FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Tanda, G Munzar, P Goldberg, SR AF Tanda, G Munzar, P Goldberg, SR TI Self-administration behavior is maintained by the psychoactive ingredient of marijuana in squirrel monkeys SO NATURE NEUROSCIENCE LA English DT Article ID RHESUS-MONKEYS; RECEPTOR; CANNABINOIDS C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA. Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20007 USA. Univ Cagliari, Dept Toxicol, I-09126 Cagliari, Italy. Univ Cagliari, CNR, Ctr Neuropharmacol, I-09126 Cagliari, Italy. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Tanda, Gianluigi/B-3318-2009 OI Tanda, Gianluigi/0000-0001-9526-9878 NR 14 TC 200 Z9 211 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2000 VL 3 IS 11 BP 1073 EP 1074 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 405TX UT WOS:000167177600008 PM 11036260 ER PT J AU Erickson, CA Jagadeesh, B Desimone, R AF Erickson, CA Jagadeesh, B Desimone, R TI Clustering of perirhinal neurons with similar properties following visual experience in adult monkeys SO NATURE NEUROSCIENCE LA English DT Article ID INFERIOR TEMPORAL CORTEX; FREQUENCY-DISCRIMINATION TASK; SOMATOSENSORY CORTICAL MAP; OCULAR DOMINANCE COLUMNS; PRIMARY MOTOR CORTEX; LONG-TERM-MEMORY; INFEROTEMPORAL CORTEX; RECOGNITION MEMORY; OWL MONKEYS; HIPPOCAMPAL-FORMATION AB The functional organization of early visual areas seems to be largely determined during development. However, the organization of areas important for learning and memory, such as perirhinal cortex, may be modifiable in adults. To test this hypothesis, we recorded from pairs of neurons in perirhinal cortex of macaques while they viewed multiple complex stimuli. For novel stimuli, neuronal response preferences for pairs of nearby neurons and far-apart neurons were uncorrelated. However, after one day of experience with the stimuli, response preferences of nearby neurons became more similar. We conclude that specific visual experience induces development of clusters of perirhinal neurons with similar stimulus preferences. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. RP Erickson, CA (reprint author), NIMH, Neuropsychol Lab, Bldg 49,Room 1B80, Bethesda, MD 20892 USA. NR 50 TC 78 Z9 79 U1 1 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2000 VL 3 IS 11 BP 1143 EP 1148 DI 10.1038/80664 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 405TX UT WOS:000167177600020 PM 11036272 ER PT J AU Olden, K Wilson, S AF Olden, K Wilson, S TI Environmental health and genomics: visions and implications SO NATURE REVIEWS GENETICS LA English DT Editorial Material ID HUMAN-GENETICS; POLYMORPHISMS; PROJECT AB The relationship between genes and the environment can be compared to a loaded gun and its trigger, A loaded gun by itself causes no harm; it is only when the trigger is pulled that the potential Tor harm is released, Genetic susceptibility creates an analogous situation, where the loaded gun is one or a combination of susceptibility genes (alleles) and the trigger is an environmental exposure. The key object ve of the Environmental Genome Project is to identify alleles that confer susceptibility to the adverse effects of environmental agents. Here we discuss the goals of the Environmental Genome Project, its implications and, in particular, its potential effect on our ability to assess human disease risk in the future. C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Olden, K (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. NR 10 TC 72 Z9 75 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD NOV PY 2000 VL 1 IS 2 BP 149 EP 153 DI 10.1038/35038586 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 381LB UT WOS:000165763400020 PM 11253655 ER PT J AU Mattson, MP AF Mattson, MP TI Apoptosis in neurodegenerative disorders SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID SPINAL-CORD INJURY; AMYOTROPHIC-LATERAL-SCLEROSIS; TRAUMATIC BRAIN INJURY; MOTOR-NEURON DISEASE; AMYLOID-PRECURSOR PROTEIN; FIBROBLAST-GROWTH-FACTOR; TRANSGENIC MOUSE MODELS; CELL-DEATH; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE AB Neuronal death underlies the symptoms of many human neurological disorders, including Alzheimer's, Parkinson's and Huntington's diseases, stroke, and amyotrophic lateral sclerosis. The identification of specific genetic and environmental factors responsible for these diseases has bolstered evidence for a shared pathway of neuronal death - apoptosis - involving oxidative stress, perturbed calcium homeostasis, mitochondrial dysfunction and activation of cysteine proteases called caspases. These death cascades are counteracted by survival signals, which suppress oxyradicals and stabilize calcium homeostasis and mitochondrial function. With the identification of mechanisms that either promote or prevent neuronal apoptosis come new approaches for preventing and treating neurodegenerative disorders. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 107 TC 860 Z9 896 U1 18 U2 137 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD NOV PY 2000 VL 1 IS 2 BP 120 EP 129 DI 10.1038/35040009 PG 10 WC Cell Biology SC Cell Biology GA 381LX UT WOS:000165765300016 PM 11253364 ER PT J AU Norvell, JC Machalek, AZ AF Norvell, JC Machalek, AZ TI Structural genomics programs at the US National Institute of General Medical Sciences - Foreword SO NATURE STRUCTURAL BIOLOGY LA English DT Editorial Material C1 Natl Inst Gen Med Sci, Bethesda, MD 20892 USA. RP Norvell, JC (reprint author), Natl Inst Gen Med Sci, Bethesda, MD 20892 USA. NR 0 TC 56 Z9 61 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD NOV PY 2000 VL 7 SU S BP 931 EP 931 DI 10.1038/80694 PG 1 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 563YQ UT WOS:000176285900003 PM 11103990 ER PT J AU Harris, PLR Zhu, XW Pamies, C Rottkamp, CA Ghanbari, HA McShea, A Feng, Y Ferris, DK Smith, MA AF Harris, PLR Zhu, XW Pamies, C Rottkamp, CA Ghanbari, HA McShea, A Feng, Y Ferris, DK Smith, MA TI Neuronal polo-like kinase in Alzheimer disease indicates cell cycle changes SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer disease; cell cycle; cytoskeleton; pathogenesis; phosphorylation; polo-like kinase; tau ID PROTEIN-KINASE; PROGNOSTIC-SIGNIFICANCE; ABNORMAL PHOSPHORYLATION; MICROTUBULE-BINDING; DROSOPHILA POLO; PLK EXPRESSION; TAU-PROTEIN; IDENTIFICATION; GENE; LOCALIZATION AB Neurons of adults apparently lack the components necessary to complete the cell division process. Therefore. in Alzheimer disease. the increased expression of cell cycle-related proteins in degenerating neurons likely leads to an interrupted mitotic process associated with cytoskeletal abnormalities and, ultimately, neuronal degeneration. In this study, to further delineate the role of mitotic processes in the pathogenesis of Alzheimer disease, we undertook a study of polo-like kinase (Plk), a protein that plays a crucial role in the cell cycle. Our results show disease-related increases in Plk in susceptible hippocampal and cortical neurons in comparison to young or age-matched controls. An increase in neuronal Plk further implicates aberrations in cell cycle control in the pathogenesis of Alzheimer disease and provides a novel mechanistic basis for therapeutic intervention. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. Panacea Pharmaceut, Rockville, MD 20850 USA. Fred Hutchinson Canc Res Ctr, Program Canc Biol, Seattle, WA 98109 USA. NCI, FCRCD, Frederick, MD 21702 USA. RP Smith, MA (reprint author), Case Western Reserve Univ, Inst Pathol, 2085 Adelbert Rd, Cleveland, OH 44106 USA. RI Smith, Mark/A-9053-2009; Zhu, Xiongwei/A-9629-2009 FU NINDS NIH HHS [NS34684] NR 47 TC 39 Z9 43 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 2000 VL 21 IS 6 BP 837 EP 841 DI 10.1016/S0197-4580(00)00218-9 PG 5 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 388EH UT WOS:000166164100009 PM 11124427 ER PT J AU Brooks, PJ AF Brooks, PJ TI Brain atrophy and neuronal loss in alcoholism: a role for DNA damage? SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE oxidative damage; DNA repair; lipid peroxidation; acetaldehyde; neurodegeneration ID NUCLEOTIDE EXCISION-REPAIR; A XERODERMA-PIGMENTOSUM; RNA-POLYMERASE-II; GABA(A) RECEPTOR; SKIN-CANCER; RAT-BRAIN; GLUTAMATERGIC NEUROTRANSMISSION; NEUROLOGICAL ABNORMALITIES; ULTRAVIOLET-RADIATION; THIAMINE-DEFICIENCY AB Chronic alcohol abuse has deleterious effects on several organs in the body including the brain. Neuroradiological studies have demonstrated that the brains of chronic alcoholics undergo loss of both gray and white matter volumes. Neuropathological studies using unbiased stereological methods have provided evidence for loss of neurons in specific parts of the brain in chronic alcoholics. The purpose of this paper is to propose a mechanism for this alcohol related neuronal loss. The hypothesis is based on the neurodegeneration observed in patients with the genetic disorder xeroderma pigmentosum (XP), who lack the capacity to carry out a specific type of DNA repair called nucleotide excision repair (NER). Some XP patients develop a progressive atrophic neurodegeneration, termed XP neurological disease, indicating that endogenous DNA damage that is normally repaired by NER has the capacity to cause neuronal death. Accumulating evidence indicates that the neurodegenerative DNA damage that is responsible for neuronal loss in XP patients results from reactive oxygen species (ROS) and lipid peroxidation products, and has the capacity to inhibit gene expression by RNA polymerase II. Therefore, the following model is proposed: chronic alcohol abuse results in increased levels of ROS and lipid peroxidation products in neurons, which results in an overwhelming burden on the NER pathway, and increased steady state levels of DNA lesions that inhibit gene expression. This results in neuronal death either by reduction in the levels of essential gene products or by apoptosis. The implications of this model for future studies are discussed. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NIAAA, Mol Neurobiol Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Brooks, PJ (reprint author), NIAAA, Mol Neurobiol Sect, Neurogenet Lab, NIH, 12420 Parktown Dr,MSC 8110, Bethesda, MD 20892 USA. NR 87 TC 45 Z9 48 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD NOV-DEC PY 2000 VL 37 IS 5-6 BP 403 EP 412 DI 10.1016/S0197-0186(00)00051-6 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 355KC UT WOS:000089384000002 PM 10871692 ER PT J AU Heinz, A Goldman, D AF Heinz, A Goldman, D TI Genotype effects on neurodegeneration and neuroadaptation in monoaminergic neurotransmitter systems SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE dopamine; serotonin; brain reward system; alcoholism; neurotoxicity ID DOPAMINE TRANSPORTER GENE; RECEPTOR-BINDING CHARACTERISTICS; ALCOHOL-DEPENDENT PATIENTS; DRD2 VARIANT SER311CYS; FREELY MOVING RATS; I-123 BETA-CIT; SEROTONIN TRANSPORTER; ALLELIC ASSOCIATION; D2 RECEPTOR; IN-VIVO AB Neuroadaptation and neurodegeneration in central dopaminergic and serotonergic systems are central to vulnerability, process and consequences of addictive behavior. Serotonergic dysfunction has been associated with behavior disinhibition and negative mood states that may predispose to excessive alcohol intake, while alcohol-induced stimulation of dopaminergic neurotransmission may encode the reinforcing properties of alcohol consumption. Chronic alcohol intake induces neuroadaptive reductions in striatal dopamine transporter (DAT) and D2 receptor availability, which were reversible during early abstinence. A polymorphism of the DAT gene (SLC6A3) was associated with the in vivo transporter availability in the putamen of abstinent alcoholics and control subjects. The same genotype was associated with severity of alcohol withdrawal symptoms, hypothetically due to interactions of genotype and alcohol-induced neuroadaptation. Reduction in raphe serotonin transporter (5-HTT) availability was observed in abstinent male alcoholics and it may be the result of neurodegeneration rather than reversible neuroadaptation. Neurotoxic reduction in 5-HTT protein expression seems to be limited to homozygous carriers of a long, more transcriptionally active allele of a promoter repeat polymorphism of the 5-HTT gene (SCL6A4). This genotype was also associated with a low level of acute unpleasant effects of alcohol consumption, a factor predisposing to excessive alcohol intake. The time course of neuroadaptation and recovery of monoaminergic neurotransmission in alcohol intake and withdrawal imply that monoamine transporter genotype could profoundly influence alcohol-induced reinforcement and, perhaps, contribute to neurochemical changes which are long lasting or permanent. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Cent Inst Mental Hlth, Dept Addict Behav & Addict Med, Mannheim, Germany. NIAAA, Bethesda, MD USA. RP Heinz, A (reprint author), Cent Inst Mental Hlth, Dept Addict Behav & Addict Med, Mannheim, Germany. EM heinza@as200.zi-mannheim.de RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 73 TC 26 Z9 26 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD NOV-DEC PY 2000 VL 37 IS 5-6 BP 425 EP 432 DI 10.1016/S0197-0186(00)00057-7 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 355KC UT WOS:000089384000004 PM 10871694 ER PT J AU Rudolph, JG Lemasters, JJ Crews, FT AF Rudolph, JG Lemasters, JJ Crews, FT TI Effects of NMDA and ferrous sulfate on oxidation and cell death in primary neuronal cultures SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE cellular oxidation; NMDA; ferrous sulfate; excitotoxicity ID METHYL-D-ASPARTATE; MAMMALIAN BRAIN NEURONS; NITRIC-OXIDE FORMATION; OXYGEN FREE-RADICALS; PARKINSONS-DISEASE; CORTICAL-NEURONS; MEDIATED EXCITOTOXICITY; SUPEROXIDE-DISMUTASE; RECEPTOR ACTIVATION; NEUROTOXICITY AB Excessive oxidative radical production has been implicated in a variety of neurodegerative processes including NMDA (N-methyl-D-aspartate) mediated excitotoxicity. To determine the relationship of oxidation to NMDA-receptor mediated neuronal death, we exposed rat primary cortical neuronal cultures to ferrous sulfate and the fluorescent dyes dichlorofluorescin diacetate (H2DCF) and propidium iodide (PI) to monitor reactive oxygen species (ROS) and cell death, respectively in the same cultures. Ferrous sulfate (FeSO4) caused a dose-dependent increase in cellular oxidation with an ED50 of approximately 136 mu M. Levels of oxidation increased over time reaching maximum levels between 15 and 25 min. Ferrous sulfate (ED50 approximate to 241 mu M) treatment for 25 min caused a delayed and progressive neuronal death that was comparable to NMDA (100 mu M, 25 min) delayed neuronal death. NMDA (100 CIM, 25 min) alone did not result in measurable increases of DCF fluorescence, However, when combined with 40 mu M FeSO4, NMDA dose-dependently increased H2DCF fluorescence. Despite the increase in DCF oxidation, combinations of FeSO4 with NMDA did not synergize or accelerate NMDA-receptor mediated or glutamate-mediated excitotoxicity. Although excessive amounts FeSO4 induced oxidation can cause delayed neuronal death, these findings suggest that oxidative stress is not the key factor in triggering the NMDA mediated excitotoxic cascade. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Univ N Carolina, Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. RP Rudolph, JG (reprint author), NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 31 TC 8 Z9 8 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD NOV-DEC PY 2000 VL 37 IS 5-6 BP 497 EP 507 DI 10.1016/S0197-0186(00)00053-X PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 355KC UT WOS:000089384000011 PM 10871701 ER PT J AU Frank, JA AF Frank, JA TI Advances in multiple sclerosis - Preface SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 NIH, Ctr Clin, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. RP Frank, JA (reprint author), NIH, Ctr Clin, Lab Diagnost Radiol Res, 10 Ctr Dr,MSC 1074,Bldg 10,Room B1N256, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD NOV PY 2000 VL 10 IS 4 BP XIII EP XIII PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 431BD UT WOS:000168611300001 ER PT J AU Stuerzebecher, S Martin, R AF Stuerzebecher, S Martin, R TI Neuroimmunology of multiple sclerosis and experimental allergic encephalomyelitis SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID MYELIN BASIC-PROTEIN; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; T-CELL CLONES; NECROSIS-FACTOR-ALPHA; 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE; VASCULAR ENDOTHELIAL-CELLS; ALTERED PEPTIDE LIGANDS; CLASS-II MOLECULES; HUMAN GLIAL-CELLS AB The potential causes, immunopathology, and treatment of multiple sclerosis (MS) are summarized in this article. Findings from a well-examined animal model for MS, experimental allergic encephalomyelitis (EAE), are described and used to illustrate the paths of research in MS. Data from a recent clinical trial with a modified myelin peptide provide support for concepts deduced from EAE. The authors stress that the complexity of the disease requires new techniques to capture the influence of single or combined treatment approaches. C1 NINDS, Neuroimmunol Branch, NIH, Cellular Immunol Sect, Bethesda, MD 20892 USA. Schering AG, Cardiovasc & CNS, Berlin, Germany. RP Stuerzebecher, S (reprint author), NINDS, Neuroimmunol Branch, NIH, Cellular Immunol Sect, Bldg 10,Rm 5B-16,10 Ctr Dr,MSC 1400, Bethesda, MD 20892 USA. NR 216 TC 2 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD NOV PY 2000 VL 10 IS 4 BP 649 EP + PG 22 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 431BD UT WOS:000168611300004 PM 11359717 ER PT J AU Butman, JA Frank, JA AF Butman, JA Frank, JA TI Overview of imaging in multiple sclerosis and white matter disease SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID CLINICALLY ISOLATED SYNDROMES; VIRCHOW-ROBIN SPACES; REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY; CORPUS-CALLOSUM ATROPHY; MAGNETIZATION-TRANSFER; FOLLOW-UP; SPIN-ECHO; PULSE SEQUENCES; OPTIC NEURITIS; HYPOINTENSE LESIONS AB MR imaging is the dominant paraclinical test for evaluating multiple sclerosis (MS) because of its exquisite sensitivity to white matter pathology. Knowledge of the signal characteristics of MS lesions, anatomic distribution of lesions, differential diagnosis, and most important, the clinical context, markedly improve the specificity of the MR examination. MR imaging findings can be used to predict future conversion to clinically definite MS before a second clinical exacerbation. C1 NIH, Imaging Sci Program, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIH, Lab Diagnost Radiol Res, Clin Ctr, Bethesda, MD 20892 USA. RP Butman, JA (reprint author), NIH, Imaging Sci Program, Dept Diagnost Radiol, Bldg 10,Room 1C660,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 NR 86 TC 2 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD NOV PY 2000 VL 10 IS 4 BP 669 EP + PG 21 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 431BD UT WOS:000168611300005 PM 11359718 ER PT J AU Frank, JA McFarland, HF AF Frank, JA McFarland, HF TI How to participate in a multiple sclerosis clinical trial SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID LESION VOLUME MEASUREMENTS; MAGNETIC-RESONANCE TECHNIQUES; MONITORING DISEASE-ACTIVITY; SECONDARY-PROGRESSIVE MS; PLACEBO-CONTROLLED TRIAL; CONVENTIONAL SPIN-ECHO; SURROGATE END-POINTS; INTERFERON BETA-1B; LOAD MEASUREMENTS; DOUBLE-BLIND AB MR imaging has made a significant contribution to the understanding of the natural history of multiple sclerosis (MS). MR imaging is an important technique for investigating the pathologic process in the MS patient's brain and spinal cord, and it is now considered an essential part of all clinical trials being performed on new agents in the treatment of MS. This article provides an overview for those wishing to become involved in MS clinical research. Discussion includes the use of conventional and newer MR imaging techniques in clinical trials, current thoughts regarding the role of MR imaging as a surrogate outcome measure, and various types of trial designs. C1 NINDS, Natl Inst Hlth, Neuroimmunol Branch, Bethesda, MD 20892 USA. NIH, LDRR, Clin Ctr, Bethesda, MD 20892 USA. RP Frank, JA (reprint author), NIH, LDRR, Clin Ctr, Bldg 10,Room B1N256,10 Ctr Dr,MSC 1074, Bethesda, MD 20892 USA. NR 56 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD NOV PY 2000 VL 10 IS 4 BP 817 EP + PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 431BD UT WOS:000168611300014 PM 11359727 ER PT J AU Hyman, S AF Hyman, S TI Mental illness: Genetically complex disorders of neural circuitry and neural communication SO NEURON LA English DT Editorial Material ID SCHIZOPHRENIA; GENES C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Hyman, S (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. NR 16 TC 25 Z9 26 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 2000 VL 28 IS 2 BP 321 EP 323 DI 10.1016/S0896-6273(00)00110-0 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 377CE UT WOS:000165493700006 PM 11144341 ER PT J AU LaMantia, AS Bhasin, N Rhodes, K Heemskerk, J AF LaMantia, AS Bhasin, N Rhodes, K Heemskerk, J TI Mesenchymal/epithelial induction mediates olfactory pathway formation SO NEURON LA English DT Article ID MIDBRAIN CREST CELLS; CARDIAC NEURAL CREST; RETINOIC-ACID; SONIC-HEDGEHOG; SMALL-EYE; BULB DEVELOPMENT; CHICK-EMBRYOS; AXONAL GROWTH; MOUSE EMBRYOS; ADULT-RAT AB In the olfactory pathway, as in the limbs, branchial arches, and heart, mesenchymal/epithelial induction, mediated by retinoic acid (RA), FGF8, sonic hedgehog (shh), and the BMPs, defines patterning, morphogenesis, and differentiation. Neuronal differentiation in the olfactory epithelium and directed growth of axons in the nascent olfactory nerve depend critically upon this inductive interaction. When RA, FGF8, shh, or BMP signaling is disrupted, distinct aspects of olfactory pathway patterning and differentiation are compromised. Thus, a cellular and molecular mechanism that facilitates musculoskeletal and vascular development elsewhere in the embryo has been adapted to guide the differentiation of the olfactory pathway in the developing forebrain. C1 Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. NINDS, Bethesda, MD 20892 USA. RP LaMantia, AS (reprint author), Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. FU NICHD NIH HHS [HD29178] NR 92 TC 116 Z9 117 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 2000 VL 28 IS 2 BP 411 EP 425 DI 10.1016/S0896-6273(00)00121-5 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 377CE UT WOS:000165493700017 PM 11144352 ER PT J AU Westergaard, GC Chavanne, TJ Lussier, ID Suomi, SJ Higley, JD AF Westergaard, GC Chavanne, TJ Lussier, ID Suomi, SJ Higley, JD TI Hormonal correlates of hand preference in free-ranging primates SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cortisol; testosterone; laterality; development; rhesus macaques ID MONKEYS MACACA-MULATTA; RHESUS-MONKEYS; CEREBRAL LATERALIZATION; BIOLOGICAL MECHANISMS; LEFT-HANDEDNESS; HOMOSEXUAL MEN; TESTOSTERONE; ASSOCIATIONS; HYPOTHESIS; HEMISPHERE AB In this research we examined hormonal correlates of hand preference in free-ranging primates. Specifically, we tested the hypothesis that levels oft he stress hormone cortisol nod the male sex hormone testosterone are correlated with handedness in male rhesus macaques (Macaca mulatta). We found significant positive relationships between cortisol and testosterone levels sampled during adolescnece ann the frequency of right- versus left-hand use sampled during adulthood. These data indicate that adolescent measures of cortisol and testosterone are correlated with hemispheric specialization in adult free-ranging primates. C1 LABS Virginia Inc, Div Res & Dev, Yemassee, SC 29902 USA. NICHHD, Comparat Ethol Lab, Poolesville, MD USA. NIAAA, Clin Studies Lab, Poolesville, MD USA. RP Westergaard, GC (reprint author), LABS Virginia Inc, Div Res, 95 Castle Hall Rd,POB 557, Yemassee, SC 29902 USA. NR 22 TC 21 Z9 21 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2000 VL 23 IS 5 BP 502 EP 507 DI 10.1016/S0893-133X(00)00141-X PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 363ZL UT WOS:000089867500002 PM 11027915 ER PT J AU Newlin, DB Wong, CJ Stapleton, JM London, ED AF Newlin, DB Wong, CJ Stapleton, JM London, ED TI Intravenous cocaine decreases cardiac vagal tone, vagal index (derived in Lorenz space), and heart period complexity (approximate entropy) in cocaine abusers SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cocaine; heart rate; vagal tone; parasympathetic; sympathetic; approximate entropy; respiratory sinus arrhythmia; chaos ID CORONARY-OCCLUSION; REGULARITY; ATROPINE; HUMANS; MECHANISMS; RESPONSES; PLACEBO; ALCOHOL; SYSTEM; BRAIN AB We assessed the effects of i.v. cocaine on parasympathetic and sympathetic nervous system activity, and on the complexity vs. regularity of changes in heart rate over time. Fourteen otherwise healthy men with histories of i.v. cocaine abuse received bolus injections of cocaine (20 mg or 40 mg) and placebo (saline) on different days. Cardiovascular measures derived from the electrocardiogram. including heart rate, Forges' vagal forts (respiratory sinus arrhythmia), the 0.10 Hz rhythm, Toichi's vagal index, Toichi's sympathetic index, and approximate entropy (ApEn), were measured continuously. As predicted, cocaine produced tachycardia, accompanied by pronounced decreases in response to 40 mg cocaine in two different vagal tone indexes that precisely mirrored Nle increases ill heart rate. The measure of sympathetic (and vagal) neural( influences on the heart (0.10 Hz wave) also decreased in response to cocaine. Converging evidence from Toichi's vagal index supported the conclusion that fire tachycardia from cocaine was due to withdrawal,nl of cardiac vagal tone. These findings, and evidence that cocaine decreased cardiovascular complexity, contradict the prevailing assumption that the mechanism by rc,which cocaine produces tachycardia is sympathetic (beta-adrenergic). We discuss implications for cardiac arrhythmias associated with cocaine abuse and death dire to overdose. Published by Elsevier Science Inc. C1 NIDA, IRP, Mol Neurobiol Branch, Baltimore, MD 21224 USA. RP Newlin, DB (reprint author), NIDA, IRP, Mol Neurobiol Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 37 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2000 VL 23 IS 5 BP 560 EP 568 DI 10.1016/S0893-133X(00)00135-4 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 363ZL UT WOS:000089867500008 PM 11027921 ER PT J AU Kennel, SJ Mirzadeh, S Hurst, GB Foote, LJ Lankford, TK Glowienka, KA Chappell, LL Kelso, JR Davern, SM Safavy, A Brechbiel, MW AF Kennel, SJ Mirzadeh, S Hurst, GB Foote, LJ Lankford, TK Glowienka, KA Chappell, LL Kelso, JR Davern, SM Safavy, A Brechbiel, MW TI Labeling and distribution of linear peptides identified using in vivo phage display selection for tumors SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE peptides; phage display; tumors; distribution; radioiodination; Bi-213; bifunctional DTPA ligands ID N-SUCCINIMIDYL 3-IODOBENZOATE; ALPHA-PARTICLE EMITTER; IN-VIVO; MONOCLONAL-ANTIBODIES; BOMBESIN ANALOG; GROWTH-FACTOR; LOCALIZATION; RECEPTOR; INVIVO; LUNG AB To develop targeting molecules to be used for vascular targeting of short half lived cc-emitters for radioimmunotherapy, linear peptide phage display libraries were selected in vivo for binding to IC-12 rat tracheal tumors growing in severe combined immune deficient mice. After three rounds of selection, 15 phage clones were analyzed for DNA sequence, and the deduced translation products of cDNA inserts were compared. Three consensus sequences were chosen from three separate experimental selection series and peptides of these sequences with added -gly-gly-tyr were obtained. Peptides were radiolabeled on tyrosine with I-125 and the biodistribution in tumor-bearing mice was determined. The radioiodinated peptides were stable in vitro and when injected in tumor-bearing mice similar to3.0 %ID/g accumulated in the tumor; however, much of the I-125 was found in the gastrointestinal tract and thyroid, indicative of dehalogenation of the Labeled peptide. Radiolabeling peptide 2 with N-succinimidyl-3-I-125-iodobenzoate resulted in faster excretion, which in turn resulted in lower levels in tumor and other organs, especially thyroid and gastrointestinal tract. Peptide 2 was derivatized with the bifunctional isothiocyanates of cyclohexyl-B diethylenetriaminepentaacetic acid (DTPA) or CHX-A" DTPA by direct conjugation or with a hydroxylamine derivative of 1B4M-DTPA (2-(p[O-(carboxamylmethyl)hydroxylamine]benzyl)-6-methyl-diethylenetriamine-N,N,N',N",N"-pentaacetic acid ) coupled at the N terminus. The primary molecular species in the conjugated products were shown by mass spectrometry to have one DTPA per peptide. Peptide chelate conjugates were radiolabeled with Bi-213 and the products tested for biodistribution in tumor bearing mice. The data show that chelation of Bi-213 to peptides was accomplished by both the direct method of DTPA attachment and by the method using the linker at the N-terminus, Only small amounts of peptide accumulated at tumor sites. We conclude that phage display is a powerful tool to select peptides with restricted binding specificity; however, the peptides isolated to date do not bind with high retention to tumor sites in vivo. NUCL IVIED BIOL 27;8: 815-825, 2000. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN 37831 USA. Oak Ridge Natl Lab, Div Chem & Analyt Sci, Oak Ridge, TN 37831 USA. NCI, Chem Sect, ROB, DCS,NIH, Bethesda, MD USA. Univ Alabama, Dept Radiat Oncol, Birmingham, AL USA. RP Kennel, SJ (reprint author), Oak Ridge Natl Lab, Div Life Sci, Bldg 4500S,Rm F150, Oak Ridge, TN 37831 USA. NR 46 TC 24 Z9 27 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD NOV PY 2000 VL 27 IS 8 BP 815 EP 825 DI 10.1016/S0969-8051(00)00149-9 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 392VQ UT WOS:000166433600018 PM 11150716 ER PT J AU Yusufzai, TM Wolffe, AP AF Yusufzai, TM Wolffe, AP TI Functional consequences of Rett syndrome mutations on human MeCP2 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CPG-BINDING PROTEIN-2; METHYLATED DNA; HISTONE DEACETYLASE; CHROMOSOMAL PROTEIN; CHROMATIN STRUCTURE; TRANSCRIPTION; GENE; REPRESSION; DOMAIN; COMPLEX AB The neurodevelopmental disorder known as Rett syndrome has recently been linked to the methyl-CpG- binding transcriptional repressor, MeCP2. In this report we examine the consequences of these mutations on the function of MeCP2. The ability to bind specifically to methylated DNA and the transcription repression capabilities are tested, as well as the stability of proteins in vivo. We find that all missense mutations (R106W, R133C, F155S, T158M) within the methyl-binding domain impair selectivity for methylated DNA, and that all nonsense mutations (L138X; R168X, E235X, R255X, R270X, V288X, R294X) that-truncate all or some of the transcriptional repression domain (TRD) affect the ability to repress transcription and have decreased levels of stability in vivo. Two missense mutations, one in the TRD (R306C) and one in the C-terminus (E397K), had no noticeable effects on MeCP2 function. Together, these results provide evidence of how Rett syndrome mutations can affect distinct functions of MeCP2 and give insight into these mutations that may contribute to the disease. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Sangamo Biosci Inc, Point Richmond Tech Ctr, Richmond, CA 94804 USA. RP Yusufzai, TM (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. NR 28 TC 83 Z9 85 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 1 PY 2000 VL 28 IS 21 BP 4172 EP 4179 DI 10.1093/nar/28.21.4172 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 372ZL UT WOS:000165263900017 PM 11058114 ER PT J AU Knebel, AR Bentz, E Barnes, P AF Knebel, AR Bentz, E Barnes, P TI Dyspnea management in alpha-1 antitrypsin deficiency: Effect of oxygen administration SO NURSING RESEARCH LA English DT Article DE dyspnea; oxygen inhalation therapy; emphysema ID OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW LIMITATION; QUALITY-OF-LIFE; ALPHA-1-ANTITRYPSIN DEFICIENCY; CHRONIC-BRONCHITIS; EXERCISE ABILITY; WALKING TEST; BREATHLESSNESS; PERFORMANCE; DISABILITY AB Background: A deficiency of alpha-1 antitrypsin (AAT) can lead to pulmonary disease in middle-aged adults in whom dyspnea management can be a significant issue. Objective: The research addressed whether short-term oxygen (O-2) administration during activities might decrease dyspnea and improve exercise performance in nonhypoxemic patients with emphysema caused by a deficiency of alpha-1 antitrypsin. Method: This was a double-blind, randomized crossover study of 31 subjects with a deficiency of AAT (mean +/- SD, age = 47 +/- 7), moderate emphysema and a resting PaO2 > 70 mm Hg. Oxygen saturation (SpO(2)), 6-minute walk distance, and end of walk dyspnea were measured during three practice walks and during walks with nasal cannula administration of O-2 (intervention) and compressed air (control). Results: Repeated measures analysis of variance (ANOVA) showed significant differences across the walks for SpO(2) (F = 18.9, p = 0.0001), B-minute walk distance (F = 6.07, p = 0.004), and dyspnea (F = 4.44, p = 0.016). Using post hoc contrasts, SpO(2) was the only variable that differed between O-2 and compressed air (p < 0.0001). There was, however. an interaction effect of gender with O-2 for dyspnea (F = 9.85, p = 0.004). Mean values showed that men did not benefit from O-2 (p = 0.87). However, women experienced less dyspnea when receiving O-2 as compared with compressed air (p = 0.0025), and although not statistically significant, the lower dyspnea with O-2 corresponded with an increased walk distance of 79 feet.) Conclusions: O-2 administration may be useful for reducing dyspnea during exercise in selected populations. C1 NINR, NIH, Bethesda, MD 20892 USA. Allegheny Univ, Meadville, PA USA. NHLBI, Clin Ctr, Nursing Dept, Pulm Crit Care Branch,NIH, Bethesda, MD 20892 USA. RP Knebel, AR (reprint author), NINR, NIH, Bldg 31,Rm 5B10,31 Ctr Dr MSC 2178, Bethesda, MD 20892 USA. NR 32 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD NOV-DEC PY 2000 VL 49 IS 6 BP 333 EP 338 DI 10.1097/00006199-200011000-00007 PG 6 WC Nursing SC Nursing GA 453LT UT WOS:000169917900006 PM 11093698 ER PT J AU Weyer, C Pratley, RE Lindsay, RS Tataranni, PA AF Weyer, C Pratley, RE Lindsay, RS Tataranni, PA TI Relationship between birth weight and body composition, energy metabolism, and sympathetic nervous system activity later in life SO OBESITY RESEARCH LA English DT Article DE intrauterine programming; obesity; energy expenditure; autonomic nervous system; Pima Indians ID GLUCOSE-TOLERANCE; ADULT HYPERTENSION; INSULIN-RESISTANCE; FUEL UTILIZATION; INFANT GROWTH; FETAL GROWTH; OBESITY; WOMEN; GAIN; EXPENDITURE AB Objective: Epidemiological studies suggest that high birth weight might be associated with an increased risk of obesity later in life. Programming of metabolic, endocrine, and/or autonomic pathways during intrauterine development has been proposed to explain this association. Research Methods and Procedures: To determine the relationship between birth weight and body composition and energy metabolism later in life, we measured fat mass and fat-free mass (hydrodensitometry or double-energy X-ray absorptiometry), 24-hour energy expenditure, sleeping metabolic rate, and 24-hour respiratory quotient (respiratory chamber) in 272 adult nondiabetic Pima Indians (161 males/ III females, age 25 +/- 5 years, mean +/- SD). In these subjects, birth weight varied over a wide range (2000 to 5000 g). Individuals known to be offspring of diabetic pregnancies were excluded. In 44 of the 272 subjects, muscle sympathetic nerve activity was assessed by microneurography. Results: Birth weight was positively correlated with adult height (r = 0.20, p < 0.001) and fat-free mass (r = 0.21, p < 0.001), but not with fat mass (r = 0.01, not significant). Sleeping metabolic rate, adjusted for age, sex, fat-free mass, and fat mass, was negatively related to birth weight (r -0.13, p < 0.05), whereas adjusted 24-hour energy expenditure (r = 0.07, not significant) and 24-hour respiratory quotient (r = -0.09, not significant) were not. There was no relationship between birth weight and muscle sympathetic nerve activity (r = 0.12, not significant, n = 44). Discussion: In Pima Indians who are not offspring of diabetic pregnancies, high birth weight is associated with increased height and lean body mass, but not with increased adiposity later in life. Although high birth weight may be associated with relatively low resting energy expenditure, it is not associated with major abnormalities in 24-hour energy metabolism or with low muscle sympathetic nerve activity later in life. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Weyer, C (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Room 5-41, Phoenix, AZ 85016 USA. NR 43 TC 40 Z9 40 U1 0 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD NOV PY 2000 VL 8 IS 8 BP 559 EP 565 DI 10.1038/oby.2000.72 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 385TJ UT WOS:000166019500003 PM 11156431 ER PT J AU Troisi, RJ Cowie, CC Harris, MI AF Troisi, RJ Cowie, CC Harris, MI TI Hormone replacement therapy and glucose metabolism SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID DEPENDENT DIABETES-MELLITUS; POSTMENOPAUSAL WOMEN; ESTROGEN REPLACEMENT; CARBOHYDRATE-METABOLISM; INSULIN-RESISTANCE; RISK; LIPIDS AB Objective: To determine whether hormone replacement therapy (HRT) alters glucose metabolism. Methods: Cross-sectional data from the third National Health and Nutrition Examination Survey (1988-1994) included levels of hemoglobin A(1c) in women with diagnosed diabetes and levels of hemoglobin A(1c) fasting and 2-hour glucose, and fasting insulin and C-peptide in women without diagnosed diabetes. We compared mean values for these measures among never, current, and past users of HRT with adjustment for confounders. Types of hormones were not studied. Results: Hormone replacement therapy was used by 8.6% of diabetic women and 16.7% of women without diagnosed diabetes; 19.3% and 18.5%, respectively, had used HRT in the past. Current use approximately doubled among diabetic women between 1988-1991 and 1991-1994. Current users had lower hemoglobin A(1c) and fasting plasma glucose levels but higher 2-hour glucose levels compared with never and past users. After adjustment for confounding factors, hemoglobin A(1c) levels were 0.1% lower, fasting glucose levels were 3 mg/dL lower, and 2-hour glucose levels were 15 mg/dL higher in current users. Pasting serum insulin and C-peptide levels were not associated with HRT use. Duration of HRT use among current users and time since cessation among former users were not associated with measures of glucose metabolism. Conclusion: The prevalence of HRT in the United States among diabetic women is approximately half that of women without diabetes diagnoses, although it appears to be increasing. Postmenopausal hormones appear to have no adverse effect on basal glucose metabolism but are associated with slightly elevated postchallenge glucose levels. (Obstet Gynecol 2000;96:665-70. (C) 2000 by The American College of Obstetricians and Gynecologists). C1 NIDDKD, Natl Diabet Data Grp, NIH, Bethesda, MD 20892 USA. Social & Sci Syst Inc, Bethesda, MD USA. RP Harris, MI (reprint author), NIDDKD, Natl Diabet Data Grp, NIH, 6707 Democracy Blvd,Room 695,MSC-5460, Bethesda, MD 20892 USA. NR 19 TC 10 Z9 10 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2000 VL 96 IS 5 BP 665 EP 670 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 367WK UT WOS:000090084300006 ER PT J AU Tewari, KS AF Tewari, KS TI The adventure of the three abnormal paps SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 Univ Calif Irvine, Med Ctr, Dept Obstet & Gynecol,Div Gynecol Oncol, NCI,Designated Chao Family Comprehens Canc Ctr, Orange, CA 92868 USA. RP Tewari, KS (reprint author), Univ Calif Irvine, Med Ctr, Dept Obstet & Gynecol,Div Gynecol Oncol, NCI,Designated Chao Family Comprehens Canc Ctr, 101 City Dr, Orange, CA 92868 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2000 VL 96 IS 5 BP 795 EP 798 DI 10.1016/S0029-7844(00)01011-5 PN 1 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 367WK UT WOS:000090084300031 PM 11042321 ER PT J AU Papageorgiou, T Hearns-Stokes, R Peppas, D Segars, JH AF Papageorgiou, T Hearns-Stokes, R Peppas, D Segars, JH TI Clitoroplasty with preservation of neurovascular pedicles SO OBSTETRICS AND GYNECOLOGY LA English DT Article AB Background: Optimal sexual function after surgical correction of clitoral hypertrophy requires an adequate postoperative innervation and vascular supply to the glans clitoris. Several clitoroplasty methods have been reported, but few describe preservation of dorsal and ventral neurovascular bundles in sexually mature women. Case: A aa-year-old woman with clitoromegaly caused by non-salt-wasting classic 21-hydroxylase deficiency presented for a second surgical procedure after an operation in her infancy. The erect clitoral length exceeded 7.5 cm. Clitoral reduction was done through a semicircular incision in the phallus, with preservation of dorsal and ventral neurovascular pedicles. Conclusion: preservation of ventral and dorsal vascular pedicles at clitoroplasty had a satisfactory result in sexually mature women. (Obstet Gynecol 2000;96:821-3.). C1 NICHHD, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Dept Surg, Div Urol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. RP Segars, JH (reprint author), NICHHD, 6705 Rockledge Dr,Suite 800, Bethesda, MD 20892 USA. NR 8 TC 11 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2000 VL 96 IS 5 SU S BP 821 EP 823 DI 10.1016/S0029-7844(00)01031-0 PN 2 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 368QX UT WOS:000090130000010 PM 11094221 ER PT J AU Wynn, TA Hoffmann, KF AF Wynn, TA Hoffmann, KF TI Defining a schistosomiasis vaccination strategy - Is really Th1 versus Th2? SO PARASITOLOGY TODAY LA English DT Article ID PROTECTIVE IMMUNITY; MANSONI CERCARIAE; MICE; IGE; INFECTION; EOSINOPHILS; RESISTANCE; RESPONSES; ANTIBODY; IL-12 AB Successful vaccine development for schistosomiasis has been hindered by a lack of consensus on the type of immune response that would provide maximum levels of protective immunity and incomplete knowledge of the key antiparasite effector mechanisms. Many vaccine studies conducted in mice support type-1-cytokine-mediated effector mechanisms, while acquired resistance in humans correlates with type-2-cytokine-mediated responses. However, recent data from cytokine-knockout mice suggest that choosing between these opposing pathways may be less important than previously hypothesized, as discussed here by Thomas Wynn and Karl Hoffmann. C1 NIAID, Schistosomiasis Immunol & Pathol Unit, Immunobiol Sect, Lab Parasit Dis,NIH, Bethesda, MD 20892 USA. RP Wynn, TA (reprint author), NIAID, Schistosomiasis Immunol & Pathol Unit, Immunobiol Sect, Lab Parasit Dis,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 43 TC 47 Z9 51 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD NOV PY 2000 VL 16 IS 11 BP 497 EP 501 DI 10.1016/S0169-4758(00)01788-9 PG 5 WC Parasitology SC Parasitology GA 369RH UT WOS:000165080400011 PM 11063861 ER PT J AU Bornschein, RL Chisolm, JJ Damokosh, AI Dockery, DW Fay, ME Jones, RL Rhoads, GG Ragan, NB Rogan, WJ Salganik, M Schwarz, DF Ware, JH Wedeen, RP Serwint, J Brophy, M Davoli, CT Denckla, MB Farfel, MR Goldstein, GW Rubin, J Berger, O Dietrich, KN Wesolowski, C Wilkins, S Maynard-Wentzel, G Mortensen, ME Adubato, S El-safty, M Heenehan, M Sheffet, A Ty, A Campbell, C Gill, FM Guinn, J Henretig, F Knight, D Radcliffe, J Schwarz, DF Bowman, BB Gunter, E Huff, D Jones, RL Miller, DT Paschal, DC Bernstein, AJ Kotlov, TV Salganik, M Angle, CR Faison, J Gehlbach, SH Gray-Little, B James, SA Moye, LA Needleman, HL AF Bornschein, RL Chisolm, JJ Damokosh, AI Dockery, DW Fay, ME Jones, RL Rhoads, GG Ragan, NB Rogan, WJ Salganik, M Schwarz, DF Ware, JH Wedeen, RP Serwint, J Brophy, M Davoli, CT Denckla, MB Farfel, MR Goldstein, GW Rubin, J Berger, O Dietrich, KN Wesolowski, C Wilkins, S Maynard-Wentzel, G Mortensen, ME Adubato, S El-safty, M Heenehan, M Sheffet, A Ty, A Campbell, C Gill, FM Guinn, J Henretig, F Knight, D Radcliffe, J Schwarz, DF Bowman, BB Gunter, E Huff, D Jones, RL Miller, DT Paschal, DC Bernstein, AJ Kotlov, TV Salganik, M Angle, CR Faison, J Gehlbach, SH Gray-Little, B James, SA Moye, LA Needleman, HL CA Treatment Lead Exposed Children TL TI Safety and efficacy of succimer in toddlers with blood lead levels of 20-44 mu g/dL SO PEDIATRIC RESEARCH LA English DT Article ID CINCINNATI LEAD; EXPOSURE; CHILDREN; COHORT; INTELLIGENCE; AGE AB Although lead encephalopathy has virtually disappeared from the United States, thousands of children still have sufficient lead exposure to produce cognitive impairment. It is not known whether treating children with blood lead levels < 45 g/dL (2.2 muM) is beneficial and can be done with acceptable safety. We conducted a 780-child, placebo-controlled, randomized trial of up to three courses of succimer in children with blood lead levels of 20-44 mug/dL (1.0-2.1 muM). Children were aged 12-33 mo, 77% were African-American, 7% were Hispanic, and they Lived in deteriorating inner city housing. Placebo-treated children had a gradual decrease in blood lead level. Succimer-treated children had an abrupt drop in blood lead level, followed by rebound. The mean blood lead level of the succimer-treated children during the 6 mo after initiation of treatment was 4.5 mug/dL (95% confidence intervals, 3.7 to 5.3 mug/dL; 0.22 muM, 0.18 to 0.26 muM) lower than that of placebo-treated children. There were more scalp rashes in succimer-treated children (3.5% versus 1.3%) and an unanticipated excess of trauma. Succimer lowers blood lead level with few side effects. The unanticipated excess of trauma requires confirmation. C1 TLC Clin Ctr, Baltimore, MD USA. Johns Hopkins Hosp, TLC Clin Ctr, Baltimore, MD 21287 USA. Kennedy Krieger Inst, TLC Clin Ctr, Baltimore, MD 21205 USA. Univ Maryland, TLC Clin Ctr, College Pk, MD 20742 USA. TLC Clin Ctr, Cincinnati, OH USA. TLC Clin Ctr, Columbus, OH USA. Univ Cincinnati, Med Ctr, TLC Clin Ctr, Cincinnati, OH 45221 USA. Childrens Hosp Columbus, TLC Clin Ctr, Columbus, OH 43205 USA. TLC Clin Ctr, Newark, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, TLC Clin Ctr, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, TLC Clin Ctr, Newark, NJ 07103 USA. TLC Clin Ctr, Philadelphia, PA USA. Childrens Hosp Philadelphia, Joseph Stokes Jr Res Inst, TLC Clin Ctr, Philadelphia, PA 19104 USA. CDC, Nutr Biochem Branch, TLC Clin Ctr, Atlanta, GA 30333 USA. Harvard Univ, Sch Publ Hlth, TLC Clin Ctr, Cambridge, MA 02138 USA. NIEHS, Project Off, TLC Clin Ctr, Res Triangle Pk, NC 27709 USA. RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 18 TC 26 Z9 28 U1 0 U2 2 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 NOV PY 2000 VL 48 IS 5 BP 593 EP 599 PG 7 WC Pediatrics SC Pediatrics GA 367CV UT WOS:000090044900007 ER PT J AU Balboni, G Salvadori, S Guerrini, R Bianchi, C Santagada, V Calliendo, G Bryant, SD Lazarus, LH AF Balboni, G Salvadori, S Guerrini, R Bianchi, C Santagada, V Calliendo, G Bryant, SD Lazarus, LH TI Opioid pseudopeptides containing heteroaromatic or heteroaliphatic nuclei SO PEPTIDES LA English DT Article DE agonism; antagonism; Dmt; Dmt-Tic pharmacophore; opioid peptides; peptide synthesis; pharmacological bioassays; receptor affinities ID HIGH-AFFINITY; RECEPTOR SELECTIVITY; PEPTIDE ANTAGONISTS; ANALOGS; DESIGN; DERMORPHIN; MU; PHARMACOPHORE; DELTORPHINS; POTENT AB In lieu of H-Dmt-Tic-OH, H-Dmt-analogues included 2-amino-3(1H-benzoimidazol-2-yl)-propionic acid, N(Bzl)Gly, L-octahydroindole-2-carboxylic acid, [3S-(3 alpha ,4a beta ,8a beta)]-decahydro-3-isoquinoline carboxylic acid, benzimidazole-, pyridoindole- or spiroinden-derivatives, or C-terminally modified. L- or D-Ala, Sar, or Pro were spacers between aromatic nuclei. Only H-Dmt-(Xaa-)-pyridoindole exhibited high affinities with delta and mu antagonism. The peptides competed equally against [H-3]DPDPE (delta agonist) or [H-3]N,N(CH3)(2)-Dmt-Tic-OH (delta antagonist) signaling a single delta binding site. The data confirm the importance of Tic for delta affinity and antagonism, while heterocyclic or heteroaliphatic nuclei, or spacer exert effects on mu- and delta -receptor properties. (C) 2000 Published by Elsevier Science Inc. C1 NIEHS, LCBRA, Res Triangle Pk, NC 27707 USA. Univ Cagliari, Dept Toxicol, I-09126 Cagliari, Italy. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. Univ Ferrara, Inst Pharmacol, I-44100 Ferrara, Italy. Univ Naples, Dept Med Chem & Toxicol, I-80134 Naples, Italy. RP Lazarus, LH (reprint author), NIEHS, LCBRA, Res Triangle Pk, NC 27707 USA. OI Guerrini, Remo/0000-0002-7619-0918; SALVADORI, Severo/0000-0002-8224-2358 NR 46 TC 18 Z9 19 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV PY 2000 VL 21 IS 11 BP 1663 EP 1671 DI 10.1016/S0196-9781(00)00315-6 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 379UK UT WOS:000165660800010 PM 11090920 ER PT J AU Wellner, RB Hoque, ATMS Goldsmith, CM Baum, BJ AF Wellner, RB Hoque, ATMS Goldsmith, CM Baum, BJ TI Evidence that aquaporin-8 is located in the basolateral membrane of rat submandibular gland acinar cells SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE aquaporin; confocal microscopy; immunofluorescence; salivary glands; salivary secretion ID WATER CHANNEL PROTEIN; MOLECULAR-CLONING; LACRIMAL GLANDS; PLASMA-MEMBRANE; SALIVARY-GLANDS; FLUID SECRETION; IMMUNOLOCALIZATION; TRANSLOCATION; TRAFFICKING; EXPRESSION AB It is possible that, during primary saliva formation, aquaporins (AQPs) facilitate transcellular water flow across acinar cells to the lumina of salivary glands. In the rat submandibular gland (rSMG) AQP5 is localized in the apical membranes of acinar cells. The pres ence of a basolateral AQP in the same cell type has not been reported. We have therefore used immunofluorescence confocal microscopy to determine the subcellular localization of a newly discovered aquaporin, AQP8, in rSMG epithelial cells. The antibodies we used were made against the amino- or carboxyl-terminus (anti-rAQP8(NT) and anti-rAQP8(CT), respectively) of an AQP8 cloned from rat pancreas and liver (rAQP8). Two lines of evidence suggest that both antibodies are suitable for immunolocalization studies. First, results of immunofluorescence confocal microscopy studies show that both antibodies bind to the plasma membranes of 293 cells infected with an adenovirus encoding rAQP8. Second, results of immunoblots of membranes from infected cells suggest that both antibodies bind to glycosylated and non-glycosylated forms of rAQP8. When tested in frozen sections of rSMG, we could not detect the binding of anti-rAQP8(NT) to any membranes. In contrast, anti-rAQP8(NT) binds to the basolateral membranes of acinar (but not ductal) epithelia, suggesting that rAQP8 resides in the basolateral membranes of acinar cells. Lack of anti-rAQP(NT) binding to basolateral membranes suggests that this epitope is not available in the membranes. Our evidence for the basolateral localization of rAQP8 in acinar cells, coupled with previous findings that AQP5 is localized apically in the same cells, raises the possibility that water crosses the acinar epithelium through these channels during primary saliva formation. C1 Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. RP Wellner, RB (reprint author), Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. NR 30 TC 28 Z9 30 U1 1 U2 1 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 NOV PY 2000 VL 441 IS 1 BP 49 EP 56 DI 10.1007/s004240000396 PG 8 WC Physiology SC Physiology GA 378XW UT WOS:000165611500006 PM 11205061 ER PT J AU Aitchison, KJ Gonzalez, FJ Quattrochi, LC Sapone, A Zhao, JH Zaher, H Elizondo, G Bryant, C Munro, J Collier, DA Makoff, AJ Kerwin, RW AF Aitchison, KJ Gonzalez, FJ Quattrochi, LC Sapone, A Zhao, JH Zaher, H Elizondo, G Bryant, C Munro, J Collier, DA Makoff, AJ Kerwin, RW TI Identification of novel polymorphisms in the 5 ' flanking region of CYP1A2, characterization of interethnic variability, and investigation of their functional significance SO PHARMACOGENETICS LA English DT Article DE cytochrome P450; CYP1A2; promoter; pharmacogenetics; genotype ID ARYL-HYDROCARBON RECEPTOR; CYTOCHROME-P450 ENZYMES; HETEROCYCLIC AMINES; 5'-FLANKING REGION; METABOLITE RATIOS; XANTHINE-OXIDASE; CAFFEINE; GENE; 3-METHYLCHOLANTHRENE; PHENOTYPES AB CYP1A2 activity has been demonstrated to be bimodally or trimodally distributed in several populations, consistent with a codominant or recessive functional genetic polymorphism. However, studies aimed at identifying polymorphisms in CYP1A2 have not yet adequately accounted for this distribution pattern. To search for functional polymorphisms, we performed genome-walking, polymerase chain reaction (PCR) sequencing, and cloning, and identified three novel polymorphisms in the 5' flanking region of CYP1A2: a T(-3591)G substitution, a G(-3595)T substitution, and a T-3605 insertion. The frequency of the T-3591G substitution was determined by a PCR-restriction fragment length polymorphism assay, and found to be significantly higher (P < 0.0001) in Taiwanese (allele frequency 0.128, n = 125) compared to Caucasians (0.017, n = 87) or African Americans (0.024, n = 104). The functional consequence of the T(-3591)G and the G(-3595)T substitutions was determined by site-directed mutagenesis followed by transient transfection experiments. The T(-3591)G mutation was shown to be nonfunctional, while although the G(-3595)T mutation appeared to result in an increase in promoter activity, this was only to a small degree and therefore unlikely to be important in vivo. In addition, we report 532 bases of 5' flanking sequence further upstream than that reported to date, and four sequence discrepancies compared to the original published sequence (G(-3649)C, T-3650, DeltaA(-4072), and C-4093 ins). Pharmacogenetics 10:695-704 (C) 2000 Lippincott Williams & Wilkins. C1 Inst Psychiat, Sect Biostat & Genet Epidemiol, London SE5 8AF, England. NCI, Met Lab, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Kings Coll London, Sch Med & Dent, Clin Age Res Unit, London, England. RP Aitchison, KJ (reprint author), Inst Psychiat, Sect Biostat & Genet Epidemiol, 1 Windsor Walk,Denmark Hill, London SE5 8AF, England. EM sphakja@iop.kcl.ac.uk RI Sapone, Andrea/E-6704-2013; Aitchison, Katherine/G-4476-2013; OI Aitchison, Katherine/0000-0002-1107-3024; Sapone, Andrea/0000-0001-8496-6977 FU NCI NIH HHS [CA46934]; NIGMS NIH HHS [GM54477] NR 53 TC 25 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD NOV PY 2000 VL 10 IS 8 BP 695 EP 704 DI 10.1097/00008571-200011000-00004 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 385JX UT WOS:000166001600004 PM 11186132 ER PT J AU Jun, JH Schindler, CW AF Jun, JH Schindler, CW TI Dextromethorphan alters methamphetamine self-administration in the rat SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE dextromethorphan; methamphetamine; self-administration; food control; NMDA antagonist; rat ID EXTRACELLULAR DOPAMINE; NUCLEUS-ACCUMBENS; BEHAVIORAL SENSITIZATION; INTRAVENOUS COCAINE; MORPHINE-TOLERANCE; NMDA RECEPTORS; TIME COURSE; AMPHETAMINE; COMBINATION; DEPENDENCE AB Various lines of evidence indicate that methamphetamine (METH) self-administration in rats is under dopaminergic control, and NMDA receptors have been shown to control the release of dopamine at its synapse. Consequently, the aim of this study was to observe the effects of dextromethorphan (DM), a non-competitive NMDA antagonist, in rats self-administering METH. The hypothesis was that acute pretreatment of DM (25 mg/kg) would alter response to METH. DM significantly altered self-administration by reducing the number of correct responses for three METH self-administration doses (0.05, 0.1, 0.25 mg/kg). The same pretreatment did not affect responding for food reward. These findings show that the DM was able to selectively alter METH self-administration. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Schindler, CW (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 27 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD NOV PY 2000 VL 67 IS 3 BP 405 EP 409 DI 10.1016/S0091-3057(00)00317-8 PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 388DX UT WOS:000166163100002 PM 11164066 ER PT J AU Castanon, N Scearce-Levie, K Lucas, JJ Rocha, B Hen, R AF Castanon, N Scearce-Levie, K Lucas, JJ Rocha, B Hen, R TI Modulation of the effects of cocaine by 5-HT1B receptors: a comparison of knockouts and antagonists SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE 5-HT1B receptors; cocaine; GR127935; locomotor activity; behavioral sensitization; c-fos induction; C57B1/6J mice; 129/Sv mice ID STRIATAL DOPAMINE RELEASE; VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; MICE LACKING; SEROTONIN; RATS; STIMULATION; AGONIST; ACTIVATION; REINFORCEMENT AB Serotonergic transmission has been suggested to modulate the effects of cocaine. However, the specific receptors underlying this phenomenon have not been identified. To evaluate the role of the 5-HT1B receptor in mediating the actions of cocaine, we used two model systems: knockout (KO) mice lacking the 5-HT1B receptor and an acute treatment with the 5-HT1B/1D antagonist GR127935. GR127935 attenuated the ability of cocaine to stimulate locomotion and induce c-fos expression in the striatum. However, GR127935 had no apparent effect on the rewarding or sensitizing effects of cocaine. In contrast, as demonstrated previously, the 5-HT1B receptor KO mice showed a heightened locomotor response to cocaine, as well as an increased propensity to self-administer cocaine, Thus, an acute pharmacological blockade of the 5-HT1B receptor decreases some effects of cocaine, while a constitutive genetic KO of the same receptor has opposite effects. These results suggest that compensatory changes have taken place during the development of the 5-HT1B KO mice, which may have rendered these mice more vulnerable to cocaine. The 5-HT1B KO mice should therefore be considered as a genetic model of vulnerability to drug abuse rather than a classic pharmacological tool. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. NIDA, IRP, Baltimore, MD 21224 USA. Univ Autonoma Madrid, CSIC, CBMSO, E-28049 Madrid, Spain. Gladstone Inst, San Francisco, CA 94131 USA. Inst Francis Magendie, INSERM, U394, F-33077 Bordeaux, France. RP Hen, R (reprint author), Columbia Univ, Ctr Neurobiol & Behav, 722 W 168th St, New York, NY 10032 USA. OI Lucas, Jose J./0000-0003-1597-3916 FU NIDA NIH HHS [DA09862] NR 46 TC 67 Z9 67 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD NOV PY 2000 VL 67 IS 3 BP 559 EP 566 DI 10.1016/S0091-3057(00)00389-0 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 388DX UT WOS:000166163100022 PM 11164086 ER PT J AU Kapasi, ZF Catlin, PA Joyner, DR Lewis, ML Schwartz, AL Townsend, EL AF Kapasi, ZF Catlin, PA Joyner, DR Lewis, ML Schwartz, AL Townsend, EL TI The effects of intense physical exercise on secondary antibody response in young and old mice SO PHYSICAL THERAPY LA English DT Article DE intense exercise training; old mice; secondary antibody response ID BETA-ENDORPHIN; IMMUNE-RESPONSE; SYSTEM; CELLS; LYMPHOCYTES; ENKEPHALIN; HORMONES AB Background and Purpose. Based largely on data from young subjects, intense physical exercise is believed to suppress immune function. In addition, immune function, including secondary antibody response, declines with advancing age. Therefore, intense exercise in old subjects may further suppress the secondary antibody response. The purpose of this in vivo study was to investigate the effects of intense physical exercise on secondary antibody response in young (6-8 weeks) and old (22-24 months) C57BL/6 mice. Subjects and Methods. Data were obtained from 22 young and 18 old C57BL/6 mice that were immunized to human serum albumin (HSA) and randomly divided into 3 groups. Two groups were exposed to a single bout of Intense exercise to exhaustion and immediately boosted with an injection of HSA. The first group did not exercise further, but the second group continued with daily bouts of intense exercise to exhaustion for 9 days. The third group (control group) did:not undergo intense exercise, but received the booster injection of HSA at the same time as the other groups. Ten days after the HSA booster injection, when high level of antibodies are produced in secondary antibody response, serum anti-HSA antibodies were measured by enzyme-linked immunosorbent assay. Results. Young mice did not show suppression of secondary antibody response following intense exercise. However, old mice, exposed to a single bout of intense exercise, had an enhanced response similar to the response seen in young control mice. Conclusion and Discussion. The widely accepted hypothesis of immunosuppression resulting from intense exercise may not be true for old mice. C1 Emory Univ, Sch Med, Dept Rehabil Med, Div Phys Therapy, Atlanta, GA 30322 USA. Tooele Valley Healthcare Syst, Tooele, UT USA. Washington Hosp Ctr, Washington, DC 20010 USA. Emory Univ Hosp, Ctr Rehabil Med, Atlanta, GA USA. Univ Virginia, NICHD, Study Early Child Care & Youth D, Charlottesville, VA USA. RP Kapasi, ZF (reprint author), Emory Univ, Sch Med, Dept Rehabil Med, Div Phys Therapy, 1441 Clifton Rd NE, Atlanta, GA 30322 USA. NR 33 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD NOV PY 2000 VL 80 IS 11 BP 1076 EP 1086 PG 11 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 369DP UT WOS:000165051000002 PM 11046195 ER PT J AU Lane, DS Zapka, J Breen, N Messina, CR Fotheringham, DJ AF Lane, DS Zapka, J Breen, N Messina, CR Fotheringham, DJ CA NCI Breast Canc Screening Consorti TI A systems model of clinical preventive care: The case of breast cancer screening among older women SO PREVENTIVE MEDICINE LA English DT Article DE mammography; utilization; health service accessibility; socioeconomic factors; physician's practice patterns; physicians; aged ID LOW-INCOME WOMEN; FEE-FOR-SERVICE; MAMMOGRAPHY USE; HEALTH MAINTENANCE; CONTROLLED TRIAL; UNITED-STATES; MEDICAL-CARE; SELF-REPORTS; PHYSICIAN; COVERAGE AB Background. In older women covered by Medicare, relationships among physician recommendation, mammography in the past 2 years, and clinical breast examination (CBE) in the past year were systematically explored with a variety of predisposing, enabling, and situational factors identified in the Systems Model of Clinical Preventive Care. Methods. A population-based survey of women age 65 years and older was conducted in five National Cancer Institute's Breast Cancer Screening Consortium geographic areas. Analyses focused on women with a regular physician and site of care (n = 5318), Results. Physician recommendation and mammography use declined with women's increasing age and increased with income, education, and insurance. CBE and mammography increased with number of physicians and breast cancer family history; mammography use decreased with worsening health status, Recommendations were higher among physicians who were younger, female, and internists, Family practitioners were older and male; women who saw family practitioners reported characteristics associated with decreased screening-lower income, education, and insurance-and seeing only one physician, Conclusions, Public policy and health system changes that create a uniform system of finance and service performance expectations may reduce the persistent discrepancy in physician recommendation and mammography use due to sociodemographics and physician specialty. (C) 2000 American Health Foundation and Academic Press. C1 SUNY Stony Brook, Sch Med, Dept Prevent Med, Stony Brook, NY 11794 USA. Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Worcester, MA 01655 USA. NCI, Bethesda, MD 20892 USA. Informat Mangement Serv Inc, Silver Spring, MD 20904 USA. RP Lane, DS (reprint author), SUNY Stony Brook, Sch Med, Dept Prevent Med, Stony Brook, NY 11794 USA. FU NCI NIH HHS [CA44990, N01-CN-85122-01, CA45003] NR 65 TC 40 Z9 40 U1 4 U2 6 PU ACADEMIC PRESS INC 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 NOV PY 2000 VL 31 IS 5 BP 481 EP 493 DI 10.1006/pmed.2000.0747 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 372GH UT WOS:000165225600005 PM 11071828 ER PT J AU Simons-Morton, DG Hogan, P Dunn, AL Pruitt, L King, AC Levine, BD Miller, ST AF Simons-Morton, DG Hogan, P Dunn, AL Pruitt, L King, AC Levine, BD Miller, ST TI Characteristics of inactive primary care patients: Baseline data from the activity counseling trial SO PREVENTIVE MEDICINE LA English DT Article DE physical activity; exercise; patient education; health behavior ID AMERICAN-HEART-ASSOCIATION; PHYSICAL-ACTIVITY PROGRAMS; CARDIAC REHABILITATION; HEALTH-PROFESSIONALS; CLINICAL CARDIOLOGY; UNITED-STATES; EXERCISE; PREVENTION; PROMOTION; PROJECT AB Background. Although many primary care patients are inactive, being able to classify even small amounts and intensities of activity and factors associated with these activity levels could be helpful for physicians who are trying to motivate their patients to become more physically active. Methods. Sociodemographics, physical activity, fitness, other cardiovascular risk factors, and psychosocial measures were measured at baseline in the 874 patients in the Activity Counseling Trial. Patients were categorized into three groups: (1) no moderate-to-vigorous physical activity (MVPA), (2) some moderate but no vigorous activity, and (3) some vigorous activity. Multiple logistic regression was used to determine factors cross-sectionally associated with activity intensity, Results. One or more cardiovascular risk factors in addition to physical inactivity were present in 84% of participants. Maximal oxygen uptake averaged 25.2 ml/kg/min 85% had poor to fair aerobic fitness. Physical activity averaged 32.7 kcal/kg/day, with 13.5 min of MVPA/day; 26% engaged in some vigorous activity, 11% engaged in no MVPA, In unadjusted analyses, gender, age, race, education, income, employment, smoking, alcohol use, and exercise self-efficacy were associated with activity intensity (P = 0.05-0.001), A greater percentage engaged in moderate than in vigorous activity in all subgroups. In multiple logistic regression analyses, odds ratios (95% confidence intervals) for engaging in vigorous activity were 0.39 (0.28, 0.56) for women, 0.38 (0.19, 0.75) for 65+ compared with 35- to 44-year-olds, and 1.14 (1.06, 1.22) for 10-unit increases in performance self-efficacy score. Conclusions. Most primary care patients who are physically inactive have additional cardiovascular risk factors, particularly overweight and obesity. All subgroups pursue moderate-intensity activity more often than vigorous activity. Women, older persons, and those with lower exercise self-efficacy are less likely to engage in vigorous activity. (C) 2000 American Health Foundation and Academic Press. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27157 USA. Cooper Inst Aerob Res, Dallas, TX 75230 USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Texas, SW Med Ctr, Dallas, TX 75231 USA. Presbyterian Med Ctr, INst Exercise & Environm Med, Dallas, TX 75231 USA. Methodist Hosp, Memphis, TN 38104 USA. RP Simons-Morton, DG (reprint author), NHLBI, Div Epidemiol & Clin Applicat, 6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA. EM simonsd@nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC-45136, N01-HC-45135, N01-HC-45137] NR 47 TC 18 Z9 19 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD NOV PY 2000 VL 31 IS 5 BP 513 EP 521 DI 10.1006/pmed.2000.0733 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 372GH UT WOS:000165225600008 PM 11071831 ER PT J AU Trejnen-Moslen, M West, AB Shipp, BK Atchison, CR Balakumaran, A Hargus, SJ Pohl, R Dalker, DH Aronson, JF Hoffmann, WE AF Trejnen-Moslen, M West, AB Shipp, BK Atchison, CR Balakumaran, A Hargus, SJ Pohl, R Dalker, DH Aronson, JF Hoffmann, WE TI Drug enterocyte abducts: A possible causal factor for diclofenac enteropathy in rats. SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Univ Illinois, Coll Med, Dept Vet Pathobiol, Urbana, IL 61801 USA. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NYU Med Ctr, Dept Pathol, New York, NY 10016 USA. Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77550 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD NOV PY 2000 VL 225 IS 2 BP 167 EP 167 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 368RW UT WOS:000090132200034 ER PT J AU Zimniak, P Singh, SP Nanduri, B Awasthi, YC Xiao, B Ji, XH AF Zimniak, P Singh, SP Nanduri, B Awasthi, YC Xiao, B Ji, XH TI Glutathione transferases and the defense against lipid peroxidation and oxidative stress: Insights into the molecular mechanism of cellular protection. SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NCI, Frederick Canc Res Dev Ctr, Frederick, MD USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. VA Hosp, Little Rock, AR USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD NOV PY 2000 VL 225 IS 2 BP 174 EP 174 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 368RW UT WOS:000090132200064 ER PT J AU Post, RM Speer, AM Weiss, SRB Li, H AF Post, RM Speer, AM Weiss, SRB Li, H TI Seizure models: Anticonvulsant effects of ECT and rTMS SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE anticonvulsant; depression; electroconvulsive therapy; kindling; neuropeptides; neurotrophic factors; positron emission tomography; repetitive transcranial magnetic stimulation; seizure; thyrotropin releasing hormone ID TRANSCRANIAL MAGNETIC STIMULATION; THYROTROPIN-RELEASING-HORMONE; AMYGDALA-KINDLED SEIZURES; AFFECTIVE-ILLNESS; RESISTANT DEPRESSION; MESSENGER-RNA; TOLERANCE; MOOD; CARBAMAZEPINE; EXPRESSION AB 1. A variety of enzymes, peptides, neurotrophic factors and their receptors show complex cascades of alterations with amygdala-kindled seizure progression; some represent compensatory adaptations that could become new targets of therapeutics. 2. Non-convulsant brain stimulation with repetitive transcranial magnetic stimulation (rTMS) may be able to engage some of the neuro-adaptive effects of ECT without the necessity of inducing a seizure. 3. Data from preclinical and clinical studies raise the possibility that non-convulsant stimulation achieved by high or low frequency rTMS may be able to alter neurotransmitters, neuropeptides, and neurotrophic factors, leading to frequency- and region-dependent changes in neural excitability. 4. Individual depressed patients show differential responses to two weeks high vs. low frequency rTMS, as revealed by the inverse correlation of degree of improvement in depression achieved by these two frequencies. 5. Preliminary data from rTMS and positron emission tomography(PET) studies reveal moderately sustained differential effects of rTMS frequency on regional cerebral neural activity in depressed patients. 6. These data suggest the possibility that an individual's level of baseline rCBF or rCMRglu on PET would help predict which rTMS frequency might be the most appropriate treatment for their depression. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, 10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. NR 49 TC 10 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD NOV PY 2000 VL 24 IS 8 BP 1251 EP 1273 DI 10.1016/S0278-5846(00)00138-X PG 23 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 377MN UT WOS:000165517500003 PM 11125852 ER PT J AU Eisenmesser, EZ Kapust, RB Nawrocki, JP Mazzulla, MJ Pannell, LK Waugh, DS Byrd, RA AF Eisenmesser, EZ Kapust, RB Nawrocki, JP Mazzulla, MJ Pannell, LK Waugh, DS Byrd, RA TI Expression, purification, refolding, and characterization of recombinant human interleukin-13: Utilization of intracellular processing SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE fusion protein; interleukin-13; IL-13; maltose-binding protein; refolding; cytokine ID MALTOSE-BINDING PROTEIN; NUCLEAR-MAGNETIC-RESONANCE; ANTIGEN-INDUCED IL-4; ESCHERICHIA-COLI; PSEUDOMONAS EXOTOXIN; BACKBONE DYNAMICS; INCLUSION-BODIES; INTERLEUKIN-4/INTERLEUKIN-13 RECEPTOR; 15-LIPOXYGENASE EXPRESSION; TYROSINE PHOSPHORYLATION AB Interleukin-13 (IL-13) is a pleiotropic cytokine that elicits both proinflammatory and anti-inflammatory immune responses. Recent studies underscore its role in several diseases, including asthma and cancer. Solution studies of IL-13 and its soluble receptors may facilitate the design of antagonists/agonists which would require milligram quantities of specifically labeled protein. A synthetic gene encoding human IL-13 (hIL-13) was inserted into the pMAL-c2 vector with a cleavage site for the tobacco etch virus (TEV) protease. Coexpression of the fusion protein and TEV protease led to in vivo cleavage, resulting in high levels of hIL-13 production. hIL-13, localized to inclusion bodies, was purified and refolded to yield approximately 2 mg per liter of bacteria grown in minimal media. Subsequent biochemical and biophysical analysis of both the unlabeled and N-15-labeled protein revealed a bioactive helical monomer. In addition, the two disulfide bonds were unambiguously demonstrated to be Cys29-Cys57 and Cys45-Cys71 by a combined proteolytic digestion and mass spectrometric analysis. (C) 2000 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, Macromol NMR Sect, Struct Biophys Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Prot Engn Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Byrd, RA (reprint author), NCI, Frederick Canc Res & Dev Ctr, Macromol NMR Sect, Struct Biophys Lab, Frederick, MD 21702 USA. RI Byrd, R. Andrew/F-8042-2015 OI Byrd, R. Andrew/0000-0003-3625-4232 NR 69 TC 17 Z9 18 U1 0 U2 3 PU ACADEMIC PRESS INC 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 NOV PY 2000 VL 20 IS 2 BP 186 EP 195 DI 10.1006/prep.2000.1283 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 371WP UT WOS:000165202500007 PM 11049743 ER PT J AU Ramirez, BE Voloshin, ON Camerini-Otero, RD Bax, A AF Ramirez, BE Voloshin, ON Camerini-Otero, RD Bax, A TI Solution structure of DinI provides insight into its mode of RecA inactivation SO PROTEIN SCIENCE LA English DT Article DE bicelle; DinI; dipolar coupling; liquid crystal; NMR; Pf1; RecA ID RESIDUAL DIPOLAR COUPLINGS; LIQUID-CRYSTALLINE MEDIUM; PROTEIN-STRUCTURE; ORIENTED MACROMOLECULES; ALIGNMENT TENSOR; CHEMICAL-SHIFTS; NMR STRUCTURES; FREE R; PHASE; RESTRAINTS AB The Escherichia coli RecA protein triggers both DNA repair and mutagenesis in a process known as the SOS response. The 81-residue E. coli protein DinI inhibits activity of RecA in vivo. The solution structure of DinI has been determined by multidimensional triple resonance NMR spectroscopy, using restraints derived from two sets of residual dipolar couplings, obtained in bicelle and phage media, supplemented with J couplings and a moderate number of NOE restraints. DinI has an alpha/beta fold comprised of a three-stranded beta -sheet and two alpha -helices. The beta -sheet topology is unusual: the central strand is flanked by a parallel and an antiparallel strand and the sheet is remarkably flat. The structure of DinI shows that six negatively charged Glu and Asp residues on DinI's kinked C-terminal alpha -helix form an extended, negatively charged ridge. We propose that this ridge mimics the electrostatic character of the DNA phospodiester backbone, thereby enabling DinI to compete with single-stranded DNA for RecA binding. Biochemical data confirm that DinI is able to displace ssDNA from RecA. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Rm 126, Bethesda, MD 20892 USA. NR 52 TC 57 Z9 59 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD NOV PY 2000 VL 9 IS 11 BP 2161 EP 2169 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 388QG UT WOS:000166192500011 PM 11152126 ER PT J AU Ma, BY Xiong, JJ Lubkowski, J Nussinov, R AF Ma, BY Xiong, JJ Lubkowski, J Nussinov, R TI Homology modeling and molecular dynamics simulations of lymphotactin SO PROTEIN SCIENCE LA English DT Article DE beta-sheet; chemokine; homology modeling; lymphotactin; MD simulation ID HUMAN INTERLEUKIN-8 RECEPTOR; LYMPHOID-TISSUE CHEMOKINE; CC-CHEMOKINE; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; BINDING; RESOLUTION; NMR; CHEMOATTRACTANT; DIMER AB We have modeled the structure of human lymphotactin (hLpnt), by homology modeling and molecular dynamics simulations. This chemokine is unique in having a single disulfide bond and a long C-terminal tail. Because other structural classes of chemokines have two pairs of Cys residues, compared to one in Lpnt, and because it: has been shown that both disulfide bonds are required for stability and function, the question arises how the Lpnt maintains its structural integrity. The initial structure of hLpnt was constructed by homology modeling. The first 63 residues in the monomer of hLpnt were modeled using the structure of the human CC chemokine, RANTES, whose sequence appeared most similar. The structure of the long C-terminal tail, missing in RANTES, was taken from the human muscle fatty-acid binding protein. In a Protein Data Bank search, this protein was found to contain a sequence that was most homologous to the long tail. Consequently, the modeled hLpnt C-terminal tail consisted of both alpha -helical anti beta -motifs. The complete model of the hLpnt monomer consisted of two alpha -helices located above the five-stranded beta -sheet. Molecular dynamics simulations of the solvated initial model have indicated that the stability of the predicted fold is related to the geometry of Pro78. The five-stranded beta -sheet appeared to be preserved only when Pro78 was modeled in the cis conformation. Simulations were also performed both for the C-terminal truncated forms of the hLpnt that contained one or two (CC chemokine-like) disulfide bands, and for the chicken Lpnt (cLpnt). Our MD simulations indicated that the turn region (T30-G34) in hLpnt is important for the interactions with the receptor, and that the long C-terminal region stabilizes both the turn (T30-G34) and the five-stranded beta -sheet. The major conclusion from our theoretical studies is that the lack of one disulfide bond and the extension of the C-terminus in hLptn are mutually complementary. It is very likely that removal of two Cys residues sufficiently destabilizes the structure of a chemokine molecule, particularly the core beta -sheet, to abolish its biological function. However, this situation is rectified by the long C-terminal segment. The role of this long region is most likely to stabilize the first beta -turn region and alpha -helix H1, explaining how this chemokine can function with a single disulfide bond. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, SAIC Frederick,Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Program Struct Biol, Macromol Crystallog Lab, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, SAIC Frederick,Intramural Res Support Program, Bldg 469,Rm 151, Frederick, MD 21702 USA. RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X NR 40 TC 2 Z9 2 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD NOV PY 2000 VL 9 IS 11 BP 2192 EP 2199 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 388QG UT WOS:000166192500014 ER PT J AU Galperin, MY Grishin, NV AF Galperin, MY Grishin, NV TI The synthetase domains of cobalamin biosynthesis amidotransferases CobB and CobQ belong to a new family of ATP-dependent amidoligases, related to dethiobiotin synthetase SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE vitamin B12 biosynthesis; acetyl phosphate; bacterial cell division; MinD protein; enzyme family; domain structure; genome analysis ID CARBAMOYL-PHOSPHATE SYNTHETASE; COBYRINIC ACID A,C-DIAMIDE; COLI DIVISION SITE; ACETYL-COENZYME-A; ESCHERICHIA-COLI; METHANOSARCINA-THERMOPHILA; PHOSPHOTRANSACETYLASE GENE; PSEUDOMONAS-DENITRIFICANS; ANTHRANILATE SYNTHASE; SEQUENCE-ANALYSIS AB Phosphotransacetylases of Escherichia coli and several other bacteria contain an additional 350-aa N-terminal fragment that is not required for phosphotransacetylase activity. Sequence analysis of this fragment revealed that it is closely related to a family of ATP-dependent enzymes that also includes dethiobiotin synthetase and the synthetase domains of two amidotransferases involved in cobalamin biosynthesis, cobyrinic acid a,c-diamide synthase (CobB) and cobyric acid synthase (CobQ), Further database searches showed that this enzyme family is also related to the MinD family of ATPases involved in regulation of cell division in bacteria and archaea. Analysis of sequence conservation in the members of this enzyme family using the structure of dethiobiotin synthetase active site as a guide allowed us to suggest a model for the interaction of CobB and CobQ with their respective substrates. CobB and CobQ were also found to contain unusual Triad family (class I) glutamine amidotransferase domains with conserved Cys and His residues, but lacking the Glu residue of the catalytic triad. These results should help in understanding the enzymology of cobalamin biosynthesis and in resolving the role of phosphotransacetylase in regulation of the carbon flow to and from acetate, Proteins 2000;41:238-247. Published 2000 Wiley-Liss, Inc.dagger C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,Room 805, Bethesda, MD 20894 USA. OI Galperin, Michael/0000-0002-2265-5572 NR 64 TC 17 Z9 17 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD NOV 1 PY 2000 VL 41 IS 2 BP 238 EP 247 DI 10.1002/1097-0134(20001101)41:2<238::AID-PROT80>3.0.CO;2-L PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 362GN UT WOS:000089770400008 PM 10966576 ER PT J AU Evans, J Reeves, B Platt, H Leibenau, A Goldman, D Jefferson, K Nutt, D AF Evans, J Reeves, B Platt, H Leibenau, A Goldman, D Jefferson, K Nutt, D TI Impulsiveness, serotonin genes and repetition of deliberate self-harm (DSH) SO PSYCHOLOGICAL MEDICINE LA English DT Article ID TRYPTOPHAN-HYDROXYLASE GENE; MONOAMINE METABOLITES; CEREBROSPINAL-FLUID; PERSONALITY; POLYMORPHISM; DISORDER; TWINS; HTR2C; SUICIDALITY; VARIANTS AB Background. Few studies have investigated independent associations of psychological, biological and social variables with repeated deliberate self-harm (DSH). Serotonin function has been linked to impulsive and suicidal behaviour and genetic polymorphisms have been identified within the serotonin system that could account for this link. This study tested hypotheses linking impulsiveness, genetic polymorphisms of tryptophan hydroxylase (TPH) and the 5-HT2c receptor and repeated DSH. Methods. Individuals presenting after DSH were interviewed, completed personality questionnaires and gave venous blood samples. Genotypes were determined for TPH intron7 and 5-HT2c (cys-ser) polymorphisms. Follow-up to identify repetition of DSH was for 1 year. Results. Males with the 5-HT2c serine variant were more impulsive than those with the cysteine variant (0.39 standardized units, P = 0.041, 95 % CI 0.017 to 0.076). There was no association between impulsiveness and the TPH intron7 polymorphism overall but a weak association with the L allele in men (0.41 standardized units, P = 0.05, 95 % CI 0.001 to 0.82). Impulsiveness, although high in the group as a whole, did not distinguish those who repeated DSH. Conclusions. The personality trait of impulsiveness may in part be related to genotypes of the 5-HT2c receptor and TPH gene in men. Impulsiveness does not differ between those who do and do not repeat DSH. C1 Univ Bristol, Div Psychiat, Bristol BS2 8DZ, Avon, England. Royal Coll Surg England, Clin Effectiveness Unit, London WC2A 3PN, England. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. RP Evans, J (reprint author), Univ Bristol, Div Psychiat, 41 St Michaels Hill, Bristol BS2 8DZ, Avon, England. RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Evans, Jonathan/0000-0003-3171-640X NR 37 TC 57 Z9 58 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD NOV PY 2000 VL 30 IS 6 BP 1327 EP 1334 DI 10.1017/S0033291799002822 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 373JE UT WOS:000165285000008 PM 11097073 ER PT J AU Denicoff, KD Leverich, GS Nolen, WA Rush, AJ McElroy, SL Keck, PE Suppes, T Altshuler, LL Kupka, R Frye, MA Hatef, J Brotman, MA Post, RM AF Denicoff, KD Leverich, GS Nolen, WA Rush, AJ McElroy, SL Keck, PE Suppes, T Altshuler, LL Kupka, R Frye, MA Hatef, J Brotman, MA Post, RM TI Validation of the prospective NIMH-Life-Chart Method (NIMH-LCM (TM)-p) for longitudinal assessment of bipolar illness SO PSYCHOLOGICAL MEDICINE LA English DT Article ID WORKSHOP REPORT; DISORDER; RELIABILITY; VALIDITY AB Background. Systematic and accurate depiction of a patient's course of illness is crucial for assessing the efficacy of maintenance treatments for bipolar disorder. This need to rate the longterm prospective course of illness led to the development of the National Institute of Mental Health prospective Life Chart Methodology (NIMH-LCMTM-p or LCM), The NIMH-LCMTM-p allows for the daily assessment of mood and episode severity based on the degree of mood associated functional impairment. We have previously presented preliminary evidence of the reliability and validity of the LCM, and its utility in clinical trials. This study is a further and more extensive validation of the clinician rated NIMH-LCMTM-p. Methods. Subjects included 270 bipolar patients from the five sites participating in the Stanley Foundation Bipolar Network. Daily prospective LCM ratings on the clinician form were initiated upon entry, in addition to at least monthly ratings with the Inventory of Depressive Symptomatology-clinician rated (IDS-C), the Young Mania Rating Scale (YMRS) and the Global Assessment of Functioning (GAF). We correlated appropriate measures and time domains of the LCM with the IDS-C, YMRS and GAF. Results. Severity of depression on the LCM and on the IDS-C were highly correlated in 270 patients (r = -0.785, P < 0.001). Similarly, a strong correlation was found between LCM mania and the YMRS (r = 0.656, P < 0.001) and between the LCM average severity of illness and the GAF (r = -0.732, P < 0.001). Conclusions. These data further demonstrate the validity and potential utility of the NIMH-LCMTM-p for the detailed daily longitudinal assessment of manic and depressive severity and course, and response to treatment. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. NAMI Res Inst, Stanley Fdn Bipolar Network, Bethesda, MD USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Cincinnati, Coll Med, Biol Psychiat Program, Dept Psychiat, Cincinnati, OH USA. Univ Calif Los Angeles, VA Med Ctr, Los Angeles, CA USA. Willem Arntsz Huis & Univ Med Ctr Utrecht, HC Rumke Grp, Utrecht, Netherlands. RP Denicoff, KD (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Room 3N212,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. RI Brotman, Melissa/H-7409-2013; Nolen, Willem/E-9006-2014 NR 21 TC 99 Z9 100 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD NOV PY 2000 VL 30 IS 6 BP 1391 EP 1397 DI 10.1017/S0033291799002810 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 373JE UT WOS:000165285000014 PM 11097079 ER PT J AU Koscielniak, J Devasahayam, N Moni, MS Kuppusamy, P Yamada, K Mitchell, JB Krishna, MC Subramanian, S AF Koscielniak, J Devasahayam, N Moni, MS Kuppusamy, P Yamada, K Mitchell, JB Krishna, MC Subramanian, S TI 300 MHz continuous wave electron paramagnetic resonance spectrometer for small animal in vivo imaging SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID ESR SPECTROSCOPY; FREE-RADICALS; FREQUENCY; OXYGENATION; METABOLISM; HEART; PROBE AB Design and construction of an electron paramagnetic resonance (EPR) spectrometer, operating in the continuous wave mode in the radio frequency (rf) region, and capable of performing spectroscopy and in vivo imaging of paramagnetic spin probes is described. A resonant frequency of 300 MHz was chosen to provide the required sensitivity at nontoxic levels of commonly used spin probes and penetration of the rf in small animals. Three major components, the magnet, the radio frequency signal detection bridge, and the data acquisition module are described in this article. Integration of a rapid scan capability to reduce imaging time is also described. Two- and three-dimensional EPR images of the spin probe distribution in phantom objects as well as from in vivo experiments are reported. From the EPR images, morphology of some internal organs could be recognized. EPR images of the spin probe distribution in mice suggest differences in perfusion of the spin probe between normal and tumor regions. Addition of a spectral dimension to spatial images should enable differentiation of oxygen status in normal and pathological conditions. [S0034-6748(00)03811-9]. C1 NCI, Radiat Biol Branch, Div Clin Sci, Baltimore, MD 21224 USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21224 USA. RP Krishna, MC (reprint author), NIH, Bldg 10,Room B3 B69, Bethesda, MD 20892 USA. RI Yamada, Ken-ichi/E-6318-2012 NR 31 TC 43 Z9 43 U1 0 U2 3 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD NOV PY 2000 VL 71 IS 11 BP 4273 EP 4281 AR PII [S0034-6748(00)03811-9] DI 10.1063/1.1318917 PG 9 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 369TY UT WOS:000165084100046 ER PT J AU Kanik, KS Wilder, RL AF Kanik, KS Wilder, RL TI Hormonal alterations in rheumatoid arthritis, including the effects of pregnancy SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID PITUITARY-ADRENAL AXIS; TUMOR-NECROSIS-FACTOR; CORTICOTROPIN-RELEASING HORMONE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; DISEASE-ACTIVITY; POSTMENOPAUSAL WOMEN; ORAL-CONTRACEPTIVES; MENSTRUAL-CYCLE; REPLACEMENT THERAPY; GROWTH-HORMONE AB Rheumatoid arthritis (RA) is a complex multifactorial disease in which environmental, genetic, gender, and age-related factors are operating. Hormonal and immunological changes during pregnancy and the postpartum period are associated with profound changes in disease severity and incidence. There is evidence that some hormonal therapies can modify disease severity and decrease disease susceptibility. C1 NIAMS, Inflammatory Joint Dis Sect, ARB, NIH, Bethesda, MD 20892 USA. Univ S Florida, Coll Med, Div Rheumatol, Tampa, FL USA. RP Wilder, RL (reprint author), NIAMS, Inflammatory Joint Dis Sect, ARB, NIH, Bldg 10,Room 9N240, Bethesda, MD 20892 USA. NR 156 TC 47 Z9 48 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2000 VL 26 IS 4 BP 805 EP + DI 10.1016/S0889-857X(05)70170-8 PG 20 WC Rheumatology SC Rheumatology GA 369QM UT WOS:000165078500007 PM 11084945 ER PT J AU Cutolo, M Wilder, RL AF Cutolo, M Wilder, RL TI Different roles for androgens and estrogens in the susceptibility to autoimmune rheumatic diseases SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID BLOOD MONONUCLEAR-CELLS; HUMAN SYNOVIAL MACROPHAGES; PITUITARY-ADRENAL AXIS; SYSTEMIC LUPUS-ERYTHEMATOSUS; TUMOR-NECROSIS-FACTOR; SEX-HORMONES; IMMUNOGLOBULIN PRODUCTION; GONADAL-STEROIDS; PRIMARY CULTURES; IMMUNE-RESPONSE AB Androgens and estrogens modulate susceptibility and progression to autoimmune rheumatic disease. At any concentration, androgens seem to be primarily suppressive on cellular and humoral immunity whereas at physiologic concentrations, estrogens seem to enhance humoral immunity and decrease cellular immunity. C1 Univ Genoa, Dept Internal Med, Div Rheumatol, I-16132 Genoa, Italy. NIAMSD, Inflammatory Joint Dis Sect, NIH, Bethesda, MD 20892 USA. RP Cutolo, M (reprint author), Univ Genoa, Dept Internal Med, Div Rheumatol, Viale Benedetto XV 6, I-16132 Genoa, Italy. NR 67 TC 100 Z9 105 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2000 VL 26 IS 4 BP 825 EP + DI 10.1016/S0889-857X(05)70171-X PG 16 WC Rheumatology SC Rheumatology GA 369QM UT WOS:000165078500008 PM 11084946 ER PT J AU Yang, J Bogerd, H Le, SY Cullen, BR AF Yang, J Bogerd, H Le, SY Cullen, BR TI The human endogenous retrovirus K Rev response element coincides with a predicted RNA folding region SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE nuclear export; retrovirus; Rev; RNA binding; RNA structure ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEAR EXPORT; MESSENGER-RNA; THERMODYNAMIC PARAMETERS; SECONDARY STRUCTURES; ACTIVATION DOMAIN; GENE-EXPRESSION; TRANS-ACTIVATOR; TARGET SEQUENCE; IN-VIVO AB Human endogenous retrovirus K (HERV-K) is the name given to an similar to 30-million-year-old family of endogenous retroviruses present at >50 copies per haploid human genome, Previously, the HERV-K were shown to encode a nuclear RNA export factor, termed K-Rev, that is the functional equivalent of the H-Rev protein encoded by human immunodeficiency virus type 1, HERV-K was also shown to contain a cis-acting target element, the HERV-K Rev response element (K-RRE), that allowed the nuclear export of linked RNA transcripts in the presence of either K-Rev or H-Rev. Here, we demonstrate that the functionally defined K-RRE coincides with a statistically highly significant unusual RNA folding region and present a potential RNA secondary structure for the similar to 416-nt K-RRE, Both in vitro and in vivo assays of sequence specific RNA binding were used to map two primary binding sites for K-Rev, and one primary binding site for H-Rev, within the K-RRE. Of note, all three binding sites map to discrete predicted RNA stem-loop subdomains within the larger K-RRE structure, Although almost the entire 416-nt K-RRE was required for the activation of nuclear RNA export in cells expressing K-Rev, mutational inactivation of the binding sites for K-Rev resulted in the selective loss of the K-RRE response to K-Rev but not to H-Rev. Together, these data strongly suggest that the K-RRE, like the H-RRE, coincides with an extensive RNA secondary structure and identify specific sites within the K-RRE that can recruit either K-Rev or H-Rev to HERV-K RNA transcripts. C1 Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Genet, Durham, NC 27710 USA. NCI, Frederick Canc Res Ctr, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. RP Cullen, BR (reprint author), Duke Univ, Med Ctr, Howard Hughes Med Inst, Room 426 CARL Bldg,Res Dr, Durham, NC 27710 USA. NR 48 TC 20 Z9 21 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD NOV PY 2000 VL 6 IS 11 BP 1551 EP 1564 DI 10.1017/S135583820000100X PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 375GV UT WOS:000165391900008 PM 11105755 ER PT J AU McDermott, DH Murphy, PM AF McDermott, DH Murphy, PM TI Chemokines and their receptors in infectious disease SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCYTE CHEMOATTRACTANT PROTEIN-1; SARCOMA-ASSOCIATED HERPESVIRUS; LONG-TERM NONPROGRESSORS; CD4(+) T-CELLS; HIV-1 INFECTION; COUPLED RECEPTOR; SMALL-MOLECULE; MICE LACKING; IN-VIVO C1 NIAID, Mol Signaling Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Mol Signaling Sect, Host Def Lab, NIH, 10 Ctr Dr,Bldg 10,Room 11N113, Bethesda, MD 20892 USA. OI McDermott, David/0000-0001-6978-0867 NR 121 TC 15 Z9 15 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD NOV PY 2000 VL 22 IS 4 BP 393 EP 415 DI 10.1007/s002810000052 PG 23 WC Immunology; Pathology SC Immunology; Pathology GA 383PV UT WOS:000165892100005 PM 11155443 ER PT J AU Hertle, RW AF Hertle, RW TI Examination and refractive management of patients with nystagmus SO SURVEY OF OPHTHALMOLOGY LA English DT Review ID RETINAL IMAGE STABILIZATION; NORMAL APPEARING FUNDI; CONGENITAL NYSTAGMUS; VISUAL-ACUITY; MANIFEST LATENT; CONTACT-LENSES; WAVE-FORM; OSCILLOPSIA; CHILDREN AB Patients with nystagmus present unique challenges to the ophthalmologist. These patients can be difficult to examine and refract. Treatment options to improve vision or reduce disturbing visual symptoms are limited, which is disappointing to the patient and frustrating to the clinician. This paper will provide the clinician with one method of clinically organizing nystagmus, describe the patients who may benefit from optical treatments, and discuss the methodology used in their implementation. Techniques that will be discussed include patient examination and objective and subjective refraction. Optical treatments discussed included spectacles, prisms, contact lenses, and retinal image stabilization. (Surv Ophthalmol 45:215-222, 2000. (C) 2000 by Elsevier Science Inc. All rights reserved.). C1 NEI, LSR, NIH, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Dept Ophthalmol, Bethesda, MD USA. Walter Reed Army Med Ctr, Dept Ophthalmol, Washington, DC 20307 USA. RP Hertle, RW (reprint author), NEI, LSR, NIH, Bldg 49 Room 2A50, Bethesda, MD 20892 USA. NR 51 TC 18 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD NOV-DEC PY 2000 VL 45 IS 3 BP 215 EP 222 DI 10.1016/S0039-6257(00)00153-3 PG 8 WC Ophthalmology SC Ophthalmology GA 389KC UT WOS:000166236300003 PM 11094245 ER PT J AU Doudet, DJ Holden, JE Jivan, S McGeer, E Wyatt, RJ AF Doudet, DJ Holden, JE Jivan, S McGeer, E Wyatt, RJ TI In vivo PET studies of the dopamine D2 receptors in rhesus monkeys with long-term MPTP-induced parkinsonism SO SYNAPSE LA English DT Article DE raclopride; dopamine D2 receptors; long-term MPTP-induced parkinsonism ID POSITRON EMISSION TOMOGRAPHY; PROGRESSIVE SUPRANUCLEAR PALSY; C-11 RACLOPRIDE; RAT-BRAIN; REVEAL DOPAMINE-D2; SYNAPTIC DOPAMINE; SUBSTANTIA-NIGRA; 6-OHDA LESIONS; D-2 RECEPTORS; ANIMAL-MODELS AB Studies of dopamine (DA) receptor binding in early parkinsonian patients, or in models of Parkinson's disease, have revealed a supersensitivity of the DB-like receptor subtype as compared to age-matched controls. The lack of upregulation in advanced patients is often attributed to the effects of prolonged antiparkinsonian therapy, but the impact of therapy vs. intrinsic mechanisms in untreated patients or animals with long-term lesions of the DA nigrostriatal pathway has been difficult to address. We studied, in vivo, by PET using the DA D2 receptor ligand raclopride, the status of the DA receptors in normal rhesus monkeys and those with acute (3 months) or long-term (10 years) MPTP-induced nigrostriatal lesions. Compared to age-matched controls, there was no change in raclopride binding in MPTP-treated animals without parkinsonian symptoms. There was a significant increase in raclopride binding in the putamen (but not caudate nucleus) of all the animals displaying rigidity, hypo- and bradykinesia. This increase was greater in the animals with acute lesions (32%) than with established, long-term lesions (18%). There was no correlation between the postmortem striatal DA concentrations and in vivo raclopride binding but there was a correlation between PET raclopride binding and [H-3]radopride binding in vitro. Complex changes in D2 receptor binding occur in various stages of parkinsonism. Antiparkinsonian therapy is unlikely to be solely responsible for the lack of upregulation found in advanced parkinsonian patients but may be a contributing factor. (C) 2000 Wiley-Liss, Inc. C1 Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC V6T 2B5, Canada. Univ British Columbia, Kinsmen Lab Neurol Res, Vancouver, BC V6T 2B5, Canada. Univ British Columbia, TRIUMF, Vancouver, BC V6T 2B5, Canada. Univ Wisconsin, Dept Med Phys, Madison, WI USA. NIMH, Neuropsychiat Branch, NIH, Bethesda, MD 20892 USA. RP Doudet, DJ (reprint author), Univ British Columbia, Dept Med, Div Neurol, Rm M36,Purdy Pavil,2221 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. NR 55 TC 36 Z9 37 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 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 2000 VL 38 IS 2 BP 105 EP 113 DI 10.1002/1098-2396(200011)38:2<105::AID-SYN1>3.0.CO;2-S PG 9 WC Neurosciences SC Neurosciences & Neurology GA 361WQ UT WOS:000089747600001 PM 11018784 ER PT J AU Shippenberg, TS Rea, W Slusher, BS AF Shippenberg, TS Rea, W Slusher, BS TI Modulation of behavioral sensitization to cocaine by NAALADase inhibition SO SYNAPSE LA English DT Article DE cocaine; glutamate; NAALADase; sensitization; N-acetyl-aspartyl-glutamate ID LINKED ACIDIC DIPEPTIDASE; METABOTROPIC GLUTAMATE RECEPTORS; VENTRAL TEGMENTAL AREA; ASPARTYL-L-GLUTAMATE; N-ACETYLASPARTYLGLUTAMATE; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; REGIONAL DISTRIBUTION; RAT-BRAIN; AMPHETAMINE AB Sensitization to cocaine has been attributed to alterations in excitatory amino acid and dopamine neurotransmission in the mesolimbic system. The present study sought to determine whether inhibition of NAALADase, an enzyme that cleaves glutamate from the endogenous neuropeptide, N-acetyl-aspartyl-glutamate (NAAG), attenuates sensitization to the psychomotor stimulant effects of cocaine. Rats received daily injections of cocaine (20.0 mg/kg/day; i.p.) or saline for 5 days. Fifteen minutes prior to these injections they received an i.p. injection of the NAALADase inhibitor, 2-PMPA (50.0-100 mg/kg), or vehicle. Locomotor activity and stereotypy produced by a challenge dose of cocaine (15.0 mg/kg) were assessed 3 days later. Acute cocaine administration increased locomotor activity in control animals. In animals with a prior history of cocaine administration, the behavioral response to cocaine was significantly enhanced. In animals that had received 8-PMPA in combination with cocaine, the enhancement of cocaine-induced locomotor activity was attenuated. No alteration in cocaine-evoked activity was observed in animals that had received once daily injections of 8-PMPA, alone. Acute administration of 2-PMPA also did not modify saline-induced locomotor activity or activity produced by an acute cocaine challenge. These data demonstrate that NAALADase inhibition attenuates the development of sensitization to the locomotor-activating effects of cocaine. Furthermore, this action cannot be attributed to an antagonism of the acute effects of cocaine. (C) 2000 Wiley-Liss, Inc. C1 NIDA, Integrat Neurosci Unit, Behav Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. Guilford Pharmaceut Inc, Dept Res, Baltimore, MD USA. RP Shippenberg, TS (reprint author), NIDA, Integrat Neurosci Unit, Behav Neurosci Lab, Intramural Res Program,NIH, POB 5180, Baltimore, MD 21224 USA. NR 43 TC 22 Z9 23 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 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 2000 VL 38 IS 2 BP 161 EP 166 DI 10.1002/1098-2396(200011)38:2<161::AID-SYN7>3.0.CO;2-G PG 6 WC Neurosciences SC Neurosciences & Neurology GA 361WQ UT WOS:000089747600007 PM 11018790 ER PT J AU Cohen, RM Carson, RE Sunderland, T AF Cohen, RM Carson, RE Sunderland, T TI Opiate receptor avidity in the thalamus is sexually dimorphic in the elderly SO SYNAPSE LA English DT Article DE 6-deoxy-6-beta-[F-18]fluoronaltrexone; positron emission tomography; basal ganglia ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; HUMAN-BRAIN; SEX-DIFFERENCES; DEMENTIA; GENDER; FEMALE; SCALE AB Opiate receptor avidity (B'(max)/F-D), was measured in the subcortex of nine females (five healthy subjects, four Alzheimer patients) and 15 males (seven healthy subjects, eight Alzheimer patients), 51-75 years of age, with the opiate receptor antagonist 6-deoxy-6-beta-[F-18]fluoronaltrexone (cyclofoxy, CF) and a positron emission tomograph. CF avidity was 27.5% less in the thalamus of healthy women compared to healthy men and 48.5% less in Alzheimer disease female patients compared to male patients. (C) 2000 Wiley-Liss, Inc. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Cohen, RM (reprint author), NIH, Cerebral Metab Lab, Bldg 10,Room 3N218,10 Ctr Dr,MSC 1274, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 24 TC 7 Z9 8 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 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 2000 VL 38 IS 2 BP 226 EP 229 DI 10.1002/1098-2396(200011)38:2<226::AID-SYN13>3.0.CO;2-# PG 4 WC Neurosciences SC Neurosciences & Neurology GA 361WQ UT WOS:000089747600013 PM 11018796 ER PT J AU Fujinaga, M Lowe, LA Kuehn, MR AF Fujinaga, M Lowe, LA Kuehn, MR TI alpha(1)-Adrenergic stimulation perturbs the left-right asymmetric expression pattern of nodal during rat embryogenesis SO TERATOLOGY LA English DT Article ID SITUS-INVERSUS; NITROUS-OXIDE; BODY STRUCTURES; EMBRYOS; GENE; MICE; PATHWAY; PERIOD; MOUSE; INV AB Background: Normal development of the left/right (L/R) body axis leads to the characteristic sidedness of asymmetric body structures, e.g., the left-sided heart. Several genes are now known to be expressed with L/R asymmetry during embryogenesis, including nodal, a member of the transforming growth factor-beta (TGF-beta) family. Mutations or experimental treatments that affect L/R development, such as those that cause situs inversus (reversal of the sidedness of asymmetric body structures), have been shown to alter or abolish nodal's asymmetric expression. Methods: In the present study, we examined the effects on nodal expression of alpha (1)-adrenergic stimulation, known to cause a 50% incidence of situs inversus in rat embryos grown in culture, using reverse transcription-polymerase chain reaction assay and whole-mount in situ hybridization assay. Results: In embryos cultured with phenylephrine, an alpha (1)-adrenergic agonist, nodal's normal asymmetric expression only in the left lateral plate mesoderm was altered. In some treated embryos, nodal expression was detected in either the left or right lateral plate mesoderm. However, most treated embryos lacked lateral plate mesoderm expression. In addition, the embryos that did show expression were at a later stage than when nodal expression is normally found. Conclusions: Our results demonstrate that alpha (1)-adrenergic stimulation delays the onset and perturbs the normal asymmetric pattern of nodal expression. Either of these effects might contribute to situs inversus. (C) 2000 Wiley-Liss, Inc. C1 Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. VA Palo Alto Hlth Care Syst, Anesthesiol Serv, Palo Alto, CA 94304 USA. Univ London, Imperial Coll Sci Technol & Med, Magill Dept Anaesthet, London SW10 9NH, England. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Fujinaga, M (reprint author), Chelsea & Westminster Hosp, Magill Dept Anaesthet, 369 Fulham Rd, London SW10 9NH, England. RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 NR 42 TC 3 Z9 3 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD NOV PY 2000 VL 62 IS 5 BP 317 EP + DI 10.1002/1096-9926(200011)62:5<317::AID-TERA5>3.0.CO;2-L PG 9 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 368NH UT WOS:000090123400005 PM 11029149 ER PT J AU Ghanayem, BI Wang, HB Sumner, S AF Ghanayem, BI Wang, HB Sumner, S TI Using cytochrome P-450 gene knock-out mice to study chemical metabolism, toxicity, and carcinogenicity SO TOXICOLOGIC PATHOLOGY LA English DT Article ID ARYL-HYDROCARBON RECEPTOR; HUMAN LIVER-MICROSOMES; NULL MUTANT MICE; MESSENGER-RNA; ACETAMINOPHEN ACTIVATION; MOUSE CHROMOSOME-9; BENZENE METABOLISM; CYP2E1 EXPRESSION; OXIDATIVE STRESS; RAT AB Cytochrome P-450 (CYP) enzymes are heme-containing proteins that carry out oxidative metabolism of a wide range of structurally diverse exogenous chemicals and therapeutic agents as well as endogenous compounds. For some of these xenobiotics, oxidative metabolism results in the formation of toxic, mutagenic, or carcinogenic metabolites. In the past, the role of CYP enzymes in metabolism and chemical-induced toxicity was studied indirectly through use of specific antibodies or inducers and inhibitors of these enzymes. Progress in molecular biology and the ability to bioengineer animal models that do not express CYP1A2, CYP1A1, CYP1B1, CYP2E1, or both CYP1A2 and CYP2E1 isozymes has allowed for direct investigations of the in vivo role of these enzymes in the metabolism, toxicity, and carcinogenicity of xenobiotics. This article reviews research conducted to date that utilizes these genetically bioengineered mice in metabolism, toxicity, or carcinogenicity studies of chemicals. Some studies showed a positive correlation between in vivo results and in vitro predictions for the role of a specific CYP in chemical-induced effects, whereas other studies did not support in vitro predictions. Work reviewed herein demonstrates the importance of using animal models for investigating the role of specific CYP enzymes in metabolism and chemical-induced toxicity or carcinogenicity rather than relying solely on in vitro techniques. Eventually, studies of this nature will facilitate a more accurate assessment of human risks with regard to chemicals by helping us to understand the relationships between chemical metabolism, carcinogenicity, and polymorphisms in CYP enzymes. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Ghanayem, BI (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233 B3-10, Res Triangle Pk, NC 27709 USA. NR 79 TC 40 Z9 42 U1 0 U2 1 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 2000 VL 28 IS 6 BP 839 EP 850 DI 10.1177/019262330002800613 PG 12 WC Pathology; Toxicology SC Pathology; Toxicology GA 380XG UT WOS:000165728700013 PM 11127301 ER PT J AU Toraason, M Sussman, G Biagini, R Meade, J Beezhold, D Germolec, D AF Toraason, M Sussman, G Biagini, R Meade, J Beezhold, D Germolec, D TI Latex allergy in the workplace SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Society-of-Toxicology CY MAR, 2000 CL PHILADELPHIA, PENNSYLVANIA SP Soc Toxicol DE natural rubber latex (NRL); latex allergy; contact dermatitis; hypersensitivity ID NATURAL-RUBBER LATEX; CLASS-I CHITINASES; IGE ANTIBODIES; CROSS-REACTIVITY; FRUIT SYNDROME; CELL EPITOPES; B-CELL; PREVALENCE; IDENTIFICATION; SENSITIZATION AB While less than 1% of the general population is sensitized to latex, the U.S. Occupational Safety and Health Administration estimates that 8-12% of health-care workers are sensitized. The major source of workplace exposure is powdered natural rubber latex (NRL) gloves. NRL is harvested from Hevea brasiliensis trees and ammoniated to prevent coagulation resulting in the hydrolysis of the latex proteins. Prior to use in manufacturing, the latex is formulated by the addition of multiple chemicals. Thus, human exposure is to a mixture of residual chemicals and hydrolyzed latex peptides. Clinical manifestations include irritant contact dermatitis, allergic contact dermatitis (type IV), and type I immediate hypersensitivity response. Type I (IgE-mediated) NRL allergy includes contact urticaria, systemic urticaria, angioedema, rhinitis, conjunctivitis, bronchospasm, and anaphylaxis. Taking an accurate history, including questions on atopic status, food allergy, and possible reactions to latex devices makes diagnosis of type-I latex allergy possible. To confirm a diagnosis, either in vivo skin prick testing (SPT) or in vitro assays for latex-specific IgE are performed. While the SPT is regarded as a primary confirmatory test for IgE-mediated disease, the absence of a U.S. Food and Drug Administration-licensed Hevea brasiliensis latex extract has restricted its use in diagnosis. Serological tests have, therefore, become critically important as alternative diagnostic tests. Three manufacturers currently have FDA clearance for in vitro tests, to detect NRL-specific IgE. The commercially available assays may disagree on the antibody status of an individual serum, which may be due to the assay's detecting anti-NRL IgEs to different allergenic NRL proteins. Sensitized individuals produce specific IgE antibody to at least 10 potent Hevea allergens, Hev b l-Hev b 10, each of which differs in its structure, size, and net charge. The relative content and ratios of Hevs in the final allergen preparation most probably could effect diagnostic accuracy. The Hev proteins have been cloned and expressed as recombinant proteins. Sequencing demonstrates both unique epitopes and sequences commonly found in other plant proteins. Sequence homology helps to explain the cross reactivity to a variety of foods experienced by latex allergic individuals. The development of recombinant allergens provides reagents that should improve the diagnostic accuracy of tests for latex allergy. Although clinical and exposure data have been gathered on the factors affecting response in latex-allergic individuals, less is known regarding the development of sensitization. Coupled with in vitro dermal penetration studies, murine models have been established to investigate the route of exposure in the development of latex sensitization. Time-course and dose-response studies have shown subcutaneous, intratracheal, or topical administrations of non-ammoniated latex proteins to induce IgE production. Both in vitro penetration and in vivo studies highlight the importance of skin condition in the development of latex allergy, with enhanced penetration and earlier onset of IgE production seen with experimentally abraded skin. The diagnosis of latex allergy is complicated by these variables, which in turn hinder the development of intervention strategies. Further epidemiological assessment is needed to more explicitly define the scope, trends, and demographics of latex allergy. Diagnostic accuracy can be improved through greater knowledge of proteins involved in the development of latex allergy, and better documentation of the presently available diagnostic tests. In vivo and in vitro models can elucidate mechanisms of sensitization and provide an understanding of the role of the exposure route in latex allergy-associated diseases. Together, these efforts can lead to intervention strategies for reducing latex allergy in the workplace. C1 NIOSH, Robert A Taft Labs, Div Appl Res & Technol, Cincinnati, OH 45226 USA. Univ Toronto, Toronto, ON M4V 1R2, Canada. Guthrie Res Inst, Sayre, PA 18840 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Toraason, M (reprint author), NIOSH, Robert A Taft Labs, Div Appl Res & Technol, C23,4676 Columbia Pkwy, Cincinnati, OH 45226 USA. EM mtorasson@cdc.gov NR 58 TC 23 Z9 25 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 NOV PY 2000 VL 58 IS 1 BP 5 EP 14 DI 10.1093/toxsci/58.1.5 PG 10 WC Toxicology SC Toxicology GA 368MZ UT WOS:000090122500004 PM 11053535 ER PT J AU Halmes, NC Roberts, SM Tolson, JK Portier, CJ AF Halmes, NC Roberts, SM Tolson, JK Portier, CJ TI Reevaluating cancer risk estimates for short-term exposure scenarios SO TOXICOLOGICAL SCIENCES LA English DT Article DE risk assessment; carcinogenicity; cancer bioassays; estimating cancer risks; stop-exposure studies ID RELATIVE SUSCEPTIBILITY; INTERNAL MEASURES; 2-STAGE MODEL; CARCINOGENICITY; HUMANS; ANIMALS AB Estimates of cancer risk from short-term exposure to carcinogens generally rely on cancer potency values derived from chronic, lifetime-exposure studies and assume that exposures of limited duration are associated with a proportional reduction in cancer risk. The validity of this approach was tested empirically using data from both chronic lifetime and stop-exposure studies of carcinogens conducted by the National Toxicology Program. Eleven compounds were identified as having data sufficient for comparison of relative cancer potencies from short-term versus lifetime exposure, The data were modeled using the chronic data alone, and also using the chronic and the stop-exposure data combined, where stop-exposure doses were adjusted to average lifetime exposure. Maximum likelihood estimates of the dose corresponding to a 1% added cancer risk (ED01) were calculated along with their associated 95% upper and lower confidence bounds. Statistical methods were used to evaluate the degree to which adjusted stop-exposures produced risks equal to those estimated from the chronic exposures. For most chemical/cancer endpoint combinations, inclusion of stop-exposure data reduced the ED,,, indicating that the chemical had greater apparent potency under stop-exposure conditions, For most chemicals and endpoints, consistency in potency between continuous and stop-exposure studies was achieved when the stop-exposure doses were averaged over periods of less than a lifetime-in some cases as short as the exposure duration itself, While the typical linear adjustments for less-than-lifetime exposure in cancer risk assessment can theoretically result in under- or overestimation of risks, empirical observations in this analysis suggest that an underestimation of cancer risk from short-term exposures is more likely. C1 Univ Florida, Ctr Environm & Human Toxicol, Gainesville, FL 32611 USA. TERRA Inc, Denver, CO USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Roberts, SM (reprint author), Univ Florida, Ctr Environm & Human Toxicol, Box 110885, Gainesville, FL 32611 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 34 TC 18 Z9 18 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2000 VL 58 IS 1 BP 32 EP 42 DI 10.1093/toxsci/58.1.32 PG 11 WC Toxicology SC Toxicology GA 368MZ UT WOS:000090122500007 PM 11053538 ER PT J AU Morgan, DL Price, HC O'Connor, RW Seely, JC Ward, SM Wilson, RE Cunningham, MC AF Morgan, DL Price, HC O'Connor, RW Seely, JC Ward, SM Wilson, RE Cunningham, MC TI Upper respiratory tract toxicity of inhaled methylvinyl ketone in F344 rats and B6C3F1 mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE methylvinyl ketone; 3-buten-2-one; alpha,beta-unsaturated ketones; inhalation; upper respiratory tract; nasal cavity; gaseous irritant ID DOSE LEVELS; AMES TEST; GAS; EPITHELIUM; CHEMICALS; ACROLEIN; MUTAGENS AB The National Toxicology Program is conducting a chemical class study to investigate the structure-activity relationships for the toxicity of alpha,beta -unsaturated ketones. Methylvinyl ketone (MVK) was selected for study because it is a representative straight-chain aliphatic alpha,beta -unsaturated ketone and because of its extensive use and widespread exposure. Short-term inhalation studies of MVK were conducted to provide toxicity data for comparison with other alpha,beta -unsaturated ketones and for use in designing chronic toxicity and carcinogenicity studies. In 2-week studies, rats and mice were exposed to 0, 0.25, 0.5, 1, 2, 4, or 8 ppm MVK 6 h/day, 5 days/week for 12 exposures. Morbidity and early deaths occurred in all male and female rats after 1 exposure and in 2 male mice after 10 exposures to 8 ppm. Rats exhibited nasal cavity toxicity and lung necrosis at 4 ppm. No toxicity was observed in animals exposed to less than 2 ppm. Based on these results a 13-week study was conducted at 0, 0.5, 1, and 2 ppm MVK. As observed in the 2-week study, the nasal cavity was the main target organ and rats were more sensitive than mice. Respiratory and olfactory epithelial necrosis were prominent by day 21 in the rat. At study termination these lesions were still evident but not as severe as noted earlier. Additionally, changes such as olfactory epithelial regeneration and metaplasia (respiratory) as well as respiratory epithelial hyperplasia and metaplasia (squamous) were clearly evident. Nasal lesions in mice were limited to a subtle squamous metaplasia of transitional and/or respiratory epithelium covering predominantly the tips of naso- and maxilloturbinates in Levels I and II. A transient, leukopenia was observed in rats exposed to 2 ppm, however, this effect was not present after 13 weeks of exposure. In mice, leukocyte counts were significantly decreased at all exposure concentrations after 13 weeks of exposure. Absolute testicular and epididymal weights and sperm counts were decreased at the high dose only. MVK can be characterized as a reactive, direct-acting gaseous irritant. MVK exposure causes the same nasal cavity lesions as the cyclic alpha,beta -unsaturated ketone, 2-cyclohexen-1-one, although at lower exposure concentrations. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Mantech Environm Technol Inc, Res Triangle Pk, NC 27709 USA. PATHCO Inc, Res Triangle Pk, NC 27709 USA. RP Morgan, DL (reprint author), NIEHS, POB 12233,Mail Stop IF-00, Res Triangle Pk, NC 27709 USA. NR 39 TC 13 Z9 13 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 NOV PY 2000 VL 58 IS 1 BP 182 EP 194 DI 10.1093/toxsci/58.1.182 PG 13 WC Toxicology SC Toxicology GA 368MZ UT WOS:000090122500024 PM 11053555 ER PT J AU Moran, JH Mitchell, LA Bradbury, JA Qu, W Zeldin, DC Schnellmann, RG Grant, DF AF Moran, JH Mitchell, LA Bradbury, JA Qu, W Zeldin, DC Schnellmann, RG Grant, DF TI Analysis of the cytotoxic properties of linoleic acid metabolites produced by renal and hepatic P450s SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID GLOMERULAR MESANGIAL CELLS; HUMAN LIVER-MICROSOMES; ARACHIDONIC-ACID; MOLECULAR-CLONING; EPOXYEICOSATRIENOIC ACIDS; CYTOCHROMES P450; BISALLYLIC HYDROXYLATION; OMEGA-HYDROXYLASE; PROXIMAL TUBULES; LUNG LAVAGES AB Cytochrome P450 epoxidation of linoleic acid produces biologically active metabolites which have been associated with many pathological conditions that often lead to acute renal failure. In the present study, we evaluated the ability of specific cytochrome P450s to produce linoleic acid monoepoxides. We then tested the cytotoxic properties of linoleic acid, linoleic acid monoepoxides, and corresponding diols in a rabbit renal proximal tubule model. CYP1A2, CYP2E1, CYP2J2, CYP2J3, CYP2J5, and CYP2J9 metabolized linoleic acid at rates comparable to arachidonic acid and produced linoleic acid monoepoxides as major products. Cytotoxicity studies showed that linoleic acid, linoleic acid monoepoxides, and corresponding diols are toxic at pathologically relevant concentrations (100-500 muM). Concentration-dependent studies showed that linoleic acid and linoleic acid monoepoxides are the most toxic and induce mitochondrial dysfunction prior to cell death. Cytoprotectants known to block cell death associated with mitochondrial dysfunction and oxidative stress did not prevent cell death induced by linoleic acid and linoleic acid monoepoxides. This study shows that P450s in the CYP1 and CYP2 gene families metabolize linoleic acid to linoleic acid monoepoxides and that the monoepoxides, as well as linoleic acid, disrupt mitochondrial function without causing oxidative stress. (C) 2000 Academic Press. C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Grant, DF (reprint author), Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, 4301 W Markham,Slot 638, Little Rock, AR 72205 USA. FU NIEHS NIH HHS [ES09129]; NIGMS NIH HHS [GM56708] NR 58 TC 44 Z9 49 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 1 PY 2000 VL 168 IS 3 BP 268 EP 279 DI 10.1006/taap.2000.9053 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 400WB UT WOS:000166893700011 PM 11042099 ER PT J AU Huizing, M Anikster, Y Gahl, WA AF Huizing, M Anikster, Y Gahl, WA TI Hermansky-Pudlak syndrome and related disorders of organelle formation SO TRAFFIC LA English DT Review DE Albinism; Chediak-Higashi syndrome; granule; Griscelli syndrome; Hermansky-Pudlak syndrome; metabolic defect; storage pool deficiency; transport; vesicle ID CHEDIAK-HIGASHI-SYNDROME; AP-3 ADAPTER COMPLEX; PIGMENT GRANULE BIOGENESIS; GRAY PLATELET SYNDROME; VON-WILLEBRAND-FACTOR; WISTAR FURTH RAT; PALE EAR EP; PULMONARY FIBROSIS; OCULOCUTANEOUS ALBINISM; PROTEIN COMPLEX AB Hermansky-Pudlak syndrome (HPS) consists of a group of genetically heterogeneous disorders which share the clinical findings of oculocutaneous albinism, a platelet storage pool deficiency, and some degree of ceroid lipofuscinosis. Related diseases share some of these findings and may exhibit other symptoms and signs but the underlying defect in the entire group of disorders involves defective intracellular vesicle formation, transport or fusion. Two HPS-causing genes, HPS1 and ADTB3A, have been isolated but the function of only the latter has been determined. ADTB3A codes for the beta 3A subunit of adaptor complex-3, responsible for vesicle formation from the trans-Golgi network (TGN). The many HPS patients who do not have HPS1 or ADTB3A mutations have their disease because of mutations in other genes. Candidates for these HPS-causing genes include those responsible for mouse models of HPS or for the 'granule' group of eye color genes in Drosophila. Each gene responsible for a subset of HPS or a related disorder codes for a protein which almost certainly plays a pivotal role in vesicular trafficking, inextricably linking clinical and cell biological interests in this group of diseases. C1 NICHHD, Heritable Disorders Branch, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NICHHD, Heritable Disorders Branch, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA. NR 117 TC 98 Z9 98 U1 2 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-9219 J9 TRAFFIC JI Traffic PD NOV PY 2000 VL 1 IS 11 BP 823 EP 835 DI 10.1034/j.1600-0854.2000.011103.x PG 13 WC Cell Biology SC Cell Biology GA 379EF UT WOS:000165627400003 PM 11208073 ER PT J AU Barr, VA Phillips, SA Taylor, SI Haft, CR AF Barr, VA Phillips, SA Taylor, SI Haft, CR TI Overexpression of a novel sorting nexin, SNX15, affects endosome morphology and protein trafficking SO TRAFFIC LA English DT Article DE endocytosis; fluorescence microscopy; organelle morphology; protein trafficking; sorting nexin ID TRANS-GOLGI NETWORK; LYSOSOMAL MEMBRANE-GLYCOPROTEINS; MANNOSE 6-PHOSPHATE RECEPTOR; LOCALIZATION; COMPARTMENT; COMPLEX; FAMILY; TGN38; YEAST; INTERNALIZATION AB Sorting nexin (SNX) 15 is a novel member of the SNX family of proteins. Although the functions of most SNXs have not yet been determined, several family members (e.g., SNX1, SNX2 SNX3, and SNX8) are orthologs of yeast proteins involved in protein trafficking. Overexpression of myc-tagged SNX15 in COS-7 cells altered the morphology of several endosomal compartments. In transient transfection experiments, myc-SNX15 was first seen in small punctate spots and small ring structures. Later, myc-SNX15 was found in larger rings. Finally, myc-SNX15 was observed in large, amorphous membrane-limited structures. These structures contained proteins from lysosomes, late endosomes, early endosomes, and the trans-Golgi network. However, the morphology of the endoplasmic reticulum and Golgi was not affected by overexpression of myc-SNX15. In myc-SNX15-overexpressing cells, the endocytosis of transferrin was severely inhibited and endocytosis of tac-trans-Golgi network (TGN) 38 and tac-furin was slowed. In addition, the recycling of internalized tac-TGN38 and tac-furin was also inhibited. Both the morphological and biochemical data indicate that SNX15 prays a crucial role in trafficking through the endocytic pathway. This is the first demonstration that a mammalian SNX protein is involved in protein trafficking. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Barr, VA (reprint author), NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NR 40 TC 41 Z9 41 U1 1 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-9219 J9 TRAFFIC JI Traffic PD NOV PY 2000 VL 1 IS 11 BP 904 EP 916 DI 10.1034/j.1600-0854.2000.011109.x PG 13 WC Cell Biology SC Cell Biology GA 379EF UT WOS:000165627400009 PM 11208079 ER PT J AU Anantharaman, V Aravind, L AF Anantharaman, V Aravind, L TI Cache - a signaling domain common to animal Ca2+ channel subunits and a class of prokaryotic chemotaxis receptors SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID LIGAND-BINDING DOMAIN; CALCIUM-CHANNEL; PROTEINS; BACTERIA C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Anantharaman, V (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. OI Anantharaman, Vivek/0000-0001-8395-0009 NR 18 TC 97 Z9 99 U1 0 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD NOV PY 2000 VL 25 IS 11 BP 535 EP 537 DI 10.1016/S0968-0004(00)01672-8 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 373BD UT WOS:000165267800005 PM 11084361 ER PT J AU Vogel, AM Weinstein, BM AF Vogel, AM Weinstein, BM TI Studying vascular development in the zebrafish SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Article ID RECEPTOR TYROSINE KINASES; GROWTH-FACTOR VEGF; INSERTIONAL MUTAGENESIS; CARDIOVASCULAR-SYSTEM; EMBRYONIC-DEVELOPMENT; TRANSGENIC ZEBRAFISH; POSITIONAL CLONING; GFP REPORTER; DANIO-RERIO; GENE AB The zebrafish, a genetically accessible vertebrate with an externally developing, optically clear embryo, is ideally suited for in vivo functional dissection of the embryonic development of the circulatory system. Here, we review the advantages of the zebrafish as a model system for studying vascular development, and describe genetic and experimental tools, methods and resources that have been developed to exploit these advantages. We also discuss briefly how some of these tools and methods can be brought to bear on problems of relevance to human health. (Trends Cardiovasc Med 2000;10:352-360). (C) 2001, Elsevier Science Inc. C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Weinstein, BM (reprint author), NICHD, Genet Mol Lab, NIH, Bldg 6B,Room 309,6 Ctr Dr, Bethesda, MD 20892 USA. NR 59 TC 27 Z9 28 U1 0 U2 10 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD NOV PY 2000 VL 10 IS 8 BP 352 EP 360 DI 10.1016/S1050-1738(01)00068-8 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 432LT UT WOS:000168693800006 PM 11369262 ER PT J AU Aravind, L AF Aravind, L TI Exploring histones and their relatives with the Histone Sequence Database SO TRENDS IN GENETICS LA English DT Editorial Material C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD NOV PY 2000 VL 16 IS 11 BP 517 EP 518 DI 10.1016/S0168-9525(00)02115-6 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 370LL UT WOS:000165124500010 PM 11203386 ER PT J AU Mattson, MP AF Mattson, MP TI Creatine: prescription for bad genes and a hostile environment? SO TRENDS IN NEUROSCIENCES LA English DT Article C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 3 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 2000 VL 23 IS 11 BP 511 EP 511 DI 10.1016/S0166-2236(00)01697-0 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 373BG UT WOS:000165268100003 ER PT J AU Feneley, MR Landis, P Simon, I Metter, EJ Morrell, CH Carter, HB Walsh, PC AF Feneley, MR Landis, P Simon, I Metter, EJ Morrell, CH Carter, HB Walsh, PC TI Today men with prostate cancer have larger prostates SO UROLOGY LA English DT Article ID HYPERPLASIA; VOLUME AB Objectives. To examine the relationship between prostate size and the method of cancer detection in men with organ-confined prostate cancer, and compare prostate size in men with and without cancer. Methods. Prostate volume was evaluated in 720 men who had undergone radical prostatectomy for Stage Tie or Stage T2 cancer. Men with Stage T2 cancer were divided into those treated before 1989 (when widespread prostate-specific antigen [PSA] testing began), or not. Gland volume was also examined in 265 men participating in the Baltimore Longitudinal Study of Aging who had no clinical evidence of cancer. Volumes were compared using linear regression to allow for age. Results. Prostate volume in men with Stage Tie cancer was statistically significantly larger than in men with Stage T2 cancer diagnosed in the pre-PSA era after adjusting for age (P = 0.0001), and statistically significantly larger than in men without cancer above age 47 years based on 95% confidence intervals. Prostate volumes in men with Stage T2 cancer diagnosed in the pre-PSA era and in men without cancer were not statistically significantly different. Conclusions. Prostate volume in men with PSA-detected, organ-confined cancer is larger than in men with palpable organ-confined cancer diagnosed in either the pre-PSA era or PSA era. These discrepancies may reflect a diagnostic bias due to the effect of benign prostatic hyperplasia on serum PSA that results in the selection of men with larger prostates for biopsy. UROLOGY 56: 839-842, 2000. (C) 2000, Elsevier Science Inc. C1 Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Loyola Coll, Dept Math Sci, Baltimore, MD 21210 USA. RP Carter, HB (reprint author), Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Marburg 403,600 N Wolfe St, Baltimore, MD 21287 USA. NR 7 TC 22 Z9 22 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD NOV PY 2000 VL 56 IS 5 BP 839 EP 842 DI 10.1016/S0090-4295(00)00738-X PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 375LK UT WOS:000165400700028 PM 11068313 ER PT J AU Varma, A Kwon-Chung, KJ AF Varma, A Kwon-Chung, KJ TI Characterization of the L4I gene in Cryptococcus neoformans: its application as a selectable transformation marker for cycloheximide resistance SO YEAST LA English DT Article DE transformation; cycloheximide; Cryptococcus neoformans; selection marker ID RIBOSOMAL DNA; VIRULENCE; CONSTRUCTION; PROMOTER; YEAST AB A transformation system using resistance to the antibiotic cycloheximide as a dominant selectable marker was developed for the pathogenic yeast Cryptococcus neoformans. A 3.5 kb DNA fragment containing a gene encoding the ribosomal protein L41 was cloned from a wild-type strain of C, neoformans which is sensitive to cycloheximide. The open reading frame of the L41 gene contains five introns and encodes a protein of 107 amino acids, which is similar to those reported for other yeasts. The cycloheximide resistance gene to be used as a marker was constructed by replacing a DNA segment of the mild-type L41 gene, which contained the amino acid proline at its 56th position with a homologous DNA segment from a mutant strain resistant to cycloheximide that contained leucine in that position. Cycloheximide resistant transformants were obtained by electroporation on YEPD plates, supplemented with 10-20 mug/ml cycloheximide, at a maximum efficiency of 300 transformants/mug plasmid DNA, While with other genes, most transformants of serotype D in C. neoformans maintain the transforming DNA as episomes, the cycloheximide-resistant transformants were all the result of ectopic genomic integration events. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 NIAID, Mol Microbiol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. NR 17 TC 6 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD NOV PY 2000 VL 16 IS 15 BP 1397 EP 1403 DI 10.1002/1097-0061(200011)16:15<1397::AID-YEA636>3.0.CO;2-1 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 381UB UT WOS:000165780900005 PM 11054820 ER PT J AU Camitta, MG Bradbury, JA Gabel, SA Langenbach, R Zeldin, DC Murphy, E AF Camitta, MG Bradbury, JA Gabel, SA Langenbach, R Zeldin, DC Murphy, E TI Cyclooxygenase-1 and-2 knockout mice show increased ischemic injury, but improved recovery after preconditioning SO CIRCULATION LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. NIEHS, NIH, Res Triangle Pk, NC 27709 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 14 BP 5 EP 5 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300015 ER PT J AU Cross, HR Murphy, E Black, RG Auchampach, J Steenbergen, C AF Cross, HR Murphy, E Black, RG Auchampach, J Steenbergen, C TI Overexpression of the cardiac A3 adenosine receptor (A3r) protects the ischemic heart SO CIRCULATION LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Univ Louisville, Louisville, KY 40292 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 16 BP 6 EP 6 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300017 ER PT J AU Wang, SQ Song, LS Lakatta, EG Cheng, H AF Wang, SQ Song, LS Lakatta, EG Cheng, H TI Calcium sparklets: Fundamental trigger events of cardiac excitation-contraction coupling SO CIRCULATION LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 17 BP 6 EP 6 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300018 ER PT J AU Gaussin, V Van de Putte, T Mishina, Y Zwijsen, A Huylebroeck, D Behringer, RR Schneider, MD AF Gaussin, V Van de Putte, T Mishina, Y Zwijsen, A Huylebroeck, D Behringer, RR Schneider, MD TI Cardiac-specific deletion of ALK3, the type IA receptor for bone morphogenetic proteins, unmasks an essential, myocyte-autonomous role in the mid-gestation heart SO CIRCULATION LA English DT Meeting Abstract C1 Penn State Univ, Danville, PA USA. Univ Louvain, Louvain, Belgium. NIEHS, NIH, Durham, NC USA. MD Anderson Canc Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 60 BP 15 EP 15 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300061 ER PT J AU Chen, W Srinivasan, SR Hallman, MD Elkasabany, AM Boerwinkle, E Ellsworth, D Berenson, GS AF Chen, W Srinivasan, SR Hallman, MD Elkasabany, AM Boerwinkle, E Ellsworth, D Berenson, GS TI Influence of lipoprotein lipase serine 447 stop polymorphism on tracking of triglycerides and HDL cholesterol from childhood to adulthood and familial risk of coronary artery disease: The Bogalusa Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Tulane Univ, Med Ctr, New Orleans, LA USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 133 BP 31 EP 31 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300134 ER PT J AU Hu, QH Yu, ZX Ferrans, VJ Takeda, K Irani, K Zlegelstein, RC AF Hu, QH Yu, ZX Ferrans, VJ Takeda, K Irani, K Zlegelstein, RC TI NADPH oxidase-stimulated intracellular ROS play an important role in histamine-stimulated Ca2+ oscillations in human endothelial cells SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 158 BP 36 EP 36 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300158 ER PT J AU Angkeow, P Deshpande, SS Ozaki, M Finkel, T Irani, K AF Angkeow, P Deshpande, SS Ozaki, M Finkel, T Irani, K TI Redox factor-1 suppresses hypoxia-reoxygenation-induced oxidative stress in human vascular endothelial SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 181 BP 40 EP 40 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300181 ER PT J AU Weiss, CR Arai, AE Bui, M Balaban, RS Cannon, RO AF Weiss, CR Arai, AE Bui, M Balaban, RS Cannon, RO TI Evidence of arterial wall inflammation in humans by MRI SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NIH, NHLBI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 192 BP 42 EP 42 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300192 ER PT J AU Amar, M Knapper, C Fruchart-Najib, J Paigen, B Lab, J Wood, D Paiz, J Brewer, HB Santamarina-Fojo, S AF Amar, M Knapper, C Fruchart-Najib, J Paigen, B Lab, J Wood, D Paiz, J Brewer, HB Santamarina-Fojo, S TI Pro-atherogenic role of hepatic lipase in the development of murine atherosclerosis SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Inst Pasteur, F-59019 Lille, France. Jackson Lab, Bar Harbor, ME 04609 USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 206 BP 45 EP 45 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300206 ER PT J AU Lambert, G Sakai, N Striker, GE Francois, TL Vaisman, BL Paigen, B Najib-Fruchart, J Csako, G Neufeld, EB Peterson, KM Brewer, HB Santamarina-Fojo, S AF Lambert, G Sakai, N Striker, GE Francois, TL Vaisman, BL Paigen, B Najib-Fruchart, J Csako, G Neufeld, EB Peterson, KM Brewer, HB Santamarina-Fojo, S TI LCAT deficiency protects against atherosclerosis in mouse models SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Miami, FL USA. Jackson Lab, Bar Harbor, ME 04609 USA. Inst Pasteur, F-59019 Lille, France. NIH, Bethesda, MD 20892 USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 209 BP 46 EP 46 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300209 ER PT J AU Shamburek, RD Nong, ZY Fyfe, JC Hoyt, RF Brewer, HB AF Shamburek, RD Nong, ZY Fyfe, JC Hoyt, RF Brewer, HB TI Renal HDL catabolism: Roles of cubilin and megalin receptors in ApoA-I catabolism in the canine cubilin dysfunctional animal model SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Michigan State Univ, E Lansing, MI 48824 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 213 BP 46 EP 46 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300213 ER PT J AU Speir, E Yu, ZX Takeda, K Ferrans, VJ Cannon, RO AF Speir, E Yu, ZX Takeda, K Ferrans, VJ Cannon, RO TI Reciprocal transcriptional repression of estrogen receptors and p65/RelA is regulated by the p300 integrator. SO CIRCULATION LA English DT Meeting Abstract C1 NIH, 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 242 BP 52 EP 52 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300242 ER PT J AU Burnett, MS Gaydos, CA Madico, GE Paigen, B Quinn, TC Epstein, SE AF Burnett, MS Gaydos, CA Madico, GE Paigen, B Quinn, TC Epstein, SE TI Atherosclerosis in ApoE knockout mice infected with multiple pathogens SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Washington Hosp Ctr, Washington, DC 20010 USA. RI Gaydos, Charlotte/E-9937-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 247 BP 53 EP 53 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300247 ER PT J AU Prasad, A Zhu, JH Halcox, JPJ Mincemoyer, R Schenke, WH Zalos, G Waclawiw, MA Epstein, SE Quyyumi, AA AF Prasad, A Zhu, JH Halcox, JPJ Mincemoyer, R Schenke, WH Zalos, G Waclawiw, MA Epstein, SE Quyyumi, AA TI Relation between infections and endothelial dysfunction SO CIRCULATION LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD 20892 USA. Washington Hosp Ctr, Washington, DC 20010 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 245 BP 53 EP 53 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300245 ER PT J AU Desantis, P Babauglu, MO Pezzullo, JC Abernethy, DR Freedman, JE AF Desantis, P Babauglu, MO Pezzullo, JC Abernethy, DR Freedman, JE TI Impaired production of platelet-derived nitric oxide in human subjects with a polymorphic variant of endothelial nitric oxide synthase SO CIRCULATION LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NIH, NIA, Baltimore, MD USA. NR 0 TC 0 Z9 1 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 289 BP 61 EP 61 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300289 ER PT J AU Halcox, JPJ Chaudhury, PP Prasad, A Waclawiw, MA Mincemoyer, R Epstein, NE Moss, J Quyyumi, AA AF Halcox, JPJ Chaudhury, PP Prasad, A Waclawiw, MA Mincemoyer, R Epstein, NE Moss, J Quyyumi, AA TI Effect of the Glu298asp missense mutation of the endothelial nitric oxide synthase gene on human coronary microvascular function. SO CIRCULATION LA English DT Meeting Abstract C1 NIH, NHLBI, Rockville, MD USA. NIH, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 290 BP 62 EP 62 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300290 ER PT J AU Cross, HR Steenbergen, C Kranias, EG Murphy, E AF Cross, HR Steenbergen, C Kranias, EG Murphy, E TI Role of nitric oxide in protection from myocardial ischemic injury in female phospholamban (PLB) knock-out mice SO CIRCULATION LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. Univ Cincinnati, Cincinnati, OH USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 441 BP 93 EP 93 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300440 ER PT J AU Cross, HR Murphy, E Lefkowitz, RJ Steenbergen, C AF Cross, HR Murphy, E Lefkowitz, RJ Steenbergen, C TI Role of nitric oxide synthase (NOS) in protection from myocardial ischemic injury in female, vs. male, beta(2)-adrenergic receptor (beta(2)AR) overexpressor mice SO CIRCULATION LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 444 BP 94 EP 94 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300443 ER PT J AU Ouyang, P Kelemen, MD Younes, N Livengood, S Verter, JI Thompson, PD Cobb, FR Gordon, DJ AF Ouyang, P Kelemen, MD Younes, N Livengood, S Verter, JI Thompson, PD Cobb, FR Gordon, DJ CA WAVE Investigators TI Effect of risk factors on brachial endothelial vasodilator function in women with established coronary disease: A substudy of the Women's Angiographic Vitamins and Estrogen (WAVE) trial SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. George Washington Univ, Washington, DC USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Hartford Hosp, Hartford, CT 06115 USA. Duke Univ, Med Ctr, Durham, NC USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 511 BP 107 EP 107 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300510 ER PT J AU Merz, CNB Johnson, BD Sharaf, BL Pauley, D Reis, SE Reichek, N Rogers, WJ Kelsey, SF Pohost, GM Sopko, G AF Merz, CNB Johnson, BD Sharaf, BL Pauley, D Reis, SE Reichek, N Rogers, WJ Kelsey, SF Pohost, GM Sopko, G TI Migraine headaches, angina and CAD in women: The NHLBI-sponsored WISE study SO CIRCULATION LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Pittsburgh, Pittsburgh, PA USA. Rhode Isl Hosp, Providence, RI 02903 USA. Univ Florida, Gainesville, FL USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Alabama, Birmingham, AL USA. NHLBI, NIH, Bethesda, MD 20892 USA. RI Reis, Steven/J-3957-2014 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 515 BP 108 EP 108 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300514 ER PT J AU Paniagua, OA Bryant, MB Panza, JA AF Paniagua, OA Bryant, MB Panza, JA TI Impaired role of nitric oxide in the shear stress regulation of microvascular tone in patients with hypercholesterolemia SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 566 BP 118 EP 118 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300565 ER PT J AU Boheler, KR Brugh, SA Riordon, DR Koban, MU AF Boheler, KR Brugh, SA Riordon, DR Koban, MU TI Cardiac-restricted expression of the NCX1 gene promoter in transgenic mice SO CIRCULATION LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. Natl Heart & Lung Inst, London, England. 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 679 BP 140 EP 140 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300677 ER PT J AU Yang, HT Lakatta, EG Boheler, KR AF Yang, HT Lakatta, EG Boheler, KR TI Site-directed excision and replacement of a ryanodine receptor 2 (RyR2) gene exon in embryonic stem cells and differentiation in vitro to cardiac myocytes SO CIRCULATION LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 684 BP 141 EP 141 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300682 ER PT J AU Zhu, Y Yang, HT Boheler, KR AF Zhu, Y Yang, HT Boheler, KR TI Identification of novel transcripts implicated in the progression to a senescent myocardium: Results from microarrays SO CIRCULATION LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 3 Z9 3 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 689 BP 142 EP 142 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300687 ER PT J AU Knollmann, S Casimiro, M Vary, J Pfeifer, K Ebert, SN AF Knollmann, S Casimiro, M Vary, J Pfeifer, K Ebert, SN TI Disruption of the KvLQT1 gene in mice produces a Long-QT phenotype SO CIRCULATION LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 732 BP 150 EP 151 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300730 ER PT J AU Tong, HY Steenbergen, C Murphy, E AF Tong, HY Steenbergen, C Murphy, E TI Phosphatidylinositol-3-kinase signals preconditioning via activation of PKC and NO SO CIRCULATION LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 744 BP 155 EP 155 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300742 ER PT J AU Roman, BB Montogomery, DG Del Nido, P Koretsky, AP Solaro, RJ Buttrick, PM AF Roman, BB Montogomery, DG Del Nido, P Koretsky, AP Solaro, RJ Buttrick, PM TI Targeted mutation of protein kinase C phosphorylation sites on cardiac troponin I (TnI) alters cardiac function in vivo SO CIRCULATION LA English DT Meeting Abstract C1 Univ Illinois, Chicago, IL USA. Harvard Univ, Sch Med, Boston, MA USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 767 BP 159 EP 160 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300765 ER PT J AU Paolocci, N Saavedra, FW Miranda, KM Espey, MG Isoda, T Wink, DA Kass, DA AF Paolocci, N Saavedra, FW Miranda, KM Espey, MG Isoda, T Wink, DA Kass, DA TI Novel and potent inotropic and selective venodilatory action of nitroxyl anion in intact dogs SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009 NR 0 TC 1 Z9 1 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 776 BP 161 EP 161 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300774 ER PT J AU Prinzen, FW Wyman, BT Hunter, WC Faris, OP McVeigh, ER AF Prinzen, FW Wyman, BT Hunter, WC Faris, OP McVeigh, ER TI Effects of single and bi-ventricular facing on the temporal and spatial dynamics of ventricular contraction SO CIRCULATION LA English DT Meeting Abstract C1 Maastricht Univ, Maastricht, Netherlands. Johns Hopkins Univ, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 777 BP 161 EP 162 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300775 ER PT J AU Goldmuntz, E Bamford, R Dela Cruz, J Roessler, E Muenke, M AF Goldmuntz, E Bamford, R Dela Cruz, J Roessler, E Muenke, M TI Mutations of the EGF-CFC gene, cryptic, in human transposition of the great arteries and double outlet right ventricle SO CIRCULATION LA English DT Meeting Abstract C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 781 BP 162 EP 162 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300779 ER PT J AU Zhu, WZ Zheng, M Ziman, B Kobilka, BK Xiao, RP AF Zhu, WZ Zheng, M Ziman, B Kobilka, BK Xiao, RP TI Switch beta(2)-adrenergic signaling from survival to apoptotic by inhibiting G(i beta gamma)-PI3K-AKT pathway in adult mouse cardiomyocytes SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Howard Hughes Med Inst, Stanford, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 806 BP 167 EP 167 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300804 ER PT J AU Gladwin, MT Shelhamer, JH Schechter, AN Pease-Fye, ME Waclawiw, MA Panza, JA Ognibene, FP Cannon, RO AF Gladwin, MT Shelhamer, JH Schechter, AN Pease-Fye, ME Waclawiw, MA Panza, JA Ognibene, FP Cannon, RO TI Role of circulating nitrite and S-nitrosohemoglobin in regulating regional vascular flow in man SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 831 BP 172 EP 173 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300829 ER PT J AU Kuramochi, T Zhou, YY Zhang, SJ Fedorova, OV Bagrov, AY Lakatta, EG Xiao, RP AF Kuramochi, T Zhou, YY Zhang, SJ Fedorova, OV Bagrov, AY Lakatta, EG Xiao, RP TI Negative contraction-frequency relation mediated by dysfunction of CaMKII in myocytes from failing rat hearts. SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 967 BP 199 EP 199 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300964 ER PT J AU Weiss, CR Aletras, AH London, JF Epstein, FH Taylor, JL Balaban, RS Arai, AE AF Weiss, CR Aletras, AH London, JF Epstein, FH Taylor, JL Balaban, RS Arai, AE TI Simultaneous differentiation of stunned, infarcted, and normal myocardium using magnetization transfer contrast enhanced cine MRI SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 996 BP 205 EP 205 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300993 ER PT J AU Koshimizu, TA Stojilkovic, SS AF Koshimizu, TA Stojilkovic, SS TI Contributions of the C-terminal domain to the control of P2X receptor desensitization SO CIRCULATION LA English DT Meeting Abstract C1 Yamanashi Med Univ, Yamanashi, Japan. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1003 BP 206 EP 206 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301000 ER PT J AU Liang, BT Jacobson, KA AF Liang, BT Jacobson, KA TI Efficiency of adenosine receptor coupling in cardioprotection: Efficacy of partial A1 and A3 agonists SO CIRCULATION LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 1005 BP 206 EP 207 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301002 ER PT J AU Chesley, A Neuss, M Monticone, R Crow, MT AF Chesley, A Neuss, M Monticone, R Crow, MT TI Regulation of NF-kappa B activity by the muscle-specific repressor of apoptosis, ARC SO CIRCULATION LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. German Heart Inst, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1036 BP 214 EP 214 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301033 ER PT J AU Pyle, WG Koretsky, AP Del Nido, P De Tombe, PP Solaro, RJ AF Pyle, WG Koretsky, AP Del Nido, P De Tombe, PP Solaro, RJ TI Basal phosphorylation of cardiac troponin IS43/S45 reduces cross-bridge cycling. SO CIRCULATION LA English DT Meeting Abstract C1 Univ Illinois, Chicago, IL USA. NINDS, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 1039 BP 214 EP 214 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301036 ER PT J AU Macgowan, GA Du, CW Wieczorek, DF Koretsky, AP AF Macgowan, GA Du, CW Wieczorek, DF Koretsky, AP TI Effects of overexpression of beta-tropomyosin on calcium handling, energy expenditure and force-frequency relationships in isolated perfused mouse hearts SO CIRCULATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. Univ Cincinnati, Cincinnati, OH USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1043 BP 215 EP 215 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301040 ER PT J AU Nozaki, N Nemoto, S Defreitas, G Engel, DJ Baumgarten, G Sivasubramanian, N Carballo, E Blackshear, PJ Carabello, BA Mann, DL AF Nozaki, N Nemoto, S Defreitas, G Engel, DJ Baumgarten, G Sivasubramanian, N Carballo, E Blackshear, PJ Carabello, BA Mann, DL TI Hemodynamic overload induced myocardial cytokine gene regulation occurs through a novel mechanism that involves tristetraprolin SO CIRCULATION LA English DT Meeting Abstract C1 Winters Ctr Heart Failure Res, Houston, TX USA. Houston VAMC, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1081 BP 223 EP 223 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301078 ER PT J AU Brandes, RP Miller, FJ Holland, SM Busse, R Goriach, A AF Brandes, RP Miller, FJ Holland, SM Busse, R Goriach, A TI The NADPH oxidase subunit p47phox contributes to vascular superoxide anion generation SO CIRCULATION LA English DT Meeting Abstract C1 Univ Hosp Frankfurt Main, Frankfurt Main, Germany. Univ Iowa, Iowa City, IA USA. NIH, Bethesda, MD 20892 USA. Univ Frankfurt Hosp, Frankfurt, Germany. RI Miller Jr, Francis/N-7312-2015; Miller, Francis/F-3801-2017 OI Miller Jr, Francis/0000-0001-5822-0549; Miller, Francis/0000-0001-5822-0549 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 1133 BP 233 EP 233 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301129 ER PT J AU Sharma, A Halcox, JPJ Prasad, A Sartorius, C Epstein, NE Quyyumi, AA AF Sharma, A Halcox, JPJ Prasad, A Sartorius, C Epstein, NE Quyyumi, AA TI Influence of bradykinin B-2 receptor polymorphism on the prevalence of coronary atherosclerosis, hypertension, and vascular function SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1196 BP 245 EP 245 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301192 ER PT J AU Halcox, JPJ Nour, KA Sharma, A Zalos, G Quyyumi, AA AF Halcox, JPJ Nour, KA Sharma, A Zalos, G Quyyumi, AA TI Sildenafil and human coronary vascular function SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 1245 BP 254 EP 254 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301240 ER PT J AU O'Donnell, CJ Larson, MG Cupples, LA Feng, D Caunt, D D'Agostino, RB Myers, RH Tofler, GH AF O'Donnell, CJ Larson, MG Cupples, LA Feng, D Caunt, D D'Agostino, RB Myers, RH Tofler, GH TI A genome-wide scan for circulating levels of plasminogen activator inhibitor-1 and tissue plasminogen activator in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02118 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 1260 BP 257 EP 257 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301255 ER PT J AU Larson, MG O'Donnell, CJ Cupples, LA Feng, D Caunt, D D'Agostino, RB Myers, RH Tofler, GH AF Larson, MG O'Donnell, CJ Cupples, LA Feng, D Caunt, D D'Agostino, RB Myers, RH Tofler, GH TI Evidence for a gene on chromosome 10 influencing factor VII levels: A genome-wide scan in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02118 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 1268 BP 259 EP 259 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301263 ER PT J AU Patel, SB Lee, MH Gordon, D Ott, J Kojima, H Kwiterowich, P Brownstein, MJ Salen, G Ose, L Mietinnen, TA Pegoraro, R Hidaka, H AF Patel, SB Lee, MH Gordon, D Ott, J Kojima, H Kwiterowich, P Brownstein, MJ Salen, G Ose, L Mietinnen, TA Pegoraro, R Hidaka, H TI Fine mapping and genetic analyses of sitosterolemia: Founder effects in at least two geographic areas SO CIRCULATION LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Rockefeller Univ, New York, NY 10021 USA. Shiga Univ Med Sci, Shiga, Japan. Johns Hopkins Univ, Baltimore, MD USA. NHGRI, NIMH, Bethesda, MD 20892 USA. UMDNJ, Newark, NJ USA. Univ Oslo, Rikshosp, N-0027 Oslo, Norway. Univ Helsinki, Helsinki, Finland. Univ Natal, ZA-4001 Durban, South Africa. Sanyo Elect Co Ltd, Tokyo, Japan. 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 1357 BP 277 EP 277 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301352 ER PT J AU Paolocci, N Saavedra, FW Gluzband, YA Stein, L Hejazi, M Isoda, T Kass, DA AF Paolocci, N Saavedra, FW Gluzband, YA Stein, L Hejazi, M Isoda, T Kass, DA TI Metalloproteinase (MMP) enzyme inhibition prevents synergistic diastolic stiffening and MMP expression by angiotensin-II and evolving cardiac failure SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 1426 BP 291 EP 291 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301420 ER PT J AU Iso, T Hamamori, Y Sartorelli, V Kedes, LH AF Iso, T Hamamori, Y Sartorelli, V Kedes, LH TI The HERP repressors, novel partners for HES/hairy in Notch signaling SO CIRCULATION LA English DT Meeting Abstract C1 Univ So Calif, Los Angeles, CA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1442 BP 294 EP 295 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301436 ER PT J AU Ohtani, S Lundberg, MS Monticone, R Crow, MT AF Ohtani, S Lundberg, MS Monticone, R Crow, MT TI The differential sensitivity of medial and neointimal vascular smooth muscle cells (VSMCs) to apoptosis is linked to the muscle-specific repressor of apoptosis, ARC SO CIRCULATION LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1496 BP 305 EP 306 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301491 ER PT J AU Yang, XP Freeman, L Peterson, KM Knapper, C Remaley, A Francois, TL Blackmon, E Duverger, N Denefle, P Brewer, HB Santamarina-Fojo, S AF Yang, XP Freeman, L Peterson, KM Knapper, C Remaley, A Francois, TL Blackmon, E Duverger, N Denefle, P Brewer, HB Santamarina-Fojo, S TI The human ABCA1 gene and promoter: Regulation of human ABCA1 gene expression by cholesterol SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, MDB, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Aventis, Evry, France. NR 0 TC 2 Z9 2 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 1521 BP 310 EP 310 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301516 ER PT J AU Chinetti, G Lestavel, S Remaley, A Neve, B Torra, IP Minnich, A Jaye, M Duverger, N Brewer, HB Fruchart, JC Clavey, V Staels, B AF Chinetti, G Lestavel, S Remaley, A Neve, B Torra, IP Minnich, A Jaye, M Duverger, N Brewer, HB Fruchart, JC Clavey, V Staels, B TI PPAR alpha and PPAR gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABC-1 pathway. SO CIRCULATION LA English DT Meeting Abstract C1 Inst Pasteur, F-59019 Lille, France. NHLBI, MDB, NIH, Bethesda, MD 20892 USA. Aventis, Vitry Sur Seine, France. NHLBI, NIH, Bethesda, MD 20892 USA. RI Neve, B/J-6008-2014; Staels, Bart/N-9497-2016; chinetti, giulia/Q-6901-2016; Lestavel, Sophie/B-4658-2017 OI Staels, Bart/0000-0002-3784-1503; chinetti, giulia/0000-0001-8048-8138; Lestavel, Sophie/0000-0001-7839-4757 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1524 BP 311 EP 311 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301519 ER PT J AU Ito, T Sabol, SL Amar, M Knapper, C Duarte, C Shamburek, RD Meyn, S Santamarina-Fojo, S Brewer, HB AF Ito, T Sabol, SL Amar, M Knapper, C Duarte, C Shamburek, RD Meyn, S Santamarina-Fojo, S Brewer, HB TI Adenovirus-mediated expression establishes an in vivo role for human ABCG1 (ABC8) in lipoprotein metabolism SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 1525 BP 311 EP 311 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301520 ER PT J AU Neufeld, EB Remaley, A Demosky, S Stonik, J Cooney, AM Santamarina-Fojo, S Blanchette-Mackie, J Brewer, HB AF Neufeld, EB Remaley, A Demosky, S Stonik, J Cooney, AM Santamarina-Fojo, S Blanchette-Mackie, J Brewer, HB TI Cellular localization and trafficking of human ABCA1 SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Cell Biochem & Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1527 BP 311 EP 312 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301522 ER PT J AU Hodgin, JB Krege, JH Korach, KS Smithies, O Maeda, N AF Hodgin, JB Krege, JH Korach, KS Smithies, O Maeda, N TI Estrogen receptor alpha is required for estrogen's inhibitory effect on atherosclerosis in ApoE -/- mice SO CIRCULATION LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. NIEHS, NIH, Res Triangle Pk, NC 27709 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 1561 BP 318 EP 318 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301556 ER PT J AU Zuzak, KJ Schaeberle, MD Gladwin, MT Cannon, RO Levin, IW AF Zuzak, KJ Schaeberle, MD Gladwin, MT Cannon, RO Levin, IW TI Noninvasive measurement of tissue oxygenation using visible reflectance hyperspectral imaging before and during nitric oxide synthase inhibition. SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1628 BP 332 EP 332 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301623 ER PT J AU Bogdanov, K Vinogradova, T Cheng, H Lakatta, EG AF Bogdanov, K Vinogradova, T Cheng, H Lakatta, EG TI Acceleration of beating rate in rabbit sino-atrial node cells by sympathetic stimulation is mediated via enhanced Ca2+ release from ryanodine receptors. SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1648 BP 336 EP 336 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301643 ER PT J AU Combs, CA Balaban, RS AF Combs, CA Balaban, RS TI High-resolution imaging of dehydrogenase activity within living ventricular myocytes using fluorescence photobleaching recovery SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1695 BP 345 EP 345 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301690 ER PT J AU Territo, PR French, SA Evans, FJ Balaban, RS AF Territo, PR French, SA Evans, FJ Balaban, RS TI Rapid kinetic relationship between NADH and mV02: Evidence for non-equilibrium kinetic control of oxidative phosphorylation. SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1691 BP 345 EP 345 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301686 ER PT J AU Territo, PR Smith, MF Rettmann, DW Taylor, JL Szajek, LP Bacharach, SL Eckelman, WC Piwinica-Worms, DF Dilsizian, V Balaban, RS AF Territo, PR Smith, MF Rettmann, DW Taylor, JL Szajek, LP Bacharach, SL Eckelman, WC Piwinica-Worms, DF Dilsizian, V Balaban, RS TI Tc-94m-SESTAMIBI as a steady-state probe for cardiac mitochondrial membrane potential, in vivo: Effect of workload and partial uncoupling. SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Washington Univ, St Louis, MO USA. NHLBI, NIH, Bethesda, MD 20892 USA. RI Rettmann, Dan/G-5265-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1967 BP 404 EP 404 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301962 ER PT J AU Exner, DV Dries, DL Domanski, MJ Konstam, MA Quinones, MA Greenberg, B AF Exner, DV Dries, DL Domanski, MJ Konstam, MA Quinones, MA Greenberg, B TI Prognostic value of a central, core laboratory, left ventricular ejection fraction measurement over routinely-determined values: Implications for future cardiovascular clinical trials. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. New England Med Ctr, Boston, MA 02111 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Calif San Diego, San Diego, CA 92103 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2003 BP 412 EP 412 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301998 ER PT J AU Epstein, AE Vidiallet, HJ Greene, HL Simmons, T AF Epstein, AE Vidiallet, HJ Greene, HL Simmons, T CA AFFIRM Investigators TI Characterization of patients with various frequencies of atrial fibrillation in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study SO CIRCULATION LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. Axio Res Corp, Seattle, WA USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2152 BP 442 EP 442 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302147 ER PT J AU Meltser, HM Laurienzo, JM Curiel, RV Panza, JA AF Meltser, HM Laurienzo, JM Curiel, RV Panza, JA TI Diminished contractile reserve at baseline is associated with the need for valve replacement during follow-up in asymptomatic patients with chronic severe aortic regurgitation SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2169 BP 446 EP 446 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302164 ER PT J AU Gardin, JM Weissman, NJ Leung, CY Panza, JA Fernicola, D Davis, KD Constantine, G Reid, CL AF Gardin, JM Weissman, NJ Leung, CY Panza, JA Fernicola, D Davis, KD Constantine, G Reid, CL TI One year echocardiographic follow-up of patients previously treated with phentermine-fenfluramine or dexfenfluramine SO CIRCULATION LA English DT Meeting Abstract C1 Univ Calif Irvine, Irvine, CA USA. Washington Hosp Ctr, Washington, DC 20010 USA. NIH, NHLBI, Bethesda, MD 20892 USA. VA Med Ctr, Washington, DC USA. Wyeth Ayerst Res, Philadelphia, PA 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2302 BP 474 EP 474 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302296 ER PT J AU Sitges, M Jones, M Shiota, T Prior, DL Tsujino, H Cardon, LA Zetts, AD Garcia, MJ Thomas, JD AF Sitges, M Jones, M Shiota, T Prior, DL Tsujino, H Cardon, LA Zetts, AD Garcia, MJ Thomas, JD TI Interaliasing distance of the flow convergence surface for determining mitral regurgitant volume: A validation study in a chronic animal model. SO CIRCULATION LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. NHLBI, LAMS, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2304 BP 474 EP 474 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302298 ER PT J AU Kwong, RY Schussheim, AE London, JF Davis, J Balaban, RS Arai, AE AF Kwong, RY Schussheim, AE London, JF Davis, J Balaban, RS Arai, AE TI Pilot study of MRI to evaluate chest pain compatible with myocardial ischemia SO CIRCULATION LA English DT Meeting Abstract C1 NIH, 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2363 BP 486 EP 486 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302357 ER PT J AU Aletras, AH Wen, H Kwong, RY Arai, AE AF Aletras, AH Wen, H Kwong, RY Arai, AE TI Strain analysis of human MI using dual-echo DENSE: An automated quantitative MRI method SO CIRCULATION LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2368 BP 487 EP 487 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302362 ER PT J AU Schussheim, AE Kwong, RY London, JF Davis, J Balaban, RS Arai, AE AF Schussheim, AE Kwong, RY London, JF Davis, J Balaban, RS Arai, AE TI MRI can triage low and medium risk patients with chest pain: Prospective evaluation of cardiac magnetic resonance imaging in the emergency room SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2372 BP 488 EP 488 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302366 ER PT J AU Okin, PM Fabsitz, RR Lee, ET Galloway, JM Howard, BV AF Okin, PM Fabsitz, RR Lee, ET Galloway, JM Howard, BV TI Principal component analysis of T-wave improves prediction of cardiovascular mortality in men and women compared with QT dispersion: The Strong Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Cornell Univ, Weill Med Coll, New York, NY USA. NIH, NHLBI, Bethesda, MD 20892 USA. Univ Oklahoma, Oklahoma City, OK USA. Univ Arizona, Tucson, AZ USA. Med Res Inst, Washington, DC USA. NR 0 TC 1 Z9 1 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2394 BP 492 EP 493 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302388 ER PT J AU Exner, DV Dries, DL McAreavey, D Domanski, MJ Singh, SN AF Exner, DV Dries, DL McAreavey, D Domanski, MJ Singh, SN TI Coronary bypass graft surgery is associated with a reduced risk of sudden death, independent of the severity of ventricular dysfunction. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Washington Vet Hosp, Washington, DC 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2440 BP 502 EP 502 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302434 ER PT J AU Jenkins, LS Eleanor, S Brodsky, M Mateski, D Chung, MK Rocco, TA Mikel, M AF Jenkins, LS Eleanor, S Brodsky, M Mateski, D Chung, MK Rocco, TA Mikel, M CA AFFIRM Investigators TI Quality of life in patients with atrial fibrillation: Baseline data from AFFIRM SO CIRCULATION LA English DT Meeting Abstract C1 Univ Maryland, Baltimore, MD 21201 USA. NIH, NHLBI, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Axio Res Corp, Seattle, WA USA. NR 0 TC 4 Z9 4 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2488 BP 512 EP 512 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302482 ER PT J AU Bagrov, AY Fridman, AI Matveev, SA Agalakova, NI Fedorova, OV Lakatta, EG AF Bagrov, AY Fridman, AI Matveev, SA Agalakova, NI Fedorova, OV Lakatta, EG TI Marinobufagenin, an endogenous ligand of ouabain-resistant alpha-1 Na/K ATPase and a novel natriuretic factor is a marker of heart failure severity SO CIRCULATION LA English DT Meeting Abstract C1 NIH, NIA, GRC, Baltimore, MD USA. SM Kirov Mil Med Acad, St Petersburg, Russia. NIH, NIA, Baltimore, MD USA. NIH, NIA, Gerontol Res Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2509 BP 516 EP 516 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302503 ER PT J AU Scuteri, A Stuehlinger, MC Cooke, JP Fleg, JL Anderson, DE AF Scuteri, A Stuehlinger, MC Cooke, JP Fleg, JL Anderson, DE TI Asymmetric dimethylarginine plasma concentrations correlate with blood pressure response to salt loading in normotensive postmenopausal women SO CIRCULATION LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. Stanford Univ, Sch Med, Stanford, CA 94305 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2516 BP 517 EP 518 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302510 ER PT J AU Bittner, V Johnson, BD Merz, CNB Pauly, DF Reis, SE Reichek, N Pohost, GM Sharaf, BL Kelsey, SF Stylianou, M Sopko, G AF Bittner, V Johnson, BD Merz, CNB Pauly, DF Reis, SE Reichek, N Pohost, GM Sharaf, BL Kelsey, SF Stylianou, M Sopko, G TI Challenges in diagnosing CAD in women SO CIRCULATION LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Univ Pittsburgh, Pittsburgh, PA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Florida, Gainesville, FL USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Rhode Isl Hosp, Providence, RI USA. NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RI Reis, Steven/J-3957-2014 NR 0 TC 1 Z9 1 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2649 BP 545 EP 545 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302643 ER PT J AU Sachdev, V Meltser, HM Freidlin, RZ Stine, AM Laurienzo, JM Panza, JA AF Sachdev, V Meltser, HM Freidlin, RZ Stine, AM Laurienzo, JM Panza, JA TI Quantitative assessment of wall motion abnormalities in patients with acute myocardial infarction using real-time 3-dimensional echocardiography SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2780 BP 563 EP 563 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302724 ER PT J AU Katz, RJ Mak, IT Zhu, JH Csako, G Quyyumi, AA Borum, M Wasserman, AG AF Katz, RJ Mak, IT Zhu, JH Csako, G Quyyumi, AA Borum, M Wasserman, AG TI Coronary calcification, inflammation and prooxidant stress SO CIRCULATION LA English DT Meeting Abstract C1 George Washington Univ, Washington, DC USA. Washington Hosp Ctr, Washington, DC 20010 USA. NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2796 BP 577 EP 577 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302790 ER PT J AU Kitsiou, AN Bacharach, SL Miller-Davis, C Dilsizian, V AF Kitsiou, AN Bacharach, SL Miller-Davis, C Dilsizian, V TI Myocardial blood flow in reversible chronic left ventricular dysfunction SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2805 BP 578 EP 579 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302799 ER PT J AU Benjamin, EJ McNamara, RL Ding, JZ Arnett, DK Liebson, PR Tyroler, HA Cooper, LS Taylor, H Hutchinson, RG Skelton, TN AF Benjamin, EJ McNamara, RL Ding, JZ Arnett, DK Liebson, PR Tyroler, HA Cooper, LS Taylor, H Hutchinson, RG Skelton, TN TI Left ventricular mass and prevalent MRI cerebrovascular disease in an African American cohort: The ARIC study SO CIRCULATION LA English DT Meeting Abstract C1 Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Johns Hopkins Univ, Baltimore, MD USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. Univ Minnesota, Minneapolis, MN USA. Rush Med Coll, Chicago, IL 60612 USA. Univ N Carolina, Chapel Hill, NC USA. NHLBI, NIH, Bethesda, MD USA. Univ Mississippi, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. NR 0 TC 1 Z9 1 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2841 BP 586 EP 586 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302835 ER PT J AU Exner, DV Dries, DL Domanski, MJ Cohn, JN AF Exner, DV Dries, DL Domanski, MJ Cohn, JN TI Enalapril therapy and outcome in black versus white patients enrolled in the studies of left ventricular dysfunction. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2873 BP 592 EP 593 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302866 ER PT J AU Fleg, JL Bos, AG Brant, LH O'Connor, FC Talbot, LA Wright, JG Lakatta, EG AF Fleg, JL Bos, AG Brant, LH O'Connor, FC Talbot, LA Wright, JG Lakatta, EG TI Longitudinal decline of aerobic capacity accelerates with age SO CIRCULATION LA English DT Meeting Abstract C1 NIANIH, Baltimore, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIH, NIA, Gerontol Res Ctr, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2918 BP 602 EP + PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302910 ER PT J AU Schulman, SP Gerstenblith, G Fleg, JL O'Connor, FC Zieman, SN Lakatta, EG AF Schulman, SP Gerstenblith, G Fleg, JL O'Connor, FC Zieman, SN Lakatta, EG TI Relationship of age and sex on ventricular vascular coupling at rest and exercise. SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. NIANIH, Baltimore, MD USA. NIH, NIA, Gerontol Res Ctr, Baltimore, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2920 BP 602 EP 602 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302912 ER PT J AU Bittner, V Johnson, BD Merz, CNB Reis, SE Reichek, N Pohost, GM Sharaf, BL Kelsey, SF Stylianou, M Sopko, G AF Bittner, V Johnson, BD Merz, CNB Reis, SE Reichek, N Pohost, GM Sharaf, BL Kelsey, SF Stylianou, M Sopko, G TI Impact of serum estradiol levels and estrogen therapy on CAD prevalence SO CIRCULATION LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Univ Pittsburgh, Pittsburgh, PA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Rhode Isl Hosp, Providence, RI USA. NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RI Reis, Steven/J-3957-2014 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2960 BP 610 EP 611 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302952 ER PT J AU Davies, CH Lee, JS Jones, M Detmer, PR Li, XN Mack, G AF Davies, CH Lee, JS Jones, M Detmer, PR Li, XN Mack, G TI Quantification of aortic (Ao) regurgitant volumes using a 3-dimensional digital color Doppler method in a chronic animal model SO CIRCULATION LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NHLBI, LAMS, Bethesda, MD 20892 USA. ATL Ultrasound, Bothell, WA 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2957 BP 610 EP 610 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302949 ER PT J AU Ahmed, S Shapiro, EP O'Connor, FC Fleg, JL AF Ahmed, S Shapiro, EP O'Connor, FC Fleg, JL TI Is midwall left ventricular fractional shortening attenuated by normative aging? SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIH, Baltimore, MD USA. NIA, Baltimore, MD 21224 USA. GRC, Baltimore, MD USA. NIANIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3033 BP 625 EP 625 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303025 ER PT J AU Lowes, BD Gilbert, EM Lindenfeld, JA Zelis, R Domanski, MJ Eichhorn, EJ Krause-Steinrauf, H Bristow, MR AF Lowes, BD Gilbert, EM Lindenfeld, JA Zelis, R Domanski, MJ Eichhorn, EJ Krause-Steinrauf, H Bristow, MR TI Differential effects of beta-blocking agents on adrenergic activity. SO CIRCULATION LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. Penn State Univ, University Pk, PA 16802 USA. NIH, NHLBI, Bethesda, MD USA. RI bristow, michael/G-7850-2011 NR 0 TC 6 Z9 6 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 3048 BP 628 EP 629 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303040 ER PT J AU Sitges, M Shiota, T Tsujino, H Qin, JX Bauer, F Agler, DA Cardon, LA Panza, JA AF Sitges, M Shiota, T Tsujino, H Qin, JX Bauer, F Agler, DA Cardon, LA Panza, JA TI Real-time three-dimensional color-Doppler evaluation of the flow convergence surface for quantification of mitral regurgitation SO CIRCULATION LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3053 BP 629 EP 629 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303045 ER PT J AU Lee, JS Jones, M Zetts, AD Detmer, PR Li, XN Rusk, RA AF Lee, JS Jones, M Zetts, AD Detmer, PR Li, XN Rusk, RA TI Quantifying aortic regurgitation (AR) from aortic (Ao) and pulmonary (PA) stroke volumes using a 3-dimensional (3D) digital color Doppler method in a chronic animal model SO CIRCULATION LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NHLBI, LAMS, Bethesda, MD 20892 USA. ATL Ultrasound, Bothell, WA 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 3055 BP 630 EP + PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303047 ER PT J AU Li, XK Martin, SL Lennon, D Zetts, AD Li, XN Sahn, DJ AF Li, XK Martin, SL Lennon, D Zetts, AD Li, XN Sahn, DJ TI A semiautomated method for quantifying mitral regurgitation volume using an inter-aliasing distance method from digital color M-mode traces: An in vivo validation SO CIRCULATION LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. ATL Ultrasound, Bothell, WA USA. NHLBI, LAMS, 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 3056 BP 630 EP 630 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303048 ER PT J AU Wyse, DG AF Wyse, DG CA AFFIRM Investigators TI Baseline characteristics of patients with atrial fibrillation - The AFFIRM Study. SO CIRCULATION LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD 20892 USA. Univ Calgary, Calgary, AB, Canada. NR 0 TC 1 Z9 1 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 3246 BP 671 EP 671 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303238 ER PT J AU Page, RL Zipes, DP Powell, JL Luceri, RM Gold, MR Peters, RW Follmann, DA Russo, AM Bigger, JT Kim, CH Sung, RJ McBurnie, MA AF Page, RL Zipes, DP Powell, JL Luceri, RM Gold, MR Peters, RW Follmann, DA Russo, AM Bigger, JT Kim, CH Sung, RJ McBurnie, MA TI Patterns of death in the antiarrhythmics versus implantable defibrillators (AVID) study registry: Evidence that the increased winter mortality is due to sudden death SO CIRCULATION LA English DT Meeting Abstract C1 Univ Texas, Dallas, TX 75230 USA. Indiana Univ, Indianapolis, IN 46204 USA. Univ Washington, Seattle, WA 98195 USA. Florida Arrhythmia Consultants, Ft Lauderdale, FL USA. Univ Maryland, Baltimore, MD 21201 USA. NIH, Bethesda, MD 20892 USA. Univ Penn, Hlth Syst, Philadelphia, PA 19104 USA. Columbia Univ, New York, NY USA. Univ Rochester, Rochester, NY USA. Stanford Univ, Stanford, CA 94305 USA. RI Page, Richard/L-5501-2014 OI Page, Richard/0000-0001-5603-1330 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3257 BP 674 EP + PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303249 ER PT J AU Singh, JP Larson, MG O'Donnell, CJ Tsuji, H Caunt, D Levy, D AF Singh, JP Larson, MG O'Donnell, CJ Tsuji, H Caunt, D Levy, D TI Genome scan linkage results for heart rate variability: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 3306 BP 684 EP 684 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303298 ER PT J AU Wassmuth, R Abdul-Nour, K London, JF Rettmann, DW Halcox, JPJJ Dilsizian, V Arai, AE AF Wassmuth, R Abdul-Nour, K London, JF Rettmann, DW Halcox, JPJJ Dilsizian, V Arai, AE TI Validation of qualitative readings in dobutamine stress perfusion MRI SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RI Rettmann, Dan/G-5265-2015 NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3319 BP 686 EP 686 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303311 ER PT J AU Haider, AW Laron, M Levy, D AF Haider, AW Laron, M Levy, D TI Antecedent pulse pressure predicts adverse outcomes after first myocardial infarction SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Framingham Heart Dis Epidemiol Study, Framingham, MA 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 3366 BP 696 EP 696 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303358 ER PT J AU Dries, DL Sweitzer, NK Drazner, MH Exner, DV Stevenson, LW AF Dries, DL Sweitzer, NK Drazner, MH Exner, DV Stevenson, LW TI Diabetes aggravates heart failure progression in ischemic but not non-ischemic heart failure SO CIRCULATION LA English DT Meeting Abstract C1 SW Texas State Univ, Dallas, TX USA. Brigham & Womens Hosp, Boston, MA 02115 USA. SW Texas State Univ, Med Ctr, Dallas, TX USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3475 BP 718 EP 719 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303467 ER PT J AU Lader, EW Debra, E Hunsberger, S Garg, R McSherry, F AF Lader, EW Debra, E Hunsberger, S Garg, R McSherry, F TI The effect of digoxin on quality of life in patients with heart failure SO CIRCULATION LA English DT Meeting Abstract C1 NYU, Sch Med, New York, NY USA. NIH, NHLBI, Bethesda, MD 20892 USA. VA Med Ctr, Perry Point, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3479 BP 719 EP 719 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303471 ER PT J AU Nour, KA Amegashie, E Rehman, A Webb, M Miller-Davis, C Carson, J Kitsiou, A Dilsizian, V Quyyumi, AA AF Nour, KA Amegashie, E Rehman, A Webb, M Miller-Davis, C Carson, J Kitsiou, A Dilsizian, V Quyyumi, AA TI Effect of beta blockade on coronary vascular tone during EX-induced myocardial ischemia SO CIRCULATION LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3651 BP 756 EP 756 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303643 ER PT J AU Nour, KA Amegashie, E Webb, M Rehman, A Miller-Davis, C Carson, J Kitsiou, A Dilsizian, V Quyyumi, AA AF Nour, KA Amegashie, E Webb, M Rehman, A Miller-Davis, C Carson, J Kitsiou, A Dilsizian, V Quyyumi, AA TI Coronary vascular effects of exercise and dobutamine: Differences between physiologic and pharmacologic stress modalities. SO CIRCULATION LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3717 BP 769 EP 770 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303709 ER PT J AU Mizelle, KM Mack, G Mehwald, PS Zetts, AD AF Mizelle, KM Mack, G Mehwald, PS Zetts, AD TI Calculation of pulmonary regurgitant (PR) volume and regurgitant fraction in an animal model of chronic pulmonary regurgitation: A new 3D digital color Doppler laminar flow method SO CIRCULATION LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NHLBI, LAMS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3732 BP 773 EP 773 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303724 ER PT J AU Eichhorn, EJ Domanski, MJ Adams, K Anderson, JL Bristow, MR Carson, P Yancy, CW Krause-Steinrauf, H AF Eichhorn, EJ Domanski, MJ Adams, K Anderson, JL Bristow, MR Carson, P Yancy, CW Krause-Steinrauf, H TI Effect of beta-blockade on mortality in African-Americans: The beta-blocker evaluation of survival trial. SO CIRCULATION LA English DT Meeting Abstract C1 Univ Texas, SW Med Ctr, Dallas, TX USA. NIH, NHLBI, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Utah, Salt Lake City, UT USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. VAMC, Washington, DC USA. VAMC, Palo Alto, CA USA. RI bristow, michael/G-7850-2011 NR 0 TC 8 Z9 8 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 3759 BP 778 EP 778 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303751 ER PT J AU Eichhorn, EJ Domanski, MJ Adams, K Bristow, MR Carson, P Yancy, CW Krause-Steinrauf, H AF Eichhorn, EJ Domanski, MJ Adams, K Bristow, MR Carson, P Yancy, CW Krause-Steinrauf, H TI Hemodynamic, myocardial functional and neurohormonal responses to beta-blockade in Black vs non-Black patients in BEST SO CIRCULATION LA English DT Meeting Abstract C1 Univ Texas, SW Med Ctr, Dallas, TX USA. NIH, NHLBI, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. VAMC, Washington, DC USA. VAMC, Palo Alto, CA USA. RI bristow, michael/G-7850-2011 NR 0 TC 8 Z9 8 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 3757 BP 778 EP 778 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303749 ER PT J AU Anderson, JL Krause-Steinrauf, H Goldman, S Clemson, B Domanski, MJ Hager, D Mann, D Massie, B McNamara, DM Murray, D Oren, R Rogers, WJ AF Anderson, JL Krause-Steinrauf, H Goldman, S Clemson, B Domanski, MJ Hager, D Mann, D Massie, B McNamara, DM Murray, D Oren, R Rogers, WJ TI Failure of benefit and early hazard of bucindolol in Class IV heart failure. SO CIRCULATION LA English DT Meeting Abstract C1 Univ Utah, Salt Lake City, UT USA. VAMC, Palo Alto, CA USA. VAMC, Tucson, AZ USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Connecticut, Storrs, CT 06269 USA. VAMC, Houston, TX USA. VAMC, San Francisco, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. Univ Alabama, Tuscaloosa, AL 35487 USA. NR 0 TC 1 Z9 1 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 3765 BP 779 EP 780 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303757 ER PT J AU Gottdiener, JS Tracy, RP Arnold, AM Kitzman, DW Kuller, LH Boineau, R AF Gottdiener, JS Tracy, RP Arnold, AM Kitzman, DW Kuller, LH Boineau, R TI Atrial and brain natriuretic peptide as predictors of incident congestive heart failure in elderly. The Cardiovascular Health Study. SO CIRCULATION LA English DT Meeting Abstract C1 St Francis Hosp, Roslyn, NY USA. Univ Vermont, Burlington, VT USA. Univ Washington, Seattle, WA 98195 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NIH, NHLBI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3773 BP 781 EP 781 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303765 ER PT J AU Campia, U Choucair, WK Bryant, MB Cardillo, C Panza, JA AF Campia, U Choucair, WK Bryant, MB Cardillo, C Panza, JA TI Role of vasoactive prostanoids in the regulation of vascular tone and endothelial vasodilator function in patients with hypertension and in patients with hypercholesterolemia SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3780 BP 783 EP 783 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303772 ER PT J AU Sheps, DS Pepine, CJ Becker, LC Goldberg, AD Stone, PH Taylor, H Cohen, JD Kaufmann, PG McMahom, R Barton, BA AF Sheps, DS Pepine, CJ Becker, LC Goldberg, AD Stone, PH Taylor, H Cohen, JD Kaufmann, PG McMahom, R Barton, BA TI Mental stress ischemia predicts mortality: Results from the Psychophysiological Investigations of Myocardial Ischemia (PIMI) Study. SO CIRCULATION LA English DT Meeting Abstract C1 Univ Florida, Gainesville, FL USA. Johns Hopkins Univ, Baltimore, MD USA. Henry Ford Hosp, Detroit, MI 48202 USA. Harvard Univ, Boston, MA 02115 USA. Univ Mississippi, Jackson, MS 39216 USA. St Louis Univ, St Louis, MO 63103 USA. NIH, Bethesda, MD 20892 USA. Maryland Med Res Inst, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3814 BP 790 EP 790 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303806 ER PT J AU Shirani, J Alaeddini, J Pick, R Dilsizian, V AF Shirani, J Alaeddini, J Pick, R Dilsizian, V TI Do transmural left ventricular biopsies from asynergic regions provide accurate representation of tissue viability? SO CIRCULATION LA English DT Meeting Abstract C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3819 BP 791 EP 791 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303811 ER PT J AU Schussheim, AE Aletras, AH Kwong, RY Balaban, RS Arai, AE AF Schussheim, AE Aletras, AH Kwong, RY Balaban, RS Arai, AE TI Quantitative MRI analysis of human myocardial infarction suggest benefits of infarct-nulling contrast SO CIRCULATION LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3904 BP 808 EP 808 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303896 ER PT J AU Bella, JN Palmieri, V Roman, MJ Liu, JE Welty, TK Lee, ET Fabsitz, RR Howard, BV Devereux, RB AF Bella, JN Palmieri, V Roman, MJ Liu, JE Welty, TK Lee, ET Fabsitz, RR Howard, BV Devereux, RB TI Impact of left ventricular mass indexed for fat-free mass on prognosis in American Indians: The Strong Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Cleveland VA Med Ctr, Cleveland, OH USA. Cornell Univ, Weill Med Coll, New York, NY USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. Univ Oklahoma, Oklahoma City, OK USA. NIH, NHLBI, Bethesda, MD USA. Medlantic Res Inst, Washington, DC USA. NR 0 TC 1 Z9 1 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 4018 BP 836 EP 836 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304009 ER PT J AU Lloyd-Jones, DM Larson, MG Beiser, A Leip, E D'Agostino, RB Wilson, PW Levy, D AF Lloyd-Jones, DM Larson, MG Beiser, A Leip, E D'Agostino, RB Wilson, PW Levy, D TI Framingham risk score and lifetime risk of coronary heart disease SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RI Lloyd-Jones, Donald/C-5899-2009 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 4046 BP 842 EP 842 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304037 ER PT J AU Di Bari, M Franse, LV Kritchevsky, SB Newman, AB Harris, TB Cummings, S Marchionni, N Pahor, M AF Di Bari, M Franse, LV Kritchevsky, SB Newman, AB Harris, TB Cummings, S Marchionni, N Pahor, M TI Cardiovascular medications and muscle wasting in older adults SO CIRCULATION LA English DT Meeting Abstract C1 Univ Florence, Florence, Italy. Vrije Univ Amsterdam, Amsterdam, Netherlands. Univ Tennessee, Memphis, TN USA. Univ Pittsburgh, Pittsburgh, PA USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. RI DI BARI, MAURO/J-1524-2012 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 4049 BP 843 EP 843 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304040 ER PT J AU Gottdiener, JS Tracy, RP Arnold, AM Kitzman, DW Kuller, LH Boineau, R AF Gottdiener, JS Tracy, RP Arnold, AM Kitzman, DW Kuller, LH Boineau, R TI Atrial and brain natriuretic peptide in community based elderly: Relation to age, coronary heart disease, LV function, and left atrial size. The Cardiovascular Health Study. SO CIRCULATION LA English DT Meeting Abstract C1 St Francis Hosp, Roslyn, NY USA. Univ Vermont, Burlington, VT USA. Univ Washington, Seattle, WA 98195 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Pittsburgh, Pittsburgh, PA USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 4058 BP 844 EP 844 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304049 ER PT J AU Lloyd-Jones, DM Larson, MG Beiser, A Leip, E D'Agostino, RB Kannel, WB Murabito, JM Vasan, RS Benjamin, EJ Levy, D AF Lloyd-Jones, DM Larson, MG Beiser, A Leip, E D'Agostino, RB Kannel, WB Murabito, JM Vasan, RS Benjamin, EJ Levy, D TI High blood pressure contributes to increased lifetime risk of congestive heart failure SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 4055 BP 844 EP 844 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304046 ER PT J AU Vupputuri, S He, J Batuman, V Ogden, LG Bazzano, LA Loria, CM Whelton, PK AF Vupputuri, S He, J Batuman, V Ogden, LG Bazzano, LA Loria, CM Whelton, PK TI Relationship between blood lead and blood pressure among whites and African-Americans: The Third National Health and Nutrition Examination Survey (NHANES III) SO CIRCULATION LA English DT Meeting Abstract C1 Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 4056 BP 844 EP 844 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304047 ER PT J AU Liao, DP Boerwinkle, E Pankow, J Evans, G Morrison, AC Chambless, LE Sharrett, RA Heiss, G AF Liao, DP Boerwinkle, E Pankow, J Evans, G Morrison, AC Chambless, LE Sharrett, RA Heiss, G TI Associations of angiotensin converting enzyme insertion/deletion (ACE I/D) and angiotensin II type 1 receptor gene A -> C (AGT-R1) polymorphisms with hypertension: the ARIC study. SO CIRCULATION LA English DT Meeting Abstract C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Hershey, PA 17033 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Univ N Carolina, Chapel Hill, NC USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 4060 BP 845 EP 845 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304051 ER PT J AU Bazzano, LA He, J Ogden, LG Vupputuri, S Loria, CM Myers, L Whelton, PK AF Bazzano, LA He, J Ogden, LG Vupputuri, S Loria, CM Myers, L Whelton, PK TI Dietary intake of folic acid and reduced rick of stroke in US men and women: NHANES I Epidemiologic Follow-up Study SO CIRCULATION LA English DT Meeting Abstract C1 Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. NHLBI, NIH, Bethesda, MD 20892 USA. Tulane Univ, Med Ctr, New Orleans, LA 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 4133 BP 861 EP 861 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304124 ER PT J AU Murabito, JM Nieto, K Evans, JC Wilson, PW AF Murabito, JM Nieto, K Evans, JC Wilson, PW TI Peripheral arterial disease in the Framingham Offspring Study: Prevalence and clinical determinants SO CIRCULATION LA English DT Meeting Abstract C1 Framingham Heart Dis Epidemiol Study, Framingham, MA USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 4142 BP 862 EP 863 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304133 ER PT J AU Bernick, CB Kuller, LH Dulberg, C Longstreth, WT Manolio, TA Beauchamp, NJ Price, TR AF Bernick, CB Kuller, LH Dulberg, C Longstreth, WT Manolio, TA Beauchamp, NJ Price, TR TI Infarction identified on brain MRI and risk of clinical stroke in the cardiovascular health study SO CIRCULATION LA English DT Meeting Abstract C1 Univ Nevada, Las Vegas, NV 89154 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Washington, Seattle, WA 98195 USA. NIH, NHLBI, Bethesda, MD USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S BP 864 EP 864 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304138 ER PT J AU Palmieri, V Celentano, A Roman, MJ Lewis, MR De Simone, G Welty, TK Lee, ET Fabsitz, RR Robbins, DC Best, L Howard, BV AF Palmieri, V Celentano, A Roman, MJ Lewis, MR De Simone, G Welty, TK Lee, ET Fabsitz, RR Robbins, DC Best, L Howard, BV TI High fibrinogen predicts cardiovascular mortality independently of traditional risk factors and echocardiographic abnormalities. The Strong Heart Study. SO CIRCULATION LA English DT Meeting Abstract C1 Cornell Univ, Weill Med Coll, New York, NY USA. Univ Naples Federico II Hosp, Naples, Italy. Univ Vermont, Burlington, VT USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. Univ Oklahoma, Oklahoma City, OK USA. NHLBI, NIH, Bethesda, MD 20892 USA. Medstar Res Inst, Washington, DC 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 4154 BP 866 EP 866 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304145 ER PT J AU McNamara, RL Ding, JZ Cooper, LS Chambless, LE Rosamond, WD AF McNamara, RL Ding, JZ Cooper, LS Chambless, LE Rosamond, WD TI Trends in coronary angiography after first acute myocardial infarction in the ARIC Communities, 1987-1997 SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 4163 BP 867 EP 868 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304154 ER PT J AU Smith, NL Barzilay, JI Shaffer, D Savage, PJ Heckbert, SR Kuller, LH Kronmal, RA Resnick, HE Psaty, BM AF Smith, NL Barzilay, JI Shaffer, D Savage, PJ Heckbert, SR Kuller, LH Kronmal, RA Resnick, HE Psaty, BM TI Fasting and 2-hour post-challenge glucose measures and risk of cardiovascular disease in the elderly: The Cardiovascular Health Study SO CIRCULATION LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. Kaiser Permanente, Atlanta, GA USA. NIH, NHLBI, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIH, NIA, 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 4176 BP 871 EP 871 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304167 ER PT J AU Liu, JE Palmieri, W Robbins, DC Roman, MJ Bella, JN Fabsitz, RR Lee, ET Welty, TK Howard, BV AF Liu, JE Palmieri, W Robbins, DC Roman, MJ Bella, JN Fabsitz, RR Lee, ET Welty, TK Howard, BV TI Albuminuria is a potent marker for worse systolic and diastolic function in type II diabetes (DM): The strong heart study SO CIRCULATION LA English DT Meeting Abstract C1 Cornell Univ, Weill Med Coll, New York, NY USA. Medstar Res Inst, Washington, DC USA. NIH, NHLBI, Bethesda, MD 20892 USA. Univ Oklahoma, Oklahoma City, OK USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 4180 BP 872 EP 872 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304171 ER PT J AU Koyanagi, M Egashira, K Kitamoto, S Ni, WH Shimokawa, H Takeya, M Yoshimura, T Takeshita, A AF Koyanagi, M Egashira, K Kitamoto, S Ni, WH Shimokawa, H Takeya, M Yoshimura, T Takeshita, A TI Role of monocyte chemoattractant protein-1 in cardiovascular remodeling induced by chronic blockade of nitric oxide synthesis SO CIRCULATION LA English DT Article DE endothelium-derived factors; remodeling; growth substances; inflammation; cell adhesion molecules; proteins ID LONG-TERM BLOCKADE; CONVERTING ENZYME-ACTIVITY; ANGIOTENSIN-II; ENDOTHELIAL-CELLS; ATHEROSCLEROTIC LESIONS; CHEMOTACTIC PROTEIN-1; MONOCLONAL-ANTIBODY; EXPRESSION; RATS; INHIBITION AB Background-Chronic inhibition of endothelial nitric oxide (NO) synthesis by the administration of N-omega-nitro-L-arginine methyl ester (L-NAME) to rats induces early vascular inflammatory changes (monocyte infiltration into coronary vessels and monocyte chemoattractant protein-1 [MCP-1] expression) as well as subsequent arteriosclerosis (medial thickening and perivascular fibrosis) and cardiac fibrosis. However, the role of MCP-1 in this process is not known. Methods and Results-We investigated the effect of a specific monoclonal anti-MCP-1 neutralizing antibody in rats treated with L-NAME to determine the role of monocytes in the regulation of cardiovascular remodeling. We found increased expression of MCP-1 mRNA in vascular endothelial cells and monocytes in inflammatory lesions, Cotreatment with an anti-MCP-1 antibody, but not with control IgG, prevented the L-NAME-induced early inflammation and reduced late coronary vascular medial thickening. In contrast, the anti-MCP-1 antibody did not decrease the development of perivascular fibrosis, the expression of transforming growth factor (TGF)-beta (1) mRNA, or systolic pressure overload induced by L-NAME administration. Conclusions-These results suggest that MCP-1 is necessary for the development of medial thickening as well as monocyte recruitment, In contrast, the pathogenesis of fibrosis may involve other factors, such as TGF-beta (1). C1 Kyushu Univ, Grad Sch Med Sci, Dept Cardiovasc Med, Higashi Ku, Fukuoka 8128582, Japan. Kumamoto Univ, Sch Med, Dept Pathol 2, Kumamoto 860, Japan. NCI, Immunobiol Lab, Immunopathol Sect, Frederick, MD 21701 USA. RP Egashira, K (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Cardiovasc Med, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. RI U-ID, Kyushu/C-5291-2016 NR 34 TC 82 Z9 92 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 BP 2243 EP 2248 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GM UT WOS:000090109400024 PM 11056100 ER PT J AU Horkay, F Basser, PJ Hecht, AM Geissler, E AF Horkay, F Basser, PJ Hecht, AM Geissler, E TI Osmotic and SANS observations on sodium polyacrylate hydrogels in physiological salt solutions SO MACROMOLECULES LA English DT Article ID POLYMER GELS; TRANSITIONS; SCATTERING AB The volume transition induced by the addition of calcium into lightly cross-linked fully neutralized sodium polyacrylate hydrogels, swollen in 40 mM NaCl solutions, is investigated by osmotic swelling pressure and small-angle neutron scattering (SANS) measurements. In this reversible transition, the polymer volume fraction psi changes by more than an order of magnitude. The longitudinal osmotic modulus M-os deduced from macroscopic measurements shows an abrupt increase at the transition. The intensity of the scattered radiation can be decomposed into a static and a dynamic component. The former exhibits Pored scattering behavior, while the latter obeys an Orstein-Zernike relation. The observed intensity of the dynamic part has a maximum at the transition and exhibits a functional dependence on the calcium concentration, which is similar to that of the osmotic susceptibility psi (2)/M-os, determined from direct osmotic measurements. C1 NICHD, Sect Tissue Biophys & Bomimet, Lab Integrated & Med Biophys, NIH, Bethesda, MD 20892 USA. Univ Grenoble 1, Lab Spectrometrie Phys, CNRS UMR 55588, F-38402 St Martin Dheres, France. RP Horkay, F (reprint author), NICHD, Sect Tissue Biophys & Bomimet, Lab Integrated & Med Biophys, NIH, 13 S Dr, Bethesda, MD 20892 USA. RI Basser, Peter/H-5477-2011 NR 30 TC 39 Z9 39 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0024-9297 J9 MACROMOLECULES JI Macromolecules PD OCT 31 PY 2000 VL 33 IS 22 BP 8329 EP 8333 DI 10.1021/ma000972r PG 5 WC Polymer Science SC Polymer Science GA 370UL UT WOS:000165140700033 ER PT J AU Jackson, TR Brown, FD Nie, ZZ Miura, K Foroni, L Sun, JL Hsu, VW Donaldson, JG Randazzo, PA AF Jackson, TR Brown, FD Nie, ZZ Miura, K Foroni, L Sun, JL Hsu, VW Donaldson, JG Randazzo, PA TI ACAPs are Arf6 GTPase-activating proteins that function in the cell periphery SO JOURNAL OF CELL BIOLOGY LA English DT Article DE actin; ADP-ribosylation factor; GTPase-activating proteins; membrane traffic; pleckstrin homology domain ID ADP-RIBOSYLATION FACTOR; GUANINE-NUCLEOTIDE-EXCHANGE; GOLGI MEMBRANES; BINDING-PROTEIN; BREFELDIN-A; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; DOWNSTREAM EFFECTOR; ORGANELLE STRUCTURE; ACTIN CYTOSKELETON; PHOSPHOLIPASE-D AB The GTP-binding protein ADP-ribosylation factor 6 (Arf6) regulates endosomal membrane trafficking and the actin cytoskeleton in the cell periphery. GTPase-activating proteins (GAPs) are critical regulators of Arf function, controlling the return of Arf to the inactive GDP-bound state. Here, we report the identification and characterization of two Arf6 GAPs, ACAP1 and ACAP2. Together with two previously described Arf GAPs, ASAP1 and PAP, they can be grouped into a protein family defined by several common structural motifs including coiled coil, pleckstrin homology, Arf GAP, and three complete ankyrin-repeat domains. All contain phosphoinositide-dependent GAP activity. ACAP1 and ACAP2 are widely expressed and occur together in the various cultured cell lines we examined. Similar to ASAP1, ACAP1 and ACAP2 were recruited to and, when overexpressed. inhibited the formation of platelet-derived growth factor (PDGF)-induced dorsal membrane ruffles in NIH 3T3 fibroblasts. However, in contrast with ASAP1, ACAP1 and ACAP2 functioned as Arf6 GAPs. In vitro, ACAP1 and ACAP2 preferred Arf6 as a substrate, rather than Arf1 and Arf5, more so than did ASAP1. In HeLa cells, overexpression of either ACAP blocked the formation of Arf6-dependent protrusions. In addition, ACAP1 and ACAP2 were recruited to peripheral, tubular membranes, where activation of Arf6 occurs to allow membrane recycling back to the plasma membrane. ASAP1 did not inhibit Arf6-dependent protrusions and was not recruited by Arf6 to tubular membranes. The additional effects of ASAP1 on PDGF-induced ruffling in fibroblasts suggest that multiple Arf GAPs function coordinately in the cell periphery. C1 NCI, Cellular Oncol Lab, Div Basic Sci, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, Bethesda, MD 20892 USA. UCL Royal Free & Univ Coll, London Med Sch, Dept Hematol, London NW3 2AF, England. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Randazzo, PA (reprint author), NCI, Cellular Oncol Lab, Div Basic Sci, 37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM randazzo@helix.nih.gov NR 56 TC 125 Z9 129 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 30 PY 2000 VL 151 IS 3 BP 627 EP 638 DI 10.1083/jcb.151.3.627 PG 12 WC Cell Biology SC Cell Biology GA 369YC UT WOS:000165094500013 PM 11062263 ER PT J AU Yordanov, AT Deal, K Garmestani, K Kobayashi, H Herring, B Waldmann, TA Brechbiel, MW AF Yordanov, AT Deal, K Garmestani, K Kobayashi, H Herring, B Waldmann, TA Brechbiel, MW TI Synthesis and biodistribution study of a new At-211-calix[4]arene complex SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE astatine; calixarene; macrocycle; complex; biodistribution; alpha-radioimmunotherapy of cancer ID ANTIBODIES AB The preparation and characterization of a new tetramercaptocalix[4]arene and its At-211 complex is described. The in vivo stability of the complex has been evaluated in nude mice for the purpose of alpha -radioimmunotherapy of cancer. The study shows that while this complex lacks adequate stability in vivo, At-211 may behave as a heavy metal ion and may be successfully sequestered for biomedical applications. C1 NCI, Radioimmune & Inorgan Chem, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. RP Yordanov, AT (reprint author), NCI, Radioimmune & Inorgan Chem, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 15 TC 9 Z9 9 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD OCT 30 PY 2000 VL 43 IS 12 BP 1219 EP 1225 DI 10.1002/1099-1344(20001030)43:12<1219::AID-JLCR409>3.0.CO;2-P PG 7 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 365ML UT WOS:000089955000009 ER PT J AU O'Connor, SM Stenger, DA Shaffer, KM Maric, D Barker, JL Ma, W AF O'Connor, SM Stenger, DA Shaffer, KM Maric, D Barker, JL Ma, W TI Primary neural precursor cell expansion, differentiation and cytosolic Ca2+ response in three-dimensional collagen gel SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE three-dimensional matrix; collagen; neural precursor cell; proliferation; differentiation; rat cerebral cortex; Ca2+ imaging; immunocytochemistry ID CENTRAL-NERVOUS-SYSTEM; STEM-CELLS; 3-DIMENSIONAL CULTURES; EXTRACELLULAR-MATRIX; HIPPOCAMPAL-NEURONS; PROGENITOR CELLS; IN-VITRO; REPAIR; REGENERATION; EXPRESSION AB To investigate the ability to culture neural precursor cells in a three-dimensional (3D) collagen gel, neuroepithelial cells were isolated from embryonic day 13 rat cortex, dispersed within type I collagen and maintained for up to 30 days in vitro. Cultured in Neuorobasal medium supplemented with B27 containing basic fibroblast growth factor, the collagen-entrapped precursor cells actively expanded and formed clone-like clusters. Many cells in the center of the cluster were proliferating as revealed by 5-bromo-2'-deoxyuridine uptake. Some cells began to migrate away from the center at 5 days and were labeled by either neuronal marker neuron-specific beta -tubulin (TuJ1) or astrocytic marker glial fibrillary acidic protein. The differentiated neurons (TuJ1(+)) exhibited characteristic cytosolic Ca2+ oscillations in response to excitatory neurotransmitter glutamate. These findings suggest the suitability of the 3D culture system for the proliferation and differentiation of neural precursor cells. (C) 2000 Elsevier Science B.V. All rights reserved. C1 USN, Ctr Biomol Sci & Engn, Res Lab, Washington, DC 20375 USA. Geocenters Inc, Rockville, MD 20852 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Ma, W (reprint author), USN, Ctr Biomol Sci & Engn, Res Lab, Washington, DC 20375 USA. NR 45 TC 60 Z9 62 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD OCT 30 PY 2000 VL 102 IS 2 BP 187 EP 195 DI 10.1016/S0165-0270(00)00303-4 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 369YF UT WOS:000165094800011 PM 11040415 ER PT J AU Gulson, BL Mizon, KJ Palmer, JM Korsch, MJ Donnelly, JB AF Gulson, BL Mizon, KJ Palmer, JM Korsch, MJ Donnelly, JB TI Urinary excretion of lead during pregnancy and postpartum SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article DE urine; blood; lead isotopes; adult females; bone; pregnancy; postpartum; calcium; renal conservation ID BLOOD LEAD; BONE; LACTATION; MOBILIZATION; ABSORPTION; METABOLISM; SKELETON; CALCIUM; DENSITY; PERIOD AB We have compared lead isotopic ratios and lead concentrations in 53 spot urine and 59 24-h urine samples from 13 subjects covering the interval from pre-pregnancy through 180 days postpartum to estimate the amount of lead excreted in urine and renal clearance relative to blood. The total amount of lead excreted in 24-h urine samples ranges from 0.8 to 5.9 mu g Pb with an arithmetic mean of 2.2 +/- 1.1 mu g (geometric mean 1.90 mu g). This compares with amounts of 0.9-10 mu g of extra lead per day estimated to be released into blood from the skeleton during pregnancy and postpartum. There were no differences in excretion rates during the trimesters of pregnancy and between pregnancy and postpartum time periods. The renal clearance relative to blood ranged from 0.8 to 10 g/h (arithmetic mean 3.2 +/- 1.9; geometric mean 2.7). Renal clearance relative to blood was somewhat higher in trimesters 2 and 3 compared with postpartum 150-180 days (P = 0.004, 0.006, respectively). Reassessment of earlier published blood and dietary data for Australian pregnant controls indicates there is no increased gastrointestinal absorption of lead during pregnancy and postpartum. This differs from calcium, which shows increased absorption during late pregnancy. In light of the inconvenience of sampling and potential contamination at the low levels of lead found in most of these subjects, we do not consider the 24 fi urines to provide sufficient useful information. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Macquarie Univ, Grad Sch Environm, Sydney, NSW 2109, Australia. CSIRO, DEM, N Ryde, NSW 2113, Australia. NIEHS Res, Res Triangle Pk, NC 27709 USA. JB Donnelly & Associates Pty Ltd, Castle Hill, NSW 2154, Australia. RP Gulson, BL (reprint author), Macquarie Univ, Grad Sch Environm, Sydney, NSW 2109, Australia. RI Donnelly, John/D-1188-2009 FU NIEHS NIH HHS [N01-ES-05292] NR 22 TC 7 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD OCT 30 PY 2000 VL 262 IS 1-2 BP 49 EP 55 DI 10.1016/S0048-9697(00)00536-2 PG 7 WC Environmental Sciences SC Environmental Sciences & Ecology GA 364VW UT WOS:000089915300005 PM 11059841 ER PT J AU Abiose, A Homeida, M Liese, B Molyneux, D Remme, H AF Abiose, A Homeida, M Liese, B Molyneux, D Remme, H TI Onchocerciasis control strategies SO LANCET LA English DT Letter ID TRANSMISSION C1 Natl Eye Inst, Onchocerciasis Control Programme W Africa, Expert Advisory Comm, Kaduna, Nigeria. Univ Khartoum, Programme Onchocerciasis Control, Tech Consultat Comm Africa, Khartoum, Sudan. World Bank, Africa Reg, Washington, DC 20433 USA. Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. WHO, CH-1211 Geneva, Switzerland. RP Molyneux, D (reprint author), Natl Eye Inst, Onchocerciasis Control Programme W Africa, Expert Advisory Comm, PMB 2267, Kaduna, Nigeria. NR 5 TC 25 Z9 25 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 28 PY 2000 VL 356 IS 9240 BP 1523 EP 1523 DI 10.1016/S0140-6736(05)73271-2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 367NA UT WOS:000090067300050 PM 11081557 ER PT J AU Arnold, EV Keefer, LK Hrabie, JA AF Arnold, EV Keefer, LK Hrabie, JA TI Reaction of nitric oxide with benzyl cyanide to yield a bis-diazeniumdiolated imidate SO TETRAHEDRON LETTERS LA English DT Article DE nitrogen oxides; nitriles; imidic acids and derivatives; diazenes ID MECHANISM AB The reaction of nitric oxide with benzyl cyanide in the presence of sodium methoxide forms the bis-diazeniumdiolated imidate, PhC[C(OMe)=NH][N(O)NO-Na+](2). This compound decomposes in acidic media to yield nitric oxide, nitrous oxide and 2-oximino-2-phenylacetic acid methyl ester. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. RP Hrabie, JA (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 17 TC 15 Z9 15 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD OCT 28 PY 2000 VL 41 IS 44 BP 8421 EP 8424 DI 10.1016/S0040-4039(00)01535-5 PG 4 WC Chemistry, Organic SC Chemistry GA 370YE UT WOS:000165150200005 ER PT J AU Briscoe, RJ Cabrera, CL Baird, TJ Rice, KC Woods, JH AF Briscoe, RJ Cabrera, CL Baird, TJ Rice, KC Woods, JH TI Antalarmin blockade of corticotropin releasing hormone-induced hypertension in rats SO BRAIN RESEARCH LA English DT Article DE corticotropin releasing hormone; corticotropin releasing hormone antagonist; alpha-helical CRH9-41; antalarmin; blood pressure; rat ID FACTOR RECEPTORS; ANTAGONIST; CRF; CP-154,526; PEPTIDE; DESIGN; STRESS AB Central administration of CRH results in endocrinological. cardiovascular, and behavioral effects that suggest stress or anxiety. Among these is a marked presser response. Parenteral administration of CRH, however, results in hypotension. We used parenteral administration of antalarmin, a novel, small molecule CRH1 receptor antagonist, and alpha -helical CRH9-41, a peptidic CRHR1/CRHR2 antagonist to attempt to determine the receptor mechanisms through which CRH is acting in both of these situations. Our results suggest that the hypertension produced by central CRH administration is mediated through central CRHR1 receptors, whereas the hypertension produced by parenteral CRH administration is mediated through peripheral CRHR2 receptors. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. RP Woods, JH (reprint author), Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. FU NIDA NIH HHS [DA 000254] NR 14 TC 32 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 27 PY 2000 VL 881 IS 2 BP 204 EP 207 DI 10.1016/S0006-8993(00)02742-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 368BV UT WOS:000090098500014 PM 11036160 ER PT J AU Uhlmann, F Wernic, D Poupart, MA Koonin, EV Nasmyth, K AF Uhlmann, F Wernic, D Poupart, MA Koonin, EV Nasmyth, K TI Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast SO CELL LA English DT Article ID SISTER-CHROMATID SEPARATION; SACCHAROMYCES-CEREVISIAE; DNA-REPLICATION; SECONDARY STRUCTURE; CUT2 PROTEOLYSIS; FISSION YEAST; BUDDING YEAST; IDENTIFICATION; INHIBITOR; CELLS AB In eukaryotic cells, replicated DNA strands remain physically connected until their segregation to opposite poles of the cell during anaphase. This "sister chromatid cohesion" is essential for the alignment of chromosomes on the mitotic spindle during metaphase. Cohesion depends on the multisubunit cohesin complex, which possibly forms the physical bridges connecting sisters. Proteolytic cleavage of cohesin's Scc1 subunit at the metaphase to anaphase transition is essential for sister chromatid separation and depends on a conserved protein called separin. We show here that separin is a cysteine protease related to caspases that alone can cleave Scc1 in vitro. Cleavage of Scc1 in metaphase arrested cells is sufficient to trigger the separation of sister chromatids and their segregation to opposite cell poles. C1 Res Inst Mol Pathol, A-1030 Vienna, Austria. Boehringer Ingelheim Canada Ltd, Laval, PQ H7S 2G5, Canada. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Nasmyth, K (reprint author), Res Inst Mol Pathol, Dr Bohr Gasse 7, A-1030 Vienna, Austria. NR 52 TC 513 Z9 526 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 27 PY 2000 VL 103 IS 3 BP 375 EP 386 DI 10.1016/S0092-8674(00)00130-6 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 368YB UT WOS:000090144100004 PM 11081625 ER PT J AU Vinogradova, TM Zhou, YY Bogdanov, KY Yang, DM Kuschel, M Cheng, HP Xiao, RP AF Vinogradova, TM Zhou, YY Bogdanov, KY Yang, DM Kuschel, M Cheng, HP Xiao, RP TI Sinoatrial node pacemaker activity requires Ca2+/calmodulin-dependent protein kinase II activation SO CIRCULATION RESEARCH LA English DT Article DE sinoatrial node; L-type Ca2+ channel; Ca2+/calmodulin-dependent kinase II; local Ca2+ signaling ID RABBIT SINUS NODE; ELECTRICAL-ACTIVITY; CALCIUM CURRENTS; ATRIAL NODE; CAM KINASE; CELLS; CALMODULIN; INHIBITOR; HEART; MECHANISM AB Cardiac beating arises from the spontaneous rhythmic excitation of sinoatrial (SA) node cells. Here we report that SA node pacemaker activity is critically dependent on Ca2+/calmodulin-dependent protein kinase II (CaMKII). In freshly dissociated rabbit single SA node cells, inhibition of CaMKII by a specific peptide inhibitor, autocamtide-2 inhibitory peptide (AIP, 10 mu mol/L), or by KN-93 (0.1 to 3.0 mu mol/L), but not its inactive analog, KN-92, depressed the rate and amplitude of spontaneous action potentials (APs) in a dose-dependent manner. Strikingly, 10 mu mol/L AIP and 3 mu mol/L KN-93 completely arrested SA node cells, which indicates that basal CaMKII activation is obligatory to the genesis of pacemaker AP. To understand the ionic mechanisms of the CaMKII: effects, we measured L-type Ca2+ current (I-Ca,I-L), which contributes both to AP upstroke and to pacemaker depolarization. KN-93 (1 mu mol/L), but not its inactive analog, KN-92, decreased I-Ca,I-L amplitude from 12+/-2 to 6+/-1 pA/pF without altering the shape of the current-voltage relationship. Both AIP and KN-93 shifted the midpoint of the steady-state inactivation curve leftward and markedly slowed the recovery of I-Ca,I-L from inactivation. Similar results were observed using the fast Ca2+ chelator BAPTA, whereas the slow Ca2+ chelator EGTA had no significant effect, which suggests that CaMKII activity is preferentially regulated by local Ca2+ transients. Indeed, confocal immunocytochemical imaging showed that active CaMKII is highly localized beneath the surface membrane in the vicinity of L-type channels and that ATP and KN-93 significantly reduced CaMKII activity. Thus, we conclude that CaMKII plays a vital role in regulating cardiac pacemaker activity mainly via modulating I-Ca,I-L inactivation and reactivation, and local Ca2+ is critically involved in these processes. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Beijing Univ, Coll Life Sci, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, 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 33 TC 104 Z9 105 U1 0 U2 6 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 OCT 27 PY 2000 VL 87 IS 9 BP 760 EP 767 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 372DJ UT WOS:000165218800009 PM 11055979 ER PT J AU Guo, NH Kawamoto, S AF Guo, NH Kawamoto, S TI An intronic downstream enhancer promotes 3 ' splice site usage of a neural cell-specific exon SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PRE-MESSENGER-RNA; TRACT-BINDING-PROTEIN; VERTEBRATE NONMUSCLE MYOSIN; ALTERNATIVE EXON; SR-PROTEINS; DEVELOPMENTAL CONSEQUENCES; SEQUENCE ELEMENTS; PREMESSENGER RNA; FACTOR U2AF(35); CHAIN-B AB The human nonmuscle myosin heavy chain B gene contains a 30-nucleotide alternative exon, N30, that is included in the mRNA from neural cells but is skipped in all other cells. We have previously identified an intronic distal downstream enhancer (IDDE) region that is required for neural cell-specific inclusion of N30, In this study, me investigated the mechanism by which the IDDE promotes N30 exon usage. In vitro splicing analysis using neural cell nuclear extracts and two-exon pre-mRNA substrates, which consist of the N30 exon and either the upstream (E5) or downstream (E6) exon, demonstrates that the IDDE activates upstream E5-N30 splicing by facilitating early prespliceosome complex formation. The IDDE has no effect on N30-E6 splicing where the IDDE resides. Inspection of splice site consensus sequences shows that a polypyrimidine (Py) tract preceding N30 is suboptimal for U2AF binding. Optimizing the Py tract completely relieves the requirement for the IDDE in E5-N30 splicing in vitro. In transfected cells, the wild-type minigene transcripts, which consist of three exons, E5, N30, and E6, undergo neural cell-specific and IDDE-dependent alternative splicing of N30, Optimizing the Py tract in minigenes also completely relieves the requirement for the IDDE in N30 inclusion. Furthermore, overexpression of the truncated U2AF65, which contains the arginine and serine dipeptide-rich domain and linker domain, but lacks the RNA binding domain, selectively inhibits the IDDE-mediated N30 inclusion in mRNA from the wild-type minigene in a dominant negative fashion. These results support the hypothesis that the IDDE facilitates the recognition of the 3' splice site preceding N30 by a network of protein-protein interactions implicated in the recruitment of U2AF to a suboptimal Py tract. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Kawamoto, S (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Rm 8N202,10 Ctr Dr,MSC 1762, Bethesda, MD 20892 USA. NR 57 TC 17 Z9 17 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 27 PY 2000 VL 275 IS 43 BP 33641 EP 33649 DI 10.1074/jbc.M005597200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 368EK UT WOS:000090104600065 PM 10931847 ER PT J AU Zadorozhnaja, TD Little, RE Miller, RK Mendel, NA Taylor, RJ Presley, BJ Gladen, BC AF Zadorozhnaja, TD Little, RE Miller, RK Mendel, NA Taylor, RJ Presley, BJ Gladen, BC TI Concentrations of arsenic, cadmium, copper, lead, mercury, and zinc in human placentas from two cities in Ukraine SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID BREAST-MILK; DRINKING-WATER; PREGNANT-WOMEN; BIRTH-WEIGHT; HEAVY-METALS; 2 CITIES; EXPOSURE; BLOOD; AREA; ACCUMULATION AB Ukraine is a highly industrialized country with major environmental problems and deteriorating reproductive health. Heavy metals are known reproductive toxins; a study was undertaken to determine whether they were present at sufficient concentrations to be playing a major role in these health problems. Placental concentrations of arsenic, cadmium, copper, lead mercury, and zinc were determined in 200 women from the general population of two urban areas of Ukraine, Kyiv and Dniprodzerzhinsk. Arsenic was detected in only 5% of the samples, lead in 22%, and mercury in 28%. Cadmium was detected in almost all samples, with a median of 5.2 ng/g. Concentrations of lead, mercury, and cadmium were low compared to those reported elsewhere, while zinc and copper concentrations were comparable. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Inst Pediat Obstet & Gynecol, Kyiv, Ukraine. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Kyiv Med Acad Post Diploma Educ, Kyiv, Ukraine. Texas A&M Univ, College Stn, TX USA. RP Gladen, BC (reprint author), NIEHS, Biostat Branch, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. NR 39 TC 42 Z9 44 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD OCT 27 PY 2000 VL 61 IS 4 BP 255 EP 263 DI 10.1080/00984100050136571 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 368RZ UT WOS:000090132500003 PM 11071319 ER PT J AU Wong, P Pfeffer, BA Bernstein, SL Chambers, ML Chader, GJ Zakeri, ZF Wu, YQ Wilson, MR Becerra, SP AF Wong, P Pfeffer, BA Bernstein, SL Chambers, ML Chader, GJ Zakeri, ZF Wu, YQ Wilson, MR Becerra, SP TI Clusterin protein diversity in the primate eye SO MOLECULAR VISION LA English DT Article ID APOLIPOPROTEIN-J EXPRESSION; RETINAL-PIGMENT EPITHELIUM; RAT VENTRAL PROSTATE; MOLECULAR CHARACTERIZATION; MULTIFUNCTIONAL PROTEIN; SULFATED GLYCOPROTEIN-2; RETINITIS-PIGMENTOSA; TRPM-2 CLUSTERIN; GENE; COMPLEMENT AB Purpose: The clusterin gene encodes a multi-functional protein that has been identified in different tissues, including a number of different eye tissues, primarily in the mouse and to a much lesser extent in humans. Clusterin has been implicated in a number of cellular processes such as lipid transport, membrane integrity, apoptosis, and neurodegeneration, all of which could be important to the biology of the eye. In the current communication, we provide data that confirms the expression of clusterin in a number of different human eye tissues and establishes the expression profile of this gene in monkey derived eye tissues. The issue that we sought to examine is whether a broad profile of clusterin expression in the eye is consistent in primates (monkey and human). Methods: The majority of our study was done using monkey eye tissues. Where possible, we have used human tissues in order to confirm published findings. Northern and western analysis was performed using tissues derived from monkey eyes. In situ hybridization and immunochemistry were carried out on human eye sections. Results: Clusterin mRNA is expressed in primate lens, cornea, limbus, sclera, orbital muscle, ciliary body, retina, RPE/ choroid, and RPE cells in culture. Western analysis revealed that two major groups of clusterin exist in the eye, a high molecular weight group (>100 kDa) and a second group consisting of at least five clusterin species that are all approximately 80 kDa. Analysis of conditioned media from RPE cells cultured on permeable supports suggests that different forms of clusterin display alternative patterns of secretion. Conclusions: Clusterin is expressed in a broad range of eye tissues in both human and monkey, suggesting that this is a characteristic feature in primates. We demonstrate for the first time that a diverse number of clusterin isoforms were observed in monkey eye tissues by western analysis. Meanwhile, the molecular size of clusterin mRNA detected in the array of tissues are identical in size, suggesting that the nature of the diversity in clusterin forms is due to post-translational modifications. In addition, new insights were made in defining clusterin expression in ciliary body, cornea, and the retinal pigment epithelium. C1 Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada. Univ Alberta, Dept Ophthalmol, Edmonton, AB T6G 2E9, Canada. Univ Alberta, Dept Med Genet, Edmonton, AB T6G 2E9, Canada. Bausch & Lomb Pharmaceut, Pearl River, NY USA. Univ Maryland, Dept Ophthalmol, Baltimore, MD 21201 USA. Fdn Fighting Blindness Inc, Hunt Valley, MD USA. CUNY Queens Coll, New York, NY USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Wollongong, Dept Biol Sci, Wollongong, NSW 2500, Australia. RP Wong, P (reprint author), Univ Alberta, Dept Biol Sci, G504 Biol Sci CTR, Edmonton, AB T6G 2E9, Canada. OI Wilson, Mark/0000-0002-9551-7445 NR 40 TC 21 Z9 21 U1 1 U2 4 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 OCT 27 PY 2000 VL 6 IS 23 BP 184 EP 191 PG 8 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 367RF UT WOS:000090074700001 PM 11054462 ER PT J AU Borde, V Goldman, ASH Lichten, M AF Borde, V Goldman, ASH Lichten, M TI Direct coupling between meiotic DNA replication and recombination initiation SO SCIENCE LA English DT Article ID DOUBLE-STRAND BREAKS; YEAST CHROMOSOME-III; SACCHAROMYCES-CEREVISIAE; MEIOSIS; MRE11; TIME; ACTIVATION; MUTATIONS; CHROMATIN; ORIGINS AB During meiosis in Saccharomyces cerevisiae, DNA replication occurs 1.5 to 2 hours before recombination initiates by DNA double-strand break formation. We show that replication and recombination initiation are directly linked. Blocking meiotic replication prevented double-strand break formation in a replication-checkpoint-independent manner, and delaying replication of a chromosome segment specifically delayed break formation in that segment. Consequently, the time between replication and break formation was held constant in all regions. We suggest that double-strand break formation occurs as part of a process initiated by DNA replication, which thus determines when meiotic recombination initiates on a regional rather than a cell-wide basis. C1 NCI, Div Basic Sci, Biochem Lab, Bethesda, MD 20892 USA. Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England. RP Lichten, M (reprint author), NCI, Div Basic Sci, Biochem Lab, Bethesda, MD 20892 USA. RI Borde, Valerie/G-5228-2012; Lichten, Michael/C-5795-2013 OI Lichten, Michael/0000-0001-9707-2956 NR 25 TC 164 Z9 171 U1 0 U2 6 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 OCT 27 PY 2000 VL 290 IS 5492 BP 806 EP 809 DI 10.1126/science.290.5492.806 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367ND UT WOS:000090067600049 PM 11052944 ER PT J AU Topol, IA Tawa, GJ Caldwell, RA Eissenstat, MA Burt, SK AF Topol, IA Tawa, GJ Caldwell, RA Eissenstat, MA Burt, SK TI Acidity of organic molecules in the gas phase and in aqueous solvent SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID DENSITY-FUNCTIONAL THEORY; CONTINUUM DIELECTRIC THEORY; SOLVATION FREE-ENERGIES; MOLLER-PLESSET METHODS; AB-INITIO; CONFORMATIONAL ENERGIES; GAUSSIAN-2 THEORY; MODEL; THERMOCHEMISTRY; THERMODYNAMICS AB Using a combination of ab initio, DFT and continuum solvation methods, the gas phase and aqueous acidities for a set of weak organic acids with high pK(a) values, which cannot be measured experimentally in aqueous solvent, have been calculated. Comparison of the computed and experimental data for different terms used in the thermodynamic cycle for the calculation of pK(a) values allowed us to estimate that the errors in the pK(a) calculations are of order of 2 pK(a) units, i.e., less than 10% of the expected pK(a) values for the studied weak organic acids. It is shown that inclusion of explicit water molecules in the solute cavity of compounds with pK(a) values over 40 could lead to dubious results due to the inappropriate description of the corresponding anion solvation. Acidity trends for compounds in the gas phase and in aqueous solvent were found to be different, due to the effects of aqueous solvation. C1 NCI, Frederick Canc Res & Dev Ctr, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Struct Biochem Program, SAIC Frederick, Frederick, MD 21702 USA. Univ Texas, Dept Chem, Richardson, TX 75083 USA. RP Topol, IA (reprint author), NCI, Frederick Canc Res & Dev Ctr, Adv Biomed Comp Ctr, SAIC Frederick, POB B, Frederick, MD 21702 USA. NR 57 TC 58 Z9 58 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD OCT 26 PY 2000 VL 104 IS 42 BP 9619 EP 9624 DI 10.1021/jp001938h PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 369QD UT WOS:000165077700030 ER PT J AU Freitas-Junior, LH Bottius, E Pirrit, LA Deitsch, KW Scheidig, C Guinet, F Nehrbass, U Wellems, TE Scherf, A AF Freitas-Junior, LH Bottius, E Pirrit, LA Deitsch, KW Scheidig, C Guinet, F Nehrbass, U Wellems, TE Scherf, A TI Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P-falciparum SO NATURE LA English DT Article ID PARASITE PLASMODIUM-FALCIPARUM; ANTIGENIC VARIATION; INFECTED ERYTHROCYTES; ACQUIRED-IMMUNITY; CEREBRAL MALARIA; ADHERENCE; SURFACE; TRANSCRIPTION; EXPRESSION; PHENOTYPES AB Persistent and recurrent infections by Plasmodium falciparum malaria parasites result from the ability of the parasite to undergo antigenic variation and evade host immune attack(1,2). P. falciparum parasites generate high levels of variability in gene families that comprise virulence determinants of cytoadherence and antigenic variation(3-7), such as the var genes. These genes encode the major variable parasite protein (PfEMP-1), and are expressed in a mutually exclusive manner at the surface of the erythrocyte infected by P. falciparum(8-12). Here we identify a mechanism by which var gene sequences undergo recombination at frequencies much higher than those expected from homologous crossover events alone(13). These recombination events occur between sub-telomeric regions of heterologous chromosomes, which associate in clusters near the nuclear periphery in asexual blood-stage parasites or in bouquet-like configurations near one pole of the elongated nuclei in sexual parasite forms. We propose that the alignment of var genes in heterologous chromosomes facilitates gene conversion and promotes the diversity of antigenic and adhesive phenotypes. The association of virulence factors with a specific nuclear subcompartment may also have implications for variation during mitotic recombination in asexual blood stages. C1 Inst Pasteur, Unite Biol Interact Hote Parasite, CNRS, URA 1960, F-75724 Paris 15, France. Inst Pasteur, Lab Biol Cellulaire Noyau, CNRS, URA 1773, F-75724 Paris, France. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Scherf, A (reprint author), Inst Pasteur, Unite Biol Interact Hote Parasite, CNRS, URA 1960, 25 Rue Dr Roux, F-75724 Paris 15, France. RI Scherf, Artur/A-9674-2014; Freitas-Junior, Lucio/C-8677-2011 OI Freitas-Junior, Lucio/0000-0002-8904-7897 NR 32 TC 321 Z9 324 U1 1 U2 19 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 26 PY 2000 VL 407 IS 6807 BP 1018 EP 1022 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 366XX UT WOS:000090032500047 PM 11069183 ER PT J AU Nabel, GJ Sullivan, NJ AF Nabel, GJ Sullivan, NJ TI Antibodies and resistance to natural HIV infection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL DEPLETION; VIREMIA C1 NIH, Bethesda, MD 20892 USA. RP Nabel, GJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 13 Z9 13 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 26 PY 2000 VL 343 IS 17 BP 1263 EP 1265 DI 10.1056/NEJM200010263431711 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 366PQ UT WOS:000090014100011 PM 11071680 ER PT J AU Davey, RT Capra, WB AF Davey, RT Capra, WB TI Viral load in treatment with antiretroviral therapy and interleukin 2 - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIAID, NIH, Bethesda, MD 20892 USA. Chiron Corp, Emeryville, CA 94608 USA. RP Davey, RT (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 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 OCT 25 PY 2000 VL 284 IS 16 BP 2055 EP 2056 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 364QA UT WOS:000089902100018 PM 11042747 ER PT J AU Lu, XB Silver, J AF Lu, XB Silver, J TI Ecotropic murine leukemia virus receptor is physically associated with caveolin and membrane rafts SO VIROLOGY LA English DT Article DE MLV receptor; CAT1; rafts; caveolin ID AMINO-ACID TRANSPORTER; PLASMA-MEMBRANE; CHOLESTEROL; FUSION; HEMAGGLUTININ; RETROVIRUSES; PROTEINS; DOMAINS; ENTRY; EXPRESSION AB We used a Sindbis virus expression system to stably express a chimeric ecotropic murine leukemia virus (MLV) receptor gene, CAT1, fused to green fluorescent protein (gfp) in BHK cells. The chimeric gene was expressed on the cell surface and functioned as an MLV receptor. Using gfp as an epitope tag, we found that CATI cross-immunoprecipitated with caveolin, a cellular protein associated non-clathrin-coated endocytic vesicles. Biochemical studies showed that CATI copurified with caveolin in a detergent-insoluble membrane fraction that forms cholesterol-rich "rafts" on the cell surface. Disruption of rafts by methyl-beta -cyclodextrin, a drug that extracts cholesterol, reduced susceptibility to MLV without decreasing surface CATI. The results indicate that association of the MLV receptor with cholesterol-rich rafts is important for an early step in virus infection. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Silver, J (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 336, Bethesda, MD 20892 USA. OI Silver, Jonathan/0000-0001-9231-6368 NR 39 TC 59 Z9 59 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 25 PY 2000 VL 276 IS 2 BP 251 EP 258 DI 10.1006/viro.2000.0555 PG 8 WC Virology SC Virology GA 371YH UT WOS:000165206500004 PM 11040117 ER PT J AU Kawagishi-Kobayashi, M Cao, CN Lu, JM Ozato, K Dever, TE AF Kawagishi-Kobayashi, M Cao, CN Lu, JM Ozato, K Dever, TE TI Pseudosubstrate inhibition of protein kinase PKR by swine pox virus C8L gene product SO VIROLOGY LA English DT Article ID STRANDED-RNA-BINDING; INITIATION FACTOR-II; VACCINIA VIRUS; SACCHAROMYCES-CEREVISIAE; TRANSLATIONAL CONTROL; ALPHA-SUBUNIT; SEQUENCE-ANALYSIS; DNA-SEQUENCE; K3L PROTEIN; INTERFERON AB The interferon-induced protein kinase PKR is activated upon binding double-stranded RNA and phosphorylates the translation initiation factor eIF2 alpha on Ser-51 to inhibit protein synthesis in virally infected cells. Swinepox virus C8L and vaccinia virus K3L gene products structurally resemble the amino-terminal third of eIF2 alpha. We demonstrate that the C8L protein, like the K3L protein, can reverse the toxic effects caused by high level expression of human PKR in yeast cells. In addition, expression of either the K3L or C8L gene product was found to reverse the inhibition of reporter gene translation caused by PKR expression in mammalian cells. The inhibitory function of the K3L and C8L gene products in these assays was found to be critically dependent on residues near the carboxyl-termini of the proteins including a sequence motif shared among eIF2 alpha and the C8L and K3L gene products. Thus, despite significant sequence differences both the C8L and K3L proteins function as pseudosubstrate inhibitors of PKR. (C) 2000 Academic Press. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Dever, TE (reprint author), NICHHD, Lab Eukaryot Gene Regulat, NIH, 6 Ctr Dr, Bethesda, MD 20892 USA. OI Dever, Thomas/0000-0001-7120-9678 NR 44 TC 28 Z9 28 U1 2 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 25 PY 2000 VL 276 IS 2 BP 424 EP 434 DI 10.1006/viro.2000.0561 PG 11 WC Virology SC Virology GA 371YH UT WOS:000165206500020 PM 11040133 ER PT J AU Brown, P Preece, M Brandel, JP Sato, T McShane, L Zerr, I Fletcher, A Will, RG Pocchiari, M Cashman, NR d'Aignaux, JH Cervenakova, L Fradkin, J Schonberger, LB Collins, SJ AF Brown, P Preece, M Brandel, JP Sato, T McShane, L Zerr, I Fletcher, A Will, RG Pocchiari, M Cashman, NR d'Aignaux, JH Cervenakova, L Fradkin, J Schonberger, LB Collins, SJ TI Iatrogenic Creutzfeldt-Jakob disease at the millennium SO NEUROLOGY LA English DT Review DE aaaaaaaa ID PRION PROTEIN GENOTYPE; HUMAN GROWTH-HORMONE; PERSON TRANSMISSION; TRANSPLANTATION; GRAFT AB The causes and geographic distribution of 267 cases of iatrogenic Creutzfeldt-Jakob disease (CJD) are here updated at the millennium. Small numbers of still-occurring cases result from disease onsets after longer and longer incubation periods following infection by cadaveric human growth hormone or dura mater grafts manufactured and distributed before the mid-1980s. The proportion of recipients acquiring CJD from growth hormone varies from 0.3 to 4.4% in different countries, and acquisition from dura mater varies between 0.02 and 0.05% in Japan (where most cases occurred), Incubation periods can extend up to 30 years, and cerebellar onsets predominate in both hormone and graft recipients (in whom the site of graft placement had no effect on the clinical presentation). Homozygosity at codon 129 of the PRNP gene is over-represented in both forms of disease; it has no effect on the incubation period of graft recipients, but may promote shorter incubation periods in hormone cases. Knowledge about potential high-risk sources of contamination gained during the last quarter century, and the implementation of methods to circumvent them, should minimize the potential for iatrogenic contributions to the current spectrum of CJD. C1 NINDS, CNS Studies Lab, NIH, Bethesda, MD 20892 USA. NINDS, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. UCL, Inst Child Hlth, London, England. Grp Hosp Pitie Salpetriere, U360 INSERM, Ctr Natl Reference Malad CJ, Paris, France. Khonodai Hosp, Chiba, Japan. Univ Gottingen, Neurol Klin & Poliklin, D-3400 Gottingen, Germany. Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. Western Gen Hosp, CJD Surveillance Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Ist Super Sanita, Virol Lab, I-00161 Rome, Italy. Canadian CJD Surveillance Syst, Ottawa, ON, Canada. Univ Toronto, Toronto, ON, Canada. Amer Red Cross, Jerome H Holland Lab, Rockville, MD USA. CDC, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. RP Brown, P (reprint author), NINDS, CNS Studies Lab, NIH, Bldg 36,Room 4A-05,36 Convent Dr,MSC 4122, Bethesda, MD 20892 USA. EM brownp@ninds.nih.gov NR 19 TC 347 Z9 359 U1 3 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 24 PY 2000 VL 55 IS 8 BP 1075 EP 1081 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 366PB UT WOS:000090012800003 PM 11071481 ER PT J AU Bookheimer, SY Zeffiro, TA Blaxton, TA Gaillard, W Theodore, WH AF Bookheimer, SY Zeffiro, TA Blaxton, TA Gaillard, W Theodore, WH TI Activation of language cortex with automatic speech tasks SO NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; BLOOD-FLOW; INTRAVENOUS (H2O)-O-15; PREFRONTAL CORTEX; HUMAN BRAIN; PET IMAGES; LOCALIZATION; ANATOMY; LATERALIZATION; COMPREHENSION AB Objective: To identify automatic speech tasks that reliably demonstrate increased regional cerebral blood flow (rCBF) in Broca's and Wernicke's areas of the cortex using PET. Background: Localizing language with direct cortical stimulation mapping requires that patients have a stable baseline on tests that engage eloquent cortex. For dysphasic patients or younger children, automatic speech tasks such as counting are often used in lieu of more complex language tests. Evidence from both lesion and neuroimaging studies suggests that these tasks may not adequately engage language cortices. In this study, we examined rCBF during automatic oromotor and speech tasks of varying complexity to identify those eliciting increased CBF in Broca's and Wernicke's areas. Methods: Eight normal volunteers underwent PET during rest, tongue movements, and three automatic speech tasks: repeating a phoneme sequence, repeating the months of the year, and reciting a memorized prose passage. Images were averaged across subjects and compared across tasks for regional localization and laterality. Results: Whereas all activation tasks produced increased relative CBF in brain regions that correlated with articulation and auditory processing, only the two tasks that used real words (versus phonemes) showed left-lateralized rCBF increases in posterior superior temporal lobe (Wernicke's area), and only the prose repetition task produced left lateralized activity in Broca's area. Conclusions: Whereas automatic speech typically does not engage language cortex, repeating a memorized prose passage showed unambiguous activation in both Broca's and Wernicke's areas. These results caution against the use of common automatic speech tasks for mapping eloquent cortex and suggest an alternative task for those with poor language abilities or acquired dysphasia who cannot perform standardized language tests reliably. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD USA. RP Bookheimer, SY (reprint author), Univ Calif Los Angeles, Sch Med, Ahmanson Lovelace Brain Mapping Ctr, 660 Charles Young Dr, Los Angeles, CA 90095 USA. NR 47 TC 80 Z9 84 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 24 PY 2000 VL 55 IS 8 BP 1151 EP 1157 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 366PB UT WOS:000090012800015 PM 11071493 ER PT J AU Plassman, BL Havlik, RJ Steffens, DC Helms, MJ Newman, TN Drosdick, D Phillips, C Gau, BA Welsh-Bohmer, KA Burke, JR Guralnik, JM Breitner, JCS AF Plassman, BL Havlik, RJ Steffens, DC Helms, MJ Newman, TN Drosdick, D Phillips, C Gau, BA Welsh-Bohmer, KA Burke, JR Guralnik, JM Breitner, JCS TI Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E GENOTYPE; TRAUMATIC BRAIN INJURY; AGING TWIN VETERANS; DIAGNOSIS; ONSET; QUESTIONNAIRE; ASSOCIATION; RELIABILITY; REGISTRY; SEQUELAE AB Background: The association between antecedent head injury and AD is inconsistent. Objective: To examine the association between early adult head injury, as documented by military hospital records, and dementia in late life; and to evaluate the interaction between head injury and APOE epsilon4 as risk factors for dementia. Methods: The study had a population-based prospective historical cohort design. It included men who were World War II Navy and Marine veterans, and were hospitalized during their military service with a diagnosis of either a nonpenetrating head injury or another unrelated condition. In 1996 to 1997, military medical records were abstracted to document; the occurrence and details of closed head injury. The entire sample was then evaluated for dementia and AD using a multistage procedure. There were 548 veterans with head injury and 1228 without head injury who completed all assigned stages of the study. The authors estimated risk of dementia, specifically AD, using proportional hazards models. Results: Both moderate head injury (hazard ratio [HR] = 2.32; CI = 1.04 to 5.17) and severe head injury (HR = 4.51; CI = 1.77 to 11.47) were associated with increased risk of AD. Results mere similar for dementia in general. The results for mild head injury were inconclusive. When the authors stratified by the number of APOE epsilon4 alleles, they observed a nonsignificant trend toward a stronger association between AD and head injury in men with more epsilon4 alleles. Conclusions: Moderate and severe head injuries in young men may be associated with increased risk of AD and other dementias in late life. However, the authors cannot exclude the possibility that other unmeasured factors may be influencing this association. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC 27706 USA. Duke Univ, Med Ctr, Dept Neurol, Durham, NC 27706 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21218 USA. RP Plassman, BL (reprint author), Box 41,905 W Main St,Suite 25D, Durham, NC 27701 USA. RI Burke, James/E-4245-2016 OI Burke, James/0000-0002-3408-7787 FU NIA NIH HHS [N01-AG-4-2142] NR 40 TC 346 Z9 355 U1 4 U2 27 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 24 PY 2000 VL 55 IS 8 BP 1158 EP 1166 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 366PB UT WOS:000090012800016 PM 11071494 ER PT J AU Cantos, R Cole, LK Acampora, D Simeone, A Wu, DK AF Cantos, R Cole, LK Acampora, D Simeone, A Wu, DK TI Patterning of the mammalian cochlea SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT National Academy of Sciences Colloquium on Auditory Neuroscience - Development, Transduction, and Integration CY MAY 19-21, 2000 CL IRVINE, CA SP Natl Acad Sci ID MOUSE INNER-EAR; MUTATIONS AFFECTING DEVELOPMENT; BRANCHIOOTORENAL BOR SYNDROME; HOMEOBOX GENE; MICE LACKING; TARGETED DISRUPTION; CRANIAL NERVES; SENSORY ORGANS; HUMAN HOMOLOG; MUTANT MICE AB The mammalian cochlea is sophisticated in its function and highly organized in its structure. Although the anatomy of this sense organ has been well documented, the molecular mechanisms underlying its development have remained elusive. Information generated from mutant and knockout mice in recent years has increased our understanding of cochlear development and physiology. This article discusses factors important for the development of the inner ear and summarizes cochlear phenotypes of mutant and knockout mice, particularly Otx and Otx2. We also present data on gross development of the mouse cochlea. C1 Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA. CNR, Int Inst Genet & Biophys, I-80125 Naples, Italy. Kings Coll London, MRC, Ctr Dev Neurobiol, London SE1 1UL, England. RP Wu, DK (reprint author), Natl Inst Deafness & Other Commun Disorders, 5 Res Court,Room 2B34, Rockville, MD 20850 USA. EM wud@nidcd.nih.gov RI Cantos Coll, Raquel /A-6318-2013; Acampora, Dario/C-2156-2013 OI Cantos Coll, Raquel /0000-0002-5516-0074; NR 73 TC 80 Z9 83 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 24 PY 2000 VL 97 IS 22 BP 11707 EP 11713 DI 10.1073/pnas.97.22.11707 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367PQ UT WOS:000090071000009 PM 11050199 ER PT J AU Chao, C Saito, S Anderson, CW Appella, E Xu, Y AF Chao, C Saito, S Anderson, CW Appella, E Xu, Y TI Phosphorylation of murine p53 at Ser-18 regulates the p53 responses to DNA damage SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-KINASE; ES CELLS; ATM; SERINE-15; TRANSACTIVATION; ACETYLATION; ACTIVATION; APOPTOSIS; RADIATION; MUTATION AB Ser-15 of human p53 (corresponding to Ser-18 of mouse p53) is phosphorylated by ataxia-telangiectasia mutated (ATM) family kinases in response to ionizing radiation (IR) and UV light, To determine the effects of phosphorylation of endogenous murine p53 at Ser-18 on biological responses to DNA damage, we introduced a missense mutation (Ser-18 to Ala) by homologous recombination into both alleles of the endogenous p53 gene in mouse embryonic stem (ES) cells. Our analyses showed that phosphorylation of murine p53 at Ser-18 in response to IR or UV radiation was required for a full p53-mediated response to these DNA damage-inducing agents. In contrast, phosphorylation of p53 at Ser-18 was not required for ATM-dependent cellular resistance after exposure to IR, Additionally, efficient acetylation of the C terminus of p53 in response to DNA damage did not require phosphorylation of murine p53 at Ser-18. C1 Univ Calif San Diego, Div Biol, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Xu, Y (reprint author), Univ Calif San Diego, Div Biol, 9500 Gilman Dr, La Jolla, CA 92093 USA. FU NIGMS NIH HHS [GM52825] NR 38 TC 120 Z9 122 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 OCT 24 PY 2000 VL 97 IS 22 BP 11936 EP 11941 DI 10.1073/pnas.220252297 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367PQ UT WOS:000090071000044 PM 11035798 ER PT J AU Tsai, CJ Maizel, JV Nussinov, R AF Tsai, CJ Maizel, JV Nussinov, R TI Anatomy of protein structures: Visualizing how a one-dimensional protein chain folds into a three-dimensional shape SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE protein folding; anatomy; hydrophobic folding unit; building block ID BOVINE ALPHA-LACTALBUMIN; LIMITED PROTEOLYSIS; GLOBULAR-PROTEINS; INITIATION SITES; LOCAL-STRUCTURE; MOLTEN GLOBULE; PEPTIDE MODELS; UNITS; HAIRPIN; BINDING AB Here, we depict the anatomy of protein structures in terms of the protein folding process. Via an iterative, top-down dissecting procedure, tertiary structures are spliced down to reveal their anatomy: first,to produce domains (defined by visual three-dimensional inspection criteria); then, hydrophobic folding units (HFU); and, at the end of a multilevel process, a set of building blocks. The resulting anatomy tree organization not only clearly depicts the organization of a one-dimensional polypeptide chain in three-dimensional space but also straightforwardly describes the most likely folding pathway(s). Comparison of the tree with the formation of the hydrophobic folding units through combinatorial assembly of the building blocks illustrates how the chain folds in a sequential or a complex folding pathway. Further, the tree points to the kinetics of the folding, whether the chain is a fast or a slow folder, and the probability of misfolding. Our ability to successfully dissect the protein into an anatomy tree illustrates that protein folding is a hierarchical process and further validates a building blocks protein folding model. C1 NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Fac Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Tsai, CJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Sci Applicat Int Corp, Bldg 469,Room 151, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 44 TC 62 Z9 63 U1 1 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 OCT 24 PY 2000 VL 97 IS 22 BP 12038 EP 12043 DI 10.1073/pnas.97.22.12038 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367PQ UT WOS:000090071000061 PM 11050234 ER PT J AU Senkevich, TG White, CL Koonin, EV Moss, B AF Senkevich, TG White, CL Koonin, EV Moss, B TI A viral member of the ERV1/ALR protein family participates in a cytoplasmic pathway of disulfide bond formation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE poxvirus; vaccinia virus; thiol oxidoreductase; glutaredoxin ID OPEN READING FRAME; VACCINIA VIRUS; ESCHERICHIA-COLI; LIVER-REGENERATION; VIRION ENVELOPE; GLUTAREDOXIN; GENE; FUSION; THIOREDOXIN; EXPRESSION AB Proteins of the ERV1/ALR family are encoded by all eukaryotes and cytoplasmic DNA viruses for which substantial sequence information is available. Nevertheless, the roles of these proteins are imprecisely known. Multiple alignments of ERV1/ALR proteins indicated an invariant C-X-X-C motif, but no similarity to the thioredoxin fold was revealed by secondary structure predictions. We chose a virus model to investigate the role of these proteins as thiol oxidoreductases. When cells were infected with a mutant vaccinia virus in which the E10R gene encoding an ERV1/ALR family protein was repressed, the disulfide bonds of three other viral proteins-namely, the L1R and F9L proteins and the G4L glutaredoxin-were completely reduced. The same outcome occurred when Cys-43 or Cys-46, the putative redox cysteines of the E10R protein, was mutated to serine. These two cysteines were disulfide bonded during a normal virus infection but not if the synthesis of other viral late proteins was inhibited or the E10R protein was expressed by itself in uninfected cells, suggesting a requirement for an upstream viral thiol oxidoreductase. Remarkably, the cysteine-containing domains of the E10R and L1R viral membrane proteins and the glutaredoxin are in the cytoplasm, in which assembly of vaccinia virions occurs, rather than in the oxidizing environment of the endoplasmic reticulum, These data indicated a viral pathway of disulfide bond formation in which the E10R protein has a central role. By extension, the ERV1/ALR family may represent a ubiquitous class of cellular thiol oxidoreductases that interact with glutaredoxins or thioredoxins. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. NR 33 TC 113 Z9 117 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 OCT 24 PY 2000 VL 97 IS 22 BP 12068 EP 12073 DI 10.1073/pnas.210397997 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367PQ UT WOS:000090071000066 PM 11035794 ER PT J AU Kawahara, A Wilm, T Solnica-Krezel, L Dawid, IB AF Kawahara, A Wilm, T Solnica-Krezel, L Dawid, IB TI Antagonistic role of vega1 and bozorok/dharma homeobox genes in organizer formation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SPEMANNS ORGANIZER; XENOPUS EMBRYOS; ZEBRAFISH; EXPRESSION; INDUCTION; PATHWAY; SPECIFICATION; GASTRULATION; PREGASTRULA; ACTIVIN AB During zebrafish development, zygotic gene expression initiated at the midblastula transition converts maternal information on embryo polarity into a transcriptional read-out. Expression of a homeobox gene, vega1, is activated at midblastula transition in all blastomeres, but is down-regulated dorsally before gastrulation. Ubiquitous expression of vega1 is maintained in bozozok mutants, in which the dorsal-specific homeobox gene bozorok/dharma (boz/dha) is disrupted and organizer formation is impaired. Vega1 inhibits expression of boz/dha and organizer-specific genes, and causes ventralization resulting in a headless phenotype. In contrast, VP16-vega1, a fusion including the Vega1 homeodomain and VP16 activation domain, elicits ectopic expression of organizer genes and suppresses several aspects of the boz mutant phenotype. We propose that boz/dha-dependent down-regulation of vega1 in the dorsal region is an early essential step in organizer formation in zebrafish. C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Biol Mol, Nashville, TN 37235 USA. RP Dawid, IB (reprint author), NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. NR 33 TC 52 Z9 55 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 24 PY 2000 VL 97 IS 22 BP 12121 EP 12126 DI 10.1073/pnas.97.22.12121 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367PQ UT WOS:000090071000075 PM 11050240 ER PT J AU Srikantan, V Zou, ZQ Petrovics, G Xu, L Augustus, M Davis, L Livezey, JK Connell, T Sesterhenn, IA Yoshino, K Buzard, GS Mostofi, FK McLeod, DG Moul, JW Srivastava, S AF Srikantan, V Zou, ZQ Petrovics, G Xu, L Augustus, M Davis, L Livezey, JK Connell, T Sesterhenn, IA Yoshino, K Buzard, GS Mostofi, FK McLeod, DG Moul, JW Srivastava, S TI PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE riboregulator; differential display; androgen regulation; noncoding RNA ID NONCODING RNA; MEMBRANE ANTIGEN; SERINE-PROTEASE; MESSENGER-RNA; EXPRESSION; DISEASE; NKX3.1 AB A prostate-specific gene, PCGEM1, was identified by differential display analysis of paired normal and prostate cancer tissues. Multiple tissue Northern blot analysis revealed that PCGEM1 was expressed exclusively in human prostate tissue. Analysis of PCGEM1 expression in matched normal and primary tumor specimens revealed tumor-associated overexpression in 84% of patients with prostate cancer by in situ hybridization assay and in 56% of patients by reverse transcription-PCR assay. Among various prostate: cancer cell lines analyzed, PCGEM1 expression was detected only in the androgen receptor-positive cell line LNCaP. Extensive DNA sequence analysis of the PCGEM1 cDNA and genomic DNA revealed that PCGEM1 lacks protein-coding capacity and suggests that it may belong to an emerging class of noncoding RNAs, also called "riboregulators." The PCGEM1 locus was mapped to chromosome 2q32, Taken together, the remarkable prostate-tissue specificity and androgen-dependent expression of PCGEM1 as well as its elevated expression in a significant percentage of tumor tissues suggest specific functions of PCGEM1 in the biology and tumorigenesis of the prostate gland. C1 Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA. NCI, Dept Genet, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Genitourinary Pathol, Washington, DC 20307 USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Sci Applicat Int Corp, Frederick, MD 21702 USA. Walter Reed Army Med Ctr, Dept Surg, Urol Serv, Washington, DC 20307 USA. RP Srivastava, S (reprint author), Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA. NR 26 TC 171 Z9 188 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 24 PY 2000 VL 97 IS 22 BP 12216 EP 12221 DI 10.1073/pnas.97.22.12216 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367PQ UT WOS:000090071000092 PM 11050243 ER PT J AU Sun, MK Nelson, TJ Alkon, DL AF Sun, MK Nelson, TJ Alkon, DL TI Functional switching of GABAergic synapses by ryanodine receptor activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYCLIC ADP-RIBOSE; CA2+ RELEASE CHANNELS; POSTSYNAPTIC POTENTIALS; SYNAPTIC PLASTICITY; PYRAMIDAL CELLS; IN-VITRO; RAT; CALCIUM; NEURONS; HIPPOCAMPUS AB The role of the ryanodine receptor (RyR) in modifiability of synapses made by the basket interneurons onto the hippocampal CA1 pyramidal cells was examined in rats. Associating single-cell RyR activation with postsynaptic depolarization increased intracellular free Ca2+ concentrations and reversed the basket interneuron-CA1 inhibitory postsynaptic potential into an excitatory postsynaptic potential. This synaptic transformation was accompanied by a shift of the reversal potential from that of chloride toward that of bicarbonate, This inhibitory postsynaptic potential-excitatory postsynaptic potential transformation was prevented by blocking RyR or carbonic anhydrase. Associated postsynaptic depolarization and RyR activation, therefore, changes GABAergic synapses from excitation filters to amplifier and, thereby, shapes information flow through the hippocampal network. C1 NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. RP Sun, MK (reprint author), NINDS, Lab Adapt Syst, NIH, Bldg 36,Room 4A24,36 Convent Dr, Bethesda, MD 20892 USA. NR 47 TC 14 Z9 14 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 24 PY 2000 VL 97 IS 22 BP 12300 EP 12305 DI 10.1073/pnas.210396697 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367PQ UT WOS:000090071000107 PM 11027306 ER PT J AU Uwaifo, GI AF Uwaifo, GI TI Hypertensive emergencies SO LANCET LA English DT Letter ID TETANUS C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Uwaifo, GI (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10 N 262, Bethesda, MD 20892 USA. RI Uwaifo, Gabriel/M-2361-2016 OI Uwaifo, Gabriel/0000-0002-6962-9304 NR 5 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 21 PY 2000 VL 356 IS 9239 BP 1442 EP 1442 DI 10.1016/S0140-6736(05)74084-8 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 365XQ UT WOS:000089976100062 PM 11052613 ER PT J AU Vanham, G Penne, L Allemeersch, H Kestens, L Willems, B van der Groen, G Jeang, KT Toossi, Z Rich, E AF Vanham, G Penne, L Allemeersch, H Kestens, L Willems, B van der Groen, G Jeang, KT Toossi, Z Rich, E TI Modeling HIV transfer between dendritic cells and T cells: importance of HIV phenotype, dendritic cell-T cell contact and T-cell activation SO AIDS LA English DT Article DE HIV transfer; HIV bio-phenotype; dendritic cells; CD4 T cells; HLA-DR ID HUMAN-IMMUNODEFICIENCY-VIRUS; LANGERHANS CELLS; PRODUCTIVE INFECTION; VIRAL REPLICATION; RHESUS MACAQUES; ANTIGEN; TYPE-1; MACROPHAGES; EXPRESSION; EFFICIENT AB Objective: To study the requirements for HIV transfer between dendritic cells (DC) and CD4 T cells, using an in vitro model, combined with flow cytometry. Methods: Immature DC and macrophages (MA) were generated from monocytes. After infection, DC or MA were cultured alone or with purified CD4 T cells. Intracellular HIV was measured, using (1) the monocyte (MO)-tropic AD8 HIV, endowed with enhanced green fluorescent protein (EGFP); and (2) intracellular staining of laboratory HIV strains and clones from primary isolates. Results: (1) Clone AD8-EGFP infected DC and MA with equal efficiency, but the virus was preferentially transferred from DC to autologous T cells. (2) DC were more productively infected with R5/NSI, as compared to X4/SI, HIV, but both HIV phenotypes were easily transmitted to autologous T4 cells. (3) HIV-infected DC transferred the virus to T cells across a semi-permeable membrane, if the T cells were in contact with non-infected DC. (4) Go-culture of T cells with autologous non-infected DC induced T-cell activation. HIV-infected DC selectively increased HLA-DR on T cells and HLA-DR (+) T cells were preferential targets for HIV transfer. (5) Resting Ba-L-infected CD4 T cells were able to transmit the virus 'inversely' to co-cultured DC. Conclusion: HIV transfer between monocyte-derived dendritic cells and autologous CD4 T cells was directly demonstrated using flow cytometry. The transfer proceeded in both directions, depended on cellular contact and was associated with partial T-cell activation. This model, representing relevant in vivo targets of HIV, is useful to further investigate interactions between HIV, DC and T cells, without the need for primary ex vivo DC. (C) 2000 Lippincott Williams & Wilkins. C1 Inst Trop Med, Virol Lab, Dept Microbiol, B-2000 Antwerp, Belgium. Inst Trop Med, Immunol Lab, B-2000 Antwerp, Belgium. NIH, Mol Virol Sect, Mol Microbiol Lab, Bethesda, MD 20892 USA. Case Western Reserve Univ Hosp, Dept Med, Cleveland, OH 44106 USA. RP Vanham, G (reprint author), Inst Trop Med, Immunol Lab, 155 Natl Str, B-2000 Antwerp, Belgium. RI Jeang, Kuan-Teh/A-2424-2008 FU NHLBI NIH HHS [HL 51636, HL 53247, HL57940] NR 44 TC 28 Z9 30 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 20 PY 2000 VL 14 IS 15 BP 2299 EP 2311 DI 10.1097/00002030-200010200-00011 PG 13 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 371AL UT WOS:000165155400010 PM 11089618 ER PT J AU Gray, RH Kiwanuka, N Quinn, TC Sewankambo, NK Serwadda, D Mangen, FW Lutalo, T Nalugoda, F Kelly, R Meehan, M Chen, MZ Li, CJ Wawer, MJ AF Gray, RH Kiwanuka, N Quinn, TC Sewankambo, NK Serwadda, D Mangen, FW Lutalo, T Nalugoda, F Kelly, R Meehan, M Chen, MZ Li, CJ Wawer, MJ CA Rakai Project Team TI Male circumcision and HIV acquisition and transmission: cohort studies in Rakai, Uganda SO AIDS LA English DT Article DE acquisition; circumcision; discordant couples; HIV; transmission; viral load ID IMMUNODEFICIENCY-VIRUS TYPE-1; SEXUALLY-TRANSMITTED DISEASES; AIDS-PREVENTION; COMMUNITY TRIAL; INFECTION; TANZANIA; SEROCONVERSION; RISK; MEN AB Background: Male circumcision is associated with reduced HIV acquisition. Methods: HIV acquisition was determined in a cohort of 5507 HIV-negative Ugandan men, and in 187 HIV-negative men in discordant relationships. Transmission was determined in 223 HIV-positive men with HIV-negative partners. HIV incidence per 100 person years (py) and adjusted rate ratios (RR) and 95% confidence intervals (CI) were estimated by Poisson regression. HIV-1 serum viral load was determined for the seropositive partners in HIV-discordant couples. Results: The prevalence of circumcision was 16.5% fbr all men; 99.1% in Muslims and 3.7% in non-Muslims. Circumcision was significantly associated with reduced HIV acquisition in the cohort as a whole (RR 0.53, CI 0.33-0.87), but not among non-Muslim men. Prepubertal circumcision significantly reduced HIV acquisition (RR 0.49, CI 0.26-0.82), but postpubertal circumcision did not. In discordant couples with HIV-negative men, no serconversions occurred in 50 circumcised men, whereas HIV acquisition was 16.7 per 100 py in uncircumcised men (P = 0.004). In couples with HIV-positive men, HIV transmission was significantly reduced in circumcised men with HIV viral loads less than 50 000 copies/ml (P = 0.02). Interpretation: Prepubertal circumcision may reduce male HIV acquisition in a general population, but the protective effects are confounded by cultural and behavioral factors in Muslims. In discordant couples, circumcision reduces HIV acquisition and transmission. The assessment of circumcision for HIV prevention is complex and requires randomized trials. (C) 2000 Lippincott Williams & Wilkins. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Populat & Family Hlth Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Infect Dis, Bethesda, MD USA. NIAID, Bethesda, MD 20892 USA. Uganda Virus Res Inst, Rakai Project, Entebbe, Uganda. Makerere Univ, Dept Med, Kampala, Uganda. Makerere Univ, Clin Epidemiol Unit, Kampala, Uganda. Makerere Univ, Inst Publ Hlth, Kampala, Uganda. Columbia Univ, Sch Publ Hlth, Ctr Populat & Family Hlth, New York, NY 10027 USA. RP Gray, RH (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Populat & Family Hlth Sci, Room 4030,615 N Wolfe St, Baltimore, MD 21205 USA. RI Quinn, Thomas/A-2494-2010; OI Sewankambo, Nelson/0000-0001-9362-053X FU NIAID NIH HHS [R01 AI34826, R01 AI34826S]; NICHD NIH HHS [5P30HD06826] NR 21 TC 161 Z9 170 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 20 PY 2000 VL 14 IS 15 BP 2371 EP 2381 DI 10.1097/00002030-200010200-00019 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 371AL UT WOS:000165155400018 PM 11089626 ER PT J AU Dana, RR Eigsti, C Holmes, KL Leto, TL AF Dana, RR Eigsti, C Holmes, KL Leto, TL TI A regulatory role for ADP-ribosylation factor 6 (ARF6) in activation of the phagocyte NADPH oxidase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOLIPASE-D ACTIVITY; GTP-BINDING-PROTEIN; HUMAN-NEUTROPHILS; PLASMA-MEMBRANE; MAMMALIAN-CELLS; OXIDATIVE BURST; HL-60 CELLS; TRANSLOCATION; INVOLVEMENT; REQUIREMENT AB In activated neutrophils NADPH oxidase is regulated through various signaling intermediates, including heterotrimeric G proteins, kinases, GTPases, and phospholipases, ADP-ribosylation factor (ARF) describes a family of GTPases associated with phospholipase D (PLD) activation. PLD is implicated in NADPH oxidase activation, although it is unclear whether activation of PLD by ARF is linked to receptor-mediated oxidase activation. We explored whether ARF participates in NADPH oxidase activation by formyl-methionine-leucine-phenylalanine (fMLP) and whether this involves PLD. Using multicolor forward angle light scattering analyses to measure superoxide production in differentiated neutrophil-like PLB-985 cells, we tested enhanced green fluorescent fusion proteins of wild-type ARF1 or ARF6, or their mutant counterparts. The ARF6(Q67L) mutant defective in GTP hydrolysis caused increased superoxide production, whereas the ARF6(T27N) mutant defective in GTP binding caused diminished responses to fMLP. The ARF1 mutants had no effect on fMLP responses, and none of the ARF proteins affected phorbol 12-myristate 13-acetate-elicited oxidase activity. PLD inhibitors 1-butanol and 2,3-diphosphoglycerate, or the ARF6(N48R) mutant assumed to be defective in PLD activation, blocked fMLP-elicited oxidase activity in transfected cells. The data suggest that ARF6 but not ARF1 modulates receptor-mediated NADPH oxidase activation in a PLD-dependent mechanism. Because PMA-elicited NADPH oxidase activation also appears to be PLD-dependent, but ARF-independent, ARF6 and protein kinase C may act through distinct pathways, both involving PLD. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Flow Cytometry Sect, NIH, Bethesda, MD 20892 USA. RP Leto, TL (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Rm 11N106, Bethesda, MD 20892 USA. NR 41 TC 26 Z9 26 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 20 PY 2000 VL 275 IS 42 BP 32566 EP 32571 DI 10.1074/jbc.M005406200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 366KD UT WOS:000090003800027 PM 10931844 ER PT J AU Kaldis, P Cheng, AY Solomon, MJ AF Kaldis, P Cheng, AY Solomon, MJ TI The effects of changing the site of activating phosphorylation in CDK2 from threonine to serine SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIN-DEPENDENT KINASES; RING FINGER PROTEIN; CELL-CYCLE; BUDDING YEAST; SACCHAROMYCES-CEREVISIAE; CATALYTIC SUBUNIT; STRUCTURAL BASIS; CDC28 MUTATION; IN-VITRO; CAK AB Cyclin-dependent kinases (CDKs) that control cell, cycle progression are regulated in many ways, including activating phosphorylation of a conserved threonine residue. This essential phosphorylation is carried out by the CDK-activating kinase (CAK). Here we examine the effects of replacing this threonine residue in human CDK2 by serine. We found that cyclin A bound equally well to wild-type CDK2 (CDK2(Thr-160)) or to the mutant CDK2 (CDK2(Ser-160)). I, the absence of activating phosphorylation, CDK2(Ser-160)-cyclin A complexes were more active than wild-type CDK2(Thr-160)-cyclin A complexes. In contrast, following activating phosphorylation, CDK2(Ser-160)-cyclin A complexes were less active than phosphorylated CDK2(Thr-160)-cyclin A complexes, reflecting a much smaller effect of activating phosphorylation on CDK2(Ser-160). The kinetic parameters for phosphorylating histone H1 were similar for mutant and wild-type CDK2, ruling out a general defect in catalytic activity. Interestingly, the CDK2(Ser-160) mutant was selectively defective in phosphorylating a peptide derived from the C-terminal domain of RNA polymerase II. CDK2(Ser-160) was efficiently phosphorylated by CAKs, both human p40(MO15)(CDK7)-cyclin H and budding yeast Caklp. In fact, the k(cat) values for phosphorylation of CDK2(Ser-160) were significantly higher than for phosphorylation of CDK2(Thr-160), indicating that CDK2(Ser-160) is actually phosphorylated more efficiently than wild-type CDK2. In contrast, dephosphorylation proceeded more slowly with CDK2(Ser-160) than with wild-type CDK2, either in HeLa cell extract or by purified PP2C beta. Combined with the more efficient phosphorylation of CDK2(Ser-160) by CAK, we suggest that one reason for the conservation of threonine as the site of activating phosphorylation may be to favor unphosphorylated CDKs following the degradation of cyclins. C1 Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. RP Kaldis, P (reprint author), NCI, Frederick Canc Res & Dev Ctr, Regulat Cell Growth Lab, Bldg 560,W 7th St, Frederick, MD 21702 USA. RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 FU NIGMS NIH HHS [GM47830] NR 59 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 20 PY 2000 VL 275 IS 42 BP 32578 EP 32584 DI 10.1074/jbc.M003212200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 366KD UT WOS:000090003800029 PM 10931829 ER PT J AU Majone, F Jeang, KT AF Majone, F Jeang, KT TI Clastogenic effect of the human T-cell leukemia virus type I tax oncoprotein correlates with unstabilized DNA breaks SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MICRONUCLEI; PROTEIN; REPAIR; GENE; IDENTIFICATION; CHROMOSOMES; INDUCTION AB Expression of the human T-cell leukemia virus type I (HTLV-I) Tax oncoprotein rapidly engenders DNA damage as reflected in a significant increase of micronuclei (MN) in cells, To understand better this phenomenon, we have investigated the DNA content of MN induced by Tax. Using an approach that we termed FISHI, fluorescent in situ hybridization and incorporation, we attempted to characterize MN with centric or acentric DNA fragments for the presence or absence of free 3'-OH ends. Free 3'-OH ends were defined as those ends accessible to in situ addition of digoxigenin-dUTP using terminal deoxynucleotidyl transferase. MN were also assessed for centromeric sequences using standard fluorescent in situ hybridization (FISH). Combining these results, we determined that Tax oncoprotein increased the frequency of MN containing centric DNA with free 3'-OH and decreased the frequency of MN containing DNA fragments that had incorporation-inaccessible 3'-ends. Recently, it has been suggested that intracellular DNA breaks without detectable 3'-OH ends are stabilized by the protective addition of telomeric caps, while breaks with freely detectable 3'-OH are uncapped and are labile to degradation, incomplete replication, and loss during cell division. Accordingly, based on increased detection of free 3'-OH-containing DNA fragments, we concluded that HTLV-I Tax interferes with protective cellular mechanism(s) used normally for stabilizing DNA breaks. C1 Univ Padua, Dept Biol, I-35131 Padua, Italy. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Majone, F (reprint author), Univ Padua, Dept Biol, Viale G Colombo 3, I-35131 Padua, Italy. RI Jeang, Kuan-Teh/A-2424-2008 NR 25 TC 59 Z9 59 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 20 PY 2000 VL 275 IS 42 BP 32906 EP 32910 DI 10.1074/jbc.C000538200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 366KD UT WOS:000090003800073 PM 10969065 ER PT J AU Hoover, DM Rajashankar, KR Blumenthal, R Puri, A Oppenheim, JJ Chertov, O Lubkowski, J AF Hoover, DM Rajashankar, KR Blumenthal, R Puri, A Oppenheim, JJ Chertov, O Lubkowski, J TI The structure of human beta-defensin-2 shows evidence of higher order oligomerization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MEMBRANE PERMEABILIZATION; ANTIMICROBIAL PEPTIDES; DIFFRACTION DATA; HUMAN DEFENSINS; LIPID BILAYERS; OUTER-MEMBRANE; BETA-DEFENSINS; PROTEIN; CRYSTALLOGRAPHY; REFINEMENT AB Defensins are small cationic peptides that are crucial components of innate immunity, serving as both antimicrobial agents and chemoattractant molecules. The specific mechanism of antimicrobial activity involves permeabilization of bacterial membranes. It has been postulated that individual monomers oligomerize to form a pore through anionic membranes, although the evidence is only indirect. Here, we report two high resolution x-ray structures of human beta -defensin-2 (hBD2). The phases were experimentally determined by the multiwavelength anomalous diffraction method, utilizing a novel, rapid method of derivatization with halide ions. Although the shape and charge distribution of the monomer are similar to those of other defensins, an additional alpha -helical region makes this protein topologically distinct from the mammalian alpha- and beta -defensin structures reported previously. hBD2 forms dimers topologically distinct from that of human neutrophil peptide-3. The quaternary octameric arrangement of hBD2 is conserved in two crystal forms. These structures provide the first detailed description of dimerization of beta -defensins, and we postulate that the mode of dimerization of hBD2 is representative of other beta -defensins. The structural and electrostatic properties of the hBD2 octamer support an electrostatic charge-based mechanism of membrane permeabilization by beta -defensins, rather than a mechanism based on formation of bilayer-spanning pores. C1 NCI, Macromol Crystallog Lab, Program Struct Biol, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. Brookhaven Natl Lab, Upton, NY 11973 USA. NCI, Lab Expt & Computat Biol, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. RP Lubkowski, J (reprint author), NCI, Macromol Crystallog Lab, Program Struct Biol, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 40 TC 206 Z9 224 U1 2 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 20 PY 2000 VL 275 IS 42 BP 32911 EP 32918 DI 10.1074/jbc.M006098200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 366KD UT WOS:000090003800074 PM 10906336 ER PT J AU Chong, NW Bernard, M Klein, DC AF Chong, NW Bernard, M Klein, DC TI Characterization of the chicken serotonin N-acetyltransferase gene - Activation via clock gene heterodimer/e box interaction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CIRCADIAN CLOCK; PINEAL-GLAND; TRANSCRIPTION FACTOR; MELATONIN SYNTHESIS; MESSENGER-RNA; RETINA; EXPRESSION; PROTEIN; RHYTHMS; LOOP AB The abundance of serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) mRNA in the chicken pineal gland exhibits a circadian rhythm, which is translated into a circadian rhythm in melatonin production. Here we have started to elucidate the molecular basis of the circadian rhythm in chicken AANAT (cAANAT), The 5'-flanking region of the cAANAT gene was isolated and found to contain an E box DNA element that confers strong luciferase reporter activity. In transfection experiments using chicken pineal cells, an E box mutation dramatically decreased reporter activity. Northern blot analysis indicated that several putative clock genes (bmal1, Clock, and MOP4) are co-expressed in the chicken pineal gland. bmal1 mRNA is expressed in a rhythmic manner in the chicken pineal gland, with peak levels at early subjective night, coincident with the increase in cAANAT expression. Co-transfection experiments in COS cells demonstrated that chicken BMAL1/CLOCK and human BMAL1/MOP4 heterodimers bound the AANAT E box element and enhanced transcription. These observations suggest that binding of clock gene heterodimers to the cAANAT E box is a critical element in the expression of the cAANAT gene in vitro. C1 NICHD, Sect Neuroendocrinol, Lab Dev Neurobiol, NIH, Bethesda, MD 20892 USA. RP Klein, DC (reprint author), NICHD, Sect Neuroendocrinol, Lab Dev Neurobiol, NIH, Bldg 49,Rm 6A80, Bethesda, MD 20892 USA. NR 66 TC 97 Z9 102 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 20 PY 2000 VL 275 IS 42 BP 32991 EP 32998 DI 10.1074/jbc.M005671200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 366KD UT WOS:000090003800084 PM 10931848 ER PT J AU Zhang, WY Ishii, I Kruth, HS AF Zhang, WY Ishii, I Kruth, HS TI Plasmin-mediated macrophage reversal of low density lipoprotein aggregation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN ATHEROSCLEROTIC LESIONS; SURFACE-CONNECTED COMPARTMENTS; SMOOTH-MUSCLE CELLS; LIPID-RICH CORE; MONOCYTE-DERIVED MACROPHAGES; ACTIVATOR EXPRESSION; ELECTRON-MICROSCOPY; CORONARY-ARTERIES; GENE-EXPRESSION; DEFICIENT MICE AB Evidence suggests that aggregated low density lipoprotein (AgLDL) accumulates in atherosclerotic lesions. Previously, we showed that AgLDL induces and enters surface-connected compartments (SCC) in human monocyte-derived macrophages by a process we have named patocytosis, Most AgLDL taken up by these macrophages in the absence of serum is stored in SCC and remains undegraded, We now show that macrophages released AgLDL (prepared by vortexing or treatment with phospholipase C or sphingomyelinase) from their SCC when exposed to 10% human lipoprotein-deficient serum (LPDS), Macrophages also took up AgLDL in the presence of LPDS, but subsequently released it. In both cases, the released AgLDL was disaggregated, Although the AgLDL that macrophages took up could not pass through a 0.45-mum filter, >60% of AgLDL could pass this filter after release from the macrophages. Disaggregation of AgLDL was verified by gel-filtration chromatography and electron microscopy that also showed particles larger than LDL, reflecting fusion of LDL that aggregates. The factor in serum that mediated AgLDL release and disaggregation was plasmin generated from plasminogen by macrophage urokinase plasminogen activator. AgLDL release was decreased >90% by inhibitors of plasmin (E-amino caproic acid and antiplasminogen mAb), and also by inhibitors of urokinase plasminogen activator (plasminogen activator inhibitor-1 and anti-urokinase plasminogen activator mAb), Moreover, plasminogen could substitute for LPDS and produce similar macrophage release and disaggregation of AgLDL. Because only plasmin bound to the macrophage surface is protected from serum plasmin inhibitors, interaction of AgLDL with macrophages was necessary for reversal of its aggregation by LPDS. The released disaggregated LDL particles were competent to stimulate LDL receptor-mediated endocytosis in cultured fibroblasts, Macrophage-mediated disaggregation of aggregated and fused LDL is a mechanism for transforming LDL into lipoprotein structures size-consistent with lipid particles found in atherosclerotic lesions. C1 NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10,Rm 5N-113,10 Ctr Dr,MSC 1422, Bethesda, MD 20892 USA. NR 56 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 20 PY 2000 VL 275 IS 42 BP 33176 EP 33183 DI 10.1074/jbc.M908714199 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 366KD UT WOS:000090003800107 PM 10942782 ER PT J AU Xie, J Guo, Q Zhu, HY Wooten, MW Mattson, MP AF Xie, J Guo, Q Zhu, HY Wooten, MW Mattson, MP TI Protein kinase C iota protects neural cells against apoptosis induced by amyloid beta-peptide SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Alzheimer's disease; calcium; caspase; mitochondrial membrane potential; oxidative stress ID NF-KAPPA-B; MANGANESE SUPEROXIDE-DISMUTASE; ALZHEIMERS-DISEASE; HIPPOCAMPAL-NEURONS; CALCIUM HOMEOSTASIS; PRECURSOR PROTEIN; PC12 CELLS; MUTANT PRESENILIN-1; OXIDATIVE STRESS; PEROXYNITRITE PRODUCTION AB Protein kinase C (PKC) isoforms are increasingly recognized as playing important roles in the regulation of neuronal plasticity and survival. Recent findings from studies of non-neuronal cells suggest that atypical isoforms of PKC can modulate apoptosis in various paradigms. Because increasing data support a role for neuronal apoptosis in the pathogenesis of Alzheimer's disease (AD), we tested the hypothesis that PKCiota (PKCL) can modify vulnerability of neural cells to apoptosis induced by amyloid beta -peptide (ABP), a cytotoxic peptide linked to neuronal degeneration in AD. Overexpression of PKCL increased the resistance of PC12 cells to apoptosis induced by ABP. Associated with the increased resistance to apoptosis were improved mitochondrial function and reduced activity of caspases. In addition, ABP-induced increases in levels of oxidative stress and intracellular calcium levels were attenuated in cells overexpressing PKCL. These findings suggest that PKCL prevents apoptosis induced by ABP by interrupting the cell death process at a very early step, thereby allowing the cells to maintain ion homeostasis and mitochondrial function. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. Auburn Univ, Dept Biol Sci, Auburn, AL 36849 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, GRC 4F01,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 56 TC 28 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT 20 PY 2000 VL 82 IS 1-2 BP 107 EP 113 DI 10.1016/S0169-328X(00)00187-X PG 7 WC Neurosciences SC Neurosciences & Neurology GA 367XW UT WOS:000090088000011 ER PT J AU Yadid, G Harvey-White, JD Kopin, IJ Goldstein, DS AF Yadid, G Harvey-White, JD Kopin, IJ Goldstein, DS TI Estimation of striatal dopamine spillover and metabolism in vivo SO NEUROREPORT LA English DT Article DE dopamine; extracellular fluid; microdialysis; pharmacodynamics; striatum; turnover ID AMPHETAMINE-INDUCED ROTATION; EXTRACELLULAR DOPAMINE; IN-VIVO; CONSCIOUS RATS; MICRODIALYSIS; COCAINE; RELEASE; TRANSPORTER; BRAIN AB A microdialysis probe with an attached microinjection cannula was inserted into rat striatum. [H-3]dopamine (or [C-14]sucrose as a reference substance for diffusion) was infused via the cannula, with microdialysate sampled for concentrations of endogenous and [H-3]-labeled dopamine and its metabolites. The calculated specific activities of the [H-3]-labeled metabolites led to the conclusions that striatal extracellular dopamine undergoes inactivation mainly by extraneuronal but also by neuronal uptake and intracellular metabolism. Some of the dopamine taken up into nerve terminals slowly re-enters (spillover) the extracellular fluid unchanged. This spillover was calculated to be about 5 pmol/min. Destruction of dopaminergic terminals increases the turnover of vesicular stores in the surviving terminals, both by increased vesicular leakage and by increased release into the extracellular fluid. NeuroReport 11:3367-3373 (C) 2000 Lippincott Williams & Wilkins. C1 Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel. NINDS, NIH, Clin Neurosci Branch, Bethesda, MD USA. RP Yadid, G (reprint author), Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel. NR 25 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT 20 PY 2000 VL 11 IS 15 BP 3367 EP 3373 DI 10.1097/00001756-200010200-00021 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 366MY UT WOS:000090010200016 PM 11059904 ER PT J AU Bom, D Curran, DP Kruszewski, S Zimmer, SG Strode, JT Kohlhagen, G Du, W Chavan, AJ Fraley, KA Bingcang, AL Latus, LJ Pommier, Y Burke, TG AF Bom, D Curran, DP Kruszewski, S Zimmer, SG Strode, JT Kohlhagen, G Du, W Chavan, AJ Fraley, KA Bingcang, AL Latus, LJ Pommier, Y Burke, TG TI The novel silatecan 7-tert-butyldimethylsilyl-10-hydroxycamptothecin displays high lipophilicity, improved human blood stability, and potent anticancer activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DNA TOPOISOMERASE-I; HUMAN SERUM-ALBUMIN; HAMSTER DC3F CELLS; ANTITUMOR AGENTS; CAMPTOTHECIN DERIVATIVES; CYTO-TOXICITY; LACTONE RING; INHIBITION; ANALOGS; DRUGS AB We describe the rational design and synthesis of B- and A,B-ring-modified camptothecins. The key alpha -hydroxy-delta -lactone pharmacophore in 7-tert-butyldimethylsilyl-10-hydroxycamptothecin (DB-67, 14) displays superior stability in human blood when compared with clinically relevant camptothecin analogues. In human blood 14 displayed a t(1/2) of 130 min and a percent lactone at equilibrium value of 30%. The tert-butyldimethylsilyl group renders the new agent 25-times more lipophilic than camptothecin, and 14 is readily incorporated, as its active lactone form, into cellular and liposomal bilayers. In addition, the dual 7-alkylsilyl and 10-hydroxy substitution in 14 enhances drug stability in the presence of human serum albumin. Thus, the net lipophilicity and the altered human serum albumin interactions together function to promote the enhanced blood stability. In vitro cytotoxicity assays using multiple different cell lines derived from eight distinct tumor types indicate that 14 is of comparable potency to camptothecin and 10-hydroxycamptothecin, as well as the FDA-approved camptothecin analogues topotecan and CPT-11. In addition, cell-free cleavage assays reveal that 14 is highly active and forms more stable top1 cleavage complexes than camptothecin or SN-38. The impressive blood stability and cytotoxicity profiles for 14 strongly suggest that it is an excellent candidate for additional in vivo pharmacological and efficacy studies. C1 Univ Kentucky, Dept Chem, Lexington, KY 40506 USA. Univ Kentucky, Coll Pharm, Div Pharmaceut Sci, Lexington, KY 40506 USA. Univ Kentucky, Coll Med, Dept Microbiol & Immunol, Lexington, KY 40506 USA. Univ Kentucky, Markey Canc Ctr, Expt Therapeut Program, Lexington, KY 40506 USA. NCI, Mol Pharmacol Program, Bethesda, MD 20892 USA. Tigen Pharmaceut Inc, Lexington, KY 40506 USA. RP Burke, TG (reprint author), Univ Kentucky, Dept Chem, ASTeCC Bldg, Lexington, KY 40506 USA. RI Kruszewski, Stefan/H-3265-2014 FU NCI NIH HHS [CA63653, CA75761]; NIGMS NIH HHS [GM31678] NR 35 TC 94 Z9 95 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 19 PY 2000 VL 43 IS 21 BP 3970 EP 3980 DI 10.1021/jm000144o PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 368HL UT WOS:000090111600019 PM 11052802 ER PT J AU Kim, CH Oda, T Itoh, M Jiang, D Artinger, KB Chandrasekharappa, SC Driever, W Chitnis, AB AF Kim, CH Oda, T Itoh, M Jiang, D Artinger, KB Chandrasekharappa, SC Driever, W Chitnis, AB TI Repressor activity of headless/Tcf3 is essential for vertebrate head formation SO NATURE LA English DT Article ID HOMEOBOX GENE; SPEMANN ORGANIZER; XENOPUS EMBRYOS; BETA-CATENIN; ZEBRAFISH; WNT; LOCALIZATION; EXPRESSION; ANTAGONIST; INDUCTION AB The vertebrate organizer can induce a complete body axis when transplanted to the ventral side of a host embryo(1) by virtue of its distinct head and trunk inducing properties. Wingless/Wnt antagonists secreted by the organizer have been identified as head inducers(2-4). Their ectopic expression can promote head formation, whereas ectopic activation of Wnt signalling during early gastrulation blocks head formation(5-7). These observations suggest that the ability of head inducers to inhibit Wnt signalling during formation of anterior structures is what distinguishes them from trunk inducers that permit the operation of posteriorizing Wnt signals(8). Here we describe the zebrarsh headless (hdl) mutant and show that its severe head defects are due to a mutation in T-cell factor-3 (Tcf3), a member of the Tcf/Lef family(9,10). Loss of Tcf3 function in the hdl mutant reveals that hdl represses Wnt target genes. We provide genetic evidence that a component of the Wnt signalling pathway is essential in vertebrate head formation and patterning. C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Freiburg, Inst Zool, D-79104 Freiburg, Germany. RP Chitnis, AB (reprint author), NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. FU NICHD NIH HHS [F32 HD008209, F32 HD008209-04] NR 29 TC 258 Z9 267 U1 1 U2 5 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 19 PY 2000 VL 407 IS 6806 BP 913 EP 916 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 364PZ UT WOS:000089901900054 PM 11057671 ER PT J AU Conner, EA Lemmer, ER Omori, M Wirth, PJ Factor, VM Thorgeirsson, SS AF Conner, EA Lemmer, ER Omori, M Wirth, PJ Factor, VM Thorgeirsson, SS TI Dual functions of E2F-1 in a transgenic mouse model of liver carcinogenesis SO ONCOGENE LA English DT Article DE hepatocellular adenoma; hepatocellular carcinoma; c-myc; p53; mouse ID CELL-CYCLE CONTROL; GROWTH-FACTOR-ALPHA; C-MYC; HEPATOCELLULAR-CARCINOMA; S-PHASE; MICE; CANCER; TRANSCRIPTION; EXPRESSION; APOPTOSIS AB Deregulation of E2F transcriptional control has been implicated in oncogenic transformation. Consistent with this idea, we recently demonstrated that during hepatocarcinogenesis in c-myc/TGF alpha double transgenic mice, there is increased expression of E2F-1 and E2F-2, as well as induction of putative E2F target genes. Therefore, we generated transgenic mice expressing E2F-1 under the control of the albumin enhancer/promoter to test the hypothesis that E2F family members may contribute to liver tumor development. Overexpression of E2F-1 resulted in mild but persistent increases in cell proliferation and death during postnatal liver growth, and no increases in hepatic regenerative growth in response to partial hepatectomy. Nevertheless, from 2 months postnatally E2F-1 transgenic mice exhibited prominent hepatic histological abnormalities including preneoplastic foci adjacent to portal tracts and pericentral large cell dysplasia. From 6 to 8 months onward, there was an abrupt increase in the number of neoplastic nodules ('adenomas') with 100% incidence by 10 months. Some adenomas shelved evidence of malignant transformation, and two of six mice killed at IZ months showed trabecular hepatocellular carcinoma. Endogenous c-myc was up-regulated in the early stages of E2F-1 hepatocarcinogenesis, whereas p53 was overexpressed in the tumors, suggesting that both E2F-1-mediated proliferation and apoptosis are operative but at different stages of hepatocarcinogenesis. In conclusion, E2F-1 overexpression in the liver causes dysplasia and tumors and suggests a cooperation between E2F-1 and c-myc oncogenes during liver oncogenesis. C1 NCI, NIH, Expt Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, NIH, Expt Carcinogenesis Lab, Div Basic Sci, 37 Convent Dr MSC4255,Bldg 37,Room 3C28, Bethesda, MD 20892 USA. NR 40 TC 96 Z9 100 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 19 PY 2000 VL 19 IS 44 BP 5054 EP 5062 DI 10.1038/sj.onc.1203885 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 365CD UT WOS:000089930100002 PM 11042693 ER PT J AU Brandenberger, M Tschierske, M Giachino, P Wada, A Berger-Bachi, B AF Brandenberger, M Tschierske, M Giachino, P Wada, A Berger-Bachi, B TI Inactivation of a novel three-cistronic operon tcaR-tcaA-tcaB increases teicoplanin resistance in Staphylococcus aureus SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE teicoplanin; methicillin; resistance; tcaRAB operon; inactivation; Straphylococcus aureus ID VANCOMYCIN AB A novel teicoplanin-associated operon termed tcaR-tcaA-tcaB was identified by Tn917-mediated insertional mutagenesis. Resistance to teicoplanin rose 4-fold by insertional inactivation of tcaA or by deletion of the entire operon. tcaA encodes a hypothetical transmembrane protein with a metal-binding motif, possibly a sensor-transducer. tcaB codes for a membrane-associated protein, which has sequence homologies to a bicyclomycin resistance protein. The two genes are preceded by tcaR encoding a putative regulator with sequence homologies to the transcriptional regulator MarR. The fact that tcaA inactivation as well as deletion of tcaRAB produced the same increase in teicoplanin resistance confirmed the association of tcaRAB with teicoplanin susceptibility. Cotransductional crosses showed that the level of teicoplanin resistance produced by these insertions was strain-dependent and that in the methicillin-resistant strain COL, it was paired with a remarkable decrease in methicillin resistance. This allowed to postulate that tcaRAB may be involved in some way in cell wall biosynthesis, and that teicoplanin may interact with TcaA and/or TcaB either directly or indirectly. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Zurich, Inst Med Microbiol, CH-8028 Zurich, Switzerland. NIAID, Dept Bacteriol, Shinjuku Ku, Tokyo 1628640, Japan. RP Berger-Bachi, B (reprint author), Univ Zurich, Inst Med Microbiol, Gloriastr 32, CH-8028 Zurich, Switzerland. NR 19 TC 37 Z9 42 U1 1 U2 9 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 OCT 18 PY 2000 VL 1523 IS 2-3 BP 135 EP 139 DI 10.1016/S0304-4165(00)00133-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 370VH UT WOS:000165142900001 PM 11042376 ER PT J AU Cornilescu, G Bax, A AF Cornilescu, G Bax, A TI Measurement of proton, nitrogen, and carbonyl chemical shielding anisotropies in a protein dissolved in a dilute liquid crystalline phase SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SOLID-STATE NMR; TRIPLE-RESONANCE EXPERIMENTS; NUCLEAR-MAGNETIC-RESONANCE; ORIENTED PHOSPHOLIPID MICELLES; CROSS-CORRELATED RELAXATION; SHIFT POWDER PATTERNS; HIGH-RESOLUTION NMR; PEPTIDE-BOND; DIPOLAR COUPLINGS; BACKBONE DYNAMICS AB The changes in a solute's chemical shifts between an isotropic and a liquid crystalline phase provide information on thr magnitude and orientation of the chemical shielding tensors relative to the molecule's alignment frame. Such chemical shift changes have been measured for the polypeptide backbone C', N, and HN resonances in the protein ubiquitin. Perdeuterated ubiquitin was dissolved in a medium containing a small volume fraction of phospholipid bicelles, which switches from an isotropic to a liquid crystalline phase at ca. 25 degreesC. The one-bond H-1-N-15 dipolar couplings provide a reference to determine the protein alignment tensor, using a vibrationally corrected H-1-N-15 bond length of 1.04 Angstrom, corresponding to r(CN) = 1.33 Angstrom. Assuming all atoms of a given type have the same chemical shielding anisotropy (CSA) tensor, the average C' tensor values are sigma (11) = -75 ppm, sigma (22) = -12 ppm, and sigma (33) = 87 ppm for C-13' with an angle between sigma (11) and the C'-N bond of 38 degrees, and sigma (33) orthogonal to the peptide plane. Similarly, for N-15, sigma (11) = -108 ppm, sigma (22) = 46 ppm, and sigma (33) = 63 ppm, with an angle of 19 degrees between the H-N vector and the sigma (11) axis, and sigma (22) orthogonal to the peptide plane. For H-N, the commonly used approximation of an axially symmetric shielding tensor is found to be invalid, and best fit tensor values are sigma (11) = -6 ppm, sigma (22) = 0 ppm, and sigma (33) = 6 ppm, with the sigma (11) axis orthogonal to the peptide plane and sigma (33) roughly parallel to the H-N bond vector. Considerable differences in CSA are found when separately considering residues in helical and extended regions of the polypeptide chain. For C-13' and N-15, the scatter in the correlation between experimental chemical shift changes and those predicted on the basis of the structure and a uniform CSA tensor is dominated by uncertainty in the protein structure and by the fact that the uniform CSA assumption is not valid. Upper limits for the degree of this intrinsic variation in the CSA tensor are obtained From these correlations. For H-1(N), th, scatter is completely dominated by intrinsic variations in the CSA tensor at the different sites. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Joined Biophys Grad Program, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 126, Bethesda, MD 20892 USA. RI Cornilescu, Gabriel/H-3113-2011 OI Cornilescu, Gabriel/0000-0002-1204-8904 NR 84 TC 174 Z9 174 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 18 PY 2000 VL 122 IS 41 BP 10143 EP 10154 DI 10.1021/ja0016194 PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 368FT UT WOS:000090107600032 ER PT J AU Sausville, EA AF Sausville, EA TI Dragons 'round the fleece again: STI571 versus alpha 1 acid glycoprotein SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID TYROSINE KINASE; DRUG-BINDING; IN-VIVO; INHIBITOR; CELLS C1 NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Sausville, EA (reprint author), NIH, 6130 Execut Blvd,Suite EPN 8000, Rockville, MD 20852 USA. NR 18 TC 9 Z9 9 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 18 PY 2000 VL 92 IS 20 BP 1626 EP 1627 DI 10.1093/jnci/92.20.1626 PG 2 WC Oncology SC Oncology GA 363HW UT WOS:000089830600001 PM 11036101 ER PT J AU Loeve, F Brown, ML Boer, R Habbema, JDF AF Loeve, F Brown, ML Boer, R Habbema, JDF TI Re: Improving the cost-effectiveness of colorectal cancer screening SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 Erasmus Univ, Fac Med, Dept Publ Hlth iMGZ, NL-3000 DR Rotterdam, Netherlands. NCI, Appl Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Loeve, F (reprint author), Erasmus Univ, Fac Med, Dept Publ Hlth iMGZ, POB 1738, NL-3000 DR Rotterdam, Netherlands. RI Boer, Rob/E-6473-2015 OI Boer, Rob/0000-0003-0680-001X NR 2 TC 2 Z9 2 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 18 PY 2000 VL 92 IS 20 BP 1691 EP 1692 DI 10.1093/jnci/92.20.1691 PG 2 WC Oncology SC Oncology GA 363HW UT WOS:000089830600016 PM 11036117 ER PT J AU McCray, AT AF McCray, AT TI Better access to information about clinical trials SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIALS; HEALTH-CARE; COCHRANE-COLLABORATION; SYSTEMATIC REVIEWS; UNPUBLISHED TRIALS; BARRIERS; PARTICIPANTS; REGISTRIES; MISCONDUCT; REGISTERS AB Access to information about clinical trials is important to researchers, health care professionals, and patients. Many have argued for the establishment of clinical trials registries, citing their substantial benefits. Although some registries do exist, it has been difficult to create comprehensive, easily accessible systems. This paper briefly reviews existing registries, discusses the challenges in building registries, and reviews some of their benefits. The paper concludes with a description of a new, extensive Web-based registry called ClinicalTrials.gov (http://clinicaltrials.gov/), which was developed at the National Institutes of Health (NIH) by the National Library of Medicine as a result of recent legislation calling for a comprehensive, publicly accessible registry of clinical trials. The first version of the system became available in late February 2000 and contains information about approximately 5000 trials. The first release contains primarily NIH-sponsored trials, and new trials are regularly added to the system. Subsequent versions will contain information about trials sponsored by other federal agencies and by the private sector. The system was developed in accordance with basic informatics principles, including adherence to standards, usability considerations, and iterative testing and evaluation. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP McCray, AT (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 36 TC 42 Z9 42 U1 0 U2 2 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 OCT 17 PY 2000 VL 133 IS 8 BP 609 EP 614 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 364RH UT WOS:000089906300006 PM 11033590 ER PT J AU Felson, DT Lawrence, RC Dieppe, PA Hirsch, R Helmick, CG Jordan, JM Kington, RS Lane, NE Nevitt, MC Zhang, YQ Sowers, M McAlindon, T Spector, TD Poole, AR Yanovski, SZ Ateshian, G Sharma, L Buckwalter, JA Brandt, KD Fries, JF AF Felson, DT Lawrence, RC Dieppe, PA Hirsch, R Helmick, CG Jordan, JM Kington, RS Lane, NE Nevitt, MC Zhang, YQ Sowers, M McAlindon, T Spector, TD Poole, AR Yanovski, SZ Ateshian, G Sharma, L Buckwalter, JA Brandt, KD Fries, JF TI Osteoarthritis: New Insights. Part 1: The Disease and Its Risk Factors SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID BONE-MINERAL DENSITY; RADIOGRAPHIC KNEE OSTEOARTHRITIS; ESTROGEN REPLACEMENT THERAPY; INTERSTITIAL FLUID PRESSURIZATION; CANINE ARTICULAR-CARTILAGE; TIBIAL PLATEAU FRACTURES; 1ST NATIONAL-HEALTH; HIP OSTEOARTHRITIS; OSTEO-ARTHRITIS; FOLLOW-UP AB Osteoarthritis is the most common form of arthritis, affecting millions of people in the United States. It is a complex disease whose etiology bridges biomechanics and biochemistry. Evidence is growing for the role of systemic factors (such as genetics, dietary intake, estrogen use, and bone density) and of local biomechanical factors (such as muscle weakness, obesity, and joint laxity). These risk factors are particularly important in weight-bearing joints, and modifying them may present opportunities for prevention of osteoarthritis-related pain and disability. Major advances in management to reduce pain and disability are yielding a panoply of available treatments ranging from nutriceuticals to chondrocyte transplantation, new oral anti-inflammatory medications, and health education. This article is part 1 of a two-part summary of a National Institutes of Health conference. The conference brought together experts on osteoarthritis from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of osteoarthritis onset, progression, and disability. Part 1 focuses on a new understanding of what osteoarthritis is and on risk factors that predispose to disease occurrence. It concludes with a discussion of the impact of osteoarthritis on disability. C1 Boston Univ Sch Med, Boston, MA 02118 USA. Natl Inst Arthrit & Musculoskeletal & Skin Dis, NIH, Bethesda, MD 20892 USA. Univ Bristol, MRC Hlth Serv Res Collaborat, Bristol BS8 2PR, Avon, England. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Examinat Stat, Hyattsville, MD 20782 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC 27599 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Examinat Stat, Hyattsville, MD 20782 USA. Univ Calif San Francisco, Div Rheumatol, San Francisco, CA 94110 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94105 USA. Boston Univ Sch Med, Arthrit Ctr, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. St Thomas Hosp, Twin Res & Genet Epidemiol Unit, London SE1 7EH, England. McGill Univ, Shriners Hosp Children, Joint Dis Lab, Quebec City, PQ H3G1A6, Canada. McGill Univ, Dept Surg, Quebec City, PQ H3G1A6, Canada. NIH, Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD 20892 USA. Columbia Univ, Orthoped Res Lab, New York, NY 10032 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Iowa Hosp, Dept Orthopaed, Iowa City, IA 52242 USA. Indiana Univ Sch Med, Rheumatol Div, Indianapolis, IN 46202 USA. Stanford Univ Sch Med, Palo Alto, CA 94304 USA. RP Lawrence, RC (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis, NIH, Bldg 45,Room 5AS-37G, Bethesda, MD 20892 USA. RI Spector, Tim/F-6533-2012; OI Zhang, Yuqing/0000-0001-7954-1149; Felson, David/0000-0002-2668-2447 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH); NIH Office of Disease Prevention; NIH National Center for Complementary and Alternative Medicine; NIH Office of Research on Women's Health; NIH Office of Behavioral and Social Sciences Research; NIH National Center for Medical Rehabilitation Research; National Institute of Child Health and Human Development; Centers for Disease Control and Prevention; Arthritis Foundation; American Academy of Orthopaedic Surgeons FX The conference was initiated, organized, and funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH), which also coordinated and funded the reporting of the proceedings. Cofunding for the conference was provided by the NIH Office of Disease Prevention, NIH National Center for Complementary and Alternative Medicine, NIH Office of Research on Women's Health, NIH Office of Behavioral and Social Sciences Research, NIH National Center for Medical Rehabilitation Research, National Institute of Child Health and Human Development, Centers for Disease Control and Prevention, Arthritis Foundation, and American Academy of Orthopaedic Surgeons. NR 119 TC 1062 Z9 1106 U1 29 U2 299 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 17 PY 2000 VL 133 IS 8 BP 635 EP 646 DI 10.7326/0003-4819-133-8-200010170-00016 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 364RH UT WOS:000089906300020 PM 11033593 ER PT J AU Park, D Pandey, SK Maksimova, E Kole, S Bernier, M AF Park, D Pandey, SK Maksimova, E Kole, S Bernier, M TI Akt-dependent antiapoptotic action of insulin is sensitive to farnesyltransferase inhibitor SO BIOCHEMISTRY LA English DT Article ID FOCAL ADHESION KINASE; PROTEIN-KINASE; P21(RAS)-GTP FORMATION; RAS TRANSFORMATION; EPITHELIAL-CELLS; GROWTH-FACTOR; APOPTOSIS; ACTIVATION; RECEPTOR; DEATH AB CHO cells expressing the human insulin receptors (IR) were used to evaluate the effect of the potent farnesyltransferase inhibitor, manumycin, on insulin antiapoptotic function. Cell treatment with manumycin blocked insulin's ability to suppress pro-apoptotic caspase-3 activity which led to time-dependent proteolytic cleavage of two nuclear target proteins. The Raf-1/MEK/ERK cascade and I he serine/threonine protein kinase Akt are two survival pathways that may be activated in response to insulin. We tested the hypothesis that inhibition of farnesylated Ras was causally related to manumycin-induced apoptosis and showed that the response to manumycin was found to be independent of K-Ras function because membrane association and activation of endogenous K-Ras proteins in terms of GTP loading and ERK activation were unabated following treatment with manumycin. Moreover, blocking p21Ras/Raf-1/MEK/ERK cascade by the expression of a transdominant inhibitory mSOS1 mutant in CHO-IR cells kept cells sensitive to the antiapoptotic action of insulin. Insulin-dependent activation of AM was blocked by 4 h treatment with manumycin (P < 0.01), a kinetic too rapid to be explained by Ras inhibition. This study suggests that the depletion of short-lived farnesylated proteins by manumycin suppresses the antiapoptotic action of insulin at least in part by disrupting Akt activation but not that of the K-Ras/Raf-1/ERK-dependent cascade. C1 NIA, Diabet Sect, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. RP Bernier, M (reprint author), NIA, Diabet Sect, Clin Invest Lab, NIH, Shock Dr,Box 23, Baltimore, MD 21224 USA. OI Bernier, Michel/0000-0002-5948-368X NR 47 TC 15 Z9 16 U1 1 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 OCT 17 PY 2000 VL 39 IS 41 BP 12513 EP 12521 DI 10.1021/bi000995y PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 372BQ UT WOS:000165214100001 PM 11027130 ER PT J AU Gu, YJ Singh, SV Ji, XH AF Gu, YJ Singh, SV Ji, XH TI Residue R216 and catalytic efficiency of a murine class alpha glutathione S-transferase toward benzo[a]pyrene 7(R),8(S)-diol 9(S),10(R)-epoxide SO BIOCHEMISTRY LA English DT Article ID SUBSTRATE-BINDING SITE; POLYCYCLIC AROMATIC-HYDROCARBONS; REGION DIOL EPOXIDES; EXCEPTIONAL ACTIVITY; OPTICAL ENANTIOMERS; CONJUGATION; P1-1; 7-BETA,8-ALPHA-DIHYDROXY-9-ALPHA,10-ALPHA-OXY-7,8,9,10-TETRAHYDROBENZO(A )PYRENE; 7,8-DIOL-9,10-EPOXIDES; ARCHITECTURE AB Murine class alpha glutathione S-transferase Al-l (mGSTA1-1), unlike mammalian class alpha GSTs. is the most efficient in the glutathione (GSH) conjugation of the ultimate carcinogenic metabolite of benzo[a]pyrene, (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] [Hu: X., Srivastava, S. K., Xia, H., Awasthi, Y. C., and Singh, S. V. (1996) J. Biol. Chem. 271, 32684-32688]. Here, we report the crystal structures of mGSTA1-1 in complex with GSPI and with the GSH conjugate of (+)-anti-BPDE (GSBpd) at 1.9 and 2.0 Angstrom resolution, respectively. Both crystals belong to monoclinic space group C2 with one dimer in the asymmetric unit. The structures reveal that, within one subunit, the GSH moiety interacts with residues Y8, R14, K44, Q53, V54, Q66, and T67, whereas the hydrophobic moiety of GSBpd interacts with the side chains of F9, R14, M207, A215, R216, F219, and I221. In addition, the GSH moiety interacts with D100 and R130 from the other subunit across the dimer interface. The structural comparison between mGSTA1-1.GSH and mGSTA1-1.GSBpd reveals significant conformational differences. The movement of helix alpha9 brings the residues on the helix into direct interaction with the product. Most noticeable are the positional displacement and conformational change of R216, one of the residues located in helix a9. The side chain of R216, which points away from the H-site in the mGSTA1-1.GSH complex, probes into the active site and becomes parallel with the aromatic ring system of GSBpd. Moreover, the guanidinium group of R216 shifts similar to8 A and forms a strong hydrogen bond with the C8 hydroxyl group of GSBpd, suggesting that the electrostatic assistance provided by the guanidinium group facilitates the ring-opening reaction of (+)-anti-BPDE. The structure of mGCSTA1-1.GSBpd is also compared with those of hGSTP1-1 [V104,A113].GSBpd, hGSPA1-1.S-benzylglutathione, and mgSTA4-4.4-S-gutathionyl-5-pentyltetrahydrofuran-2-ol. The comparison provides further evidence that supports the functional roles of R216 and helix alpha9. The lack of mobility of helix alpha9 and/or the lack of electrostatic assistance from R216 may be responsible for the relatively lower activity of hGSTA1-1, mGSTA4-4, and hGSTP1-1 toward (+)-anti-BPDE. C1 NCI, Frederick Canc Res & Dev Ctr, Program Struct Biol, Frederick, MD 21702 USA. Mercy Hosp, Canc Res Lab, Pittsburgh, PA 15219 USA. RP Ji, XH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Program Struct Biol, Bldg 539,POB B, Frederick, MD 21702 USA. RI Gu, Yijun/B-6017-2012; Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NCI NIH HHS [R01 CA76346, CA55589] NR 35 TC 16 Z9 18 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 17 PY 2000 VL 39 IS 41 BP 12552 EP 12557 DI 10.1021/bi001396u PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 372BQ UT WOS:000165214100005 PM 11027134 ER PT J AU Goldman, RC Baizman, ER Branstrom, AA Longley, CB AF Goldman, RC Baizman, ER Branstrom, AA Longley, CB TI Differential antibacterial activity of moenomycin analogues on Gram-positive bacteria SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PENICILLIN-BINDING PROTEINS; ESCHERICHIA-COLI K-12; PEPTIDOGLYCAN; BIOSYNTHESIS; TRANSGLYCOSYLATION; POLYMERIZATION; INHIBITION; MEMBER; UNIT AB The moenomycin trisaccharide degradation product and synthetic disaccharide analogues based on the disaccharide core were bactericidal to Gram-positive bacteria, inhibited lipid II polymerization, and inhibited cell wall synthesis in Entercoccus faecalis. Truncating moenomycin to the trisaccharide, and building upon the core disaccharide have both led to molecules possessing properties not shared with their respective parent structures. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Adv Med Inc, Cranbury, NJ 08512 USA. RP Goldman, RC (reprint author), NIAID, NIH, MSC 7616,6700B Rockledge Dr, Bethesda, MD 20892 USA. NR 17 TC 17 Z9 18 U1 0 U2 1 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 OCT 16 PY 2000 VL 10 IS 20 BP 2251 EP 2254 DI 10.1016/S0960-894X(00)00443-1 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 365MV UT WOS:000089955800004 PM 11055331 ER PT J AU Andrus, MB Turner, TM Sauna, ZE Ambudkar, SV AF Andrus, MB Turner, TM Sauna, ZE Ambudkar, SV TI Synthesis and preliminary analysis of a P-glycoprotein-specific [H-3]-benzophenone photoaffinity label based on (-)-stipiamide SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID MULTIDRUG-RESISTANCE REVERSAL; SITES; LOCALIZATION; REAGENTS; AFFINITY; BINDING AB A benzophenone photoaffinity label 9 based on the polyene natural product (-)-stipiamide has been constructed using a diaminoethane spacer and the radioactive agent [H-3]-BZDC (N-succinimidyl p-benzoyl-(2,3-H-3)-dehydrocinnamate). Photoaffinity experiments show specific binding to human P-glycoprotein (Pgp) in the presence of cis-flupentixol but not with cyclosporin A. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA. NCI, NIH, Cell Biol Lab, Div Basic Sci, Bethesda, MD 20878 USA. RP Andrus, MB (reprint author), Brigham Young Univ, Dept Chem & Biochem, C100 BNSN, Provo, UT 84602 USA. RI Ambudkar, Suresh/B-5964-2008 FU NIGMS NIH HHS [GM57275]; NINDS NIH HHS [NS29632] NR 18 TC 11 Z9 11 U1 0 U2 4 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 OCT 16 PY 2000 VL 10 IS 20 BP 2275 EP 2278 DI 10.1016/S0960-894X(00)00439-X PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 365MV UT WOS:000089955800010 PM 11055337 ER PT J AU Tsai, YC Dukat, M Slassi, A MacLean, N Demchyshyn, L Savage, JE Roth, BL Hufesein, S Lee, M Glennon, RA AF Tsai, YC Dukat, M Slassi, A MacLean, N Demchyshyn, L Savage, JE Roth, BL Hufesein, S Lee, M Glennon, RA TI N-1-(benzenesulfonyl)tryptamines as novel 5-HT6 antagonists SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID SEROTONIN RECEPTOR; RAT-BRAIN; LOCALIZATION; BINDING; EXPRESSION; AFFINITY; CLONING; POTENT; SITES AB N-1-Benzenesulfonyl-5-methoxy-N,N-dimethyltryptamine (BS/5-OMe DMT; 5) was shown to bind at human 5-HT6 serotonin receptors with high affinity (K-i = 2.3 nM) relative to serotonin (K-i = 78 nM). Structural variation failed to result in significantly enhanced affinity. BS/5-OMe DMT acts as an antagonist of 5-HT-stimulated adenylate cyclase (pA(2) = 8.88 nM) and may represent the first member of a novel class of 5-HT6 antagonists. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Richmond, VA 23298 USA. NPS Allelix Corp, Mississauga, ON L4V 1V7, Canada. Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, NIMH Psychoact Drug Screening Program, Cleveland, OH 44106 USA. RP Glennon, RA (reprint author), Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Med Coll Virginia Campus, Richmond, VA 23298 USA. RI Roth, Bryan/F-3928-2010 NR 22 TC 93 Z9 96 U1 1 U2 3 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 OCT 16 PY 2000 VL 10 IS 20 BP 2295 EP 2299 DI 10.1016/S0960-894X(00)00453-4 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 365MV UT WOS:000089955800015 PM 11055342 ER PT J AU Ho, YSJ Burden, LM Hurley, JH AF Ho, YSJ Burden, LM Hurley, JH TI Structure of the GAF domain, a ubiquitous signaling motif and a new class of cyclic GMP receptor SO EMBO JOURNAL LA English DT Article DE cGMP; crystal structure; GAF domain; GMP receptor; YKG9 ID CGMP-SPECIFIC PHOSPHODIESTERASE; PHOTOACTIVE YELLOW PROTEIN; CRYSTAL-STRUCTURE; BINDING-SITES; NITRIC-OXIDE; PHOTORECEPTOR PHOSPHODIESTERASE; ALLOSTERIC SITES; PAS DOMAIN; CAMP; GENE AB GAF domains are ubiquitous motifs present in cyclic GMP (cGMP)-regulated cyclic nucleotide phosphodiesterases, certain adenylyl cyclases, the bacterial transcription factor FhlA, and hundreds of other signaling and sensory proteins from all three kingdoms of life. The crystal structure of the Saccharomyces cerevisiae YKG9 protein was determined at 1.9 Angstrom resolution. The structure revealed a fold that resembles the PAS domain, another ubiquitous signaling and sensory transducer, YKG9 does not bind cGMP, but the isolated first GAF domain of phosphodiesterase 5 binds with K-d = 650 nM. The cGMP binding site of the phosphodiesterase GAF domain was identified by homology modeling and site-directed mutagenesis, and consists of conserved Arg, Asn, Lys and Asp residues. The structural and binding studies taken together show that the cGMP binding GAF domains form a new class of cyclic nucleotide receptors distinct from the regulatory domains of cyclic nucleotide-regulated protein kinases and ion channels. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 59 TC 196 Z9 203 U1 2 U2 20 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 16 PY 2000 VL 19 IS 20 BP 5288 EP 5299 DI 10.1093/emboj/19.20.5288 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 364YP UT WOS:000089921900003 PM 11032796 ER PT J AU Koch, PJ de Viragh, PA Scharer, E Bundman, D Longley, MA Bickenbach, J Kawachi, Y Suga, Y Zhou, ZJ Huber, M Hohl, D Kartasova, T Jarnik, M Steven, AC Roop, DR AF Koch, PJ de Viragh, PA Scharer, E Bundman, D Longley, MA Bickenbach, J Kawachi, Y Suga, Y Zhou, ZJ Huber, M Hohl, D Kartasova, T Jarnik, M Steven, AC Roop, DR TI Lessons from loricrin-deficient mice: Compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein SO JOURNAL OF CELL BIOLOGY LA English DT Article DE loricrin; knockout mice; cornified envelope; small proline-rich protein; repetin ID EPIDERMAL DIFFERENTIATION COMPLEX; PROLINE-RICH PROTEIN-1; HUMAN-CHROMOSOME 1Q21; EMBRYONIC STEM-CELLS; KERATINOCYTE TRANSGLUTAMINASE; LAMELLAR ICHTHYOSIS; STRATUM-CORNEUM; VOHWINKELS-KERATODERMA; STRUCTURAL PROTEINS; BINDING PROTEINS AB The epidermal cornified cell envelope (CE) is a complex protein-lipid composite that replaces the plasma membrane of terminally differentiated keratinocytes, This lamellar structure is essential for the barrier function of the skin and has the ability to prevent the loss of water and ions and to protect from environmental hazards. The major protein of the epidermal CE is loricrin, contributing similar to 70% by mass. We have generated mice that are deficient for this protein. These mice showed a delay in the formation of the skin barrier in embryonic development. At birth, homozygous mutant mice weighed less than control littermates and showed skin abnormalities, such as congenital erythroderma with a shiny, translucent skin. Tape stripping experiments suggested that the stratum corneum stability was reduced in newborn Lor(-/-) mice compared with wild-type controls. Isolated mutant CEs were more easily fragmented by sonication in vitro, indicating a greater susceptibility to mechanical stress. Nevertheless, we did not detect impaired epidermal barrier function in these mice, Surprisingly, the skin phenotype disappeared 4-5 d after birth. At least one of the compensatory mechanisms preventing a more severe skin phenotype in newborn Lor(-/-) mice is an increase in the expression of other CE components, such as SPRRP2D and SPRRP2H, members of the family of "small proline rich proteins", and repetin, a member of the "fused gene" subgroup of the S100 gene family. C1 Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA. Juntendo Univ, Sch Med, Dept Dermatol, Tokyo 1138421, Japan. Univ Lausanne, Dept Dermatol, Lab Cutaneous Biol, CH-1011 Lausanne, Switzerland. NIAMSD, Skin Biol Lab, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Lab, Bethesda, MD 20892 USA. RP Roop, DR (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, 1 Baylor Plaza, Houston, TX 77030 USA. FU NIAMS NIH HHS [AR40240] NR 61 TC 160 Z9 160 U1 1 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 16 PY 2000 VL 151 IS 2 BP 389 EP 400 DI 10.1083/jcb.151.2.389 PG 12 WC Cell Biology SC Cell Biology GA 365JT UT WOS:000089948700020 PM 11038185 ER PT J AU Suga, Y Jarnik, M Attar, PS Longley, MA Bundman, D Steven, AC Koch, PJ Roop, DR AF Suga, Y Jarnik, M Attar, PS Longley, MA Bundman, D Steven, AC Koch, PJ Roop, DR TI Transgenic mice expressing a mutant form of loricrin reveal the molecular basis of the skin diseases, Vohwinkel syndrome and progressive symmetric erythrokeratoderma SO JOURNAL OF CELL BIOLOGY LA English DT Article DE loricrin; transgenic; erythrokeratoderma; Vohwinkel's syndrome ID CORNIFIED CELL-ENVELOPE; PROLINE-RICH PROTEIN-1; EPIDERMAL-KERATINOCYTES; LOCALIZATION SIGNALS; MUTATION; KERATODERMA; GENE; NUCLEAR; IDENTIFICATION; ANTIBODIES AB Mutations in the cornified cell envelope protein loricrin have been reported recently in some patients with Vohwinkel syndrome (VS) and progressive symmetric erythrokeratoderma (PSEK). To establish a causative relationship between loricrin mutations and these diseases, we have generated transgenic mice expressing a COOH-terminal truncated form of loricrin that is similar to the protein expressed in VS and PSEK patients. At birth, transgenic mice (ML.VS) exhibited erythrokeratoderma with an epidermal barrier dysfunction. 4 d after birth, high-expressing transgenic animals showed a generalized scaling of the skin, as well as a constricting band encircling the tail and, by day 7, a thickening of the footpads. Histologically, ML.VS transgenic mice also showed retention of nuclei in the stratum corneum, a characteristic feature of VS and PSEK, Immunofluorescence and immunoelectron microscopy showed the mutant loricrin protein in the nucleus and cytoplasm of epidermal keratinocytes, but did not detect the protein ill the cornified cell envelope. Transfection experiments indicated that the COOH-terminal domain of the mutant loricrin contains a nuclear localization signal. To determine whether the ML.VS phenotype resulted from dominant-negative interference of the transgene with endogenous loricrin, we mated the ML.VS transgenics with loricrin knockout mice. A severe phenotype was observed in mice that lacked expression of wild-type loricrin. Since loricrin knockout mice are largely asymptomatic (Koch, P.K., P.A. de Viragh, E. Scharer, D. Bundman, M.A. Longley, J. Bickenbach, Y. Kawachi, Y. Suga, 2. Zhon, M. Huber, et al., J. Cell Biol. 152:389-400, this issue), this phenotype may be attributed to expression of the mutant form of loricrin. Thus, deposition of the mutant protein in the nucleus appears to interfere with late stages of epidermal differentiation, resulting in a VS-like phenotype. C1 Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA. Juntendo Univ, Sch Med, Dept Dermatol, Tokyo 113, Japan. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Roop, DR (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, 1 Baylor Plaza, Houston, TX 77030 USA. FU NIAMS NIH HHS [AR40240] NR 27 TC 39 Z9 42 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 16 PY 2000 VL 151 IS 2 BP 401 EP 412 DI 10.1083/jcb.151.2.401 PG 12 WC Cell Biology SC Cell Biology GA 365JT UT WOS:000089948700021 PM 11038186 ER PT J AU Steinert, PM AF Steinert, PM TI The complexity and redundancy of epithelial barrier function SO JOURNAL OF CELL BIOLOGY LA English DT Editorial Material ID CORNIFIED CELL-ENVELOPE; CROSS-LINKING; TRANSGLUTAMINASE-1; INVOLUCRIN; ENVOPLAKIN; PRECURSOR; PROTEINS C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Steinert, PM (reprint author), NIAMS, Skin Biol Lab, NIH, Bldg 425,Room 425, Bethesda, MD 20892 USA. NR 20 TC 54 Z9 55 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 16 PY 2000 VL 151 IS 2 BP F5 EP F7 DI 10.1083/jcb.151.2.F5 PG 3 WC Cell Biology SC Cell Biology GA 365JT UT WOS:000089948700002 PM 11038193 ER PT J AU Zhu, JF Huang, H Guo, LY Stonehouse, T Watson, CJ Hu-Li, J Paul, WE AF Zhu, JF Huang, H Guo, LY Stonehouse, T Watson, CJ Hu-Li, J Paul, WE TI Transient inhibition of interleukin 4 signaling by T cell receptor ligation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE cytokine signal transduction; T cell activation and differentiation; cross-talk; calcineurin; mitogen-activated protein kinase ID HUMAN IL-4 RECEPTOR; GENE-EXPRESSION; TH2 CELLS; TYROSINE PHOSPHORYLATION; SYNERGISTIC ACTIVATION; HEMATOPOIETIC-CELLS; HUMAN MONOCYTES; PROTEIN-KINASE; UP-REGULATION; STAT6 AB Interleukin (IL)-4 and IL-12 together with T cell receptor (TCR) engagement are crucial for the differentiation of CD4+ T cells into T helper (Th)2 or Th1 cells, respectively. Although IL-4 receptors (IL-4Rs) but not IL-12Rs are expressed on naive CD4(+) T cells, IL-4 has no apparent advantage over IL-12 in driving naive T cell differentiation when the cells are primed with both IL-4 and IL-12 in vitro. It was found that IL-4-induced phosphorylation of Janus kinases 1 and 3, IL-4R alpha, signal transducer and activator of transcription 6, and insulin receptor substrate 2 was strikingly but transiently inhibited by TCR Ligation both in conventional and TCR transgenic T cells, TCR engagement also blocked the expression of an IL-4-inducible gene. Signals induced by other cytokines, including IL-e, IL-6, and interferon alpha, but not by insulin-like growth factor 1, were also blocked by TCR engagement. The capacity of various inhibitors to reverse TCR-mediated inhibition of IL-4 signaling suggested that activation of the Ras-mitogen-activated protein kinase pathway and of the calcineurin pathway contribute to desensitizing IL-4R. IL-4 responsiveness returned at about the time (similar to 12 h) that IL-12-mediated signaling was first observed. Thus, through different mechanisms, neither IL-4R nor IL-12R has any clear advantage in polarizing cells; rather, the availability of cytokine is probably the limiting factor in this process. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Rm 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. RI Zhu, Jinfang/B-7574-2012 NR 48 TC 50 Z9 50 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 16 PY 2000 VL 192 IS 8 BP 1125 EP 1134 DI 10.1084/jem.192.8.1125 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 366BA UT WOS:000089983900006 PM 11034602 ER PT J AU Kovalchuk, AL Qi, CF Torrey, TA Taddesse-Heath, L Feigenbaum, L Park, SS Gerbitz, A Klobeck, G Hoertnagel, K Polack, A Bornkamm, GW Janz, S Morse, HC AF Kovalchuk, AL Qi, CF Torrey, TA Taddesse-Heath, L Feigenbaum, L Park, SS Gerbitz, A Klobeck, G Hoertnagel, K Polack, A Bornkamm, GW Janz, S Morse, HC TI Burkitt lymphoma in the mouse SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE Burkitt lymphoma; locus control region; mouse lymphoma; MYC; translocation ID POSITION-INDEPENDENT EXPRESSION; C-MYC; TRANSGENIC MICE; B-CELLS; GENE; TRANSCRIPTION; TRANSLOCATION; REGION; LOCUS; SELECTION AB Chromosomal translocations juxtaposing the MYC protooncogene with regulatory sequences of immunoglobulin (Ig) H chain or kappa (Ig kappa) or lambda (Ig lambda) L chain genes and effecting deregulated expression of MYC are the hallmarks of human Burkitt lymphoma (BL). Here we report that lymphomas with striking similarities to BL develop in mice bearing a mutated human MYC gene controlled by a reconstructed Ig lambda locus encompassing all the elements required for establishment of locus control in vitro. Diffusely infiltrating lymphomas with a typical starry sky appearance occurred in multiple founders and an established line, indicating independence from positional effects. Monoclonal IgM(+)CD5(-)CD23(-) tumors developed from an initially polyclonal population of B cells. These results demonstrate chat the phenotype of B lineage lymphomas induced by MYC dysregulation is highly dependent on cooperativity among the regulatory elements that govern expression of the protooncogene and provide a new system for studying the pathogenesis of BL. C1 NIAID, LIP, NIH, Bethesda, MD 20892 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Frederick Canc Res Ctr, NIH, Frederick, MD 21702 USA. Inst Klin Mol Biol & Tumorgenet, D-81377 Munich, Germany. Univ Munich, Inst Physiol Chem, D-80336 Munich, Germany. RP Morse, HC (reprint author), NIAID, LIP, NIH, 7 Ctr Dr,Rm 7-304,MSC 0760, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 NR 30 TC 114 Z9 117 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 16 PY 2000 VL 192 IS 8 BP 1183 EP 1190 DI 10.1084/jem.192.8.1183 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 366BA UT WOS:000089983900012 PM 11034608 ER PT J AU Yokoyama, Y Chaitman, BR Hardison, RM Guo, P Krone, R Stocke, K Gussak, I Attubato, MJ Rautaharju, PM Sopko, G Detre, KM AF Yokoyama, Y Chaitman, BR Hardison, RM Guo, P Krone, R Stocke, K Gussak, I Attubato, MJ Rautaharju, PM Sopko, G Detre, KM TI Association between new electrocardiographic abnormalities after coronary revascularization and five-year cardiac mortality in BARI randomized and registry patients SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID WAVE MYOCARDIAL-INFARCTION; BYPASS-SURGERY; ANGIOPLASTY; TRIAL; DISEASE; CLASSIFICATION; REGRESSION; SELECTION; NOVACODE; CRITERIA AB There are few data comparing the relative frequency of new electrocardiagraphic (ECG) abnormalities after coronary artery bypass grafting (CABG) compared with percutaneous transluminal coronary angioplasty (PTCA) and their association with long-term cardiac mortality. The study population consisted of 3,373 patients who were either randomized or eligible to be randomized to CABG or PTCA in the BARI trial. The frequency of new postprocedural ECG abnormalities was significantly greater after a CABG procedure than after PTCA. The incidence of new postprocedural major Q waves, ST-segment elevation, and T-wave abnormalities were significantly more frequent after CABG. After PTCA in = 1,869), the 5-year cardiac mortality rates associated with the new development of major Q waves, ST-seg- ment elevation, ST-segment depression, T-wave abnormalities, or no abnormality was 18.1%, 8.5%, 8.9%, 6.0%, and 5.4%, respectively. After CABG (n = 1,427), 5-year cardiac mortality rates were 8.0%, 4.2%, 3.8%, 2.8%6 and 3.7%, respectively. The adjusted relative risk of 5-year cardiac mortality for new Q-wave abnormalities was 2.6 after CABG (p <0.04) and 4.6 after PTCA (p <0.01). Thus, patients who undergo CABG have more postinitial procedural ECG abnormalities than patients who undergo PTCA. Cardiac mortality is significantly increased by the new development of postprocedural Minnesota code Q-wave abnormalities regardless of whether patients undergo CABG or PTCA. (C) 2000 by Excerpta Medico, Inc. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Coordinating Ctr, Pittsburgh, PA 15261 USA. St Louis Univ, Ctr Hlth Sci, St Louis, MO 63103 USA. Washington Univ, St Louis, MO USA. NYU, New York, NY USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. NHLBI, Bethesda, MD 20892 USA. RP Detre, KM (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Coordinating Ctr, 130 DeSoto St, Pittsburgh, PA 15261 USA. FU NHLBI NIH HHS [HL38610, HL38512, HL38518, HL38529, HL38642, HL38514-6, HL38532, HL42145, HL38509, HL38524-5, HL38556, HL38493, HL38504] NR 29 TC 15 Z9 15 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 2000 VL 86 IS 8 BP 819 EP 824 DI 10.1016/S0002-9149(00)01099-7 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 363KA UT WOS:000089833800002 PM 11024394 ER PT J AU Blum, A Schenke, WH Hathaway, L Mincemoyer, R Csako, G Waclawiw, MA Cannon, RO AF Blum, A Schenke, WH Hathaway, L Mincemoyer, R Csako, G Waclawiw, MA Cannon, RO TI Effects of estrogen and the selective estrogen receptor modulator raloxifene on markers of inflammation in postmenopausal women SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; C-REACTIVE PROTEIN; HORMONE REPLACEMENT THERAPY; CORONARY HEART-DISEASE; HUMAN ATHEROSCLEROSIS; PLASMA-CONCENTRATION; EXPRESSION; RISK; CHOLESTEROL; ICAM-1 AB We measured soluble markers of inflammation in 23 healthy postmenopausal women after conjugated equine estrogens (CEE) 0.25 mg, raloxifene 60 mg, or placebo, each for 1 month, in a randomized, double-blind, 3-period trial. GEE, but not raloxifene, increased levels of C-reactive protein and matrix metalloproteinase-9 relative to placebo values; however, CEE reduced levels of cell adhesion molecules to a greater degree than raloxifene. C1 NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Clin Pathol, Bethesda, MD 20892 USA. RP Blum, A (reprint author), NHLBI, Cardiol Branch, Bldg 10, Bethesda, MD 20892 USA. NR 20 TC 33 Z9 35 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 2000 VL 86 IS 8 BP 892 EP + DI 10.1016/S0002-9149(00)01116-4 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 363KA UT WOS:000089833800019 PM 11024411 ER PT J AU Umbach, DM AF Umbach, DM TI Invited commentary: On studying the joint effects of candidate genes and exposures SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID QUANTITATIVE TRAIT LOCI; ENVIRONMENT INTERACTIONS; DISEQUILIBRIUM; ASSOCIATION; LINKAGE; DESIGN C1 NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Umbach, DM (reprint author), NIEHS, Biostat Branch, NIH, Mail Drop A3-303,POB 12233, Res Triangle Pk, NC 27709 USA. NR 18 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 2000 VL 152 IS 8 BP 701 EP 703 DI 10.1093/aje/152.8.701 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 364RK UT WOS:000089906500002 PM 11052547 ER PT J AU Gilpin, EA Stillman, FA Hartman, AM Gibson, JT Pierce, JP AF Gilpin, EA Stillman, FA Hartman, AM Gibson, JT Pierce, JP TI Index for US state tobacco control initial outcomes SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE outcome assessment (health care); public health; smoking; tobacco ID CIGARETTE CONSUMPTION; SMOKING PREVALENCE; WORKPLACE AB Public health tobacco control efforts have increasingly targeted communities in addition to individuals. Before population smoking decreases, effectiveness might be detected from initial outcomes reflecting these efforts, such as higher cigarette prices or more workplace and home smoking restrictions. Presumably, these initial outcomes will eventually influence smoking behavior. State-specific estimates of percentages of the population working or living under smoking bans are available from the 1992-1993 tobacco use supplement to the Current Population Survey, conducted annually by the US Bureau of the Census. In addition, the tobacco industry reports the average state cigarette price yearly. The authors constructed a tobacco control initial outcomes index (IOI) by using values of these variables for each state and correlated it with state-specific adult (aged greater than or equal to 25 years) and youth (aged 15-24 years) smoking prevalence computed from the Current Population Survey and per capita cigarette consumption data computed from sales and Census Bureau data. Both adult smoking prevalence (r = -0.70) and per capita consumption (r = -0.73) were significantly correlated with the IOI; youth smoking prevalence correlated less well (r = -0.34). Although the analysis is not definitive, deseasonalized 1983-1997 consumption trends for IOI-based tertile groups were divergent beginning in 1993, with the high IOI group showing the greatest decrease. A high relative IOI index may be predictive of future smoking decreases and should be considered when tobacco control efforts are evaluated. C1 Univ Calif San Diego, Ctr Canc, Canc Prevent & Control Program, La Jolla, CA 92037 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Informat Management Serv, Silver Spring, MD USA. RP Pierce, JP (reprint author), Univ Calif San Diego, Ctr Canc, Canc Prevent & Control Program, La Jolla, CA 92037 USA. FU NCI NIH HHS [CA72092] NR 40 TC 27 Z9 27 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 2000 VL 152 IS 8 BP 727 EP 738 DI 10.1093/aje/152.8.727 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 364RK UT WOS:000089906500005 PM 11052550 ER PT J AU Sillanaukee, P Massot, N Jousilahti, P Vartiainen, E Sundvall, J Olsson, U Poikolainen, K Ponnio, M Allen, JP Alho, H AF Sillanaukee, P Massot, N Jousilahti, P Vartiainen, E Sundvall, J Olsson, U Poikolainen, K Ponnio, M Allen, JP Alho, H TI Dose response of laboratory markers to alcohol consumption in a general population SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alcohol drinking; gamma-glutamyltransferase; transferrin ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; LIVER-DISEASE; SERUM; INDIVIDUALS; ABUSE; WOMEN AB The dose response to alcohol use of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and their combination (gamma-CDT) was studied in an age- and gender-stratified, random sample from Finland in 1997. A linear association with a threshold between alcohol consumption and the three markers was observed. Body mass index was negatively associated with CDT and positively with GGT. Age was positively associated with GGT and gamma-CDT. In conclusion, CDT appears to be an early phase marker of alcohol consumption. The combined marker, gamma-CDT was less associated with factors such as body mass index but more strongly correlated with alcohol consumption than were the two markers separately. C1 Pharmacia & Upjohn Diagnost AB, Alcohol Related Dis, Uppsala, Sweden. Tampere Univ, Sch Med, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Dept Clin Chem, Tampere, Finland. Karolinska Inst, Dept Neurosci, Stockholm, Sweden. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Tampere Sch Publ Hlth, Tampere, Finland. Natl Publ Hlth Inst, Dept Biochem, Helsinki, Finland. Swedish Univ Agr Sci, Dept Biometry & Informat, Uppsala, Sweden. Jarvenpaa Addict Hosp, Haarajoki, Finland. Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, Helsinki, Finland. NIAAA, Rockville, MD 20852 USA. Univ Helsinki, Alcohol Dis Res Unit, Helsinki, Finland. RP Sillanaukee, P (reprint author), Oy Finnish Immunotechnol Ltd, Lenkkeilijankatu 8, Tampere 33520, Finland. NR 23 TC 40 Z9 41 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 2000 VL 152 IS 8 BP 747 EP 751 DI 10.1093/aje/152.8.747 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 364RK UT WOS:000089906500007 PM 11052552 ER PT J AU Yang-Boja, E DeFilippes, F Fales, HM AF Yang-Boja, E DeFilippes, F Fales, HM TI Electrospray mass spectra of three proprietary detergents SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE M-PER; Y-PER; B-PER; proprietary ionic and nonionic detergents; monkey kidney cell; collision-induced dissociation; electrospray mass spectra; 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonate (Chaps); N-tetradecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate; n-octyl-beta-D-thioglucopyranoside; and n-octyl-beta-D-thiogalactopyranoside ID SPECTROMETRY AB We have determined the major ingredients of the commercially available reagents M-PER, Y-PER, and B-PER from Pierce Chemical Co. using electrospray mass spectrometry. These three proprietary reagents have been widely used in the biochemical community as cell membrane dissolving tools during the initial step of protein purification. However, the identity and mechanism of these reagents remained unknown. In this paper, we identified these reagents as 3-[(3-cholamidopropyl) dimethylammonio]-l-propanesulfonate, N-tetradecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate, and n-octyl-beta -D-thioglucopyranoside, respectively. In addition, we wish to stress here the increasing importance of the role of electrospray mass spectrometry in the analysis of such proprietary biological preparations which are increasingly finding their way into the biochemical literature. C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Fales, HM (reprint author), NHLBI, NIH, 10 Ctr Dr,MSC 1676,Bldg 10,Room 7N-318, Bethesda, MD 20892 USA. NR 3 TC 7 Z9 7 U1 1 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD OCT 15 PY 2000 VL 285 IS 2 BP 205 EP 210 DI 10.1006/abio.2000.4734 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 367NW UT WOS:000090069200003 PM 11017703 ER PT J AU Manji, HK Moore, GJ Chen, G AF Manji, HK Moore, GJ Chen, G TI Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers: Implications for the pathophysiology and treatment of manic-depressive illness SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Depression in the 21st Century: New Insight into Drug Development and Neurobiology CY FEB 02-22, 2000 CL DANA POINT, CALIFORNIA DE mood disorders; lithium; valproate; manic-depressive illness; bcl-2; MAP kinase; neurite; neurotrophic; N-acetylaspartate; gray matter ID GLYCOGEN-SYNTHASE KINASE-3; SIGNAL-TRANSDUCTION PATHWAYS; REDUCES TAU-PHOSPHORYLATION; FAMILY TRANSCRIPTION FACTOR; CHRONIC LITHIUM TREATMENT; CEREBELLAR GRANULE CELLS; DISPLAY PCR REVEALS; DIFFERENTIAL DISPLAY; BETA-CATENIN; PROTEIN-PHOSPHORYLATION AB Recent neuroimaging studies have demonstrated regional central nervous system volume reductions in mood disorders, findings that are complemented by postmortem observations of cell atrophy and loss. It is thus noteworthy that lithium and valproate have recently been demonstrated to robustly increase the expression of the cytoprotective protein bcl-2 in the central nervous system. Chronic lithium not only exerts neuroprotective effects in several preclinical paradigms but also enhances hippocampal neurogenesis. Valproate robustly promotes neurite outgrowth and activates the ERK mitogen-activated protein kinase pathway, a signaling pathway utilized by many endogenous neurotrophic factors. Consistent with its preclinical neurotrophic/neuroprotective effects, chronic lithium treatment of patients with manic-depressive illness increases brain N-acetylaspartate (a putative marker of neuronal viability and function) levels, an effect that is localized almost exclusively to gray matter. To determine if lithium was producing neuropil increases quantitative three-dimensional magnetic resonance imaging studies were undertaken, which revealed that chronic lithium significantly increases total gray matter volume in the human brain of patients with manic-depressive illness. Together, these results suggest that a reconceptualization about the optimal long-term treatment of recurrent mood disorders is warranted. Optimal long-term treatment for these severe illnesses may only be achieved by the early use of agents with neurotrophic/neuroprotective effects, irrespective of the primary, symptomatic treatment. Biol Psychiatry 2000;48:740-754 (C) 2000 Society of Biological Psychiatry. C1 Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Mol Pathophysiol Lab, Detroit, MI USA. Wayne State Univ, Sch Med, Cellular & Clin Neurobiol Program, Detroit, MI USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, 10 Ctr Dr,10-4N-222,MSC 1381, Bethesda, MD 20892 USA. RI Moore, Gregory/E-7184-2010; Chen, Guang/A-2570-2017 OI Moore, Gregory/0000-0001-8541-3194; FU NIMH NIH HHS [R01-MH57743, R01-MH59107] NR 100 TC 251 Z9 256 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 2000 VL 48 IS 8 BP 740 EP 754 DI 10.1016/S0006-3223(00)00979-3 PG 15 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 369FX UT WOS:000165056200005 PM 11063971 ER PT J AU Kaufman, J Plotsky, PM Nemeroff, CB Charney, DS AF Kaufman, J Plotsky, PM Nemeroff, CB Charney, DS TI Effects of early adverse experiences on brain structure and function: Clinical implications SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Depression in the 21st Century: New Insight into Drug Development and Neurobiology CY FEB 02-22, 2000 CL DANA POINT, CALIFORNIA DE depression; corticotropin-releasing hormone (CRH); child abuse; animal models ID CORTICOTROPIN-RELEASING-FACTOR; POSTTRAUMATIC-STRESS-DISORDER; PREFRONTAL CORTICAL PROJECTIONS; PITUITARY-ADRENOCORTICAL AXIS; RECURRENT MAJOR DEPRESSION; CA3 PYRAMIDAL NEURONS; HIPPOCAMPAL VOLUME; PARAVENTRICULAR NUCLEUS; CEREBROSPINAL-FLUID; MATERNAL SEPARATION AB Child abuse is associated with markedly elevated rates of major depression and other psychiatric disorders in adulthood. This article reviews preclinical studies examining the effects of early stress, factors that modify the impact of these experiences, and neurobiological changes associated with major depression. Preclinical studies demonstrate that early stress can alter the development of the hypothalamic-pituitary-adrenal axis, hypothalamic and extrahypothalamic corticotropin releasing hormone, monoaminergic, and gamma -aminobutyric acid/benzodiazepine systems, Stress has also been shown to promote structural and functional alterations in brain regions similar to those seen in adults with depression. Emerging data suggest, however, that the long-term effects of early sa-ess can be moderated by genetic factors and the quality of the subsequent caregiving environment, These effects also can be prevented or reversed with various pharmacologic interventions. Preclinical studies of early stress can provide valuable insights in understanding the pathophysiology and treatment of major depression. They also can provide an important tool to use to investigate interactions between genes and environments in determining an individual's sensitivity to stress, More research is needed to understand how inherent factors interact with experiences of abuse and other psychosocial factors to confer vulnerability to develop depression, Biol Psychiatry 2000;48: 778-790 (C) 2000 Society of Biological Psychiatry. C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. NIMH, Bethesda, MD 20892 USA. RP Kaufman, J (reprint author), Yale Univ, Sch Med, Dept Psychiat, Univ Towers,Suite 2H,100 York St, New Haven, CT 06511 USA. NR 121 TC 281 Z9 289 U1 4 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 2000 VL 48 IS 8 BP 778 EP 790 DI 10.1016/S0006-3223(00)00998-7 PG 13 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 369FX UT WOS:000165056200008 PM 11063974 ER PT J AU Fujita, M Charney, DS Innis, RB AF Fujita, M Charney, DS Innis, RB TI Imaging serotonergic neurotransmission in depression: Hippocampal pathophysiology may mirror global brain alterations SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Depression in the 21st Century: New Insight into Drug Development and Neurobiology CY FEB 02-22, 2000 CL DANA POINT, CALIFORNIA DE stress; corticosteroids; pindolol; emission tomography; neurogenesis; drug effect ID PLACEBO-CONTROLLED TRIAL; POSITRON-EMISSION-TOMOGRAPHY; DEXAMETHASONE SUPPRESSION TEST; 5-HT1A RECEPTOR RADIOLIGAND; MAJOR DEPRESSION; SUICIDE VICTIMS; DOUBLE-BLIND; RADIOACTIVE METABOLITES; BINDING-SITES; IN-VIVO AB The recent development of [carbonyl-C-11]WAY-100635 for serotonin (5-HT)(1A) and [F-18]setoperone and [F-18]altanserin for 5-HT2A positron emission tomography receptor imaging has allowed studies of 5-HT neurotransmission in depressive disorders. The hippocampus is likely to be art important brain structure in the pathophysiology of depression because it may mediate both cognitive deficits and hypercortisolemia found in this disorder. Decreased 5-HT1A binding was reported in the medial temporal cortex, which receives dense 5-HT innervation, and also throughout neocortical regions. Because the 5-HT1A antagonist pindolol may hasten antidepressant effects of selective serotonin reuptake inhibitor medications, its receptor occupancy has been measured in both presynaptic and postsynaptic sires. The results are controversial but suggest that pindolol has preferential occupancy of somatodendritic autoreceptors in the raphe. The results of 5-HT2A receptors are mixed, with one showing a significant decrease in the right orbitoinsular cortex and three not detecting a significant change, The disparate findings in patients with depression almost certainly reflect the heterogeneity of the disorder, and we highlight the utility of the hippocampus as a useful target region not only to compare depressed subjects with healthy subjects bur also to correlate findings with cognitive function and activity of the limbic-hypothalamic-pituitary axis system. Biol Psychiatry 2000;48:801-812 (C) 2000 Society of Biological Psychiatry. C1 VA Connecticut Healthcare Syst, W Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Psychiat, W Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Pharmacol, W Haven, CT 06516 USA. NIMH, Program Mood & Anxiety Disorders, Bethesda, MD 20892 USA. RP Fujita, M (reprint author), VA Connecticut Healthcare Syst, 116A2,950 Campbell Ave, W Haven, CT 06516 USA. FU NIMH NIH HHS [MH30929, MH58620] NR 103 TC 39 Z9 39 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 2000 VL 48 IS 8 BP 801 EP 812 DI 10.1016/S0006-3223(00)00960-4 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 369FX UT WOS:000165056200010 PM 11063976 ER PT J AU Moses, EL Drevets, WC Smith, G Mathis, CA Kalro, BN Butters, MA Leondires, MP Greer, PJ Lopresti, B Loucks, TL Berga, SL AF Moses, EL Drevets, WC Smith, G Mathis, CA Kalro, BN Butters, MA Leondires, MP Greer, PJ Lopresti, B Loucks, TL Berga, SL TI Effects of estradiol and progesterone administration on human serotonin 2A receptor binding: A PET study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE estradiol; progesterone; PET; neurotrophin; behavior; 5-HT2A ID POSITRON-EMISSION-TOMOGRAPHY; MESSENGER-RNA EXPRESSION; CEREBRAL BLOOD-FLOW; HUMAN-BRAIN; 5-HYDROXYTRYPTAMINE(2A) RECEPTORS; MENOPAUSAL WOMEN; F-18 ALTANSERIN; ESTROGEN; CORTEX; RAT AB Background: Preclinical studies demonstrate that 17 beta -estradiol (E-2) increases serotonin-2A receptor (5-HT2AR) density in rat frontal cortex. Methods: We investigated the impact of hormone replacement therapy on 5-HT2AR binding potential (BP) using positron emission tomography and [F-18]altanserin in five postmenopausal women. Subjects were imaged at baseline, following 8 to 14 weeks of transdermal E-2, 0.1 mg/d, and following 2 to 6 weeks of E-2 plus micronized progesterone (P) 100 mg per os twice daily. Regional BPs in the anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex were calculated by Logan analysis. Results: There was a main effect of time (p =.017) for 5-HT2AR BP, which increased 21.2% +/- 2.6% following combined E-2 and P administration relative to baseline. This effect was evident in all cerebral cortex regions examined. Conclusions: 5-HT2AR BP increased in widespread areas of the cerebral cortex following combined E-2 + P administration. Biol Psychiatry 2000;48:854-860 (C) 2000 Society of Biological Psychiatry. C1 Univ Pittsburgh, Magee Womens Res Inst, Dept Ob Gyn ReproSci, Pittsburgh, PA USA. Univ Pittsburgh, Magee Womens Res Inst, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Magee Womens Res Inst, Dept Radiol, Pittsburgh, PA USA. NICHD, NIH, ERRB, Bethesda, MD USA. N Shore Long Isl Jewish Hlth Care Syst, Psychiat Res & Neurosci Res Ctr, Glen Oaks, NY USA. RP Moses, EL (reprint author), Magee Womens Hosp, Dept OB GYN RS, 300 Halket St, Pittsburgh, PA 15213 USA. RI Mathis, Chester/A-8607-2009 FU NIMH NIH HHS [MH/HD50748, MH01713, MH16804] NR 32 TC 106 Z9 107 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 2000 VL 48 IS 8 BP 854 EP 860 DI 10.1016/S0006-3223(00)00967-7 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 369FX UT WOS:000165056200014 PM 11063980 ER PT J AU Schuck, P Rossmanith, P AF Schuck, P Rossmanith, P TI Determination of the sedimentation coefficient distribution by least-squares boundary modeling SO BIOPOLYMERS LA English DT Article DE molar mass distribution; particle size-distribution; sedimentation coefficient; regularization ID ANALYTICAL ULTRACENTRIFUGATION; VELOCITY EXPERIMENTS; LAMM EQUATION; SOLUTES; SYSTEMS; MASS AB A new method is presented for the calculation of apparent sedimentation coefficient distribution g*(s) for the size-distribution analysis of polymers is sedimentation velocity experiments. Direct linear least-squares boundary modeling by a superposition of sedimentation profiles of ideal nondiffusing particles is employed. It can be combined with algebraic noise decomposition techniques for the application to interference optical ultracentrifuge data at low loading concentrations with significant systematic noise components. Because of the use of direct boundary modeling, residuals are available for assessment of the quality of the fits and the consistency of the g*(s) distribution with the experimental data. The method can be combined with regularization techniques based on F statistics, such as used in the program CONTIN, or alternatively, the increment of s values can be adjusted empirically. The method is simple, has advantageous statistical properties, and reveals precise sedimentation coefficients. The new least-squares 1s-g*(s) exhibits a very high robustness and resolution if data acquired over a large time interval are analyzed. This can result in a high resolution if data acquired over a large time interval are analyzed. This can result in a high resolution for large particles, and for samples with a high degree of heterogeneity. Because the method does not require a high frequency of scans, it can also be easily used in experiments with the absorbance optical scanning system. (C) 2000 John Wiley & Sons, Inc. C1 NIH, Mol Interact Resource Bioengn & Phys Sci Program, ORS, Bethesda, MD 20892 USA. BASF AG, Polymer Phys, Solid State Phys, D-67053 Ludwigshafen, Germany. RP Schuck, P (reprint author), NIH, Mol Interact Resource Bioengn & Phys Sci Program, ORS, Bldg 13,Rm 3N17,13 South Dr, Bethesda, MD 20892 USA. OI Schuck, Peter/0000-0002-8859-6966 NR 36 TC 196 Z9 198 U1 2 U2 17 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD OCT 15 PY 2000 VL 54 IS 5 BP 328 EP 341 DI 10.1002/1097-0282(20001015)54:5<328::AID-BIP40>3.0.CO;2-P PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 353TC UT WOS:000089290700004 PM 10935973 ER PT J AU Sloand, EM Maciejewski, J Kumar, P Kim, S Chaudhuri, A Young, N AF Sloand, EM Maciejewski, J Kumar, P Kim, S Chaudhuri, A Young, N TI Protease inhibitors stimulate hematopoiesis and decrease apoptosis and ICE expression in CD34(+) cells SO BLOOD LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; BONE-MARROW; PROGENITOR CELLS; FAS ANTIGEN; INTERLEUKIN-1-BETA-CONVERTING ENZYME; MEDIATED APOPTOSIS; PERIPHERAL-BLOOD; IN-VITRO; ACTIVATION; REPLICATION AB Highly active retroviral therapy has been associated with a decline in the frequency of cytopenia in patients with human immunodeficiency virus (HIV) infection. This may result from lower hematologic toxicity of newer antiviral drugs and their increased efficacy against HIV-I, Protease inhibitors, in addition to their effects on HIV replication, appear to affect various cellular functions. Recently, it was reported that ritonavir inhibited caspase-1 expression in normal CD4(+) cells. it was hypothesized that protease inhibitors may improve hematopoietic function owing to their direct effects on the bone marrow progenitor cells. When ritonavir was added to methylcellulose cultures of bone marrow cells from HIV-infected patients and normal controls, colony formation increased 2.4-fold (n = 5) in control cultures and 4-fold (n = 5) in cultures of cells from HIV-infected patients. In the presence of ritonavir, cultures of CD34(+) cells showed markedly decreased apoptosis in comparison with untreated cultures (45% decrease in apoptotic cell number; n = 6). A synthetic inhibitor of caspase 1 (Ac-Tyr-Val-Ala-Asp-aldehyde [single-letter amino acid codes]), which inhibits activation of several caspases including CPP32 and interleukin 1 beta -converting enzyme (ICE or caspase 1), also decreased the rate of apoptosis and enhanced colony formation by progenitor cells derived from HIV-infected patients (3-fold; n = 5), In ritonavir-treated samples derived from HIV-infected individuals, the number of cells expressing ICE also decreased. In conclusion, HIV protease inhibitors may, by blocking the caspase-dependent apoptotic pathway, overcome inhibition of hematopoiesis seen in patients with HIV infection, an effect unrelated to their antiviral activity. (C) 2000 by The American Society of Hematology. C1 NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Div Infect Dis, Washington, DC 20007 USA. RP Sloand, EM (reprint author), NHLBI, Natl Inst Hlth, 31 Ctr Dr,MSC 2490,Bldg 31,Rm 4A11, Bethesda, MD 20892 USA. NR 24 TC 57 Z9 60 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2000 VL 96 IS 8 BP 2735 EP 2739 PG 5 WC Hematology SC Hematology GA 366KA UT WOS:000090003500014 PM 11023506 ER PT J AU Li, YW Bendandi, M Dong, YP Dunbar, C Munshi, N Jagannath, S Kwak, LW Lyerly, HK AF Li, YW Bendandi, M Dong, YP Dunbar, C Munshi, N Jagannath, S Kwak, LW Lyerly, HK TI Tumor-specific recognition of human myeloma cells by idiotype-induced CD8(+) T cells SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; MONOCLONAL GAMMOPATHIES; DENDRITIC CELLS; CD4+; VACCINATION; LYMPHOCYTES; LYMPHOMA; IMMUNITY; LIGAND; MICE AB Immunoglobulin secreted by myeloma cells contains a unique antigenic determinant (idiotype [Id]) that may serve as a tumor-specific antigen. Although Id-protein-specific T-cell responses have been reported in patients with myeloma, it is not known whether primary myeloma tumor cells can present naturally processed Id peptides on their surface as a target. We immunized 2 healthy human stem-cell donors with Id proteins from their recipients. T cells from the immunized donors released high levels of T-helper I-type cytokines in response to stimulation with myeloma cells from their recipients, The T-cell-mediated cytokine response to tumor cells was blocked by a major histocompatibility complex (MHC) class I monoclonal antibody, whereas the response to soluble Id protein was dependent on MHC class II. To investigate whether id-specific CD8(+) T cells can recognize and kill autologous myeloma cells, we generated T cells from peripheral blood mononuclear cells from a third patient with myeloma by means of in vitro stimulation with autologous dendritic cells pulsed with Id protein. Tumor-specific lysis of myeloma cells was demonstrated by the lack of killing of autologous nonmalignant B cells or natural killer-sensitive K562 cells. Lysis of autologous myeloma targets was restricted by MHC class I molecules. These data represent the first report of class I-restricted T-cell recognition of fresh autologous myeloma targets and formally demonstrate that human myeloma cells can serve as targets of an Id-specific T-cell response. (C) 2000 by The American Society of Hematology. C1 NCI, Frederick Canc Res & Dev Ctr, Div Clin Sci, Dept Expt Transplantat & Immunol,Med Branch, New York, NY 10014 USA. Duke Univ, Med Ctr, Dept Surg, Ctr Genet & Cellular Therapies, Durham, NC 27706 USA. Duke Univ, Med Ctr, Dept Immunol, Ctr Genet & Cellular Therapies, Durham, NC 27706 USA. Duke Univ, Med Ctr, Dept Pathol, Ctr Genet & Cellular Therapies, Durham, NC 27706 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Dept Med, Little Rock, AR 72205 USA. RP Kwak, LW (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Clin Sci, Dept Expt Transplantat & Immunol,Med Branch, Bldg 567,Room 205, New York, NY 10014 USA. RI Lyerly, Herbert/B-6528-2014 OI Lyerly, Herbert/0000-0002-0063-4770 NR 18 TC 93 Z9 95 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2000 VL 96 IS 8 BP 2828 EP 2833 PG 6 WC Hematology SC Hematology GA 366KA UT WOS:000090003500026 PM 11023518 ER PT J AU Ge, NL Rudikoff, S AF Ge, NL Rudikoff, S TI Insulin-like growth factor I is a dual effector of multiple myeloma cell growth SO BLOOD LA English DT Article ID PROTEIN-KINASE CASCADE; PHOSPHATIDYLINOSITOL 3'-KINASE; SIGNAL-TRANSDUCTION; DISEASE-ACTIVITY; INTERLEUKIN-6; LINES; AKT; PROLIFERATION; DEATH; BAD AB Multiple myeloma (MM) is an invariably fatal disease that accounts for approximately 1% to 2% of all human cancers. Surprisingly little is known about the cellular pathways contributing to growth of these tumors. Although the cytokine interleukin-6 has been suggested to be the major stimulus for myeloma cell growth, the role of a second potential growth factor, insulin-like growth factor I(IGF-I), has been less clearly defined. The IGF-I signaling cascade in 8 MM cell lines was examined. In 7 of these, the IGF-I receptor (IGF-IR) was expressed and autophosphorylated in response to ligand. Downstream of IGF-IR, insulin receptor substrate 1 was phosphorylated, leading to the activation of phosphatidylinositol-3'-kinase (PI-3K), PI-3K, in turn, regulated 2 distinct pathways. The first included Akt and Bad, leading to an inhibition of apoptosis; the second included the mitogen-activated protein klnase (MAPK), resulting in proliferation. Biologic relevance of this pathway was demonstrated because in vitro IGF-I induced both an antiapoptotic and a proliferative effect. Importantly, in vivo administration of IGF-I in SCID mice inoculated with the OPM-2 line led to approximately twice the growth rate of tumor cells as in controls. These results suggest that IGF-I activates at least 2 pathways effecting myeloma cell growth and contributes significantly to expansion of these cells in vivo. (C) 2000 by The American Society of Hematology. C1 NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rudikoff, S (reprint author), NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. NR 38 TC 121 Z9 125 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2000 VL 96 IS 8 BP 2856 EP 2861 PG 6 WC Hematology SC Hematology GA 366KA UT WOS:000090003500030 PM 11023522 ER PT J AU Shen, WP Li, BQ Wetzel, MA Rogers, TJ Henderson, EE Su, SB Gong, WH Le, YY Sargeant, R Dimitrov, DS Oppenheim, JJ Wang, JM AF Shen, WP Li, BQ Wetzel, MA Rogers, TJ Henderson, EE Su, SB Gong, WH Le, YY Sargeant, R Dimitrov, DS Oppenheim, JJ Wang, JM TI Down-regulation of the chemokine receptor CCR5 by activation of chemotactic formyl peptide receptor in human monocytes SO BLOOD LA English DT Article ID VIRUS TYPE-1 GP41; HIV-1 INFECTION; CELL FUSION; CHEMOATTRACTANTS; NEUTROPHILS; RANTES; DESENSITIZATION; PHOSPHORYLATION; IDENTIFICATION; MECHANISMS AB Interactions between cell surface receptors are important regulatory elements in the complex host responses to infections. In this study, it is shown that a classic chemotactic factor, the bacterial chemotactic peptide N-formyl-methionyl-leucylphenyl-alanine (fMLF), rapidly induced a protein-kinase-C-mediated serine phosphorylation and down-regulation of the chemokine receptor CCR5, which serves as a major human immunodeficiency virus (HIV)-1 coreceptor. The fMLF binding to its receptor, formyl peptide receptor (FPR), resulted in significant attenuation of cell responses to CCR5 ligands and in inhibition of HIV-1-enveiopeglycoprotein-mediated fusion and infection of cells expressing CD4, CCR5, and FPR, The finding that the expression and function of CCR5 can be regulated by peptides that use an unrelated receptor may provide a novel approach to the design of anti-inflamatory and antiretroviral agents. (C) 2000 by The American Society of Hematology. C1 NCI, Frederick Canc Res & Dev Ctr, DBS, LMI, Frederick, MD 21702 USA. NCI, SAIC Frederick, Div Basic Sci, Lab Expt & Computat Biol, Frederick, MD 21702 USA. NCI, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. Millennium Biotechnol, Prod Dev, Ramona, CA USA. Temple Univ, Sch Med, Dept Immunol & Microbiol, Philadelphia, PA 19122 USA. RP Wang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, DBS, LMI, Bldg 560,Rm 31-40, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000]; NIDA NIH HHS [DA06650, DA11130] NR 35 TC 39 Z9 41 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2000 VL 96 IS 8 BP 2887 EP 2894 PG 8 WC Hematology SC Hematology GA 366KA UT WOS:000090003500034 PM 11023526 ER PT J AU Nelson, MA Radmacher, MD Simon, R Aickin, M Yang, JM Panda, L Emerson, J Roe, D Adair, L Thompson, F Bangert, J Leong, SPL Taetle, R Salmon, S Trent, J AF Nelson, MA Radmacher, MD Simon, R Aickin, M Yang, JM Panda, L Emerson, J Roe, D Adair, L Thompson, F Bangert, J Leong, SPL Taetle, R Salmon, S Trent, J TI Chromosome abnormalities in malignant melanoma: clinical significance of nonrandom chromosome abnormalities in 206 cases SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID OVARIAN ADENOCARCINOMA; SOLID TUMORS; HUMAN CANCER; BAND 1P36; EXPRESSION AB We report the cytogenetic abnormalities from a series of 206 primary malignant melanoma specimens referred to a single institution. A total of 169 out of 206 unique cases had chromosome breakpoints, A previously described statistical method was used to detect nonrandom distribution of chromosome breakpoints at the level of chromosome regions. Nonrandom occurrence of chromosome breakpoints (indicating that the observed number of breaks significantly exceeded the expected number of breaks) was detected in 28 regions, suggesting a hierarchy of genetic abnormalities in melanoma. Clinical variables and tumor characteristics were analyzed for associations with the presence of any nonrandom chromosome breakpoints; with individual, nonrandomly involved chromosome regions; and with paired, nonrandomly involved chromosome regions. No nonrandomly involved chromosome regions or pairs of regions appeared to significantly affect survival. These results identify recurring, nonrandom chromosome abnormalities in malignant melanoma. These results suggest that recurring, nonrandom chromosome alterations play a key role in the etiology and/or progression of malignant melanoma and identify targets within the genome for molecular genetic studies. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Arizona, Arizona Canc Ctr, Oncol Mol Lab, Tucson, AZ 85724 USA. Univ Arizona, Dept Med, Tucson, AZ 85724 USA. Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Mt Zion Canc Ctr, San Francisco, CA USA. NHGRI, Canc Genet Lab, Bethesda, MD 20892 USA. RP Nelson, MA (reprint author), Univ Arizona, Arizona Canc Ctr, Oncol Mol Lab, Rm 39636,1515 N Campbell Ave, Tucson, AZ 85724 USA. FU NCI NIH HHS [CA41183, CA23074]; NIEHS NIH HHS [ES9532] NR 27 TC 23 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD OCT 15 PY 2000 VL 122 IS 2 BP 101 EP 109 DI 10.1016/S0165-4608(00)00281-8 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 379AB UT WOS:000165617800007 PM 11106819 ER PT J AU Grubbs, CJ Lubet, RA Koki, AT Leahy, KM Masferrer, JL Steele, VE Kelloff, GJ Hill, DL Seibert, K AF Grubbs, CJ Lubet, RA Koki, AT Leahy, KM Masferrer, JL Steele, VE Kelloff, GJ Hill, DL Seibert, K TI Celecoxib inhibits N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder cancers in male B6D2F1 mice and female Fischer-344 rats SO CANCER RESEARCH LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; CYCLOOXYGENASE-2 INHIBITOR; N-BUTYL-N-(4-HYDROXYBUTYL)NITROSAMINE; EXPRESSION; CHEMOPREVENTION; CARCINOGENESIS; INDUCTION; PIROXICAM; COX-2 AB Epidemiological studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) may have a role in the prevention of human cancers, A number of preclinical studies have also suggested that inhibition of cyclooxygenase (COX) with NSAIDs has an anticancer effect in animal models of colon, urinary bladder, skin, and breast. In these studies, we evaluated the COX-2 inhibitor celecoxib in two rodent models of urinary bladder cancer. Male B6D2F1 mice treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) developed transitional and squamous fell urinary bladder cancers, many of which grew rapidly and caused substantial morbidity that required sacrifice of the mice. Groups of mice received various daily doses of celecoxib in the diet (1250, 500, or 200 mg/kg of diet) beginning 7 days before the initiation of 12 weekly doses of OH-BBN, Mice were checked weekly for the presence of palpable urinary bladder masses. The study was terminated at 8 months following the initial treatment with OH-BBN. The percentage of mice with large palpable bladder lesions, which necessitated sacrifice of the mice, was 40% in the OH-BBN control group, In contrast, only 10% of all celecoxib-treated mice required sacrifice before the scheduled termination of the experiment, implying that all three doses of celecoxib inhibited the formation of large palpable lesions. Celecoxib did not significantly alter the incidence of preneoplastic bladder lesions, but did dose-dependently decrease the total number of urinary bladder cancers/mouse, palpable plus microscopic, by 77, 57, and 43% at dosages of 1250, 500, and 200 mg of celecoxib/kg of diet, respectively. In the second model, female Fischer-344 rats were administered OI-I-BBN twice/week fur a period of 8 necks. After 8 months, all rats developed preneoplastic lesions, whereas roughly 60% of the rats developed relatively small urinary bladder ranters. Rats were treated continually with celecoxib in the diet (500 or 1000 mg/kg of diet) beginning either 1 week prior to the initial OA-BBN treatment or beginning 1 week following the last ON-BBN treatment, Neither celecoxib treatment regimen significantly altered the number of preneoplastic lesions. Whereas celecoxib treatment initiated prior to OH-BBN administration decreased ranter incidence roughly 65%, celecoxib treatment initiated beginning 1 week after the last dose of OH-BBN profoundly decreased cancer incidence (>95%). Celecoxib did not alter the body weights of the mice or rats, or cause other signs of toxicity at any of the doses studied. Taken together these results demonstrate that: (a) celecoxib effectively inhibits tumor growth and enhances survival in the mouse model of urinary bladder cancer; and (b) celecoxib profoundly inhibits development of urinary bladder cancers in the rat model even when administered following the last dose of OH-BBN. Clinical trials will be necessary to determine whether COX-2 inhibitors will provide a clinical benefit in human bladder cancer. C1 NCI, Div Canc Prevent, Chemoprevent Branch, Bethesda, MD 20892 USA. Univ Alabama, Dept Surg, Chemoprevent Ctr, Birmingham, AL 35294 USA. GD Searle Monsanto Co, St Louis, MO 63167 USA. RP Lubet, RA (reprint author), NCI, Div Canc Prevent, Chemoprevent Branch, EPN 201,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 27 TC 208 Z9 227 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2000 VL 60 IS 20 BP 5599 EP 5602 PG 4 WC Oncology SC Oncology GA 367HC UT WOS:000090054800002 PM 11059745 ER PT J AU Salnikow, K Costa, M Figg, WD Blagosklonny, MV AF Salnikow, K Costa, M Figg, WD Blagosklonny, MV TI Hyperinducibility of hypoxia-responsive genes without p53/p21-dependent checkpoint in aggressive prostate cancer SO CANCER RESEARCH LA English DT Article ID LACTATE-DEHYDROGENASE-A; INDUCIBLE FACTOR-1; SOLID TUMORS; CELLS; P53; EXPRESSION; APOPTOSIS; GROWTH; TRANSFORMATION; PROLIFERATION AB Hypoxia limits tumor growth but selects for higher metastatic potential. We tested the functional activity of hypoxia-inducible factor-1 (HIF-1) in prostate cell lines ranging from normal epithelial cells (PrEC), hormone-dependent LNCaP, hormone-independent DU145, PC-3 to highly metastatic PC-3M cancer cell lines. We found that HIF-1-stimulated transcription was the lowest in PrEC and LNCaP cells and the highest in PC-3M cells. The induction by hypoxia of the HIF-1 dependent genes Cap43 and GAPDH was the highest in the most aggressive PC-3M cancer cells, Because these advanced prostate cancer cell lines have lost p53 function, this further shifts a balance from p53 to HIF-1 transcriptional regulation, and a high ratio of HIF-1-dependent:p53-dependent transcription was a marker of the advanced malignant phenotype. Transient transfection of HIF-1 alpha expression vector induced transcription from p21 promoter construct in prostate cancer cell lines. Furthermore, hypoxia slightly induced p21 mRNA in these cells. However, neither expression of p21 nor hypoxia caused growth arrest in PC-3M cells. Therefore, high inducibility of HIF-1-dependent genes, loss of p53 functions with high ratio of HIF-1-dependent:p53-dependent transcription, and loss of sensitivity to p21 inhibition is a part of hypoxic phenotype associated with aggressive cancer behavior. C1 NYU, Sch Med, Kaplan Comprehens Canc Ctr, Nelson Inst Environm Med, New York, NY 10016 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Salnikow, K (reprint author), NYU, Sch Med, Kaplan Comprehens Canc Ctr, Nelson Inst Environm Med, New York, NY 10016 USA. RI costa, max/H-1754-2012; Figg Sr, William/M-2411-2016 FU NCI NIH HHS [CA16087]; NIEHS NIH HHS [ES05512, ES00260] NR 24 TC 70 Z9 74 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2000 VL 60 IS 20 BP 5630 EP 5634 PG 5 WC Oncology SC Oncology GA 367HC UT WOS:000090054800009 PM 11059752 ER PT J AU Lan, L Trempus, C Gilmour, SK AF Lan, L Trempus, C Gilmour, SK TI Inhibition of ornithine decarboxylase (ODC) decreases tumor vascularization and reverses spontaneous tumors in ODC/Ras transgenic mice SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MOUSE SKIN CARCINOGENESIS; HA-RAS ONCOGENE; ALPHA-DIFLUOROMETHYLORNITHINE; PERMEABILITY FACTOR; CYCLIN D1; EPIDERMAL PAPILLOMAS; IN-VIVO; POLYAMINE BIOSYNTHESIS; IRREVERSIBLE INHIBITOR AB We have shown that ornithine decarboxylase (ODC) overexpression in the skin of TG.AC v-Ha-ras transgenic mice induces the formation of spontaneous skin carcinomas. Treatment of ODC/Ras double transgenic mice with alpha -difluoromethylornithine (DFMO), a specific inhibitor of ODC enzyme activity, causes a rapid regression of these spontaneous tumors. DFMO treatment led to dramatic decreases in ODC activity and putrescine levels, but v-Ha-ras expression was not affected in the regressed tumors. Moreover, cyclin D1 continued to be strongly expressed in the basal epithelial cells of regressed tumors, and there was no decrease in the proliferative index of these same tumor cells, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling analyses revealed increased DNA fragmentation in DFMO regressed tumors compared with similarly sized spontaneous tumors from ODC/Ras transgenic mice not treated with DFMO. Moreover, the blood vessel count was significantly decreased in regressed tumors within the first four days of DFMO treatment. The decreased vasculature in DFMO regressed tumors was not attributable to altered expression of murine vascular endothelial growth factor (VEGF) isoforms, Elevated levels of ODC activity in the skin of K6/ODC transgenic mice increased the dermal vascularization compared with that in nontransgenic normal littermates. Our results suggest that ODC stimulates an angiogenic factor(s) other than VEGF and/or may play a key role in a cell survival effector pathway of Ras that is independent of a Ras-induced proliferation pathway. C1 Lankenau Inst Med Res, Wynnewood, PA 19096 USA. NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. RP Gilmour, SK (reprint author), Lankenau Inst Med Res, 100 Lancaster Ave, Wynnewood, PA 19096 USA. FU NCI NIH HHS [CA70739] NR 80 TC 49 Z9 51 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2000 VL 60 IS 20 BP 5696 EP 5703 PG 8 WC Oncology SC Oncology GA 367HC UT WOS:000090054800019 PM 11059762 ER PT J AU O'Brien, SJ Gallo, R Essex, M AF O'Brien, SJ Gallo, R Essex, M TI Dr Takis Papas - Cover legend SO CANCER RESEARCH LA English DT Biographical-Item C1 NCI, Frederick, MD 21701 USA. Univ Maryland, Baltimore, MD 21201 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP O'Brien, SJ (reprint author), NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2000 VL 60 IS 20 BP U14 EP U14 PG 1 WC Oncology SC Oncology GA 367HC UT WOS:000090054800001 ER PT J AU Kingma, DW Taylor, JD Patrick, J Solis, C Weiner, MP Stetler-Stevenson, M AF Kingma, DW Taylor, JD Patrick, J Solis, C Weiner, MP Stetler-Stevenson, M TI Luminex100: A rapid detection system for deleted Epstein-Barr viral latent membrane protein-1 polymerase chain reaction products SO CYTOMETRY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Glaxo Wellcome Inc, Genom Sci Dept, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 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 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT 15 PY 2000 VL 42 IS 5 MA 20 BP 318 EP 318 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 366DG UT WOS:000089989100028 ER PT J AU Lamb, LS Harding, SA Stetler-Stevenson, M Best, R Bridges, K Koon, R Henslee-Downey, PJ AF Lamb, LS Harding, SA Stetler-Stevenson, M Best, R Bridges, K Koon, R Henslee-Downey, PJ TI Flow cytometry, cytogenetics, and morphologic analysis to detect minimal recurrent leukemia following allogeneic bone marrow transplantation SO CYTOMETRY LA English DT Meeting Abstract C1 S Carolina Canc Ctr, Columbia, SC USA. NCI, Pathol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT 15 PY 2000 VL 42 IS 5 MA 21 BP 318 EP 318 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 366DG UT WOS:000089989100029 ER PT J AU Nakao, LS Kadiiska, MB Mason, RP Grijalba, MT Augusto, O AF Nakao, LS Kadiiska, MB Mason, RP Grijalba, MT Augusto, O TI Metabolism of acetaldehyde to methyl and acetyl radicals: In vitro and in vivo electron paramagnetic resonance spin-trapping studies SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE acetaldehyde metabolism; ethanol metabolism; methyl radical; acetyl radical; xanthine oxidase; submitochondrial particles; spin trap; free radicals ID ALCOHOLIC LIVER-DISEASE; IN-VIVO; XANTHINE-OXIDASE; CARBON-TETRACHLORIDE; CHEMI-LUMINESCENCE; HYDROXYL RADICALS; OXIDATIVE STRESS; ETHANOL; GENERATION; PROTEIN AB Acetaldehyde oxidation by enzymes and cellular fractions has been previously shown to produce radicals that have been characterized as superoxide anion, hydroxyl, and acetyl radicals. Here, we report that acetaldehyde metabolism by xanthine oxidase, submitochondrial particles and whole rats produces both the acetyl and the methyl radical, although only the latter was unambiguously identified in vivo. Electron paramagnetic resonance (EPR) characterization of both radicals was possible by the use of two spin traps, 5,5-dimethyl l-pyrroline N-oxide (DMPO) and alpha-(4-pyridyl l-oxide)-N-t-butylnitrone (POBN), and of acetaldehyde labeled with C-13. The POBN-acetyl radical adduct proved to be unstable, but POBN was employed to monitor acetaldehyde metabolism by Sprague-Dawley rats because previous studies have shown its usefulness for in vivo spin trapping. EPR analysis of the bile collected from treated and control rats showed the presence of the POBN-methyl and of an unidentified, biomolecule-derived, POBN adduct. Because decarbonylation of the acetyl radical is one of the routes for methyl radical formation from acetaldehyde, detection of the latter in bile provides strong evidence for the production of both radicals in vivo. The results may be relevant to understanding the toxic effects of acetaldehyde itself and of its more relevant biological precursor, ethanol. (C) 2000 Elsevier Science Inc. C1 Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05513970 Sao Paulo, Brazil. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Augusto, O (reprint author), Univ Sao Paulo, Inst Quim, Dept Bioquim, Caixa Postal 26077, BR-05513970 Sao Paulo, Brazil. RI Augusto, Ohara/D-3839-2012 OI Augusto, Ohara/0000-0002-7220-4286 NR 48 TC 29 Z9 30 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD OCT 15 PY 2000 VL 29 IS 8 BP 721 EP 729 DI 10.1016/S0891-5849(00)00374-9 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 367VT UT WOS:000090082700004 PM 11053773 ER PT J AU Rinehart-Kim, J Johnston, M Birrer, M Bos, T AF Rinehart-Kim, J Johnston, M Birrer, M Bos, T TI Alterations in the gene expression profile of MCF-7 breast tumor cells in response to c-Jun SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CHICKEN-EMBRYO FIBROBLASTS; GLUCOCORTICOID RECEPTOR; ACTIVATOR PROTEIN-1; TISSUE INHIBITOR; DNA-BINDING; ADHESION MOLECULE; FAMILY MEMBERS; AP-1 ACTIVITY; CANCER CELLS; V-JUN AB MCF7 breast tumor cells overexpressing human c-Jun exhibit a transformed phenotype characterized not only by increased tumorigenicity but also by enhanced motility and invasion, The cellular phenotypic response to c-Jun overexpression is likely due, at least in part, to altered patterns of gene expression. In order to begin to understand the complexities by which elevated production of c-Jun alters the state of the cell, we have profiled the expression of 588 different genes by comparative hybridization. By using this approach, we have identified a total of 21 upregulated or downregulated gene targets responsive to c-Jun overexpression. Interestingly, 8 of these genes have been previously found associated with c-Jun or AP-I activity and therefore provide internal validation for this approach to target gene discovery. The remaining 13 genes represent potential new c-Jun regulated target genes, Genomic sequence information was available for 15 of the 21 genes identified in this screen. Analysis of these genomic sequences revealed the presence of AP-I or AP-I-like sequences in 12 of the 15 genes examined. Consistent with a direct mechanism of target regulation:by c-Jun, gel shift analysis of selected AP-I-containing promoter regions revealed elevated and specific binding by proteins present in nuclear extracts of c-Jun expressing MCF7 cells. Int. J. Cancer 88:180-190, 2000. (C) 2000 Wiley-Liss, Inc. C1 Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23501 USA. NCI, Med Branch, Div Clin Sci, Rockville, MD USA. RP Bos, T (reprint author), Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, POB 1980, Norfolk, VA 23501 USA. FU NCI NIH HHS [R01CA51982] NR 60 TC 37 Z9 38 U1 0 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 OCT 15 PY 2000 VL 88 IS 2 BP 180 EP 190 DI 10.1002/1097-0215(20001015)88:2<180::AID-IJC6>3.0.CO;2-H PG 11 WC Oncology SC Oncology GA 359UD UT WOS:000089629700006 PM 11004666 ER PT J AU Matikainen, MP Sankila, R Schleutker, J Kallioniemi, OP Pukkala, E AF Matikainen, MP Sankila, R Schleutker, J Kallioniemi, OP Pukkala, E TI Nationwide cancer family ascertainment using Finnish Cancer Registry data on family names and places of birth for 35,761 prostate cancer patients SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NONPOLYPOSIS COLON-CANCER; SUSCEPTIBILITY LOCUS; COLORECTAL-CANCER; BREAST-CANCER; CHROMOSOME; GENE; MUTATIONS; LINKAGE; GENOME AB Identification of predisposition loci to complex diseases, such as prostate cancer, requires high-quality family material, the ascertainment of which is often laborious, time-consuming and inaccurate with conventional methods. Here, we describe a new method for rapid, nationwide cancer family ascertainment using Finnish Cancer Registry data on 35,761 prostate cancer cases over a 40-year period, As members of a prostate cancer family are likely to share the same family name and place of birth, we stratified all prostate cancer cases by these 2 parameters (10,721 different names and 596 municipalities). Data were compared with the distribution of family names and places of birth for all 3.3 million Finnish men to derive standardized prevalence ratios (SPRs), A significantly elevated SPR of prostate cancer was detected for 468 (1.6%) of the 28,459 evaluable combinations of family name and place of birth. Of the 20 highest SPR values, 19 corresponded to true nuclear families, most of these having 3 or more affected cases. Two-thirds of our 50 previously established Finnish prostate cancer families were classified among this 1.6% fraction of the highest SPR values. Finally, many of the highest SPR values originated from municipalities in southern and south-western Finland, To explore whether such clusters could highlight local founder effects, we applied genealogical research to link together several families with elevated SPRs and identified an extended family with 20 prostate cancer cases with common ancestors in the early seventeenth century, In summary, a rapid novel method was developed and validated for identification of prostate cancer families from nationwide cancer registry data and for the identification of putative regional founder effects. Int. J. Cancer 88:307-312, 2000, (C) 2000 Wiley-Liss, Inc. C1 Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Tampere, Finland. Seinajoki Cent Hosp, Dept Surg, Seinajoki, Finland. Finnish Canc Registry, FIN-00170 Helsinki, Finland. Int Agcy Res Canc, F-69372 Lyon, France. NIH, Canc Genet Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Matikainen, MP (reprint author), Univ Tampere, Inst Med Technol, Canc Genet Lab, POB 607, FIN-33101 Tampere, Finland. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 FU NHGRI NIH HHS [N01-HG-55389] NR 19 TC 6 Z9 6 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 15 PY 2000 VL 88 IS 2 BP 307 EP 312 DI 10.1002/1097-0215(20001015)88:2<307::AID-IJC25>3.0.CO;2-7 PG 6 WC Oncology SC Oncology GA 359UD UT WOS:000089629700025 PM 11004685 ER PT J AU Berry, DA Muss, HB Thor, AD Dressler, L Liu, ET Broadwater, G Budman, DR Henderson, IC Barcos, M Hayes, D Norton, L AF Berry, DA Muss, HB Thor, AD Dressler, L Liu, ET Broadwater, G Budman, DR Henderson, IC Barcos, M Hayes, D Norton, L TI HER-2/neu and p53 expression versus tamoxifen resistance in estrogen receptor-positive, node-positive breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOCRINE THERAPY; C-ERBB-2 PROTEIN; DOSE INTENSITY; GROWTH; MARKER; OVEREXPRESSION; AMPLIFICATION; CARCINOMAS; PREDICTION; ONCOGENE AB Purpose: An association between the overexpression of proto-oncogene HER-2/neu and resistance to tamoxifen in estrogen receptor (ER)-positive primary and metastatic breast cancer has been suggested. We examine a possible interaction between HER-S/neu or p53 expression and tamoxifen effectiveness in patients with ER-positive, node-positive disease treated with cyclophosphamide, doxorubicin, and fluorauracil in a large adjuvant chemotherapy trial (Cancer and Leukemia Group B [CALGB] 8541). Tamoxifen assignment was not randomised-physician discretion wets used for premenopausal and postmenopausal women. Trial protocol then specified assignment to postmenopausal women with ER-pasitive tumors, although not all took tamoxifen. Patients and Methods: CALGB 8541 assessed HER-2/neu expression in patients with ER-positive disease by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) and amplification by differential polymerase chain reaction (PCR). IHC assessed expression of p53. Univariate and multivariate proportional hazards models assessed tamoxifen-HER-2/neu status interactions and tamoxifen-p53 status interactions. Results: HER-2/neu status wets available for 651 patients with ER-pasitive disease; 650, 608, and 353 patients were assessed by IHC, PCR, and FISH, respectively. Approximately one half received tamoxifen. Reduction in risk of disease recurrence or death resulting from tamoxifen wets approximately 37% (32% with overexpression and 39% with normal expression of HER-2/neu; n = 155 by IHC). The tamoxifen-HER-2/neu status interaction wets not significant in multivariate analysis of all three HER-2/ neu assessment methods. Tamoxifen-p53 interaction did not significantly predict outcome. Conclusion: Disease-free and overall survival benefit of tamoxifen in patients with ER-positive, node-positive breast cancer does not depend on HER-2/neu or p53 status. Our data suggest that neither HER-S/neu nor p53 expression should be used to determine assignment of tamoxifen. (C) 2000 by American Society of Clinical Oncology. C1 Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Duke Univ, Leukemia Grp B, Durham, NC 27706 USA. Univ N Carolina, Chapel Hill, NC USA. Ctr Canc, Burlington, VT USA. Northwestern Univ, Evanston Hosp, Evanston, IL 60201 USA. NCI, Div Clin Sci, Washington, DC USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. N Shore Univ Hosp, Manhasset, NY USA. Roswell Pk Canc Ctr, Buffalo, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Berry, DA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biostat, 1515 Holcombe Blvd,Box 213, Houston, TX 77030 USA. RI Liu, Edison/C-4141-2008 FU NCI NIH HHS [CA31946] NR 23 TC 120 Z9 133 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 15 PY 2000 VL 18 IS 20 BP 3471 EP 3479 PG 9 WC Oncology SC Oncology GA 367TG UT WOS:000090077100004 PM 11032587 ER PT J AU Kantarjian, HM Talpaz, M Smith, TL Cortes, J Giles, FJ Rios, MB Mallard, S Gajewski, A Murgo, A Cheson, B O'Brien, S AF Kantarjian, HM Talpaz, M Smith, TL Cortes, J Giles, FJ Rios, MB Mallard, S Gajewski, A Murgo, A Cheson, B O'Brien, S TI Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CYTOGENETIC CLONAL EVOLUTION; INTERFERON-ALPHA THERAPY; CONTINUOUS-INFUSION; SURVIVAL; REMISSION; INDUCTION; TRIAL; DRUG AB Purpose: To evaluate the efficacy and toxicity profiles of a combination regimen of hamoharringtonine (HHT) and low-dose cytarabine (ara-C) in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who had experienced treatment failure with interferon alfa (IFN alpha) therapy. Patients and Methods: One hundred five patients were treated: 100 in chronic phase (15 with cytogenetic clonal evolution) and five in accelerated phase. Their median age was 52 years; all had been treated unsuccessfully with IFN alpha; 94% were in late chronic phase; 43% held been exposed to ara-C and 11% had been exposed to HHT. Patients received HHT 2.5 mg/m(2) by continuous infusion daily for 5 days and ara-C 15 mg/m2 daily in two subcutaneous injections for 5 days every 4 weeks. The outcome of the 100 patients in chronic phase was compared with a previous study group of 73 patients treated with HHT alone. Results: Overall, the complete hematologic response (CHR) rate in chronic phase was 72%; the cytogenetic response rate was 32% (major response, 15%; complete response, 5%). Toxicities were acceptable, mostly related to moderate diarrhea (3%), headaches (3%), cardiovascular events (3%), and myelosuppression-associated complications (3% to 14%). With a median follow-up period of 25 months, the estimated 4-year survival rate wets 55%. Response rates were identical with HHT plus ara-C versus HHT alone, but the survival was significantly longer with the combination after accounting for diffrences in the study groups and by multivariate analysis. Conclusion: The combination regimen of HHT and ara-C is effective and safe in patients with CML who have experienced treatment failure with IFN alpha and needs to be investigated together with IFN alpha as part of front-line CML therapy. The addition of ara-C did not improve the response rates but may have improved survival, perhaps through suppression of clones related to disease transformation. (C) 2000 by American Society of Clinical Oncology. C1 Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. MD Anderson Canc Ctr, Dept Bioimmunotherapy, Houston, TX USA. MD Anderson Canc Ctr, Dept Biostat, Houston, TX USA. MD Anderson Canc Ctr, Dept Blood & Bone Marrow Transplantat, Houston, TX USA. NCI, Bethesda, MD 20892 USA. RP Kantarjian, HM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Box 61,1515 Holcombe Blvd, Houston, TX 77030 USA. NR 40 TC 56 Z9 61 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 15 PY 2000 VL 18 IS 20 BP 3513 EP 3521 PG 9 WC Oncology SC Oncology GA 367TG UT WOS:000090077100010 PM 11032593 ER PT J AU Friedman, HS Pluda, J Quinn, JA Ewesuedo, RB Long, L Friedman, AH Cokgor, I Colvin, OM Haglund, MM Ashley, DM Rich, JN Sampson, J Pegg, AE Moschel, RC McLendon, RE Provenzale, JM Stewart, ES Tourt-Uhlig, S Garcia-Turner, AM Herndon, JE Bigner, DD Dolan, ME AF Friedman, HS Pluda, J Quinn, JA Ewesuedo, RB Long, L Friedman, AH Cokgor, I Colvin, OM Haglund, MM Ashley, DM Rich, JN Sampson, J Pegg, AE Moschel, RC McLendon, RE Provenzale, JM Stewart, ES Tourt-Uhlig, S Garcia-Turner, AM Herndon, JE Bigner, DD Dolan, ME TI Phase I trial of carmustine plus O-6-benzylguanine for patients with recurrent or progressive malignant glioma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY; BRAIN-TUMOR XENOGRAFTS; ALKYLATING-AGENTS; CYTO-TOXICITY; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; BIS-CHLOROETHYLNITROSOUREA; ONCOLOGY-GROUP; HELA-CELLS; DNA; SENSITIVITY AB Purpose: The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O-6-alkylguanine-DNA alkyltransferase (AGT), which removes chloroethylation or methylation damage from the O-6 position of guanine. O-6-benlylguanine (O-6-BG) is an AGT substrate that inhibits AGT by suicide inactivation. We conducted a phase I trial of carmustine (BCNU) plus O-6-BG to define the toxicity and maximum-tolerated dose (MTD) of BCNU in conjunction with the preadministration of O-6-BG with recurrent or progressive malignant glioma. Patients and Methods: Patients were treated with O-6-BG at a dose of 100 mg/m(2) followed 1 hour later by BCNU. Cohorts of three to six patients were treated with escalating doses of BCNU, and patients were observed for at least 6 weeks before being considered assessable for toxicity. Plasma samples were collected and analyzed for O-6-BG, 8-oxa-O-6-BG, and 8-oxoguanine concentration. Results: Twenty-three patients were treated (22 with glioblastoma multiforme and one with anaplastic astrocytoma). Four dose levels of BCNU (13.5, 27, 40, and 55 mg/m(2)) were evaluated, with the highest dose level being complicated by grade 3 or 4 thrombocytopenia and neutropenia. O-6-BG rapidly disappeared from plasma (elimination half-life = 0.54 +/- 0.14 hours) and was converted to ct longer-lived metabolite, 8-oxo-O-6-BG (elimination half-life = 5.6 +/- 2.7 hours) and further to 8-oxoguanine. There was no detectable O-6-BG 5 hours after the start of the O-6-BG infusion; however, 8-oxo-O-6-BG and 8-oxoguanine concentrations were detected 25 hours after O-6-BG infusion. The mean area under the concentration-time curve (AUC) of 8-oxo-O-6-BG was 17.5 times greater than the mean AUC for O-6-BG. Conclusion: These results indicate that the MTD of BCNU when given in combination with O-6-BG at a dose of 100 mg/m(2) is 40 mg/m(2) administered at 6-week intervals. This study provides the foundation for a phase II trial of O-6-BG plus BCNU in nitrosourea-resistant malignant glioma. (C) 2000 by American Society of Clinical Oncology. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. Penn State Univ, Milton S Hershey Med Ctr, Sch Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. Penn State Univ, Milton S Hershey Med Ctr, Sch Med, Dept Pharmacol, Hershey, PA 17033 USA. NCI, Frederick Canc Res & Dev Ctr, Adv Biosci Labs, Chem Carcinogenesis Lab, Frederick, MD USA. NCI, Investigat Drug Branch, NIH, Bethesda, MD 20892 USA. Royal Childrens Hosp, Melbourne, Vic, Australia. RP Friedman, HS (reprint author), Duke Univ, Med Ctr, Dept Surg, DUMC-3624, Durham, NC 27710 USA. FU NCI NIH HHS [CA57725]; NINDS NIH HHS [NS20023, NS30245] NR 49 TC 96 Z9 98 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 15 PY 2000 VL 18 IS 20 BP 3522 EP 3528 PG 7 WC Oncology SC Oncology GA 367TG UT WOS:000090077100011 PM 11032594 ER PT J AU Ishaq, M Fan, M Natarajan, V AF Ishaq, M Fan, M Natarajan, V TI Accumulation of RXR alpha during activation of cycling human T lymphocytes: Modulation of RXRE transactivation function by mitogen-activated protein kinase pathways SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RETINOID-X-RECEPTOR; SIGNAL-TRANSDUCTION PATHWAYS; INDUCED DOWN-REGULATION; INDUCED APOPTOSIS; C-JUN; CYCLOSPORINE-A; ACID RECEPTOR; REQUIRES PHOSPHORYLATION; 9-CIS-RETINOIC ACID; CELL HYBRIDOMAS AB We have previously reported that the activation of resting human immature peripheral blood T (PBT) lymphocytes is associated with the loss of retinoid X receptor alpha (RXR alpha) expression, In the present study, we have demonstrated that, unlike resting cells, activation of cycling human mature PET lymphocytes, and T lymphocyte leukemia cell lines is accompanied by the accumulation of RXR alpha mRNA and protein. Interestingly, cyclosporin A further augmented RXR alpha expression, indicating the involvement of calcineurin pathways in the process. 9-cis retinoic acid inhibited the accumulation, suggesting that retinoids can regulate the synthesis of their own receptors during T cell activation, Transfection analysis in Jurkat cells, using RXRE-dependent reporter assays, showed that RXR alpha accumulated during T cell activation was transcriptionally inactive. To investigate the mechanism of such inhibition, the role of two mitogen-activated protein kinase pathways, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), in modulating RXRE-dependent transcription, was explored, The expression of constitutively active MAP/ERK kinase kinase 1 (MEKK1) inhibited RXRE-dependent transcription, whereas dominant negative MEKK1 increased the transcription, indicating the involvement of JNK signaling pathways in the process. In contrast, expression of constitutively active MEK1, which activates ERK pathway, enhanced RXRE-dependent activation, When both were activated simultaneously, JNK pathway was dominant over ERK pathway and resulted in inhibition of RXRE-mediated transcription. These data demonstrate a dual regulatory control of RXR alpha expression during the activation of resting and cycling T lymphocytes and indicate a dynamic balance between JNK and ERK pathways in modulating RXRE-mediated transactivation. C1 Sci Applicat Int Corp, NCI, Frederick Canc Res & Dev Ctr, Mol Cell Biol Lab, Frederick, MD 21702 USA. RP Ishaq, M (reprint author), Sci Applicat Int Corp, NCI, Frederick Canc Res & Dev Ctr, Mol Cell Biol Lab, Bldg 550,Room 104, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 55 TC 19 Z9 22 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 OCT 15 PY 2000 VL 165 IS 8 BP 4217 EP 4225 PG 9 WC Immunology SC Immunology GA 362BK UT WOS:000089758600009 PM 11035054 ER PT J AU He, R Tan, L Browning, DD Wang, JM Ye, RD AF He, R Tan, L Browning, DD Wang, JM Ye, RD TI The synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met is a potent chemotactic agonist for mouse formyl peptide receptor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID N-FORMYLPEPTIDE RECEPTOR; METHIONYL-LEUCYL-PHENYLALANINE; PROTEIN-COUPLED RECEPTORS; CHEMOATTRACTANT RECEPTOR; PHOSPHOINOSITIDE HYDROLYSIS; SUPEROXIDE GENERATION; HUMAN NEUTROPHILS; CDNA; ACTIVATION; IDENTIFICATION AB Formyl peptides are potent neutrophil chemoattractants. In humans and rabbits, the formyl peptide receptor (FPR) binds N-formyl-Met-Leu-Phe (fMLF) with high affinity (K-d approximate to 1 nM), The mouse FPR (mFPR) is a low-affinity receptor for fMLF (K-d approximate to 100 nM); therefore, other agonists for this receptor may exist. Using mFPR-transfected rat basophilic leukemia cells, we found that a recently identified synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm) is a potent agonist for mFPR, WKYMVm induced calcium mobilization with an EC50 of 1.2-1.5 nM, Optimal chemotaxis was achieved with I nM of WKYMVm, but it required 100 nM of fMLF. WKYMVm stimulated rapid and potent phosphorylation of the mitogen-activated protein kinases extracellular signal-related kinases 1 and 2 when used at 50 nM, Pertussis toxin only partially blocked calcium mobilization and production of inositol I,4,5-trisphosphate in the stimulated mFPR cells, suggesting the possibility that this receptor couples to G alpha proteins other than Gi and Go. Competitive binding and desensitization data suggest that both peptides interact with the same receptor but may use nonoverlapping binding sites because WKYMVm was unable to effectively displace [H-3]fMLF bound to mFPR, These results provide evidence for the presence of an alternative potent agonist for mFPR, and suggest a potential usage of WKYMVm for probing the ligand-receptor interactions with the murine formyl peptide receptor homologs. C1 Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL 60612 USA. NCI, Frederick Canc Res Facil, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21701 USA. RP Ye, RD (reprint author), Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL 60612 USA. RI Ye, Richard/O-5223-2016 OI Ye, Richard/0000-0002-2164-5620 FU NIAID NIH HHS [AI33503] NR 38 TC 58 Z9 58 U1 1 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 OCT 15 PY 2000 VL 165 IS 8 BP 4598 EP 4605 PG 8 WC Immunology SC Immunology GA 362BK UT WOS:000089758600057 PM 11035102 ER PT J AU Mirotznik, RR Zheng, X Stanley, EF AF Mirotznik, RR Zheng, X Stanley, EF TI G-protein types involved in calcium channel inhibition at a presynaptic nerve terminal SO JOURNAL OF NEUROSCIENCE LA English DT Article DE nerve terminal; G-protein; G-protein type; calcium channel; presynaptic; calcium channel modulation; calcium channel inhibition; transmitter release; synaptic strength; chick; calyx synapse; chick ciliary ganglion ID N-TYPE CA2+; SYMPATHETIC NEURONS; ADENYLATE-CYCLASE; SENSORY NEURONS; CURRENTS; MODULATION; RECEPTORS; RELEASE AB The inhibition of presynaptic calcium channels via G-protein-dependent second messenger pathways is a key mechanism of transmitter release modulation. We used the calyx-type nerve terminal of the chick ciliary ganglion to examine which G-proteins are involved in the voltage-sensitive inhibition of presynaptic N-type calcium channels. Adenosine caused a prominent inhibition of the calcium current that was totally blocked by pretreatment with pertussis toxin (PTX), consistent with an exclusive involvement of G(o)/G(i) in the G-protein pathway. Immunocytochemistry was used to localize these G-protein types to the nerve terminal and its transmitter release face. We used two approaches to test for modulation by other G-protein types. First, we treated the terminals with ligands for a variety of G-protein-linked neurotransmitter receptor types that have been associated with different G-protein families. Although small inhibitory effects were observed, these could all be eliminated by PTX, indicating that in this terminal the Gi family is the sole transmitter-induced G-protein inhibitory pathway. Second, we examined the kinetics of calcium channel inhibition by uncaging the nonselective and irreversible G-protein activator GTP gamma S, bypassing the receptors. A large fraction of the rapid GTP gamma-induced inhibition persisted, consistent with a G(o)/G(i)-independent pathway. Immunocytochemistry identified G(q),G(11),G(12), and G(13) as potential PTX-insensitive second messengers at this terminal. Thus, our results suggest that whereas neurotransmitter-mediated calcium channel inhibition is mainly, and possibly exclusively, via G(o)/G(i), other rapid PTX-insensitive G-protein pathways exist that may involve novel, and perhaps transmitter-independent, activating mechanisms. C1 NINDS, Synapt Mech Sect, NIH, Bethesda, MD 20892 USA. RP Stanley, EF (reprint author), Toronto Western Res Inst, Cellular & Mol Biol Div, MP14-320,399 Bathurst St, Toronto, ON M5T 2S8, Canada. NR 28 TC 40 Z9 43 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 OCT 15 PY 2000 VL 20 IS 20 BP 7614 EP 7621 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 361ZC UT WOS:000089753300018 PM 11027221 ER PT J AU Bansal, A Singer, JH Hwang, BJ Xu, W Beaudet, A Feller, MB AF Bansal, A Singer, JH Hwang, BJ Xu, W Beaudet, A Feller, MB TI Mice lacking specific nicotinic acetylcholine receptor subunits exhibit dramatically altered spontaneous activity patterns and reveal a limited role for retinal waves in forming ON and OFF circuits in the inner retina SO JOURNAL OF NEUROSCIENCE LA English DT Article DE retinal waves; calcium imaging; visual system development; cholinergic amacrine cells; nicotinic receptor subunits; spontaneous activity ID CHOLINERGIC AMACRINE CELLS; EMBRYONIC CHICK RETINA; SPONTANEOUS RHYTHMIC ACTIVITY; MEDIATED AFFERENT ACTIVITY; GANGLION-CELLS; RABBIT RETINA; MAMMALIAN RETINA; DENDRITIC STRATIFICATION; NEONATAL HIPPOCAMPUS; ALPHA-CONOTOXIN AB Before phototransduction, spontaneous activity in the developing mammalian retina is required for the appropriate patterning of retinothalamic connections, and there is growing evidence that this activity influences the development of circuits within the retina itself. We demonstrate here that the neural substrate that generates waves in the mouse retina develops through three distinct stages. First, between embryonic day 16 and birth [postnatal day 0 (P0)], we observed both large, propagating waves inhibited by nicotinic acetylcholine receptor (nAChR) antagonists and small clusters of cells displaying nonpropagating, correlated calcium increases that were independent of nAChR activation. Second, between P0 and P11, we observed only larger propagating waves that were abolished by toxins specific to alpha 3 and beta 2 subunit-containing nAChRs. Third, between P11 and P14 (eye opening) we observed propagating activity that was abolished by ionotropic glutamate receptor antagonists. The time course of this developmental shift was dramatically altered in retinas from mice lacking the beta 2 nAChR subunit or the beta 2 and beta 4 subunits. These retinas exhibited a novel circuit at P0, no spontaneous correlated activity between P1 and P8, and the premature induction at P8 of an ionotropic glutamate receptor-based circuit. Retinas from postnatal mice lacking the alpha 3 nAChR subunit exhibited spontaneous, correlated activity patterns that were similar to those observed in embryonic wild-type mice. In alpha 3-/- and beta 2-/- mice, the development and distribution of cholinergic neurons and processes and the density of retinal ganglion cells (RGCs) and the gross segregation of their dendrites into ON and OFF sublaminae were normal. However, the refinement of individual RGC dendrites is delayed. These results indicate that retinal waves mediated by nAChRs are involved in, but not required for, the development of neural circuits that define the ON and OFF sublamina of the inner plexiform layer. C1 NINDS, Synapse Format & Funct Unit, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Feller, MB (reprint author), NINDS, Synapse Format & Funct Unit, NIH, 36 Convent Dr,36-5B16, Bethesda, MD 20892 USA. FU NIDA NIH HHS [DA-12661] NR 77 TC 240 Z9 242 U1 0 U2 10 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 OCT 15 PY 2000 VL 20 IS 20 BP 7672 EP 7681 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 361ZC UT WOS:000089753300025 PM 11027228 ER PT J AU Meredith, GE De Souza, IEJ Hyde, TM Tipper, G Wong, ML Egan, MF AF Meredith, GE De Souza, IEJ Hyde, TM Tipper, G Wong, ML Egan, MF TI Persistent alterations in dendrites, spines, and dynorphinergic synapses in the nucleus accumbens shell of rats with neuroleptic-induced dyskinesias SO JOURNAL OF NEUROSCIENCE LA English DT Article DE tardive dyskinesia; vacuous chewing movement; D1 receptor; D2 receptor; odds ratio; opioid peptide ID CHRONIC HALOPERIDOL TREATMENT; VACUOUS CHEWING MOVEMENTS; INDUCED ORAL DYSKINESIAS; TARDIVE-DYSKINESIA; MORPHOLOGICAL-CHANGES; VENTRAL STRIATUM; NEUROPSYCHIATRIC DISORDERS; STRIATOPALLIDAL NEURONS; EXTRACELLULAR GLUTAMATE; SUBSTANTIA INNOMINATA AB Chronic treatment of humans or experimental animals with classical neuroleptic drugs can lead to abnormal, tardive movements that persist long after the drugs are withdrawn. A role in these neuroleptic-induced dyskinesias may be played by a structural change in the shell of the nucleus accumbens where the opioid peptide dynorphin is upregulated in treated rats that show vacuous chewing movements (VCMs). The shell of the nucleus accumbens normally contains a dense plexus of dynorphinergic fibers especially in its caudomedial part. After 27 weeks of haloperidol administration and 18 weeks of withdrawal, the immunoreactive labeling of this plexus is intensified when compared with that after vehicle treatment. In addition, medium spiny neurons here show a significant increase in spine density, dendritic branching, and numbers of terminal segments. In the VCM-positive animals, the dendritic surface area is reduced, and dynorphin-positive terminals contact more spines and form more asymmetrical specializations than do those in animals without the syndrome (VCM-negative and vehicle-treated groups). Persistent, neuroleptic-induced oral dyskinesias could therefore be caused by incontrovertible alterations, involving terminal remodeling or sprouting, to the synaptic connectivity of the accumbal shell. C1 Univ Missouri, Sch Med, Dept Basic Med Sci, Kansas City, MO 64108 USA. Univ Dublin Trinity Coll, Dept Zool, Dublin 2, Ireland. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Univ Dublin Trinity Coll, Dept Anat, Dublin 2, Ireland. Open Univ, Dept Biol Sci, Milton Keynes MK7 6AA, Bucks, England. RP Meredith, GE (reprint author), Univ Missouri, Sch Med, Dept Basic Med Sci, 2411 Holmes Rd, Kansas City, MO 64108 USA. EM meredithg@umkc.edu NR 69 TC 38 Z9 38 U1 1 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 OCT 15 PY 2000 VL 20 IS 20 BP 7798 EP 7806 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 361ZC UT WOS:000089753300041 PM 11027244 ER PT J AU Kaelin-Lang, A Cohen, LG AF Kaelin-Lang, A Cohen, LG TI Enhancing the quality of studies using transcranial magnetic and electrical stimulation with a new computer-controlled system SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE transcranial magnetic stimulation; motor evoked potential; virtual instrument; motor cortex ID MOTOR EVOKED-POTENTIALS; CORTEX; ACQUISITION; PROGRAM AB Transcranial magnetic (TMS) and electrical (TES) stimulation of the human brain have become useful tools in neurophysiological and neuropsychological research. Here we describe an integrated system that allows experimental control, data recording and analysis of neurophysiological and neuropsychological TMS and TES procedures (including motor thresholds, recruitment curves, intracortical inhibition and facilitation with paired pulses). The system uses a multifunction input/output board and a set of virtual instruments (VI) programmed with the Labview graphical programming language. It also includes online curve fitting of recruitment curves using the Boltzmann sigmoid function and monitoring of the preinnervation grade of the target muscle. Modules for neuropsychological stimulus presentation or faster repetitive stimulation can be easily added. This system yields more accurate data recording and analysis in a user friendly and unified environment. (C) 2000 Published by Elsevier Science B.V. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Kaelin-Lang, A (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bldg 10,Room 5N234,10 Ctr Dr,MSC 1430, Bethesda, MD 20892 USA. EM kaelina@ninds.nih.gov; cohenl@ninds.nih.gov NR 21 TC 52 Z9 52 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD OCT 15 PY 2000 VL 102 IS 1 BP 81 EP 89 DI 10.1016/S0165-0270(00)00284-3 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 359UC UT WOS:000089629600009 PM 11000414 ER PT J AU Kaneko, KJ DePamphilis, ML AF Kaneko, KJ DePamphilis, ML TI Soggy, a spermatocyte-specific gene, lies 3.8 kb upstream of and antipodal to TEAD-2, a transcription factor expressed at the beginning of mouse development SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MAMMALIAN DEVELOPMENT; FAMILY AB Investigation of the regulatory region of mTEAD-2, a gene expressed at the beginning of mouse preimplantation development, led to the surprising discovery of another gene only 3.8 kb upstream of mTEAD-2, Here we show that this new gene is a single copy, testis-specific gene called Soggy (mSgy) that produces a single, dominant mRNA similar to1.3 kb in length. It is transcribed in the direction opposite to mTEAD-2, thus placing the regulatory elements of these two genes in close proximity. mSgy contains three methionine codons that could potentially act as translation start sites, but most mSGY protein synthesis in vitro was initiated from the first Met codon to produce a full-length protein, suggesting that mSGY normally consists of 230 amino acids (26.7 kDa), Transcription began at a cluster of nucleotides similar to 150 bp upstream of the first Met codon using a TATA-less promoter contained within the first 0.9 kb upstream. The activity of this promoter was repressed by upstream sequences between -0.9 and -2.5 kb in cells that did not express mSgy, but this repression was relieved in cells that did express mSgy, mSgy mRNA was detected in embryos only after day 15 and in adult tissues only in the developing spermatocytes of seminiferous tubules, suggesting that mSgy is a spermatocyte-specific gene. Since mTEAD-2 and mSgy were not expressed in the same cells, the mSgy/mTEAD-2 focus provides a unique paradigm for differential regulation of gene expression during mammalian development. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Kaneko, KJ (reprint author), NICHHD, NIH, Bldg 6, Bethesda, MD 20892 USA. NR 22 TC 29 Z9 32 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 15 PY 2000 VL 28 IS 20 BP 3982 EP 3990 DI 10.1093/nar/28.20.3982 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 365MD UT WOS:000089954300018 PM 11024178 ER PT J AU Dawson, PA Marini, JC AF Dawson, PA Marini, JC TI Hammerhead ribozymes selectively suppress mutant type I collagen mRNA in osteogenesis imperfecta fibroblasts SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EXPRESSION; ANTISENSE; CLEAVAGE; VITRO; FIBRILLIN-1; INHIBITION; DISORDERS; CELLS; BONE; VIVO AB Ribozymes are a promising agent for the gene therapy of dominant negative genetic disorders by allele-specific mRNA suppression. To test allele-specific mRNA suppression in cells, we used fibroblasts from a patient with osteogenesis imperfecta (OI), These cells contain a mutation in one alpha1(I) collagen allele which both causes the skeletal disorder and generates a novel ribozyme cleavage site. In a preliminary in vitro assay, ribozymes cleaved mutant RNA substrate whereas normal substrate was left intact. For the studies in cell culture we generated cell lines stably expressing active (AR) and inactive (IR) ribozymes targeted to mutant alpha1(I) collagen mRNA, Quantitative competitive RT-PCR analyses of type I collagen mRNA, normalized to p-actin expression levels, revealed that the level of mutant alpha1(I) collagen mRNA was significantly decreased by similar to 50% in cells expressing AR. Normal alpha1(I) collagen mRNA showed no significant reduction when AR or IR was expressed from the pH beta APr-1-neo vector and a small (10-20%) but significant reduction when either ribozyme was expressed from the pCl.neo vector. In clonal lines derived from cells expressing AR the level of ribozyme expression correlated with the extent of reduction in the mutant:normal alpha1(I) mRNA ratio, ranging from 0.33 to 0.96, Stable expression of active ribozyme did not affect cell viability, as assessed by growth rates. Ribozyme cleavage of mutant mRNA results in a reduction in mutant type I collagen protein, as demonstrated by SDS-urea-PAGE, This is the first report of ribozymes causing specific suppression of an endogenous mutant mRNA in cells derived from a patient with a dominant negative genetic disorder. C1 NICHD, Sect Connect Tissue Disorders, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Marini, JC (reprint author), Bldg 10,Room 9S241,10 Ctr Dr,MSC 1830, Bethesda, MD 20892 USA. RI Dawson, Paul/B-1268-2012 NR 20 TC 39 Z9 39 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 15 PY 2000 VL 28 IS 20 BP 4013 EP 4020 DI 10.1093/nar/28.20.4013 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 365MD UT WOS:000089954300022 PM 11024182 ER PT J AU Sneyd, J LeBeau, A Yule, D AF Sneyd, J LeBeau, A Yule, D TI Traveling waves of calcium in pancreatic acinar cells: model construction and bifurcation analysis SO PHYSICA D LA English DT Article DE calcium waves; mathematical model; traveling waves; bifurcation theory; inositol trisphosphate receptor; homoclinic bifurcations; T-point; pancreatic acinar cells ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; CA2+ OSCILLATIONS; INSP(3) RECEPTOR; DIFFERENT PATTERNS; SURFACE-REACTION; DIFFUSION; PROPAGATION; SIMPLIFICATION; TRANSITION; MECHANISM AB We construct and study a model for intracellular calcium wave propagation, with particular attention to pancreatic acinar cells. The model is based on a model of the inositol trisphosphate (IP3) receptor, which assumes that calcium modulates the binding affinity of IP3 to the receptor. Two versions of the model, one simpler than the other, are studied numerically. In both versions, solitary waves in the excitable regime arise via homoclinic bifurcations in the traveling wave equations. As the background concentration of IP3 is increased, the wave speed increases, and for some values of the IP3 concentration, the initial pulse gives rise to secondary pulses that travel in both directions. This can give rise to irregular spatio-temporal behavior, or to trains of pulses. In the simpler model, these secondary waves are related to the presence of a T-point, a heteroclinic cycle, and an associated spiral of homoclinic orbits, which terminate the branch of homoclinic orbits. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA. NIH, Math Res Branch, Bethesda, MD USA. Univ Michigan, Dept Physiol, Ann Arbor, MI 48109 USA. RP Sneyd, J (reprint author), Massey Univ, Inst Informat & Math Sci, Albany Campus,Private Bag 102-904,N Shore Mail Ct, Auckland, New Zealand. RI Sneyd, James/C-8995-2009 OI Sneyd, James/0000-0001-7305-2862 NR 43 TC 39 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-2789 J9 PHYSICA D JI Physica D PD OCT 15 PY 2000 VL 145 IS 1-2 BP 158 EP 179 DI 10.1016/S0167-2789(00)00108-1 PG 22 WC Mathematics, Applied; Physics, Multidisciplinary; Physics, Mathematical SC Mathematics; Physics GA 358EU UT WOS:000089545200010 ER PT J AU Blaszczyk, J Shi, G Yan, H Ji, X AF Blaszczyk, J Shi, G Yan, H Ji, X TI Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 angstrom resolution SO STRUCTURE LA English DT Article DE antimicrobial agent; folate; HPPK; pterin; pyrophosphokinase; X-ray crystallography ID 6-HYDROXYMETHYL-7,8-DIHYDROPTERIN PYROPHOSPHOKINASE; ESCHERICHIA-COLI AB Background: Folates are essential for life. Unlike mammals, most microorganisms must synthesize folates de novo. 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate pathway, and therefore is an ideal target for developing novel antimicrobial agents. HPPK from Escherichia coli is 158-residue thermostable protein that provides a convenient model system for mechanistic studies. Crystal structures have been reported for HPPK without bound ligand, containing an HP analog, and complexed with an HF analog, two Mg2+ ions, and ATP. Results: We present the 1.25 Angstrom crystal structure of HPPK in complex with HP, two Mg2+ ions, and AMPCPP (an ATP analog that inhibits the enzymatic reaction). This structure demonstrates that the enzyme seals the active center where the reaction occurs. The comparison with unligated HPPK reveals dramatic conformational changes of three flexible loops and many sidechains. The coordination of Mg2+ ions has been defined and the roles of 26 residues have been derived. Conclusions: HPPK-HP-MgAMPCPP mimics most closely the natural ternary complex of HPPK and provides details of protein-substrate interactions. The coordination of the two Mg2+ ions helps create the correct geometry for the one-step reaction of pyrophosphoryl transfer, for which we suggest an in-line single displacement mechanism with some associative character in the transition state. The rigidity of the adenine-binding pocket and hydrogen bonds are responsible for adenosine specificity. The nonconserved residues that interact with the substrate might be responsible for the species-dependent properties of an isozyme. C1 NCI, Frederick Canc Res & Dev Ctr, Program Struct Biol, Frederick, MD 21702 USA. Michigan State Univ, Dept Biochem, E Lansing, MI 48824 USA. RP Ji, X (reprint author), NCI, Frederick Canc Res & Dev Ctr, Program Struct Biol, Frederick, MD 21702 USA. EM jix@ncifcrf.gov RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NIGMS NIH HHS [GM51901] NR 23 TC 60 Z9 61 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD OCT 15 PY 2000 VL 8 IS 10 BP 1049 EP 1058 DI 10.1016/S0969-2126(00)00502-5 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 420TW UT WOS:000168022200005 PM 11080626 ER PT J AU Tully, DB Collins, BJ Overstreet, JD Smith, CS Dinse, GE Mumtaz, MM Chapin, RE AF Tully, DB Collins, BJ Overstreet, JD Smith, CS Dinse, GE Mumtaz, MM Chapin, RE TI Effects of arsenic, cadmium, chromium, and lead on gene expression regulated by a battery of 13 different promoters in recombinant HepG2 cells SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE arsenic; cadmium; chromium; lead; chemical mixtures ID DNA-DAMAGING AGENTS; CONTROLLING INDUCIBLE EXPRESSION; PLANAR AROMATIC-COMPOUNDS; NF-KAPPA-B; BINDING ACTIVITY; GROWTH ARREST; LIVER-CELLS; METALLOTHIONEIN; INDUCTION; TRANSCRIPTION AB Toxic metals occur naturally at low concentrations throughout the environment, but are found in higher concentrations at many of the hazardous waste sites on the EPA Superfund list. As part of the Agency for Toxic Substances and Disease Registry (ATSDR) mandate to evaluate the toxicity of metals and mixtures, we chose four of the high-priority metal pollutants from ATSDR's HAZ-DAT list, including arsenic, cadmium, chromium, and lead, to test in a commercially developed assay system, CAT-Tox(L) (Xenometrix). This assay employs a battery of recombinant HepG2 cell lines to test the transcriptional activation capacity of xenobiotics in any of 13 different signal transduction pathways. Our specific aims were to identify metal-responsive promoters and determine whether the pattern of gene expression changed with a mixture of metals. Humic acid was used in all assays as a carrier to help solubilize the metals and, in all cases, the cells were exposed to the humic acid-metal mixture for 48 h. Humic acid alone, at 50-100 muM, showed moderate activation of the XRE promoter, but little other notable activity. As(V), at doses of 50-250 muM, produced a complex profile of activity showing significant dose-dependent induction of the hMTIIA, GST Ya, HSP70, FOS, XRE, NF kappa BRE, GADD153, p53RE, and CRE promoters. Pb(II) showed dose-related induction of the GST Ya, XRE, hMTIIA, GRP78, and CYP IA1 promoters at doses in the range of 12-100 muM. Cd(II), at 1.25-15 muM, yielded significant dose-dependent induction of hMTIIA, XRE, CYP IA1, GST Ya, HSP70, NF kappa BRE, and FOS. Whereas Cr(III) yielded small, though significant inductions of the CRE, FOS, GADD153, and XRE promoters only at the highest dose (750 muM), Cr(VI) produced significant dose-related inductions of the p53RE, FOS, NF kappa BRE, XRE, GADD45, HSP70, and CRE promoters at much lower doses, in the range of 5-10 muM. Assays testing serial dilutions of a mixture comprising 7.5 muM Cd(II), 750 muM Cr(III), and 100 muM Pb(II) (the combination of metals most frequently found at National Priority List sites) showed significant dose-dependent induction of the hMTIIA promoter, but failed to show dose-related induction of any other promoter and showed no evidence of synergistic activation of gene expression by the metals in this mixture. Our results thus show metal activation of gene expression through several previously unreported signal transduction pathways, including As(V) induction of GST Ya, FOS, XRE, NFkBRE, GADD153, p53RE, and CRE; Pb(II) induction of GST Ya, XRE, Cyp IA1, and GADD153; Cd(II) induction of NFkBRE, Cyp IA1, XRE, and GST Ya; and Cr(VI) induction of p53RE, XRE, GADD45, HSP70, and CRE promoters, and thus suggest new insights into the biochemical mechanisms of toxicity and carcinogenicity of metals. It is also an important finding that no evidence of synergistic activity was detected with the mixture of Cd(II), Cr(III), and Pb(II) tested in these assays. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Dis & Med Program, Res Triangle Pk, NC 27709 USA. Publ Hlth Serv, Agcy Tox Subst & Dis Registry, US Dept Hlth & Human Serv, Atlanta, GA 30333 USA. RP Tully, DB (reprint author), NIEHS, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. OI Chapin, Robert/0000-0002-5997-1261 NR 84 TC 104 Z9 108 U1 3 U2 17 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT 15 PY 2000 VL 168 IS 2 BP 79 EP 90 DI 10.1006/taap.2000.9014 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 371YQ UT WOS:000165207200001 PM 11032763 ER PT J AU Sinclair, JF Szakacs, JG Wood, SG Walton, HS Bement, JL Gonzalez, FJ Jeffery, EH Wrighton, SA Bement, WJ Sinclair, PR AF Sinclair, JF Szakacs, JG Wood, SG Walton, HS Bement, JL Gonzalez, FJ Jeffery, EH Wrighton, SA Bement, WJ Sinclair, PR TI Short-term treatment with alcohols causes hepatic steatosis and enhances acetaminophen hepatotoxicity in Cyp2e1(-/-) mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID CULTURED RAT HEPATOCYTES; HUMAN LIVER-MICROSOMES; MICROVESICULAR STEATOSIS; INTRAGASTRIC ALCOHOL; CYTOCHROME-P450 3A; DRUG-METABOLISM; BETA-OXIDATION; ETHANOL; EXPRESSION; CYP3A AB CYP2E1 has been reported to have an essential role in alcohol-mediated increases in hepatic steatosis and acetaminophen hepatotoxicity. We found that pretreatment of Cyp2e1(-/-) mice with ethanol plus isopentanol, the predominant alcohols in alcoholic beverages, for 7 days resulted in micro- and macrovesicular steatosis in the livers of all mice, as well as a dramatic increase in acetaminophen hepatotoxicity. Zn Cyp2e1(-/-) mice administered up to 600 mg acetaminophen/kg alone and euthanized 7 h later, there was no increase in serum levels of ALT. In Cyp2e1(-/-) mice pretreated with ethanol and isopentanol, subsequent exposure to 400 or 600 mg acetaminophen/kg resulted in centrilobular necrosis in all mice with maximal elevation in serum levels of ALT. Acetaminophen-mediated liver damage was similar in males and females. Hepatic microsomal levels of APAP activation in untreated females were similar to those in males treated with the alcohols. However, the females, like the males, required pretreatment with the alcohols in order to increase APAP hepatotoxicity. These findings suggest that, in the Cyp2e1(-/-) mice, the alcohol-mediated increase in acetaminophen hepatotoxicity involves the contribution of other factors, in addition to induction of CYP(s) that activate acetaminophen. Alternatively, CYP-mediated activation of acetaminophen measured in vitro may not reflect the actual activity in vivo. Our findings that a 7-day treatment with ethanol and isopentanol causes extensive hepatic steatosis and increases acetaminophen hepatotoxicity in Cyp2e(-/-) mice indicate that CYP2E1 is not essential for either response. (C) 2000 Academic Press. C1 Vet Adm Med Ctr, Res 151, White River Junction, VT 05009 USA. Vet Adm Med Ctr, Salt Lake City, UT 84148 USA. Dartmouth Med Sch, Dept Pharmacol Toxicol, Hanover, NH 03756 USA. Dartmouth Med Sch, Dept Biochem, Hanover, NH 03756 USA. NIH, Bethesda, MD 20892 USA. Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. Lilly Res Labs, Dept Drug Disposit, Indianapolis, IN 46285 USA. RP Sinclair, JF (reprint author), Vet Adm Med Ctr, Res 151, White River Junction, VT 05009 USA. NR 55 TC 21 Z9 21 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT 15 PY 2000 VL 168 IS 2 BP 114 EP 122 DI 10.1006/taap.2000.9023 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 371YQ UT WOS:000165207200004 PM 11032766 ER PT J AU Zelko, I Negishi, M AF Zelko, I Negishi, M TI Phenobarbital-elicited activation of nuclear receptor CAR in induction of cytochrome P450 genes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE phenobarbital; nuclear receptor; cytochrome P450; CYP gene; induction; nuclear translocation; signal transduction; drug metabolism ID RESPONSIVE ENHANCER MODULE; VITAMIN-D RECEPTORS; RAT CYP2B2 GENE; GLUCOCORTICOID RECEPTOR; 5'-FLANKING REGION; TRANSGENIC MICE; PROTEIN; LIVER; TRANSLOCATION; LOCALIZATION AB Phenobarbital (PE) increases metabolic capability of hepatocytes by its ability to activate numerous genes encoding various xenochemical-metabolizing enzymes such as cytochrome P450s and specific transferases. More than 35 years since PB induction was first reported, the key nuclear receptor CAR that mediates the induction has now been identified, and the molecular/cellular mechanism involving multiple signal transduction pathways has begun to be unraveled. In response to PB exposure, CAR in the cytoplasm translocates into the nucleus, forms a heterodimer with the retinoid X receptor, and activates the PB response enhancer element leading to the concerted induction of numerous genes. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Zelko, Igor/L-2673-2013 OI Zelko, Igor/0000-0003-3976-3884 NR 39 TC 92 Z9 102 U1 0 U2 4 PU ACADEMIC PRESS INC 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 OCT 14 PY 2000 VL 277 IS 1 BP 1 EP 6 DI 10.1006/bbrc.2000.3557 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 367PJ UT WOS:000090070400001 PM 11027630 ER PT J AU Chen, ZG Eggerman, TL Potosky, D Arborati, M Patterson, AP AF Chen, ZG Eggerman, TL Potosky, D Arborati, M Patterson, AP TI Calcium increases apolipoprotein B mRNA editing SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; CULTURED RAT HEPATOCYTES; MESSENGER-RNA; INDUCED APOPTOSIS; BINDING PROTEIN; CACO-2 CELLS; SECRETION; INHIBITION; APOBEC-1; BIOSYNTHESIS AB ApoB-100 and apoB-48 are major components of chylomicrons, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), The two proteins are generated from a single apoB mRNA by apoB mRNA editing which induces an in-frame stop codon in apoB mRNA Apolipoprotein B (apoB) mRNA editing is an important determinant of the proportion of full-length (apoB-100) and truncated (apoB-48) proteins in total apoB metabolism. Calcium is involved in the regulation of secretion and synthesis of VLDL and apoB. In this paper, we demonstrate for the first time that the amount of edited apoB mRNA in the cultured cells Caco-2 and McA7777 is markedly increased by calcium. Increasing extracellular calcium concentration, calcium ionophore (A23187 and ionomycin) treatment, and depleting calcium stores and raising cytoplasmic calcium concentration by thapsigargin increase apoB mRNA editing up to threefold in a dose dependent manner. Calcium has no direct stimulative effect on apoB mRNA editing in an in vitro editing system. The editing increase by extracellular calcium is not related to alterations of APOBEC-1 mRNA expression. These data suggest that calcium is not only involved in the regulation of apolipoprotein metabolism but also apoB mRNA editing. (C) 2000 Academic Press. C1 NHLBI, NIH, Bethesda, MD 20892 USA. US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Patterson, AP (reprint author), NHLBI, NIH, 6000 Execut Blvd,Suite 302, Bethesda, MD 20892 USA. NR 40 TC 8 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC 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 OCT 14 PY 2000 VL 277 IS 1 BP 221 EP 227 DI 10.1006/bbrc.2000.3668 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 367PJ UT WOS:000090070400038 PM 11027667 ER PT J AU Bocharov, AV Vishnyakova, TG Baranova, IN Remaley, AT Patterson, AP Eggerman, TL AF Bocharov, AV Vishnyakova, TG Baranova, IN Remaley, AT Patterson, AP Eggerman, TL TI Heat shock protein 60 is a high-affinity high-density lipoprotein binding protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE high-density lipoprotein-binding protein; heat shock protein 60 ID CELLULAR CHOLESTEROL EFFLUX; HIGH-TEMPERATURE; SR-BI; APOLIPOPROTEIN; HSP60; RECEPTOR; CELLS; ASSOCIATION; CHAPERONIN; CLONING AB A new 55-kDa HDL/apolipoprotein binding protein was demonstrated in plasma membrane preparations of the human cell lines and primary cultured hepatocytes, Analysis of specific binding by ligand immunoblots of HDL, apoA-I, and apoA-II to a partially purified S5-kDa PA-I plasma membrane preparation demonstrated a K-d,K-HDL = 50 nM (10 mug/ml), K-d,K-apoA-II = 20 nM (0.4 mug/ml), and K-d,K-apoA-I = 330 nM (10 mug/ml). Following preparative SDS-PAGF electrophoresis of a plasma membrane preparation isolated from human PA-I cells, fractions with apoA-II binding activity were collected, concentrated, and subjected to two-dimensional electrophoresis. Internal microprotein sequencing of the 55-kDa protein band revealed the binding protein as being heat shock protein 60 (hsp60), The hsp60 monoclonal antibody LK-1 blocked apoA-II binding to the 55-kDa HBP preparation. In summary, these results provide a potential mechanism to explain the known association between immunity developed against hsp60 and the development of atherosclerosis, (C) 2000 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, OTRR, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. RP Eggerman, TL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, OTRR, 8800 Rockville Pike,NIH Campus Bldg 29B,Room 2NN1, Bethesda, MD 20892 USA. NR 52 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC 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 OCT 14 PY 2000 VL 277 IS 1 BP 228 EP 235 DI 10.1006/bbrc.2000.3663 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 367PJ UT WOS:000090070400039 PM 11027668 ER PT J AU Jeohn, GH Kim, WG Hong, JS AF Jeohn, GH Kim, WG Hong, JS TI Time dependency of the action of nitric oxide in lipopolysaccharide-interferon-gamma-induced neuronal cell death in murine primary neuron-glia co-cultures SO BRAIN RESEARCH LA English DT Article DE nitric oxide; lipopolysaccharide; neurons; glia; neurotoxicity; primary cell culture; cytokines ID TYROSINE KINASE INHIBITORS; ASTROCYTE-ENRICHED CULTURES; SYNTHASE EXPRESSION; CYTOKINE PRODUCTION; PROTEIN-KINASES; MIXED GLIA; MICROGLIA; INDUCTION; NEUROTOXICITY; INVOLVEMENT AB We investigated the time-dependency of the action of nitric oxide (NO) on glia-mediated neuronal cell death. Cortical neuron-glia co-cultures were treated with lipopolysaccharide and interferon gamma (LPS/LFN gamma). The production of NO was first detectable 9 h after the exposure to LPS/IFN gamma and increased for up to 48 h. A significant neuronal cell death was observed 36-48 h after treatment with LPS/IFN gamma. The NO generated at the initial stage of NO synthesis (about 12 h) following exposure to LPS/IFN gamma was found to be critical for LPS/IFN gamma -induced neurotoxicity. Furthermore, the rate of NO production at the initial stage of NO synthesis was correlated linearly with the extent of neuronal cell death. These findings suggest that the maximal rate of NO synthesis, instead of the accumulated NO2- level, is a sensitive index for predicting endotoxin-induced cytotoxicity. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, Nihon Univ, Res Triangle Pk, NC 27709 USA. RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, Nihon Univ, POB 12233, Res Triangle Pk, NC 27709 USA. NR 29 TC 35 Z9 36 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 13 PY 2000 VL 880 IS 1-2 BP 173 EP 177 DI 10.1016/S0006-8993(00)02737-2 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 365MT UT WOS:000089955600019 PM 11033002 ER PT J AU Ventura, ON Kieninger, M Cachau, RE Suhai, S AF Ventura, ON Kieninger, M Cachau, RE Suhai, S TI Density functional computational thermochemistry: determination of the enthalpy of formation of sulfine, CH2=S=O, at room temperature SO CHEMICAL PHYSICS LETTERS LA English DT Article ID GAS-PHASE BASICITY; CHEMISTRY; EXCHANGE; RADICALS; OXIDES; HEAT; BOND AB Density functional and coupled-cluster calculations using Pople's basis sets up to 6-311++G(3df,2pd) have been employed to determine the heat of formation of sulfine, CH2SO, 1, using the isodesmic reaction CH2S + SO2 = CH2SO + SO, Other reactions, employed previously to determine the enthalpy of formation of sulfine at the CAS-SDCI/ CASSCF ab initio level, were used as well. The analysis of the results shows that: (a) the errors in the calculation of the enthalpies for the individual molecules do cancel reasonably only for the isodesmic reaction, and not for those used previously; (b) density functional methods produce smaller errors than CCSDT in the calculation of the enthalpies of formation of the molecules involved in this reaction; (c) the actual heat of formation of sulfine is determined as Delta H-f(298.15)o(l) = -52 +/- 10 kJ/mol, more in agreement with the prediction of Benson than with the ab initio value derived by Ruttink et al,; (d) the proton affinity of sulfine, calculated at the density functional level (792.0 kJ/mol) agrees reasonably well with the experimental result, 787.6 +/- 2.6 kJ/mol, but the enthalpy of formation of 1 derived from this proton affinity using the assumptions of Ruttink or Bouchoux is in disagreement with the value determined previously. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Republ, Fac Quim, DeQuiFiM, MTC Lab, Montevideo 11800, Uruguay. NCI, Frederick Biomed Supercomp Ctr, Frederick, MD 21702 USA. DKFZ, Abt Mol Biophys, D-69120 Heidelberg, Germany. RP Ventura, ON (reprint author), Univ Republ, Fac Quim, DeQuiFiM, MTC Lab, CC 1157, Montevideo 11800, Uruguay. NR 25 TC 15 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD OCT 13 PY 2000 VL 329 IS 1-2 BP 145 EP 153 DI 10.1016/S0009-2614(00)00989-1 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 367TU UT WOS:000090078200022 ER PT J AU Xiao, RP AF Xiao, RP TI Cell logic for dual coupling of a single class of receptors to G(s) and G(i) proteins SO CIRCULATION RESEARCH LA English DT Editorial Material ID CONGESTIVE-HEART-FAILURE; BETA(2)-ADRENERGIC RECEPTOR; CARDIAC MYOCYTES; PERTUSSIS-TOXIN; TRANSGENIC MICE; RAT; HYPERTROPHY; ALPHA; PHOSPHORYLATION; APOPTOSIS C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Xiao, RP (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 36 TC 25 Z9 30 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT 13 PY 2000 VL 87 IS 8 BP 635 EP 637 PG 3 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 369AP UT WOS:000090149900001 PM 11029395 ER PT J AU Macdonald, JM Haas, AL London, RE AF Macdonald, JM Haas, AL London, RE TI Novel mechanism of surface catalysis of protein adduct formation - NMR studies of the acetylation of ubiquitin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-ACETYLIMIDAZOLE; NONENZYMATIC GLYCOSYLATION; AMADORI REARRANGEMENT; GROWTH-HORMONE; AMINO-GROUPS; GLYCATION; SITES; IDENTIFICATION; HEMOGLOBIN; SPECIFICITY AB Reactivity of surface lysyl residues of proteins with a broad range of chemical agents has been proposed to be dependent on the catalytic microenvironment of the residue. We have investigated the acetylation of wild type ubiquitin and of the UbH68N mutant to evaluate the potential contribution of His-68 to the reactivity of Lys-6, which is about 4 Angstrom distant. These studies were performed using [1-C-13]acetyl salicylate or [1,1'-C-13(2)]acetic anhydride, and the acetylated products were detected by two-dimensional heteronuclear multiple quantum coherence spectroscopy. The results demonstrate that His-68 makes a positive contribution to the rate of acetylation of Lys-6 by labeled aspirin. Additionally, a pair of transient resonances is observed after treatment of wild type ubiquitin with the labeled acetic anhydride but not upon treatment of the H68N mutant. These resonances are assigned to the acetylated His-68 residue. The loss of intensity of the acetylhistidine resonances is accompanied by an increase in intensity of the acetyl-lys-g peak, supporting the existence of a transacetylation process between the acetylhistidine 68 and lysine 6 residues located on the protein surface. Hence, this may be the first direct demonstration of a catalytic intermediate forming on the protein surface. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, NIH, MR-01,Box 12233, Res Triangle Pk, NC 27709 USA. NR 31 TC 10 Z9 10 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 13 PY 2000 VL 275 IS 41 BP 31908 EP 31913 DI 10.1074/jbc.M000684200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 363VT UT WOS:000089858900051 PM 10906321 ER PT J AU Baglia, FA Badellino, KO Ho, DH Dasari, VR Walsh, PN AF Baglia, FA Badellino, KO Ho, DH Dasari, VR Walsh, PN TI A binding site for the kringle II domain of prothrombin in the Apple 1 domain of factor XI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COAGULATION-FACTOR-XI; MOLECULAR-WEIGHT KININOGEN; BLOOD-COAGULATION; FUNCTIONAL-CHARACTERIZATION; HAGEMAN-FACTOR; HEAVY-CHAIN; ACTIVATION; THROMBIN; PLASMA; IDENTIFICATION AB Previously we defined binding sites for high molecular weight kininogen (HK) and thrombin in the Apple 1 (Al) domain of factor XI (FM). Since prothrombin (and Ca2+) can bind FXI and can substitute for HK (and Zn2+) as a cofactor for FXI binding to platelets, we have attempted to identify a prothrombin-binding site in FXI. The recombinant Al domain (rAl, Glu(1)-Ser(90)) inhibited the saturable, specific and reversible binding of prothrombin to FXI, whereas neither the rA2 domain (Ser(90)-Ala(181)), rA3 domain (Ala(181)-Val(271)), nor rA4 domain (Phe(272)-Glu(361)) inhibited prothrombin binding to FXI. Kinetic binding studies using surface plasmon resonance showed binding of FXI (K-d similar to 71 nn) and the rAl domain (K-d similar to 239 nM) but not rA2, rA3, or rA4 to immobilized prothrombin. Reciprocal binding studies revealed that synthetic peptides (encompassing residues Ala(45)-Ser(86)) containing both HK- and thrombin-binding sites, inhibit I-125-rAl (Glu(1)-Ser(90)) binding to prothrombin, I-125-prothrombin binding to FXI, and 125I-prothrombin fragment 2 (Ser(156)-Arg(271)) binding to FXI. However, homologous prekallikrein-derived peptides (encompassing Pro(45)-Gly(86)) did not inhibit FXI rAl binding to prothrombin. The peptides Ala(45)-Arg(54), Phe(56)-Val(71), and Asp(72)-Ser(86), derived from sequences of the Al domain of FXI, acted synergistically to inhibit I-125-rAl binding to prothrombin. Mutant rAl peptides (V64A and I77A), which did not inhibit FXI binding to III, retained full capacity to inhibit rAl domain binding to prothrombin, and mutant rAl peptides Ala(45)-Ala(54) (D51A) and Val(59)-Arg(70) (E66A), which did not inhibit FXI binding to thrombin, retained full capacity to inhibit rAl domain binding to prothrombin. Thus, these experiments demonstrate that a prothrombin binding site exists in the Al domain of FXI spanning residues Ala(45)-Ser(86) that is contiguous with but separate and distinct from the HK- and thrombin-binding sites and that this interaction occurs through the kringle II domain of prothrombin. C1 Temple Univ, Sch Med, Sol Sherry Thrombosis Res Ctr, Philadelphia, PA 19140 USA. Temple Univ, Sch Med, Dept Med, Philadelphia, PA 19140 USA. Temple Univ, Sch Med, Dept Biochem, Philadelphia, PA 19140 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Walsh, PN (reprint author), Temple Univ, Sch Med, Sol Sherry Thrombosis Res Ctr, 3400 N Broad St, Philadelphia, PA 19140 USA. FU NHLBI NIH HHS [HL56914, HL56153, HL46213] NR 33 TC 26 Z9 26 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 13 PY 2000 VL 275 IS 41 BP 31954 EP 31962 DI 10.1074/jbc.M005465200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 363VT UT WOS:000089858900057 PM 10924522 ER PT J AU Henklein, P Bruns, K Sherman, MP Tessmer, U Licha, K Kopp, J de Noronha, CMC Greene, WC Wray, V Schubert, U AF Henklein, P Bruns, K Sherman, MP Tessmer, U Licha, K Kopp, J de Noronha, CMC Greene, WC Wray, V Schubert, U TI Functional and structural characterization of synthetic HIV-1 Vpr that transduces cells, localizes to the nucleus, and induces G(2) cell cycle arrest SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL PROTEIN-R; PREINTEGRATION COMPLEX; BIOLOGICAL FUNCTIONS; TERMINAL DOMAIN; GAG PRECURSOR; P6 DOMAIN; IN-VIVO; TYPE-1; INFECTION AB Human immunodeficiency virus (HIV) Vpr contributes to nuclear import of the viral pre-integration complex and induces G(2), cell cycle arrest. We describe the production of synthetic Vpr that permitted the first studies on the structure and folding of the full-length protein. Vpr is unstructured at neutral pH whereas under acidic conditions or upon addition of trifluorethanol it adopts a-helical structures. Vpr forms dimers in aqueous trifluorethanol, whereas oligomers exist in pure water. H-1 NMR spectroscopy allows the signal assignment of N- and C-terminal amino acid residues; however, the central section of the molecule is obscured by self-association. These findings suggest that the in vivo folding of Vpr may require structure-stabilizing interacting factors such as previously described interacting cellular and viral proteins or nucleic acids. In biological studies we found that Vpr is efficiently taken up from the extracellular medium by cells in a process that occurs independent of other HIV-1 proteins and appears to be independent of cellular receptors. Following cellular uptake, Vpr is efficiently imported into the nucleus of transduced cells. Extracellular addition of Vpr induces G(2), cell cycle arrest in dividing cells. Together, these findings raise the possibility that circulating forms of Vpr observed in HIV-infected patients may exert biological effects on a broad range of host target cells. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Kidney Dis Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Humboldt Univ, Inst Biochem, D-10115 Berlin, Germany. Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-20251 Hamburg, Germany. Gesell Biotechnol Forsch GmbH, Dept Mol Struct Res, D-38124 Braunschweig, Germany. Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 USA. Free Univ Berlin, Inst Diagnost Res GmbH, D-1000 Berlin, Germany. RP Schubert, U (reprint author), NIAID, Viral Dis Lab, NIH, Rm 205,Bldg 4,4 Ctr Dr,MSC 0440, Bethesda, MD 20892 USA. OI Kopp, Jeffrey/0000-0001-9052-186X FU NIAID NIH HHS [R01 AI45324] NR 51 TC 86 Z9 88 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 13 PY 2000 VL 275 IS 41 BP 32016 EP 32026 DI 10.1074/jbc.M004044200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 363VT UT WOS:000089858900065 PM 10903315 ER PT J AU Kapus, A Di Ciano, C Sun, JG Zhan, X Kim, L Wong, TW Rotstein, OD AF Kapus, A Di Ciano, C Sun, JG Zhan, X Kim, L Wong, TW Rotstein, OD TI Cell volume-dependent phosphorylation of proteins of the cortical cytoskeleton and cell-cell contact sites - The role of Fyn and FER kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SRC FAMILY KINASES; CADHERIN CATENIN COMPLEX; HAMSTER OVARY CELLS; TYROSINE PHOSPHORYLATION; BETA-CATENIN; BINDING PROTEIN; GROWTH-FACTOR; ADHERENS JUNCTIONS; SIGNAL TRANSDUCER; OSMOTIC-STRESS AB Cell volume affects diverse functions including cytoskeletal organization, but the underlying signaling pathways remained undefined. We have shown previously that shrinkage induces Fyn-dependent tyrosine phosphorylation of the cortical actin-binding protein, cortactin, Because FER kinase was implicated in the direct phosphorylation of cortactin, we investigated the osmotic responsiveness of FER and its relationship to Fyn and cortactin. Shrinkage increased FER activity and tyrosine phosphorylation, These effects were abolished by the Src family inhibitor PP2 and strongly mitigated in Fyn-deficient but not in Src-deficient cells. FER overexpression caused cortactin phosphorylation that was further enhanced by hypertonicity. Exchange of tyrosine residues 421, 466, and 482 for phenylalanine prevented cortactin phosphorylation by hypertonicity and strongly decreased it upon FER overexpression, suggesting that FER targets primarily the same osmo-sensitive tyrosines, Because constituents of the cell-cell contacts are substrates of Fyn and FER, we investigated the effect of shrinkage on the adherens junctions. Hypertonicity provoked Fyn-dependent tyrosine phosphorylation in beta-catenin, alpha-catenin, and p120(Cas) and caused the dissociation of beta-catenin from the contacts, This process was delayed in Fyn-deficient or PP2-treated cells. Thus, FER is a volume-sensitive kinase downstream from Fyn, and the Fyn/FER pathway may contribute to the cell size-dependent reorganization of the cytoskeleton and the cell-cell contacts. C1 Toronto Gen Hosp, Dept Surg, Toronto, ON M5G 1L7, Canada. Univ Toronto, Toronto, ON M5G 1L7, Canada. Amer Red Cross, Jerome H Holland Lab, Dept Expt Pathol, Rockville, MD 20855 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. RP Kapus, A (reprint author), Toronto Gen Hosp, Dept Surg, Rm CCRW 2-850,101 Coll St, Toronto, ON M5G 1L7, Canada. NR 58 TC 69 Z9 70 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 13 PY 2000 VL 275 IS 41 BP 32289 EP 32298 DI 10.1074/jbc.M003172200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 363VT UT WOS:000089858900101 PM 10921917 ER PT J AU Gottesman, MM Shmookler, SR AF Gottesman, MM Shmookler, SR TI Math and science education: Training the teachers SO SCIENCE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. Mongomery Cty Publ Sch, Rockville, MD 20850 USA. RP Gottesman, MM (reprint author), NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT 13 PY 2000 VL 290 IS 5490 BP 273 EP 273 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363CW UT WOS:000089818100018 ER PT J AU Sun, M Goldin, E Stahl, S Falardeau, JL Kennedy, JC Acierno, JS Bove, C Kaneski, CR Nagle, J Bromley, MC Colman, M Schiffmann, R Slaugenhaupt, SA AF Sun, M Goldin, E Stahl, S Falardeau, JL Kennedy, JC Acierno, JS Bove, C Kaneski, CR Nagle, J Bromley, MC Colman, M Schiffmann, R Slaugenhaupt, SA TI Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel SO HUMAN MOLECULAR GENETICS LA English DT Article ID ABNORMAL TRANSPORT; SKIN FIBROBLASTS; VARIANT AB Mucolipidosis type IV (MLIV) is a developmental neurodegenerative disorder characterized by severe neurologic and ophthalmologic abnormalities, The MLIV gene, ML4 (MCOLN1), has recently been localized to chromosome 19p13.2-13.3 by genetic linkage. Here we report the cloning of a novel transient receptor potential cation channel gene and show that this gene is mutated in patients with the disorder, ML4 encodes a protein, which we propose to call mucolipin, which has six predicted transmembrane domains and is a member of the polycystin II subfamily of the Drosophila transient receptor potential gene family. The role of a potential receptor-stimulated cation channel defect in the pathogenesis of mucolipidosis IV is discussed. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, DNA Sequencing Facil, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Harvard Inst Human Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. RP Sun, M (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. OI Kaneski, Christine/0000-0003-1453-2502 FU NINDS NIH HHS [R01-NS39995] NR 20 TC 210 Z9 223 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 12 PY 2000 VL 9 IS 17 BP 2471 EP 2478 DI 10.1093/hmg/9.17.2471 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 367KZ UT WOS:000090061400001 PM 11030752 ER PT J AU Obmolova, G Ban, C Hsieh, P Yang, W AF Obmolova, G Ban, C Hsieh, P Yang, W TI Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA SO NATURE LA English DT Article ID ESCHERICHIA-COLI; REPLICATION FIDELITY; MUTATOR PHENOTYPES; THERMUS-AQUATICUS; ATP-BINDING; RECOGNITION; MUTATIONS; RECOMBINATION; HYDROLYSIS; SUBUNIT AB DNA mismatch repair is critical for increasing replication fidelity in organisms ranging from bacteria to humans. MutS protein, a member of the ABC ATPase superfamily, recognizes mispaired and unpaired bases in duplex DNA and initiates mismatch repair. Mutations in human MutS genes cause a predisposition to hereditary nonpolyposis colorectal cancer as well as sporadic tumours. Here we report the crystal structures of a MutS protein and a complex of MutS with a heteroduplex DNA containing an unpaired base. The structures reveal the general architecture of members of the MutS family, an induced-fit mechanism of recognition between four domains of a MutS dimer and a heteroduplex kinked at the mismatch, a composite ATPase active site composed of residues from both MutS subunits, and a transmitter region connecting the mismatch-binding and ATPase domains. The crystal structures also provide a molecular framework for understanding hereditary nonpolyposis colorectal cancer mutations and for postulating testable roles of MutS. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Yang, Wei/D-4926-2011; Ban, Changill/F-5426-2013 OI Yang, Wei/0000-0002-3591-2195; NR 47 TC 434 Z9 439 U1 4 U2 45 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 12 PY 2000 VL 407 IS 6805 BP 703 EP 710 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 362JB UT WOS:000089773900032 PM 11048710 ER PT J AU Szefler, S Weiss, S Tonascia, A Adkinson, NF Bender, B Cherniack, R Donithan, M Kelly, HW Reisman, J Shapiro, GG Sternberg, AL Strunk, R Taggart, V Van Natta, M Wise, R Wu, M Zeiger, R AF Szefler, S Weiss, S Tonascia, A Adkinson, NF Bender, B Cherniack, R Donithan, M Kelly, HW Reisman, J Shapiro, GG Sternberg, AL Strunk, R Taggart, V Van Natta, M Wise, R Wu, M Zeiger, R CA Childhood Asthma Management Progr TI Long-term effects of budesonide or nedocromil in children with asthma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INHALED CORTICOSTEROIDS; CHILDHOOD ASTHMA; BECLOMETHASONE DIPROPIONATE; MANAGEMENT PROGRAM; PULMONARY-FUNCTION; LUNG-FUNCTION; MILD ASTHMA; ADULT LIFE; GROWTH; DURATION AB Background: Antiinflammatory therapies, such as inhaled corticosteroids or nedocromil, are recommended for children with asthma, although there is limited information on their long-term use. Methods: We randomly assigned 1041 children from 5 through 12 years of age with mild-to-moderate asthma to receive 200 microg of budesonide (311 children), 8 mg of nedocromil (312 children), or placebo (418 children) twice daily. We treated the participants for four to six years. All children used albuterol for asthma symptoms. Results: There was no significant difference between either treatment and placebo in the primary outcome, the degree of change in the forced expiratory volume in one second (FEV(sub 1), expressed as a percentage of the predicted value) after the administration of a bronchodilator. As compared with the children assigned to placebo, the children assigned to receive budesonide had a significantly smaller decline in the ratio of FEV(sub 1) to forced vital capacity (FVC, expressed as a percentage) before the administration of a bronchodilator (decline in FEV(sub 1):FVC, 0.2 percent vs. 1.8 percent). The children given budesonide also had lower airway responsiveness to methacholine, fewer hospitalizations (2.5 vs. 4.4 per 100 person-years), fewer urgent visits to a caregiver (12 vs. 22 per 100 person-years), greater reduction in the need for albuterol for symptoms, fewer courses of prednisone, and a smaller percentage of days on which additional asthma medications were needed. As compared with placebo, nedocromil significantly reduced urgent care visits (16 vs. 22 per 100 person-years) and courses of prednisone. The mean increase in height in the budesonide group was 1.1 cm less than in the placebo group (22.7 vs. 23.8 cm, P=0.005); this difference was evident mostly within the first year. The height increase was similar in the nedocromil and placebo groups. Conclusions: In children with mild-to-moderate asthma, neither budesonide nor nedocromil is better than placebo in terms of lung function, but inhaled budesonide improves airway responsiveness and provides better control of asthma than placebo or nedocromil. The side effects of budesonide are limited to a small, transient reduction in growth velocity. (N Engl J Med 2000;343:1054-63.) (C) 2000, Massachusetts Medical Society. C1 Johns Hopkins Univ, Childhood Asthma Management Program, Coordinating Ctr, Baltimore, MD 21205 USA. Asthma Inc, Seattle, WA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA. Natl Jewish Med & Res Ctr, Chairs Off, Denver, CO USA. Univ Calif San Diego, San Diego, CA 92103 USA. Kaiser Permanente, San Diego, CA USA. Univ New Mexico, Albuquerque, NM 87131 USA. Washington Univ, Bone Age Reading Ctr, St Louis, MO USA. Johns Hopkins Asthma & Allergy Ctr, Dermatol Allergy & Clin Immunol Reference Lab, Baltimore, MD USA. McKesson Bioserv Corp, Drug Distribut Ctr, Rockville, MD USA. Univ Wisconsin, Fundus Photog Reading Ctr, Madison, WI USA. Natl Jewish Med & Res Ctr, Patient Educ Ctr, Denver, CO USA. PDS Instrumentat, Louisville, CO USA. NHLBI, Project Off, Bethesda, MD 20892 USA. Natl Jewish Med & Res Ctr, Immunol & Complement Lab, Denver, CO USA. Univ Iowa, Coll Pharm, Div Pharmaceut Serv, Iowa City, IA 52242 USA. RP Tonascia, A (reprint author), Johns Hopkins Univ, Childhood Asthma Management Program, Coordinating Ctr, 615 N Wolfe St,Rm 5010, Baltimore, MD 21205 USA. OI Williams, Paul/0000-0003-3300-1328; Wise, Robert/0000-0002-8353-2349 NR 51 TC 785 Z9 811 U1 2 U2 27 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 12 PY 2000 VL 343 IS 15 BP 1054 EP 1063 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 362FA UT WOS:000089766900001 ER PT J AU Lee, JH Han, SU Cho, H Jennings, B Gerrard, B Dean, M Schmidt, L Zbar, B Vande Woude, GF AF Lee, JH Han, SU Cho, H Jennings, B Gerrard, B Dean, M Schmidt, L Zbar, B Vande Woude, GF TI A novel germ line juxtamembrane Met mutation in human gastric cancer SO ONCOGENE LA English DT Article DE gastric cancer; germ line; juxtamembrane Met mutation ID HEPATOCYTE GROWTH-FACTOR; PAPILLARY RENAL CARCINOMAS; SCATTER FACTOR; TYROSINE KINASE; FACTOR RECEPTOR; C-MET; EPITHELIAL-CELLS; PROTOONCOGENE PRODUCT; SOMATIC MUTATIONS; TUMORIGENICITY AB Activating mutations in the Met receptor tyrosine kinase, both germline and somatic, have been identified in human papillary renal cancer. Here we report a novel germline missense Met mutation, P1009S, in a patient with primary gastric cancer. The dosage of the mutant Met DNA was elevated in the tumor when compared to its matched normal DNA. Therefore, as with hereditary renal papillary cancer, the mutant Met allele may also be selectively duplicated in the tumor. Different from previously reported Met mutations, which occur in the tyrosine kinase domain, this missense mutation is located at the juxtamembrane domain, and is not constitutively activated. However, following treatment with HGF/SF, the P1009S mutant Met protein, expressed in NIH3T3 cells, displays increased and persistent tyrosine phosphorylation compared to the wild-type Met. Importantly, these cells also form colonies in soft agar, and are highly tumorigenic in athymic nude mice. A second nucleotide change in this region of Met, T1010I, was found in a breast cancer biopsy and a large cell lung cancer cell line. Although this previously reported 'polymorphism' did not stimulate NIH3T3 cell growth in soft agar, it was more active than the wild-type Met in the athymic nude mice tumorigenesis assay, suggesting that it may have effects on tumorigenesis. Met has been shown to be highly expressed in human gastric carcinoma cell lines, and our results raise the possibility that activating missense Met mutations could contribute to tumorigenesis of gastric cancer. C1 Van Andel Res Inst, Grand Rapids, MI 49503 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Ajou Univ, Sch Med, Dept Surg, Paldal Gu, Suwon 442749, South Korea. Ajou Univ, Sch Med, Dept Biochem, Paldal Gu, Suwon 442749, South Korea. Norfolk & Norwich Healthcare NHS Trust, Norwich, Norfolk, England. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Div Intramural Res Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. RP Vande Woude, GF (reprint author), Van Andel Res Inst, 333 Bostwick,NE, Grand Rapids, MI 49503 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CO-56000] NR 47 TC 221 Z9 226 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 12 PY 2000 VL 19 IS 43 BP 4947 EP 4953 DI 10.1038/sj.onc.1203874 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 363KF UT WOS:000089834300001 PM 11042681 ER PT J AU Larson, VD Williams, DW Henderson, WG Luethke, LE Beck, LB Noffsinger, D Wilson, RH Dobie, RA Haskell, GB Bratt, GW Shanks, JE Stelmachowicz, P Studebaker, GA Boysen, AE Donahue, A Canalis, R Fausti, SA Rappaport, BZ AF Larson, VD Williams, DW Henderson, WG Luethke, LE Beck, LB Noffsinger, D Wilson, RH Dobie, RA Haskell, GB Bratt, GW Shanks, JE Stelmachowicz, P Studebaker, GA Boysen, AE Donahue, A Canalis, R Fausti, SA Rappaport, BZ CA NIDCD VA Hearing Aid Clin Trial Gr TI Efficacy of 3 commonly used hearing aid circuits - A crossover trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COMPRESSION; IMPAIRMENT; BENEFIT; PERFORMANCE; PROFILE; QUALITY; GAIN; LIFE AB Context Numerous studies have demonstrated that hearing aids provide significant benefit for a wide range of sensorineural hearing loss, but no carefully controlled, multicenter clinical trials comparing hearing aid efficacy have been conducted. Objective To compare the benefits provided to patients with sensorineural hearing loss by 3 commonly used hearing aid circuits. Design Double-blind, 3-period, 3-treatment crossover trial conducted from May 1996 to February 1998. Setting Eight audiology laboratories at Department of Veterans Affairs medical centers across the United States. Patients A sample of 360 patients with bilateral sensorineural hearing loss (mean age, 67.2 years; 57% male, 78.6% white). Intervention Patients were randomly assigned to 1 of 6 sequences of linear peak clipper (PC), compression limiter (CL), and wide dynamic range compressor (WDRC) hearing aid circuits. All patients wore each of the 3 bearing aids, which were installed in identical casements, for 3 months, Main Outcome Measures Results of tests of speech recognition, sound quality, and subjective hearing aid benefit, administered at baseline and after each 3-month intervention with and without a hearing aid. At the end of the experiment, patients ranked the 3 hearing aid circuits. Results Each circuit markedly improved speech recognition, with greater improvement observed for soft and conversationally loud speech (all 52-dB and 62-dB conditions, P less than or equal to .001). All 3 circuits significantly reduced the frequency of problems encountered in verbal communication. Some test results suggested that CL and WDRC circuits provided a significantly better listening experience than PC circuits in word recognition (P = .002), loudness (P = .003), overall liking (P = .001), aversiveness of environmental sounds (P = .02), and distortion (P = .02). In the rank-order ratings, patients preferred the CL hearing aid circuits more frequently (41.6%) than the WDRC (29.8%) and the PC (28.6%) (P = .001 for CL vs both WDRC and PC). Conclusions Each circuit provided significant benefit in quiet and noisy listening situations. The CL and WDRC circuits appeared to provide superior benefits compared with the PC, although the differences between them were much less than the differences between the aided vs unaided conditions. C1 Dept Vet Affairs Med Ctr, Washington, DC USA. Hines VA Cooperat Studies Program, Coordinating Ctr, Hines, IL USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA USA. Dept Vet Affairs Med Ctr, Mt Home, TN USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Dept Vet Affairs Med Ctr, Iowa City, IA 52242 USA. Dept Vet Affairs Med Ctr, Nashville, TN 37212 USA. Dept Vet Affairs Med Ctr, Long Beach, CA USA. Boys Town Natl Res Hosp, Omaha, NE 68131 USA. Univ Memphis, Memphis, TN 38152 USA. Univ Calif Los Angeles, Harborview Med Ctr, Los Angeles, CA USA. Dept Vet Affairs Med Ctr, Portland, OR USA. Dept Vet Affairs Med Ctr, Albuquerque, NM USA. RP Larson, VD (reprint author), Howard Leight Ind, 7828 Waterville Rd, San Diego, CA 92154 USA. OI dobie, robert/0000-0003-3833-1772 NR 35 TC 47 Z9 49 U1 2 U2 5 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 OCT 11 PY 2000 VL 284 IS 14 BP 1806 EP 1813 DI 10.1001/jama.284.14.1806 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 359PW UT WOS:000089622100032 PM 11025833 ER PT J AU Nagababu, E Rifkind, JM AF Nagababu, E Rifkind, JM TI Reaction of hydrogen peroxide with ferrylhemoglobin: Superoxide production and heme degradation SO BIOCHEMISTRY LA English DT Article ID RED-BLOOD-CELLS; SPERM WHALE MYOGLOBIN; LIPID-PEROXIDATION; ENDOTHELIAL-CELLS; FREE-RADICALS; HEMOGLOBIN; OXIDATION; OXYGEN; DAMAGE; MECHANISM AB The reaction of Fe(II) hemoglobin (Hb) but not Fe(III) hemoglobin (metHb) with hydrogen peroxide results in degradation of the heme moiety. The observation that heme degradation was inhibited by compounds, which react with ferrylHb such as sodium sulfide, and peroxidase substrates (ABTS and o-dianisidine), demonstrates that ferrylHb formation is required for heme degradation. A reaction involving hydrogen peroxide and ferrylHb was demonstrated by the finding that heme degradation was inihibited by the addition of catalase which removed hydrogen peroxide even after the maximal level of ferrylHb was reached. The reaction of hydrogen peroxide with ferrylHb to produce heme degradation products was shown by electron paramagnetic resonance to involve the one-electron oxidation of hydrogen peroxide to the oxygen free radical, superoxide. The inhibition by sodium sulfide of both superoxide production and the formation of fluorescent heme degradation products links superoxide production with heme degradation. The inability to produce heme degradation products by the reaction of metHb with hydrogen peroxide was explained by the fact that hydrogen peroxide reacting with oxoferrylHb undergoes a two-electron oxidation, producing oxygen instead of superoxide. This reaction does not produce heme degradation, but is responsible for the catalytic removal of hydrogen peroxide. The rapid consumption of hydrogen peroxide as a result of the metHb formed as an intermediate during the reaction of reduced hemoglobin with hydrogen peroxide was shown to limit the extent of heme degradation. C1 NIA, Sect Mol Dynam, Mol & Cellular Biol Lab, NIH, Baltimore, MD 21224 USA. RP Rifkind, JM (reprint author), NIA, Sect Mol Dynam, Mol & Cellular Biol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 70 TC 117 Z9 120 U1 2 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 10 PY 2000 VL 39 IS 40 BP 12503 EP 12511 DI 10.1021/bi992170y PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 363CB UT WOS:000089815700046 PM 11015232 ER PT J AU List, HJ Smith, CL Martinez, E Harris, VK Danielsen, M Riegel, AT AF List, HJ Smith, CL Martinez, E Harris, VK Danielsen, M Riegel, AT TI Effects of antiandrogens on chromatin remodeling and transcription of the integrated mouse mammary tumor virus promoter SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE androgen receptor; cyproterone acetate; hydroxyflutamide; flutamide; chromatin; transcription; MMTV promoter ID ANDROGEN RECEPTOR COACTIVATOR; IN-VIVO; GLUCOCORTICOID RECEPTOR; HUMAN PROSTATE; GENE-EXPRESSION; MMTV PROMOTER; ACTIVATION; NUCLEOSOME; BINDING; DIHYDROTESTOSTERONE AB Inhibition of the ligand-activated androgen receptor (AR) by antiandrogens plays an important role in the treatment of various hyperandrogenic disorders including prostate cancer. However, the molecular mechanisms of antiandrogen activity in vivo remain unclear. In this study we analyzed the effects of cyproterone acetate (CPA), flutamide (F), and hydroxyflutamide (OHF) on transcriptional activation and chromatin remodeling of the genomically integrated mouse mammary tumor virus (MMTV), promoter. This promoter has provided an excellent model system to study the impact of steroid hormones on transcriptional activation in the context of a defined chromatin structure. The MMTV hormone response element is positioned on a phased nucleosome, which becomes remodeled in response to steroids. We utilized this model system in mouse L-cell fibroblasts that contain a stably integrated MMTV promoter. In these cells, dihydrotestosterone (DHT) induced a large increase of AR protein levels that correlated with transcriptional activation and chromatin remodeling of the MMTV promoter Coadministration of DHT and CPA or DHT and OHF in these cells inhibited the increase of AR levels, which resulted in a strong blockage of transcriptional activation and chromatin remodeling of the MMTV promoter. In contrast, F had no significant influence on these activities, We conclude that a major portion of the antiandrogenic effects of CPA and OHF in vivo are mediated by the reduction of AR levels. (C) 2000 Academic Press. C1 Georgetown Univ, Dept Oncol, Vincent T Lombardi Canc Ctr, Washington, DC 20007 USA. Georgetown Univ, Dept Biochem & Mol Biol, Vincent T Lombardi Canc Ctr, Washington, DC 20007 USA. NIH, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP Riegel, AT (reprint author), Georgetown Univ, Dept Oncol, Vincent T Lombardi Canc Ctr, Res Bldg,E307,3970 Reservoir Rd, Washington, DC 20007 USA. RI Danielsen, Mark/B-1606-2008 OI Danielsen, Mark/0000-0002-0923-9945 NR 29 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 10 PY 2000 VL 260 IS 1 BP 160 EP 165 DI 10.1006/excr.2000.5018 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 362RK UT WOS:000089791900016 PM 11010820 ER PT J AU Abu-Shakra, A McQueen, ET Cunningham, ML AF Abu-Shakra, A McQueen, ET Cunningham, ML TI Rapid analysis of base-pair substitutions induced by mutagenic drugs through their oxygen radical or epoxide derivatives SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE mutagenesis; nitric oxide; diepoxybutane; treosulphan; Ames II (TM) strains; oxidative damage ID SALMONELLA TESTER STRAINS; NITRIC-OXIDE; DNA-DAMAGE; HYDROGEN-PEROXIDE; TARGET SEQUENCES; CELLS; GENOTOXICITY; TREOSULPHAN; REVERTANTS; CANCER AB Among the drugs that induce base-pair substitution mutations in the Salmonella reversion assay are the nitric oxide (NO)-delivery drag, diethylamine NONOate (DeaNO), and the ovarian cancer chemotherapeutic drug, treosulphan (TE). The present study compared the mutation spectra generated by DeaNO and TE in the hisG46 strains, TA1535 and TA100, the hisG428 strain, TA102, and the six Ames II(TM) 7000 series strains. Using these strains, it was feasible to conduct rapid analysis of the type and magnitude of induced mutation without resorting to DNA amplification and sequencing. A putative hydrolysis product of TE, 1,2:3,4-diepoxybutane (DEB), and hydrogen peroxidie (H2O2) were included in the study to allow for further comparisons between epoxide-induced damage and that induced by the hydroxyl radical. TE (0.93 mu mole/pl) induced 16.8-fold-over-background reversion or a mutagenicity ratio (MR) of 16.8 in TA1535. The response was weaker in TA100 (MR of 3), and negative in strain TA102. Only two Ames II(TM) strains demonstrated sensitivity to TE, and they were TA7004 (CG:AT) and TA7005 (GC:AT). Like TE, DeaNO (33 mu mole/pl) was mutagenic in TA1535 (MR of 24.6), TA100 (MR of 5.3), TA7004 (MR of 13.7), and TA7005 (MR of 7.7), and non-mutagenic in TA102. These results showed a preferential sensitivity to reversion of the -CCC- target in TA100 and TA1535, and a lack of sensitivity to reversion of the -TAA- target in TA102. In addition, they elucidated the selectivity of the Ames II(TM) strains, with AT targets showing little or no sensitivity to reversion. The TE-epoxide derivative DEB was mutagenic in TA1535 and TA7004, but in contrast to TE, DEB was mutagenic in TA102. Interestingly, TA102 was reverted by :DEB and H2O2 but not by TE or DeaNO. This study showed that analysis of mutations is achievable using the battery of strains listed above. The fact that DNA damage can be detected by reversion at specific bases offers a tool for understanding the mechanisms through which drugs may exert their DNA and cellular damage. (C) 2000 Elsevier Science B.V. All rights reserved. C1 N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC USA. RP Abu-Shakra, A (reprint author), N Carolina Cent Univ, Dept Biol, 1801 Fayetteville St, Durham, NC 27707 USA. FU PHS HHS [S0 608049] NR 35 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD OCT 10 PY 2000 VL 470 IS 1 BP 11 EP 18 DI 10.1016/S1383-5718(00)00084-X PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 356QU UT WOS:000089454700002 PM 10986471 ER PT J AU Gilron, I Booher, SL Rowan, JS Smoller, B Max, MB AF Gilron, I Booher, SL Rowan, JS Smoller, B Max, MB TI A randomized, controlled trial of high-dose dextromethorphan in facial neuralgias SO NEUROLOGY LA English DT Article ID IDIOPATHIC TRIGEMINAL NEURALGIA; RECEPTOR ANTAGONIST KETAMINE; PAINFUL DIABETIC NEUROPATHY; POSTHERPETIC NEURALGIA; NR2B SUBUNIT; DOUBLE-BLIND; PLACEBO; AMITRIPTYLINE; MK-801; RAT AB Background: NMDA glutamate receptor antagonists such as ketamine and dextromethorphan reduce pain in certain neuropathic pain conditions. However, there have been no controlled trials of NMDA antagonists in facial neuralgias. Methods: A randomized, double-blind, crossover trial compared 6 weeks of oral dextromethorphan with active placebo (low-dose lorazepam) in 19 patients, stratified into three groups: 11 with facial pain and possible trigeminal neuropathy, five with anesthesia dolorosa, and three with idiopathic trigeminal neuralgia. Dosage was titrated in each patient to the highest level reached without disrupting normal activities. Results: Patients completing the trial included 10 with possible trigeminal neuropathy, four with anesthesia dolorosa, and two with trigeminal neuralgia. In patients with possible trigeminal neuropathy and anesthesia dolorosa, dextromethorphan decreased pain by a mean of only 2 to 4%, and these estimates were not significant. Both patients with trigeminal neuralgia had more pain during dextromethorphan treatment than during placebo treatment. Of three patients who demonstrated an analgesic response to dextromethorphan during the main trial, only one repeatedly responded in four subsequent confirmatory drug-placebo crossovers. Conclusions: Dextromethorphan shows little or no analgesic efficacy in pain due to possible trigeminal neuropathy and anesthesia dolorosa. Additional trials are necessary to conclusively evaluate the efficacy of NMDA-receptor antagonists in trigeminal neuralgia. C1 Natl Inst Dental & Craniofacial Res, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. RP Max, MB (reprint author), Natl Inst Dental & Craniofacial Res, Pain & Neurosensory Mechanisms Branch, NIH, Rm 3C-405, Bethesda, MD 20892 USA. FU NIDCR NIH HHS [1Z01DE00366-16] NR 44 TC 38 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 10 PY 2000 VL 55 IS 7 BP 964 EP 971 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 360ZD UT WOS:000089696500012 PM 11061252 ER PT J AU Pak, JH Huang, FL Li, JF Balschun, D Reymannn, KG Chiang, C Westphal, H Huang, KP AF Pak, JH Huang, FL Li, JF Balschun, D Reymannn, KG Chiang, C Westphal, H Huang, KP TI Involvement of neurogranin in the modulation of calcium/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: A study with knockout mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LONG-TERM POTENTIATION; C SUBSTRATE; RAT-BRAIN; GLUTAMATE RECEPTORS; RC3 PROTEIN; PHOSPHORYLATION; CALMODULIN; HIPPOCAMPUS; FACILITATION AB Neurogranin/RC3 is a neural-specific Ca2+-sensitive calmodulin (CaM)-binding protein whose Cam-binding affinity is modulated by phosphorylation and oxidation, Here we show that deletion of the Ng gene in mice did not result in obvious developmental or neuroanatomical abnormalities but caused an impairment of spatial learning and changes in hippocampal short- and long-term plasticity (paired-pulse depression, synaptic fatigue, long-term potentiation induction). These deficits were accompanied by a decreased basal level of the activated Ca2+/CaM-dependent kinase II (CaMKII) (approximate to 60% of wild type). Furthermore, hippocampal slices of the mutant mice displayed a reduced ability to generate activated CaMKII after stimulation of protein phosphorylation and oxidation by treatments with okadaic acid and sodium nitroprusside, respectively. These results indicate a central role of Ng in the regulation of CaMKII activity with decisive influences on synaptic plasticity and spatial learning. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Leibniz Inst Neurobiol, Dept Neurophysiol, D-39008 Magdeburg, Germany. Leibniz Inst Neurobiol, Project Grp Neuropharmacol, D-39008 Magdeburg, Germany. RP Huang, KP (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. NR 32 TC 128 Z9 139 U1 3 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 10 PY 2000 VL 97 IS 21 BP 11232 EP 11237 DI 10.1073/pnas.210184697 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700023 PM 11016969 ER PT J AU Lai, ZN Han, I Zirzow, G Brady, RO Reiser, J AF Lai, ZN Han, I Zirzow, G Brady, RO Reiser, J TI Intercellular delivery of a herpes simplex virus VP22 fusion protein from cells infected with lentiviral vectors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTENNAPEDIA HOMEODOMAIN; NONDIVIDING CELLS; 3RD HELIX; TRANSDUCTION; PARTICLES AB Effective gene therapy depends on the efficient transfer of therapeutic genes and their protein products to target cells. Lentiviral vectors appear promising for virus-mediated gene delivery and longterm expression in nondividing cells. The herpes simplex virus type 1 tegument protein VP22 has recently been shown to mediate intercellular transport of proteins, raising the possibility that it may he helpful in a setting where the global delivery of therapeutic proteins is desired, To investigate the effectiveness of lentiviral vectors to deliver genes encoding proteins fused to VP22, and to test whether the system is sufficiently potent to allow protein delivery from transduced cells in vitro and in vivo, fusion constructs of VP22 and the enhanced green fluorescent protein (EGFP) were prepared and delivered into target cells by using HIV-l-based lentiviral vectors. To follow the spread of VP22-EGFP to other cells, transduced COS-7 cells were coplated with a number of different cell types, including brain choroid plexus cells, human endothelial cells, H9 cells, and HeLa cells. We found that VP22-EGFP fusion proteins were transported from transduced cells to recipient cells and that such fusion proteins accumulated in the nucleus and in the cytoplasm of such cells. To determine the ability to deliver fusion proteins in vivo, we injected transduced H9 cells as well as the viral vector directly into the brain of mice. We present evidence that VP22-EGFP fusion proteins were transported effectively from lentivirus transduced cells in vivo. We also show that the VP22-EGFP fusion protein encoded by the lentivirus is transported between cells. Our data indicate that such fusion proteins are present in the nucleus and in the cytoplasm of neighboring cells. Therefore, lentiviral vectors may provide a potent biological system for delivering genes encoding therapeutic proteins fused to VP22. C1 Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Sch Med, Gene Therapy Program, New Orleans, LA 70112 USA. RP Brady, RO (reprint author), Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bldg 10,Rm 3D-04, Bethesda, MD 20892 USA. NR 21 TC 38 Z9 40 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 10 PY 2000 VL 97 IS 21 BP 11297 EP 11302 DI 10.1073/pnas.97.21.11297 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700034 PM 11027330 ER PT J AU Yamauchi, T Yamauchi, J Kuwata, T Tamura, T Yamashita, T Bae, N Westphal, H Ozato, K Nakatani, Y AF Yamauchi, T Yamauchi, J Kuwata, T Tamura, T Yamashita, T Bae, N Westphal, H Ozato, K Nakatani, Y TI Distinct but overlapping roles of histone acetylase PCAF and of the closely related PCAF-B/GCN5 in mouse embryogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-DAMAGE; P53; ACETYLTRANSFERASES; SIMILARITY; OCTAMER; COMPLEX; LACKING; MUSCLE; P300; TAFS AB PCAF plays a role in transcriptional activation, cell-cycle arrest, and cell differentiation in cultured cells. PCAF contributes to transcriptional activation by acetylating chromatin and transcription factors through its intrinsic histone acetylase activity. In this report, we present evidence for the in vivo function of PCAF and the closely related PCAF-B/GCN5. Mice lacking PCAF are developmentally normal without a distinct phenotype. In PCAF null-zygous mice, protein levels of PCAF-B/GCN5 are drastically elevated in lung and liver, where PCAF is abundantly expressed in wild-type mice. suggesting that PCAF-B/GCN5 functionally compensates for PCAF. In contrast, animals lacking PCAF-B/GCN5 die between days 9.5 and 11.5 of gestation. Normally, PCAF-B/GCN5 mRNA is expressed at high levels already by day a. whereas PCAF mRNA is first detected on day 12.5, which may explain, in part, the distinct knockout phenotypes, These results provide evidence that PCAF and PCAF-B/GCN5 play distinct but functionally overlapping roles in embryogenesis. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Nakatani, Y (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NR 20 TC 139 Z9 140 U1 1 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 OCT 10 PY 2000 VL 97 IS 21 BP 11303 EP 11306 DI 10.1073/pnas.97.21.11303 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700035 PM 11027331 ER PT J AU Aravind, L Watanabe, H Lipman, DJ Koonin, EV AF Aravind, L Watanabe, H Lipman, DJ Koonin, EV TI Lineage-specific loss and divergence of functionally linked genes in eukaryotes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RNA-POLYMERASE; PROTEIN SEQUENCES; GENOME SEQUENCE; C-ELEGANS; DNA; TRANSCRIPTION; INTERFERENCE; EVOLUTION; ARCHAEAL; DOMAINS AB By comparing 4,344 protein sequences from fission yeast Schizosaccharomyces pombe with all available eukaryotic sequences, we identified those genes that are conserved in S. pombe and nonfungal eukaryotes but are missing or highly diverged in the baker's yeast Saccharomyces cerevisiae. Since the radiation from the common ancestor with S. pombe, S. cerevisiae appears to have lost about 300 genes, and about 300 more genes have diverged by far beyond expectation. The most notable feature of the set of genes lost in S. cerevisiae is the coelimination of functionally connected groups of proteins, such as the signalosome and the spliceosome components. We predict similar coelimination of the components of the posttranscriptional gene-silencing system that includes the recently identified RNA-dependent RNA polymerase. Because one of the functions of posttranscriptional silencing appears to be "taming" of retrotransposons, the loss of this system in yeast could have triggered massive retrotransposition. resulting in elimination of introns and subsequent loss of spliceosome components that become dispensable. As the genome database grows, systematic analysis of coordinated gene loss may become a general approach for predicting new components of functional systems or even defining previously unknown functional complexes. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 41 TC 195 Z9 198 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 10 PY 2000 VL 97 IS 21 BP 11319 EP 11324 DI 10.1073/pnas.200346997 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700038 PM 11016957 ER PT J AU Gerton, JL DeRisi, J Shroff, R Lichten, M Brown, PO Petes, TD AF Gerton, JL DeRisi, J Shroff, R Lichten, M Brown, PO Petes, TD TI Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DOUBLE-STRAND BREAKS; CHROMOSOME-III; HIS4 LOCUS; GENE-EXPRESSION; MEIOSIS; DNA; REPLICATION; GENOME; SITES; ORGANIZATION AB In the yeast Saccharomyces cerevisiae, meiotic recombination is initiated by double-strand DNA breaks (DsBs). Meiotic DsBs occur at relatively high frequencies in some genomic regions (hotspots) and relatively low frequencies in others (coldspots). We used DNA microarrays to estimate variation in the level of nearby meiotic DSBs for all 6.200 yeast genes. Hotspots were nonrandomly associated with regions of high G + C base composition and certain transcriptional profiles. Coldspots were nonrandomly associated with the centromeres and telomeres. C1 Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Biochem, Stanford, CA 94305 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Gerton, JL (reprint author), Univ N Carolina, Dept Biol, CB 3280, Chapel Hill, NC 27599 USA. RI Lichten, Michael/C-5795-2013 OI Lichten, Michael/0000-0001-9707-2956 FU NCI NIH HHS [T32 CA009156, T32 CA09156]; NHGRI NIH HHS [HG00983]; NIGMS NIH HHS [GM24110, R01 GM024110] NR 35 TC 309 Z9 316 U1 1 U2 10 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 OCT 10 PY 2000 VL 97 IS 21 BP 11383 EP 11390 DI 10.1073/pnas.97.21.11383 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700049 PM 11027339 ER PT J AU Ozaki, K Kikly, K Michalovich, D Young, PR Leonard, WJ AF Ozaki, K Kikly, K Michalovich, D Young, PR Leonard, WJ TI Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GAMMA-CHAIN; SIGNAL-TRANSDUCTION; DNA; ASSOCIATION; PREDICTION; REGIONS; GENE AB We have identified a type I cytokine receptor, which we have termed novel interleukin receptor(NILR), that is most related to the IL-2 receptor beta chain (IL-2R beta) and physically adjacent to the IL-4 receptor ru chain gene on chromosome 16, NILR mRNA is most highly expressed in thymus and spleen, and is induced by phyto-hemagglutinin in human peripheral blood mononuclear cells. NILR protein was detected on human 7 cell lymphotropic virus type I-transformed T cell lines, Raji B cells, and YT natural killer-like cells. Artificial homodimerization of the NILR cytoplasmic domain confers proliferation to Ba/F3 murine pro-B cells but not to 32D myeloid progenitor cells or CTLL-2 murine helper T cells. In these latter cells, heterodimerization of IL-2R beta and the common cytokine receptor gamma chain (gamma(c)) cytoplasmic domains allows potent proliferation, whereas such heterodimerization of NILR with ye does not. This finding suggests that NILR has signaling potential but that a full understanding of its signaling partner(s) is not yet clear. Like IL-2R beta, NILR associates with Jak1 and mediates stats activation. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. SmithKline Beecham Pharmaceut, Dept Immunol, King Of Prussia, PA 19406 USA. SmithKline Beecham Pharmaceut, Dept Bioinformat, King Of Prussia, PA 19406 USA. SmithKline Beecham Pharmaceut, Dept Mol Biol, King Of Prussia, PA 19406 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 24 TC 214 Z9 227 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 10 PY 2000 VL 97 IS 21 BP 11439 EP 11444 DI 10.1073/pnas.200360997 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700058 PM 11016959 ER PT J AU Marks-Konczalik, J Dubois, S Losi, JM Sabzevari, H Yamada, N Feigenbaum, L Waldmann, TA Tagaya, Y AF Marks-Konczalik, J Dubois, S Losi, JM Sabzevari, H Yamada, N Feigenbaum, L Waldmann, TA Tagaya, Y TI IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NATURAL-KILLER-CELLS; RECEPTOR-BETA-CHAIN; DELTA T-CELLS; INTERLEUKIN-2 RECEPTOR; MESSENGER-RNA; GROWTH-FACTOR; ALPHA-CHAIN; IN-VIVO; CYTOKINE; PROLIFERATION AB A transgenic (Tg) mouse expressing human IL-15 was generated to define the role of IL-15 in the normal immune response. Overexpression of IL-15 resulted in an increase of NK, CD44(hi)CD8 memory T cells, and gamma delta T cells. Additionally, we observed the emergence of a novel type of NK-T cells with CD8 alpha alpha' expression. Due to the expansion and activation of NK cells, the IL-15Tg mouse showed enhanced innate immunity. In adaptive T cell immunity, the roles of IL-15 contrasted with those of IL-2. IL-15 inhibited IL-2-induced T cell death, which plays a role in the maintenance of peripheral self-tolerance. IL-15 thus seems to contribute to enhanced immune memory by selectively propagating memory T cells and by blocking T cell death mediated by IL-2. C1 NCI, Frederick Canc Res & Dev Ctr, Metab Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Tumor Immunol & Biol Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Dermatol Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Transgen Mouse Model, Sci Applicat Int Corp Frederick,NIH, Bethesda, MD 20892 USA. RP Tagaya, Y (reprint author), NCI, Frederick Canc Res & Dev Ctr, Metab Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. NR 35 TC 262 Z9 270 U1 2 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 OCT 10 PY 2000 VL 97 IS 21 BP 11445 EP 11450 DI 10.1073/pnas.200363097 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700059 PM 11016962 ER PT J AU Xiao, H Neuveut, C Tiffany, HL Benkirane, M Rich, EA Murphy, PM Jeang, KT AF Xiao, H Neuveut, C Tiffany, HL Benkirane, M Rich, EA Murphy, PM Jeang, KT TI Selective CXCR4 antagonism by Tat: Implications for in vivo expansion of coreceptor use by HIV-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chemokine antagonist; viral coreceptor ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHEMOKINE RECEPTOR CXCR4; T-CELLS; DISEASE PROGRESSION; HUMAN MONOCYTE; TROPIC HIV-1; IN-VIVO; TYPE-1; INFECTION; PROTEIN AB Chemokines and chemokine receptors play important roles in HIV-1 infection and tropism, CCR5 is the major macrophage-tropic: coreceptor for HIV-1 whereas CXC chemokine receptor 4 (CXCR4) serves the counterpart function for T cell-tropic viruses. An outstanding biological mystery is why only R5-HIV-1 is initially detected in new seroconvertors who are exposed to R5 and X4 viruses. Indeed, X4 virus emerges in a minority of patients and only in the late stage of disease, suggesting that early negative selection against HIV-1-CXCR4 interaction may exist. Here, we report that the HIV-1 Tat protein, which is secreted from virus-infected cells, is a CXCR4-specific antagonist. Soluble Tat selectively inhibited the entry and replication of X4, but not R5, virus in peripheral blood mononuclear cells (PBMCs). We propose that one functional consequence of secreted Tat is to select against X4 viruses, thereby influencing the early in vivo course of HIV-1 disease. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 47 TC 231 Z9 238 U1 1 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 OCT 10 PY 2000 VL 97 IS 21 BP 11466 EP 11471 DI 10.1073/pnas.97.21.11466 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700063 PM 11027346 ER PT J AU Chen, XJ Hedlund, LW Moller, HE Chawla, MS Maronpot, RR Johnson, GA AF Chen, XJ Hedlund, LW Moller, HE Chawla, MS Maronpot, RR Johnson, GA TI Detection of emphysema in rat lungs by using magnetic resonance measurements of He-3 diffusion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ELASTASE-INDUCED EMPHYSEMA; HYPERPOLARIZED HE-3; PULMONARY-EMPHYSEMA; GAS-DIFFUSION; POROUS-MEDIA; MICROSCOPY; DISEASE; ACID AB Emphysema is a pulmonary disease characterized by alveolar wall destruction, resulting in enlargement of gas exchange spaces without fibrosis, This condition is a part of chronic obstructive pulmonary disease (COPD), which causes 3.5% of deaths worldwide [Anonymous (1990) World Health Stat Q. Special, 1-51] and contributes greatly to the global burden of disease [Murray, C, J, & Lopez, A. D. (1996) Science 274, 740-743]. Alveolar regeneration has been shown in animal models and could have potential for clinical treatment of early-stage emphysema, However, current techniques for detection of emphysema are not sensitive at the initial stages. Early-stage human panacinar emphysema is modeled in elastase-treated animals. Here, we provide an in vivo imaging method for differentiating normal and emphysematous rat lungs by measuring the apparent diffusion coefficient (ADC) of hyperpolarized He-3 by using magnetic resonance imaging. These data show that the ADC is significantly larger in elastase-treated rats, indicating alveolar expansion. Whereas these rats were clinically asymptomatic, conventional histology confirmed presence of injury. Our results indicate that measurement of the hyperpolarized He-3 ADC can be a valuable research tool and has potential application in the clinical setting. C1 Duke Univ, Med Ctr, Ctr In Vivo Microscopy, Durham, NC 27710 USA. Univ Munster, Inst Chem Phys, D-48149 Munster, Germany. NIEHS, Div Chem Pathol & Toxicol, Res Triangle Pk, NC 27709 USA. RP Johnson, GA (reprint author), Care Of Fitzsimons EG, Duke Univ, Med Ctr, Ctr In Vivo Microscopy, Box 3302, Durham, NC 27710 USA. RI Moller, Harald/A-1565-2008; OI Moller, Harald/0000-0002-5659-1925; Hedlund, Laurence/0000-0001-5275-0397; Johnson, G.Allan/0000-0002-7606-5447 FU NCRR NIH HHS [P41 RR005959, P41 RR05959]; NHLBI NIH HHS [R01 HL 55348, R01 HL055348] NR 29 TC 118 Z9 119 U1 0 U2 17 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 OCT 10 PY 2000 VL 97 IS 21 BP 11478 EP 11481 DI 10.1073/pnas.97.21.11478 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700065 PM 11027348 ER PT J AU Gladwin, MT Shelhamer, JH Schechter, AN Pease-Fye, ME Waclawiw, MA Panza, JA Ognibene, FP Cannon, RO AF Gladwin, MT Shelhamer, JH Schechter, AN Pease-Fye, ME Waclawiw, MA Panza, JA Ognibene, FP Cannon, RO TI Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SICKLE-CELL HEMOGLOBIN; XANTHINE-OXIDASE; BIOLOGICAL-SYSTEMS; ENDOTHELIAL-CELLS; RELAXING FACTOR; OXYGEN-BINDING; NITROSATION; KINETICS; REDUCTION; CYSTEINE AB To determine the relative contributions of endothelial-derived nitric oxide (NO) vs. intravascular nitrogen oxide species in the regulation of human blood flow, we simultaneously measured forearm blood flow and arterial and venous levels of plasma nitrite, LMW-SNOs and HMW-SNOs, and red cell S-nitrosohemoglobin (SNO-Hb). Measurements were made at rest and during regional inhibition of NO synthesis, followed by forearm exercise. Surprisingly, we found significant circulating arterial-venous plasma nitrite gradients, providing a novel delivery source for intravascular NO. Further supporting the notion that circulating nitrite is bioactive, the consumption of nitrite increased significantly with exercise during the inhibition of regional endothelial synthesis of NO. The role of circulating S-nitrosothiols and SNO-Hb in the regulation of basal vascular tone is less certain. We found that low-molecular-weight S-nitrosothiols were undetectable and S-nitroso-albumin levels were two logs lower than previously reported. In fact, S-nitroso-albumin primarily formed in the venous circulation, even during NO synthase inhibition. Whereas SNO-Hb was measurable in the human circulation (brachial artery levels of 170 nM in whole blood), arterial-venous gradients were not significant, and delivery of NO from SNO-Hb was minimal. In conclusion, we present data that suggest (i) circulating nitrite is bioactive and provides a delivery gradient of intravascular NO, (ii) S-nitroso albumin does not deliver NO from the lungs to the tissue but forms in the peripheral circulation, and (iii) SNO-Hb and 5-nitrosothiols play a minimal role in the regulation of basal vascular tone, even during exercise stress. 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. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NIDDKD, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 39 TC 302 Z9 310 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 10 PY 2000 VL 97 IS 21 BP 11482 EP 11487 DI 10.1073/pnas.97.21.11482 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700066 PM 11027349 ER PT J AU Cisar, JO Xu, DQ Thompson, J Swaim, W Hu, L Kopecko, DJ AF Cisar, JO Xu, DQ Thompson, J Swaim, W Hu, L Kopecko, DJ TI An alternative interpretation of nanobacteria-induced biomineralization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CALCIUM PHOSPHATE; STONE FORMATION; CALCIFICATION; NANNOBACTERIA; LIPIDS; ROCKS AB The reported isolation of nanobacteria from human kidney stones raises the intriguing possibility that these microorganisms are etiological agents of pathological extraskeletal calcification [Kajander, E. O. & Ciftcioglu. N. (1998) Proc. Natl. Acad. Sci. USA 95, 8274-8279]. Nanobacteria were previously isolated from FBS after prolonged incubation in DMEM. These bacteria initiated biomineralization of the culture medium and were identified in calcified particles and biofilms by nucleic acid stains, 16S rDNA sequencing, electron microscopy. and the demonstration of a transferable biomineralization activity. We have now identified putative nanobacteria, not only from FBS, but also from human saliva and dental plaque after the incubation of 0.45-mu m membrane-filtered samples in DMEM. Although biomineralization in our "cultures" was transferable to fresh DMEM. molecular examination of decalcified biofilms failed to detect nucleic acid or protein that would be expected from growth of a living entity. In addition, biomineralization was not inhibited by sodium azide. Furthermore, the 169 rDNA sequences previously ascribed to Nanobacterium sangoineum and Nanobacterium sp. were found to be indistinguishable from those of an environmental microorganism, Phyllobacterium mysinacearum, that has been previously detected as a contaminant in PCR. Thus. these data do not provide plausible support for the existence of a previously undiscovered bacterial genus. Instead, we provide evidence that biomineralization previously attributed to nanobacteria may be initiated by nonliving macromolecules and transferred on "subculture" by self-propagating microcrystalline apatite. C1 NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NIDCR, Cellular Imaging Core, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20892 USA. RP Cisar, JO (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 302, Bethesda, MD 20892 USA. EM john.cisar@nih.gov NR 27 TC 148 Z9 162 U1 2 U2 21 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 OCT 10 PY 2000 VL 97 IS 21 BP 11511 EP 11515 DI 10.1073/pnas.97.21.11511 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700071 PM 11027350 ER PT J AU Zieler, H Dvorak, JA AF Zieler, H Dvorak, JA TI Invasion in vitro of mosquito midgut cells by the malaria parasite proceeds by a conserved mechanism and results in death of the invaded midgut cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AEDES-AEGYPTI MIDGUT; VACUOLAR PROTON ATPASE; PLASMODIUM-GALLINACEUM; ANOPHELES-STEPHENSI; INFECTED MACROPHAGES; CONTINUOUS-CULTURE; APOPTOSIS; FALCIPARUM; EPITHELIUM; ERYTHROCYTES AB Using an in vitro culture system, we observed the migration of malaria ookinetes on the surface of the mosquito midgut and invasion of the midgut epithelium. Ookinetes display constrictions during migration to the midgut surface and a gliding motion once on the luminal midgut surface. Invasion of a midgut cell always occurs at its lateral apical surface. Invasion is rapid and is often followed by invasion of a neighboring midgut cell by the ookinete. The morphology of the invaded cells changes dramatically after invasion, and invaded cells die rapidly. Midgut cell death is accompanied by activation of a caspase-3-like protease. suggesting cell death is apoptotic. The events occurring during invasion were identical for two different species of Plasmodium and two different genera of mosquitoes; they probably represent a universal mechanism of mosquito midgut penetration by the malaria parasite. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Dvorak, JA (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. NR 50 TC 105 Z9 107 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 10 PY 2000 VL 97 IS 21 BP 11516 EP 11521 DI 10.1073/pnas.97.21.11516 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700072 PM 11027351 ER PT J AU Greenwood, PM Sunderland, T Friz, JL Parasuraman, R AF Greenwood, PM Sunderland, T Friz, JL Parasuraman, R TI Genetics and visual attention: Selective deficits in healthy adult carriers of the epsilon 4 allele of the apolipoprotein E gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE aging; Alzheimer's disease; genetic risk; memory; spatial attention ID ALZHEIMERS-DISEASE; VISUOSPATIAL ATTENTION; SPATIAL ATTENTION; CHOLINERGIC IMPAIRMENTS; SUSTAINED-ATTENTION; WORKING-MEMORY; E GENOTYPE; DEMENTIA; SEARCH; DECLINE AB The epsilon 4 allele of the apolipoprotein E (APOE) gene is associated with altered brain physiology in healthy adults before old age, but concomitant deficits in cognition on standardized tests of cognitive function have not been consistently demonstrated. We hypothesized that sensitive and specific assessment of basic attentional functions that underlie complex cognition would reveal evidence of impairment in otherwise asymptomatic individuals. We found that as early as middle age, nondemented carriers of the epsilon 4 allele of the APOE gene showed deficits when visual attention was spatially directed by cues in tasks of visual discrimination acid visual search, in comparison to those without the epsilon 4 allele (epsilon 2 and epsilon 3 carriers). Two component attentional operations were selectively affected: (i) shifting spatial attention following invalid location cues, and (ii) adjusting the spatial scale of attention during visual search. These changes occurred only in the presence of the epsilon 4 allele and without decline in other aspects of attention (vigilance), memory, or general cognition. The results show that specific components of visual attention are affected by APOE genotype and that the course of cognitive aging is subject to selective alteration by a genetic trait. C1 Catholic Univ Amer, Cognit Sci Lab, Washington, DC 20064 USA. NIMH, Geriatr Psychiat Branch, Bethesda, MD 20894 USA. RP Parasuraman, R (reprint author), Catholic Univ Amer, Cognit Sci Lab, Washington, DC 20064 USA. FU NIA NIH HHS [AG07569, AG12387] NR 64 TC 98 Z9 99 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 OCT 10 PY 2000 VL 97 IS 21 BP 11661 EP 11666 DI 10.1073/pnas.97.21.11661 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700097 PM 11027364 ER PT J AU Feller, JA Smallwood, S Skiadopoulos, MH Murphy, BR Moyer, SA AF Feller, JA Smallwood, S Skiadopoulos, MH Murphy, BR Moyer, SA TI Comparison of identical temperature-sensitive mutations in the L polymerase proteins of Sendai and parainfluenza3 viruses SO VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; AMINO-ACID SUBSTITUTIONS; RNA-SYNTHESIS; VACCINE CANDIDATE; MESSENGER-RNA; L-GENE; ABERRANT POLYADENYLATION; TYPE-3; REPLICATION; ATTENUATION AB The L subunit of the RNA-dependent RNA polymerase of negative strand RNA viruses is believed to possess all the enzymatic activities necessary for viral transcription and replication. Mutations in the L proteins of human parainfluenza virus type 3 (PIV3) and vesicular stomatitis virus (VSV) have been shown to confer temperature sensitivity to the viruses; however, their specific defects have not been determined. Mutant PIV3 L proteins expressed from plasmids were tested for temperature sensitivity in transcription and replication in a minigenome reporter system in cells and for in vitro transcription from purified PIV3 template. The single L mutants, Y942H and L992F, were temperature sensitive (ts) in both assays, although viral RNA synthesis was not completely abolished at the nonpermissive temperature. Surprisingly, the T1558I L mutant was not ts, although its cognate virus was ts. Thus the ts defect in this virus may be due to the abrogation of an essential interaction of the mutant polymerase with a host cell component, which is not measured by the RNA synthesis assays. Most of the combinations of the PIV3 L mutations were not additive and did not show temperature sensitivity in in vitro transcription. Since they were ts in the minigenome assay in vivo, replication appears to be specifically defective. The ts mutations in PIV3 and VSV L proteins were also substituted into the Sendai L protein to compare the defects in related systems. Only Sendai Y942H L was ts in both transcription and replication. One Sendai L mutant, L992F, gave much better replication than transcription. Several other mutants could transcribe but not replicate in vitro, while replication in vivo was normal. (C) 2000 Academic Press. C1 Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moyer, SA (reprint author), Univ Florida, Coll Med, Dept Mol Genet & Microbiol, POB 100266, Gainesville, FL 32610 USA. FU NIAID NIH HHS [AI 14594] NR 31 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2000 VL 276 IS 1 BP 190 EP 201 DI 10.1006/viro.2000.0535 PG 12 WC Virology SC Virology GA 367XY UT WOS:000090088300020 PM 11022007 ER PT J AU Zhu, YD Rota, P Wyatt, L Tamin, A Rozenblatt, S Lerche, N Moss, B Bellini, W McChesney, M AF Zhu, YD Rota, P Wyatt, L Tamin, A Rozenblatt, S Lerche, N Moss, B Bellini, W McChesney, M TI Evaluation of recombinant vaccinia virus - Measles vaccines in infant rhesus macaques with preexisting measles antibody SO VIROLOGY LA English DT Article ID T-CELL RESPONSES; MATERNAL ANTIBODIES; IMMUNE-RESPONSE; PROTECTIVE IMMUNITY; VIRAL REPLICATION; VACCINATION; IMMUNIZATION; INFECTION; MICE; GLYCOPROTEIN AB immunization of newborn infants with standard measles vaccines is not effective because of the presence of maternal antibody. In this study, newborn rhesus macaques were immunized with recombinant vaccinia Viruses expressing measles virus hemagglutinin (H) and fusion (F) proteins, using the replication-competent WR strain of vaccinia virus or the replication-defective MVA strain. The infants were boosted at 2 months and then challenged intranasally with measles virus at 5 months of age. Some of the newborn monkeys received measles immune globulin (MIG) prior to the first immunization, and these infants were compared to additional infants that had maternal measles-neutralizing antibody In the absence of measles antibody, vaccination with either Vector induced neutralizing antibody, cytotoxic T cell (CTL) responses to measles virus and protection from systemic measles infection and skin rash. The infants vaccinated with the MVA vector developed lower measles-neutralizing antibody titers than those vaccinated with the WR vector, and they sustained a transient measles viremia upon challenge. Either maternal antibody or passively transferred MIG blocked the humoral response to vaccination with bath WR and MVA, and the frequency of positive CTL responses was reduced. Despite this inhibition of vaccine-induced immunity, there was a reduction in peak viral loads and skin rash after measles virus challenge in many of the infants with preexisting measles antibody. Therefore, vaccination using recombinant Vectors such as poxviruses may be able to prevent the severe disease that often accompanies measles in infants. (C) 2000 Academic Press. C1 Univ Calif Davis, Calif Reg Primate Res Ctr, Davis, CA 95616 USA. Univ Calif Davis, Sch Med, Dept Pathol, Davis, CA 95616 USA. Ctr Dis Control & Prevent, Measles Virus Sect, Resp & Enter Viruses Branch, Div Viral & Rickettsial Dis,Nat Ctr Infect Dis, Atlanta, GA 30333 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP McChesney, M (reprint author), Univ Calif Davis, Calif Reg Primate Res Ctr, Davis, CA 95616 USA. FU NCRR NIH HHS [RR-00169]; PHS HHS [U50/CCU913348] NR 51 TC 39 Z9 39 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2000 VL 276 IS 1 BP 202 EP 213 DI 10.1006/viro.2000.0564 PG 12 WC Virology SC Virology GA 367XY UT WOS:000090088300021 PM 11022008 ER PT J AU Sokoloff, L AF Sokoloff, L TI Seymour Kety, MD 1915-2000 - In memoriam SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Biographical-Item C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, Bldg 36, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 9 PY 2000 VL 96 IS 5 BP 585 EP 589 DI 10.1002/1096-8628(20001009)96:5<585::AID-AJMG1>3.0.CO;2-3 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 360PX UT WOS:000089677400001 ER PT J AU Leshner, AI AF Leshner, AI TI Vulnerability to addiction: New research opportunities - Introduction SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Editorial Material C1 NIDA, NIH, Bethesda, MD 20892 USA. RP Leshner, AI (reprint author), 6001 Execut Blvd,Room 5274,MSC9581, Bethesda, MD 20891 USA. NR 0 TC 11 Z9 11 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 9 PY 2000 VL 96 IS 5 BP 590 EP 591 DI 10.1002/1096-8628(20001009)96:5<590::AID-AJMG2>3.0.CO;2-2 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 360PX UT WOS:000089677400002 PM 11054764 ER PT J AU Vandenbergh, DJ Rodriguez, LA Hivert, E Schiller, JH Villareal, G Pugh, EW Lachman, H Uhl, GR AF Vandenbergh, DJ Rodriguez, LA Hivert, E Schiller, JH Villareal, G Pugh, EW Lachman, H Uhl, GR TI Long forms of the dopamine receptor (DRD4) gene VNTR are more prevalent in substance abusers: No interaction with functional alleles of the catechol-o-methyltransferase (COMT) gene SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE association; drug abuse; DRD3; functional allele; behavior genetics ID NOVELTY SEEKING; D3 RECEPTOR; ALCOHOL DEPENDENCE; POLYSUBSTANCE ABUSERS; ASSOCIATION; POLYMORPHISM; POPULATION; D2; SCHIZOPHRENIA; VARIANTS AB Substance abuse is a complex behavior that is caused by both environmental and genetic factors. Work to understand the genetic factors has focused on genes related to dopamine activity because of its critical role in rewarding and reinforcing behaviors, The DRD3 and other dopamine receptor subtypes are expressed in many areas of the limbic system, and have been the objects of study for their possible roles in several neuropsychiatric disorders. Interest in variants of the D4 gene was heightened by reports that some alleles were more frequent in individuals who score high on Novelty Seeking, an aspect of personality that may be related to drug seeking behavior, We now show that the long form of the DRD4 gene is more frequent in individuals with high quantity/frequency of drug use compared to controls (chi(2) = 5.7, df = 1, P = 0.017, odds ratio = 1.89, CI = 1.1-3.2), There is no difference in DRD3 allele frequencies in these samples, and there is no interaction of DRD4 alleles with those of the catecholamine-o-methyltransferase gene (COMT) that we previously identified to be more frequent in substance abusers than controls [Vandenbergh, et al,: 1997: Am. J. Med. Gen. 74:439-442]. Am. J, Med, Genet, (Neuropsychiatr. Genet.) 96: 678-683, 2000, Published 2000 Wiley-Liss, Inc.(dagger). C1 NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD USA. Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10467 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. NR 39 TC 44 Z9 44 U1 4 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 9 PY 2000 VL 96 IS 5 BP 678 EP 683 DI 10.1002/1096-8628(20001009)96:5<678::AID-AJMG15>3.0.CO;2-8 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 360PX UT WOS:000089677400015 PM 11054777 ER PT J AU Wu, TJ Trevisan, M Genco, RJ Dorn, JP Falkner, KL Sempos, CT AF Wu, TJ Trevisan, M Genco, RJ Dorn, JP Falkner, KL Sempos, CT TI Periodontal disease and risk of cerebrovascular disease - The First National Health and Nutrition Examination Survey and its follow-up study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; DENTAL INFECTIONS; ATHEROSCLEROSIS; ASSOCIATION; INFORMATION; INFARCTION; MORTALITY; ENDOTOXIN; SMOKING AB Background: Periodontal disease has been found to be a potential risk factor for coronary heart disease. However, its association with cerebrovascular accidents (CVAs) is much less studied. Methods: This study examines the association between periodontal disease and CVA. The study cohort comprises 9962 adults aged 25 to 74 years who participated in the First National Health and Nutrition Examination Survey and its follow-up study. Baseline periodontal status was categorized into (1) no periodontal disease, (2) gingivitis, (3) periodontitis, and (4) edentulousness. All CVAs (International Classification of Diseases, Ninth Revision [ICD-9], codes 430-438) were ascertained by hospital records for nonfatal events and death certificates for fatal events. The first CVA, nonfatal or fatal, was used to define incidence. Relative risks were estimated by hazard ratios from the Cox proportional hazard model with adjustment for several demographic variables and well-established cardiovascular risk factors. Weights were used to generate risk estimates. Results: Periodontitis is a significant risk factor for total CVA and, in particular, nonhemorrhagic stroke (ICD-9, 433-434 and 436-438). Compared with no periodontal disease, the relative risks (95% confidence intervals) for incident nonhemorrhagic stroke were 1.24 (0.74-2.08) for gingivitis, 2.11 (1.30-3.42) for periodontitis, and 1.41 (0.96-2.06) for edentulousness. For total CVA, the results were 1.02 (0.70-1.48) for gingivitis, 1.66 (1.15-2.39) for periodontitis, and 1.23 (0.91-1.66) for edentulousness. Increased relative risks for total CVA and nonhemorrhagic stroke associated with periodontitis were also seen in white men, white women, and African Americans. Similar results were found for fatal CVA. Conclusion: Periodontal disease is an important risk factor for total CVA and, in particular, nonhemorrhagic stroke. C1 SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. Natl Inst Hlth, Off Res Minor Hlth, Bethesda, MD USA. RP Wu, TJ (reprint author), SUNY Buffalo, Dept Social & Prevent Med, 3435 Main St, Buffalo, NY 14214 USA. FU NIDCR NIH HHS [DE04898, DE07034, DE12085] NR 35 TC 249 Z9 257 U1 0 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 9 PY 2000 VL 160 IS 18 BP 2749 EP 2755 DI 10.1001/archinte.160.18.2749 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 357XQ UT WOS:000089527600005 PM 11025784 ER PT J AU Glynn, RJ Chae, CU Guralnik, JM Taylor, JO Hennekens, CH AF Glynn, RJ Chae, CU Guralnik, JM Taylor, JO Hennekens, CH TI Pulse pressure and mortality in older people SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; DIASTOLIC BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; PREDICTING RISK; ARTERIAL DISTENSIBILITY; SYSTOLIC HYPERTENSION; NORMOTENSIVE SUBJECTS; AORTIC COMPLIANCE; RANDOMIZED TRIAL; LOADING SEQUENCE AB Background: In older people, observational data are unclear concerning the relationships of systolic and diastolic blood pressure with cardiovascular and total mortality. We examined which combinations of systolic, diastolic, pulse, and mean arterial pressure best predict total and cardiovascular mortality in older adults. Methods: In 1981, the National Institute on Aging initiated its population-based Established Populations for Epidemiologic Studies of the Elderly in 3 communities. At baseline, 9431 participants, aged 65 to 102 years, had blood pressure measurements, along with measures of medical history, use of medications, disability, and physical function. During an average follow-up of 10.6 years among survivors, 4528 participants died, 2304 of cardiovascular causes. Results: In age- and sex-adjusted survival analyses, the lowest overall death rate occurred among those with systolic pressure less than 130 mm Hg and diastolic pressure 80 to 89 mm Hg; relative to this group, the highest death rate occurred in those with systolic pressure of 160 mm Hg or more and diastolic pressure less than 70 mm Hg (relative risk, 1.90; 95% confidence interval, 1.47-2.46). Both low diastolic pressure and elevated systolic pressure independently predicted increases in cardiovascular (P<.001) and total(P<.001) mortality. Pulse pressure correlated strongly with systolic pressure (R=0.82) but was a slightly stronger predictor of both cardiovascular and total mortality. ln a model containing pulse pressure and other potentially confounding variables, diastolic pressure (P=.88) and mean arterial pressure (P=.11) had no significant association with mortality. Conclusions: Pulse pressure appears to be the best single measure of blood pressure in predicting mortality in older people and helps explain apparently discrepant results for low diastolic blood pressure. C1 Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. E Boston Neighborhood Hlth Ctr, E Boston, MA USA. Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth Med, Miami, FL USA. RP Glynn, RJ (reprint author), Brigham & Womens Hosp, Div Prevent Med, Dept Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NIA NIH HHS [AG02107] NR 70 TC 146 Z9 162 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 9 PY 2000 VL 160 IS 18 BP 2765 EP 2772 DI 10.1001/archinte.160.18.2765 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 357XQ UT WOS:000089527600007 PM 11025786 ER PT J AU Cohen, RM Carson, RE Saunders, RC Doudet, DJ AF Cohen, RM Carson, RE Saunders, RC Doudet, DJ TI Opiate receptor avidity is increased in rhesus monkeys following unilateral optic tract lesion combined with transections of corpus callosum and hippocampal and anterior commissures SO BRAIN RESEARCH LA English DT Article DE neurodegeneration; 6-deoxy-6-beta-[F-18]fluoronaltrexone; positron emission tomography; cortex; visual system ID SUPER-SENSITIVITY; RAT-BRAIN; KAPPA; ENKEPHALIN; AGONISTS; DECREASE; DISEASE; BINDING; DORSAL; MPTP AB Opiate receptor avidity (B-max'/K-D) was measured in four rhesus monkeys following unilateral lesioning of the optic tract combined with transection of the corpus callosum and the hippocampal and anterior commissures depriving one hemisphere of visual input (Tract and Split), two animals with transection of commissures only (Split), and nine healthy monkeys with positron emission tomography (PET) and 6-deoxy-6-beta-[F-18]fluoronaltrexone (cyclofoxy, CF), a mu- and kappa -opiate receptor antagonist. Opiate receptor avidity was found to be significantly higher in the Tract and Split animals, only, bilaterally, throughout the lateral cortex and in the cingulate and posterior putamen (41-117%). Ipsilateral changes were consistently greater than those contralateral, but this asymmetry was of statistical significance only in the parietal and occipital cortices. Cyclofoxy avidity was decreased in the medial cortex of both the Tract and Split and Split animals (similar to 25%), The results suggest that opiate pathways undergo extensive alteration in response to changes in brain functional activities brought about through hemispheric visual deprivation. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIMH, Geriatr Psychiat Branch, NIH, Bethesda, MD 20892 USA. NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Cohen, RM (reprint author), NIMH, Geriatr Psychiat Branch, NIH, Bldg 10,Room 3N218,10 Ctr Dr,MSC 1274, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 28 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 6 PY 2000 VL 879 IS 1-2 BP 1 EP 6 DI 10.1016/S0006-8993(00)02528-2 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 362DG UT WOS:000089762900001 PM 11010998 ER PT J AU Labarre, M Butterworth, J St-Onge, S Payza, K Schmidhammer, H Salvadori, S Balboni, G Guerrini, R Bryant, SD Lazarus, LH AF Labarre, M Butterworth, J St-Onge, S Payza, K Schmidhammer, H Salvadori, S Balboni, G Guerrini, R Bryant, SD Lazarus, LH TI Inverse agonism by Dmt-Tic analogues and H5 378, a naltrindole analogue SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Dmt-Tic; inverse agonism; antagonism ID DELTA-OPIOID RECEPTOR; ANTAGONISTS; PHARMACOPHORE; PEPTIDES AB The potent delta-opioid receptor antagonist H-2',6-L-tyrosine(Dmt)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic-OH) exhibited partial inverse agonism (EC(50) = 6.35 nM, E(max) = - 18.87%) for [(35)S]GTP gamma S binding and H-Dmt-Tic-NH(2) was a neutral antagonist (no effect up to 30 mu M). In contrast N,N(CH(3))(2)-Dmt-Tic-NH(2) was a full inverse agonist (EC(50) = 2.66 nM, E(max) = -35.95%) similar to ICI 174864 ([N,N-diallyl-Tyr(1),Aib(2,3),Leu(5)]enkephaline) but with a 3.5-fold higher EC(50) In comparison, naltrindole was a neutral antagonist while its analogue HS 378 was a partial inverse agonist (E(max) = - 12.99%). (C) 2000 Elsevier Science B.V. All rights reserved. C1 Natl Inst Environm Hlth Sci, LCBRA, Res Triangle Pk, NC 27709 USA. AstraZeneca R&D, Dept Pharmacol, St Laurent, PQ H4S 1Z9, Canada. Univ Innsbruck, Inst Pharmaceut Chem, A-6020 Innsbruck, Austria. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. Univ Cagliari, Dept Toxicol, I-09126 Cagliari, Italy. RP Lazarus, LH (reprint author), Natl Inst Environm Hlth Sci, LCBRA, Res Triangle Pk, NC 27709 USA. EM lazarus@niehs.nih.gov NR 8 TC 21 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 6 PY 2000 VL 406 IS 1 BP R1 EP R3 DI 10.1016/S0014-2999(00)00636-1 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 360YB UT WOS:000089694000024 PM 11011049 ER PT J AU Henklein, P Kinder, R Schubert, U Bechinger, B AF Henklein, P Kinder, R Schubert, U Bechinger, B TI Membrane interactions and alignment of structures within the HIV-1 Vpu cytoplasmic domain: effect of phosphorylation of serines 52 and 56 SO FEBS LETTERS LA English DT Article DE solid-state nuclear magnetic resonance; oriented lipid bilayer; viral membrane protein; amphipathic helix; CD4 degradation; nuclear magnetic resonance structure determination ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-U VPU; CHEMICAL-SHIFT TENSORS; STATE NMR-SPECTROSCOPY; SOLID-STATE; N-15 NMR; POWDER PATTERNS; CONFORMATION; DEGRADATION; CD4 AB The cytoplasmic domain of the HIV-1 accessory protein Vpu is involved in the binding and degradation of the viral receptor CD4. In order to analyze previous structural models in the context of membrane environments, regions of Vpu(CYTO) incorporating particular conformational features have been synthesized and labelled with N-15 at selected backbone amides. Well-oriented proton-decoupled N-15 solid-state NMR spectra with N-15 chemical shifts at the most upfield position indicate that the amphipathic helix within [N-15-Leu 45]-Vpu(27-57) strongly interacts with mechanically aligned POPC bilayers and adopts an orientation parallel to the membrane surface. No major changes in the topology of this membrane-associated amphipathic helix were observed upon phosphorylation of serine residues 52 and 56, although this modification regulates biological function of Vpu. In contrast, [N-15-Ala 62]-Vpu(51-81) exhibits a pronounced N-15 chemical shift anisotropy. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Max Planck Inst Biochem, D-82152 Martinsried, Germany. Humboldt Univ, Inst Biochem, D-10115 Berlin, Germany. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-2000 Hamburg, Germany. RP Bechinger, B (reprint author), Max Planck Inst Biochem, Klopferspitz 18A, D-82152 Martinsried, Germany. NR 32 TC 40 Z9 41 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 6 PY 2000 VL 482 IS 3 BP 220 EP 224 DI 10.1016/S0014-5793(00)02060-3 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 363RA UT WOS:000089847300011 PM 11024464 ER PT J AU Boulanger, A Liu, SY Henningsgaard, AA Yu, S Redmond, TM AF Boulanger, A Liu, SY Henningsgaard, AA Yu, S Redmond, TM TI The upstream region of the Rpe65 gene confers retinal pigment epithelium-specific expression in vivo and in vitro and contains critical octamer and E-box binding sites SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR OTF-1; HELIX-LOOP-HELIX; MESSENGER-RNA; VISUAL CYCLE; CONGENITAL AMAUROSIS; MICROSOMAL PROTEIN; SEQUENCE ELEMENTS; TRANSGENIC MICE; FACTOR OCT-1; CELL LINE AB RPE65 is essential for all-trans- to Il-cis-retinoid isomerization, the hallmark reaction of the retinal pigment epithelium (RPE). Here, we identify regulatory elements in the Rpe65 gene and demonstrate their functional relevance to Rpe65 gene expression. We show that the 5' flanking region of the mouse Rpe65 gene, like the human gene, lacks a canonical TATA box and consensus GC and CAAT boxes. The mouse and human genes do share several cis acting elements, including an octamer, a nuclear factor one (NFI) site, and two E-box sites, suggesting a conserved mode of regulation. A mouse Rpe65 promoter/beta-galactosidase transgene containing bases -655 to +52 (TR4) of the mouse 5' flanking region was sufficient to direct high RPE-specific expression in transgenic mice, whereas shorter fragments (-297 to +52 or -188 to +52) generated only background activity. Furthermore, transient transfection of analogous TR4/luciferase constructs also directed high reporter activity in the human RPE cell line D407 but weak activity in the non-RPE cell Lines HeLa, HepG2, and HS27. Functional binding of potential transcription factors to the octamer sequence, AP-4, and NFI sites was demonstrated by directed mutagenesis, electrophoretic mobility shift assay, and cross linking. Mutations of these sites abolished binding and corresponding transcriptional activity and indicated that octamer and E-box transcription factors synergistically regulate the RPE65 promoter function. Thus, we have identified the regulatory region in the Rpe65 gene that accounts for tissue-specific expression in the RPE and found that octamer and E-box transcription factors play a critical role in the transcriptional regulation of the Rpe65 gene. C1 NEI, LRCMB, Bethesda, MD 20892 USA. RP Boulanger, A (reprint author), NEI, LRCMB, Bldg 6,Rm 339,6 Ctr Dr,MSC 2740, Bethesda, MD 20892 USA. OI Redmond, T. Michael/0000-0002-1813-5291 NR 51 TC 37 Z9 38 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 6 PY 2000 VL 275 IS 40 BP 31274 EP 31282 DI 10.1074/jbc.M003441200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 362DE UT WOS:000089762700075 PM 10896939 ER PT J AU Huang, Y Hamada, M Maraia, RJ AF Huang, Y Hamada, M Maraia, RJ TI Isolation and cloning of four subunits of a fission yeast TFIIIC complex that includes an ortholog of the human regulatory protein TFIIIC beta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE-III; TATA-BINDING PROTEIN; TRANSCRIPTION FACTOR; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; DNA-BINDING; ACETYLTRANSFERASE ACTIVITY; S-POMBE; GENE; EXPRESSION AB Eukaryotic tRNA genes are controlled by proximal and downstream elements that direct transcription by RNA polymerase (pol) III. Transcription factors (TFs) that reside near the initiation site are related in Saccharomyces cerevisiae and humans, while those that reside at or downstream of the B box share no recognizable sequence relatedness. Human TFIIIC beta is a transcriptional regulator that exhibits no homology to S. cerevisiae sequences on its own. We cloned an essential Schizosaccharomyces pombe gene that encodes a protein, Sfc6p, with homology to the S. cerevisiae TFIIIC subunit, TFC6p, that extends to human TFIIIC beta. We also isolated and cloned S. pombe homologs of three other TFIIIC subunits, Sfc3p, Sfc4p, and Sfc1p, the latter two of which are conserved from S. cerevisiae to humans, while the former shares homology with the S. cerevisiae B box-binding homolog only. Sfc6p is a component of a sequence-specific DNA-binding complex that also contains the B box-binding homolog, Sfc3p. Immunoprecipitation of Sfc3p further revealed that Sfc1p, Sfc3p, Sfc4p, and Sfc6p are associated in vivo and that the isolated Sfc3p complex is active for pol III-mediated transcription of a S. pombe tRNA gene in vitro. These results establish a link between the downstream pol III TFs in yeast and humans. C1 NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP 6 Ctr Dr,Rm 416, Bethesda, MD 20892 USA. EM maraiar@mail.nih.gov NR 54 TC 17 Z9 21 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 6 PY 2000 VL 275 IS 40 BP 31480 EP 31487 DI 10.1074/jbc.M004635200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 362DE UT WOS:000089762700102 PM 10906331 ER PT J AU Lovas, G Palkovits, M Komoly, S AF Lovas, G Palkovits, M Komoly, S TI Increased c-Jun expression in neurons affected by lysolecithin-induced demyelination in rats SO NEUROSCIENCE LETTERS LA English DT Article DE lysolecithin-induced demyelination; c-Jun; galanin ID TRANSCRIPTION FACTORS; MULTIPLE-SCLEROSIS; MESSENGER PLASTICITY; AXONAL DAMAGE; AXOTOMY; GALANIN; LESIONS; BRAIN; KROX; FOS AB The objective of this study was to investigate whether the expression of c-Jun is involved in the neuronal response to experimental demyelination. Lysolecithin-induced demyelination was generated in two distinct neural systems in rats: in the pontocerebellar and the septohippocampal pathways. Six days after the stereotaxic injections of lysolecithin, expression of the immediate early gene c-Jun was visualized by immunohistochemistry. Lesion-specific expression of the Jun protein was observed in neurons whose axons transverse the demyelinated area. Unlike the neural response to axotomy, lysolecithin treatment did not alter the expression of the neuropeptide galanin in the septohippocampal pathway. These results suggest that c-Jun protein expression might represent one step in the neuronal response to demyelination and that this response mig ht be distinct in its downstream events from axotomy. (C) 2000 Elsevier Science Ireland Ltd. Al I rights reserved. C1 NINDS, Lab Dev Neurogenet, NIH, Bethesda, MD 20892 USA. Semmelweis Univ Affiliate, Jahn Ferenc Teaching Hosp, Dept Neurol, H-1204 Budapest, Hungary. Semmelweis Univ, Fac Med, Lab Neuromorphol, H-1094 Budapest, Hungary. RP Lovas, G (reprint author), NINDS, Lab Dev Neurogenet, NIH, Bldg 36,Room 5D-09,36 Convent Dr,MSC 4160, Bethesda, MD 20892 USA. EM lovasg@ninds.nih.gov RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 17 TC 5 Z9 7 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 6 PY 2000 VL 292 IS 2 BP 71 EP 74 DI 10.1016/S0304-3940(00)01469-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 358YE UT WOS:000089584100001 PM 10998551 ER PT J AU Panza, F Solfrizzi, V Torres, F Mastroianni, F Colacicco, AM Basile, AM Capurso, C D'Introno, A Del Parigi, A Capurso, A AF Panza, F Solfrizzi, V Torres, F Mastroianni, F Colacicco, AM Basile, AM Capurso, C D'Introno, A Del Parigi, A Capurso, A TI Apolipoprotein E in Southern Italy: protective effect of epsilon 2 allele in early- and late-onset sporadic Alzheimer's disease SO NEUROSCIENCE LETTERS LA English DT Article DE apolipoprotein E; Alzheimer's disease; allele epsilon 2; protective factors; dementia; Southern Italy ID VASCULAR DEMENTIA; E POLYMORPHISM; ASSOCIATION; RISK; CENTENARIANS; FREQUENCIES AB Apolipoprotein E (apoE) polymorphism was evaluated in 81 sporadic late onset Alzheimer's disease (LOAD) patients, 28 sporadic early-onset Alzheimer's disease (EOAD) and 92 sex- and age-matched healthy controls from Apulia, Southern Italy. ApoE genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism method. The frequency of apoE epsilon 4 allele was significantly higher in EOAD patients than in the control group, but not in LOAD patients. Furthermore, EOAD patients carrying epsilon 4 allele had lower age at onset of AD symptoms (about 4.5 years). In the whole sample, epsilon 4 was associated to AD by an odds ratio of 2.14, while it increased up to 6.55 in <65 years old subjects. Finally, in both <65 and greater than or equal to 65 subgroups of subjects, epsilon 2 played a protective role against the development of AD. It is concluded that the geographic decreasing trend of epsilon 4 allele and the age at onset may influence the association of apoE polymorphism with sporadic AD in a Southern Italian sample. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Bari Policlin, Dept Geriatr, Ctr Aging Brain, Memory Unit, I-70124 Bari, Italy. NIDDKD, NIH, Phoenix, AZ 85016 USA. RP Capurso, A (reprint author), Univ Bari Policlin, Dept Geriatr, Ctr Aging Brain, Memory Unit, I-70124 Bari, Italy. OI Panza, Francesco/0000-0002-7220-0656 NR 20 TC 29 Z9 30 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 OCT 6 PY 2000 VL 292 IS 2 BP 79 EP 82 DI 10.1016/S0304-3940(00)01447-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 358YE UT WOS:000089584100003 PM 10998553 ER PT J AU Martiniuk, F Chen, A Donnabella, V Arvanitopoulos, E Slonim, AE Raben, N Plotz, P Rom, WN AF Martiniuk, F Chen, A Donnabella, V Arvanitopoulos, E Slonim, AE Raben, N Plotz, P Rom, WN TI Correction of glycogen storage disease type II by enzyme replacement with a recombinant human acid maltase produced by over-expression in a CHO-DHFRneg cell line SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE methotrexate; acid maltase; glycogen storage disease type II; Pompe's disease; recombinant human acid maltase (rhGAA); over-expression CHO cell line ID HIGH-LEVEL PRODUCTION; ALPHA-GLUCOSIDASE; POMPE-DISEASE; GENETIC-HETEROGENEITY; LYSOSOMAL-ENZYMES; MOLECULAR-WEIGHT; SKELETAL-MUSCLE; MESSENGER-RNA; DNA; DEFICIENCY AB Inherited genetic deficiency of lysosomal acid alpha glucosidase or acid maltase (GAA) results in the autosomal recessive glycogen storage disease type II (GSD II), To investigate whether we could generate a functional recombinant human GAA (rhGAA) for enzyme replacement therapy, we subcloned the cDNAs for human GAA and mouse dihydrofolate reductase (DHFR) into DHFRneg Chinese hamster ovary cells and established a stable cotransformant that expressed rhGAA. We cultured the recombinant cells in media with progressively increasing concentrations of methotrexate and found that human GAA enzyme activity increased to over 2,000 IU per gram protein. Importantly, the human GAA enzyme activity correlated to equivalent amounts of human GAA protein by rocketimmunoelectrophoresis. We confirmed that the human GAA enzyme activity corresponded to an amplification in human GAA mRNA by Northern analysis and human GAA cDNA copy number by Southern analysis. Exposing the rhGAA to human GSDII fibroblast cells or patient's lymphocytes or monocytes resulted in uptake of the rhGAA and reversal of the enzymatic defect. Mannose-6-phosphate in the media blocked uptake. GAA -/- mice were treated with the rhGAA at 1 mg/kg, which resulted in heterozygous levels of GAA in tissues, most notably skeletal muscle, heart and diaphragm after two infusions, More importantly, after multiple infusions, hind, and fore-limb muscle weakness was reversed. This rhGAA would be ideal for enzyme replacement therapy in GSD II. (C) 2000 Academic Press. C1 NYU, Med Ctr, Dept Med, Div Pulm, New York, NY 10016 USA. N Shore Univ Hosp, Div Pediat Endocrinol & Metab, Manhasset, NY 11030 USA. NIAMS, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Martiniuk, F (reprint author), NYU, Med Ctr, Dept Med, Div Pulm, New Bellevue 6N5,550 1st Ave, New York, NY 10016 USA. FU PHS HHS [MO100096] NR 37 TC 14 Z9 14 U1 1 U2 2 PU ACADEMIC PRESS INC 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 OCT 5 PY 2000 VL 276 IS 3 BP 917 EP 923 DI 10.1006/bbrc.2000.3555 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 362TL UT WOS:000089794300018 PM 11027569 ER PT J AU Wittschieben, J Shivji, MKK Lalani, E Jacobs, MA Marini, F Gearhart, PJ Rosewell, I Stamp, G Wood, RD AF Wittschieben, J Shivji, MKK Lalani, E Jacobs, MA Marini, F Gearhart, PJ Rosewell, I Stamp, G Wood, RD TI Disruption of the developmentally regulated Rev31 gene causes embryonic lethality SO CURRENT BIOLOGY LA English DT Article ID DAMAGE-INDUCED MUTAGENESIS; DNA-POLYMERASE-ZETA; SACCHAROMYCES-CEREVISIAE; XERODERMA-PIGMENTOSUM; CATALYTIC SUBUNIT; REPAIR; MUTATIONS; ENCODES; XI AB The REV3 gene encodes the catalytic subunit of DNA polymerase (pol) zeta, which can replicate past certain types of DNA lesions [1], Saccharomyces cerevisiae rev3 mutants are viable and have lower rates of spontaneous and DNA-damage-induced mutagenesis [2], Reduction in the level of Rev31, the presumed catalytic subunit of mammalian pol zeta, decreased damage-induced mutagenesis in human cell lines [3]. To study the function of mammalian Rev31,we inactivated the gene in mice, Two exons containing conserved DNA polymerase motifs were replaced by a cassette encoding G418 resistance and beta -galactosidase, under the control of the Rev31 promoter. Surprisingly, disruption of Rev31 caused mid-gestation embryonic lethality, with the frequency of Rev31(-/-) embryos declining markedly between 9.5 and 12.5 days post coitum (dpc), Rev31(-/-) embryos were smaller than their heterozygous littermates and showed retarded development. Tissues in many areas were disorganised, with significantly reduced cell density, Rev31 expression, traced by beta -galactosidase staining, was first detected during early somitogenesis and gradually expanded to other tissues of mesodermal origin, including extraembryonic membranes. Embryonic death coincided with the period of more widely distributed Rev31 expression. The data demonstrate an essential function for murine Rev31 and suggest that bypass of specific types of DNA lesions by pol zeta is essential for cell viability during embryonic development in mammals. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Imperial Canc Res Fund, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. Hammersmith Hosp, Imperial Sch, Sch Med, Dept Histopathol, London W12 0NN, England. NIA, Gerontol Res Ctr, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. RP Wood, RD (reprint author), Imperial Canc Res Fund, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. RI Wood, Richard/E-7855-2011; Marini, Federica/A-9841-2017 OI Wood, Richard/0000-0002-9495-6892; Marini, Federica/0000-0002-9495-2349 NR 12 TC 128 Z9 129 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 5 PY 2000 VL 10 IS 19 BP 1217 EP 1220 DI 10.1016/S0960-9822(00)00725-9 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 366DB UT WOS:000089988600024 PM 11050392 ER PT J AU Cushman, M Jayaraman, M Vroman, JA Fukunaga, AK Fox, BM Kohlhagen, G Strumberg, D Pommier, Y AF Cushman, M Jayaraman, M Vroman, JA Fukunaga, AK Fox, BM Kohlhagen, G Strumberg, D Pommier, Y TI Synthesis of new indeno[1,2-c]isoquinolines: Cytotoxic non-camptothecin topoisomerase I inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CYTOSTATIC DRUGS; BACTERIAL SYSTEM; DNA; COMPLEXES; MUTAGENICITY; DERIVATIVES; INDUCTION; AGENT AB In an attempt to design and synthesize potential anticancer agents acting by inhibition of topoisomerase I (top1), a new series of indenoisoquinolines was prepared and tested for cytotoxicity in human cancer cell cultures and for activity against top1. The synthesis relied on the condensation of substituted Schiff bases with homophthalic anhydrides to produce cis-3-aryl-4-carboxyisoquinolones that were cyclized to indenoisoquinolines in the presence of thionyl chloride, Both top1 inhibitory activity and cytotoxicity maximized in a single compound, 6-[3-(2-hydroxyethyl)aminopropyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline hydrochloride (19a), which proved to be a very potent top1 inhibitor having a 110 nM mean graph midpoint (MGM) when tested for cytotoxicity in 55 human cancer cell cultures. A number of structurally related indenoisoquinolines were also obtained that had both potent cytotoxicity as well as top1 inhibitory activity. The key feature of the more potent compounds was the presence of an aminoalkyl side chain on the indenoisoquinoline nitrogen atom. The DNA cleavage patterns induced by top1 in the presence of the indenoisoquinolines were different from those-seen with camptothecin. Some of the cleavage sites induced by the indenoisoquinolines were different from those seen with camptothecin, and conversely, camptothecin induced unique cleavage sites not apparent with the indenoisoquinolines. However, both camptothecin and the indenoisoquinolines also induced DNA cleavage sites that were the same in both series but varied in intensity. In addition, some of the DNA cleavages seen with the free base of 19a (compound 18c) in the presence of top 1 were inhibited at higher drug concentrations, suggesting either a direct inhibition of the enzyme or an alternative mechanism involving DNA intercalation. Consistent with intercalation, compound 18c did unwind DNA. C1 Purdue Univ, Sch Pharm & Pharm Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NCI, Div Basic Sci, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharm Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. FU NCI NIH HHS [N01-CM-67260]; OHS HRSA HHS [ST32CA09634] NR 23 TC 107 Z9 109 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 5 PY 2000 VL 43 IS 20 BP 3688 EP 3698 DI 10.1021/jm000029d PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 361LR UT WOS:000089725000011 PM 11020283 ER PT J AU Irwin, M Marin, MC Phillips, AC Seelan, RS Smith, DI Liu, WG Flores, ER Tsai, KY Jacks, T Vousden, KH Kaelin, WG AF Irwin, M Marin, MC Phillips, AC Seelan, RS Smith, DI Liu, WG Flores, ER Tsai, KY Jacks, T Vousden, KH Kaelin, WG TI Role for the p53 homologue p73 in E2F-1-induced apoptosis SO NATURE LA English DT Article ID P53-INDEPENDENT APOPTOSIS; LI-FRAUMENI; DNA-BINDING; IN-VIVO; E2F-1; FAMILY; OVEREXPRESSION; PROTEIN; DOMAIN; CELLS AB The transcription factor E2F-1 induces both cell-cycle progression and, in certain settings, apoptosis. E2F-1 uses both p53-dependent and p53-independent pathways to kill cells(1-8). The p53-dependent pathway involves the induction by E2F-1 of the human tumour-suppressor protein p14ARF, which neutralizes HDM2 (human homologue of MDM2) and thereby stabilizes the p53 protein(9). Here we show that E2F-1 induces the transcription of the p53 homologue p73. Disruption of p73 function inhibited E2F-1-induced apoptosis in p53-defective tumour cells and in p53(-/-) mouse embryo fibroblasts. We conclude that activation of p73 provides a means for E2F-1 to induce death in the absence of p53. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Regulat Cell Growth Lab, FCRDC, Frederick, MD 21702 USA. Mayo Clin & Mayo Fdn, Mayo Med Sch, Dept Lab Med & Pathol, Rochester, MN 55905 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Marin Vieira, Maria del Carmen/B-8108-2015 OI Marin Vieira, Maria del Carmen/0000-0002-7149-287X NR 29 TC 481 Z9 491 U1 4 U2 18 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 5 PY 2000 VL 407 IS 6804 BP 645 EP 648 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 362HP UT WOS:000089772800051 PM 11034215 ER PT J AU Du Villard, J Wicker, R Crespo, P Russo, D Filetti, S Gutkind, JS Sarasin, A Suarez, HG AF Du Villard, J Wicker, R Crespo, P Russo, D Filetti, S Gutkind, JS Sarasin, A Suarez, HG TI Role of the cAMP and MAPK pathways in the transformation of mouse 3T3 fibroblasts by a TSHR gene constitutively activated by point mutation SO ONCOGENE LA English DT Article DE TSHR gene; mouse fibroblasts; transformation; pathways ID HUMAN THYROTROPIN RECEPTOR; PROTEIN-COUPLED RECEPTORS; BETA-GAMMA-SUBUNITS; ALPHA-1B-ADRENERGIC RECEPTOR; MALIGNANT TRANSFORMATION; SIGNAL-TRANSDUCTION; GERMLINE MUTATIONS; THYROID CARCINOMAS; KINASE-A; RAS AB Constitutive activating mutations of the TSHR gene, have been detected in about 30 per cent of hyperfunctioning human thyroid adenomas and in a minority of differentiated thyroid carcinomas. The mutations activating the TSHR gene(s) in the thyroid carcinomas, were located at the codon 623 changing an Ala to a Ser (GCC-->TCC) or in codon 632 changing a Thr to Ala or Ile (ACC-->GCC or ACC-->ATC). In order to study if the constitutively activated TSHR gene(s) has played a role in the determination of the malignant phenotype presented by these tumors, we investigated: (1) the transforming capacity after transfection of mouse 3T3 cells, of a TSHR cDNA activated by an Ala-->Ser mutation in codon 623 or an Thr-Ile mutation in codon 632 and (2) the pathway(s) eventually responsable(s) for the malignant phenotype of the cells transformed by these constitutively activated TSHR cDNAs, Our results show that (1) the TSHRM623 or(M632) cDNAs give rise to 3T3 clones presenting a fully neoplastic phenotype (growth in agar and nude mouse tumorigenesis); this phenotype was weaker in the cells transformed by the 632 cDNA; (2) suggest that the fully transformed phenotype of our 3T3 cells, may be the consequence of the additive effect of the activation of at least two different pathways: the cAMP pathway through G(alpha s) and the Ras dependent MAPK pathway through G(beta gamma) and PI3K and (3) show that the PI3K isoform playing a key role as an effector in the MAPK pathway activation in our 3T3-transformed cells is PI3K gamma. Signaling from PI3K gamma to MAPK appears to require in our murine cellular system a tyrosine kinase (still not characterized), Shc, Grb2, Sos, Ras and Raf. It is proposed that the constitutively activated TSHR genes detected in the thyroid carcinomas, may have played an oncogenic role, participating in their development through these two pathways. C1 Inst Rech Canc, CNRS IFR 89, Lab Instabil Genet & Canc, UPR 2169, F-94801 Villejuif, France. Univ Cantabria, Fac Med, Dept Mol Biol, Santander 39011, Spain. Univ Catanzaro, Dip Med Sperimentale & Clin, Cattedra Endocrinol, I-88100 Catanzaro, Italy. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Suarez, HG (reprint author), Inst Rech Canc, CNRS IFR 89, Lab Instabil Genet & Canc, UPR 2169, 7 Rue Guy Moquet,BP 8, F-94801 Villejuif, France. RI Gutkind, J. Silvio/A-1053-2009; Crespo, Piero/M-3273-2014 OI Crespo, Piero/0000-0003-2825-7783 NR 38 TC 11 Z9 11 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 5 PY 2000 VL 19 IS 42 BP 4896 EP 4905 DI 10.1038/sj.onc.1203852 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 362BB UT WOS:000089757800012 PM 11039907 ER PT J AU Wipf, P Reeves, JT Balachandran, R Giuliano, KA Hamel, E Day, BW AF Wipf, P Reeves, JT Balachandran, R Giuliano, KA Hamel, E Day, BW TI Synthesis and biological evaluation of a focused mixture library of analogues of the antimitotic marine natural product curacin A SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CYANOBACTERIUM LYNGBYA-MAJUSCULA; COLCHICINE SITE; AGENT; TUBULIN; (+)-CURACIN-A; CONDENSATION; THIAZOLINE; ETHER AB The marine natural product curacin A served as the lead compound for the combinatorial synthesis of 6-compound mixture libraries. Fluorous trapping with a vinyl ether tag was used to streamline purification of the heterogeneous multicomponent reaction products and provide chemically clearly defined mixtures. The screening profile of one mixture library, 17mix, was attractive enough to warrant the re-synthesis of the individual compounds, and an evaluation of their biological effects validated the composite data previously obtained on the product mixture. The most active of these compounds inhibited tubulin polymerization with an IC50 of ca. 1 mu M, showed an average growth inhibition activity GI(50) of ca. 250 nM, inhibited [H-3]colchicine binding to tubulin, and blocked mitotic progression at nanomolar concentrations. These compounds represent some of the most patent synthetic curacin A analogues identified to date but have simplified structures, greater water solubility, and increased chemical stability. C1 Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15238 USA. Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15238 USA. Cellom Inc, Pittsburgh, PA 15238 USA. NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diagnosis, Dev Therapeut Program,Screening Technol Branch, Frederick, MD 21702 USA. RP Wipf, P (reprint author), Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. NR 37 TC 86 Z9 88 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 4 PY 2000 VL 122 IS 39 BP 9391 EP 9395 DI 10.1021/ja002213u PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 360WP UT WOS:000089690600007 ER PT J AU Mandler, R Wu, CC Sausville, EA Roettinger, AJ Newman, DJ Ho, DK King, CR Yang, DJ Lippman, ME Landolfi, NF Dadachova, E Brechbiel, MW Waldmann, TA AF Mandler, R Wu, CC Sausville, EA Roettinger, AJ Newman, DJ Ho, DK King, CR Yang, DJ Lippman, ME Landolfi, NF Dadachova, E Brechbiel, MW Waldmann, TA TI Immunoconjugates of geldanamycin and anti-HER2 monoclonal antibodies: Antiproliferative activity on human breast carcinoma cell lines SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID INTERLEUKIN-2 RECEPTOR; ANTITUMOR-ACTIVITY; ERBB-2 GENE; IN-VIVO; CANCER; PROTEIN; THERAPY; EXPRESSION; ONCOGENE; TARGET AB Background: HER2 is a membrane receptor whose overexpression is strongly associated with poor prognosis in breast carcinomas. Inhibition of HER2 activity can reduce tumor growth, which led to the development of Herceptin, an anti-HER2 monoclonal antibody (MAb) that is already in clinical use, However, the objective response rate to Herceptin monotherapy is quite low. HER2 activity can also be inhibited by the highly cytotoxic antibiotic geldanamycin (GA), However, GA is not used clinically because of its adverse toxicity. Our purpose was to enhance the inhibitory activity of anti-HER2 MAb by coupling it to GA. Methods: We synthesized 17-(3-aminopropylamino)GA (17-APA-GA) and conjugated it to the anti-HER2 MAb e21, to form e21:GA, The noninternalizing anti-HER2 MAb AE1 was used as a control. Internalization assays and western blot analyses were used to determine whether the anti-HER2 MAbs and their immunoconjugates were internalized into HER2-expressing cells and reduced HER:! levels. All statistical tests were two-sided. Results: The immunoconjugate e21:GA inhibited the proliferation of HER2-overexpressing cell lines better than unconjugated e21 (concentration required for 50% inhibition = 40 versus 1650 mu g/mL, respectively). At 15 mu g/mL, e21:GA reduced HER2 levels by 86% within 16 hours, whereas unconjugated e21, 17-APA-GA, or AE1:GA reduced HER2 levels by only 20%, These effects were not caused by release of 17-APA-GA from the immunoconjugate because immunoconjugates containing [H-3]GA were stable in serum at 37 degrees C, Furthermore, e21:GA did not significantly inhibit proliferation of the adult T-cell leukemia cell line HuT102, which is HER2 negative yet highly sensitive to GA. Conclusions: Our findings suggest that conjugating GA to internalizing MAbs enhances the inhibitory effect of the MAbs, This approach might also be applied in cellular targeting via growth factors and may be of clinical interest. C1 NCI, Div Clin Sci, Metab Branch, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diagnost, Dev Therapeut Program, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diagnost, Nat Prod Branch, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC USA. Prot Design Labs, Fremont, CA USA. RP Mandler, R (reprint author), NIH, Bldg 10,Rm 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. RI Dadachova, Ekaterina/I-7838-2013 NR 37 TC 49 Z9 50 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 4 PY 2000 VL 92 IS 19 BP 1573 EP 1581 DI 10.1093/jnci/92.19.1573 PG 9 WC Oncology SC Oncology GA 358NC UT WOS:000089563300011 PM 11018093 ER PT J AU Potosky, AL Legler, J Albertsen, PC Stanford, JL Gilliland, FD Hamilton, AS Eley, JW Stephenson, RA Harlan, LC AF Potosky, AL Legler, J Albertsen, PC Stanford, JL Gilliland, FD Hamilton, AS Eley, JW Stephenson, RA Harlan, LC TI Health outcomes after prostatectomy or radiotherapy for prostate cancer: Results from the prostate cancer outcomes study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID QUALITY-OF-LIFE; RADICAL RETROPUBIC PROSTATECTOMY; EXTERNAL-BEAM RADIATION; LONG-TERM SURVIVAL; SEXUAL FUNCTION; THERAPY; MEN; RELIABILITY; EXPERIENCE; CARCINOMA AB Background: Radical prostatectomy and external beam radiotherapy are the two major therapeutic options for treating clinically localized prostate cancer, Because survival is often favorable regardless of therapy, treatment decisions may depend on other therapy-specific health outcomes. In this study, we compared the effects of two treatments on urinary, bowel, and sexual functions and on general health-related quality-of-life outcomes over a 2-year period following initial treatment, Methods: A diverse cohort of patients aged 55-74 years who were newly diagnosed with clinically localized prostate cancer and received either radical prostatectomy (n = 1156) or external beam radiotherapy (n = 435) were included in this study. A propensity score was used to balance the two treatment groups because they differed in some baseline characteristics. This score was used in multivariable cross-sectional and longitudinal regression analyses comparing the treatment groups, All statistical tests were two-sided, Results: Almost 2 years after treatment, men receiving radical prostatectomy were more likely than men receiving radiotherapy to be incontinent (9.6% versus 3.5%; P<.001) and to have higher rates of impotence (79.6% versus 61.5%; P<.001), although large, statistically significant declines in sexual function were observed in both treatment groups. In contrast, men receiving radiotherapy reported greater declines in bowel function than did men receiving radical prostatectomy, All of these differences remained after adjustments for propensity score. The treatment groups were similar in terms of general health-related quality of life. Conclusions: There are important differences in urinary, bowel, and sexual functions over 2 years after different treatments for clinically localized prostate cancer. In contrast to previous reports, these outcome differences reflect treatment delivered to a heterogeneous group of patients in diverse health care settings. These results provide comprehensive and representative information about long-term treatment complications to help guide and inform patients and clinicians about prostate cancer treatment decisions. C1 NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Div Urol, Farmington, CT USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. New Mexico Tumor Registry, Albuquerque, NM USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. Emory Univ, Rollins Sch Publ Hlth, Georgia Ctr Canc Stat, Atlanta, GA 30322 USA. Univ Utah, Dept Med, Div Urol, Salt Lake City, UT 84112 USA. RP Potosky, AL (reprint author), NIH, EPN, Rm 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. NR 39 TC 329 Z9 332 U1 2 U2 15 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 4 PY 2000 VL 92 IS 19 BP 1582 EP 1592 DI 10.1093/jnci/92.19.1582 PG 11 WC Oncology SC Oncology GA 358NC UT WOS:000089563300012 PM 11018094 ER PT J AU Chen, TT Chute, JP Feigal, E Johnson, BE Simon, R AF Chen, TT Chute, JP Feigal, E Johnson, BE Simon, R TI A model to select chemotherapy regimens for phase III trials for extensive-stage small-cell lung cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SOUTHWEST-ONCOLOGY-GROUP; RANDOMIZED CLINICAL-TRIAL; CISPLATIN PLUS ETOPOSIDE; LEUKEMIA GROUP-B; COMBINATION CHEMOTHERAPY; ALTERNATING CHEMOTHERAPY; DOSE CYCLOPHOSPHAMIDE; PROGNOSTIC FACTORS; RADIATION-THERAPY; CARCINOMA AB Background: Many more phase ZI studies have favorable outcomes than the subsequent phase III trials, We used historical data from phase II and phase III studies for patients with extensive-stage small-cell lung cancer (SCLC) to generate a statistical model to provide assistance in selecting chemotherapy regimens from phase II studies for subsequent use in phase III randomized studies. Methods: Information from 21 phase III trials for patients with extensive-stage SCLC initiated during the period from 1972 through 1990 was reviewed to identify those that were preceded by phase II studies of the same regimen. We used data from all the trial pairs to develop a statistical model in which the number of patients, the median survival of patients, and the number of deaths observed in the phase II trial are used to estimate the statistical power of the subsequent phase III trial. All statistical tests were two-sided. Results: Nine phase II studies were identified that preceded phase III trials of the same regimen. The regimens from two phase II studies with the greatest expected power in the phase III trial (0.62 and 0.58) both demonstrated significantly prolonged survival when compared with standard treatment in subsequent phase III trials (P<.001 and P = .002, respectively). The regimens from six of the other phase LT studies, for which the median power expected in the phase III trial was 0.28 (range, 0.19-0.52), showed no difference when compared with standard treatment in a phase III trial. Conclusions: Phase II studies for particular regimens that have an expected power of greater than 0.55 provide a reasonable basis for proceeding with a phase III trial. C1 NCI, Div Canc Treatment & Diag, Biometr Res Branch, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Med Branch, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Div Hematol Oncol, Bethesda, MD USA. Natl Naval Med Ctr, Naval Med Res Ctr, Bethesda, MD USA. RP Chen, TT (reprint author), Univ Maryland, Greenebaum Canc Ctr, Biostat Sect, 22 S Greene St, Baltimore, MD 21201 USA. NR 39 TC 29 Z9 29 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 4 PY 2000 VL 92 IS 19 BP 1601 EP 1607 DI 10.1093/jnci/92.19.1601 PG 7 WC Oncology SC Oncology GA 358NC UT WOS:000089563300014 PM 11018096 ER PT J AU You, WC Zhang, L Gail, MH Chang, YS Liu, WD Ma, JL Li, JY Jin, ML Hu, YR Yang, CS Blaser, MJ Correa, P Blot, WJ Fraumeni, JF Xu, GW AF You, WC Zhang, L Gail, MH Chang, YS Liu, WD Ma, JL Li, JY Jin, ML Hu, YR Yang, CS Blaser, MJ Correa, P Blot, WJ Fraumeni, JF Xu, GW TI Gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID STOMACH-CANCER; CHINESE POPULATION; PRECANCEROUS LESIONS; INFECTION; CARCINOMA; FERRITIN; PROGRESSION; ASSOCIATION; SHANDONG; COHORT AB Background: Gastric cancer is generally thought to arise through a series of gastric mucosal changes, but the determinants of the precancerous lesions are not well understood. To identify such determinants, me launched a follow-up study in 1989-1990 among 3433 adults in Linqu County, China, a region with very high rates of gastric cancer. Methods: Data on cigarette smoking, alcohol consumption, and other characteristics of the participants were obtained by interview in 1989-1990, when an initial endoscopy was taken. At study entry, antibodies to Helicobacter pylori were assayed in 2646 adults (77% of people screened), and levels of serum micronutrients were measured in approximately 450 adults. Follow-up endoscopic and histopathologic examinations were conducted in 1994. Antibodies to H. pylori, levels of serum micronutrients, and other baseline characteristics were compared between subjects whose condition showed progression to dysplasia or gastric cancer from study entry to 1994 and subjects with no change or with regression of their lesions over the same time frame. All P values are two-sided. Results: The presence of H, pylori at baseline was associated with an increased risk of progression to dysplasia or gastric cancer (odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.2-2.6). The risk of progression to dysplasia or gastric cancer also was moderately increased with the number of years of cigarette smoking. In contrast, the risk of progression was decreased by 80% (OR = 0.2; 95% CI = 0.1-0.7) among subjects with baseline ascorbic acid levels in the highest tertile compared with those in Conclusions: H. pylori infection, cigarette smoking, and low levels of dietary vitamin C may contribute to the progression of precancerous lesions to gastric cancer in this high-risk population. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Beijing Med Univ, Beijing Inst Canc Res, Beijing 100083, Peoples R China. Beijing Med Univ, Sch Oncol, Beijing 100083, Peoples R China. Publ Hlth Bur, Shandong, Peoples R China. Westat, Rockville, MD USA. Rutgers State Univ, Piscataway, NJ USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Dept Vet Affairs Med Ctr, Nashville, TN 37212 USA. Louisiana State Univ, Med Ctr, New Orleans, LA USA. Int Epidemiol Inst, Rockville, MD USA. RP You, WC (reprint author), NIH, EPS, Rm 8030, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01CP05631, N01CP15620, N01CP95660] NR 32 TC 164 Z9 178 U1 1 U2 9 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 4 PY 2000 VL 92 IS 19 BP 1607 EP 1612 DI 10.1093/jnci/92.19.1607 PG 6 WC Oncology SC Oncology GA 358NC UT WOS:000089563300015 PM 11018097 ER PT J AU Currier, JS Williams, PL Koletar, SL Cohn, SE Murphy, RL Heald, AE Hafner, R Bassily, EL Lederman, HM Knirsch, C Benson, CA Valdez, H Aberg, JA McCutchan, JA AF Currier, JS Williams, PL Koletar, SL Cohn, SE Murphy, RL Heald, AE Hafner, R Bassily, EL Lederman, HM Knirsch, C Benson, CA Valdez, H Aberg, JA McCutchan, JA CA AIDS Clin Trials Grp 362 Study Tea TI Discontinuation of Mycobacterium avium complex prophylaxis in patients with antiretroviral therapy-induced increases in CD4+ cell count - A randomized, double-blind, placebo-controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; IMMUNODEFICIENCY-VIRUS INFECTION; CYTOMEGALOVIRUS RETINITIS; MAINTENANCE THERAPY; DISEASE PROGRESSION; HIV-INFECTION; AIDS PATIENTS; LYMPHADENITIS; AZITHROMYCIN; INITIATION AB Background: Patients infected with HIV who experience increases in CD4(+) cell counts are at reduced risk for opportunistic infections. However, the safety of discontinuing prophylaxis against Mycobacterium avium complex has been uncertain. Objective: To compare the rate of M. avium complex infection in patients with increased CD4(+) cell counts who receive azithromycin and those receiving placebo. Design: Randomized, double-blind, placebo-controlled trial. Setting: 29 university-based clinical centers in the United States. Participants: 643 HIV-1-infected patients with a previous CD4(+) cell count less than 0.05 x 10(9) cells/L and a sustained increase to greater than 0.10 x 10(9) cells/L during antiretroviral therapy. Intervention: Azithromycin, 1200 mg once weekly (n = 321), or matching placebo (n = 322). Measurements: Mycobacterium avium complex cultures, CD4+ cell counts, and clinical evaluations for AIDS-defining illnesses and bacterial infections were done every 8 weeks. Plasma HIV-1 RNA levels were measured at 16-week intervals. Results: During follow-up (median, 16 months), 2 cases of M. avium complex infection were reported among the 321 patients assigned to placebo (incidence rate, 0.5 event per 100 person-years [95% CI, 0.06 to 1.83 events per 100 person-years]) compared with no cases among the 322 patients assigned to azithromycin (CI, 0 to 0.92 events per 100 person-years), resulting in a treatment difference of 0.5 event per 100 person-years (CI, -0.20 to 1.21 events per 100 person-years) for placebo versus azithromycin. Both cases were atypical in that M. avium complex was localized to the vertebral spine. Patients receiving azithromycin were more likely than those receiving placebo to discontinue treatment with the study drug permanently because of adverse events (8% vs. 2%; hazard ratio, 0.24 [CI, 0.10 to 0.57]). Conclusions: Prophylaxis against Mycobacterium avium complex can safely be withdrawn or withheld in adults with HIV infection who experience increases in CD4(+) cell count while receiving antiretroviral therapy. C1 Univ Calif Los Angeles, Los Angeles, CA 90095 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Northwestern Univ, Sch Med, Evanston, IL 60208 USA. Duke Univ, Med Ctr, Durham, NC USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Pfizer Inc, New York, NY USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Currier, JS (reprint author), Univ Calif Los Angeles, 10833 LeConte Ave,Room BH-412, Los Angeles, CA 90095 USA. OI Murphy, Robert/0000-0003-3936-2052 NR 42 TC 86 Z9 88 U1 0 U2 0 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 OCT 3 PY 2000 VL 133 IS 7 BP 493 EP 503 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 360QG UT WOS:000089678300001 PM 11015162 ER PT J AU Emanuel, EJ Fairclough, D Clarridge, BC Blum, D Bruera, E Penley, WC Schnipper, LE Mayer, RJ AF Emanuel, EJ Fairclough, D Clarridge, BC Blum, D Bruera, E Penley, WC Schnipper, LE Mayer, RJ TI Attitudes and practices of US oncologists regarding euthanasia and physician-assisted suicide SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID WASHINGTON-STATE; REQUESTS; DEATH AB Background: The practices of euthanasia and physician-assisted suicide remain controversial. Objective: To achieve better understanding of attitudes and practices regarding euthanasia and physician-assisted suicide in the context of end-of-life care. Design: Cohort study. Setting: United States. Participants: 3299 oncologists who are members of the American Society of Clinical Oncology. Measurements: Responses to survey questions on attitudes toward euthanasia and physician-assisted suicide for a terminally ill patient with prostate cancer who has unremitting pain, requests for and performance of euthanasia and physician-assisted suicide, and sociodemographic characteristics. Results: Of U.S. oncologists surveyed, 22.5% supported the use of physician-assisted suicide for a terminally ill patient with unremitting pain and 6.5% supported euthanasia Oncologists who were reluctant to increase the dose of intravenous morphine for terminally ill patients in excruciating pain (odds ratio [OR], 0.61 [95% CI, 0.48 to 0.77]) and had sufficient time to talk to dying patients about end-of-life care issues (OR, 0.79 [CI, 0.71 to 0.87]) were less likely to support euthanasia or physician-assisted suicide. During their career, 3.7% of surveyed oncologists had performed euthanasia and 10.8% had performed physician-assisted suicide. Oncologists who were reluctant to increase the morphine dose for patients in excruciating pain (OR, 0.58 [CI, 0.43 to 0.79]) and those who believed that they had received adequate training in end-of-life care (OR, 0.86 [CI, 0.79 to 0.95]) were less likely to have performed euthanasia or physician-assisted suicide. Oncologists who reported not being able to obtain all the care that a dying patient needed were more likely to have performed euthanasia (P = 0.001). Conclusions: Requests for euthanasia and physician-assisted suicide are likely to decrease as training in end-of-life care improves and the ability of physicians to provide this care to their patients is enhanced. C1 Dana Farber Canc Inst, Dept Med Adult Oncol, Boston, MA 02115 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. AMC Canc Res Ctr, Denver, CO USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Canc Care Inc, New York, NY USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Baptist Hosp, Nashville, TN USA. RP Mayer, RJ (reprint author), Dana Farber Canc Inst, Dept Med Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 17 TC 91 Z9 91 U1 1 U2 3 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 OCT 3 PY 2000 VL 133 IS 7 BP 527 EP 532 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 360QG UT WOS:000089678300004 PM 11015165 ER PT J AU Sarosy, GA Reed, E AF Sarosy, GA Reed, E TI Autologous stem-cell transplantation in ovarian cancer: Is more better? SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID INDUCTION CHEMOTHERAPY; THERAPY; PROGNOSIS C1 NCI, Med Ovarian Canc Sect, Bethesda, MD 20892 USA. RP Sarosy, GA (reprint author), NCI, Med Ovarian Canc Sect, 6116 Execut Blvd,Suite 3002B,MSC 8321, Bethesda, MD 20892 USA. NR 15 TC 1 Z9 1 U1 0 U2 0 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 OCT 3 PY 2000 VL 133 IS 7 BP 555 EP 556 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 360QG UT WOS:000089678300009 PM 11015170 ER PT J AU Udelson, JE Dilsizian, V Laham, RJ Chronos, N Vansant, J Blais, M Galt, JR Pike, M Yoshizawa, C Simons, M AF Udelson, JE Dilsizian, V Laham, RJ Chronos, N Vansant, J Blais, M Galt, JR Pike, M Yoshizawa, C Simons, M TI Therapeutic angiogenesis with recombinant fibroblast growth factor-2 improves stress and rest myocardial perfusion abnormalities in patients with severe symptomatic chronic coronary artery disease SO CIRCULATION LA English DT Article DE angiogenesis; heart diseases; growth substances ID VIABLE MYOCARDIUM; CANINE MODEL; GENE-THERAPY; HUMAN HEART; ISCHEMIA; TL-201; SCINTIGRAPHY; TOMOGRAPHY; INJECTION; REDUCTION AB Background-We report the effects of the administration of recombinant fibroblast growth factor-2 (rFGF-2) protein on myocardial perfusion using single photon emission computed tomography imaging in humans with advanced coronary disease. Methods and Results-A total of 59 patients with coronary disease that was not amenable to mechanical revascularization underwent intracoronary (n=45) or intravenous (n=14) administration of rFGF-2 in ascending doses, Changes in perfusion were evaluated at baseline and again at 29, 57, and 180 days after rFGF-2 administration. In this uncontrolled study, perfusion scans were analyzed by 2 observers who were blinded to patient identity and test sequence; scans were displayed in random order, with scans from nonstudy patients randomly interspersed to enhance blinding. Combining all dose groups, a reduction occurred in the per-segment reversibility score (reflecting the magnitude of inducible ischemia) from 1.7+/-0.4 at baseline to 1.1+/-0.6 at day 29 (P<0.001), 1.2+/-0.7 at day 57 (P<0.001), and 1.1+/-0.7 at day 180 (P<0.001). The 37 patients with evidence of resting hypoperfusion had evidence of improved resting perfusion: their per-segment rest perfusion score of 1.5+/-0.5 at baseline decreased to 1.0+/-0.8 at day 29 (P<0.001), 1.0+/-0.8 at day 57 (P=0.003), and 1.1+/-0.9 at day 180 (P=0.11). Conclusions-These preliminary data suggest that the administration of rFGF-2 to patients with advanced coronary disease resulted in an attenuation of stress-induced ischemia and an improvement in resting myocardial perfusion; these findings are consistent with a favorable effect of therapeutic angiogenesis. C1 Tufts Univ, New England Med Ctr Hosp, Sch Med, Div Cardiol,Cardiac Imaging Core Lab, Boston, MA 02111 USA. NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Angiogenesis Res Ctr, Boston, MA 02215 USA. Atlanta Cardiol Grp, Atlanta, GA USA. Emory Univ, Emory Univ Hosp, Sch Med, Atlanta, GA 30322 USA. Chiron Corp, Emeryville, CA 94608 USA. RP Udelson, JE (reprint author), New England Med Ctr, Div Cardiol, Box 70,750 Washington St, Boston, MA 02111 USA. RI Simons, Michael/G-8553-2014 OI Simons, Michael/0000-0003-0348-7734 NR 31 TC 112 Z9 122 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 3 PY 2000 VL 102 IS 14 BP 1605 EP 1610 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 359CB UT WOS:000089593000003 PM 11015335 ER PT J AU Stec, JJ Silbershatz, H Tofler, GH Matheney, TH Sutherland, P Lipinska, I Massaro, JM Wilson, PFW Muller, JE D'Agostino, RB AF Stec, JJ Silbershatz, H Tofler, GH Matheney, TH Sutherland, P Lipinska, I Massaro, JM Wilson, PFW Muller, JE D'Agostino, RB TI Association of fibrinogen with cardiovascular risk factors and cardiovascular disease in the Framingham Offspring Population SO CIRCULATION LA English DT Article DE fibrinogen; cardiovascular disease; Framingham Offspring Study ID CORONARY HEART-DISEASE; HEMOSTATIC FACTORS; MYOCARDIAL-INFARCTION; PLASMA-FIBRINOGEN; BODY-WEIGHT; HEALTHY-MEN; FACTOR-VII; SMOKING; ALCOHOL; AGE AB Background-Fibrinogen has been identified as an independent risk factor for cardiovascular disease and associated with traditional cardiovascular risk factors. Also, the role of elevated fibrinogen in thrombosis suggests that it may be on the causal pathway for certain risk factors to exert their effect. These associations remain incompletely characterized. Moreover, the optimal fibrinogen assay for risk stratification is uncertain. Methods and Results-In 2632 subjects from cycle 5 of the Framingham Offspring Population, fibrinogen levels were determined with a newly developed immunoprecipitation test (American Biogenetic Sciences) and the functional Clauss method. With the immunoprecipitation method, there were significant linear trends across fibrinogen tertiles (P<0.001) for age, body mass index, smoking, diabetes mellitus, total cholesterol, HDL cholesterol, and triglycerides in men and women. The Clauss method had significant results (P<0.030), except for triglycerides in men. Fibrinogen levels were higher for those with compared with those without cardiovascular disease. After covariate adjustment, fibrinogen remained significantly higher in those with cardiovascular disease with the use of the immunoprecipitation test (P=0.035 and P=0.018 for men and women, respectively) but not with the Clauss method. Conclusions-Fibrinogen was associated with traditional cardiovascular risk factors. Elevation of fibrinogen may provide a mechanism for risk factors to exert their effect, Also, fibrinogen levels were higher among subjects with cardiovascular disease compared with those without disease. The immunoprecipitation test showed a stronger association with cardiovascular disease than the Clauss method, suggesting that it may be a useful screening tool to identify individuals at increased thrombotic risk. C1 Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med,Cardiovasc Div, Inst Prevent Cardiovasc Dis, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. NIH, Framingham, MA USA. RP D'Agostino, RB (reprint author), Boston Univ, Dept Math & Stat, 111 Cummington St, Boston, MA 02215 USA. FU NHLBI NIH HHS [N01HC-38038, R01-HL-48157] NR 24 TC 136 Z9 148 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 3 PY 2000 VL 102 IS 14 BP 1634 EP 1638 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 359CB UT WOS:000089593000008 PM 11015340 ER PT J AU Jensen, MR Audolfsson, T Factor, VM Thorgeirsson, SS AF Jensen, MR Audolfsson, T Factor, VM Thorgeirsson, SS TI In vivo expression and genomic organization of the mouse cyclin I gene (Ccni) SO GENE LA English DT Article DE cell cycle; cyclin family; gene structure ID MESSENGER-RNA; INDUCED HEPATOCARCINOGENESIS; CHROMOSOMAL LOCALIZATION; DNA-DAMAGE; G1 GENE; G2; SEQUENCE; PROTEIN AB Cyclins control cell-cycle progression by regulating the activity of cyclin-dependent kinases. Cyclin I was recently added to the cyclin family of proteins because of the presence of a cyclin box motif in the deduced amino-acid sequence. Cyclin I may share functional roles with cyclin G1 and G2 because of the high structural similarity between their deduced amino-acid sequences. However, the biological and functional roles of this subclass of cyclins remain obscure. The mouse cyclin G1 and G2 genes have previously been cloned and characterized. In this report, we describe the cloning of the mouse homolog of cyclin I. The cyclin I cDNA sequence was used to determine the genomic organization of the mouse cyclin I gene which co-localizes with cyclin G2 to chromosome 5E3.3-F1.3. Cyclin I was transcribed from seven exons distributed over more than 19 kb of genomic sequence. The expression of cyclin I was determined in various tissues, but no clear correlation with the proliferative state was found. Furthermore, in contrast to cyclin G1, cyclin I expression was stable during cell-cycle progression after partial hepatectomy in both the absence and presence of DNA damage. Transient expression of cyclin I-green fluorescent protein (GFP) fusion proteins in cell lines showed that cyclin I was distributed throughout the cell in contrast with the mainly cytoplasmic localization of cyclin G2 and nuclear localization of cyclin GI. Our results indicate that despite the close structural similarity between cyclin G1, G2 and I, these three proteins are likely to have distinct biological roles. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NCI, NIH, Div Basic Sci, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, NIH, Div Basic Sci, Expt Carcinogenesis Lab, 37 Convent Dr,MSC4255,Bldg 37,Room 3C28, Bethesda, MD 20892 USA. RI Jensen, Michael/E-9677-2011 NR 27 TC 14 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 3 PY 2000 VL 256 IS 1-2 BP 59 EP 67 DI 10.1016/S0378-1119(00)00361-9 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 371GG UT WOS:000165170000008 PM 11054536 ER PT J AU Gonzalez, M Rasulova, F Maurizi, MR Woodgate, R AF Gonzalez, M Rasulova, F Maurizi, MR Woodgate, R TI Subunit-specific degradation of the UmuD/D ' heterodimer by the ClpXP protease: the role of trans recognition in UmuD ' stability SO EMBO JOURNAL LA English DT Article DE ATP-dependent protease; degradation signal; SOS mutagenesis; UmuD ID ESCHERICHIA-COLI; SOS MUTAGENESIS; DEPENDENT PROTEASES; TAGGING SYSTEM; MU-TRANSPOSASE; PROTEINS; PROTEOLYSIS; DNA; REGULATOR; CLEAVAGE AB The Escherichia coli UmuD' protein is a subunit of the recently described error-prone DNA polymerase, pol V, UmuD' is initially synthesized as an unstable and mutagenically inactive pro-protein, UmuD, Upon processing, UmuD' assumes a relatively stable conformation and becomes mutagenically active. While UmuD and UmuD' by themselves exist in vivo as homodimers, when together they preferentially interact to form heterodimers. Quite strikingly, it is in this context that UmuD' becomes susceptible to ClpXP-mediated proteolysis. Here we report a novel targeting mechanism designed for degrading the mutagenically active UmuD' subunit of the UmuD/D' heterodimer complex, while leaving the UmuD protein intact. Surprisingly, a signal that is essential and sufficient for targeting UmuD' for degradation was found to reside on UmuD not UmuD', UmuD was also shown to be capable of channeling an excess of UmuD' to ClpXP for degradation, thereby providing a mechanism. whereby cells can limit error-prone DNA replication. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. EM woodgate@helix.nih.gov NR 44 TC 84 Z9 85 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD OCT 2 PY 2000 VL 19 IS 19 BP 5251 EP 5258 DI 10.1093/emboj/19.19.5251 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 362RM UT WOS:000089792100021 PM 11013227 ER PT J AU Tissier, A Frank, EG McDonald, JP Iwai, S Hanaoka, F Woodgate, R AF Tissier, A Frank, EG McDonald, JP Iwai, S Hanaoka, F Woodgate, R TI Misinsertion and bypass of thymine-thymine dimers by human DNA polymerase iota SO EMBO JOURNAL LA English DT Article DE DNA polymerase eta; DNA polymerase zeta; Rah30; Rad30B; xeroderma pigmentosum variant ID XERODERMA-PIGMENTOSUM VARIANT; MOUSE HOMOLOGS; REPLICATION; EXTRACTS; CELLS; GENE; ZETA; ETA; PHOTOPRODUCTS; TRANSFERASE AB Human DNA polymerase iota (pol iota) is a recently discovered enzyme that exhibits extremely low fidelity on undamaged DNA templates. Here, we show that pol iota is able to facilitate limited translesion replication of a thymine-thymine cyclobutane pyrimidine dimer (CPD), More importantly, however, the bypass event is highly erroneous. Gel kinetic assays reveal that pol iota misinserts T or G opposite the 3' T of the CPD similar to 1.5 times more frequently than the correct base, A. While pol iota is unable to extend the T T mispair significantly, the G T mispair is extended and the lesion completely bypassed, with the same efficiency as that of the correctly paired A T base pair. By comparison, pol iota readily misinserts two bases opposite a 6-4 thymine-thymine pyrimidine-pyrimidone photoproduct (6-4PP), but complete lesion bypass is only a fraction of that observed with the CPD. Our data indicate, therefore, that pol iota possesses the ability to insert nucleotides opposite UV photoproducts as well as to perform unassisted translesion replication that is likely to be highly mutagenic. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, Bethesda, MD 20892 USA. Biomol Engn Res Inst, Osaka 5650874, Japan. Osaka Univ, Inst Mol & Cellular Biol, Suita, Osaka 5650871, Japan. CREST, Japan Sci & Technol Corp, Suita, Osaka 5650871, Japan. RIKEN, Inst Phys & Chem Res, Wako, Saitama 3510198, Japan. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, Bethesda, MD 20892 USA. NR 34 TC 164 Z9 172 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 2 PY 2000 VL 19 IS 19 BP 5259 EP 5266 DI 10.1093/emboj/19.19.5259 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 362RM UT WOS:000089792100022 PM 11013228 ER PT J AU Schaeffer, EM Broussard, C Debnath, J Anderson, S McVicar, DW Schwartzberg, PL AF Schaeffer, EM Broussard, C Debnath, J Anderson, S McVicar, DW Schwartzberg, PL TI Tec family kinases modulate thresholds for thymocyte development and selection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE gene-targeted mice; signal transduction; Itk; Rlk/Txk; T cell receptor ID T-CELL-RECEPTOR; CLASS-II MHC; ANTIGEN RECEPTOR; TYROSINE KINASE; NEGATIVE SELECTION; LINEAGE COMMITMENT; POSITIVE SELECTION; PROTEIN-KINASE; MEDIATED ACTIVATION; TRANSGENIC MICE AB Tec family kinases are implicated in T cell receptor (TCR) signaling, and combined mutation of inducible T cell kinase (Itk) and resting lymphocyte kinase (Rlk)/Txk in mice dramatically impairs mature T cell function. Nonetheless, mutation of these kinases still permits T cell development. While itk(-/-) mice exhibit mild reductions in T cells with decreased CD4/CD8 cell ratios, rlk(-/-)itk(-/-) mice have improved total T cell numbers yet maintain decreased CD4/CD8 ratios. Using TCR transgenics and an in vitro thymocyte deletion model, we demonstrate that mutation of Tec kinases causes graded defects in thymocyte selection, leading to a switch from negative to positive selection in rlk(-/-)itk(-/-) animals. The reduction in both positive and negative selection and decreased CD4/CD8 ratios con-elates with decreased biochemical parameters of TCR signaling, specifically defects in capacitive Ca2+ influx and activation of the mitogen-activated kinases extracellular signal-regulated kinase 1 and 2. Thus, Tec kinases influence cell fate determination by modulating TCR signaling, leading to altered thresholds for thymocyte selection. These results provide support for a quantitative model for thymic development and provide evidence that defects in negative selection can substantially alter thymic cellularity. C1 NHGRI, NIH, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. RP Schwartzberg, PL (reprint author), NHGRI, NIH, Bldg 49-4A38,49 Convent Dr, Bethesda, MD 20892 USA. RI McVicar, Daniel/G-1970-2015 NR 54 TC 104 Z9 104 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 2 PY 2000 VL 192 IS 7 BP 987 EP 1000 DI 10.1084/jem.192.7.987 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 361QD UT WOS:000089733000007 PM 11015440 ER PT J AU Zorov, DB Filburn, CR Klotz, LO Zweier, JL Sollott, SJ AF Zorov, DB Filburn, CR Klotz, LO Zweier, JL Sollott, SJ TI Reactive oxygen species (ROS)-induced ROS release: A new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE mitochondria; redox; heart; nitric oxide; Ca2+ sparks ID RAT-LIVER MITOCHONDRIA; NITRIC-OXIDE; CELL-DEATH; CYCLOSPORINE-A; CALCIUM; APOPTOSIS; HEART; PORE; MECHANISMS; CHANNEL AB We sought to understand the relationship between reactive oxygen species (ROS) and the mitochondrial permeability transition (MPT) in cardiac myocytes based on the observation of increased ROS production at sites of spontaneously deenergized mitochondria. We devised a new model enabling incremental ROS accumulation in individual mitochondria in isolated cardiac myocytes via photoactivation of tetramethylrhodamine derivatives, which also served to report the mitochondrial transmembrane potential, Delta Psi. This ROS accumulation reproducibly triggered abrupt (and sometimes reversible) mitochondrial depolarization. This phenomenon was ascribed to MPT induction because (a) bongkrekic acid prevented it and (b) mitochondria became permeable for calcein (similar to 620 daltons) concurrently with depolarization. These photodynamically produced "triggering" ROS caused the MPT induction, as the ROS scavenger Trolox prevented it. The time required for triggering ROS to induce the MPT was dependent on intrinsic cellular ROS-scavenging redox mechanisms, particularly glutathione. MPT induction caused by triggering ROS coincided with a burst of mitochondrial ROS generation, as measured by dichlorofluorescein fluorescence, which we have termed mitochondrial "ROS-induced ROS release" (RIRR). This MPT induction/RIRR phenomenon in cardiac myocytes often occurred synchronously and reversibly among long chains of adjacent mitochondria demonstrating apparent cooperativity. The observed link between MPT and RIRR could be a fundamental phenomenon in mitochondrial and cell biology. C1 NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. NIA, Biol Chem Lab, Intramural Res Program, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Electron Paramagnet Resonance Ctr, Baltimore, MD 21224 USA. AN Belozersky Inst Physico Chem Biol, Dept Bioenerget, Moscow 119899, Russia. RP Sollott, SJ (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr,NIH, Box 13,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NHLBI NIH HHS [HL38324, HL52315, HL63744, R01 HL038324, R01 HL063744] NR 48 TC 707 Z9 753 U1 6 U2 41 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 2 PY 2000 VL 192 IS 7 BP 1001 EP 1014 DI 10.1084/jem.192.7.1001 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 361QD UT WOS:000089733000008 PM 11015441 ER PT J AU Yang, D Chen, Q Schmidt, AP Anderson, GM Wang, JM Wooters, J Oppenheim, JJ Chertov, O AF Yang, D Chen, Q Schmidt, AP Anderson, GM Wang, JM Wooters, J Oppenheim, JJ Chertov, O TI LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE cathelicidin; hCAP18; chemotaxis; phagocyte; lymphocyte ID ANTIBACTERIAL PEPTIDE; PROTEIN; IDENTIFICATION; CHEMOKINES; 7-TRANSMEMBRANE; EXPRESSION; DEFENSINS; IMMUNITY; DOMAIN; BETA AB We have previously shown that antimicrobial peptides like defensins have the capacity to mobilize leukocytes in host defense. LL-37 is the cleaved antimicrobial 37-residue, COOH-terminal peptide of hCAP18 (human cationic antimicrobial protein with a molecular size of 18 kD), the only identified member in humans of a family of proteins called cathelicidins. LL-37/hCAP18 is produced by neutrophils and various epithelial cells. Here we report that LL-37 is chemotactic for, and can induce Ca2+ mobilization in, human monocytes and formyl peptide receptor-like 1 (FPRL1)-transfected human embryonic kidney 293 cells. LL-37-induced Ca2+ mobilization in monocytes can also be cross-desensitized by an FPRL1-specific agonist. Furthermore, LL-37 is also chemotactic for human neutrophils and T lymphocytes that are known to express FPRL1. Our results suggest that, in addition to its microbicidal activity, LL-37 may contribute to innate and adaptive immunity by recruiting neutrophils, monocytes, and T cells to sites of microbial invasion by interacting with FPRL1. C1 NCI, Frederick Canc Res & Dev Ctr, IRSP, SAIC,NIH, Frederick, MD 21701 USA. Sci Applicat Int Corp, Div Basic Sci, Mol Immunoregulat Lab, Frederick, MD USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD USA. Magainin Pharmaceut Inc, Plymouth Meeting, PA 19462 USA. Genet Inst, Cambridge, MA 02140 USA. RP Chertov, O (reprint author), NCI, Frederick Canc Res & Dev Ctr, IRSP, SAIC,NIH, Bldg 560,Rm 31-19, Frederick, MD 21701 USA. NR 29 TC 290 Z9 298 U1 0 U2 13 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 2 PY 2000 VL 192 IS 7 BP 1069 EP 1074 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 361QD UT WOS:000089733000014 ER PT J AU Tatum, JL Hoffman, JM AF Tatum, JL Hoffman, JM TI Role of imaging in clinical trials of antiangiogenesis therapy in oncology SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 NCI, Biomed Imaging Program, Rockville, MD USA. RP Tatum, JL (reprint author), POB 980470, Richmond, VA 23298 USA. NR 0 TC 14 Z9 16 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2000 VL 7 IS 10 BP 798 EP 799 DI 10.1016/S1076-6332(00)80628-5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 361NQ UT WOS:000089729500003 PM 11048877 ER PT J AU Blankenberg, FG Eckelman, WC Strauss, W Welch, MJ Alavi, A Anderson, C Bacharach, S Blasberg, RG Graham, MM Weber, W AF Blankenberg, FG Eckelman, WC Strauss, W Welch, MJ Alavi, A Anderson, C Bacharach, S Blasberg, RG Graham, MM Weber, W TI Role of radionuclide imaging in trials of antiangiogenic therapy SO ACADEMIC RADIOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; INDUCIBLE FACTOR-I; MUSCARINIC CHOLINERGIC RECEPTORS; ENDOTHELIAL-CELL MIGRATION; NEGATIVE BREAST-CARCINOMA; HUMAN-MELANOMA CELLS; KINASE GENE-TRANSFER; ALPHA-V INTEGRINS; GROWTH-FACTOR; TUMOR ANGIOGENESIS C1 Lucile Packard Childrens Hosp, Dept Radiol, Palo Alto, CA 94304 USA. NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. Div Nucl Med, Stanford, CA USA. Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO USA. Hosp Univ Penn, Div Nucl Med, Philadelphia, PA 19104 USA. Washington Univ, Sch Med, Dept Radiat Sci, St Louis, MO USA. NIH, Imaging Sci Program, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Iowa, Dept Nucl Med, Iowa City, IA USA. Tech Univ Munich, Dept Nucl Med, D-8000 Munich, Germany. RP Blankenberg, FG (reprint author), Lucile Packard Childrens Hosp, Dept Radiol, 725 Welch Rd, Palo Alto, CA 94304 USA. NR 156 TC 27 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2000 VL 7 IS 10 BP 851 EP 867 DI 10.1016/S1076-6332(00)80633-9 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 361NQ UT WOS:000089729500008 PM 11048882 ER PT J AU Hoffman, JM Menkens, AE AF Hoffman, JM Menkens, AE TI Molecular imaging in cancer: Future directions and goals of the National Cancer Institute SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 NCI, Biomed Imaging Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Hoffman, JM (reprint author), NCI, Biomed Imaging Program, Div Canc Treatment & Diag, EPN-800,6130 Execut Blvd,MSC 7440, Bethesda, MD 20892 USA. NR 0 TC 10 Z9 11 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2000 VL 7 IS 10 BP 905 EP 907 DI 10.1016/S1076-6332(00)80671-6 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 361NQ UT WOS:000089729500013 PM 11048885 ER PT J AU Kazzi, SNJ Schurch, S McLaughlin, KL Romero, R Janisse, J AF Kazzi, SNJ Schurch, S McLaughlin, KL Romero, R Janisse, J TI Surfactant phospholipids and surface activity among preterm infants with respiratory distress syndrome who develop bronchopulmonary dysplasia SO ACTA PAEDIATRICA LA English DT Article DE bronchopulmonary dysplasia; chronic lung disease; low birthweight infants; surface tension measurements ID CAPTIVE BUBBLE METHOD; CHRONIC LUNG-DISEASE; PHOSPHATIDYLCHOLINE; CELLS AB Our objective was to determine if preterm infants with respiratory distress syndrome who develop bronchopulmonary dysplasia have abnormalities in surfactant phospholipids and/or function. Tracheal aspirate samples obtained from preterm infants with respiratory distress syndrome on days I, 3-5, 7-10, 14-17, 21-24 and 27-30 were analyzed for total phospholipids and phospholipids fractions by determination of total phospholipid phosphorus and thin layer chromatography, respectively. Surfactant properties were assessed with captive bubble surfactometer, Sixteen out of 56 (29%) infants died during the first 30 d of life. Infants who died were more immature, required more ventilatory support and had a surfactant with lower surface-tension-reducing properties than infants who survived (p < 0.05). Surviving infants were divided into group I (no bronchopulmonary dysplasia at 27-30 d, n = 25) and group II (with bronchopulmonary dysplasia at 27-30 d, n = 15). No significant differences in concentrations of surfactant phospholipids nor measurements of surface tension were noted among groups of infants, Surfactant therapy after birth was associated with a significant increase in concentrations of total phospholipids, lecithin, phosphatidylinositol and lower surface-tension measurements at 3-5 d of age among surviving infants (p < 0.01). Abnormalities in concentrations of surfactant phospholipids or surfactant function could not be demonstrated during the first month of Life among preterm infants with respiratory distress syndrome who develop bronchopulmonary dysplasia. C1 NICHHD, Dept Pediat, NIH, Detroit, MI USA. NICHHD, Ctr Hlth Effect Res, NIH, Detroit, MI USA. NICHHD, Perinatol Res Branch, NIH, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. Univ Calgary, Hlth Sci Ctr, Dept Med Physiol & Med, Calgary, AB T2N 4N1, Canada. RP Kazzi, SNJ (reprint author), Hutzel Hosp, Dept Pediat, 4707 St Antoine Blvd, Detroit, MI 48201 USA. NR 27 TC 9 Z9 9 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD OCT PY 2000 VL 89 IS 10 BP 1218 EP 1225 DI 10.1080/080352500750027600 PG 8 WC Pediatrics SC Pediatrics GA 366MU UT WOS:000090009800016 PM 11083379 ER PT J AU Miller, KD Piscitelli, SC Davey, RT AF Miller, KD Piscitelli, SC Davey, RT TI Herpes zoster in an HIV-negative man on ritonavir SO AIDS PATIENT CARE AND STDS LA English DT Article ID ANTIRETROVIRAL THERAPY C1 NIAID, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Miller, KD (reprint author), NIH, Ctr Clin, Bldg 10,Room 8C410, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD OCT PY 2000 VL 14 IS 10 BP 527 EP 528 DI 10.1089/108729100750018272 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 366HF UT WOS:000089999200002 PM 11054935 ER PT J AU Lamas, GA Lee, K Sweeney, M Leon, A Yee, R Ellenbogen, K Greer, S Wilber, D Silverman, R Marinchak, R Bernstein, R Mittleman, RS Lieberman, EH Sullivan, C Zorn, L Flaker, G Schron, E Orav, EJ Goldman, L AF Lamas, GA Lee, K Sweeney, M Leon, A Yee, R Ellenbogen, K Greer, S Wilber, D Silverman, R Marinchak, R Bernstein, R Mittleman, RS Lieberman, EH Sullivan, C Zorn, L Flaker, G Schron, E Orav, EJ Goldman, L TI The Mode Selection Trial (MOST) in sinus node dysfunction: Design, rationale, and baseline characteristics of the first 1000 patients SO AMERICAN HEART JOURNAL LA English DT Article ID DUAL-CHAMBER; PACEMAKER SYNDROME; RANDOMIZED TRIAL; ATRIAL; DISEASE; MORBIDITY; SURVIVAL; BENEFIT; SINGLE AB Background More than 200,000 permanent pacemakers will be implanted in the United States in 2000 at a cost of more than $2 billion. Sick sinus syndrome (SSS) will likely account for approximately half of all cases necessitating implantation. Pacemaker technology permits the selection of ventricular (single-chamber) or dual-chamber devices. However, clinical and outcomes data are inadequate to support a clear recommendation that one or the other type of device be used. Methods The Mode Selection Trial (MOST) is a single-blind study supported by the National Heart, Lung, and Blood institute designed to enroll 2000 patients with SSS. All patients will receive a DDDR pacemaker programmed to WIR or DDDR before implantation. The average time of follow-up will be 3 years. MOST has a >90% power to detect a 25% reduction in the primary end point-nonfatal stroke or total (all cause) mortality-in the DDDR-treated group. Secondary end points will include health-related quality of life and cost effectiveness, atrial fibrillation, and development of pacemaker syndrome. Prespecified subgroups for analysis will include women and the elderly. Enrollment was completed in October 1999, with a total of 2010 patients. Results The median age of the first 1000 enrolled patients is 74 years, with 25% of patients 80 years or older. Women comprise 49%, and 17% are nonwhite, predominantly black (13%). Before pacemaker implantation, 22% of patients reported a history of congestive heart failure, 11% coronary angioplasty, and 25% coronary bypass surgery. Supraventricular tachycardia including atrial fibrillation was present in 53% of patients. A prior stroke was reported by 12%. Antiarrhythmic therapy was in use in 18% of patients. Conclusions MOST will fill the clinical need for carefully designed prospective studies to define the benefits of dual-chamber versus single-chamber ventricular pacing in patients with SSS. The MOST population is typical of the overall pacemaker population in the United Slates. Thus the final results of MOST should be clinically generalizable. C1 Mt Sinai Med Ctr, Div Cardiol, Miami Beach, FL 33140 USA. Univ Miami, Sch Med, Miami Beach, FL 33140 USA. Duke Clin Res Inst, Durham, NC USA. Duke Univ, Sch Med, Durham, NC USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Emory Univ, Crawford Long Hosp, Atlanta, GA 30365 USA. Univ Western Ontario Hosp, London, ON N6A 5A5, Canada. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Clin Invest Specialists Inc, Little Rock, AR USA. Univ Chicago Hosp, Chicago, IL 60637 USA. Heart Care Ctr, Fayetteville, AR USA. Lankenau Hosp, Wynnewood, PA USA. Sentara Norfolk Gen Hosp, Norfolk, VA USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Univ Tampa, Community Hosp, Tampa, FL 33606 USA. Univ Missouri, Hosp & Clin, Columbia, MO USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Lamas, GA (reprint author), Mt Sinai Med Ctr, Div Cardiol, 4300 Alton Rd, Miami Beach, FL 33140 USA. NR 31 TC 75 Z9 86 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2000 VL 140 IS 4 BP 541 EP 551 DI 10.1067/mhj.2000.109652 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360XL UT WOS:000089692600001 PM 11011325 ER PT J AU Hornberger, LK Lipshultz, SE Easley, KA Colan, SD Schwartz, M Kaplan, S Starc, TJ Ayres, NA Lai, WW Moodie, DS Kasten-Sportes, C Sanders, SP AF Hornberger, LK Lipshultz, SE Easley, KA Colan, SD Schwartz, M Kaplan, S Starc, TJ Ayres, NA Lai, WW Moodie, DS Kasten-Sportes, C Sanders, SP CA P2C2HIV Study Grp TI Cardiac structure and function in fetuses of mothers infected with HIV: The prospective (PCHIV)-C-2-H-2 multicenter study SO AMERICAN HEART JOURNAL LA English DT Article ID CROSS-SECTIONAL ECHOCARDIOGRAPHY; FLOW VELOCITY WAVEFORMS; HUMAN-FETAL HEART; PLACENTAL RESISTANCE; GESTATIONAL-AGE; MENSTRUAL AGE; PREGNANCY; GROWTH AB Background This study was designed to determine ii vertically transmitted HIV infection and maternal injection with HIV are associated with altered cardiovascular structure and function in utero. Methods Fetal achocardioaraphy was performed in 173 fetuses of 169 HIV-infected mothers (mean gestational age, 33.0 weeks; SD = 3.7 weeks) at 5 centers. Biparietal diameter, femur length, cardiovascular dimensions, and Doppler velocities through atrioventricular and semilunar valves and the umbilical artery were measured. Measurements were converted to z scores based on published normal data. Results Fetuses determined after birth to be HIV-infected had similar echocordiogrophic findings as fetuses later determined to be HIV-uninfected except for slightly smaller left ventricular diastolic dimensions (P= .01). The femur length (P= .03) was also smaller in the fetuses postnatally identified as HIV-infected. Differences in cardiovascular dimensions and Doppler velocities were identified between fetuses of HIV-infected women and previously published normal fetal data. The reason For the differences may be a result of maternal HIV infection, maternal risk factors, or selection bias in the external control data. Conclusions Vertically transmitted HIV infection may be associated with reduced left ventricular size but not with altered cardiac function in utero. Fetuses of HIV-infected mothers may have abnormal cardiovascular structure and function and increased placental vascular resistance, regardless of whether the fetuses are subsequently found to be infected with HIV. C1 Harvard Univ, Childrens Hosp, Dept Cardiol, Dept Pediat,Sch Med, Boston, MA 02115 USA. Boston Med Ctr, Dept Pediat, Boston, MA USA. Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Pediat, Div Pediat Cardiol, Cleveland, OH 44195 USA. Univ Calif Los Angeles, Med Ctr, Dept Pediat, Div Pediat Cardiol, Los Angeles, CA 90024 USA. Columbia Univ, Sch Med, Dept Pediat, Div Pediat Cardiol,Presbyterian Hosp, New York, NY 10027 USA. Baylor Coll Med, Dept Pediat, Div Pediat Cardiol, Houston, TX 77030 USA. Mt Sinai Sch Med, Dept Pediat, Div Pediat Cardiol, New York, NY USA. NHLBI, Bethesda, MD 20892 USA. RP Hornberger, LK (reprint author), Hosp Sick Children, Div Cardiol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Easley, Kirk/K-6910-2015; OI Easley, Kirk/0000-0003-4419-2617; Sanders, Stephen/0000-0003-3521-4044 FU NCRR NIH HHS [M01 RR000645, M01 RR002172, M01 RR000533, M01 RR000188, K01 RR000188, M01 RR000865, M01 RR000043]; NHLBI NIH HHS [N01-HR-96039, N01 HR096043, N01 HR096037, N01-HR-96038] NR 25 TC 25 Z9 26 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2000 VL 140 IS 4 BP 575 EP 584 DI 10.1067/mhj.2000.109645 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360XL UT WOS:000089692600006 PM 11011330 ER PT J AU Granger, CB Keavney, B Francomano, C Olsson, G Yusuf, S AF Granger, CB Keavney, B Francomano, C Olsson, G Yusuf, S TI Recommendations for national and local regulatory authorities concerning research in genetic markers of disease SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Symposium on Genetics of Coronary Heart Disease CY APR 08-10, 1999 CL LEESBURG, VIRGINIA C1 Duke Clin Res Inst, Cardiac Care Unit, Durham, NC 27715 USA. Univ Oxford, Oxford, England. NHGRI, Bethesda, MD 20892 USA. AstraZeneca, Molndal, Sweden. McMaster Univ, Hamilton, New Zealand. RP Granger, CB (reprint author), Duke Clin Res Inst, Cardiac Care Unit, POB 17969, Durham, NC 27715 USA. RI Granger, Christopher/D-3458-2014 OI Granger, Christopher/0000-0002-0045-3291 NR 1 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2000 VL 140 IS 4 BP S3 EP S5 DI 10.1067/mhj.2000.110350 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360XL UT WOS:000089692600024 PM 11011309 ER PT J AU Weyer, C Walford, RL Harper, IT Milner, M MacCallum, T Tataranni, PA Ravussin, E AF Weyer, C Walford, RL Harper, IT Milner, M MacCallum, T Tataranni, PA Ravussin, E TI Energy metabolism after 2 y of energy restriction: the Biosphere 2 experiment SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE metabolic rate; physical activity; energy restriction; aging; energy conservation; Biosphere 2 ID BODY-COMPOSITION; SYMPATHETIC ACTIVITY; DIETARY RESTRICTION; CALORIC RESTRICTION; FEEDBACK SIGNALS; GENE-EXPRESSION; OBESE WOMEN; FAT GAIN; EXPENDITURE; HUMANS AB Background: An adaptive decrease in energy expenditure (EE) in response to 6 mo of severely restricted energy intake was shown in a classic semistarvation study-the Minnesota experiment. Objective: Our objective was to examine whether such adaptation also occurs in response to less severe but sustained energy restriction. Design: Body composition, l-wk total EE (TEE), 24-h sedentary EE, and spontaneous physical activity were measured in 8 healthy subjects (4 men and 4 women) at the end of 2-y confinement inside Biosphere 2. Unexpectedly, the a food supply was markedly restricted during most of the confinement and all subjects experienced a marked, sustained weight loss (9.1 +/- 6.6 kg; P < 0.001) from the low-energy (7000-11000 kJ/d), low-fat (9% of energy), but nutrient-dense, diet they consumed. Results: The TEE inside Biosphere 2, assessed 3 wk before exit, averaged 10700 +/- 560 kJ/d (n = 8). Within 1 wk after exit, the adjusted 24-h EE and spontaneous physical activity were lower in the biospherians (n = 5) than in 152 control subjects (6% and 45%, respectively; both P < 0.01). Six months after exit and return to an ad libitum diet, body weight had increased to preentry levels; however, adjusted 24-h EE and spontaneous physical activity were still significantly lower than in control subjects. Conclusions: In lean humans. an adaptive decrease in EE appears to occur not only in states of life-threatening undernutrition, but also in response to less severe energy restriction sustained over several years. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85106 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA. Paragon Dev Co, Tucson, AZ USA. RP Weyer, C (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St, Phoenix, AZ 85106 USA. RI Biguzzi, Felipe/E-4724-2015 NR 54 TC 107 Z9 108 U1 0 U2 11 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2000 VL 72 IS 4 BP 946 EP 953 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 357JF UT WOS:000089494200010 PM 11010936 ER PT J AU Maciejewski, JP Kim, S Sloand, E Selleri, C Young, NS AF Maciejewski, JP Kim, S Sloand, E Selleri, C Young, NS TI Sustained long-term hematologic recovery despite a marked quantitative defect in the stem cell compartment of patients with aplastic anemia after immunosuppressive therapy SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE aplastic anemia; stem cells; progenitors; long-term bone marrow cultures ID CULTURE-INITIATING CELLS; PRIMITIVE HEMATOPOIETIC-CELLS; BONE-MARROW TRANSPLANTATION; LIMITING DILUTION; TELOMERE LENGTH; RECONSTITUTION; INVITRO; BLOOD; VIVO AB Previously, we reported that patients with aplastic anemia (AA) have profoundly decreased numbers of hematopoietic progenitor and stem cells as measured in the longterm culture initiating cell (LTC-IC) assay (Blood 1996;88:1983-1991). We now present results of a long-term prospective study of LTC-IC numbers in peripheral blood (PB) and bone marrow (BM) of patients treated with antithymocyte globulin and cyclosporin A. Numbers of secondary colony forming cells (secondary CFC) in long-term bone marrow culture (LTBMC) were used to quantitate LTC-IC. BM (N = 35) and PB (N = 41) secondary CFC from both untreated severe AA patients and responders to immunosuppressive therapy who were sampled up to 6 years after initial treatment were compared. Normal controls showed 148 +/- 38 (N = 17) and 16 +/- 3 (N = 14) secondary CFC per 10(6) in BM and PB, respectively. In cross-sectional analysis, prior to therapy, AA patients showed 2.6 +/- 1 (mean +/- SD) secondary CFC/10(6) BM MNC; within the first year after initial treatment (N = 14), secondary CFC number rose modestly to 8.2 +/- 2.2/10(6) MNC, and further increased to 15.8 +/- 7 (N = 17) at 2 years and 16.2 +/- 7/10(6) MNC (N = 25) 3 years after treatment. There was no further improvement in the secondary CFC numbers at 4, 5, and greater than or equal to 6 years (N = 37). Thus, while BM secondary CFC increased about 6-fold at 3 years post-therapy compared to presentation, they remained about only 10% of normal despite hematologic recovery. Similar data were obtained for PB, with approximately 4-fold increase in secondary CFC numbers within 2 years of therapy, to about 15% of normal values. We confirmed these observations in patients studied serially over a period of 4 years: initial secondary CFC were 2.35 +/- 1/10(6) BM MNC and 0.11 +/- 0.1/10(6) PB MNC improving to an average of 6 +/- 1.2 (BM; N = 12)and 2.4 +/- 1/10(6) MNC (PB; N= 14). In many cases of partial recovery, PB counts improve but do not normalize. When we studied secondary CFC numbers only in patients who achieved complete normalization of PB counts (ANC > 1,500/mm(3); platelets >10(5)/mm(3) and absolute reticulocytes >5 x 10(4)/mm(3)), BM secondary CFC were significantly higher than in patients with partial recovery; the PB secondary CFC number was modestly increased but remained below the normal values. Within the group of patients with complete recovery, there was no correlation between the secondary CFC and time after initial treatment. In addition, there also was no correlation between the secondary CFC number at presentation and the quality of hematopoietic recovery. Despite a limited expansion potential of a severely reduced stem cell pool, their numbers are sufficient to provide a long-term supply of mature blood cells. Published 2000 Wiley-Liss, Inc.(dagger) C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Univ Naples Federico II, Div Hematol, Naples, Italy. RP Maciejewski, JP (reprint author), NHLBI, Hematol Branch, Bldg 10,Room 7C108, Bethesda, MD 20892 USA. NR 25 TC 18 Z9 20 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD OCT PY 2000 VL 65 IS 2 BP 123 EP 131 DI 10.1002/1096-8652(200010)65:2<123::AID-AJH6>3.0.CO;2-M PG 9 WC Hematology SC Hematology GA 355CQ UT WOS:000089368400006 PM 10996829 ER PT J AU Bamford, RN de la Cruz, J Roessler, E Saplakoglu, U Burdine, R Goldmuntz, E Shen, M Schier, A Casey, B Muenke, M AF Bamford, RN de la Cruz, J Roessler, E Saplakoglu, U Burdine, R Goldmuntz, E Shen, M Schier, A Casey, B Muenke, M TI Mutations in the EGF-CFC gene, CRYPTIC cause human Left-Right axis abnormalities and Transposition of the Great Arteries. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Rutgers State Univ, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. NYU, Skirball Inst, New York, NY 10016 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1 BP 10 EP 10 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700002 ER PT J AU Yu, A Zhao, C Broman, KW Jang, W Mungall, AJ Dunham, I Weber, JL AF Yu, A Zhao, C Broman, KW Jang, W Mungall, AJ Dunham, I Weber, JL TI Genome-wide comparison of human genetic and physical maps. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Marshfield Med Res Fdn, Ctr Med Genet, Marshfield, WI 54449 USA. Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Wellcome Trust, Sanger Ctr, Hinxton, Cambs, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2 BP 10 EP 10 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700005 ER PT J AU Everett, LA Belyantseva, IA Noben-Trauth, K Cantos, R Chen, A Thakkar, SI Hoogstraten-Miller, SL Kachar, B Wu, DK Green, ED AF Everett, LA Belyantseva, IA Noben-Trauth, K Cantos, R Chen, A Thakkar, SI Hoogstraten-Miller, SL Kachar, B Wu, DK Green, ED TI Targeted disruption of mouse Pds provides key insight about the inner-ear defects encountered in Pendred syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD 20892 USA. NIH, Nat Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 19 BP 13 EP 13 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700020 ER PT J AU Wilcox, ER Naz, S Riazuddin, S Smith, TN Belyantseva, I Burton, Q Ben-Yosef, T Griffith, AJ Morell, RJ Wu, DK Kachar, B Riazuddin, S Friedman, TB AF Wilcox, ER Naz, S Riazuddin, S Smith, TN Belyantseva, I Burton, Q Ben-Yosef, T Griffith, AJ Morell, RJ Wu, DK Kachar, B Riazuddin, S Friedman, TB TI Mapping DFNB29 and cloning this novel nonsyndromic deafness gene on chromosome 21q22. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIDCD, Mol Genet Lab, Rockville, MD USA. NIH, NIDCD, LMB, Sect Sensory Cell Regenerat & Dev, Rockville, MD USA. Ctr Excellence Mol Biol, Lahore, Pakistan. NIH, NIDCD, LCB, Sect Struct Cell Biol, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 18 BP 13 EP 13 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700017 ER PT J AU Brown, SA Brown, LY Muenke, M AF Brown, SA Brown, LY Muenke, M TI Heterozygous mutations in the gene ZIC2 are a significant cause of sporadic holoprosencephaly (HPE): 15 cases; recurrence of an alanine tract expansion. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Columbia Univ, New York, NY 10027 USA. Med Genet Branch, NIH, NHGRI, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 24 BP 14 EP 14 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700023 ER PT J AU Olivos-Glander, IM Blancato, J Meck, J Biesecker, LG AF Olivos-Glander, IM Blancato, J Meck, J Biesecker, LG TI GLI3 deletions associated with Greig cephalopolysyndactyly and implications for phenotypic overlap with Acrocallosal syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, GDRB, Bethesda, MD USA. Georgetown Univ, Inst Mol Hum Gen, Washington, DC USA. Georgetown Univ, Dept Obstet & Gynaecol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 25 BP 14 EP 14 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700026 ER PT J AU Bishop, DT Goldstein, A Demenais, F AF Bishop, DT Goldstein, A Demenais, F CA Melanoma Genet Consortium TI Geographical variation in CDKN2A penetrance for melanoma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 St James Univ Hosp, Imperial Canc Res Fund, Gen Epid Lab, Leeds, W Yorkshire, England. NCI, Genet Epidemiol Branch, Bethesda, MD USA. INSERM, F-75654 Paris 13, France. RI Demenais, Florence/G-3298-2013 OI Demenais, Florence/0000-0001-8361-0936 NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 33 BP 16 EP 16 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700036 ER PT J AU Koivisto, PA Ikonen, T Matikainen, M Mononen, N Helin, HJ Tommola, S Tammela, T Schleutker, J Kallioniemi, OP AF Koivisto, PA Ikonen, T Matikainen, M Mononen, N Helin, HJ Tommola, S Tammela, T Schleutker, J Kallioniemi, OP TI Association of a novel E-cadherin gene coding region SNP with prostate cancer in a large population-based study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Tampere Univ, IMT, Canc Genet Lab, Tampere, Finland. Tampere Univ Hosp, Dept Pathol, Tampere, Finland. NIH, NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 37 BP 16 EP 16 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700038 ER PT J AU Stephan, DA Howell, G Bailey-Wilson, J Smith, JR Schleutker, J Baffoe-Bonnie, A Hu, P Joseph, S Malechek, L Papadopolous, N Robbins, CR Gildea, D Makalowska, I Carpten, JD Budendorf, L Hieskanen, M Zucchi, I Isaacs, W Trent, JM AF Stephan, DA Howell, G Bailey-Wilson, J Smith, JR Schleutker, J Baffoe-Bonnie, A Hu, P Joseph, S Malechek, L Papadopolous, N Robbins, CR Gildea, D Makalowska, I Carpten, JD Budendorf, L Hieskanen, M Zucchi, I Isaacs, W Trent, JM CA Prostate Invest Grp TI Toward a gene at Xq27.3 responsible for hereditary prostate cancer (HPC-X). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 CNMC, Res Ctr Genet Med, Washington, DC USA. NIH, NHGRI, Bethesda, MD USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Columbia Univ, New York, NY 10027 USA. Sanger Ctr, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 34 BP 16 EP 16 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700034 ER PT J AU Lundberg, YW Greer, KA Zhao, J Xiong, W Pavan, WJ Biesecker, LG Finnell, RH AF Lundberg, YW Greer, KA Zhao, J Xiong, W Pavan, WJ Biesecker, LG Finnell, RH TI Mapping of a chromosomal locus for valproic acid-induced neural tube defects. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Dept Pediat & Genet, Omaha, NE USA. Texas A&M Univ, College Stn, TX 77843 USA. NIH, NHGRI, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 58 BP 20 EP 20 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700058 ER PT J AU Riazuddin, S Castelein, CM Friedman, TB Lalwani, AK Griffith, AJ Naz, S Smith, TN Liburd, NA Mastroianni, MA Riazuddin, S Wilcox, ER AF Riazuddin, S Castelein, CM Friedman, TB Lalwani, AK Griffith, AJ Naz, S Smith, TN Liburd, NA Mastroianni, MA Riazuddin, S Wilcox, ER TI A dominant modifier, DFNM1 protects seven individuals from DFNB26 hearing impairment. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIDCD, Genet Mol Lab, Rockville, MD USA. Ctr Excellence Mol Biol, Lahore, Pakistan. Univ Calif San Francisco, Lab Mol Otol, San Francisco, CA USA. NIH, NIDCD, NeuroOtol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 56 BP 20 EP 20 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700057 ER PT J AU Mohlke, KL Lange, EM Valle, T Collins, FS Boehnke, M AF Mohlke, KL Lange, EM Valle, T Collins, FS Boehnke, M CA FUSION Study TI Marker-marker linkage disequilibrium extends beyond 1 cM on chromosome 20 in Finns. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 86 BP 25 EP 25 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700087 ER PT J AU Smith, MW Lautenberger, J Shin, HD Washburn, K O'Brien, SJ AF Smith, MW Lautenberger, J Shin, HD Washburn, K O'Brien, SJ TI Gene mapping across tens of centiMorgans in admixed populations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, SAIC, IRSP, Lab Genom Divers, Frederick, MD USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RI Smith, Michael/B-5341-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 91 BP 25 EP 25 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700092 ER PT J AU Lee, CS Xue, Y Zhang, X Wang, W AF Lee, CS Xue, Y Zhang, X Wang, W TI A protein complex involved in Werner syndrome links premature aging to DNA repair. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIA, Genet Lab, Baltimore, MD USA. SmithKline Beecham Pharmaceut, King Of Prussia, PA 19406 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 99 BP 28 EP 28 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700100 ER PT J AU Biesecker, BB Peters, KT Francomano, CA AF Biesecker, BB Peters, KT Francomano, CA TI Living with Marfan syndrome: perceptions of the condition and its management. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Med Genet Branch, Bethesda, MD USA. Penn State Univ, Dept Behav Hlth, University Pk, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 115 BP 32 EP 32 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700115 ER PT J AU Green, MJ Biesecker, BB McInerney, A Fost, N AF Green, MJ Biesecker, BB McInerney, A Fost, N TI Can an interactive computer program educate patients about breast cancer susceptibility, and does it influence their intent to undergo testing? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Penn State Coll Med, Dept Humanities, Hershey, PA USA. NIH, NHGRI, Med Genet Branch, Bethesda, MD USA. Univ Wisconsin, Dept Pediat, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 119 BP 33 EP 33 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700120 ER PT J AU Douglas, JA Gruber, SB Gillanders, E Trent, JM Boehnke, M AF Douglas, JA Gruber, SB Gillanders, E Trent, JM Boehnke, M TI Use of experimentally constructed haplotypes in linkage and linkage disequilibrium studies. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 122 BP 34 EP 34 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700122 ER PT J AU Ghebranious, N Che, J David, D Fan, Y Zhao, C Marth, G Doktycz, M Weber, JL AF Ghebranious, N Che, J David, D Fan, Y Zhao, C Marth, G Doktycz, M Weber, JL TI Human diallelic insertion/deletion polymorphisms. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Marshfield Med Res Fdn, Ctr Med Genet, Marshfield, WI USA. NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD USA. Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 124 BP 34 EP 34 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700123 ER PT J AU Schiffmann, R Kopp, JB Austin, H Moore, DF Sabnis, S Weibel, T Balow, JE Brady, RO AF Schiffmann, R Kopp, JB Austin, H Moore, DF Sabnis, S Weibel, T Balow, JE Brady, RO TI Efficacy and safety of enzyme replacement therapy for Fabry disease demonstrated by a double-blind placebo-controlled trial. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA. AFIP, Div Nephrol, Washington, DC USA. NR 0 TC 5 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 135 BP 38 EP 38 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700138 ER PT J AU Francis, PJ Chung, JJ Yasui, M Berry, V Wyatt, MK Wistow, G Moore, AT Agre, P Bhattacharya, SS AF Francis, PJ Chung, JJ Yasui, M Berry, V Wyatt, MK Wistow, G Moore, AT Agre, P Bhattacharya, SS TI Functional analyses of lens aquaporin mutants linked to human cataracts. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Inst Ophthalmol, London, England. Moorfields Eye Hosp, London, England. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. NEI, NIH, Bethesda, MD USA. Addenbrookes Hosp, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 142 BP 40 EP 40 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700145 ER PT J AU Liu, CY Badner, JA Christian, SL Guroff, JJ Detera-Wadleigh, SD Gershon, ES AF Liu, CY Badner, JA Christian, SL Guroff, JJ Detera-Wadleigh, SD Gershon, ES TI Further linkage evidence for a bipolar disorder susceptibility locus on 13q32. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. NIMH, NIH, Bethesda, MD USA. Hunan Med Univ, Natl Lab Med Genet, Changsha, Peoples R China. RI Liu, Chunyu/G-7561-2012 OI Liu, Chunyu/0000-0002-5986-4415 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 183 BP 47 EP 47 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700184 ER PT J AU Silander, K Watanabe, R Valle, T Mohlke, K Stringham, H Doheny, K Pugh, E Bergman, R Tuomilehto, J Collins, F Boehnke, M AF Silander, K Watanabe, R Valle, T Mohlke, K Stringham, H Doheny, K Pugh, E Bergman, R Tuomilehto, J Collins, F Boehnke, M CA FUSION Study Grp TI Genome scan results of an independent set of Finnish affected sibling pairs with type 2 diabetes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 193 BP 48 EP 48 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700192 ER PT J AU Feitosa, MF Borecki, IB Rich, SS Arnett, DK Sholinsky, P Myers, RH Province, MA AF Feitosa, MF Borecki, IB Rich, SS Arnett, DK Sholinsky, P Myers, RH Province, MA TI Genome scan for body mass index in the National Heart, Lung, and Blood Institute Family Heart Study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Minnesota, Minneapolis, MN USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Boston, MA 02215 USA. RI Feitosa, Mary/K-8044-2012 OI Feitosa, Mary/0000-0002-0933-2410 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 197 BP 49 EP 49 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700197 ER PT J AU Hsu, AP Tsai, EJ Anderson, SM Fischer, RE Malech, H Buckley, RH Puck, JM AF Hsu, AP Tsai, EJ Anderson, SM Fischer, RE Malech, H Buckley, RH Puck, JM TI Unusual X-linked SCID phenotype due to mutation of the poly-A addition signal of IL2RG. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, NIH, Res Scholars Program, Coconut Grove, FL 33133 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Duke Univ, Sch Med, Dept Pediat, Durham, NC 27706 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 206 BP 50 EP 50 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700207 ER PT J AU Modi, WS Goedert, JJ O'Brien, TR Buchbinder, S Giorgi, J Rinaldo, C Donfield, S O'Brien, SJ AF Modi, WS Goedert, JJ O'Brien, TR Buchbinder, S Giorgi, J Rinaldo, C Donfield, S O'Brien, SJ TI A promoter allele in the eotaxin chemokine gene protects against HIV-1 infection. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Frederick Canc Res, SAIC, Frederick, MD USA. NCI, Frederick, MD 21702 USA. NCI, Rockville, MD 20852 USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. Univ Calif Los Angeles, Dept Med, CIC, Los Angeles, CA 90095 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 221 BP 53 EP 53 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700221 ER PT J AU Johnston, JJ Kelley, RI Crawford, TO Morton, DH Agarwala, R Koch, T Schaffer, AA Francomano, CA Biesecker, LG AF Johnston, JJ Kelley, RI Crawford, TO Morton, DH Agarwala, R Koch, T Schaffer, AA Francomano, CA Biesecker, LG TI A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Clin Special Children, Strasburg, PA 17579 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Konrad Zuse Zentrum Informationstech, Berlin, Germany. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 0 Z9 0 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 229 BP 54 EP 54 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700228 ER PT J AU Slavotinek, A Stone, E Heckinlively, J Green, J Heon, E Musarella, M Parfrey, P Sheffield, V Biesecker, L AF Slavotinek, A Stone, E Heckinlively, J Green, J Heon, E Musarella, M Parfrey, P Sheffield, V Biesecker, L TI Bardet-Biedl syndrome is caused by mutations in the MKKS gene, a putative chaperonin. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Iowa, Howard Hughes Med Inst, Dept Ophth, Iowa City, IA 52242 USA. Univ Iowa, Dept Peds, Iowa City, IA USA. Harbor UCLA Med Ctr, Dept Ophth, Torrance, CA 90509 USA. Mem Univ Newfoundland, Fac Med, St Johns, NF, Canada. Univ Toronto, Dept Ophth, Toronto, ON, Canada. Long Isl Coll Hosp, Brooklyn, NY 11201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 234 BP 55 EP 55 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700235 ER PT J AU Rose, PS Levy, HP Johnston, JJ Davis, J Griffith, AJ Liberfarb, RM Francomano, CA AF Rose, PS Levy, HP Johnston, JJ Davis, J Griffith, AJ Liberfarb, RM Francomano, CA TI Proposed diagnostic criteria for Stickler syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIDCD, NIH, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 235 BP 56 EP 56 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700236 ER PT J AU Hacia, JG Fang, NY Greiner, TC Armitage, JO Chan, WC Vose, J Weisenburger, D Mayer, RA Collins, FS AF Hacia, JG Fang, NY Greiner, TC Armitage, JO Chan, WC Vose, J Weisenburger, D Mayer, RA Collins, FS TI ATM mutation detection in lymphomas using oligonucleotide microarrays. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, GMMB, Bethesda, MD USA. UNMC, Omaha, NE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 290 BP 66 EP 66 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700291 ER PT J AU Hostetter, GH Andersen, CL Bubendorf, L Kononen, J Dougherty, E Grigoryan, A Kallioniemi, O AF Hostetter, GH Andersen, CL Bubendorf, L Kononen, J Dougherty, E Grigoryan, A Kallioniemi, O TI Design of an automated spot counting program for interphase FISH on the tissue microarray. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Canc Genet Branch, Bethesda, MD USA. Texas A&M Univ, CAMDI, College Stn, TX 77843 USA. RI Andersen, Claus Lindbjerg/A-9217-2012; Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011; Andersen, Claus/C-1477-2017 OI Andersen, Claus Lindbjerg/0000-0002-7406-2103; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Andersen, Claus/0000-0002-7406-2103 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 318 BP 71 EP 71 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700319 ER PT J AU Podolski, J Byrski, T Zajaczek, S Druck, T Zimonjic, DB Popescu, NC Kata, G Borowska, A Gronwald, J Lubinski, J Huebner, K AF Podolski, J Byrski, T Zajaczek, S Druck, T Zimonjic, DB Popescu, NC Kata, G Borowska, A Gronwald, J Lubinski, J Huebner, K TI Characterization of a familial RCC-associated t(2;3)(q33;q21) chromosome translocation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Pomeranian Acad Med, Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland. Univ Szczecin, Dept Human Ecol, Szczecin, Poland. Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Med Ctr Postgrad Educ, Dept Urol, Warsaw, Poland. RI BYRSKI, Tomasz/I-2844-2014; Gronwald, Jacek/A-4576-2017 OI Gronwald, Jacek/0000-0002-3643-2871 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 326 BP 73 EP 73 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700329 ER PT J AU Sun, L Fong, Y Sham, JST Guo, Y Deng, M Liang, Q Zhang, H Zhou, H Tideman, H Trent, JM Guan, XY AF Sun, L Fong, Y Sham, JST Guo, Y Deng, M Liang, Q Zhang, H Zhou, H Tideman, H Trent, JM Guan, XY TI Analysts of genetic alterations in primary nasopharyngeal carcinoma by comparative genomic hybridization (CGH). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Sun Yat Sen Univ Med Sci, Ctr Canc, Hong Kong, Peoples R China. Univ Hong Kong, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 331 BP 74 EP 74 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700332 ER PT J AU Guan, XY Zhou, H Sham, JST Zhang, H Trent, JM AF Guan, XY Zhou, H Sham, JST Zhang, H Trent, JM TI Characterization of a complex chromosome rearrangement involving 6q in a melanoma cell line: Isolation of a candidate tumor suppressor gene interrupted by the breakpoint at 6q16. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Hong Kong, Dept Clin Oncol, Hong Kong, Peoples R China. NIH, NHGRI, Canc Genet Branch, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 342 BP 75 EP 75 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700343 ER PT J AU Roschke, AV Stover, K Tonon, G Schaffer, AA Kirsch, IR AF Roschke, AV Stover, K Tonon, G Schaffer, AA Kirsch, IR TI A "static" karyotype in epithelial cancer cell lines despite ongoing chromosomal instability. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Dept Genet, Med Branch, Bethesda, MD USA. NCBI, Computat Biol Branch, Bethesda, MD USA. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 339 BP 75 EP 75 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700339 ER PT J AU Brown, KM Stephan, DA Zhang, J Heiskanen, M Bethel, G Robbins, CR Carder, C Mungall, A Meltzer, PS Trent, JM AF Brown, KM Stephan, DA Zhang, J Heiskanen, M Bethel, G Robbins, CR Carder, C Mungall, A Meltzer, PS Trent, JM TI Cloning of a recurrent site of chromosome translocation in cutaneous melanoma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Res Ctr Genet Med, CNMC, Washington, DC USA. GWU Genet, Washington, DC USA. NIH, NHGRI, Bethesda, MD USA. Sanger Ctr, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 351 BP 77 EP 77 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700351 ER PT J AU Riggins, GJ Loging, WT Lal, A Siu, I Boon, C Turner, C Strausberg, RL AF Riggins, GJ Loging, WT Lal, A Siu, I Boon, C Turner, C Strausberg, RL TI SAGEmap: A gene expression resource for the Cancer Genome Anatomy Project. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. NCI, Canc Genome Anat Project, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 357 BP 78 EP 78 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700359 ER PT J AU Balsara, BR Pel, J De Rienzo, A Simon, D Tosolini, A Lu, YY Shen, F Fan, X Lin, WY Buetow, KH London, WT Testa, JR AF Balsara, BR Pel, J De Rienzo, A Simon, D Tosolini, A Lu, YY Shen, F Fan, X Lin, WY Buetow, KH London, WT Testa, JR TI Human hepatocellular carcinoma is characterized by a highly consistent pattern of genomic imbalances, including frequent loss of 16q23.1-24.1. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Med Coll Penn & Hahnemann Univ, Sch Med, Philadelphia, PA 19102 USA. Beijing Inst Canc Res, Dept Biochem & Mol Biol, Beijing, Peoples R China. Shanghai Med Univ, Haimen City Canc Prevent Inst, Shanghai 200032, Peoples R China. NCI, Lab Populat Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 361 BP 79 EP 79 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700364 ER PT J AU Parry, DM Makariou, E Baser, NE AF Parry, DM Makariou, E Baser, NE TI Predictors of vestibular schwannoma growth in neurofibromatosis 2 (NF2). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Radiol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 360 BP 79 EP 79 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700361 ER PT J AU Shugart, YY Hemminki, K Vaittinen, P Kingman, A AF Shugart, YY Hemminki, K Vaittinen, P Kingman, A TI Evidence for apparent anticipation and heterogeneity in familial Hodgkin's disease and non-Hodgkin's lymphoma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, CIDR, Baltimore, MD 21218 USA. Karolinska Inst, Dept Biosci, Huddinge, Sweden. Natl Board Hlth & Welf, Ctr Epidemiol, Stockholm, Sweden. NIH, Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 407 BP 86 EP 86 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700408 ER PT J AU Kallioniemi, AH Monni, OM Kononen, J Barlund, M Mousses, S Weaver, JD Bittner, M Chen, Y Torhorst, J Sauter, G Kallioniemi, OP AF Kallioniemi, AH Monni, OM Kononen, J Barlund, M Mousses, S Weaver, JD Bittner, M Chen, Y Torhorst, J Sauter, G Kallioniemi, OP TI High-resolution analysis of gene copy number changes across the genome in hundreds of tumors: CGH on cDNA microarrays followed by FISH analysis on tissue microarrays identify genes involved in DNA amplifications at 17q23 in breast cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Canc Genet Branch, Bethesda, MD USA. Univ Tampere, Inst Med Technol, Tampere, Finland. Tampere Univ Hosp, Tampere, Finland. Univ Basel, Inst Pathol, Basel, Switzerland. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 430 BP 90 EP 90 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700429 ER PT J AU Crabtree, JS Scacheri, PC Novotny, EA Garrett-Beal, L Chen, A Edgemon, KA Marx, SJ Spiegel, AM Chandrasekharappa, SC Collins, FS AF Crabtree, JS Scacheri, PC Novotny, EA Garrett-Beal, L Chen, A Edgemon, KA Marx, SJ Spiegel, AM Chandrasekharappa, SC Collins, FS TI Knockout of the mouse MEN1 gene gives a lethal phenotype in the heterozygous chimera. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 440 BP 92 EP 92 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700440 ER PT J AU Andersen, CL Monni, OM Kononen, J Barlund, M Bucher, C Hass, P Nocicito, A Bissig, H Sauter, G Kallioniemi, OP Kallioniemi, A AF Andersen, CL Monni, OM Kononen, J Barlund, M Bucher, C Hass, P Nocicito, A Bissig, H Sauter, G Kallioniemi, OP Kallioniemi, A TI High-throughput gene copy number analysis in 4700 tumors: FISH analysis on tissue microarrays identifies multiple tumor types with amplification of the MB-174 gene, a novel amplified gene originally found in breast cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Canc Genet Branch, Bethesda, MD USA. Danish Canc Soc, Aarhus, Denmark. Tampere Univ, Inst Med Technol, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Tampere, Finland. Univ Basel, Inst Pathol, Basel, Switzerland. RI bucher, christoph/A-2520-2008; Andersen, Claus Lindbjerg/A-9217-2012; Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011; Andersen, Claus/C-1477-2017 OI Andersen, Claus Lindbjerg/0000-0002-7406-2103; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Andersen, Claus/0000-0002-7406-2103 NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 448 BP 93 EP 93 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700447 ER PT J AU Kanaan, YM Kpenu, E Utley, K Brody, LC Dunston, GM Whitfield-Broome, C AF Kanaan, YM Kpenu, E Utley, K Brody, LC Dunston, GM Whitfield-Broome, C TI BRCA2 mutations in African Americans. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Howard Univ, Coll Med, Dept Microbiol, Washington, DC 20059 USA. Howard Univ, Coll Med, Dept Biochem, Washington, DC 20059 USA. Howard Univ, Coll Med, Dept Biol Mol, Washington, DC 20059 USA. Howard Univ, Ctr Canc, Ctr Human Genome, Washington, DC 20059 USA. NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 455 BP 94 EP 94 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700456 ER PT J AU Opalka, B Bardenheuer, W Marquitan, G Werner, N Juelicher, K Topal, H Horikawa, I Barrett, JC Schuette, J AF Opalka, B Bardenheuer, W Marquitan, G Werner, N Juelicher, K Topal, H Horikawa, I Barrett, JC Schuette, J TI Towards identification of a senescence associated gene/tumor suppressor gene (TSG) in the NRC-2 locus in human chromosome band 3p14. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Essen Gesamthsch, Innere Med Klin, Essen, Germany. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 453 BP 94 EP 94 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700455 ER PT J AU Wong, EY Le, TT Bruchez, MP Phillips, VE Jiang, Y Gooden, GC Treadway, JA Larson, JP Lai, JH Bittner, ML AF Wong, EY Le, TT Bruchez, MP Phillips, VE Jiang, Y Gooden, GC Treadway, JA Larson, JP Lai, JH Bittner, ML TI Detection of single-nucleotide polymorphism and expression analysis using microspheres encoded with quantum dot semiconductor nanocrystals. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Quantum Dot Corp, Palo Alto, CA 94303 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RI Bruchez, Marcel/C-2271-2009 OI Bruchez, Marcel/0000-0002-7370-4848 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 458 BP 95 EP 95 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700458 ER PT J AU Monni, OM Barlund, M Kononen, J Mousses, S Weaver, JD Bittner, M Chen, Y Torhorst, J Sauter, G Kallioniemi, OP Kallioniemi, A AF Monni, OM Barlund, M Kononen, J Mousses, S Weaver, JD Bittner, M Chen, Y Torhorst, J Sauter, G Kallioniemi, OP Kallioniemi, A TI Expression screening to identify target genes of chromosomal alterations: cDNA microarray reveals a novel amplified, overexpressed and rearranged gene MB-17A at 17q23 in breast cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Tampere, Finland. Univ Basel, Inst Pathol, Basel, Switzerland. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 464 BP 96 EP 96 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700464 ER PT J AU Hu, CA Yu, J Lin, WW Donald, SP Sun, XY Almashanu, S Steel, G Phang, J Valle, D AF Hu, CA Yu, J Lin, WW Donald, SP Sun, XY Almashanu, S Steel, G Phang, J Valle, D TI Overexpression of proline oxidase, a late p53-induced-apoptosis gene (PIG6), induces apoptosis in cancer cells. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Inst Med Genet, Baltimore, MD USA. Predoctoral Training Program Human Genet, JHMI, Baltimore, MD USA. NIH, NCI, FCRDC, BRL, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 476 BP 98 EP 98 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700476 ER PT J AU Orozco, L Atkinson, T Macias, M Garcia, F Ridaura, C Dean, M AF Orozco, L Atkinson, T Macias, M Garcia, F Ridaura, C Dean, M TI Loss of heterozygosity and RB1 mutations associated with retinoblastoma in Mexican patients. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Inst Nacl Pediat, Dept Human Genet, Mexico City, DF, Mexico. Inst Nacl Pediat, Dept Pathol, Mexico City, DF, Mexico. NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD USA. IPN, CICATA, Interinst Program Mol Biomed, Mexico City, DF, Mexico. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 486 BP 100 EP 100 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700487 ER PT J AU MacDonald, T Brown, KM Cogen, PH Chen, YW Rood, B Packer, RJ Stephan, DA AF MacDonald, T Brown, KM Cogen, PH Chen, YW Rood, B Packer, RJ Stephan, DA TI Identification of expression changes of prognostic and therapeutic value in metastasizing medulloblastoma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. George Washington Univ, Washington, DC USA. NIH, NHGRI, Bethesda, MD USA. RI MacDonald, Tobey/D-4554-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 500 BP 102 EP 102 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700500 ER PT J AU Tsai, YY McGlynn, KA Cassidy, AB Hu, Y Arnold, J Engstrom, PF Buetow, KH AF Tsai, YY McGlynn, KA Cassidy, AB Hu, Y Arnold, J Engstrom, PF Buetow, KH TI Identification of lung cancer susceptibility genes after adjusting for population stratification. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, DCEG, Bethesda, MD USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 521 BP 105 EP 105 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700522 ER PT J AU Tseng, TL Chen, YMA Struewing, JP Buetow, K AF Tseng, TL Chen, YMA Struewing, JP Buetow, K TI Identification and characterization of novel polymorphisms/mutations in the glycine N-methyltransferase gene in liver cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Lab Populat Genet, Bethesda, MD 20892 USA. Natl Yang Ming Univ, Sch Med, Inst Publ Hlth, Div Prevent Med, Taipei 112, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 520 BP 105 EP 105 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700519 ER PT J AU Lipkin, SM Wang, V Kirsch, I Hadley, D Lynch, H Collins, F AF Lipkin, SM Wang, V Kirsch, I Hadley, D Lynch, H Collins, F TI Absence of MLH3 coding sequence germline mutations in HNPCC families. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, GMBB, NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Creighton Univ, Omaha, NE 68178 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 530 BP 107 EP 107 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700530 ER PT J AU Levy, HP Johnston, JJ Davis, J Balog, J Rose, PS Schaffer, A Dietz, H Francomano, CA AF Levy, HP Johnston, JJ Davis, J Balog, J Rose, PS Schaffer, A Dietz, H Francomano, CA TI A new connective tissue disorder with features overlapping those of Ehlers-Danlos, Marfan and Stickler syndromes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 545 BP 110 EP 110 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700546 ER PT J AU Lacbawan, F Schonberg, S Walton, D Koroulakis, P Thackray, H AF Lacbawan, F Schonberg, S Walton, D Koroulakis, P Thackray, H TI Complex cardiac anomalies in deletion 9p22, duplication 5q34 of maternal origin: a case report. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. American Med Lab, Chantilly, VA USA. NIH, NHGRI, Med Genet Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 575 BP 115 EP 115 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700576 ER PT J AU Goker-Alpan, O Kozma, C Nelson, LM Francomano, CA AF Goker-Alpan, O Kozma, C Nelson, LM Francomano, CA TI Premature ovarian failure and marfanoid features: A new association? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, HDB, NIH, Bethesda, MD USA. Georgetown Univ, Med Ctr, Dept Genet, Washington, DC 20007 USA. NICHD, DEB, NIH, Bethesda, MD USA. NHGRI, MGB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 581 BP 116 EP 116 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700582 ER PT J AU Kaler, SG Thackray, H AF Kaler, SG Thackray, H TI Sternal cleft with supraumbilical midline raphe and hemangiomas: An X-linked lethal syndrome? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NINDS, Clin Neurosci Program, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NIH, NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 589 BP 117 EP 117 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700589 ER PT J AU Ng, D Schonberg, S Luban, N Kaler, S AF Ng, D Schonberg, S Luban, N Kaler, S TI Molecular basis of Bernard-Souller syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NICHD, Bethesda, MD 20892 USA. Amer Med Lab, Chantilly, VA USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NIH, NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 587 BP 117 EP 117 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700588 ER PT J AU Dent, KM Chen, Z Issa, B Meloni-Ehrig, A Shepard, R Forsyth, D Zhu, X Carroll, K Guan, X Brothman, A Carey, J AF Dent, KM Chen, Z Issa, B Meloni-Ehrig, A Shepard, R Forsyth, D Zhu, X Carroll, K Guan, X Brothman, A Carey, J TI Two patients with distinct structural anomalies of chromosome 10 determined by advanced molecular cytogenetic techniques. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Utah, Salt Lake City, UT 84112 USA. Univ Utah, Cytogenet Lab, Salt Lake City, UT USA. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 598 BP 118 EP 118 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700599 ER PT J AU Russell, HF Power, TJ Mitchell, LE Robins, PM Ross, JL Muenke, M AF Russell, HF Power, TJ Mitchell, LE Robins, PM Ross, JL Muenke, M TI Turner Syndrome: A genetic model for Attention-Deficit/Hyperactivity Disorder. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. Dupont Hosp Children, Wilmington, DE USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NHGRI, Med Genet Branch, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 630 BP 124 EP 124 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700633 ER PT J AU Gropman, AL Levin, SW Yao, L Lin, T Suchy, S Sabnis, S Hadley, D Nussbaum, RL AF Gropman, AL Levin, SW Yao, L Lin, T Suchy, S Sabnis, S Hadley, D Nussbaum, RL TI A novel mutation in exon 22 underlies a mild cognitive phenotype and atypical renal features in a patient with oculocerebral renal syndrome (OCRL). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Neurogenet Branch, Bethesda, MD 20892 USA. NICHHD, NIH, Heritable Disorders Branch, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Dept Pediat, Washington, DC 20307 USA. NIH, Lab Genet Dis Res, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 654 BP 128 EP 128 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700657 ER PT J AU Cornejo, L Garca, E Chavira, S Muenke, M Saavedra, D AF Cornejo, L Garca, E Chavira, S Muenke, M Saavedra, D TI Clinical data and molecular analysis in twenty-four Mexican Apert syndrome patients. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Autonomous Hidalgo State Univ, Sch Med, Sci Hlth Inst, Pachuca De Soto, Mexico. IMSS, CIBO, W Biol Res Ctr, Guadalajara, Jalisco, Mexico. IMSS, CIBO, Mexican Social Segur Inst, Guadalajara, Jalisco, Mexico. Gen Hosp Dr Manuel Gea Gonzalez, Mexico City, DF, Mexico. NHGRI, Clin Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 686 BP 133 EP 133 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700688 ER PT J AU Ho, VC Ho, NC AF Ho, VC Ho, NC TI Monozygotic twins with fetal akinesia: The value of clinico-pathological work-up in predicting recurrence risks. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Univ Singapore, Dept Oral Pathol, Singapore 117548, Singapore. NIH, NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 687 BP 133 EP 133 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700686 ER PT J AU Saavedra, D Cornejo, L de la Fuente, B Ortiz-Monasterio, F Muenke, M AF Saavedra, D Cornejo, L de la Fuente, B Ortiz-Monasterio, F Muenke, M TI Facial Clefting Syndrome: A new autosomal recessive entity in Mexican population. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Hosp Dr Manuel Gea Giz, Mexico City, DF, Mexico. Autonomous Hidalgo State Univ, Sch Med, Hlth Sci Inst, Pachuca De Soto, Mexico. Autonomous Nuevo Leon Univ, Fac Med, Monterrey, Mexico. NHGRI, Med Genet Brach, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 725 BP 140 EP 140 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700726 ER PT J AU Hay, BN Schonberg, SA Lacbawan, F AF Hay, BN Schonberg, SA Lacbawan, F TI Clinical and cytogenetic findings in an infant with rec(8)dup(8p) and mosaic trisomy 8. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD USA. American Med Lab Inc, Chantilly, VA USA. Childrens Natl Med Ctr, Dept Med Genet, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 774 BP 149 EP 149 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700775 ER PT J AU Herrera, LM Mumm, S Forabosco, A Waeltz, PW Ruini, L Nagaraja, R Esposito, T Rocchi, M Shlessinger, D AF Herrera, LM Mumm, S Forabosco, A Waeltz, PW Ruini, L Nagaraja, R Esposito, T Rocchi, M Shlessinger, D TI X/autosomal translocations in the Xq region associated with premature ovarian failure fall both within and outside genes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIA, Genet Lab, Baltimore, MD USA. Univ Washington, Sch Med, Div Bone & Mineral Dis, Seattle, WA USA. Barnes Jewish Hosp, St Louis, MO 63110 USA. Univ Modena & Reggio Emilia, Dept Morphol & Legal Med Sci, Modena, Italy. Inst Genet, Bari, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 880 BP 166 EP 166 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700879 ER PT J AU Karkera, JD Du, Y Roessler, E Banfi, S Ballabio, A Muenke, M AF Karkera, JD Du, Y Roessler, E Banfi, S Ballabio, A Muenke, M TI Role of VAX1 and VAX2 in holoprosencephaly. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. Telethon Inst Genet & Med, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 894 BP 169 EP 169 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700895 ER PT J AU Jaradat, SA Tanaka, T O'neill, L Boheler, K Ko, MSH AF Jaradat, SA Tanaka, T O'neill, L Boheler, K Ko, MSH TI Global analysis of gene expression patterns during differentiation of embryonic stem cells. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Baltimore, MD USA. NIA, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 906 BP 171 EP 171 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700907 ER PT J AU Wassif, CA Zhao, Y Mackem, S Westphal, H Porter, FD AF Wassif, CA Zhao, Y Mackem, S Westphal, H Porter, FD TI Limb and CNS malformations in Lhx2-l-: LhxB9-l- mutant embryos. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 HBD, Bethesda, MD USA. NICHD, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. LMGD, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 914 BP 173 EP 173 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700917 ER PT J AU Kuehn, MR Lowe, LA Yamada, S Yamaguchi, T AF Kuehn, MR Lowe, LA Yamada, S Yamaguchi, T TI Asymmetric lateral plate and midline nodal expression in the proper development of laterality in the mouse embryo. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Osaka Univ, Fac Dent, Suita, Osaka 5650871, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 922 BP 174 EP 174 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700924 ER PT J AU Mansfield, EA Chae, JJ Komarow, H Brotz, T Centola, M Kastner, DL AF Mansfield, EA Chae, JJ Komarow, H Brotz, T Centola, M Kastner, DL TI Pyrin, the FMF protein, colocalizes with microtubules in vivo and in vitro. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, ARBNIAMS, Bethesda, MD 20892 USA. NIH, EIBNCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 931 BP 176 EP 176 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700930 ER PT J AU Kim, PS Iyer, RK Lu, KV Yu, H Karemi, A Kern, RM Tai, D Miller, J Cederbaum, SD Grody, WW AF Kim, PS Iyer, RK Lu, KV Yu, H Karemi, A Kern, RM Tai, D Miller, J Cederbaum, SD Grody, WW TI Expression of Macaca fascicularis liver arginase in erythrocytes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Div Genet, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Mental Retardat Res Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Pediat, Los Angeles, CA 90024 USA. NIDDKD, NIH, Biol Chem Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 967 BP 182 EP 182 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700966 ER PT J AU Park, JK Tayebi, N Callahan, M Samimi, R Sidransky, E AF Park, JK Tayebi, N Callahan, M Samimi, R Sidransky, E TI The evolutionary origins of the pseudogenes for glucocerebrosidase and metaxin on human chromosome 1q21. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 974 BP 183 EP 183 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700975 ER PT J AU Kim, AJ Ko, M Schlessinger, D AF Kim, AJ Ko, M Schlessinger, D TI X-linked RING zinc finger, ZNF127-Xp is active during mouse embryonic development. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Genet Lab, Baltimore, MD USA. NIA, IRP, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 978 BP 184 EP 184 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700980 ER PT J AU King, LM Francomano, CA AF King, LM Francomano, CA TI Characterization of PDZ1, a gene in Xq13.1 encoding a protein with a single PDZ domain expressed in human bone marrow stromal cells. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 976 BP 184 EP 184 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700979 ER PT J AU Leyne, M Mull, J Gill, SP Cuajungco, MP Karbott, C Johnson, B Robbins, CM Makalowska, I Pinkett, HW Maayan, C Axelrod, FB Blumenfeld, A Brownstein, M Gusella, JF Slaugenhaupt, SA AF Leyne, M Mull, J Gill, SP Cuajungco, MP Karbott, C Johnson, B Robbins, CM Makalowska, I Pinkett, HW Maayan, C Axelrod, FB Blumenfeld, A Brownstein, M Gusella, JF Slaugenhaupt, SA TI Analysis and complete genomic sequence of the refined 178 kb Familiar Dysautonomia candidate region on chromosome 9q31. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Harvard Inst Human Genet, Boston, MA USA. Natl Inst Hlth, Bethesda, MD USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. NYU, Med Ctr, New York, NY 10016 USA. RI Brownstein, Michael/B-8609-2009; Cuajungco, Math/B-2647-2008 OI Cuajungco, Math/0000-0003-0749-9564 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 990 BP 186 EP 186 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700992 ER PT J AU Galdzicka, M Damschroder-Williams, P Hirshman, G Long, R Kashani, A Winfield, S Martin, BM Kleijer, WJ Ginns, EI AF Galdzicka, M Damschroder-Williams, P Hirshman, G Long, R Kashani, A Winfield, S Martin, BM Kleijer, WJ Ginns, EI TI Variation in the clinical manifestations in Ellis van Creveld may result from differential expression of the EVC gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, NIH, Clin Neurosci Branch, Bethesda, MD USA. Erasmus Univ, Rotterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 994 BP 187 EP 187 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700997 ER PT J AU Soares, ML Centola, M Chae, J Saraiva, MJ Kastner, DL AF Soares, ML Centola, M Chae, J Saraiva, MJ Kastner, DL TI Human transthyretin intronic open reading frames are not independently expressed in vivo or part of functional transcripts. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. Inst Biol Mol & Celular, Amyloid Unit, Porto, Portugal. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1000 BP 188 EP 188 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701003 ER PT J AU Tayebi, N Park, JK Madike, V Sidransky, E AF Tayebi, N Park, JK Madike, V Sidransky, E TI A duplication of the glucocerebrosidase pseudogene and a metaxin fusion gene found in patients with Gaucher disease and in normal controls. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Clin Neurosci Branch, Bethesda, MD 20892 USA. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1005 BP 189 EP 189 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701006 ER PT J AU Spirina, O Bykhovskaya, Y Kajava, AV O'Brien, TW Nierlich, DP Mougey, EB Sylvester, JE Graack, HR Wittmann-Liebold, B Fischel-Ghodsian, N AF Spirina, O Bykhovskaya, Y Kajava, AV O'Brien, TW Nierlich, DP Mougey, EB Sylvester, JE Graack, HR Wittmann-Liebold, B Fischel-Ghodsian, N TI Heart-specific splice-variant of human mitochondrial ribosomal protein L5 (MRP-L5). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Cedars Sinai Med Ctr, Los Angeles, CA 90024 USA. NIH, Ctr Mol Modeling, Bethesda, MD 20892 USA. Univ Florida, Gainesville, FL USA. Nemours Childrens Cli, Jacksonville, FL USA. Free Univ Berlin, Max Delbruck Ctr, D-1000 Berlin, Germany. RI Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1018 BP 191 EP 191 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701021 ER PT J AU Durmowicz, MC Cui, CY Schlessinger, D AF Durmowicz, MC Cui, CY Schlessinger, D TI Hierarchical control of ectodysplasin-A expression: Involvement of the Wnt and EGFR pathways. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIGMS, Bethesda, MD 20892 USA. NIH, NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1034 BP 193 EP 193 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701035 ER PT J AU Chiba-Falek, O Orrison, BM Touchman, JW Dehejia, A Polymeropoulos, MH Nussbaum, RL AF Chiba-Falek, O Orrison, BM Touchman, JW Dehejia, A Polymeropoulos, MH Nussbaum, RL TI Analysis of the human alpha-synuclein promoter. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, GDRB, NIH, Bethesda, MD 20892 USA. NISC, NIH, Gaithersburg, MD USA. Novartis Pharmaceut, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1040 BP 194 EP 194 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701041 ER PT J AU Yan, B Plotz, P AF Yan, B Plotz, P TI Identification of a silencer element of the human acid maltase gene in normal human fibroblast cells and Glycogenesis type II fibroblast cells. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1048 BP 196 EP 196 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701051 ER PT J AU Thompson, TE Rogan, PK Risinger, JI Taylor, JA AF Thompson, TE Rogan, PK Risinger, JI Taylor, JA TI Alternative splicing of DNA Polymerase beta mRNA in normal tissues and bladder cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Univ Missouri, Sch Med, Childrens Mercy Hosp, Med Genet Sect, Kansas City, MO 64108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1053 BP 197 EP 197 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701054 ER PT J AU Huo, L Roessler, E Chuang, PT McMahon, AP Muenke, M AF Huo, L Roessler, E Chuang, PT McMahon, AP Muenke, M TI The Sonic Hedgehog signaling pathway: analysis of the Hedgehog Interacting Protein and HNF-3 beta genes as potential causes of holoprosencephaly. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Harvard Univ, Biolabs, Dept Mol & Cellular Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1062 BP 198 EP 198 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701064 ER PT J AU Xu, S Ladak, R Swanson, DA McInnes, RR Valle, D AF Xu, S Ladak, R Swanson, DA McInnes, RR Valle, D TI PHR1, a PH domain-containing, integral membrane protein expressed predominantly in primary sensory neurons. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Predoctoral Traning Program, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Inst Med Genet, Baltimore, MD USA. Hosp Sick Children, Res Inst, Program Dev Biol, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Res Inst, Program Genet, Toronto, ON M5G 1X8, Canada. Natl Human Genome Res INst, Genet & Mol Biol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1075 BP 200 EP 200 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701074 ER PT J AU Justice, CM Miller, NH Marosy, B Pugh, EW Wilson, AF AF Justice, CM Miller, NH Marosy, B Pugh, EW Wilson, AF TI Stratification for complex disorders with genetic heterogeneity comprising both X-linked and autosomal dominant forms of inheritance: Families with familiar idiopathic scoliosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Genomet Sect, Baltimore, MD USA. NIH, Baltimore, MD USA. Johns Hopkins Univ, Dept Orthopaed Surg, Baltimore, MD USA. Johns Hopkins Univ, CIDR, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1131 BP 210 EP 210 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701130 ER PT J AU Papanicolaou, GJ Siffert, W Stunkard, AJ Wilson, AF Platte, P AF Papanicolaou, GJ Siffert, W Stunkard, AJ Wilson, AF Platte, P TI Statistical genetic analysis of a G-protein beta 3 subunit C825T allelic variant in the Old-Order Amish. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Genometr Sect, Baltimore, MD USA. Univ Hosp essen, Dept Pharmacol, Essen, Germany. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Trier, Ctr Psychobiol & Psychosomat Res, D-54286 Trier, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1145 BP 213 EP 213 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701146 ER PT J AU Lindsay, RS Kobes, S Knowler, WC Hanson, RL AF Lindsay, RS Kobes, S Knowler, WC Hanson, RL TI A variance components method of linkage analysis to assess parent-of-origin effects on body mass index. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, NIH, Phoenix, AZ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1177 BP 218 EP 218 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701177 ER PT J AU Radel, M Vallejo, RL Iwata, N Aragon, R Naukkarinen, H Virkkunnen, M Long, JC Goldman, D AF Radel, M Vallejo, RL Iwata, N Aragon, R Naukkarinen, H Virkkunnen, M Long, JC Goldman, D TI Linkage and association analyses of sequence variants of the GABRA6, GABRB2, and GABRG2 gene cluster and alcohol dependence in a Finnish sample. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, DICBR, NIH, Bethesda, MD 20892 USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1207 BP 223 EP 223 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701207 ER PT J AU Peila, R Havlik, R Launer, LJ AF Peila, R Havlik, R Launer, LJ TI Genetic susceptibility, systolic hypertension and the risk of poor cognitive function. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIA, EDB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1290 BP 237 EP 237 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701293 ER PT J AU Diehl, SR Khoshnevisan, MH Wu, T Sun, C Mazeheri, M Long, R Chisholm, AM AF Diehl, SR Khoshnevisan, MH Wu, T Sun, C Mazeheri, M Long, R Chisholm, AM TI Single nucleotide polymorphisms (SNPs) in alcohol dehydrogenases and risk of oral clefts in humans: different effects of maternal and child genotypes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDCR, Craniofacial Epidemiol & Genet Branch, NIH, Bethesda, MD USA. Lancaster Cleft Palate Clin, Lancaster, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1298 BP 238 EP 238 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701300 ER PT J AU Tishler, PV Carey, VJ Reed, T Fabsitz, RR AF Tishler, PV Carey, VJ Reed, T Fabsitz, RR TI Genotype determines the effect of cigarette smoking on pulmonary function. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, VA Med Ctr, W Roxbury, MA USA. Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1297 BP 238 EP 238 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701297 ER PT J AU Pandya, A Oelrich, K Amos, KS Morell, RJ Xia, XJ Albertorio, J Xiu, XZ Blanton, SH Friedman, TB Nance, WE AF Pandya, A Oelrich, K Amos, KS Morell, RJ Xia, XJ Albertorio, J Xiu, XZ Blanton, SH Friedman, TB Nance, WE TI Connexin(Cx) testing in a nationwide repository of sampler from deaf probands: Relevance to clinical practice. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Gallaudet Univ, Washington, DC 20002 USA. NIDCD, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1305 BP 240 EP 240 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701307 ER PT J AU Donorum, EA Graff, J Brown, K Smith, D Behai, A Peterson, K Bernstein, S Stephan, DA Wistow, G AF Donorum, EA Graff, J Brown, K Smith, D Behai, A Peterson, K Bernstein, S Stephan, DA Wistow, G TI Construction of a 10,000 element human eye cDNA array for distribution to the scientific community. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 CNMC, Res Ctr Genet Med, Washington, DC USA. George Washington Univ, Sch Med, Washington, DC USA. NEI, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1388 BP 255 EP 255 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701389 ER PT J AU Riz, I Spruill, A Kumar, A Stephan, DA AF Riz, I Spruill, A Kumar, A Stephan, DA TI Double-stranded RNA binding protein nuclear factor 90 (NF90) is involved in transcriptional activation of antlviralpathway genes causing resistance to HIV-1 in vitro. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 George Washington Univ, Washington, DC USA. CNMC, Res Ctr Genet Med, Washington, DC USA. NHGRI, NIH, Bethesda, MD 20892 USA. RI kumari, uttara/P-6779-2016 OI kumari, uttara/0000-0001-9628-4770 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1389 BP 255 EP 255 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701392 ER PT J AU Chines, PS Silander, K Narisu, N Erdos, MR Voltz, AK Mohlke, K Collins, FS AF Chines, PS Silander, K Narisu, N Erdos, MR Voltz, AK Mohlke, K Collins, FS TI A simple, efficient procedure for mapping SNPs to genomic sequence. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, GMBB, Bethesda, MD 20892 USA. NHGRI, IDRB, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1397 BP 256 EP 256 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701399 ER PT J AU Jia, L Young, M Powell, J Touchman, J Bouffard, G Ho, NC Hotchkiss, R Robey, P Francomano, CA AF Jia, L Young, M Powell, J Touchman, J Bouffard, G Ho, NC Hotchkiss, R Robey, P Francomano, CA TI The Skeletal Genome Anatomy Project (SGAP): A Web site for investigation of skeletal biology. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIDCR, Bone Res Branch, NIH, Bethesda, MD USA. CIT, NIH, Bethesda, MD USA. NIH Intamural Sequencing Ctr, NIH, Bethesda, MD USA. Hosp Special Surg, New York, NY 10021 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1400 BP 257 EP 257 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701401 ER PT J AU Ho, NC Jia, L Driscoll, CC Gutter, EM Francomano, CA AF Ho, NC Jia, L Driscoll, CC Gutter, EM Francomano, CA TI A skeletal gene database. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. Ohio Univ, Dept Biol Sci, Athens, OH 45701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1430 BP 262 EP 262 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701431 ER PT J AU Gorospe, JR Hamed, SA Sutherland-Smith, A Kendrick-Jones, J Hoffman, EP AF Gorospe, JR Hamed, SA Sutherland-Smith, A Kendrick-Jones, J Hoffman, EP TI High throughput complete sequence screening of the dystrophin cDNA reveals a common duplication mutation, and over diagnosis of dystrophinopathy in Becker Dystrophy. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC USA. NIH, NHGRI, Bethesda, MD USA. Med Res Counsel Lab Mol Biol, Struct Studies Div, Cambridge, England. RI Sutherland-Smith, Andrew/F-1813-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1485 BP 271 EP 271 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701488 ER PT J AU Rosenberg, MJ Kelley, RI Davis, J Biesecker, LG AF Rosenberg, MJ Kelley, RI Davis, J Biesecker, LG TI Physical mapping of Amish microcephaly on 17q. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD USA. Johns Hopkins Univ, Kennedy Krieger Inst 2, Dept Pediat, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1494 BP 272 EP 272 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701493 ER PT J AU Nwokoro, NA Rother, KI Papanicolaou, D Chrousos, G Porter, FD AF Nwokoro, NA Rother, KI Papanicolaou, D Chrousos, G Porter, FD TI Compensated adrenal insufficiency in Smith-Lemli-Opitz syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NICHD, HDB, Bethesda, MD USA. NIH, NIDDK, Bethesda, MD USA. NIH, NICHD, DEB, Bethesda, MD USA. NIH, NICHD, PREB, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1531 BP 279 EP 279 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701534 ER PT J AU Porter, FD Zhu, P Kratz, L Krakowiak, PA Battaile, K Steiner, RD Stewart, RR Kelley, RI Nwokoro, NA Wassif, CA AF Porter, FD Zhu, P Kratz, L Krakowiak, PA Battaile, K Steiner, RD Stewart, RR Kelley, RI Nwokoro, NA Wassif, CA TI Phenotypic, biochemical, and neurophysiological characterization of a SLOS mouse model. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NICHD, HDB, Bethesda, MD USA. NIH, NIAAA, LMCN, Bethesda, MD USA. Kennedy Krieger Inst, Baltimore, MD USA. OHSU, Portland, OR USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1536 BP 280 EP 280 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701537 ER PT J AU Krakowiak, PA Javitt, N Wassif, CA Nwokoro, NN Porter, FD AF Krakowiak, PA Javitt, N Wassif, CA Nwokoro, NN Porter, FD TI Clinical, mutational and enzymatic analysis of Smith-Lemli-Opitz syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NICHD, Heritable Disorders, Bethesda, MD USA. NYU, Med Ctr, New York, NY 10016 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1560 BP 284 EP 284 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701561 ER PT J AU Nagaraju, K Raben, N Lee, E Rochon, P Lu, N Yap, G Manetz, S Plotz, P AF Nagaraju, K Raben, N Lee, E Rochon, P Lu, N Yap, G Manetz, S Plotz, P TI T cell dependent immune response in a knockout model of lysosomal storage disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIAMS, ARB, Bethesda, MD USA. NIH, NIAID, Bethesda, MD USA. RI Rochon, Paula/J-2918-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1565 BP 284 EP 284 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701566 ER PT J AU Huizing, M Anikster, Y Gahl, WA AF Huizing, M Anikster, Y Gahl, WA TI Characterization of a pseudogene homologous to the UDP-N-acetylglucosamine 2-epimerase gene; relevance for mutation detection in patients with sialuria. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NICHD, Heritable Disorders Branch, Sect Human Biochem Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1569 BP 285 EP 285 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701571 ER PT J AU Huang, K Ali, Y Zheng, Z O'Brien-Jenkins, A Ning, C Reynolds, R Segal, S Bernard, DJ Winshaw-Boris, A Stambolian, D AF Huang, K Ali, Y Zheng, Z O'Brien-Jenkins, A Ning, C Reynolds, R Segal, S Bernard, DJ Winshaw-Boris, A Stambolian, D TI A mouse model of galactose-induced cataracts. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Penn, Dept Genet & Ophthamol, Philadelphia, PA USA. Childrens Hosp Philadelphia, Div Biochem Dev & Mol Dis, Philadelphia, PA 19104 USA. NIH, NHGRI, Genet Dis Branch, Bethesda, MD USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1587 BP 288 EP 288 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701589 ER PT J AU Introne, WJ Rausche, M Anikster, Y Gilbert, F Gahl, WA AF Introne, WJ Rausche, M Anikster, Y Gilbert, F Gahl, WA TI Alkaptonuria: New studies of an old disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. NICHD, Heritable Disorders Branch, Bethesda, MD 20892 USA. Cornell Med Ctr, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1590 BP 289 EP 289 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701591 ER PT J AU Krasnewich, D Andrews, D Tayebi, N Goker, O Orvisky, E Sidransky, E AF Krasnewich, D Andrews, D Tayebi, N Goker, O Orvisky, E Sidransky, E TI Clinical presentations of American patients with congenital disorders of glycosylation (CDG). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD USA. NIH, NIMH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1597 BP 290 EP 290 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701600 ER PT J AU Orvisky, E Thackray, H Sidransky, E Parker, M St John, E Krasnewich, D AF Orvisky, E Thackray, H Sidransky, E Parker, M St John, E Krasnewich, D TI Glycobiologic approaches to a novel case of Congenital Disorder of Glycosylation (CDG). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIMH, Bethesda, MD USA. NIH, NHGRI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1596 BP 290 EP 290 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701597 ER PT J AU Thackray, H Abdulla, I Krasnewich, D AF Thackray, H Abdulla, I Krasnewich, D TI Near-syncopal episodes in an adult with mild type Hunter Syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1608 BP 292 EP 292 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701609 ER PT J AU Clifford, R Edmonson, M Scherpbier, T Hu, Y Macdonald, R Yip, P Braun, A Buetow, K AF Clifford, R Edmonson, M Scherpbier, T Hu, Y Macdonald, R Yip, P Braun, A Buetow, K TI Single nucleotide polymorphism discovery by the Cancer Genome Anatomy Project. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. Sequenom Inc, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1656 BP 300 EP 300 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701655 ER PT J AU Kurima, K Szymko, Y Rudy, S Morell, RJ Friedman, TB Griffith, AJ AF Kurima, K Szymko, Y Rudy, S Morell, RJ Friedman, TB Griffith, AJ TI Genetic map localization of DFNA34 and DFNA36, two autosomal dominant non-syndromic deafness loci. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIDCD, Neurootol Branch, Rockville, MD USA. NIH, NIDCD, Genet Mol Lab, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1654 BP 300 EP 300 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701654 ER PT J AU Lee, MH Lu, K Gordon, D Ott, J Kojima, H Kwiterowich, PO Brownstein, MJ Salen, G Ose, L Mietinnen, T Pegoraro, R Hidaka, H Sakuma, N Pandya, A Patel, S AF Lee, MH Lu, K Gordon, D Ott, J Kojima, H Kwiterowich, PO Brownstein, MJ Salen, G Ose, L Mietinnen, T Pegoraro, R Hidaka, H Sakuma, N Pandya, A Patel, S TI Fine-mapping and Genetic analyses of Sitosterolemia: Founder effects in at least three geographic areas. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Shiga Univ Med Sci, Shiga, Japan. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Univ Helsinki, FIN-00014 Helsinki, Finland. Univ Natal, ZA-4001 Durban, South Africa. Rockefeller Univ, New York, NY 10021 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NIH, NHGRI, Bethesda, MD USA. Rikshosp, Oslo, Norway. Sanyo Elect Co Ltd, Tokyo, Japan. Nagoya City Univ, Dept Med 3, Nagoya, Aichi, Japan. Med Coll Virginia, Dept Human Genet, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1717 BP 310 EP 310 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701718 ER PT J AU Li, XC Saal, HM Friedman, TB Friedman, RA AF Li, XC Saal, HM Friedman, TB Friedman, RA TI A new gene for autosomal dominant nonsyndromic sensorineural hearing loss (DFNA32) maps to 11p15. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 House Ear Res Inst, Dept Cell & Mol Biol, Los Angeles, CA 90034 USA. Univ Cincinnati, Coll Med, Div Human Genet, Childrens Hosp,Med Ctr, Cincinnati, OH USA. NIDCD, Mol Genet Lab, NIH, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1727 BP 312 EP 312 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701729 ER PT J AU Martin, ER Hardy, SW Bass, MP Kaplan, NL AF Martin, ER Hardy, SW Bass, MP Kaplan, NL TI Sampling considerations for family-based tests of association. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA. N Carolina State Univ, Program Stat Genet, Raleigh, NC 27695 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1724 BP 312 EP 312 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701725 ER PT J AU Choi, MS Zhang, Z Mukherjee, AB AF Choi, MS Zhang, Z Mukherjee, AB TI Uteroglobin gene - Polymorphism and genetic susceptibility to asthma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Heritable Disorders Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1757 BP 317 EP 317 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701759 ER PT J AU Atwood, LD Grabrick, DM Wilson, AF AF Atwood, LD Grabrick, DM Wilson, AF TI Effect of covariates on quantitative trait linkage analysis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Minnesota, Inst Human Genet, Minneapolis, MN 55455 USA. Mayo Clin & Mayo Fdn, Rochester, MN USA. NHGRI, NIH, IDRB, Genometr Sect, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1784 BP 322 EP 322 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701785 ER PT J AU Ming, JE Du, YZ George, RA Ryan, SG Richieri-Costa, A Muenke, M AF Ming, JE Du, YZ George, RA Ryan, SG Richieri-Costa, A Muenke, M TI X-linked cleft palate and ankyloglossia: Refinement of the minimal critical region in Xq21.3. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. Univ Sao Paulo, Dept Clin Genet, HRAC, Bauru, SP, Brazil. NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. RI Richieri-Costa, Antonio/B-2514-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1802 BP 325 EP 325 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701803 ER PT J AU Hanson, RL Lindsay, RS Kobes, S Knowler, WC AF Hanson, RL Lindsay, RS Kobes, S Knowler, WC TI Assessing parent-of-origen effects in linkage analysis of quantitative traits. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, DAES, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1818 BP 327 EP 327 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701817 ER PT J AU Mandal, DM Sorant, AJM Wilson, AF Bailey-Wilson, JE AF Mandal, DM Sorant, AJM Wilson, AF Bailey-Wilson, JE TI Model-dependent linkage analysis and Type I error rate under random ascertainment. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. NIH, NHGRI, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1821 BP 328 EP 328 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701824 ER PT J AU Ehringer, MA Thompson, J Conroy, O Xu, Y Yang, F Canniff, J Beeson, M Gordon, L Bennett, B Goldman, D Schuckit, M Johnson, TE Sikela, JM AF Ehringer, MA Thompson, J Conroy, O Xu, Y Yang, F Canniff, J Beeson, M Gordon, L Bennett, B Goldman, D Schuckit, M Johnson, TE Sikela, JM TI Progress toward gene identification for alcohol-related phenotypes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. NIAAA, NIH, Rockville, MD 20852 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1828 BP 329 EP 329 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701828 ER PT J AU Witmer, PD Adams, MK Dizon, JS Goldstein, JL Wheaton, AM Dong, PN Doheny, KF Pugh, EW Nussbaum, RL Hunter, K Brownstein, MJ AF Witmer, PD Adams, MK Dizon, JS Goldstein, JL Wheaton, AM Dong, PN Doheny, KF Pugh, EW Nussbaum, RL Hunter, K Brownstein, MJ TI The characterization and development of a highly informative mouse short tandem repeat (STR) marker set. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD USA. NIH, NHGRI, NIMH, Genet Lab, Bethesda, MD USA. Perkin Elmer Corp, PE Biosyst, Foster City, CA USA. NIH, NHGRI, Inherited Dis Res Branch, Baltimore, MD USA. NIH, NCI, Lab Populat Genet, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1849 BP 332 EP 332 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701850 ER PT J AU Fitzpatrick, DL Rausche, R Huizing, M Castellan, C Donazzan, G Gahl, WA AF Fitzpatrick, DL Rausche, R Huizing, M Castellan, C Donazzan, G Gahl, WA TI A new polymorphism in the Hermansky-Pudlak syndrome gene HPS-1; relevance for mutation detection. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Gen Hosp, Dept Clin Genet, Bolzano, Italy. Gen Hosp, Dept Pulmonol, Bolzano, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1859 BP 334 EP 334 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701861 ER PT J AU Wolford, JK Blunt, D Ballecer, C Ossowski, V Bogardus, C Prochazka, M AF Wolford, JK Blunt, D Ballecer, C Ossowski, V Bogardus, C Prochazka, M TI A 4 Mb physical map of a type 2 diabetes mellitus locus on human chromosome 1q. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, PECRB, NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1857 BP 334 EP 334 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701860 ER PT J AU Voltz, AK Braun, A Chines, PS Doheny, KF Hilliard, MS Little, DP Witmar, PD Nussbaum, RL AF Voltz, AK Braun, A Chines, PS Doheny, KF Hilliard, MS Little, DP Witmar, PD Nussbaum, RL TI Developing a SNP map of the human genome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, DIR, Baltimore, MD USA. NIH, IDRB, Baltimore, MD USA. NIH, NHGRI, Baltimore, MD USA. Sequenom Inc, San Diego, CA USA. DIR, Bethesda, MD USA. GMBB, Bethesda, MD USA. NHGRI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, CIDR, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1872 BP 336 EP 336 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701871 ER PT J AU Jiao, X Lee, J Iwata, F Hayakawa, M Kanal, A Munier, FL Schorderet, DF Chen, MS Kaiser-Kupfer, M Hejtmancik, JF AF Jiao, X Lee, J Iwata, F Hayakawa, M Kanal, A Munier, FL Schorderet, DF Chen, MS Kaiser-Kupfer, M Hejtmancik, JF TI Genetic linkage of Bietti crystallin cornel-retinal dystrophy to chromosome 4q35. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NEI, Ophthalmic Genet & Clin Serv Branch, Bethesda, MD 20892 USA. Juntendo Univ, Sch Med, Tokyo, Japan. Jules Gonin Eye Hosp, Div Med Genet, Oculgenet Unit, Lausanne, Switzerland. Natl Taiwan Univ Hosp, Dept Ophthalmol, Taipei, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1876 BP 337 EP 337 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701876 ER PT J AU McNeil, DE Linehan, WM Glenn, GM AF McNeil, DE Linehan, WM Glenn, GM TI Challenges of two rare syndromes affecting the nervous system in members of one large kindred. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, DCEG, Genet Epidemiol Branch, Rockville, MD USA. NCI, DCS, Urolog Oncol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1887 BP 339 EP 339 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701889 ER PT J AU Vacha, SJ Gooden, G Peters, K Cohen, MM Meltzer, P Biesecker, LG AF Vacha, SJ Gooden, G Peters, K Cohen, MM Meltzer, P Biesecker, LG TI Identification of candidate genes for proteus syndrome by microarray analysis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD USA. Dalhousie Univ, Halifax, NS B3H 3J5, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1925 BP 345 EP 345 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701926 ER PT J AU Feng, J Buzin, CH Craddock, N Jones, I Cook, E Goldman, D Heston, LL Sommer, SS AF Feng, J Buzin, CH Craddock, N Jones, I Cook, E Goldman, D Heston, LL Sommer, SS TI DOVAM-S: Evidence for generic scanning conditions and application to the steroid receptor gene family. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 City Hope Natl Med Ctr, Dept Mol Genet, Duarte, CA 91010 USA. Univ Birmingham, Birmingham, W Midlands, England. Univ Chicago, Chicago, IL USA. NIAAA, Bethesda, MD USA. Univ Washington, Seattle, WA 98195 USA. RI Jones, Ian/B-4925-2009; turton, miranda/F-4682-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1966 BP 352 EP 352 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701965 ER PT J AU Wevrick, R Lee, S Kozlov, S Bischof, JM Kuny, SL Chibuk, TK Hernandez, L Stewart, CL AF Wevrick, R Lee, S Kozlov, S Bischof, JM Kuny, SL Chibuk, TK Hernandez, L Stewart, CL TI Characterization of the necdin gene family and its role in Prader-Willi syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Alberta, Dept Med Genet, Edmonton, AB, Canada. NCI, Frederick Canc Res & Dev Ctr, Lab Canc & Dev Biol, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1972 BP 353 EP 353 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701971 ER PT J AU Ross, JL Russell, HF Power, TJ Mazzocco, MM Muenke, M Pfendner, E Boehm, CB Zinn, AR AF Ross, JL Russell, HF Power, TJ Mazzocco, MM Muenke, M Pfendner, E Boehm, CB Zinn, AR TI Absent imprinting effects on verbal IQ in girls with Turner syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Pediat, Philadelphia, PA 19107 USA. Univ Penn, Sch Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Med, Kennedy Inst, Baltimore, MD 21205 USA. Natl Human Genome Res Inst, NIH, Med Genet Branch, Bethesda, MD USA. Univ Texas, SW Med Sch, McDermott Ctr Human Growth & Dev, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1988 BP 356 EP 356 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701988 ER PT J AU Erdos, MR Douglas, JA Watanabe, RM Braun, A Oeth, P Johnston, C Mohlke, K Valle, T Buchanan, TA Bergman, RN Collins, FS Boehnke, M Tuomilehto, J AF Erdos, MR Douglas, JA Watanabe, RM Braun, A Oeth, P Johnston, C Mohlke, K Valle, T Buchanan, TA Bergman, RN Collins, FS Boehnke, M Tuomilehto, J CA FUSION Study Grp TI The PPAR-gamma 2 Pro12Ala variant: association with type 2 diabetes, trait differences, and interaction with the beta(3)-adrenergic receptor. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. Sequenom Ind Genom, San Diego, CA USA. Natl Publ Hlth Inst, Helsinki, Finland. Univ So Calif, Los Angeles, CA 90089 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1997 BP 357 EP 357 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701998 ER PT J AU Schultz, R McColley, A Malik, N Westphal, H Murray, J AF Schultz, R McColley, A Malik, N Westphal, H Murray, J TI Screening EDN-1 and LHX-8 for mutations associated with nonsyndromic cleft lip and palate. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Iowa, Dept Genet, Iowa City, IA USA. NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2002 BP 358 EP 358 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702001 ER PT J AU Lachtermacher, MB Smith, KD Gerrard, B Dean, M AF Lachtermacher, MB Smith, KD Gerrard, B Dean, M TI Screening of peroxisomal ABC genes in X-ALD patients. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Canc Inst, LGD, Frederick, MD USA. Kennedy Krieger Inst, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2021 BP 361 EP 361 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702022 ER PT J AU Abuya, P Ashley-Koch, A Wolpert, CM Menold, MM Matsumoto, N Basu, S Greenblatt, DM Powell, CM Cuccaro, ML Ledbetter, DH Green, ED Vance, JM Pericak-Vance, MA Gilbert, JR AF Abuya, P Ashley-Koch, A Wolpert, CM Menold, MM Matsumoto, N Basu, S Greenblatt, DM Powell, CM Cuccaro, ML Ledbetter, DH Green, ED Vance, JM Pericak-Vance, MA Gilbert, JR TI Isolation and analysis of Autism candidate genes on 7q. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. Univ S Carolina, W S Hall Psychiat Inst, Columbia, SC 29208 USA. NIH, NHGRI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2025 BP 362 EP 362 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702027 ER EF