 EP 237 DI 10.1034/j.1600-051X.2003.00157.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 652UA UT WOS:000181397700009 PM 12631181 ER PT J AU Bonne, O Shemer, Y Hom, RC Gorali, Y Katz, M Shalev, AY AF Bonne, O Shemer, Y Hom, RC Gorali, Y Katz, M Shalev, AY TI A randomized, double-blind, placebo-controlled study of classical homeopathy in generalized anxiety disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CONTROLLED TRIALS; DILUTE ANTISERUM; CLINICAL-TRIALS; COMPLEMENTARY; MAINTENANCE; DEPRESSION; EFFICACY; MEDICINE; IGE AB Background: Homeopathy is commonly used for the treatment of medical and psychological conditions. Such prevalent use, however, is not supported by robust, methodologically sound research. This study evaluates the effect of homeopathic treatment in generalized anxiety disorder, a prevalent mental disorder characterized by an enduring pattern of excessive apprehension and distress and by mental and bodily complaints. Method: Forty-four patients with DSM-IV generalized anxiety disorder participated in a randomized, double-blind, placebo-controlled 10-week trial of individually tailored homeopathic remedy. Homeopathic therapy was administered by an expert who followed the traditional routines of homeopathic diagnosis and prescription. Thirty-nine subjects completed the study (20 in the active treatment group and 19 in the placebo group). Subjects' symptoms were rated before treatment and after 5 and 10 weeks of treatment, with the Hamilton Rating Scale for Anxiety (HAM-A) as main outcome measure. Additional measures of outcome included the Brief Symptom Inventory, the Psychological General Well-Being Index, the Hamilton Rating Scale for Depression, the Beck Depression Inventory, Spielberger's State-Trait Anxiety Inventory, and a Visual Analogue Scale of subjective distress. Results: Significant (p < .05) improvement in most measures, including the HAM-A, was observed in both the active treatment and placebo groups, yet no group effect was observed. Conclusion: The effect of homeopathic treatment on mental symptoms of patients with generalized anxiety disorder did not differ from that of placebo. The improvement in both conditions was substantial. Improvement of such magnitude may account for the current belief in the efficacy of homeopathy and the current increase in the use of this practice. C1 Hadassah Univ, Sch Med, Dept Psychiat, Jerusalem, Israel. Israeli Assoc Complementary Med, Tel Aviv, Israel. Hadassah Univ Hosp, Dept Psychiat, IL-91120 Jerusalem, Israel. RP Bonne, O (reprint author), NIMH, Mood & Anxiety Disorders Program, 15K North Dr,Room 200, Bethesda, MD 20892 USA. NR 39 TC 25 Z9 26 U1 7 U2 17 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 2003 VL 64 IS 3 BP 282 EP 287 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 662NU UT WOS:000181954600008 PM 12716269 ER PT J AU Lee, RE Protopopova, M Crooks, E Slayden, RA Terrot, M Barry, CE AF Lee, RE Protopopova, M Crooks, E Slayden, RA Terrot, M Barry, CE TI Combinatorial lead optimization of [1,2]-diamines based on ethambutol as potential antituberculosis preclinical candidates SO JOURNAL OF COMBINATORIAL CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; SHORT-COURSE CHEMOTHERAPY; MYCOBACTERIUM-TUBERCULOSIS; DRUG-RESISTANCE; ANTIMYCOBACTERIAL ACTIVITY; INFLUENZA; BIOSYNTHESIS; STRATEGY; STRAINS; AVIUM AB Despite relatively modest potency, ethambutol (EMB, (S,S)-[N,N-di-2-amino-1-butanol]ethylenediamine) is a mainstay of contemporary chemotherapy for the treatment of tuberculosis. We have developed a solid-phase synthesis of 1,2-diamine analogues of EMB using a novel acylation-reduction sequence that is compatible with high-throughput 96-well format chemistry. Using this procedure, we have synthesized 63 238 diamine analogues in pools of 10 that are suitable for testing. MIC and a target-based reporter assay were used to direct deconvolution of 2796 individual compounds from these mixtures, and the 69 most potent molecules were resynthesized in milligram quantities for hit confirmation. Purification of these individual active diamine analogues allowed the identification of 26 compounds with activity equal to or greater than EMB. Amines which occurred most frequently in active compounds included many with large hydrophobic moieties, suggesting that optimization was perhaps selecting for the isoprenoid binding site of the arabinosyltransferase target of EMB. N-Geranyl-N'-(2-adamantyl)ethane-1,2-diamine (109), the most active of these diamines, displayed a 14-35-fold improvement in activity in vitro against Mycobacterium tuberculosis, as compared to EMB. C1 NIAID, TB Res Sect, NIH, Rockville, MD 20850 USA. Sequella Inc, Rockville, MD 20850 USA. Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA. RP Barry, CE (reprint author), NIAID, TB Res Sect, Twinbrook 2,Rm 239,12441 Parklawn Dr, Rockville, MD 20852 USA. EM clifton_barry@nih.gov RI Barry, III, Clifton/H-3839-2012; Lee, Richard/J-4997-2013; Slayden, Richard/O-8626-2016 OI Lee, Richard/0000-0002-2397-0443; Slayden, Richard/0000-0001-6857-7277 FU Intramural NIH HHS [Z01 AI000693-15] NR 36 TC 155 Z9 163 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-4766 J9 J COMB CHEM JI J. Comb. Chem. PD MAR-APR PY 2003 VL 5 IS 2 BP 172 EP 187 DI 10.1021/cc020071p PG 16 WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary SC Chemistry; Pharmacology & Pharmacy GA 655DK UT WOS:000181535900015 PM 12625709 ER PT J AU Fackler, I DeClue, JE Rust, H Vu, PA Kutzner, H Rutten, A Kaddu, S Sander, CA Volkenandt, M Johnson, MW Vinters, HV Wienecke, R AF Fackler, I DeClue, JE Rust, H Vu, PA Kutzner, H Rutten, A Kaddu, S Sander, CA Volkenandt, M Johnson, MW Vinters, HV Wienecke, R TI Loss of expression of tuberin and hamartin in tuberous sclerosis complex-associated but not in sporadic angiofibromas SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-1; TSC2 PRODUCT TUBERIN; GENE-PRODUCT; HETEROZYGOSITY; REGION; ANGIOMYOLIPOMAS; COLOCALIZATION AB Background: Angiofibromas occur sporadically, and they develop in most patients with tuberous sclerosis complex (TSC), which is associated with alterations of the tumor suppressor genes TSC1 or TSC2. Loss of tuberin, the protein product of TSC2, has been shown in the interstitial fibroblast compartment of TSC-associated angiofibromas. It is unclear whether there is also a loss of hamartin, the product of TSC1 in TSC-associated and sporadic angiofibromas. Methods: The expression of hamartin and tuberin was analyzed by immunohistochemistry in 59 TSC-associated and 12 sporadic angiofibromas using affinity-purified antibodies. Results: Loss of expression of both tuberin and hamartin was detected in 14 angiofibromas, loss of only tuberin in three, and loss of only hamartin in four TSC-associated angiofibromas; but there was no loss in the sporadic angiofibromas. Only the interstitial cells, but not the vascular cells, showed a loss of expression of tuberin or hamartin. Conclusions: Loss of tuberin or hamartin occurred in a minority of the TSC-linked angiofibromas, but not in the sporadic angiofibromas. The absence of both tuberin and hamartin in some of the tumors suggests that the stability of tuberin and hamartin, which are believed to form an active complex in vivo , is negatively affected by the absence of either of the partners. C1 Univ Munich, Dept Dermatol, D-80337 Munich, Germany. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Dermatohisopathol Gemeinschaftspraxis, Friedrichshafen, Germany. Graz Univ, Dept Dermatol, Graz, Austria. Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. RP Wienecke, R (reprint author), Univ Munich, Dept Dermatol, Frauenlobstr 9-11, D-80337 Munich, Germany. NR 28 TC 5 Z9 6 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD MAR PY 2003 VL 30 IS 3 BP 174 EP 177 DI 10.1034/j.1600-0560.2003.2o066.x PG 4 WC Dermatology; Pathology SC Dermatology; Pathology GA 656WE UT WOS:000181633400002 PM 12641776 ER PT J AU Gastwirth, JL AF Gastwirth, JL TI Issues arising in using samples as evidence in trademark cases SO JOURNAL OF ECONOMETRICS LA English DT Article DE law and economics; sample evidence; sensitivity analysis; survey evidence; trademark litigation AB This article reviews the use of survey evidence in cases involving alleged infringement of trademarks. Because courts do not admit "hearsay" evidence, at first, courts were reluctant to accept evidence based on a sample or portion of the relevant population. Some early cases that led to the legal acceptance of samples and surveys are described. The role of survey evidence in a variety of types of trademark litigation, e.g., dilution or deceptive advertising are illustrated with data from actual cases. (C) 2002 Elsevier Science B.V. All rights reserved. C1 George Washington Univ, Dept Stat, Washington, DC 20052 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Gastwirth, JL (reprint author), George Washington Univ, Dept Stat, Funger Hall 315, Washington, DC 20052 USA. NR 32 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0304-4076 J9 J ECONOMETRICS JI J. Econom. PD MAR PY 2003 VL 113 IS 1 BP 69 EP 82 AR PII S0304-4076(02)00167-7 DI 10.1016/S0304-4076(02)00167-7 PG 14 WC Economics; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Business & Economics; Mathematics; Mathematical Methods In Social Sciences GA 648JJ UT WOS:000181147400005 ER PT J AU Takahashi, T Schoemaker, MJ Trott, KR Simon, SL Fujimori, K Nakashima, N Fukao, A Saito, H AF Takahashi, T Schoemaker, MJ Trott, KR Simon, SL Fujimori, K Nakashima, N Fukao, A Saito, H TI The relationship of thyroid cancer with radiation exposure from nuclear weapon testing in the Marshall islands SO JOURNAL OF EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 12th International Thyroid Congress CY OCT 22-27, 2000 CL KYOTO, JAPAN DE thyroid cancer; Marshall Islands; radioactive fallout; radiation exposure; bikini atoll AB The US nuclear weapons testing program in the Pacific conducted between 1946 and 1958 resulted in radiation exposure in the Marshall Islands. The potentially widespread radiation exposure from radio-iodines of fallout has raised concerns about the risk of thyroid cancer in the Marshallese population. The most serious exposures and its health hazards resulted from the hydrogen-thermonuclear bomb test, the Castle BRAVO, on March 1, 1954. Between 1993 and 1997, we screened 3,709 Marshallese for thyroid disease who were born before the BRAVO test. It was 60% of the entire population at risk and who were still alive at the time of our examinations. We diagnosed 30 thyroid cancers and found 27 other study participants who had been operated for thyroid cancer before our screening in this group. Fifty-seven Marshallese born before 1954 (1.5%) had thyroid cancer or had been operated for thyroid cancer. Nearly all (92%) of these cancers were papillary carcinoma. We derived estimates of individual thyroid dose proxy from the BRAVO test in 1954 on the basis of published age-specific doses estimated on Utirik atoll and Cs-137 deposition levels on the atolls where the participants came from. There was suggestive evidence that the prevalence of thyroid cancer increased with category of estimated dose to the thyroid. C1 Yamagata Univ, Sch Med, Dept Publ Hlth, Yamagata 9909585, Japan. NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. Tohoku Univ, Grad Sch Med, Div Surg Oncol, Sendai, Miyagi 980, Japan. Nagasaki Univ, Sch Med, Dept Social Med, Nagasaki, Japan. RP Takahashi, T (reprint author), Yamagata Univ, Sch Med, Dept Publ Hlth, 2-2-2,Iidanishi, Yamagata 9909585, Japan. NR 23 TC 22 Z9 25 U1 2 U2 12 PU JAPAN EPIDEMIOLOGICAL ASSOC PI TOCHIGI PA JICHI MEDICAL SCHOOL, DEPT PUBLIC HEALTH, 3311-1 YAKUSHIJI, MINAMIKAWACH, TOCHIGI, 329-0498, JAPAN SN 0917-5040 J9 J EPIDEMIOL JI J. Epidemiol. PD MAR PY 2003 VL 13 IS 2 BP 99 EP 107 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 735BU UT WOS:000186093200006 PM 12675119 ER PT J AU Sutherland, R Pipe, ME Schick, K Murray, J Gobbo, C AF Sutherland, R Pipe, ME Schick, K Murray, J Gobbo, C TI Knowing in advance: The impact of prior event information on memory and event knowledge SO JOURNAL OF EXPERIMENTAL CHILD PSYCHOLOGY LA English DT Article DE memory development; event representation; preparation; knowledge and memory ID LONG-TERM RETENTION; CHILDRENS MEMORY; POSTEVENT INFORMATION; EXPERIENCE; REPRESENTATIONS; SUGGESTIBILITY; PARTICIPATION; TESTIMONY; RECALL AB We examined the influence of newly acquired information on children's memory and general representation of a personally experienced event. Thirty-five children between the ages of 5 and 7 years participated in the novel event (Visiting the Pirate). The day before participating, children were: (1) provided with new information specific to the up-coming event; (2) engaged in a discussion generally related to the event topic based on existing knowledge; or (3) discussed an unrelated topic. Advance information specific to the event led to better recall and, in particular, to better integration of the experience into a general event representation both soon after the event and at a follow-up interview 4 months later, whereas general discussion of the topic without the event specific information neither enhanced memory reports nor facilitated the integration of event information. Providing information in advance can have significant effects on memory and knowledge acquisition although many variables, including those relating to the specific content of the information, will affect this relation. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD 20892 USA. Univ Padua, Padua, Italy. RP Pipe, ME (reprint author), NICHHD, Sect Social & Emot Dev, Rockledge 1 Ctr,Suite 8048,6705 Rockledge Dr, Bethesda, MD 20892 USA. NR 60 TC 21 Z9 21 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-0965 J9 J EXP CHILD PSYCHOL JI J. Exp. Child Psychol. PD MAR PY 2003 VL 84 IS 3 BP 244 EP 263 DI 10.1016/S0022-0965(03)00021-3 PG 20 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 670UX UT WOS:000182428500004 PM 12706386 ER PT J AU Strober, W Fuss, IJ Nakamura, K Kitani, A AF Strober, W Fuss, IJ Nakamura, K Kitani, A TI Recent advances in the understanding of the induction and regulation of mucosal inflammation SO JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the Japanese-Society-of-Gastroenterology CY APR 24-26, 2002 CL ASAHIKAWA, JAPAN SP Japanese Soc Gastroenterol DE inflammation; cytokine; regulatory cells ID GROWTH-FACTOR-BETA; CD4(+) T-CELLS; EXPERIMENTAL COLITIS; BOWEL-DISEASE; INTESTINAL INFLAMMATION; MURINE COLITIS; CROHNS-DISEASE; ORAL TOLERANCE; TGF-BETA; MICE C1 NIAID, Mucosal Immun Sect, Clin Invest Lab, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, Bethesda, MD 20892 USA. NR 27 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0944-1174 J9 J GASTROENTEROL JI J. Gastroenterol. PD MAR PY 2003 VL 38 SU 15 BP 55 EP 58 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 662VF UT WOS:000181969000015 PM 12698873 ER PT J AU Tewari, D Notkins, AL Zhou, P AF Tewari, D Notkins, AL Zhou, P TI Inhibition of HIV-1 replication in primary human T cells transduced with an intracellular anti-HIV-1 P17 antibody gene SO JOURNAL OF GENE MEDICINE LA English DT Article DE intracellular antibody; AIDS/HIV; primary T lymphocytes; gene therapy ID IMMUNODEFICIENCY-VIRUS TYPE-1; SINGLE-CHAIN ANTIBODY; PERIPHERAL-BLOOD LYMPHOCYTES; FIBRONECTIN FRAGMENTS; REVERSE-TRANSCRIPTASE; RETROVIRAL VECTORS; GROWTH ADVANTAGE; PROTECTIVE GENE; LEUKEMIA-VIRUS; CD34(+) CELLS AB Background Previously we reported that human CD4(+) T cell lines stably expressing anti-HIV-1 gag p17 scFv/Ckappa in the cytosol or nucleus were resistant to HIV-1 challenge. Inhibition of HIV-1 by anti-HIV-1 gag p17 scFv/Ckappa occurred at both the pre- and post-integration steps of the viral cycle. To simulate more closely the in vivo infection process, in this study we tested anti-HIV-1 activity of anti-HIV-1 gag p17 scFv/Ckappa in primary human T cells. Methods Anti-HIV-1 gag p17 scFv/Ckappa gene that is targeted into cytoplasm was inserted into a MMLV vector and transfected into packaging cell line PT67. The recombinant virus was used to transduce primary human T cells and human CD4(+) T cell line Jurkat. Following transduction, transduction efficiency, transgene expression, and cell phenotypes were studied. Transduced cells were then challenged with 100 TCID50 of HIV-1 IIIB and primary isolate 5AO12. Following challenge, HIV-1 replication was monitored by p24 production. Results Both transduced Jurkat and primary human T cells expressed the transgene. The expression of the transgene did not alter cell growth and CD4 or CD8 expression. However, HIV-1 replication in scFv/Ckappa-transduced Jurkat cells was inhibited by nearly 90% as compared with vector controls. More importantly, HIV-1 replication in primary human T cells from multiple donors transduced with the anti-HIV-1 gag p17 scFv/Ckappa gene was inhibited by as much as 99% as compared with primary T cells transduced with the vector control. The inhibition of replication was not due to interference in viral entry or reverse transcription. The less that HIV-1 replicated in different donor cells, the higher the degree of protection. Conclusions The expression of the anti-HIV-1 gag p17 scFv/Ckappa gene construct in primary human T cells renders these cells resistant to HIV-1 and points to the potential clinical usefulness of this gene construct for anti-HIV-1 gene therapy. Published in 2003 by John Wiley Sons, Ltd. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, Expt Med Sect, NIH, Bethesda, MD 20892 USA. RP Zhou, P (reprint author), SW Fdn Biomed Res, Dept Virol & Immunol, San Antonio, TX 78245 USA. NR 41 TC 10 Z9 11 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAR PY 2003 VL 5 IS 3 BP 182 EP 189 DI 10.1002/jgm.336 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 662WU UT WOS:000181972700002 PM 12666184 ER PT J AU Boyer, J Kutzler, M Robinson, T Choo, A Chattergoon, M Muthumani, K Calarota, S Otero, M Lewis, M Schadeck, EB Sidhu, M Egan, MA Pavlakis, G Israel, Z Eldridge, J Weiner, DB AF Boyer, J Kutzler, M Robinson, T Choo, A Chattergoon, M Muthumani, K Calarota, S Otero, M Lewis, M Schadeck, EB Sidhu, M Egan, MA Pavlakis, G Israel, Z Eldridge, J Weiner, DB TI Th1 plasmid cytokine enhancement of RNA optimized plasmid DNA vaccine potency suggests attainment of an important milestone in DNA vaccine development with importance for the clinic SO JOURNAL OF GENE MEDICINE LA English DT Meeting Abstract CT 2nd International Symposium on Molecular Diagnostics and Skin Gene therapy CY MAR 27-29, 2003 CL DUSSELDORF, GERMANY C1 Univ Penn, Philadelphia, PA 19104 USA. Wyeth Ayerst Res, Dept Viral Vaccines Immunol, Pearl River, NY 10965 USA. NCI, Frederick, MD 21701 USA. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAR PY 2003 VL 5 IS 3 BP S30 EP S31 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 662WU UT WOS:000181972700099 ER PT J AU Pfuetzner, W Terunuma, A Tock, CL Taichman, L Vogel, JC AF Pfuetzner, W Terunuma, A Tock, CL Taichman, L Vogel, JC TI Topical colchicine selection of keratinocytes transduced with the multidrug resistance gene (MDR1) can sustain and enhance transgene expression in vivo SO JOURNAL OF GENE MEDICINE LA English DT Meeting Abstract CT 2nd International Symposium on Molecular Diagnostics and Skin Gene therapy CY MAR 27-29, 2003 CL DUSSELDORF, GERMANY C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAR PY 2003 VL 5 IS 3 BP S11 EP S11 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 662WU UT WOS:000181972700038 ER PT J AU Wang, E Panelli, MC Mocellin, S Marincola, FM AF Wang, E Panelli, MC Mocellin, S Marincola, FM TI What can we learn from gene profiling for classification and therapy of melanoma? SO JOURNAL OF GENE MEDICINE LA English DT Meeting Abstract CT 2nd International Symposium on Molecular Diagnostics and Skin Gene therapy CY MAR 27-29, 2003 CL DUSSELDORF, GERMANY C1 NIH, Immunogenet Lab, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAR PY 2003 VL 5 IS 3 BP S9 EP S10 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 662WU UT WOS:000181972700033 ER PT J AU Anishkin, A Gendel, V Sharifi, NA Chiang, CS Shirinian, L Guy, HR Sukharev, S AF Anishkin, A Gendel, V Sharifi, NA Chiang, CS Shirinian, L Guy, HR Sukharev, S TI On the conformation of the COOH-terminal domain of the large mechanosensitive channel MscL SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE amphipathic helix; coiled coil; MD simulation; disulfide trapping; channel gating ID SECONDARY STRUCTURE PREDICTION; MOLECULAR-DYNAMICS SIMULATIONS; ESCHERICHIA-COLI-CELLS; 5-STRANDED COILED-COIL; ION-CHANNEL; MYCOBACTERIUM-TUBERCULOSIS; POTASSIUM CHANNEL; SOLVATION PARAMETERS; CRYSTAL-STRUCTURE; PROTEIN-STRUCTURE AB COOH-terininal (S3) domains are conserved within the MscL family of bacterial mechanosensitive channels, but their function remains unclear. The X-ray structure of MscL from Mycobacterium tuberculosis (TbM-scL) revealed cytoplasmic domains forming a pentameric bundle (Chang, G., R.H. Spencer, A.T. Lee, M.T. Barclay, and D.C. Rees. 1998. Science. 282:2220-2226). The helices, however, have an unusual orientation in which hydrophobic sidechains face outside while charged residues face inside, possibly due to specific crystallization conditions. Based on the structure of pentameric cartilage protein, we modeled the COOH-terminal region of E. coli MscL to better satisfy the hydrophobicity criteria, with sidechains of conserved aliphatic residues all inside the bundle. Molecular dynamic simulations predicted higher stability for this conformation compared with one modeled after the crystal structure of TbMscL, and suggested distances for disulfide trapping experiments. The single cysteine mutants L121C and I125C formed dimers under ambient conditions and more so in the presence of an oxidant. The double-cysteine mutants, L121C/L122C and L128C/L129C, often cross-link into tetrameric and pentameric structures, consistent with the new model. Patch-clamp examination of these double mutants under moderately oxidizing or reducing conditions indicated that the bundle cross-linking neither prevents the channel from opening nor changes thermodynamic parameters of gating. Destabilization of the bundle by replacing conservative leucincs with small polar residues, or complete removal of COOH-terminal domain (Delta110-136 mutation), increased the occupancy of subconducting states but did not change gating parameters substantially The Delta110-136 truncation mutant was functional in in vivo osmotic shock assays; however, the amount of ATP released into the shock medium was considerably larger than in controls. The data strongly suggest that in contrast to previous gating models (Sukharev, S., M. Betanzos, C.S. Chiang, and H.R. Guy. 2001a. Nature. 409:720-724.), S3 domains are stably associated in both closed and open conformations. The bundle-like assembly of cytoplasmic helices provides stability to the open conformation, and may function as a size-exclusion filter at the cytoplasmic entrance to the MscL pore, preventing loss of essential metabolites. C1 Univ Maryland, Dept Biol, College Pk, MD 20742 USA. NCI, Lab Expt & Computat Biol, CCR, NIH, Bethesda, MD 20892 USA. RP Sukharev, S (reprint author), Univ Maryland, Dept Biol, Bldg 144, College Pk, MD 20742 USA. OI Sukharev, Sergei/0000-0002-4807-9665 FU NINDS NIH HHS [R01 NS039314, NS39314-01] NR 55 TC 52 Z9 57 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD MAR PY 2003 VL 121 IS 3 BP 227 EP 244 DI 10.1085/jgp.20028768 PG 18 WC Physiology SC Physiology GA 653QG UT WOS:000181447800004 PM 12601086 ER PT J AU Lips, KR Green, DE Papendick, R AF Lips, KR Green, DE Papendick, R TI Chytridiomycosis in wild frogs from southern Costa Rica SO JOURNAL OF HERPETOLOGY LA English DT Article ID POPULATION DECLINES; MORTALITY AB In 1993, the amphibian fauna of Las Tablas, Costa Rica, began to decline, and by 1998 approximately 50% of the species formerly present could no longer be found. Three years later, at the Reserva Forestal Fortuna, in western Panama, a site approximately 75 km east southeast of Las Tablas, KRL encountered a mass die-off of amphibians and a subsequent decline in abundance and species richness. The epidemiological features of the anuran population declines and die-offs at both sites were similar, suggesting a similar cause. Herein we document the presence of the fungus, Batrachochytrium dendrobatidis, in dead and dying wild frogs collected at Las Tablas just prior to population declines of several anuran species. C1 So Illinois Univ, Dept Zool, Carbondale, IL 62901 USA. NIH, ORS VRP, Bethesda, MD 20892 USA. Zool Soc San Diego, Dept Pathol, San Diego, CA 92112 USA. RP Lips, KR (reprint author), So Illinois Univ, Dept Zool, Carbondale, IL 62901 USA. OI Lips, Karen/0000-0002-2719-1551 NR 6 TC 73 Z9 88 U1 0 U2 10 PU SOC STUDY AMPHIBIANS REPTILES PI ST LOUIS PA C/O ROBERT D ALDRIDGE, ST LOUIS UNIV, DEPT BIOLOGY, 3507 LACLEDE, ST LOUIS, MO 63103 USA SN 0022-1511 J9 J HERPETOL JI J. Herpetol. PD MAR PY 2003 VL 37 IS 1 BP 215 EP 218 DI 10.1670/0022-1511(2003)037[0215:CIWFFS]2.0.CO;2 PG 4 WC Zoology SC Zoology GA 731WX UT WOS:000185910400034 ER PT J AU Kim, K Khaled, AR Reynolds, D Young, HA Lee, CK Durum, SK AF Kim, K Khaled, AR Reynolds, D Young, HA Lee, CK Durum, SK TI Characterization of an interleukin-7-dependent thymic cell line derived from a p53(-/-) mouse SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE interieukin-7; IL-7; thymocyte; thymus; T cell development; apoptosis ID RECEPTOR-DEFICIENT MICE; ACUTE LYMPHOBLASTIC-LEUKEMIA; RESCUES T-LYMPHOPOIESIS; COMMON GAMMA-CHAIN; C-MYC EXPRESSION; FLT3 LIGAND; IL-7 RECEPTOR; IN-VIVO; PHOSPHATIDYLINOSITOL 3-KINASE; BCL-X AB In order to study the response of T cells to IL-7, we aimed to generate an IL-7-dependent thymocyte line. CD4(-)CD8(-)thymocytes from a p53(-)/(-) mouse were continuously propagated in interleukin-7 (IL-7), and after 2 months there developed an immortal line termed "D1." The D1 line has retained a stable dependency on IL-7. Withdrawal of IL-7 from D1 cells induced arrest in G1 phase of the cell cycle, followed by apoptosis. In addition to IL-7, several other cyrokines that employ gamma(e) as part of their receptor were also capable of stimulating D I cell survival and proliferation. Gene induction by IL-7 was analyzed in D1 cells using RNase protection and array analysis and revealed a number of transcripts potentially involved in cell cycle, apoptosis and signaling. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NCI, Mol Immunoregulat Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. NCI, Expt Immunol Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. RP Durum, SK (reprint author), NCI, Mol Immunoregulat Lab, Ctr Canc Res, Bldg 560,Rm 31-71, Ft Detrick, MD 21702 USA. NR 50 TC 34 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAR 1 PY 2003 VL 274 IS 1-2 BP 177 EP 184 AR PII S0022-1759(02)00513-6 DI 10.1016/S0022-1759(02)00513-6 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 654KN UT WOS:000181496200016 PM 12609543 ER PT J AU Roederer, M Koup, RA AF Roederer, M Koup, RA TI Optimized determination of T cell epitope responses SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE peptide; flow cytometry; immunogenicity ID HIV-1 INFECTION; FLOW-CYTOMETRY; CYTOMEGALOVIRUS; INDIVIDUALS AB Pools of overlapping peptides corresponding to specific antigens are frequently used to identify T cell immune responses to vaccines or pathogens. While the response to the entire pool of peptides provides important information, it is often desirable to also know to which individual peptides within the pool the immune responses are directed. In this report, we analyzed various ways of deconvoluting an immune response to a pool of peptides to determine the number of different peptides to which the T cells are responding. We used a Monte Carlo simulation to optimize the construction of peptide pools that could identify responses to individual peptides using the fewest numbers of assays and patient material. We find that the number of assays required to deconvolute a pool increases by the logarithm of the number of peptides within the pool; however, the optimum configuration of pools changes dramatically according to the number of responses to individual peptides that are expected to be in the sample. Our simulation will help in the design of clinical trials in which the breadth of the response is being measured, by allowing a calculation for the minimum amount of blood that needs to be collected. In addition, our results guide the design and implementation of the experiments to deconvolute the responses to individual peptide epitopes. (C) 2002 Elsevier Science B.V. All fights reserved. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Roederer, M (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA. RI Roederer, Mario/G-1887-2011 NR 10 TC 39 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAR 1 PY 2003 VL 274 IS 1-2 BP 221 EP 228 AR PII S0022-1759(02)00423-4 DI 10.1016/S0022-1759(02)00423-4 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 654KN UT WOS:000181496200020 PM 12609547 ER PT J AU Mazzoni, A Leifer, CA Mullen, GED Kennedy, MN Klinman, DM Segal, DM AF Mazzoni, A Leifer, CA Mullen, GED Kennedy, MN Klinman, DM Segal, DM TI Cutting edge: Histamine inhibits IFN-alpha release from plasmacytoid dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; INTERFERON-ALPHA; INFLUENZA-VIRUS; CPG-DNA; EXPRESSION; MONOCYTES; IMMUNITY; RESPOND; BLOOD AB Plasmacytoid dendritic cells (DC) are professional APC and a major source of type I IFN following viral infection. We previously showed that histamine alters the cytokine profiles of maturing monocyte-derived DC resulting in a change from Th1 to Th2 in their T cell polarizing function. In this study, we show that human plasmacytoid DC, activated by either CpG oligodeoxynucleotides or viral infection, also respond to histamine through H2 receptors, leading to a marked down-regulation of IFN-alpha and TNF-alpha and a moderate switch in their capacity to polarize naive T cells. Our findings provide an explanation for low levels of type I IFN frequently observed in atopic individuals. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Segal, DM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. NR 28 TC 54 Z9 59 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2003 VL 170 IS 5 BP 2269 EP 2273 PG 5 WC Immunology SC Immunology GA 648JD UT WOS:000181146800003 PM 12594246 ER PT J AU Doan, LL Kitay, MK Yu, Q Singer, A Herblot, S Hoang, T Bear, SE Morse, HC Tsichlis, PN Grimes, HL AF Doan, LL Kitay, MK Yu, Q Singer, A Herblot, S Hoang, T Bear, SE Morse, HC Tsichlis, PN Grimes, HL TI Growth factor independence-1B expression leads to defects in T cell activation, IL-7 receptor alpha expression, and T cell lineage commitment SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ZINC-FINGER PROTEIN; IN-VIVO; THYMOCYTE DIFFERENTIATION; NEGATIVE SELECTION; CD4(+)CD8(+) THYMOCYTES; DEFICIENT MICE; CD8 LINEAGE; GFI-1; BCL-2; INTERLEUKIN-7 AB T cell differentiation in the thymus is dependent upon signaling through the TCR and is characterized by the resulting changes in expression patterns of CD4 and CD8 surface coreceptor molecules. Although recent studies have characterized the effects of proximal TCR signaling on T cell differentiation, the downstream integration of these signals remains largely unknown. The growth factor independence-1 (GFI1) and GFI1B transcriptional repressors may regulate cytokine signaling pathways to affect lymphocyte growth and survival. In this study, we show that Gfi1 expression is induced upon induction of the T cell program. Gfi1B expression is low and dynamic during T cell development, but is terminated in mature thymocytes. Transgenic expression of GFI1 and GFI1B in T cells allowed us to determine the functional consequences of constitutive expression. GFI1 potentiates response to TCR stimulation and IL-2, whereas GFI1B-transgenic T cells are defective in T cell activation. Moreover, GFI1B-transgenic thymocytes display reduced expression of the late-activation marker IL-7Ralpha, and a decrease in CD4(-)8(+) single-positive T cells that can be mitigated by transgenic expression of BCL2 or GFI1. These data show that GFI1 and GFI1B are functionally unique, and implicate a role for GFI1 in the integration of activation and survival signals. C1 Univ Louisville, Inst Cellular Therapeut, Sch Med, Louisville, KY 40202 USA. Univ Louisville, Sch Med, Dept Surg, Louisville, KY 40202 USA. NCI, Dept Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. Clin Res Inst Montreal, Montreal, PQ H2W 1R7, Canada. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Tufts New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. RP Grimes, HL (reprint author), Univ Louisville, Inst Cellular Therapeut, Sch Med, Baxter Biomed Res Bldg,Suite 404-F,570 S Preston, Louisville, KY 40202 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [CA56110] NR 42 TC 43 Z9 44 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2003 VL 170 IS 5 BP 2356 EP 2366 PG 11 WC Immunology SC Immunology GA 648JD UT WOS:000181146800015 PM 12594258 ER PT J AU Williams, KL Zullo, AJ Kaplan, MH Brutkiewicz, RR Deppmann, CD Vinson, C Taparowsky, EJ AF Williams, KL Zullo, AJ Kaplan, MH Brutkiewicz, RR Deppmann, CD Vinson, C Taparowsky, EJ TI BATF transgenic mice reveal a role for activator protein-1 in NKT cell development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KILLER T-CELLS; NATURAL-KILLER; TRANSCRIPTION FACTORS; DEFICIENT MICE; CUTTING EDGE; NEGATIVE REGULATOR; B-ATF; AP-1; EXPRESSION; LYMPHOCYTES AB The importance of regulated AP-1 activity during T cell development was assessed using transgenic mice overexpressing BATF, a basic leucine zipper transcription factor and an AP-1 inhibitor. BATF transgenic animals possess normal thymic cellularity and all major T cell subsets, but show impaired thymocyte proliferation in vitro and no induction of IL-2, IL-4, IL-5, IL-10, and IL-13 expression. Since NKT cells are largely responsible for cytokine production in the thymus, this population was examined by detection of the Valpha14-Jalpha281 TCR, flow cytometry of NK1.1(+) TCRbeta(+) cells, and analysis of cytokine production by heat-stable Ag-low thymocytes and peripheral NKT cells stimulated in vivo. Results show a severe under-representation of NKT cells in BATF transgenic animals, providing the first evidence that the precise control of AP-1-mediated transcription is critical for the proper emergence of thymus-derived NKT cells in the mouse. C1 Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA. NIH, Biochem Lab, Bethesda, MD 20892 USA. RP Taparowsky, EJ (reprint author), Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. EM ejt@bilbo.bio.purdue.edu FU NCI NIH HHS [CA78264]; NIAID NIH HHS [AI45515, AI46455]; NIGMS NIH HHS [T32GM08298] NR 48 TC 35 Z9 38 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2003 VL 170 IS 5 BP 2417 EP 2426 PG 10 WC Immunology SC Immunology GA 648JD UT WOS:000181146800022 PM 12594265 ER PT J AU Kinter, AL Umscheid, CA Arthos, J Cicala, C Lin, Y Jackson, R Donoghue, E Ehler, L Adelsberger, J Rabin, RL Fauci, AS AF Kinter, AL Umscheid, CA Arthos, J Cicala, C Lin, Y Jackson, R Donoghue, E Ehler, L Adelsberger, J Rabin, RL Fauci, AS TI HIV envelope induces virus expression from resting CD4(+) T cells isolated from HIV-infected individuals in the absence of markers of cellular activation or apoptosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; BLOOD MONONUCLEAR-CELLS; FOCAL ADHESION KINASE; MACROPHAGE-TROPIC HIV; CROSS-LINKING; TYPE-1 RNA; REPLICATION; INDUCTION; SIGNAL AB Resting CD4(+) T cells containing integrated HIV provirus constitute one of the long-lived cellular reservoirs of HIV in vivo. This cellular reservoir of HIV had been thought to be quiescent with regard to virus replication based on the premise that HIV production in T cells is inexorably linked to cellular activation as determined by classical activation markers. The transition of T cells within this HIV reservoir from a resting state to an activated HIV-producing state is believed to be associated with a shorten life span due to susceptibility to activation-associated apoptosis. Evidence is mounting, however, that HIV production may occur in T cells that have not undergone classic T cell activation. HIV encodes several proteins, including envelope and Nef, which trigger a variety of signaling pathways associated with cellular activation, thereby facilitating HIV replication in nondividing cells. The present study demonstrates that production of infectious virus from resting CD4(+) T cells isolated from HIV-infected individuals can be induced following exposure of these cells to HIV-1 recombinant (oligomeric gp140) envelope protein. Envelope-mediated induction of HIV expression occurs in the presence of reverse transcriptase inhibitors and is not associated with markers of classic T cell activation, proliferation, or apoptosis. The ability of HIV envelope to induce virus replication in HIV-infected resting CD4(+) T cells without triggering apoptosis provides a mechanism for the virus itself to directly participate in the maintenance of HIV production from this cellular reservoir. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, AIDS Monitoring Lab, Frederick, MD 21702 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Kinter, AL (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A17,10 Ctr Dr,MSC-1576, Bethesda, MD 20892 USA. FU PHS HHS [N01-C012400] NR 44 TC 41 Z9 42 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 MAR 1 PY 2003 VL 170 IS 5 BP 2449 EP 2455 PG 7 WC Immunology SC Immunology GA 648JD UT WOS:000181146800026 PM 12594269 ER PT J AU Oh, S Hodge, JW Ahlers, JD Burke, DS Schlom, J Berzofsky, JA AF Oh, S Hodge, JW Ahlers, JD Burke, DS Schlom, J Berzofsky, JA TI Selective induction of high avidity CTL by altering the balance of signals from APC SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; CELL-RECEPTOR AFFINITY; PULSED DENDRITIC CELLS; IN-VITRO; IMMUNODOMINANT EPITOPE; PROTECTIVE IMMUNITY; FUNCTIONAL AVIDITY; ANTIGEN; PEPTIDE; COSTIMULATION AB High avidity CTL are most effective at clearing viruses and cancer cells. Therefore, understanding the mechanisms involved in induction of high avidity CTL is critical for effective vaccines. However, no vaccine approach to selectively induce high avidity CTL in vivo has been discovered. In a new approach, signals from MHC class I (signal 1) and costimulatory molecules (signal 2) were adjusted by varying Ag dose and by use of recombinant poxvirus expressing a triad of costimulatory molecules (B7-1, ICAM-1, and LFA-3), respectively. Independent of CTL avidity, a strong signal I resulted in an increased frequency of CD8(+) CTL. However, a strong signal 2 was necessary for the induction of high avidity CD8(+) CTL that killed target cells more efficiently, and signal 2 played a more crucial role in the absence of a strong signal 1. Only CTL induced with strong signal 2 killed tumor cells endogenously expressing low levels of Ag. Signal 2 contributed to the induction of high avidity CD8(+) CTL in both primary and secondary responses. Thus, although signal 2 has been known to increase the quantity of CTL response, in this study we show that it also improves the quality of CTL response. Our data also suggested that dendritic cells play an important role in induction of high avidity CD8(+) CTL in vivo. This strategy to selectively induce higher avidity CTL may lead to more effective vaccines for viruses and cancer. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA. RP Berzofsky, JA (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bldg 10,Room 6B-12,Mail Stop Code 1578, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015; OI Hodge, James/0000-0001-5282-3154; /0000-0002-5704-8094 NR 40 TC 96 Z9 100 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2003 VL 170 IS 5 BP 2523 EP 2530 PG 8 WC Immunology SC Immunology GA 648JD UT WOS:000181146800035 PM 12594278 ER PT J AU Eglite, S Morin, JM Metzger, H AF Eglite, S Morin, JM Metzger, H TI Synthesis and secretion of monocyte chemotactic protein-1 stimulated by the high affinity receptor for IgE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KINASE-C INHIBITOR; MAST-CELLS; CHEMOATTRACTANT PROTEIN-1; LYN KINASE; ACTIVATION; MECHANISM; RELEASE AB In prior studies aggregation of the high affinity receptors for IgE, FcepsilonRI, on a rat mast cell line, RBL-2H3, stimulated transcription of the gene for monocyte chemotactic protein-1 (MCP-1) and secretion of the protein. Unexpectedly, those delayed events appeared much less constrained by kinetic proofreading than had been documented for other receptor-initiated responses. The results of the present experiments are consistent with the proposal that the biosynthesis and secretion of MCP-1 result from a soluble messenger formed in the reaction cascades initiated by the receptor, and that Ca2+ could serve as that messenger. Interestingly, whereas receptor-mediated signals were required for transcription of the gene for MCP-1 and secretion of the chemokine, such signals were not required for the intervening step of translation of its mRNA. C1 Natl Inst Arthrit & Musculoskeletal Dis, Sect Chem Immunol, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Metzger, H (reprint author), Natl Inst Arthrit & Musculoskeletal Dis, Sect Chem Immunol, Arthrit & Rheumatism Branch, NIH, Room 9N-228,10 Ctr Dr, Bethesda, MD 20892 USA. NR 27 TC 9 Z9 10 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2003 VL 170 IS 5 BP 2680 EP 2687 PG 8 WC Immunology SC Immunology GA 648JD UT WOS:000181146800054 PM 12594297 ER PT J AU Murphy, WJ Welniak, L Back, T Hixon, J Subleski, J Seki, N Wigginton, JM Wilson, SE Blazar, BR Malyguine, AM Sayers, TJ Wiltrout, RH AF Murphy, WJ Welniak, L Back, T Hixon, J Subleski, J Seki, N Wigginton, JM Wilson, SE Blazar, BR Malyguine, AM Sayers, TJ Wiltrout, RH TI Synergistic anti-tumor responses after administration of agonistic antibodies to CD40 and IL-2: Coordination of dendritic and CD8(+) cell responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECOMBINANT INTERLEUKIN-2 THERAPY; T-CELLS; IN-VITRO; NK CELLS; LIGAND; EXPRESSION; ACTIVATION; CARCINOMA; ANTITUMOR; ANTI-CD40 AB In cancer, the coordinate engagement of professional APC and Ag-specific cell-mediated effector cells may be vital for the induction of effective antitumor responses. We speculated that the enhanced differentiation and function of dendritic cells through CD40 engagement combined with IL-2 administration to stimulate T cell expansion would act coordinately to enhance the adaptive immune response against cancer. In mice bearing orthotopic metastatic renal cell carcinoma, only the combination of an agonist Ab to CD40 and IL-2, but neither agent administered alone, induced complete regression of metastatic tumor and specific immunity to subsequent rechallenge in the majority of treated mice. The combination of anti-CD40 and IL-2 resulted in significant increases in dendritic cell and CD8(+) T cell number in advanced tumor-bearing mice compared with either agent administered singly. The antitumor effects of anti-CD40 and IL-2 were found to be dependent on CD8(+) T cells, IFN-gamma, IL-12 p40, and Fas ligand. CD40 stimulation and IL-2 may therefore be of use to promote antitumor responses in advanced metastatic cancer. C1 Univ Nevada, Sch Med, Dept Microbiol, Reno, NV 89557 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. Chiron Corp, Prot Therapeut, Emeryville, CA 94608 USA. Univ Minnesota, Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. RP Murphy, WJ (reprint author), Univ Nevada, Sch Med, Dept Microbiol, ARF Room 342,Mail Stop 199, Reno, NV 89557 USA. RI Sayers, Thomas/G-4859-2015 FU NCI NIH HHS [N01CO12400, R01CA72669, R01CA95572] NR 31 TC 63 Z9 67 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2003 VL 170 IS 5 BP 2727 EP 2733 PG 7 WC Immunology SC Immunology GA 648JD UT WOS:000181146800060 PM 12594303 ER PT J AU Xu, H Montgomery, SP Preston, EH Tadaki, DK Hale, DA Harlan, DM Kirk, AD AF Xu, H Montgomery, SP Preston, EH Tadaki, DK Hale, DA Harlan, DM Kirk, AD TI Studies investigating pretransplant donor-specific blood transfusion, rapamycin, and the CD154-specific antibody IDEC-131 in a nonhuman primate model of skin allotransplantation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RENAL-ALLOGRAFT REJECTION; LONG-TERM SURVIVAL; T-CELLS; MONOCLONAL-ANTIBODY; ANTI-CD154 ANTIBODY; ISLET ALLOGRAFTS; CD40 LIGAND; ENDOTHELIAL-CELLS; CD154; TOLERANCE AB Anti-CD154 variably prolongs allograft survival in nonhuman primates. Rodent studies suggest that adding pretransplant donor-specific transfusion (DST) and/or rapamycin to anti-CD154 improves survival. The CD154-specific Ab IDEC-131 was tested alone and in combination with rapamycin for its ability to inhibit rhesus NMRs. The ability of the Ab to block endothelial activation was also assessed. IDEC-131 was then tested alone and in combination with DST and/or rapamycin for its ability to prevent rejection of full-thickness, MHC-mismatched rhesus skin allografts. Animals were monitored for donor-specific hyporesponsiveness by MLR and alloantibody determination. IDEC-131 modestly inhibited rhesus MLRs and inhibited CD154-dependent endothelial cell activation. Rapamycin combined with IDEC-131 additively inhibited MLRs. IDEC-131 modestly prolonged allograft survival when compared with no treatment, rapamycin alone, or DST plus rapamycin. Adding DST to IDEC-131 did not prolong survival beyond IDEC-131 alone. IDEC-131 plus rapamycin was effective in prolonging graft survival, although animals had episodes of acute rejection before graft demise. Therapy with IDEC-131, rapamycin, and DST induced long-term allograft survival without intermittent acute rejection. However, no evidence for MLR inhibition was seen, and most animals eventually developed alloantibody. All animals ultimately rejected their grafts after drug withdrawal. IDEC-131 modestly prolongs rhesus skin allograft survival. Rapamycin and rapamycin plus DST improves the efficacy of IDEC-131 in prolonging allograft survival. IDEC-131, rapamycin, and DST are a promising combination for clinical evaluation in allotransplantation. C1 NIDDKD, Transplantat & Autoimmun Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Kirk, AD (reprint author), Room 11S-219,Bldg 10,Ctr Dr, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 FU NIAID NIH HHS [U19 AI43900-01] NR 26 TC 46 Z9 48 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2003 VL 170 IS 5 BP 2776 EP 2782 PG 7 WC Immunology SC Immunology GA 648JD UT WOS:000181146800066 PM 12594309 ER PT J AU Smith, JW Kurt, RA Baher, AG Denman, S Justice, L Doran, T Gilbert, T Alvord, WG Urba, WJ AF Smith, JW Kurt, RA Baher, AG Denman, S Justice, L Doran, T Gilbert, T Alvord, WG Urba, WJ TI Immune effects of escalating doses of granulocyte-macrophage colony-stimulating factor added to a fixed, low-dose, inpatient interleukin-2 regimen: A randomized phase I trial in patients with metastatic melanoma and renal cell carcinoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE granulocyte-macrophage colony-stimulating factor; immunotherapy; interleukin-2; melanoma; renal cell carcinoma ID CONTINUOUS INFUSION INTERLEUKIN-2; NECROSIS-FACTOR-ALPHA; HUMAN-MONOCYTES; SERUM LEVELS; RECEPTOR EXPRESSION; MALIGNANT-MELANOMA; HUMAN-LYMPHOCYTES; BLOOD MONOCYTES; IL-2 RECEPTOR; GM-CSF AB Previous studies in cancer patients demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulated the interleukin (IL)-2 receptor on T lymphocytes and monocytes suggesting that subsequently administered IL-2 would produce greater immune effects. The authors treated 21 patients with metastatic renal cell carcinoma and melanoma on a randomized phase I study to test this hypothesis. All 21 patients received a fixed dose of IL-2 (72,000 IU/kg every 8 hours for 5 days) administered intravenously as an inpatient. Patients were randomized to receive IL-2 alone or in combination with GM-CSF at a dose of 125 or 250 mcg/m(2)/d (Sargramostim; Immunex Corporation, WA, U.S.A.) daily for 7 days by subcutaneous injection starting on day 1, the day before IL-2 treatment. The results from this study demonstrated that GM-CSF did not worsen the toxicities produced by IL-2 alone. Grade 3 confusion occurred in four patients, three who received IL-2 alone. No partial or complete tumor responses were seen. Assays of serum soluble IL-2 receptor (sIL2R) and neopterin, measures of T cell and monocyte activation, respectively, demonstrated a significant increase in sIL2R but not neopterin, 24 hours after the first dose of GM-CSF. In combination with IL-2, the higher dose of GM-CSF (250 mcg/m(2)) produced higher sIL2R levels on days 3 and 7 than the 125-mcg/m(2) dose of GM-CSF or IL-2 alone. Although neopterin levels did not increase after I day of GM-CSF, the addition of IL-2 resulted in a significantly increased neopterin level on day 3 at the higher dose of GM-CSF. On day 7, neopterin levels in all three groups were similarly increased over baseline. Ten days after treatment, neopterin levels had returned to normal, but sIL2R levels remained markedly increased (12 fold) over baseline in the higher GM-CSF dose group. The authors conclude that 1) monocyte activation was not significantly enhanced by I day of GM-CSF treatment; 2) the 250-mcg/m(2) GM-CSF dose plus IL-2 produced superior T cell activation compared with a lower dose of GM-CSF plus IL-2 or to IL-2 alone; and 3) the combination of GM-CSF and IL-2 was safe and tolerable but was not associated with any clinical responses. C1 Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Portland, OR 97213 USA. Immunex Res & Dev Corp, Seattle, WA 98101 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Smith, JW (reprint author), Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, 4805 NE Glisan,5F40, Portland, OR 97213 USA. NR 44 TC 14 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAR-APR PY 2003 VL 26 IS 2 BP 130 EP 138 DI 10.1097/00002371-200303000-00005 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 652VF UT WOS:000181401000005 PM 12616104 ER PT J AU Heimann, DM Rosenberg, SA AF Heimann, DM Rosenberg, SA TI Continuous intravenous administration of live genetically modified Salmonella typhimurium in patients with metastatic melanoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Letter C1 NCI, Surg Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Heimann, DM (reprint author), Bldg 10,Room 2B42,9000 Rockville Pike, Bethesda, MD USA. FU Intramural NIH HHS [Z01 SC003811-33] NR 1 TC 39 Z9 40 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAR-APR PY 2003 VL 26 IS 2 BP 179 EP 180 DI 10.1097/00002371-200303000-00011 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 652VF UT WOS:000181401000011 PM 12616110 ER PT J AU Mofenson, LM AF Mofenson, LM TI Tale of two epidemics - The continuing challenge of preventing mother-to-child transmission of human immunodeficiency virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID PERINATAL HIV-1 TRANSMISSION; VERTICAL TRANSMISSION; RANDOMIZED TRIAL; ORAL ZIDOVUDINE; COTE-DIVOIRE; WOMEN; REDUCTION; THAILAND; PROGRAM; TYPE-1 C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Rockville, MD 20852 USA. RP Mofenson, LM (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, 6100 Execut Blvd,Rm 4B11, Rockville, MD 20852 USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 30 TC 18 Z9 18 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 1 PY 2003 VL 187 IS 5 BP 721 EP 724 DI 10.1086/367905 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 649LF UT WOS:000181209400001 PM 12599044 ER PT J AU Hoshino, Y Wagner, M Yan, XY Perez-Schael, I Kapikian, AZ AF Hoshino, Y Wagner, M Yan, XY Perez-Schael, I Kapikian, AZ TI Horizontal transmission of rhesus monkey rotavirus-based quadrivalent vaccine during a phase 3 clinical trial in Caracas, Venezuela SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Conference on Vaccines for Enteric Diseases (VED 2001) CY SEP 12-14, 2001 CL TAMPERE, FINLAND ID POLYMERASE CHAIN-REACTION; YOUNG-CHILDREN; INFANTS; EFFICACY; SAFETY; GASTROENTERITIS; INTUSSUSCEPTION; PREVENTION; SEROTYPE-1; SPECIMENS AB During a phase 3 clinical trial of rhesus monkey rotavirus-based quadrivalent vaccine in Venezuela, 2207 infants received 3 oral doses of vaccine (4 x 10(5) plaque-forming units/dose) or placebo at ages similar to2, 3, and 4 months; 219 (14%) of 1537 stools obtained during 1550 diarrheal episodes in postvaccination surveillance were rotavirus-positive by enzyme-linked immunosorbent assay. With the use of various VP7 and VP4 primers for genotyping purposes, 213 of 219 rotavirus-positive stools were analyzed by reverse-transcription polymerase chain reaction. Twenty-nine (14%) of 213 rotavirus-positive stools contained at least 2 distinct rotavirus strains: a low-titered vaccine strain(s) and a second strain that, when possible, was studied further and found to be a wild-type rotavirus strain. The titer of vaccine viruses in 19 stools that plaqued directly in cell cultures ranged from 10(1) to 10(3) plaque-forming units/0.5 mL of a 10% stool suspension. Reassortants of vaccine virus and wild-type human rotavirus were not detected. C1 NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Cent Univ Venezuela, Minist Sanidad, Inst Biomed, Caracas, Venezuela. RP Hoshino, Y (reprint author), NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bldg 50,Rm 6308,50 South Dr,MSC 8026, Bethesda, MD 20892 USA. NR 43 TC 7 Z9 8 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 MAR 1 PY 2003 VL 187 IS 5 BP 791 EP 800 DI 10.1086/368387 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 649LF UT WOS:000181209400010 PM 12599053 ER PT J AU Guide, SV Stock, F Gill, VJ Anderson, VL Malech, HL Gallin, JI Holland, SM AF Guide, SV Stock, F Gill, VJ Anderson, VL Malech, HL Gallin, JI Holland, SM TI Reinfection, rather than persistent infection, in patients with chronic granulomatous disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID STAPHYLOCOCCUS-AUREUS BACTEREMIA; LUNG-TRANSPLANT RECIPIENTS; FIELD GEL-ELECTROPHORESIS; CYSTIC-FIBROSIS PATIENTS; TO-PERSON TRANSMISSION; PSEUDOMONAS-CEPACIA; CLOSTRIDIUM-DIFFICILE; MOLECULAR EPIDEMIOLOGY; BURKHOLDERIA-CEPACIA; VENTILATED PATIENTS AB Chronic granulomatous disease (CGD) is characterized by severe recurrent infections with Staphylococcus aureus, certain gram-negative rods, Nocardia species, and fungi. When infections with the same species recur, they may represent relapses or new infections. We collected organisms from infections that occurred between 1992 and 2000 in patients with CGD and determined the biochemical phenotypes, in vitro antibiotic susceptibility patterns, and pulsed-field gel electrophoresis (PFGE) patterns of the organisms causing the initial and recurrent infections. Recurrence of infection with Burkholderia cepacia or Serratia marcescens was caused by a new strain in 9 of 10 cases (P = .001). Recurrent S. aureus infections were caused by new strains in 7 of 8 cases (P = .006). In patients with CGD, recurrence of infection with the same bacterial species after appropriate antibiotic therapy usually represents new infection. C1 NIH, Warren G Magnuson Clin Ctr, Clin Res Training Program, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Microbiol Serv, Dept Lab Med, Bethesda, MD 20892 USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. Stanford Univ, Palo Alto, CA 94304 USA. RP Holland, SM (reprint author), Bldg 10,Rm 11N103,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. NR 38 TC 32 Z9 32 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 1 PY 2003 VL 187 IS 5 BP 845 EP 853 DI 10.1086/368388 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 649LF UT WOS:000181209400016 PM 12599059 ER PT J AU Mirza, NM Palmer, M Kadow, K Rosche, C Yanovski, JA AF Mirza, NM Palmer, M Kadow, K Rosche, C Yanovski, JA TI High prevalence of obesity, but no association between adiposity and early feeding practices in Latino children and adolescents SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Clinical Research 2003 Meeting CY MAR 13-16, 2003 CL BALTIMORE, MARYLAND C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. NIH, Unit Growth & Obes, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2003 VL 51 SU 2 BP S357 EP S357 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 652QW UT WOS:000181390700007 ER PT J AU Rao, DA Cutting, SM Chen, YW Semino-Mora, C Bakay, M Devaney, JM Plotz, P Hoffman, EP AF Rao, DA Cutting, SM Chen, YW Semino-Mora, C Bakay, M Devaney, JM Plotz, P Hoffman, EP TI Pathway construction in dysferlin-deficiency: Contrasting alterations in potocytotic and endocytotic vesicle trafficking SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Clinical Research 2003 Meeting CY MAR 13-16, 2003 CL BALTIMORE, MARYLAND C1 Childrens Natl Med Ctr, Ctr Genet Med, Washington, DC 20010 USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2003 VL 51 SU 2 BP S368 EP S368 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 652QW UT WOS:000181390700072 ER PT J AU la Sala, A Ferrari, D Di Virgilio, F Idzko, M Norgauer, J Girolomoni, G AF la Sala, A Ferrari, D Di Virgilio, F Idzko, M Norgauer, J Girolomoni, G TI Alerting and tuning the immune response by extracellular nucleotides SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE dendritic cell; monocyte; ATP; chemokine; IL-12 ID HUMAN DENDRITIC CELLS; ADENOSINE-TRIPHOSPHATE; P2Y RECEPTORS; IN-VITRO; ATP; RELEASE; MATURATION; EXPRESSION; CALCIUM; MICE AB The interplay between pro- and anti-inflammatory mechanisms during inflammatory and immune responses is critical for avoiding excessive tissue damage. Extracellular nucleotides (e.g., adenosine 5'-triphosphate) may represent constitutive signals that can alert the immune system of abnormal cell death. Relatively high doses of nucleotides induce rapid release of proinflammatory mediators and favor pathogen killing. However, recent findings on antigen presenting cells, particularly dendritic cells, revealed a more complex role for these molecules. Chronic exposure to low-dose nucleotides can redirect cellular responses to prototypic activation stimuli, leading to suppressed inflammation and immune deviation. J. Leukoc. Biol. 73: 339-343; 2003. C1 NIAID, Immune Cell Interact Unit, Mucosal Immun Sect, Lab Clin Invest,NIH, Bethesda, MD 20892 USA. IRCCS, Ist Dermopat Immacolata, Immunol Lab, Rome, Italy. Univ Freiburg, Dept Expt Dermatol, Freiburg, Germany. Univ Ferrara, Interdisciplinary Ctr Study Inflammat, Sect Gen Pathol, Dept Expt & Diagnost Med, I-44100 Ferrara, Italy. RP la Sala, A (reprint author), NIAID, Immune Cell Interact Unit, Mucosal Immun Sect, Lab Clin Invest,NIH, 10 Ctr Dr,11-N214, Bethesda, MD 20892 USA. RI la Sala, Andrea/A-3228-2009; Ferrari, Davide/F-5644-2015 OI la Sala, Andrea/0000-0003-1268-6516; Ferrari, Davide/0000-0002-5727-9204 NR 36 TC 124 Z9 125 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 2003 VL 73 IS 3 BP 339 EP 343 DI 10.1189/jlb.0802418 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 755EW UT WOS:000187391600003 PM 12629147 ER PT J AU Pajevic, S Basser, PJ AF Pajevic, S Basser, PJ TI Parametric and non-parametric statistical analysis of DT-MRI data SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE diffusion; tensor; MR; MRI; bootstrap; multivariate; normal; distribution ID DIFFUSION-TENSOR MRI; HUMAN BRAIN; AXONAL PROJECTIONS; B-MATRIX; ANISOTROPY; NOISE; IMAGES; SPECTROSCOPY; FEATURES; TRACKING AB In this work parametric and non-parametric statistical methods are proposed to analyze Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) data. A Multivariate Normal Distribution is proposed as a parametric statistical model of diffusion tensor data when magnitude MR images contain no artifacts other than Johnson noise. We test this model using Monte Carlo (MC) simulations of DT-MRI experiments. The non-parametric approach proposed here is an implementation of bootstrap methodology that we call the DT-MRI bootstrap. It is used to estimate an empirical probability distribution of experimental DT-MRI data, and to perform hypothesis tests on them. The DT-MRI bootstrap is also used to obtain various statistics of DT-MRI parameters within a single voxel, and within a region of interest (ROI); we also use the bootstrap to study the intrinsic variability of these parameters in the ROI, independent of background noise. We evaluate the DT-MRI bootstrap using MC simulations and apply it to DT-MRI data acquired on human brain in vivo, and on a phantom with uniform diffusion properties. Published by Elsevier Science (USA). C1 NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Basser, PJ (reprint author), NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, 13 South Dr,Bldg 13,Room 3W16, Bethesda, MD 20892 USA. RI Basser, Peter/H-5477-2011 NR 40 TC 100 Z9 101 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAR PY 2003 VL 161 IS 1 BP 1 EP 14 DI 10.1016/S1090-7807(02)00178-7 PG 14 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 664FW UT WOS:000182051900001 PM 12660106 ER PT J AU Roth-Deri, I Zangen, A Aleli, M Goelman, RG Pelled, G Nakash, R Gispan-Herman, I Green, T Shaham, Y Yadid, G AF Roth-Deri, I Zangen, A Aleli, M Goelman, RG Pelled, G Nakash, R Gispan-Herman, I Green, T Shaham, Y Yadid, G TI Effect of experimenter-delivered and self-administered cocaine on extracellular beta-endorphin levels in the nucleus accumbens SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE arcuate nucleus; cocaine; drug self-administration; beta-endorphin; extinction; microdialysis ID CONDITIONED PLACE PREFERENCE; CORTICOTROPIN-RELEASING FACTOR; DELTA-OPIOID RECEPTORS; INTRAVENOUS COCAINE; DOPAMINE RELEASE; ENDOGENOUS OPIOIDS; ATTENUATES ACQUISITION; SEEKING BEHAVIOR; ARCUATE NUCLEUS; DRUG-ADDICTION AB beta-endorphin is an endogenous opioid peptide that has been hypothesized to be involved in the behavioral effects of drugs of abuse including psychostimulants. Using microdialysis, we studied the effect of cocaine on extracellular levels of beta-endorphin in the nucleus accumbens, a brain region involved in the reinforcing effects of psychostimulant drugs. Experimenter-delivered cocaine (2 mg/kg, i.v.) increased extracellular beta-endorphin immunoreactive levels in the nucleus accumbens, an effect attenuated by 6-hydroxy-dopamine lesions or systemic administration of the D-1-like receptor antagonist, SCH-23390 (0.25 mg/kg, i.p.). The effect of cocaine on beta-endorphin release in the nucleus accumbens was mimicked by a local perfusion of dopamine (5 mum) and was blocked by coadministration of SCH-23390 (10 mum). Self-administered cocaine (1 mg/kg/infusion, i.v.) also increased extracellular beta-endorphin levels in the nucleus accumbens. In addition, using functional magnetic resonance imaging, we found that cocaine (1 mg/kg, i.v.) increases regional brain activity in the nucleus accumbens and arcuate nucleus. We demonstrate an increase in beta-endorphin release in the nucleus accumbens following experimenter-delivered and self-administered cocaine mediated by the local dopaminergic system. These findings suggest that activation of the beta-endorphin neurons within the arcuate nucleus-nucleus accumbens pathway may be important in the neurobiological mechanisms underlying the behavioral effects of cocaine. C1 Bar Ilan Univ, Fac Life Sci, Neuropharmacol Sect, IL-52900 Ramat Gan, Israel. Hadassah Hebrew Univ Hosp, Dept Med Biophys & Nucl Med, Jerusalem, Israel. NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD USA. RP Yadid, G (reprint author), Bar Ilan Univ, Fac Life Sci, Neuropharmacol Sect, IL-52900 Ramat Gan, Israel. RI shaham, yavin/G-1306-2014 NR 79 TC 67 Z9 70 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2003 VL 84 IS 5 BP 930 EP 938 DI 10.1046/j.1471-4159.2003.01584.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 646VH UT WOS:000181055900004 PM 12603818 ER PT J AU Chen, SY Samuel, W Fariss, RN Duncan, T Kutty, RK Wiggert, B AF Chen, SY Samuel, W Fariss, RN Duncan, T Kutty, RK Wiggert, B TI Differentiation of human retinal pigment epithelial cells into neuronal phenotype by N-(4-hydroxyphenyl)retinamide SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cellular retinaldehyde-binding protein; fenretinide; neurofilament; neuronal differentiation; retinal pigment epithelial cell; retinoic acid ID EMBRYONAL CARCINOMA-CELLS; HEAT-SHOCK PROTEINS; F9 TERATOCARCINOMA CELLS; GROWTH-FACTOR RECEPTORS; DEVELOPING RAT RETINA; BINDING PROTEINS; DEVELOPMENTAL EXPRESSION; DARK-ADAPTATION; NERVOUS-SYSTEM; ARPE-19 CELLS AB ARPE-19, a human retinal pigment epithelial (RPE) cell line, has been widely used in studies of RPE function as well as gene expression. Here, we report the novel finding that N -(4-hydroxyphenyl)retinamide (fenretinide), a synthetic retinoic acid derivative and a potential chemopreventive agent against cancer, induced the differentiation of ARPE-19 cells into a neuronal phenotype. The treated cells lost their epithelial phenotype and exhibited a typical neuronal shape with long processes (four to five times longer than the cell body). The onset of fenretinide-induced neuronal differentiation was dose and time dependent, started within 1-2 days, and lasted at least 4 weeks. Immunohistochemical studies indicated that the expression of neurofilament proteins (NF160 and NF200), calretinin and neural cell adhesion molecule was increased in these differentiated cells. Western blot analysis indicated that cellular retinaldehyde-binding protein, which is normally expressed in RPE cells, was decreased in treated cells. Protein analysis on a two-dimensional gel followed by matrix-assisted laser desorption ionization-time of flight mass spectrometric analysis demonstrated that heat-shock protein 70 was increased after fenretinide treatment. Thus, fenretinide, a synthetic retinoid, is able to induce neuronal differentiation of human RPE cells in culture. C1 NEI, Biochem Sect, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Pathophysiol Sect, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Wiggert, B (reprint author), NEI, Biochem Sect, Retinal Cell & Mol Biol Lab, NIH, Bldg 6 Room 338,6 Ctr Dr, Bethesda, MD 20892 USA. NR 65 TC 24 Z9 25 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2003 VL 84 IS 5 BP 972 EP 981 DI 10.1046/j.1471-4159.2003.01608.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 646VH UT WOS:000181055900008 PM 12603822 ER PT J AU Li, Q Wichems, CH Ma, L Van de Kar, LD Garcia, F Murphy, DL AF Li, Q Wichems, CH Ma, L Van de Kar, LD Garcia, F Murphy, DL TI Brain region-specific alterations of 5-HT2A and 5-HT2C receptors in serotonin transporter knockout mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE DOI binding; in situ hybridization; 5-HT2A mRNA; 5-HT2C mRNA; G(q/11) proteins; hormones ID OBSESSIVE-COMPULSIVE DISORDER; LONG-TERM FLUOXETINE; NEUROENDOCRINE RESPONSES; BEHAVIORAL-RESPONSES; HORMONE RESPONSES; G(O) PROTEINS; MALE-RATS; DESENSITIZATION; REDUCTION; ANXIETY AB The aim of the present studies was to determine the effects of reduced or absent serotonin (5-HT) transporters (5-HTTs) on 5-HT2A and 5-HT2C receptors. The density of 5-HT2C receptors was significantly increased in the amygdala and choroid plexus of 5-HTT knockout mice. On the other hand, the density of 5-HT2A receptors was significantly increased in the hypothalamus and septum, but reduced in the striatum, of 5-HTT knockout mice. However, 5-HT2A mRNA was not changed in any brain region measured. 5-HT2C mRNA was significantly reduced in the choroid plexus and lateral habenula nucleus of these mice. The function of 5-HT2A receptors was evaluated by hormonal responses to (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Oxytocin, but not adrenocorticotrophic hormone or corticosterone, responses to DOI were significantly greater in 5-HTT knockout mice. In addition, G(q) and G(11) proteins were not significantly changed in any brain region measured. The present results suggest that the constitutive alteration in the function of 5-HTTs changes the density of 5-HT2A and 5-HT2C receptors in a brain region-specific manner. These changes may not be mediated by alterations in their gene expression or in the level of G(q/11) proteins. The alterations in these receptors may be related to the altered behaviors of 5-HTT knockout mice. C1 NIMH, Clin Sci Lab, NIH, Ctr Clin, Bethesda, MD 20892 USA. Loyola Univ Chicago, Dept Pharmacol, Stritch Sch Med, Maywood, IL USA. RP Li, Q (reprint author), NIMH, Clin Sci Lab, NIH, Ctr Clin, Room 3D41,10 Ctr Dr MSC-1264,Bldg 10, Bethesda, MD 20892 USA. NR 41 TC 85 Z9 87 U1 0 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2003 VL 84 IS 6 BP 1256 EP 1265 DI 10.1046/j.1471-4159.2003.01607.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 651QF UT WOS:000181331300004 PM 12614326 ER PT J AU Romero, AA Gross, SR Cheng, KY Goldsmith, NK Geller, HM AF Romero, AA Gross, SR Cheng, KY Goldsmith, NK Geller, HM TI An age-related increase in resistance to DNA damage-induced apoptotic cell death is associated with development of DNA repair mechanisms SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE granule neuron; ionizing irradiation ID NUCLEOTIDE EXCISION-REPAIR; CEREBELLAR GRANULE NEURONS; CYTOSINE-ARABINOSIDE; XERODERMA-PIGMENTOSUM; OXIDATIVE STRESS; POLYMERASE-BETA; NERVOUS-SYSTEM; COMET ASSAY; TIME-COURSE; P53 AB Neurons in the developing brain die via apoptosis after DNA damage, while neurons in the adult brain are generally resistant to these insults. The basis for this resistance is a matter of conjecture. We report here that cerebellar granule neurons (CGNs) in culture lose their competence to die in response to DNA damage as a function of time in culture. CGNs at either 1 day in vitro (DIV) or 7 DIV were treated with the DNA damaging agents camptothecin, UV or gamma-irradiation and neuronal survival measured. The younger neurons were effectively killed by these agents, while the older neurons displayed a significant resistance to killing. Neuronal survival did not change with time in culture when cells were treated with C2-ceramide or staurosporine, agents which do not target DNA. The resistance to UV irradiation developed over time in culture and was not due to changes in mitotic rate. Increases in DNA strand breakage, up-regulation of the levels of both p53 and its phosphorylated form and nuclear translocation of p53 were equivalent in both older and younger neurons, indicating a comparable p53 stress response. In addition, we show that treatment of older neurons with pharmacological inhibitors of distinct components of the DNA repair machinery promotes the accumulation of DNA damage and sensitizes these cells to the toxic effects of UV exposure. These data demonstrate that older neurons appear to be more proficient in DNA repair in comparison to their younger counterparts, and that this leads to increased survival after DNA damage. C1 UMDNJ Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ USA. RP Geller, HM (reprint author), NHLBI, NIH, 10 Ctr Dr MSC 1754,Bldg 10,Room 8C213, Bethesda, MD 20892 USA. OI Geller, Herbert/0000-0002-7048-6144; gross, stephane/0000-0002-0867-8866 FU NIEHS NIH HHS [P01 ES10874]; NINDS NIH HHS [R01 NS 36443] NR 60 TC 21 Z9 28 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2003 VL 84 IS 6 BP 1275 EP 1287 DI 10.1046/j.1471-4159.2003.01629.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 651QF UT WOS:000181331300006 PM 12614328 ER PT J AU Lu, L Liu, ZY Huang, MS Zhang, ZY AF Lu, L Liu, ZY Huang, MS Zhang, ZY TI Dopamine-dependent responses to cocaine depend on corticotropin-releasing factor receptor subtypes SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE behavioral response; cocaine reward; corticotropin-releasing factor antagonist; dopamine; nucleus accumbens; ventral tegmental area ID STRESS-INDUCED RELAPSE; CONDITIONED PLACE PREFERENCE; MESSENGER-RIBONUCLEIC-ACID; RAT-BRAIN; BEHAVIORAL SENSITIZATION; HORMONE RECEPTOR-2; OPIATE WITHDRAWAL; BETA-ENDORPHIN; CRF2 RECEPTORS; ANTAGONIST AB The effects on locomotor response to cocaine challenge, acquisition of cocaine conditioned place preference and cocaine-induced dopamine (DA) release in nucleus accumbens and ventral tegmental area by the non-specific corticotropin-releasing factor (CRF) receptors antagonist alpha-helical CRF, the selective CRF receptor subtype 1 antagonist CP-154,526 and the selective CRF receptor subtype 2 antagonist anti-sauvagine-30 (AS-30) were investigated in rats. Both alpha-helical CRF (10 mug, i.c.v.) and CP-154,526 (3 mug, i.c.v.) decreased the cocaine-induced distance travelled, whereas AS-30 (3 mug, i.c.v.) did not show such an effect. The CRF receptor antagonists also have significant effects on stereotype counts induced by cocaine injection, in which the alpha-helical CRF or CP-154,526 but not AS-30 did significantly reduce the stereotype counts. alpha-Helical CRF (10 mug) prior to each injection of cocaine blocked cocaine conditioned place preference with no significant difference observed in the time spent in the drug-paired side between post- and pre-training and both 1 and 3 mug CP-154,526 also had significant inhibitory effects on cocaine-induced place preference. However, pre-treatment with an i.c.v. infusion of AS-30 (1 or 3 mug) prior to each injection of cocaine did not affect the acquisition of conditioned place preference. The alpha-helical CRF and CP-154,526 reduced extracellular DA levels of nucleus accumbens and ventral tegmental area in response to the injection of cocaine. However, both alpha-helical CRF and CP-154,526 did not modify extracellular DA levels under basal conditions. In contrast, the i.c.v. infusion of AS-30 had no effects on either the basal DA or the cocaine-induced increase in DA release in nucleus accumbens and ventral tegmental area. These findings demonstrate that activation of the CRF receptor is involved in behavioral and neurochemical effects of cocaine challenge and cocaine reward and that the role of CRF receptor subtypes 1 and 2 in cocaine-induced locomotion, reward and DA release is not identical. The CRF receptor subtype 1 is largely responsible for the action of the CRF system on cocaine locomotion and reward. These results suggest that the CRF receptor antagonist, particularly the CRF receptor subtype 1 antagonist, might be of some value in the treatment of cocaine addiction and cocaine-related behavioral disorders. C1 NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD 21224 USA. W China Univ Med Sci, Inst Mental Hlth, Chengdu 610041, Peoples R China. Fudan Univ, Med Ctr, Shanghai 200433, Peoples R China. Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA. RP Lu, L (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 60 TC 49 Z9 50 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2003 VL 84 IS 6 BP 1378 EP 1386 DI 10.1046/j.1471-4159.2003.01635.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 651QF UT WOS:000181331300016 PM 12614338 ER PT J AU Singer, HS Loiselle, CR Lee, O Garvey, MA Grus, FH AF Singer, HS Loiselle, CR Lee, O Garvey, MA Grus, FH TI Anti-basal ganglia antibody abnormalities in Sydenham chorea SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE Sydenham chorea; anti-basal ganglia antibodies; ELISA; Western blot; discriminant analysis ID NATURAL AUTOANTIBODIES; ANTINEURONAL ANTIBODIES; DISCRIMINANT-ANALYSIS; MEGABLOT TECHNIQUE; TOURETTES-SYNDROME; RHEUMATIC-FEVER; GLOBAL ANALYSIS; REPERTOIRES; SERUM; REACTIVITIES AB Anti-basal ganglia antibodies (ABGA) were measured in nine children with Sydenham chorea (SC) and compared to nine controls. Enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) methods were used to detect ABGA against supernatant (S1), pellet, and synaptosomal preparations from adult and pediatric postmortem caudate, putamen, and globus pallidus. ELISA optical density (013) values were higher in SC patients than controls across all preparations, but did not reach a level of significance. Although WB identified multiple bands in all subjects, discriminant analysis showed that the mean binding patterns of SC patients were significantly different from control, most notably in the caudate S1 fraction (Wilks' lambda=0.011,p<0.0001). Numerous antigens contributed to differences between groups; the two most defining molecular masses were at 126 and 113 kDa. In contrast to WB with discriminant analysis, ELISA measurements did not significantly differentiate between the SC group and controls. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. Univ Mainz, Augenklin, Dept Ophthalmol, D-55101 Mainz, Germany. RP Singer, HS (reprint author), Johns Hopkins Univ Hosp, Div Pediat Neurol, Jefferson St Bldg 124,600 N Wolfe St, Baltimore, MD 21287 USA. FU NINDS NIH HHS [R01 NS37706] NR 42 TC 33 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAR PY 2003 VL 136 IS 1-2 BP 154 EP 161 DI 10.1016/S0165-5728(03)00034-1 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 660PC UT WOS:000181840700019 PM 12620655 ER PT J AU Kusunoki, M Goldberg, ME AF Kusunoki, M Goldberg, ME TI The time course of perisaccadic receptive field shifts in the lateral intraparietal area of the monkey SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SACCADIC EYE-MOVEMENTS; SUPERIOR COLLICULUS; RESPONSE PROPERTIES; VISUAL RESPONSES; PARIETAL CORTEX; NEURONS; MACAQUE; REPRESENTATION; LOCATION; POSITION AB Neurons in the lateral intraparietal area of the monkey (LIP) have visual receptive fields in retinotopic coordinates when studied in a fixation task. However, in the period immediately surrounding a saccade these receptive fields often shift, so that a briefly flashed stimulus outside the receptive field will drive the neurons if the eye movement will bring the spatial location of that vanished stimulus into the receptive field. This is equivalent to a transient shift of the retinal receptive field. The process enables the monkey brain to process a stimulus in a spatially accurate manner after a saccade, even though the stimulus appeared only before the saccade. We studied the time course of this receptive field shift by flashing a task-irrelevant stimulus for 100 ms before, during, or after a saccade. The stimulus could appear in receptive field as defined by the fixation before the saccade (the current receptive field) or the receptive field as defined by the fixation after the saccade (the future receptive field). We recorded the activity of 48 visually responsive neurons in LIP of three hemispheres of two rhesus monkeys. We studied 45 neurons in the current receptive field task, in which the saccade removed the stimulus from the receptive field. Of these neurons 29/45 (64%) showed a significant decrement of response when the stimulus appeared 250 ms or less before the saccade, as compared with their activity during fixation. The average response decrement was 38% for those cells showing a significant (P < 0.05 by t-test) decrement. We studied 39 neurons in the future receptive field task, in which the saccade brought the spatial location of a recently vanished stimulus into the receptive field. Of these 32/39 (82%) had a significant response to stimuli flashed for 100 ms in the future receptive field, even 400 ms before the saccade. Neurons never responded to stimuli moved by the saccade from a point outside the receptive field to another point outside the receptive field. Neurons did not necessarily show any saccadic suppression for stimuli moved from one part of the receptive field to another by the saccade. Stimuli flashed <250 ms before the saccade-evoked responses in both the presaccadic and the postsaccadic receptive fields, resulting in an increase in the effective receptive field size, an effect that we suggest is responsible for perisaccadic perceptual inaccuracies. C1 New York State Psychiat Inst & Hosp, Unit 87, New York, NY 10032 USA. NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. Univ Oxford, MRC, Cognit & Brain Sci Unit, Oxford OX1 3UD, England. Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. Columbia Univ Coll Phys & Surg, Ctr Neurobiol & Behav, Keck Mahoney Inst Brain & Cognit, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. RP Goldberg, ME (reprint author), New York State Psychiat Inst & Hosp, Unit 87, 1051 Riverside Dr, New York, NY 10032 USA. FU NEI NIH HHS [R01 EY014978, R01 EY017039] NR 28 TC 121 Z9 122 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 2003 VL 89 IS 3 BP 1519 EP 1527 DI 10.1152/jn.00519.2002 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 653GG UT WOS:000181426400033 PM 12612015 ER PT J AU Ren, J Lee, S Pagliardini, S Gerard, M Stewart, CL Greer, JJ Wevrick, R AF Ren, J Lee, S Pagliardini, S Gerard, M Stewart, CL Greer, JJ Wevrick, R TI Absence of Ndn, encoding the Prader-Willi syndrome-deleted gene necdin, results in congenital deficiency of central respiratory drive in neonatal mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Prader-Willi; apnea; necdin; medulla; breathing; newborn ID PRE-BOTZINGER COMPLEX; STEM-SPINAL CORD; RHYTHM GENERATION; PACEMAKER NEURONS; VENTILATORY RESPONSES; PREBOTZINGER COMPLEX; MESSENGER-RNA; IN-VIVO; BRAIN; MOUSE AB necdin (Ndn) is one of a cluster of genes deleted in the neurodevelopmental disorder Prader-Willi syndrome. necdin is upregulated during neuronal differentiation and is thought to play a role in cell cycle arrest in terminally differentiated neurons. Most necdin-deficient Ndn(tm2Stw) mutant pups carrying a targeted replacement of Ndn with a lacZ reporter gene die in the neonatal period of apparent respiratory insufficiency. We now demonstrate that the defect can be explained by abnormal neuronal activity within the putative respiratory rhythm-generating center, the pre-Botzinger complex. Specifically, the rhythm is unstable with prolonged periods of depression of respiratory rhythmogenesis. These observations suggest that the developing respiratory center is particularly sensitive to loss of necdin activity and may reflect abnormalities of respiratory rhythm-generating neurons or conditioning neuromodulatory drive. We propose that necdin deficiency maycontribute to observed respiratory abnormalities in individuals with Prader-Willi syndrome through a similar suppression of central respiratory drive. C1 Univ Alberta, Dept Physiol, Ctr Neurosci, Edmonton, AB T6G 2M7, Canada. Univ Alberta, Dept Med Genet, Edmonton, AB T6G 2M7, Canada. CEA Saclay, Div Biochem & Mol Genet, F-91191 Gif Sur Yvette, France. NCI, Lab Canc & Dev Biol, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Greer, JJ (reprint author), Univ Alberta, Dept Physiol, Ctr Neurosci, Edmonton, AB T6G 2M7, Canada. RI GERARD, Matthieu/D-2235-2014; OI GERARD, Matthieu/0000-0001-8956-0597; Wevrick, Rachel/0000-0002-3343-5794; Pagliardini, Silvia/0000-0002-1482-9173 NR 42 TC 81 Z9 83 U1 0 U2 2 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 MAR 1 PY 2003 VL 23 IS 5 BP 1569 EP 1573 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 653RJ UT WOS:000181450600003 PM 12629158 ER PT J AU Malkova, L Mishkin, M AF Malkova, L Mishkin, M TI One-trial memory for object-place associations after separate lesions of hippocampus and posterior parahippocampal region in the monkey SO JOURNAL OF NEUROSCIENCE LA English DT Article DE parahippocampal cortex; hippocampus; object-place associations; location memory; ibotenic acid; rhesus monkeys ID INFERIOR PARIETAL LOBULE; TEMPORAL-LOBE LESIONS; RHESUS-MONKEY; PRE-SUBICULUM; CORTICOCORTICAL CONNECTIONS; EXCITOTOXIC LESIONS; PERIRHINAL CORTEX; RECOGNITION; LOCATION; PARASUBICULUM AB In earlier studies of one-trial spatial memory in monkeys (Parkinson et al., 1988; Angeli et al., 1993), severe and chronic memory impairment for both object-place association and place alone was found after ablation of the hippocampal formation. The results appeared to provide the first clear-cut evidence in the monkey of the essential role of the hippocampus in spatial memory, but that interpretation neglected the inclusion in the lesion of the underlying posterior parahippocampal region. To determine the separate contributions of the hippocampus and posterior parahippocampal region to these spatial forms of one-trial memory, we trained 10 rhesus monkeys, as before, to remember the spatial positions of either two different trial-unique objects overlying two of the wells in a three-well test tray (object-place trials) or simply two of the three wells (place trials). Six of the monkeys then received ibotenic acid lesions restricted to the hippocampal formation (group H), and the four others received selective ablations of the posterior parahippocampal region (group P), comprising mainly parahippocampal cortex, parasubiculum, and presubiculum. Group H was found to be completely unaffected postoperatively on both types of trials, whereas group P sustained an impairment on both types equal in magnitude to that observed after the combined lesions in the original studies. Thus, contrary to the previous interpretation, one-trial memory for object-place association and, perhaps more fundamentally, one-trial memory for two different places appear to be critically dependent not on the hippocampal formation but rather on the posterior parahippocampal region. C1 Georgetown Univ, Dept Pharmacol, Med Ctr, Washington, DC 20007 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Malkova, L (reprint author), Georgetown Univ, Dept Pharmacol, Med Ctr, W217 NRB,3950 Reservoir Rd NW, Washington, DC 20007 USA. FU NIA NIH HHS [AG14580]; NICHD NIH HHS [HD3997]; NINDS NIH HHS [NS20576] NR 60 TC 136 Z9 140 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 MAR 1 PY 2003 VL 23 IS 5 BP 1956 EP 1965 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 653RJ UT WOS:000181450600046 PM 12629201 ER PT J AU Schmitt, A Mossner, R Gossmann, A Fischer, IG Gorboulev, V Murphy, DL Koepsell, H Lesch, KP AF Schmitt, A Mossner, R Gossmann, A Fischer, IG Gorboulev, V Murphy, DL Koepsell, H Lesch, KP TI Organic cation transporter capable of transporting serotonin is up-regulated in serotonin transporter-deficient mice SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE organic cation transporter; serotonin transporter knockout; brain; compensatory mechanism ID EXTRANEURONAL MONOAMINE TRANSPORTER; FUNCTIONAL-CHARACTERIZATION; NERVOUS-SYSTEM; EXPRESSION; CLONING; NEURONS; BRAIN; MOUSE; LOCALIZATION; PLACENTA AB The serotonin (5HT) transporter (5HTT) regulates serotonergic neurotransmission by mediating the reuptake of 5HT from the synaptic cleft. Although lacking the high affinity and selectivity of the 5HTT, the brain expresses a large number of other transporters, including the polyspecific organic cation transporters (OCTs). OCT1 and OCT3, members of the potential-sensitive organic cation transporter gene family, physiologically transport a wide spectrum of organic cations. In addition, both transporters mediate low-affinity 5HT transport and, therefore, may participate in the clearance of excessive 5HT. Because concentrations of extracellular 5HT are increased in the brain of 5HTT-deficient mice, they are a model for investigating the role of OCTs in 5HT system homeostasis. Here, we analyzed OCT1 and OCT3 gene expression in the brain of 5HTT knockout mice by semi-quantitative competitive polymerase chain reaction and in situ hybridization. We demonstrate that, in 5HTT-deficient mice, OCT3 mRNA concentrations were significantly increased in the hippocampus, but not in other brain regions, including cortex, striatum, cerebellum, and brainstem. In contrast, no difference in OCT1 expression was detected between 5HTT knockout and control mice. Up-regulation of OCT3 expression and enhanced low-affinity 5HT uptake may limit the adverse effects of elevated extracellular 5HT and may play a critical role in maintaining 5HT-dependent functions of the hippocampus in the absence of 5HTT. (C) 2002 Wiley-Liss, Inc. C1 Univ Wurzburg, Dept Psychiat & Psychotherapy, D-97080 Wurzburg, Germany. Univ Wurzburg, Inst Anat & Cell Biol, D-97080 Wurzburg, Germany. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Schmitt, A (reprint author), Univ Wurzburg, Dept Psychiat & Psychotherapy, Fuchsleinstr 15, D-97080 Wurzburg, Germany. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 35 TC 50 Z9 53 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR 1 PY 2003 VL 71 IS 5 BP 701 EP 709 DI 10.1002/jnr.10521 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 650CK UT WOS:000181244700009 PM 12584728 ER PT J AU Sansur, CA Heiss, JD DeVroom, HL Eskioglu, E Ennis, R Oldfield, EH AF Sansur, CA Heiss, JD DeVroom, HL Eskioglu, E Ennis, R Oldfield, EH TI Pathophysiology of headache associated with cough in patients with Chiari I malformation SO JOURNAL OF NEUROSURGERY LA English DT Article DE headache; Arnold-Chiari malformation; syringomyelia; cerebrospinal fluid pressure; physiology ID SYRINGOMYELIA AB Object. The aim of this study was to evaluate the pathophysiology underlying headache associated with cough in patients with Chiari I tonsillar abnormality. The authors hypothesized that peak intrathecal pressure during coughing is higher in patients with headache aggravated by cough than in patients without or in healthy volunteers. In addition, the authors evaluated the use of intrathecal pressure during cough as a means of assessing obstruction to the free flow of cerebrospinal fluid (CSF) at the craniocervical junction. Methods. Twenty-six adult patients with Chiari I malformation and syringomyelia, four adult patients with Chiari I malformation without syringomyelia, and 15 healthy volunteers were prospectively studied. Testing before surgery included the following: 1) clinical evaluation for the presence of headache associated with cough; and 2) evaluation of lumbar subarachnoid pressure at rest, during three to five coughs, while performing the Valsalva maneuver, during jugular compression, and after removal of CSF. Patients underwent suboccipital craniectomy, C-1 laminectomy, and duraplasty. Testing was repeated 6 months after surgery. Conclusions. Peak intrathecal pressures during cough and at baseline were elevated in patients with headache associated with cough compared with either patients without headache or healthy volunteers. After surgery, intrathecal pressures during cough were significantly lower than preoperative values and headache aggravated by cough was resolved partially or completely. Headache linked to coughing in patients with Chiari I malformation is associated with sudden increased intrathecal pressure caused by obstruction to the free flow of CSF in the subarachnoid space. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Heiss, JD (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,10-5D37,MSC-1414, Bethesda, MD 20892 USA. NR 14 TC 48 Z9 50 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAR PY 2003 VL 98 IS 3 BP 453 EP 458 DI 10.3171/jns.2003.98.3.0453 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 653WW UT WOS:000181460900001 PM 12650413 ER PT J AU Nguyen, TT Pannu, YS Sung, C Dedrick, RL Walbridge, S Brechbiel, MW Garmestani, K Beitzel, M Yordanov, AT Oldfield, EH AF Nguyen, TT Pannu, YS Sung, C Dedrick, RL Walbridge, S Brechbiel, MW Garmestani, K Beitzel, M Yordanov, AT Oldfield, EH TI Convective distribution of macromolecules in the primate brain demonstrated using computerized tomography and magnetic resonance imaging SO JOURNAL OF NEUROSURGERY LA English DT Article DE drug delivery; central nervous system; brain; neurosurgery; convection-enhanced delivery; Macaca mulatta; rat ID ENHANCED DELIVERY; INFUSION; FLOW AB Object. Convection-enhanced delivery (CED), the delivery and distribution of drugs by the slow bulk movement of fluid in the extracellular space, allows delivery of therapeutic agents to large volumes of the brain at relatively uniform concentrations. This mode of drug delivery offers great potential for the treatment of many neurological disorders, including brain tumors, neurodegenerative diseases, and seizure disorders. An analysis of the treatment efficacy and toxicity of this approach requires confirmation that the infusion is distributed to the targeted region and that the drug concentrations are in the therapeutic range. Methods. To confirm accurate delivery of therapeutic agents during CED and to monitor the extent of infusion in real time, albumin-linked surrogate tracers that are visible on images obtained using noninvasive techniques (iopanoic acid [IPA] for computerized tomography [CT] and Gd-diethylenetriamine pentaacetic acid for magnetic resonance [MR] imaging) were developed and investigated for their usefulness as surrogate tracers during convective distribution of a macromolecule. The authors infused albumin-linked tracers into the cerebral hemispheres of monkeys and measured the volumes of distribution by using CT and MR imaging. The distribution volumes measured by imaging were compared with tissue volumes measured using quantitative autoradiography with [C-14]bovine serum albumin coinfused with the surrogate tracer. For in vivo determination of tracer concentration, the authors examined the correlation between the concentration of the tracer in brain homogenate standards and CT Hounsfield units. They also investigated the long-term effects of the surrogate tracer for CT scanning, IPA-albumin, on animal behavior, the histological characteristics of the tissue, and parenchymal toxicity after cerebral infusion. Conclusions. Distribution of a macromolecule to clinically significant volumes in the brain is possible using convection. The spatial dimensions of the tissue distribution can be accurately defined in vivo during infusion by using surrogate tracers and conventional imaging techniques, and it is expected that it will be possible to determine local concentrations of surrogate tracers in voxels of tissue in vivo by using CT scanning. Use of imaging surrogate tracers is a practical, safe, and essential tool for establishing treatment volumes during high-flow interstitial microinfusion of the central nervous system. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10 Room 5D37,10 Ctr Dr,MSC 1414, Bethesda, MD 20892 USA. RI Kipke, Daryl/A-2167-2009 NR 17 TC 69 Z9 71 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAR PY 2003 VL 98 IS 3 BP 584 EP 590 DI 10.3171/jns.2003.98.3.0584 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 653WW UT WOS:000181460900020 PM 12650432 ER PT J AU Yanovski, S AF Yanovski, S TI Sugar and fat: Cravings and aversions SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 2001 Annual Meeting CY MAR 31-APR 04, 2001 CL ORLANDO, FLORIDA SP Amer Soc Nutr Sci DE obesity; eating disorders; binge eating; macronutrient craving ID BRAIN-SEROTONIN CONTENT; BINGE-EATING DISORDER; FOOD ADDICTION; OBESE WOMEN; CHOCOLATE; INVOLVEMENT; PREFERENCE; EATERS; DRUG; DIET AB Food cravings are extremely common, particularly among women. Cravings are frequently reported for specific types of foods, including chocolate and foods high in both sugar and fat. Cravings for specific macronutrients, such as carbohydrate, have been postulated to result from a physiological need to alter neurotransmitters in such states as eating disorders, affective disorders or obesity. However, studies of such cravings are often confounded by differing sensory properties of high and low carbohydrate foods. There is some evidence that sweet, high fat foods are preferred by women with binge-eating disorders and that those preferences are mediated by the endogenous opioid system. Aversion to fat is seen primarily in women with anorexia nervosa. However, it is possible that changes in fat preference may be achieved through behavioral or pharmacological approaches. An understanding of food cravings and aversions may lead to improved methods for the prevention and treatment of obesity and eating disorders. C1 NIDDKD, Bethesda, MD 20892 USA. RP Yanovski, S (reprint author), NIDDKD, Bethesda, MD 20892 USA. NR 30 TC 43 Z9 45 U1 2 U2 12 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAR PY 2003 VL 133 IS 3 BP 835S EP 837S PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 652VC UT WOS:000181400700035 PM 12612163 ER PT J AU Potischman, N Freudenheim, JL AF Potischman, N Freudenheim, JL TI Biomarkers of nutritional exposure and nutritional status: An overview SO JOURNAL OF NUTRITION LA English DT Editorial Material DE biomarkers; diet assessment; epidemiology; nutrition; methodology C1 SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Freudenheim, JL (reprint author), SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. NR 11 TC 51 Z9 52 U1 1 U2 13 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAR PY 2003 VL 133 IS 3 SU S BP 873S EP 874S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 655GQ UT WOS:000181543300001 PM 12612172 ER PT J AU Potischman, N AF Potischman, N TI Biologic and methodologic issues for nutritional biomarkers SO JOURNAL OF NUTRITION LA English DT Article DE biomarkers; diet assessment; epidemiology; nutrition; methodology ID DRIED BLOOD SPOTS; BETA-CAROTENE; INTESTINAL-ABSORPTION; BREAST-CANCER; PLASMA CAROTENOIDS; VEGETABLES; LYCOPENE; SERUM; BIOAVAILABILITY; RETINOL AB Nutritional biomarkers are used for a variety of purposes in large-scale population surveys and epidemiologic studies as well as smaller clinical studies. The main reasons for using nutritional biomarkers are to provide measures of nutritional status that have less error than dietary data, nutrient status for nutrients with inadequate dietary data, to obtain a more proximal and integrated assessment of nutrient status that incorporates metabolism, to assess dietary change and compliance in intervention studies, and dietary intake for the validation of dietary questionnaires. However, often there is oversight by the investigators regarding biologic and laboratory issues, which have implications for the utility of nutritional biomarkers. This article reviews some of the physiologic issues that contribute to between-person variability in nutrient status and the utility and meaning of specimens from various body compartments. Issues related to the collection and storage of biologic specimens are addressed, although it is recommended that investigators contact laboratory colleagues at the beginning of any study for updated information. The necessity for blind quality surveillance of laboratory analyses beyond the normal procedures employed by collaborating laboratories also is addressed. The advantages and disadvantages of nutritional biomarkers are reviewed, especially in comparison with using dietary methodology. C1 NCI, Bethesda, MD 20892 USA. Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. RP Potischman, N (reprint author), NCI, Bethesda, MD 20892 USA. NR 56 TC 69 Z9 70 U1 3 U2 12 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAR PY 2003 VL 133 IS 3 SU S BP 875S EP 880S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 655GQ UT WOS:000181543300002 PM 12612173 ER PT J AU Lester, BM LaGasse, L Seifer, R Tronick, EZ Bauer, CR Shankaran, S Bada, HS Wright, LW Smeriglio, VL Liu, J Finnegan, LP Maza, PL AF Lester, BM LaGasse, L Seifer, R Tronick, EZ Bauer, CR Shankaran, S Bada, HS Wright, LW Smeriglio, VL Liu, J Finnegan, LP Maza, PL TI The Maternal Lifestyle Study (MLS): Effects of prenatal cocaine and/or opiate exposure on auditory brain response at one month SO JOURNAL OF PEDIATRICS LA English DT Article ID LIFE-STYLE; SUBSTANCE EXPOSURE; STEM RESPONSE; TERM INFANTS; PRETERM; ABUSE; MATURATION; PREGNANCY; OUTCOMES; MECONIUM AB Objective To study absolute and interpeak latencies of the auditory brain response in infants exposed to cocaine and/or opiates in utero. Study design The sample included 477 exposed and 554 comparison infants matched for race, sex, and gestational age. Mothers were recruited at 4 urban university-based centers; most were black, receiving public assistance, and had received adequate prenatal care. Exposure was determined by meconium assay and self-report with alcohol, marijuana, and tobacco present in both groups. At I month, infants were tested by masked examiners with the auditory brain response. Results Analyses were conducted for exposed and comparison groups and for level of prenatal cocaine exposure with adjustment for covariates (alcohol, marijuana, tobacco, gestational age at birth, social class, and site). Heavy prenatal cocaine exposure (greater than or equal to3 days per week, first trimester) led to an increase in the I-III, I-V, and III-V interpeak latencies and to a shorter latency to peak I. Infants with prenatal opiate exposure showed a longer latency to peak V and a longer III-I interpeak latency. Conclusions Prenatal cocaine and/or opiate exposure affects neural transmission. of these effects requires a large sample with control for gestational age, other drugs, and level cocaine use. C1 Brown Univ, Women & Infants Hosp, Infant Dev Ctr, Sch Med, Providence, RI 02905 USA. Bradley Hosp, Providence, RI USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Univ Miami, Sch Med, Miami, FL USA. Wayne State Univ, Sch Med, Detroit, MI USA. Univ Tennessee, Sch Med, Memphis, TN 38163 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NIDA, NIH, Bethesda, MD 20892 USA. NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. Adm Children Youth & Families, Washington, DC USA. RP Lester, BM (reprint author), Brown Univ, Women & Infants Hosp, Infant Dev Ctr, Sch Med, 101 Dudley St, Providence, RI 02905 USA. OI Seifer, Ronald/0000-0003-4879-2839 FU NICHD NIH HHS [N01-HD-2-3159, U10 HD 21385, U10 HD 21397, U10 HD 27856, U10 HD27904]; NIDA NIH HHS [U10 DA024119] NR 30 TC 34 Z9 35 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 2003 VL 142 IS 3 BP 279 EP 285 DI 10.1067/mpd.2003.112 PG 7 WC Pediatrics SC Pediatrics GA 658YL UT WOS:000181748600017 PM 12640376 ER PT J AU Nony, PA Schnellmann, RG AF Nony, PA Schnellmann, RG TI Mechanisms of renal cell repair and regeneration after acute renal failure SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PROXIMAL TUBULE CELLS; ISCHEMIA-INDUCED LOSS; EPITHELIAL-CELLS; GROWTH-FACTORS; REPERFUSION INJURY; ACTIN CYTOSKELETON; TOXICANT INJURY; FOCAL ADHESIONS; PRIMARY CULTURE; TISSUE-CULTURE AB In many cases, acute renal failure (ARF) is the result of proximal tubular cell injury and death and can arise in a variety of clinical situations, especially following renal ischemia and drug or toxicant exposure. Although much research has focused on the cellular events leading to ARF, less emphasis has been placed on the mechanisms of renal cell repair and regeneration, although ARF is reversed in over half of those who acquire it. Studies using in vivo and in vitro models have demonstrated the importance of proliferation, migration, and repair of physiological functions of injured renal proximal tubular cells (RPTC) in the reversal of ARF. Growth factors have been shown to produce migration and proliferation of injured RPTC, although the specific mechanisms through which growth factors promote renal regeneration in vivo are unclear. Recently, interactions between integrins and extracellular matrix proteins such as collagen IV were shown to promote the repair of physiological functions in injured RPTC. Specifically, collagen IV synthesis and deposition following cellular injury restored integrin polarity and promoted repair of mitochondrial function and active Na+ transport. Furthermore, exogenous collagen IV, but not collagen I, fibronectin, or laminin, promoted the repair of physiological functions without stimulating proliferation. These findings suggest the importance of establishing and/or maintaining collagen IV-integrin interactions in the stimulation of repair of physiological functions following sublethal cellular injury. Furthermore, the pathway that stimulates repair is distinct from that of proliferation and migration and may be a viable target for pharmacological intervention. C1 Med Univ S Carolina, Dept Pharmaceut Sci, Charleston, SC 29425 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Pharmaceut Sci, POB 250140,280 Calhoun St, Charleston, SC 29425 USA. NR 63 TC 103 Z9 107 U1 0 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 2003 VL 304 IS 3 BP 905 EP 912 DI 10.1124/jpet.102.035022 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648XP UT WOS:000181176900002 PM 12604664 ER PT J AU Madhavan, L Freed, WJ Anantharam, V Kanthasamy, AG AF Madhavan, L Freed, WJ Anantharam, V Kanthasamy, AG TI 5-hydroxytryptamine 1A receptor activation protects against N-methyl-D-aspartate-induced apoptotic cell death in striatal and mesencephalic cultures SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MAGNOCELLULAR NUCLEUS BASALIS; LARGE T-ANTIGEN; PARKINSONS-DISEASE; 5-HT1A RECEPTOR; DOPAMINERGIC-NEURONS; CASPASE-3-LIKE PROTEASES; MOTOR COMPLICATIONS; RAT-BRAIN; KINASE; MECHANISMS AB Apoptosis and glutamate-mediated excitotoxicity may play a role in the pathogenesis of many neurodegenerative disorders, including Parkinson's disease (PD). In the present study, we investigated whether stimulation of the 5-hydroxytryptamine 1A (5-HT1A) receptor attenuates N-methyl-D-aspartate-(NMDA) and 1-methyl-4- phenylpyridinium (MPP+)- induced apoptotic cell death in cell culture models. A brief exposure (20 min) of M213-2O striatal cells to NMDA and glutamate produced a delayed increase in caspase-3 activity and DNA fragmentation in a dose- and time-dependent manner. NMDA-induced caspase-3 activity and DNA fragmentation were almost completely blocked by the 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and (R)-5-fluoro-8hydroxy-2-(dipropylamino)- tetralin (R-UH-301). Additionally, the protective effects of 8-OH-DPAT and R-UH-301 on NMDA-induced caspase-3 activation and apoptosis were reversed by pretreatment with the 5-HT1A antagonists N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide (WAY 100635) and S-UH-301, respectively. Similarly, dose- and time-dependent increases in caspase-3 activity and DNA fragmentation were observed in rat primary mesencephalic neurons after a brief exposure to NMDA and glutamate. Caspase-3 activation and DNA fragmentation in primary mesencephalic neurons were almost completely inhibited by 8-OH-DPAT. This neuroprotective effect of 8-OH-DPAT was reversed by WAY 100635. Additionally, 8-OH-DPAT blocked tyrosine hydroxylase (TH)-positive cell death after NMDA exposure and also almost completely attenuated the NMDA-induced Ca2+ influx in primary mesencephalic cultures. Furthermore, 8-OH-DPAT and R-UH-301 blocked apoptotic cell death in the primary mesencephalic neurons that were exposed to the Parkinsonian toxin MPP+. Together, these results suggest that 5-HT1A receptor stimulation may be a promising pharmacological approach in the development of neuroprotective agents for PD. C1 Iowa State Univ, Parkinsons Disorder Res Lab, Dept Biomed Sci, Ames, IA 50011 USA. Natl Inst Drug Abuse, Cellular Neurobiol Branch, Baltimore, MD USA. RP Kanthasamy, AG (reprint author), Iowa State Univ, Parkinsons Disorder Res Lab, Dept Biomed Sci, 2008 Vet Med Bldg, Ames, IA 50011 USA. FU NINDS NIH HHS [R01-NS38644] NR 41 TC 42 Z9 43 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 2003 VL 304 IS 3 BP 913 EP 923 DI 10.1124/jpet.102.044370 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648XP UT WOS:000181176900003 PM 12604665 ER PT J AU Bowie, D Garcia, EP Marshall, J Traynelis, SF Lange, GD AF Bowie, D Garcia, EP Marshall, J Traynelis, SF Lange, GD TI Allosteric regulation and spatial distribution of kainate receptors bound to ancillary proteins SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID LIGAND-BINDING CORE; GLUTAMATE-RECEPTOR; CONCANAVALIN-A; PDZ DOMAINS; DIFFERENTIAL REGULATION; K+ CHANNELS; KINASE-A; DESENSITIZATION; ACTIVATION; MODULATION AB A diverse range of accessory proteins regulates the behaviour of most ligand- and voltage-gated ion channels. For glutamate receptor 6 (GluR6) kainate receptors, two unrelated proteins, concanavalin-A (Con-A) and postsynaptic density protein 95 (PSD-95), bind to extra- and intracellular domains, respectively, but are reported to exert similar effects on GluR6 desensitization behaviour. We have tested the hypothesis that distinct allosteric binding sites control GluR6 receptors via a common transduction pathway. Rapid agonist application to excised patches revealed that neither Con-A nor PSD-95 affect the onset of desensitization. The rate of desensitization elicited by 10 MM L-glutamate was similar in control (tau(fast) = 5.5 +/- 0.4 ms), Con-A-treated patches (tau(fast) = 6.1 +/- 0.5 ms) and patches containing PSD-95 and GluR6 receptors (tau(fast) = 4.7 +/- 0.6 ms). Likewise, the time course of recovery from GluR6 desensitization was similar in both control and Con-A conditions, whereas PSD-95 accelerated recovery almost twofold. Peak and steady-state (SS) dose-response relationships to glutamate were unchanged by lectin treatment (e.g. control, EC50(ss) = 31 +/- 28 muM vs Con-A, EC50(SS) = 45 +/- 9 muM, n = 6), suggesting that Con-A does not convert non-conducting channels with high agonist affinity into an open conformation. Instead, we demonstrate that the effects of Con-A on macroscopic responses reflect a shift in the relative contribution of different open states of the channel. In contrast, the effect of PSD-95 on recovery behaviour suggests that the association between kainate receptors and cytoskeletal proteins regulates signalling at glutamatergic synapses. Our results show that Con-A and PSD-95 regulate kainate receptors via distinct allosteric mechanisms targeting selective molecular steps in the transduction pathway. C1 McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada. Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USA. NINDS, Instrumentat & Comp Sect, NIH, Bethesda, MD 20892 USA. RP Bowie, D (reprint author), McGill Univ, Dept Pharmacol & Therapeut, Room 1317,McInteyte Med Sci Bldg,3655 Sir William, Montreal, PQ, Canada. FU NIMH NIH HHS [R01 MH062144, R01 MH62144]; NINDS NIH HHS [R01 NS036654, R01 NS039309, R01 NS36654, R01 NS39309] NR 41 TC 46 Z9 47 U1 0 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAR 1 PY 2003 VL 547 IS 2 BP 373 EP 385 DI 10.1113/jphysiol.2002.033076 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 690VE UT WOS:000183570500004 PM 12562952 ER PT J AU Woods, AS Moyer, SC Wang, HYJ Wise, RA AF Woods, AS Moyer, SC Wang, HYJ Wise, RA TI Interaction of chlorisondamine with the neuronal nicotinic acetylcholine receptor SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE noncovalent interactions; protein epitopes; quaternary amines; ganglionic blockers ID ASSISTED-LASER-DESORPTION/IONIZATION; CATION-PI INTERACTIONS; MASS-SPECTROMETRY; GAS-PHASE; STRIATAL SYNAPTOSOMES; MEDIATED RELEASE; FOLDING PROBLEM; BINDING-SITE; METAL-IONS; PROTEIN AB An epitope was found on the alpha2-nicotinic isoform of the neuronal nicotinic acetylcholine receptor that would likely form salt bridges with quaternary ammonium compounds and a cation-pi interaction with the pi-cloud of an aromatic ring. Chlorisondamine, a nicotinic antagonist, exerts a long-lasting, if not permanent, blockade of the ion channel gated by acetylcholine. Blocking of the ion channel prevents nicotine from exerting its rewarding effect on the CNS. Chlorisondamine contains two quaternary ammonium groups and a tetrachloroisoindoline ring. We propose that chlorisondamine interacts with an epitope on the pi2 isoform of the rat neuronal nicotinic receptor (residues 388-402, GEREET-EEEEEEEDE), where one or both of the quaternary ammonium groups of chlorisondamine form a salt bridge with either a glutamic acid side chain or a phosphate group, whereas the tetrachlorobenzene portion of the tetrachloroisoindoline ring interacts with the guanidinium group of arginine in a cation-pi association. In this work, a new way of probing the interaction of a receptor epitope (pi2) with organic molecules (chlorisondamine and hexachlorobenzene) was undertaken using matrix assisted laser desorption/ionization mass spectrometry. C1 Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA. RP Woods, AS (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Wise, Roy/A-6465-2012 NR 46 TC 21 Z9 21 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD MAR-APR PY 2003 VL 2 IS 2 BP 207 EP 212 DI 10.1021/pr025578h PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 665WD UT WOS:000182143500011 PM 12716135 ER PT J AU Penedo, FJ Gonzalez, JS Dahn, JR Antoni, M Malow, R Costa, P Schneiderman, N AF Penedo, FJ Gonzalez, JS Dahn, JR Antoni, M Malow, R Costa, P Schneiderman, N TI Personality, quality of life and HAART adherence among men and women living with HIV/AIDS SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE HIV; AIDS; personality; quality of life; HAART adherence ID IMMUNODEFICIENCY-VIRUS INFECTION; SELF-REPORTED ADHERENCE; PIR FACET SCALES; OF-LIFE; HIV-INFECTION; DISEASE; CONSCIENTIOUSNESS; AGREEABLENESS; POPULATION; PREDICTORS AB Very few studies have documented relations between personality traits and quality of life among individuals living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). Some have shown that poor perceived quality of life as determined by a sense of purpose may be associated with inadequate adherence to highly active antiretroviral treatment (HAART) in this population. Although adequate HAART adherence is critical to achieve the full therapeutic effects of newly and highly effective regimens, very little is known of how both personality factors and HIV-specific quality of life may impact adherence to these medication regimens. This study evaluated relations among personality traits, quality of life and HAART adherence among 116 men and women living with HIV/AIDS. Results showed that personality traits such as neuroticism were significantly associated with poorer quality of life, whereas conscientiousness and extraversion were associated with better quality of life. In contrast, personality traits were not directly related to HAART adherence. Both higher overall functioning and lower medication worries scores were significantly associated with HAART adherence. Findings suggest that personality traits are associated with HIV-specific quality of life on the one hand, and that HIV-specific quality of life is related to HAART adherence on the other. Future studies assessing the efficacy of psychosocial interventions in improving quality of life and HAART adherence should consider the role of personality traits in promoting better quality of life. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Univ Miami, Dept Psychol, Coral Gables, FL 33134 USA. Univ Miami, Dept Psychiat & Behav Sci, Coral Gables, FL 33134 USA. NIA, Baltimore, MD 21224 USA. RP Penedo, FJ (reprint author), Univ Miami, Dept Psychol, POB 248185, Coral Gables, FL 33134 USA. OI Costa, Paul/0000-0003-4375-1712 FU NIMH NIH HHS [P01 MH49548] NR 40 TC 48 Z9 53 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD MAR PY 2003 VL 54 IS 3 BP 271 EP 278 AR PII S0022-3999(02)00482-8 DI 10.1016/S0022-3999(02)00482-8 PG 8 WC Psychiatry SC Psychiatry GA 653YE UT WOS:000181464000012 PM 12614837 ER PT J AU Chen, SK Hsieh, WA Tsai, MH Chen, CC Hong, AI Wei, YH Chang, WP AF Chen, SK Hsieh, WA Tsai, MH Chen, CC Hong, AI Wei, YH Chang, WP TI Age-associated decrease of oxidative repair enzymes, human 8-oxoguanine DNA glycosylases (hOgg1), in human aging SO JOURNAL OF RADIATION RESEARCH LA English DT Article DE Ogg1; aging; polymorphism; 8-oxoguanine; glycosylase ID BASE EXCISION-REPAIR; DAMAGED DNA; 8-HYDROXYGUANINE; POLYMORPHISM; ENDONUCLEASE; ACCUMULATION; PROTEIN; CELLS; OGG1 AB 8-Oxoguanine has been shown to be a dominant cause of oxidative DNA damage by oxygen free radicals in eukaryotic cells. The 8-oxoguanine repair-specific enzyme 8-oxoguanine-DNA glycosylase (hOgg1) was recently cloned and was observed to conduct mainly short-patch base-excision repair. It has also been suggested that reactive oxygen species play an important role in the cellular aging process. We explored the association between the hOgg1 enzyme activity in somatic cells of human subjects of various ages and the role of hOgg1(326) genetic polymorphism. An 8-oxoguanine-containing 28 mer oligonucleotide was end-labeled with gamma-P-32 ATP and incubated with protein extracts from peripheral blood lymphocytes (PBL) from 78 healthy individuals ranging in age from newborn to 91 years old. The hOgg1 repair activity toward the radiolabelled 8-oxoguanine-containing DNA was determined, and the results indicated a significant age-dependent decrease in the hOgg1 activity in their lymphocytes. Significantly reduced activity was also shown in those with Cysteine/Cysteine genotypes. The genders of the subjects were not shown to be associated. These results provide an important observation regarding the cellular hOgg1 activity in somatic cells during the normal human aging processes. C1 Natl Yang Ming Univ, Inst Environm Hlth Sci, Taipei 112, Taiwan. NIH, Natl Res Inst, Bethesda, MD 20892 USA. Natl Yang Ming Univ, Inst Biochem, Taipei, Taiwan. Tzu Chi Univ, Inst Aboriginal Hlth, Hwalien, Taiwan. Natl Yang Ming Univ, Inst Biochem, Taipei, Taiwan. Natl Miaoli Gen Hosp, Taipei 11200, Taiwan. RP Chang, WP (reprint author), Natl Yang Ming Univ, Inst Environm Hlth Sci, Taipei 112, Taiwan. NR 20 TC 62 Z9 64 U1 0 U2 4 PU JAPAN RADIATION RESEARCH SOC PI CHIBA PA C/O NAT INST RADIOLOGICAL SCI 9-1 ANAGAWA-4-CHOME INAGE-KU, CHIBA, 263, JAPAN SN 0449-3060 J9 J RADIAT RES JI J. Radiat. Res. PD MAR PY 2003 VL 44 IS 1 BP 31 EP 35 PG 5 WC Biology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA 696BV UT WOS:000183866200005 PM 12841596 ER PT J AU Petzke, F Gracely, RH Park, KM Ambrose, K Clauw, DJ AF Petzke, F Gracely, RH Park, KM Ambrose, K Clauw, DJ TI What do tender points measure? Influence of distress on 4 measures of tenderness SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE tender points; pain; tenderness; psychophysical; distress; fibromyalgia ID FIBROMYALGIA SYNDROME; GENERAL-POPULATION; PAIN THRESHOLD; CLASSIFICATION; MECHANISMS AB Objective. To examine the relationship between current pain, distress, and ascending and random measures of tenderness. Methods. Manual tender point counts and dolorimeter measures of the pressure pain threshold were determined in a sample of 47 women representative of the general population with respect to tenderness. In addition, discrete pressure stimuli of varying intensities to the left thumb were applied in random fashion. Distress was measured with the Brief Symptom Inventory and the Beck Depression Inventory, and pain was evaluated with the Short Form McGill Pain. Questionnaire. Results. Only the random measure of tenderness was relatively independent of an individual's current psychological state. The respective correlation coefficients between measures of tenderness and psychological state were generally greatest for the manual tender point count and also significant for the dolorimeter measures. In contrast; all measures were highly correlated with ratings of spontaneous pain, again with the manual tender point count showing the strongest, and the random method the weakest, correlations. Linear regression analysis replicated the results of the correlational analysis. Conclusion. As a measure of tenderness, the number of positive tender points is clearly influenced by an individual's distress. Other more sophisticated measures of tenderness that randomly present stimuli in an unpredictable fashion appear to be relatively immune to these biasing effects, although our results obtained in a research setting have yet to be replicated in clinical practice. C1 Georgetown Univ, Chron Pain & Fatigue Res Ctr, Ctr Med, Washington, DC 20057 USA. George Washington Univ, Ctr Med, Dept Anesthesiol, Washington, DC USA. NIDC, PNMB, Clin Measurement & Mechanisms Unit, NIH, Bethesda, MD USA. RP Clauw, DJ (reprint author), Univ Michigan, Ctr Med, 101 Simpson, Ann Arbor, MI 48109 USA. NR 20 TC 81 Z9 81 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 2003 VL 30 IS 3 BP 567 EP 574 PG 8 WC Rheumatology SC Rheumatology GA 652GU UT WOS:000181372100025 PM 12610818 ER PT J AU Sprince, NL Park, H Zwerling, C Lynch, CF Whitten, PS Thu, K Burmeister, LF Gillette, PP Alavanja, MCR AF Sprince, NL Park, H Zwerling, C Lynch, CF Whitten, PS Thu, K Burmeister, LF Gillette, PP Alavanja, MCR TI Risk factors for animal-related injury among Iowa large-livestock farmers: A case-control study nested in the agricultural health study SO JOURNAL OF RURAL HEALTH LA English DT Article ID OCCUPATIONAL INJURIES; OLDER WORKERS; HAZARD SURVEILLANCE; PROSPECTIVE COHORT; FAMILY HEALTH; PREVALENCE; DISABILITIES; IMPAIRMENTS; RETIREMENT; ACCIDENTS AB Context: Although farmers are at risk for injuries from contact with large livestock, few previous studies have examined risk factors for animal-related injuries. Purpose: This case-control study, nested in the Agricultural Health Study, aimed to assess risk factors for animal-related injury among Iowa large-livestock farmers. Methods: A screener questionnaire sent to 6999 farmers identified 116 farmers with large livestock who has an animal-related injury requiring medical advice/treatment in the previous year. Several possible risk factors for injury were assessed by comparing these farmers with 342 farmers who had livestock but were not injured in the previous year. findings: A multiple logistic regression analysis showed significant associations between animal-related injury and the use of a hearing aid (odds ratio [OR] = 5.4 [95% CI, 1.6 to 18.0]), doctor-diagnosed arthritis or rheumatism (OR = 3.0 [95% CI, 1.7 to 5.2]), education beyond high school (OR = 1.8 [95% CI, 1.1 to 2.8]), and a younger age. Farmers engaged in off-farm work were less likely to sustain animal-related injuries (OR = 0.4 [95% CI, 0.2 to 0.8]). Conclusions: This is the first study to show associations between animal-related injury and a younger age, hearing difficulties, and doctor-diagnosed arthritis. Hearing loss and arthritis, which are more common among farmers than among other workers, may be particularly important risk factors to address in future preventive studies. C1 Univ Iowa, Coll Publ Hlth, Dept Environm & Occupat Hlth, Iowa City, IA 52242 USA. Ewha Womans Univ, Dept Prevent Med, Seoul, South Korea. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA. Univ Iowa, Coll Publ Hlth, Dept Occupat Hlth & Environm Hlth, Iowa City, IA 52242 USA. Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA 52242 USA. No Illinois Univ, Dept Anthropol, De Kalb, IL 60115 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Sprince, NL (reprint author), Univ Iowa, Coll Publ Hlth, Dept Environm & Occupat Hlth, 100 Oakdale Campus, Iowa City, IA 52242 USA. EM nancy-sprince@uiowa.edu FU ODCDC CDC HHS [R49CCR703640-10] NR 43 TC 33 Z9 35 U1 3 U2 6 PU NATL RURAL HEALTH ASSOC PI KANSAS CITY PA ONE WEST ARMOUR BLVD, STE 301, KANSAS CITY, MO 64111 USA SN 0890-765X J9 J RURAL HEALTH JI J. Rural Health PD SPR PY 2003 VL 19 IS 2 BP 165 EP 173 DI 10.1111/j.1748-0361.2003.tb00558.x PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 658JX UT WOS:000181718800012 PM 12696853 ER PT J AU Simons-Morton, BG Crump, AD AF Simons-Morton, BG Crump, AD TI Association of parental involvement and social competence with school adjustment and engagement among sixth graders SO JOURNAL OF SCHOOL HEALTH LA English DT Article ID PSYCHOLOGICAL ADJUSTMENT; EARLY ADOLESCENCE; MIDDLE SCHOOL; MOTIVATION; YOUTH; GIRLS; PEER AB To identify factors associated with school adjustment and engagement, 1,267 sixth graders in four middle schools in one US school district were surveyed at the beginning (Time 1) of the school year, 1,081 (85.3%) of whom were surveyed again at the end (Time 2). School adjustment was higher for girls than boys at both Time 1 and Time 2 and the decline was less for girls than boys and Whites than Blacks. School engagement also declined significantly from Time 1 to Time 2, but no differences existed among subgroups. In multiple linear regression analyses, female gender, school engagement, social competence, parental involvement, and depressive symptoms (negative association) assessed at Time 1 were associated with school adjustment assessed cross-sectionally at Time 1 and prospectively at Time 2. Social competence and parental involvement assessed at Time I were associated with school engagement assessed at Time 1 and Time 2. Findings confirm the decline in school adjustment and engagement during middle school and provide evidence that parental involvement and social competence may be protective against declines in these variables. C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA. NIDA, Prevent Res Branch, NIH, Bethesda, MD 20892 USA. RP Simons-Morton, BG (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,7B05, Rockville, MD 20852 USA. EM Bruce_SimonsMorton@nih.gov; acrump@mail.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 35 TC 34 Z9 34 U1 3 U2 9 PU AMER SCHOOL HEALTH ASSOC PI KENT PA PO BOX 708, KENT, OH 44240 USA SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD MAR PY 2003 VL 73 IS 3 BP 121 EP 126 PG 6 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA 658XL UT WOS:000181746300006 PM 12683346 ER PT J AU Pianta, RC AF Pianta, RC TI Untitled SO JOURNAL OF SCHOOL PSYCHOLOGY LA English DT Editorial Material C1 Univ Virginia, NICHD, Study Early Childcare, Charlottesville, VA 22908 USA. RP Pianta, RC (reprint author), Univ Virginia, NICHD, Study Early Childcare, POB 800784, Charlottesville, VA 22908 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-4405 J9 J SCHOOL PSYCHOL JI J. Sch. Psychol. PD MAR-APR PY 2003 VL 41 IS 2 BP 99 EP 100 DI 10.1016/S0022-4405(03)00027-X PG 2 WC Psychology, Educational SC Psychology GA 664GR UT WOS:000182053800001 ER PT J AU Hinshaw, JE Milligan, RA AF Hinshaw, JE Milligan, RA TI Nuclear pore complexes exceeding eightfold rotational symmetry SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE assembly; disassembly; electron microscopy; image analysis; nuclear envelope; nuclear pore complex; Xenopus oocyte ID SCANNING ELECTRON-MICROSCOPY; FIELD-EMISSION; MEMBRANE-PROTEIN; BIOLOGICAL MACROMOLECULES; CRYOELECTRON MICROSCOPY; CYTOPLASMIC TAIL; SINGLE PARTICLES; TRANSPORT; ARCHITECTURE; MITOSIS AB Nuclear pore complexes are rotationally symmetric structures that span the nuclear envelope and provide channels for nucleocytoplasmic traffic. These large complexes normally consist of eight spokes arranged around a central channel, although, occasionally, 9- and 10-fold nuclear pore complexes are found in preparations of Xenopus oocyte macronuclei. Here we examine these unusual nuclear pore complexes by negative stain electron microscopy and image analysis and compare the results with data previously obtained from 8-fold structures. The details in two-dimensional and three-dimensional maps indicate that the substructure of the spoke is the same in 8-, 9- and 10-fold nuclear pore complexes: therefore, the spoke is likely an immutable structural component. In all three variant forms, the spacing between adjacent annular subunits, which surround the central channel, is identical. Distances between spokes at higher radius decrease in the 9- and 10-fold nuclear pore complexes. These data imply that the most important connections holding the nuclear pore complex together are those between adjacent annular subunits and that these interactions may play a predominant role in nuclear pore complex assembly. Circumferential connections mediated by ring subunits and radial arms presumably further stabilize the structure and are flexible enough to accommodate additional spokes. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Cell Biol, Ctr Integrat Mol Biosci, La Jolla, CA 92037 USA. RP Hinshaw, JE (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, 8 Ctr Dr,Bldg 8,Room 419, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM 44932] NR 62 TC 27 Z9 28 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD MAR PY 2003 VL 141 IS 3 BP 259 EP 268 DI 10.1016/S1047-8477(02)00626-3 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 660YX UT WOS:000181864400008 PM 12648571 ER PT J AU Studenski, S Perera, S Wallace, D Chandler, JM Duncan, PW Rooney, E Fox, M Guralnik, JM AF Studenski, S Perera, S Wallace, D Chandler, JM Duncan, PW Rooney, E Fox, M Guralnik, JM TI Physical performance measures in the clinical setting SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE geriatric assessment; risk assessment; locomotion; health maintenance organizations; hospitalization; activities of daily living ID COMPREHENSIVE GERIATRIC ASSESSMENT; LOWER-EXTREMITY FUNCTION; OLDER ADULTS; SUBSEQUENT DISABILITY; PREDICTIVE-VALIDITY; HEALTH SURVEY; MORTALITY; DECLINE; RISK; CARE AB OBJECTIVES: To assess the ability of gait speed alone and a three-item lower extremity performance battery to predict 12-month rates of hospitalization, decline in health, and decline in function in primary care settings serving older adults. DESIGN: Prospective cohort study. SETTING: Primary care programs of a Medicare health maintenance organization (HMO) and Veterans Affairs (VA) system. PARTICIPANTS: Four hundred eighty-seven persons aged 65 and older. MEASUREMENTS: Lower extremity performance Established Population for Epidemiologic Studies of the Elderly (EPESE) battery including gait speed, chair stands, and tandem balance tests; demographics; health care use; health status; functional status; probability of repeated admission scale (Pra); and primary physician's hospitalization risk estimate. RESULTS: Veterans had poorer health and higher use than HMO members. Gait speed alone and the EPESE battery predicted hospitalization; 41% (21/51) of slow walkers (gait speed <0.6 m/s) were hospitalized at least once, compared with 26% (70/266) of intermediate walkers (0.6-1.0 m/s) and 11% (15/136) of fast walkers (>1.0 m/s) (P < .0001). The relationship was stronger in the HMO than in the VA. Both performance measures remained independent predictors after accounting for Pra. The EPESE battery was superior to gait speed when both Pra and primary physician's risk estimate were included. Both performance measures predicted decline in function and health status in both health systems. Performance measures, alone or in combination with self-report measures, were more able to predict outcomes than self-report alone. CONCLUSION: Gait speed and a physical performance battery are brief, quantitative estimates of future risk for hospitalization and decline in health and function in clinical populations of older adults. Physical performance measures might serve as easily accessible "vital signs" to screen older adults in clinical settings. C1 Univ Kansas, Med Ctr, Ctr Aging, Kansas City, KS 66103 USA. Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66103 USA. Univ Kansas, Med Ctr, Dept Prevent Med, Kansas City, KS 66103 USA. Univ Kansas, Med Ctr, Dept Hlth Policy & Management, Kansas City, KS 66103 USA. Rho World Inc, Chapel Hill, NC USA. Merck Res Labs, Blue Bell, PA USA. Dept Vet Affairs, Kansas City, MO USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Studenski, S (reprint author), VA Pittsburgh GRECC, Dept Geriatr Med, 3471 5th Ave Suite 500, Pittsburgh, PA 15213 USA. RI Perera, Subashan/D-7603-2014 FU NIA NIH HHS [AG 14635] NR 44 TC 485 Z9 491 U1 5 U2 36 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2003 VL 51 IS 3 BP 314 EP 322 DI 10.1046/j.1532-5415.2003.51104.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 646GW UT WOS:000181028100004 PM 12588574 ER PT J AU Newman, AB Haggerty, CL Goodpaster, B Harris, T Kritchevsky, S Nevitt, M Miles, TP Visser, M AF Newman, AB Haggerty, CL Goodpaster, B Harris, T Kritchevsky, S Nevitt, M Miles, TP Visser, M CA Hlth Aging Body Composition Res Gr TI Strength and muscle quality in a well-functioning cohort of older adults: The Health, Aging and Body Composition Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE strength; muscle quality; sarcopenia; aging ID CROSS-SECTIONAL AREA; X-RAY ABSORPTIOMETRY; FAT-FREE MASS; SKELETAL-MUSCLE; ELDERLY MEN; WOMEN; AGE; DISABILITY; WEAKNESS; SIZE AB OBJECTIVES: To determine whether lower lean mass and higher fat mass have independent effects on the loss of strength and muscle quality in older adults and might explain part of the effect of age. DESIGN: Single-episode, cross-sectional analyses of a cohort of subjects in the Health, Aging and Body Composition (Health ABC) Study. SETTING: Ambulatory clinic and research laboratory. PARTICIPANTS: Two thousand six hundred twenty-three men and women aged 70 to 79 from the Health ABC Study. MEASUREMENTS: Upper and lower extremity strength was measured using isokinetic (knee extension) and isometric (grip strength) dynamometers. Body composition (lean mass and fat mass) was determined by measuring lean mass of upper and lower extremities and the total body by dual-energy x-ray absorptiometry. Muscle quality was ascertained by taking the ratio of strength to muscle mass for both upper and lower extremities. RESULTS: Upper and lower extremity strength and muscle quality decreased as age increased. Most of the explained variance in strength was due to differences in muscle mass, but, in those at the extremes of body fat and lower leg muscle quality, the association with body fat was independent of the effect of age. Although blacks had greater muscle strength and mass than whites, leg muscle quality tended to be lower in blacks than in whites. Upper extremity strength adjusted for lean mass and muscle quality were also associated inversely and independently with age, body fat, and black race. CONCLUSION: In this older cohort, lower strength with older age was predominantly due to a lower muscle mass. Age and body fat also had significant inverse associations with strength and muscle quality. Both preservation of lean mass and prevention of gain in fat may be important in maintaining strength and muscle quality in old age. C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. Univ Texas, Dept Family Practice, San Antonio, TX 78285 USA. Vrije Univ Amsterdam, Inst Res Extramural Med, Amsterdam, Netherlands. RP Newman, AB (reprint author), Univ Pittsburgh, Sch Med, Div Geriatr Med, 3520 5th Ave,Suite 300, Pittsburgh, PA 15213 USA. RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Miles, Toni/0000-0003-0823-2319; Haggerty, Catherine/0000-0002-9849-7865 FU NIA NIH HHS [N01 AG 62101, N01 AG 62103, N01 AG 62106] NR 28 TC 190 Z9 196 U1 6 U2 27 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2003 VL 51 IS 3 BP 323 EP 330 DI 10.1046/j.1532-5415.2003.51105.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 646GW UT WOS:000181028100005 PM 12588575 ER PT J AU Talbot, LA Gaines, JM Huynh, TN Metter, EJ AF Talbot, LA Gaines, JM Huynh, TN Metter, EJ TI A home-based pedometer-driven walking program to increase physical activity in older adults with osteoarthritis of the knee: A preliminary study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pedometer; physical activity; muscle strength; function ID SENIORS TRIAL FAST; MUSCLE STRENGTH; EXERCISE; ARTHRITIS; DISABILITY; FITNESS; PERFORMANCE; DISEASE; WOMEN; MANAGEMENT AB OBJECTIVES: To determine whether a home-based pedometer-driven walking program with arthritis self-management education (Walk +) would increase physical activity, muscle strength, and functional performance in older adults with osteoarthritis (OA) of the knee as opposed to arthritis self-management education alone (EDU). DESIGN: A randomized two-by-three (group-by-time) design with participants assigned to Walk + (n = 17, mean age +/- standard deviation = 69.6 +/- 6.7) or EDU (n = 17, age = 70.8 +/- 4.7). SETTING: Community located in the Baltimore-Washington area. PARTICIPANTS: Thirty-four community-dwelling adults, aged 60 and older with symptomatic knee OA and self-reported functional impairment. INTERVENTIONS: Both groups received 12 hours of the Arthritis Self-Management program over 12 weeks and were followed for an additional 12 weeks. In addition, the Walk + group received individualized instruction in the use of a pedometer, with the goal of increasing their step count by 30% of their baseline step count. MEASUREMENTS: The outcome measures were physical activity (daily step counts and total activity vector magnitude as measured by a pedometer and Tritrac-R3D accelerometer), quadriceps femoris strength (isometric peak torque), and functional performance tasks (100-foot walk-turn-walk, timed stair climb, timed chair rise, and pain status). RESULTS: Daily steps walked showed a significant group-by-time interaction (P = .04) after controlling for age. From baseline to completion of training, a 23% increase in daily steps occurred in the Walk + group and a 15% decrease in the EDU group. Although steps increased in the Walk + group, total activity vector magnitude was maintained, suggesting a more efficient gait. The Walk + group became quicker than the EDU group in the normal-pace walk-turn-walk (P = .04). An isometric strength gain of 21% postintervention was seen in the Walk + group, compared with a loss of 3.5% in the EDU group. CONCLUSION: In older adults with symptomatic knee OA, Walk + appears to increase walking, with improvements in muscle strength and walking performance. The use of a home-based pedometer-driven program to increase physical activity, strength, and function in this population warrants further research. C1 Johns Hopkins Univ, Sch Nursing, Baltimore, MD 21205 USA. Erickson Fdn, Baltimore, MD USA. OConnor Hosp, San Jose, CA USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Talbot, LA (reprint author), Johns Hopkins Univ, Sch Nursing, 525 N Wolfe St,Rm 445, Baltimore, MD 21205 USA. NR 32 TC 147 Z9 147 U1 4 U2 31 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2003 VL 51 IS 3 BP 387 EP 392 DI 10.1046/j.1532-5415.2003.51113.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 646GW UT WOS:000181028100013 PM 12588583 ER PT J AU Shumway-Cook, A Patla, A Stewart, A Ferrucci, L Ciol, MA Guralnik, JM AF Shumway-Cook, A Patla, A Stewart, A Ferrucci, L Ciol, MA Guralnik, JM TI Environmental components of mobility disability in community-living older persons SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE mobility; disability; aging; environment ID DISABLEMENT AB OBJECTIVES: To examine the relationship between characteristics of the physical environment and mobility disability in community-living older persons. DESIGN: Cross-sectional study conducted on three groups of community-dwelling older adults. SETTING: Community-dwelling older people in Seattle, Washington, and Waterloo, Ontario, Canada. PARTICIPANTS: Fifty-four older adults (greater than or equal to70) were recruited from two geographic sites and grouped according to level of physical function (elite, physically able, physically disabled). MEASUREMENT: Subjects reported on frequency of encounter versus avoidance of 24 features of the physical environment, grouped into eight dimensions, using a five-point ordinal scale (never, rarely, sometimes, often, always). Never and rarely responses were combined and coded as not encountered or not avoided, whereas the sometimes, often or always responses were combined and coded as encountered or avoided. RESULTS: Disabled older adults reported fewer encounters with and concomitantly greater avoidance of physical challenges to mobility than nondisabled older adults. However, both encounter and avoidance varied by environmental dimension. CONCLUSION: Results support the hypothesis that mobility disability results from an interaction of individual and environmental factors. Mobility disability is associated with avoidance of some, but not all, physically challenging features within the environment, suggesting that some environmental features may disable community mobility more than others. C1 Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Waterloo, Dept Kinesiol, Waterloo, ON N2L 3G1, Canada. Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA 94143 USA. INRCA, Florence, Italy. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Shumway-Cook, A (reprint author), Univ Washington, Dept Rehabil Med, Box 356490, Seattle, WA 98195 USA. NR 17 TC 87 Z9 90 U1 0 U2 14 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2003 VL 51 IS 3 BP 393 EP 398 DI 10.1046/j.1532-5415.2003.51114.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 646GW UT WOS:000181028100014 PM 12588584 ER PT J AU Locatis, C Fontelo, P Sneiderman, C Ackerman, M Uijtdehaage, S Candler, C Stensaas, S Dennis, S AF Locatis, C Fontelo, P Sneiderman, C Ackerman, M Uijtdehaage, S Candler, C Stensaas, S Dennis, S TI Webcasting videoconferences over IP: A synchronous communication experiment SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article AB A multipoint videoconference was webcast live to an audience who could communicate with conference panelists and each other via chat. The videoconference, webcast, and chat were done entirely over the Internet. Seven panelists at four conference sites that had Internet2 connectivity and were located in different time zones within the continental United States discussed the topic of "Evaluating Health Professions Education and Information Resources on the Web." This discussion was broadcast to individuals and groups at various U.S. locations who had expressed an interest in the topic and had sufficient connectivity for receiving the video stream. Webcast recipients could log on a chat server and type questions and comments to the panelists and other viewers. The experiment's rationale, procedures, and outcomes are described, and issues associated with the use of the technologies are identified. C1 Natl Lib Med, Bethesda, MD 20894 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Oklahoma, Coll Med, Oklahoma City, OK 73190 USA. Univ Utah, Ctr Hlth Sci, Salt Lake City, UT USA. RP Locatis, C (reprint author), Natl Lib Med, Bldg 38A,Room B1N-30F,8600 Rockville Pike, Bethesda, MD 20894 USA. OI Uijtdehaage, Sebastian/0000-0001-8598-4683 NR 12 TC 14 Z9 15 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAR-APR PY 2003 VL 10 IS 2 BP 150 EP 153 DI 10.1197/jamia.M1170 PG 4 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 660RT UT WOS:000181847300004 PM 12595404 ER PT J AU Ge, Y ElNaggar, M Sze, SK Bin Oh, H Begley, TP McLafferty, FW Boshoff, H Barry, CE AF Ge, Y ElNaggar, M Sze, SK Bin Oh, H Begley, TP McLafferty, FW Boshoff, H Barry, CE TI Top down characterization of secreted proteins from Mycobacterium tuberculosis by electron capture dissociation mass spectrometry SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID MULTIPLY-CHARGED IONS; POLYACRYLAMIDE-GEL ELECTROPHORESIS; INFRARED MULTIPHOTON DISSOCIATION; EXTRACELLULAR PROTEINS; KDA; IDENTIFICATION; GLYCOSYLATION; ANTIGENS; SEQUENCE; DEFINITION AB Secreted proteins of Mycobacterium tuberculosis are implicated in its disease pathogenesis and so are considered as potential diagnostic and vaccine candidates. The search for these has been slow, even though the entire genome sequence of M. tuberculosis is now available; of the 620 protein spots resolved by 2-D gel electrophoresis, 114 secreted proteins have been identified, but for only 13 has the primary structure been partly characterized. For comparison, in this top down mass spectrometry (MS) approach the secreted proteins were precipitated from cell culture filtrate, resuspended, and examined directly by electrospray ionization (ESI) Fourier transform MS. The ESI spectra of three precipitates showed 93, 535, and 369 molecular weight (M-r) values, for a total of 689 different values. However, only similar to10% of these values matched (+/-1 Da) the DNA predicted M-r values, but these identifications were unreliable. Of nine molecular ions characterized by MS/MS, only one protein match was confirmed, and its isotopic molecular ions were overlapped by those of another protein. MS/MS identified a total of ten proteins by sequence tag search, of which three were unidentified previously. The low success of M-r matching was due to unusually extensive posttranslational modifications, including loss of a signal sequence, loss of the N-terminal residue, proteolytic degradation, oxidation, and glycosylation. Although in eubacteria the latter is relatively rare, a 9 kDa protein showed 7 hexose attachments and two 20 kDa proteins each had 20 attachments. For MS/MS, electron capture dissociation was especially effective. (C) 2003 American Society for Mass Spectrometry. C1 Cornell Univ, Baker Lab, Dept Chem & Biol Chem, Ithaca, NY 14853 USA. NICID, TB Res Sect, NIH, Rockville, MD USA. RP McLafferty, FW (reprint author), Cornell Univ, Baker Lab, Dept Chem & Biol Chem, Ithaca, NY 14853 USA. RI Oh, Han Bin/B-5390-2011; Barry, III, Clifton/H-3839-2012; Begley, Tadhg/B-5801-2015; ElNaggar, Mariam/H-3669-2016 OI ElNaggar, Mariam/0000-0001-9259-0148 FU Intramural NIH HHS [Z01 AI000783-11]; NIDDK NIH HHS [DK44083]; NIGMS NIH HHS [GM16609] NR 42 TC 55 Z9 57 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD MAR PY 2003 VL 14 IS 3 BP 253 EP 261 DI 10.1016/S1044-0305(02)00913-3 PG 9 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 655PL UT WOS:000181561400010 PM 12648932 ER PT J AU Dunson, DB Colombo, B AF Dunson, DB Colombo, B TI Bayesian modeling of markers of day-specific fertility SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE fertility awareness; growth curve; hierarchical model; latent variables; natural family planning; ovulation method ID SMOOTHING SPLINE MODELS; MENSTRUAL-CYCLE; LONGITUDINAL DATA; TWODAY ALGORITHM; REGRESSION; PROBABILITIES; PREGNANCY; OVULATION; DURATION; CURVE AB Cervical mucus hydration increases during the fertile interval before ovulation. Because sperm. can only penetrate mucus having a high water content, cervical secretions provide a reliable marker of the fertile days of the menstrual cycle. This article develops a Bayesian approach for modeling of daily observations of cervical mucus and applies the approach to assess heterogeneity among women and cycles from a given woman with respect to the increase in mucus hydration during the fertile interval. The proposed model relates the mucus observations to an underlying normal mucus hydration score, which varies relative to a peak hydration day. Uncertainty in the timing of the peak is accounted for, and a novel, weighted mixture model is used to characterize heterogeneity in distinct features of the underlying mean function. Prior information on the mucus hydration trajectory is incorporated, and a Markov chain Monte Carlo approach is developed. Based on data from a study of daily fecundability, there appears to be substantial heterogeneity among women in detected preovulatory increases in mucus hydration, but only minimal differences among cycles from a given woman. C1 Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. Univ Padua, Dept Stat, Padua, Italy. RP Dunson, DB (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, MD A3-03, Res Triangle Pk, NC 27709 USA. NR 40 TC 11 Z9 11 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2003 VL 98 IS 461 BP 28 EP 37 DI 10.1198/016214503388619067 PG 10 WC Statistics & Probability SC Mathematics GA 673MJ UT WOS:000182584500004 ER PT J AU Chatterjee, N Chen, YH Breslow, NE AF Chatterjee, N Chen, YH Breslow, NE TI A pseudoscore estimator for regression problems with two-phase sampling SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE measurement error; missing data; pseudolikelihood; response selective sampling; restricted sampling; semiparametric inference ID 2-STAGE CASE-CONTROL; MAXIMUM-LIKELIHOOD; LOGISTIC-REGRESSION; COVARIATE DATA; MODELS; INFORMATION; PARAMETERS; STATISTICS; 2-PHASE; DESIGN AB Two-phase stratified sampling designs yield efficient estimates of population parameters in regression models while minimizing the costs of data collection. In measurement error problems, for example, error-free covariates are ascertained only for units selected in a validation sample. Estimators proposed heretofore for such designs require all units to have positive probability of being selected. We describe a new semiparametric estimator that relaxes this assumption and that is applicable to, for example, case-only or control-only validation sampling for binary regression problems. It uses a weighted empirical covariate distribution, with weights determined by the regression model, to estimate the score equations. Implementation is relatively easy for both discrete and continuous outcome data. For designs that are amenable to alternative methods, simulation studies show that the new estimator outperforms the currently available weighted and pseudolikelihood methods and often achieves efficiency comparable to that of semiparametric maximum likelihood. The simulations also demonstrate the vulnerability of the case-only or control-only designs to model misspecification. These results are illustrated by the analysis of data from a population-based case-control study of leprosy. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Acad Sinica, Inst Stat Sci, Taipei 115, Taiwan. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Stat, Seattle, WA 98195 USA. RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA. NR 34 TC 55 Z9 55 U1 1 U2 4 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2003 VL 98 IS 461 BP 158 EP 168 DI 10.1198/016214503388619184 PG 11 WC Statistics & Probability SC Mathematics GA 673MJ UT WOS:000182584500016 ER PT J AU Hwang, JJ Uchio, EM Pavlovich, CP Pautler, SE Libutti, SK Linehan, WM Walther, MM AF Hwang, JJ Uchio, EM Pavlovich, CP Pautler, SE Libutti, SK Linehan, WM Walther, MM TI Surgical management of multi-organ visceral tumors in patients with von Hippel-Lindau disease: a single stage approach SO JOURNAL OF UROLOGY LA English DT Article DE Hippel-Lindau disease; pheochromocytoma; surgery; laparoscopy ID RENAL-CELL CARCINOMA; NEUROENDOCRINE TUMORS; PANCREATIC LESIONS; GENETIC-ANALYSIS; SPARING SURGERY; NATURAL-HISTORY; PHEOCHROMOCYTOMA AB Purpose: We assessed surgical feasibility of a 1-stage multi-organ approach for multiple visceral tumors in patients with von Hippel-Lindau disease. Materials and Methods: A total of 14 men and 15 women with von Hippel-Lindau disease underwent simultaneous multi-organ surgery for multiple adrenal, renal and pancreatic tumors at the National Cancer Institute between 1988 and 2001. Perioperative and followup data were analyzed retrospectively. The Mann-Whitney U test was used for statistical analysis. Results: Surgery involving 2 or more organs (mean 2.4 procedures per patient, range 2 to 4) was performed in all patients and concurrent pancreatic operations were performed in 12 (41%). Overall a combined 71 procedures, were performed including 4 cases (13%) treated laparoscopically. Mean +/- SD operative time and estimated blood loss were 464 +/- 142 minutes (range 206 to 830) and 2,798 +/- 4,285 cc (300 to 20,000), respectively. In 16 patients (55%) blood transfusion was administered intraoperatively. At a median followup of 21 months (range 5 to 151) renal tumors recurred in 8 patients (28%), requiring further kidney operations, but no patient had pancreatic or adrenal recurrence. The overall complication rate was 38%, and there was no operative mortality. Conclusions: A single stage surgical approach for multi-organ visceral tumors is a viable option for patients with von Hippel-Lindau disease. With careful patient selection and surgical planning combined procedures can be safely performed in 1 operative setting. C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Hwang, JJ (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 21 TC 8 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2003 VL 169 IS 3 BP 895 EP 898 DI 10.1097/01.ju.0000049518.15260.1f PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 644KM UT WOS:000180916500017 PM 12576808 ER PT J AU Friedman, MA Wood, BJ AF Friedman, MA Wood, BJ TI Precipitation of gadolinium and ethanol during nerve block SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter ID INTERVENTIONAL RADIOLOGY C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Friedman, MA (reprint author), NIH, Dept Diagnost Radiol, Bldg 10,Room 1C660, Bethesda, MD 20892 USA. FU Intramural NIH HHS [NIH0010126778, Z01 CL040013-01] NR 2 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAR PY 2003 VL 14 IS 3 BP 394 EP 394 DI 10.1097/01.RVI.0000058416.01661.E5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 656GZ UT WOS:000181601400018 PM 12631648 ER PT J AU Liu, SL Duh, FM Lerman, MI Miller, AD AF Liu, SL Duh, FM Lerman, MI Miller, AD TI Role of virus receptor Hyal2 in oncogenic transformation of rodent fibroblasts by sheep betaretrovirus Env proteins SO JOURNAL OF VIROLOGY LA English DT Article ID LYSOSOMAL HYALURONIDASE; CHROMOSOME 3P21.3; MAMMALIAN-CELLS; RETROVIRUS; JAAGSIEKTE; EXPRESSION; VECTORS; DELETION; REGION; GENES AB The ovine betaretroviruses jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV) cause contagious cancers in the lungs and upper airways of sheep and goats. Oncogenic transformation assays using mouse and rat fibroblasts have localized the transforming activity to the Env proteins encoded by these viruses, which require the putative lung and breast cancer tumor suppressor hyaluronidase 2 (Hyal2) to promote virus entry into cells. These results suggested the hypothesis that the JSRV and ENTV Env proteins cause cancer by inhibiting the tumor suppressor activity of Hyal2. Consistent with this hypothesis, we show that human Hyal2 and other Hyal2 orthologs that can promote virus entry, including rat Hyal2, can suppress transformation by the Env proteins of JSRV and ENTV. Furthermore, we provide direct evidence for binding of the surface (SU) region of JSRV Env to human and rat Hyal2. However, mouse Hyal2 did not mediate entry of virions bearing JSRV or ENTV Env proteins, bound JSRV SU poorly if at all, and did not suppress transformation by the JSRV or ENTV Env proteins, indicating that mouse Hyal2 plays no role in transformation of mouse fibroblasts and that the Env proteins can transform at least some cells by a Hyal2-independent mechanism. Expression of human Hyal2 in mouse cells expressing JSRV Env caused a marked reduction in Env protein levels, indicating that human Hyal2 suppresses Env-mediated transformation in mouse cells by increasing Env degradation rather than by exerting a more general Env-independent tumor suppressor activity. C1 Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. NCI, Canc Res Ctr, Immunobiol Lab, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. RP Miller, AD (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, 1100 Fairview Ave N,Room C2-023, Seattle, WA 98109 USA. RI Liu, Shan-Lu/L-5923-2016; OI Liu, Shan-Lu/0000-0003-1620-3817; Miller, Dusty/0000-0002-3736-3660 FU NCI NIH HHS [T32-CA09437, N01CO12400, T32 CA009437]; NHLBI NIH HHS [HL54881, P50 HL054881]; NIDDK NIH HHS [P30 DK047754, DK47754]; PHS HHS [C012400, C056000] NR 21 TC 50 Z9 57 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2003 VL 77 IS 5 BP 2850 EP 2858 DI 10.1128/JVI.77.5.2850-2858.2003 PG 9 WC Virology SC Virology GA 645VF UT WOS:000180999700006 PM 12584308 ER PT J AU Dey, B Del Castillo, CS Berger, EA AF Dey, B Del Castillo, CS Berger, EA TI Neutralization of human immunodeficiency virus type 1 by sCD4-17b, a single-chain chimeric protein, based on sequential interaction of gp120 with CD4 and coreceptor SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; ENVELOPE GLYCOPROTEIN; SOLUBLE CD4; CHEMOKINE RECEPTOR; EFFICIENT NEUTRALIZATION; CONFORMATIONAL-CHANGES; BINDING-SITE; CELL-FUSION; HIV-1; INFECTION AB We designed a novel single-chain chimeric protein, designated sCD4-17b, for neutralization of human immunodeficiency virus type 1 (HIV-1). The recombinant protein contains domains 1 and 2 of soluble CD4 (sCD4), connected via a flexible polypeptide linker to a single-chain variable region construct of 17b, a human monoclonal antibody that targets a conserved CD4-induced epitope on gp120 overlapping the coreceptor binding region. We hypothesized that the sCD4 moiety would bind gp120 and expose the 17b epitope; the 17b moiety would then bind, thereby blocking coreceptor interaction and neutralizing infection. The sCD4-17b protein, expressed by a recombinant vaccinia virus, potently neutralized a prototypic R5 clade B primary isolate, with a 50% inhibitory concentration of 3.2 nM (0.16 mug/ml) and >95% neutralization at 32 nM (1.6 mug/ml). The individual components (sCD4 and 17b, singly or in combination) had minimal effects at these concentrations, demonstrating that the activity of sCD4-17b reflected the ability of a single chimeric molecule to bind gp120 simultaneously via two independent moieties. sCD4-17b was highly potent compared to the previously characterized broadly cross-reactive neutralizing monoclonal antibodies IgGb12, 2G12, and 2F5. Multiple primary isolates were neutralized, including two previously described as antibody resistant. Neutralization occurred for both R5 and X4 strains and was not restricted to clade B. However, several primary isolates were insensitive over the concentration range tested, despite the known presence of binding sites for both CD4 and 17b. sCD4-17b has potential utility for passive immunization against HIV-1 in several contexts, including maternal transmission, postexposure prophylaxis, and sexual transmission (topical microbicide). C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 237, Bethesda, MD 20892 USA. OI del Castillo-Hegyi, Christie/0000-0002-7522-6026 NR 50 TC 52 Z9 54 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2003 VL 77 IS 5 BP 2859 EP 2865 DI 10.1128/JVI.77.5.2859-2865.2003 PG 7 WC Virology SC Virology GA 645VF UT WOS:000180999700007 PM 12584309 ER PT J AU Dybul, M Daucher, M Jensen, MA Hallahan, CW Chun, TW Belson, M Hidalgo, B Nickle, DC Yoder, C Metcalf, JA Davey, RT Ehler, L Kress-Rock, D Nies-Kraske, E Liu, SY Mullins, JI Fauci, AS AF Dybul, M Daucher, M Jensen, MA Hallahan, CW Chun, TW Belson, M Hidalgo, B Nickle, DC Yoder, C Metcalf, JA Davey, RT Ehler, L Kress-Rock, D Nies-Kraske, E Liu, SY Mullins, JI Fauci, AS TI Genetic characterization of rebounding human immunodeficiency virus type 1 in plasma during multiple interruptions of highly active antiretroviral therapy SO JOURNAL OF VIROLOGY LA English DT Article ID CHRONIC HIV-1 INFECTION; STRUCTURED TREATMENT INTERRUPTIONS; PROTEASE INHIBITORS; HIV/AIDS TREATMENT; PERIPHERAL-BLOOD; AIDS; POPULATIONS; REPLICATION; EVOLUTION; CELLS AB Various strategies of interrupting highly active antiretroviral therapy (HAART) are being investigated for the treatment of human immunodeficiency virus (HIV) infection. Interruptions of greater than 2 weeks frequently result in rebound of plasma HIV RNA. In order to discern changes in the viral population that might occur during cycles of treatment interruption, we evaluated the homology of HIV-1 envelope gene sequences over time in 12 patients who received four to seven cycles of 4 weeks off HAART followed by 8 weeks on HAART by using the heteroduplex tracking assay and novel statistical tools. HIV populations in 9 of 12 patients diverged from those found in the first cycle in at least one subsequent cycle. The substantial genetic changes noted in HIV ennu did not correlate with increased or decreased log changes in levels of plasma HIV RNA (P > 0.5). Thus, genetic changes in HIV ennu itself did not contribute in a systematic way to changes in levels of plasma viremia from cycle to cycle of treatment interruption. In addition, the data suggest that there may be multiple compartments contributing to the rebound of plasma viremia and to viral diversity from cycle to cycle of intermittent therapy. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. RP Dybul, M (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 31 Rm 7A-03, Bethesda, MD 20892 USA. NR 43 TC 34 Z9 35 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2003 VL 77 IS 5 BP 3229 EP 3237 DI 10.1128/JVI.77.5.3229-3237.2003 PG 9 WC Virology SC Virology GA 645VF UT WOS:000180999700044 PM 12584346 ER PT J AU Davis, DA Brown, CA Newcomb, FM Boja, ES Fales, HM Kaufman, J Stahl, SJ Wingfield, P Yarchoan, R AF Davis, DA Brown, CA Newcomb, FM Boja, ES Fales, HM Kaufman, J Stahl, SJ Wingfield, P Yarchoan, R TI Reversible oxidative modification as a mechanism for regulating retroviral protease dimerization and activation SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELL LEUKEMIA-VIRUS; HIV-1 PROTEASE; TYPE-1 PROTEASE; ACUTE INFECTION; IN-VITRO; CLEAVAGE; PROTEINASE; SUBSTRATE; PRECURSOR AB Human immunodeficiency virus protease activity can be regulated by reversible oxidation of a sulfur-containing amino acid at the dimer interface. We show here that oxidation of this amino acid in human immunodeficiency virus type I protease prevents dimer formation. Moreover, we show that human T-cell leukemia virus type I protease can be similarly regulated through reversible glutathionylation of its two conserved cysteine residues. Based on the known three-dimensional structures and multiple sequence alignments of retroviral proteases, it is predicted that the majority of retroviral proteases have sulfur-containing amino acids at the dimer interface. The regulation of protease activity by the modification of a sulfur-containing amino acid at the dimer interface may be a conserved mechanism among the majority of retroviruses. C1 NCI, CCR, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Biophys Chem, NIH, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. RP Davis, DA (reprint author), NCI, CCR, HIV & AIDS Malignancy Branch, NIH, 9000 Rockville Pike,Bldg 10,Rm 10S255, Bethesda, MD 20892 USA. NR 26 TC 29 Z9 29 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2003 VL 77 IS 5 BP 3319 EP 3325 DI 10.1128/JVI.77.5.3319-3325.2003 PG 7 WC Virology SC Virology GA 645VF UT WOS:000180999700055 PM 12584357 ER PT J AU Ott, DE Coren, LV Sowder, RC Adams, J Schubert, U AF Ott, DE Coren, LV Sowder, RC Adams, J Schubert, U TI Retroviruses have differing requirements for proteasome function in the budding process SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTIOUS-ANEMIA VIRUS; MURINE LEUKEMIA-VIRUS; ROUS-SARCOMA VIRUS; UBIQUITIN-ACTIVATING ENZYME; VESICULAR STOMATITIS-VIRUS; LATE ASSEMBLY DOMAIN; PROLINE-RICH MOTIF; GAG POLYPROTEIN; PROTEIN LIGASES AB Proteasome inhibitors reduce the budding of human immunodeficiency virus types 1 (HIV-1) and 2, simian immunodeficiency virus, and Rous sarcoma virus. To investigate this effect further, we examined the budding of other retroviruses from proteasome inhibitor-treated cells. The viruses tested differed in their Gag organization, late (L) domain usage, or assembly site from those previously examined. We found that proteasome inhibition decreased the budding of murine leukemia virus (plasma membrane assembly, PPPY L domain) and Mason-Pfizer monkey virus (cytoplasmic assembly, PPPY L domain), similar to the reduction observed for HIV-1. Thus, proteasome inhibitors can affect the budding of a virus that assembles within the cytoplasm. However, the budding of mouse mammary tumor virus (MMTV; cytoplasmic assembly, unknown L domain) was unaffected by proteasome inhibitors, similar to the proteasome-independent budding previously observed for equine infectious anemia virus (plasma membrane assembly, YPDL L domain). Examination of MMTV particles detected Gag-ubiquitin conjugates, demonstrating that an interaction with the ubiquitination system occurs during assembly, as previously found for other retroviruses. For all of the cell lines tested, the inhibitor treatment effectively inactivated proteasomes, as measured by the accumulation of polyubiquitinated proteins. The ubiquitination system was also inhibited, as evidenced by the loss of monoubiquitinated histones from treated cells. These results and those from other viruses show that proteasome inhibitors reduce the budding of viruses that utilize either a PPPY- or PTAP-based L domain and that this effect does not depend on the assembly site or the presence of monoubiquitinated Gag in the virion. C1 SAIC Frederick Inc, AIDS Vaccine Program, NCI, Ft Detrick, MD 21702 USA. Millennium Pharmaceut, Cambridge, MA 02139 USA. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. Heinrich Pette Inst Expt Virol & Immunol, D-20251 Hamburg, Germany. RP Ott, DE (reprint author), SAIC Frederick Inc, AIDS Vaccine Program, NCI, Ft Detrick, MD 21702 USA. FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 67 TC 45 Z9 46 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2003 VL 77 IS 6 BP 3384 EP 3393 DI 10.1128/JVI.77.6.3384-3393.2003 PG 10 WC Virology SC Virology GA 652FZ UT WOS:000181370300004 PM 12610113 ER PT J AU Szajner, P Jaffe, H Weisberg, AS Moss, B AF Szajner, P Jaffe, H Weisberg, AS Moss, B TI Vaccinia virus G7L protein interacts with the A30L protein and is required for association of viral membranes with dense viroplasm to form immature virions SO JOURNAL OF VIROLOGY LA English DT Article ID BACTERIOPHAGE-T7 RNA-POLYMERASE; ENVELOPE PROTEIN; INTRACELLULAR MOVEMENT; PROGENY VACCINIA; MORPHOGENESIS; GENE; MICROTUBULES; RECOMBINANT; EXPRESSION; RIFAMPICIN AB The vaccinia virus A30L protein is required for the association of electron-dense, granular, proteinaceous material with the concave surfaces of crescent membranes, an early step in viral morphogenesis. For the identification of additional proteins involved in this process, we used an antibody to the A30L protein, or to an epitope appended to its C terminus, to capture complexes from infected cells. A prominent 42-kDa protein was resolved and identified by mass spectrometry as the vaccinia virus G7L protein. This previously uncharacterized protein was expressed late in infection and was associated with immature virions and the cores of mature particles. In order to study the role of the G7L protein, a conditional lethal mutant was made by replacing the G7L gene with an inducible copy. Expression of G7L and formation of infectious virus was dependent on the addition of inducer. Under nonpermissive conditions, morphogenesis was blocked and viral crescent membranes and immature virions containing tubular elements were separated from the electron-dense granular viroplasm, which accumulated in large spherical masses. This phenotype was identical to that previously obtained with an inducible, conditional lethal A30L mutant. Additional in vivo and in vitro experiments provided evidence for the direct interaction of the A30L and G7L proteins and demonstrated that the stability of each one was dependent on its association with the other. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NINDS, Prot Peptide Sequence Facil, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Genet, Grad Program, Washington, DC 20052 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 40 TC 40 Z9 44 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2003 VL 77 IS 6 BP 3418 EP 3429 DI 10.1128/JVI.77.6.3418-3429.2003 PG 12 WC Virology SC Virology GA 652FZ UT WOS:000181370300008 PM 12610117 ER PT J AU Yang, RC Day, PM Yutzy, WH Lin, KY Hung, CF Roden, RBS AF Yang, RC Day, PM Yutzy, WH Lin, KY Hung, CF Roden, RBS TI Cell surface-binding motifs of L2 that facilitate papillomavirus infection SO JOURNAL OF VIROLOGY LA English DT Article ID MINOR CAPSID PROTEIN; VIRUS-LIKE PARTICLES; COTTONTAIL RABBIT PAPILLOMAVIRUS; COMMON NEUTRALIZATION EPITOPE; OPEN READING FRAMES; BOVINE PAPILLOMAVIRUS; N-TERMINUS; ALPHA-6 INTEGRIN; L1; RECEPTOR AB Human papillomavirus type 16 (HPV16) is the primary etiologic agent of cervical carcinoma, whereas bovine papillomavirus type 1 (BPV1) causes benign fibropapillomas. However, the capsid proteins, L1 and L2, of these divergent papillomaviruses exhibit functional conservation. A peptide comprising residues I to 88 of BPV1 L2 binds to a variety of cell lines, but not to the monocyte-derived cell line D32, and blocks BPV1 infection of mouse C127 cells. Residues 13 to 31 of HPV16 L2 and BPV1 L2 residues I to 88 compete for binding to the cell surface, and their binding, unlike that of HPV16 L1/L2 virus-like particles, is unaffected by heparinase or trypsin pretreatment of HeLa cells. A fusion of HPV16 L2 peptide 13-31 and GFP binds (K-d, similar to1 nM) to similar to45,000 receptors per HeLa cell. Furthermore, mutation of L2 residues 18 and 19 or 21 and 22 significantly reduces both the ability of the HPV16 L2 13-31-GFP fusion protein to bind to SiHa cells and the infectivity of HPV16 pseudovirions. Antibody to BPV1 L2 peptides comprising residues 115 to 135 binds to intact BPV1 virions, but fails to neutralize at a 1:10 dilution. However, deletion of residues 91 to 129 from L2 abolishes the infectivity of BPV1, but not their binding to the cell surface. In summary, L2 residues 91 to 129 contain epitopes displayed on the virion surface and are required for infection, but not virion binding to the cell surface. Upon the binding of papillomavirus to the cell surface, residues 13 to 31 of L2 interact with a widely expressed, trypsin- and heparinase-resistant cell surface molecule and facilitate infection. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Roden, RBS (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Ross 512B,720 Rutland Ave, Baltimore, MD 21205 USA. NR 52 TC 61 Z9 71 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2003 VL 77 IS 6 BP 3531 EP 3541 DI 10.1128/JVI.77.6.3531-3541.2003 PG 11 WC Virology SC Virology GA 652FZ UT WOS:000181370300019 PM 12610128 ER PT J AU Muntner, P He, J Vupputuri, S Coresh, J Batuman, V AF Muntner, P He, J Vupputuri, S Coresh, J Batuman, V TI Blood lead and chronic kidney disease in the general United States population: Results from NHANES III SO KIDNEY INTERNATIONAL LA English DT Article DE chronic kidney disease; lead exposure; hypertension ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; SERUM CREATININE; RENAL-FUNCTION; BONE LEAD; US POPULATION; EXPOSURE; NEPHROPATHY; PRESSURE; INSUFFICIENCY AB Background. High lead exposure is associated with hypertension and renal dysfunction but the effect of low-level environmental exposure is not as well studied. Methods. We examined the association between blood lead and renal function among a representative sample of the civilian noninstitutionalized United States population with and without hypertension, age 20 years old or older, participating in the Third National Health and Nutrition Examination Survey (NHANES III) (N = 15,211). Elevated serum creatinine was defined as greater than or equal to99(th) percentile of each race-sex specific distribution for healthy young adults and chronic kidney disease (CKD) as a glomerular filtration rate (GFR) <60 mL/min estimated using the Modification of Diet in Renal Disease (MDRD) formula. Results. Among persons with and without hypertension, mean blood lead was 4.21 and 3.30 ug/dL, respectively, the prevalence of elevated serum creatinine was 11.5% and 1.8%, respectively, and CKD was 10.0% and 1.1%, respectively. Among persons with hypertension, a graded association was present between higher quartile of blood lead and a higher odds ratio of both an elevated serum creatinine and CKD. Comparing the highest to lowest quartile of blood lead, the multivariate adjusted odds ratio (95% CI) of an elevated serum creatinine and CKD were 2.41 (1.46, 3.97) and 2.60 (1.52, 4.45), respectively. The analogous adjusted odds ratios (95% CI) among normotensives were 1.09 (0.53, 2.22) and 1.09 (0.41, 2.89), respectively. Associations were consistent when modeling lead as a continuous variable and in all subgroups except smokers. Conclusion. In the United States population with hypertension, exposure to lead, even at low levels, is associated with CKD. Reduction of lead exposure may reduce the burden of CKD in the community. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. Johns Hopkins Med Inst, Dept Epidemiol Biostat & Med, Baltimore, MD 21205 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Muntner, P (reprint author), Tulane Univ SPHTM, Dept Epidemiol, 1430 Tulane Ave,SL-18, New Orleans, LA 70112 USA. OI Batuman, Vecihi/0000-0002-1800-9009 NR 37 TC 93 Z9 96 U1 1 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2003 VL 63 IS 3 BP 1044 EP 1050 DI 10.1046/j.1523-1755.2003.00812.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 643FX UT WOS:000180852200026 PM 12631086 ER PT J AU Lu, B AF Lu, B TI BDNF and activity-dependent synaptic modulation SO LEARNING & MEMORY LA English DT Review ID NERVE GROWTH-FACTOR; LONG-TERM-POTENTIATION; FACTOR MESSENGER-RNA; RAT VISUAL-CORTEX; NEUROTROPHIC FACTOR BDNF; DEVELOPING NEUROMUSCULAR SYNAPSES; MONOCULAR DEPRIVATION DECREASES; CONSTITUTIVE SECRETORY PATHWAY; CULTURED HIPPOCAMPAL-NEURONS; DOMINANCE COLUMN FORMATION AB It is widely accepted that neuronal activity plays a pivotal role in synaptic plasticity. Neurotrophins have emerged recently as potent factors for synaptic modulation. The relationship between the activity and neurotrophic regulation of synapse development and plasticity, however, remains unclear. A prevailing hypothesis is that activity-dependent synaptic modulation is mediated by neurotrophins. An important but unresolved issue is how diffusible molecules such as neurotrophins achieve local and synapsc-specific modulation. In this review, I discuss several potential mechanisms with which neuronal activity could control the synapse-specificity of neurotrophin regulation, with particular emphasis on BDNF. Data accumulated in recent years suggest that neuronal activity regulates the transcription of BDNF gene, the transport of BDNF mRNA and protein into dendrites, and the secretion of BDNF protein. There is also evidence for activity-dependent regulation of the trafficking of the BDNF receptor, TrkB, including its cell surface expression and ligand-induced endocytosis. Further study of these mechanisms will help us better understand how neurotrophins could mediate activity-dependent plasticity in a local and synapse-specific manner. C1 NICHHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Lu, B (reprint author), NICHHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. NR 196 TC 504 Z9 524 U1 3 U2 34 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD MAR-APR PY 2003 VL 10 IS 2 BP 86 EP 98 DI 10.1101/lm.54603 PG 13 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 662KG UT WOS:000181945400002 PM 12663747 ER PT J AU Navolanic, PM Pui, CH Larson, RA Bishop, MR Pearce, TE Cairo, MS Goldman, SC Jeha, SC Shanholtz, CB Leonard, JP McCubrey, JA AF Navolanic, PM Pui, CH Larson, RA Bishop, MR Pearce, TE Cairo, MS Goldman, SC Jeha, SC Shanholtz, CB Leonard, JP McCubrey, JA TI Elitek (TM)-rasburicase: an effective means to prevent and treat hyperuricemia associated with tumor lysis syndrome, a Meeting Report, Dallas, Texas, January 2002 SO LEUKEMIA LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE-RENAL-FAILURE; MALIGNANCY-ASSOCIATED HYPERURICEMIA; ASPERGILLUS-FLAVUS URICASE; RECOMBINANT URATE OXIDASE; NON-HODGKINS-LYMPHOMA; BURKITTS-LYMPHOMA; METABOLIC COMPLICATIONS; PEDIATRIC-ONCOLOGY; CELL LYMPHOMA AB Renal precipitation of uric acid associated with tumor lysis syndrome (TLS) is a major complication in the management of leukemia, lymphoma, and other drug-sensitive cancers. Management of hyperuricema has historically consisted of administration of allopurinol, hydration, alkalinization to maintain pH between 7.0 and 7.3, and in some cases diuresis. Allopurinol, a xanthine analogue, blocks xanthine oxidase and formation of uric acid. Urate oxidase converts uric acid to allantoin, which is 5-10 times more soluble than uric acid. Homo sapiens cannot express urate oxidase because of a nonsense mutation. Urate oxidase was initially purified from Aspergillus flavus fungus. Treatment with this nonrecombinant product had been effective in preventing renal precipitation of uric acid in cancer patients, but was associated with a relatively high frequency of allergic reactions. This enzyme was recently cloned from A. flavus and is now manufactured as a recombinant protein. Clinical trials have shown this drug to be more effective than allopurinol for prevention and treatment of hyperuricemia in leukemia and lymphoma patients. This drug has been approved in Europe as well as the US and several clinical trials are in progress to further determine its clinical utility in other patient subsets. The purpose of this meeting was to discuss usefulness of recombinant urate oxidase, also known as rasburicase, Fasturtec(R), and Elitek(TM), for the management of TLS in certain cancer patients. C1 E Carolina Univ, Brody Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA. St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Univ Chicago, Pritzker Sch Med, Hematol Oncol Sect, Chicago, IL 60637 USA. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. Sanofi Synthelabo SA, Oncol Business Unit, Paris, France. Columbia Univ, Dept Pediat, New York, NY 10027 USA. Columbia Univ, Dept Med, New York, NY USA. Columbia Univ, Dept Pathol, New York, NY USA. N Texas Hosp Children Med City, Dallas, TX USA. Univ Texas, MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA. Univ Maryland, Sch Med, Dept Med, Div Hematol & Med Oncol, Baltimore, MD 21201 USA. Cornell Univ, Weill Med Coll, Div Hematol Oncol, New York, NY USA. E Carolina Univ, Brody Sch Med, Leo Jenkins Canc Ctr, Greenville, NC USA. RP McCubrey, JA (reprint author), E Carolina Univ, Brody Sch Med, Dept Microbiol & Immunol, Brody Bldg 5N98C, Greenville, NC 27858 USA. OI Shanholtz, Carl/0000-0003-3938-178X FU NCI NIH HHS [CA21765, R01CA51025] NR 53 TC 48 Z9 53 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAR PY 2003 VL 17 IS 3 BP 499 EP 514 DI 10.1038/sj.leu.2402847 PG 16 WC Oncology; Hematology SC Oncology; Hematology GA 660GK UT WOS:000181825300005 PM 12646938 ER PT J AU Plasschaert, SLA de Bont, ESJM Kamps, WA van der Kolk, DM Morisaki, K Scheffer, GL Scheper, RJ Vellenga, E de Vries, EGE AF Plasschaert, SLA de Bont, ESJM Kamps, WA van der Kolk, DM Morisaki, K Scheffer, GL Scheper, RJ Vellenga, E de Vries, EGE TI Functional activity of breast cancer resistance protein (BCRP) in acute lymphoblastic leukemia SO LEUKEMIA LA English DT Meeting Abstract CT 5th International Symposium on Leukemia and Lymphoma CY MAR 12-15, 2003 CL VRIJE UNIV, AMSTERDAM, NETHERLANDS HO VRIJE UNIV C1 Univ Groningen Hosp, Groningen, Netherlands. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. VU Univ Med Ctr, Amsterdam, Netherlands. Univ Groningen Hosp, Groningen, Netherlands. NR 0 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2003 VL 17 IS 3 MA O16 BP 662 EP 662 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 660GK UT WOS:000181825300051 ER PT J AU Moody, TW Chiles, J Moody, E Sieczkiewicz, GJ Kohn, EC AF Moody, TW Chiles, J Moody, E Sieczkiewicz, GJ Kohn, EC TI CAI inhibits the growth of small cell lung cancer cells SO LUNG CANCER LA English DT Article DE CAI; small cell lung cancer; proliferation; cytosolic calcium; FAK; VEGF ID FOCAL ADHESION KINASE; CALCIUM INFLUX INHIBITOR; BOMBESIN-LIKE PEPTIDES; TYROSINE PHOSPHORYLATION; CARBOXYAMIDO-TRIAZOLE; SIGNAL-TRANSDUCTION; TUMOR ANGIOGENESIS; RECEPTOR; INVASION; METASTASIS AB The effects of carboxyamido-triazole (CAI) on small cell lung cancer (SCLC) cells were investigated. Using SCLC cell lines NCI-H209 or H345, 20 muM CAI had little effect on basal cytosolic Ca2+ but inhibited the ability of 10 nM bombesin (1313) or I nM neurotensin (NT) to elevate cytosolic Ca2+. Also, CAI, impaired the ability of 1313 or NT to cause tyrosine phosphorylation of focal adhesion kinase. In contrast, CAI did not affect the ability of (I-125-Tyr 4)BB or I-125-NT to bind with high affinity to NCI-H345 cells. These results indicate that CAI impairs SCLC second messenger activation, but not neuropeptide receptor binding. Using a MTT growth assay, CAI inhibited the proliferation of NCI-H209 or H345 cells in a concentration-dependent manner with little proliferation occurring using 100 muM CAI. Also, CAI inhibited colony formation of NCI-H209 or H345 cells in a close-dependent manner in vitro. In vivo, CAI (2 mg/day by gavage) inhibited significantly NCI-H209 xenograft proliferation in nude mice. Animals treated daily with CAI had significantly reduced CD31 immunostaining of microvessels in the tumor. Also, CAI inhibited the increase in vascular endothelial cell growth factor (VEGF) mRNA after addition of 1313 to SCLC cells. These results suggest that CAI inhibits the growth of SCLC cells as well as the angiogenesis of SCLC tumors in a VEGF-dependent manner. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Off Director, CCR, Bethesda, MD 20892 USA. Pathol Lab, Bethesda, MD 20892 USA. RP Moody, TW (reprint author), NCI, Off Director, CCR, Bldg 31,Room 3A34,31 Ctr Dr, Bethesda, MD 20892 USA. NR 49 TC 19 Z9 22 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 2003 VL 39 IS 3 BP 279 EP 288 DI 10.1016/S0169-5002(02)00525-1 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 655MR UT WOS:000181557000005 PM 12609566 ER PT J AU Tailor, DR Roy, A Regatte, RR Charagundla, SR McLaughlin, AC Leigh, JS Reddy, R AF Tailor, DR Roy, A Regatte, RR Charagundla, SR McLaughlin, AC Leigh, JS Reddy, R TI Indirect O-17-magnetic resonance imaging of cerebral blood flow in the rat SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE T-1 rho-dispersion imaging; (H2O)-O-17; cerebral blood flow; brain mapping ID HIGH-RESOLUTION MEASUREMENT; NUCLEAR-MAGNETIC-RESONANCE; F-19 NMR-SPECTROSCOPY; TRACER BOLUS PASSAGES; OXYGEN-CONSUMPTION; CONTRAST AGENTS; FAIR TECHNIQUE; O-17; PERFUSION; BRAIN AB Proton T-1p dispersion MRI is demonstrated for indirect, in vivo detection of O-17 in the brain. This technique, which may be readily implemented on any clinical MRI scanner, is applied towards high-resolution, quantitative mapping of cerebral blood flow (CBF) in the rat by monitoring the clearance of O-17-enriched water. Strategies are derived and employed for 1) quantitation of absolute H-2 O-17 tracer concentration from a ratio of high- and low-frequency spin-locked T-1p images, and 2) mapping CBF without having to transform the T-1p signal to H-2 O-17 tracer concentration. Absolute regional blood flow was mapped in a single 3-mm brain slice at an in-plane resolution of 0.4 x 0.8 mm within a 5-min tracer washout time; these data are consistent with the less localized CBF measurements reported in the literature. T-1p- weighted imaging yields excellent signal-to-noise ratios, spatiotemporal resolution, and anatomical contrast for mapping CBF. (C) 2003 Wiley-Liss, Inc. C1 Univ Penn, Sch Med, Dept Radiol, MMRRCC,B1 Stellar Chance Labs, Philadelphia, PA 19104 USA. Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. RP Tailor, DR (reprint author), Univ Penn, Sch Med, Dept Radiol, MMRRCC,B1 Stellar Chance Labs, Philadelphia, PA 19104 USA. RI Regatte, Ravinder/K-2364-2014; OI Regatte, Ravinder/0000-0002-4607-7682; Reddy, Ravinder/0000-0003-4580-2392 FU NCRR NIH HHS [RR02305]; NINDS NIH HHS [R29-NS35625] NR 39 TC 21 Z9 22 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD MAR PY 2003 VL 49 IS 3 BP 479 EP 487 DI 10.1002/mrm.10403 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 651AL UT WOS:000181297200010 PM 12594750 ER PT J AU Gupta, SN Solaiyappan, M Beache, GM Arai, AE Foo, TKF AF Gupta, SN Solaiyappan, M Beache, GM Arai, AE Foo, TKF TI Fast method for correcting image misregistration due to organ motion in time-series MRI data SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE image registration; motion correction; perfusion imaging; BOLD imaging ID MAGNETIC-RESONANCE; MYOCARDIAL PERFUSION; BRAIN IMAGES; DYNAMIC MR; REGISTRATION; ALGORITHM; ALIGNMENT AB Time-series MRI data often suffers from image misalignment due to patient movement and respiratory and other physiologic motion during the acquisition process. It is necessary that this misalignment be corrected prior to any automated quantitative analysis. In this article a fast and automated technique for removing in-plane misalignment from time-series MRI data is presented. The method is computationally efficient, robust, and fine-tuned for the clinical setting. The method was implemented and tested on data from 21 human subjects, including myocardial perfusion imaging, renal perfusion imaging, and bloodoxygen level-dependent cardiac T-2(star) imaging. In these applications 10-fold or better reduction in image misalignment is reported. The improvement after registration on representative time-intensity curves is shown. Although the method currently corrects translation motion using image center of mass, the mathematical framework of our approach may be extended to correct rotation and other higher-order displacements. (C) 2003 Wiley-Liss, Inc. C1 GE Med Syst, Appl Sci Lab, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD USA. Univ Maryland, Med Ctr, Dept Radiol, Cardiovasc Imaging & Physiol Ctr, Baltimore, MD 21201 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Gupta, SN (reprint author), Johns Hopkins Univ Hosp, GE Med Syst, Room MRI 110,600 N WOlfe St, Baltimore, MD 21287 USA. NR 32 TC 29 Z9 29 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD MAR PY 2003 VL 49 IS 3 BP 506 EP 514 DI 10.1002/mrm.10394 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 651AL UT WOS:000181297200014 PM 12594754 ER PT J AU Tracy, BL Ivey, FM Metter, EJ Fleg, JL Siegel, EL Hurley, BF AF Tracy, BL Ivey, FM Metter, EJ Fleg, JL Siegel, EL Hurley, BF TI A more efficient magnetic resonance imaging-based strategy for measuring quadriceps muscle volume SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE knee extensor; aging; MRI; cross-sectional area ID SKELETAL-MUSCLE; BODY-COMPOSITION; STRENGTH; MEN; ACTIVATION; THIGH; YOUNG; WOMEN; SPACEFLIGHT; EXERCISE AB Purpose: To determine the accuracy of several magnetic resonance imaging (MRI)-based strategies for assessment of quadriceps muscle volume (MV) and changes in MV with training. Methods: Images were acquired along the length of both thighs from young (26 +/- 3 yr, N = 23) and older (69 +/- 3 yr, N = 24) men and women before and after strength training. The quadriceps cross-sectional area (QCSA) of each section was measured before and after training. MV was directly assessed using all of the sections (each 9-mm thick with a I-mm gap). Alternative estimates of MV were calculated using increasingly greater intervals between sections: every 1.1 cm (MV2), 3.1 cm (MV4), 5.1 cm (MV6), 7.1 cm (MV8), 9.1 cm (MV10), and a single QCSA (L1). The 95% limits of agreement (LOA, +/- 2 SD) between each alternative measure and the criterion measure MV were determined with Bland and Altman plots. Regression was used to predict MV from L1 and to obtain the standard error of the estimate (SEE). Results: Before training, the 95% LOA with MV for the alternative measures ranged from 0.7% to 6.36% of MV, and the prediction of MV from L1 yielded a SEE x 2 of 14.1% of MV. For change in the alternative measures, the 95% LOA ranged from 10.3% to 26.3% of the total change in MV, and the prediction of DeltaMV from DeltaL1 yielded a SEE x 2 of 60% of the change in MV. Conclusion: Increasingly greater intervals between axial MRI sections result in substantially reduced agreement with a criterion measure of MV. The use of one axial section results in relatively higher error and thus should be used only when large effect sizes are expected. C1 Univ Colorado, Dept Kinesiol & Appl Physiol, Boulder, CO 80309 USA. Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Tracy, BL (reprint author), Univ Colorado, Dept Kinesiol & Appl Physiol, UCB 354, Boulder, CO 80309 USA. FU NIA NIH HHS [1-AG-4-2148, T32 AG00219] NR 34 TC 61 Z9 61 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAR PY 2003 VL 35 IS 3 BP 425 EP 433 DI 10.1249/01.MSS.0000053722.53302.D6 PG 9 WC Sport Sciences SC Sport Sciences GA 652NZ UT WOS:000181386400007 PM 12618571 ER PT J AU Treuth, MS Sherwood, NE Butte, NF McClanahan, B Obarzanek, E Zhou, A Ayers, C Adolph, A Jordan, J Jacobs, DR Rochon, J AF Treuth, MS Sherwood, NE Butte, NF McClanahan, B Obarzanek, E Zhou, A Ayers, C Adolph, A Jordan, J Jacobs, DR Rochon, J TI Validity and reliability of activity measures in African-American girls for GEMS SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE accelerometer; pedometer; physical activity assessment; self-report questionnaires; children; inactivity ID CHILDRENS PHYSICAL-ACTIVITY; SELF-REPORT; VALIDATION; PEDOMETER; ACCELEROMETRY; ACTOMETER; YOUTH AB Purpose: To determine the reliability and validity of physical activity monitors and self-report instruments suitable for young African-American girls. Methods: A validation study was conducted by the Girls health Enrichment Multi-site Studies (GEMS) research team to compare an accelerometer with a pedometer and two self-report instruments for assessing physical activity in African-American girls, age 8-9 yr. Girls (N = 68) attended two clinic visits spaced 4 d apart. Each girl wore a MTI/CSA accelerometer (used as the criterion standard for validity) and a pedometer simultaneously for four consecutive days. Girls completed on two occasions a 24-h physical activity checklist of yesterday and usual activities, including sedentary activities (GEMS Activity Questionnaire, GAQ), and a 3-d computerized self-report instrument (Activitygram). Results: Girls were (mean +/- SD) 9.0 +/- 0.6 yr old and had a body mass index of 19.4 kg(.)m(-2). Reliability measured by intraclass correlations (ICC) and Pearson correlation coefficients (r) were calculated for the MTI/CSA (ICC = 0.37, P < 0.0001), pedometer (ICC = 0.08, P = 0.094), Activitygram (ICC = 0.24) (P = 0.005), and GAQ for physical (r = 0.80, P < 0.0001) and sedentary (r = 0.3-0.5, P < 0.005) activities. Significant Pearson correlations between the MTI/CSA and the other instruments, as a measure of validity, were observed for the 4-d average pedometer score (r = 0.47, P < 0.0001), 3-d average Activitygram score (r = 0.37, P = 0.002), and the average of the two yesterday and two usual GAQ activity scores for a subset of 18 physical activities questions (r = 0.27, P = 0.03; and r = 0.29, P = 0.02, respectively). The MTI/CSA was uncorrelated with single day scores from the three other instruments. Conclusion: The reliability of the instruments tested was acceptable, except the pedometer. Validity correlations were significant when more than one day was used. Self-report instruments need further development for improved reliability and validity. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Human Nutr, Baltimore, MD 21205 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Oslo, Inst Nutr Res, Oslo, Norway. USDA ARS, Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX USA. Univ Memphis, Ctr Community Hlth, Memphis, TN 38152 USA. NHLBI, NIH, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. RP Treuth, MS (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Human Nutr, 615 N Wolfe St, Baltimore, MD 21205 USA. RI Schmoelz, Camilie/D-1707-2012 OI Schmoelz, Camilie/0000-0003-2221-9954 FU NHLBI NIH HHS [U01 HL62662, U01 HL62663, HL65160, U01 HL62668, U01 HL62732] NR 19 TC 106 Z9 107 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAR PY 2003 VL 35 IS 3 BP 532 EP 539 DI 10.1249/01.MSS.0000053702.03884.3F PG 8 WC Sport Sciences SC Sport Sciences GA 652NZ UT WOS:000181386400023 PM 12618587 ER PT J AU Sospedra, M Pinilla, C Martin, R AF Sospedra, M Pinilla, C Martin, R TI Use of combinatorial peptide libraries for T-cell epitope mapping SO METHODS LA English DT Article ID INDIVIDUAL AMINO-ACIDS; IDENTIFICATION; LIGANDS; LYMPHOCYTES; SPECIFICITY; POTENCY; MIMICS; CLONE; TCR AB T lymphocytes play important roles not only in infectious diseases and autoimmunity, but also in immune responses against tumors. For many of these disorders, the relevant target antigens are not known. Designing effective methods that allow the search for T-cell epitopes is therefore an important goal in the areas of infectious diseases, oncology, vaccine development, and numerous other biomedical specialties. So far, the strategies used to examine T-cell recognition have been based largely on mapping T-cell epitopes with overlapping peptides from known proteins or with entire proteins, e.g., from a specific virus, bacterium, or human tissue. These approaches are tedious and have a number of limitations. It is, for example, almost impossible to isolate T cells that infiltrate an organ or infectious site and identify their specificity unless one already has a concept as to which antigens may be relevant. During recent years, a number of laboratories have developed less biased approaches that employ either the selection of putative T-cell epitopes based on the prediction of binding to certain major histocompatibilty complex (MHC) molecules and peptide or protein libraries that have been generated in expression systems, e.g. phage, or rely on combinatorial peptide chemistry. The latter technique has been refined by a number of laboratories including ours. Bead-bound or, preferably, positional scanning synthetic and soluble combinatorial peptide libraries allow the identification of T-cell epitopes within complex mixtures of proteins even for T cells that have been expanded from an organ infiltrate with a polyclonal stimulus. The practical steps that are involved in the latter method are described in this article. Published by Elsevier Science (USA). C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. RP Martin, R (reprint author), NINDS, Neuroimmunol Branch, NIH, 10 Ctr Dr,MSC 1400, Bethesda, MD 20892 USA. NR 20 TC 29 Z9 30 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD MAR PY 2003 VL 29 IS 3 BP 236 EP 247 DI 10.1016/S1046-2023(02)00346-8 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 664FK UT WOS:000182050900004 PM 12725789 ER PT J AU Shakarian, AM Joshi, MB Yamage, M Ellis, SL Debrabant, A Dwyer, DM AF Shakarian, AM Joshi, MB Yamage, M Ellis, SL Debrabant, A Dwyer, DM TI Members of a unique histidine acid phosphatase family are conserved amongst a group of primitive eukaryotic human pathogens SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Leishmania; trypanosomatid; protozoan parasite; human pathogen; pulse field gel electrophoresis; histidine acid phosphatase; enzyme; genome; chromosome ID LEISHMANIA-DONOVANI PROMASTIGOTES; SURFACE-MEMBRANE; TRYPANOSOMA-BRUCEI; CELLULAR-LOCALIZATION; MEXICANA; CLONING; GENE; IDENTIFICATION; PURIFICATION; AMASTIGOTES AB Recently, we identified and characterized the genes encoding several distinct members of the histidine-acid phosphatase enzyme family from Leishmania donovani, a primitive protozoan pathogen of humans. These included genes encoding the heavily phosphorylated/glycosylated, tartrate-sensitive, secretory acid phosphatases (Ld SAcP-1 and Ld SAcP-2) and the unique, tartrate-resistant, externally-oriented, surface membrane-bound acid phosphatase (Ld MAcP) of this parasite. It had been previously suggested that these enzymes may play essential roles in the growth, development and survival of this organism. In this report, to further examine this hypothesis, we assessed whether members of the L. donovani histidine-acid phosphatase enzyme family were conserved amongst other pathogenic Leishmania and related trypanosomatid parasites. Such phylogenetic conservation would clearly indicate an evolutionary selection for this family of enzymes and strongly suggest and support an important functional role for acid phosphatases to the survival of these parasites. Results of pulsed field gel electrophoresis and Southern blotting showed that homologs of both the Ld SAcPs and Ld MAcP were present in each of the visceral and cutaneous Leishmania species examined (i.e. isolates of L. donovani, L. infantum, L. tropica, L. major and L. mexicana, respectively). Further, results of enzyme assays showed that all of these organisms expressed both tartrate-sensitive and tartrate-resistant acid phosphatase activities. In addition, homologs of both the Ld SAcPs and Ld MAcP genes and their corresponding enzyme activities were also identified in two Crithidia species (C. fasciculata and C. luciliae) and in Leptomonas seymouri. In contrast, Trypanosoma brucei, Trypanosoma cruzi and Phytomonas serpens had only very-low levels of such enzyme activities. Cumulatively, results of this study showed that homologs of the Ld SAcPs and Ld MAcP are conserved amongst all pathogenic Leishmania sps. suggesting that they may play significant functional roles in the growth, development and survival of all members of this important group of human pathogens. C1 NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Salve Regina Univ, Dept Biol & Biomed Sci, Newport, RI USA. US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. RP Dwyer, DM (reprint author), NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr,MSC-0425, Bethesda, MD 20892 USA. EM ddwyer@niaid.nih.gov NR 38 TC 17 Z9 18 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAR PY 2003 VL 245 IS 1-2 BP 31 EP 41 DI 10.1023/A:1022851914014 PG 11 WC Cell Biology SC Cell Biology GA 658YC UT WOS:000181747800004 PM 12708742 ER PT J AU Kumaraswamy, E Carlson, BA Morgan, F Miyoshi, K Robinson, GW Su, D Wang, SL Southon, E Tessarollo, L Lee, BJ Gladyshev, VN Hennighausen, L Hatfield, DL AF Kumaraswamy, E Carlson, BA Morgan, F Miyoshi, K Robinson, GW Su, D Wang, SL Southon, E Tessarollo, L Lee, BJ Gladyshev, VN Hennighausen, L Hatfield, DL TI Selective removal of the selenocysteine tRNA([Ser]Sec) Gene (Trsp) in mouse mammary epithelium SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSFER-RNA; GLUTATHIONE-PEROXIDASE; THIOREDOXIN REDUCTASES; CANCER SUSCEPTIBILITY; TRANSFER RNASEC; MAMMALIAN-CELLS; TRANSGENIC MICE; TUMOR-FORMATION; BRCA1; SELENIUM AB Mice homozygous for an allele encoding the selenocysteine (Sec) tRNA([Ser]Sec) gene (Trsp) flanked by loxP sites were generated. Cre recombinase-dependent removal of Trsp in these mice was lethal to embryos. To investigate the role of Trsp in mouse mammary epithelium, we deleted this gene by using transgenic mice carrying the Cre recombinase gene under control of the mouse mammary tumor virus (MMTV) long terminal repeat or the whey acidic protein promoter. While both promoters target Cre gene expression to mammary epithelium, MMTV-Cre is also expressed in spleen and skin. Sec tRNA([Ser]Sec) amounts were reduced by more than 70% in mammary tissue with either transgene, while in skin and spleen, levels were reduced only with MMTV-Cre. The selenoprotein population was selectively affected with MMTV-Cre in breast and skin but not in the control tissue, kidney. Moreover, within affected tissues, expression of specific selenoproteins was regulated differently and often in a contrasting manner, with levels of Sep15 and the glutathione peroxidases GPx1 and GPx4 being substantially reduced. Expression of the tumor suppressor genes BRCA1 and p53 was also altered in a contrasting manner in MMTV-Cre mice, suggesting greater susceptibility to cancer and/or increased cell apoptosis. Thus, the conditional Trsp knockout mouse allows tissue-specific manipulation of Sec tRNA and selenoprotein expression, suggesting that this approach will provide a useful tool for studying the role of selenoproteins in health. C1 NCI, Ctr Canc Res, Basic Res Lab, Sect Mol Biol Selenium,NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Beadle Ctr, Dept Biochem, Lincoln, NE 68588 USA. NCI, Ctr Canc Res, Mouse Canc Genet Program, Neural Dev Sect, Frederick, MD 21701 USA. Seoul Natl Univ, Sch Biol Sci, Genet Mol Lab, Seoul 151742, South Korea. RP Hatfield, DL (reprint author), NCI, Ctr Canc Res, Basic Res Lab, Sect Mol Biol Selenium,NIH, Bldg 37,Room 2D09, Bethesda, MD 20892 USA. RI Su, Dan/B-1972-2010; Robinson, Gertraud/I-2136-2012; Gladyshev, Vadim/A-9894-2013 FU NCI NIH HHS [CA080946, R01 CA080946]; NIGMS NIH HHS [GM065204, R01 GM065204, R37 GM065204] NR 45 TC 70 Z9 70 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2003 VL 23 IS 5 BP 1477 EP 1488 DI 10.1128/MCB.23.5.1477-1488.2003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 651AJ UT WOS:000181297000001 PM 12588969 ER PT J AU Janssen, RAJ Kim, PN Mier, JW Morrison, DK AF Janssen, RAJ Kim, PN Mier, JW Morrison, DK TI Overexpression of kinase suppressor of Ras upregulates the high-molecular-weight tropomyosin isoforms in ras-transformed NIH 3T3 fibroblasts SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN BREAST-LESIONS; RHO-KINASE; SIGNAL-TRANSDUCTION; ALPHA-TROPOMYOSIN; DOWN-REGULATION; MAP KINASE; POLYPEPTIDE EXPRESSION; NONMUSCLE TROPOMYOSIN; FOCAL ADHESIONS; CULTURED-CELLS AB The down-regulation of the high-molecular-weight isoforms of tropomyosin (TM) is considered to be an essential event in cellular transformation. In ras-transformed fibroblasts, the suppression of TM is dependent on the activity of the Raf-1 kinase; however, the requirement for other downstream effectors of Ras, such as MEK and ERK, is less clear. In this study, we have utilized the mitogen-activated protein kinase scaffolding protein Kinase Suppressor of Ras (KSR) to further investigate the regulation of TM and to clarify the importance of MEK/ERK signaling in this process. Here, we report that overexpression of wild-type KSR1 in ras-transformed fibroblasts restores TM expression and induces cell flattening and stress fiber formation. Moreover, we find that the transcriptional activity of a TM-alpha promoter is decreased in ras-transformed cells and that the restoration of TM by KSR1 coincides with increased transcription from this promoter. Although ERK activity was suppressed in cells overexpressing KSR1, ERK inhibition alone was insufficient to upregulate TM expression. The KSR1-mediated effects on stress fiber formation and TM transcription required the activity of the ROCK kinase, because these effects could be suppressed by the ROCK inhibitor, Y27632. Overexpression of KSR1 did not directly regulate ROCK activity, but did permit the recoupling of ROCK to the actin polymerization machinery. Finally, all of the KSR1-induced effects were mediated by the C-terminal domain of KSR1 and were dependent on the KSR-MEK interaction. C1 Natl Canc Inst, Regulat Cell Growth Lab, Frederick, MD 21702 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Janssen, RAJ (reprint author), Univ Nijmegen, Ctr Med, Ctr Mol Life Sci, TIL 187,POB 9101, NL-6500 HB Nijmegen, Netherlands. FU NCI NIH HHS [CA74401] NR 66 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2003 VL 23 IS 5 BP 1786 EP 1797 DI 10.1128/MCB.23.5.1786-1797.2003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 651AJ UT WOS:000181297000028 PM 12588996 ER PT J AU Schaaf, MJM Cidlowski, JA AF Schaaf, MJM Cidlowski, JA TI Molecular determinants of glucocorticoid receptor mobility in living cells: The importance of ligand affinity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID STEROID-HORMONE RECEPTORS; NF-KAPPA-B; NUCLEAR MATRIX; DNA-BINDING; ANDROGEN RECEPTOR; MINERALOCORTICOID RECEPTORS; SUBNUCLEAR TRAFFICKING; FUNCTIONAL ANTAGONISM; GENE-TRANSCRIPTION; HNRNP-U AB The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR), which is activated upon ligand binding, and can alter the expression of target genes either by transrepression or transactivation. We have applied FRAP (fluorescence recovery after photobleaching) to quantitatively assess the mobility of the yellow fluorescent protein (YFP)-tagged human GR alpha-isoform (hGRalpha) in the nucleus of transiently transfected COS-1 cells and to elucidate determinants of its mobility. Addition of the high-affinity agonist dexamethasone markedly decreases the mobility of the receptor in a concentration-dependent manner, whereas low-affinity ligands like corticosterone decrease the mobility to a much lesser extent. Analysis of other hGRalpha ligands differing in affinity suggests that it is the affinity of the ligand that is a major determinant of the decrease in mobility. Similar results were observed for two hGRalpha antagonists, the low-affinity antagonist ZK98299 and the high-affinity antagonist RU486. The effect of ligand affinity on mobility was confirmed with the hGRalpha mutant Q642V, which has an altered affinity for triamcinolone acetonide, dexamethasone, and corticosterone. Analysis of hGRalpha deletion mutants indicates that both the DNA-binding domain and the ligand-binding domain of the receptor are required for a maximal ligand-induced decrease in receptor mobility. Interestingly, the mobility of transfected hGRalpha differs among cell types. Finally, the proteasome inhibitor MG132 immobilizes a subpopulation of unliganded receptors, via a mechanism requiring the DNA-binding domain and the N-terminal part of the ligand-binding domain. Ligand binding makes the GR resistant to the immobilizing effect of MG132, and this effect depends on the affinity of the ligand. Our data suggest that ligand binding induces a conformational change of the receptor which is dependent on the affinity of the ligand. This altered conformation decreases the mobility of the receptor, probably by targeting the receptor to relatively immobile nuclear domains with which it transiently associates. In addition, this conformational change blocks immobilization of the receptor by MG132. C1 NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. NR 63 TC 126 Z9 130 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2003 VL 23 IS 6 BP 1922 EP 1934 DI 10.1128/MCB.23.6.1922-1934.2003 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 653FG UT WOS:000181424100008 PM 12612067 ER PT J AU Miller, SJ Li, HZ Rizvi, TA Huang, Y Johansson, G Bowersock, J Sidani, A Vitullo, J Vogel, K Parysek, LA DeClue, JE Ratner, N AF Miller, SJ Li, HZ Rizvi, TA Huang, Y Johansson, G Bowersock, J Sidani, A Vitullo, J Vogel, K Parysek, LA DeClue, JE Ratner, N TI Brain lipid binding protein in axon-Schwann cell interactions and peripheral nerve tumorigenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NEUROFIBROMATOSIS TYPE-1 GENE; MOUSE-TUMOR MODEL; DIFFERENTIAL REGULATION; EXPRESSION PATTERN; MALIGNANT GLIOMA; RADIAL GLIA; B-FABP; ACID; NF1; GROWTH AB Loss of axonal contact characterizes Schwann cells in benign and malignant peripheral nerve sheath tumors (MPNST) from neurofibromatosis type 1 (NF1) patients. Tumor Schwann cells demonstrate NF1 mutations, elevated Ras activity, and aberrant epidermal growth factor receptor (EGFR) expression. Using cDNA microarrays, we found that brain lipid binding protein (BLBP) is elevated in an EGFR-positive subpopulation of Nf1 mutant mouse Schwann cells (Nf1(-/-) TXF) that grows away from axons; BLBP expression was not affected by farnesyltransferase inhibitor, an inhibitor of H-Ras. BLBP was also detected in EGFR-positive cell lines derived from Nf1:p53 double mutant mice and human MPNST. BLBP expression was induced in normal Schwann cells following transfection with EGFR but not H-Ras12V. Furthermore, EGFR-mediated BLBP expression was not inhibited by dominant-negative H-Ras, indicating that BLBP expression is downstream of Ras-independent EGFR signaling. BLBP-blocking antibodies enabled process outgrowth from Nf1(-/-) TXF cells and restored interaction with axons, without affecting cell proliferation or migration. Following injury, BLBP expression was induced in normal sciatic nerves when nonmyelinating Schwann cells remodeled their processes. These data suggest that BLBP, stimulated by Ras-independent pathways, regulates Schwann cell-axon interactions in normal peripheral nerve and peripheral nerve tumors. C1 Univ Cincinnati, Coll Med, Dept Cell Biol Neurobiol & Anat, Cincinnati, OH 45267 USA. NCI, Lab Cellular Oncol, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. RP Ratner, N (reprint author), Univ Cincinnati, Coll Med, Dept Cell Biol Neurobiol & Anat, 231 Bethesda Ave, Cincinnati, OH 45267 USA. FU NINDS NIH HHS [R01 NS028840, NS 28840] NR 59 TC 28 Z9 28 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2003 VL 23 IS 6 BP 2213 EP 2224 DI 10.1128/MCB.23.6.2213-2224.2003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 653FG UT WOS:000181424100032 PM 12612091 ER PT J AU Senatorov, VV Charles, V Reddy, PH Tagle, DA Chuang, DM AF Senatorov, VV Charles, V Reddy, PH Tagle, DA Chuang, DM TI Overexpression and nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase in a transgenic mouse model of Huntington's disease SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID NEURONAL INTRANUCLEAR INCLUSIONS; AGE-INDUCED APOPTOSIS; LENGTH HD CDNA; ALZHEIMERS-DISEASE; CEREBELLAR NEURONS; DNA FRAGMENTATION; MUTANT HUNTINGTIN; CAG REPEAT; CELL-DEATH; MICE AB Huntington's disease is due to an expansion of CAG repeats in the huntingtin gene. Huntingtin interacts with several proteins including glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We performed immunohistochemical analysis of GAPDH expression in the brains of transgenic mice carrying the huntingtin gene with 89 CAG repeats. In all wild-type animals examined, GAPDH was evenly distributed among the different cell types throughout the brain. In contrast, the majority of transgenic mice showed GAPDH overexpression, with the most prominent GAPDH changes observed in the caudate putamen, globus pallidus, neocortex, and hippocampal formation. Double staining for NeuN and GFAP revealed that GAPDH overexpression occurred exclusively in neurons. Nissl staining analysis of the neocortex and caudate putamen indicated 24 and 27% of cell loss in transgenic mice, respectively. Subcellular fluorescence analysis revealed a predominant increase in GAPDH immunostaining in the nucleus. Thus, we conclude that mutation of huntingtin is associated with GAPDH overexpression and nuclear translocation in discrete populations of brain neurons. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Inst Neurol Sci, Neurogenet Lab, Beaverton, OR 97006 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. NR 55 TC 48 Z9 54 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD MAR PY 2003 VL 22 IS 3 BP 285 EP 297 DI 10.1016/S0144-7431(02)00013-1 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 668VJ UT WOS:000182313600001 PM 12691731 ER PT J AU Mazur, J Jernigan, RL Sarai, A AF Mazur, J Jernigan, RL Sarai, A TI Conformational effects of DNA stretching SO MOLECULAR BIOLOGY LA English DT Article DE propeller twist; DNA flexibility; stress-strain relation ID DOUBLE-HELICAL DNA; SEQUENCE DEPENDENCE; ESCHERICHIA-COLI; B-DNA; MOLECULES; PROTEIN; SIMULATION; FILAMENTS; FORCE AB DNA is an extensible molecule, and an extended conformation of DNA is involved in some biological processes. We have examined the effect of elongation stress on the conformational properties of DNA base pairs by conformational analysis. The calculations show that stretching does significantly affect the conformational properties and flexibilities of base pairs. In particular, we have found that the propeller twist in base pairs reverses its sign upon stretching. The energy profile analysis indicates that electrostatic interactions make a major contribution to the stabilization of the positive-propeller-twist configuration in stretched DNA. This stretching also results in a monotonic decrease in the helical twist angle, tending to unwind the double helix. Fluctuations in most variables initially increase upon stretching, because of unstacking of base pairs, but then the fluctuations decrease as DNA is stretched further, owing to the formation of specific interactions between base pairs induced by the positive propeller twist. Thus, the stretching of DNA has particularly significant effects upon DNA flexibility. These changes in both the conformation and flexibility of base pairs probably have a role in functional interactions with proteins. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Adv Biomed Comp Ctr, Frederick, MD 21701 USA. NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. RIKEN, Tsukuba Inst, Tsukuba, Ibaraki 3050074, Japan. RP Mazur, J (reprint author), 104 Brooksby Village Dr, Peabody, MA 01960 USA. RI Jernigan, Robert/A-5421-2012 NR 32 TC 2 Z9 3 U1 1 U2 4 PU MAIK NAUKA/INTERPERIODICA PI NEW YORK PA C/O KLUWER ACADEMIC-PLENUM PUBLISHERS, 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0026-8933 J9 MOL BIOL+ JI Mol. Biol. PD MAR-APR PY 2003 VL 37 IS 2 BP 240 EP 249 DI 10.1023/A:1023397622116 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 676XN UT WOS:000182778000011 ER PT J AU Porter, D Lahti-Domenici, J Keshaviah, A Bae, YK Argani, P Marks, J Richardson, A Cooper, A Strausberg, R Riggins, GJ Schnitt, S Gabrielson, E Gelman, R Polyak, K AF Porter, D Lahti-Domenici, J Keshaviah, A Bae, YK Argani, P Marks, J Richardson, A Cooper, A Strausberg, R Riggins, GJ Schnitt, S Gabrielson, E Gelman, R Polyak, K TI Molecular markers in ductal carcinoma in situ of the breast SO MOLECULAR CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; GENE-EXPRESSION; SERIAL ANALYSIS; CLUSTER-ANALYSIS; HUMAN EPIDERMIS; PROTEIN; PSORIASIN; CLONING; CANCER; PROGRESSION AB Gene expression patterns in ductal carcinoma in situ (DCIS), and in invasive, and metastatic breast tumors were determined using serial analysis of gene expression (SAGE). We used mRNA in situ hybridization to examine gene expression at the cellular level and immunohistochemistry on tissue microarrays to determine association between gene expression patterns and histopathologic characteristics of the tumors. We found that that the most dramatic transcriptome change occurs at the normal to DCIS transition, while there is no clear universal "in situ" or "invasive" tumor molecular signature. From the 16,430 transcripts analyzed, we identified only 5 and 11 that were preferentially up-regulated in DCIS and invasive tumors, respectively. The majority of invasive cancer specific SAGE tags correspond to novel genes. The genes we identified may define biologically and clinically meaningful subgroups of DCIS with a high risk of progression to invasive disease. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Faulkner & Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. NCI, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D740C, Boston, MA 02115 USA. EM Kornelia_Polyak@dfci.harvard.edu FU NCI NIH HHS [CA89393, CA88843] NR 31 TC 183 Z9 190 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAR PY 2003 VL 1 IS 5 BP 362 EP 375 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 660QR UT WOS:000181844300004 PM 12651909 ER PT J AU Welsh, SJ Williams, RR Birmingham, A Newman, DJ Kirkpatrick, DL Powis, G AF Welsh, SJ Williams, RR Birmingham, A Newman, DJ Kirkpatrick, DL Powis, G TI The thioredoxin redox inhibitors 1-methylpropyl 2-imidazolyl disulfide and pleurotin inhibit hypoxia-induced factor 1 alpha and vascular endothelial growth factor formation SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID INDUCIBLE FACTOR 1-ALPHA; UBIQUITIN-PROTEASOME PATHWAY; BREAST-CANCER CELLS; GENE-EXPRESSION; FACTORS HIF-1-ALPHA; NORMOXIC CONDITIONS; TUMOR ANGIOGENESIS; DIRECT ASSOCIATION; UP-REGULATION; NECK-CANCER AB Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a critical role in tumor growth by increasing resistance to apoptosis and the production of angiogenic factors such as vascular endothelial growth factor (VEGF). HIF-1 is a heterodimer comprised of oxygen-regulated HIF-1alpha and constitutively expressed HIF-1beta subunits. The redox protein thioredoxin-1 (Trx-1), which is found at high levels in many human cancers, increases both aerobic and hypoxia-induced HIF-1alpha protein in cells leading to increased expression of HIF-regulated genes. We have investigated whether two cancer drugs that inhibit Trx-1 signaling, PX-12 (1-methylpropyl 2-imidazolyl disulfide) and pleurotin, decrease HIF-1alpha protein levels and the expression of downstream target genes. Treatment of MCF-7 human breast cancer and HT-29 human colon carcinoma cells with PX-12 and pleurotin prevented the hypoxia (1% oxygen)-induced increase in HIF-1a protein. HIF-1-trans-activating activity, VEGF formation, and inducible nitric oxide synthase were also decreased by treatment with PX-12 and pleurotin under hypoxic conditions. PX-12 and pleurotin also decreased HIF-1alpha protein levels and HIF-1alpha transactivation in RCC4 renal cell carcinoma cells that constitutively overexpress HIF-1alpha protein because of loss of the pVHL gene, indicating that HIF-is is inhibited independently of the pVHL pathway. HIF-1a and VEGF protein levels in MCF-7 tumor xenografts in vivo were decreased by PX-12 treatment of mice. The results suggest that inhibition of HIF-1alpha by Trx-1 inhibitors may contribute to the growth inhibitory and antitumor activity of these agents. C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. NCI, Nat Prod Branch, Frederick, MD 21702 USA. Proix Pharmaceut, Tucson, AZ 85750 USA. RP Welsh, SJ (reprint author), Univ Arizona, Arizona Canc Ctr, 1515 N Campbell Ave, Tucson, AZ 85724 USA. EM swelsh@azcc.arizona.edu FU NCI NIH HHS [CA17094, CA52995, CA98920] NR 74 TC 192 Z9 203 U1 1 U2 16 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAR PY 2003 VL 2 IS 3 BP 235 EP 243 PG 9 WC Oncology SC Oncology GA 659BL UT WOS:000181757100006 PM 12657718 ER PT J AU Husain, SR Kawakami, K Kawakami, M Puri, RK AF Husain, SR Kawakami, K Kawakami, M Puri, RK TI Interleukin-4 receptor-targeted cytotoxin therapy of androgen-dependent and -independent prostate carcinoma in xenograft models SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CIRCULARLY PERMUTED INTERLEUKIN-4; PSEUDOMONAS EXOTOXIN; CANCER-THERAPY; PHASE-II; ANTITUMOR-ACTIVITY; FUSION PROTEIN; CELL CARCINOMA; GROWTH-FACTORS; ANIMAL-MODELS; TOXIN AB Prostate cancer is the most commonly diagnosed solid tumors in United States men. Survival with advanced prostate cancer is dismal because of a lack of effective treatments. Overexpression of interleukin 4 receptors (IL-4R) on prostate carcinoma cells makes them suitable targets for the interleukin 4 (IL-4) fused Pseudomonas exotoxin, IL-4 cytotoxin (IL4-CTx). Androgen-dependent (LNCaP) and -independent (DU145) human prostate cancer cell lines overexpress IL-4Rs and are exquisitely sensitive to IL4-CTx. Using LNCaP and DU145 cell lines, IC50 values of 4.5 +/- 2.0 and 6.5 +/- 0.5 ng/ml, respectively, were obtained for IL4-CTx in protein synthesis inhibition assays. Primary cultures established from prostate tumor biopsies were equally sensitive to the cytotoxic effects of IL4-CTx. Reverse transcription-PCR analysis, although not quantitative, indicated the presence of mRNA for IL-4Ralpha, a primary subunit of the IL-4R receptor complex in prostate carcinoma cell lines, primary cultures, benign prostatic hyperplasia, and prostate carcinoma tissues. Immunohistochemistry studies revealed the presence of IL-4R in benign prostatic hyperplasia and prostate carcinomas. Five daily (QD) injections of IL4-CTx (100 mug/kg) administered im., i.p., or intratumoral (i.t.) caused several complete responses in nude mice with s.c. DU145 and LNCaP tumors. i.t. injections of IL4-CTx elicited tumor regression in a dose-dependent manner with complete responses occurring in 100% of the animals when treated with IL4-CTx (500 mug/kg) given five OD injections. Administration of IL4-CTx i.t. (500 mug/kg) either 10 times OD or six injections on alternate days elicited complete responses in 40% of mice with DU145 tumors that were three times larger (67 mm(2)) on initiation of treatments. IL4-CTx appeared to be well tolerated. On the basis of these results, combining i.t. injections of IL4-CTx with systemic administration may provide an effective strategy for treating patients with advanced, refractory prostate cancer. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. EM Puri@cber.fda.gov NR 43 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAR PY 2003 VL 2 IS 3 BP 245 EP 254 PG 10 WC Oncology SC Oncology GA 659BL UT WOS:000181757100007 PM 12657719 ER PT J AU Covell, DG Wallqvist, A Rabow, AA Thanki, N AF Covell, DG Wallqvist, A Rabow, AA Thanki, N TI Molecular classification of cancer: Unsupervised self-organizing map analysis of gene expression microarray data SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID HUMAN-BREAST-CANCER; CELL CARCINOMA; GROWTH; PREDICTION; DIAGNOSIS; GLIOMAS; MARKER; ALPHA; SIGNATURES; MECHANISM AB An unsupervised self-organizing map-based clustering strategy has been developed to classify tissue samples from an oligonucleotide microarray patient database. Our method is based on the likelihood that a test data vector may have a gene expression fingerprint that is shared by more than one tumor class and as such can identify datasets that cannot be unequivocally assigned to a single tumor class. Our self-organizing map analysis completely separated the tumor from the normal expression datasets. Within the 14 different tumor types, classification accuracies on the order of similar to80% correct were achieved. Nearly perfect classifications were found for leukemia, central nervous system, melanoma, uterine, and lymphoma tumor types, with very poor classifications found for colorectal, ovarian, breast, and lung tumors. Classification results were further analyzed to identify sets of differentially expressed genes between tumor and normal gene expressions and among each tumor class. Within the total pool of 1139 genes most differentially expressed in this dataset, subsets were found that could be vetted according to previously published literature sources to be specific tumor markers. Attempts to classify gene expression datasets from other sources found a wide range of classification accuracies. Discussions about the utility of this method and the quality of data needed for accurate tumor classifications are provided. C1 NCI, Sci Applicat Int Corp Frederick, Div Dev Therapeut,Lab Computat Technol, Screening Technol Branch, Frederick, MD 21702 USA. RP Covell, DG (reprint author), NCI, Sci Applicat Int Corp Frederick, Div Dev Therapeut,Lab Computat Technol, Screening Technol Branch, Bldg 1052,Room 238, Frederick, MD 21702 USA. OI wallqvist, anders/0000-0002-9775-7469 FU NCI NIH HHS [N01-CO-12400] NR 60 TC 52 Z9 54 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAR PY 2003 VL 2 IS 3 BP 317 EP 332 PG 16 WC Oncology SC Oncology GA 659BL UT WOS:000181757100015 PM 12657727 ER PT J AU Chae, JJ Komarow, HD Cheng, J Wood, G Raben, N Liu, PP Kastner, DL AF Chae, JJ Komarow, HD Cheng, J Wood, G Raben, N Liu, PP Kastner, DL TI Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis SO MOLECULAR CELL LA English DT Article ID FAMILIAL MEDITERRANEAN FEVER; CASPASE RECRUITMENT DOMAIN; NF-KAPPA-B; CONTAINING APAF1-LIKE PROTEIN; REGULATES ACTIVATION; RECEPTOR ANTAGONIST; MICE DEFICIENT; GENE; ASC; INDUCTION AB Familial Mediterranean fever (FMF) is an inherited disorder characterized by recurrent episodes of fever and inflammation. Most patients with FMF carry missense mutations in the C-terminal half of the pyrin protein. To study the physiologic role of pyrin, we generated mice expressing a truncated pyrin molecule that, similar to FMF patients, retains the full PYRIN domain. Bacterial lipopolysaccharide (LPS) induces accentuated body temperatures and increased lethality in homozygous mutant mice. When stimulated, macrophages from these mice produce increased amounts of activated caspase-1 and, consequently, elevated levels of mature IL-1beta. Full-length pyrin competes in vitro with caspase-1 for binding to ASC, a known caspase-1 activator. Apoptosis is impaired in macrophages from pyrin-truncation mice through an IL-1-independent pathway. These data support a critical role for pyrin in the innate immune response, possibly by acting on ASC, and suggest a biologic basis for the selection of hypomorphic pyrin variants in man. C1 NIAMSD, Inflammatory Biol Sect, Genet & Genom Branch, Bethesda, MD 20892 USA. NHGRI, Oncogenesis & Dev Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NIAMSD, Connect Tissue Dis Sect, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. RP Chae, JJ (reprint author), NIAMSD, Inflammatory Biol Sect, Genet & Genom Branch, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 48 TC 256 Z9 265 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR PY 2003 VL 11 IS 3 BP 591 EP 604 DI 10.1016/S1097-2765(03)00056-X PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 664EX UT WOS:000182049700007 PM 12667444 ER PT J AU Harding, HP Zhang, YH Zeng, HQ Novoa, I Lu, PD Calfon, M Sadri, N Yun, C Popko, B Paules, R Stojdl, DF Bell, JC Hettmann, T Leiden, JM Ron, D AF Harding, HP Zhang, YH Zeng, HQ Novoa, I Lu, PD Calfon, M Sadri, N Yun, C Popko, B Paules, R Stojdl, DF Bell, JC Hettmann, T Leiden, JM Ron, D TI An integrated stress response regulates amino acid metabolism and resistance to oxidative stress SO MOLECULAR CELL LA English DT Article ID UNFOLDED-PROTEIN RESPONSE; INITIATION-FACTOR 2-ALPHA; DISULFIDE-BOND FORMATION; HEME OXYGENASE-1 GENE; TRANSFER-RNA BINDING; ENDOPLASMIC-RETICULUM; TRANSCRIPTION FACTOR; TRANSLATIONAL CONTROL; MAMMALIAN-CELLS; SACCHAROMYCES-CEREVISIAE AB Eukaryotic cells respond to unfolded proteins in their endoplasmic reticulum (ER stress), amino acid starvation, or oxidants by phosphorylating the alpha subunit of translation initiation factor 2 (eIF2alpha). This adaptation inhibits general protein synthesis while promoting translation and expression of the transcription factor ATF4. Atf4(-/-) cells are impaired in expressing genes involved in amino acid import, glutathione biosynthesis, and resistance to oxidative stress. Perk(-/-) cells, lacking an upstream ER stress-activated eIF2alpha kinase that activates Atf4, accumulate endogenous peroxides during ER stress, whereas interference with the ER oxidase ERO1 abrogates such accumulation. A signaling pathway initiated by eIF2alpha phosphorylation protects cells against metabolic consequences of ER oxidation by promoting the linked processes of amino acid sufficiency and resistance to oxidative stress. C1 NYU, Sch Med, Skirball Inst, New York, NY 10016 USA. NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA. Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Ottawa Reg Canc Ctr, Ottawa, ON K1H 8L6, Canada. Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA. RP Ron, D (reprint author), NYU, Sch Med, Skirball Inst, New York, NY 10016 USA. RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Novoa, Isabel/0000-0003-1821-1685 FU NIDDK NIH HHS [DK47119]; NIEHS NIH HHS [ES08681] NR 59 TC 1360 Z9 1403 U1 22 U2 125 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR PY 2003 VL 11 IS 3 BP 619 EP 633 DI 10.1016/S1097-2765(03)00105-9 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 664EX UT WOS:000182049700009 PM 12667446 ER PT J AU Cerritelli, SM Frolova, EG Feng, CG Grinberg, A Love, PE Crouch, RJ AF Cerritelli, SM Frolova, EG Feng, CG Grinberg, A Love, PE Crouch, RJ TI Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice SO MOLECULAR CELL LA English DT Article ID TRANSCRIPTION FACTOR-A; RIBONUCLEASE-H; SUBCELLULAR-LOCALIZATION; SACCHAROMYCES-CEREVISIAE; REVERSE TRANSCRIPTION; LEADING-STRAND; GENE ENCODES; CYTOCHROME-C; R-LOOP; REPLICATION AB Although ribonucleases H (RNases H) have long been implicated in DNA metabolism, they are not required for viability in prokaryotes or unicellular eukaryotes. We generated Rnaseh1(-/-) mice to investigate the role of RNase H1 in mammals and observed developmental arrest at E8.5 in null embryos. A fraction of the mainly nuclear RNase H1 was targeted to mitochondria, and its absence in embryos resulted in a significant decrease in mitochondrial DNA content, leading to apoptotic cell death. This report links RNase H1 to generation of mitochondrial DNA, providing direct support for the strand-coupled mechanism of mitochondrial DNA replication. These findings also have important implications for therapy of mitochondrial dysfunctions and drug development for the structurally related RNase H of HIV. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Crouch, RJ (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NR 49 TC 152 Z9 155 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR PY 2003 VL 11 IS 3 BP 807 EP 815 DI 10.1016/S1097-2765(03)00088-1 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 664EX UT WOS:000182049700024 PM 12667461 ER PT J AU Hovey, RC Harris, J Hadsell, DL Lee, AV Ormandy, CJ Vonderhaar, BK AF Hovey, RC Harris, J Hadsell, DL Lee, AV Ormandy, CJ Vonderhaar, BK TI Local insulin-like growth factor-II mediates prolactin-induced mammary gland development SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID EPITHELIAL-CELL GROWTH; BREAST-CANCER CELLS; RECEPTOR ISOFORM-A; IGF-II; MESSENGER-RNA; BINDING-PROTEINS; TRANSGENIC MICE; EXPRESSION; MOUSE; GENE AB Prolactin (PRL) is a major determinant of mammary epithelial cell proliferation during alveolar development in sexually mature and pregnant mice. To date, it has not been clear whether PRL effects these responses alone or by also invoking the action of autocrine/paracrine growth factors. In this study, we provide evidence that part of the effect of PRL on mammary gland growth is mediated by IGF-II. During sexual maturity and in early pregnancy, the level of IGF-II mRNA in the mammary gland was increased concurrent with increased PRL receptor expression. The level of IGF-II mRNA was reduced in mammary tissue from PRL receptor(-/-) mice during early pregnancy, and explants of mouse mammary gland and HC11 mammary epithelial cells both increased their expression of IGF-II after exposure to PRL in vitro. These findings coincided with the demonstration that IGF-II stimulated alveolar development in mammary glands in whole organ culture. PRL was most efficacious in stimulating IGF-II gene transcription from promoter 3 of the mouse IGF-II gene in vitro. Insight into the mechanism by which PRL induced IGF-II expression was provided by the fact that it was blocked by the Jak2 inhibitor AG490 and the MAPK inhibitor PD98059. Finally, induction of insulin receptor substrate (IRS)-1 in the mammary glands of PRL-treated mice and induction of IRS-1 and IRS-2 after treatment with PRL plus progesterone indicates that these molecules are induced by PRL as potential signaling intermediates downstream from IGF-I/insulin receptors. Together, these data demonstrate a role for IGF-II as a mediator of PRL action in the mouse mammary gland during ductal branching and alveolar development. C1 NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. Garvan Inst Med Res, Canc Res Program, Darlinghurst, NSW 2010, Australia. Baylor Coll Med, USDA, Agr Res Serv, Childrens Nutr Res Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. RP Hovey, RC (reprint author), Univ Vermont, Dept Anim Sci, Lactat & Mammary Gland Biol Grp, Rm 121,Terrill Hall, Burlington, VT 05405 USA. RI Ormandy, Chris/G-4165-2014 FU NCI NIH HHS [R01-CA-94118] NR 49 TC 67 Z9 68 U1 1 U2 4 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR PY 2003 VL 17 IS 3 BP 460 EP 471 DI 10.1210/me.2002-0214 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 653FK UT WOS:000181424400014 PM 12554791 ER PT J AU Cohen, GN Barbe, V Flament, D Galperin, M Heilig, R Lecompte, O Poch, O Prieur, D Querellou, J Ripp, R Thierry, JC Van der Oost, J Weissenbach, J Zivanovic, Y Forterre, P AF Cohen, GN Barbe, V Flament, D Galperin, M Heilig, R Lecompte, O Poch, O Prieur, D Querellou, J Ripp, R Thierry, JC Van der Oost, J Weissenbach, J Zivanovic, Y Forterre, P TI An integrated analysis of the genome of the hyperthermophilic archaeon Pyrococcus abyssi SO MOLECULAR MICROBIOLOGY LA English DT Review ID HORIZONTAL GENE EXCHANGE; TRANSFER-RNA SYNTHETASE; REPLICATION FACTOR-C; BACTERIAL HYPERTHERMOPHILES; HYDROTHERMAL VENT; DNA-POLYMERASES; PHYLOGENETIC CHARACTERIZATION; BIOCHEMICAL-CHARACTERIZATION; THERMUS-THERMOPHILUS; TRANSCRIPTION FACTOR AB The hyperthermophilic euryarchaeon Pyrococcus abyssi and the related species Pyrococcus furiosus and Pyrococcus horikoshii , whose genomes have been completely sequenced, are presently used as model organisms in different laboratories to study archaeal DNA replication and gene expression and to develop genetic tools for hyperthermophiles. We have performed an extensive re-annotation of the genome of P. abyssi to obtain an integrated view of its phylogeny, molecular biology and physiology. Many new functions are predicted for both informational and operational proteins. Moreover, several candidate genes have been identified that might encode missing links in key metabolic pathways, some of which have unique biochemical features. The great majority of Pyrococcus proteins are typical archaeal proteins and their phylogenetic pattern agrees with its position near the root of the archaeal tree. However, proteins probably from bacterial origin, including some from mesophilic bacteria, are also present in the P. abyssi genome. C1 Univ Paris 11, Inst Genet & Microbiol, Ctr Univ Orsay, UMR 8621,CNRS, F-91405 Orsay, France. Inst Pasteur, F-75724 Paris 15, France. CNS, F-91057 Evry, France. Ifremer, Ctr Brest, DRV, VP,LMBE, F-29280 Plouzane, France. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. IGBMC, CNRS, F-67404 Illkirch Graffenstaden, France. Univ Bretagne Occidentale, IUEM, F-29280 Plouzane, France. Wageningen Univ, NL-6703 CT Wageningen, Netherlands. RP Forterre, P (reprint author), Univ Paris 11, Inst Genet & Microbiol, Ctr Univ Orsay, UMR 8621,CNRS, Bat 409, F-91405 Orsay, France. RI QUERELLOU, JOEL/E-9747-2010; Lecompte, Odile/F-4741-2011; Galperin, Michael/B-5859-2013 OI Lecompte, Odile/0000-0002-2005-460X; Galperin, Michael/0000-0002-2265-5572 NR 110 TC 134 Z9 615 U1 0 U2 20 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAR PY 2003 VL 47 IS 6 BP 1495 EP 1512 DI 10.1046/j.1365-2958.2003.03381.x PG 18 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 652HF UT WOS:000181373200002 PM 12622808 ER PT J AU Newman, D Sakaue, M Koo, JS Kim, KS Baek, SJ Eling, T Jetten, AM AF Newman, D Sakaue, M Koo, JS Kim, KS Baek, SJ Eling, T Jetten, AM TI Differential regulation of nonsteroidal anti-inflammatory drug-activated gene in normal human tracheobronchial epithelial and lung carcinoma cells by retinoids SO MOLECULAR PHARMACOLOGY LA English DT Article ID TGF-BETA SUPERFAMILY; GROWTH-FACTOR-BETA; MACROPHAGE INHIBITORY CYTOKINE; AU-RICH ELEMENTS; MESSENGER-RNA; CANCER CELLS; POSTTRANSCRIPTIONAL REGULATION; MORPHOGENETIC PROTEIN; APOPTOSIS; EXPRESSION AB In this study, we analyze the effect of several retinoids on the expression of nonsteroidal anti-inflammatory drug-activated gene (NAG-1) in normal human tracheobronchial epithelial (HTBE) cells and several lung carcinoma cell lines. The retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN) greatly enhances the expression of NAG-1 mRNA and protein in a time- and dose-dependent manner in human lung adenocarcinoma H460 cells and several other carcinoma cell lines. This induction was specific for AHPN because retinoic acid, a retinoic acid receptor-, and a retinoid X receptor pan-agonist were unable to induce NAG-1, suggesting that this induction is not mediated through activation of retinoid receptors. Although NAG-1 is a p53-responsive gene, AHPN-induced NAG-1 expression does not require p53. The induction of NAG-1 expression by AHPN is caused at least in part by an 8-fold increase in the stability of NAG-1 mRNA. In contrast to carcinoma cells, NAG-1 expression is effectively induced by retinoic acid and the RAR-selective pan-agonist in normal HTBE cells and accompanies the inhibition of squamous differentiation and the initiation of normal differentiation. In vivo, NAG-1 expression was observed in the normal tracheobronchial epithelium, whereas no expression was found in either squamous metaplastic tracheal epithelium or in sections of human lung tumors. Our results suggest that the induction of NAG-1 expression by retinoids in normal HTBE and lung carcinoma cells is regulated by distinct mechanisms and is associated with different biological processes. The linkage between AHPN treatment and NAG-1 expression revealed in this study provides a new mechanism for the antitumorigenic activity of AHPN. C1 NIEHS, Lab Pulm Pathobol, Cell Biol Sect,Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Eicosanoid Biochem Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Jetten, AM (reprint author), NIEHS, Lab Pulm Pathobol, Cell Biol Sect,Div Intramural Res, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. OI Baek, Seung/0000-0001-7866-7778; Jetten, Anton/0000-0003-0954-4445 NR 40 TC 47 Z9 50 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2003 VL 63 IS 3 BP 557 EP 564 DI 10.1124/mol.63.3.557 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 649HL UT WOS:000181201400012 PM 12606762 ER PT J AU Aslamkhan, AG Han, YH Yang, XP Zalups, RK Pritchard, JB AF Aslamkhan, AG Han, YH Yang, XP Zalups, RK Pritchard, JB TI Human renal organic anion transporter 1-dependent uptake and toxicity of mercuric-thiol conjugates in Madin-Darby canine kidney cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID INORGANIC MERCURY; BASOLATERAL UPTAKE; P-AMINOHIPPURATE; N-ACETYLCYSTEINE; PROXIMAL TUBULE; EXPRESSION CLONING; MOLECULAR-CLONING; RAT-KIDNEY; CYSTEINE; HOMOCYSTEINE AB Mercuric ions are highly reactive and form a variety of organic complexes or conjugates in vivo. The renal proximal tubule is a primary target for mercury uptake and toxicity, and circumstantial evidence implicates organic anion transporters in these processes. To test this hypothesis directly, the transport and toxicity of mercuric-thiol conjugates were characterized in a Madin-Darby canine kidney cell line stably transfected with the human organic anion transporter 1 (hOAT1). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-terazolium bromide assays (for mitochondrial dehydrogenase) confirmed that mercuric conjugates of the thiols N-acetylcysteine (NAC), cysteine, or glutathione were more toxic in hOAT1-transfected cells than in the non-transfected cells. The NAC-Hg2+ conjugate was most cytotoxic, inducing greater than 50% cellular death over 18 h at a concentration of 100 muM. The cytotoxic effects were fully reversed by probenecid (an OAT1 inhibitor) and partially reversed by p-aminohippurate (an OAT1 substrate). Toxicity of this conjugate was reduced by the OAT1-exchangeable dicarboxylates alpha-ketoglutarate, glutarate, and adipate, but not by succinate, a nonexchangeable dicarboxylate. 203 Hg-uptake studies showed probenecid-sensitive uptake of mercury-thiol conjugates in the hOAT1-transfected cells. The apparent Km for the NAC-Hg2+ conjugate was 44 +/- 9 muM. Uptake of the NAC-Hg2+ conjugate was cis-inhibited by glutarate, but not by methylsuccinate, paralleling their effects on toxicity. Probenecid-sensitive transport of the NAC-Hg2+ conjugate was also shown to occur in Xenopus laevis oocytes expressing the hOAT1 or the rOAT3 transporters, suggesting that OAT3 may also transport thiol-Hg2+ conjugates. Thus, renal accumulation and toxicity of thiol-Hg2+ conjugates may depend in part on the activity of the organic transport system. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Mercer Univ, Sch Med, Div Basic Med Sci, Macon, GA 31207 USA. RP Pritchard, JB (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233,F1-03, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [ES05980, ES05157, ES11288] NR 43 TC 59 Z9 59 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2003 VL 63 IS 3 BP 590 EP 596 DI 10.1124/mol.63.3.590 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 649HL UT WOS:000181201400016 PM 12606766 ER PT J AU Offertaler, L Mo, FM Batkai, S Liu, J Begg, M Razdan, RK Martin, BR Bukoski, RD Kunos, G AF Offertaler, L Mo, FM Batkai, S Liu, J Begg, M Razdan, RK Martin, BR Bukoski, RD Kunos, G TI Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor SO MOLECULAR PHARMACOLOGY LA English DT Article ID CA2+-INDUCED RELAXATION; HYPERPOLARIZING FACTOR; INDUCED HYPOTENSION; MESENTERIC-ARTERY; CORONARY-ARTERIES; SENSORY NERVES; CB1 RECEPTORS; ANANDAMIDE; ENDOCANNABINOIDS; VASORELAXATION AB The cannabinoid analog abnormal cannabidiol [abn-cbd; (-) 4-(3-3,4-trans-p-menthadien-[1,8]-yl)-olivetol] does not bind to CB1 or CB2 receptors, yet it acts as a full agonist in relaxing rat isolated mesenteric artery segments. Vasorelaxation by abn-cbd is endothelium-dependent, pertussis toxin-sensitive, and is inhibited by the BKCa channel inhibitor charybdotoxin, but not by the nitric-oxide synthase inhibitor N-omega-nitro-L-arginine methyl ester or by the vanilloid VR1 receptor antagonist capsazepine. The cannabidiol analog O-1918 does not bind to CB1 or CB2 receptors and does not cause vasorelaxation at concentrations up to 30 muM, but it does cause concentration-dependent (1-30 muM) inhibition of the vasorelaxant effects of abn-cbd and anandamide. In anesthetized mice, O-1918 dose-dependently inhibits the hypotensive effect of abn-cbd but not the hypotensive effect of the CB1 receptor agonist (-)-11-OH-Delta(9)-tetrahydro-cannabinol dimethylheptyl. In human umbilical vein endothelial cells, abn-cbd induces phosphorylation of p42/44 mitogen-activated protein kinase and protein kinase B/Akt, which is inhibited by O-1918, by pertussis toxin or by phosphatidylinositol 3 (PI3) kinase inhibitors. These findings indicate that abn-cbd is a selective agonist and that O-1918 is a selective, silent antagonist of an endothelial "anandamide receptor", which is distinct from CB1 or CB2 receptors and is coupled through G(i)/G(o) to the PI3 kinase/Akt signaling pathway. C1 NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. Organix Inc, Woburn, MA USA. Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA. N Carolina Cent Univ, Cardiovasc Dis Res Program, Durham, NC USA. RP Kunos, G (reprint author), NIAAA, Lab Physiol Studies, NIH, 12420 Parklawn Dr,MSC-8115, Bethesda, MD 20892 USA. RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014 NR 41 TC 152 Z9 159 U1 0 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2003 VL 63 IS 3 BP 699 EP 705 DI 10.1124/mol.63.3.699 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 649HL UT WOS:000181201400030 PM 12606780 ER PT J AU Wen, LT Caldwell, CC Knowles, AF AF Wen, LT Caldwell, CC Knowles, AF TI Poly(ADP-ribose) polymerase activation and changes in Bax protein expression associated with extracellular ATP-mediated apoptosis in human embryonic kidney 293-P2X(7) cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID NUCLEOTIDE RECEPTOR; DENDRITIC CELLS; P-2Z RECEPTOR; DEATH; INDUCTION; P2X(7); MICE; HEPATOCYTES; DEFICIENT; FAMILY AB Extracellular ATP is a potent signaling factor that modulates a variety of cellular functions through the activation of P2 purinergic receptors. Extracellular ATP at higher concentrations exerts cytostatic as well as cytotoxic effects in a variety of cell systems, the mechanism of which is not fully understood. In this study, we used cultured human embryonic kidney (HEK) cells stably transfected with human P2X(7) receptors (HEK-P2X(7)) to investigate the mechanism of ATP-induced cell death. The cytotoxic effects of ATP in HEK-P2X(7) cells were dose- and time-dependent, whereas ADP, AMP, and UTP had no effect. ATP treatment induced a significant increase in apoptotic HEK-P2X(7) cells as ascertained by the terminal deoxynucleotidyl transferase dUTP nick-end labeling technique and flow cytometry. An ATP-induced decrease in the pro-apoptotic bax gene expression was detected by apoptosis-related cDNA microarray analysis, which correlated with a decrease of Bax protein expression. Western blot analysis revealed that ATP treatment resulted in the processing of pro-caspase 3 to its active form and cleavage of the nuclear enzyme, poly(ADP-ribose) polymerase (PARP). Both ATP-induced molecular alterations in HEK-P2X(7) cells (i.e., decrease of Bax expression and increase of PARP cleavage) were blocked by the purinergic P2X(7) receptor antagonist oxidized ATP. In conclusion, we demonstrated the importance of the P2X(7) receptor in ATP induced cell death of HEK-P2X(7) cells, which seems to be independent of bax expression; however, the activation of caspases is required. C1 San Diego State Univ, Dept Biol, Microchem Core Facil, San Diego, CA 92182 USA. San Diego State Univ, Dept Chem, San Diego, CA 92182 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Wen, LT (reprint author), San Diego State Univ, Dept Biol, Microchem Core Facil, 5500 Campanile Dr, San Diego, CA 92182 USA. OI Caldwell, Charles/0000-0003-1692-4550 NR 39 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2003 VL 63 IS 3 BP 706 EP 713 DI 10.1124/mol.63.3.706 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 649HL UT WOS:000181201400031 PM 12606781 ER PT J AU Monks, A Harris, E Hose, C Connelly, J Sausville, EA AF Monks, A Harris, E Hose, C Connelly, J Sausville, EA TI Genotoxic profiling of MCF-7 breast cancer cell line elucidates gene expression modifications underlying toxicity of the anticancer drug 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole SO MOLECULAR PHARMACOLOGY LA English DT Article ID TGF-BETA SUPERFAMILY; GROWTH-FACTOR-BETA; IN-VITRO; ANTITUMOR BENZOTHIAZOLES; TRANSCRIPTION FACTORS; BIOLOGICAL PROPERTIES; STRESS RESPONSES; CDNA MICROARRAY; DNA-DAMAGE; 2-(4-AMINOPHENYL)BENZOTHIAZOLES AB A candidate antitumor agent, 2-(4-amino-3-methylphenyl)-5fluorobenzothiazole(5F-203), was empirically discovered through the National Cancer Institute's Anticancer Drug Screen from a unique growth inhibitory-response profile, indicating a novel mechanism of action. 5F-203 activates the CYP1 family of cytochrome P450, involving aryl hydrocarbon receptor translocation into the nucleus. To characterize more completely the pathways involved in 5F-203 toxicity, cDNA microarrays were used to determine gene expression changes in MCF-7, a 5F-203-sensitive breast cancer cell line, after treatment with 1 muM 5F-203. The mRNA expression of CYP1A1 and CYP1B1 were both increased approximately 20-fold after 24 h, but less after 6 h of treatment, confirming previous results. However, the most pronounced drug-induced change was in the PLAB gene, encoding one of the bone morphogenic proteins in the trans-forming growth factor-beta (TGF-beta) superfamily. Other induced gene expressions included the apoptosis-initiating receptor TNFRSF6 (CD95/FAS), the DNA-damage response genes CDKN1A (p21/Cip1), p53-induced gene-3, and DNA binding protein 2. In contrast, the transcription factor c-Myc showed reduced expression. Western blot analysis also showed induction of p53 protein expression in response to 5F-203 treatment. In contrast to the MCF-7 data, MDA-MB-435, a cancer cell line resistant to 5F-203, showed no change in expression of any of these genes or the p53 protein under the same conditions of 5F-203 treatment. These data are consistent with the idea that CYP1A1 and CYP1B1 activation leads to 5F-203 toxicity through DNA damage-induced apoptosis, as well as signaling through a variant member of the TGF-beta superfamily. C1 NCI Frederick, SAIC Frederick Inc, Screening Technol Branch, Lab Funct Genom, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Rockville, MD USA. RP Monks, A (reprint author), NCI Frederick, SAIC Frederick Inc, Screening Technol Branch, Lab Funct Genom, POB B,Bldg 432, Frederick, MD 21702 USA. FU PHS HHS [N01-C0-12400] NR 28 TC 42 Z9 43 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2003 VL 63 IS 3 BP 766 EP 772 DI 10.1124/mol.63.3.766 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 649HL UT WOS:000181201400037 PM 12606787 ER PT J AU Davenport, MD Novak, MA Meyer, JS Tiefenbacher, S Higley, JD Lindell, SG Champoux, M Shannon, C Suomi, SJ AF Davenport, MD Novak, MA Meyer, JS Tiefenbacher, S Higley, JD Lindell, SG Champoux, M Shannon, C Suomi, SJ TI Continuity and change in emotional reactivity in rhesus monkeys throughout the prepubertal period SO MOTIVATION AND EMOTION LA English DT Article DE salivary; plasma; cortisol; rhesus; rearing ID SALIVARY CORTISOL; MACACA-MULATTA; ADRENOCORTICAL-RESPONSE; INDIVIDUAL-DIFFERENCES; PEER INTERACTIONS; BINDING GLOBULIN; EARLY EXPERIENCE; POLYVAGAL THEORY; SELF-REGULATION; SERUM CORTISOL AB We examined continuity and change in emotional reactiviy as assessed by hypothalamic-pituitary-adrenal (HPA) activity in rhesus monkeys. Plasma samples were obtained from mother-peer-reared and surrogate-peer-reared monkeys and assayed for cortisol concentrations at 5 time points in infancy. Both plasma and saliva samples were collected for cortisol assay from the same monkeys as 1-, 2-, and 3-year-old juveniles, respectively. Plasma cortisol concentrations increased during the first 5 months of life and decreased from 1 to 3 years of age. Females consistently had higher plasma cortisol concentrations than males. Plasma cortisol concentrations were lower in surrogate-peer-reared than mother-peer-reared monkeys during the first month of life. Juvenile plasma cortisol concentrations were significantly correlated with infant cortisol levels at all but the earliest time point. Analysis of salivary cortisol from a subset of animals showed a similar age-related decline and the presence of a significant rearing effect, with lower concentrations in surrogate-peer-reared juveniles, but no sex difference. Salivary and plasma cortisol concentrations in these animals were significantly correlated. C1 Univ Massachusetts, Dept Psychol, Neurosci & Behav Program, Amherst, MA 01003 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. NIAAA, Clin Studies Lab, Bethesda, MD USA. NICHHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. RP Davenport, MD (reprint author), Univ Massachusetts, Dept Psychol, Neurosci & Behav Program, Tobin Hall, Amherst, MA 01003 USA. OI Meyer, Jerrold/0000-0002-8382-7075 NR 54 TC 18 Z9 18 U1 0 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0146-7239 J9 MOTIV EMOTION JI Motiv. Emot. PD MAR PY 2003 VL 27 IS 1 BP 57 EP 76 DI 10.1023/A:1023626425807 PG 20 WC Psychology, Experimental; Psychology, Social SC Psychology GA 673MN UT WOS:000182584900004 ER PT J AU Misteli, T AF Misteli, T TI A nucleolar disappearing act in somatic cloning SO NATURE CELL BIOLOGY LA English DT Editorial Material ID RIBOSOMAL-RNA; DYNAMICS AB One of the earliest structural changes in cloning by nuclear transfer is the disassembly of the nucleolus. The first insights into the molecular mechanisms of this event have now emerged and the results have tantalising implications for nucleolar architecture. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 14 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAR PY 2003 VL 5 IS 3 BP 183 EP 184 DI 10.1038/ncb0303-183 PG 2 WC Cell Biology SC Cell Biology GA 651LY UT WOS:000181322500004 PM 12646869 ER PT J AU Ross, KE Cohen-Fix, O AF Ross, KE Cohen-Fix, O TI Multitasking at mitotic exit SO NATURE CELL BIOLOGY LA English DT Editorial Material ID BUDDING YEAST; ANAPHASE; SEPARASE; CLEAVAGE; CDC14; LOCALIZATION; PHOSPHATASE; NUCLEOLUS; SECURIN; BINDING AB Separase is a conserved protease that activates the metaphase-to-anaphase transition by cleaving the link between sister chromatids. Furthermore, in Saccharomyces cerevisiae, separase is also involved in promoting mitotic exit through regulating Cdc14 release. A new study now suggests that the mitotic exit function of separase is independent from its protease activity. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ross, KE (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, 8 Ctr Dr, Bethesda, MD 20892 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAR PY 2003 VL 5 IS 3 BP 188 EP 190 DI 10.1038/ncb0303-188 PG 3 WC Cell Biology SC Cell Biology GA 651LY UT WOS:000181322500007 PM 12646872 ER PT J AU Drenth, JPH Morsche, RHMT Smink, R Bonifacino, JS Jansen, JBMJ AF Drenth, JPH Morsche, RHMT Smink, R Bonifacino, JS Jansen, JBMJ TI Germline mutations in PRKCSH are associated with autosomal dominant polycystic liver disease SO NATURE GENETICS LA English DT Article ID PROTEIN-KINASE-C; KIDNEY-DISEASE; GENE; ENCODES; IDENTIFICATION; RECEPTORS; CELLS AB Polycystic liver disease (PCLD, OMIM 174050) is a dominantly inherited condition characterized by the presence of multiple liver cysts of biliary epithelial origin. Fine mapping established linkage to marker D19S581 (Z(max)=9.65; theta=0.01) in four large Dutch families with PCLD. We identified a splice-acceptor site mutation (1138-2A-->G) in PRKCSH in three families, and a splice-donor site mutation (292+1G-->C) in PRKCSH segregated completely with PCLD in another family. The protein encoded by PRKCSH, here named hepatocystin, is predicted to localize to the endoplasmic reticulum. These findings establish germline mutations in PRKCSH as the probable cause of PCLD. C1 Univ Med Ctr St Radboud, Dept Med, Div Gastroenterol & Hepatol, Nijmegen, Netherlands. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Drenth, JPH (reprint author), Univ Med Ctr St Radboud, Dept Med, Div Gastroenterol & Hepatol, Nijmegen, Netherlands. RI Drenth, J.P.H./H-8025-2014; te Morsche, Rene/P-9143-2015; OI Bonifacino, Juan S./0000-0002-5673-6370 NR 13 TC 113 Z9 120 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2003 VL 33 IS 3 BP 345 EP 347 DI 10.1038/ng1104 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 651GT UT WOS:000181312700010 PM 12577059 ER PT J AU Bruniquel, D Schwartz, RH AF Bruniquel, D Schwartz, RH TI Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process SO NATURE IMMUNOLOGY LA English DT Article ID 5-METHYLCYTOSINE DNA GLYCOSYLASE; GAMMA PROMOTER DEMETHYLATION; T-CELL DIFFERENTIATION; IN-VIVO; HISTONE ACETYLATION; CYCLE PROGRESSION; IL-2 GENE; IFN-GAMMA; EXPRESSION; METHYLATION AB A role for DNA demethylation in transcriptional regulation of genes expressed in differentiated somatic cells remains controversial. Here, we define a small region in the promoter-enhancer of the interleukin-2 (II2) gene that demethylates in T lymphocytes following activation, and remains demethylated thereafter. This epigenetic change was necessary and sufficient to enhance transcription in reporter plasmids. The demethylation process started as early as 20 minutes after stimulation and was not prevented by a G1 to S phase cell cycle inhibitor that blocks DNA replication. These results imply that this demethylation process proceeds by an active enzymatic mechanism. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 47 TC 312 Z9 325 U1 1 U2 9 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2003 VL 4 IS 3 BP 235 EP 240 DI 10.1039/ni887 PG 6 WC Immunology SC Immunology GA 649HH UT WOS:000181201000011 PM 12548284 ER PT J AU Stefanova, I Hemmer, B Vergelli, M Martin, R Biddison, WE Germain, RN AF Stefanova, I Hemmer, B Vergelli, M Martin, R Biddison, WE Germain, RN TI TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways SO NATURE IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; PROTEIN-TYROSINE-PHOSPHATASE; ALTERED PEPTIDE LIGANDS; N-TERMINAL REGION; ANTIGEN RECEPTOR; CUTTING EDGE; ZETA-PHOSPHORYLATION; LINEAGE COMMITMENT; PARTIAL AGONISTS; KINASE P56(LCK) AB Functional discrimination between structurally similar self and foreign antigens is a main attribute of adaptive immunity. Here we describe two feedback mechanisms in T lymphocytes that together sharpen and amplify initial signaling differences related to the quality of T cell receptor (TCR) engagement. Weakly binding ligands predominantly trigger a negative feedback loop leading to rapid recruitment of the tyrosine phosphatase SHP-1, followed by receptor desensitization through inactivation of Lck kinase. In contrast, strongly binding ligands efficiently activate a positive feedback circuit involving Lck modification by ERK, preventing SHP-1 recruitment and allowing the long-lasting signaling necessary for gene activation. The characteristics of these pathways suggest that they constitute an important part of the mechanism allowing T cells to discriminate between self and foreign ligands. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Mol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, 10 Ctr Dr,MSC-1892, Bethesda, MD 20892 USA. NR 60 TC 280 Z9 286 U1 4 U2 14 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2003 VL 4 IS 3 BP 248 EP 254 DI 10.1038/ni895 PG 7 WC Immunology SC Immunology GA 649HH UT WOS:000181201000013 PM 12577055 ER PT J AU Grimbacher, B Hutloff, A Schlesier, M Glocker, E Warnatz, K Drager, R Eibel, H Fischer, B Schaffer, AA Mages, HW Kroczek, RA Peter, HH AF Grimbacher, B Hutloff, A Schlesier, M Glocker, E Warnatz, K Drager, R Eibel, H Fischer, B Schaffer, AA Mages, HW Kroczek, RA Peter, HH TI Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency SO NATURE IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; B-CELLS; IGA DEFICIENCY; INDUCIBLE COSTIMULATOR; GERMINAL CENTER; BONE-MARROW; CD40 LIGAND; MEMORY; DIFFERENTIATION; ACTIVATION AB No genetic defect is known to cause common variable immunodeficiency (CVID), a heterogeneous human disorder leading to adult-onset panhypogammaglobulinemia. In a search for CVID candidate proteins, we found four of 32 patients to lack ICOS, the "inducible costimulator" on activated T cells, due to an inherited homozygous deletion in the ICOS gene. T cells from these individuals were normal with regard to subset distribution, activation, cytokine production and proliferation. In contrast, naive, switched and memory B cells were reduced. The phenotype of human ICOS deficiency, which differs in key aspects from that of the ICOS-/- mouse, suggests a critical involvement of ICOS in T cell help for late B cell differentiation, class-switching and memory B cell generation. C1 Univ Freiburg, Sch Med, Div Clin Immunol & Rheumatol, D-79106 Freiburg, Germany. Robert Koch Inst, D-13353 Berlin, Germany. Univ Hosp Freiburg, Clin Res Unit Rheumatol, D-79106 Freiburg, Germany. NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. RP Peter, HH (reprint author), Univ Freiburg, Sch Med, Div Clin Immunol & Rheumatol, Hugstetter Str 55, D-79106 Freiburg, Germany. RI Schaffer, Alejandro/F-2902-2012; Hutloff, Andreas/D-1781-2014 OI Hutloff, Andreas/0000-0002-0572-8151 NR 54 TC 413 Z9 429 U1 2 U2 9 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2003 VL 4 IS 3 BP 261 EP 268 DI 10.1038/ni902 PG 8 WC Immunology SC Immunology GA 649HH UT WOS:000181201000015 PM 12577056 ER PT J AU Waldmann, TA AF Waldmann, TA TI Immunotherapy: past, present and future SO NATURE MEDICINE LA English DT Review ID B-CELL LYMPHOMA; COLONY-STIMULATING FACTOR; REGULATORY T-CELLS; MONOCLONAL-ANTIBODY; IN-VIVO; INTERLEUKIN-2 RECEPTOR; RECOMBINANT IMMUNOTOXIN; METASTATIC MELANOMA; ANTITUMOR IMMUNITY; CHEMOTHERAPY PLUS AB Harnessing the immune system to treat chronic infectious diseases or cancer is a major goal of immunotherapy. Among others, impediments to this aim include host failure to identify tumor antigens, tolerance to self and negative immunoregulatory mechanisms. But with recent progress, active and passive immunotherapy are proving themselves as effective therapeutic strategies. C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 70 TC 296 Z9 320 U1 8 U2 56 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2003 VL 9 IS 3 BP 269 EP 277 DI 10.1038/nm0303-269 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 651GN UT WOS:000181312300026 PM 12612576 ER PT J AU Dietrich, A Gollasch, M Chubanov, V Schnitzler, MMY Dubrovska, G Herz, U Renz, H Gudermann, T Birnbaumer, L AF Dietrich, A Gollasch, M Chubanov, V Schnitzler, MMY Dubrovska, G Herz, U Renz, H Gudermann, T Birnbaumer, L TI Studies on TRPC6 deficient mice reveal its non-redundant role in the regulation of smooth muscle tone SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 44th Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und -Toxikologie/20th Gesellschaft-fur-Umwelt-Mutationsforschung CY MAR 17-20, 2003 CL MAINZ, GERMANY SP Deutsch Gesell Exptl & Klin Pharm & Toxikol, Gesell Umwelt-Mutat Forsch C1 Univ Marburg, Inst Pharmakol & Toxikol, D-3550 Marburg, Germany. Univ Marburg, Klin Chem & Mol Diagnost, D-3550 Marburg, Germany. Max Delbruck Centrum, Franz Volhard Klin, Berlin, Germany. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RI Dietrich, Alexander/G-8619-2013 NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2003 VL 367 SU 1 MA 238 BP R63 EP R63 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 670XN UT WOS:000182435500249 ER PT J AU Hesslinger, C Parravicini, V Ziegler, I Hultner, L Rivera, J Pfeilschifter, J AF Hesslinger, C Parravicini, V Ziegler, I Hultner, L Rivera, J Pfeilschifter, J TI Regulation of tetrahydrobiopterin and nitric oxide synthesis during mast cell activation: Implications for allergy and innate immunity SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 44th Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und -Toxikologie/20th Gesellschaft-fur-Umwelt-Mutationsforschung CY MAR 17-20, 2003 CL MAINZ, GERMANY SP Deutsch Gesell Exptl & Klin Pharm & Toxikol, Gesell Umwelt-Mutat Forsch C1 Univ Frankfurt Klinikum, Pharmazentrum Klinikum, D-60590 Frankfurt, Germany. NIAMS, NIH, Bethesda, MD 20892 USA. GSF Forschungszentrum Umwelt & Gesundheit, KMOLBI, D-81377 Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2003 VL 367 SU 1 MA 154 BP R42 EP R42 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 670XN UT WOS:000182435500165 ER PT J AU Yo, Y Braun, MC Barisoni, L Mobaraki, H Lu, HY Shrivastav, S Owens, J Kopp, JB AF Yo, Y Braun, MC Barisoni, L Mobaraki, H Lu, HY Shrivastav, S Owens, J Kopp, JB TI Anti-mouse mesangial cell serum induces acute glomerulonephropathy in mice SO NEPHRON EXPERIMENTAL NEPHROLOGY LA English DT Article DE nephrotoxic serum; apoptosis; cell proliferation ID NEPHROTOXIC NEPHRITIS; PROLIFERATIVE NEPHRITIS; DEFICIENT MICE; ANTI-THY-1 ANTIBODIES; EXPERIMENTAL-MODELS; IMMUNE-COMPLEXES; MASUGI NEPHRITIS; VASCULAR CHANGES; TRANSGENIC MICE; IV COLLAGEN AB In order to develop a model in mouse similar to anti-Thy-1 nephritis in the rat, we prepared sheep antiserum against SV40-transformed mouse mesangial (MES 13) cells. In vivo, the anti-mouse mesangial cell serum-treated mice showed severe azotemia that peaked at day 6 and proteinuria that peaked at day 8, in a dose-dependent fashion. Light microscopy and electron microscopy showed duplication of glomerular basement membranes, mesangiolysis, subendothelial and mesangial electron-dense deposits, and foot process effacement. Intraglomerular tuft cell number was significantly reduced at day 4 and there were increased numbers of apoptotic cells at days 2 and 4. SCID mice and mice lacking C3 manifested similar responses to anti-mouse mesangial cell serum, suggesting that T cells, B cells and complement are not required for glomerular injury in this model. In vitro, anti-mouse mesangial cell serum-treated mesangial cells showed greater release of lactate dehydrogenase, decreased cell survival, and increased apoptotic cell death. Anti-mouse mesangial cell serum induces glomerulopathy characterized by mesangiolysis and mesangial cell apoptosis, and followed by cellular proliferation. C1 NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. NIAID, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. NIH, Vet Resource Program, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIDDKD, Kidney Dis Sect, NIH, Bldg 10,Room 3N116,10 Ctr Dr, Bethesda, MD 20892 USA. NR 48 TC 4 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2129 J9 NEPHRON EXP NEPHROL JI Nephron Exp. Nephrol PD MAR PY 2003 VL 93 IS 3 BP 92 EP 106 DI 10.1159/000069551 PG 15 WC Urology & Nephrology SC Urology & Nephrology GA 742UR UT WOS:000186536900002 ER PT J AU Inskip, PD Tarone, RE Hatch, EE Wilcosky, TC Selker, RG Fine, HA Black, PM Loeffler, JS Shapiro, WR Linet, MS AF Inskip, PD Tarone, RE Hatch, EE Wilcosky, TC Selker, RG Fine, HA Black, PM Loeffler, JS Shapiro, WR Linet, MS TI Laterality of brain tumors SO NEUROEPIDEMIOLOGY LA English DT Article DE brain cancer; brain tumors; laterality; glioma; meningioma; acoustic neuroma; epidemiology ID CELLULAR-TELEPHONE USE; WHITE-MATTER; CANCER; RISK; HISTOPATHOLOGY; CLASSIFICATION; PERFORMANCE; HEMISPHERE; DIAGNOSIS; GLIOMAS AB Tumor laterality was evaluated with respect to presenting symptoms and demographic factors among 489 adults with histologically confirmed glioma (354 high-grade, 135 low-grade), 197 with meningioma, and 96 with acoustic neuroma. The ratio of left-sided to right-sided tumors did not differ significantly from 1.00 for any of the major tumor types. Low-grade glioma and meningioma occurred nonsignificantly more often on the left side, whereas high-grade glioma and acoustic neuroma occurred nonsignificantly more often on the right side. Aphasia or mental status changes were significantly more common among glioma patients with tumors on the left side than among those with tumors on the right side. Associations between tumor laterality and symptoms may influence the probability or timing of diagnosis, possibly differentially by marital status. Copyright (C) 2003 S. Karger AG, Basel. C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Res Triangle Inst, Epidemiol & Med Studies Program, Res Triangle Pk, NC 27709 USA. Western Penn Hosp, Div Neurosurg, Pittsburgh, PA 15224 USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Radiat Oncol Branch, Boston, MA 02114 USA. St Josephs Hosp, Barrow Neurol Inst, Dept Neurol, Phoenix, AZ USA. RP Inskip, PD (reprint author), Execut Plaza S,Room 7052, Bethesda, MD 20892 USA. EM inskippe@mail.nih.gov OI Hatch, Elizabeth/0000-0001-7901-3928 FU NCI NIH HHS [N01-CP-15679-01] NR 39 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PD MAR-APR PY 2003 VL 22 IS 2 BP 130 EP 138 DI 10.1159/000068747 PG 9 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 657ZC UT WOS:000181695400006 PM 12629279 ER PT J AU Hole, WT Srinivasan, S AF Hole, WT Srinivasan, S TI Adding NeuroNames to the UMLS metathesaurus SO NEUROINFORMATICS LA English DT Editorial Material C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Hole, WT (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PD SPR PY 2003 VL 1 IS 1 BP 61 EP 63 DI 10.1385/NI:1:1:061 PG 3 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 735CL UT WOS:000186094800004 PM 15055393 ER PT J AU Dalakas, MC Dagvadorj, A Goudeau, B Park, KY Takeda, K Simon-Casteras, M Vasconcelos, O Sambuughin, N Shatunov, A Nagle, JW Sivakumar, K Vicart, P Goldfarb, LG AF Dalakas, MC Dagvadorj, A Goudeau, B Park, KY Takeda, K Simon-Casteras, M Vasconcelos, O Sambuughin, N Shatunov, A Nagle, JW Sivakumar, K Vicart, P Goldfarb, LG TI Progressive skeletal myopathy, a phenotypic variant of desmin myopathy associated with desmin mutations SO NEUROMUSCULAR DISORDERS LA English DT Article DE desmin related myopathy; desminopathy; myofibrillar myopathy; distal myopathy; cardiomyopathy; desmin gene mutation ID DOMINANT DISTAL MYOPATHY; INTERMEDIATE FILAMENTS; MYOFIBRILLAR MYOPATHY; MISSENSE MUTATION; GENE; CARDIOMYOPATHY; MUTAGENESIS; PROTEINS; DISEASE; DOMAIN AB Desmin myopathy is a familial or sporadic disorder characterized by the presence of desmin mutations that cause skeletal muscle weakness associated with cardiac conduction block, arrhythmia and heart failure. Distinctive histopathologic features include intracytoplasmic accumulation of desmin-reactive deposits and electron-dense granular aggregates in skeletal and cardiac muscle cells. We describe two families with features of adult-onset slowly progressive skeletal myopathy without cardiomyopathy. N342D point mutation was present in the desmin helical rod domain in patients of family 1, and 1451M mutation was found in the non-helical tail domain in patients of family 2. Of interest, the same 1451M mutation has previously been reported in patients with cardiomyopathy and no signs of skeletal myopathy. Some carriers of the 1451M mutation did not develop any disease, suggesting incomplete penetrance. Expression studies demonstrated inability of the N342D mutant desmin to form cellular filamentous network, confirming the pathogenic role of this mutation, but the network was not affected by the tail-domain 1451M mutation. Progressive skeletal myopathy is a rare phenotypic variant of desmin myopathy allelic to the more frequent cardio-skeletal form. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NINDS, NIH, Bethesda, MD 20892 USA. Univ Paris 06, F-75013 Paris, France. NHLBI, NIH, Bethesda, MD 20892 USA. Barrow Neurol Inst, Phoenix, AZ 85013 USA. RP Goldfarb, LG (reprint author), NINDS, NIH, Bldg 10,Room 4B37,10 Cent Dr,MSC 1361, Bethesda, MD 20892 USA. EM goldfarbl@ninds.nih.gov RI Shatunov, Aleksey/E-6946-2011 NR 30 TC 37 Z9 39 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD MAR PY 2003 VL 13 IS 3 BP 252 EP 258 DI 10.1016/S0960-8966(02)00271-7 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 658XQ UT WOS:000181746700007 PM 12609507 ER PT J AU Kroeze, WK Hufeisen, SJ Popadak, BA Renock, S Steinberg, SA Ernsberger, P Jayathilake, K Meltzer, HY Roth, BL AF Kroeze, WK Hufeisen, SJ Popadak, BA Renock, S Steinberg, SA Ernsberger, P Jayathilake, K Meltzer, HY Roth, BL TI HI-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE atypical antipsychotic drugs; clozapine; weight gain; H-1-histamine receptors ID INVERSE AGONIST; SEROTONIN RECEPTORS; CLINICAL POTENCY; MICE LACKING; UCP FAMILY; CLOZAPINE; DOPAMINE; SCHIZOPHRENIA; H-1-RECEPTOR; BINDING AB As a result of superior efficacy and overall tolerability, atypical antipsychotic drugs have become the treatment of choice for schizophrenia and related disorders, despite their side effects. Weight gain is a common and potentially serious complication of some antipsychotic drug therapy, and may be accompanied by hyperlipidemia, hypertension and hyperglycemia and, in some extreme cases, diabetic ketoacidosis. The molecular mechanism(s) responsible for antipsychotic drug-induced weight gain are unknown, but have been hypothesized to be because of interactions of antipsychotic drugs with several neurotransmitter receptors, including 5-HT2A and 5-HT2C serotonin receptors, H-1-histamine receptors, alpha(1) - and alpha(2)-adrenergic receptors, and m3-muscarinic receptors. To determine the receptor(s) likely to be responsible for antipsychotic-drug-induced weight gain, we screened 17 typical and atypical antipsychotic drugs for binding to 12 neurotransmitter receptors. H-1-histamine receptor affinities for this group of typical and atypical antipsychotic drugs were significantly correlated with weight gain (Spearman rho=-0.72; p<0.01), as were affinities for alpha(1A) adrenergic (rho=-0.54; p<0.05), S-HT2C (rho=-0.49; p<0.05) and 5-HT6 receptors (rho=-0.54; p<0.05), whereas eight other receptors' affinities were not. A principal components analysis showed that affinities at the H-1, alpha(2A), alpha(2B), 5-HT2A, 5-HT2C, and 5-HT6 receptors were most highly correlated with the first principal component, and affinities for the D-2, 5-HT1A, and 5-HT7 receptors were most highly correlated with the second principal component. A discriminant functions analysis showed that affinities for the H-1 and alpha(1A) receptors were most highly correlated with the discriminant function axis. The discriminant function analysis, as well as the affinity for the H-1-histamine receptor alone, correctly classified 15 of the 17 drugs into two groups; those that induce weight gain and those that do not. Because centrally acting H-1-histamine receptor antagonists are known to induce weight gain with chronic use, and because H-1-histamine receptor affinities are positively correlated with weight gain among typical and atypical antipsychotic drugs, it is recommended that the next generation of atypical antipsychotic drugs be screened to avoid H-1-histamine receptors. C1 Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Psychoact Drug Screening Program, NIMH, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. RP Kroeze, WK (reprint author), Case Western Reserve Univ, Sch Med, Dept Biochem, RM W463,10900 Euclid Ave, Cleveland, OH 44106 USA. RI Roth, Bryan/F-3928-2010; Ernsberger, Paul/O-2702-2014; Meltzer, Herbert/E-8131-2013 OI Ernsberger, Paul/0000-0003-2372-2500; FU NIMH NIH HHS [K02MH01366, N02MH80005] NR 41 TC 440 Z9 453 U1 0 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2003 VL 28 IS 3 BP 519 EP 526 DI 10.1038/sj.npp.1300027 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 662UY UT WOS:000181968300010 PM 12629531 ER PT J AU Herning, RI Better, WE Tate, K Umbricht, A Preston, KL Cadet, JL AF Herning, RI Better, WE Tate, K Umbricht, A Preston, KL Cadet, JL TI Methadone treatment induces attenuation of cerebrovascular deficits associated with the prolonged abuse of cocaine and heroin SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE heroin; cocaine; methadone; cerebral perfusion; cerebrovascular resistance; polysubstance abuse ID CEREBRAL BLOOD-FLOW; TRANSCRANIAL DOPPLER SONOGRAPHY; TECHNETIUM-99M-HMPAO SPECT; MULTIINFARCT DEMENTIA; DEPENDENT PATIENTS; WITHDRAWAL; PULSATILITY; PERFUSION; BUPRENORPHINE; PERFORMANCE AB Opiate replacement therapy has been useful in reducing heroin use and in keeping patients in treatment programs. However, neuropsychological and neurophysiological effects of this treatment regimen have not been evaluated systematically. To determine whether methadone treatment reduces the magnitude of cerebral blood flow alternations in polysubstance (heroin and cocaine) abusers, we compared blood flow parameters in control subjects (n = 26), polysubstance abusers (n = 28) maintained on methadone for 24 weeks, and polysubstance abusers (n = 22) who. were not seeking treatment. Blood flow velocity was recorded from the anterior and middle cerebral arteries using transcranial Doppler sonography on an outpatient visit. The pulsatility index, a measure of cerebrovascular resistance, was significantly (p<0.05) increased in both groups of polysubstance abusers compared to control subjects. Increased pulsatility in the two groups of substance abusers suggests constriction of the small cortical arteries. Nevertheless, the methadone-maintained polysubstance abusers had significantly lower pulsatility values than the nontreatment substance-abusing group. These findings suggest that maintenance on methadone might have significant beneficial neurovascular effects on this population of patients. C1 NIDA, Mol Neuropsychiat Sect, IRP, NIH, Baltimore, MD 21224 USA. NIDA, Treatment Sect, NIH, Baltimore, MD 21224 USA. RP Herning, RI (reprint author), NIDA, Mol Neuropsychiat Sect, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 41 TC 5 Z9 5 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2003 VL 28 IS 3 BP 562 EP 568 DI 10.1038/sj.npp.1300073 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 662UY UT WOS:000181968300017 PM 12629538 ER PT J AU Wittenberg, GF Chen, R Ishii, K Bushara, KO Taub, E Gerber, LH Hallett, M Cohen, LG AF Wittenberg, GF Chen, R Ishii, K Bushara, KO Taub, E Gerber, LH Hallett, M Cohen, LG TI Constraint-induced therapy in stroke: Magnetic-stimulation motor maps and cerebral activation SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE positron emission tomography; transcranial magnetic stimulation; cerebral infarction; subcortical; clinical trial ID INDUCED MOVEMENT THERAPY; UPPER EXTREMITY; CORTICAL REORGANIZATION; ISCHEMIC-STROKE; LEARNED NONUSE; FORCED USE; CORTEX; RECOVERY; PERFORMANCE; INFARCTION AB Constraint-induced movement therapy (CI), a standardized intensive rehabilitation intervention, was given to patients a year or more following stroke. The goal was to determine if CI was more \ effective than a less-intensive control intervention in changing motor function and/or brain physiology and to gain insight into the mechanisms underlying this recovery process. Subjects were recruited and randomized more than 1 Year after a single subcortical infarction. Clinical assessments performed before and after the intervention and at 6 months postintervention included the Wolf Motor Function Test (WMFT), the Motor Activily Log (MAI), and the Assessment of Motor and Process Skills (AMPS). Transcranial magnetic stimulation was used to map the motor cortex. Positron emission tomography was used to measure changes in motor task-related activation due to the intervention. MAI. increased by 1.08 after CI therapy and decreased by 0.01 qfter control therapy. The difference between groups was significant (P < 0.001). Changes in WMFT and AMPS were not sign ficantl different between groups. Cerebral activation during a motor task decreased significantly, and motor map size increased in the affected hemisphere motor cortex in CI patients but not in control patients.Both changes may reflect neurons to produce movement. C1 NINDS, HCPS, NIH, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Rehabil Med, Bethesda, MD 20892 USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. RP Cohen, LG (reprint author), NINDS, HCPS, NIH, 9000 Rockville Pike,Bldg 10,Rm 5N226, Bethesda, MD 20892 USA. EM cohenl@ninds.nih.gov RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 35 TC 191 Z9 204 U1 3 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD MAR PY 2003 VL 17 IS 1 BP 48 EP 57 DI 10.1177/0888439002250456 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 846WH UT WOS:000223349400006 PM 12645445 ER PT J AU Wang, J Chen, GQ Lu, B Wu, CP AF Wang, J Chen, GQ Lu, B Wu, CP TI GDNF acutely potentiates Ca2+ channels and excitatory synaptic transmission in midbrain dopaminergic neurons SO NEUROSIGNALS LA English DT Article DE neurotrophic factors; voltage-gated calcium channels; calcium imaging; neuronal culture; substantia nigra ID NEUROTROPHIC FACTOR GDNF; NIGRA PARS COMPACTA; MICE LACKING GDNF; IN-VIVO; NONDOPAMINERGIC NEURONS; SUBSTANTIA-NIGRA; NERVOUS-SYSTEM; NEUROMUSCULAR-JUNCTIONS; RECEPTOR SUBUNITS; RAT AB Glial cell line-derived neurotrophic factor (GDNF) is best known for its long-term survival effect on dopaminergic neurons in the ventral midbrain. A recent study showed that acute application of GDNF to these neurons suppresses A-type potassium channels and potentiates neuronal excitability. Here we have characterized the acute effects of GDNF on Ca2+ channels and synaptic transmission. GDNF rapidly and reversibly potentiated the high voltage-activated (HVA) Ca2+ channel currents in cultured dopaminergic neurons. Analyses of channel kinetics indicate that GDNF decreased the activation time constant, increased the inactivation and deactivation time constants of HVA Ca2+ channel currents. Ca2+ imaging experiments demonstrate that GDNF facilitated Ca2+ influx induced by membrane depolarization. To investigate the physiological consequences of the Ca2+ channel modulation, we examined the acute effects of GDNF on excitatory synaptic transmission at synapses made by these dopaminergic neurons, which co-release the transmitter glutamate. Within 3 min of application, GDNF increased the amplitude of spontaneous and evoked excitatory autaptic- or multiple-postsynaptic currents. The frequency as well as the amplitude of miniature excitatory postsynaptic currents was also increased. These results reveal, for the first time, an acute effect of GDNF on synaptic transmission and its potential mechanisms, and suggest that an important function of GDNF for midbrain dopaminergic neurons is the acute modulation of transmission and ion channels. Copyright (C) 2003 S. Karger AG, Basel. C1 Chinese Acad Sci, Inst Neurosci, Shanghai, Peoples R China. NICHD, Unit Synapse Dev & Plast, NIH, Bethesda, MD USA. RP Wang, J (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 115 Life Sci Addit, Berkeley, CA 94720 USA. RI Lu, Bai/A-4018-2012; Wang, Jun/N-8472-2015; Wang, Jun/M-2337-2016 OI Wang, Jun/0000-0002-0085-4722; Wang, Jun/0000-0002-0085-4722 NR 46 TC 23 Z9 25 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-862X J9 NEUROSIGNALS JI Neurosignals PD MAR-APR PY 2003 VL 12 IS 2 BP 78 EP 88 DI 10.1159/000071817 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology; Neurosciences SC Biochemistry & Molecular Biology; Biophysics; Cell Biology; Neurosciences & Neurology GA 707EU UT WOS:000184497100004 PM 12876402 ER PT J AU Harry, GJ AF Harry, GJ TI Emerging technologies in neurotoxicology SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 NIEHS, Neurotoxicol Grp, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAR PY 2003 VL 24 IS 2 MA 7 BP 288 EP 288 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000018 ER PT J AU Olden, K AF Olden, K TI The NIEHS Collaborative Centers for Parkinson's disease research program - An innovative approach SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAR PY 2003 VL 24 IS 2 MA 19 BP 293 EP 293 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000030 ER PT J AU d'Hellencourt, CL Harry, GJ AF d'Hellencourt, CL Harry, GJ TI Differential gene expression in laser captured hippocampal pyramidal and dentate granule cells in chemically-induced neurodegeneration SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 20th International Neurotoxicology Conference on Emerging Issues in Neurotoxicology CY NOV 18-21, 2002 CL LITTLE ROCK, ARKANSAS C1 NIEHS, Neurotoxicol Grp, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAR PY 2003 VL 24 IS 2 MA 58 BP 308 EP 308 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 654RZ UT WOS:000181511000067 ER PT J AU Weinberger, DR AF Weinberger, DR TI Towards a genetic architecture of schizophrenia SO NORDIC JOURNAL OF PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0803-9488 J9 NORD J PSYCHIAT JI Nord. J. Psychiatr. PD MAR PY 2003 VL 57 IS 2 BP 92 EP 93 PG 2 WC Psychiatry SC Psychiatry GA 678UV UT WOS:000182885600037 ER PT J AU Wegienka, G Baird, DD Hertz-Picciotto, I Harlow, SD Steege, JF Hill, MC Schectman, JM Hartmann, KE AF Wegienka, G Baird, DD Hertz-Picciotto, I Harlow, SD Steege, JF Hill, MC Schectman, JM Hartmann, KE TI Self-reported heavy bleeding associated with uterine leiomyomata SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID TRANSVAGINAL ULTRASONOGRAPHY; SUBMUCOUS MYOMAS; UNITED-STATES; HYSTERECTOMY; DIAGNOSIS; SONOHYSTEROGRAPHY; HYSTEROSCOPY; SONOGRAPHY; ACCURACY AB OBJECTIVE: To characterize the relationship between self-reported bleeding symptoms and uterine leiomyoma size and location. METHODS: The leiomyoma status of a randomly selected sample of women aged 35-49 in the Washington, DC, area was determined using abdominal and transvaginal ultrasound to measure size and location of leiomyomata found at screening. Women were asked about symptoms of heavy bleeding (gushing-type bleeding, long menses, pad/tampon use) in a telephone interview. Using multivariable regression, we examined the relationships between leiomyoma characteristics and heavy bleeding symptoms among 910 premenopausal women. RESULTS: Women with leiomyomata (n = 596) were more likely to report gushing-type bleeding than women without leiomyomata; risk increased with leiomyoma size. Adjusted relative risks with 95% confidence intervals (Cl) for women in each leiomyoma size category compared with the reference category (women without leiomyomata) were as follows: adjusted relative risk of 1.4 (95% CI 1.1, 1.9) for diffuse only, adjusted relative risk of 1.4 (95% CI 1.1, 1.8) for small leiomyomata (less than 2 cm), adjusted relative risk of 1.6 (95% CI 1.3,2.0) for medium leiomyomata (2-5 cm), and adjusted relative risk of 1.9 (95% Cl 1.5, 2.5) for large leiomyomata (greater than 5 cm). Reported use of eight or more pads/tampons on the heaviest days of menstrual bleeding increased with leiomyoma size, with a nearly 2.5-fold risk for women with large leiomyomata compared with women without leiomyomata (adjusted relative risk of 2.4; 95% CI 1.8, 3.1). Nonsubmucosal leiomyomata were associated with essentially the same increase in heavy bleeding as submuscosal leiomyomata of similar size. CONCLUSION: Small leiomyomata were associated with increased risk of heavy bleeding, and risk increased with size. Contrary to published articles, nonsubmucosal leiomyomata were associated with heavy bleeding to the same extent as submucosal leiomyomata. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ Calif Davis, Dept Epidemiol & Prevent Med, Davis, CA 95616 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. George Washington Univ, Med Ctr, Dept Radiol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Hlth Care Sci, Washington, DC 20037 USA. RP Wegienka, G (reprint author), NIEHS, Epidemiol Branch, Mail Drop A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. OI Baird, Donna/0000-0002-5544-2653 NR 18 TC 87 Z9 90 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 2003 VL 101 IS 3 BP 431 EP 437 DI 10.1016/S0029-7844(02)03121-6 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 652BW UT WOS:000181360500005 PM 12636944 ER PT J AU Duerr, A Heilig, CM Meikle, SF Cu-Uvin, S Klein, RS Rompalo, A Sobel, JD AF Duerr, A Heilig, CM Meikle, SF Cu-Uvin, S Klein, RS Rompalo, A Sobel, JD CA HER Study Grp TI Incident and persistent vulvovaginal candidiasis among human immunodeficiency virus-infected women: Risk factors and severity SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID HIV-SEROPOSITIVE WOMEN; VAGINAL CANDIDIASIS; VULVO-VAGINITIS; COLONIZATION AB OBJECTIVE: To examine risk factors for vulvovaginal candidiasis among women with or at risk for human immunodeficiency virus (HIV) infection. METHODS: Data were from 856 HIV-infected women and 421 at-risk uninfected women observed semiannually at four study sites from April 1993 through February 1999. At enrollment women were 15-55 years old and had no acquired immunodeficiency syndrome-defining conditions. Three definitions for vulvovaginal candidiasis of differing severity were constructed using data from vaginal Candida culture and Gram stains scored for yeast and three signs on pelvic examination (vulvovaginal edema, erythema, or discharge): 1) culture or Gram stain positivity plus at least one clinical sign, 2) culture or Gram stain positivity plus at least two clinical signs, and 3) visible yeast on Gram stain plus at least one clinical sign. RESULTS: The prevalence and cumulative incidence of each definition of vulvovaginal candidiasis were greater among HIV-infected women than among women not infected with HIV (P < .01 for all comparisons). Stratified by status at the preceding visit, vulvovaginal candidiasis was most likely among women with prior vulvovaginal candidiasis, least likely among women without earlier Candida colonization, and intermediately likely among women with preceding subclinical Candida colonization. Among HIV-infected women, lower CD4 count and higher HIV viral load were associated with vulvovaginal candidiasis. Several other factors were independently associated with vulvovaginal candidiasis, with strong associations for diabetes mellitus and pregnancy in particular. Vulvovaginal candidiasis was not more severe among HIV-infected women. CONCLUSION: Vulvovaginal candidiasis occurred with higher incidence and greater persistence, but not greater severity, among HIV-infected women. C1 Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, HIV Sect, Atlanta, GA 30341 USA. NICHHD, Bethesda, MD 20892 USA. Brown Univ, Providence, RI 02912 USA. Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. Johns Hopkins Univ, Baltimore, MD USA. Wayne State Univ, Detroit, MI USA. RP Duerr, A (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, HIV Sect, Mailstop K-34,4770 Buford Highway NE, Atlanta, GA 30341 USA. RI Heilig, Charles/C-2753-2008 OI Heilig, Charles/0000-0003-1075-1310 FU ODCDC CDC HHS [U64/CCU 506831, U64/CCU 306802, U64/CCU 206798, U64/CCU 106975] NR 18 TC 23 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 2003 VL 101 IS 3 BP 548 EP 556 DI 10.1016/S0029-7844(02)02729-1 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 652BW UT WOS:000181360500022 PM 12636961 ER PT J AU Cox, TA AF Cox, TA TI The role of unilateral temporal artery biopsy - Discussion SO OPHTHALMOLOGY LA English DT Editorial Material C1 NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. RP Cox, TA (reprint author), NIH, 31 Ctr Dr,MSC 2510,Bldg 31,Room 6A52, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 2003 VL 110 IS 3 BP 548 EP 548 DI 10.1016/S0161-6420(02)01759-1 PG 1 WC Ophthalmology SC Ophthalmology GA 649XK UT WOS:000181233100026 ER PT J AU Hiller, R Sperduto, RD Reed, GF D'Agostino, RB Wilson, PWF AF Hiller, R Sperduto, RD Reed, GF D'Agostino, RB Wilson, PWF TI Serum lipids and age-related lens opacities: A longitudinal investigation - The Framingham studies SO OPHTHALMOLOGY LA English DT Article ID BEAVER DAM EYE; DENSITY-LIPOPROTEIN CHOLESTEROL; DISEASE RISK-FACTORS; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; CIGARETTE-SMOKING; HEALTH OUTCOMES; CATARACT; POPULATION; HYPERTRIGLYCERIDEMIA AB Objective: To investigate Whether serum lipid/lipoprotein levels are independent risk factors for nuclear, cortical, or posterior subcapsular (PSC) cataracts. Design: Case-control study nested in a cohort study. Participants and Methods: Eye examinations were conducted on surviving members of the Framingham Offspring Heart Study cohort from 1989 to 1991 (Framingham Offspring Eye Study) to determine cataract case-control status. Data from the Framingham Offspring Heart Study, including fasting serum total cholesterol, high-density lipoprotein cholesterol, and triglyceride measurements collected first in 1971, again approximately 8 years later, and approximately every 4 years thereafter were used to examine associations between lipid levels (mean levels across examinations and slope of measurements over time) and the presence of specific cataract types. The multistage analyses included 1869 persons aged 45 years and older. Main Outcome Measures: A standardized grading system was used to grade cortical, nuclear, and PSC cataracts. Results: The median age of participants was 55 years; 49% were males. In multivariable logistic regression models adjusted for potential confounders, fasting hypertriglyceridemia (greater than or equal to 250 mg/dl) was associated with an increased risk of PSC cataract in men (P = 0.02). High-density lipoprotein cholesterol levels less than or equal to 35 mg/dl were associated with PSC cataract in men at a borderline level of significance (P = 0.09). No associations were noted between serum lipid/lipoprotein variables and risk of cortical or nuclear cataract. Conclusions: These findings suggest that hypertriglyceridemia, a potentially modifiable factor, is associated with the development of PSC cataract in men. C1 NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Sch Med, Endocrinol Sect, Boston, MA 02118 USA. RP Hiller, R (reprint author), NEI, Div Epidemiol & Clin Res, Bldg 31,Room 6A52,31 Ctr Dr, Bethesda, MD 20892 USA. FU NEI NIH HHS [N01 EY 92109]; NHLBI NIH HHS [N01 HC 38038] NR 39 TC 23 Z9 25 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 2003 VL 110 IS 3 BP 578 EP 583 DI 10.1016/S0161-6420(02)01762- PG 6 WC Ophthalmology SC Ophthalmology GA 649XK UT WOS:000181233100032 PM 12623825 ER PT J AU Park, JK Orvisky, E Tayebi, N Kaneski, C Lamarca, ME Stubblefield, BK Martin, BM Schiffmann, R Sidransky, E AF Park, JK Orvisky, E Tayebi, N Kaneski, C Lamarca, ME Stubblefield, BK Martin, BM Schiffmann, R Sidransky, E TI Myoclonic epilepsy in Gaucher disease: genotype-phenotype insights from a rare patient subgroup SO PEDIATRIC RESEARCH LA English DT Article ID ACID BETA-GLUCOSIDASE; SOMATOSENSORY-EVOKED-POTENTIALS; HUMAN GLUCOCEREBROSIDASE GENE; GRADIENT GEL-ELECTROPHORESIS; UNIQUE GENOTYPE; MUTATIONS; IDENTIFICATION; TYPE-1; ALLELES; ADULT AB Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, presents with a wide spectrum of manifestations. Although Gaucher disease has been divided into three clinical types, patients with atypical presentations continue to be recognized. A careful phenotypic and genotypic assessment of patients with unusual symptoms may help define factors that modify phenotype in this disorder. One such example is a rare subgroup of patients with type 3 Gaucher disease who develop progressive myoclonic epilepsy. We evaluated 16 patients with myoclonic epilepsy, nine of whom were diagnosed by age 4 y with severe visceral involvement and myoclonus, and seven with a more chronic course, who were studied between ages 22 and 40. All of the patients had abnormal horizontal saccadic eye movements. Fourteen different genotypes were encountered, yet there were several shared alleles, including V394L (seen on two alleles), G377S (seen on three alleles), and L444P, N188S, and recombinant alleles (each found on four alleles). V394L, G377S, and N188S are mutations that have previously been associated with non-neuronopathic Gaucher disease. The spectrum of genotypes differed significantly from other patients with type 3 Gaucher disease, where genotypes L444P/L444P and R463C/null allele predominated. Northern blot studies revealed a normal glucocerebrosidase transcript, whereas Western studies showed that the patients studied lacked the processed 56 kD isoform of the enzyme, consistent with neuronopathic Gaucher disease. Brain autopsy samples from two patients demonstrated elevated levels of glucosylsphingosine, a toxic glycolipid, which could contribute to the development of myoclonus. Thus, although there were certain shared mutant alleles found in these patients, both the lack of a shared genotype and the variability in clinical presentations suggest that other modifiers must contribute to this rare phenotype. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), Sect Mol Neurogenet, 49 Convent Dr,MSC 4405,49-B1EE16, Bethesda, MD 20892 USA. OI Kaneski, Christine/0000-0003-1453-2502 NR 71 TC 43 Z9 47 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAR PY 2003 VL 53 IS 3 BP 387 EP 395 DI 10.1203/01.PDR.0000049515.79882.94 PG 9 WC Pediatrics SC Pediatrics GA 648GY UT WOS:000181143200005 PM 12595585 ER PT J AU Vernacchio, L Corwin, MJ Lesko, SM Vezina, RM Hunt, CE Hoffman, HJ Willinger, M Mitchell, AA AF Vernacchio, L Corwin, MJ Lesko, SM Vezina, RM Hunt, CE Hoffman, HJ Willinger, M Mitchell, AA TI Sleep position of low birth weight infants SO PEDIATRICS LA English DT Article DE sudden infant death syndrome; low birth weight; sleep ID DEATH-SYNDROME; UNITED-STATES; AGE AB Objectives. To describe sleep positions among low birth weight infants, variations in sleep position according to birth weight, and changes in sleep position over time. To analyze risk factors and influences associated with prone sleep. Design. Prospective cohort study. Setting. Massachusetts and Ohio, 1995-1998. Study Participants. Mothers of 907 low birth weight infants. Results. At 1, 3, and 6 months after hospital discharge, the prevalence of prone sleeping was 15.5%, 26.8%, and 28.3%, respectively. The corresponding rates for supine sleeping were 23.8%, 37.9%, and 50.2% and for side sleeping were 57.3%, 32.4%, and 20.6%. Very low birth weight (VLBW) infants (<1500 g) were most likely to be placed in the prone position. From 1995 through 1998, prone sleeping 1 month after hospital discharge declined among all low birth weight infants from 19.9% to 11.4%; among VLBW infants, the decline in prone sleeping was replaced almost entirely by an increase in side sleeping, whereas in larger low birth weight infants, it was replaced primarily by supine sleeping. Among mothers who placed their infants to sleep in nonprone positions, professional medical advice was cited most frequently as the most influential reason, whereas among mothers of prone-sleeping infants, the infant's preference was cited most frequently. However, mothers of prone-sleeping VLBW infants also frequently cited the influence of medical professionals and nursery practices as most important in the choice of sleeping position. The factors most strongly associated with prone sleeping were single marital status (odds ratio [OR]: 3.0; 95% confidence interval [CI]: 1.5-6.2), black race (OR: 2.6; 95% CI: 1.5-4.5), birth weight <1500 g (OR: 2.4; 95% CI: 1.3-4.3), and multiparity (OR: 2.1, 95% CI: 1.2-3.5). Conclusions. Prone sleep decreased among low birth weight infants from 1995 to 1998. However, VLBW infants, who are at very high risk for sudden infant death syndrome, are more likely to sleep prone than larger low birth weight infants. C1 Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Med Coll Ohio, Dept Pediat, Toledo, OH 43699 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Vernacchio, L (reprint author), Boston Univ, Slone Epidemiol Ctr, 1010 Commonwealth Ave, Boston, MA 02215 USA. OI Vernacchio, Louis/0000-0002-2012-5404 FU NICHD NIH HHS [N01-HD-4-3221] NR 19 TC 27 Z9 27 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2003 VL 111 IS 3 BP 633 EP 640 DI 10.1542/peds.111.3.633 PG 8 WC Pediatrics SC Pediatrics GA 650ZD UT WOS:000181294000046 PM 12612248 ER PT J AU Offit, PA Hackett, CJ AF Offit, PA Hackett, CJ TI Addressing parents' concerns: Do vaccines cause allergic or autoimmune diseases? SO PEDIATRICS LA English DT Article DE vaccines; vaccine safety; asthma; allergies; multiple sclerosis; diabetes; chronic arthritis ID HEPATITIS-B VACCINATION; RESISTANT LYME ARTHRITIS; MYELIN BASIC-PROTEIN; NERVOUS-SYSTEM DEMYELINATION; DEPENDENT DIABETES-MELLITUS; T-CELL RESPONSES; MULTIPLE-SCLEROSIS; INFLUENZA VACCINATION; BORRELIA-BURGDORFERI; THROMBOCYTOPENIC PURPURA AB Anecdotal case reports and uncontrolled observational studies in the medical literature claim that vaccines cause chronic diseases such as asthma, multiple sclerosis, chronic arthritis, and diabetes. Several biological mechanisms have been proposed to explain how vaccines might cause allergic or autoimmune diseases. For example, allergic diseases might be caused by prevention of early childhood infections (the "hygiene hypothesis"), causing a prolongation of immunoglobulin E-promoting T-helper cell type 2-type responses. However, vaccines do not prevent most common childhood infections, and large well-controlled epidemiologic studies do not support the hypothesis that vaccines cause allergies. Autoimmune diseases might occur after immunization because proteins on microbial pathogens are similar to human proteins ("molecular mimicry") and could induce immune responses that damage human cells. However, wild-type viruses and bacteria are much better adapted to growth in humans than vaccines and much more likely to stimulate potentially damaging self-reactive lymphocytes. Consistent with critical differences between natural infection and immunization, well-controlled epidemiologic studies do not support the hypothesis that vaccines cause autoimmunity. Flaws in proposed biological mechanisms that explain how vaccines might cause chronic diseases are consistent with the findings of many well-controlled large epidemiologic studies that fail to show a causal relationship. C1 Univ Penn, Sch Med, Div Infect Dis, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. RP Offit, PA (reprint author), Univ Penn, Sch Med, Div Infect Dis, Childrens Hosp Philadelphia, Abramson Res Bldg,Rm 1202C,34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. OI Hackett, Charles/0000-0003-4586-9669 NR 92 TC 45 Z9 48 U1 1 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2003 VL 111 IS 3 BP 653 EP 659 DI 10.1542/peds.111.3.653 PG 7 WC Pediatrics SC Pediatrics GA 650ZD UT WOS:000181294000048 PM 12612250 ER PT J AU Nelson, KB Bauman, ML AF Nelson, KB Bauman, ML TI Thimerosal and autism? SO PEDIATRICS LA English DT Editorial Material ID SEYCHELLES CHILD-DEVELOPMENT; METHYLMERCURY EXPOSURE; NEURONAL MIGRATION; MINAMATA-DISEASE; BEHAVIOR CHECKLIST; MERCURY TOXICITY; INFANTILE-AUTISM; PINK DISEASE; BRAIN; PREVALENCE C1 NINDS, NEB, NIH, Neuroepidemiol Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Childrens Neurol Serv, Boston, MA 02114 USA. RP Nelson, KB (reprint author), NINDS, NEB, NIH, Neuroepidemiol Branch, Bldg 10,Room 5S221, Bethesda, MD 20892 USA. NR 59 TC 60 Z9 65 U1 3 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2003 VL 111 IS 3 BP 674 EP 679 DI 10.1542/peds.111.3.674 PG 7 WC Pediatrics SC Pediatrics GA 650ZD UT WOS:000181294000053 PM 12612255 ER PT J AU Kies, S Vuong, C Hille, M Peschel, A Meyer, C Gotz, F Otto, M AF Kies, S Vuong, C Hille, M Peschel, A Meyer, C Gotz, F Otto, M TI Control of antimicrobial peptide synthesis by the agr quorum sensing system in Staphylococcus epidermidis: activity of the lantibiotic epidermin is regulated at the level of precursor peptide processing SO PEPTIDES LA English DT Article DE Staphylococcus epidermidis; quorum sensing; lantibiotics; protease AB The accessory gene regulator (agr) quorum sensing system in staphylococci is responsible for the regulation of surface proteins and exoproteins, including many virulence factors in the pathogenic species Staphylococcus aureus and S. epidermidis. Strain S. epidermidis Tu3298 produces the lantibiotic epidermin. An isogenic agr deletion mutant of this strain showed a strong reduction of epidermin production. Detailed analysis of the impact of agr on epidermin biosynthesis revealed that agr does not interfere with the transcription of epidermin biosynthetic genes, but controls the extracellular processing of the N-terminal leader peptide by the EpiP protease. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Univ Tubingen, D-72076 Tubingen, Germany. NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Otto, M (reprint author), Univ Tubingen, Waldhauserstr 70-8, D-72076 Tubingen, Germany. OI Otto, Michael/0000-0002-2222-4115 NR 29 TC 20 Z9 22 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD MAR PY 2003 VL 24 IS 3 BP 329 EP 338 DI 10.1016/S0196-9781(03)00046-9 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 680XV UT WOS:000183006100001 PM 12732329 ER PT J AU Rothman, RB Vu, N Wang, XY Xu, H AF Rothman, RB Vu, N Wang, XY Xu, H TI Endogenous CART peptide regulates mu opioid and serotonin 5-HT2A receptors SO PEPTIDES LA English DT Article DE CART peptide; serotonin receptor; opioid receptor ID ANTI-OPIATE PEPTIDES; BINDING-SITES; ALPHA(2)-ADRENOCEPTOR SUBTYPES; TRANSCRIPT CART; FOOD-INTAKE; HUMAN BRAIN; COCAINE; MORPHINE; MEMBRANES; RATS AB Previous experiments conducted in this laboratory showed that intracerebroventricular (i.c.v.) administration of IgG antibodies directed against selected neuropeptides changed the density of CNS receptors, suggesting that neuropeptides in the cerebrospinal fluid can perform a regulatory role. To further test this hypothesis, we administered anti-CART peptide (the peptide product of cocaine amphetamine related transcript) IgG to rats via the i.c.v. route, and measured the density of opioid mu and delta receptors, beta-adrenergic and alpha(2)-adrenergic receptors and serotonin 5-HT2A receptors using ligand binding methods. We also used Western blots to determine the expression level of the mu, delta and 5-HT2A receptors. The results demonstrated that anti-CART peptide IgG up-regulates mu and 5-HT2A receptor in the hippocampus and caudate We conclude that CART peptides in the cerebrospinal fluid may exert regulatory effects in the brain. (C) 2003 Elsevier Science Inc. All rights reserved. C1 NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 24 TC 9 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD MAR PY 2003 VL 24 IS 3 BP 413 EP 417 DI 10.1016/S0196-9781(03)00056-1 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 680XV UT WOS:000183006100011 PM 12732339 ER PT J AU Oz, M Spivak, CE AF Oz, M Spivak, CE TI Effects of extracellular sodium on mu-opioid receptors coupled to potassium channels coexpressed in Xenopus oocytes SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE flame photometry; GIRK; mu-opioid receptor; sodium effect; voltage clamp; Xenopus oocyte ID G-PROTEIN ACTIVATION; MOLECULAR-PROPERTIES; ADENYLATE-CYCLASE; LINKED RECEPTORS; BRAIN MEMBRANES; DRUG EFFICACY; K+ CHANNELS; RAT-BRAIN; BINDING; AGONIST AB Wild-type or mutant H297N or H297Q of the mu-opioid receptor were co-expressed with the inwardly rectifying potassium channel GIRK1 in oocytes from Xenopus laevis. Under voltage clamp, pairs of concentration response curves were generated using the agonist normorphine in a bathing medium containing 38.5 mM sodium or an identical medium in which the sodium was replaced by an equimolar concentration of choline. The maximum currents were greater in the presence of sodium by about 30% at wild-type receptors and by about 100% at the mutant receptors. The EC50 values tended to increase somewhat as well, though these differences reached statistical significance only for the mutant H297Q. Flame photometry detected no change in the intracellular sodium or potassium concentrations of oocytes, suggesting that the effect of sodium was solely extracellular. Thus sodium, long known for its effects on in vitro ligand binding at mu-opioid receptors, also affects overall transduction as revealed in the Xenopus oocyte model of a complete, living cell system. C1 NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,DH HS, Baltimore, MD 21224 USA. RP Spivak, CE (reprint author), NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,DH HS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Oz, Murat/E-2148-2012 NR 34 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD MAR PY 2003 VL 445 IS 6 BP 716 EP 720 DI 10.1007/s00424-002-1002-y PG 5 WC Physiology SC Physiology GA 666XU UT WOS:000182202400011 PM 12632192 ER PT J AU Yu, AM Idle, JR Byrd, LG Krausz, KW Kupfer, A Gonzalez, FJ AF Yu, AM Idle, JR Byrd, LG Krausz, KW Kupfer, A Gonzalez, FJ TI Regeneration of serotonin from 5-methoxytryptamine by polymorphic human CYP2D6 SO PHARMACOGENETICS LA English DT Article DE CYP2D6; 5-hydroxytryptamine; 5-methoxytryptamine; melatonin ID N-ACETYL-SEROTONIN; GUINEA-PIG ILEUM; PINEAL-GLAND; HUMAN-BRAIN; MESOCRICETUS-AURATUS; MONOAMINE-OXIDASE; MELATONIN; RAT; RECEPTORS; 5-METHOXYINDOLES AB Polymorphic cytochrome P450 2D6 (CYP2D6) is expressed in several types of central neurons but its function in human brain is currently unknown. Using recombinant enzymes and CYP2D6-transgenic mice, we established that 5-methoxytryptamine (5-MT), a metabolite and precursor of melatonin, is a specific and high-turnover endogenous substrate of CYP2D6. This potent serotonergic neuromodulator in numerous physiological systems binds tightly to recombinant CYP2D6 enzyme with an equilibrium dissociation constant (K-s) of 23.4 mumol/l, and is O-demethylated to serotonin (5-hydroxytryptamine, 5-HT) with a high turnover of 51.7 min(-1) and low Michaelis-Menten constant of 19.5 mumol/l. The production of 5-HT from 5-MT catalyzed by CYP2D6 was inhibited by selective serotonin reuptake inhibitors, and their inhibition potency (K-i, mumol/l) decreased in the order of fluoxetine (0.411) > norfluoxetine (1.38) > fluvoxamine (10.1) > citalopram (10.9). Liver microsomes prepared from CYP2D6-transgenic mice showed about 16-fold higher 5-MT O-demethylase activity than that from wild-type mice. After the intravenous co-administration of 5-MT (110 mg/ kg) and pargyline (20 mg/kg), serum 5-HT level was about 3-fold higher in CYP2D6-transgenic mice than wild-type mice. When dosed with alpha,alpha,beta,beta-d(4)-5-MT, alpha,alpha,beta,beta-d(4)-5-HT was detected in CYP2D6 transgenic mouse serum, and its content was much higher than wild-type mouse. alpha,alpha,beta,beta-d(4-)5-HT was not produced in CYP2D6-transgenic mice pretreated with quinidine. The regeneration of 5-HT from 5-MT provides the missing link in the serotonin - melatonin cycle. Up to 10% of the population lacks this enzyme. It is proposed that this common inborn error in 5-MT O-demethylation to serotonin influences a range of neurophysiologic and pathophysiologic events. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Univ Bern, Dept Clin Pharmacol, CH-3010 Bern, Switzerland. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Rm 2A19A, Bethesda, MD 20892 USA. OI Idle, Jeff/0000-0002-6143-1520 NR 53 TC 115 Z9 118 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD MAR PY 2003 VL 13 IS 3 BP 173 EP 181 DI 10.1097/01.fpc.0000054066.98065.7b PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 657BP UT WOS:000181645800007 PM 12618595 ER PT J AU Zhao, HY Pfeiffer, R Gail, MH AF Zhao, HY Pfeiffer, R Gail, MH TI Haplotype analysis in population genetics and association studies SO PHARMACOGENOMICS LA English DT Review DE complex disease; genetic association; haplotype; linkage disequilibrium; population genetics ID SINGLE-NUCLEOTIDE POLYMORPHISMS; COMMON DISEASE GENES; LINKAGE DISEQUILIBRIUM; HUMAN GENOME; MAXIMUM-LIKELIHOOD; SEQUENCE VARIATION; CLADISTIC-ANALYSIS; COMPLEX DISEASES; RECOMBINATION; FREQUENCIES AB Several studies of haplotype structures in the human genome in various populations have been published recently. Such knowledge may provide valuable information on human evolutionary history and lead to the development of more efficient strategies to identify genetic variants that increase susceptibility to human diseases. in this review, we summarize the current understanding of haplotype structure, diversity, and distribution in the human genome, with a focus on statistical issues in using haplotypes for studies of population genetics and evolutionary history, as well as to identify genetic variants underlying complex human traits. C1 Yale Univ, Dept Epidemiol & Publ Hlth, Sch Med, New Haven, CT 06520 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Zhao, HY (reprint author), Yale Univ, Dept Epidemiol & Publ Hlth, Sch Med, New Haven, CT 06520 USA. RI Pfeiffer, Ruth /F-4748-2011 FU NIGMS NIH HHS [GM59507] NR 59 TC 100 Z9 105 U1 1 U2 12 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD MAR PY 2003 VL 4 IS 2 BP 171 EP 178 DI 10.1517/phgs.4.2.171.22636 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 654CB UT WOS:000181475000006 PM 12605551 ER PT J AU Doyle, ME Egan, JM AF Doyle, ME Egan, JM TI Pharmacological agents that directly modulate insulin secretion SO PHARMACOLOGICAL REVIEWS LA English DT Review ID PANCREATIC BETA-CELLS; GLUCAGON-LIKE PEPTIDE-1; K-ATP CHANNELS; PROTEIN-KINASE-A; TYPE-2 DIABETES-MELLITUS; PENTAMIDINE-INDUCED HYPOGLYCEMIA; SOMATOSTATIN RECEPTOR SUBTYPES; ANGIOTENSIN-CONVERTING ENZYME; B-CELLS; GLUCOSE-TOLERANCE AB Blood glucose levels are sensed and controlled by the release of hormones from the islets of Langerhans in the pancreas. The beta-cell, the insulin-secreting cell in the islet, can detect subtle increases in circulating glucose levels and a cascade of molecular events spanning the initial depolarization of the beta-cell membrane culminates in exocytosis and optimal insulin secretion. Here we review these processes in the context of pharmacological agents that have been shown to directly interact with any stage of insulin secretion. Drugs that modulate insulin secretion do so by opening the K-ATP channels, by interacting with cell-surface receptors, by altering second-messenger responses, by disrupting the beta-cell cytoskeletal framework, by influencing the molecular reactions at the stages of transcription and translation of insulin, and/or by perturbing exocytosis of the insulin secrenels are the sulfonylureas, the benzoic acid derivatives, the imidazolines, and the quinolines, which are channel openers, and finally diazoxide, which closes these channels. Methylxanthines also work at the cell membrane level by antagonizing the purinergic receptors and thus increase insulin secretion. Other drugs have effects at multiple levels, such as the calcineurin inhibitors and somatostatin. Some drugs used extensively in research, e.g., colchicine, which is used to study vesicular transport, have no effect at the pharmacological doses used in clinical practice. We also briefly discuss those drugs that have been shown to disrupt beta-cell function in a clinical setting but for which there is scant information on their mechanism of action. C1 NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA. RP Egan, JM (reprint author), NIA, Diabet Sect, NIH, 23,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 300 TC 136 Z9 141 U1 0 U2 11 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD MAR PY 2003 VL 55 IS 1 BP 105 EP 131 DI 10.1124/pr.55.1.7 PG 27 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 651AH UT WOS:000181296900005 PM 12615955 ER PT J AU Horne, MK Figg, WD Arlen, P Gulley, J Parker, C Lakhani, N Parnes, H Dahut, WL AF Horne, MK Figg, WD Arlen, P Gulley, J Parker, C Lakhani, N Parnes, H Dahut, WL TI Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer SO PHARMACOTHERAPY LA English DT Article ID PHASE-II TRIAL; DEEP-VEIN THROMBOSIS; MULTIPLE-MYELOMA; RECEIVING THALIDOMIDE; ANGIOGENESIS; THERAPY; INHIBITOR; CARCINOMA AB Study Objective. To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. Design. Retrospective analysis of a randomized phase II trial. Setting. National Institutes of Health clinical research center. Patients. Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer. Intervention. Each patient received either intravenous docetaxel 30 mg/m(2)/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression. Measurements and Main Results. None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025). Conclusion. The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens. C1 NCI, Mol Pharmacol Sect, Canc Therapeut Branch, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. WG Magnuson Clin Ctr, Dept Lab Med, Serv Hematol, Bethesda, MD USA. NCI, Metastat Prostate Canc Clin, Med Oncol Clin Res Unit, Canc Res Ctr, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Canc Therapeut Branch, Canc Res Ctr,NIH, Bldg 10,Room 5A01,MSC1910,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 21 TC 25 Z9 25 U1 2 U2 2 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAR PY 2003 VL 23 IS 3 BP 315 EP 318 DI 10.1592/phco.23.3.315.32106 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 650JL UT WOS:000181259900007 PM 12627929 ER PT J AU Kholmurodov, KT Altaisky, MV Puzynin, IV Darden, T Filatov, FP AF Kholmurodov, KT Altaisky, MV Puzynin, IV Darden, T Filatov, FP TI Methods of molecular dynamics for simulation of physical and biological processes SO PHYSICS OF PARTICLES AND NUCLEI LA English DT Article ID PARTICLE MESH EWALD; SUPERSATURATED VAPOR NUCLEATION; CAPILLARY CONDENSATION; SLIT PORE; TRANSITION-METALS; SURFACE-DIFFUSION; NUCLEIC-ACIDS; LARGE SYSTEMS; LIQUID WATER; FORCE-FIELD AB A review of the studies in computer simulation of physical and biological systems with the methods of molecular dynamics (MD) is given. Special features of computer simulation of molecular and atomic systems with parallel and vector computations are considered. Computations applying the methods of MD simulation to molecular-level studies of dynamics (including nucleation phenomena) in condensed-matter systems (e.g., clusters, liquids, etc.) are carried out. C1 Joint Inst Nucl Res, Informat Technol Lab, Dubna 141980, Moscow Oblast, Russia. NIEHS, Lab Quantitat & Computat Biol, Res Triangle Pk, NC 27709 USA. Russian Acad Med Sci, Natl Hematol Res Ctr, Lab Bacteriol & Prevent AIDS & Viral Hepatitis, Moscow 125167, Russia. RP Kholmurodov, KT (reprint author), Joint Inst Nucl Res, Informat Technol Lab, Dubna 141980, Moscow Oblast, Russia. RI Altaisky, Mikhail/H-1056-2015 OI Altaisky, Mikhail/0000-0002-0614-0720 NR 100 TC 3 Z9 3 U1 0 U2 1 PU INTERPERIODICA PI BIRMINGHAM PA PO BOX 1831, BIRMINGHAM, AL 35201-1831 USA SN 1063-7796 J9 PHYS PART NUCLEI JI Phys. Part. Nuclei PD MAR-APR PY 2003 VL 34 IS 2 BP 244 EP 263 PG 20 WC Physics, Particles & Fields SC Physics GA 662RE UT WOS:000181961100005 ER PT J AU Klabunde, CN Frame, PS Meadow, A Jones, E Nadel, M Vernon, SW AF Klabunde, CN Frame, PS Meadow, A Jones, E Nadel, M Vernon, SW TI A national survey of primary care physicians' colorectal cancer screening recommendations and practices SO PREVENTIVE MEDICINE LA English DT Article DE colorectal cancer; screening; primary care; health services delivery ID FECAL-OCCULT-BLOOD; RANDOMIZED CONTROLLED TRIAL; FLEXIBLE SIGMOIDOSCOPY; HOSPITAL VOLUME; SURGEON VOLUME; PREVENTION; MORTALITY; POLYPECTOMY; COLONOSCOPY; GUIDELINES AB Background. National data on providers' colorectal cancer (CRC) screening knowledge, attitudes, and practices are sparse. This study assessed primary care physicians' (PCPs') beliefs about the effectiveness of CRC screening, their recommendations for screening, their perceptions of the influence of published guidelines on their CRC screening recommendations, and how they conduct CRC screening in their clinical practices. Methods. A questionnaire was administered to a nationally representative sample of practicing PCPs. Of 1718 eligible physicians, 1235 (72%) responded. Results. Only 2% of PCPs said they did not recommend CRC screening. Over 80% indicated that they most often recommend CRC screening with fecal occult blood testing and/or flexible sigmoidoscopy, although colonoscopy was perceived as the more effective screening modality. Nearly two-thirds of obstetrician/gynecologists and one-fourth of other practitioners reported conducting fecal occult blood testing exclusively by digital rectal exam. Only 29% of PCPs said they perform sigmoidoscopy. Estimated volumes of ordering, performing, or referring for CRC screening were low, and <20% reported that three-fourths or more of their older patients were up to date with CRC screening as recommended by the physician. Many PCPs reported recommending CRC screening at nonstandard starting ages or too-frequent intervals. Conclusions. Awareness of CRC screening among PCPs in the United States is high. However, knowledge gaps about the timing and frequency of screening and suboptimal screening delivery were evident. (C) 2003 American Health Foundation and Elsevier Science (USA). All rights reserved. C1 NCI, Hlth Serv, Appl Res Program, Bethesda, MD 20892 USA. NCI, Econ Branch, Appl Res Program, Bethesda, MD 20892 USA. Univ Rochester, Sch Med & Dent, Dept Family Med, Rochester, NY USA. Tri Cty Family Med, New York, NY USA. Ctr Medicare, Off Res Dev & Informat, Baltimore, MD USA. Medicaid Serv, Baltimore, MD USA. Natl Inst Hlth, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. RP Klabunde, CN (reprint author), NCI, Hlth Serv, Appl Res Program, Execut Plaza N Room 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-PC-85169]; PHS HHS [99FED06571] NR 52 TC 148 Z9 149 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAR PY 2003 VL 36 IS 3 BP 352 EP 362 DI 10.1016/S0091-7435(02)00066-X PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 661RY UT WOS:000181904600011 PM 12634026 ER PT J AU Oriji, GK AF Oriji, GK TI Role of metoprolol, B1-adrenoceptor antagonist, thromboxane A2 and nitric oxide in CsA-induced hypertension SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE cyclosporine A; metoprolol; thromboxane A2; nitrate/nitrite; protein kinase C; rats; aortic rings ID HIGH-SODIUM DIET; RENAL-TRANSPLANT RECIPIENTS; PERFUSED RAT KIDNEYS; CYCLOSPORINE-A; HUMAN FOREARM; TREATED RATS; NEPHROTOXICITY; RESPONSES; PROPRANOLOL; DYSFUNCTION AB Chronic treatment with cyclosporine A (CsA), a potent immunosuppressive agent, is associated with the development of arterial hypertension. The effect of CsA on vascular responses was determined in Sprague Dawley rats and rat aortic rings. Male rats weighing 250-300 g were given either CsA (25 mg/kg/day) in olive oil or vehicle by intraperitoneal (ip) injection for 7 days. CsA administration produced a 42% increase (P<0.001) in mean arterial pressure (MAP) which reached a plateau after 3 days. The level of both nitrate/nitrite (NO2/NO3), metabolites of nitric oxide (NO), decreased by 50% (P<0.001), but the level of thromboxane A2 (TBXA2) increased by 75% (P < 0.001), in the urine. When 10(-9) M of CsA was added acutely to intact aortic rings from untreated rats, NO2/NO3 production decreased by 83% (P < 0.011), but TBXA2 production increased by 86% (P < 0.001). The effects of CsA were reversed both in vivo and in vitro by pretreatment with metoprolol (15 mg/kg/day ip), B1-adrenoceptor antagonist. There were no changes in MAP and tension in rats treated with metoprolol alone. In addition, in aorta of rats that were treated with CsA ip for 7 days, CsA significantly activated protein kinase C (PKC) translocation. This suggests that PKC mediate, in part, CsA-induced hypertension. In summary, CsA inhibits endothelial NO formation, activate PKC, and increase TBXA2 production, with resulting increase in MAP, and this changes can be overcome by pretreatment with metoprolol. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. RP Oriji, GK (reprint author), Docs Nursing Jobs Inc, 807 Suffield Dr, Gaithersburg, MD 20878 USA. NR 29 TC 7 Z9 8 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD MAR PY 2003 VL 68 IS 3 BP 233 EP 238 AR PII S0952-3278(02)00276-4 DI 10.1016/S0952-3278(02)00276-4 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 648KE UT WOS:000181149900007 PM 12591008 ER PT J AU Vickrey, JF Logsdon, BC Proteasa, G Palmer, S Winters, MA Merigan, TC Kovari, LC AF Vickrey, JF Logsdon, BC Proteasa, G Palmer, S Winters, MA Merigan, TC Kovari, LC TI HIV-1 protease variants from 100-fold drug resistant clinical isolates: expression, purification, and crystallization SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE HIV protease; multi-drug resistance; codon bias; crystallization ID HUMAN-IMMUNODEFICIENCY-VIRUS; STRUCTURE-BASED DESIGN; TRANSITION-STATE ANALOG; REVERSE-TRANSCRIPTASE; CRYSTAL-STRUCTURE; CRYSTALLOGRAPHIC STRUCTURE; ESCHERICHIA-COLI; DNA-SYNTHESIS; INHIBITORS; MUTANT AB High-resolution X-ray crystallographic structures of HIV-1 protease clinical variants complexed with licensed inhibitors are essential to understanding the fundamental cause of protease drug resistance. There is a need for structures of naturally evolved HIV-1 proteases from patients failing antiretroviral therapy. Here, we report the expression, purification, and crystallization of clinical isolates of HIV-1 protease that have been characterized to be more than 100 times less susceptible to US FDA approved protease inhibitors. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI 48201 USA. NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. Stanford Univ, Ctr AIDS Res, Stanford, CA 94305 USA. RP Kovari, LC (reprint author), Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, 540 E Canfield Ave, Detroit, MI 48201 USA. FU NIGMS NIH HHS [GM 62990] NR 41 TC 15 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD MAR PY 2003 VL 28 IS 1 BP 165 EP 172 DI 10.1016/S1046-5928(02)00650-2 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 664LT UT WOS:000182063100022 PM 12651121 ER PT J AU Enoch, MA Xu, K Ferro, E Harris, CR Goldman, D AF Enoch, MA Xu, K Ferro, E Harris, CR Goldman, D TI Genetic origins of anxiety in women: a role for a functional catechol-O-methyltransferase polymorphism SO PSYCHIATRIC GENETICS LA English DT Article DE anxiety; genes; catechol-O-methyltransferase; Tridimensional Personality Questionnaire; low-voltage alpha electroencephalogram; norepinephrine ID OBSESSIVE-COMPULSIVE DISORDER; PROMOTER POLYMORPHISM; BIPOLAR DISORDER; ALPHA-EEG; ASSOCIATION; TRAITS; ALLELE; COMT; ALCOHOLISM; RISK AB Objective Women are more prone to anxiety than men. The catechol-O-methyltransferase functional polymorphism, Val158Met, is likely to be implicated in anxiety vulnerability. We hypothesized that, particularly in women, the lowactivity Met158 allele would be associated with higher anxiety scores and a biological trait, low-voltage alpha resting electroencephalogram (EEG), previously associated with alcoholism and anxiety disorders. Methods DNA was obtained from two independent groups of participants ascertained as community samples: 149 predominantly Caucasian individuals (92 women, 57 men), and 252 Plains American Indians (149 women, 103 men). Dimensional measures of anxiety (Tridimensional Personality Questionnaire harm avoidance subscales HA1 and HA2) were obtained and DSM-III-R lifetime psychiatric diagnoses were determined. EEGs were recorded and EEG phenotypes assigned. Result In both populations, women showed significant associations between catechol-O-methyltransferase genotype and elevated harm avoidance scores, and the Met158/Met158 genotype was most strongly associated: predominantly Caucasian participants: HA1, P=0.03, HA2, P=0.03; and Plains American Indians: HA2, P=0.01. This was also the case with low-voltage alpha resting EEG: predominantly Caucasian participants: P=0.01, odds ratio=5.0 (95% confidence interval, 1.3-18.7); Plains American Indians: P=0.03, odds ratio=3.7 (95% confidence interval, 1.1-12.7). Conclusions The results of the present study suggest that an inherited difference in catecholamine metabolism is important in the pathogenesis of anxiety in women. Psychiatr Genet 13:33-41 (C) 2003 Lippincott Williams Wilkins. C1 NIAAA, Neurogenet Lab, DICBR, NIH, Bethesda, MD 20892 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 44 TC 184 Z9 192 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD MAR PY 2003 VL 13 IS 1 BP 33 EP 41 DI 10.1097/01.ypg.0000054709.85338.c3 PG 9 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 655DE UT WOS:000181535400006 PM 12605099 ER PT J AU Mojtabai, R Rosenheck, RA Wyatt, RJ Susser, ES AF Mojtabai, R Rosenheck, RA Wyatt, RJ Susser, ES TI Use of VA aftercare following military discharge among patients with serious mental disorders SO PSYCHIATRIC SERVICES LA English DT Article ID HEALTH-SERVICES; VIETNAM ERA; CARE; VETERANS; SCHIZOPHRENIA; COVERAGE; MODELS AB Objective: This study examined the use of Department of Veterans Affairs (VA) aftercare services among patients with serious mental disorders who were discharged from the military after a first admission to a Department of Defense (DoD) hospital. Methods:, Administrative data from the DoD and VA health systems were linked to identify active-duty servicemen and women who were hospitalized in a military hospital with a diagnosis of major depression, bipolar disorder, or schizophrenia between 1993 and 1996 and who were subsequently discharged from the military Split population survival analysis was used to examine separately the correlates of contact with VA outpatient mental health services and, among those who had contact, the time to contact after military discharge. Results: Fifty-two percent of 2,861 identified individuals had received outpatient care from VA mental health clinics by the end of September 1998. The rate of contact was lower than in virtually all studies of aftercare following hospital discharge. Women, older persons, and persons with schizophrenia or bipolar disorder were more likely to con-tact VA outpatient mental health services than men, younger persons, and those with major depression. Among those who made contact, older persons had a longer time to contact. Conclusions: Many people who leave the military because of serious mental illness do not receive aftercare from the VA. The reasons for such low rates of contact are not clear. Identifying patients who need aftercare but do not receive it and ensuring that they have access to needed services remains an important challenge for the DoD and the VA. C1 Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. NE Program Evaluat Ctr, Dept Vet Affairs, West Haven, CT USA. NIMH, Neuropsychiat Branch, Bethesda, MD 20892 USA. Columbia Univ, Dept Epidemiol, Joseph L Mailman Sch Publ Hlth, New York, NY 10027 USA. RP Mojtabai, R (reprint author), 2600 Netherland Ave,Apartment 805, Bronx, NY 10463 USA. EM rm322@columbia.edu FU NIMH NIH HHS [K01-MH-01754] NR 29 TC 7 Z9 7 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2003 VL 54 IS 3 BP 383 EP 388 DI 10.1176/appi.ps.54.3.383 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BI UT WOS:000222757900018 PM 12610248 ER PT J AU Epstein, DH Hawkins, WE Covi, L Umbricht, A Preston, KL AF Epstein, DH Hawkins, WE Covi, L Umbricht, A Preston, KL TI Cognitive-behavioral therapy plus contingency management for cocaine use: Findings during treatment and across 12-month follow-up SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article; Proceedings Paper CT 63rd Annual Scientific Meeting of the College-of-Problems-on-Drug-Dependence CY JUN, 2001 CL SCOTTSDALE, ARIZONA SP Coll Problems Drug Dependence ID VOUCHER-BASED REINFORCEMENT; ABSTINENCE REINFORCEMENT; METHADONE-MAINTENANCE; REGRESSION-MODELS; PSYCHOTHERAPY; PHARMACOTHERAPY; DEPENDENCE; ABUSERS AB Contingency management (CM) rapidly reduces cocaine use, but its effects subside after treatment. Cognitive-behavioral therapy (CBT) produces reductions months after treatment. Combined, the 2 might be complementary. One hundred ninety-three cocaine-using methadone-maintained outpatients were randomly assigned to 12 weeks of group therapy (CBT or a control condition) and voucher availability (CM contingent on cocaine-negative urine or noncontingent). Follow-ups occurred 3, 6, and 12 months posttreatment. Primary outcome was cocaine-negative urine (urinalysis 3 times/week during treatment and once at each follow-up). During treatment, initial effects of CM were dampened by CBT. Posttreatment, there were signs of additive benefits, significant in 3- versus 12-month contrasts. Former CBT participants were also more likely to acknowledge cocaine use and its effects and to report employment. C1 Natl Inst Drug Abuse, Intramural Res Program, Treatment Sect, Clin Pharmacol & Therapeut Branch, Baltimore, MD 21224 USA. Florida Atlantic Univ, Sch Social Work, Boca Raton, FL 33431 USA. Sinai Hosp, Addict Recovery Program, Baltimore, MD 21215 USA. RP Epstein, DH (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Treatment Sect, Clin Pharmacol & Therapeut Branch, 5500 Nath Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU NIDA NIH HHS [Z01 DA000175-11] NR 35 TC 71 Z9 72 U1 3 U2 8 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD MAR PY 2003 VL 17 IS 1 BP 73 EP 82 DI 10.1037/0893-164X.17.1.73 PG 10 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 656CB UT WOS:000181590300009 PM 12665084 ER PT J AU Desai, RI Terry, P AF Desai, RI Terry, P TI Evidence of cross-tolerance between behavioural effects of nicotine and cocaine in mice SO PSYCHOPHARMACOLOGY LA English DT Article DE nicotine; cocaine; tolerance; sensitization; locomotor activity; grooming; rearing; mice ID LOCOMOTOR-ACTIVITY; CIGARETTE-SMOKING; DOPAMINERGIC SYSTEM; INTRAVENOUS COCAINE; NUCLEUS-ACCUMBENS; DRUG-USE; RATS; SENSITIZATION; AMPHETAMINE; RECEPTORS AB Rationale: Studies have reported that chronic exposure to nicotine does not alter the effects of cocaine on locomotor activity, and vice versa. However, the apparent lack of effect of one drug on the behavioural response to the other may be due to an exclusive focus on locomotor activity as the target behaviour. Objective: To test whether repeated pretreatment with nicotine causes tolerance or sensitization to cocaine's effects on diverse behaviours: locomotion, rearing, grooming, and immobility. Similarly, the effects of repeated cocaine treatment on the acute response to nicotine were also tested. Methods: Mice were pretreated with 14 injections of nicotine (0.3 mg/kg), cocaine (5 mg/kg) or saline, the injections being given once daily, except for three breaks of two days each. Two days after the final pretreatment injection, mice were given a challenge injection of saline, cocaine (3 or 5 mg/kg) or nicotine (0.3 or 1 mg/kg), and observed in a large test cage for 40 min using a time-sampling procedure. Results: Repeated administration of either drug produced some tolerance to subsequent challenge with the same dose of the drug. Prior nicotine exposure significantly attenuated cocaine-induced decreases in grooming and increases in rearing, but did not significantly affect other behaviours. In contrast, prior cocaine exposure failed to alter nicotine's effects on any behaviour. Conclusions: Cross-tolerance between nicotine and cocaine (but not vice-versa) can be demonstrated if several behaviours are observed; measures of locomotor activity are less sensitive to the effect. The asymmetrical pattern of cross-tolerance may be due to differential inhibition of dopamine uptake by the two drugs. C1 Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England. RP NIDA, Medicat Discovery Res Branch, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. EM rdesai@intra.nida.nih.gov NR 66 TC 12 Z9 12 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 2003 VL 166 IS 2 BP 111 EP 119 DI 10.1007/s00213-002-1319-4 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 656DK UT WOS:000181593400003 PM 12545328 ER PT J AU Fantegrossi, WE Godlewski, T Karabenick, RL Stephens, JM Ullrich, T Rice, KC Woods, JH AF Fantegrossi, WE Godlewski, T Karabenick, RL Stephens, JM Ullrich, T Rice, KC Woods, JH TI Pharmacological characterization of the effects of 3,4-methylenedioxymethamphetamine ("ecstasy") and its enantiomers on lethality, core temperature, and locomotor activity in singly housed and crowded mice SO PSYCHOPHARMACOLOGY LA English DT Article DE MDMA; aggregate toxicity; 5-HT; thermoregulation; hyperthermia ID BODY-TEMPERATURE; SUBSTITUTED AMPHETAMINES; 5-HT2C RECEPTORS; MDMA; NEUROTOXICITY; RAT; SEROTONIN; RELEASE; METHYLENEDIOXYMETHAMPHETAMINE; HYPERTHERMIA AB Rationale: Few studies have directly compared the effects of methylenedioxymethamphetamine (MDMA, "ecstasy") and its enantiomers across measures. Objectives: To investigate the capacity of MDMA and its stereoisomers to produce aggregate toxicity in mice, the influence of 5-HT2 receptors, 5-HT transporters, and ambient temperature on this effect, and to directly compare the racemate and its enantiomers in terms of their effects on core temperature and locomotor activity with and without various serotonergic pretreatments. Methods: Mice were injected with various doses of MDMA and its stereoisomers in various housing conditions, with and without pretreatments of serotonergic drugs, and at two distinct ambient temperatures; lethality was quantified 2 h after MDMA administration. For temperature/activity studies, mice were injected with various doses of MDMA and its enantiomers, with and without ketanserin, MDL100907, or fluoxetine pretreatments, and core temperature and locomotor activity data were collected for 24 h. Results: Racemic MDMA and its isomers produced aggregate toxicity in mice. The lethal effects of racemic MDMA and its enantiomers were differentially attenuated by the various serotonergic pretreatments and manipulation of the ambient temperature across housing conditions. Racemic and S(+)-MDMA produced hyperthermic effects in mice, while R(-)-MDMA did not. The pretreatment drugs attenuated the hyperthermic effects of racemic MDMA, but were less effective in blocking S(+)-MDMA-induced hyperthermia. Racemic MDMA and both enantiomers stimulated locomotor activity, although R(-)-MDMA was least effective. The pretreatments all reduced the locomotor stimulant effects of racemic MDMA but potentiated S(+)-MDMAinduced hyperlocomotion. Conclusions: The MDMA isomers have heterogeneous effects that can be demonstrated across a wide range of endpoints. C1 Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Psychol, Biopsychol Program, Ann Arbor, MI 48109 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Fantegrossi, WE (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, 1301 MSRB 3, Ann Arbor, MI 48109 USA. FU NIDA NIH HHS [DA05923, DA09161] NR 34 TC 76 Z9 76 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 2003 VL 166 IS 3 BP 202 EP 211 DI 10.1007/s00213-002-1261-5 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 666XP UT WOS:000182202000002 PM 12563544 ER PT J AU Ruiz-Padial, E Sollers, JJ Vila, J Thayer, JF AF Ruiz-Padial, E Sollers, JJ Vila, J Thayer, JF TI The rhythm of the heart in the blink of an eye: Emotion-modulated startle magnitude covaries with heart rate variability SO PSYCHOPHYSIOLOGY LA English DT Article DE startle; heart rate variability; emotion; parasympathetic ID PREFRONTAL CORTEX; NEUROVISCERAL CONCOMITANTS; RESPIRATORY FREQUENCY; AMYGDALA; ANXIETY; REFLEX; DEPRESSION; SYSTEM; PERIOD; FEAR AB Emotion-modulated startle is a robust phenomenon that has been demonstrated in a wide range of experimental situations. Similarly, heart rate variability (HRV) has been associated with a diverse range of processes including affective and attentional regulation. The present study sought to examine the relationship between these two important measures of affective behavior. Ninety female participants viewed pleasant, neutral, and unpleasant pictures while exposed to acoustic startle stimuli. The eyeblink startle was recorded both during the affective foregrounds and during intertrial intervals. HRV was assessed during a resting baseline and relationships between HRV and startle magnitudes examined. Results indicated that resting HRV was inversely related to startle magnitude during both intertrial intervals and affective foregrounds. In addition, the participants with the highest HRV showed the most differentiated emotion-modulated startle effects, whereas those with the lowest HRV, compared to those with the highest HRV, showed significantly potentiated startle to neutral foregrounds and marginally potentiated startle to pleasant foregrounds. The findings are consistent with models that posit that prefrontal cortical activity modulates subcortical motivation circuits. These results have important implications for the use of startle probe methodology and for HRV in the study of emotional regulation and dysregulation. C1 NIA, GRC, LPC, Baltimore, MD 21224 USA. Univ Granada, Dept Clin Psychol, Granada, Spain. Univ Jaen, Dept Psychol, Jaen, Spain. RP Thayer, JF (reprint author), NIA, GRC, LPC, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Vila, Jaime/F-9719-2010; Ruiz Padial, Elisabeth/G-8962-2011 OI Vila, Jaime/0000-0002-1767-8606; NR 50 TC 61 Z9 64 U1 5 U2 27 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAR PY 2003 VL 40 IS 2 BP 306 EP 313 DI 10.1111/1469-8986.00032 PG 8 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 652VJ UT WOS:000181401300015 PM 12820871 ER PT J AU Weiss, CR Aletras, AH London, JF Taylor, JL Epstein, FH Wassmuth, R Balaban, RS Arai, AE AF Weiss, CR Aletras, AH London, JF Taylor, JL Epstein, FH Wassmuth, R Balaban, RS Arai, AE TI Stunned, infarcted, and normal myocardium in dogs: Simultaneous differentiation by using gadolinium-enhanced cine MR imaging with magnetization transfer contrast SO RADIOLOGY LA English DT Article DE animals; experimental study; heart, experimental studies; magnetic resonance (MR), magnetization transfer contrast; myocardium, infarction; myocardium, MR ID ECHO-TRAIN READOUT; GD-DTPA; STRESS ECHOCARDIOGRAPHY; FUNCTIONAL RECOVERY; SIZE; REPERFUSION; INJURY; ISCHEMIA; QUANTIFICATION; NECROSIS AB PURPOSE: To simultaneously differentiate stunned, infarcted, and normal myocardial regions by using gadolinium-enhanced cine magnetic resonance (MR) imaging with magnetization transfer contrast. MATERIALS AND METHODS: Twelve dogs were imaged on days 1 and 8 after transient 90-minute coronary artery occlusion. A magnetization transfer contrast with echo-train readout (MTET) MR sequence was performed before and 30 minutes after gadolinium contrast enhancement. Ex vivo analysis consisted of MR imaging, microsphere blood flow analysis, and triphenyltetrazolium chloride (TTC) staining. A paired two-tailed t test was used to compare wall thickening from day I t to day 8. Linear regression and Bland-Altman analyses were used to compare infarct size depicted with MTET imaging with that seen on TTC-stained tissue. RESULTS: Severe wall motion abnormalities were detected in all dogs. At TTC analysis, seven dogs had evidence of myocardial infarction and five had evidence of stunned myocardium. The mean percentages of left ventricular wall thickening in regions were 2% +/- 4 (SD), 4% +/- 8, and 33% +/- 5, respectively. Wall thickening did not improve in the infarcted zones, but it improved to nearly normal levels in the stunned region 1 week after induced occlusion (mean, 40% +/- 8; P < .02). MTET images clearly depicted infar ted myocardium as brighter than both the normal and stunned myocardial regions but, darker than the blood pool. In vivo MTET infarct volume correlated with ex Vivo TTC analysis data (y = 1.01 x + 0.00, R = 0.98, standard error of the estimate = 0.019). CONCLUSION: One day after myocardial ischemia, MTET during one MR imaging examination enabled simultaneous differentiation of infarcted, stunned, and normal myocardial regions on the basis of gadolinium enhancement and regional function. ((C)) RSNA, 2003. C1 NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bldg 10,10 Ctr Dr,Rm B1D416,MSC 1061, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009; OI Balaban, Robert/0000-0003-4086-0948; Aletras, Anthony/0000-0002-3786-3817 NR 31 TC 24 Z9 24 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2003 VL 226 IS 3 BP 723 EP 730 DI 10.1148/radiol.2263012196 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 649QV UT WOS:000181220200015 PM 12616019 ER PT J AU Magai, C Kerns, MD Consedine, NS Fyffe, D AF Magai, C Kerns, MD Consedine, NS Fyffe, D TI Depression in older ethnic groups - A test of the generality of the social precursors model SO RESEARCH ON AGING LA English DT Article DE depression; older adults; social precursors; ethnicity ID AFRICAN-AMERICAN; LIFE EVENTS; AGE; SYMPTOMS; PREVALENCE; COMMUNITY; SUPPORT; HEALTH; 10-YEAR-OLD; POPULATION AB The generality of George's model of the social precursors of depression was tested in a sample of older persons (N = 803) from three ethnic groups: U.S.-born African Americans, African Caribbeans, and U.S.-bom European Americans. The social precursors model includes demographic variables, early events and achievements, later events and achievements, social integration, vulnerability and protective factors, and provoking agents and coping efforts. Zero-order correlations indicated that nearly all the predictor variables were significantly associated with depression. A test of the overall model with all six stages was followed by separate regressions for each ethnic group. Four of the six stages of the model contributed unique variance to the prediction of depressed affect in European Americans but only two in the case of African Americans and African Caribbeans. The most robust and consistent predictor of depression was the sixth-stage variables of stress and emotion regulation. C1 Long Isl Univ, Ctr Studies Ethn & Human Dev, Greenvale, NY 11548 USA. NIA, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. RP Magai, C (reprint author), Long Isl Univ, Ctr Studies Ethn & Human Dev, Greenvale, NY 11548 USA. RI Consedine, Nathan/A-8876-2012 NR 64 TC 7 Z9 7 U1 3 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0164-0275 J9 RES AGING JI Res. Aging PD MAR PY 2003 VL 25 IS 2 BP 144 EP 171 DI 10.1177/0164027502250017 PG 28 WC Gerontology SC Geriatrics & Gerontology GA 644PP UT WOS:000180927500003 ER PT J AU Resnick, SM Berenbaum, S AF Resnick, SM Berenbaum, S TI CAAD Symposium - 14th Annual Symposium on Research on Aging: Aging, hormones, and cognition SO RESEARCH QUARTERLY FOR EXERCISE AND SPORT LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. Penn State Univ, University Pk, PA 16802 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ALLIANCE HEALTH PHYS EDUC REC & DANCE PI RESTON PA 1900 ASSOCIATION DRIVE, RESTON, VA 22091 USA SN 0270-1367 J9 RES Q EXERCISE SPORT JI Res. Q. Exerc. Sport PD MAR PY 2003 VL 74 IS 1 SU S BP A93 EP A93 PG 1 WC Hospitality, Leisure, Sport & Tourism; Psychology, Applied; Psychology; Sport Sciences SC Social Sciences - Other Topics; Psychology; Sport Sciences GA 657MH UT WOS:000181670600240 ER PT J AU Allerson, CR Martinez, A Yikilmaz, E Rouault, TA AF Allerson, CR Martinez, A Yikilmaz, E Rouault, TA TI A high-capacity RNA affinity column for the purification of human IRP1 and IRP2 overexpressed in Pichia pastoris SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE 5 '-aminoalkyl tether; affinity chromatography; iron regulatory proteins; iron-responsive element (IRE); protein purification; RNA-binding proteins; thiol-modified sepharose ID IRON-RESPONSIVE ELEMENT; BINDING-PROTEIN; REGULATORY PROTEIN-2; HETEROLOGOUS PROTEINS; SULFUR CLUSTER; HAIRPIN LOOP; ACONITASE; DEGRADATION; EXPRESSION; SITE AB Regulated expression of proteins involved in mammalian iron metabolism is achieved in part through the interaction of the iron regulatory proteins IRP1 and IRP2 with highly conserved RNA stem-loop structures, known as iron-responsive elements (IREs), that are located within the 5' or 3' untranslated regions of regulated transcripts. As part of an effort to determine the structures of the IRP-IRE complexes using crystallographic methods, we have developed an efficient process for obtaining functionally pure IRP1 and IRP2 that relies upon the improved overexpression (>10 mg of soluble IRP per liter of culture) of each human IRP in the yeast Pichia pastoris and large-scale purification using RNA affinity chromatography. Despite the utility of RNA affinity chromatography in the isolation of RNA-binding proteins, current methods for preparing RNA affinity matrices produce columns of low capacity and limited stability. To address these limitations, we have devised a simple method for preparing stable, reusable, high-capacity RNA affinity columns. This method utilizes a bifunctional linker to covalently join a 5'-amino tethered RNA with a thiol-modified Sepharose, and can be used to load 150 nmole or more of RNA per milliliter of solid support. We demonstrate here the use of an IRE affinity column in the large-scale purification of IRP1 and IRP2, and suggest that the convenience of this approach will prove attractive in the analysis of other RNA-binding proteins. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 38 TC 13 Z9 13 U1 1 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD MAR PY 2003 VL 9 IS 3 BP 364 EP 374 DI 10.1261/rna.2143303 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 706HD UT WOS:000184447500012 PM 12592010 ER PT J AU Kitiyakara, C Kopp, JB Eggers, P AF Kitiyakara, C Kopp, JB Eggers, P TI Trends in the epidemiology of focal segmental glomerulosclerosis SO SEMINARS IN NEPHROLOGY LA English DT Review ID ADULT NEPHROTIC SYNDROME; STAGE RENAL-DISEASE; GLOMERULAR-DISEASE; RACIAL-DIFFERENCES; AFRICAN-AMERICANS; NATIONAL REGISTRY; KIDNEY-DISEASE; BIOPSY; CHILDREN; GLOMERULONEPHRITIS C1 NIDDKD, Kidney Dis Sect, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDDKD, Epidemiol Res Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Mahidol Univ, Ramathibodi Hosp, Dept Med, Bangkok 10700, Thailand. RP Kopp, JB (reprint author), NIDDKD, Kidney Dis Sect, NIH, Dept Hlth & Human Serv, 10-3N116, Bethesda, MD 20892 USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 49 TC 73 Z9 77 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 2003 VL 23 IS 2 BP 172 EP 182 DI 10.1053/snep.2003.50025 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 663DN UT WOS:000181991100007 PM 12704577 ER PT J AU Hostetter, TH AF Hostetter, TH TI Hyperfiltration and glomerulosclerosis SO SEMINARS IN NEPHROLOGY LA English DT Review ID ANGIOTENSIN-II BLOCKADE; REMNANT KIDNEY MODEL; REDUCED RENAL MASS; GLOMERULAR INJURY; FOLLOW-UP; PROGRESSIVE GLOMERULOSCLEROSIS; SEGMENTAL GLOMERULOSCLEROSIS; UNILATERAL NEPHRECTOMY; SALT HYPERTENSION; RAT C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Hostetter, TH (reprint author), NIDDKD, NIH, 6707 Democracy Blvd,Room 645, Bethesda, MD 20892 USA. NR 43 TC 87 Z9 90 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 2003 VL 23 IS 2 BP 194 EP 199 DI 10.1053/snep.2003.50017 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 663DN UT WOS:000181991100009 PM 12704579 ER PT J AU Solomon, SB Banks, SM Gerstenberger, E Csako, G Bacher, JD Thomas, ML Costello, R Eichacker, PQ Danner, RL Natanson, C AF Solomon, SB Banks, SM Gerstenberger, E Csako, G Bacher, JD Thomas, ML Costello, R Eichacker, PQ Danner, RL Natanson, C TI Sympathetic blockade in a canine model of gram-negative bacterial peritonitis SO SHOCK LA English DT Article DE epidural blockade; sepsis; celiac plexus blockade; pain management; bacterial peritonitis ID FACTOR-ALPHA PRODUCTION; CELIAC PLEXUS BLOCK; HUMAN SEPTIC SHOCK; THERAPEUTIC TRIAL; MORPHINE; DOGS; SEPSIS; PAIN; STIMULATION; BUPIVACAINE AB We investigated, in a well-established canine model of human sepsis, the effects of two different techniques of sympathetic blockade during bacterial peritonitis on pain relief, hemodynamics, and survival rate. Twenty-two purposebred beagles (12-28 months old, weighing 10-12 kg) were studied. Fourteen animals received an epidural infusion of bupivicaine and morphine, and the other eight received either a celiac plexus block (n = 4) or a sham block (n = 4). Eighteen of the 22 animals received an intraperitoneal challenge of Escherichia coli(1-10 x 10(9) CFU kg(-1) body weight). At comparable doses of intraperitoneal-implanted E coli (2.5-5 x 10(9) CFU kg(-1) body weight), the addition of sympathetic blockade produced a synergistic decrease in survival times (P = 0.002) and mean left ventricular ejection fraction (P = 0.008), and increase in creatinine levels (P = 0.02). There was also a significant increase in tumor necrosis factor (TNF) levels (P = 0.004) and decrease in blood endotoxin clearance (P = 0.006) associated with sympathetic blockade during sepsis. The celiac plexus-blocked animals had no improvement in pain scores, and subjectively looked clinically worse than animals with sepsis without a celiac plexus block. In contrast, the epidural block was effective in blocking the pain and discomfort associated with low lethality doses of intraperitoneal bacteria reflected by no increase in pain scores compared with animals not receiving bacterial challenge. This study shows that during severe bacterial peritonitis, maintenance of sympathetic tone irrespective of pain relief provided is necessary for clearance of bacterial toxins, control of proinflammatory mediator release, hemodynamic stability, and survival. C1 NIH, Bethesda, MD 20892 USA. RP Solomon, SB (reprint author), NIH, Bldg 10,Room 7D43,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 31 TC 9 Z9 9 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD MAR PY 2003 VL 19 IS 3 BP 215 EP 222 DI 10.1097/01.shk.0000046087.84161.cb PG 8 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 648UG UT WOS:000181168500004 PM 12630520 ER PT J AU Shahar, E Chambless, LE Rosamond, WD Boland, LL Ballantyne, CM McGovern, PG Sharrett, AR AF Shahar, E Chambless, LE Rosamond, WD Boland, LL Ballantyne, CM McGovern, PG Sharrett, AR TI Plasma lipid profile and incident ischemic stroke - The Atherosclerosis Risk in Communities (ARIC) Study SO STROKE LA English DT Article DE cholesterol; lipids; stroke, ischemic ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY HEART-DISEASE; APOLIPOPROTEIN-A-I; IMPROVED LIPOLYTIC EFFICIENCY; NORTHERN MANHATTAN STROKE; 21-YEAR FOLLOW-UP; SERUM-CHOLESTEROL; BLOOD COLLECTION; ENZYMATIC DETERMINATION; TOTAL MORTALITY AB Background and Purpose-The role of circulating lipids and lipoproteins in the pathogenesis of ischemic stroke remains uncertain despite 3 decades of research. We examined this issue in a large population-based cohort. Methods-Between 1987 and 1989, 14 175 middle-aged men and women, free of clinical cardiovascular disease, took part in the first examination of the Atherosclerosis Risk in Communities (ARIC) study cohort. Baseline measurements included plasma levels of LDL cholesterol, HDL cholesterol, apolipoprotein B, apolipoprotein A-1, and triglycerides and myriad risk factors for cardiovascular disease. The cohort was followed for cardiovascular disease end points. Results-Over an average follow-up of 10 years (142 704 person-years at risk), we documented clinical ischemic stroke in 305 participants (161 men and 144 women). After multivariable adjustment for stroke risk factors, categorical and spline regression analyses of the entire sample, as well as the sample of men alone, revealed weak and inconsistent associations between ischemic stroke and each of the 5 lipid factors. Among women, the most consistent findings were decreasing risk of ischemic stroke within the top half of the distribution of HDL cholesterol and increasing risk within the lower range of the triglyceride distribution. Conclusions-The relation of circulating cholesterol to ischemic stroke does not resemble its well-known relation to coronary heart disease. Either the pathogenesis of a substantial proportion of ischemic strokes does not involve classic atherosclerotic mechanisms, or the effect of plasma lipids on atherogenesis is substantially different in the intracranial vascular bed. C1 Univ Minnesota, Div Epidemiol, Minneapolis, MN 55454 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Shahar, E (reprint author), Univ Minnesota, Div Epidemiol, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. RI Ballantyne, Christie/A-6599-2008 FU NHLBI NIH HHS [N01-HC-55015, N01 HC-55021, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55022] NR 75 TC 150 Z9 161 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2003 VL 34 IS 3 BP 623 EP 631 DI 10.1161/01.STR.0000057812.51734.FF PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 653ZJ UT WOS:000181466700014 PM 12624282 ER PT J AU Worrall, BB Azhar, S Nyquist, PA Ackerman, RH Hamm, TL DeGraba, TJ AF Worrall, BB Azhar, S Nyquist, PA Ackerman, RH Hamm, TL DeGraba, TJ TI Interleukin-1 receptor antagonist gene Polymorphisms in carotid atherosclerosis SO STROKE LA English DT Article; Proceedings Paper CT 25th International Stroke Conference CY FEB 10, 2000 CL NEW ORLEANS, LOUISIANA SP Amer Heart Assoc DE atherosclerosis; carotid artery diseases; cytokines; interleukin-1 receptor antagonist; polymorphism ID DISEASE; ASSOCIATION; INFLAMMATION; VARIANTS; IL-1RA AB Background and Purpose-Inflammation plays an important role in the development of atherosclerosis. The gene for the counterinflammatory cytokine interleukin-1 receptor antagonist (IL-1ra) is polymorphic, and high frequencies of allele 2 have been found to be associated with other inflammatory diseases. This study examined the association of allele and carrier frequencies of the IL-1ra gene with the presence of carotid atherosclerosis and plaque symptomaticity. Methods-A total of 328 subjects identified as having carotid atherosclerosis or no atherosclerosis (controls) participated. Blood was obtained for DNA determination. Results-Frequency of allele 2 was significantly greater in patients with atherosclerosis compared with nonatherosclerotic subjects. No difference was seen between symptomatic and asymptomatic atherosclerosis patients. Noncarriage of allele 2 was associated with reduced likelihood of atherosclerosis (odds ratio [OR], 0.44; 95% CI, 0.27 to 0.71). The homozygous carrier state for allele 2 was associated with greater likelihood of atherosclerosis (unadjusted OR, 7.30; 95% CI, 2.31 to 22.94; adjusted OR, 13.78; 95% CI, 1.94 to 97.9). A gene-dose effect was detected. Conclusions-These data suggest that allele 2 of the IL-1ra gene represents a susceptibility factor in the development of carotid atherosclerosis. Further investigation appears warranted. C1 Natl Naval Med Res Inst, Clin Stroke Res Unit, Dept Neurol, Bethesda, MD 20889 USA. Univ Virginia, Dept Neurol, Charlottesville, VA USA. Univ Virginia, Dept Hlth Evaluat Sci, Charlottesville, VA USA. NINDS, Stroke Branch, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP DeGraba, TJ (reprint author), Natl Naval Med Res Inst, Clin Stroke Res Unit, Dept Neurol, Bldg 9,2nd Deck,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM TJDeGraba@bethesda.med.navy.mil NR 15 TC 37 Z9 42 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2003 VL 34 IS 3 BP 790 EP 793 DI 10.1161/01.STR.0000057815.79289.EC PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 653ZJ UT WOS:000181466700044 PM 12624309 ER PT J AU Vautrin, J Barker, JL AF Vautrin, J Barker, JL TI Presynaptic quantal plasticity: Katz's original hypothesis revisited SO SYNAPSE LA English DT Review DE transmitter release; calcium spike; excitability; exocytosis; extracellular matrix ID RAT HIPPOCAMPAL-NEURONS; MOUSE NEUROMUSCULAR-JUNCTION; SPONTANEOUS TRANSMITTER RELEASE; SYNAPTIC VESICLE CYCLE; MOTOR-NERVE TERMINALS; END-PLATE POTENTIALS; CA2+ CHANNELS; CELL-SURFACE; LIPID RAFTS; NEUROTRANSMITTER RELEASE AB Changes in the amplitudes of signals conveyed at synaptic contacts between neurons underlie many brain functions and pathologies. Here we review the possible determinants of the amplitude and plasticity of the elementary postsynaptic signal, the miniature. In the absence of a definite understanding of the molecular mechanism releasing transmitters, we investigated a possible alternative interpretation. Classically, both the quantal theory and the vesicle theory predict that the amount of transmitter producing a miniature is determined presynaptically prior to release and that rapid changes in miniature amplitude reflect essentially postsynaptic alterations. However, recent data indicates that short-term and long-lasting changes in miniature amplitude are in large part due to changes in the amount of transmitter in individual released packets that show no evidence of preformation. Current representations of transmitter release derive from basic properties of neuromuscular transmission and endocrine secretion. Reexamination of overlooked properties of these two systems indicate that the amplitude of miniatures may depend as much, if not more, on the Ca2+ signals in the presynaptic terminal than on the number of postsynaptic receptors available or on vesicle's contents. Rapid recycling of transmitter and its possible adsorption at plasma and vesicle lumenal membrane surfaces suggest that exocytosis may reflect membrane traffic rather than actual transmitter release. This led us to reconsider the disregarded hypothesis introduced by Fatt and Katz (1952; J Physiol 117:109-128) that the excitability of the release site may account for the "quantal effect" in fast synaptic transmission. In this case, changes in excitability of release sites would contribute to the presynaptic quantal plasticity that is often recorded. (C) 2002 Wiley-Liss, Inc. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP INSERM, U254, 71,Rue Navacelles, F-34090 Montpellier, France. EM vautrinj@univ-montp2.fr NR 149 TC 22 Z9 23 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-4476 EI 1098-2396 J9 SYNAPSE JI Synapse PD MAR PY 2003 VL 47 IS 3 BP 184 EP 199 DI 10.1002/syn.10161 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 632BK UT WOS:000180203100004 PM 12494401 ER PT J AU Wu, GG Cheng, LH Li, Z Deng, ZH Zou, HY Wei, TL Zhou, D Li, DC Gao, SQ Zhao, TM AF Wu, GG Cheng, LH Li, Z Deng, ZH Zou, HY Wei, TL Zhou, D Li, DC Gao, SQ Zhao, TM TI Identification of a new HLA allele, A*1114, in a Chinese family SO TISSUE ANTIGENS LA English DT Article DE cloning of HLA-A*1114; HLA-A allele; PCR-SSP; point mutation AB A novel HLA-A allele, A*1114, was initially detected in two generations of a Chinese family by unusual polymerase chain reaction based sequence-specific primers ( PCR-SSP) reaction patterns and ambiguous sequence-based typing (SBT). Molecular cloning and sequencing analysis indicated that this new allele differs from HLA-A*1102 by three nucleotide substitutions in exon 3, 524 A-->G, 526 G-->C, and 527 C-->G, thus changing codon 175 from His to Arg (CAT-->CGT) and codon 176 from Ala to Arg (GCG-->CGG). Segregation analysis showed that the proband inherited his mother's HLA haplotype A*1114, B*5801, DRB1*1405. The serologic equivalent of A*1114 is a split antigen HLA-A11.2. A PCR-SSP method was developed to distinguish A*1114 from other A*11 alleles. No further individuals with A*1114 were found in 5000 Chinese bone marrow donors. C1 NIAID, Mol & Cellular Immunogenet Sect, NIH, Bethesda, MD 20892 USA. Shenzhen Inst Transfus Med, Shenzhen, 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. NR 4 TC 12 Z9 19 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAR PY 2003 VL 61 IS 3 BP 253 EP 255 DI 10.1034/j.1399-0039.2003.00032.x PG 3 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 667YJ UT WOS:000182262200008 PM 12694575 ER PT J AU Wu, GG Cheng, LH Zhou, D Deng, ZH Zou, HY Wei, TL Li, Z Li, DC Gao, SQ Zhao, TM AF Wu, GG Cheng, LH Zhou, D Deng, ZH Zou, HY Wei, TL Li, Z Li, DC Gao, SQ Zhao, TM TI Identification of a novel allele HLA-B*5610 in a Chinese potential bone marrow donor SO TISSUE ANTIGENS LA English DT Article DE cloning of HLA-B*5610; HLA-B allele; PCR-SSP; point mutation AB A novel HLA-B allele, B*5610, has been identified in a potential bone marrow donor, his mother and brother using DNA-based typing and molecular cloning methods. The B*5610 allele differs from the closest matching HLA sequence of B*5602 by two nucleotide substitutions in exon 3, 559 C-->A and 560 T-->C, resulting in an amino acid change from Leu (CTG) to Thr (ACG) at codon 187. This new allele was segregated together with A*24020101 and DRB1*140101 in the proband's family. Serology study revealed that B*5610 is associated with B22 specificity. A PCR-SSP method was developed to distinguish B*5610 from other B*56 alleles. No further individuals with B*5610 were detected in 5000 Chinese bone marrow blood donors. C1 NIAID, Mol & Cellular Immunogenet Sect, NIH, Bethesda, MD 20892 USA. Shenzhen Inst Transfus Med, Shenzhen, 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. NR 2 TC 8 Z9 15 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAR PY 2003 VL 61 IS 3 BP 256 EP 258 DI 10.1034/j.1399-0039.2003.00031.x PG 3 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 667YJ UT WOS:000182262200009 PM 12694576 ER PT J AU Boorman, GA AF Boorman, GA TI Tribute to Dr. Carel Hollander SO TOXICOLOGIC PATHOLOGY LA English DT Biographical-Item C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Boorman, GA (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAR-APR PY 2003 VL 31 IS 2 BP 208 EP 208 DI 10.1080/01926230390183634 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 648XC UT WOS:000181175500006 ER PT J AU Rao, GN Crockett, PW AF Rao, GN Crockett, PW TI Effect of diet and housing on growth, body weight, survival and tumor Incidences of B6C3F1 mice in chronic studies SO TOXICOLOGIC PATHOLOGY LA English DT Article DE NIH-07 diet; NTP-2000 diet; housing; body weight; survival; liver tumors; lung tumors; mice ID TERM RODENT CARCINOGENICITY; BREAST-CANCER; FISCHER-344 RATS; FIBER; TOXICOLOGY; NTP-2000; PROTEIN; FAT AB Diet is one of the most important environmental factors influencing growth, body weight, survival, and age-related diseases of rodents in chronic studies. NIH-07 open formula diet was the selected diet for the NTP studies from 1980 to 1994. A new diet designated as NTP-2000 diet is the current diet for mice in the NTP studies beginning in 1994. This report is a summary of results of untreated control groups of B6C3F1 mice fed NTP-2000 or NIH-07 diet from several retrospective 2-year dosed-feed and inhalation studies for differences in growth, body weight, survival, and tumor incidences. The dosed-feed studies were conducted in 3 different facilities located in the United States, and all the inhalation studies were conducted in 1 facility. During dosed-feed studies, male and female mice housed in polycarbonate cages and fed the NTP-2000 diet had lower maximum body weights than those fed NIH-07 diet. However, during inhalation studies, mice housed in wire mesh cages and fed the NTP-2000 diet had higher maximum body weights than the mice fed NIH-07 diet. Survival was higher in groups fed NTP-2000 diet irrespective of sex, housing conditions, or body weight compared to the corresponding groups fed NIH-07 diet. Survival was higher in mice housed in polycarbonate cages irrespective of diet and sex compared to the respective sex and diet groups housed in wire mesh cages. During inhalation studies, survival of male and female mice fed NTP-2000 diet was higher than that of the groups fed NIH-07 diet, although the body weights of NTP-2000 diet groups were higher than those of the groups fed NIH-07 diet. When the NTP-2000 diet was used, male and female mice in dosed-feed studies and male mice in inhalation studies had markedly lower incidences of liver tumors than the corresponding groups fed NIH-07 diet. Significant decreases in the incidences of lung tumors were observed only in the male groups fed NTP-2000 diet during dosed-feed studies. These results suggest that body weight may not be the major contributing factor for mortality and liver tumors and that an interaction between diet and housing conditions appears to affect the growth, survival and tumor incidences of B6C3F1 mice. C1 Analyt Sci Inc, Durham, NC 27713 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Crockett, PW (reprint author), Analyt Sci Inc, Durham, NC 27713 USA. NR 38 TC 19 Z9 19 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAR-APR PY 2003 VL 31 IS 2 BP 243 EP 250 DI 10.1080/01926230390183742 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 648XC UT WOS:000181175500012 PM 12696586 ER PT J AU Mousses, S Bertone, P Madou, M Walt, D AF Mousses, S Bertone, P Madou, M Walt, D TI Genomic and proteomic array formats on the cutting-edge. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Tufts Univ, Medford, MA 02155 USA. Univ Calif Irvine, Irvine, CA 92717 USA. Yale Univ, New Haven, CT USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 8 BP 2 EP 2 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500009 ER PT J AU Scott, GN Betz, J Yetley, EA Smith, CS AF Scott, GN Betz, J Yetley, EA Smith, CS TI Medicinal herbals and dietary supplements. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Natl Inst Environm Hlth, Res Triangle Pk, NC USA. US FDA, College Pk, MD USA. NIH, Bethesda, MD 20892 USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 7 BP 2 EP 2 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500008 ER PT J AU Vaidya, VS Shankar, K Dixon, D Lock, EA Mehendale, HM AF Vaidya, VS Shankar, K Dixon, D Lock, EA Mehendale, HM TI Mechanisms of stimulated tissue repair in survival from acute renal tubular necrosis: Role of mapk pathway. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Louisiana, Dept Toxicol, Monroe, LA USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Syngenta CTL, Macclesfield, Cheshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 45 BP 9 EP 10 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500047 ER PT J AU Diwan, BA Waalkes, MP AF Diwan, BA Waalkes, MP TI The inability to produce the major forms of metallothionein renders mice hypersensitive to the chronic toxic effects of lead, including renal hyperplasia, while preventing inclusion body formation. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 SAIC, Frederick, MD USA. NIEHS, Inorgan Carcinogeneis Sect, LCC, NCI, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 70 BP 15 EP 15 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500072 ER PT J AU Faqi, AS Kozub, N Crowell, JA McCormick, DL AF Faqi, AS Kozub, N Crowell, JA McCormick, DL TI Neonatal estrogenization induces hypospadia and infertility in female rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 IIT, Res Inst, Chicago, IL 60616 USA. Natl Canc Inst, Div Canc Prevent, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 119 BP 25 EP 25 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500122 ER PT J AU Jefferson, WN Padilla-Banks, E Newbold, RR AF Jefferson, WN Padilla-Banks, E Newbold, RR TI Altered gene expression in the murine uterus following developmental treatment with genistein, a soy phytoestrogen. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 123 BP 26 EP 26 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500126 ER PT J AU Jokinen, MP Walkers, NJ Brix, AE Sells, DM Nyska, A AF Jokinen, MP Walkers, NJ Brix, AE Sells, DM Nyska, A TI Exacerbation of cardiovascular patholgies in female Sprague-Dawley rats following chronic treatment with 3,3,4,4,5-pentachlorobiphenyl (PCB126) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Sapir Med Ctr, Kefar Sava, Israel. Pathol Associates Inc, W Chester, OH USA. Harlan Biotech Israel Ltd, Rehovot, Israel. Univ Virginia, Dept Stat, Charlottesville, VA USA. Hebrew Univ Jerusalem, Fac Med Dent, Jerusalem, Israel. Hebrew Univ Jerusalem, Dept Biochem, Jerusalem, Israel. NR 0 TC 1 Z9 1 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 142 BP 30 EP 30 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500145 ER PT J AU Nyska, A Shabat, S Long, PH Ezov, N Levin-Harrus, T Paddada, S Rehdlich, M Yedgar, S Nyska, M AF Nyska, A Shabat, S Long, PH Ezov, N Levin-Harrus, T Paddada, S Rehdlich, M Yedgar, S Nyska, M TI Bone injury in a chemically induced rat model of human hemolytic disorders associated with thrombosis - Comparative pathological and MRI investigation. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC USA. Pathol Associates Inc, W Chester, OH USA. Harlan Biotech Israel Ltd, Rehovot, Israel. Univ Virginia, Dept Stat, Charlottesville, VA USA. Hebrew Univ Jerusalem, Fac Med Dent, Jerusalem, Israel. Hebrew Univ Jerusalem, Dept Biochem, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 143 BP 30 EP 30 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500146 ER PT J AU Stonerook, M Hassler, C Tosca, P Merrill, J Vasconcelos, D Smith, A AF Stonerook, M Hassler, C Tosca, P Merrill, J Vasconcelos, D Smith, A TI Cardiotoxicity study of NSC-638850 (UCN-01) and cytostar (Ara-C) given alone or in combination to beagle dogs. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Battelle Mem Inst, Columbus, OH 43201 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 171 BP 36 EP 36 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500174 ER PT J AU Morgan, DL Dill, JA Su, Y Westerberg, B Price, HC Shines, CJ Smith, CS AF Morgan, DL Dill, JA Su, Y Westerberg, B Price, HC Shines, CJ Smith, CS TI Evaluation of the chemical and physical properties of cellulose insulation aerosols and the potential acute pulmonary toxicity SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UT SP Soc Toxicol C1 NIEHS, Res Triangle Pk, NC USA. Battelle Pacific NW Labs, Richland, WA USA. Man Tech Environm Technol Inc, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 212 BP 44 EP 44 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500215 ER PT J AU Algaier, J Barnes, SM Canham, BA Decker, K Porter, AJ Harris, RK Clark, AP Overstreet, D Smith, CS AF Algaier, J Barnes, SM Canham, BA Decker, K Porter, AJ Harris, RK Clark, AP Overstreet, D Smith, CS TI Stabilization and analysis of pyrogallol (PG) in rat blood and in receptor fluid media. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Midwest Res Inst, Kansas City, MO USA. NIEHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 224 BP 46 EP 47 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500227 ER PT J AU Krishnaraj, R Crowell, J Levine, BS Pezzuto, J Morrissey, RL AF Krishnaraj, R Crowell, J Levine, BS Pezzuto, J Morrissey, RL TI Twenty-eight day toxicity study of the cancer chemopreventive agent 4-bromoflavone in rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Illinois, Chicago, IL USA. Pathol Associates Inc, Chicago, IL USA. NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 223 BP 46 EP 46 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500226 ER PT J AU Guo, TL Zhang, LX Brown, RD Germolec, DR White, KL AF Guo, TL Zhang, LX Brown, RD Germolec, DR White, KL TI Pyrogallol induces weak contact sensitization but strong irritation in female BALB/c mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Virginia Commonwealth Univ, Richmond, VA USA. NIEHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 249 BP 52 EP 52 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500252 ER PT J AU Mason, RP Lemasters, JJ AF Mason, RP Lemasters, JJ TI Free radicals in the toxicology of alcohols SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC USA. Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 265 BP 55 EP 55 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500268 ER PT J AU Heindel, J Shiverick, K AF Heindel, J Shiverick, K TI Gene-environment interactions in utero: The fetal basis of adult disease. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC USA. Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 271 BP 56 EP 56 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500274 ER PT J AU Mason, RP AF Mason, RP TI An in vivo ESR spin-trapping study: Free radical generation in rats from methanol and formate intoxication - Role of the fenton reaction. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 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 MAR PY 2003 VL 72 SU S MA 269 BP 56 EP 56 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500272 ER PT J AU Foster, P Turner, K Sar, M Barlow, N AF Foster, P Turner, K Sar, M Barlow, N TI Effects of environmental antiandrogens during fetal reproductive development: Consequences for the adult. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC USA. CIIT, Ctr Hlth Res, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 275 BP 57 EP 57 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500278 ER PT J AU Newbold, R AF Newbold, R TI Diethylstilbestrol(DES) exposure during development alters uterine gene expression: Influence on cancer later in life. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 276 BP 57 EP 57 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500279 ER PT J AU Bucher, JR Abdo, K AF Bucher, JR Abdo, K TI National toxicology program studies of hexavalent chromium. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 281 BP 58 EP 58 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500284 ER PT J AU Kim, AS Xie, H Mikheev, AM Sullivan, RC Zarbl, H AF Kim, AS Xie, H Mikheev, AM Sullivan, RC Zarbl, H TI Gene expression profiling of normal mammary tissues from rat strains sensitive and resistant to mammary carcinogenesis. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, NIEHS, Ctr Ecogenet & Environm Hlth, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 297 BP 61 EP 62 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500300 ER PT J AU Herr, DW Graff, JE Little, PB George, N Morgan, DL Sills, RC AF Herr, DW Graff, JE Little, PB George, N Morgan, DL Sills, RC TI 12 week exposure to carbonyl sulfide produces brain lesions and changes in brainstem auditory (BAER) and somatosensory (SEP) evoked potentials in Fischer 344N rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US EPA, Neurotoxicol, Durham, NC USA. Pathol Associates Inc, Res Triangle Pk, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 347 BP 72 EP 72 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500350 ER PT J AU Deldos, KB Weis, CC Olson, G Bucci, TJ Newbold, RR AF Deldos, KB Weis, CC Olson, G Bucci, TJ Newbold, RR TI A five generation reproductive toxicity assessment of the soy isoflavone genistein in CD Sprague-Dawley rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCTR, Jefferson, AR USA. Pathol Associates Int, Jefferson, AR USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 368 BP 76 EP 76 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500371 ER PT J AU Zhong, Z Connor, HD Mason, RP Moss, N Lemasters, JJ Thurman, RG AF Zhong, Z Connor, HD Mason, RP Moss, N Lemasters, JJ Thurman, RG TI Free radical formation in the rat kidney induced by cyclosporin A: Prevention by dietary glycine, renal denervation, and green tea polyphenols. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ N Carolina, Chapel Hill, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 396 BP 82 EP 82 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500399 ER PT J AU Ress, NB Roycroft, JH Hailey, JR Haseman, JK Chou, BJ Renne, R Dill, JA Miller, RA Bucher, JR AF Ress, NB Roycroft, JH Hailey, JR Haseman, JK Chou, BJ Renne, R Dill, JA Miller, RA Bucher, JR TI Toxic and carcinogenic effects in the lungs of rats and mice exposed to vanadium pentoxide by whole-body inhalation. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, NTP, Res Triangle Pk, NC 27709 USA. Battelle Toxicol NW, Richland, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 412 BP 85 EP 85 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500415 ER PT J AU Moser, G Elmore, A Spalding, J Streicker, M Goldsworthy, T Cannon, R AF Moser, G Elmore, A Spalding, J Streicker, M Goldsworthy, T Cannon, R TI Dermal exposure of male and female hemizygous Tg.AC and FVB/N mice for 52 weeks to n-nitrosodiethylamine (DEN). SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Integrated Lab Syst, Res Triangle Pk, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 420 BP 86 EP 87 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500423 ER PT J AU He, Y Craven, HR Barnes, DK Bell, DA AF He, Y Craven, HR Barnes, DK Bell, DA TI Differential response of human cell lines to arsenic: Evaluation of candidate genes. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 483 BP 100 EP 100 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500486 ER PT J AU Roberts, ES Charboneau, L Liotta, L Petricoin, E Dreher, KL AF Roberts, ES Charboneau, L Liotta, L Petricoin, E Dreher, KL TI Alterations in airway intracellular signaling pathways following air pollution particle (PM) exposure using laser capture microdissection and protein array technologies. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 N Carolina State Univ, Coll Vet Med, Raleigh, NC USA. NIH, Bethesda, MD 20892 USA. US FDA, CBER, Rockville, MD 20857 USA. US EPA, NHEERL, Res Triangle Pk, NC 27711 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 513 BP 106 EP 106 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500516 ER PT J AU Portier, CJ AF Portier, CJ TI Implications of epigenetic effects for modeling dose-response. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, ETP, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 548 BP 113 EP 113 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500551 ER PT J AU Merrick, BA Hartis, JE AF Merrick, BA Hartis, JE TI Conducting parallel genomics and proteomics studies: Comparative responses in gene expression. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 554 BP 114 EP 114 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500557 ER PT J AU Burback, BL Graves, S Smith, C Fomby, L AF Burback, BL Graves, S Smith, C Fomby, L TI The use of a validated method for the analysis of thujone in preliminary toxicokinetic rodent plasma and brain samples. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Battelle Mem Inst, Toxicol Columbus, Columbus, OH 43201 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 704 BP 145 EP 146 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500710 ER PT J AU Lebetkin, EH Chen, L Burka, LT AF Lebetkin, EH Chen, L Burka, LT TI Disposition of juglone in male F344 rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, LPC, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 711 BP 147 EP 147 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500717 ER PT J AU Valentine, JL Anderson, SA Yueh, Y Brine, DR Sparacino, CM Collins, BJ AF Valentine, JL Anderson, SA Yueh, Y Brine, DR Sparacino, CM Collins, BJ TI Toxicokinetics of AZT when administered in combination with trimethoprim and sulfamethoxazole to mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 RTI, Res Triangle Pk, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 718 BP 148 EP 148 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500724 ER PT J AU Bruno, ME Merrick, BA Iida, M Anna, CH Harris, JE Dubin, JR Tomer, KB Sills, RC Devereux, TR AF Bruno, ME Merrick, BA Iida, M Anna, CH Harris, JE Dubin, JR Tomer, KB Sills, RC Devereux, TR TI Differential expression of proteins during early mouse liver carcinogenesis induced by non-genotoxic model carcinogens oxazepam and Wyeth-14,643. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, NCT, Res Triangle Pk, NC 27709 USA. NIEHS, NCT, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 739 BP 152 EP 153 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500745 ER PT J AU Miller, MC Pittman, GS Collins, JB Grissom, SE Tucker, CJ Bushel, PR Paules, RS Bell, DA AF Miller, MC Pittman, GS Collins, JB Grissom, SE Tucker, CJ Bushel, PR Paules, RS Bell, DA TI Gene expression profiles: Evaluation of analytical and biological noise in cell lines. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, DIR, LCBRA GR, Res Triangle Pk, NC 27709 USA. NIEHS, DIR, OSD MA, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 735 BP 152 EP 152 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500741 ER PT J AU Paris, MW Strickland, JA Tice, RR Stokes, WS AF Paris, MW Strickland, JA Tice, RR Stokes, WS TI Establishment of rat LD50 reference values for chemicals tested in a validation study of in vitro cytotoxicity assays. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 ILS Inc, Res Triangle Pk, NC USA. NIEHS, NICEATM, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 760 BP 156 EP 157 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500765 ER PT J AU Strickland, JA Stokes, WS Casati, S Paris, MW Worth, AP Raabe, H Cao, C Clothier, R Harbell, J Curren, R Haseman, J Tice, RR AF Strickland, JA Stokes, WS Casati, S Paris, MW Worth, AP Raabe, H Cao, C Clothier, R Harbell, J Curren, R Haseman, J Tice, RR TI Design of a validation study to evaluate in vitro cytotoxicity assays for predicting rodent and human acute systemic toxicity. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 ILS Inc, Res Triangle Pk, NC USA. NIEHS, NICEATM, Res Triangle Pk, NC 27709 USA. JRC, ECVAM, Ispra, Italy. IIVS Inc, Gaithersburg, MD USA. USA, Edgewood Chem Biol Ctr, Aberdeen Proving Ground, MD USA. Univ Nottingham, Nottingham NG7 2RD, England. NR 0 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 761 BP 157 EP 157 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500766 ER PT J AU Tice, RR Daston, G Brown, T Shane, BS Inhof, CJ Zeiger, E Stokes, WS AF Tice, RR Daston, G Brown, T Shane, BS Inhof, CJ Zeiger, E Stokes, WS TI ICCVAM/NICEATM expert panel recommendations for the standardization and validation of in vitro estrogen receptor (ER) and androgen receptor (AR) binding assays. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 ILS Inc, Res Triangle Pk, NC USA. NIEHS, NICEATM, Res Triangle Pk, NC 27709 USA. Procter & Gamble, Cincinnati, OH USA. Johns Hopkins Univ, Baltimore, MD USA. Errol Zeiger Consulting, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 763 BP 157 EP 157 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500768 ER PT J AU Langenbach, R Nyska, A Brodsky, B Wormser, U AF Langenbach, R Nyska, A Brodsky, B Wormser, U TI Effects of sulfur mustard on skin toxicity in COX-1- and COX-2-deficient mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, Lab Expt Pathol, NIH, Res Triangle Pk, NC USA. Hebrew Univ Jerusalem, Inst Life Sci, IL-91904 Jerusalem, Israel. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 784 BP 162 EP 162 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500790 ER PT J AU Wormser, U Brodsky, B Sintov, A Casillas, RP Nyska, A AF Wormser, U Brodsky, B Sintov, A Casillas, RP Nyska, A TI Protective effects of topical iodine containing anti-inflammatory drugs against sulfur mustard-induced skin lesions. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Hebrew Univ Jerusalem, Inst Life Sci, IL-91904 Jerusalem, Israel. Ben Gurion Univ Negev, Inst Appl Res, IL-84105 Beer Sheva, Israel. Med Res & Evaluat Facil, Columbus, OH USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 785 BP 162 EP 162 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500791 ER PT J AU Tennant, R Wilson, S AF Tennant, R Wilson, S TI Advances in toxicogenomics: NIEHS National Center for Toxicogenomics. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 801 BP 165 EP 165 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500807 ER PT J AU Kang, Y Waalkes, MP AF Kang, Y Waalkes, MP TI Molecular mechanisms of cardiovascular toxicity of metals and metalloids. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Louisville, Sch Med, Louisville, KY 40292 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 807 BP 166 EP 166 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500813 ER PT J AU Tennant, R AF Tennant, R TI An approach to the classification of toxicological effects using microarray and proteomic technologies. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 804 BP 166 EP 166 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500810 ER PT J AU Waalkes, MP AF Waalkes, MP TI Novel insights into the cardiovascular toxicities of metals and metalloids. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 808 BP 166 EP 166 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500814 ER PT J AU Madden, MC Kadiiska, M AF Madden, MC Kadiiska, M TI Novel insights into the toxicology of lung oxidative stress. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US EPA, ORD, NHEERL, HSD,Clin Res Branch, Chapel Hill, NC USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 812 BP 167 EP 167 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500818 ER PT J AU Kadiiska, MB AF Kadiiska, MB TI Oxidative damage induced by CCL4 and ozone: Validation of biomarkers. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 815 BP 168 EP 168 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500821 ER PT J AU Reen, RK Ramadoss, P Jeffrey, PM Gonzalez, FJ Perdew, GH AF Reen, RK Ramadoss, P Jeffrey, PM Gonzalez, FJ Perdew, GH TI Establishment and characterization of simian virus 40 immortalized AhR-null mouse hepatocytes and their use to assess the role of the ah receptor in gene regulation. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, State Coll, PA USA. NCI, Lab Metab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 860 BP 177 EP 177 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500866 ER PT J AU Easterling, M Portier, CJ AF Easterling, M Portier, CJ TI Development of a physiologically-based pharmacokinetic model for the study of 2-methylimidazole kinetics. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Analyt Sci Inc, Durham, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 872 BP 179 EP 179 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500878 ER PT J AU Whitaker, SY Koken, PJ Portier, CJ AF Whitaker, SY Koken, PJ Portier, CJ TI A physiologically based pharmacokinetic model for gavage and I.V administration of methyleugenol in F344/N rats and B6C3F1 mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Lab Computat Biol & Risk Anal, NIH, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 873 BP 179 EP 180 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500879 ER PT J AU Chang, HF Hudson, VW Hazard, GF AF Chang, HF Hudson, VW Hazard, GF TI Haz-Map: Occupational health information for the public. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIH, Natl Lib Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 895 BP 184 EP 184 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500901 ER PT J AU Shankar, K Vaidya, VS Manautou, JE Corron, JC Bucci, TJ Liu, J Waalkes, MP Mehendale, HM AF Shankar, K Vaidya, VS Manautou, JE Corron, JC Bucci, TJ Liu, J Waalkes, MP Mehendale, HM TI PPAR-alpha activation is essential for diabetes-induced resistance against acetaminophen hepatotoxicity. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NE Louisiana Univ, Monroe, LA 71209 USA. Univ Connecticut, Dept Pharmacol Sci, Storrs, CT 06269 USA. Toxicogenom, Chapel Hill, NC USA. Pathol Associates Intl, NCTR, Jefferson, AR USA. NIEHS, Inorgan Carcinogenesis Sect, NCI, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 946 BP 195 EP 195 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500952 ER PT J AU Ju, C Reilly, T Bourdi, M Radonovich, M Brady, J George, J Pohl, L AF Ju, C Reilly, T Bourdi, M Radonovich, M Brady, J George, J Pohl, L TI Protective role of Kupffer cells in acetaminophen-induced hepatic injury in mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 953 BP 197 EP 197 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500959 ER PT J AU Welch, K Reilly, T Brady, J Pise-Masison, C Radonovich, M Pohl, L AF Welch, K Reilly, T Brady, J Pise-Masison, C Radonovich, M Pohl, L TI Investigating the polygenic control of susceptibility to drug-induced liver disease (DILD) using varied strains of mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NHLBI, US Dept HHS, NIH, Bethesda, MD 20892 USA. NCI, US Dept HHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 954 BP 197 EP 197 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500960 ER PT J AU Shipp, BK Kaphalia, L Atchison, CR Pohl, LR Aronson, JF Moslen, MT AF Shipp, BK Kaphalia, L Atchison, CR Pohl, LR Aronson, JF Moslen, MT TI Levamisole attenuates diclofenac-induced enteropathy in rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Gradient Corp, Cambridge, MD USA. Univ Texas, Med Branch, Galveston, TX 77555 USA. USA, Med Res Inst Chem Def, Aberdeen Proving Ground, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 984 BP 203 EP 203 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500990 ER PT J AU Schaaper, RM Dunn, RL Pavlov, YI AF Schaaper, RM Dunn, RL Pavlov, YI TI Toxic and mutagenic effects of base analogs. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 992 BP 205 EP 205 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500998 ER PT J AU Jiang, G Skorvaga, M van Houten, B Geacintov, N States, J AF Jiang, G Skorvaga, M van Houten, B Geacintov, N States, J TI Structure-dependent incision of stereoisomeric BPDE adducts by B-caldotenax universitvrabc excision nuclease. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Louisville, Louisville, KY 40292 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NYU, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1003 BP 207 EP 207 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501009 ER PT J AU Levine, BS Krishnaraj, R Morrissey, R Kapetanovic, I Crowell, J Pezzuto, JM AF Levine, BS Krishnaraj, R Morrissey, R Kapetanovic, I Crowell, J Pezzuto, JM TI Twenty-eight day toxicity study of the cancer chemopreventive agent 4-bromoflavone in dogs. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Illinois, Chicago, IL 60680 USA. Pathol Associates Inc, Chicago, IL USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1020 BP 210 EP 211 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501026 ER PT J AU Bollinger, L Tosca, P Ryan, M Brooker, M Grossi, I Smith, A AF Bollinger, L Tosca, P Ryan, M Brooker, M Grossi, I Smith, A TI Toxicity evaluation of halichondrin B analog in mice and beagle dogs following multiple intravenous exposures. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Battelle Mem Inst, Columbus, OH 43201 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1021 BP 211 EP 211 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501027 ER PT J AU Merrill, J Brooker, M Grossi, I Smith, A AF Merrill, J Brooker, M Grossi, I Smith, A TI Administration of 1-O-octadecyl-2-0-methyl-sn-glycero-1-D-deoxy-myo-inositol (OMDPI) in a hydroxypropyl-B-cyclodextrin vehicle reduces toxicity. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Battelle Mem Inst, Columbus, OH 43201 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1022 BP 211 EP 211 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501028 ER PT J AU Liu, J Xie, Y Ward, JM Diwan, BA Waalkes, MP AF Liu, J Xie, Y Ward, JM Diwan, BA Waalkes, MP TI Toxicogenomic analysis of aberrant gene expression in liver and liver tumors induced by transplacental exposure to inorganic arsenic in mice SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Inorgan Carcinogenesis Sect, LCC, NCI, Res Triangle Pk, NC 27709 USA. Natl Canc Inst, Frederick, MD USA. SAIC Frederick, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1038 BP 214 EP 214 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501044 ER PT J AU Liu, L Xie, Y Ward, JM Diwan, BA Waalkes, MP AF Liu, L Xie, Y Ward, JM Diwan, BA Waalkes, MP TI Toxicogenomic analysis of aberrant gene expression in liver and liver tumors induced by transplacental exposure to inorganic arsenic in mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. VA Med Ctr, Kansas City, MO USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1035 BP 214 EP 214 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501041 ER PT J AU Waalkes, MP Chen, H Xie, Y Diwan, BA Liu, J AF Waalkes, MP Chen, H Xie, Y Diwan, BA Liu, J TI Aberrant gene expression in liver and liver tumors induced by transplacental exposure to inorganic arsenic. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Inorgan Carcinogenesis Sect, LCC, NCI, Res Triangle Pk, NC 27709 USA. SAIC Frederick, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1037 BP 214 EP 214 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501043 ER PT J AU Xie, Y Liu, J Liu, Y Klaassen, CD Waalkes, MP AF Xie, Y Liu, J Liu, Y Klaassen, CD Waalkes, MP TI Toxicokinetic and genomic analysis of chronic arsenic exposure in multidrug-resistence double knockout mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Carcinogenesis Sect, LCC, NCI, Res Triangle Pk, NC 27709 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1039 BP 214 EP 215 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501045 ER PT J AU Achanzar, WE Lamar, PC Prozialeck, WC Webber, MM Waalkes, MP AF Achanzar, WE Lamar, PC Prozialeck, WC Webber, MM Waalkes, MP TI Specific changes in cadherin expression and localization are associated with cadmium-induced malignant transformation of human prostate epithelial cells. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Inorgan Carcinogenesis Sect, LCC, NCI, Res Triangle Pk, NC 27709 USA. Midwestern Univ, Downers Grove, IL 60515 USA. Michigan State Univ, E Lansing, MI 48824 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1043 BP 215 EP 215 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501049 ER PT J AU Benbrahim-Tallaa, L Achanzar, WE Brambila, EM Webber, MM Waalkes, MP AF Benbrahim-Tallaa, L Achanzar, WE Brambila, EM Webber, MM Waalkes, MP TI Altered gene expression associated with arsenite-induced malignant transformation of human prostate epithelial cells. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Inorgan Carcinogenesis Sect, LCC, NCI, Res Triangle Pk, NC 27709 USA. Univ Autonoma Puebla, Puebla 72570, Mexico. Michigan State Univ, E Lansing, MI 48824 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1042 BP 215 EP 215 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501048 ER PT J AU Brambila, EM Achanzar, WE Diwan, BA Chen, H Webber, MM Waalkes, MP AF Brambila, EM Achanzar, WE Diwan, BA Chen, H Webber, MM Waalkes, MP TI Malignant transformation and DNA hypomethylation in human prostate epithelial cells chronically exposed to inorganic arsenite. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Autonoma Puebla, Puebla 72570, Mexico. NIEHS, Carcinogenesis Sect, LCC, NCI, Res Triangle Pk, NC 27709 USA. SAIC, Frederick, MD USA. Michigan State Univ, E Lansing, MI 48824 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1041 BP 215 EP 215 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501047 ER PT J AU Chen, H Waalkes, MP AF Chen, H Waalkes, MP TI Chromosome alterations and hyperproliferation associated with chronic arsenic exposure. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Inorgan Carcinogenesis Sect, LCC, NCI, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1040 BP 215 EP 215 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501046 ER PT J AU Qu, W Diwan, BA Waalkes, MP AF Qu, W Diwan, BA Waalkes, MP TI Aberrant oncogene expression associated with cadmium-induced malignant transformation in rat liver cells. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Inorgan Carcinogenesis Sect, LCC, NCI, Res Triangle Pk, NC 27709 USA. SAIC Frederick, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1046 BP 216 EP 216 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501052 ER PT J AU Hudson, VW Chang, HF Mashayekhi, B AF Hudson, VW Chang, HF Mashayekhi, B TI Altbib: Alternatives to animal testing database. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIH, Natl Lib Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1063 BP 219 EP 219 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501069 ER PT J AU Shane, BS Stegeman, J Wilson, EM Inhof, CJ Tice, RR Zeiger, E Stokes, WS AF Shane, BS Stegeman, J Wilson, EM Inhof, CJ Tice, RR Zeiger, E Stokes, WS TI ICCVAM/NICEATM expert panel recommendations for the standardization and validation of in vitro estrogen receptor (ER) and androgen receptor (AR) transcriptional activation (TA) assays. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 ILS Inc, Res Triangle Pk, NC USA. NIEHS, NICEATM, Res Triangle Pk, NC 27709 USA. Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA. Univ N Carolina, Chapel Hill, NC USA. Errol Zeiger Consulting, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1071 BP 221 EP 221 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501077 ER PT J AU Ramos, KS Johnson, CD Falahatpisheh, MH Thomas, T Beremand, P Tadesse, M Lu, KP Balagurunathan, Y Afshari, CA Dougherty, R AF Ramos, KS Johnson, CD Falahatpisheh, MH Thomas, T Beremand, P Tadesse, M Lu, KP Balagurunathan, Y Afshari, CA Dougherty, R TI Application of clustering methodologies to the analysis of altered cellular phenotypes induced by oxidative stress. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Texas A&M Univ, Ctr Environm & Rural Hlth, College Stn, TX USA. Natl Inst Environm Hlth Sci, Microarray Ctr, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1084 BP 223 EP 223 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501090 ER PT J AU Paules, RS Hamadeh, HK Afshari, CA Tennant, RW Bushel, PR AF Paules, RS Hamadeh, HK Afshari, CA Tennant, RW Bushel, PR TI Toxicogenomics and the quest for predictive toxicology. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Natl Inst Environm Hlth Sci, Microarray Ctr, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, Natl Ctr Toxicogenomics, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1086 BP 224 EP 224 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501092 ER PT J AU Walker, V Ghanayem, B AF Walker, V Ghanayem, B TI Mutagenicity at the HPRT locus of T-cells following exposure of wild-type and cytochrome P4502E1-null mice to acrylonitrile. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Lovelace Resp Res Inst, Albuquerque, NM USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1108 BP 228 EP 228 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501114 ER PT J AU French, JE AF French, JE TI Identification of carcinogens using TRP53 heterozygous null mice and loss of heterozygosity at the TRP53 locus. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1112 BP 229 EP 229 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501118 ER PT J AU Xie, A Walker, NJ Wang, D AF Xie, A Walker, NJ Wang, D TI The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on triggered-afterdepolarizations in isolated rat ventricular myocytes. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ S Carolina, Coll Pharm, Columbia, SC 29208 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1123 BP 231 EP 231 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501129 ER PT J AU Maciag, AE Sithanandam, G Kasprzak, KS Anderson, LM AF Maciag, AE Sithanandam, G Kasprzak, KS Anderson, LM TI Expression of mutant K-rasV12 in mouse lung epithelial cells increases generation of peroxides through cox-2, resulting in DNA damage. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. SAIC Frederick, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1142 BP 235 EP 235 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501148 ER PT J AU Martinez, JM Baek, S Eling, TE Walker, NJ AF Martinez, JM Baek, S Eling, TE Walker, NJ TI Regulation of EGR-1 by TCDD in human lung epithelial cells. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1153 BP 237 EP 237 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501159 ER PT J AU Lomnitski, L Padilla-Banks, E Jefferson, WN Nyska, A Grossman, S Newbold, RR AF Lomnitski, L Padilla-Banks, E Jefferson, WN Nyska, A Grossman, S Newbold, RR TI Lack of estrogenic or anti-estrogenic activity of the antioxidant NAO found in spinach. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. Bar Ilan Univ, Inst Life Sci, Ramat Gan, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1242 BP 255 EP 255 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501247 ER PT J AU Haugen, A Hamadeh, HK Collins, J Bushel, P Miller, J Tucker, CJ Gordenin, A Karthikeyan, G Afshari, C Van Houten, B AF Haugen, A Hamadeh, HK Collins, J Bushel, P Miller, J Tucker, CJ Gordenin, A Karthikeyan, G Afshari, C Van Houten, B TI Evolutionarily conserved responses to arsenic in yeast and human cells. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1281 BP 263 EP 263 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501286 ER PT J AU Pi, J Wei, Q Waalkes, MP Kumagai, Y AF Pi, J Wei, Q Waalkes, MP Kumagai, Y TI Arsenic impacts Nrf2 transcription factor and related gene expression in cultured keratinocyte cells. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, NCI, Inorgan Carcinogenesis Sect, LCC, Res Triangle Pk, NC 27709 USA. Univ Tsukuba, Inst Community Med, Dept Environm Med, Tsukuba, Ibaraki 305, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1306 BP 268 EP 269 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501313 ER PT J AU Trouba, KJ Geisenhoffer, KM Germolec, DR AF Trouba, KJ Geisenhoffer, KM Germolec, DR TI Mitogen and stress signal transduction pathways contribute to sodium arsenite-induced cyclooxygenase-2 expression in normal human epidermal keratinocytes. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1309 BP 269 EP 269 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501316 ER PT J AU Nesnow, S Roop, BC Lambert, G Kadiiska, M Mason, RP Cullen, WR Mass, MJ AF Nesnow, S Roop, BC Lambert, G Kadiiska, M Mason, RP Cullen, WR Mass, MJ TI DNA damage induced by methylated trivalent arsenicals is mediated by reactive oxygen species. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US EPA, Div Environm Carcinogenesis, Res Triangle Pk, NC 27711 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Univ British Columbia, Dept Chem, Vancouver, BC, Canada. NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1314 BP 270 EP 270 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501321 ER PT J AU Bowman, CJ Barlow, NJ Turner, KJ Wallace, DG Foster, PM AF Bowman, CJ Barlow, NJ Turner, KJ Wallace, DG Foster, PM TI Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rat. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Ctr Hlth Res, CIIT, Res Triangle Pk, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1336 BP 275 EP 275 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501343 ER PT J AU Foster, RM Turner, KJ Sar, M Barlo, NJ Gaido, KW Bowman, CJ AF Foster, RM Turner, KJ Sar, M Barlo, NJ Gaido, KW Bowman, CJ TI Molecular characterization of the developing rat Wolffian ducts following in utero exposure to di(n-butyl) phthalate. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Res Triangle Pk, NC 27709 USA. Ctr Hlth Res, CIIT, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1335 BP 275 EP 275 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501342 ER PT J AU Turner, KJ McIntyre, BS Phillips, SL Barlow, NJ Bowman, CJ Foster, PM AF Turner, KJ McIntyre, BS Phillips, SL Barlow, NJ Bowman, CJ Foster, PM TI Effects of in utero exposure to linuron on rat Wolffian duct development. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Ctr Hlth Res, CIIT, Res Triangle Pk, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1337 BP 275 EP 275 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501344 ER PT J AU Barlow, NJ Phillips, SL Wallace, DG Sar, M Gaido, KW Foster, PM AF Barlow, NJ Phillips, SL Wallace, DG Sar, M Gaido, KW Foster, PM TI Fetal testicular gene expression following in utero exposure to di(n-butyl) phthalate: Alteration of key androgen-related genes. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Ctr Hlth Res, CIIT, Res Triangle Pk, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1340 BP 276 EP 276 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501347 ER PT J AU Krawetz, SA Ostermeier, G Thompson, KE Dix, DJ Miller, D Goodrich, R Diamond, MP AF Krawetz, SA Ostermeier, G Thompson, KE Dix, DJ Miller, D Goodrich, R Diamond, MP TI The male gamete as a paternal marker of genetic insult. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Wayne State Univ, Inst Sci & Comp, Detroit, MI USA. Wayne State Univ, NICHD, Reprod Med Network, Detroit, MI USA. Wayne State Univ, Dept Ob Gyn, Detroit, MI USA. US EPA, ORD, NHEERL, Reprod Toxicol Div, Res Triangle Pk, NC USA. Univ Leeds, Dept Ob Gyn, Leeds LS2 9JT, W Yorkshire, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1344 BP 276 EP 277 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501351 ER PT J AU Fornace, AJ Amundson, SA Koch-Paiz, C Lee, R AF Fornace, AJ Amundson, SA Koch-Paiz, C Lee, R TI Gene expression in response to low dose ionizing radiation: A functional genomics approach. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1345 BP 277 EP 277 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501352 ER PT J AU George, M Murr, A Goldman, J Herbert, C Joe, R Melnick, R Geter, D DeAngelo, AB AF George, M Murr, A Goldman, J Herbert, C Joe, R Melnick, R Geter, D DeAngelo, AB TI Evaluation of the toxicity of bromochloroacetic acid administered for 26 weeks in drinking water to B6C3F1 mice and F344 rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US EPA, NHEERL, Res Triangle Pk, NC USA. So Res Inst, Birmingham, AL USA. NIEHS, NTP, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1460 BP 300 EP 301 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501466 ER PT J AU Tosca, P Grossi, I Brooker, M Turner, N Chang, E Donohue, S AF Tosca, P Grossi, I Brooker, M Turner, N Chang, E Donohue, S TI Toxicity comparison of liposomes comprised of dioleoyltrimethylammonium propane : dioleoylphosphatidylethanolamine (DOTAP : DOPE) or dimethyldioctadecylammonium bromide : dioleoylphosphatidylethanolamin E (DDAB : DOPE) following multiple IV injections in Fischer 344 rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Battelle Mem Inst, Columbus, OH USA. Georgetown Univ, Washington, DC USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1472 BP 303 EP 303 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501478 ER PT J AU Moomaw, CR Foley, JF Nyska, A AF Moomaw, CR Foley, JF Nyska, A TI Enhanced expression of vascular coagulation adhesion molecule (VCAM-1) in 2-butoxyethanol-induced hemolysis and thrombosis in female rats. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1512 BP 311 EP 311 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501518 ER PT J AU Sanders, JM Abu-Shakra, A Burka, LT Cunningham, ML AF Sanders, JM Abu-Shakra, A Burka, LT Cunningham, ML TI Mutagenicity studies of urinary metabolites from rats treated orally with local anesthetics. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Res Triangle Pk, NC USA. NCSU, Raleigh, NC USA. NCCU, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1531 BP 315 EP 315 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501537 ER PT J AU Ghanayem, BI El Hadri, L Chanas, B Ferguson, LC Burka, LT AF Ghanayem, BI El Hadri, L Chanas, B Ferguson, LC Burka, LT TI Comparative metabolism of cis and trans crotononitrile (CrN) to cyanide using cytochrome P405 2E1-null and wild type mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1545 BP 318 EP 318 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501551 ER PT J AU Hoffler, U Ghanayem, BI AF Hoffler, U Ghanayem, BI TI Inhibition of urethane metabolism and bioaccumulation in cytochrome P450 2E1-null mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Meharry Med Coll, Nashville, TN 37208 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1546 BP 318 EP 319 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501552 ER PT J AU Wolf, KK Wood, S Bement, J Bement, W Wrighton, S Jeffery, E Gonzalez, F Sinclair, P Sinclair, J AF Wolf, KK Wood, S Bement, J Bement, W Wrighton, S Jeffery, E Gonzalez, F Sinclair, P Sinclair, J TI CYP2E1 is not specific for formation of 6-hydroxychlorzoxazone in vivo. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Dartmouth Coll Sch Med, Hanover, NH USA. VA Med Ctr, White River Jct, VT USA. Lilly Res Labs, Indianapolis, IN USA. Univ Illinois, Urbana, IL 61801 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1542 BP 318 EP 318 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501548 ER PT J AU El Hadri, L Chanas, B Ghanayem, BI AF El Hadri, L Chanas, B Ghanayem, BI TI Comparative metabolism of acrylonitrile and methacrylonitrile to cyanide: Studies using cytochrome P4502E1 (CYP2E1)- and microsomal epoxide hydrolase (MEH)-null mice. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1548 BP 319 EP 319 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501554 ER PT J AU Yao, J Li, Y Chang, M Wu, H Goodman, JE Liu, X Liu, H Mesecar, AD van Breemen, RB Yager, JD Bolton, JL AF Yao, J Li, Y Chang, M Wu, H Goodman, JE Liu, X Liu, H Mesecar, AD van Breemen, RB Yager, JD Bolton, JL TI Equine catechol estrogen 4-hydroxyequilenin is a substrate and an inhibitor of catechol-o-methyltransferase. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Illinois, Chicago, IL USA. Johns Hopkins Univ, Baltimore, MD USA. NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1557 BP 321 EP 321 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501564 ER PT J AU Gallagher, EP Gardner, JL Huisden, CM Doi, AM Moneypenny, CG AF Gallagher, EP Gardner, JL Huisden, CM Doi, AM Moneypenny, CG TI Hematopoietic stem cells as targets for transplacental toxicants. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Florida, Gainesville, FL USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1562 BP 322 EP 322 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501569 ER PT J AU Gorman, N Trask, H Bement, W Sinclair, J Gerhard, G Smith, A Gonzalez, F Sinclair, P AF Gorman, N Trask, H Bement, W Sinclair, J Gerhard, G Smith, A Gonzalez, F Sinclair, P TI Hexachlorobenzene increases uroporphyria in mice without increasing CYP1A2. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 VA Med Ctr, White River Jct, VT USA. Dartmouth Coll Sch Med, Hanover, NH USA. Univ Leicester, MRC Toxicol Unit, Leicester, Leics, England. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1568 BP 323 EP 323 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501575 ER PT J AU Mckarns, SC Schwartz, RH AF Mckarns, SC Schwartz, RH TI Differential regulation of IL-2 gene transcription by TGF-beta 1 in naive and effector/memory CD4(+) T cells. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIAID, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1608 BP 331 EP 332 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501615 ER PT J AU Davis, BJ Fenton, S AF Davis, BJ Fenton, S TI Environmental modulation of puberty SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Lab Women, Res Triangle Pk, NC USA. US EPA, Res Triangle Pk, NC 27711 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1616 BP 333 EP 333 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501623 ER PT J AU Forman, MR AF Forman, MR TI A longer puberty in humans: What in the world will become of it? SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1618 BP 333 EP 334 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501625 ER PT J AU Irwin, R Boorman, GA Paules, R Heinloth, A Terman, RW Snell, ML Cunningham, ML AF Irwin, R Boorman, GA Paules, R Heinloth, A Terman, RW Snell, ML Cunningham, ML TI Gene expression changes in F344 rats following a pharmacological dose of acetaminophen. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1648 BP 340 EP 340 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501655 ER PT J AU O'Brien, BM Messer, D Porter, A Brackman, K Harris, RK Clark, AP Algaier, JW Overstreet, D Smith, CS AF O'Brien, BM Messer, D Porter, A Brackman, K Harris, RK Clark, AP Algaier, JW Overstreet, D Smith, CS TI Analytical method validation of Ginkgo biloba L. powder extract dosed in 0.5% (w/v) aqueous methylcellulose. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Midwest Res Inst, Kansas City, MO 64110 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1667 BP 343 EP 344 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501674 ER PT J AU Weber, HA Hodges, AE Moody, LA O'Brien, BM Guthrie, JR Harris, RK Clark, AP Overstreet, D Smith, CS AF Weber, HA Hodges, AE Moody, LA O'Brien, BM Guthrie, JR Harris, RK Clark, AP Overstreet, D Smith, CS TI Chemical characterization of pine bark and grape seed extracts. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Midwest Res Inst, Kansas City, MO 64110 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1666 BP 343 EP 343 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501673 ER PT J AU Graves, S Burback, B Smith, C AF Graves, S Burback, B Smith, C TI Characterization of ginseng for use in toxicity studies. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Res Triangle Pk, NC 27709 USA. Battelle Mem Inst, Toxicol Columbus, Columbus, OH USA. NR 0 TC 1 Z9 1 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1669 BP 344 EP 344 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501676 ER PT J AU Gray, D Rottinghaus, G Porter, A Oberlies, N Kim, N McGivney, R Harris, R Clark, A Overstreet, D Smith, C AF Gray, D Rottinghaus, G Porter, A Oberlies, N Kim, N McGivney, R Harris, R Clark, A Overstreet, D Smith, C TI A rapid extraction and isolation method for the determination of pyrrolizidine alkaloids in comfrey. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Midwest Res Inst, Kansas City, MO 64110 USA. Univ Missouri, Columbia, MO USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1668 BP 344 EP 344 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501675 ER PT J AU Brix, AE Jokinen, MP Walker, NJ Sells, DM Nyska, A AF Brix, AE Jokinen, MP Walker, NJ Sells, DM Nyska, A TI Characterization of bronchial metaplasia in rats exposed to 3,3,4,4,5-pentachlorobiphenyl (PCB 126). SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. A Charles River Co, Pathol Associates, Durham, NC USA. EPL, Res Triangle Pk, NC USA. Battelle Columbus, Columbus, OH USA. RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1757 BP 362 EP 362 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501764 ER PT J AU Seguin, B Ju, C Pohl, L Uetrecht, J AF Seguin, B Ju, C Pohl, L Uetrecht, J TI Penicillamine (PA)-induced autoimmunity: New insight into the mechanism of covalent binding in vivo. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Univ Toronto, Toronto, ON, Canada. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1810 BP 373 EP 373 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501817 ER PT J AU Patterson, RM Vega-Lloyo, L Trouba, KJ Teague, JA Germolec, DR AF Patterson, RM Vega-Lloyo, L Trouba, KJ Teague, JA Germolec, DR TI Arsenic-induced alterations in contact hypersensitivity. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 NIEHS, LMT, Res Triangle Pk, NC 27709 USA. CINVESTAV, Natl Polytech Inst, Mexico City 14000, DF, Mexico. RI Vega, Libia/C-3391-2013 OI Vega, Libia/0000-0002-4993-5267 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1828 BP 376 EP 377 PG 2 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501835 ER PT J AU Moser, VC Padilla, S Barone, S Smialowicz, RJ Harris, MW Chapin, RE AF Moser, VC Padilla, S Barone, S Smialowicz, RJ Harris, MW Chapin, RE TI A comparison of multiple toxicities following developmental exposure to pesticides: Neurotoxicity, immunotoxicity and reproductive toxicity. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 US EPA, NHEERL, Res Triangle Pk, NC USA. NIEHS, NTP, Res Triangle Pk, NC USA. Pfizer, Groton, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1883 BP 388 EP 388 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501890 ER PT J AU Zalups, DK Aslamkhan, A Barfuss, DW Ahmad, S AF Zalups, DK Aslamkhan, A Barfuss, DW Ahmad, S TI Madin-Darby canine kidney (MDCK) cells gain the ability to transport mercuric conjugates of cysteine (CYS) or N-acteylcysteine (NAC) after being stably transfected with OAT1. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Mercer Univ, Sch Med, Macon, GA 31207 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Georgia State Univ, Atlanta, GA 30303 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1946 BP 401 EP 401 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501953 ER PT J AU Drew, WL Tegtmeier, G Alter, HJ Laycock, ME Miner, RC Busch, MP AF Drew, WL Tegtmeier, G Alter, HJ Laycock, ME Miner, RC Busch, MP TI Frequency and duration of plasma CMV viremia in seroconverting blood donors and recipients SO TRANSFUSION LA English DT Article ID CYTOMEGALO-VIRUS INFECTIONS; BONE-MARROW TRANSPLANTATION; LEUKOCYTE-REDUCTION; MONONUCLEAR-CELLS; PRODUCTS; PREVENTION; DNA; FILTRATION; INFANTS AB BACKGROUND: Both CMV-seronegative blood and unscreened, filtered blood carry a low but definite risk of transmitting CMV infection. To explain this residual risk, evidence of cell-free viremia was sought in seroconverting and seroprevalent blood donors and seroconverting transfusion recipients by means of a plasma-based assay for CMV DNA. STUDY DESIGN AND METHODS: A CMV DNA PCR assay (COBAS Amplicor CMV Monitor, Roche) was used to detect CMV DNA in 384 paired plasma samples from 192 donors who seroconverted to anti-CMV, 488 anti-CMV EIA-positive samples from 60 seroprevalent donors, and 113 serial samples from 11 seroconverting recipients with posttransfusion CMV hepatitis. RESULTS: Three of 384 samples from 192 seroconverting donors had low levels of plasma CMV DNA (4001600 copies/mL); one donor was positive before seroconversion, and the other two, after seroconversion. None of the 488 serial samples from 60 anti-CMV-positive donors contained CMV DNA in plasma. Three of 11 recipients demonstrated transient plasma viremia that temporally coincided with seroconversion. CONCLUSIONS: Plasma CMV DNA was detected in a small percentage of seroconverting blood donors and a larger percentage of recipients but was undetectable in seroprevalent donors. Plasma viremia in seroconverting donors may partially explain the low residual risk of CMV transmission by both CMV-seronegative and WBC-reduced seropositive blood. C1 Univ Calif San Francisco, Mt Zion Med Ctr, San Francisco, CA 94115 USA. Blood Ctr Pacific, San Francisco, CA USA. Community Blood Ctr Greater Kansas City, Kansas City, MO USA. NIH, Bethesda, MD 20892 USA. Blood Syst Inc, Scottsdale, AZ USA. RP Drew, WL (reprint author), Univ Calif San Francisco, Mt Zion Med Ctr, 1600 Divisadero St,Box 1629, San Francisco, CA 94115 USA. EM Lawrence.Drew@clinlab.ucsfmedctr.org NR 19 TC 37 Z9 37 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 2003 VL 43 IS 3 BP 309 EP 313 DI 10.1046/j.1537-2995.2003.00337.x PG 5 WC Hematology SC Hematology GA 658QU UT WOS:000181732600004 PM 12675714 ER PT J AU Caruccio, L Bettinotti, M Matsuo, K Sharon, V Stroncek, D AF Caruccio, L Bettinotti, M Matsuo, K Sharon, V Stroncek, D TI Expression of human neutrophil antigen-2a (NB1) is increased in pregnancy SO TRANSFUSION LA English DT Article ID MONOCLONAL-ANTIBODIES; GENE-FREQUENCIES; MOLECULAR-BASIS; CD177; GLYCOPROTEIN; PATHOGENESIS AB BACKGROUND: The expression of human neutrophil antigen-2a (HNA-2a) or NB1 is highly variable. This study investigated variations in neutrophil expression of HNA-2a by comparing the expression of epitopes recognized by three HNA-2a-specific CD177 antibodies among healthy adults and pregnant women. STUDY DESIGN AND METHODS: Flow cytometry was used to compare the neutrophil reactions of three CD177 antibodies (MEM-166, TAG4, and 7D8) among 52 healthy adults. Because HNA-2a expression is greater in women than men, neutrophils were studied from 21 women early in pregnancy and 23 women late in pregnancy. RESULTS: All three CD177 antibodies reacted with two populations of neutrophils: a brightly staining population and a dimly staining population. Among the 52 healthy adults, there was no difference in the mean size of the brightly reactive population of neutrophils recognized by each antibody (46 +/- 23% for MEM-166, 49 23% for TAG4, and 49 23% for 7D8), and all three antibodies were specific for HNA-2a. For all three antibodies the size of the antigen bright neutrophil population was greater on neutrophils collected both early and late in pregnancy than in healthy adults. There was no difference in the size of the antigen bright population among neutrophils tested early and late in pregnancy. CONCLUSION: HNA-2a antigen expression increases in pregnancy. Some of the variations in neutrophil expression of HNA-2a among individuals is likely due to differences in gene regulation or differences in post-translational protein modifications rather than gene polymorphisms. C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. Kurume Univ, Dept Internal Med 1, Kurume, Fukuoka 830, Japan. RP Stroncek, D (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, 10 Ctr Dr,MSC-1184,Bldg 10, Bethesda, MD 20892 USA. EM dstroncek@dtm.cc.nih.gov NR 20 TC 19 Z9 20 U1 0 U2 3 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 2003 VL 43 IS 3 BP 357 EP 363 DI 10.1046/j.1537-2995.2003.00320.x PG 7 WC Hematology SC Hematology GA 658QU UT WOS:000181732600012 PM 12675722 ER PT J AU Steven, AC Aebi, U AF Steven, AC Aebi, U TI The next ice age: cryo-electron tomography of intact cells SO TRENDS IN CELL BIOLOGY LA English DT Editorial Material ID CRYOELECTRON TOMOGRAPHY AB Recent advances in electron tomography are beginning to reveal the internal structure of eukaryotic cells in their native states in three dimensions at molecular resolution. These observations represent the culmination of years of effort to develop protocols for automated data collection, image reconstruction and cryogenic preservation. Cryo-tomograms of Dictyostelium cells depict distinct populations of ribosomes, proteasomes and networks of actin filaments interconnected by branching or bundling, apparently controlled by strategically placed actin-associated proteins. C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Basel, Bioctr, ME Muller Inst Struct Biol, CH-4056 Basel, Switzerland. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. EM Alasdair_Steven@nih.gov; Ueli.Aebi@unibas.ch NR 15 TC 48 Z9 50 U1 0 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD MAR PY 2003 VL 13 IS 3 BP 107 EP 110 DI 10.1016/S0962-8924(03)00023-0 PG 4 WC Cell Biology SC Cell Biology GA 658PF UT WOS:000181728800001 PM 12628341 ER PT J AU Kim, T Tao-Cheng, JH Eiden, LE Loh, YP AF Kim, T Tao-Cheng, JH Eiden, LE Loh, YP TI The role of chromogranin A and the control of secretory granule genesis and maturation SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Letter ID PC12 CELLS; EXPRESSION; PATHWAY; GLANDS C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, EM Facil, NIH, Bethesda, MD 20892 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. EM ypl@codon.nih.gov OI Eiden, Lee/0000-0001-7524-944X NR 13 TC 16 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD MAR PY 2003 VL 14 IS 2 BP 56 EP 57 AR PII S1043-2760(02)00041-3 DI 10.1016/S1043-2760(02)00041-3 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 658PJ UT WOS:000181729100004 PM 12591171 ER PT J AU Kondrashov, FA Koonin, EV AF Kondrashov, FA Koonin, EV TI Evolution of alternative splicing: deletions, insertions and origin of functional parts of proteins from intron sequences SO TRENDS IN GENETICS LA English DT Article ID EXON DUPLICATION; MESSENGER-RNAS; EXPRESSION; DATABASE; LOCALIZATION; GENERATION; ISOFORMS; CLONING; HSP105; GENES AB Alternative splicing is thought to be a major source of functional diversity in animal proteins. We analyzed the evolutionary conservation of proteins encoded by alternatively spliced genes and predicted the ancestral state for 73 cases of alternative splicing (25 insertions and 48 deletions). The amino acid sequences of most of the inserts in proteins produced by Alternative splicing are as conserved as the surrounding sequences. Thus, alternative splicing often creates novel isoforms by the insertion of new, functional protein sequences that probably originated from noncoding sequences of introns. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Kondrashov, FA (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM fkondras@ncbi.nlm.nih.gov RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 NR 25 TC 75 Z9 80 U1 2 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAR PY 2003 VL 19 IS 3 BP 115 EP 119 DI 10.1016/S0168-9525(02)00029-X PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 655ZW UT WOS:000181584500002 PM 12615001 ER PT J AU Glazko, GV Koonin, EV Rogozin, IB Shabalina, SA AF Glazko, GV Koonin, EV Rogozin, IB Shabalina, SA TI A significant fraction of conserved noncoding DNA in human and mouse consists of predicted matrix attachment regions SO TRENDS IN GENETICS LA English DT Article ID NUCLEAR MATRIX; INTERGENIC REGIONS; GENE-EXPRESSION; SEQUENCES; MAR; ENHANCER; ELEMENTS; GENOMES; CLUSTER AB Noncoding DNA in the human-mouse orthologous intergenic regions contains 'islands' of conserved sequences, the functions of which remain largely unknown. We hypothesized that some of these regions might be matrix-scaffold attachment regions, MARs (or S/MARs). MARs comprise one of the few classes of eukaryotic noncoding DNA with an experimentally characterized function, being involved in the attachment of chromatin to the nuclear matrix, chromatin remodeling and transcription regulation. To test our hypothesis, we analyzed the co-occurrence of predicted MARs with highly conserved noncoding DNA regions in human-mouse genomic alignments. We found that 11% of the conserved noncoding DNA consists of predicted MARs. Conversely, more than half of the predicted MARs co-occur with one or more independently identified conserved sequence blocks. An excess of conserved predicted MARs is seen in intergenic regions preceding 5' ends of genes, suggesting that these MARs are primarily involved in transcriptional control. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Penn State Univ, Inst Mol Evolut Genet, Mueller Lab 328, University Pk, PA 16802 USA. Penn State Univ, Dept Biol, Mueller Lab 328, University Pk, PA 16802 USA. RP Shabalina, SA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 45,8600 Rockville Pike, Bethesda, MD 20894 USA. RI Shabalina, Svetlana/N-8939-2013 OI Shabalina, Svetlana/0000-0003-2272-7473 NR 25 TC 68 Z9 77 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAR PY 2003 VL 19 IS 3 BP 119 EP 124 DI 10.1016/S0168-9525(03)00016-7 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 655ZW UT WOS:000181584500003 PM 12615002 ER PT J AU Merlino, G Noonan, FP AF Merlino, G Noonan, FP TI Modeling gene-environment interactions in malignant melanoma SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID COMPARATIVE GENOMIC HYBRIDIZATION; FIBROBLAST-GROWTH-FACTOR; MAMMALIAN UV RESPONSE; ULTRAVIOLET-RADIATION; CUTANEOUS MELANOMA; TRANSGENIC MICE; HUMAN SKIN; XERODERMA-PIGMENTOSUM; MELANOCYTIC LESIONS; TUMOR-SUPPRESSOR AB Many cancers are the pathological consequence of environmentally initiated disruptions to cellular genetic control mechanisms. For most cancers the relevant environmental carcinogens have not been identified, but one major exception is cutaneous malignant melanoma, for which the primary environmental agent is solar ultraviolet (UV) radiation. Hence, melanomagenesis represents a potential model of detrimental gene-environment interaction. Although the underlying genetic basis of melanoma is currently being elucidated, fundamental questions concerning UV and the mechanisms by which it operates remain unanswered. Significant progress has recently been made in creating UV-responsive, genetically tractable mouse models of melanoma that accurately recapitulate human disease. These models are providing novel insights into how the genome and environment interact in vivo. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Environm & Occupat Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC 20037 USA. RP Merlino, G (reprint author), NCI, Mol Biol Lab, Bldg 37,Room 5002, Bethesda, MD 20892 USA. NR 83 TC 17 Z9 18 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD MAR PY 2003 VL 9 IS 3 BP 102 EP 108 DI 10.1016/S1471-4914(03)00006-6 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 666UJ UT WOS:000182194600004 PM 12657431 ER PT J AU Mattson, MP Shea, TB AF Mattson, MP Shea, TB TI Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders SO TRENDS IN NEUROSCIENCES LA English DT Review ID METHYLENETETRAHYDROFOLATE REDUCTASE DEFICIENCY; BETA-SYNTHASE DEFICIENCY; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; FOLIC-ACID; PLASMA HOMOCYSTEINE; S-ADENOSYLMETHIONINE; CEREBROSPINAL-FLUID; OXIDATIVE STRESS; APOLIPOPROTEIN-E AB Folate is a cofactor in one-carbon metabolism, during which it promotes the remethylation of homocysteine-a cytotoxic sulfur-containing amino acid that can induce DNA strand breakage, oxidative stress and apoptosis. Dietary folate is required for normal development of the nervous system, playing important roles regulating neurogenesis and programmed cell death. Recent epidemiological and experimental studies have linked folate deficiency and resultant increased homocysteine levels with several neurodegenerative conditions, including stroke, Alzheimer's disease and Parkinson's disease. Moreover, genetic and clinical data suggest roles for folate and homocysteine in the pathogenesis of psychiatric disorders. A better understanding of the roles of folate and homocysteine in neuronal homeostasis throughout life is revealing novel approaches for preventing and treating neurological disorders. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Univ Massachusetts, Dept Biol Sci, Ctr Cellular Neurobiol & Neurodegenerat Res, Lowell, MA 01854 USA. RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 103 TC 446 Z9 462 U1 4 U2 44 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAR PY 2003 VL 26 IS 3 BP 137 EP 146 DI 10.1016/S0166-2236(03)00032-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 651YQ UT WOS:000181351900007 PM 12591216 ER PT J AU Sheffler, DJ Roth, BL AF Sheffler, DJ Roth, BL TI Salvinorin A: the 'magic mint' hallucinogen finds a molecular target in the kappa opioid receptor SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID SALVIA-DIVINORUM; DITERPENE; DRUG AB Salvinorin A, a neoclerodane diterpene, is the most potent naturally occurring hallucinogen known and rivals the synthetic hallucinogen lysergic acid diethylamide in potency. Recently, the molecular target of salvinorin A was identified as the kappa opioid receptor (KOR). Salvinorin A represents the only known non-nitrogenous KOR selective agonist. Based on the selectivity of salvinorin A for the KOR, this receptor represents a potential molecular target for the development of drugs to treat disorders characterized by alterations in perception, including schizophrenia, Alzheimer's disease and bipolar disorder. C1 Case Western Reserve Univ, Sch Med, Natl Inst Mental Hlth, Psychoact Drug Screening Program, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. RP Roth, BL (reprint author), Case Western Reserve Univ, Sch Med, Natl Inst Mental Hlth, Psychoact Drug Screening Program, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM roth@biocserver.BIOC.cwru.edu RI Roth, Bryan/F-3928-2010 NR 19 TC 102 Z9 104 U1 1 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 MAR PY 2003 VL 24 IS 3 BP 107 EP 109 DI 10.1016/S0165-6147(03)00027-0 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 660BV UT WOS:000181814700002 PM 12628350 ER PT J AU Porzio, G Ficorella, C Marchetti, P Ballatori, E Mattei, A Ruggeri, B Di Orio, F Roila, F Cortesi, E Costantini, M Casali, P Licitra, L Mencaglia, E Tamburini, M Massidda, B AF Porzio, G Ficorella, C Marchetti, P Ballatori, E Mattei, A Ruggeri, B Di Orio, F Roila, F Cortesi, E Costantini, M Casali, P Licitra, L Mencaglia, E Tamburini, M Massidda, B CA Italian Grp Evaluation Outcomes On TI Non clinical factors as determinants of the use of breast conservative surgery in Italy SO TUMORI LA English DT Article DE breast cancer; conservative surgery ID CONSERVING SURGERY; CANCER PATIENTS; THERAPY; PATIENT; MASTECTOMY; CARCINOMA; CHOICE AB The aims of the study were to evaluate the trend of breast conservative surgery (BCS) in Italian breast cancer patients and to identify its nonclinical determinants. Data of 2062 patients surgically treated patients for primary breast cancer were evaluated; 788 (38.0%) had been submitted to breast conservative surgery. A different percentage of breast conservative surgery was found with respect to geographic patient's residence (North, 41.1%; Central, 37.6%; South, 33.0%). Multifactorial analysis showed that time since diagnosis, age at diagnosis and nonclinical factors, such as geographic area of residence and level of education, were significantly associated with breast conservative surgery. C1 Univ Aquila, Dipartimento Med Sperimentale, Med Oncol Unit, I-67100 Laquila, Italy. Univ Aquila, Med Stat Unit, I-67100 Laquila, Italy. Med Oncol Unit, Perugia, Italy. Univ Roma La Sapienza, Div Med Oncol, I-00185 Rome, Italy. Natl Canc Inst, Genoa, Italy. Ist Nazl Tumori, I-20133 Milan, Italy. Univ Cagliari, Dept Med Oncol, I-09124 Cagliari, Italy. Div Med Oncol, Perugia, Italy. Univ Aquila, Med Stat Unit, I-67100 Laquila, Italy. Div Med Oncol, San Giovanni Rotondo, Italy. San Carlo Borromeo Hosp, Div Med Oncol, Milan, Italy. S Giovanni AS Hosp, Div Med Oncol, Turin, Italy. Div Med Oncol, Ferrara, Italy. Careggi Univ & Hosp, Radiotherapy Oncol Unit, Florence, Italy. Div Med Oncol, Modena, Italy. Ist Ricerca Cancro, Genoa, Italy. Div Med Oncol, Venice, Italy. Univ Verona, Dept Med Oncol, I-37100 Verona, Italy. Med Oncol Div 2, Cagliari, Italy. S Orsola M Malpighi Hosp, Radiotherapy Oncol Div, Bologna, Italy. Santa Chiara Hosp, Div Med Oncol, Pisa, Italy. Univ Sassari, Div Med Oncol, I-07100 Sassari, Italy. Univ Cagliari, Div Med Oncol, I-09124 Cagliari, Italy. Regina Elena Hosp, Med Oncol Div 2, Rome, Italy. Santa Chiara Hosp, Med Oncol Unit, Trent, Italy. S Gerardo Hosp, Div Med Oncol, Monza, Italy. Radiotherapy Oncol Div, Cagliari, Italy. Med Oncol Serv, Fermo, Italy. Div Med Oncol, Mantova, Italy. Div Med Oncol, Forli, Italy. Div Med Oncol, Alessandria, Italy. Univ Ancona, Div Med Oncol, I-60128 Ancona, Italy. Med Oncol Div 3, Cagliari, Italy. Ist Ricerca Cancro, Radiotherapy Oncol Div, Genoa, Italy. S Eugenio Hosp, Med Oncol Serv, Rome, Italy. Ctr Riferimento Oncol, Radiotherapy Oncol Div, I-33081 Aviano, Italy. S Paolo Hosp, Med Oncol Serv, Savona, Italy. Natl Canc Inst, Div Med Oncol, I-20133 Milan, Italy. Radiotherapy Oncol Div, Rovigo, Italy. Div Med Oncol, Ragusa, Italy. Piove Sacco, Div Med Oncol, Padua, Italy. S Giovanni & Paolo Hosp, Radiotherapy Oncol Div, Venice, Italy. Regina Elena Hosp, Div Med Oncol 1, Rome, Italy. Div Med Oncol, Aosta, Italy. Negrar Hosp, Div Med Oncol, Verona, Italy. S Spirito Hosp, Med Oncol Serv, Casale Monferrato, Alessandria, Italy. Med Oncol Serv, Ancona, Italy. Univ Naples, Dept Med Oncol, I-80138 Naples, Italy. Univ Roma La Sapienza, Dept Med Oncol, I-00185 Rome, Italy. S Lazzaro Hosp, Med Oncol Ctr, Alba, Cuneo, Italy. Radiotherapy Oncol Div, Trento, Italy. Inst Internal Med & Oncol Sci, Perugia, Italy. Natl Canc Inst Pascale, Med Oncol Div B, Naples, Italy. S Corona Hosp, Med Oncol Serv, Pietra Ligure, Savona, Italy. S Filippo Neri Hosp, Div Med Oncol, Rome, Italy. Gemelli Hosp, Radiotherapy Oncol Ctr, Rome, Italy. Med Oncol Serv, Padua, Italy. Univ Bari, Div Med Oncol, Policlin Hosp, I-70121 Bari, Italy. Regina Elena Hosp, Div Med Oncol, Rome, Italy. Univ Aquila, Med Oncol Serv, I-67100 Laquila, Italy. Div Med Oncol, Milan, Italy. SM Annunziata Hosp, Med Oncol Serv, Florence, Italy. Univ Palermo, Inst Clin Med, I-90133 Palermo, Italy. Med Oncol Serv, Perugia, Italy. Univ Palermo, Cattedra Med Oncol, I-90133 Palermo, Italy. Francavilla Fontana, Div Internal Med, Brindisi, Italy. Div Med Oncol, Bolzano, Italy. Med Oncol Serv, Salerno, Italy. Univ Cagliari, Dept Internal Med Sci, Div Med Oncol, I-09124 Cagliari, Italy. Med Ematol Div, Catanzaro, Italy. Clin Oncol, Catanzaro, Italy. Umberto I Hosp, Div Internal Med, Med Oncol Serv, Siracusa, Italy. Cardarelli Hosp, Div Med Oncol, Naples, Italy. S Camillo Forlanini Hosp, Pneumoncol Unit 5, Rome, Italy. Natl Canc Inst Pascale, Med Oncol Div A, Naples, Italy. S Croce Hosp, Med Oncol Ctr, Cuneo, Italy. Div Med Oncol, Ancona, Italy. Radiotherapy Oncol Div, Belluno, Italy. Binaghi Hosp, Pneumol Div 1, Cagliari, Italy. Radiotherapy Oncol Div, Udine, Italy. RP Porzio, G (reprint author), Univ Aquila, Dipartimento Med Sperimentale, Med Oncol Unit, I-67100 Laquila, Italy. RI costantini, massimo/G-1443-2012; Marchetti, Paolo/K-1469-2016; MATTEI, Antonella/M-6579-2016 OI MATTEI, Antonella/0000-0001-6420-8116 NR 22 TC 0 Z9 0 U1 0 U2 1 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD MAR-APR PY 2003 VL 89 IS 2 BP 168 EP 172 PG 5 WC Oncology SC Oncology GA 694NR UT WOS:000183781100012 ER PT J AU Zaragoza, C Barrera, R Centeno, F Tapia, JA Duran, E Gonzalez, M Mane, MC AF Zaragoza, C Barrera, R Centeno, F Tapia, JA Duran, E Gonzalez, M Mane, MC TI SDS-PAGE and Western blot of urinary proteins in dogs with leishmaniasis SO VETERINARY RESEARCH LA English DT Article DE leishmaniasis; proteinuria; dog; SDS-PAGE; Western blot ID POLYACRYLAMIDE GEL-ELECTROPHORESIS; POLYMERASE-CHAIN-REACTION; VISCERAL LEISHMANIASIS; CANINE LEISHMANIASIS; INFANTUM; DIAGNOSIS; SEQUENCE; ANTIGEN AB Canine leishmaniasis is an endemic disease in the Mediterranean area caused by the protozoan Leishmania infantum, which usually produces renal failure. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blot using antibodies to IgG and IgA from dogs were carried out in the urine of 22 dogs with leishmaniasis diagnosed by ELISA and confirmed by PCR, and 20 healthy dogs. The results were compared to renal function laboratory tests and to those from a histopathological study of the kidneys from sick animals that died naturally or were euthanized. Five different bands with molecular weights ranging from 10 to 110 kDa were obtained from the electrophoresis of the urine of healthy dogs. 33.5% of total proteins corresponded to low molecular weight proteins and the other proteins had middle and high molecular weights. However, in the group with leishmaniasis, a maximum of 11 different bands with molecular weights ranging from 10 kDa to 150 kDa were displayed in the electrophoresis of the urine. The urine electrophoretic pattern in the sick dogs was classified as mixed ( proteins with high and low molecular weights) because low molecular weight proteins made up 57.9% and the rest of the proteins had middle and high molecular weights. In Western blot, none of the healthy dogs showed excretion of IgG and/or IgA, whereas IgG and IgA were detected in the Western blot of urine of 68% and 55% respectively of dogs with leishmaniasis. The results obtained in the leishmaniasis group agreed with glomerular and tubular damage, which were confirmed by the histopathological findings. C1 Univ Extremadura, Dept Med & Sanidad Anim, Fac Vet, Caceres 10004, Spain. Univ Extremadura, Dept Bioquim Biol Mol & Genet, Fac Vet, Caceres 10004, Spain. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. Univ Complutense Madrid, Fac Vet, Dept Patol Anim 2, Madrid, Spain. RP Zaragoza, C (reprint author), Univ Extremadura, Dept Med & Sanidad Anim, Fac Vet, Avda Univ S-N, Caceres 10004, Spain. RI Centeno, Francisco/F-7287-2016; Tapia, Jose/C-5181-2008 OI Tapia, Jose/0000-0002-3614-6867 NR 42 TC 19 Z9 19 U1 2 U2 10 PU E D P SCIENCES PI LES ULIS CEDEXA PA 7, AVE DU HOGGAR, PARC D ACTIVITES COURTABOEUF, BP 112, F-91944 LES ULIS CEDEXA, FRANCE SN 0928-4249 J9 VET RES JI Vet. Res. PD MAR-APR PY 2003 VL 34 IS 2 BP 137 EP 151 DI 10.1051/vetres:2002061 PG 15 WC Veterinary Sciences SC Veterinary Sciences GA 696GW UT WOS:000183880100001 PM 12657206 ER PT J AU Day, PM Lowy, DR Schiller, JT AF Day, PM Lowy, DR Schiller, JT TI Papillomaviruses infect cells via a clathrin-dependent pathway SO VIROLOGY LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; VIRUS-LIKE PARTICLES; EPIDERMAL GROWTH-FACTOR; BOVINE PAPILLOMAVIRUS; COATED VESICLES; CULTURED-CELLS; IN-VITRO; INTERLEUKIN-2 RECEPTORS; MAMMALIAN-CELLS; ANIMAL-CELLS AB In this study we have examined the pathway by which papillomaviruses infect cells, using bovine papillomavirus (BPV) virions and mouse C127 cells as the model system. By confocal microscopy, the entry of BPV virions, BPV virus-like particles (VLPs), and HPV16 VLPs were very similar. In dually exposed cells, HPV-16 VLPs and BPV virions colocalized intracellularly. BPV VLPs colocalized with AP-2, a clathrin adapter molecular and a marker of the clathrin-dependent endocytic pathway; and also with transferrin receptor, a marker of early endosomes; and Lamp-2, a marker of late endosomes and lysosomes. BPV infection was detected within 12 h of virion cell-surface binding, as measured by an RT-PCR assay. Infection was prevented by several pharmacologic inhibitors, including chlorpromazine, which blocks clathrin-dependent endocytosis and the lysosomotropic agent, bafilomycin A. By contrast, two inhibitors of caveolae-dependent uptake, filipin and nystatin, did not prevent BPV infection. We conclude that papillomaviruses infect cells via clathrin-dependent receptor-mediated endocytosis. Surprisingly, the kinetics of internalization were unusually slow for this mechanism, with the t(1/2) of entry of BPV-1 being approximately 4 h versus 5-15 min for a typical ligand. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NCI, Cellular Oncol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, Div Basic Sci, NIH, Bldg 36,Room 1D-32, Bethesda, MD 20892 USA. NR 76 TC 136 Z9 148 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 1 PY 2003 VL 307 IS 1 BP 1 EP 11 DI 10.1016/S0042-6822(02)00143-5 PG 11 WC Virology SC Virology GA 664FL UT WOS:000182051000001 PM 12667809 ER PT J AU Mohan, KVK Kulkarni, S Glass, RI Bai, ZS Atreya, CD AF Mohan, KVK Kulkarni, S Glass, RI Bai, ZS Atreya, CD TI A human vaccine strain of lamb rotavirus (Chinese) NSP4 gene: Complete nucleotide sequence and phylogenetic analyses SO VIRUS GENES LA English DT Article DE enterotoxin; genotypes; homology; NS28; phylogeny ID NONSTRUCTURAL GLYCOPROTEIN NSP4; GROUP-C ROTAVIRUSES; GROUP-A; ENDOPLASMIC-RETICULUM; MUTATIONS; PROTEIN; VIRUS; ENTEROTOXIN; DIARRHEA; VP4 AB A lamb strain of rotavirus has recently been licensed for use in China as a live vaccine to prevent rotavirus diarrhea in children. As rotavirus NSP4, especially the cytotoxic domain alone is considered to be associated with diarrhea, we sequenced gene segment 10, which encodes NSP4, of lamb rotavirus. Comparative analyses was performed to identify differences from human rotavirus strains, that might be associated with attenuation, and to ascertain whether the lamb rotavirus gene fits among the NSP4 of other sequenced rotavirus strains. Our comparative nucleotide sequence analysis suggests its close identity (91.17% homology) with that of group-A equine rotavirus (strain H123). Multiple alignment of the deduced amino acid sequence of lamb NSP4 with that of other group A rotaviruses demonstrated homology ranging from 63.42% with that of porcine YM strain to 93.71% with equine H123 strain of rotavirus. A group A-specific NSP4 monoclonal antibody recognized the glycosylated and unglycosylated forms of the protein from virus-infected lysates, suggesting a well-conserved group-specificity of the lamb NSP4. Phylogenetic analysis of the lamb rotavirus gene, with 60 other NSP4 gene sequences of human and animal rotavirus strains, demonstrated that the lamb rotavirus strain belongs to genotype A. Comparative analysis also revealed that although it is a vaccine strain, the NSP4 cytotoxic domain of lamb strain demonstrated an overall amino acid conservation similar to that of other strains, whose NSP4 alone causes diarrhea in animal models. These results taken together with our previous observations clearly reaffirm the idea that the attenuation phenotype of rotaviruses does not involve NSP4 cytotoxic domain, perhaps due to the suppression of NSP4 cytotoxic activity by other rotaviral proteins. C1 US FDA, Sect Viral Pathogenesis & Vaccine Adverse React, Lab Pediat & Resp Viral Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. CDCP, Viral Gastroenteritis Sect, Resp & Enter Viruses Branch, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. Lanzhou Inst Biol Prod, Lanzhou 730046, Gansu Province, Peoples R China. RP Atreya, CD (reprint author), US FDA, Sect Viral Pathogenesis & Vaccine Adverse React, Lab Pediat & Resp Viral Dis, Ctr Biol Evaluat & Res, Bldg 29A,Room 2C-11,HFM-460,NIH Campus,8800 Rockv, Bethesda, MD 20892 USA. NR 32 TC 9 Z9 10 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PD MAR PY 2003 VL 26 IS 2 BP 185 EP 192 DI 10.1023/A:1023491514820 PG 8 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA 671JT UT WOS:000182462200009 PM 12803470 ER PT J AU Conner, EA Lemmer, ER Sanchez, A Factor, VM Thorgeirsson, SS AF Conner, EA Lemmer, ER Sanchez, A Factor, VM Thorgeirsson, SS TI E2F1 blocks and c-Myc accelerates hepatic ploidy in transgenic mouse models SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE ploidy; E2F1; c-myc; liver ID CELL-GROWTH CONTROL; LIVER CARCINOGENESIS; HEPATOCELLULAR-CARCINOMA; DNA-SYNTHESIS; RAT-LIVER; GENOMIC INSTABILITY; GENE-EXPRESSION; RB/E2F PATHWAY; DIPLOID GROWTH; CYCLE CONTROL AB Previously, we have shown that over-expression of either E2F1 or c-Myc promotes hepatocarcinogenesis and that E2F1 mice acquire HCC more rapidly than c-Myc transgenic mice. We also found that co-expression of E2F1/c-Myc further accelerates liver cancer development. Here we describe that the deregulated expression of these two transcription factors also affects hepatic ploidy during post-natal liver growth and before the onset of tumors. Oncogenic activity of E2F1 and/or c-Myc was associated with a persistent increase in hepatocyte proliferation. However, E2F1-mediated cell proliferation favored the predominance of diploid cells characteristic of pre-neoplastic type of liver growth whereas c-Myc functioned to accelerate age-related hepatocyte polyploidization. Similarly, proliferative advantage conferred by co-expression of E2F1 and c-Myc increased the frequency of diploid cells at a young age. Thus, the opposing effects of E2F1 and c-Myc on hepatocyte ploidy suggest that these two transcription factors have different mechanisms by which they control liver proliferation/maturation and ultimately, carcinogenesis. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37,Room 4146A,37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA. RI Sanchez, Aranzazu/H-7810-2015 OI Sanchez, Aranzazu/0000-0001-9145-6633 NR 57 TC 30 Z9 32 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 28 PY 2003 VL 302 IS 1 BP 114 EP 120 DI 10.1016/S0006-291X(03)00125-6 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 654KW UT WOS:000181496900019 PM 12593856 ER PT J AU Paltoo, D Woodson, K Taylor, P Albanes, D Virtamo, J Tangrea, J AF Paltoo, D Woodson, K Taylor, P Albanes, D Virtamo, J Tangrea, J TI Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene and risk of prostate cancer among men in a large cancer prevention study SO CANCER LETTERS LA English DT Article DE genetic polymorphism; prostate cancer; peroxisome proliferator-activated receptor-gamma; Pro12Ala polymorphism ID TOF MASS-SPECTROMETRY; INSULIN SENSITIVITY; ALPHA-TOCOPHEROL; BETA-CAROTENE; FATTY-ACIDS; EXPRESSION; OBESITY; VARIANT; ASSOCIATION; LIGANDS AB The nuclear hormone receptor peroxisome proliferator-activated receptor-gamma (PPAR-gamma) may play a role in prostate carcinogenesis. We examined the association between the PPAR-gamma Pro12Ala polymorphism and prostate cancer risk in a cohort of Finnish male smokers. In a nested case-control analysis that included 193 prostate cancer cases and 188 matched controls, we found no significant association between this polymorphism and prostate cancer risk (odds ratio, OR = 1.27, 95% confidence interval, CI: 0.83-1.94), or significant trend or association with tumor stage (OR = 1.28, 95% CI: 0.54-3.04 for metastatic disease) or grade (OR = 1.57, 95% CI: 0.63-3.91 for poorly differentiated disease). The Pro12Ala polymorphism does not appear to play a significant role in prostate cancer risk in this cohort of men. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RP Paltoo, D (reprint author), NCI, Canc Prevent Studies Branch, Ctr Canc Res, 6116 Execut Blvd,Suite 705,MSC 8314, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01 CN 45035, N01 CN45165] NR 32 TC 32 Z9 36 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 28 PY 2003 VL 191 IS 1 BP 67 EP 74 DI 10.1016/S0304-3835(02)00617-1 PG 8 WC Oncology SC Oncology GA 655ZB UT WOS:000181582400009 PM 12609711 ER PT J AU Anand, M Chakraburtty, K Marton, MJ Hinnebusch, AG Kinzy, TG AF Anand, M Chakraburtty, K Marton, MJ Hinnebusch, AG Kinzy, TG TI Functional interactions between yeast translation eukaryotic elongation factor (eEF) 1A and eEF3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR-III EF-3; SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE EXCHANGE; TRANSFER-RNA; PHENOTYPIC SUPPRESSION; PROTEIN-SYNTHESIS; SEQUENCE-ANALYSIS; ATPASE; MUTATIONS; RIBOSOMES AB The translation elongation machinery in fungi differs from other eukaryotes in its dependence upon eukaryotic elongation factor 3 (eEF3). eEF3 is essential in vivo and required for each cycle of the translation elongation process in vitro. Models predict eEF3 affects the delivery of cognate aminoacyl-tRNA, a function performed by eEF1A, by removing deacylated tRNA from the ribosomal Exit site. To dissect eEF3 function and its link to the A-site activities of eEF1A, we have identified a temperature-sensitive allele of the YEF3 gene. The F650S substitution, located between the two ATP binding cassettes, reduces both ribosome-dependent and intrinsic ATPase activities. In vivo this mutation increases sensitivity to aminoglycosidic drugs, causes a 50% reduction of total protein synthesis at permissive temperatures, slows run-off of polyribosomes, and reduces binding to eEF1A. Reciprocally, excess eEF3 confers synthetic slow growth, increased drug sensitivity, and reduced translation in an allele specific fashion with an E122K mutation in the GTP binding domain of eEF1A. In addition, this mutant form of eEF1A shows reduced binding of eEF3. Thus, optimal in vivo interactions between eEF3 and eEF1A are critical for protein synthesis. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Microbiol Mol Genet & Immunol, Piscataway, NJ 08854 USA. Med Coll Wisconsin, Dept Biochem, Milwaukee, WI USA. NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Kinzy, TG (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Microbiol Mol Genet & Immunol, 675 Hoes Ln, Piscataway, NJ 08854 USA. FU NIGMS NIH HHS [R01 GM57483] NR 44 TC 42 Z9 44 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 FEB 28 PY 2003 VL 278 IS 9 BP 6985 EP 6991 DI 10.1074/jbc.M209224200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649EZ UT WOS:000181195100047 PM 12493761 ER PT J AU Garman, SC Simcoke, WN Stowers, AW Garboczi, DN AF Garman, SC Simcoke, WN Stowers, AW Garboczi, DN TI Structure of the C-terminal domains of merozoite surface protein-1 from Plasmodium knowlesi reveals a novel histidine binding site SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MALARIA VACCINE CANDIDATE; INHIBIT PARASITE GROWTH; CRYSTAL-STRUCTURE; FALCIPARUM MEROZOITES; HUMAN-ERYTHROCYTES; SERUM ANTIBODIES; DISULFIDE BONDS; FRAGMENT; INVASION; COMPLEX AB The protozoan parasite Plasmodium causes malaria, with hundreds of millions of cases recorded annually. Protection against malaria infection can be conferred by antibodies against merozoite surface protein (MSP)-1, making it an attractive vaccine candidate. Here we present the structure of the C-terminal domains of MSP-1 (known as MSP-1,9) from Plasmodium knowlesi. The structure reveals two tightly packed epidermal growth factor-like domains oriented head to tail. In domain 1, the molecule displays a histidine binding site formed primarily by a highly conserved tryptophan. The protein carries a pronounced overall negative charge primarily due to the large number of acidic groups in domain 2. To map protein binding surfaces on MSP-1(19), we have analyzed the crystal contacts in five different crystal environments, revealing that domain 1 is highly preferred in protein-protein interactions. A comparison of MSP-1(19), structures from P. knowlesi, P. cynomolgi, and P. falciparum shows that, although the overall protein folds are similar, the molecules show significant differences in charge distribution. We propose the histidine binding site in domain 1 as a target for inhibitors of protein binding to MSP-1, which might prevent invasion of the merozoite into red blood cells. C1 NIAID, Immunogenet Lab, Struct Biol Sect, NIH, Rockville, MD 20852 USA. NIAID, Malaria Vaccine Dev Unit, Parasit Dis Lab, NIH, Rockville, MD 20852 USA. RP Garman, SC (reprint author), NIAID, Immunogenet Lab, Struct Biol Sect, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 45 TC 26 Z9 26 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 FEB 28 PY 2003 VL 278 IS 9 BP 7264 EP 7269 DI 10.1074/jbc.M210716200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649EZ UT WOS:000181195100082 PM 12493733 ER PT J AU Jung, YJ Isaacs, JS Lee, S Trepel, J Neckers, L AF Jung, YJ Isaacs, JS Lee, S Trepel, J Neckers, L TI Microtubule disruption utilizes an NF kappa B-dependent pathway to stabilize HIF-1 alpha protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1; TUMOR-SUPPRESSOR PROTEIN; MESSENGER-RNA EXPRESSION; PROSTATE-CANCER CELLS; TRANSCRIPTION FACTOR; GENE-EXPRESSION; FACTOR 1-ALPHA; KINASE-C; INTERLEUKIN-1 PRODUCTION; ANTIMICROTUBULE AGENTS AB Hypoxia-inducible factor (HIF)-1alpha levels are elevated in normoxic cells undergoing physiological processes involving large scale microtubule reorganization, such as embryonic development, wound healing, and tumor cell metastasis. Although alterations in microtubules affect numerous cellular responses, no data have yet implicated microtubule dynamics in HIF-1alpha regulation. To investigate the effect of microtubule change upon HIF-1alpha regulation, we treated cells with the microtubule-depolymerizing agents (MDAs) colchicine, vinblastine or nocodazole. We demonstrate that these agents are able to induce transcriptionally active HIF-1. MDA-mediated induction of HIF-1alpha required microtubule depolymerization, since HIF-1alpha levels were unchanged in cells treated with either the microtubule-stabilizing agent paclitaxel, or an inactive form of colchicine, or in colchicine-resistant cells. HIF-1 induction was dependent upon cellular transcription, as transcription inhibitors abrogated HIF-1alpha protein up-regulation. The ability of transcriptional inhibitors to interfere with HIF-1alpha accumulation was specific to the MDA-initiated pathway, as they were ineffective in preventing hypoxia-mediated HIF-1 induction, which occurs by a distinct post-translational pathway. Moreover, we provide evidence implicating a requirement for NFkappaB transcription in the HIF-1 induction mediated by MDAs. The ability of MDAs to induce HIF-1alpha is dependent upon activation of NFkappaB, since inhibition of NFkappaB either pharmacologically or by transfection of an NFkappaB super-repressor plasmid abrogated this induction. Collectively, these data support a model in which NFkappaB is a focal point for the convergence of MDA-mediated signaling events leading to HIF-1 induction, thus revealing a novel aspect of HIF-1alpha regulation and function. C1 NCI, Cell & Canc Biol Branch, Canc Res Ctr, NIH, Rockville, MD 20850 USA. NCI, Med Oncol Clin Res Unit, CCR, NIH, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Cell & Canc Biol Branch, Canc Res Ctr, NIH, Rockville, MD 20850 USA. NR 62 TC 70 Z9 73 U1 2 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 FEB 28 PY 2003 VL 278 IS 9 BP 7445 EP 7452 DI 10.1074/jbc.M209804200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649EZ UT WOS:000181195100105 PM 12488445 ER PT J AU Cheng, AW Wang, SQ Yang, DM Xiao, RP Mattson, MP AF Cheng, AW Wang, SQ Yang, DM Xiao, RP Mattson, MP TI Calmodulin mediates brain-derived neurotrophic factor cell survival signaling upstream of Akt kinase in embryonic neocortical neurons SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CULTURED HIPPOCAMPAL-NEURONS; PHOSPHATIDYLINOSITOL 3-KINASE; INTRACELLULAR CA2+; NERVOUS-SYSTEM; GROWTH-FACTOR; SYMPATHETIC NEURONS; SYNAPTIC PLASTICITY; CALCIUM; ACTIVATION; PATHWAY AB As a calcium-sensing protein, calmodulin acts as a transducer of the intracellular calcium signal for a variety of cellular responses. Although calcium is an important regulator of neuronal survival during development of the nervous system and is also implicated in the pathogenesis of neurodegenerative disorders, it is not known if calmodulin mediates these actions of calcium. To determine the role of calmodulin in regulating neuronal survival and death, we overexpressed calmodulin with mutations in all four Ca2+-binding sites (CaM(1-4)) or with disabled C-terminal Ca2+-binding sites (CaM(3,4)) in cultured neocortical neurons by adenoviral gene transfer. Long-term neuronal survival was decreased in neurons overexpressing CaM(1-4) and CaM(3,4), which could not be rescued by brain-derived neurotrophic factor (BDNF). The basal level of Akt kinase activation was decreased, and the ability of BDNF to activate Akt was completely abolished in neurons overexpressing CaM(1-4) or CaM(3,4). In contrast, BDNF-induced activation of p42/44 MAPKs was unaffected by calmodulin mutations. Treatment of neurons with calmodulin antagonists and a phosphatidylinositol 3-kinase inhibitor blocked the ability of BDNF to prevent neuronal death, whereas inhibitors of calcium/calmodulin-dependent protein kinase II did not. Our findings demonstrate a pivotal role for calmodulin in survival signaling by BDNF in developing neocortical neurons by activating a transduction pathway involving phosphatidylinositol 3-kinase and Akt. In addition, our findings show that the C-terminal Ca2+-binding sites are critical for calmodulin-mediated cell survival signaling. C1 NIA, Neurosci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Peking Univ, Coll Life Sci, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 66 TC 68 Z9 70 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 FEB 28 PY 2003 VL 278 IS 9 BP 7591 EP 7599 DI 10.1074/jbc.M207232200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649EZ UT WOS:000181195100122 PM 12488453 ER PT J AU Patterson, AP Chen, ZA Rubin, DC Moucadel, V Iovanna, JL Brewer, HB Eggerman, TL AF Patterson, AP Chen, ZA Rubin, DC Moucadel, V Iovanna, JL Brewer, HB Eggerman, TL TI Developmental regulation of apolipoprotein B mRNA editing is an autonomous function of small intestine involving homeobox gene Cdx1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPITHELIAL-CELLS; CATALYTIC SUBUNIT; DOWN-REGULATION; GROWTH-HORMONE; RAT-LIVER; EXPRESSION; DIFFERENTIATION; SECRETION; PROLIFERATION; PROMOTES AB Apolipoprotein B mRNA editing is developmentally regulated in the human and rodent small intestine, changing from < 1% at day 14 to similar to90% by day 20 in the rat fetus. This regulation is coincident with the developmental formation of the crypt-to-villus axis functional unit, a continuous and rapidly renewing system involving cell generation, migration, and differentiation. Utilizing small intestine isografts implanted into the subcutaneous tissue of adult recipients, apolipoprotein B mRNA editing was developmentally up-regulated, parallel to that seen with an intact control. In contrast, apoB mRNA expression remains nearly constant in the isograft, unlike the normal intact small intestine. Immunohistochemical analyses demonstrated that apoB-4 protein existed predominantly in well differentiated enterocytes along the villus surface whereas apoB-100 was in the lamina propria and crypts. Apoll mRNA editing levels were very low in the crypt-like rat intestinal cell line, IEC-6 (similar to0.3%), but very high in well differentiated enterocytes (similar to91.5%). The expression of homeobox gene Cdx1 increased 18-fold in small intestine in vivo during the same time course when apoB mRNA editing increased from similar to2 to similar to90%. The overexpression of Cdx1 in IEC-6 cells increased apoB mRNA editing over 10-fold compared with the vector control. This increase was associated with a significant increase of activating factor ACF, a component of the apoB mRNA editing complex. Taken together, these data suggest that the developmental regulation of apoB mRNA editing is an autonomous cytodifferentiation function of small intestine for which homeobox gene Cdx1 may play an important role. C1 NHLBI, Off Biotechnol Activ, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. INSERM E116, Lab Rech Physiol & Pathol Digest, F-13009 Marseille, France. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. NIH, Dept Lab Med, WG Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Eggerman, TL (reprint author), NHLBI, Off Biotechnol Activ, NIH, 6705 Rockledge Dr,Suite 750, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [R01-DK46122] NR 51 TC 14 Z9 17 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 FEB 28 PY 2003 VL 278 IS 9 BP 7600 EP 7606 DI 10.1074/jbc.M201601200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649EZ UT WOS:000181195100123 PM 12493769 ER PT J AU Sasahara, K McPhie, P Minton, AP AF Sasahara, K McPhie, P Minton, AP TI Effect of dextran on protein stability and conformation attributed to macromolecular crowding SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein stability; molecular crowding; molten globule; excluded volume; dextran ID MOLTEN GLOBULE STATE; NATURALLY-OCCURRING OSMOLYTES; EGG-WHITE LYSOZYME; X-RAY-SCATTERING; CYTOCHROME-C; THERMODYNAMIC CONSEQUENCES; CIRCULAR-DICHROISM; SELF-ASSOCIATION; DNA-POLYMERASE; HEAT-CAPACITY AB Thermally induced transition curves of hen egg-white lysozyme were measured in the presence of several concentrations of dextran at pH 2.0 by near-UV and far-UV CD. The transition curves were fitted to a two-state model by a non-linear, least-squares method to obtain the transition temperature (T-m), enthalpy change (DeltaH(u)(T-m)), and free energy change (DeltaG(u)(T)) of the unfolding transition. An increase in T-m and almost constant DeltaH(u)(T-m) values were observed in the presence of added dextran at concentrations exceeding ca 100 g l(-1). In addition, dextran-induced conformational changes of fully unfolded protein were investigated by CD spectroscopy. Addition of high concentrations of dextran to solutions of acid-unfolded cytochrome c at pH 2.0 results in a shift of the CD spectrum from that characteristic of the fully unfolded polypeptide to that characteristic of the more compact, salt-induced molten globule state, a result suggesting that the molten globule-like state is stabilized relative to the fully unfolded form in crowded environments. Both observations are in qualitative accord with predictions of a previously proposed model for the effect of intermolecular excluded volume (macromolecular crowding) on protein stability and conformation. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Sasahara, K (reprint author), NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. OI Minton, Allen/0000-0001-8459-1247 NR 68 TC 192 Z9 200 U1 3 U2 50 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 FEB 28 PY 2003 VL 326 IS 4 BP 1227 EP 1237 DI 10.1016/S0022-2836(02)01443-2 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 652VQ UT WOS:000181401900020 PM 12589765 ER PT J AU Stylianou, M Proschan, M Flournoy, N AF Stylianou, M Proschan, M Flournoy, N TI Estimating the probability of toxicity at the target dose following an up-and-down design SO STATISTICS IN MEDICINE LA English DT Article DE phase I trial; toxicity; biased coin up-and-down design; isotonic regression; dose finding ID CONTINUAL REASSESSMENT METHOD; I CLINICAL-TRIAL; PHASE-I; CANCER AB One of the most important aspects of a phase I trial or other acute toxicity study is estimating accurately the probability of toxicity that is associated with the recommended dose. We use the biased coin up-and-down design to allocate and isotonic regression to estimate toxicity probabilities and determine the recommended dose. We then derive, using bootstrap methods, an estimate of the probability of toxicity at the recommended dose. Small sample properties of this estimator are also evaluated. Published in 2003 by John Wiley Sons, Ltd. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. American Univ, Dept Math & Stat, Washington, DC 20016 USA. RP Stylianou, M (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,Room 8220, Bethesda, MD 20892 USA. NR 11 TC 27 Z9 29 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD FEB 28 PY 2003 VL 22 IS 4 BP 535 EP 543 DI 10.1002/sim.1351 PG 9 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 644TW UT WOS:000180936300003 PM 12590412 ER PT J AU Fox, JD Routzahn, KM Bucher, MH Waugh, DS AF Fox, JD Routzahn, KM Bucher, MH Waugh, DS TI Maltodextrin-binding proteins from diverse bacteria and archaea are potent solubility enhancers SO FEBS LETTERS LA English DT Article DE maltose-binding protein; MBP; inclusion body; fusion protein; solubility enhancer ID MALTOSE-BINDING; ESCHERICHIA-COLI; RECOMBINANT PROTEINS; THERMOCOCCUS-LITORALIS; FUSION PROTEINS; EXPRESSION; TRANSPORT AB Escherichia coli maltose-binding protein (MBP) is frequently used as an affinity tag to facilitate the purification of recombinant proteins. An important additional attribute of MBP is its remarkable ability to enhance the solubility of its fusion partners. MBPs are present in a wide variety of microorganisms including both mesophilic and thermophilic bacteria and archaea. In the present study, we compared the ability of MBPs from six diverse microorganisms (E. coli, Pyrococcus furiosus, Thermococcus litoralis, Vibrio cholerae, Thermotoga maritima, and Yersinia pestis) to promote the solubility of eight different aggregation-prone proteins in E. coli. In contrast to glutathione S-transferase (GST), all of these MBPs proved to be effective solubility enhancers and some of them were even more potent solubilizing agents than E. coli MBP. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 NCI, Prot Engn Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Waugh, DS (reprint author), NCI, Prot Engn Sect, Macromol Crystallog Lab, POB B, Frederick, MD 21702 USA. NR 21 TC 66 Z9 72 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD FEB 27 PY 2003 VL 537 IS 1-3 BP 53 EP 57 DI 10.1016/S0014-5793(03)00070-X PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 651DA UT WOS:000181304100010 PM 12606030 ER PT J AU Scamvougeras, A Kigar, DL Jones, D Weinberger, DR Witelson, SF AF Scamvougeras, A Kigar, DL Jones, D Weinberger, DR Witelson, SF TI Size of the human corpus callosum is genetically determined: an MRI study in mono and dizygotic twins SO NEUROSCIENCE LETTERS LA English DT Article DE corpus callosum; twins; human; heritability; genetics; imaging ID MONOZYGOTIC TWINS; BRAIN SIZE; MORPHOLOGY; SEX AB The factors determining the large variation seen in human corpus callosum (CC) morphology are as yet unknown. In this study heritability of CC size was assessed by comparing the concordance of CC midsagittal area in 14 monozygotic and 12 dizygotic twin pairs with a mean age of 27 years, using magnetic resonance imaging and various methods of calculating trait heritability. Heritability was high regardless of method of assessment. The application of a structural equation model resulted in the estimate that 94% of the variance in CC midsagittal size is attributable to the genome. This indicates that under normal conditions and before the effects of normal aging, there is very modest influence of the environment on CC morphology. The results suggest that correlates of CC size, such as the pattern of cerebral lateralization, cognitive abilities and neuropsychiatric dysfunction may be associated with the genetic determinants of CC morphology. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 McMaster Univ, Albert Einstein Irving Zucker Chair Neurosci, Dept Psychiat & Behav Neurosci, Hamilton, ON L8N 3Z5, Canada. Univ British Columbia, Dept Psychiat, Neuropsychiat Unit, Vancouver, BC, Canada. NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Witelson, SF (reprint author), McMaster Univ, Albert Einstein Irving Zucker Chair Neurosci, Dept Psychiat & Behav Neurosci, 1200 Main St W, Hamilton, ON L8N 3Z5, Canada. FU NINDS NIH HHS [NS18954] NR 24 TC 39 Z9 40 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD FEB 27 PY 2003 VL 338 IS 2 BP 91 EP 94 DI 10.1016/S0304-3940(02)01333-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 646BE UT WOS:000181014300001 PM 12566160 ER PT J AU Pickford, F Onstead, L Camacho-Prihar, C Hardy, J McGowan, E AF Pickford, F Onstead, L Camacho-Prihar, C Hardy, J McGowan, E TI Expression of mBRI(2) in mice SO NEUROSCIENCE LETTERS LA English DT Article DE familial British dementia; BRI; in situ hybridization; gene expression; protein expression ID FAMILIAL BRITISH DEMENTIA; GENE; PROTEINS; SEQUENCE; PEPTIDE AB Mutations in the BRI2 gene cause the autosomal dominant neurodegenerative diseases familial British dementia (FBD) and familial Danish dementia (FDD). BRI2 is a member of a family of type 2 integral transmembrane spanning proteins, including mBRI(2), its murine homologue. The function of BRI2 is unknown. Northern and Western analyses and in situ hybridization were employed to determine the expression of mBRI(2) in the mouse. mBRI(2) mRNA was expressed in several tissues including the liver, heart, lung, and ubiquitously throughout the brain. mBRI(2) protein was detected at high levels in many brain regions. Murine BRI2 expression is similar to that described in the human brain but does not fully explain the distribution of pathology seen in FBD and FDD. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Mayo Clin Jacksonville, Dept Neurosci, Jacksonville, FL 32224 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP McGowan, E (reprint author), Mayo Clin Jacksonville, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. RI Hardy, John/C-2451-2009 NR 14 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD FEB 27 PY 2003 VL 338 IS 2 BP 95 EP 98 DI 10.1016/S0304-3940(02)01356-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 646BE UT WOS:000181014300002 PM 12566161 ER PT J AU Brown, RS Russo, MW Lai, M Shiffman, ML Richardson, MC Everhart, JE Hoofnagle, JH AF Brown, RS Russo, MW Lai, M Shiffman, ML Richardson, MC Everhart, JE Hoofnagle, JH TI A survey of liver transplantation from living adult donors in the United States SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GRAFTS; UNINEPHRECTOMY; MORTALITY; SURVIVAL; PATIENT; LOBE AB BACKGROUND The transplantation of the right lobe of a liver from a living adult donor into an adult recipient has been performed increasingly frequently in the United States. Although the use of grafts from living donors is standard practice in transplantation in children, their use in adults remains controversial. METHODS To study the use of liver transplantation from a living donor, we sent a 24-item questionnaire to all liver-transplantation programs in the United States. Data on indications, evaluation, and outcomes were analyzed with the use of univariate and multivariate methods. Data on recent transplantations were gathered from the Scientific Registry of Transplant Recipients and directly from the transplantation programs. RESULTS Questionnaires were returned by 84 of the 122 programs (69 percent) describing the results of 449 adult-to-adult transplantations of partial livers from living donors that were performed in 42 centers. Fourteen centers had performed more than 10 such transplantations each and together accounted for 80 percent of such transplantations. Centers that performed such transplantations also performed more transplantations of livers from cadaveric donors and more transplantations from living donors in children than centers that did not perform the adult-to-adult procedure (P=0.002 and P=0.001, respectively). A total of 45 percent of potential donors who were evaluated eventually donated a lobe of their liver; 99 percent of these donors were genetically or emotionally related to the recipient. Complications in the donor were more frequent in the centers performing the fewest transplantations from living donors in adults and included biliary complications requiring intervention (in 6.0 percent), reoperation (in 4.5 percent), and death (in one donor [0.2 percent]). Among the recipients, 1.6 percent did not meet criteria for receipt of a cadaveric transplant; cancer, retransplantation, and acute liver failure were uncommon indications for transplantation from a living donor. Biliary complications occurred in 22.0 percent of recipients, and vascular complications occurred in 9.8 percent. CONCLUSIONS Adult-to-adult liver transplantation from a living donor is increasingly performed in the United States but is concentrated in a few large-volume centers. Mortality among donors is low, but complications in the donor are relatively common. C1 Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. New York Presbyterian Hosp, Ctr Liver Dis & Transplantat, New York, NY USA. Virginia Commonwealth Univ Hlth Syst, Dept Med, Richmond, VA USA. NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. RP Brown, RS (reprint author), Columbia Presbyterian Med Ctr, Ctr Liver Dis & Transplantat, 622 W 168th St,PH 14, New York, NY 10036 USA. NR 25 TC 296 Z9 318 U1 2 U2 8 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 FEB 27 PY 2003 VL 348 IS 9 BP 818 EP 825 DI 10.1056/NEJMsa021345 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 648WE UT WOS:000181173300009 PM 12606737 ER PT J AU Sundar, S Berman, J AF Sundar, S Berman, J TI Miltefosine for indian visceral leishmaniasis - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Banaras Hindu Univ, Varanasi 221005, Uttar Pradesh, India. Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Sundar, S (reprint author), Banaras Hindu Univ, Varanasi 221005, Uttar Pradesh, India. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 FEB 27 PY 2003 VL 348 IS 9 BP 857 EP 858 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 648WE UT WOS:000181173300020 ER PT J AU Fruchter, O AF Fruchter, O TI Hemofiltration and peritoneal dialysis in infection-associated acute renal failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Fruchter, O (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 FEB 27 PY 2003 VL 348 IS 9 BP 859 EP 859 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 648WE UT WOS:000181173300023 ER PT J AU Kyng, KJ May, A Brosh, RM Cheng, WH Chen, C Becker, KG Bohr, VA AF Kyng, KJ May, A Brosh, RM Cheng, WH Chen, C Becker, KG Bohr, VA TI The transcriptional response after oxidative stress is defective in Cockayne syndrome group B cells SO ONCOGENE LA English DT Article DE microarray; Cockayne syndrome; transcription; DNA repair; DNA damage; aging ID RNA-POLYMERASE-II; ACTIVATED PROTEIN-KINASE; GENE-EXPRESSION PROFILE; BASE EXCISION-REPAIR; HEAT-SHOCK PROTEINS; CALORIC RESTRICTION; HYDROGEN-PEROXIDE; GENOME-WIDE; DNA-REPAIR; SKIN FIBROBLASTS AB Cockayne syndrome (CS) is a human hereditary disease belonging to the group of segmental progerias, and the clinical phenotype is characterized by postnatal growth failure, neurological dysfunction, cachetic dwarfism, photosensitivity, sensorineural hearing loss, and retinal degradation. CS-B cells are defective in transcription-coupled DNA repair, base excision repair, transcription, and chromatin structural organization. Using array analysis, we have examined the expression profile in CS complementation group B (CS-B) fibroblasts after exposure to oxidative stress (H2O2) before and after complete complementation with the CSB gene. The following isogenic cell lines were compared: CS-B cells (CS-B null), CS-B cells complemented with wild-type CSB (CS-B wt), and a stably transformed cell fine with a point mutation in the ATPase domain of CSB (CS-B ATPase mutant). In the wt rescued cells, we detected significant induction ( > two-fold) of 112 genes out of the 6912 analysed. The patterns suggested an induction or upregulation of genes involved in several DNA metabolic processes including DNA repair, transcription, and signal transduction. In both CS-B mutant cell lines, we found a general deficiency in transcription after oxidative stress, suggesting that the CSB protein influenced the regulation of transcription of certain genes. Of the 6912 genes, 122 were differentially regulated by more than two-fold. Evidently, the ATPase function of CSB is biologically important as the deficiencies seen in the ATPase mutant cells are very similar to those observed in the CS-B-null cells. Some major defects are in the transcription of genes involved in DNA repair, signal transduction, and ribosomal functions. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. NIA, DNA Array Unit, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), Aarhus Univ, Danish Ctr Mol Gerontol, Dept Mol & Struct Biol, DK-8000 Aarhus C, Denmark. OI Kyng, Kasper Jacobsen/0000-0001-7940-1656; Becker, Kevin/0000-0002-6794-6656 NR 55 TC 46 Z9 47 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 27 PY 2003 VL 22 IS 8 BP 1135 EP 1149 DI 10.1038/sj.onc.1206187 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 650EK UT WOS:000181249700003 PM 12606941 ER PT J AU Qiu, CP Yu, MS Shan, L Snyderwine, EG AF Qiu, CP Yu, MS Shan, L Snyderwine, EG TI Allelic imbalance and altered expression of genes in chromosome 2q11-2q16 from rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine SO ONCOGENE LA English DT Article DE heterocyclic amines; allelic imbalance; quantitative real-time polymerase chain reaction; microsatellite instability; loss of heterozygosity; gene expression; rat chromosome 2q ID RASGTPASE ACTIVATING PROTEIN; SPRAGUE-DAWLEY RATS; BREAST-CANCER; EPITHELIAL-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; MICROSATELLITE INSTABILITY; PROSTATE-CANCER; ONCOSTATIN-M; DIETARY-FAT; TUMORS AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a compound found in cooked meat, is a mammary gland carcinogen in rats. Comparative genomic hybridization of PhIP-induced rat mammary gland carcinomas revealed loss in the centromeric region of 2q, a region known to carry the mammary carcinoma susceptibility 1 (Mcs1) gene and several other genes relevant to carcinogenesis. Allelic imbalance, specifically microsatellite instability and loss of heterozygosity, was examined in mammary gland carcinomas induced by PhIP in Sprague-Dawley (SD) x Wistar Furth F1 hybrid rats. In a polymerase chain reaction (PCR)-based assay with 34 microsatellite markers coinciding to 2q11-2q16, nine markers revealed allelic imbalance. The frequency of imbalance in the tumors varied from 10 to 100% depending on the specific marker. However, none of the markers coinciding with the Mcs1 gene locus showed allelic imbalance, suggesting that alterations at this locus were not associated with PhIP-induced rat mammary gland cancer. The expression of several genes physically mapped to 2q11-2q16 and potentially involved in carcinogenesis including Ccnb (cyclin B1), Ccnh (cyclin H), Rasa (Ras GAP), RasgrJ2, Pi3kr1 (p85alpha), and Il6st (gp130) was also examined by quantitative real-time PCR and immunohistochemistry (IHC) across a large bank of PhIP-induced SD rat mammary gland carcinomas. By quantitative real-time PCR, the mRNA expression of Rasa, Pi3kr1, Ccnh, and 1l6st in carcinomas was, respectively, 22-, 20-, three- and threefold higher in carcinomas than in control mammary gland tissues (P<0.05, Student's t-test). A statistically sixfold lower expression of Rasgrf 2 was detected in carcinomas whereas no significant change in Ccnb1 expression was observed. The findings from quantitative real-time PCR were confirmed by IHC for each gene. In addition, the proliferation index in mammary gland carcinomas as assessed by PCNA was found to correlate with the overexpression of Cyclin H by IHC analysis (P<0.05, Spearman Rank Order Correlation). The findings from the current study implicate molecular alterations in the proximal region of 2q in PhIP-induced rat mammary gland carcinomas. C1 NCI, Ctr Canc Res,Lab Expt Carcinogenesis, Chem Carcinogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Snyderwine, EG (reprint author), NCI, Ctr Canc Res,Lab Expt Carcinogenesis, Chem Carcinogenesis Sect, NIH, Bldg 37,Room 4134,37 Convent Dr MSC 4262, Bethesda, MD 20892 USA. NR 41 TC 11 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 27 PY 2003 VL 22 IS 8 BP 1253 EP 1260 DI 10.1038/sj.onc.1206233 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 650EK UT WOS:000181249700015 PM 12606953 ER PT J AU Paik, HC Hoffmann, SC Egan, TM AF Paik, HC Hoffmann, SC Egan, TM TI Pulmonary preservation studies: Effects on endothelial function and pulmonary adenine nucleotides SO TRANSPLANTATION LA English DT Article ID CANINE LUNG PRESERVATION; UNIVERSITY-OF-WISCONSIN; LOW-POTASSIUM DEXTRAN; ISCHEMIA-REPERFUSION INJURY; EURO-COLLINS SOLUTION; FLUSH-PERFUSION; UW-SOLUTION; TRANSPLANTATION; VIABILITY; METABOLISM AB Background. Lung transplantation is an effective therapy plagued by a high incidence of early graft dysfunction, in part because of reperfusion injury. The optimal preservation solution for lung transplantation is unknown. We performed experiments using an isolated perfused rat lung model to test the effect of lung preservation with three solutions commonly used in clinical practice. Methods. Lungs were retrieved from Sprague-Dawley rats and flushed with one of three solutions: modified Euro-Collins (MEC), University of Wisconsin (UW), or low potassium dextran and glucose (LPDG), then stored cold for varying periods before reperfusion with Earle's balanced salt solution using the isolated perfused rat lung model. Outcome measures were capillary filtration coefficient (Kfc), wet-to-dry weight ratio, and lung tissue levels of adenine nucleotides and cyclic AMP. Results. All lungs functioned well after 4 hr of storage. By 6 hr, UW-flushed lungs had a lower Kfc than LPDG-Rushed lungs. After 8 hr of storage, only UW-flushed lungs had a measurable Kfc. Adenine nucleotide levels were higher in UW-flushed lungs after prolonged storage. Cyclic AMP levels correlated with Kfc in all groups. Conclusions. Early changes in endothelial permeability seemed to be better attenuated in lungs flushed with UW compared with LPDG or MEC; this was associated with higher amounts of adenine nucleotides. MEC-flushed lungs failed earlier than LPDG-flushed or UW-flushed lungs. The content of the solution may be more important for lung preservation than whether the ionic composition is intracellular or extracellular. C1 Univ N Carolina, Dept Surg, Div Cardiothorac Surg, Chapel Hill, NC 27599 USA. Yonsei Univ, Yongdong Severance Hosp, Coll Med, Seoul 120749, South Korea. NIDDK, Navy Transplantat & Autoimmun Branch, T Cell Funct Sect, AFRRI, Bethesda, MD 20892 USA. RP Egan, TM (reprint author), Univ N Carolina, Dept Surg, Div Cardiothorac Surg, CB 7065,108 Burnett Womack Bldg, Chapel Hill, NC 27599 USA. NR 33 TC 4 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 27 PY 2003 VL 75 IS 4 BP 439 EP 444 DI 10.1097/01.TP.0000045685.09601.9E PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 650BG UT WOS:000181242000004 PM 12605106 ER PT J AU Busch, MP Kleinman, SH Nemo, GJ AF Busch, MP Kleinman, SH Nemo, GJ TI Current and emerging infectious risks of blood transfusions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID UNITED-STATES; SAFETY; DISEASE; NAT C1 Blood Ctr Pacific, San Francisco, CA 94118 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Blood Syst Inc, Scottsdale, AZ USA. Westat Corp, Rockville, MD USA. Univ British Columbia, Victoria, BC, Canada. NHLBI, Bethesda, MD 20892 USA. RP Busch, MP (reprint author), Blood Ctr Pacific, 270 Masonic Ave, San Francisco, CA 94118 USA. FU NHLBI NIH HHS [N01-HB-97077]; PHS HHS [47114-97079, 47114-97080, 47114-97082, 47114-77078, 47114-97081] NR 28 TC 167 Z9 175 U1 0 U2 3 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 FEB 26 PY 2003 VL 289 IS 8 BP 959 EP 962 DI 10.1001/jama.289.8.959 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 648BK UT WOS:000181129800002 PM 12597733 ER PT J AU Jones, DW Appel, LJ Sheps, SG Roccella, EJ Lenfant, C AF Jones, DW Appel, LJ Sheps, SG Roccella, EJ Lenfant, C TI Measuring blood pressure accurately - New and persistent challenges SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID AUTOMATED SPHYGMOMANOMETRY; MEASURING DEVICES; HYPERTENSION; ABC C1 Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. Johns Hopkins Med Inst, Dept Epidemiol & Int Hlth, Baltimore, MD 21205 USA. Mayo Clin, Rochester, MN USA. NHLBI, Bethesda, MD 20892 USA. RP Jones, DW (reprint author), Univ Mississippi, Med Ctr, Dept Med, 2500 N State St, Jackson, MS 39216 USA. NR 30 TC 112 Z9 118 U1 1 U2 8 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 FEB 26 PY 2003 VL 289 IS 8 BP 1027 EP 1030 DI 10.1001/jama.289.8.1027 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 648BK UT WOS:000181129800031 PM 12597757 ER PT J AU Hanson, GR Li, TK AF Hanson, GR Li, TK TI Public health implications of excessive alcohol consumption SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID ABUSE C1 NIDA, Bethesda, MD 20892 USA. NIAAA, NIH, US Dept HHS, Bethesda, MD USA. RP Hanson, GR (reprint author), NIDA, 6001 Execut Blvd,Room 5274,MSC9581, Bethesda, MD 20892 USA. NR 15 TC 26 Z9 26 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 FEB 26 PY 2003 VL 289 IS 8 BP 1031 EP 1032 DI 10.1001/jama.289.8.1031 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 648BK UT WOS:000181129800032 PM 12597758 ER PT J AU Moiseyev, G Crouch, RK Goletz, P Oatis, J Redmond, TM Ma, JX AF Moiseyev, G Crouch, RK Goletz, P Oatis, J Redmond, TM Ma, JX TI Retinyl esters are the substrate for isomerohydrolase SO BIOCHEMISTRY LA English DT Article ID RETINALDEHYDE-BINDING PROTEIN; ALL-TRANS-RETINOL; LEBER CONGENITAL AMAUROSIS; PIGMENT EPITHELIAL-CELLS; VISUAL CYCLE; VITAMIN-A; CHILDHOOD BLINDNESS; RPE65 MUTATIONS; BETA-CAROTENE; ENERGY-SOURCE AB Regeneration of 11-cis retinal from all-trans retinol in the retinal pigment epithelium (RPE) is a critical step in the visual cycle. The enzyme(s) involved in this isomerization process has not been identified and both all-trans retinol and all-trans retinyl esters have been proposed as the substrate. This study is to determine the substrate of the isomerase enzyme or enzymatic complex. Incubation of bovine RPE microsomes with all-trans [H-3]-retinol generated both retinyl esters and 11-cis retinol. Inhibition of lecithin retinol acyltransferase (LRAT) with 10-N-acetamidodecyl chloromethyl ketone (AcDCMK) or cellular retinol-binding protein I (CRBP) diminished the generation of both retinyl esters and 11 -cis retinol from all-trans retinol. The 11 -cis retinol production correlated with the retinyl ester levels, but not with the all-trans retinol levels in the reaction mixture. When retinyl esters were allowed to form prior to the addition of the LRAT inhibitors, a significant amount of isomerization product was generated. Incubation of all-trans [H-3]-retinyl palmitate with RPE microsomes generated 11-cis retinol without any detectable production of all-trans retinol. The RPE65 knockout (Rpe65(-/-)) mouse eyecup lacks the isomerase activity, but LRAT activity remains the same as that in the wild-type (WT) mice. Retinyl esters in WT mice plateau at 8 weeks-of-age, but Rpe65(-/-) mice continue to accumulate retinyl esters with age (e.g., at 36 weeks, the levels are 20 x that of WT). Our data indicate that the retinyl esters are the substrate of the isomerization reaction. C1 Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29425 USA. NEI, Lab Retinal Cell & Mol Biol, Bethesda, MD USA. RP Ma, JX (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA. OI Redmond, T. Michael/0000-0002-1813-5291 FU NEI NIH HHS [EY04939, EY12231, EY12600] NR 51 TC 86 Z9 87 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 25 PY 2003 VL 42 IS 7 BP 2229 EP 2238 DI 10.1021/bi026911y PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647NE UT WOS:000181098800046 PM 12590612 ER PT J AU Combadiere, C Potteaux, S Gao, JL Esposito, B Casanova, S Lee, EJ Debre, P Tedgui, A Murphy, PM Mallat, Z AF Combadiere, C Potteaux, S Gao, JL Esposito, B Casanova, S Lee, EJ Debre, P Tedgui, A Murphy, PM Mallat, Z TI Decreased atherosclerotic lesion formation in CX3CR1/apolipoprotein E double knockout mice SO CIRCULATION LA English DT Article DE atherosclerosis; leukocytes; receptors; inflammation ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; FRACTALKINE RECEPTOR CX(3)CR1; CORONARY-ARTERY DISEASE; LOW-DENSITY-LIPOPROTEIN; CHEMOKINE FRACTALKINE; TARGETED DELETION; DEFICIENT MICE; POLYMORPHISM; HYPERCHOLESTEROLEMIA; ACCUMULATION AB Background-Fractalkine (CX3CL1), a CX3C chemokine, is expressed in the vessel wall and mediates the firm adhesion and chemotaxis of leukocytes expressing its receptor, CX3CR1. A polymorphism in the CX3CR1 gene is associated with low CX3CR1 expression and reduced risk of acute coronary disease in humans. Methods and Results-We generated CX3CR1-deficient mice (CX3CR1(-/-)) by targeted gene disruption and crossed them with the proatherogenic apolipoprotein E-deficient mice (apoE(-/-)). Here we show that the extent of lipid-stained lesions in the thoracic aorta was reduced by 59% in CX3CR1/apoE double knockout mice compared with their CX3CR1(+/+)/apoE(-/-) littermates. The development of atherosclerosis in the aortic sinus was also markedly altered in the double knockout mice, with 50% reduction in macrophage accumulation. Although lesions of CX3CR1(-/-) mice were smaller in size, they retained a substantial accumulation of smooth muscle cells and collagen, features consistent with a stable plaque phenotype. Finally, CX3CR1(+/-) /apoE(-/-)mice showed the same reduction in atherosclerosis as the CX3CR1(-/-)/apoE(-/-) mice. Conclusions-The CX3CR1-CX3CL1 pathway seems to play a direct and critical role in monocyte recruitment and atherosclerotic lesion development in a mouse model of human atherosclerosis. C1 Hop Lariboisiere, INSERM, U541, Inst Federat Rech Circulat Paris 7, F-75010 Paris, France. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Hop La Pitie Salpetriere, INSERM, U543, Lab Immunol Cellulaire & Tissulaire, Paris, France. NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. RP Mallat, Z (reprint author), Hop Lariboisiere, INSERM, U541, Inst Federat Rech Circulat Paris 7, 41 Bd Chapelle, F-75010 Paris, France. RI Mallat, Ziad/D-4041-2012; Combadiere, Christophe/I-5639-2013; OI Combadiere, Christophe/0000-0002-1755-4531; Mallat, Ziad/0000-0003-0443-7878 NR 31 TC 323 Z9 335 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 25 PY 2003 VL 107 IS 7 BP 1009 EP 1016 DI 10.1161/01.CIR.0000057548.68243.42 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800030 PM 12600915 ER PT J AU Appel, LJ Champagne, C Cooper, L Elmer, P Harsha, D Lin, PH Obarzanek, E Stevens, V Svetkey, L Vollmer, W Young, D AF Appel, LJ Champagne, C Cooper, L Elmer, P Harsha, D Lin, PH Obarzanek, E Stevens, V Svetkey, L Vollmer, W Young, D TI Main results of PREMIER, a clinical trial of comprehensive lifestyle modification SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. NHLBI, Bethesda, MD 20892 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Maryland, College Pk, MD 20742 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 FEB 25 PY 2003 VL 107 IS 7 MA 33 BP E7007 EP E7007 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800073 ER PT J AU Bild, DE Detrano, R Liu, K Shahar, E Guerci, A Jackson, S Peterson, D AF Bild, DE Detrano, R Liu, K Shahar, E Guerci, A Jackson, S Peterson, D TI Ethnic differences in coronary calcification: The multi-ethnic study of atherosclerosis SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 NHLBI, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Res & Educ Inst, Torrance, CA USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Minnesota, Minneapolis, MN USA. St Francis Hosp, Roslyn, NY USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Washington, Seattle, WA 98195 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 FEB 25 PY 2003 VL 107 IS 7 MA 28 BP E7006 EP E7006 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800068 ER PT J AU Bryson, CL Smith, NL Kuller, L Manolio, T Paulo, C Lewis, W Boyko, E Furberg, C Psaty, BM AF Bryson, CL Smith, NL Kuller, L Manolio, T Paulo, C Lewis, W Boyko, E Furberg, C Psaty, BM TI Relative risk of heart failure in an elderly population treated with peripheral alpha-1 antagonists SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 VA Puget Sound Healthcare Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Pittsburgh, PA USA. NHLBI, Bethesda, MD 20892 USA. Johns Hopkins, Baltimore, MD USA. Univ Calif Davis, Sacramento, CA 95817 USA. Wake Forest Univ, Winston Salem, NC 27109 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 FEB 25 PY 2003 VL 107 IS 7 MA P52 BP E7020 EP E7020 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800133 ER PT J AU Fox, CS Corey, D Larson, MG Polak, JF Wolf, PA D'Agostino, RB Tofler, GH Lindpaintner, K O'Donnell, CJ AF Fox, CS Corey, D Larson, MG Polak, JF Wolf, PA D'Agostino, RB Tofler, GH Lindpaintner, K O'Donnell, CJ TI Evidence for association of the angiotensinogen locus with carotid intimal medial thickness SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Boston, MA 02215 USA. Royal N Shore Hosp, Sydney, NSW, Australia. Roche Genet, Basel, Switzerland. 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 FEB 25 PY 2003 VL 107 IS 7 MA P64 BP E7022 EP E7022 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800146 ER PT J AU Fox, CS Sullivan, L D'Agostino, R Wilson, PW AF Fox, CS Sullivan, L D'Agostino, R Wilson, PW TI Modest effect of diabetes duration on CVD risk: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 7 Z9 7 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 FEB 25 PY 2003 VL 107 IS 7 MA P47 BP E7019 EP E7019 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800128 ER PT J AU Greenland, P Liu, K Daviglus, ML Nelson, JC Psaty, B Schreiner, P Olson, J Burke, G AF Greenland, P Liu, K Daviglus, ML Nelson, JC Psaty, B Schreiner, P Olson, J Burke, G TI Favorable risk factor profile ("low risk") is associated with less subclinical atherosclerosis: The MESA study SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Washington, Seattle, WA 98195 USA. Univ Minnesota, Minneapolis, MN USA. NHLBI, Bethesda, MD 20892 USA. Wake Forest Univ, Winston Salem, NC 27109 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 FEB 25 PY 2003 VL 107 IS 7 MA P129 BP E7035 EP E7035 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800210 ER PT J AU Harris, JI Hibbeln, JR Salem, N Muldoon, MF AF Harris, JI Hibbeln, JR Salem, N Muldoon, MF TI Statin treatment alters fatty acid composition in hypercholesterolemic patients SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NIAAA, NIH, Sect Nutr Neurosci, Lab Membrane Biophys & Biochem, 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 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 25 PY 2003 VL 107 IS 7 MA P119 BP E7033 EP E7033 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800200 ER PT J AU Kennedy, M Solomon, C Newman, AB Criqui, MH Manolio, TA Burke, GL Polak, JF Enright, P Cushman, M AF Kennedy, M Solomon, C Newman, AB Criqui, MH Manolio, TA Burke, GL Polak, JF Enright, P Cushman, M TI Predictors of worsening ankle-arm index in the elderly: The Cardiovascular Health Study (CHS) SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 Univ Vermont, Colchester, VT USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif San Diego, San Diego, CA 92103 USA. NHLBI, Bethesda, MD 20892 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Arizona, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 25 PY 2003 VL 107 IS 7 MA P3 BP E7010 EP E7010 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800085 ER PT J AU Lewis, CE West, DS Loriz, C Kiefe, C Hulley, S AF Lewis, CE West, DS Loriz, C Kiefe, C Hulley, S TI Predictors of 15-year weight gain in a bi-racial cohort of young adults: The CARDIA Study SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 Univ Alabama, Birmingham, AL USA. NHLBI, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 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 FEB 25 PY 2003 VL 107 IS 7 MA 11 BP E7003 EP E7003 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800051 ER PT J AU Muntner, P Raggi, P Whelton, PK Gordon, D He, J AF Muntner, P Raggi, P Whelton, PK Gordon, D He, J TI Awareness, treatment and control of high blood cholesterol in the United States: Results of the Third National Health and Nutrition Examination Survey (NHANES III) SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 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 FEB 25 PY 2003 VL 107 IS 7 MA P77 BP E7025 EP E7025 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800158 ER PT J AU Resnick, HE Fabsitz, R Devereux, R Jones, K McDermott, M Howard, BV AF Resnick, HE Fabsitz, R Devereux, R Jones, K McDermott, M Howard, BV TI Long-term progression of peripheral arterial disease in American Indians: The Strong Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 MedStar Res Inst, Hyattsville, MD USA. NHLBI, Bethesda, MD 20892 USA. Cornell Med Ctr, New York, NY USA. Northwestern Univ, Chicago, IL 60611 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 FEB 25 PY 2003 VL 107 IS 7 MA P60 BP E7021 EP E7021 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800141 ER PT J AU Sutton-Tyrrell, K Kupelian, V Havlik, RJ Simonsick, E Najjar, S Spurgeon, HA Lakatta, E Pahor, M Kritchevsky, S Newman, AB AF Sutton-Tyrrell, K Kupelian, V Havlik, RJ Simonsick, E Najjar, S Spurgeon, HA Lakatta, E Pahor, M Kritchevsky, S Newman, AB TI Association of aortic pulse wave velocity with mortality in older adults SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 Univ Pittsburgh, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Tennessee, Memphis, TN 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 FEB 25 PY 2003 VL 107 IS 7 MA P132 BP E7036 EP E7036 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800213 ER PT J AU Keith, B Xu, Y Grem, JL AF Keith, B Xu, Y Grem, JL TI Measurement of the anti-cancer agent gemcitabine in human plasma by high-performance liquid chromatography SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE gemcitabine ID CELL LUNG-CANCER; PHASE-I; 2',2'-DIFLUORODEOXYCYTIDINE; PHARMACOLOGY AB A reversed-phase HPLC assay has been developed to determine the concentration of the anti-metabolite 2',2'-difluorodeoxycytidine (gemcitabine, dFdC) in human plasma over the concentration range of 0.5-150 muM (0.13-39.44 mug/ml), and 2',2'-difluorodeoxyuridine (dFdU), the deaminated, inactive metabolite, over the range of 1.0-227 muM (0.26-60 mug/ml). After the addition of 20 nmol 2'-fluorodeoxycytidine (FdC) as an internal standard, 0.5-ml samples of plasma were subjected to acetonitrile precipitation, followed by analysis using a gradient reversed-phase HPLC assay with UV detection. A Phenomenex Columbus(TM) C-18 column, 5 mum, 150x4.6 mm, and a Waters C-18,C- 4mum, Nova-Pak Sentry guard column were used to achieve separation. FdC, dFdC and dFdU were monitored at 282, 269 and 258 nm, respectively, on a Waters 996 photodiode array detector. The mobile phase, run at a total flow-rate of 1.5 ml/min, was composed of two solvents: 50 mM ammonium acetate pH 5.0 in either 2% (solvent A) or 10% methanol (solvent B, v/v); 100% solvent A was run for 17 min, followed by a linear gradient to 100% solvent B over 14 min. FdC, dFdC and dFdU were resolved from endogenous compounds and had retention times of 13.6 +/- 0.5, 18.1 +/- 1.1 and 29.0 +/- 0.6 min, respectively. The assay was useful in measuring the plasma levels of both atialytes in samples obtained from adult cancer patients participating in a Phase I trial of gemcitabine given as either a 1- or 2-h infusion weekly for 3 of 4 weeks. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NCI, Canc Therapeut Branch, Ctr Canc Res, Natl Naval Med Ctr, Bethesda, MD 20889 USA. RP Grem, JL (reprint author), NCI, Canc Therapeut Branch, Ctr Canc Res, Natl Naval Med Ctr, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 10 TC 26 Z9 27 U1 0 U2 4 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 FEB 25 PY 2003 VL 785 IS 1 BP 65 EP 72 AR PII S1570-0232(02)00859-0 DI 10.1016/S1570-0232(02)00859-0 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 638VJ UT WOS:000180592700006 PM 12535839 ER PT J AU Strozyk, D Blennow, K White, LR Launer, LJ AF Strozyk, D Blennow, K White, LR Launer, LJ TI CSF A beta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study SO NEUROLOGY LA English DT Article ID FLUID DRAINAGE PATHWAYS; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; INTERSTITIAL FLUID; APOLIPOPROTEIN-E; BRAIN; TAU; ANGIOPATHY; DEMENTIA; BETA-AMYLOID((1-42)) AB Objective: To investigate the relationship of amyloid neuropathology to postmortem CSF Abeta 42 levels in an autopsy sample of Japanese American men from the population-based Honolulu-Asia Aging Study. Methods: In 1991, participants were assessed and diagnosed with dementia (including subtype) based on published criteria. At death CSF was obtained from the ventricles. Neuritic plaques (NP) and diffuse plaques in areas of the neocortex and hippocampus were examined using Bielschowsky silver stains. Cerebral amyloid angiopathy (CAA) was measured by immunostaining for beta4 amyloid in cerebral vessels in the neocortex. Neuropathologically confirmed AD was diagnosed using Consortium to Establish a Registry for Alzheimer's Disease criteria. In 155 autopsy samples, log transformed linear regression models were used to examine the association of NP and CAA to Abeta 42 levels, controlling for clinical dementia severity, time between diagnosis and death, age at death, brain weight, hours between death and collection of CSF, education, and APOE genotype. Results: Higher numbers of NP in the neocortex (p trend = 0.001) and in the hippocampus (p trend = 0.03) were strongly associated with lower levels of Abeta 42. Individuals with CAA had lower Abeta 42 levels (beta coefficient = -0.48; 95% CI -0.9, -0.1). Compared to participants with a diagnosis of clinical dementia, those with pathologically confirmed AD had lower Abeta 42 levels (P coefficient = -0.74; 95% CI -1.4, -0.1). Conclusion: The current study suggests that lower Abeta 42 levels reflect neuropathologic processes implicated in amyloid-related pathologies, such as NP and CAA. C1 NIA, LEDB, NIH, Bethesda, MD 20892 USA. Sahlgrens Univ Hosp, Dept Clin Neurosci, Molndal, Sweden. Pacific Hlth Res Inst, Honolulu, HI USA. RP Strozyk, D (reprint author), NIA, LEDB, NIH, Gateway Bldg 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. NR 27 TC 285 Z9 292 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 25 PY 2003 VL 60 IS 4 BP 652 EP 656 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 679XV UT WOS:000182948000023 PM 12601108 ER PT J AU Mattson, MP AF Mattson, MP TI Will caloric restriction and folate protect against AD and PD? SO NEUROLOGY LA English DT Article ID PLASMA HOMOCYSTEINE CONCENTRATIONS; AMYLOID-BETA-PEPTIDE; DIETARY RESTRICTION; PARKINSONS-DISEASE; ALZHEIMER-DISEASE; DOPAMINERGIC-NEURONS; MOLECULAR MECHANISMS; HIPPOCAMPAL-NEURONS; DENTATE GYRUS; BRAIN-DAMAGE AB Recent epidemiologic studies of different sample populations have suggested that the risk of AD and PD may be increased in individuals with high-calorie diets and in those with increased homocysteine levels. Dietary restriction and supplementation with folic acid can reduce neuronal damage and improve behavioral outcome in mouse models of AD and PD. Animal studies have shown that the beneficial effects of dietary restriction result, in part, from increased production of neurotrophic factors and cytoprotective protein chaperones in neurons. By keeping homocysteine levels low, folic acid can protect cerebral vessels and can prevent the accumulation of DNA damage in neurons caused by oxidative stress and facilitated by homocysteine. Although further studies are required in humans, the emerging data suggest that high-calorie diets and elevated homocysteine levels may render the brain vulnerable to neurodegenerative disorders. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr 4F01, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 47 TC 72 Z9 77 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 25 PY 2003 VL 60 IS 4 BP 690 EP 695 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 679XV UT WOS:000182948000028 PM 12601113 ER PT J AU Morocz, IA Karni, A Haut, S Lantos, G Liu, G AF Morocz, IA Karni, A Haut, S Lantos, G Liu, G TI fMRI of triggerable aurae in musixogenic epilepsy SO NEUROLOGY LA English DT Article ID FUNCTIONAL MRI; BRAIN AB The authors studied a patient with musicogenic epilepsy triggered by one specific musical piece using 3D PRESTO fMRI. During epileptic aurae initiated by the stimulus, signal increases were found in the left anterior temporal lobe, correlating with ictal EEG and SPECT showing a left anterior temporal focus, and the right gyrus rectus. Because fMRI indicated a cascade of recruitment of the ventral frontal lobes by epileptogenic music, left anterior temporal lobe activity could be secondary to a right gyros rectus focus, possibly triggered by emotional processing of music. C1 Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. Yeshiva Univ Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Neuroradiol, Jacobi Med Ctr, Bronx, NY 10461 USA. Univ Haifa, Dept Sci, Brain Behav Res Ctr, IL-31999 Haifa, Israel. NIH, Biomed Imaging Program, Rockville, MD USA. RP Morocz, IA (reprint author), Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. NR 10 TC 27 Z9 30 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 25 PY 2003 VL 60 IS 4 BP 705 EP 709 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 679XV UT WOS:000182948000032 PM 12601117 ER PT J AU Foley, DJ Brock, DB Lanska, DJ AF Foley, DJ Brock, DB Lanska, DJ TI Trends in dementia mortality from two National Mortality Followback Surveys SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; UNITED-STATES; PREVALENCE AB The National Center for Health Statistics conducted National Mortality Followback Surveys (NMFS) in 1986 and 1993. The next-of-kin's report of a physician's diagnosis of AD before death and a listing of AD or other dementia as the underlying cause increased significantly among women but remained stable among men. Currently, AD is among the top 10 leading causes of death in elderly white men and women in the United States. C1 NIA, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Tomah, WI USA. Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA. RP Foley, DJ (reprint author), NIA, 7201 Wisconsin Ave,Suite 3C309, Bethesda, MD 20892 USA. NR 10 TC 12 Z9 12 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 25 PY 2003 VL 60 IS 4 BP 709 EP 711 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 679XV UT WOS:000182948000033 PM 12601118 ER PT J AU Foster, A Wu, HF Chen, WB Williams, W Bowen, WD Matsumoto, RR Coop, A AF Foster, A Wu, HF Chen, WB Williams, W Bowen, WD Matsumoto, RR Coop, A TI 1,4-dibenzylpiperazines possess anticocaine activity SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID SIGMA-RECEPTOR LIGANDS; COCAINE ABUSE; ATTENUATE; ANALOGS; BINDING; MICE; PHARMACOTHERAPIES; BD1008 AB N,N-Dibenzylpiperazines have high affinity for sigma receptors, and we aimed to increase their anticocaine activity by introducing substituents known to enhance such activity in other sigma ligands. Ligands with high affinity for sigma-1 receptors resulted, but their activity in attenuating cocaine-induced convulsions did not cot-relate with sigma-l binding affinity, and may be more closely related to their sigma-2 binding affinities. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NIDDKD, Med Chem Lab, Bethesda, MD 20892 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pharmaceut Sci, Coll Pharm, Oklahoma City, OK 73117 USA. RP Coop, A (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, 20 N Pine St, Baltimore, MD 21201 USA. FU NIDA NIH HHS [DA-13978, DA-11979] NR 16 TC 22 Z9 22 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD FEB 24 PY 2003 VL 13 IS 4 BP 749 EP 751 DI 10.1016/S0960-894X(02)01034-X PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 645UX UT WOS:000180998900036 PM 12639573 ER PT J AU Ghebranious, N Vaske, D Yu, AD Zhao, CF Marth, G Weber, JL AF Ghebranious, N Vaske, D Yu, AD Zhao, CF Marth, G Weber, JL TI STRP Screening Sets for the human genome at 5 cM density SO BMC GENOMICS LA English DT Article ID TANDEM-REPEAT POLYMORPHISMS; HIGH-RESOLUTION; LINKAGE DISEQUILIBRIUM; GENETIC-MARKERS; DNA-POLYMERASE; MICROSATELLITES; POPULATION; RECOMBINATION; TRINUCLEOTIDE; MUTATION AB Background: Short tandem repeat polymorphisms (STRPs) are powerful tools for gene mapping and other applications. A STRP genome scan of 10 cM is usually adequate for mapping single gene disorders. However mapping studies involving genetically complex disorders and especially association (linkage disequilibrium) often require higher STRP density. Results: We report the development of two separate 10 cM human STRP Screening Sets (Sets 12 and 52) which span all chromosomes. When combined, the two Sets contain a total of 782 STRPs, with average STRP spacing of 4.8 cM, average heterozygosity of 0.72, and total sex-average coverage of 3535 cM. The current Sets are comprised almost entirely of STRPs based on tri- and tetranucleotide repeats. We also report correction of primer sequences for many STRPs used in previous Screening Sets. Detailed information for the new Screening Sets is available from our web site: http://research.marshfieldclinic.org/genetics. Conclusion: Our new human STRP Screening Sets will improve the quality and cost effectiveness of genotyping for gene mapping and other applications. C1 Marshfield Clin Res Fdn, Ctr Med Genet, Marshfield, WI 54449 USA. Pioneer HiBred Int Inc, Johnston, IA USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. Marshfield Clin Res Fdn, Mol Diagnost Genotyping Lab, Marshfield, WI 54449 USA. RP Weber, JL (reprint author), Marshfield Clin Res Fdn, Ctr Med Genet, Marshfield, WI 54449 USA. EM ghebranious.nader@marshfieldclinic.org; dave.vaske@pioneer.com; yua@cmg.mfldclin.edu; zhaoc@cmg.mfldclin.edu; marth@ncbi.nlm.nih.gov; weberj@cmg.mfldclin.edu FU NHLBI NIH HHS [HV48141, N01HV48141] NR 36 TC 29 Z9 29 U1 0 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 FEB 24 PY 2003 VL 4 AR 6 DI 10.1186/1471-2164-4-6 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 659DV UT WOS:000181763000001 PM 12600278 ER PT J AU Trapani, V Patel, V Leong, CO Ciolino, HP Yeh, GC Hose, C Trepel, JB Stevens, MFG Sausville, EA Loaiza-Perez, AI AF Trapani, V Patel, V Leong, CO Ciolino, HP Yeh, GC Hose, C Trepel, JB Stevens, MFG Sausville, EA Loaiza-Perez, AI TI DNA damage and cell cycle arrest induced by 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203, NSC 703786) is attenuated in aryl hydrocarbon receptor deficient MCF-7 cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE 2-(4-aminophenyl)benzothiazoles; aryl hydrocarbon receptor; CYPIAI; DNA damage; S-phase arrest; MCF-7 ID BREAST-CANCER CELLS; IN-VITRO; ANTITUMOR BENZOTHIAZOLES; BIOLOGICAL PROPERTIES; MEDIATES SENSITIVITY; 2-(4-AMINOPHENYL)BENZOTHIAZOLES; CYP1A1; LINES; INDUCTION; ADDUCTS AB The fluorinated benzothiazole analogue 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203, NSC 703786) is a novel agent with potent and selective antitumour properties and, in the form of its L-lysylamide prodrug Phortress (NSC 7 10305), is a current candidate for early phase clinical studies. Previous findings have indicated that cytochrome P450 IAI (CYPIAI) may play a role in the antitumour activity of molecules in the benzothiazole series including the nonfluorinated parent compound 2-(4-amino-3methyiphenyl)benzothiazole (DF 203, NSC 674495) (Kashiyama et al, 1999; Chua et a, 2000; Loaiza-Perez et a], 2002). In this study, we assessed and verified that a fully functional aryl hydrocarbon receptor (AhR) signalling pathway is a necessary requisite for the induction of efficient cytotoxicity by 5F 203 in MCF-7 wild-type sensitive cells. Drug exposure caused MCF-7 sensitive cells to arrest in G I and S phase, and induced DNA adduct formation, in contrast to AhR-deficient AhR-deficient AHR(100) MCF-7 cells. In sensitive MCF-7 cells, induction of CYPIAI and CYPIBI transcription (measured by luciferase reporter assay and real-time reverse transcriptasepolymerase chain reaction (RT-PCR)), and 7-ethoxyresorufin-O-deethylase (EROD) activity was demonstrated, following treatment with 5 F 203. In contrast, in resistant AH(R100) cells, drug treatment did not affect CYPIAI and CYPIBI transcription and EROD activity. Furthermore, AHR(100) cells failed to produce either protein/DNA complexes on the xenobiotic responsive element (XRE) sequence of CYPIAI promoter (measured by electrophoretic mobility shift assay) or DNA adiducts. The data confirm that activation of the AhR signalling pathway is an important feature of the antitumour activity of 5F 203. (C) 2003 Cancer Research UK. C1 NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. Univ Nottingham, Sch Pharmaceut Sci, Nottingham NG7 2RD, England. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD USA. Natl Canc Inst, Cellular Def & Carcinogenesis Sect, Basic Res Lab, Canc Res Ctr,NIH, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, Frederick, MD 21702 USA. NCI, Med Oncol Clin Res Unit, Med Branch, NIH, Bethesda, MD 20892 USA. RP Loaiza-Perez, AI (reprint author), NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, 9000 Rockville Pike,Blgd 10,Rm 6N115, Bethesda, MD 20892 USA. OI Trapani, Valentina/0000-0002-0259-6624 NR 33 TC 69 Z9 73 U1 0 U2 5 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 FEB 24 PY 2003 VL 88 IS 4 BP 599 EP 605 DI 10.1038/sj.bjc.6600722 PG 7 WC Oncology SC Oncology GA 655DC UT WOS:000181535200018 PM 12592376 ER PT J AU D'Amato, M Flugy, AM Alaimo, G Bauder, B Kohn, EC De Leo, G Alessandro, R AF D'Amato, M Flugy, AM Alaimo, G Bauder, B Kohn, EC De Leo, G Alessandro, R TI Role of calcium in E-selectin induced phenotype of T84 colon carcinoma cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE E-selectin; calcium signaling; metastasis; colon carcinoma; tumor cells ID TYROSINE PHOSPHORYLATION; TRANSENDOTHELIAL MIGRATION; SIGNAL-TRANSDUCTION; HUMAN-NEUTROPHILS; CA2+ INFLUX; RECEPTOR; ADHESION; ACTIVATION; REQUIRES; PROTEIN AB The adhesion of cancer cells to the endothelium during the metastatic process involves the interaction of specific cell-cell adhesion receptors on the cell surface. E-selectin on endothelial cells and sialyl Lewis X carbohydrate component on tumor cells are mainly implicated in the adhesion of colon carcinoma cells to the endothelium of target organ. In this paper we show that binding of E-selectin to T84 colon tumor cells causes approximately a twofold increase in intracellular calcium concentration. In particular, using two inhibitors of receptor operated calcium channels, CAI and SK&F 96365, we present evidences that the augmentation in cytoplasmic calcium originates from ionic influx from extracellular sources. Furthermore, we demonstrated that modulation of [Ca2+](i) by engagement of E-selectin receptor starts signal transduction pathways that affect cell spreading, tyrosine phosphorylation signaling, and cancer cell motility. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Palermo, Dipartimento Biopatol & Metodol Biomed, I-90133 Palermo, Italy. NCI, Pathol Lab, Mol Signaling Sect, Bethesda, MD 20892 USA. RP Alessandro, R (reprint author), Univ Palermo, Dipartimento Biopatol & Metodol Biomed, Via Divisi 83, I-90133 Palermo, Italy. NR 37 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 21 PY 2003 VL 301 IS 4 BP 907 EP 914 DI 10.1016/S0006-291X(03)00062-7 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 652CT UT WOS:000181362800015 PM 12589798 ER PT J AU Van, QN Chmurny, GN Veenstra, TD AF Van, QN Chmurny, GN Veenstra, TD TI The depletion of protein signals in metabonomics analysis with the WET-CPMG pulse sequence SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; NMR DIFFUSION MEASUREMENTS; PATTERN-RECOGNITION; H-1-NMR SPECTROSCOPY; CHEMICAL-SHIFTS; SUPPRESSION; BIOFLUIDS; MACROMOLECULES; PLASMA; PHASE AB Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical tool capable of providing a comprehensive metabolic profile of biofluids such as urine, plasma, and serum. Unfortunately, when measuring serum and plasma, the high protein concentration can obscure the signals originating from low molecular weight metabolites. We evaluated the use of different parameters within the Carr-Purcell-Meiboom-Gill (CPMG) pulse train of fast spin-echoes to remove the macromolecular signal contribution in one-dimensional proton (H-1) NMR spectra. Experimental parameters such as the refocusing delay in the CPMG pulse train, pulse miscalibration, and recycle time were examined to assess the ability to remove the protein signals from the spectrum without causing a deleterious effect on the signals originating from free, low molecular weight metabolites. The H-1-NMR spectra of a variety of serum samples spiked with 2'-deoxyadenosine were acquired using various acquisition parameters. Our results show that the delay used in the CPMG spin-echo and the combination of the acquisition pulse flip angle and recycle time are the two major factors affecting the observed metabolite signal amplitudes in the resulting H-1-NMR spectrum. Published by Elsevier Science (USA). C1 NCI, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), NCI, SAIC Frederick Inc, POB B,Bldg 469,Rm 160, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 42 TC 25 Z9 29 U1 1 U2 8 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 FEB 21 PY 2003 VL 301 IS 4 BP 952 EP 959 DI 10.1016/S0006-291X(03)00079-2 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 652CT UT WOS:000181362800022 PM 12589805 ER PT J AU Kriebel, PW Barr, VA Parent, CA AF Kriebel, PW Barr, VA Parent, CA TI Adenylyl cyclase localization regulates streaming during chemotaxis SO CELL LA English DT Article ID DEPENDENT PROTEIN-KINASE; MYOSIN HEAVY-CHAIN; DICTYOSTELIUM-DISCOIDEUM; CHEMOATTRACTANT RECEPTOR; MEDIATED ACTIVATION; CELL POLARITY; NEUTROPHIL CHEMOTAXIS; LIVING CELLS; CAMP; MORPHOGENESIS AB We studied the role of the adenylyl cyclase ACA in Dictyostelium discoideum chemotaxis and streaming. In this process, cells orient themselves in a head to tail fashion as they are migrating to form aggregates. We show that cells lacking ACA are capable of moving up a chemoattractant gradient, but are unable to stream. Imaging of ACA-YFP reveals plasma membrane labeling highly enriched at the uropod of polarized cells. This localization requires the actin cytoskeleton but is independent of the regulator CRAC and the effector PKA. A constitutively active mutant of ACA shows dramatically reduced uropod enrichment and has severe streaming defects. We propose that the asymmetric distribution of ACA provides a compartment from which cAMP is secreted to locally act as a chemoattractant, thereby providing a unique mechanism to amplify chemical gradients. This could represent a general mechanism that cells use to amplify chemotactic responses. C1 NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37 Room 1E24, Bethesda, MD 20892 USA. NR 45 TC 100 Z9 102 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD FEB 21 PY 2003 VL 112 IS 4 BP 549 EP 560 DI 10.1016/S0092-8674(03)00081-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 650FP UT WOS:000181252600012 PM 12600317 ER PT J AU Lakatta, EG Maltsev, VA Bogdanov, KY Stern, MD Vinogradova, TM AF Lakatta, EG Maltsev, VA Bogdanov, KY Stern, MD Vinogradova, TM TI Cyclic variation of intracellular calcium - A critical factor for cardiac pacemaker cell dominance SO CIRCULATION RESEARCH LA English DT Article DE sinoatrial node; beta-adrenergic stimulation; ryanodine receptor; submembrane Ca2+ release ID RABBIT SINOATRIAL NODE; NA+-CA2+ EXCHANGE CURRENT; SARCOPLASMIC-RETICULUM; CA2+ RELEASE; RYANODINE RECEPTOR; MATHEMATICAL-MODEL; ACTION-POTENTIALS; BEATING RATE; HEART; STIMULATION AB While a diversity of cell types and distribution within the sinoatrial node and cell-cell interactions add complexity to a complete elucidation of the heart's pacemaker function, it has become clear that cyclic variation of submembrane [Ca2+] and activation of the Na+-Ca2+ exchanger during diastolic depolarization (DD) act in concert with ion channels to confer on sinoatrial node cells (SANCs) their status of dominance with respect to pacemaker function. Studies using confocal microscopy indicate that subsarcolemmal Ca2+ release via ryanodine receptors occurs not only in response to the action potential (AP) upstroke, but also during the DD, and this is augmented by beta-adrenergic receptor (beta-AR) stimulation. Spontaneous APs simulated by mathematical SANC models beat at a faster rate when this subsarcolemmal Ca2+ waveform measured under beta-AR stimulation is introduced into the modeling scheme. Thus, in future investigation of pacemaker functioning in health, disease, and disease therapies the "bar ought to be raised" to embrace the impact of cyclic variation in submembrane [Ca2+] on pacemaker function. The full text of this article is available at http://www.circresaha.org. C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr,Box 13, Baltimore, MD 21224 USA. NR 29 TC 63 Z9 66 U1 0 U2 4 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 FEB 21 PY 2003 VL 92 IS 3 BP E45 EP E50 DI 10.1161/01.RES.0000055920.64384.FB PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 651AX UT WOS:000181298800016 PM 12595348 ER PT J AU Cawley, NX Chino, M Maldonado, A Rodriguez, YM Loh, YP Ellman, JA AF Cawley, NX Chino, M Maldonado, A Rodriguez, YM Loh, YP Ellman, JA TI Synthesis and characterization of the first potent inhibitor of yapsin 1 - Implications for the study of yapsin-like enzymes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID YEAST ASPARTIC PROTEASE-3; OPIOMELANOCORTIN-CONVERTING ENZYME; HUMAN PARATHYROID-HORMONE; CANDIDA-ALBICANS; YEAST-ASPARTIC-PROTEASE-3 YAP3; IN-VIVO; GENE; PURIFICATION; EXPRESSION; SECRETION AB The potent peptidic inhibitor, Y1, of the basic residue-specific yeast aspartyl protease, yapsin 1, was synthesized and characterized. The inhibitor was based on the peptide sequence of a cholecystokinin(13-33) analog that yapsin 1 cleaved with an efficiency of 5.2 x 10(5) M-1 S-1 (Olsen, V., Guruprasad, K., Cawley, N. X., Chen, H. C., Blundell, T. L., and Loh, Y. P. (1998) Biochemistry 37, 2768-2777). The apparent K-i of Y1 for the inhibition of yapsin 1 was determined to be 64.5 nm, and the mechanism is competitive. Y2 was also developed as an analog of Y1 for coupling to agarose beads. The resulting inhibitor-coupled agarose beads were successfully used to purify yapsin I to apparent homogeneity from conditioned medium of a yeast expression system. Utilization of this new reagent greatly facilitates the purification of yapsin 1 and should also enable the identification of new yapsin-like enzymes from mammalian and nonmammalian sources. In this regard, Y1 also efficiently inhibited Sap9p, a secreted aspartyl protease from the human pathogen, Candida albicans, which has specificity for basic residues similar to yapsin 1 and might provide the basis for the prevention or control of its virulence. A single-step purification of Sap9p from conditioned medium was also accomplished with the inhibitor column. N-terminal amino acid sequence analysis yielded two sequences indicating that Sap9p is composed of two subunits, designated here as alpha and beta, similar to yapsin 1. C1 NICHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Combinatorial Chem Dept, Berkeley, CA 94704 USA. RP Cawley, NX (reprint author), 49 Convent Dr,MSC 4480,Bldg 49-5A38, Bethesda, MD 20892 USA. RI Ellman, Jonathan/C-7732-2013 FU NIGMS NIH HHS [GM54051] NR 33 TC 11 Z9 12 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 FEB 21 PY 2003 VL 278 IS 8 BP 5523 EP 5530 DI 10.1074/jbc.M207230200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400008 PM 12468548 ER PT J AU Cashel, M Hsu, LM Hernandez, VJ AF Cashel, M Hsu, LM Hernandez, VJ TI Changes in conserved region 3 of Escherichia coli sigma(70) reduce abortive transcription and enhance promoter escape SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OPEN-COMPLEX-FORMATION; RNA CHAIN INITIATION; LAC UV5 PROMOTER; IN-VIVO; TERNARY COMPLEXES; BACILLUS-SUBTILIS; PROTEIN P4; POLYMERASE; DNA; INVITRO AB Mutations within the Escherichia coli rpoD gene encoding amino acid substitutions in conserved region 3 of the (70)(sigma) subunit of E. coli RNA polymerase restore normal stress responsiveness to strains devoid of the stress alarmone, guanosine-3',5'-(bis)pyrophosphate (ppGpp). The presence of a mutant protein, either sigma(70)(P504L) or sigma(70)(S506F), suppresses the physiological defects in strains devoid of ppGpp. In vitro, when reconstituted into RNA polymerase holoenzyme, these a mutants confer unique transcriptional properties, namely they reduce the probabilities of forming abortive RNAs. Here we investigated the behavior of these mutant enzymes during transcription of the highly abortive cellular promoter, gal P2. No differences between mutant and wildtype enzymes were observed prior to and including open complex formation. Remarkably, the mutant enzymes produced drastically reduced levels of gal P2 abortive RNAs and increased production of full-length gal P2 RNAs relative to the wild-type enzyme, leading to greatly reduced ratios of abortive to productive RNAs. These results are attributed mainly to a decreased formation of unproductive initial transcribing complexes with the mutant polymerases and increased rates of promoter escape. Altered transcription properties of these mutant polymerases arise from an alternative structure of the sigma(70) region 3.2 segment that permits efficient positioning of the nascent RNA into the RNA exit channel displacing sigma and facilitating a release. C1 SUNY Buffalo, Dept Microbiol, Ctr Microbial Pathogenesis, Buffalo, NY 14214 USA. NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Mt Holyoke Coll, Programs Biochem, S Hadley, MA 01075 USA. RP Hernandez, VJ (reprint author), SUNY Buffalo, Dept Microbiol, Ctr Microbial Pathogenesis, Buffalo, NY 14214 USA. FU NIGMS NIH HHS [GM57189] NR 45 TC 17 Z9 19 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 FEB 21 PY 2003 VL 278 IS 8 BP 5539 EP 5547 DI 10.1074/jbc.M211430200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400010 PM 12477716 ER PT J AU Baek, SJ Wilson, LC Hsi, LC Eling, TE AF Baek, SJ Wilson, LC Hsi, LC Eling, TE TI Troglitazone, a peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand, selectively induces the early growth response-1 gene independently of PPAR gamma - A novel mechanism for its anti-tumorigenic activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR EGR-1; SMOOTH-MUSCLE CELLS; COLON-CANCER CELLS; MESSENGER-RNA; CARCINOMA CELLS; RICH ELEMENT; IN-VITRO; APOPTOSIS; DIFFERENTIATION; EXPRESSION AB Troglitazone (TGZ) is a peroxisome proliferator-activated receptor gamma (PPARgamma) ligand that has pro-apoptotic activity in human colon cancer. Although TGZ binds to PPARgamma transcription factors as an agonist, emerging evidence suggests that TGZ acts independently of PPARgamma in many functions, including apoptosis. Early growth response-1 (Egr-1) transcription factor has been linked to apoptosis and shown to be activated by extracellular signal-regulated kinase (ERK). We investigated whether TGZ-induced apoptosis may be related to Egr-1 induction, because TGZ has been known to induce ERK activity. Our results show that Egr-1 is induced dramatically by TGZ but not by other PPARgamma ligands. TGZ affects Egr-1 induction at least by two mechanisms; TGZ increases Egr-1 promoter activity by 2-fold and prolongs Egr-1 mRNA stability by 3-fold. Inhibition of ERK phosphorylation in HCT-116 cells abolishes the Egr-1 induction by TGZ, suggesting its ERK-dependent manner. Further, the TGZ-induced Egr-1 expression results in increased promoter activity using a reporter system containing four copies of Egr-1 binding sites, and TGZ induces Egr-1 binding activity to Egr-1 consensus sites as assessed by gel shift assay. In addition, TGZ induces ERK-dependent phosphorylation of PPARgamma, resulting in the down-regulation of PPARgamma activity. The fact that TGZ-induced apoptosis is accompanied by the biosynthesis of Egr-1 suggests that Egr-1 plays a pivotal role in TGZ-induced apoptosis in HCT-116 cells. Our results suggest that Egr-1 induction is a unique property of TGZ compared with other PPARgamma ligands and is independent of PPARgamma activation. Thus, the up-regulation of Egr-1 may provide an explanation for the anti-tumorigenic properties of TGZ. 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. OI Baek, Seung/0000-0001-7866-7778 NR 58 TC 145 Z9 152 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 FEB 21 PY 2003 VL 278 IS 8 BP 5845 EP 5853 DI 10.1074/jbc.M208394200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400046 PM 12475986 ER PT J AU Golin, J Ambudkar, SV Gottesman, MM Habib, AD Sczepanski, J Ziccardi, W May, L AF Golin, J Ambudkar, SV Gottesman, MM Habib, AD Sczepanski, J Ziccardi, W May, L TI Studies with novel Pdr5p substrates demonstrate a strong size dependence for xenobiotic efflux SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTIPLE-DRUG RESISTANCE; SACCHAROMYCES-CEREVISIAE; GENE-PRODUCT; TRANSPORTER AB The yeast (Saccharomyces cerevisiae) multidrug transporter Pdr5p effluxes a broad range of substrates that are variable in structure and mode of action. Previous work suggested that molecular size and ionization could be important parameters. In this study, we compared the relative sensitivity of isogenic PDR5 and pdr5 strains toward putative substrates that are similar in chemical structure. Three series were used: imidazole-containing compounds, trialkyltin chlorides, and tetraalkyltin compounds. We demonstrate that the Pdr5p transporter is capable of mediating transport of substrates that neither ionize nor have electron pair donors and that are much simpler in structure than those transported by the human MDR1-encoded P-glycoprotein. Furthermore, the size of the substrate is critical and independent of any requirement for hydrophobicity. Substrates have surface volumes greater than 90 Angstrom(3) with an optimum response at similar to200-225 A(3) as determined by molecular modeling. Assays measuring the efflux from cells of [H-3]chloramphenicol and [H-3]tritylimidazole were used. A concentration-dependent inhibition of chloramphenicol transport was observed with imidazole derivatives but not with either the organotin compounds or the antitumor agent doxorubicin. In contrast, several of the organotin compounds were potent inhibitors of tritylimidazole efflux, but the Pdr5p substrate tetrapropyltin was ineffective in both assays. This argues for the existence of at least three substrate-binding sites on Pdr5p that differ in behavior from those of the mammalian P-glycoprotein. Evidence also indicates that some substrates are capable of interacting at more than one site. The surprising observation that Pdr5p mediates resistance to tetraalkyltins suggests that one of the sites might use only hydrophobic interactions to bind substrates. C1 Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. Catholic Univ Amer, Dept Chem, Washington, DC 20064 USA. NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Chem, Waukesha, WI 53188 USA. RP Golin, J (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 15 TC 49 Z9 53 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 FEB 21 PY 2003 VL 278 IS 8 BP 5963 EP 5969 DI 10.1074/jbc.M210908200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400060 PM 12496287 ER PT J AU Srivastava, M Frolova, E Rottinghaus, B Boe, SP Grinberg, A Lee, E Love, PE Pfeifer, K AF Srivastava, M Frolova, E Rottinghaus, B Boe, SP Grinberg, A Lee, E Love, PE Pfeifer, K TI Imprint control element-mediated secondary methylation imprints at the Igf2/H19 locus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BECKWITH-WIEDEMANN-SYNDROME; MOUSE H19 GENE; DNA METHYLATION; MONOALLELIC EXPRESSION; H19/IGF2 LOCUS; DELETION; REGION; MECHANISMS; UPSTREAM; ALLELE AB Understanding the molecular basis of monoallelic expression as observed at imprinted loci is helpful in understanding the mechanisms underlying epigenetic regulation. Genomic imprinting begins during gametogenesis with the establishment of epigenetic marks on the chromosomes such that paternal and maternal chromosomes are rendered distinct. During embryonic development, the primary imprint can lead to generation of secondary epigenetic modifications (secondary imprints) of the chromosomes. Eventually, either the primary imprints or the secondary imprints interfere with transcription, leading to parent-of-origin-dependent silencing of one of the two alleles. Here we investigated several aspects pertaining to the generation and functional necessity of secondary methylation imprints at the Igf2/H19 locus. At the H19 locus, these secondary imprints are, in fact, the signals mediating paternal chromosome-specific silencing of that gene. We first demonstrated that the H19 secondary methylation imprints are entirely stable through multiple cell divisions, even in the absence of the primary imprint. Second, we generated mouse mutations to determine which DNA sequences are important in mediating establishment and maintenance of the silent state of the paternal H19 allele. Finally, we analyzed the dependence of the methylation of Igf2DMR1 region on the primary methylation imprint about 90 kilobases away. C1 NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Srivastava, M (reprint author), Natl Inst Immunol, Aruna Asaf Ali Rd, New Delhi 110067, India. OI Pfeifer, Karl/0000-0002-0254-682X NR 44 TC 20 Z9 20 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 FEB 21 PY 2003 VL 278 IS 8 BP 5977 EP 5983 DI 10.1074/jbc.M208437200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400062 PM 12270940 ER PT J AU Louis, JM Ishima, R Nesheiwat, I Pannell, LK Lynch, SM Torchia, DA Gronenborn, AM AF Louis, JM Ishima, R Nesheiwat, I Pannell, LK Lynch, SM Torchia, DA Gronenborn, AM TI Revisiting monomeric HIV-1 protease - Characterization and redesign for improved properties SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VIRUS TYPE-1 PROTEASE; HUMAN-IMMUNODEFICIENCY; PROTEINASES; SUBSTRATE; SEQUENCES; STABILITY; COMPLEX AB Interactions between the C-terminal interface residues (96-99) of the mature HIV-1 protease were shown to be essential for dimerization, whereas the N-terminal residues (1-4) and Arg(87) contribute to dimer stability (Ishima, R., Ghirlando, R., Tozser, J., Gronenborn, A. M., Torchia, D. A., and Louis, J. M. (2001) J. Biol. Chem. 276, 49110-49116). Here we show that the intramonomer interaction between the side chains of Asp(29) and Arg(87) influences dimerization significantly more than the intermonomer interaction between Asp29 and Arg8'. Several mutants, including T26A, destablize the dimer, exhibit a monomer fold, and are prone to aggregation. To alleviate this undesirable property, we designed proteins in which the N- and C-terminal regions can be linked intramolecularly by disulfide bonds. In particular, cysteine residues were introduced at positions 2 and 97 or 98. A procedure for the efficient preparation of intrachain-linked polypeptides is presented, and it is demonstrated that the Q2C/L97C variant exhibits a native-like single subunit fold. It is anticipated that monomeric proteases of this kind will aid in the discovery of novel inhibitors aimed at binding to the monomer at the dimerization interface. This extends the target area of current inhibitors, all of which bind across the active site formed by both subunits in the active dimer. C1 NIDCR, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ishima, R (reprint author), NIDCR, Struct Mol Biol Unit, NIH, Bldg 30,Rm 109, Bethesda, MD 20892 USA. EM rishima@dir.nidcr.nih.gov OI Gronenborn, Angela M/0000-0001-9072-3525 NR 25 TC 45 Z9 45 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 21 PY 2003 VL 278 IS 8 BP 6085 EP 6092 DI 10.1074/jbc.M209726200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400075 PM 12468541 ER PT J AU Allen, S Heath, PR Kirby, J Wharton, SB Cookson, MR Menzies, FM Banks, RE Shaw, PJ AF Allen, S Heath, PR Kirby, J Wharton, SB Cookson, MR Menzies, FM Banks, RE Shaw, PJ TI Analysis of the cytosolic proteome in a cell culture model of familial amyotrophic lateral sclerosis reveals alterations to the proteasome, antioxidant defenses, and nitric oxide synthetic pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSGENIC MOUSE MODEL; SUPEROXIDE-DISMUTASE; SPINAL-CORD; DEPENDENT APOPTOSIS; OXIDATIVE STRESS; MOTOR-NEURONS; IN-VIVO; CU,ZN-SUPEROXIDE DISMUTASE; CEREBROSPINAL-FLUID; TYROSINE NITRATION AB Injury to motor neurons associated with mutant Cu,Zn-superoxide dismutase (SOD1)-related familial amyotrophic lateral sclerosis (FALS) results from a toxic gain-of-function of the enzyme. The mechanisms by which alterations to SOD1 elicit neuronal death remain uncertain despite intensive research effort. Analysis of the cellular proteins that are differentially expressed in the presence of mutant SOD1 represents a novel approach to investigate further this toxic gain-of-function. By using the motor neuron-like cell line NSC34 stably transfected with wild-type, G93A, or G37R mutant human SOD1, we investigated the effects of mutant human SOD1 on protein expression using proteomic approaches. Seven up-regulated proteins were identified as argininosuccinate synthase, argininosuccinate lyase, neuronal nitric-oxide synthase, RNA-binding motif protein 3, peroxiredoxin 1, proteasome subunit 65 (X), and glutathione S-transferase (GST) Alpha 2. Seven downregulated proteins were identified as GST Mu 1, GST Mu 2, GST Mu 5, a hypothetical GST Mu, GST Pi B, leukotriene B-4 12-hydroxydehydrogenase, and proteasome subunit beta5i (LMP7). GST assays demonstrated a significant reduction in the total GST activity of cells expressing mutant human SOD1. Proteasome assays demonstrated significant reductions in chymotrypsin-like, trypsin-like, and post-glutamyl-hydrolase proteasome activities. Laser capture microdissection of spinal cord motor neurons from human FALS cases, in conjunction with reverse transcriptase-PCR, demonstrated decreased levels of mRNA encoding GST Mu 1, leukotriene 134 12-hydroxydehydrogenase, and LMP7. These combined approaches provide further evidence for involvement of alterations in antioxidant defenses, proteasome function, and nitric oxide metabolism in the pathophysiology of FALS. C1 Univ Sheffield, Div Genom Med, Acad Unit Neurol, Sheffield S10 2RX, S Yorkshire, England. Univ Sheffield, Div Genom Med, Acad Unit Pathol, Sheffield S10 2RX, S Yorkshire, England. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. St James Univ Hosp, Ctr Clin Canc, Leeds LS9 7TF, W Yorkshire, England. RP Allen, S (reprint author), Univ Sheffield, Div Genom Med, Acad Unit Neurol, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England. RI Shaw, Pamela/A-5215-2009; Kirby, Janine/B-3980-2009; Wharton, Stephen/B-5117-2009; Shaw, Pamela/A-7620-2010; Shaw, Pamela/E-6193-2010; OI Kirby, Janine/0000-0002-7468-5917; Banks, Rosamonde/0000-0002-0042-8715 NR 74 TC 66 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 FEB 21 PY 2003 VL 278 IS 8 BP 6371 EP 6383 DI 10.1074/jbc.M209915200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400111 PM 12475980 ER PT J AU Yedavalli, VSRK Benkirane, M Jeang, KT AF Yedavalli, VSRK Benkirane, M Jeang, KT TI Tat and trans-activation-responsive (TAR) RNA-independent induction of HIV-1 long terminal repeat by human and murine cyclin T1 requires Sp1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; P-TEFB KINASE; POLYMERASE-II; TRANSCRIPTIONAL ELONGATION; IN-VIVO; DNA-BINDING; TYPE-1; DOMAIN; PROTEIN; COMPLEX AB P-TEFb, cyclin T1 + CDK9, is needed for the expression of cellular promoters and primate lentiviral long terminal repeats (LTRs). Curiously, cellular and lentiviral promoters differ dramatically in the requirements for positive transcriptional elongation factor (P-TEF) b activity. Lentiviral LTRs, but not cellular promoters, need an RNA-associated P-TEFb/Tat/TAR (trans-activation-responsive) RNA ternary complex. Ternary complex defective murine cycT1 is apparently inactive for lentiviral transcription. Why P-TEFb requires Tat/TAR for LTRs but not for cellular promoters remains unknown. To explore this question, we sought to determine whether DNA targeting of murine and human cyclin T1 can reconstitute a Tat/TAR-independent activity to the HIV-1 LTR. In the absence of Tat and TAR, we found that both HuCycT1 and MuCycT1 can robustly activate the HIV-1 LTR. We further showed that Sp1 is necessary and sufficient for this DNA-targeted activity. Thus, like cellular promoters, HIV-1 LTR can use P-TEFb function without a Tat/TAR RNA complex. This activity could explain recent findings of robust HIV-1 replication in rat cells that cannot form a P-TEFb/Tat/TAR moiety. C1 NIAID, Mol Microbiol Lab, Mol Virol Sect, Bethesda, MD 20892 USA. CNRS, Unite Propre Rech, Inst Genet Humaine, Lab Virol Mol & Transfert Gene, F-34296 Montpellier, France. RP Jeang, KT (reprint author), Bldg 4,Rm 306,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 58 TC 61 Z9 63 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 FEB 21 PY 2003 VL 278 IS 8 BP 6404 EP 6410 DI 10.1074/jbc.M209162200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400113 PM 12458222 ER PT J AU Touz, MC Lujan, HD Hayes, SF Nash, TE AF Touz, MC Lujan, HD Hayes, SF Nash, TE TI Sorting of encystation-specific cysteine protease to lysosome-like peripheral vacuoles in Giardia lamblia requires a conserved tyrosine-based motif SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REGULATED SECRETORY PATHWAY; TRANS-GOLGI NETWORK; SURFACE PROTEIN; ENDOPLASMIC-RETICULUM; PRIMITIVE EUKARYOTE; WALL PROTEIN; TRANSMEMBRANE DOMAIN; LOCALIZATION; EXPRESSION; DIFFERENTIATION AB Encystation-specific cysteine protease (ESCP) was the first membrane-associated protein described to be part of the lysosome-like peripheral vacuoles in the intestinal parasite Giardia lamblia. ESCP is homologous to cathepsin C enzymes of higher eukaryotes, but is distinguished from other lysosomal cysteine proteases because it possesses a transmembrane domain and a short cytoplasmic tail. Tyrosine-based motifs within tails of membrane proteins are known to participate in endosomal/lysosomal protein sorting in higher eukaryotes. In this study, we show that a YRPI motif within the ESCP cytoplasmic tail is necessary and sufficient to mediate ESCP sorting to peripheral vacuoles in Giardia. Deletion and point mutation analysis demonstrated that the tyrosine residue is critical for ESCP sorting, whereas amino acids located at the Y+1 (Arg), Y+2 (Pro), and Y+3 (lie) positions show minimal effect. Loss of the motif resulted in surface localization, whereas addition of the motif to a variant-specific surface protein resulted in lysosomal localization. Although Giardia trophozoites lack a morphologically discernible Golgi apparatus, our findings indicate that this parasite directs proteins to the lysosomes using a conserved sorting signal similar to that used by yeast and mammalian cells. Because Giardia is one of the earliest branching protist, these results demonstrate that sorting motifs for specific protein traffic developed very early during eukaryotic evolution. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Nacl Cordoba, Fac Ciencias Med, Catedra Bioquim & Biol Mol, RA-5000 Cordoba, Argentina. NIAID, Rocky Mt Lab, NIH, Hamilton, MT 59840 USA. RP Touz, MC (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Rm B1-06,900 Rockville Pike, Bethesda, MD 20892 USA. NR 49 TC 32 Z9 34 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 FEB 21 PY 2003 VL 278 IS 8 BP 6420 EP 6426 DI 10.1074/jbc.M208354200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400115 PM 12466276 ER PT J AU Oda, A Wada, I Miura, K Okawa, K Kadoya, T Kato, T Nishihara, H Maeda, M Tanaka, S Nagashima, K Nishitani, C Matsuno, K Ishino, M Machesky, LM Fujita, H Randazzo, P AF Oda, A Wada, I Miura, K Okawa, K Kadoya, T Kato, T Nishihara, H Maeda, M Tanaka, S Nagashima, K Nishitani, C Matsuno, K Ishino, M Machesky, LM Fujita, H Randazzo, P TI CrkL directs ASAP1 to peripheral focal adhesions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; ADAPTER PROTEIN; CELL-ADHESION; HUMAN PLATELETS; INTEGRIN; ARF; CYTOSKELETON; ASSOCIATION; SRC AB Searching for proteins in platelets that can interact with the N-terminal SH3 domain of CrkL (using a combination of a pull-down assay followed by mass spectrometry), we have found that human platelets express an ADP-ribosylation factor (Arf)-specific GTPase-activating protein (GAP), ASAP1, as a CrkL-binding protein. In spreading platelets, most endogenous ASAP1. is localized at peripheral focal adhesions. To determine the physiologic significance of the CrkL-ASAP1 association, we overexpressed CrkL, ASAP1, or both in combination in COS7 cells. Unlike endogenous ASAP1 in platelets, overexpressed ASAP1 showed diffuse cytoplasmic distribution. However, when co-expressed with wild-type CrkL, both endogenous and expressed ASAP1 accumulated at CrkL-induced focal adhesions. An SH2-mutated CrkL, which cannot localize at focal adhesions, failed to recruit ASAP1 into focal adhesions. Thus, CrkL appears to be a lynchpin between ASAP1 and peripheral focal adhesions. C1 Hokkaido Univ, Dept Prevent Med, Lab Environm Biol, Sch Med,Kita Ku, Sapporo, Hokkaido 0608638, Japan. NCI, CCR, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. Kirin Brewery Co LTD, Div Pharmaceut, Pharmaceut Res Labs, Gunma 3701295, Japan. Sapporo Med Univ, Sch Med, Dept Biochem 2, Sapporo, Hokkaido, Japan. Hokkaido Univ, Sch Med, Lab Mol & Cellular Pathol, Sapporo, Hokkaido 0608638, Japan. Hokkaido Univ, Coll Med Technol, Sapporo, Hokkaido 0608638, Japan. Sapporo Med Univ, Sch Med, Dept Hyg, Sapporo, Hokkaido 0608638, Japan. Univ Birmingham, Div Mol Cell Biol, Sch Biosci, Birmingham B15 2TT, W Midlands, England. RP Oda, A (reprint author), Hokkaido Univ, Dept Prevent Med, Lab Environm Biol, Sch Med,Kita Ku, N15W7, Sapporo, Hokkaido 0608638, Japan. RI Tanaka, Shinya/D-3586-2011 NR 27 TC 27 Z9 27 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 FEB 21 PY 2003 VL 278 IS 8 BP 6456 EP 6460 DI 10.1074/jbc.M210817200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400120 PM 12522101 ER PT J AU Li, CX Luo, J Li, L Cheng, ML Huang, NH Liu, J Waalkes, MP AF Li, CX Luo, J Li, L Cheng, ML Huang, NH Liu, J Waalkes, MP TI The collagenolytic effects of the traditional Chinese medicine preparation, Han-Dan-Gan-Le, contribute to reversal of chemical-induced liver fibrosis in rats SO LIFE SCIENCES LA English DT Article DE Han-Dan-Gan-Le (HDGL); carbon tetrachloride; liver fibrosis; collagen-I; collagenolysis AB Han-Dan-Gan-Le (HDGL), a Chinese herb preparation composed of Stephaniat tetrandra, Salvia miltorrhiza, Radix paeoniae, Astragalus membranaceus, and Ginkgo biloba, has been used to treat human liver fibrosis. This study was designed to examine the therapeutic effect of HDGL on chemical-induced liver fibrosis in adult Wistar rats. Liver fibrosis was produced in rats by carbon tetrachloride (1.2 ml CCl4/kg, 2 times/week, after an initial dose of 5.0 ml CCl4/kg, sc), plus a diet of 20% fat, 0.05% cholesterol (continuous) and 30% alcohol in the drinking water ad libitum (every other day) for 8 weeks. HDGL (0.5 and 1.0 g/kg, ig, daily for 6 weeks) was administered to rats 72 hrs after the last dose of CCl4 to examine its therapeutic effects on chemical-induced liver fibrosis. Upon pathological examination, the HDGL treatment had significantly reversed chemical-induced liver fibrosis and other hepatic lesions. Hepatic collagen accumulation induced by CCl4 was markedly reduced by HDGL treatment, as evidenced by hepatic collagen content and by immunohistochemical analysis of type-I collagen in liver. HDGL appeared to stimulate the collagenolytic process in the liver, as a 30-50% increase in urinary excretion of hydroxyproline was observed with HDGL treatment as compared to rats only given CCl4. In conclusion, HDGL can effectively reverse chemically induced liver fibrosis, and this appears to be due, at least in part, to the stimulation of hepatic collagenolysis, resulting in a resolution of hepatic fibrosis. (C) 2002 Published by Elsevier Science Inc. C1 Guiyang Med Coll, Dept Pharmacol, Guiyang, Peoples R China. NIEHS, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. RP Li, CX (reprint author), NIEHS, Comparat Carcinogenesis Lab, NCI, 111 Alexander Dr,Mail Drop F0-09,Rm F018A, Res Triangle Pk, NC 27709 USA. NR 22 TC 38 Z9 41 U1 1 U2 5 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 FEB 21 PY 2003 VL 72 IS 14 BP 1563 EP 1571 DI 10.1016/S0024-3205(02)02448-7 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 642HP UT WOS:000180798400002 PM 12551745 ER PT J AU Kim, UK Jorgenson, E Coon, H Leppert, M Risch, N Drayna, D AF Kim, UK Jorgenson, E Coon, H Leppert, M Risch, N Drayna, D TI Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide SO SCIENCE LA English DT Article ID RECEPTOR; FAMILY; LOCALIZATION; PERCEPTION; GENES AB The ability to taste the substance phenylthiocarbamide (PTC) has been widely used for genetic and anthropological studies, but genetic studies have produced conflicting results and demonstrated complex inheritance for this trait. We have identified a small region on chromosome 7q that shows strong linkage disequilibrium between single-nucleotide polymorphism (SNP) markers and PTC taste sensitivity in unrelated subjects. This region contains a single gene that encodes a member of the TAS2R bitter taste receptor family. We identified three coding SNPs giving rise to five haplotypes in this gene worldwide. These haplotypes completely explain the bimodal distribution of PTC taste sensitivity, thus accounting for the inheritance of the classically defined taste insensitivity and for 55 to 85% of the variance in PTC sensitivity. Distinct phenotypes were associated with specific haplotypes, which demonstrates that this gene has a direct influence on PTC taste sensitivity and that sequence variants at different sites interact with each other within the encoded gene product. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Univ Utah, Med Ctr, Dept Human Genet, Salt Lake City, UT 84112 USA. Univ Utah, Med Ctr, Red Butte Hlth Ctr, Dept Psychiat, Salt Lake City, UT 84112 USA. Kaiser Permanente, Div Res, Oakland, CA 94612 USA. RP Drayna, D (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Court, Rockville, MD 20850 USA. FU NCRR NIH HHS [M01-RR00064]; NHGRI NIH HHS [T32 HG00044]; PHS HHS [Z01-000046-04] NR 33 TC 422 Z9 431 U1 24 U2 129 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 FEB 21 PY 2003 VL 299 IS 5610 BP 1221 EP 1225 DI 10.1126/science.1080190 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 646YY UT WOS:000181065500037 PM 12595690 ER PT J AU Zubieta, JK Heitzeg, MM Smith, YR Bueller, JA Xu, K Xu, YJ Koeppe, RA Stohler, CS Goldman, D AF Zubieta, JK Heitzeg, MM Smith, YR Bueller, JA Xu, K Xu, YJ Koeppe, RA Stohler, CS Goldman, D TI COMT val(158)met genotype affects mu-opioid neurotransmitter responses to a pain stressor SO SCIENCE LA English DT Article ID CATECHOL-O-METHYLTRANSFERASE; AFFECTIVE DIMENSIONS; ANTERIOR CINGULATE; NOREPINEPHRINE; MODULATION; RECEPTORS; STRIATUM; BEHAVIOR; AMYGDALA; ORGANIZATION AB Responses to pain and other stressors are regulated by interactions between multiple brain areas and neurochemical systems. We examined the influence of a common functional genetic polymorphism affecting the metabolism of catecholamines on the modulation of responses to sustained pain in humans. Individuals homozygous for the met(158) allele of the catechol-O-methyttransferase (COMT) polymorphism (val(158)met) showed diminished regional mu-opioid system responses to pain compared with heterozygotes. These effects were accompanied by higher sensory and affective ratings of pain and a more negative internal affective state. Opposite effects were observed in val(158) homozygotes. The COMT val(158)met polymorphism thus influences the human experience of pain and may underlie interindividual differences in the adaptation and responses to pain and other stressful stimuli. C1 Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Mental Hlth Res Inst, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Radiol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. Natl Inst Alcohol & Alcoholism, Neurogenet Lab, Rockville, MD 20852 USA. RP Zubieta, JK (reprint author), Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NIDCR NIH HHS [R01 DE 12059, R01 DE 12743] NR 39 TC 684 Z9 707 U1 0 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 21 PY 2003 VL 299 IS 5610 BP 1240 EP 1243 DI 10.1126/science.1078546 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 646YY UT WOS:000181065500043 PM 12595695 ER PT J AU Mezey, E Nagy, A Szalayova, I Key, S Bratincsak, A Baffi, J Shahar, T AF Mezey, E Nagy, A Szalayova, I Key, S Bratincsak, A Baffi, J Shahar, T TI Comment on "Failure of bone marrow cells to transdifferentiate into neural cells in vivo" SO SCIENCE LA English DT Editorial Material ID HEMATOPOIETIC-CELLS; MICROGLIA; MICE C1 NINDS, Bethesda, MD 20892 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. NIMH, Bethesda, MD 20892 USA. NEI, Bethesda, MD 20892 USA. RP Mezey, E (reprint author), NINDS, Bldg 36,Room 3D-10,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Nagy, Andras/G-6465-2013 NR 11 TC 1 Z9 1 U1 0 U2 2 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 FEB 21 PY 2003 VL 299 IS 5610 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 646YY UT WOS:000181065500021 ER PT J AU Nicholas, GM Eckman, LL Newton, GL Fahey, RC Ray, S Bewley, CA AF Nicholas, GM Eckman, LL Newton, GL Fahey, RC Ray, S Bewley, CA TI Inhibition and kinetics of Mycobacterium tuberculosis and Mycobacterium smegmatis mycothiol-S-conjugate amidase by natural product inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID BROMOTYROSINE ALKALOIDS; ESCHERICHIA-COLI; SPONGE; IDENTIFICATION; BIOSYNTHESIS; DEACETYLASE; DISULFIDE; THIOLS AB The current rise in mycobacterial-related infections and disease, coupled with drug resistance, underlines the continuing need for new antimycobacterials. To this end, we have screened similar to1500 extracts derived from marine plants and invertebrates and terrestrial fungi for their ability to inhibit a newly described mycobacterial detoxification enzyme mycothiol-S-conjugate amidase (MCA). As described in this paper, our screening and chemistry efforts thus far have led to the identification of 13 natural product inhibitors that represent six different structural classes. By conducting enzyme inhibition assays using varied inhibitor and substrate concentrations, we have determined the mode of inhibition of Mycobacterium tuberculosis MCA for four of these compounds. We show that two types of bromo tyro sine-derived natural products are competitive inhibitors of MCA; while oceanapiside, an alpha,omega-bisaminohydroxy glycosphingolipid, and the fungal metabolite gliotoxin, a dithiadiketopiperazine, are simple and mixed non-competitive inhibitors, respectively. Correlation of these results with the chemical structures suggests that MCA is a metalloenzyme and that the oximinoamide and spiro-isoxazoline amide groups present in the competitive inhibitors are substrate mimics. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. RP Bewley, CA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 32 TC 69 Z9 75 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD FEB 20 PY 2003 VL 11 IS 4 BP 601 EP 608 AR PII S0968-0896(02)00345-0 DI 10.1016/S0968-0896(02)00345-0 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 640NB UT WOS:000180693900014 PM 12538025 ER PT J AU Vogt, TM Ziegler, RG Graubard, BI Swanson, CA Greenberg, RS Schoenberg, JB Swanson, GM Hayes, RB Mayne, ST AF Vogt, TM Ziegler, RG Graubard, BI Swanson, CA Greenberg, RS Schoenberg, JB Swanson, GM Hayes, RB Mayne, ST TI Serum selenium and risk of prostate cancer in US blacks and whites SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE prostate cancer; selenium; vitamin E; biomarkers; race; diet; epidemiology ID VITAMIN-E; SUBSEQUENT RISK; GLUTATHIONE-PEROXIDASE; PREVENTION TRIAL; ALPHA-TOCOPHEROL; SUPPLEMENTATION; ASSOCIATION; ANTIOXIDANTS; MORTALITY; PLASMA AB Prostate cancer is the fourth most common cancer in men worldwide and the most common cancer in men in the United States, with reported incidence rates for U.S. blacks being the highest in the world. The etiology of prostate cancer and an explanation for the racial disparity in incidence in the United States remain elusive. Epidemiologic studies suggest that selenium, an essential trace element, may protect against the disease. To further explore this hypothesis, we measured serum selenium in 212 cases and 233 controls participating in a multicenter, population-based case-control study that included comparable numbers of U.S. black and white men aged 40-79 years. Serum selenium was inversely associated with risk of prostate cancer (comparing highest to lowest quartiles, OR = 0.71, 95% Cl 0.39-1.28; p for trend = 0.11), with similar patterns seen in both blacks and whites. Cubic regression spline analysis of continuous serum selenium indicated a reduced risk of prostate cancer above concentrations of 0.135 mug/ml (median among controls) compared to a reference value set at the median of the lowest selenium quartile. Because both the selenoenzyme GPX and vitamin E can function as antioxidants, we also explored their joint effect. Consistent with other studies, the inverse association with selenium was strongest among men with low serum alpha-tocopherol concentrations. In conclusion, our results suggest a moderately reduced risk of prostate cancer at higher serum selenium concentrations, a finding that can now be extended to include U.S. blacks. Since selenium exposure varies widely throughout the world, further research on optimal concentrations for cancer prevention is justified. (C) 2002 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA. Med Univ S Carolina, Charleston, SC 29425 USA. New Jersey Dept Hlth & Senior Serv, Canc Epidemiol Serv, Trenton, NJ USA. Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. RP Ziegler, RG (reprint author), NCI, Div Canc Epidemiol & Genet, Execut Plaza S,Room 8098,6120 Execut Blvd,MSC 724, Bethesda, MD 20892 USA. OI Hayes, Richard/0000-0002-0918-661X FU NCI NIH HHS [N01-CP-51087, N01-CN-05225, N01-CN-05227, N01-CN-31022, N01-CP-51089, N01-CP-5109, N01-CP-51092]; NIA NIH HHS [T32 AG00153] NR 53 TC 67 Z9 70 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 20 PY 2003 VL 103 IS 5 BP 664 EP 670 DI 10.1002/ijc.10866 PG 7 WC Oncology SC Oncology GA 634YK UT WOS:000180369900015 PM 12494476 ER PT J AU Shrager, RI Hendler, RW AF Shrager, RI Hendler, RW TI Critical evaluation of kinetic models for bacteriorhodopsin photocycles SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID SINGULAR-VALUE DECOMPOSITION; HALOBACTERIUM-SALINARIUM; INTERMEDIATE SPECTRA; DIFFERENCE SPECTRA; RESONANCE RAMAN; ACTINIC LIGHT; SPECTROSCOPY; TRANSITIONS; RESOLUTION AB How can the field of bacteriorhodopsin (BR) photocycle kinetics come up with so many conflicting models? A brief description of the common features of various methods is given. along with the hazards of their use. We describe how our methods are chosen to avoid those hazards. Finally, a set of requirements is suggested for a good model of the BR photocycle. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Hendler, RW (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 28 TC 13 Z9 13 U1 1 U2 3 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 FEB 20 PY 2003 VL 107 IS 7 BP 1708 EP 1713 DI 10.1021/jp0273070 PG 6 WC Chemistry, Physical SC Chemistry GA 647NV UT WOS:000181100500031 ER PT J AU Fauci, AS AF Fauci, AS TI Biodefence on the research agenda SO NATURE LA English DT Editorial Material C1 NIAID, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, Dept Hlth & Human Serv, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 3 TC 15 Z9 15 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 FEB 20 PY 2003 VL 421 IS 6925 BP 787 EP 787 DI 10.1038/nature01480 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 646QA UT WOS:000181044700023 PM 12594484 ER PT J AU Mayor, U Guydosh, NR Johnson, CM Grossmann, JG Sato, S Jas, GS Freund, SMV Alonso, DOV Daggett, V Fersht, AR AF Mayor, U Guydosh, NR Johnson, CM Grossmann, JG Sato, S Jas, GS Freund, SMV Alonso, DOV Daggett, V Fersht, AR TI The complete folding pathway of a protein from nanoseconds to microseconds SO NATURE LA English DT Article ID HYDROGEN-EXCHANGE; DENATURED STATE; TEMPERATURE; STABILITY; BARNASE; ENERGY; MODEL; HELIX AB Combining experimental and simulation data to describe all of the structures and the pathways involved in folding a protein is problematical. Transition states can be mapped experimentally by phi values(1,2), but the denatured state(3) is very difficult to analyse under conditions that favour folding. Also computer simulation at atomic resolution is currently limited to about a microsecond or less. Ultrafast-folding proteins fold and unfold on timescales accessible by both approaches(4,5), so here we study the folding pathway of the three-helix bundle protein Engrailed homeodomain(6). Experimentally, the protein collapses in a microsecond to give an intermediate with much native alpha-helical secondary structure, which is the major component of the denatured state under conditions that favour folding. A mutant protein shows this state to be compact and contain dynamic, native-like helices with unstructured side chains. In the transition state between this and the native state, the structure of the helices is nearly fully formed and their docking is in progress, approximating to a classical diffusion-collision model. Molecular dynamics simulations give rate constants and structural details highly consistent with experiment, thereby completing the description of folding at atomic resolution. C1 MRC, Ctr Prot Engn, Cambridge CB2 2QH, England. CLRC Daresbury Lab, Warrington WA4 4AD, Cheshire, England. NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. RP Fersht, AR (reprint author), MRC, Ctr Prot Engn, Hills Rd, Cambridge CB2 2QH, England. RI Mayor, Ugo/F-5890-2011 OI Mayor, Ugo/0000-0003-2812-8287 NR 29 TC 363 Z9 369 U1 4 U2 54 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 20 PY 2003 VL 421 IS 6925 BP 863 EP 867 DI 10.1038/nature01428 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 646QA UT WOS:000181044700053 PM 12594518 ER PT J AU Guttmacher, AE Collins, FS AF Guttmacher, AE Collins, FS TI Genomic medicine - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NHGRI, Bethesda, MD 20892 USA. RP Guttmacher, AE (reprint author), NHGRI, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 FEB 20 PY 2003 VL 348 IS 8 BP 760 EP 760 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 646BF UT WOS:000181014400022 ER PT J AU Crowell, JA Steele, VE AF Crowell, JA Steele, VE TI AKT and the phosphatidylinositol 3-kinase/AKT pathway: Important molecular targets for lung cancer prevention and treatment SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID DEGUELIN C1 NCI, Chemoprevent Agent Dev Res Grp, EPN,Div Canc Preven, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Crowell, JA (reprint author), NCI, Chemoprevent Agent Dev Res Grp, EPN,Div Canc Preven, NIH,Dept Hlth & Human Serv, Rm 2117,MSC 7322, Bethesda, MD 20892 USA. NR 8 TC 24 Z9 25 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 FEB 19 PY 2003 VL 95 IS 4 BP 252 EP 253 PG 2 WC Oncology SC Oncology GA 645UG UT WOS:000180997300002 PM 12591974 ER PT J AU Tan-Chiu, E Wang, JP Costantino, JP Paik, S Butch, C Wickerham, DL Fisher, B Wolmark, N AF Tan-Chiu, E Wang, JP Costantino, JP Paik, S Butch, C Wickerham, DL Fisher, B Wolmark, N TI Effects of tamoxifen on benign breast disease in women at high risk for breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ESTROGEN-RECEPTOR-BETA; POSITIVE TUMORS; LESIONS; HETEROZYGOSITY; CARCINOMAS; HYPERPLASIA; EXPRESSION; ALPHA AB Background: In 1998 the National Surgical Adjuvant Breast and Bowel Project (NSABP) demonstrated that tamoxifen treatment reduced the incidence of both invasive and non-invasive breast cancer in women at high risk for the disease. We examined the effect of tamoxifen treatment on the incidence of benign breast disease and the number of breast biopsies in the same group of women. Methods: We examined the medical records of 13203 women with follow-up who participated in the NSABP Breast Cancer Prevention Trial. Included in this analysis were women who had undergone a breast biopsy and who had histologic diagnoses of adenosis, cyst, duct ectasia, fibrocystic disease, fibroadenoma, fibrosis, hyperplasia, or metaplasia. The relative risk (RR) for each histologic diagnosis was estimated for women who received tamoxifen and for women who received placebo. We also tallied the number of biopsies that women in the placebo and tamoxifen groups underwent. Results: Overall, tamoxifen treatment reduced the risk of benign breast disease by 28% (RR = 0.72, 95% confidence interval [CI] = 0.65 to 0.79). Tamoxifen therapy resulted in statistically significant reductions in the risk of adenosis (RR = 0.59, 95% CI = 0.47 to 0.73), cyst (RR = 0.66, 95% CI = 0.58 to 0.75), duct ectasia (RR = 0.72, 95% CI = 0.53 to 0.97), fibrocystic disease (RR = 0.67, 95 % CI = 0.58 to 0.77), hyperplasia (RR = 0.60, 95 % CI = 0.50 to 0.71), and metaplasia (RR = 0.51, 95% CI = 0.41 to 0.62). Tamoxifen therapy also reduced the risk for fibroadenoma (RR = 0.77, 95% CI = 0.56 to 1.04) and fibrosis (RR = 0.86, 95 % CI = 0.72 to 1.03). Compared with the placebo group, the tamoxifen group had 29% (95% CI = 23% to 34%) fewer biopsies (1048 versus 1469) and 19% fewer women who underwent a biopsy (811 versus 1019). This resulted in a 29% reduction in the risk of biopsy in women treated with tamoxifen (RR = 0.71, 95 % CI = 0.66 to 0.77). This risk reduction occurred predominantly in women younger than 50 years. Conclusion: Women in this study who received tamoxifen, especially younger women (i.e., <50 years), had a reduced incidence of clinically detected benign breast disease and underwent fewer breast biopsies. C1 Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, Pittsburgh, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, Pittsburgh, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, Pittsburgh, PA USA. RP Tan-Chiu, E (reprint author), Canc Res Network, 350 84th Ave,Suite 305, Plantation, FL 33324 USA. FU NCI NIH HHS [U10 CA 37377, U10 CA 69974] NR 24 TC 43 Z9 44 U1 0 U2 2 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 FEB 19 PY 2003 VL 95 IS 4 BP 302 EP 307 PG 6 WC Oncology SC Oncology GA 645UG UT WOS:000180997300011 PM 12591986 ER PT J AU Desnick, RJ Brady, R Barranger, J Collins, AJ Germain, DP Goldman, M Grabowski, G Packman, S Wilcox, WR AF Desnick, RJ Brady, R Barranger, J Collins, AJ Germain, DP Goldman, M Grabowski, G Packman, S Wilcox, WR TI Fabry disease, an under-recognized multisystemic disorder: Expert recommendations for diagnosis, management, and enzyme replacement therapy SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PREVIOUSLY UNTREATED PATIENTS; RECOMBINANT FACTOR-VIII; ALPHA-GALACTOSIDASE; CLINICAL MANIFESTATIONS; ATYPICAL VARIANT; GAUCHER-DISEASE; COMPLICATIONS; STORAGE; SAFETY; COHORT AB Fabry disease (alpha-galactosidase A deficiency) is an X-linked recessive lysosomal storage disorder. Although the disease presents in childhood and culminates in cardiac, cerebrovascular, and end-stage renal disease, diagnosis is often delayed or missed. This paper reviews the key signs and symptoms of Fabry disease and provides expert recommendations for diagnosis, follow-up, medical management, and the use of enzyme replacement therapy. Recommendations are based on reviews of the literature on Fabry disease, results of recent clinical trials, and expertise of the authors, all of whom have extensive clinical experience with Fabry disease and lysosomal storage disorders and represent subspecialties involved in treatment. All males and female carriers affected with Fabry disease should be followed closely, regardless of symptoms or treatment status. Clinical trials have shown that recombinant human alpha-galactosidase A replacement therapy-the only disease-specific therapy currently available for Fabry disease-is safe and can reverse substrate storage in the lysosome, the pathophysiologic basis of the disease. Enzyme replacement therapy in all males with Fabry disease (including those with end-stage renal disease) and female carriers with substantial disease manifestations should be initiated as early as possible. Additional experience is needed before more specific recommendations can be made on optimal dosing regimens for reversal; maintenance; and prevention of disease manifestations in affected males, symptomatic carrier females, children, and patients with compromised renal function. C1 CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. Univ Minnesota, Minneapolis, MN USA. Hop Europeen Georges Pompidou, Clin Genet Unit, Paris, France. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Desnick, RJ (reprint author), CUNY Mt Sinai Sch Med, Dept Human Genet, Box 1498,5th Ave & 100th St, New York, NY 10029 USA. FU NIDDK NIH HHS [5 R37 DK34045] NR 59 TC 338 Z9 364 U1 1 U2 16 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 18 PY 2003 VL 138 IS 4 BP 338 EP 346 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 646DK UT WOS:000181019400019 PM 12585833 ER PT J AU Volk, DE Thiviyanathan, V Rice, JS Luxon, BA Shah, JH Yagi, H Sayer, JM Yeh, HJC Jerina, DM Gorenstein, DG AF Volk, DE Thiviyanathan, V Rice, JS Luxon, BA Shah, JH Yagi, H Sayer, JM Yeh, HJC Jerina, DM Gorenstein, DG TI Solution structure of a cis-opened (10R)-N-6-deoxyadenosine adduct of (9S,10R)-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in a DNA duplex SO BIOCHEMISTRY LA English DT Article ID DEOXYADENOSINE N-6-AMINO GROUP; TRANS ADDITION; DIOL EPOXIDE; NMR; SPECTROSCOPY; OPPOSITE; OLIGONUCLEOTIDES; NONANUCLEOTIDE; MUTAGENICITY; SEQUENCE AB The solution structure of an 11-mer DNA duplex, d(CGGTCA*CGAGG).d(CCTCGTGACCG), containing a 10R adduct at dA* that corresponds to the cis addition of the N-6-amino group of dA(6) to (+)-(9S,IOR)-9,10-epoxy-7,8,9,10-tetrahydrobenzo[alpyrene was studied by 2D NMR methods. The NOESY cross-peak patterns indicate that the hydrocarbon is intercalated on the 5'-side of the modified base. This observation is the same as that observed for other oligonucleotides containing (10R)-dA adducts but opposite to that observed for the corresponding (10S)-dA adducts which are intercalated on the 3-side of the modified base. The hydrocarbon is intercalated from the major groove without significant disruption of either the anti glycosidic torsion angle of the modified residue or the base pairing of the modified residue with the complementary residue on the opposite strand. The ensemble of 10 structures determined exhibits relatively small variations (6-15degrees) in the characteristic hydrocarbon-base dihedral angles (alpha' and beta') as well as the glycosidic torsion angle chi. These angles are similar to those in a previously determined cis-opened benzo[a]pyrene diol epoxide-(10R)-dA adduct structure. Comparison of the present structure with the cis-opened diol epoxide adduct suggests that the absence of the 7- and 8-hydroxyl groups results in more efficient stacking of the aromatic moiety with the flanking base pairs and deeper insertion of the hydrocarbon into the helix. Relative to normal B-DNA, the duplex containing the present tetrahydroepoxide adduct is unwound at the lesion site, whereas the diol epoxide adduct structure is more tightly wound than normal B-DNA. Buckling of the adducted base pair as well as the C-5-G(18) base pair that lies immediately above the hydrocarbon is much less severe in the present adducted structure than its cis-opened diol epoxide counterpart. C1 Univ Texas, Med Branch, Sealy Ctr Struct Biol, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77555 USA. NIDDKD, Bioorgan Chem Lab, DHHS, NIH, Bethesda, MD 20892 USA. RP Gorenstein, DG (reprint author), Univ Texas, Med Branch, Sealy Ctr Struct Biol, Galveston, TX 77555 USA. RI Luxon, Bruce/C-9140-2012; OI Volk, David/0000-0002-4372-6915 FU NCI NIH HHS [1CO6CA59098]; NIEHS NIH HHS [1P30 ES06676, ES06839] NR 39 TC 27 Z9 28 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 18 PY 2003 VL 42 IS 6 BP 1410 EP 1420 DI 10.1021/bi026745u PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645BG UT WOS:000180955900007 PM 12578353 ER PT J AU Blaszczyk, J Li, Y Shi, GB Yan, HG Ji, XH AF Blaszczyk, J Li, Y Shi, GB Yan, HG Ji, XH TI Dynamic roles of arginine residues 82 and 92 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: Crystallographic studies SO BIOCHEMISTRY LA English DT Article ID ANTIBIOTIC-RESISTANCE; CRYSTAL-STRUCTURE; TERNARY COMPLEX; RESOLUTION; ANALOG AB 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate biosynthetic pathway. Arginine residues 82 and 92, strictly conserved in 35 HPPK sequences, play dynamic roles in the catalytic cycle of the enzyme. At 0.89-Angstrom resolution, two distinct conformations are observed for each of the two residues in the crystal structure of the wild-type HPPK in complex with two HP variants, two Mg2+ ions, and an ATP analogue. Structural information suggests that R92 first binds to the (x-phosphate group of ATP and then shifts to interact with the beta-phosphate as R82, which initially does not bind to ATP, moves in and binds to (x-phosphate when the pyrophosphoryl transfer is about to occur. The dynamic roles of R82 and R92 are further elucidated by five more crystal structures of two mutant proteins, R82A and R92A, with and without bound ligands. Two oxidized forms of HP are observed with an occupancy ratio of 0.50:0.50 in the 0.89-Angstrom structure. The oxidation of HP has significant impact on its binding to the protein as well as the conformation of nearby residue W89. C1 Natl Canc Inst, Macromol Crystallog Lab, Frederick, MD 21702 USA. Michigan State Univ, Dept Biochem, E Lansing, MI 48824 USA. RP Ji, XH (reprint author), Natl Canc Inst, Macromol Crystallog Lab, Frederick, MD 21702 USA. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NIGMS NIH HHS [GM51901] NR 22 TC 28 Z9 28 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 FEB 18 PY 2003 VL 42 IS 6 BP 1573 EP 1580 DI 10.1021/bi0267994 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645BG UT WOS:000180955900024 PM 12578370 ER PT J AU Li, Y Wu, Y Blaszczyk, J Ji, XH Yan, HG AF Li, Y Wu, Y Blaszczyk, J Ji, XH Yan, HG TI Catalytic roles of arginine residues 82 and 92 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: Site-directed mutagenesis and biochemical studies SO BIOCHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; THIAMIN PYROPHOSPHOKINASE; TERNARY COMPLEX; BINDING; ANALOG AB The roles of a pair of conserved positively charged residues R82 and R92 at a catalytic loop of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) have been investigated by site-directed mutagenesis and biochemical analysis. In the structure of HPPK in complex with ATP and a 6-hydroxymethyl-7,8-dihydropterin (HP) analogue, the guanidinium group of R82 forms two hydrogen bonds with the (x-phosphate and that of R92 two hydrogen bonds with the P-phosphate. In the structure of HPPK in complex with alpha,beta-methyleneadenosine triphosphate (AMPCPP, an ATP analogue) and HP, the guanidinium group of R82 has no direct interaction with AMPCPP and that of R92 forms two hydrogen bonds with the alpha-phosphate. Substitution of R82 with alanine caused a decrease in the rate constant for the chemical step by a factor of -380, but there were no significant changes in the binding energy or binding kinetics of either substrate. Substitution of R92 with alanine caused a decrease in the rate constant for the chemical step by a factor of similar to3.5 x 10(4). The mutation caused no significant changes in the binding energy or binding kinetics of MgATP. It did not cause a significant change in the binding energy of HP either but caused a decrease in the association rate constant for the binding of HP by a factor of similar to4.5 and a decrease in the dissociation rate constant by a factor of similar to10. The overall structures of the ternary complexes of both mutants were very similar to the corresponding structure of wild-type HPPK as described in the companion paper. The results suggest that R82 does not contribute to the binding of either substrate, and R92 is dispensable for the binding of MgATP but plays a role in facilitating the binding of HP. Both R82 and R92 are important for catalysis, and R92 plays a critical role in the transition state stabilization. C1 Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. NCI, Macromol Crystallog Lab, Ft Detrick, MD 21702 USA. RP Yan, HG (reprint author), Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NIGMS NIH HHS [GM51901] NR 23 TC 20 Z9 21 U1 1 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 FEB 18 PY 2003 VL 42 IS 6 BP 1581 EP 1588 DI 10.1021/bi026800z PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645BG UT WOS:000180955900025 PM 12578371 ER PT J AU Germain, RN AF Germain, RN TI T-cell activation: The power of one SO CURRENT BIOLOGY LA English DT Editorial Material ID MHC-PEPTIDE COMPLEXES; RECEPTOR; CD4 C1 NIAID, Immunol Lab, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Immunol Lab, Lymphocyte Biol Sect, NIH, Bldg 10,Rm 11N311,10 Ctr Dr,MSC-1892, Bethesda, MD 20892 USA. NR 20 TC 6 Z9 6 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 FEB 18 PY 2003 VL 13 IS 4 BP R137 EP R139 DI 10.1016/S0960-9822(03)00075-7 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 647CT UT WOS:000181075300011 PM 12593815 ER PT J AU Rivolta, C Ayyagari, R Sieving, P Berson, E Dryja, T AF Rivolta, C Ayyagari, R Sieving, P Berson, E Dryja, T TI Evaluation of the ELOVL4 gene in patients with autosomal recessive retinitis pigmentosa and Leber congenital amaurosis SO MOLECULAR VISION LA English DT Article ID MACULAR DYSTROPHY; CHROMOSOME 6Q; CRB1 GENE; MUTATIONS; LOCUS; PROTEIN; FAMILY AB Purpose: To determine whether pathogenic mutations exist in the ELOVL4 gene in patients with inherited retinal degenerations other than Stargardt-like macular dystrophy or other hereditary macular degenerations. Methods: All six exons comprising the open reading frame of the ELOVL4 gene were evaluated by single-strand conformation analysis, direct nucleotide sequencing, or both methods. Results: No pathogenic mutations were found among 84 patients with autosomal recessive retinitis pigmentosa or among 51 patients with Leber congenital amaurosis (congenital retinal blindness). Conclusions: These data support the conclusion that recessive retinitis pigmentosa and Leber congenital amaurosis are rarely if ever associated with changes in the ELOVL4 gene. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. NEI, Bethesda, MD 20892 USA. Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. RP Dryja, T (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY13198, EY00169, EY08683] NR 20 TC 8 Z9 11 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD FEB 18 PY 2003 VL 9 IS 7-8 BP 49 EP 51 PG 3 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 647FN UT WOS:000181082300002 PM 12592226 ER PT J AU Atlas, R Campbell, P Cozzarelli, NR Curfman, G Enquist, L Fink, G Flanagin, A Fletcher, J George, E Hammes, G Heyman, D Inglesby, T Kaplan, S Kennedy, D Krug, J Levinson, RE Marcus, E Metzger, H Morse, SS O'Brien, A Onderdonk, A Poste, G Renault, B Rich, R Rosengard, A Salzberg, S Scanlan, M Shenk, T Tabor, H Varmus, H Wimmer, E Yamamoto, K AF Atlas, R Campbell, P Cozzarelli, NR Curfman, G Enquist, L Fink, G Flanagin, A Fletcher, J George, E Hammes, G Heyman, D Inglesby, T Kaplan, S Kennedy, D Krug, J Levinson, RE Marcus, E Metzger, H Morse, SS O'Brien, A Onderdonk, A Poste, G Renault, B Rich, R Rosengard, A Salzberg, S Scanlan, M Shenk, T Tabor, H Varmus, H Wimmer, E Yamamoto, K CA Journal Editors Authors Grp TI Uncensored exchange of scientific results SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material C1 MIT, Natl Nucl Secur Adm, Cambridge, MA USA. Council Sci Editors, Wheat Ridge, CO USA. Amer Phytopathol Soc, Off Intellectual Freedom, St Paul, MN USA. Dept Energy, Washington, DC USA. Ctr Strateg & Int Studies, Washington, DC USA. Amer Lib Assoc, Chicago, IL USA. Off Sci & Technol Policy, Washington, DC USA. NIH, Natl Inst Arthrit & Musculoskeletal & Skin Dis, Bethesda, MD USA. Columbia Univ, New York, NY USA. Hlth Technol Networks, Gilbertsville, PA USA. Univ Penn, Philadelphia, PA USA. Inst Genom Res, Rockville, MD USA. Amer Chem Soc, Washington, DC USA. Mem Sloan Kettering Canc Ctr, New York, NY USA. SUNY Stony Brook, Stony Brook, NY USA. RI Levitt, Michael/E-4582-2012; OI Levitt, Michael/0000-0002-8414-7397; O'Brien, Alison/0000-0002-1315-3204; Salzberg, Steven/0000-0002-8859-7432 NR 0 TC 8 Z9 8 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 2003 VL 100 IS 4 BP 1464 EP 1464 DI 10.1073/pnas.0630491100 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647CA UT WOS:000181073000002 PM 12590129 ER PT J AU Li, HW Adamik, R Pacheco-Rodriguez, G Moss, J Vaughan, M AF Li, HW Adamik, R Pacheco-Rodriguez, G Moss, J Vaughan, M TI Protein kinase A-anchoring (AKAP) domains in brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ADP-RIBOSYLATION FACTORS; MOLECULAR CHARACTERIZATION; REGULATORY SUBUNITS; CAENORHABDITIS-ELEGANS; I-ALPHA; IDENTIFICATION; LOCALIZATION; ASSOCIATION; TRANSPORT; CLONING AB Like other guanine nucleotide-exchange proteins (GEPs) that activate ADP-ribosylation factor (ARIF) GTPases, brefeldin A-inhibited GEP2, BIG2, contains an approximate to200-aa Sec7 domain that is responsible for this catalytic activity and its inhibition by brefeldin A. The Sec7 domain is located near the center of the molecule and serves to accelerate replacement of GDP bound to ARIF with GTP. To explore possible functions of the N-terminal region of BIG2 (1-832), we used three coding-region constructs as bait to screen a human heart cDNA library in a yeast two-hybrid system, retrieving two unique clones that encode a type I protein kinase A (PKA) regulatory subunit, RIalpha. Coimmunoprecipitation experiments confirmed interaction of in vitro translated BIG2 and RIalpha, as well as of the endogenous proteins in cytosol of cultured HepG2 cells. Using 28 deletion mutants, we found three regions of BIG2 that interacted with R subunits of PKA. Residues 27-48 (domain A) interacted with RIalpha and RIbeta, 284-301 (domain B) interacted with RIIalpha and RIIIbeta, and 517-538 (domain C) interacted with RIalpha, RIIalpha, and RIIbeta. Sequence analysis and helical wheel projection of amino acids in the three domains revealed potential amphipathic wheel structures characteristic for binding of PKA R subunits. Western blot analysis of subcellular fractions demonstrated translocation of BIG2 (and BIG1) from cytosol to the Golgi and other membrane structures after incubation of cells with 8-Br-cAMP or forskolin. All findings are consistent with a role for BIG2 as an A kinase-anchoring protein (or AKAP) that could coordinate cAMP and ARIF regulatory pathways. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Vaughan, M (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 44 TC 57 Z9 61 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 2003 VL 100 IS 4 BP 1627 EP 1632 DI 10.1073/pnas.0337678100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647CA UT WOS:000181073000035 PM 12571360 ER PT J AU Zhang, ML Zhang, Z Garmestani, K Schultz, J Axworthy, DB Goldman, CK Brechbiel, MW Carrasquillo, JA Waldmann, TA AF Zhang, ML Zhang, Z Garmestani, K Schultz, J Axworthy, DB Goldman, CK Brechbiel, MW Carrasquillo, JA Waldmann, TA TI Pretarget radiotherapy with an anti-CD25 antibody streptavidin fusion protein was effective in therapy of leukemia/lymphoma xenografts SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID B-CELL LYMPHOMA; NUDE-MICE BEARING; Y-90 DOTA-BIOTIN; MONOCLONAL-ANTIBODY; INTERLEUKIN-2 RECEPTOR; PRECLINICAL EVALUATION; CARCINOMA XENOGRAFTS; COLON-CANCER; RADIOIMMUNOTHERAPY; TUMOR AB Although radioimmunotherapy with radiolabeled intact monoclonal antibodies has demonstrated efficacy in the treatment of lymphoma, it provides low tumor-to-normal-tissue radionuclide target ratios and unwanted prolonged radiation exposure to the bone marrow. To overcome these obstacles, the administration of the radionuclide was separated from that of the antibody by using an anti-IL-2 receptor alpha antibody single chain Fv-streptavidin fusion protein, followed by radiolabeled biotin to treat lymphoma or leukemia xenografted mice. This Pretarget approach provided extremely rapid and effective tumor targeting, permitting the use of short-lived alpha-emitting radionuclides. With the beta-emitter Y-90, all of the 10 lymphoma-xenografted mice were cured. With the alpha-emitter Bi-213, significant efficacy was obtained in treating leukemic mice, and, furthermore, when combined with immunotherapy, 7 of 10 leukemic mice were cured. Thus, Pretarget radioimmunotherapy is very promising and could represent the next generation in the treatment of lymphoma and leukemia. C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NEORX Corp, Seattle, WA 98119 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 37 TC 79 Z9 82 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 FEB 18 PY 2003 VL 100 IS 4 BP 1891 EP 1895 DI 10.1073/pnas.0437788100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647CA UT WOS:000181073000081 PM 12569172 ER PT J AU Chun, TW Justement, JS Lempicki, RA Yang, J Dennis, G Hallahan, CW Sanford, C Pandya, P Liu, SY McLaughlin, M Ehler, LA Moir, S Fauci, AS AF Chun, TW Justement, JS Lempicki, RA Yang, J Dennis, G Hallahan, CW Sanford, C Pandya, P Liu, SY McLaughlin, M Ehler, LA Moir, S Fauci, AS TI Gene expression and viral prodution in latently infected, resting CD4(+) T cells in viremic versus aviremic HIV-infected individuals SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV latency; viremia; DNA microarray ID ACTIVE ANTIRETROVIRAL THERAPY; VIRUS; REPLICATION; ERADICATION; PERSISTENCE; RESERVOIRS; TURNOVER; PROTEIN; TSG101; MODEL AB The presence of HIV-1 in latently infected, resting CD4(+) T cells has been clearly demonstrated in infected individuals; however, the extent of viral expression and the underlying mechanisms of the persistence of HIV-1 in this viral reservoir have not been fully delineated. Here, we show that resting CD4(+) T cells from the majority of viremic patients are capable of producing cell-free HIV-1 spontaneously ex vivo. The levels of HIV-1 released by resting CD4(+) T cells were not significantly reduced in the presence of inhibitors of cellular proliferation and viral replication. However, resting CD4(+) T cells from the majority of aviremic patients failed to produce virions, despite levels of HIV-1 proviral DNA and cell-associated HIV-1 RNA comparable to viremic patients. The DNA microarray analysis demonstrated that a number of genes involving transcription regulation, RNA processing and modification, and protein trafficking and vesicle transport were significantly upregulated in resting CD4(+) T cells of viremic patients compared to those of aviremic patients. These results suggest that active viral replication has a significant impact on the physiologic state of resting CD4(+) T cells in infected viremic patients and, in turn, allows release of HIV-1 without exogenous activation stimuli. In addition, given that no quantifiable virions were produced by the latent viral reservoir in the majority of aviremic patients despite the presence of cell-associated HIV-1 RNA, evidence for transcription of HIV-1 RNA in resting CD4(+) T cells of aviremic patients should not necessarily be taken as direct evidence for ongoing viral replication during effective therapy. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Immunopathogenesis & Bioinformat, NIH, Frederick, MD 21702 USA. RP Chun, TW (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 28 TC 121 Z9 123 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 2003 VL 100 IS 4 BP 1908 EP 1913 DI 10.1073/pnas.0437640100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647CA UT WOS:000181073000084 PM 12552096 ER PT J AU Voyich, JM Sturdevant, DE Braughton, KR Kobayashi, SD Lei, BF Virtaneva, K Dorward, DW Musser, JM DeLeo, FR AF Voyich, JM Sturdevant, DE Braughton, KR Kobayashi, SD Lei, BF Virtaneva, K Dorward, DW Musser, JM DeLeo, FR TI Genome-wide protective response used by group A Streptococcus to evade destruction by human polymorphonuclear leukocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROUP-A STREPTOCOCCUS; STAPHYLOCOCCUS-AUREUS; GENE-EXPRESSION; PYOGENES; IDENTIFICATION; PHAGOCYTOSIS; REGULATOR; PROTEIN AB Group A Streptococcus (GAS) evades polymorphonuclear leukocyte (PMN) phagocytosis and killing to cause human disease, including pharyngitis and necrotizing fasciitis (flesh-eating syndrome). We show that GAS genes differentially regulated during phagocytic interaction with human PMNs comprise a global pathogen-protective response to innate immunity. GAS prophage genes and genes involved in virulence, oxidative stress, cell wall biosynthesis, and gene regulation were up-regulated during PMN phagocytosis. Genes encoding novel secreted proteins were up-regulated, and the proteins were produced during human GAS infections. We discovered an essential role for the Ihk-Irr two-component regulatory system in evading PMN-mediated killing and promoting host-cell lysis, processes that would facilitate GAS pathogenesis. Importantly, the irr gene was highly expressed during human GAS pharyngitis. We conclude that a complex pathogen genetic program circumvents human innate immunity to promote disease. The gene regulatory program revealed by our studies identifies previously undescribed potential vaccine antigens and targets for therapeutic interventions designed to control GAS infections. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP DeLeo, FR (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. OI DeLeo, Frank/0000-0003-3150-2516 NR 25 TC 107 Z9 113 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 2003 VL 100 IS 4 BP 1996 EP 2001 DI 10.1073/pnas.0337370100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647CA UT WOS:000181073000099 PM 12574517 ER PT J AU Junn, E Ronchetti, RD Quezado, MM Kim, SY Mouradian, MM AF Junn, E Ronchetti, RD Quezado, MM Kim, SY Mouradian, MM TI Tissue transglutaminase-induced aggregation of alpha-synuclein: Implications for Lewy body formation in Parkinson's disease and dementia with Lewy bodies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PIG LIVER TRANSGLUTAMINASE; CROSS-LINKING; ALZHEIMERS-DISEASE; IN-VITRO; HUNTINGTONS-DISEASE; NACP/ALPHA-SYNUCLEIN; HUMAN BRAIN; PROTEIN; BINDING; INCLUSIONS AB Proteinaceous aggregates containing a-synuclein represent a feature of neurodegenerative disorders such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Despite extensive research, the mechanisms underlying a-synuclein aggregation remain elusive. Previously, tissue transglutaminase (tTGase) was found to contribute to the generation of aggregates by cross-linking pathogenic substrate proteins in Huntington's and Alzheimer's diseases. In this article, the role of tTGase in the formation of a-synuclein aggregates was investigated. Purified tTGase catalyzed alpha-synuclein cross-linking, leading to the formation of high molecular weight aggregates in vitro, and overexpression of tTGase resulted in the formation of detergent-insoluble a-synuclein aggregates in cellular models. Immunocytochemical studies demonstrated the presence of a-synuclein-positive cytoplasmic inclusions in 8% of tTGase-expressing cells. The formation of these aggregates was significantly augmented by the calcium ionophore A23187 and prevented by the inhibitor cystamine. Immunohistochemical studies on postmortem brain tissue confirmed the presence of transglutaminase-catalyzed epsilon(gamma-glutamyl)lysine cross-links in the halo of Lewy bodies in Parkinson's disease and dementia with Lewy bodies, colocalizing with alpha-synuclein. These findings, taken together, suggest that tTGase activity leads to a-synuclein aggregation to form Lewy bodies and perhaps contributes to neurodegeneration. C1 NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Burke Med Res Inst, Dept Neurosci, White Plains, NY 10605 USA. RP Mouradian, MM (reprint author), NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 62 TC 150 Z9 152 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 FEB 18 PY 2003 VL 100 IS 4 BP 2047 EP 2052 DI 10.1073/pnas.0438021100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647CA UT WOS:000181073000108 PM 12576551 ER PT J AU Grisshammer, R Tate, C AF Grisshammer, R Tate, C TI Preface: overexpression of integral membrane proteins SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Editorial Material C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. RP Grisshammer, R (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 50,Room 4503,50 South Dr, Bethesda, MD 20892 USA. RI Grisshammer, Reinhard/C-3089-2015 NR 0 TC 14 Z9 14 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD FEB 17 PY 2003 VL 1610 IS 1 BP 1 EP 1 DI 10.1016/S0005-2736(02)00706-X PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 647UM UT WOS:000181112500001 ER PT J AU Venturi, M Hunte, C AF Venturi, M Hunte, C TI Monoclonal antibodies for the structural analysis of the Na+/H+ antiporter NhaA from Escherichia coli SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Review DE membrane protein; antibody fragment; Na+/H+ antiporter; crystallization ID DEPENDENT CONFORMATIONAL CHANGE; ANGSTROM RESOLUTION; HIV-1 GP120; FRAGMENTS; PROTEIN; CRYSTALLIZATION; MEMBRANE; COMPLEX; IMMUNIZATION; CYTOPLASM AB Since their advent some 25 years ago, monoclonal antibodies have developed into powerful tools for structural and functional analysis of their cognate antigens. Together with the respective antigen binding fragments, antibodies offer exclusive capacities in detection, characterization, purification and functional assays for every given ligand. Antibody-fragment mediated crystallization represents a major advance in determining the three-dimensional structure of membrane-bound protein complexes. In this review, we focus on the methods used to generate monoclonal antibodies against the NhaA antiporter from Escherichia coli as a paradigm of secondary transporters. We describe examples on how antibodies are helpful in understanding structure and function relationships for this important class of integral membrane proteins. The generated conformation-specific antibody fragments are highly valuable reagents for co-crystallization attempts and structure determination of the antiporter. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Max Planck Inst Biophys, Abt Mol Membranbiol, D-60528 Frankfurt, Germany. NIH, Vaccine Res Ctr, Struct Biol Sect, Bethesda, MD 20892 USA. RP Hunte, C (reprint author), Max Planck Inst Biophys, Abt Mol Membranbiol, D-60528 Frankfurt, Germany. RI Hunte, Carola/E-4071-2015 OI Hunte, Carola/0000-0002-0826-3986 NR 34 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD FEB 17 PY 2003 VL 1610 IS 1 BP 46 EP 50 DI 10.1016/S0005-2736(02)00713-7 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 647UM UT WOS:000181112500006 PM 12586378 ER PT J AU Akiyama, TE Gonzalez, FJ AF Akiyama, TE Gonzalez, FJ TI Regulation of P450 genes by liver-enriched transcription factors and nuclear receptors SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article; Proceedings Paper CT 12th International Symposium on Cellular Biology of Cytochrome P450 Regulation CY SEP, 2001 CL LA GRANDE MOTTE, FRANCE DE P450; nuclear receptor; liver-enriched transcription factor; gene regulation; knockout mouse; transgenic mouse ID PREGNANE-X-RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; TISSUE-SPECIFIC EXPRESSION; LEUCINE-ZIPPER PROTEINS; BILE-ACID BIOSYNTHESIS; CIS-ACTING ELEMENT; HUMAN CYP2B6 GENE; RAT-LIVER; CHOLESTEROL 7-ALPHA-HYDROXYLASE; FACTOR-I AB Cytochrome P450s (P450s) constitute a superfamily of heme-proteins that play an important role in the activation of chemical carcinogens, detoxification of numerous xenobiotics as well as in the oxidative metabolism of endogenous compounds such as steroids, fatty acids, prostaglandins, and leukotrienes [FASEB J. 10 (1996) 1112; DNA Cell Biol. 10 (1991) 1; Pharmacol. Rev. 40 (1988) 243; Crit. Rev. Biochem. Mol. Biol. 25 (1990) 97]. In addition, some P450s have important roles in physiological processes, such as steroidogenesis and the maintenance of bile acid and cholesterol homeostasis [Science 294 (2001) 1866; Cell 103 (2000) 1]. Given their importance, the molecular mechanisms of P450 gene regulation have been intensely studied. Direct interactions between transcription factors, including nuclear receptors, with the promoters of P450 genes represent one of the primary means by which the expression of these genes is controlled. In this review, several liver-enriched transcription factors that play a role in the tissue-specific, developmental, and temporal regulation of P450s are discussed. In addition, the nuclear receptors that play a role in the fine control of cholesterol and bile acid homeostasis, in part, through their modulation of specific P450s, are discussed. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIH, Lab Metab, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NIH, Lab Metab, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 160 TC 89 Z9 96 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD FEB 17 PY 2003 VL 1619 IS 3 BP 223 EP 234 AR PII S0304-4165(02)00480-4 DI 10.1016/S0304-4165(02)00480-4 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 648FW UT WOS:000181140200002 PM 12573481 ER EF