FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ketter, TA Drevets, WC AF Ketter, TA Drevets, WC TI Neuroimaging studies of bipolar depression: functional neuropathology, treatment effects, and predictors of clinical response SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Review DE bipolar disorder; depression; positron emission tomography; single photon emission computed tomography; magnetic resonance spectroscopy ID CEREBRAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE SPECTROSCOPY; SUBGENUAL PREFRONTAL CORTEX; SEASONAL AFFECTIVE-DISORDER; INDUCED DOPAMINE RELEASE; BRAIN METABOLIC CHANGES; TOTAL SLEEP-DEPRIVATION; LATE-LIFE DEPRESSION; N-ACETYL-ASPARTATE AB Functional brain imaging studies suggest that prefrontal and anterior paralimbic components of basal ganglia-thalamocortical circuits have altered function in bipolar depression. Abnormal anterior cortical activity is a common finding in not only bipolar, but also unipolar and secondary depression. In addition, increases in subcortical anterior paralimbic activity may occur in bipolar and unipolar depression, consistent with corticolimbic dysregulation. Variability in findings may be related to differences in methodology, patterns of depressive symptoms, illness subtypes, medications, and treatment responses. Emerging data are beginning to reveal specific biochemical disturbances in prefrontal and anterior paralimbic components of basal ganglia-thalamocortical circuits in bipolar and unipolar disorders. These include changes in serotonergic and dopaminergic neurotransmission, in N-acetyl aspartate, choline, gamma-aminobutyric acid, and glutamate, phospholipid concentrations, and in high energy phosphate metabolism. Although functional brain imaging studies have advanced our knowledge of the neurobiology of bipolar depression, it remains to be established whether clinical applications will develop to facilitate diagnosis and more effectively target treatments. Published by Elsevier Science B.V. C1 Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, Bethesda, MD USA. RP Ketter, TA (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. NR 162 TC 6 Z9 8 U1 5 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD DEC PY 2002 VL 2 IS 3-4 BP 182 EP 192 AR PII S1566-2772(02)00043-9 DI 10.1016/S1566-2772(02)00043-9 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 633GE UT WOS:000180273600008 ER PT J AU Gould, TD Chen, G Manji, HK AF Gould, TD Chen, G Manji, HK TI Mood stabilizer psychopharmacology SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Review DE mood stabilizer; anticonvulsant; antiepileptic; neuroprotection; neurotrophic; depression; mania; ERK; bcl-2; protein kinase C; bipolar disorder; valproate ID PROTEIN-KINASE-C; LONG-TERM LITHIUM; SIGNAL-TRANSDUCTION PATHWAYS; ADENYLATE-CYCLASE ACTIVITY; GLYCOGEN-SYNTHASE KINASE-3; BRAIN ADENOSINE RECEPTORS; MANIC-DEPRESSIVE ILLNESS; RAT CEREBRAL-CORTEX; CHRONIC CARBAMAZEPINE TREATMENT; IMMORTALIZED HIPPOCAMPAL CELLS AB Mood stabilizers represent a class of drugs that are efficacious in the treatment of bipolar disorder. The most established medications in this class are lithium, valproic acid, and carbamazepine. In addition to their therapeutic effects for treatment of acute manic episodes, these medications often are useful as prophylaxis against future episodes and as adjunctive antidepressant medications. While important extracellular effects have not been excluded, most available evidence suggests that the therapeutically relevant targets of this class of medications are in the interior of cells. Herein we give a prospective of a rapidly evolving field, discussing common effects of mood stabilizers as well as effects that are unique to individual medications. Mood stabilizers have been shown to modulate the activity of enzymes, ion channels, arachidonic acid turnover, G protein coupled receptors and intracellular pathways involved in synaptic plasticity and neuroprotection. Understanding the therapeutic targets of mood stabilizers will undoubtedly lead to a better understanding of the pathophysiology of bipolar disorder and to the development of improved therapeutics for the treatment of this disease. Furthermore, the involvement of mood stabilizers in pathways operative in neuroprotection suggests that they may have utility in the treatment of classical neurodegenerative disorders. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIMH, Lab Mol Pathophysiol, NIH, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Lab Mol Pathophysiol, NIH, Bldg 49,Room B1EE16, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 FU Intramural NIH HHS [Z01 MH002841-04] NR 250 TC 32 Z9 34 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD DEC PY 2002 VL 2 IS 3-4 BP 193 EP 212 AR PII S1566-2772(02)00044-0 DI 10.1016/S1566-2772(02)00044-0 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 633GE UT WOS:000180273600009 PM 22707923 ER PT J AU Post, RM Speer, AM Obrocea, GV Leverich, GS AF Post, RM Speer, AM Obrocea, GV Leverich, GS TI Acute and prophylactic effects of anticonvulsants in bipolar depression SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Review DE bipolar disorder; depression; anticonvulsants; carbamazepine; lithium; valproate; lamotrigine; gabapentin ID TRANSCRANIAL MAGNETIC STIMULATION; PLACEBO-CONTROLLED TRIAL; VAGUS NERVE-STIMULATION; TERM LITHIUM TREATMENT; ANTIEPILEPTIC DRUG LEVETIRACETAM; REFRACTORY PARTIAL SEIZURES; RANDOMIZED CLINICAL-TRIAL; TYPICAL ABSENCE SEIZURES; PRELIMINARY DOUBLE-BLIND; ADD-ON THERAPY AB The anticonvulsants carbamazepine and valproate are now widely recognized and used mood stabilizers as adjuncts or alternatives to lithium carbonate. Like lithium, however, they appear to have better antimanic than antidepressant properties. In contrast, initial data suggest that lamotrigine may be an exception to this rule, with better evidence of acute and prophylactic antidepressant than antimanic effects emerging in controlled trials. Gabapentin is being widely used, although its primary antimanic and antidepressant properties have not been delineated in controlled trials, but it does appear to be useful in a number of syndromes that are often comorbid with bipolar depression, including anxiety, social phobia, obsessive-compulsive disorder, alcohol withdrawal syndromes, pain syndromes, and a variety of sleep disorders. The data are mixed regarding topiramate's acute antidepressant properties, although its positive side-effects profile of inducing weight loss may make it a particularly useful adjunct independent of its ultimate mood stabilizing properties. While initial data with tiagabine are not promising, the possible antidepressant effects of two of the newest anticonvulsants levetiracetam and zonisamide are just beginning to be evaluated. Thus, several of the compounds originally FDA-approved as anticonvulsants appear promising for their acute and long-term antidepressant effects in bipolar illness, and much work remains to be done to identify clinical and biological markers of response to individual agents and assess how they may best be utilized in clinical practice. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIMH, Dept Hlth & Human Serv, NIH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Dept Hlth & Human Serv, NIH, Biol Psychiat Branch, Bldg 10,Room 3S239,10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. NR 239 TC 16 Z9 16 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD DEC PY 2002 VL 2 IS 3-4 BP 228 EP 251 AR PII S1566-2772(02)00047-6 DI 10.1016/S1566-2772(02)00047-6 PG 24 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 633GE UT WOS:000180273600012 ER PT J AU Leppert, PC AF Leppert, PC TI Overview of women's health SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 NICHHD, Reprod Sci Branch, Populat Res Ctr, NIH, Bethesda, MD 20892 USA. RP Leppert, PC (reprint author), NICHHD, Reprod Sci Branch, Populat Res Ctr, NIH, Bldg 61EB,Room 8B01, Bethesda, MD 20892 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD DEC PY 2002 VL 45 IS 4 BP 1073 EP 1079 DI 10.1097/00003081-200212000-00015 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 620WR UT WOS:000179556900012 PM 12438885 ER PT J AU Moras, K AF Moras, K TI A tool to advance the effectiveness and dissemination of empirically supported psychotherapies and the NIMH public health research agenda SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Article DE bridging science and practice; empirically supported treatments; psychotherapy manuals; public health model; therapy dissemination ID TREATMENT MANUALS; PANIC DISORDER; ALLIANCE AB Carroll and Nuro's (this issue) stage model will likely hasten the availability of more educationally effective and clinically complete therapy manuals for both research and practice. The model is an important and concise tool for broadly disseminating knowledge about psychotherapy manual development that has accrued over the 20 years since manuals became required for federally funded therapy outcome research. The current paradigm shift to a public health research agenda, spearheaded by the National Institute of Mental Health (NIMH), is evident in the model's specifications for stage III manuals. The immense challenge for researchers to truly meet the scientific demands of stage III manuals (and the NIMH's research charge) is briefly discussed. An autobiographical case report is also presented to illustrate that manuals for empirically supported therapies are not, in all cases, as "unfriendly" to practice and practitioners as much contemporary literature suggests, and as the stage model is intended to remedy. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Moras, K (reprint author), NIDA, Behav Treatment Dev Branch, Div Treatment Res & Dev, 6001 Execut Blvd, Bethesda, MD 20892 USA. NR 21 TC 3 Z9 3 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD WIN PY 2002 VL 9 IS 4 BP 425 EP 430 DI 10.1093/clipsy/9.4.425 PG 6 WC Psychology, Clinical SC Psychology GA 614AL UT WOS:000179164600010 ER PT J AU Krause, RM AF Krause, RM TI Evolving microbes and re-emerging streptococcal disease SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID RHEUMATIC-FEVER; PERSPECTIVE AB Changes in demography, lifestyle, and agriculture are all cited as causes of emerging and re-emerging infectious diseases. Yet microbes play an active role in these events. They are constantly evolving. This article reviews the general principles of bacterial genetics that influence emergence or re-emergence of infectious diseases and discusses re-emerging streptococcal infections, which are a major public health concern today. The scarlet fever pandemic of the 19th century serves as a case study of the waxing and waning of epidemics as biological expressions of host-microbe associations. This article discusses the possible relationship between this earlier pandemic and the emergence of streptococcal toxic shock syndrome and the re-emergence of rheumatic fever, notably in the Salt Lake City area. A general strategy for confronting emerging infectious diseases is applicable to this re-emergence of streptococcal diseases. C1 NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. RP Krause, RM (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, Bldg 16,Room 202,16 Ctr Dr,MSC 6705, Bethesda, MD 20892 USA. NR 30 TC 8 Z9 8 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD DEC PY 2002 VL 22 IS 4 BP 835 EP + AR PII S0272-2712(02)00027-6 DI 10.1016/S0272-2712(02)00027-6 PG 15 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 624AE UT WOS:000179736500002 PM 12489283 ER PT J AU Willoughby, RE Nelson, KB AF Willoughby, RE Nelson, KB TI Chorioamnionitis and brain injury SO CLINICS IN PERINATOLOGY LA English DT Review ID LOW-BIRTH-WEIGHT; TUMOR-NECROSIS-FACTOR; POLYMERASE-CHAIN-REACTION; INTRAPARTUM RISK-FACTORS; AUSTRALIAN CASE-CONTROL; WHITE-MATTER LESIONS; FACTOR-ALPHA GENE; CEREBRAL-PALSY; PERIVENTRICULAR LEUKOMALACIA; INTRAUTERINE INFECTION AB This article reviews what is known about the association of chorioamnionitis and brain injury. Most studies relating chorioamnionitis to neurologic outcome in the child have concentrated on cerebral palsy (CP) [1], although some have reported associations of chorioamnionitis with an aggregated adverse outcome that included CP [2-4]. Fewer studies address outcomes measured by standardized tests of infant development [5] or evidence suggesting that maternal infections other than chorioamnionitis may increase susceptibility to later psychiatric diseases in exposed offspring [6-8]. In addition to long-term outcomes, this article discusses the association of chorioamnionitis with neurological depression in the newborn period, because that association offers information on pathways of pathogenesis and is of practical relevance to clinicians. C1 Johns Hopkins Univ Hosp, Dept Pediat, Eudowood Div Pediat Infect Dis, Baltimore, MD 21287 USA. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. RP Willoughby, RE (reprint author), Johns Hopkins Univ Hosp, Dept Pediat, Eudowood Div Pediat Infect Dis, 600 N Wolfe St,Pk 256, Baltimore, MD 21287 USA. NR 134 TC 55 Z9 58 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 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD DEC PY 2002 VL 29 IS 4 BP 603 EP + AR PII S0095-5108(02)00058-1 DI 10.1016/S0095-5108(02)00058-1 PG 20 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 627ZQ UT WOS:000179967400004 PM 12516738 ER PT J AU Woodruff-Pak, DS Lander, C Geerts, H AF Woodruff-Pak, DS Lander, C Geerts, H TI Nicotinic cholinergic modulation: Galantamine as a prototype SO CNS DRUG REVIEWS LA English DT Review DE acetylcholine; Alzheimer's disease; dementia; nicotinic acetylcholine receptors (nAChRs) ID ACETYLCHOLINE-RECEPTOR SUBUNIT; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; TORPEDO-CALIFORNICA; HIPPOCAMPAL-NEURONS; TRANSGENIC MICE; GALANTHAMINE; MEMORY; RAT; INHIBITION AB Nicotinic acetylcholine receptor pharmacology is becoming increasingly important in the clinical symptomatology of neurodegenerative diseases in general and of cognitive and behavioral aspects in particular. In addition, the concept of allosteric modulation of nicotinic acetylcholine receptors has become a research focus for the development of therapeutic agents. In this review the scientific evidence for changes in nicotinic acetylcholine receptors in Alzheimer's disease is described. Within this context, the pharmacology of galantamine, a recently approved drug for cognition enhancement in Alzheimer's disease, is reviewed along with preclinical studies of its efficacy on learning and memory. Galantamine modestly inhibits acetylcholinesterase and has an allosteric potentiating ligand effect at nicotinic receptors. The data collected in this review suggest that the unique combination of acetylcholinesterase inhibition and nicotinic acetylcholine receptor modulation offers potentially significant benefits over acetylcholinesterase inhibition alone in facilitating acetylcholine neurotransmission. C1 Albert Einstein Healthcare Network, Philadelphia, PA 19141 USA. Temple Univ, Philadelphia, PA 19141 USA. NCI Network, New York, NY USA. Inc Silico Biosci, Philadelphia, PA USA. RP Woodruff-Pak, DS (reprint author), Albert Einstein Healthcare Network, Korman Suite 100,5501 Old York Rd, Philadelphia, PA 19141 USA. NR 97 TC 39 Z9 41 U1 0 U2 6 PU NEVA PRESS PI BRANFORD PA P O BOX 347, BRANFORD, CT 06405 USA SN 1080-563X J9 CNS DRUG REV JI CNS Drug Rev. PD WIN PY 2002 VL 8 IS 4 BP 405 EP 426 PG 22 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 637NN UT WOS:000180519000006 PM 12481195 ER PT J AU Pessoa, L Kastner, S Ungerleider, LG AF Pessoa, L Kastner, S Ungerleider, LG TI Attentional control of the processing of neutral and emotional stimuli SO COGNITIVE BRAIN RESEARCH LA English DT Review DE fMRI; attention; executive function; emotion; amygdala ID HUMAN VISUAL-CORTEX; POSITRON EMISSION TOMOGRAPHY; POSTERIOR PARIETAL CORTEX; SACCADIC EYE-MOVEMENTS; SELECTIVE ATTENTION; SPATIAL ATTENTION; HUMAN BRAIN; DIRECTED ATTENTION; FACIAL EXPRESSIONS; NEURAL MECHANISMS AB A typical scene contains many different objects that compete for neural representation due to the limited processing capacity of the visual system. At the neural level, competition among multiple stimuli is evidenced by the mutual suppression of their visually evoked responses and occurs most strongly at the level of the receptive field. The competition among multiple objects can be biased by both bottom-up sensory-driven mechanisms and top-down influences, such as selective attention. Functional brain imaging studies reveal that biasing signals due to selective attention can modulate neural activity in visual cortex not only in the presence but also in the absence of visual stimulation. Although the competition among stimuli for representation is ultimately resolved within visual cortex, the source of top-down biasing signals likely derives from a distributed network of areas in frontal and parietal cortex. Competition suggests that once attentional resources are depleted, no further processing is possible, Yet, existing data suggest that emotional stimuli activate brain regions,automatically,' largely immune from attentional control. We tested the alternative possibility, namely, that the neural processing of stimuli with emotional content is not automatic and instead requires some degree of attention. Our results revealed that, contrary to the prevailing view, all brain regions responding differentially to emotional faces, including the amygdala, did so only when sufficient attentional resources were available to process the faces. Thus, similar to the processing of other stimulus categories, the processing of facial expression is under top-down control, Published by Elsevier Science B.V. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Princeton Univ, Dept Psychol, Ctr Study Brain Mind & Behav, Princeton, NJ 08544 USA. RP Pessoa, L (reprint author), NIMH, Lab Brain & Cognit, 49 Convent Dr,Bldg 49,Room 1B80, Bethesda, MD 20892 USA. RI Frank, David/E-8213-2012 NR 116 TC 231 Z9 249 U1 6 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD DEC PY 2002 VL 15 IS 1 BP 31 EP 45 AR PII S0926-6410(02)00214-8 DI 10.1016/S0926-6410(02)00214-8 PG 15 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 625CG UT WOS:000179798900003 ER PT J AU Sloan, DM Marx, BP Bradley, MM Strauss, CC Lang, PJ Cuthbert, BC AF Sloan, DM Marx, BP Bradley, MM Strauss, CC Lang, PJ Cuthbert, BC TI Examining the high-end specificity of the Beck depression inventory using an anxiety sample SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE BDI; high-end specificity; depression; anxiety ID DSM-III; RELIABILITY; DISORDERS; EVENTS AB Although the Beck Depression Inventory (BDI) is one of the most widely used measures of depression, there is some concern whether high scores on the BDI represent the nosologic category of depression or psychological distress more generally. In this study the high-end specificity of the BDI was examined using a clinical sample of anxiety-disordered individuals, a group characterized by high negative affect. Results revealed using a high BDI cut score produced moderate specificity and sensitivity rates. Additional analyses indicated an overall fair performance of the BDI in classifying depression in the anxiety sample and an optimal cut score for differentiating anxiety clients with and without comorbid depression was identified. However, using the optimal cut score resulted in nearly one third of the sample being incorrectly classified on the basis on their BDI scores. The findings underscore the importance of not relying solely on BDI scores to classify depression samples, which is a current common practice in psychological research. C1 Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. Univ Florida, Ctr Study Emot & Attent, Dept Clin & Hlth Psychol, Gainesville, FL USA. NIMH, Rockville, MD 20857 USA. RP Sloan, DM (reprint author), Temple Univ, Dept Psychol, Weiss Hall, Philadelphia, PA 19122 USA. NR 27 TC 18 Z9 18 U1 4 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD DEC PY 2002 VL 26 IS 6 BP 719 EP 727 DI 10.1023/A:1021233215457 PG 9 WC Psychology, Clinical SC Psychology GA 619HE UT WOS:000179469900003 ER PT J AU Thorgaard, GH Bailey, GS Williams, D Buhler, DR Kaattari, SL Ristow, SS Hansen, JD Winton, JR Bartholomew, JL Nagler, JJ Walsh, PJ Vijayan, MM Devlin, RH Hardy, RW Overturf, KE Young, WP Robison, BD Rexroad, C Palti, Y AF Thorgaard, GH Bailey, GS Williams, D Buhler, DR Kaattari, SL Ristow, SS Hansen, JD Winton, JR Bartholomew, JL Nagler, JJ Walsh, PJ Vijayan, MM Devlin, RH Hardy, RW Overturf, KE Young, WP Robison, BD Rexroad, C Palti, Y TI Status and opportunities for genomics research with rainbow trout SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Review DE carcinogenesis; fish; genetics; genomics; immunology; nutrition; Oncorhynchus mykiss; physiology; rainbow trout; toxicology ID MHC CLASS-I; MAJOR HISTOCOMPATIBILITY COMPLEX; VIRAL HEMORRHAGIC SEPTICEMIA; SALMON SALMO-SALAR; CYTO-TOXIC CELLS; INFECTIOUS HEMATOPOIETIC NECROSIS; CATFISH ICTALURUS-PUNCTATUS; QUANTITATIVE TRAIT LOCI; NATURAL-KILLER-CELLS; ONCORHYNCHUS-MYKISS WALBAUM AB The rainbow trout (Oncorhynchus mykiss) is one of the most widely studied of model fish species. Extensive basic biological information has been collected for this species, which because of their large size relative to other model fish species are particularly suitable for studies requiring ample quantities of specific cells and tissue types. Rainbow trout have been widely utilized for research in carcinogenesis, toxicology, comparative immunology, disease ecology, physiology and nutrition. They are distinctive in having evolved from a relatively recent tetraploid event, resulting in a high incidence of duplicated genes. Natural populations are available and have been well characterized for chromosomal, protein, molecular and quantitative genetic variation. Their ease of culture, and experimental and aquacultural significance has led to the development of clonal lines and the widespread application of transgenic technology to this species. Numerous microsatellites have been isolated and two relatively detailed genetic maps have been developed. Extensive sequencing of expressed sequence tags has begun and four BAC libraries have been developed. The development and analysis of additional genomic sequence data will provide distinctive opportunities to address problems in areas such as evolution of the immune system and duplicate genes. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Washington State Univ, Sch Biol Sci, Pullman, WA 99164 USA. Washington State Univ, Ctr Reprod Biol, Pullman, WA 99164 USA. Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. Coll William & Mary, Virginia Inst Marine Sci, Gloucester Point, VA 23062 USA. Washington State Univ, Agr Res Ctr, Pullman, WA 99164 USA. Univ Maryland, Ctr Marine Biotechnol, Columbus Ctr, Baltimore, MD 21202 USA. US Geol Survey, Western Fisheries Res Ctr, Biol Resources Div, Seattle, WA 98115 USA. Oregon State Univ, Dept Microbiol, Ctr Fish Dis Res, Corvallis, OR 97331 USA. Univ Idaho, Dept Sci Biol, Moscow, ID 83844 USA. Univ Idaho, Ctr Reprod Biol, Moscow, ID 83844 USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. Univ Waterloo, Dept Biol, Waterloo, ON N2L 3G1, Canada. Fisheries & Oceans Canada, W Vancouver, BC V7V 1N6, Canada. Univ Idaho, Dept Vet & Anim Sci, Hagerman Fish Culture Expt Stn, Hagerman, ID 83332 USA. USDA ARS, Hagerman Fish Culture Expt Stn, Hagerman, ID 83332 USA. No Arizona Univ, Dept Biol Sci, Flagstaff, AZ 86011 USA. Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. USDA ARS, Natl Ctr Cool & Cold Water Aquaculture, Kearneysville, WV 25430 USA. RP Thorgaard, GH (reprint author), Washington State Univ, Sch Biol Sci, Pullman, WA 99164 USA. EM thorglab@wsu.edu FU NIEHS NIH HHS [ES00210, ES03850, ES05705] NR 357 TC 123 Z9 128 U1 0 U2 33 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1096-4959 EI 1879-1107 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD DEC PY 2002 VL 133 IS 4 BP 609 EP 646 AR PII S1096-4959(02)00167-7 DI 10.1016/S1096-4959(02)00167-7 PG 38 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 629BL UT WOS:000180030500015 PM 12470823 ER PT J AU Hsia, J Alderman, EL Verter, JI Rogers, WJ Thompson, P Howard, BV Cobb, FR Ouyang, P Tardif, JC Higginson, L Bittner, V Barofsky, I Steffes, M Gordon, DJ Proschan, M Younes, N Waters, D AF Hsia, J Alderman, EL Verter, JI Rogers, WJ Thompson, P Howard, BV Cobb, FR Ouyang, P Tardif, JC Higginson, L Bittner, V Barofsky, I Steffes, M Gordon, DJ Proschan, M Younes, N Waters, D TI Women's Angiographic Vitamin and Estrogen trial: Design and methods SO CONTROLLED CLINICAL TRIALS LA English DT Article DE estrogen; antioxidants; coronary heart disease; coronary angiography ID CORONARY-ARTERY DISEASE; ENDOTHELIUM-DEPENDENT VASODILATION; ATHEROSCLEROTIC HEART-DISEASE; HORMONE REPLACEMENT THERAPY; HEALTH-CARE PROFESSIONALS; BASE-LINE CHARACTERISTICS; POSTMENOPAUSAL WOMEN; ANTIOXIDANT VITAMINS; E SUPPLEMENTATION; NITRIC-OXIDE AB The Women's Angiographic Vitamin and Estrogen trial was a randomized, double-blind, placebo-controlled study designed to test the efficacy of estrogen replacement and antioxidant vitamins for preventing angiographic progression of coronary artery disease. Postmenopausal women with one or more angiographically documented coronary stenoses of 15-75% at baseline were assigned in a 2X2 factorial randomization to active hormone replacement therapy (conjugated estrogens for women who had had a hysterectomy or conjugated estrogens with medroxyprogesterone for women with intact uteri) or placebo and to active vitamins E and C or their placebos. Seven clinical centers, five in the United States and two in Canada, randomized 423 women between July 1997 and July 1999. Quantitative coronary angiography was performed at baseline and repeated after projected mean follow-up of 3 years. (C) 2002 Elsevier Science Inc. All rights reserved. C1 George Washington Univ, Dept Med, Washington, DC USA. Stanford Univ, Falk Cardiovasc Res Ctr, Stanford, CA 94305 USA. George Washington Univ, Dept Stat, Washington, DC 20052 USA. Univ Alabama, Dept Cariol, Birmingham, AL USA. Hartford Hosp, Div Cardiol, Hartford, CT 06115 USA. Medstar Res Inst, Washington, DC USA. Duke Univ, Duke Ctr Living, Durham, NC USA. Johns Hopkins Bayview Med Ctr, Div Cardiol, Baltimore, MD USA. Inst Cardiol Montreal, Montreal, PQ, Canada. Univ Ottawa, Inst Heart, Ottawa, ON, Canada. Johns Hopkins Univ, Med Ctr, Div Digest Dis, Baltimore, MD 21218 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. NHLBI, NIH, Bethesda, MD 20892 USA. San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. RP Hsia, J (reprint author), 2150 Penn Ave NW 4-414, Washington, DC 20037 USA. FU NHLBI NIH HHS [N01-HV68169, N01-HV-68166, N01-HV-68167, N01-HV-68170, N01-HV-68165, N01-HV-68168] NR 83 TC 17 Z9 17 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 2002 VL 23 IS 6 BP 708 EP 727 AR PII S0197-2456(02)00237-4 DI 10.1016/S0197-2456(02)00237-4 PG 20 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 625UZ UT WOS:000179835100009 PM 12505248 ER PT J AU Berra, L De Marchi, L Costello, K Mahar, R Appleton, J Lewandowski, R Kolobow, T AF Berra, L De Marchi, L Costello, K Mahar, R Appleton, J Lewandowski, R Kolobow, T TI Early colonization of the lower respiratory tract and onset of pneumonia in sheep mechanically ventilated for 24 hours SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 32nd Critical Care Congress CY JAN 28-FEB 02, 2003 CL SAN ANTONIO, TEXAS SP Soc Crit Care Med C1 NHLBI, PCCMB, 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2002 VL 30 IS 12 SU S MA R BP A164 EP A164 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 633RM UT WOS:000180296300568 ER PT J AU Berra, L De Marchi, L Costello, K Mahar, R Appleton, J Lewandowski, R Kolobow, T AF Berra, L De Marchi, L Costello, K Mahar, R Appleton, J Lewandowski, R Kolobow, T TI Early colonization of the lower respiratory tract and onset of pneumonia in sheep mechanically ventilated for 24 hours SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 32nd Critical Care Congress CY JAN 28-FEB 02, 2003 CL SAN ANTONIO, TEXAS SP Soc Crit Care Med C1 NHLBI, PCCMB, 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2002 VL 30 IS 12 SU S MA 462 BP A111 EP A111 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 633RM UT WOS:000180296300380 ER PT J AU Berra, L De Marchi, L Mahar, R Lewandowski, R Appleton, J Costello, K Kolobow, T AF Berra, L De Marchi, L Mahar, R Lewandowski, R Appleton, J Costello, K Kolobow, T TI Coated tracheal tubes with silver-sulfadiazine and chlorhexidine eliminate/greatly reduce endotracheal tube and lung bacterial colonization during 24 hours of mechanical ventilation SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 32nd Critical Care Congress CY JAN 28-FEB 02, 2003 CL SAN ANTONIO, TEXAS SP Soc Crit Care Med C1 NHLBI, PCCMB, 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2002 VL 30 IS 12 SU S MA 58 BP A16 EP A16 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 633RM UT WOS:000180296300058 ER PT J AU Umbarger, L Ognibene, FP AF Umbarger, L Ognibene, FP TI APACHE III and 6 month, 1,2, and 3 year mortality SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 32nd Critical Care Congress CY JAN 28-FEB 02, 2003 CL SAN ANTONIO, TEXAS SP Soc Crit Care Med C1 NIH, CC CCMD, 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2002 VL 30 IS 12 SU S MA 537 BP A133 EP A133 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 633RM UT WOS:000180296300454 ER PT J AU Kanegane, H Nomura, K Miyawaki, T Tosato, G AF Kanegane, H Nomura, K Miyawaki, T Tosato, G TI Biological aspects of Epstein-Barr virus (EBV)-infected lymphocytes in chronic active EBV infection and associated malignancies SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Epstein-Barr virus (EBV); malignancies; chronic active EBV infection; T-cell lymphoma ID T-CELL LYMPHOMAS; LYMPHOPROLIFERATIVE DISORDERS; VIRAL-DNA; NASOPHARYNGEAL CARCINOMA; HEMOPHAGOCYTIC SYNDROME; HODGKINS-DISEASE; TRANSPLANT RECIPIENTS; MOSQUITO ALLERGY; ENCODING GENE; NK-CELL AB Most primary Epstein-Barr virus (EBV) infections are clinically inapparent, but occasionally EBV-infection can cause acute infectious mononucleosis. EBV has been linked to a variety of hematologic and non-hematologic malignancies. Chronic active EBV (CAEBV) infection designates a recently identified EBV-associated syndrome characterized by a variety of serious hematological disorders, including malignant lymphoma. EBV was found to infect circulating T- and/or NK-cells in patients with CAEBV infection. These EBV-infected T- and/or NK-cells express EBNA-L LMP-1, and LMP-2A, a type II form of EBV latency, which is also observed in nasopharyngeal carcinoma (NPC), Hodgkin's disease (HD), and peripheral T-cell lymphoma. CAEBV infections may thus represent a subset of EBV-associated T- and/or NK-cell lymphoproliferative disorders. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Toyama Med & Pharmaceut Univ, Fac Med, Dept Pediat, Sugitani, Toyama 9300194, Japan. NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kanegane, H (reprint author), Toyama Med & Pharmaceut Univ, Fac Med, Dept Pediat, 2630 Sugitami, Sugitani, Toyama 9300194, Japan. NR 89 TC 32 Z9 36 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD DEC PY 2002 VL 44 IS 3 BP 239 EP 249 AR PII S1040-8428(02)00115-4 DI 10.1016/S1040-8428(02)00115-4 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 625CE UT WOS:000179798700006 PM 12467964 ER PT J AU Hofmann, SR Ettinger, R Zhou, YJ Gadina, M Lipsky, P Siegel, R Candotti, F O'Shea, JJ AF Hofmann, Sigrun R. Ettinger, Rachel Zhou, Yong-Jie Gadina, Massimo Lipsky, Peter Siegel, Richard Candotti, Fabio O'Shea, John J. TI Cytokines and their role in lymphoid development, differentiation and homeostasis SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE lymphoid development; homeostasis; cytokines; tumor necrosis factor; severe combined immunodeficiency AB Purpose of review The development of lymphoid tissues as well as the ultimate differentiation of naive and memory T cells are dependent on cytokines. In this review, we will focus on recent advances in the understanding of molecular mechanisms that regulate lymphoid development, homeostasis and tolerance. Recent findings Cytokines play a critical role in the development and differentiation of lymphoid cells. In addition, newer data indicate important roles of interleukin-7 and interleukin-15 in lymphoid homeostasis and memory. Furthermore, a new family of heterodimeric cytokines comprising interleukin-12, interleukin-23 and -27 is important for differentiation of helper T cells and cell-mediated immunity. Finally the importance of tumor necrosis factor superfamily members in the development of lymphoid organs has recently been elucidated and will be discussed in detail. Summary New cytokines and receptors continue to be identified. The discovery and characterization of cytokines, their receptors and signaling molecules will provide a more complete understanding of normal lymphoid development, differentiation and function. In addition, this knowledge should improve our understanding of the pathogenesis of immunological diseases and hopefully will provide new treatment strategies. C1 [Hofmann, Sigrun R.; Zhou, Yong-Jie; Gadina, Massimo; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. [Ettinger, Rachel; Lipsky, Peter; Siegel, Richard] NIAMSD, Autoimmun Branch, Bethesda, MD 20892 USA. [Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP O'Shea, JJ (reprint author), NIAMSD, NIH, 9000 Rockville Pike,Bldg 10,Room 9N252, Bethesda, MD 20892 USA. EM osheajo@mail.nih.gov NR 110 TC 45 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-4050 EI 1473-6322 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD DEC PY 2002 VL 2 IS 6 BP 495 EP 506 DI 10.1097/01.all.0000044534.45448.bf PG 12 WC Allergy; Immunology SC Allergy; Immunology GA V33LE UT WOS:000209019500004 PM 14752332 ER PT J AU McDermott, MF Aksentijevich, I AF McDermott, Michael F. Aksentijevich, Ivona TI The autoinflammatory syndromes SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE autoinflammatory; apoptosis; chronic infantile neurologic cutaneous and articular syndrome/neonatal-onset multisystem inflammatory disease; cryopyrin/NACHT; leucine-rich repeat and pyrin domain-containing protein 3/pyrin-containing Apaf1-like protein 1; Crohn's disease; interleukin-1; nuclear factor-kappa B; NACHT; pyrin/marenostrin AB Purpose of review To review the remarkable recent progress in our understanding of a range of inflammatory conditions in humans that until recently appeared unrelated. The term autoinflammatory disease has been proposed to describe a group of disorders characterized by attacks of seemingly unprovoked inflammation without significant levels of autoantibodies and autoreactive T cells. Recent findings As the link between the innate immune response and disease susceptibility has become more apparent, some remarkable associations have emerged. The majority of hereditary periodic fevers are due to mutations in the pyrin and tumour necrosis factor receptor superfamilies of molecules, both of which are intimately involved in innate immunity. Pyrin/marenostrin protein is mutated in familial Mediterranean fever, while mutations in a related protein, cryopyrin, are associated with Muckle-Wells/familial cold urticaria and chronic infantile neurologic cutaneous and articular syndrome. Both of these proteins interact with the apoptotic speck-like protein involved in caspase-1 activation and regulation of nuclear factor kappa B transcription; furthermore cryopyrin contains regions of homology with the nucleotide-binding oligomerization domain 2 protein, which is associated with susceptibility to Crohn's disease. Variants in the leucine-rich repeat domain of nucleotide-binding oligomerization domain are found in approximately 20% of patients with Crohn's disease, depending on ethnic background, while mutations in the NACHT domain are associated with a rare dominant granulomatous disease called Blau syndrome. Summary The study of autoinflammatory disease has progressed from genetics to definition of the functional defects in these patients. Although a direct association between defective innate immune responses to bacterial components and these diseases has not been formally established, much ongoing research is aimed towards confirmation of that hypothesis. C1 [McDermott, Michael F.] Univ London, Queen Mary Sch Med & Dent, Dept Diabet & Metab Med, Mol Med Unit, London, England. [Aksentijevich, Ivona] Natl Inst Arthrit & Musculoskeletal & Skin Dis, Genet & Genom Branch, Bethesda, MD USA. RP McDermott, MF (reprint author), Royal London Hosp, 5th Floor,Alexandra Wing, London E1 1BG, England. EM M.F.McDermott@qmul.ac.uk NR 28 TC 62 Z9 65 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-4050 EI 1473-6322 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD DEC PY 2002 VL 2 IS 6 BP 511 EP 516 DI 10.1097/01.all.0000044536.45448.2d PG 6 WC Allergy; Immunology SC Allergy; Immunology GA V33LE UT WOS:000209019500006 PM 14752334 ER PT J AU Eickbush, TH Furano, AV AF Eickbush, TH Furano, AV TI Fruit flies and humans respond differently to retrotransposons SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID POLYMORPHIC ALU INSERTIONS; HUMAN GENOMIC DIVERSITY; DROSOPHILA-MELANOGASTER; TRANSPOSABLE ELEMENTS; LTR RETROTRANSPOSONS; PROCESSED PSEUDOGENES; EVOLUTIONARY DYNAMICS; RECOMBINATION RATE; SEQUENCE; CHROMOSOME AB Retrotransposable element insertions are 20 times more numerous per unit length of DNA in the large human genome compared to the small Drosophila genome. Whereas all Drosophila elements are subject to constant turnover (recent insertion and elimination by selection), this has not generally been the case for human retrotransposons. We suggest that a difference in recombination adopted by these organisms in response to the deleterious effects of interspersed repeated DNA can explain in part this fundamental difference between the evolutionary dynamics of fruit fly and human retrotransposons. C1 Univ Rochester, Dept Biol, Rochester, NY 14627 USA. NIH, Bethesda, MD 20892 USA. RP Eickbush, TH (reprint author), Univ Rochester, Dept Biol, Rochester, NY 14627 USA. EM eick@mai1.rochester.edu; avf@helix.nih.gov FU NIGMS NIH HHS [GM42790] NR 56 TC 67 Z9 67 U1 0 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 2002 VL 12 IS 6 BP 669 EP 674 DI 10.1016/S0959-437X(02)00359-3 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 611ER UT WOS:000179003900007 PM 12433580 ER PT J AU Rivera, J AF Rivera, J TI Molecular adapters in Fc epsilon RI signaling and the allergic response SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELL RECEPTOR; AFFINITY IGE RECEPTOR; STIMULATED MAST-CELLS; TYROSINE PHOSPHORYLATION; PROTEIN-KINASE; RBL-2H3 CELLS; ACTIVATION; DOMAIN; LAT; MEMBRANE AB IgE-dependent activation of mast cells is central to the allergic response. The engagement of IgE-occupied receptors initiates a series of molecular events that cause the release of preformed, and de novo synthesis of, allergic mediators. Recent investigations demonstrate a critical role for nonenzymatic proteins that facilitate the activation and coordination of biochemical signals required for mast cell activation. Among these LAT, SLP-76 and Gab2 are critically important as adapters-that facilitate events initiated by IgE receptor-dependent activation of Src family protein tyrosine kinases, Lyn and Fyn. An evaluation of the role of these adapters points to complementary but independent steps in early signaling and the possibility that preference for one or another adaptor complex may result in selective mast cell responses. C1 NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bldg 10,Room 9N-228, Bethesda, MD 20892 USA. NR 51 TC 134 Z9 134 U1 1 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 2002 VL 14 IS 6 BP 688 EP 693 DI 10.1016/S0952-7915(02)00396-5 PG 6 WC Immunology SC Immunology GA 607VZ UT WOS:000178812600002 PM 12413516 ER PT J AU Hirtz, DG Fitzsimmons, LG AF Hirtz, DG Fitzsimmons, LG TI Regulatory and ethical issues in the conduct of clinical research involving children SO CURRENT OPINION IN PEDIATRICS LA English DT Review AB Children are a uniquely vulnerable population, yet there is an overwhelming need to test safety and efficacy of therapies and preventions in the pediatric population. Results from studies in adults do not provide sufficient or accurate information. Recently, the need for research involving children has been recognized and action has been taken at the federal level to address both the need for pediatric research and the protection of the welfare and rights of children as research subjects. Other ethical and legal issues such as privacy and confidentiality of information are being addressed as well. (C) 2002 Lippincott Williams Wilkins, Inc. C1 NINDS, NSC, NIH, Bethesda, MD 20892 USA. RP Hirtz, DG (reprint author), NINDS, NSC, NIH, Room 2212,6001 Execut Blvd, Bethesda, MD 20892 USA. NR 13 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD DEC PY 2002 VL 14 IS 6 BP 669 EP 675 DI 10.1097/00008480-200212000-00003 PG 7 WC Pediatrics SC Pediatrics GA 617PY UT WOS:000179371100003 PM 12436032 ER PT J AU Sinha, N Smith-Gill, SJ AF Sinha, N Smith-Gill, SJ TI Electrostatics in protein binding and function SO CURRENT PROTEIN & PEPTIDE SCIENCE LA English DT Review ID ANTIBODY-ANTIGEN ASSOCIATION; CYTOCHROME-C PEROXIDASE; RAY STRUCTURE-ANALYSIS; ION-PAIR NETWORKS; GLUTAMATE-DEHYDROGENASE; SALT BRIDGES; PYROCOCCUS-FURIOSUS; CRYSTAL-STRUCTURE; RIBOFLAVIN SYNTHASE; ANGSTROM RESOLUTION AB Protein electrostatic properties stein from the proportion and distribution of polar and charged residues. Polar and charged residues regulate the electrostatic properties by forming short-range interactions, like salt-bridges and hydrogen-bonds, and by defining the over-all electrostatic environment in the protein. Electrostatics play a major role in defining the mechanisms of protein-protein complex formation, molecular recognitions, thermal stabilities. conformational adaptabilities and protein movements. For example:- Functional hinges, or flexible regions of the protein, lack short-range electrostatic interactions: Thermophilic proteins have higher electrostatic interactions than their mesophilic counter parts; Increase in binding specificity and affinity involve optimization of electrostatics; High affinity antibodies have higher, and stronger, electrostatic interactions with their antigens: Rigid parts of proteins have higher and stronger electrostatic interactions. In this review we address the significance of electrostatics in protein folding, binding and function. We discuss that the electrostatic properties are evolutionally selected by a protein to perform an specific function. We also provide bona fide examples to illustrate this. Additionally, using continuum electrostatic and molecular dynamics approaches we show that the "hot-spot" inter-molecular interactions in a very specific antibody-antigen binding are mainly established through charged residues. These "hot-spot" molecular interactions stay intact even during high temperature molecular dynamics simulations. while the other inter-molecular interactions, of lesser functional significance. disappear. This further corroborates the significance of charge-charge interactions in defining binding mechanisms. High affinity binding frequently involves "electrostatic steering". The forces emerge from over-all electrostatic complementarities and by the formation of charged and polar interactions. We demonstrate that although the high affinity binding of barnase-barstar and anti-hen egg white lysozyme (HEL) antibody-HEL complexes involve different molecular mechanisms, it is electrostatically regulated in both the cases. These observations, and several other studies, suggest that a fine tuning of local and global electrostatic properties are essential for protein binding and function. C1 NCI, Basic Res Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Sinha, N (reprint author), NCI, Basic Res Lab, Ctr Canc Res, NIH, Bldg 469,Rm 213, Frederick, MD 21702 USA. NR 112 TC 75 Z9 75 U1 2 U2 40 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1389-2037 J9 CURR PROTEIN PEPT SC JI Curr. Protein Pept. Sci. PD DEC PY 2002 VL 3 IS 6 BP 601 EP 614 DI 10.2174/1389203023380431 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 611NJ UT WOS:000179023900003 PM 12470214 ER PT J AU Hoffman, MP Kidder, BL Steinberg, ZL Lakhani, S Ho, S Kleinman, HK Larsen, M AF Hoffman, MP Kidder, BL Steinberg, ZL Lakhani, S Ho, S Kleinman, HK Larsen, M TI Gene expression profiles of mouse submandibular gland development: FGFR1 regulates branching morphogenesis in vitro through BMP- and FGF-dependent mechanisms SO DEVELOPMENT LA English DT Article DE microarray; fibroblast growth factor receptors; FGF3; FGF7; FGF10; BMP4; BMP7; submandibular gland; organ culture; SU5402; mouse ID GROWTH-FACTOR RECEPTOR; SRC-FAMILY KINASES; SALIVARY-GLAND; CELL-PROLIFERATION; EPITHELIAL MORPHOGENESIS; BASEMENT-MEMBRANE; MAMMARY-GLAND; FIBROBLAST; DROSOPHILA; ROLES AB Analyses of gene expression profiles at five different stages of mouse submandibular salivary gland development provide insight into gland organogenesis and identify genes that may be critical at different stages. Genes with similar expression profiles were clustered, and RT-PCR was used to confirm the developmental changes. We focused on fibroblast growth factor receptor 1 (FGFRI), as its expression is highest early in gland development. We extended our array results and analyzed the developmental expression patterns of other FGFR and FGF isoforms. The functional significance of FGFRI was confirmed by submandibular gland organ culture. Antisense oligonucleotides decreased expression of FGFR1 and reduced branching morphogenesis of the glands. Inhibiting FGFRI signaling with SU5402, a FGFR1 tyrosine kinase inhibitor, reduced branching morphogenesis. SU5402 treatment decreased cell proliferation but did not increase apoptosis. Fgfr, Fgf and Bmp gene expression was localized to either the mesenchyme or the epithelium by PCR, and then measured over time by real time PCR after SU5402 treatment. FGFR1 signaling regulates Fgfr1, Fgf1, Fgf3 and Bmp7 expression and indirectly regulates Fgf7, Fgf10 and Bmp4. Exogenous FGFs and BMPs added to glands in culture reveal distinct effects on gland morphology. Glands cultured with SU5402 were then rescued with exogenous BMP7, FGF7 or FGF10. Taken together, our results suggest specific FGFs and BMPs play reciprocal roles in regulating branching morphogenesis and FGFR1 signaling plays a central role by regulating both FGF and BMP expression. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Hoffman, MP (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, 30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. FU NIDCR NIH HHS [F32-DE14322] NR 70 TC 115 Z9 117 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC PY 2002 VL 129 IS 24 BP 5767 EP 5778 DI 10.1242/dev.00172 PG 12 WC Developmental Biology SC Developmental Biology GA 631FH UT WOS:000180157100019 PM 12421715 ER PT J AU Hamblet, NS Lijam, N Ruiz-Lozano, P Wang, JB Yang, YS Luo, ZG Mei, L Chien, KR Sussman, DJ Wynshaw-Boris, A AF Hamblet, NS Lijam, N Ruiz-Lozano, P Wang, JB Yang, YS Luo, ZG Mei, L Chien, KR Sussman, DJ Wynshaw-Boris, A TI Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure SO DEVELOPMENT LA English DT Article DE Dvl2; cardiac neural crest; DORV; PTA; somitogenesis; neural tube closure ID CELL FATE; POLARITY GENE; INT-1 PROTOONCOGENE; SIGNALING PATHWAYS; TISSUE POLARITY; LUNATIC FRINGE; AXIS FORMATION; CREST CELLS; FLOOR PLATE; MOUSE AB The murine dishevelled 2 (Dvl2) gene is an ortholog of the Drosophila segment polarity gene Dishevelled, a member of the highly conserved Wingless/Wnt developmental pathway. Dvl2-deficient mice were produced to determine the role of Dvl2 in mammalian development. Mice containing null mutations in Dvl2 present with 50% lethality in both inbred 129S6 and in a hybrid 129S6-NIH Black Swiss background because of severe cardiovascular outflow tract defects, including double outlet right ventricle, transposition of the great arteries and persistent truncus arteriosis. The majority of the surviving Dvl2(-/-) mice were female, suggesting that penetrance was influenced by sex. Expression of Pitx2 and plexin A2 was attenuated in Dvl2 null mutants, suggesting a defect in cardiac neural crest development during outflow tract formation. In addition, similar to90% of Dvl2(-/-) mice have vertebral and rib malformations that affect the proximal as well as the distal parts of the ribs. These skeletal abnormalities were more pronounced in mice deficient for both Dvl1 and Dvl2. Somite differentiation markers used to analyze Dvl2(-/-) and Dvl1(-/-);Dvl2(-/-) mutant embryos revealed mildly aberrant expression of Uncx4.1, delta I and myogenin, suggesting defects in somite segmentation. Finally, 2-3% of Dvl2(-/-) embryos displayed thoracic spina bifida, while virtually all Dvl(1/2) double mutant embryos displayed craniorachishisis, a completely open neural tube from the midbrain to the tail. Thus, Dvl2 is essential for normal cardiac morphogenesis, somite segmentation and neural tube closure, and there is functional redundancy between Dvl1 and Dvl2 in some phenotypes. C1 Univ Calif San Diego, Ctr Comprehens Canc, Dept Pediat, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Comprehens Canc, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Inst Mol Med, La Jolla, CA 92093 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20814 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. Univ Alabama, Dept Neurobiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Dept Phys Med & Rehabil, Birmingham, AL 35294 USA. RP Wynshaw-Boris, A (reprint author), Univ Calif San Diego, Ctr Comprehens Canc, Dept Pediat, 9500 Gilman Dr, La Jolla, CA 92093 USA. RI Mei, Lin/G-8755-2012 FU NINDS NIH HHS [R01 NS073159] NR 69 TC 271 Z9 281 U1 1 U2 12 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC PY 2002 VL 129 IS 24 BP 5827 EP 5838 DI 10.1242/dev.00164 PG 12 WC Developmental Biology SC Developmental Biology GA 631FH UT WOS:000180157100024 PM 12421720 ER PT J AU Hou, SX Zheng, ZY Chen, X Perrimon, N AF Hou, SX Zheng, ZY Chen, X Perrimon, N TI The JAK/STAT pathway in model organisms: Emerging roles in cell movement SO DEVELOPMENTAL CELL LA English DT Review ID JAK-STAT PATHWAY; EMBRYONIC STEM-CELLS; SELF-RENEWAL; SIGNALING PATHWAY; DROSOPHILA SPERMATOGENESIS; ZEBRAFISH GASTRULATION; CONVERGENT EXTENSION; NEGATIVE REGULATION; DICTYOSTELIUM STAT; SEX-DETERMINATION AB The JAK/STAT pathway was originally identified in mammals. Studies of this pathway in the mouse have revealed that JAK/STAT signaling plays a central role during hematopoeisis and other developmental processes. The role of JAK/STAT signaling in blood appears to be conserved throughout evolution, as it is also required during fly hematopoeisis. Studies in Dictyostelium, Drosophila, and zebrafish have shown that the JAK/STAT pathway is also required in an unusually broad set of developmental decisions, including cell proliferation, cell fate determination, cell migration, planar polarity, convergent extension, and immunity. There is increasing evidence that the versatility of this pathway relies on its cooperation with other signal transduction pathways. In this review, we discuss the components of the JAK/STAT pathway in model organisms and what is known about its requirement in cellular and developmental processes. In particular, we emphasize recent insights into the role that this pathway plays in the control of cell movement. C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Hou, SX (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Bldg 560,Room 12-70, Frederick, MD 21702 USA. EM shou@mail.ncifcrf.gov NR 105 TC 154 Z9 164 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD DEC PY 2002 VL 3 IS 6 BP 765 EP 778 DI 10.1016/S1534-5807(02)00376-3 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 624JG UT WOS:000179756100006 PM 12479803 ER PT J AU Klein, SL Strausberg, RL Wagner, L Pontius, J Clifton, SW Richardson, P AF Klein, SL Strausberg, RL Wagner, L Pontius, J Clifton, SW Richardson, P CA Washington Univ Est Sequencing Grp Natl Inst Hlth Xenopus Working Grp TI Genetic and genomic tools for Xenopus research: The NIH Xenopus initiative SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Xenopus laevis; Xenopus tropicalis; resources; ESTs; cDNA libraries; genomic libraries AB The NIH Xenopus Initiative is establishing many of the genetic and genomic resources that have been recommended by the Xenopus research community. These resources include cDNA libraries, expressed sequence tags, full-length cDNA sequences, genomic libraries, pilot projects to mutagenize and phenotype X. tropicalis, and sequencing the X. tropicalis genome. This review describes the status of these projects and explains how to access their data and resources. Current information about these activities is available on the NIH Xenopus Web site (http://www.nih.gov/science/models/xenopus/). Published 2002 Wiley-Liss, Inc.(dagger) C1 NICHHD, Genet & Teratol Branch, Rockville, MD 20852 USA. NCI, Canc Genom Off, Bethesda, MD 20892 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63130 USA. US DOE, Joint Genome Inst, Walnut Creek, CA USA. RP Klein, SL (reprint author), NICHHD, Genet & Teratol Branch, Room 4B01,6100 Execut Blvd, Rockville, MD 20852 USA. NR 0 TC 201 Z9 221 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2002 VL 225 IS 4 BP 384 EP 391 DI 10.1002/dvdy.10174 PG 8 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 622FJ UT WOS:000179635700004 PM 12454917 ER PT J AU Watanabe, M Rebbert, ML Andreazzoli, M Takahashi, N Toyama, R Zimmerman, S Whitman, M Dawid, IB AF Watanabe, M Rebbert, ML Andreazzoli, M Takahashi, N Toyama, R Zimmerman, S Whitman, M Dawid, IB TI Regulation of the Lim-1 gene is mediated through conserved FAST-1/FoxH1 sites in the first intron SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Xlim-1; Lim1; FAST-FoxH1; nodal; activin; Schmalspur ID ERYTHROID-DIFFERENTIATION FACTOR; RIGHT ASYMMETRIC EXPRESSION; MESODERM-INDUCING FACTOR; HOMEOBOX GENE; PRIMITIVE STREAK; TRANSCRIPTIONAL REGULATION; VERTEBRATE DEVELOPMENT; EARLY EMBRYOGENESIS; ORGANIZER FORMATION; SPEMANNS ORGANIZER AB The Lim-1 gene encodes a LIM-homeodomain transcription factor that is highly conserved among vertebrates and is required for successful gastrulation and head formation. The expression of this gene in the mesoderm of the gastrula is known to require an activin/nodal signal. Earlier studies have shown that the Xenopus Lim-1 (Xlim-1) gene contains an activin response element (ARE) in its first intron, which cooperates with an activin-unresponsive upstream promoter in the regulation of the gene. Here, we show that the Xlim-1 ARE contains a cluster of FAST-1/FoxH1 and Smad4 recognition sites; such sites have been shown to mediate activin/nodal responses in other genes. By using reporter constructs with mutated FAST-1/FoxH1 sites and FAST-1/FoxH1 protein chimeras, we show that the regulation of Xlim-1 by activin depends on FAST-1/FoxH1 function. Comparative studies on the zebrafish lim1 gene indicate the presence of FoxH1 sites in the first intron of this gene and provide evidence for the requirement for FoxH1 function in its regulation. These results illuminate the conserved nature of the transcriptional regulation of the Lim-1 gene in different vertebrate animals. (C) 2002 Wiley-Liss, Inc. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NYU, Sch Med, Skirball Inst Biomol Med, Dev Genet Program, New York, NY USA. RP Dawid, IB (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. OI Andreazzoli, Massimiliano/0000-0001-9633-204X NR 60 TC 20 Z9 21 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2002 VL 225 IS 4 BP 448 EP 456 DI 10.1002/dvdy.10176 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 622FJ UT WOS:000179635700009 PM 12454922 ER PT J AU Tack, CJ van Gurp, PJ Holmes, C Goldstein, DS AF Tack, CJ van Gurp, PJ Holmes, C Goldstein, DS TI Local sympathetic denervation in painful diabetic neuropathy SO DIABETES LA English DT Article ID PLASMA DIHYDROXYPHENYLGLYCOL; NERVE ACTIVITY; NOREPINEPHRINE; HUMANS; POLYNEUROPATHY; MICROCIRCULATION; NORADRENALINE; AMITRIPTYLINE; DESIPRAMINE; RESPONSES AB This study assessed whether painful diabetic neuropathy is associated with abnormal sympathetic nervous function in the affected limbs. Nine patients with diabetes (four men, five women; age 61 7 years) and painful peripheral neuropathy of the feet, but without evidence of generalized autonomic neuropathy, underwent intravenous infusion of tritiated norepinephrine (NE) and sampling of arterial and venous blood in both feet and in one arm to quantify the rate of entry of NE into the local venous plasma (NE spillover). In the same patients, positron emission tomography (PET) scanning after intravenous injection of the sympathoneural imaging agent 6-[F-18]fluorodopamine was used to visualize sympathetic innervation and after intravenous [N-13]ammonia to visualize local perfusion. The results were compared with those in the feet of normal volunteers and in an unaffected foot of patients with unilateral complex regional pain syndrome (CRPS). In addition, neurochemical results obtained in painful diabetic neuropathy were compared with those obtained in diabetic control patients with painless neuropathy and diabetic control patients without neuropathy. Local arteriovenous difference in plasma NE levels (DeltaNE(AV)) and NE spillover in the arms did not differ across the groups. However, DeltaNE(AV) in the feet was significantly less in the group with painful diabetic neuropathy than in the control groups. Also NE spillover in the feet tended to be lower in painful neuropathy. DeltaNE(AV) of diabetic control patients without neuropathy (n = 6) resembled values in the control groups without diabetes, whereas patients with painless diabetic neuropathy (n = 6) had evidence suggesting partial loss of sympathetic minervation. PET scanning revealed decreased flow-corrected 6-[F-18]fluorodopamirle-derived radioactivity in patients with painful diabetic neuropathy, compared with values in normal volunteers and patients with CRPS. The results provide neurochemical and neurointaging evidence for regionally selective sympathetic denervation in the painful feet of patients with diabetic neuropathy. C1 Univ Nijmegen, Med Ctr, Div Gen Internal Med, Nijmegen, Netherlands. NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP Tack, CJ (reprint author), Univ Nijmegen Hosp, Div Gen Internal Med, POB 9101, NL-6500 HB Nijmegen, Netherlands. RI Tack, Cees/A-2368-2014; Gurp, P.J.M./L-4342-2015 NR 47 TC 15 Z9 18 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2002 VL 51 IS 12 BP 3545 EP 3553 DI 10.2337/diabetes.51.12.3545 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 620EH UT WOS:000179520700027 PM 12453912 ER PT J AU Li, GW Hu, YH Yang, WY Jiang, YY Wang, JP Xiao, JZ Hu, ZX Pan, XR Howard, BV Bennett, PH AF Li, GW Hu, YH Yang, WY Jiang, YY Wang, JP Xiao, JZ Hu, ZX Pan, XR Howard, BV Bennett, PH TI Effects of insulin resistance and insulin secretion on the efficacy of interventions to retard development of type 2 diabetes mellitus: the DA Qing IGT and Diabetes Study SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE effects; insulin; resistance; secretion; efficiacy; intervention; type 2 diabetes ID GLUCOSE-TOLERANCE; BETA-CELL; NIDDM AB Objective: To investigate the effects of insulin resistance (IR) and insulin secretion (IS) on the development of diabetes mellitus in individuals with impaired glucose tolerance (IGT) who underwent lifestyle interventions. Methods: 284 out of 577 individuals with IGT identified by population-based screening in Da Qing, China, who were randomized to undergo diet change and/or increased physical activity had baseline fasting and 2 It post-load insulin determinations. They were followed for 6 years for the development of diabetes. IR and IS were assessed using calculated indices based on fasting plasma insulin and glucose. The interactions of IR, IS, obesity and plasma glucose and the effects of the lifestyle interventions were evaluated using Cox Proportional Hazards analysis. Results: Both IR and IS were significantly associated with the development of diabetes. Lifestyle interventions were more effective in those with lower IT and higher IS at baselin. Diet plus exercise interventions resulted in significantly lower incidence of diabetes, even after controlling for IR, IS, BMI and 2hrPG. Conclusion: Both IR and beta-cell function were predictors of diabetes in Chinese with IGT. Lifestyle intervention reduced the incidence of DM and these interventions were more effective in those with less IR. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 China Japan Friendship Hosp, Dept Endocrinol, Beijing 100029, Peoples R China. MedStar Hlth, Washington, DC USA. Natl Inst Diabet & Kidney Dis, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. RP Li, GW (reprint author), China Japan Friendship Hosp, Dept Endocrinol, Yinghua Yeast St, Beijing 100029, Peoples R China. NR 17 TC 51 Z9 57 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD DEC PY 2002 VL 58 IS 3 BP 193 EP 200 AR PII S0168-8227(02)00175-4 DI 10.1016/S0168-8227(02)00175-4 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 616XJ UT WOS:000179328500006 PM 12413779 ER PT J AU Bjornholm, M He, AR Attersand, A Lake, S Liu, SCH Lienhard, GE Taylor, S Arner, P Zierath, JR AF Bjornholm, M He, AR Attersand, A Lake, S Liu, SCH Lienhard, GE Taylor, S Arner, P Zierath, JR TI Absence of functional insulin receptor substrate-3 (IRS-3) gene in humans SO DIABETOLOGIA LA English DT Article DE adipocytes; bioinformatics; comparative genomics; diabetes; expressed sequence tag; genetics; insulin signalling; phosphatidylinositol 3-kinase; phosphotyrosine binding domain; pleckstrin homology domain ID PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOTYROSINE PROTEIN; SIGNAL-TRANSDUCTION; TISSUE EXPRESSION; GLUCOSE-TRANSPORT; SKELETAL-MUSCLE; NIDDM SUBJECTS; ADIPOCYTES; PHOSPHORYLATION; SEQUENCE AB Aim/hypothesis. Insulin receptor substrate (IRS) proteins play important roles in insulin action and pancreatic beta-cell function. At least four mammalian IRS molecules have been identified. Although genes and cDNAs encoding human IRS-1, IRS-2, and IRS-4 have been cloned, IRS-3 has been identified only in rodents. Thus, we have attempted to clone the human IRS-3 gene. Methods. Insulin-stimulated rat or human adipocytes were subjected to Western blot analysis to assess IRS-3 tyrosine phosphorylation. Human liver and adipose cDNA libraries were screened in an effort to clone IRS-3 cDNA. A PCR-based approach was designed to amplify IRS-3 cDNA. Reverse transcription PCR was carried out using mRNA from adipose tissue, liver, and skeletal muscle as templates in combination with an in silico screen using mouse IRS-1, IRS-2 and IRS-3 in a tblastn search of the draft public human genome. Results. In human adipocytes we did not detect a M-r 60 000 phosphoprotein corresponding to IRS-3, whereas in rat adipocytes IRS-3 protein and insulin-stimulated tyrosine phosphorylation was readily observed. None of the molecular approaches provided evidence for a functional IRS-3 gene in human tissue. Two deletions in human IRS-3 gene were identified using bioinformatics. The human IRS-3 gene product is predicted to lack a phosphotyrosine binding domain and also the sequence corresponding amino acid 353-407 of murine IRS-3. The contiguous sequence of genomic DNA between these two homologous regions does not have the coding information for human IRS-3. Conclusion/interpretation. In silico screening of the human IRS-3 genome region, combined with further biological and molecular validation, provides evidence against a functional IRS-3 in humans. C1 Karolinska Inst, Sect Integrat Physiol, S-17177 Stockholm, Sweden. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Biovitrum AB, Stockholm, Sweden. Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH USA. Huddinge Univ Hosp, Med & Clin Res Ctr, Stockholm, Sweden. RP Zierath, JR (reprint author), Karolinska Inst, Sect Integrat Physiol, Von Eulers Vag 4 2, S-17177 Stockholm, Sweden. OI Zierath, Juleen/0000-0001-6891-7497 FU NIDDK NIH HHS [DK42816] NR 26 TC 51 Z9 52 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2002 VL 45 IS 12 BP 1697 EP 1702 DI 10.1007/s00125-002-0945-z PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 629GG UT WOS:000180041600010 PM 12488959 ER PT J AU Vozarova, B Stefan, N Hanson, R Lindsay, RS Bogardus, C Tataranni, PA Metz, C Bucala, R AF Vozarova, B Stefan, N Hanson, R Lindsay, RS Bogardus, C Tataranni, PA Metz, C Bucala, R TI Plasma concentrations of macrophage migration inhibitory factor are elevated in Pima Indians compared to Caucasians and are associated with insulin resistance SO DIABETOLOGIA LA English DT Letter C1 NIH, Clin Diabet & Nutr Sect, Phoenix, AZ 85016 USA. RP Vozarova, B (reprint author), NIH, Clin Diabet & Nutr Sect, 4212 N 16th St,Rm 5-41, Phoenix, AZ 85016 USA. RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; Christine, Metz/0000-0002-1013-1691; Stefan, Norbert/0000-0002-2186-9595 NR 8 TC 36 Z9 36 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2002 VL 45 IS 12 BP 1739 EP 1741 DI 10.1007/s00125-002-0896-4 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 629GG UT WOS:000180041600019 PM 12552367 ER PT J AU Guo, DP von Kugelgen, I Moro, S Kim, YC Jacobson, KA AF Guo, DP von Kugelgen, I Moro, S Kim, YC Jacobson, KA TI Evidence for the recognition of non-nucleotide antagonists within the transmembrane, domains of the human P2Y(1) receptor SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE antagonists; G protein-coupled receptors; mutagenesis; phospholipase C; nucleotides ID SITE-DIRECTED MUTAGENESIS; PHOSPHOLIPASE-C; P-2-PURINOCEPTOR ANTAGONISTS; PLATELET-AGGREGATION; P2X RECEPTORS; SURAMIN; AGONIST; PPADS; P-2Y-PURINOCEPTORS; PURINOCEPTORS AB Site-directed mutagenesis was used to search for amino acid residues of the human P2Y(1) receptor involved in the binding of the P2 receptor antagonists pyridoxal-5'-phosphate-6-azophenyl-2,4-disulfonate(PPADS), its analogue 6-(2'-chloro-phenylazo)-pyridoxal-alpha(5)-phosphate (MRS 2210), the suramin analogue 8-8'-[carbonylbis(imino-3,1-phenylene)] bis(1,3,5-naphthalene-trisulfonate) (NF023), and Reactive blue 2. Receptors containing single amino acid replacements at positions in transmembrane helical domains (TMs) 3, 5, 6, and 7 critical for the activation of the receptor by nucleotide agonists were expressed in COS-7 (African green monkey kidney) cells. Inositol phosphate accumulation was induced by 2-methylthioadenosine 5'-diphosphate (2-MeSADP). In wild type human P2Y(1) receptors, PPADS (10 to 60 muM), MRS 2210 (10 muM), NF023 (100 muM), and Reactive blue 2 (10 muM) shifted the concentration-response curve of 2-MeSADP in a parallel manner to the right. For PPADS, a pA(2) value of 5.2 was estimated. The shifts caused by MRS 2210, NF023, and Reactive blue 2 corresponded to apparent pK(B) values of 5.6, 5.0, and 5.8, respectively. In K280A mutant receptors, the affinities of PPADS, MRS 2210, NF023, and Reactive blue 2 were about 6- to 60-fold lower than those observed at wild type receptors. The K280A mutation also caused an approximately 1,000-fold increase in the EC50 value of the agonist 2-MeSADP, similar to previous observations. In contrast, no major change in antagonistic potency was observed at receptors with other mutations in TMs 3, 5, 6, and 7. Thus, the residue Lys(280) (6.55), which is located within the upper third of TM 6 of the human P2Y(1) receptor, is not only critical for the activation of the receptor but also plays-an important role in the binding of pyridoxal derivatives and a number of other chemically unrelated P2 receptor antagonists. Lys(280) seems to belong to an overlapping region of the respective binding sites. Published 2003 Wiley-Liss, Inc.(dagger) C1 NIDDK, Mol Recognit Sect, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. Univ Bonn, Dept Pharmacol, D-5300 Bonn, Germany. Univ Padua, Dept Pharmaceut Sci, Padua, Italy. Kwangju Inst Sci & Technol, Dept Life Sci, Kwangju, South Korea. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Lab Bioorgan Chem, NIH, Bldg 8A,Rm B1A-17, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999] NR 30 TC 16 Z9 17 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD DEC PY 2002 VL 57 IS 4 BP 173 EP 181 DI 10.1002/ddr.10145 PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641VV UT WOS:000180768500003 PM 23105165 ER PT J AU West, KA Castillo, SS Dennis, PA AF West, KA Castillo, SS Dennis, PA TI Activation of the PI3K/Akt pathway and chemotherapeutic resistance SO DRUG RESISTANCE UPDATES LA English DT Review DE Akt; kinase; apoptosis; chemotherapy; cancer ID PROTEIN-KINASE-B; CANCER-CELL-GROWTH; SERINE-THREONINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE PATHWAY; GLYCOGEN-SYNTHASE KINASE-3; HUMAN OVARIAN-CANCER; ETHER LIPID ANALOGS; FACTOR-KAPPA-B; IN-VIVO; PHOSPHOINOSITIDE 3-KINASE AB The resistance of many types of cancer to conventional chemotherapies is a major factor undermining successful cancer treatment. In this review, the role of a signal transduction pathway comprised of the lipid kinase, phosphatidylinositol 3-kinase (PI3K), and the serine/threonine kinase, Akt (or PKB), in chemotherapeutic resistance will be explored. Activation of this pathway plays a pivotal role in essential cellular functions such as survival, proliferation, migration and differentiation that underlie the biology of human cancer. Akt activation also contributes to tumorigenesis and tumor metastasis, and as shown most recently, resistance to chemotherapy. Modulating Akt activity is now a commonly observed endpoint of chemotherapy administration or administration of chemopreventive agents. Studies performed in vitro and in vivo combining small molecule inhibitors of the PI3K/Akt pathway with standard chemotherapy have been successful in attenuating chemotherapeutic resistance. As a result, small molecules designed to specifically target Akt and other components of the pathway are now being developed for clinical use as single agents and in combination with chemotherapy to overcome therapeutic resistance. Specifically inhibiting Akt activity may be a valid approach to treat cancer and increase the efficacy of chemotherapy. Published by Elsevier Science Ltd. C1 NCI, Canc Therapeut Branch, Canc Res Ctr, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), NCI, Canc Therapeut Branch, Canc Res Ctr, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov NR 148 TC 339 Z9 358 U1 3 U2 18 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 EI 1532-2084 J9 DRUG RESIST UPDATE JI Drug Resist. Update PD DEC PY 2002 VL 5 IS 6 BP 234 EP 248 AR PII S1368-7646(02)00120-6 DI 10.1016/S1368-7646(02)00120-6 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 639NT UT WOS:000180636700003 PM 12531180 ER PT J AU Becker, M Baumann, C John, S Walker, DA Vigneron, M McNally, JG Hager, GL AF Becker, M Baumann, C John, S Walker, DA Vigneron, M McNally, JG Hager, GL TI Dynamic behavior of transcription factors on a natural promoter in living cells SO EMBO REPORTS LA English DT Article ID TUMOR VIRUS PROMOTER; GLUCOCORTICOID RECEPTOR; HORMONE; COACTIVATOR; COMPLEXES; ELONGATION; PROTEIN; GRIP1; AF-2 AB Through the use of photobleaching techniques, we examined the dynamic interaction of three members of the transcription apparatus with a target promoter in living cells. The glucocorticoid receptor (GR) interacting protein 1 (GRIP-1) exhibits a half maximal time for fluorescent recovery (tau(R)) of 5 s, reflecting the same rapid exchange as observed for GR. In contrast, the large subunit (RPB1) of RNA polymerase II (pol II) required 13 min for complete fluorescence recovery, consistent with its function as a processive enzyme. We also observe a complex induction profile for the kinetics of GR-stimulated transcription. Our results indicate that GR and GRIP-1 as components of the activating complex are in a dynamic equilibrium with the promoter, and must return to the template many times during the course of transcriptional activation. C1 NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. CNRS, ULP ESBS, INSERM, CR1,UMR 7100, F-67400 Illkirch Graffenstaden, France. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bldg 41 Room B602, Bethesda, MD 20892 USA. NR 22 TC 157 Z9 159 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD DEC PY 2002 VL 3 IS 12 BP 1188 EP 1194 DI 10.1093/embo-reports/kvf244 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 630GN UT WOS:000180099300017 PM 12446572 ER PT J AU Yakar, S Wu, YP Setser, J Rosen, CJ AF Yakar, S Wu, YP Setser, J Rosen, CJ TI The role of circulating IGF-1 - Lessons from human and animal models SO ENDOCRINE LA English DT Review DE IGF-I, -II; circulation ID GROWTH-FACTOR-I; FACTOR-BINDING-PROTEINS; MESSENGER-RIBONUCLEIC-ACID; HORMONE-RELEASING HORMONE; INSULIN SIGNAL-TRANSDUCTION; RECEPTOR GENE-EXPRESSION; BONE-MINERAL DENSITY; PROSTATE-CANCER RISK; SMOOTH-MUSCLE CELLS; TRANSGENIC MICE AB Insulin-like growth factors (IGF-I and IGF-II) play a crucial role in regulating cell proliferation and differentiation. The IGFs have mitogenic and antiapoptotic effects on normal and transformed cells. These peptide growth factors are produced by virtually all tissues and act in an endocrine, autocrine, and paracrine fashion. The endocrine form of IGF-I originates mostly (75%) from the liver and IGF-binding proteins regulate its bioactivity. Compared to other peptide growth factors, the IGFs are in abundant supply in circulation. The role of this large reservoir of IGFs has been debated for many years. in the last few years substantial progress has been made in understanding the function of the endocrine IGF-I using new animal models. This review will revisit the IGF system with particular attention to the role of circulating IGF-I in growth regulation, metabolism, and cancer. C1 NIDDK, Sect Cellular & Mol Physiol, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Yakar, S (reprint author), NIDDK, Sect Cellular & Mol Physiol, Clin Endocrinol Branch, NIH, Room 8D12,Bldg 10, Bethesda, MD 20892 USA. NR 140 TC 44 Z9 45 U1 1 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD DEC PY 2002 VL 19 IS 3 BP 239 EP 248 DI 10.1385/ENDO:19:3:239 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652DB UT WOS:000181363600004 PM 12624423 ER PT J AU Desai, KV Kavanaugh, CJ Calvo, A Green, JE AF Desai, KV Kavanaugh, CJ Calvo, A Green, JE TI Chipping away at breast cancer: insights from microarray studies of human and mouse mammary cancer SO ENDOCRINE-RELATED CANCER LA English DT Review ID GENE-EXPRESSION PATTERNS; LASER CAPTURE MICRODISSECTION; SURGICAL-ADJUVANT-BREAST; ESTROGEN-RECEPTOR-ALPHA; RAS TRANSGENIC MICE; BOWEL-PROJECT P-1; NEU ONCOGENE; CELLULAR ONCOGENES; BRCA2 MUTATIONS; ANIMAL-MODELS AB Breast cancer is the most prevalent tumor in American woman. Multiple factors, including age, diet, genetics, environment, geographic location, parity, as well as race, influence the development of this heterogeneous disease. As the process of oncogenesis involves the disruption of diverse cellular pathways including cell cycle, growth, survival, and apoptosis, the high throughput technique of microarray analyses provides a powerful insight into multiple cellular processes. These techniques determine expression patterns of thousands of genes simultaneously. Recent studies have identified particular expression patterns that can classify tumors into new groups and aid in the prediction of the natural history of the disease and the therapeutic response. This wealth of information may also form the basis for the development of new types of targeted therapies. Studies to identify the earliest molecular events in oncogenesis and progressive changes in the human disease have been difficult to perform within the same patient. The use of transgenic mouse mammary cancer models provides an opportunity to decipher molecular changes that occur at progressive stages of tumor development. This paper reviews microarray technology, and the insights gained from published breast cancer microarray analyses, and considers the contribution of microarray studies in identifying mouse cancer models that may be appropriate for answering particular experimental questions. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Green, JE (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bldg 41,Room C629,41 Lib Dr, Bethesda, MD 20892 USA. NR 107 TC 17 Z9 19 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD DEC PY 2002 VL 9 IS 4 BP 207 EP 220 DI 10.1677/erc.0.0090207 PG 14 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 648RJ UT WOS:000181164100001 PM 12542399 ER PT J AU Tjurmina, OA Armando, I Saavedra, JM Goldstein, DS Murphy, DL AF Tjurmina, OA Armando, I Saavedra, JM Goldstein, DS Murphy, DL TI Exaggerated adrenomedullary response to immobilization in mice with targeted disruption of the serotonin transporter gene SO ENDOCRINOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PITUITARY-ADRENOCORTICAL AXIS; ADRENAL CHROMAFFIN CELLS; RECEPTOR AGONIST; CONSCIOUS RATS; ELECTROCHEMICAL DETECTION; M-CHLOROPHENYLPIPERAZINE; EPINEPHRINE SECRETION; PLASMA-CATECHOLAMINE; 5-HT2A RECEPTOR AB This study examined whether serotonin transporter (5-HTT) gene knockout influences adrenomedullary, sympathoneural, or hypothalamo-pituitary-adrenal responses to acute immobilization. In conscious, cannulated mice, arterial plasma concentrations of catecholamines, ACTH, and corticosterone were measured at baseline and after 15 min of immobilization. Tissue levels of serotonin (5-HT), catecholamines, and hormones were also measured in pituitary and adrenal glands. At baseline, adrenal and pituitary 5-HT concentrations in knockout (5-HTT-/-) mice were markedly lower than those in littermate control (5-HTT+/+) mice, whereas the groups did not differ in levels of catecholamines or hormones in plasma or tissue. Immobilization increased plasma levels of cat-echolamines, ACTH, and corticosterone in all genotypes. 5-HTT-/- mice had exaggerated responses of plasma epinephrine to immobilization and significant reductions in adrenal epinephrine, norepinephrine, and 5-HT contents compared with values in littermate controls. Pituitary ACTH was significantly reduced after immobilization in 5-HTT-/- mice only, but increases in plasma ACTH and corticosterone levels did not differ between genotypes. The results suggest that one 5-HTT function is to restrain adrenomedullary activation in response to immobilization. Exaggerated adrenomedullary responses seem to be an autonomic correlate of the anxiety-like behaviors in 5-HTT knockout mice. C1 NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. NIMH, Pharmacol Sect, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Tjurmina, OA (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10,Room 3D41,10 Ctr Dr,MSC-1264, Bethesda, MD 20892 USA. NR 70 TC 82 Z9 84 U1 0 U2 5 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2002 VL 143 IS 12 BP 4520 EP 4526 DI 10.1210/en.2002-220416 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 620QK UT WOS:000179543900005 PM 12446578 ER PT J AU Suk, WA Olden, K Yang, RSH AF Suk, WA Olden, K Yang, RSH TI Chemical mixtures research: Significance and future perspectives SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE biotechnology; chemical mixtures; computer modeling; interdisciplinary collaboration; mechanistic toxicology; nanotechnology AB The study of chemical mixtures is an important area of research because of its potential impact on how risk is assessed in populations exposed to multiple environmental agents. Clearly, individuals are exposed to myriad chemical agents during their lifetime. Low-dose chronic exposure to environmental agents and the additional lifestyle factors that may affect health are extremely difficult to assess by conventional approaches. Classic scientific approaches, while serving the research community well in assessing the impact of single chemicals on the functioning of biological systems, may be inadequate to address aggregate and cumulative exposures of multiple chemicals in living systems. Over the past decades, there have been extraordinary scientific and computational technology advances. Through the incorporation of technological advances in microarrays, laser capture microdissection, imaging, and high through-put technologies, we can now study in greater detail the properties of mixtures and begin to define those characteristics that are sufficiently similar to allow extrapolation of data from one mixture to another. Bioinformatics and other computational approaches would also be integrated into this research scheme, not only for data analysis but also to develop predictive models that could be used for risk assessment. Integrated approaches that address these issues will be necessary to advance our understanding of the health relevance of exposure to mixtures. C1 Colorado State Univ, Ctr Environm Toxicol & Technol, Quantitat & Computat Toxicol Grp, Dep Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Yang, RSH (reprint author), Colorado State Univ, Ctr Environm Toxicol & Technol, Quantitat & Computat Toxicol Grp, Dep Environm & Radiol Hlth Sci, Foothills Campus,3195 Rampart Rd, Ft Collins, CO 80523 USA. FU NIEHS NIH HHS [P42 ES05949, R01 ES 09655] NR 6 TC 32 Z9 36 U1 1 U2 7 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2002 VL 110 SU 6 BP 891 EP 892 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 644RA UT WOS:000180932100001 PM 12634115 ER PT J AU Baccarelli, A Mocarelli, P Patterson, DG Bonzini, M Pesatori, AC Caporaso, N Landi, MT AF Baccarelli, A Mocarelli, P Patterson, DG Bonzini, M Pesatori, AC Caporaso, N Landi, MT TI Immunologic effects of dioxin: New results from Seveso and comparison with other studies SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review ID HUMAN IMMUNE-SYSTEM; DIBENZO-P-DIOXINS; TCDD; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; EXPOSURE; WORKERS AB Animal studies indicate that the immune system is one of the most sensitive targets of the toxic effects of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD). TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial, viral, and parasitic infections in exposed animals. Nearly 20 years after the Seveso, Italy, accident, we measured immunoglobulin and complement plasma levels in a random sample of the population in the most highly exposed zones (n = 62) and in the surrounding noncontaminated area (n = 58). Plasma IgG levels decreased with increasing TCDD plasma concentration (r = -0.35, p = 0.0002). Median IgG concentration decreased from 1,526 mg/dL in the group with the lowest (< 3.5 ppt) TCDD levels to 1,163 mg/dL in the group with the highest (20.1-89.9 ppt) TCDD levels (p = 0.002). The association was significant (P = 0.0004) after adjusting for age, sex, smoking, and consumption of domestic livestock and poultry in multiple regression analysis and persisted after exclusion of subjects with inflammatory diseases and those using antibiotics or nonsteroidal anti-inflammatory drugs. IgM, IgA, C3, and C4 plasma concentrations did not exhibit any consistent association with TCDD levels. We performed a systematic review of all the articles published between 1966 and 2001 on human subjects exposed to TCDD reporting information on circulating levels of immunoglobulins and/or complement components. The literature indicates that the evidence for effects of TCDD on humoral immunity is sparse. Methodologic issues, results, and possible sources of variation between studies are discussed. The possible long-term immunologic effects of TCDD exhibited by the participants of the present study, coupled with the increased incidence of lymphatic tumors in the area of the accident, warrant further investigation. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Milan, Dept Occupat Hlth, Milan, Italy. Univ Milan Bicocca, Dept Lab Med, Desio, Italy. Ctr Dis Control, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. RP Landi, MT (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7114, Bethesda, MD 20892 USA. RI Bonzini, Matteo/K-7540-2016; OI Bonzini, Matteo/0000-0002-6405-7554; pesatori, angela/0000-0002-0261-3252 NR 38 TC 69 Z9 72 U1 2 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2002 VL 110 IS 12 BP 1169 EP 1173 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 625HG UT WOS:000179810600018 PM 12460794 ER PT J AU Ettinger, AS Bornschein, RL Farfel, M Campbell, C Ragan, NB Rhoads, GG Brophy, M Wilkens, S Dockery, DW AF Ettinger, AS Bornschein, RL Farfel, M Campbell, C Ragan, NB Rhoads, GG Brophy, M Wilkens, S Dockery, DW TI Assessment of cleaning to control lead dust in homes of children with moderate lead poisoning-treatment of lead-exposed children trial SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE chelation; cleanup; dustwipe; environmental exposure; lead dust; lead poisoning; prevention and control ID BLOOD LEAD; ABSORPTION; SUCCIMER; ACID AB In this article we describe the assessment and control of lead dust exposure in the Treatment of Lead-exposed Children (TLC) Trial, a clinical trial of the effects of oral chelation on developmental end points in urban children with moderately elevated blood lead levels. To reduce potential lead exposure from settled dust or deteriorated paint during the drug treatment phase of the trial, the homes of 765 (98%) of the randomized children (both active and placebo drug treatment groups) were professionally cleaned. Lead dust measurements were made in a sample of 213 homes before and after cleaning. Geometric mean dust lead loadings before cleaning were 43, 29, 308, and 707 mug/ft(2) in the kitchen floor, playroom floor, playroom windowsill, and playroom window well samples respectively. Following cleaning, floor dust lead loadings were reduced on average 32% for paired floor samples (p < 0.0001), 66% for windowsills (p < 0.0001), and 93% for window wells (p < 0.0001). Cleaning was most effective for 146 homes with precleaning dust lead levels above the recommended clearance levels, with average reductions of 44%, 74%, and 93% for floors (p < 0.0001), windowsills (p < 0.0001), and window wells (p < 0.0001), respectively. Despite these substantial reductions in dust lead loadings, a single professional cleaning did not reduce the lead loadings of all dust samples to levels below current federal standards for lead in residential dust. Attainment of dust levels below current standards will require more intensive cleaning and lead hazard reduction strategies. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Epidemiol Program, Boston, MA 02115 USA. Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA. Johns Hopkins Univ, Dept Hlth Policy & Management, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. Kennedy Krieger Inst, Baltimore, MD USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Med & Dent New Jersey, Environm & Occupat Hlth Sci Inst, Piscataway, NJ 08854 USA. RP Dockery, DW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Epidemiol Program, 665 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [2 T32 ES07069-21] NR 35 TC 8 Z9 9 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2002 VL 110 IS 12 BP A773 EP A779 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 625HG UT WOS:000179810600033 PM 12460817 ER PT J AU Johnson, FM Huff, J AF Johnson, FM Huff, J TI Bioassay bashing is bad science SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID HUMAN CANCER HAZARDS; CARCINOGENESIS BIOASSAYS; CHEMICAL CARCINOGENESIS; B6C3F1 MICE; RODENT; MISCONCEPTIONS; 1,3-BUTADIENE; ALTERNATIVES; PREVENTION; INHALATION C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Johnson, FM (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 34 TC 4 Z9 4 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2002 VL 110 IS 12 BP A736 EP A737 DI 10.1289/ehp.110-a736 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 625HG UT WOS:000179810600003 PM 12460809 ER PT J AU Rogawski, MA AF Rogawski, MA TI Does P-glycoprotein play a role in pharmacoresistance to antiepileptic drugs? SO EPILEPSY & BEHAVIOR LA English DT Editorial Material ID BLOOD-BRAIN-BARRIER; RESISTANCE-ASSOCIATED PROTEIN; REFRACTORY EPILEPSY; ENDOTHELIAL-CELLS; MULTIDRUG TRANSPORTER; EXPRESSION; CARBAMAZEPINE; RATS C1 NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 20 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD DEC PY 2002 VL 3 IS 6 BP 493 EP 495 AR PII S1525-5050(02)00557-7 DI 10.1016/S1525-5050(02)00557-7 PN 1 PG 3 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 701ZQ UT WOS:000184199700004 ER PT J AU Mello, K Daly, TM Morrisey, J Vaidya, AB Long, CA Bergman, LW AF Mello, K Daly, TM Morrisey, J Vaidya, AB Long, CA Bergman, LW TI A multigene family that interacts with the amino terminus of plasmodium MSP-1 identified using the yeast two-hybrid system SO EUKARYOTIC CELL LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; FALCIPARUM MEROZOITES; 2-HYBRID SYSTEM; MALARIA; GENE; COMPLEX; YOELII; RECOMBINANT; PRECURSOR; ANTIGEN AB Merozoite surface protein 1 (MSP-1) is a high-mollecular-weight protein expressed on the surface of the malaria merozoite in a noncovalent complex with other protein molecules. MSP-1 undergoes a series of proteolytic processing events, but no precise biological role for the various proteolytic fragments of MSP-1 or for the additional proteins present in the complex is known. Through the use of the yeast two-hybrid system, we have isolated genes encoding proteins that interact with a region of the amino-terminal proteolytic fragment of MSP-1 from the mouse parasite Plasmodium yoelii. This analysis has led to the isolation of two sequence-related molecules, one of which is the P. yoelii homologue of MSP-7 originally described in Plasmodium falciparum. BLAST analysis of the P. falciparum database has revealed that there are six related protein molecules present in this species encoded near each other on chromosome 13. In P. falciparum, we designated these molecules MSRP-1 to -5. Analysis of the P. yoelii database indicates a similar chromosomal organization for the two genes in the mouse parasite species. The three P. falciparum sequences with the highest degree of homology to the P. yoelii sequences isolated in the two-hybrid screen have been characterized at the molecular level (MSRP-1 to -3). Expression analysis indicated that the mRNAs are expressed at various levels in the different asexual stages. Immunofluorescence studies colocalized the expression of the MSRP molecules and the amino-terminal portion of MSP-1 to the surfaces of trophozoites. In vitro binding experiments confirmed the interaction between MSRP-1, MSRP-2, and the amino-terminal region of P.falciparum MSP-1. C1 Drexel Univ, Coll Med, Dept Immunol & Microbiol, Div Mol Parasitol, Philadelphia, PA 19129 USA. NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD USA. RP Bergman, LW (reprint author), Drexel Univ, Coll Med, Dept Immunol & Microbiol, Div Mol Parasitol, 2900 Queen La, Philadelphia, PA 19129 USA. FU NIAID NIH HHS [R01 AI048226, AI48226] NR 30 TC 28 Z9 28 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD DEC PY 2002 VL 1 IS 6 BP 915 EP 925 DI 10.1128/EC.1.6.915-925.2002 PG 11 WC Microbiology; Mycology SC Microbiology; Mycology GA 623UX UT WOS:000179722200008 PM 12477792 ER PT J AU Perugini, MA Schuck, P Howlett, GJ AF Perugini, MA Schuck, P Howlett, GJ TI Differences in the binding capacity of human apolipoprotein E3 and E4 to size-fractionated lipid emulsions SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE Alzheimer's disease; apolipoprotein E; open conformation; lipid binding; analytical ultracentrifugation ID LOW-DENSITY LIPOPROTEINS; AMINO-ACID-SEQUENCE; TERMINAL DOMAIN; E ISOFORMS; PLASMA-LIPOPROTEINS; TRANSPORT PROTEIN; BOUNDARY ANALYSIS; AQUEOUS-SOLUTIONS; SELF-ASSOCIATION; LAMM EQUATION AB We describe sensitive new approaches for detecting and quantitating protein lipid interactions using analytical ultracentrifugation and continuous size-distribution analysis [Schuck (2000) Biophys. J. 78, 1606-1619]. The new methods were developed to investigate the binding of human apolipoprotein E (apoE) isoforms to size-fractionated lipid emulsions, and demonstrate that apoE3 binds preferentially to small lipid emulsions, whereas apoE4 exhibits a preference for large lipid particles. Although the apparent binding affilnity for large emulsions is similar (K-d approximate to 0.5 muM), the maximum binding capacity for apoE4 is significantly higher than for apoE3 (3.0 and 1.8 amino acids per phospholipid, respectively). This indicates that apoE4 has a smaller binding footprint at saturation. We propose that apoE isoforms differentiate between lipid surfaces on the basis of size, and that these differences in lipid binding are due to a greater propensity of apoE4 to adopt a more compact closed conformation. Implications for the role of apoE4 in blood lipid transport and disease are discussed. C1 Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia. NIH, OD, ORS, Div Bioengn & Phys Sci, Bethesda, MD USA. RP Perugini, MA (reprint author), Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia. OI Schuck, Peter/0000-0002-8859-6966 NR 56 TC 21 Z9 21 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD DEC PY 2002 VL 269 IS 23 BP 5939 EP 5949 DI 10.1046/j.1432-1033.2002.03319.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 617UZ UT WOS:000179380400022 PM 12444983 ER PT J AU Rohrmann, S Linseisen, J Becker, N Norat, T Sinha, R Skeie, G Lund, E Martinez, C Barricarte, A Mattisson, I Berglund, G Welch, A Davey, G Overvad, K Tjonneland, A Clavel-Chapelon, F Kesse, E Lotze, G Klipstein-Grobusch, K Vasilopoulou, E Polychronopoulos, E Pala, V Celentano, E Bueno-de-Mesquita, HB Peeters, PHM Riboli, E Slimani, N AF Rohrmann, S Linseisen, J Becker, N Norat, T Sinha, R Skeie, G Lund, E Martinez, C Barricarte, A Mattisson, I Berglund, G Welch, A Davey, G Overvad, K Tjonneland, A Clavel-Chapelon, F Kesse, E Lotze, G Klipstein-Grobusch, K Vasilopoulou, E Polychronopoulos, E Pala, V Celentano, E Bueno-de-Mesquita, HB Peeters, PHM Riboli, E Slimani, N TI Cooking of meat and fish in Europe - results from the European Prospective Investigation into Cancer and Nutrition (EPIC) SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE EPIC; meat; fish; cooking methods; 24 h recall ID DIETARY HETEROCYCLIC AMINES; GRILLED RED MEAT; BREAST-CANCER; WELL-DONE; COLORECTAL ADENOMAS; COOKED MEAT; FRIED FOODS; GENETIC-POLYMORPHISM; UNITED-STATES; PAN RESIDUES AB Objectives: There is epidemiologic evidence that the consumption of fried, grilled or barbecued meat and fish that are well-done or browned may be associated with an increased cancer risk. These high-temperature cooking methods are thought to be surrogates for mutagens and carcinogens produced in meat and fish, eg heterocyclic amines or polycyclic hydrocarbons. Since data on food cooking methods are scarce, the aim of this study was to describe the variation in meat and fish cooking methods in different parts of Europe. Design: Using a standardized 24 h recall from a sub-sample of the EPIC cohort (35 644 persons, 35-75 y old), mean daily intake of meat and fish prepared by different cooking methods and the relative contribution of the cooking methods to the overall cooking of meat and fish was calculated. Results: Whereas frying was more often noted in northern Europe, roasting and stir frying were more often used in the south. Concerning high-temperature cooking methods, their frequency of application varies between 15% in the EPIC cohort of North-Italy and 49% in the cohort of The Netherlands. Average consumption of fried, grilled and barbecued meat and fish ranges from a low of 12 g/day in the centres in southern Spain to a high of 91 g/day in northern Spain. Conclusion: High variation in both the kind of meat/fish consumed as well as its cooking methods is observed within EPIC. In order to use this variation for the evaluation of the impact of cooking methods on cancer risk, a questionnaire on meat and fish cooking methods is being developed and could be applied in the whole EPIC cohort. C1 Deutsch Krebsforschungszentrum, Div Clin Epidemiol, D-6900 Heidelberg, Germany. Int Agcy Res Canc, Unit Nutr & Canc, F-69372 Lyon, France. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Tromso, Inst Community Med, Tromso, Norway. Escuela Andaluza Salid Publ, Granada Canc Registry, Granada, Spain. Navarra Publ Univ, Dept Hlth Sci, Pamplona, Spain. Lund Univ, Dept Med Surg & Orthopaed, Malmo, Sweden. Dept Publ Hlth & Clin Med, Umea, Sweden. Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. Imperial Canc Res Fund, Canc Epidemiol Unit, Oxford, England. Univ Aarhus, Dept Epidemiol & Social Med, DK-8000 Aarhus, Denmark. Danish Canc Soc, Copenhagen, Denmark. Inst Gustave Roussy, INSERM, F-94805 Villejuif, France. German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany. Univ Athens, Dept Hyg & Epidemiol, Athens, Greece. Italian Natl Canc Inst, Epidemiol Unit, Milan, Italy. Italian Natl Canc Inst, Epidemiol Unit, Naples, Italy. Natl Inst Publ Hlth & Environm, Dept Chron Dis Epidemiol, NL-3720 BA Bilthoven, Netherlands. Univ Med Ctr, Julius Ctr Patient Oriented Res, Utrecht, Netherlands. RP Rohrmann, S (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St Rm E6133, Baltimore, MD 21205 USA. RI Welch, Ailsa/A-4850-2008; Rohrmann, Sabine/D-2113-2012; Kesse-Guyot, Emmanuelle/K-4689-2012; Linseisen, Jakob/B-5353-2014; Clavel-Chapelon, Francoise/G-6733-2014; Sinha, Rashmi/G-7446-2015; Klipstein-Grobusch , Kerstin/F-5555-2016; OI Linseisen, Jakob/0000-0002-9386-382X; Sinha, Rashmi/0000-0002-2466-7462; Klipstein-Grobusch , Kerstin/0000-0002-5462-9889; Polychronopoulos, Evangelos/0000-0001-7061-4081; Skeie, Guri/0000-0003-2476-4251 NR 48 TC 33 Z9 33 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD DEC PY 2002 VL 56 IS 12 BP 1216 EP 1230 DI 10.1038/sj.ejcn.1601494 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 638LL UT WOS:000180572400009 PM 12494307 ER PT J AU Juhasz, O Zhu, Y Garg, R Anisimov, SV Boheler, KR AF Juhasz, O Zhu, Y Garg, R Anisimov, SV Boheler, KR TI Analysis of altered genomic expression profiles in the senescent and diseased myocardium using cDNA microarrays SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Review DE cardiovascular; heart; disease; aging; microarrays; chips; genomics ID GENE-EXPRESSION; HEART-FAILURE; OLIGONUCLEOTIDE ARRAYS; MOLECULAR-MECHANISMS; CARDIAC-HYPERTROPHY; LARGE-SCALE; IDENTIFICATION; PATTERNS; SEQUENCE; MOUSE AB Cardiac function deteriorates with aging or disease. Short term, any changes in heart function may be beneficial, but long term the alterations are often detrimental. At a molecular level, functional adaptations involve quantitative and qualitative changes in gene expression. Analysis of all the RNA transcripts present in a cell's population (transcriptome) offers unprecedented opportunities to map these transitions. Microarrays (chips), capable of evaluating thousands of transcripts in one assay, are ideal for transcriptome analyses. Gene expression profiling provides information about the dynamics of total genome expression in response to environmental changes and may point to candidate genes responsible for the cascade of events that result in disease or are a consequence of aging. The aim of this review is to describe how comparisons of cellular transcriptomes by cDNA array based techniques provide information about the dynamics of total gene expression, and how the results can be applied to the study of cardiovascular disease and aging. (C) 2002 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Boheler, KR (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bohelerk@grc.nia.nih.gov NR 65 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD DEC PY 2002 VL 4 IS 6 BP 687 EP 697 AR PII S1388-9842(02)00169-1 DI 10.1016/S1388-9842(02)00169-1 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 623RY UT WOS:000179717700003 PM 12453538 ER PT J AU Dimmock, JR Jha, A Zello, GA Quail, JW Oloo, EO Nienaber, KH Kowalczyk, ES Allen, TM Santos, CL De Clercq, E Balzarini, J Manavathu, EK Stables, JP AF Dimmock, JR Jha, A Zello, GA Quail, JW Oloo, EO Nienaber, KH Kowalczyk, ES Allen, TM Santos, CL De Clercq, E Balzarini, J Manavathu, EK Stables, JP TI Cytotoxic N-[4-(3-aryl-3-oxo-1-propenyl)phenylcarbonyl]-3,5-bis(phenylmethylene)-4 -piperidones and related compounds SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE 4-piperidones; cytotoxicity; murine toxicity; structure-activity relationships ID ALPHA,BETA-UNSATURATED CARBONYL-COMPOUNDS; MANNICH-BASES; RAT-LIVER; GLUTATHIONE; INHIBITION; CHALCONES; DRUGS AB A series of 4-carboxychalcones 1 were prepared and coupled to 3,5-bis(phenylmethylene)-4-piperidone (2) giving rise to a novel series of N-[4-(3-aryl-3-oxo-1-propenyl)phenylcarbonyl]-3,5-bis(phenylmethylene)-4-piperidones (3). Molecular simplification of the amides 3 led to the formation of the corresponding N-(3-aryl-1-oxo-2-propenyl)-3,5-bis(phenylmethylene)-4-piperidones (4). A cytotoxic evaluation of the compounds in series 1-4 utilized murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In general, the compounds displayed significant toxicity; the IC(50) values of 54% of the enones were less than 10 muM when all four screens were considered and less than 1 muM for all members of series 3 in the P388 assay. Various correlations were established between the potencies of the compounds in series 1, 3 and 4 and the Hammett sigma, Hansch pi and molecular refractivity constants of the aryl substituents. Several torsion angles and interatomic distances of five representative compounds in series 3 and 4 were determined by X-ray crystallography, some of which contributed to the observed bioactivity. The marked cytotoxicity and lack of murine toxicity of most of the compounds described in this study, as well as their selective toxicity towards different tumour cell lines, revealed that development of the enones 2-4 as novel candidate antineoplastic agents should be pursued. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. Wayne State Univ, Dept Med, Detroit, MI 48201 USA. Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. Univ Alberta, Dept Pharmacol, Edmonton, AB T6G 2H7, Canada. Univ Saskatchewan, Dept Biochem, Saskatoon, SK S7N 5E5, Canada. Univ Saskatchewan, Dept Chem, Saskatoon, SK S7N 5E5, Canada. RP Dimmock, JR (reprint author), Univ Saskatchewan, Coll Pharm & Nutr, 110 Sci Pl, Saskatoon, SK S7N 5C9, Canada. EM dimmock@skyway.usask.ca RI Jha, Amitabh/B-5452-2010 OI Jha, Amitabh/0000-0002-6305-0721 NR 42 TC 34 Z9 35 U1 0 U2 5 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD DEC PY 2002 VL 37 IS 12 BP 961 EP 972 AR PII S0223-5234(02)01414-9 DI 10.1016/S0223-5234(02)01414-9 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 632FT UT WOS:000180213800005 PM 12660021 ER PT J AU Wang, MJ Lin, WW Chen, HL Chang, YH Ou, HC Kuo, JS Hong, JS Jeng, KCG AF Wang, MJ Lin, WW Chen, HL Chang, YH Ou, HC Kuo, JS Hong, JS Jeng, KCG TI Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE BV-2 cells; inducible nitric oxide synthase; NF-kappa B; p38 MAPK; superoxide ID NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; LIPID-PEROXIDATION; NERVOUS-SYSTEM; FLAVONOID ANTIOXIDANT; SUPEROXIDE-DISMUTASE; CYTOKINE PRODUCTION; KINASE ACTIVATION; OXIDATIVE STRESS AB An inflammatory response in the central nervous system mediated by activation of microglia is a key event in the early stages of the development of neurodegenerative diseases. Silymarin is a polyphenolic flavanoid derived from milk thistle that has anti-inflammatory, cytoprotective and anticarcinogenic effects. In this study, we first investigated the neuroprotective effect of silymarin against lipopolysaccharide (LPS)-induced neurotoxicity in mesencephalic mixed neuron-glia cultures. The results showed that silymarin significantly inhibited the LPS-induced activation of microglia and the production of inflammatory mediators, such as tumour necrosis factor-alpha and nitric oxide (NO), and reduced the damage to dopaminergic neurons. Therefore, the inhibitory mechanisms of silymarin on microglia activation were studied further. The production of inducible nitric oxide synthase (iNOS) was studied in LPS-stimulated BV-2 cells as a model of microglia activation. Silymarin significantly reduced the LPS-induced nitrite, iNOS mRNA and protein levels in a dose-dependent manner. Moreover, LPS could induce the activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase but not extracellular signal-regulated kinase. The LPS-induced production of NO was inhibited by the selective p38 MAPK inhibitor SB203580. These results indicated that the p38 MAPK signalling pathway was involved in the LPS-induced NO production. However, the activation of p38 MAPK was not inhibited by silymarin. Nevertheless, silymarin could effectively reduce LPS-induced superoxide generation and nuclear factor kappaB (NF-kappaB) activation. It suggests that the inhibitory effect of silymarin on microglia activation is mediated through the inhibition of NF-kappaB activation. C1 Taichung Vet Gen Hosp, Dept Educ & Res, Taichung 40705, Taiwan. Buddhist Tzu Chi Gen Hosp, Neuromed Sci Ctr, Hualien 970, Taiwan. Tzu Chi Univ, Coll Med, Hualien 970, Taiwan. Natl Taiwan Univ, Coll Med, Dept Pharmacol, Taipei, Taiwan. NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Jeng, KCG (reprint author), Taichung Vet Gen Hosp, Dept Educ & Res, Taichung 40705, Taiwan. RI Jeng, Kee Ching/C-2096-2009; OI Lin, Wan Wan/0000-0002-3207-734X NR 64 TC 119 Z9 128 U1 1 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC PY 2002 VL 16 IS 11 BP 2103 EP 2112 DI 10.1046/j.1460-9568.2002.02290.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 624QX UT WOS:000179772900010 PM 12473078 ER PT J AU Beertsen, W Holmbeck, K Niehof, A Bianco, P Chrysovergis, K Birkedal-Hansen, H Everts, V AF Beertsen, W Holmbeck, K Niehof, A Bianco, P Chrysovergis, K Birkedal-Hansen, H Everts, V TI On the role of MT1-MMP, a matrix metalloproteinase essential to collagen remodeling, in murine molar eruption and root growth SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE collagen degradation; eruption; MT1-MMP; periodontal ligament; root growth ID COLONY-STIMULATING FACTOR; TOOTH ERUPTION; BONE-RESORPTION; TURNOVER; PHAGOCYTOSIS; FIBROBLASTS; DIGESTION; MICE; RAT AB Although the connective tissues of the periodontium are subject to a high turnover rate, no conclusive evidence has yet emerged that periodontal collagen turnover is essential for the eruption of teeth or for root elongation. These processes were studied in mice deficient in MT1-MMP, a membrane type matrix metalloproteinase essential for remodeling of soft tissue hard tissue interfaces. Mandibular first molars of deficient mice and their wild-type littermates were subjected to stereological analysis in order to assess root length, eruption and the volume density of phagocytosed collagen in periodontal ligament fibroblasts. The data showed that both eruption and root elongation were severely inhibited in animals lacking the enzyme. We also found, in periodontal ligament fibroblasts from MT1-MMP-deficient mice, a massive age-related accumulation (up to 60-fold over controls) of collagen fibril-containing phagosomes. Phagolysosomes, which represent the next downstream step in collagen fibril degradation by the lysosomal pathway, did not accumulate. These observations indicate that MT1-MMP plays a central role in periodontal remodeling. The stunted root growth and the failure to erupt indicate the important role of the enzyme in tooth development. C1 Univ Amsterdam, Acad Ctr Dent Amsterdam, Dept Periodontol, Amsterdam, Netherlands. Dept Cell Biol & Histol, Amsterdam, Netherlands. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. RP Beertsen, W (reprint author), ACTA, Dept Periodontol, Louwesweg 1, NL-1066 EA Amsterdam, Netherlands. RI Beertsen, Wouter/B-5308-2013 OI Beertsen, Wouter/0000-0001-5698-5986 NR 18 TC 30 Z9 34 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD DEC PY 2002 VL 110 IS 6 BP 445 EP 451 DI 10.1034/j.1600-0722.2002.21384.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 617VK UT WOS:000179381400007 PM 12507218 ER PT J AU Giorgini, E Petrucci, R Astolfi, P Mason, RP Greci, L AF Giorgini, E Petrucci, R Astolfi, P Mason, RP Greci, L TI On the role of nitrogen monoxide (nitric oxide) in the nitration of a tyrosine derivative and model compounds SO EUROPEAN JOURNAL OF ORGANIC CHEMISTRY LA English DT Article DE nitration; nitrogen oxides; tyrosine ID ACUTE LUNG INJURY; AQUEOUS-SOLUTION; PEROXYNITRITE; NITROTYROSINE; ANTIOXIDANTS; SUPEROXIDE; CHEMISTRY; OXIDATION; SYNTHASE; KINETICS AB The nitration of tyrosine derivatives with nitrogen monoxide (nitric oxide) occurs only in the presence of dioxygen, and the hypothesized mechanism involves nitrogen dioxide (NO2). For better understanding of the reaction mechanism, the nitration of model compounds - such as 1- and 2-naphthols and their corresponding 2- and 1-nitroso derivatives with nitrogen monoxide in the presence and in the absence of dioxygen was studied. The results described here show that tyrosine and naphthols do not undergo nitrosation when they react with (NO)-N-., and so nitrosation of tyrosine in biological systems is highly unlikely. In addition, the oxidation of nitrosonaphthols reversible arrow isonitrosonaphthols by nitric oxide and its derivatives to the corresponding nitro derivatives does not involve the oxoammonium ion, as reported previously. The mechanistic proposals are supported mainly by ESR investigation and electrochemical data. ((C) Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002). C1 Univ Ancona, Dipartimento Sci Mat & Terra, I-60131 Ancona, Italy. Univ Roma La Sapienza, Dipartimento Ingn Chim, I-00616 Rome, Italy. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Greci, L (reprint author), Univ Ancona, Dipartimento Sci Mat & Terra, Via Brecce Bianche, I-60131 Ancona, Italy. EM greci@popesi.unian.it OI Astolfi, Paola/0000-0003-3226-082X NR 42 TC 6 Z9 6 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1434-193X J9 EUR J ORG CHEM JI Eur. J. Org. Chem. PD DEC PY 2002 IS 23 BP 4011 EP 4017 PG 7 WC Chemistry, Organic SC Chemistry GA 620QZ UT WOS:000179545200013 ER PT J AU Ramsey, NF Hoogduin, H Jansma, JM AF Ramsey, NF Hoogduin, H Jansma, JM TI Functional MRI experiments: acquisition, analysis and interpretation of data SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 3rd ECNP Workshop on Brain Imaging and Neuropsychopharmacology CY MAR 15-17, 2002 CL NICE, FRANCE SP ECNP DE functional neuroimaging; fMRI; methodology ID CEREBRAL-BLOOD-FLOW; BOLD FMRI STATISTICS; WORKING-MEMORY TASK; HUMAN VISUAL-CORTEX; BRAIN ACTIVATION; QUANTITATIVE ASSESSMENT; EMPIRICAL ANALYSES; NULL-HYPOTHESIS; SIGNAL; REGISTRATION AB Functional MRI is widely used to address basic and clinical neuroscience questions. In the key domains of fMRI experiments, i.e. acquisition, processing and analysis, and interpretation of data, developments are ongoing. The main issues are sensitivity for changes in fMRI signal that are associated with brain function, and the design of tasks with which brain functions are invoked. In this paper we address these issues, in terms of strengths, weaknesses and future developments. Acquisition of data is commonly achieved with techniques that measure blood oxygen level-dependent (BOLD) signal changes. Although the mechanisms that affect BOLD signal are complex and not well understood, fMRI yields results that agree with known functional topography. Sensitivity for task-related brain activity is expected to benefit from technological advances in acquisition, i.e. SENSE or parallel imaging, and higher field scanners (3 T). Data analysis is geared towards modelling sources of signal variation, i.e. reducing noise in the data time-series, and the cerebrovascular response to task-related changes in neuronal activity. Analytical algorithms such as connectivity and component analysis contribute to the extraction of meaningful information from fMRI datasets. The choice of tasks, and consequently of the statistical evaluation procedures, is best guided by the specific questions that are formulated a priori. The future is expected to bring more sophisticated questions, and tasks that allow for accurate modelling of involved brain functions. An example of a hypothesis-driven experiment is presented, where we investigated whether practise of a working memory task caused a shift in the neuronal representation of working memory or not. (C) 2002 Elsevier Science B.V./ECNP All rights reserved. C1 Univ Utrecht, Ctr Med, Dept Psychiat, Div Neurosci, NL-3584 CX Utrecht, Netherlands. Univ Groningen, BCN, NL-9713 EZ Groningen, Netherlands. NINDS, LFMI, NIH, Bethesda, MD 20892 USA. RP Ramsey, NF (reprint author), Univ Utrecht, Ctr Med, Dept Psychiat, Div Neurosci, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. NR 54 TC 23 Z9 25 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD DEC PY 2002 VL 12 IS 6 BP 517 EP 526 AR PII S0924-977X(02)00101-3 DI 10.1016/S0924-977X(02)00101-3 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 627EC UT WOS:000179919200004 PM 12468015 ER PT J AU Drevets, WC Bogers, W Raichle, ME AF Drevets, WC Bogers, W Raichle, ME TI Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 3rd ECNP Workshop on Brain Imaging and Neuropsychopharmacology CY MAR 15-17, 2002 CL NICE, FRANCE SP ECNP DE antidepressant drug treatment; positron emission tomography; regional glucose metabolism ID MEDIAL PREFRONTAL CORTEX; CEREBRAL-BLOOD-FLOW; OBSESSIVE-COMPULSIVE DISORDER; POSITRON EMISSION TOMOGRAPHY; MOOD DISORDERS; UNIPOLAR DEPRESSION; MAJOR DEPRESSION; LIMBIC SYSTEM; PARKINSONS-DISEASE; TREATMENT RESPONSE AB Neurophysiological. studies of major depression performed using PET imaging have shown abnormalities of regional cerebral blood flow (CBF) and glucose metabolism in multiple prefrontal cortical and limbic structures that have been more generally implicated in emotional processing. The current study investigated the effects of antidepressant drug treatment in these regions using PET measures of glucose metabolism. Subjects with primary MDD (n=27) were imaged while unmedicated and depressed, and, of these, 20 were rescanned following chronic antidepressant drug treatment. Regional metabolism was compared between unmedicated depressives and controls and between the pre- and post-treatment conditions in regions-of-interest (ROI) where metabolism or flow had previously been shown to be abnormal in unmedicated depressives. At baseline, the mean metabolism was increased in the left and right lateral orbital cortex/ventrolateral prefrontal cortex (PFC), left amygdala, and posterior cingulate cortex, and decreased in the subgenual ACC and dorsal medial/dorsal anterolateral PFC in the unmedicated depressives relative to controls, consistent with the results of previous studies. Following treatment, metabolism significantly decreased in the left amygdala and left subgenual ACC, and corresponding changes in the orbital and posterior cingulate cortices approached significance. The metabolic reduction in the amygdala and right subgenual ACC appeared largely limited to those subjects who both responded to treatment and remained well at 6 months follow-up, in whom the reduction in amygdala metabolism tightly correlated with the reduction in HDRS scores. The magnitude of the treatment-associated, metabolic change in the amygdala also correlated positively with the change in the stressed plasma cortisol levels measured during scanning. These data converge with those from other PET studies to indicate that primary MDD is associated with abnormal metabolism in limbic and paralimbic structures of the mesiotemporal and prefrontal cortices. Chronic antidepressant drug treatment reduces metabolism in the amygdala and ventral ACC in subjects showing a persistent, positive treatment response. In contrast, the persistence of the abnormal metabolic deficits in the dorsomedial/dorsal anterolateral PFC in MDD during treatment may conceivably relate to the histopathological changes reported in these regions in post mortem studies of MDD. (C) 2002 Elsevier Science B.V./ECNP All rights reserved. C1 NIMH, Neuroimaging Mood & Anxiety Disorders Sect, NIH, MIB, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. Washington Univ, Sch Med, Dept Neurol & Neurol Surg Neurol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, Div Radiol Sci, St Louis, MO 63110 USA. Washington Univ, Sch Med, Mc Donnell Ctr Studies Higher Brain Funct, St Louis, MO 63110 USA. RP Drevets, WC (reprint author), NIMH, Neuroimaging Mood & Anxiety Disorders Sect, NIH, MIB, 15K North Dr,Rm 203,MSC 2670, Bethesda, MD 20892 USA. EM drevetsw@intra.nimh.nih.gov FU NIMH NIH HHS [MH00928, MH51137] NR 140 TC 333 Z9 348 U1 7 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD DEC PY 2002 VL 12 IS 6 BP 527 EP 544 AR PII S0924-977X(02)00102-5 DI 10.1016/S0924-977X(02)00102-5 PG 18 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 627EC UT WOS:000179919200005 PM 12468016 ER PT J AU Duran, M Schoenberg, SO Yuh, WTC Knopp, MV van Kaick, G Essig, M AF Duran, M Schoenberg, SO Yuh, WTC Knopp, MV van Kaick, G Essig, M TI Cerebral arteriovenous malformations: morphologic evaluation by ultrashort 3D gadolinium-enhanced MR angiography SO EUROPEAN RADIOLOGY LA English DT Article DE arteriovenous malformations; ultrashort contrast-enhanced MRA; TOF MRA; angioarchitecture ID LINEAR-ACCELERATOR; RADIATION-THERAPY; RADIOSURGERY; IRRADIATION; VENOGRAPHY; CLASSIFICATION; MANAGEMENT; HEMORRHAGE; SURGERY; BRAIN AB The purpose of this study was to evaluate the usefulness of a new ultrashort contrast-enhanced (CE) MR angiography (MRA) for the morphologic evaluation of cerebral arteriovenous malformations (AVMs). The method was compared with conventional X-ray digital subtraction angiography (DSA) and time-of-flight (TOF) MRA in 22 patients to assess the angioarchitecture of the malformations which is essential for treatment planning and follow-up. Two experienced MR readers independently evaluated both techniques with regard to the assessment of feeding arteries, AVM nidus, and venous drainage patterns. Contrast-enhanced MRA was able to detect all AVMs seen on DSA, whereas the TOF MRA failed in 1 patient with a very small AVM. In the assessment of the different vessel components of the AVM there was no difference for the detection and delineation of feeding arteries and the AVM. The venous drainage patterns could always be clearly delineated in the CE MRA, whereas TOF MRA could demonstrate the exact venous drainage in only 9 patients. Contrast-enhanced MRA was found to be superior to conventional TOF MRA in the assessment of the angioarchitecture of cerebral AVMs especially regarding the assessment of the venous drainage patterns. The superiority is supported by the improved vessel-to-background contrast and contrast-to-noise ratios. The major limitations of this new technique consist of a low spatial resolution at the used time resolution which can be improved by further sequence modifications. Contrast-enhanced MRA is thus an important additional imaging technique for treatment planning and follow-up of AVMs. C1 German Canc Res Ctr, Dept Radiol, D-6900 Heidelberg, Germany. Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. NCI, Dept Radiol, Bethesda, MD 20892 USA. RP Essig, M (reprint author), German Canc Res Ctr, Dept Radiol, Neuenheimer Feld 280, D-6900 Heidelberg, Germany. NR 35 TC 36 Z9 40 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD DEC PY 2002 VL 12 IS 12 BP 2957 EP 2964 DI 10.1007/s00330-002-1418-y PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 627GL UT WOS:000179925300016 PM 12439576 ER PT J AU Holmes, EW Bingham, CM Cunningham, ML AF Holmes, EW Bingham, CM Cunningham, ML TI Hepatic expression of polymerase beta, Ref-1, PCNA, and Bax in WY 14,643-exposed rats and hamsters SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article DE peroxisome proliferator; carcinogenesis; oxidative stress ID OXIDATIVE DNA-DAMAGE; PEROXISOME PROLIFERATORS; GENE-EXPRESSION; CELL REPLICATION; SPECIES-DIFFERENCES; LIVER-REGENERATION; MITOCHONDRIAL-DNA; SYRIAN-HAMSTER; UP-REGULATION; KAPPA-B AB The hepatic levels of three protein markers of oxidative stress, polymerase beta, Ref-1, and PCNA, and of the pro-apoptotic protein, Bax, were quantitated after exposure to WY 14,643 (500 ppm in the feed) for 6 or 34 days in a rodent that is susceptible peroxisome proliferator (PP)-induced liver tumors (the Sprague Dawley rat) and in a rodent that is relatively resistant PP-induced liver tumors (the Syrian hamster). The analysis of detergent-extracted whole liver homogenates by immunoblotting showed a marked increase in the abundance of a 45-kDa variant of polymerase beta immunoreactivity and significant increases in the expression of Ref-1 and PCNA in WY 14,643-exposed rats. In contrast, WY 14,643-exposed hamsters expressed only trace levels of the polymerase beta variant and showed significant decreases in the expression of Ref-1 and PCNA. Long-term WY 14,643 exposure was associated with marked decreases in Bax expression in both species. Dose-response studies in the rat showed that the hepatic expression of the polymerase beta and Ref-1 were significantly increased after 6 clays of exposure to WY 14,643 at levels of 5 and 50 ppm, respectively. The analysis of subcellular fractions of rat liver showed that the pathological increases in the levels of polymerase beta, Ref-1, and PCNA were especially prominent in mitochondria-enriched particulate liver subfractions. These results indicate that WY 14,643 exposure is associated with an increase in oxidative stress to the liver and that liver mitochondria are a major target of WY-14,643-associated liver damage. Our data are consistent with the hypothesis that the chronic overexpression of mutagenic or oncogenic effectors like polymerase beta and Ref-1 in a setting of increased hepatocyte proliferation and decreased apoptosis may facilitate peroxisome proliferator-induced hepatocellular carcinoma in the rat. (C) 2002 Elsevier Science (USA). C1 Loyola Univ, Stritch Sch Med, Dept Pathol, Maywood, IL 60153 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Holmes, EW (reprint author), Loyola Univ, Stritch Sch Med, Dept Pathol, 103-0121,2160 S 1st Ave, Maywood, IL 60153 USA. FU NIEHS NIH HHS [1 R03 ES09783-01] NR 50 TC 6 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD DEC PY 2002 VL 73 IS 3 BP 209 EP 219 DI 10.1006/exmp.2002.2477 PG 11 WC Pathology SC Pathology GA 617BD UT WOS:000179338900007 PM 12565796 ER PT J AU Hikosaka, O Rand, MK Nakamura, K Miyachi, S Kitaguchi, K Sakai, K Lu, X Shimo, Y AF Hikosaka, O Rand, MK Nakamura, K Miyachi, S Kitaguchi, K Sakai, K Lu, X Shimo, Y TI Long-term retention of motor skill in macaque monkeys and humans SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE procedural memory; sequence task; interference; inter-manual transfer ID MEDIAL FRONTAL-CORTEX; SEQUENTIAL-PROCEDURES; VISUOMOTOR SEQUENCE; TIME-COURSE; MOVEMENTS; ACQUISITION; MEMORY; REPRESENTATIONS; PERFORMANCE; STRIATUM AB Remarkable human performance, such as playing the violin, is often based on motor skills that, once acquired, are retained for a long time. To examine how motor skills are retained, we trained monkeys and humans extensively to perform many visuomotor sequences and examined their performance after a long retention period of up to 18 months. For both monkeys and humans, we found strong evidence for long-term retention of motor skills. Each of the monkey subjects initially learned 6-18 sequences of button presses extensively by trial-and-error for up to 18 months. After a long retention period, they were asked to perform the previously learned (OLD) sequences together with completely new (NEW) sequences. The performance for OLD sequences was much better than for NEW sequences in terms of accuracy (assessed by the number of errors to criterion) and speed (assessed by the performance time). However, the retention was interfered with in two conditions, but in selective manners: (1) Learning of other sequences during the retention period interfered with accuracy, but not speed, of performance; (2) Inter-manual transfer was absent for speed, but not accuracy, of performance. The human subjects performed basically the same task as the monkeys. Each subject initially learned one sequence of 20 button presses by trial-and-error during an 8-10 day learning session. After 16 months, they were asked to perform the previously learned sequence (OLD sequence) and additional sequences including RECENT sequences (learned one day before) and NEW sequences. Their performance was considerably better on OLD and RECENT sequences than NEW sequences. Whereas the number of errors (reflecting 'accuracy') was lower for RECENT than for OLD sequences, the performance time (reflecting 'speed') was shorter for OLD than for RECENT sequences. Interestingly, the subjects were unaware that they had experienced OLD sequences. The results suggest that a motor skill is acquired and retained in two different forms, accuracy and speed. This occurs separately but concurrently. This conclusion is consistent with the hypothesis that at least two neural mechanisms operate independently to represent a motor skill. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Juntendo Univ, Sch Med, Dept Physiol, Tokyo 113, Japan. RP Hikosaka, O (reprint author), Juntendo Univ, Sch Med, Dept Physiol, Tokyo 113, Japan. NR 32 TC 43 Z9 43 U1 2 U2 17 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD DEC PY 2002 VL 147 IS 4 BP 494 EP 504 DI 10.1007/s00221-002-1258-7 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 627GF UT WOS:000179924800009 PM 12444481 ER PT J AU Compton, JG DiGiovanna, JJ Johnston, KA Fleckman, P Bale, SJ AF Compton, JG DiGiovanna, JJ Johnston, KA Fleckman, P Bale, SJ TI Mapping of the associated phenotype of an absent granular layer in ichthyosis vulgaris to the epidermal differentiation complex on chromosome 1 SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE ichthyosis vulgaris; linkage analysis; epidermal differentiation complex ID X-LINKED ICHTHYOSIS; EXPRESSION; FILAGGRIN; LINKAGE; GENE AB Ichthyosis vulgaris (IV) is a mild to severe scaling disorder of uncertain etiology estimated to affect as many as 1:250 in the population. Family studies have shown that in many cases IV follows an autosomal dominant inheritance pattern, but gene mapping studies have not been reported. To investigate the genetic basis for inherited IV, we have performed gene linkage studies in two multigenerational families where affected individuals have clinical features of IV but distinct histological features. The epidermis in this disorder characteristically displays non-specific orthohyperkeratosis Notably, a subset of IV patients with a reduced or absent granular epidermal layer (AGL) have been reported, and decreased filaggrin levels have been described in others. The prominent role of profilaggrin in human keratohyalin suggests that defects in the gene for profilaggrin (FLG), its processing of profillagrin to filaggrin, or a gene involved in profilaggrin regulation may underlie or modify the pathology in IV Family 1 had seven individuals with IV, severe heat intolerance and epidermis with 1-3 granular layers (consistent with normal epidermal histology). Ichthyosis vulgaris in this family did not segregate with FLG or other genes in the epidermal differentiation complex. In contrast, five of the six IV patients in Family 2,,all siblings, had epidermis with no granular layer. Significant evidence was obtained for linkage of IV with the associated AGL phenotype to the epidermal differentiation complex (which includes FLG) assuming either a recessive (max Lod 3.4) or dominant (max Lod 3.6) inheritance model. Sequence analysis of FLG did not reveal a mutation in the amino or carboxyl terminal portions of the coding sequence adjacent to filaggrin repeats. The AGL may represent an endophenotype for IV, and the presence of a modifier of IV pathology at this locus is discussed. C1 NIAMSD, Skin Biol Lab, NIH, Bethesda, MD USA. Brown Univ, Dept Dermatol, Providence, RI 02912 USA. Wilford Hall USAF Med Ctr, Lackland AFB, TX 78236 USA. Univ Washington, Dept Med Dermatol, Seattle, WA 98195 USA. RP Compton, JG (reprint author), GeneDx Inc, 9700 Great Seneca Highway,Suite 217, Rockville, MD 20880 USA. NR 22 TC 38 Z9 46 U1 1 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD DEC PY 2002 VL 11 IS 6 BP 518 EP 526 DI 10.1034/j.1600-0625.2002.110604.x PG 9 WC Dermatology SC Dermatology GA 630DL UT WOS:000180092200004 PM 12473059 ER PT J AU Bettelheim, FA Lizak, MJ Zigler, JS AF Bettelheim, FA Lizak, MJ Zigler, JS TI Relaxographic studies of aging normal human lenses SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE human lens; hydration; relaxographic imaging; T-1 and T-2 relaxation ID NUCLEAR MAGNETIC-RESONANCE; SENILE CATARACTOUS LENSES; AGE-RELATED-CHANGES; EYE LENSES; SYNERETIC RESPONSE; LIGHT-SCATTERING; WATER FRACTIONS; BOVINE LENSES; STATE; NMR AB Ten excised normal human lenses of various ages were studied. Seven sections of each lens, from anterior outer cortex to posterior outer cortex were imaged and the T-1 (spin-lattice) and T-2 (spin-spin) relaxation data on each section were collected. T-1 and T-2 relaxation were analysed by fitting pixel intensity to one term exponential expressions. Both T-1 and T-2 relaxation times showed minimal values in the nuclear region and maxima at the two outer cortexes. The pre-exponential terms of the fittings of both T-1 and T-2 relaxation, M-1 and M-2, were normalized in order to eliminate instrumental variations over a 2 year period. M-2 had a maximum in the nucleus and minima in the two cortexes. M-1 exhibited minimal value in the nucleus and maxima at the two cortexes. The positional dependence of T-2 relaxation times as well as that of M-2 indicated that they represent the behavior of the bound water in the lens. The positional dependence of M-1 suggests that this relaxation represents the total water that has a minimal value in the nucleus. The T-2 relaxation time decreases with increase in the age of the lens at each location. The slope of the change in T-2 relaxation time with age is greatest in the outer cortexes and diminishes as one proceeds to the nucleus. T-1 relaxation times and M-1 do not show significant change with age. This and the age dependence of the other relaxographic parameters imply that the aging of the lens involves major changes in its hydration properties that are more accentuated in the cortexes. The interpretation of these changes is in agreement with the syncretic theory of lens aging. (C) 2002 Published by Elsevier Science Ltd. C1 NEI, Lab Mechanism Ocular Dis, NIH, Bethesda, MD 20892 USA. Adelphi Univ, Dept Chem, Garden City, NY 11530 USA. NINDS, NMR Imaging Res Facil, Bethesda, MD 20892 USA. Adelphi Univ, Dept Chem, Garden City, NY 11530 USA. RP Bettelheim, FA (reprint author), NEI, Lab Mechanism Ocular Dis, NIH, 6 Ctr Dr,MSC 2735, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY-12496] NR 29 TC 7 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD DEC PY 2002 VL 75 IS 6 BP 695 EP 702 DI 10.1006/exer.2002.2056 PG 8 WC Ophthalmology SC Ophthalmology GA 627LB UT WOS:000179933700008 PM 12470971 ER PT J AU Nanavaty, UB Pawliczak, R Doniger, J Gladwin, MT Cowan, MJ Logun, C Shelhamer, JH AF Nanavaty, UB Pawliczak, R Doniger, J Gladwin, MT Cowan, MJ Logun, C Shelhamer, JH TI Oxidant-induced cell death in respiratory epithelial cells is due to DNA damage and loss of ATP SO EXPERIMENTAL LUNG RESEARCH LA English DT Article DE acute lung injury; ATP; oxidant injury; PARP; respiratory epithelium ID ADP-RIBOSE SYNTHETASE; HYDROGEN-PEROXIDE; POLY(ADP-RIBOSE) POLYMERASE; OXIDATIVE STRESS; IN-VITRO; ISCHEMIA-REPERFUSION; PHOSPHOLIPASE A(2); ENDOTHELIAL-CELLS; HEMORRHAGIC-SHOCK; INDUCED APOPTOSIS AB Oxidative stress is considered to be an important pathogenic event in ischemia-reperfusion injury, Leading to apoptosis or necrosis. We show acute cytotoxicity upon exposure to hydrogen peroxide (11202) in BEAS-2B cells and A549 cells. Single-cell gel electrophoresis showed formation of large comet tails from DNA upon oxidant exposure suggestive of DNA damage. The ATP content Of the cells decreased upon exposure to H2O2. Preincubation with 3-aminobenzamide (3-ABA), an inhibitor of poly (ADP-ribosyl) polymerase (PAPP), prevented the cytotoxicity. The decrease in the ATP content of the cells was also Prevented by 3-ABA. Increase in PARP activity was further confirmed by measuring incorporation of [P-32]-NAD into nuclear proteins in presence of the cell extracts. Markers of apoptosis were not seen in cells treated with H2O2 with or without 3-ABA pretreatment. These studies suggest that DNA damage is one of the primary reasons for oxidant-induced cell death and that PARP plays an important role in cell death due to its consumption of ATP Further elaboration of this and other pathways that consume ATP may help prevent oxidant-mediated acute lung injury. C1 NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. Med Univ Lodz, Dept Allergy & Clin Immunol, PL-90131 Lodz, Poland. RP Shelhamer, JH (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bldg 10,Room 7D43,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Pawliczak, Rafal/S-9649-2016 NR 29 TC 18 Z9 20 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD DEC PY 2002 VL 28 IS 8 BP 591 EP 607 DI 10.1080/01902140290108364 PG 17 WC Respiratory System SC Respiratory System GA 619XX UT WOS:000179503900001 PM 12490035 ER PT J AU Fu, WM Lee, J Guo, ZH Mattson, MP AF Fu, WM Lee, J Guo, ZH Mattson, MP TI Seizures and tissue injury induce telomerase in hippocampal microglial cells SO EXPERIMENTAL NEUROLOGY LA English DT Article DE dentate gyrus; hippocampus; kainic acid; neurogenesis; proliferation; TERT ID NEURAL PRECURSOR CELLS; NF-KAPPA-B; GROWTH-FACTORS; CATALYTIC SUBUNIT; ANTIGEN RECEPTOR; GENE-EXPRESSION; DENTATE GYRUS; RNA COMPONENT; BRAIN INJURY; GLIAL-CELLS AB Telomerase is a reverse transcriptase that adds repeats of a six-base DNA sequence to chromosome ends and thereby prevents their shortening during successive cell divisions. Telomerase activity and expression of the catalytic subunit of telomerase (TERT) are high in brain cells during embryonic development, but are undetectable in the adult. We now report that telomerase activity and expression of TERT are induced in the hippocampus of adult mice after administration of the seizure-inducing excitotoxin kainate. Telomerase activity is present at 24 h and 7 days after kainate administration, but is no longer detectable at 4 weeks. Because the time course of telomerase induction was similar to the time course of microglial activation, we performed studies to determine whether microglia were the source of the telomerase activity. Examination of brain sections immunostained with a TERT antibody and an antibody against a microglia-specific antigen revealed that TERT was not detectable in the uninjured brain, and was present in microglia 24 h and 7 days after kainate administration. This is the first evidence that telomerase can be induced by brain injury and the first evidence that TERT can be expressed in microglia, suggesting roles for telomerase in microglial responses to brain injury. (C) 2002 Elsevier Science (USA). 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 4F 02, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012; Lee, Jaewon/N-9064-2013 NR 49 TC 15 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 2002 VL 178 IS 2 BP 294 EP 300 DI 10.1006/exnr.2002.8030 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 628HX UT WOS:000179988500014 PM 12504888 ER PT J AU Kreitman, RJ AF Kreitman, RJ TI Recombinant fusion toxins for cancer treatment SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Editorial Material ID HAIRY-CELL LEUKEMIA; A-CHAIN IMMUNOTOXIN; REFRACTORY HODGKINS LYMPHOMA; TERM FOLLOW-UP; PHASE-I TRIAL; PSEUDOMONAS EXOTOXIN; DIPHTHERIA-TOXIN; INTERLEUKIN-4 RECEPTOR; CARCINOMA-CELLS; TARGET-CELLS C1 NCI, Clin Immunotherapy Sect, Mol Biol Lab, Div Canc Biol,NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Clin Immunotherapy Sect, Mol Biol Lab, Div Canc Biol,NIH, 9000 Rockville Pike,Bldg 37,Room 5124B, Bethesda, MD 20892 USA. NR 84 TC 9 Z9 10 U1 0 U2 0 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD DEC PY 2002 VL 2 IS 8 BP 785 EP 791 DI 10.1517/14712598.2.8.785 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 627EA UT WOS:000179918800001 PM 12517258 ER PT J AU Inoue, T Okada, H Kobayashi, T Watanabe, Y Kanno, Y Kopp, JB Nishida, T Takigawa, M Ueno, M Nakamura, T Suzuki, H AF Inoue, T Okada, H Kobayashi, T Watanabe, Y Kanno, Y Kopp, JB Nishida, T Takigawa, M Ueno, M Nakamura, T Suzuki, H TI Hepatocyte growth factor counteracts transforming growth factor-beta(1), through attenuation of connective tissue growth factor induction, and prevents renal fibrogenesis in 5/6 nephrectomized mice SO FASEB JOURNAL LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-Society-of-Nephrology CY OCT 10-17, 2001 CL SAN FRANCISCO, CA SP Amer Soc Nephrol DE transgenic mouse; fibroblast; tubular epithelial cell; collagen ID FACTOR-BETA; TRANSGENIC MICE; FACTOR GENE; C-JUN; EXPRESSION; FIBROSIS; INJURY; CELLS; RATS; FIBROBLASTS AB We investigated the mechanism of the anti-fibrotic effects of hepatocyte growth factor (HGF) in the kidney, with respect to its effect on connective tissue growth factor (CTGF), a down-stream, profibrotic mediator of transforming growth factor-beta(1) (TGF-beta(1)). In wild-type (WT) mice with 5/6 nephrectomy (Nx), HGF and TGF-beta(1) mRNAs increased transiently in the remnant kidney by week 1 after the Nx, returned to baseline levels, and increased again at weeks 4 to 12. In contrast, CTGF and 1(I) procollagen (COLI) mRNAs increased in parallel with HGF and TGF-beta(1) during the early stage, but did not re-increase during the late stage. In the case of TGF-beta(1) transgenic (TG) mice with 5/6 Nx, excess TGF-beta(1) derived from the transgene enhanced CTGF expression significantly in the remnant kidney, accordingly accelerating renal fibrogenesis. Administration of dHGF (5.0 mg/kg/day) to TG mice with 5/6 Nx for 4 weeks from weeks 2 to 6 suppressed CTGF expression in the remnant kidney, attenuating renal fibrosis and improving the survival rate. In an experiment in vitro, renal tubulointerstitial fibroblasts (TFB) were co-cultured with proximal tubular epithelial cells (PTEC). Pretreatment with HGF reduced significantly CTGF induction in PTEC by TGF-beta(1), consequently suppressing COLI synthesis in TFB. In conclusion, HGF can block, at least partially, renal fibrogenesis promoted by TGF-beta1 in the remnant kidney, via attenuation of CTGF induction. C1 Saitama Med Coll, Dept Nephrol, Moroyama, Saitama 3500495, Japan. Saitama Med Coll, Dept Urol, Moroyama, Saitama 3500495, Japan. Okayama Univ, Grad Sch Med & Dent, Dept Biochem & Mol Dent, Okayama, Japan. Osaka Univ, Grad Sch Med, Course Adv Med, Div Mol Regenerat Med, Suita, Osaka, Japan. NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Suzuki, H (reprint author), Saitama Med Coll, Dept Nephrol, 38 Morohongo, Moroyama, Saitama 3500495, Japan. EM iromichi@saitama-med.ac.jp NR 38 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD DEC PY 2002 VL 16 IS 14 BP 268 EP + DI 10.1096/fj.02-0442fje PG 18 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 638MG UT WOS:000180574300023 ER PT J AU Thiriet, N Ladenheim, B McCoy, MT Cadet, JL AF Thiriet, N Ladenheim, B McCoy, MT Cadet, JL TI Analysis of ecstasy (MDMA)-induced transcriptional responses in the rat cortex SO FASEB JOURNAL LA English DT Article DE MDMA; cortex; gene expression; cDNA arrays; SYBR green PCR ID SEROTONIN-DOPAMINE INTERACTIONS; ACTIVATED PROTEIN-KINASES; C-FOS EXPRESSION; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; METHYLENEDIOXYMETHAMPHETAMINE MDMA; SUPEROXIDE-DISMUTASE; TRANSGENIC MICE; GENE-EXPRESSION; 5-HT3 RECEPTORS; OXIDATIVE STRESS AB 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular drug of abuse. MDMA is pharmacologically classified as an entactogen because of its affinities to classical hallucinogens and stimulants. Oral ingestion of a single dose of the drug is associated with euphoria, elevated self-confidence, and heightened sensory awareness in humans. Evidence for neurotoxicity in the human serotonin (5-HT) system has been provided. In rats, a single injection of MDMA induces hyperthermia and formation of reactive oxygen species. These effects may cause MDMA-associated, long-term 5-HT depletion, with the cortex being quite sensitive to the biochemical effects of MDMA. It has been suggested that these MDMA effects may be associated with molecular changes in this brain region. To test these ideas, we have made use of the cDNA array analysis, which can provide a more global view of the molecular changes secondary to MDMA injections. Our results show that the genes regulated by MDMA encode proteins that belong to signaling pathways, transcription regulators, or xenobiotic metabolism. Our observations indicate that cortical cells respond to the acute administration of MDMA by modulating transcription of several genes that might lead to long-term changes in the brain. C1 NIDA, Mol Neuropsychiat Sect, NIH, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov NR 68 TC 24 Z9 25 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD DEC PY 2002 VL 16 IS 14 BP 1887 EP 1894 DI 10.1096/fj.02-0502com PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 638MG UT WOS:000180574300009 PM 12468453 ER PT J AU Karahalil, B Hogue, BA De Souza-Pinto, NC Bohr, VA AF Karahalil, B Hogue, BA De Souza-Pinto, NC Bohr, VA TI Base excision repair capacity in mitochondria and nuclei: tissue-specific variations SO FASEB JOURNAL LA English DT Article DE BER; repair activity; mouse tissues; oxidative stress; nucleus ID DNA-REPAIR; OLD MICE; RAT; EXPRESSION; DAMAGE; BRAIN; ENDONUCLEASE; LIVER; HEART; YOUNG AB Base excision repair is the main pathway for repair of oxidative base lesions in DNA. Mammalian cells must maintain genomic stability in their nuclear and mitochondrial genomes, which have different degrees of vulnerability to DNA damage. This study quantifies DNA glycosylase activity in mitochondria and nucleus from C57/BL6 mouse tissues including brain, liver, heart, muscle, kidney, and testis. The activities of oxoguanine DNA glycosylase (OGG1), uracil DNA glycosylase, and endonuclease III homologue 1 (NTH1) were measured using oligonucleotide substrates with DNA lesions specific for each glycosylase. Mitochondrial content was normalized to citrate synthase activity and mitochondrial function was assessed by measuring cytochrome c oxidase (COX) activity. In nuclear and mitochondrial extracts, the highest DNA glycosylase activities were in testis. Brain and heart, tissues with the highest oxidative load, did not have higher levels of OGG1 or NTH1 activity than muscle or kidney, which are more glycolytic tissues. In general, mitochondrial extracts have lower DNA glycosylase activity than nuclear extracts. There was no correlation between glycosylase activities in the mitochondrial extracts and COX activity, suggesting that DNA repair enzymes may be regulated by a mechanism different from this mitochondrial enzyme. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Gazi Univ, Fac Pharm, Dept Toxicol, TR-06330 Ankara, Turkey. RP Bohr, VA (reprint author), 5600 Nathan Shock Dr,Box 1, Baltimore, MD 21224 USA. EM bohrv@grc.nia.nih.gov RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X NR 34 TC 80 Z9 85 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD DEC PY 2002 VL 16 IS 14 BP 1895 EP 1902 DI 10.1096/fj.02-0463com PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 638MG UT WOS:000180574300010 PM 12468454 ER PT J AU Leitzmann, MF Stampfer, MJ Willett, WC Spiegelman, D Colditz, GA Giovannucci, EL AF Leitzmann, MF Stampfer, MJ Willett, WC Spiegelman, D Colditz, GA Giovannucci, EL TI Coffee intake is associated with lower risk of symptomatic gallstone disease in women SO GASTROENTEROLOGY LA English DT Article ID GALLBLADDER-DISEASE; CHOLESTEROL-METABOLISM; LIPID-PEROXIDATION; NONULCER DYSPEPSIA; PHYSICAL-ACTIVITY; CYCLIC-AMP; CAFFEINE; CONSUMPTION; SMOKING; WEIGHT AB Background & Aims: Metabolic studies have shown that coffee affects several hepatobiliary processes that are involved in cholesterol lithogenesis. We previously showed that coffee drinking was associated with a lower risk of symptomatic gallstone disease in men. Methods: We prospectively examined the association between coffee drinking and cholecystectomy, a surrogate of symptomatic gallstone disease, in a cohort of. 80,898 women age 34-59 years in 1980 who had no history of gallstone disease. Coffee consumption and cholecystectomy were reported by participants on biennial mailed questionnaires. Results: During 20 years of follow-up to the year 2000, 7,811 women reported a cholecystectomy. Compared with women who consistently reported consuming no caffeinated coffee, the multivariate relative risks (adjusting for risk factors for gallstone disease) of cholecystectomy comparing increasing categories of consistent intake of caffeinated coffee (0, 1, 2-3, and greater than or equal to4 cups/day) were 1.0, 0.91, 0.78, and 0.72 (95% confidence interval comparing extreme categories, 0.62-0.84; P value of test for trend < 0.0001). Caffeine intake from beverages and dietary sources was also inversely associated with risk of cholecystectomy. The multivariate relative risks comparing increasing categories of caffeine intake (less than or equal to25, 26-100, 101-200, 201-400, 401-800, and >800 mg/day) were 1.0, 1.03, 1.01, 0.94, 0.85, and 0.85 (95% confidence interval comparing extreme categories, 0.74-0.96; P value of test for trend <0.0001). In contrast, decaffeinated coffee was not associated with risk. Conclusions: These data suggest that consumption of caffeinated coffee may play a role in the prevention of symptomatic gallstone disease in women. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Ctr, Program Epidemiol, Boston, MA 02115 USA. RP Leitzmann, MF (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Execut Pl S,Room 3028, Rockville, MD 20852 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [5T32 CA09001-26, CA 87969]; NIDDK NIH HHS [DK 46200] NR 49 TC 46 Z9 47 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2002 VL 123 IS 6 BP 1823 EP 1830 DI 10.1053/gast.2002.37054 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 620RA UT WOS:000179545300013 PM 12454839 ER PT J AU Viner, JL Umar, A Hawk, ET AF Viner, JL Umar, A Hawk, ET TI Chemoprevention of colorectal cancer: problems, progress, and prospects SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; RANDOMIZED CONTROLLED TRIAL; ABERRANT CRYPT FOCI; FECAL-OCCULT-BLOOD; NONSTEROIDAL ANTIINFLAMMATORY DRUG; DNA MISMATCH REPAIR; COLON CARCINOGENESIS; BETA-CAROTENE; TUMOR-GROWTH; ALPHA-DIFLUOROMETHYLORNITHINE AB Although clinical efforts once focused exclusively on the diagnosis and treatment of colorectal cancer (CRC), early neoplastic changes are increasingly regarded and managed as disease entities in themselves. Indeed, carcinogenesis presents us with the Rosetta Stone of cancer prevention. By deciphering the pathways and mechanisms that underlie carcinogenesis, we learn the language of risk and discover new methods of interrupting the malignant process. Molecular prevention (ie, chemoprevention) draws upon insights into the pathogenesis of cancer to identify agents that can prevent or reduce the impact of neoplasia. Experience with the process of chemopreventive agent development is helping us test promising compounds more effectively and efficiently, however, much work remains to be done. Current systems for translating emerging knowledge into clinically applicable tools are ill-adapted to the pace and magnitude of advances in the basic sciences, imaging, and bioinformatics. We are rethinking how to overcome formidable challenges to chemoprevention, such as limited access to new agents and slow execution of clinical trials. Such complex problems are not amenable to random approaches or ad hoc research structures. A clinical resource infrastructure designed to test the absolute and relative usefulness of emerging technologies will speed the rate at which challenges to CRC chemoprevention are overcome. C1 NCI, Gastrointestinal & Other Canc Res Grp, Div Canc Prevent, EPN, Bethesda, MD 20892 USA. RP Hawk, ET (reprint author), NCI, Gastrointestinal & Other Canc Res Grp, Div Canc Prevent, EPN, Suite 2141,6130 Execut Blvd, Bethesda, MD 20892 USA. EM eh51p@nih.gov NR 99 TC 15 Z9 16 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD DEC PY 2002 VL 31 IS 4 BP 971 EP + DI 10.1016/S0889-8553(02)00055-9 PG 30 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 819ZV UT WOS:000221356500005 PM 12489273 ER PT J AU Hamilton, FA AF Hamilton, FA TI A day in court for ERCP: a plea answered SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material C1 NIDDK, Digest Dis Progrms, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Hamilton, FA (reprint author), NIDDK, Digest Dis Progrms, Div Digest Dis & Nutr, NIH, Democracy 2,6707 Democracy Blvd,Room 669, Bethesda, MD 20892 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2002 VL 56 IS 6 SU S BP S154 EP S156 DI 10.1067/mge.2002.129002 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 623WN UT WOS:000179726000002 PM 12447258 ER PT J AU Michaud, DS AF Michaud, DS TI The epidemiology of pancreatic, gallbladder, and other biliary tract cancers SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT NIH State-of-the-Science Conference - ERCP for Diagnosis and Therapy CY JAN 14-16, 2002 CL BETHESDA, MARYLAND ID POPULATION-BASED COHORT; UNITED-STATES ADULTS; RISK-FACTORS; DIABETES-MELLITUS; HEREDITARY PANCREATITIS; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; DIRECT INTERVIEWS; FAMILY HISTORY; MALE SMOKERS C1 NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. RP Michaud, DS (reprint author), NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, 6120 Execut Blvd,EPS-320 MSC 7232, Bethesda, MD 20892 USA. RI Michaud, Dominique/I-5231-2014 NR 52 TC 15 Z9 16 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2002 VL 56 IS 6 SU S BP S195 EP S200 DI 10.1067/mge.2002.129011 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 623WN UT WOS:000179726000011 PM 12447267 ER PT J AU Barlund, M Monni, O Weaver, JD Kauraniemi, P Sauter, G Heiskanen, M Kallioniemi, OP Kallioniemi, A AF Barlund, M Monni, O Weaver, JD Kauraniemi, P Sauter, G Heiskanen, M Kallioniemi, OP Kallioniemi, A TI Cloning of BCAS3 (17q23) and BCAS4 (20q13) genes that undergo amplification, overexpression, and fusion in breast cancer SO GENES CHROMOSOMES & CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; IN-SITU HYBRIDIZATION; CELL-LINES; COMPLEMENTARY-DNA; COPY NUMBER; CARCINOMAS; NEOPLASMS; REGIONS; KINASE; PS6K AB In breast cancer, several chromosomal sites frequently undergo amplification, implicating the location of genes important for tumor development and progression. Here we cloned two novel genes, breast carcinoma amplified sequence 3 (BCAS3) and 4 (BCAS4), from the two most common amplification sites in breast cancer, 17q23 and 20q13. The BCAS3 gene at 17q23 spans more than 600 kb at the genomic level and was predicted to encode a 913 amino acid nuclear protein. The BCAS4 gene at 20q13.2 encodes a 211 amino acid cytoplasmic protein. Both BCAS3 and BCAS4 represent novel genes with no homologies to any other known gene or protein. In the MCF7 breast cancer cell line, the BCAS3 and BCAS4 genes were co-amplified, and cloning of a highly overexpressed 1.3-kb transcript revealed a rearrangement fusing the last two exons of BCAS3 with BCAS4. The fusion led to a novel message in which only the first exon of BCAS4 and part of exon 23 of BCAS3 were transcribed. The BCAS4-BCAS3 fusion transcript was detected only in MCF7 cells, but the BCAS4 gene was also overexpressed in nine of 13 breast cancer cell lines. In conclusion, our results indicate that these novel genes, BCAS3 at 17q23 and BCAS4 at 20q13.2, undergo amplification, overexpression, and fusion in breast cancer and therefore may have a role in the frequent chromosomal alterations affecting these two loci. Published 2002 Wiley-Liss, Inc.(dagger). C1 Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33014 Tampere, Finland. Tampere Univ Hosp, Tampere, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Helsinki, Biomedicum Helsinki, Biomedicum Biochip Ctr, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland. Univ Basel, Inst Pathol, Basel, Switzerland. RP Kallioniemi, A (reprint author), Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33014 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; Kallioniemi, Anne/0000-0003-3552-8158 NR 24 TC 70 Z9 72 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 2002 VL 35 IS 4 BP 311 EP 317 DI 10.1002/gcc.10121 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 608ZV UT WOS:000178878900003 PM 12378525 ER PT J AU Tsai, RYL McKay, RDG AF Tsai, RYL McKay, RDG TI A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells SO GENES & DEVELOPMENT LA English DT Article DE stem cell; nucleostemin; nucleolus; GTP; cell proliferation; p53 ID CENTRAL-NERVOUS-SYSTEM; TUMOR SUPPRESSION; STABILIZES P53; MDM2; DIFFERENTIATION; P19(ARF); PROTEIN; NEURONS AB The unique property of stem cells to self-renew suggests specific mechanisms that regulate their cell-cycle progression. In the present study, we identify a novel,protein, nucleostemin, found in the nucleoli of CNS stem cells, embryonic stem cells, and several cancer cell lines and preferentially expressed by other stem cell-enriched populations. It contains an N-terminal basic domain and two GTP-binding motifs. When stem cells differentiate, nucleostemin expression decreases rapidly prior to cell-cycle exit both in vitro and in vivo. Depletion or overexpression of nucleostemin reduces cell proliferation in CNS stem cells and transformed cells. Mutation analysis indicates that excessive nucleostemin, particularly mutants that lack the GTP-regulatory domain, prevents cells from entering mitosis and causes apoptosis in a p53-dependent manner. The N-terminal basic domain specifies nucleolar localization, the p53 interaction, and is required for the cell death caused by overexpression. This work describes a novel nucleolar mechanism that controls the cell-cycle progression in CNS stem cells and cancer cells. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP McKay, RDG (reprint author), NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 27 TC 312 Z9 365 U1 0 U2 17 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 1 PY 2002 VL 16 IS 23 BP 2991 EP 3003 DI 10.1101/gad.55671 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 622LV UT WOS:000179649300003 PM 12464630 ER PT J AU Liu, PC McAndrew, PE Kaler, SG AF Liu, PC McAndrew, PE Kaler, SG TI Rapid and robust screening of the Menkes disease/occipital horn syndrome gene SO GENETIC TESTING LA English DT Article ID COPPER-TRANSPORTING ATPASE; CANDIDATE GENE; DISEASE; TRANSLOCATION; MUTATIONS; PATIENT; THERAPY; GIRL; IDENTIFICATION; EXPRESSION AB Menkes disease and occipital horn syndrome (OHS) are allelic neurogenetic disorders of copper transport associated with mutations in an X-linked gene, ATP7A. This gene encodes a copper-transporting P-type ATPase. The spectrum of mutations at the Menkes/OHS locus is estimated to include 1% chromosomal rearrangements and 15-20% large deletions, with the remaining defects involving small alterations. There is a compelling need for a rapid and reliable molecular diagnostic approach for patients and families impacted by these conditions. In addition to testing suspected affected males, carrier screening of females in Menkes/OHS families and prenatal evaluation of at-risk pregnancies will be enhanced by the wider availability of robust mutation analysis for this large (23-exon) locus. Here we describe a stepwise approach to mutation screening for these disorders that successfully identified molecular alterations in over 95% of our patient population (n = 49). This genomic DNA-based technique employs multiplex PCR, heteroduplex analysis, and direct sequencing, in a serial fashion. This approach should rind application in molecular diagnostic laboratories in the United States and other countries. Currently, only a single European center provides commercial testing for unknown mutations in Menkes/OHS patients, even though these disorders occur worldwide. C1 NICHHD, Unit Pediat Genet, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. Transgenom Inc, Gaithersburg, MD 20878 USA. RP Kaler, SG (reprint author), NICHHD, Unit Pediat Genet, Lab Clin Genom, NIH, Bldg 10,Room 9S-261,10 Ctr Dr, MSC 1834, Bethesda, MD 20892 USA. NR 40 TC 21 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD WIN PY 2002 VL 6 IS 4 BP 255 EP 260 DI 10.1089/10906570260471778 PG 6 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 631GT UT WOS:000180160300002 PM 12537648 ER PT J AU Gismondi, V Bonelli, L Sciallero, S Margiocco, P Viel, A Radice, P Mondini, P Sala, P Montera, MP Mareni, C Quaia, M Fornasarig, M Gentile, M Pietro, G Rossini, P Arrigoni, A Meucci, GM Bruzzi, P Varesco, L AF Gismondi, V Bonelli, L Sciallero, S Margiocco, P Viel, A Radice, P Mondini, P Sala, P Montera, MP Mareni, C Quaia, M Fornasarig, M Gentile, M Pietro, G Rossini, P Arrigoni, A Meucci, GM Bruzzi, P Varesco, L TI Prevalence of the E1317Q variant of the APC gene in Italian patients with colorectal adenomas SO GENETIC TESTING LA English DT Article ID POLYPOSIS-COLI; CANCER; MUTATIONS; TUMORS; FAMILY AB Loss of APC is an initial, rate-limiting event in inherited and sporadic colorectal tumorigenesis. Rare germline APC mutations have been identified in patients with multiple, colorectal adenomas. Recently, the E1317Q APC variant has been associated with a predisposition to the development of multiple colorectal adenomas. In this study, the prevalence of the E1317Q variant was examined in 181 patients with single or, multiple colorectal adenomas and in 235 controls. In all, E1317Q was identified in two of 182 patients with adenomatous polyps (1.1%) and in two of 235 controls (0.8%) (p = 0.59). The risk of harboring adenoma(s) among subjects bearing the E1317Q variant was 1.29 (95% CI 0.09-18.0). No difference in the prevalence of E1317Q between cases with single (2.0%) or multiple colorectal adenomas (0.7%) and controls (0.8%) was found. None of the subjects with a family history of colorectal cancer carried the E1317Q variant. In conclusion, our results confirm that only a very small fraction of colorectal adenomas may be associated with the presence of E1317Q. C1 Natl Canc Inst, Expt Oncol Lab, I-16132 Genoa, Italy. IRCCS, Ctr Riferimento Oncol, I-33081 Aviano, Italy. Natl Canc Inst, Italian Registry Hereditary Colorectal Tumors, I-20133 Milan, Italy. Univ Genoa, Dept Internal Med, I-16132 Genoa, Italy. IRCCS De Bellis, I-70013 Bari, Italy. S Giovanni Hosp, I-10123 Turin, Italy. Valduce Hosp, Gastroenterol Unit, I-22100 Como, Italy. RP Varesco, L (reprint author), Natl Canc Inst, Expt Oncol Lab, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. RI Radice, Paolo/O-3119-2013; OI Bruzzi, Paolo/0000-0002-7874-2077 NR 17 TC 13 Z9 14 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD WIN PY 2002 VL 6 IS 4 BP 313 EP 317 DI 10.1089/10906570260471859 PG 5 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 631GT UT WOS:000180160300010 PM 12537656 ER PT J AU Malpica, JM Fraile, A Moreno, I Obies, CI Drake, JW Garcia-Arenal, F AF Malpica, JM Fraile, A Moreno, I Obies, CI Drake, JW Garcia-Arenal, F TI The rate and character of spontaneous mutation in an RNA virus SO GENETICS LA English DT Article ID TOBACCO MOSAIC-VIRUS; TO-CELL MOVEMENT; FIDELITY; MUTAGENESIS; POPULATION; EVENTS AB Estimates of spontaneous mutation rates for RNA viruses are few and uncertain, most notably due to their dependence on tiny mutation reporter sequences that may not well represent the whole genome. We report here an estimate of the spontaneous mutation rate of tobacco mosaic virus using an 804-base cognate mutational target, the viral MP gene that encodes the movement protein (MP). Selection against newly arising mutants was countered by providing MP function from a transgene. The estimated genomic mutation rate was on the lower side of the range previously estimated for lyric animal riboviruses. We also present the first unbiased riboviral mutational spectrum. The proportion of base substitutions is the same as that in a retrovirus but is lower than that in most DNA-based organisms. Although the MP mutant frequency was 0.02-0.05, 35% of the sequenced mutants contained two or more mutations. Therefore, the mutation process in populations of TMV and perhaps of riboviruses generally differs profoundly from that in populations of DNA-based microbes and may be strongly influenced by a subpopulation of mutator polymerases. C1 Univ Politecn Madrid, Escuela Tecn Super Ingn Agron, Dept Biotecnol, E-28040 Madrid, Spain. Inst Nacl Invest & Tecnol Agraria & Alimentaria, Dept Protecc Vegetal, E-28040 Madrid, Spain. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Garcia-Arenal, F (reprint author), Univ Politecn Madrid, Escuela Tecn Super Ingn Agron, Dept Biotecnol, Ciudad Univ, E-28040 Madrid, Spain. RI Fraile, Aurora/H-1532-2015; Garcia-Arenal, Fernando/H-1603-2015 NR 34 TC 98 Z9 103 U1 1 U2 10 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 2002 VL 162 IS 4 BP 1505 EP 1511 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 637GB UT WOS:000180502300002 PM 12524327 ER PT J AU Gutacker, MM Smoot, JC Migliaccio, CAL Ricklefs, SM Hua, S Cousins, DV Graviss, EA Shashkina, E Kreiswirth, BN Musser, JM AF Gutacker, MM Smoot, JC Migliaccio, CAL Ricklefs, SM Hua, S Cousins, DV Graviss, EA Shashkina, E Kreiswirth, BN Musser, JM TI Genome-wide analysis of synonymous single nucleotide Polymorphisms in Mycobacterium tuberculosis complex organisms: Resolution of genetic relationships among closely related microbial strains SO GENETICS LA English DT Article ID MOLECULAR CHARACTERIZATION; PLASMODIUM-FALCIPARUM; TRANSMISSION DYNAMICS; BACILLUS-ANTHRACIS; PORTABLE APPROACH; BEIJING GENOTYPE; EPIDEMIOLOGY; IDENTIFICATION; DIVERSITY; ORIGIN AB Several human pathogens (e.g., Bacillus anthracis, Yersinia pestis, Bordetella pertussis, Plasmodium falciparum, and Mycobacterium tuberculosis) have very restricted unselected allelic variation in structural genes, which hinders study of the genetic relationships among strains and strain-trait correlations. To address this problem in a representative pathogen, 432 M. tuberculosis complex strains from global sources were genotyped on the basis of 230 synonymous (silent) single nucleotide polymorphisms (sSNPs) identified by comparison of four genome sequences. Eight major clusters of related genotypes were identified in M. tuberculosis sensu stricto, including a single cluster representing organisms responsible for several large outbreaks in the United States and Asia. All M. tuberculosis sensu stricto isolates of previously unknown phylogenetic position could be rapidly and unambiguously assigned to one of the eight major clusters, thus providing a facile strategy for identifying organisms that are clonally related by descent. Common clones of M. tuberculosis sensu stricto and M. bovis are distinct, deeply branching genotypic complexes whose extant members did not emerge directly from one another in the recent past. sSNP genotyping rapidly delineates relationships among closely related strains of pathogenic microbes and allows construction of genetic frameworks for examining the distribution of biomedically relevant traits such as virulence, transmissibility, and host range. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Dept Agr, Australian Reference Lab Boine Tuberculosis, S Perth, WA 6151, Australia. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Publ Hlth Res Inst, Tuberculosis Ctr, New York, NY 10016 USA. RP Musser, JM (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. FU PHS HHS [N01-A0-02738] NR 60 TC 166 Z9 178 U1 2 U2 15 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 2002 VL 162 IS 4 BP 1533 EP 1543 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 637GB UT WOS:000180502300005 PM 12524330 ER PT J AU Tanaka, TS Kunath, T Kimber, WL Jaradat, SA Stagg, CA Usuda, M Yokota, T Niwa, H Rossant, J Ko, MSH AF Tanaka, TS Kunath, T Kimber, WL Jaradat, SA Stagg, CA Usuda, M Yokota, T Niwa, H Rossant, J Ko, MSH TI Gene expression profiling of embryo-derived stem cells reveals candidate genes associated with pluripotency and lineage specificity SO GENOME RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR; MOUSE EMBRYO; PLACENTAL DEVELOPMENT; MAMMALIAN EMBRYO; MESSENGER-RNA; RETINOIC ACID; ES CELLS; DIFFERENTIATION; ESTABLISHMENT; MAINTAIN AB Large-scale gene expression profiling was performed on embryo-derived stem cell lines to identify molecular signatures of pluripotency and lineage specificity. Analysis of pluripotent embryonic stem (ES) cells, extra embryonic-restricted trophoblast stem (TS) cells, and terminally-differentiated mouse embryo fibroblast (MEF) cells identified expression profiles unique to each cell type, as well as genes common only to ES and TS cells. Whereas most of the MEF-specific genes had been characterized previously, the majority (67%) of the ES-specific genes were novel and did not include known differentiated cell markers. Comparison with microarray data from embryonic material demonstrated that ES-specific genes were underrepresented in all stages sampled, whereas TS-specific genes included known placental markers. Investigation of four novel TS-specific genes showed trophoblast-restricted expression in cell lines and in vivo, whereas one uncharacterized ES-specific gene, Esg-1, was found to be exclusively associated with pluripotency. We suggest that pluripotency requires a set of genes not expressed in other cell types, whereas lineage-restricted stem cells, like TS cells, express genes predictive of their differentiated lineage. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Univ Tokyo, Inst Med Sci, Dept Stem Cell Regulat, Tokyo, Japan. RIKEN, Ctr Dev Biol, Lab Pluripotent Cell Studies, Kobe, Hyogo, Japan. RP Ko, MSH (reprint author), NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RI Yokota, Takashi/F-6021-2011; Ko, Minoru/B-7969-2009; Yokota, Takashi/J-8483-2015; Duello, Theresa/P-5752-2015; OI Ko, Minoru/0000-0002-3530-3015; Kunath, Tilo/0000-0002-8805-7356 NR 42 TC 168 Z9 177 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD DEC PY 2002 VL 12 IS 12 BP 1921 EP 1928 DI 10.1101/gr.670002 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 621PW UT WOS:000179599400013 PM 12466296 ER PT J AU VanBuren, V Piao, Y Dudekula, DB Qian, Y Carter, MG Martin, PR Stagg, CA Bassey, UC Aiba, K Hamatani, T Kargul, GJ Luo, AG Kelso, J Hide, W Ko, MSH AF VanBuren, V Piao, Y Dudekula, DB Qian, Y Carter, MG Martin, PR Stagg, CA Bassey, UC Aiba, K Hamatani, T Kargul, GJ Luo, AG Kelso, J Hide, W Ko, MSH TI Assembly, verification, and initial annotation of the NIA mouse 7.4K cDNA clone set SO GENOME RESEARCH LA English DT Article ID DATABASE AB A set of 7407 cDNA clones (NIA mouse 7.4K) was assembled from >20 cDNA libraries constructed mainly from early mouse embryos, including several stem cell libraries. The clone set was assembled from embryonic and newborn organ libraries consisting of similar to120,000 cDNA clones, which were initially re-arrayed into a set of similar to11,000 unique cDNA clones. A set of tubes was constructed from the racks in this set to prevent contamination and potential mishandling errors in all further re-arrays. Sequences from this set (11K) were analyzed further for quality and clone identity, and high-quality clones with verified identity were re-arrayed into the final set (7.4K). The set is freely available, and a corresponding database was built to provide comprehensive annotation for those clones with known identity or homology, and has been made available through an extensive Web site that includes many link-outs to external databases and analysis servers. C1 NIA, Dev Genomics & Aging Sect, Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Western Cape, S African Natl Bioinformat Inst, ZA-7535 Bellville, South Africa. RP Ko, MSH (reprint author), NIA, Dev Genomics & Aging Sect, Genet Lab, NIH, Bethesda, MD 20892 USA. RI Ko, Minoru/B-7969-2009; Hide, Winston Hide/C-7217-2009; Carter, Mark/B-5089-2010 OI Ko, Minoru/0000-0002-3530-3015; Dudekula, Dawood/0000-0002-4054-1827; Hide, Winston Hide/0000-0002-8621-3271; NR 10 TC 37 Z9 37 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD DEC PY 2002 VL 12 IS 12 BP 1999 EP 2003 DI 10.1101/gr.633802 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 621PW UT WOS:000179599400022 PM 12466305 ER PT J AU McGlynn, KA Edmonson, MN Michielli, RA London, WT Lin, WY Chen, GC Shen, FM Buetow, KH AF McGlynn, KA Edmonson, MN Michielli, RA London, WT Lin, WY Chen, GC Shen, FM Buetow, KH TI A phylogenetic analysis identifies heterogeneity among hepatocellular carcinomas SO HEPATOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-SUPPRESSOR GENES; ALLELIC LOSS; P53 GENE; CHROMOSOME 13Q; FREQUENT LOSS; HETEROZYGOSITY; ALLELOTYPE; DELETION; MUTATION AB Primary hepatocellular carcinoma (HCC) is a significant cause of cancer morbidity and mortality on the global scale. Although epidemiologic studies have identified major risk factors for HCC, the sequence of oncogenic events at the molecular level remains poorly understood. While genetic allele loss appears to be a common event, the significance of the loss is not clear. In order to determine whether allele loss appears to be a random event among HCCs or whether patterns of loss duster in groups of tumors, a phylogenetic approach, was used to examine 32 tumors for genome-wide loss of heterozygosity employing 391 markers. Clusters identified by the phylogenetic analysis were then contrasted to compare candidate locus variation among individuals and to determine whether certain clusters exhibited higher loss rates than other dusters. The analysis found that 3 major and 1 minor cluster of loss could be identified and, further, these clusters were distinguished by variable rates of loss (cluster 1, 29%; cluster 2,21%; duster 3, 16%). The analyses also indicated that the allele loss rates in HCC were not insignificant and that the patterns of allele loss were complex. In addition, the results indicated that an individual's constitutional genotype at the EPHX1 locus may be a critical factor in determining the path of tumor evolution. In conclusion, it appears that in HCC, allele loss is not random, but dusters into definable groups that are characterized by distinctive rates of loss. C1 NCI, Div Canc Genet & Epidemiol, Rockville, MD 20852 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Haimen City Antiepidem Stn, Haimen City, Peoples R China. Shanghai Med Univ, Shanghai 200032, Peoples R China. RP McGlynn, KA (reprint author), NCI, Div Canc Genet & Epidemiol, EPS-7060,6120 Execut Bldg, Rockville, MD 20852 USA. NR 58 TC 14 Z9 15 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2002 VL 36 IS 6 BP 1341 EP 1348 DI 10.1053/jhep.2002.37261 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 620MC UT WOS:000179536300005 PM 12447857 ER PT J AU Whitaker, SY Portier, CJ AF Whitaker, SY Portier, CJ TI A controlled growth and differentiation model for non-monotonic responses SO HUMAN AND ECOLOGICAL RISK ASSESSMENT LA English DT Article DE mechanistic model; mammalian development; non-monotonic dose-response curve ID DEVELOPMENTAL TOXICOLOGY; HORMESIS AB Non-monotonic dose response (U-shaped) patterns occur when a toxic substance acts as a stimulant in small doses, but as an inhibitor in large doses. A mechanistically based mathematical model is introduced in this manuscript, and the ability of the model to demonstrate non-monotonic dose response is discussed. The biologically based dose-response model for developmental toxicology derived by Leroux et al. is extended. The original model has two basic states, precursor cells and differentiated cells, with both states subject to a linear birth-death process. As an alternative, we introduce a model that permits a highly controlled birth and death process for the precursor cells. This controlled growth and differentiation (CGD) model is the foundation for more realistic models of mammalian development. The augmented model limits the number of replications allowed in the development of an organ or tissue and more closely reflects the presence of a true stem cell population. As a result, the CGD model can be used to simulate a host of processes related to development. This paper also explores the adaptability of the CGD model to describe biological development as it relates to toxic agents with effects demonstrating non-monotonic dose response. C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Whitaker, SY (reprint author), NIEHS, Lab Computat Biol & Risk Anal, 111 TW Alexander Dr,Bldg 101,MD A3-06, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 14 TC 2 Z9 2 U1 0 U2 2 PU CRC PRESS LLC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 USA SN 1080-7039 J9 HUM ECOL RISK ASSESS JI Hum. Ecol. Risk Assess. PD DEC PY 2002 VL 8 IS 7 BP 1739 EP 1755 DI 10.1080/20028091057583 PG 17 WC Biodiversity Conservation; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 631EQ UT WOS:000180155500015 ER PT J AU DeMille, MMC Kidd, JR Ruggeri, V Palmatier, MA Goldman, D Odunsi, A Okonofua, F Grigorenko, E Schulz, LO Bonne-Tamir, B Lu, RB Parnas, J Pakstis, AJ Kidd, KK AF DeMille, MMC Kidd, JR Ruggeri, V Palmatier, MA Goldman, D Odunsi, A Okonofua, F Grigorenko, E Schulz, LO Bonne-Tamir, B Lu, RB Parnas, J Pakstis, AJ Kidd, KK TI Population variation in linkage disequilibrium across the COMT gene considering promoter region and coding region variation SO HUMAN GENETICS LA English DT Article ID CATECHOL-O-METHYLTRANSFERASE; DRD2 LOCUS; SCHIZOPHRENIA; HAPLOTYPES; IDENTIFICATION; POLYMORPHISMS; ASSOCIATION; FREQUENCIES; EXPRESSION; METABOLISM AB Catechol-O-methyl transferase (COMT) catalyzes the first step in one of the major pathways in the degradation of catecholamines. The COMT gene on chromosome 22 has been considered a candidate gene for many neuropsychiatric disorders, in part because an exon 4 single nucleotide polymorphism (SNP) in COMT causes an amino acid substitution associated with significantly altered enzyme activity. This functional variant, detected as an NlaIII restriction site polymorphism (RSP), is polymorphic in populations from around the world. A four-site haplotype spanning 28 kb effectively encompasses COMT. This haplotype is comprised of two novel polymorphisms [a tetranucleotide short tandem repeat polymorphism (STRP) in intron I and a HindIII RSP at the 5' end of COMT], the NlaIII site, and another previously published site - a Bg/I RSP at the 3' end of the gene. Overall linkage disequilibrium (LD) for this haplotype is strong and significant in 32 population samples from around the world. Conditional probabilities indicate that, in spite of moderate to strong disequilibrium in most non-African populations, the NlaIII site, although often used for prediction, would not always be a reliable predictor of allelic variation at the other sites. Because other functional variation might exist, especially regulatory variation, these findings indicate that haplotypes would be more effective indicators of possible involvement of COMT in disease etiology. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. New York State Dept Hlth, Roswell Pk Mem Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. Univ Benin, Fac Med, Dept Obstet & Gynecol, Benin, Nigeria. Yale Univ, Dept Psychol, New Haven, CT 06511 USA. Univ Wisconsin, Dept Hlth Sci, Milwaukee, WI 53201 USA. Tel Aviv Univ, Sackler Sch Med, Dept Genet, IL-69978 Tel Aviv, Israel. Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan. Univ Copenhagen, Hvidovre Hosp, Dept Psychiat, DK-2650 Hvidovre, Denmark. RP Kidd, KK (reprint author), Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; DeMille, Mellissa/0000-0001-7068-395X FU NIAAA NIH HHS [AA09379]; NIGMS NIH HHS [GM57672]; NIMH NIH HHS [MH62495]; NINDS NIH HHS [NS01795] NR 31 TC 57 Z9 60 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 2002 VL 111 IS 6 BP 521 EP 537 DI 10.1007/s00439-002-0809-0 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 623FY UT WOS:000179693700004 PM 12436243 ER PT J AU Chen, LY Pan, CJ Chou, JY AF Chen, LY Pan, CJ Chou, JY TI Structure-function analysis of the glucose-6-phosphate transporter deficient in glycogen storage disease type Ib SO HUMAN MOLECULAR GENETICS LA English DT Article ID PROTEASOME; DEGRADATION; PROTEIN; 1B; NEUTROPENIA; LACTACYSTIN; SEQUENCE; CLONING; VECTORS; DEFECT AB Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the glucose-6-phosphate transporter (G6PT), a 10 transmembrane domain endoplasmic reticulum protein. To date, 69 G6PT mutations, including 28 missenses and 2 codon deletions, have been identified in GSD-Ib patients. We previously characterized 15 of the missense and one codon deletion mutations using a pSVL-based expression assay. A lack of sensitivity in this assay limited the discrimination between mutations that lead to loss of function and mutations that leave a low residual activity. We now report an improved G6PT assay, based on an adenoviral vector-mediated expression system and its use in the functional characterization of all 30 codon mutations found in GSD-Ib patients. Twenty of the naturally occurring mutations completely abolish microsomal G6P uptake activity while the other 10 mutations, including 5 previously characterized ones, partially inactivate the transporter. This information should greatly facilitate genotype-phenotype correlation. We also report a structure-function analysis of G6PT. In addition to the 3 destabilizing mutations reported previously, we now show that the G50R, C176R, V235del, G339C and G339D mutations also compromise the G6PT stability. Mutation analysis of the amino-terminal domain of G6PT shows that it is required for optimal G6P uptake activity. Finally, we show that degradation of both wild-type and mutant G6PT is inhibited by a potent proteasome inhibitor, lactacystin, demonstrating that G6PT is a substrate for proteasome-mediated degradation. C1 NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Chou, JY (reprint author), NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bldg 10,Room 9S241, Bethesda, MD 20892 USA. NR 30 TC 34 Z9 35 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 1 PY 2002 VL 11 IS 25 BP 3199 EP 3207 DI 10.1093/hmg/11.25.3199 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 622VR UT WOS:000179668300009 PM 12444104 ER PT J AU Hermos, CR Huizing, M Kaiser-Kupfer, MI Gahl, WA AF Hermos, Christina R. Huizing, Marjan Kaiser-Kupfer, Muriel I. Gahl, William A. TI Hermansky-Pudlak Syndrome Type 1: Gene Organization, Novel Mutations, and Clinical-Molecular Review of Non-Puerto Rican Cases SO HUMAN MUTATION LA English DT Article DE albinism; mutation analysis; autosomal recessive; platelet dense bodies; storage pool deficiency; HPS1 AB Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder causing oculocutaneous albinism and a platelet storage pool deficiency, reflecting defective biosynthesis and/or processing of melanosomes and platelet dense bodies. Four human genes (HPS1, ADTB3A, HPS3, HPS4) are associated with four subtypes of HPS. The most common is HPS-1. A 16-bp duplication in exon 15 of the HPS1 gene causes HPS-1 in 450 northwest Puerto Rican patients; 13 other HPS1 mutations have been reported in non-Puerto Rican patients. We screened 26 HPS patients, who lacked a molecular diagnosis, for HPS1 defects and identified six patients with six different HPS1 mutations. Four novel mutations were discovered, including the first HPS1 missense mutation, 922T>C, in exon 8. This mutation, along with 624delG in exon 6, preserve RNA transcription, while 561delC in exon 5 and [1581delA; 1594C>A] in exon 14 produce no RNA on northern blot. One of six adult patients developed pulmonary fibrosis, and two patients ages 16 and 17 have granulomatous colitis. These complications are common among Puerto Rican HPS-1 patients but have not appeared in HPS-2 or HPS-3 patients. The diagnosis of HPS-1, available only on molecular grounds, has important prognostic and treatment implications. (C) 2002 Wiley-Liss, Inc. C1 [Hermos, Christina R.; Huizing, Marjan; Gahl, William A.] NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. [Kaiser-Kupfer, Muriel I.] NEI, Ophthalm Genet Branch, NIH, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NHGRI, NIH, 10 Ctr Dr,MSC 1851,Bldg 10,Room 10C-103, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov FU Pfizer Pharmaceutical Company; Clinical Research Training Program (CRTP) FX We thank Pfizer Pharmaceutical Company, and their sponsorship of the Clinical Research Training Program (CRTP), for their support of Christina Hermos as a 2001-2002 Clinical Research Fellow at the NIH. The authors appreciate the excellent advice and assistance of Dr. Chanika Phornphutkul regarding use of the SSCP technique, and the superb ophthalmic photography of Mr. Ernest Kuehl. NR 33 TC 40 Z9 40 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD DEC PY 2002 VL 20 IS 6 DI 10.1002/humu.9097 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA V41KK UT WOS:000209544900017 PM 12442288 ER PT J AU Gonzalez, AA Segura, AM Horiba, K Qian, SJ Yu, ZX Stetler-Stevenson, W Willerson, JT McAllister, HA Ferrans, VJ AF Gonzalez, AA Segura, AM Horiba, K Qian, SJ Yu, ZX Stetler-Stevenson, W Willerson, JT McAllister, HA Ferrans, VJ TI Matrix metalloproteinases and their tissue inhibitors in the lesions of cardiac and pulmonary sarcoidosis: An immunohistochemical study SO HUMAN PATHOLOGY LA English DT Article DE sarcoidosis; heart disease; lung disease; immunohistochemistry; metalloproteinases ID ABDOMINAL AORTIC-ANEURYSMS; HUMAN HEART; EXPRESSION; COLLAGENASE; GRANULOMA; CARDIOMYOPATHY; GELATINASE; DEGRADATION; ACTIVATION; MECHANISMS AB The pathogenesis of die tissue damage and fibrosis in sarcoidosis is poorly understood. The matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) must be considered in this regard, because they control the lysis of connective tissue components. Immunohistochemical studies (peroxidase and dual labeling for confocal microscopy) of reactivity for XIMP-1, XIMP-2, MMP-3, MMP-7, XIMP-9, and the 4 membrane-type-MMPs were made on tissues from patients with cardiac (n = 4) and pulmonary (n = 5) sarcoidosis. The granulomas were histochemically similar in both organs. The multinucleated giant cells (MGCs) showed moderate reactivity for MMP-1 and MMP-9 and variable reactivity for MMP-2 and MMp-3; in addition, they showed colocalization of MT-1-MMP, which activates MMP-2. The reactivity of epithelioid cells (ECs) was moderate for MMP-2 and mild for other MMPs. Macrophages showed weaker reactivity for MMPs than did MGCs and ECs. All 3 types of cells showed very low reactivity for TIMPs. Staining for type IV collagen showed focal damage to the basement membranes of cardiac myocytes and pulmonary alveoli near the granulomas. The cells in sarcoid granulomas contain an abundance of MMPs and a paucity of TIMPs. The MGCs also contain MT-1-MMP and thus can activate MMP-2 in the granulomas. The MMPs can cause damage to adjacent cardiac myocytes and pulmonary alveoli, leading to the interstitial fibrosis produced by sarcoidosis. C1 NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. St Lukes Episcopal Hosp, Houston, TX 77030 USA. Texas Heart Inst, Houston, TX 77025 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Yu, ZX (reprint author), NHLBI, Pathol Sect, NIH, Bldg 10,2N240,10 Ctr Dr,MSC-1518, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 33 TC 19 Z9 21 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD DEC PY 2002 VL 33 IS 12 BP 1158 EP 1164 DI 10.1053/hupa.2002.129423 PG 7 WC Pathology SC Pathology GA 629EE UT WOS:000180036800002 PM 12514782 ER PT J AU Svetkey, LP Loria, CM AF Svetkey, LP Loria, CM TI Blood pressure effects of vitamin C - What's the key question? SO HYPERTENSION LA English DT Editorial Material ID CLINICAL-TRIALS; ASCORBIC-ACID; METAANALYSIS; HYPERTENSION C1 Duke Univ, Med Ctr, Duke Hypertens Ctr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Sarah W Stedman Ctr Nutr Studies, Durham, NC 27710 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Svetkey, LP (reprint author), Duke Univ, Med Ctr, Duke Hypertens Ctr, Box 3075, Durham, NC 27710 USA. NR 13 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2002 VL 40 IS 6 BP 789 EP 791 DI 10.1161/01.HYP.0000038340.95407.43 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 625XR UT WOS:000179841300002 PM 12468557 ER PT J AU Knox, SS Hausdorff, J Markovitz, JH AF Knox, SS Hausdorff, J Markovitz, JH TI Reactivity as a predictor of subsequent blood pressure - Racial differences in the Coronary Artery Risk Development in Young Adults (CARDIA) Study SO HYPERTENSION LA English DT Article DE blood pressure; race; stress ID CARDIOVASCULAR REACTIVITY; BORDERLINE HYPERTENSIVES; EVERYDAY LIFE; MENTAL STRESS; HEART-RATE; RESPONSES; RACE; INDIVIDUALS; POPULATION; GENDER AB This study investigated the association between cardiovascular reactivity and subsequent ambulatory blood pressure in 316 black and white men and women in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Cardiovascular laboratory reactivity was examined in subjects 20 to 33 years old, and ambulatory blood pressure and heart rate were measured 3 years later. Average ambulatory pressure during a 24-hour period was regressed separately on stress reactivity and standard covariate risk factors in each race/gender subgroup. Blacks had higher blood pressure and heart rates than whites, men had higher blood pressure than women, and women had higher heart rates than men. After controlling for age, baseline systolic pressure, familial history of hypertension, smoking, alcohol consumption, body mass index, and exercise, systolic blood pressure reactivity to star tracing and cold pressor stress were significantly associated with systolic ambulatory pressure in black men and women 3 years later (partial r=0.24 to 0.37). Heart rate reactivity to video challenge and star tracing were also significantly predictive of subsequent ambulatory heart rate in blacks. Diastolic star tracing reactivity was significantly associated with subsequent ambulatory blood pressure in black women (r=0.23), and diastolic reactivity to video and star tracing were significantly predictive of ambulatory diastolic pressure in white men (r=0.39). We conclude that hyperresponsivity to stress may be a risk factor for subsequent blood pressure elevation in blacks and may be one pathway leading to the higher prevalence of hypertension in blacks than in whites. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Alabama, Dept Med, Div Aging, Birmingham, AL 35294 USA. RP Knox, SS (reprint author), NHLBI, Div Epidemiol & Clin Applicat, 2 Rockledge Ctr,6701 Rockledge Dr,Room 8120, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-48048, N01-HC-95095, N01-HC-48050, N01-HC-48047, N01-HC-48049] NR 41 TC 38 Z9 38 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2002 VL 40 IS 6 BP 914 EP 919 DI 10.1161/01.HYP.0000041417.94797.57 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 625XR UT WOS:000179841300024 PM 12468579 ER PT J AU Weed, DL AF Weed, DL TI Is the precautionary principle a principle? SO IEEE TECHNOLOGY AND SOCIETY MAGAZINE LA English DT Article ID PUBLIC-HEALTH; CASUISTRY C1 NCI, Div Canc Prevent, Rockville, MD 20852 USA. RP Weed, DL (reprint author), NCI, Div Canc Prevent, Rockville, MD 20852 USA. NR 28 TC 5 Z9 5 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0278-0097 J9 IEEE TECHNOL SOC MAG JI IEEE Technol. Soc. Mag. PD WIN PY 2002 VL 21 IS 4 BP 45 EP 48 DI 10.1109/MTAS.2003.1166567 PG 4 WC Engineering, Electrical & Electronic SC Engineering GA 632EM UT WOS:000180210800010 ER PT J AU Davis, RS Dennis, G Odom, MR Gibson, AW Kimberly, RP Burrows, PD Cooper, MD AF Davis, RS Dennis, G Odom, MR Gibson, AW Kimberly, RP Burrows, PD Cooper, MD TI Fc receptor homologs: newest members of a remarkably diverse Fc receptor gene family SO IMMUNOLOGICAL REVIEWS LA English DT Review ID MHC CLASS-I; HIGH-AFFINITY RECEPTOR; NATURAL-KILLER-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; IMMUNOGLOBULIN-LIKE RECEPTORS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; COLLAGEN-INDUCED ARTHRITIS; HUMAN-CHROMOSOME 19Q13.4; EPSILON-RI-ALPHA; INHIBITORY RECEPTOR AB Newfound relatives of the classical Fc receptors (FcR) have been provisionally named the Fc receptor homologs (FcRH). The recent identification of eight human and six mouse FcRH genes substantially increases the size and functional potential of the FcR family. The extended family of FcR and FcRH genes spans similar to15 Mb of the human chromosome 1q21-23 region, whereas in mice this family is split between chromosomes 1 and 3. The FcRH genes encode molecules with variable combinations of five subtypes of immunoglobulin (Ig) domains. The presence of a conserved sequence motif in one Ig domain subtype implies Ig Fc binding capability for many FcRH family members that are preferentially expressed by B lineage cells. In addition, most FcRH family members have consensus tyrosine-based activating and inhibitory motifs in their cytoplasmic domains, while the others lack features typical of transmembrane receptors. The FcRH family members, like the classical FcRs, come in multiple isoforms and allelic variations. The unique individual and polymorphic properties of the FcR/FcRH members indicate a remarkably diverse Fc receptor gene family with immunoregulatory function. C1 Univ Alabama, Howard Hughes Med Inst, Birmingham, AL 35294 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. Sci Applicat Int Corp, NIAID, Lab Immunopathogenesis & Bioinformat, Clin Serv Program, Frederick, MD USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Univ Alabama, Div Dev & Clin Immunol, Birmingham, AL 35294 USA. Univ Alabama, Div Hematol Oncol, Birmingham, AL 35294 USA. RP Cooper, MD (reprint author), Univ Alabama, Howard Hughes Med Inst, WTI 378,1824 6th Ave S, Birmingham, AL 35294 USA. OI Kimberly, Robert/0000-0002-5330-3086 FU NIAID NIH HHS [AI48098, AI39816]; NIAMS NIH HHS [AR49084]; NIDDK NIH HHS [DK07488] NR 145 TC 96 Z9 98 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 2002 VL 190 IS 1 BP 123 EP 136 DI 10.1034/j.1600-065X.2002.19009.x PG 14 WC Immunology SC Immunology GA 627QU UT WOS:000179946400009 PM 12493010 ER PT J AU Kedzierski, L Black, CG Goschnick, MW Stowers, AW Coppel, RL AF Kedzierski, L Black, CG Goschnick, MW Stowers, AW Coppel, RL TI Immunization with a combination of merozoite surface proteins 4/5 and 1 enhances protection against lethal challenge with Plasmodium yoelii SO INFECTION AND IMMUNITY LA English DT Article ID MULTISTAGE VACCINE CANDIDATE; CATHEPSIN-L PROTEINASES; STAGE MALARIA ANTIGENS; ASEXUAL BLOOD STAGES; FALCIPARUM MALARIA; SACCHAROMYCES-CEREVISIAE; TERMINAL FRAGMENT; IMMUNE-RESPONSES; EFFICACY TRIAL; MICE AB It is widely believed that subunit vaccines composed of multiple components will offer greater protection against challenge by malaria, and yet there is little experimental evidence to support this view. We set out to test this proposition in the Plasmodium yoelii challenge system in rodents by comparing the degree of protection conferred by immunization with a mixture of merozoite surface proteins to that conferred by single proteins. We therefore examined a defined protein mixture made of the epidermal growth factor-like domains of P. yoelli merozoite surface protein 1 (MSPI) and MSP4/5, the homologue of P. falciparum MSP4 and MSP5. In the present study we demonstrate that this combination of recombinant proteins dramatically enhances protection against lethal malaria challenge compared to either protein administered alone. Many mice immunized with the MSP4/5 plus MSPI,, combination did not develop detectable parasitemia after challenge. Combined immunization with MSP1(19) and yMSP4/5, a product characterized by lower protective efficacy, also greatly enhanced protection by reducing peak parasitemias and increasing the numbers of survivors. In some combination trials, levels of antibodies to MSP1(19) were elevated compared to the MSP1(19) alone group; however, improved protection occurred regardless of whether boosting of the anti-MSP1(19) response was observed. Boosting of anti-MSP1(19) did not appear to be due to contaminating endotoxin in the EcMSP4/5 material since enhanced protection was observed in C3H/HeJ mice, which are endotoxin insensitive. Collectively, these experiments show that multiantigen combinations offer enhanced levels of protection against asexual stage infection and suggest that combinations of MSP1, MSP4, and MSP5 should be evaluated further for use in humans. C1 Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia. NIAID, Parasit Dis Lab, NIH, Rockville, MD 20852 USA. RP Coppel, RL (reprint author), Monash Univ, Dept Microbiol, POB 53, Clayton, Vic 3800, Australia. RI Coppel, Ross/A-6626-2008; Black, Casilda/B-1519-2008 OI Coppel, Ross/0000-0002-4476-9124; Black, Casilda/0000-0002-0424-4593 NR 42 TC 30 Z9 33 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2002 VL 70 IS 12 BP 6606 EP 6613 DI 10.1128/IAI.70.12.6606-6613.2002 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 617TU UT WOS:000179377600014 PM 12438332 ER PT J AU Charo, J Sundback, M Wasserman, K Ciupitu, AMT Mirzai, B van der Zee, R Kiessling, R AF Charo, J Sundback, M Wasserman, K Ciupitu, AMT Mirzai, B van der Zee, R Kiessling, R TI Marked enhancement of the antigen-specific immune response by combining plasmid DNA-Based immunization with a Schiff base-forming drug SO INFECTION AND IMMUNITY LA English DT Article ID DIRECT GENE-TRANSFER; BARR-VIRUS EBV; TRANSGENIC MICE; SKELETAL-MUSCLE; IN-VIVO; TUBERCULOSIS; VACCINES; PROTEIN; INFLUENZA; PHARMACOKINETICS AB Although plasmid DNA (pDNA)-based immunization has proven efficacy, the level of immune responses that is achieved by this route of vaccination is often lower than that induced by traditional vaccines, especially for primates and humans. We report here a simple and potent method to enhance pDNA-based vaccination by using two different plasmids encoding viral or bacterial antigens. This method is based on coadministration of low concentrations of a recently described immunopotentiating, Schiff base-forming drug called tucaresol which has led to significant augmentation of antigen-specific humoral and cellular immune responses. Our data suggest that enhancement of the immune response with tucaresol might provide a powerful tool for the further development of pDNA-based immunization for humans. C1 Karolinska Hosp, CCK, S-17176 Stockholm, Sweden. Karolinska Inst, Microbiol & Tumor Biol Ctr, S-17177 Stockholm, Sweden. Amer Type Culture Collect, Manassas, VA 20110 USA. Univ Utrecht, Dept Immunol, Fac Vet Med, NL-3508 TD Utrecht, Netherlands. RP Charo, J (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42,10 Ctr Dr, Bethesda, MD 20892 USA. RI van der Zee, Ruurd/O-5256-2015; Charo, Jehad/K-4433-2013 OI van der Zee, Ruurd/0000-0002-4331-2755; Charo, Jehad/0000-0002-5409-9160 NR 44 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2002 VL 70 IS 12 BP 6652 EP 6657 DI 10.1128/IAI.70.12.6652-6657.2002 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 617TU UT WOS:000179377600020 PM 12438338 ER PT J AU Feng, CG Kullberg, MC Jankovic, D Cheever, AW Caspar, P Coffman, RL Sher, A AF Feng, CG Kullberg, MC Jankovic, D Cheever, AW Caspar, P Coffman, RL Sher, A TI Transgenic mice expressing human interleukin-10 in the antigen-presenting cell compartment show increased susceptibility to infection with Mycobactetium avium associated with decreased macrophage effector function and apoptosis SO INFECTION AND IMMUNITY LA English DT Article ID INTERFERON-GAMMA-PRODUCTION; T-LYMPHOCYTES; ANTIMYCOBACTERIAL IMMUNITY; TUBERCULOSIS PATIENTS; GROWTH-INHIBITION; TNF-ALPHA; IL-10; RESISTANCE; PHAGOSOME; RESPONSES AB Interleukin-10 (IL-10) is thought to play an important role in the regulation of microbial immunity. While T-cell-derived IL-10 has been shown to suppress cell-mediated immunity, there has been debate as to whether antigen presenting cell (APC)-derived cytokine can perform the same function in vivo. To assess the influence of APC-produced IL-10 on host resistance to mycobacterial infection, transgenic mice expressing human IL-10 under the control of the major histocompatibility complex class 11 promoter (hu10Tg) were infected with Mycobacterium avium, and bacterial burdens and immune responses were compared with those observed in wild-type (wt) animals. Hu10Tg mice harbored substantially higher numbers of M. avium and succumbed 16 to 18 weeks postinfection. The granulomas in infected hu10Tg mice showed marked increases in both acid-fast bacilli and host macrophages. In addition, these animals displayed a dramatic increase in hepatic fibrosis. The increased susceptibility of the hu10Tg mice to M. avium infection is independent of T-cell-produced endogenous murine IL-10, since bacterial burdens in mice derived by crossing hu10Tg mice with murine IL-10-deficient mice were not significantly different from those in hu10Tg mice. Importantly, gamma interferon (IFN-gamma) responses were not decreased in the infected transgenic animals from those in wt animals, suggesting the normal development of Th1 effector cells. In contrast, mycobacterium-induced macrophage apoptosis as well as production of TNF, nitric oxide, and IL-12p40 were strongly inhibited in hu10Tg mice. Together, these data indicate that APC-derived IL-10 can exert a major inhibitory effect on control of mycobacterial infection by a mechanism involving the suppression of macrophage effector function and apoptosis. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Inst Biomed Res, Rockville, MD USA. Dynavax Technol, Berkeley, CA USA. RP Feng, CG (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bldg 50,Room 6148,50 South Dr, Bethesda, MD 20892 USA. NR 41 TC 43 Z9 44 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2002 VL 70 IS 12 BP 6672 EP 6679 DI 10.1128/IAI.70.12.6672-6679.2002 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 617TU UT WOS:000179377600023 PM 12438341 ER PT J AU Lei, BF DeLeo, FR Reid, SD Voyich, JM Magoun, L Liu, MY Braughton, KR Ricklefs, S Hoe, NP Cole, RL Leong, JM Musser, JM AF Lei, BF DeLeo, FR Reid, SD Voyich, JM Magoun, L Liu, MY Braughton, KR Ricklefs, S Hoe, NP Cole, RL Leong, JM Musser, JM TI Opsonophagocytosis-inhibiting Mac protein of group A Streptococcus: Identification and characteristics of two genetic complexes SO INFECTION AND IMMUNITY LA English DT Article ID GROUP-A STREPTOCOCCUS; INTEGRINS ALPHA(V)BETA(3); DIVERSITY; FIBRINOGEN; DISEASE; CD11B AB Recently, it was reported that a streptococcal Mac protein (designated Mac(5005)) made by serotype M1 group A Streptococcus (GAS) is a homologue of human CD11b that inhibits opsonophagocytosis and killing of GAS by human polymorphormclear leukocytes (PMNs) (B. Lei, F. R. DeLeo, N. P. Hoe, M. R. Graham, S. M. Mackie, R. L. Cole, M. Liu, H. R. Hill, D. E. Low, M. J. Federle, J. R. Scott, and J. M. Musser, Nat. Med. 7:1298-1305, 2001). To study mac variation and expression of the Mac protein, the gene in 67 GAS strains representing 36 distinct M protein serotypes was sequenced. Two distinct genetic complexes were identified, and they were designated complex I and complex II. Mac variants in each of the two complexes were closely related, but complex I and complex II variants differed on average at 50.66 +/- 5.8 amino acid residues, most of which were located in the middle one-third of the protein. Complex I Mac variants have greater homology with CD11b than complex II variants. GAS strains belonging to serotypes M1 and M3, the most abundant M protein serotypes responsible for human infections in many case series, have complex I Mac variants. The mac gene was cloned from representative strains assigned to complexes I and II, and the Mac proteins were purified to apparent homogeneity. Both Mac variants had immunoglobulin G (IgG)-endopeptidase activity. In contrast to MaC(5005) (complex I), MaC(8345) (complex II) underwent autooxidation of its cysteine residues, resulting in the loss of IgG-endopeptidase activity. A Mac(5005) Cys94Ala site-specific mutant protein was unable to cleave IgG but retained the ability to inhibit IgG-mediated phagocytosis by human PMNs. Thus, the IgG-endopeptidase activity was not essential for the key biological function of MaC5005. Although MaC5005 and Mac(8345) each have an Arg-Gly-Asp (RGD) motif, the proteins differed in their interactions with human integrins alpha(v)beta(3) and alpha(IIb)beta(3), Binding of Mac(5005) to integrins alpha(v)beta(3) and alpha(IIb)beta(3) was mediated primarily by the RGD motif in Mac(5005), whereas binding of Mac(8345) involved the RGD motif and a region in the middle one-third of the molecule whose sequence is different in Mac(8345), and Mac(5005). Taken together, the data add to the emerging theme in GAS pathogenesis that allelic variation in virulence genes contributes to fundamental differences in host-pathogen interactions among strains. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Univ Massachusetts, Med Ctr, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA. RP Musser, JM (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. OI DeLeo, Frank/0000-0003-3150-2516 NR 37 TC 35 Z9 36 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2002 VL 70 IS 12 BP 6880 EP 6890 DI 10.1128/IAI.70.12.6880-6890.2002 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 617TU UT WOS:000179377600047 PM 12438365 ER PT J AU Collazo, CM Yap, GS Hieny, S Caspar, P Feng, CG Taylor, GA Sher, A AF Collazo, CM Yap, GS Hieny, S Caspar, P Feng, CG Taylor, GA Sher, A TI The function of gamma interferon-inducible GTP-binding protein IGTP in host resistance to Toxoplasma gondii is Stat1 dependent and requires expression in both hematopoietic and nonhematopoietic cellular compartments SO INFECTION AND IMMUNITY LA English DT Article ID NITRIC-OXIDE SYNTHASE; IFN-GAMMA; INTRACELLULAR PATHOGEN; MEDIATED-IMMUNITY; HUMAN-FIBROBLASTS; ACUTE INFECTION; MICE LACKING; GENE; CELLS; INTERLEUKIN-12 AB IGTP is a member of the 47-kDa family of gamma interferon (IFN-gamma)-induced GTPases. We have previously shown that IGTP is critical for host resistance to Toxoplasma gondii infection. In the present study, we demonstrate that T. gondii-induced IGTP expression in vivo and IFN-gamma-driven synthesis of the protein in vitro are dependent on Stat1. Consistent with this observation, Stat1-deficient animals succumbed to T. gondii infection with the same rapid kinetics as IGTP(-/-) mice. To ascertain the cellular levels at which IGTP functions in host control of acute infection, we constructed reciprocal bone marrow chimeras between IGTP-deficient and wild-type mice. Resistance to infection was observed only when IGTP was present in both hematopoietic and nonhematopoietic compartments. To assess the possible contribution of IGTP to the maintenance of parasite latency, partial chemotherapy was used to allow the establishment of chronic infection in IGTP-deficient animals. Upon cessation of drug treatment, these animals showed delayed mortality compared with similarly infected and treated IFN-gamma-deficient or inducible nitric oxide synthase-deficient mice, which succumbed rapidly. Parallel experiments performed with drug-treated bone marrow chimeras supported a role for the hematopoietic compartment in this NO-dependent, IGTP-independent control of chronic infection. Taken together, our findings demonstrate that host resistance mediated by IGTP is a Stat1-induced function which in the case of T. gondii acts predominantly to restrict acute as opposed to chronic infection. This effector mechanism requires expression of IGTP in cells of both hematopoietic and nonhematopoietic origin. In contrast, in latent infection, hematopoietically derived cells mediate resistance by means of a largely NO-dependent pathway. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27705 USA. Durham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC 27705 USA. RP Collazo, CM (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bldg 50,Room 6144,50 South Dr,MSC 8003, Bethesda, MD 20892 USA. NR 39 TC 62 Z9 65 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2002 VL 70 IS 12 BP 6933 EP 6939 DI 10.1128/IAI.70.12.6933-6939.2002 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 617TU UT WOS:000179377600054 PM 12438372 ER PT J AU Kennedy, MC Wang, J Zhang, YL Miles, AP Chitsaz, F Saul, A Long, CA Miller, LH Stowers, AW AF Kennedy, MC Wang, J Zhang, YL Miles, AP Chitsaz, F Saul, A Long, CA Miller, LH Stowers, AW TI In vitro studies with recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1): Production and activity of an AMA1 vaccine and generation of a multiallelic response SO INFECTION AND IMMUNITY LA English DT Article ID ANTIBODY-RESPONSE; MALARIA; CHABAUDI; IMMUNIZATION; INFECTION; POLYMORPHISM; INVASION; IMMUNITY; MICE; GENE AB Apical membrane antigen 1 (AMA1) is regarded as a leading malaria blood-stage vaccine candidate. While the overall structure of AMA1 is conserved in Plasmodium spp., numerous AMA1 allelic variants of P. falciparum have been described. The effect of AMA1 allelic diversity on the ability of a recombinant AMA1 vaccine to protect against human infection by different P. falciparum strains is unknown. We characterize two allelic forms of AMA1 that were both produced in Pichia pastoris at a sufficient economy of scale to be usable for clinical vaccine studies. Both proteins were used to immunize rabbits, singly and in combination, in order to evaluate their immunogenicity and the ability of elicited antibodies to block the growth of different P. falciparum clones. Both antigens, when used alone, elicited high homologous anti-AMA1 titers, with reduced strain cross-reactivity. Similarly, sera from rabbits immunized with a single antigen were capable of blocking the growth of homologous parasite strains at levels theoretically sufficient to clear parasite infections. However, heterologous inhibition was significantly reduced, providing experimental evidence that AMA1 allelic diversity is a result of immune pressure. Encouragingly, rabbits immunized with a combination of both antigens exhibited titers and levels of parasite inhibition as good as those of the single-antigen-immunized rabbits for each of the homologous parasite lines, and consequently exhibited a broadening of allelic diversity coverage. C1 NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD 20852 USA. RP Stowers, AW (reprint author), CSL Ltd, 45 Poplar Rd, Parkville, Vic 3052, Australia. RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 28 TC 189 Z9 192 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2002 VL 70 IS 12 BP 6948 EP 6960 DI 10.1128/IAI.70.12.6948-6960.2002 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 617TU UT WOS:000179377600056 PM 12438374 ER PT J AU Stowers, AW Kennedy, MC Keegan, BP Saul, A Long, CA Miller, LH AF Stowers, AW Kennedy, MC Keegan, BP Saul, A Long, CA Miller, LH TI Vaccination of monkeys with recombinant Plasmodium falciparum apical membrane antigen 1 confers protection against blood-stage malaria SO INFECTION AND IMMUNITY LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; T-CELL EPITOPE; AOTUS MONKEYS; ANTIBODY-RESPONSE; INFECTION; CHABAUDI; VACCINES; IMMUNIZATION; EFFICACY; CHALLENGE AB A major challenge facing malaria vaccine development programs is identifying efficacious combinations of antigens. To date, merozoite surface protein I (MSPI) is regarded as the leading asexual vaccine candidate. Apical membrane antigen 1 (AMA1) has been identified as another leading candidate for an asexual malaria vaccine, but without any direct in vivo evidence that a recombinant form of Plasmodium falciparum AMA1 would have efficacy. We evaluated the efficacy of a form of P. falciparum AMA1, produced in Pichia pastoris, by vaccinating Aotus vociferans monkeys and then challenging them with P. falciparum parasites. Significant protection from this otherwise lethal challenge with P. falciparum was observed. Five of six animals had delayed patency; two of these remained subpatent for the course of the infection, and two controlled parasite growth at <0.75% of red blood cells parasitized. The protection induced by AMA1 was superior to that obtained with a form of MSPI used in the same trial. The protection induced by a combination vaccine of AMA1 and MSPI was not superior to the protection obtained with AMA1 alone, although the immunity generated appeared to operate against both vaccine components. C1 NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD 20852 USA. RP Stowers, AW (reprint author), CSL Ltd, 45 Poplar Rd, Parkville, Vic 3052, Australia. RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 22 TC 141 Z9 150 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2002 VL 70 IS 12 BP 6961 EP 6967 DI 10.1128/IAI.70.12.6961-6967.2002 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 617TU UT WOS:000179377600057 PM 12438375 ER PT J AU Smoot, LM McCormick, JK Smoot, JC Hoe, NP Strickland, I Cole, RL Barbian, KD Earhart, CA Ohlendorf, DH Veasy, LG Hill, HR Leung, DYM Schlievert, PM Musser, JM AF Smoot, LM McCormick, JK Smoot, JC Hoe, NP Strickland, I Cole, RL Barbian, KD Earhart, CA Ohlendorf, DH Veasy, LG Hill, HR Leung, DYM Schlievert, PM Musser, JM TI Characterization of two novel pyrogenic toxin superantigens made by an acute rheumatic fever clone of Streptococcus pyogenes associated with multiple disease outbreaks SO INFECTION AND IMMUNITY LA English DT Article ID GROUP-A STREPTOCOCCUS; SHOCK-SYNDROME; T-CELLS; EXOTOXIN; PROTEIN; SEQUENCE; PATHOGENESIS; INVOLVEMENT; EXPRESSION; EPIDEMICS AB The pathogenesis of acute rheumatic fever (ARF) is poorly understood. We identified two contiguous bacteriophage genes, designated speL and speM, encoding novel inferred superantigens in the genome sequence of an ARF strain of serotype M18 group A streptococcus (GAS). speL and speM were located at the same genomic site in 33 serotype M18 isolates, and no nucleotide sequence diversity was observed in the 33 strains analyzed. Furthermore, the genes were absent in 13 non-M18 strains tested. These data indicate a recent acquisition event by a distinct clone of serotype M18 GAS. speL and speM were transcribed in vitro and upregulated in the exponential phase of growth. Purified SpeL and SpeM were pyrogenic and mitogenic for rabbit splenocytes and human peripheral blood mononuclear cells in picogram amounts. SpeL preferentially expanded human T cells expressing T-cell receptors Vbeta1, Vbeta5.1, and Vbeta23, and SpeM had specificity for Vbeta1 and Vbeta23 subsets, indicating that both proteins had superantigen activity. SpeL was lethal in two animal models of streptococcal toxic shock, and SpeM was lethal in one model. Serologic studies indicated that ARF patients were exposed to serotype M18 GAS, SpeL, and SpeM. The data demonstrate that SpeL and SpeM are pyrogenic toxin superantigens and suggest that they may participate in the host-pathogen interactions in some ARF patients. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. Natl Jewish Med & Res Ctr, Div Pediat Allergy & Immunol, Denver, CO 80262 USA. Univ Utah, Sch Med, Primary Childrens Med Ctr, Dept Pediat, Salt Lake City, UT 84132 USA. Univ Utah, Sch Med, Div Cardiol, Salt Lake City, UT 84132 USA. Univ Utah, Sch Med, Div Clin Immunol, Dept Pathol, Salt Lake City, UT 84132 USA. Univ Utah, Sch Med, Div Clin Immunol, Dept Pediat, Salt Lake City, UT 84132 USA. Univ Utah, Sch Med, Div Clin Immunol, Dept Med, Salt Lake City, UT 84132 USA. RP Musser, JM (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. RI McCormick, John/E-4232-2015; OI McCormick, John/0000-0003-3742-7289 FU NHLBI NIH HHS [HL36577, P01 HL036577, R01 HL036611, HL36611, HL37260, R37 HL037260]; NIAID NIH HHS [R01 AI051607, AI51607, N01-AO-22749, N01AO22749]; NIAMS NIH HHS [AR41256, R01 AR041256] NR 39 TC 41 Z9 45 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2002 VL 70 IS 12 BP 7095 EP 7104 DI 10.1128/IAI.70.12.7095-7104.2002 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 617TU UT WOS:000179377600073 PM 12438391 ER PT J AU O'Grady, NP Alexander, M Dellinger, EP Gerberding, JL Heard, SO Maki, DG Masur, H McCormick, RD Mermel, LA Pearson, ML Raad, II Randolph, A Weinstein, RA AF O'Grady, NP Alexander, M Dellinger, EP Gerberding, JL Heard, SO Maki, DG Masur, H McCormick, RD Mermel, LA Pearson, ML Raad, II Randolph, A Weinstein, RA TI Guidelines for the prevention of intravascular catheter-related infections SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Review ID CENTRAL VENOUS CATHETER; BLOOD-STREAM INFECTION; INTENSIVE-CARE-UNIT; TOTAL PARENTERAL-NUTRITION; PERIPHERAL INTRAVENOUS CATHETERS; RESISTANT STAPHYLOCOCCUS-AUREUS; RANDOMIZED CONTROLLED TRIAL; DOUBLE-BLIND TRIAL; ANTISEPTIC-IMPREGNATED CATHETER; SERRATIA-MARCESCENS BACTEREMIA AB BACKGROUND: Although many catheter-related bloodstream infections (CRBSIs) are preventable, measures to reduce these infections are not uniformly implemented. OBJECTIVE: To update an existing evidenced-based guideline that. promotes strategies to prevent CRBSIs. DATA SOURCES: The MEDLINE database, conference proceedings, and bibliographies of review articles and book chapters were searched for relevant articles. STUDIES INCLUDED: Laboratory-based studies, controlled clinical trials, prospective interventional trials, and epidemiologic investigations. OUTCOME MEASURES: Reduction in CRBSI, catheter colonization, or catheter-related infection. SYNTHESIS: The recommended preventive strategies with the strongest supportive evidence are education and training of healthcare providers who insert and maintain catheters; maximal sterile barrier precautions during central venous catheter insertion; use of a 2% chlorhexidine preparation for skin antisepsis; no routine replacement of central venous catheters for prevention of infection; and use of antiseptic/antibiofic-impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies (ie, education and training, maximal sterile barrier precautions, and 2% chlorhexidine for skin antisepsis). CONCLUSION: Successful implementation of these evidence-based interventions can reduce the risk for serious catheter-related infection. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. INS, Cambridge, MA USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Healthcare Qual Promot, Atlanta, GA USA. Univ Massachusetts, Sch Med, Dept Anesthesiol, Worcester, MA USA. Univ Wisconsin, Sch Med, Infect Dis Sect, Madison, WI USA. Univ Wisconsin, Hosp & Clin, Madison, WI USA. Rhode Isl Hosp, Div Infect Dis, Providence, RI 02903 USA. Brown Univ, Sch Med, Providence, RI USA. MD Anderson Canc Ctr, Dept Med Specialties, Houston, TX USA. Childrens Hosp, Dept Anesthesia, Boston, MA USA. Childrens Hosp, Dept Pediat, Boston, MA USA. Cook Cty Hosp, Div Infect Dis, Chicago, IL 60612 USA. Rush Med Coll, Chicago, IL USA. RP O'Grady, NP (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 183 TC 281 Z9 290 U1 0 U2 21 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD DEC PY 2002 VL 23 IS 12 BP 759 EP 769 DI 10.1086/502007 PG 11 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 628HA UT WOS:000179986300011 PM 12517020 ER PT J AU Ostrosky-Zeichner, L Rex, JH Bennett, J Kullberg, BJ AF Ostrosky-Zeichner, L Rex, JH Bennett, J Kullberg, BJ TI Deeply invasive candidiasis SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID BLOOD-STREAM INFECTIONS; INTENSIVE-CARE UNIT; IN-VITRO SUSCEPTIBILITIES; B LIPID COMPLEX; AMPHOTERICIN-B; ANTIFUNGAL AGENTS; FUNGAL-INFECTIONS; SURGICAL PATIENTS; RISK-FACTORS; CRITICALLY ILL AB The incidence of invasive candidiasis is on the rise because of increasing numbers of immunocompromised hosts and more invasive medical technology. Although identification to the species level and antifungal susceptibility testing should guide therapy, amphotericin B preparations are the usual initial therapy for severe life-threatening disease. Azole therapy has an expanding body of evidence that proves it is as effective as and safer than amphotericin B therapy. Some forms of candidiasis require a combined medical and surgical approach. C1 Univ Texas, Sch Med, Div Infect Dis, Houston, TX 77030 USA. NIH, Bethesda, MD 20892 USA. Univ Nijmegen, Med Ctr St Radboud, Dept Internal Med, NL-6500 HB Nijmegen, Netherlands. RP Ostrosky-Zeichner, L (reprint author), Univ Texas, Sch Med, Div Infect Dis, 6431 Fannin,JFB 1-728, Houston, TX 77030 USA. RI Kullberg, Bart Jan/C-8520-2013 NR 98 TC 42 Z9 44 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 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 2002 VL 16 IS 4 BP 821 EP + AR PII S0891-5520(02)00034-X DI 10.1016/S0891-5520(02)00034-X PG 16 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 646RZ UT WOS:000181049200003 PM 12512183 ER PT J AU Fleming, RV Walsh, TJ Anaissie, EJ AF Fleming, RV Walsh, TJ Anaissie, EJ TI Emerging and less common fungal pathogens SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID PENICILLIUM-MARNEFFEI INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; TRICHODERMA-LONGIBRACHIATUM INFECTION; CONTAMINATED SKIN LOTION; INTENSIVE-CARE NURSERY; IN-VITRO ACTIVITY; OF-THE-LITERATURE; TRICHOSPORON-BEIGELII; TRANSPLANT RECIPIENT; PERITONEAL-DIALYSIS AB Less common and emerging fungal pathogens are often resistant to conventional antifungal therapy and may cause severe morbidity and mortality in immunocompromised hosts. Some Scedosporium species may be completely resistant to antifungal therapy Hyaline septated filamentous fungi, such as Fusarium species, Acremonium species, Paecilomyces species, and Trichoderma species, are increasingly reported as causing invasive mycoses refractory to amphotericin B therapy. Dematiaceous septated filamentous fungi, such as Bipolaris species may cause pneumonia, sinusitis, and CNS infections that are unresponsive to current medical interventions. Trichosporon spp are resistant to the fungicidal effects of amphotericin B. An increasing number of different members of the class Zygomycetes are reported as causing lethal infections, despite aggressive medical and surgical interventions. Infections due to these and other less common and emergent fungal pathogens will likely continue to develop in the settings of selective anti-fungal pressure, permissive environmental conditions, and an expanding population of immunocompromised hosts. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 13N240, Bethesda, MD 20892 USA. EM walsh@mail.nih.gov NR 78 TC 117 Z9 126 U1 3 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0891-5520 EI 1557-9824 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 2002 VL 16 IS 4 BP 915 EP + AR PII S0891-5520(02)00041-7 DI 10.1016/S0891-5520(02)00041-7 PG 21 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 646RZ UT WOS:000181049200007 PM 12512187 ER PT J AU Harris, KM Sturm, R AF Harris, KM Sturm, R TI Adverse selection and generosity of alcohol treatment benefits SO INQUIRY-THE JOURNAL OF HEALTH CARE ORGANIZATION PROVISION AND FINANCING LA English DT Article ID MENTAL-HEALTH-CARE; MANAGED CARE; RISK CONTRACTS; PLAN; COMPETITION; PROGRAM; COSTS AB Concerns about attracting disproportionate numbers of employees with alcohol problems limit employers' willingness to offer health plans with generous alcohol treatment benefits. This paper analyzes two potential avenues of adverse selection, namely biased enrollment into plans and biased exit from plans offered by 57 employers between 1991 and 1997. We compare alcohol treatment use rates and costs of new and old enrollees between more generous and less generous plans; we also analyze disenrollment rates and enrollment duration by plan generosity for users and nonusers of alcohol treatment services. To avoid confounding benefit generosity with other plan features, in particular the use of managed care mechanisms, we compare plans that were administered in the same way by a large managed behavioral health care organization. Overall, we find no evidence of adverse selection into more generous plans. Contrary to the selection hypothesis, treatment costs of new members compared to old members are lower in firms with more generous treatment benefits than in firms with more limited benefits. Also, users of alcohol treatment services do not remain disproportionately enrolled longer in plans with generous benefits. C1 NIAAA, Div Clin & Prevent Res, Rockville, MD 20852 USA. RAND Corp, Santa Monica, CA 90406 USA. RP Harris, KM (reprint author), NIAAA, Div Clin & Prevent Res, Willco Bldg,Suite 305, Rockville, MD 20852 USA. FU NIAAA NIH HHS [N01AA01010] NR 28 TC 3 Z9 3 U1 0 U2 0 PU BLUE CROSS BLUE SHIELD ASSOC PI ROCHESTER PA 150 EAST MAIN ST, ROCHESTER, NY 14647 USA SN 0046-9580 J9 INQUIRY-J HEALTH CAR JI Inquiry-J. Health Care Organ. Provis. Financ. PD WIN PY 2002 VL 39 IS 4 BP 413 EP 428 PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 694GR UT WOS:000183766500008 PM 12638715 ER PT J AU Buchholz, DR Hsia, V Fu, L Shi, YB AF Buchholz, DR Hsia, V Fu, L Shi, YB TI In-vivo molecular mechanisms of thyroid hormone receptor during frog metamorphosis. SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 02-07, 2002 CL ANAHEIM, CALIFORNIA SP Soc Integrat & Comparat Biol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC INTEGRATIVE COMPARATIVE BIOLOGY PI MCLEAN PA 1313 DOLLEY MADISON BLVD, NO 402, MCLEAN, VA 22101 USA SN 1540-7063 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD DEC PY 2002 VL 42 IS 6 BP 1202 EP 1203 PG 2 WC Zoology SC Zoology GA 669ND UT WOS:000182356600111 ER PT J AU Piatigorsky, JJ AF Piatigorsky, JJ TI Gene sharing as an evolutionary strategy for lens crystallins. SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 02-07, 2002 CL ANAHEIM, CALIFORNIA SP Soc Integrat & Comparat Biol C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC INTEGRATIVE COMPARATIVE BIOLOGY PI MCLEAN PA 1313 DOLLEY MADISON BLVD, NO 402, MCLEAN, VA 22101 USA SN 1540-7063 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD DEC PY 2002 VL 42 IS 6 BP 1294 EP 1294 PG 1 WC Zoology SC Zoology GA 669ND UT WOS:000182356600563 ER PT J AU Klabunde, CN Sancho-Garnier, H Taplin, S Thoresen, S Ohuchi, N Ballard-Barbash, R AF Klabunde, CN Sancho-Garnier, H Taplin, S Thoresen, S Ohuchi, N Ballard-Barbash, R CA IBSN TI Quality assurance in follow-up and initial treatment for screening mammography programs in 22 countries SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE breast cancer; follow-up; mammography; quality assurance; screening; treatment ID BREAST-CANCER MORTALITY; NETHERLANDS AB Objective. To describe the quality assurance activities related to follow-up evaluation of abnormal screening mammograms and subsequent initial treatment of women determined to have breast cancer for the screening programs represented in the International Breast Cancer Screening Network (IBSN). Design. Analysis of data from a survey that included questions about screening program policies, standards, and procedures for follow-up of women with abnormal mammograms, as well as the data and measures that programs use to assess the adequacy of follow-up and initial treatment. Setting and participants. IBSN representatives in 23 countries completed a comprehensive questionnaire between May and December 1998. Results. Two-thirds of IBSN countries reported that they have a written policy or guidelines for follow-up of an abnormal mammogram; 64% require accreditation of the cytology or pathology laboratories that analyze breast specimens, or subject pathology laboratories to external audits. Of the 22 activities and measures related to quality of follow-up and initial treatment that we examined, all countries had in place at least half of them, although countries were more likely to have implemented activities and measures related to data collection and evaluation than to processes of care. Conclusions. Population-based screening mammography programs cannot achieve the goal of reducing breast cancer mortality if women with abnormal mammograms do not receive appropriate, timely follow-up and initial treatment. This study shows that IBSN countries vary in their implementation of procedures and measures to assure the quality of follow-up and initial treatment for women with abnormal screening mammograms. There is more emphasis on collecting and evaluating data than establishing mechanisms to ensure that the processes of care for follow-up and initial treatment are of high quality. C1 NCI, DCCPS, ARP, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Eidaure, Montpellier, France. Canc Registry Norway, Oslo, Norway. Tohoku Univ, Grad Sch Med, Div Surg Oncol, Sendai, Miyagi 980, Japan. RP Klabunde, CN (reprint author), NCI, DCCPS, ARP, Hlth Serv & Econ Branch, EPN Room 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 28 TC 16 Z9 16 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD DEC PY 2002 VL 14 IS 6 BP 449 EP 461 DI 10.1093/intqhc/14.6.449 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 632ZE UT WOS:000180254100003 PM 12515331 ER PT J AU Zou, XN Taylor, PR Mark, SD Chao, A Wang, W Dawsey, SM Wu, YP Qiao, YL Zheng, SF AF Zou, XN Taylor, PR Mark, SD Chao, A Wang, W Dawsey, SM Wu, YP Qiao, YL Zheng, SF TI Seasonal variation of food consumption and selected nutrient intake,in Linxian, a high risk area for esophageal cancer in China SO INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH LA English DT Article DE diet surveys; food habits; vegetables; micronutrients; esophageal neoplasm ID NUTRITION INTERVENTION TRIALS; MINERAL SUPPLEMENTATION; VITAMIN; POPULATION; DISEASE; DIET AB Linxian, China, is a region with high incidence of esopheal cancer and a history of poor nutritional status. Nutrition Intervention Trials were conducted in this area from 1985 through 1991 and found a reduction in total cancer mortality in the group receiving supplementation of beta-carotene/selenium/alpha-tocopherol. The positive results of those trials have, in part, been aseribed to the poor nutritional status of this population. To investigate more recent food patterns, nutrient intakes, and seasonal variations, in the diet, dietary surveys were conducted among the residents of Linxian in 1996. Food consumption data were collected among 104, households in spring and 106 households in autumn using a method of food inventory changes. Intake of nutrients was estimated and compared to the Chinese Recommended Dietary Allowance (RDA). In both seasons the five most common food groups consumed were cereals, fresh vegetables, yams, seasonings, and eggs. Low nutrient intakes were found for selenium (79% RDA and 66% RDA), zinc (72% RDA aid 62%.RDA), vitamin B-2 (64% RDA and 52% RDA),, and calcium (53% RDA and 39% RDA) in both spring and autumn. A large seasonal, variation was seen in the consumption of leafy vegetables, root vegetables and, eggs all of which might, have contributed to the lower intake, of vitamin A (25% RDA), vitamin C, (75 W RDA),,protein, (76% RDA), and vitamins E (78% RDA) in autumn. These indicate that the nutrient intake in Linxian is inadequate for a number of mins and minerals including those shown to, be associated with esophageal cancer. C1 Chinese Acad Med Sci, Inst Canc, Dept Canc Epidemiol, Beijing 100021, Peoples R China. Peking Union Med Coll, Beijing 100021, Peoples R China. NCI, Canc Res Ctr, Canc Prevent Studies Branch, Rockville, MD 20852 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. RP Zou, XN (reprint author), Chinese Acad Med Sci, Inst Canc, Dept Canc Epidemiol, 17 S Panjiayuan,Chaoyang Dist, Beijing 100021, Peoples R China. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 FU NCI NIH HHS [CP-50536] NR 29 TC 38 Z9 42 U1 0 U2 7 PU VERLAG HANS HUBER PI BERN 9 PA LANGGASS-STRASSE 76, CH-3000 BERN 9, SWITZERLAND SN 0300-9831 J9 INT J VITAM NUTR RES JI Int. J. Vitam. Nutr. Res. PD DEC PY 2002 VL 72 IS 6 BP 375 EP 382 DI 10.1024/0300-9831.72.6.375 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 643QF UT WOS:000180871400005 PM 12596503 ER PT J AU Chumlea, WC Guo, SS Kuczmarski, RJ Flegal, KM Johnson, CL Heymsfield, SB Lukaski, HC Friedl, K Hubbard, VS AF Chumlea, WC Guo, SS Kuczmarski, RJ Flegal, KM Johnson, CL Heymsfield, SB Lukaski, HC Friedl, K Hubbard, VS TI Body composition estimates from NHANES III bioelectrical impedance data SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE body composition; obesity; BIA; NHANES; health surveys ID FAT-FREE MASS; ADULTS; AGE; BLACK; WHITE; WATER; INDEX; RELIABILITY; POPULATION; OVERWEIGHT AB BACKGROUND: Body composition estimates for the US population are important in order to analyze trends in obesity, sarcopenia and other weight-related health conditions. National body composition estimates have not previously been available. OBJECTIVE: To use transformed bioelectrical impedance analysis (BIA) data in sex-specific, multicomponent model-derived prediction formulae, to estimate total body water (TBW), fat-free mass (FFM), total body fat (TBF), and percentage body fat (%BF) using a nationally representative sample of the US population. DESIGN: Anthropometric and BIA data were from the third National Health and Nutrition Examination Survey (NHANES III; 1988-1994). Sex-specific BIA prediction equations developed for this study were applied to the NHANES data, and mean values for TBW, FFM, TBF and %BF were estimated for selected age, sex and racial-ethnic groups. RESULTS: Among the non-Hispanic white, non-Hispanic black, and Mexican-American participants aged 12 - 80 y examined in NHANES III, 15 912 had data available for weight, stature and BIA resistance measures. Males had higher mean TBW and FFM than did females, regardless of age or racial-ethnic status. Mean TBW and FFM increased from the adolescent years to mid-adulthood and declined in older adult age groups. Females had higher mean TBF and %BF estimates than males at each age group. Mean TBF also increased with older age groups to approximately 60y of age after which it decreased. CONCLUSIONS: These mean body composition estimates for TBW, FFM, TBF and %BF based upon NHANES III BIA data provide a descriptive reference for non-Hispanic whites, non-Hispanic blacks and Mexican Americans in the US population. C1 Wright State Univ, Lifespan Hlth Res Ctr, Dept Community Hlth, Sch Med, Dayton, OH 45420 USA. NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Examinat Stat, Hyattsville, MD USA. Columbia Univ, St Lukes Roosevelt Hosp, Obes Res Ctr, New York, NY 10027 USA. USDA ARS, Grand Forks NRC, Grand Forks, ND USA. Mil Med Res & Mat Command, Mil Operat Med Program, Frederick, MD USA. NIDDK, Div Nutr Res Coordinat, NIH, Bethesda, MD USA. NIDDK, Nutr Sci Branch, NIH, Bethesda, MD USA. RP Guo, SS (reprint author), Wright State Univ, Lifespan Hlth Res Ctr, Dept Community Hlth, Sch Med, 3171 Res Blvd, Dayton, OH 45420 USA. RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X; Friedl, Karl/0000-0002-3134-8427 FU NHLBI NIH HHS [HL-53404]; NICHD NIH HHS [HD-12252, HD-27063] NR 48 TC 237 Z9 243 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 2002 VL 26 IS 12 BP 1596 EP 1609 DI 10.1038/sj.ijo.0802167 PG 14 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 626HV UT WOS:000179866500009 PM 12461676 ER PT J AU Stefan, N Vozarova, B Del Parigi, A Ossowski, V Thompson, DB Hanson, RL Ravussin, E Tataranni, PA AF Stefan, N Vozarova, B Del Parigi, A Ossowski, V Thompson, DB Hanson, RL Ravussin, E Tataranni, PA TI The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE leptin receptor; energy expenditure; physical activity level; fat cell size ID RESPIRATORY CHAMBER; MODELS; WOMEN; MICE; MEN AB Leptin regulates body weight by its receptor-mediated anorectic, thermogenic and antisteatotic effects. Recently, lower leptin binding to the soluble form of the leptin receptor (LEPR) was shown in carriers of the Arg223-encoding allele of the Gln223Arg polymorphism of the LEPR. To investigate whether this variant influences energy metabolism and adiposity in Pima Indians, we genotyped non-diabetic Pima Indians in whom we had measured body composition and 24 h energy expenditure (24 h EE), physical activity level (PAL) and 24 h respiratory quotient (24 h RQ) in a respiratory chamber (n = 268) and who had undergone percutaneous fat biopsies from the periumbilical region (n=184). Genotype was not associated with percent body fat (P > 0.39), but was associated with 24 h EE, PAL and mean subcutaneous abdominal adipocyte size (SAAS all P < 0.05). Homozygotes for the Arg223-encoding allele had lower 24 h EE (P = 0.04) and PAL (P = 0.007), but larger SAAS (P = 0.01) than Gln homozygotes. These findings are consistent with a role of the Gln223Arg polymorphism in reducing peripheral and central leptin binding to the LEPR in humans. However, these effects do not seem to have a major impact on adiposity in this population. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. NIDDKD, Diabet & Arthrit Epidemiol Sect, NIH, Phoenix, AZ 85016 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Stefan, N (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Rm 5-41, Phoenix, AZ 85016 USA. RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; de Courten, Barbora/0000-0001-8760-2511; Stefan, Norbert/0000-0002-2186-9595 NR 20 TC 61 Z9 63 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 2002 VL 26 IS 12 BP 1629 EP 1632 DI 10.1038/sj.ijo.0802161 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 626HV UT WOS:000179866500013 PM 12461680 ER PT J AU Wu, CO Yu, KF AF Wu, CO Yu, KF TI Nonparametric varying-coefficient models for the analysis of longitudinal data SO INTERNATIONAL STATISTICAL REVIEW LA English DT Article DE bootstrap; confidence bands; hypothesis testing; local polynomials; longitudinal data; smoothing methods; splines; varying coefficient models ID KERNEL REGRESSION ESTIMATION; LINEAR-MODELS; SERIAL-CORRELATION; CONFIDENCE BANDS; CLUSTERED DATA; ERRORS; CURVES; PREDICTOR; INFERENCE; SPLINE AB Longitudinal methods have been widely used in biomedicine and epidemiology to study the patterns of time-varying variables, such as disease progression or trends of health status. Data sets of longitudinal studies usually involve repeatedly measured outcomes and covariates on a set of randomly chosen subjects over time. An important goal of statistical analyses is to evaluate the effects of the covariates, which may or may not depend on time, on the outcomes of interest. Because fully parametric models may be subject to model misspecification and completely unstructured nonparametric models may suffer from the drawbacks of "curse of dimensionality", the varying-coefficient models are a class of structural nonparametric models which are particularly useful in longitudinal analyses. In this article, we present several important nonparametric estimation and inference methods for this class of models, demonstrate the, advantages,, limitations and practical implementations of these methods in different longitudinal settings, and discuss some potential directions of further research in this area. Applications of these methods are illustrated through two epidemiological examples. C1 NHLBI, Off Biostat Res, DECA, Bethesda, MD 20892 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20852 USA. RP Wu, CO (reprint author), NHLBI, Off Biostat Res, DECA, Bethesda, MD 20892 USA. NR 54 TC 13 Z9 13 U1 0 U2 3 PU INT STATISTICAL INST PI VOORBURG PA 428 PRINSES BEATRIXLAAN, 2270 AZ VOORBURG, NETHERLANDS SN 0306-7734 J9 INT STAT REV JI Int. Stat. Rev. PD DEC PY 2002 VL 70 IS 3 BP 373 EP 393 DI 10.2307/1403863 PG 21 WC Statistics & Probability SC Mathematics GA 621TW UT WOS:000179607900003 ER PT J AU Parascandola, M AF Parascandola, M TI Uncertain science and a failure of trust - The NIH radioepidemiologic tables and compensation for radiation-induced cancer SO ISIS LA English DT Article ID ASSIGNED SHARES; PROBABILITY; EXPOSURES; STATEMENT; RISKS AB In the late 1970s, the U.S. Congress was debating a number of different proposals to provide monetary compensation to residents of Utah and Nevada who had been exposed to radioactive fallout from government nuclear weapons testing in the 1950s. Yet scientists and government officials expressed concern that such a program would end up compensating many people for cancers that were not caused by the fallout. Thus, after much debate, Congress directed the National Institutes of Health to produce a set of statistical tables-the radioepidemiologic tables-to target compensation awards to "deserving" individuals. Advocates of the tables, notably Senator Orrin Hatch, argued that reliance on scientific data would provide compensation decisions with predictability and evenhandedness. Yet in the end, the effort to employ the tables failed. The substantial scientific uncertainties in the tables and in their application to individual claims failed to deliver the authority they promised. Additionally, the goal of fairness and objectivity could not be convincingly met because of persistent controversy and mistrust surrounding the govemment's role in the study of health effects of low-level radiation. C1 NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. RP Parascandola, M (reprint author), NCI, Canc Prevent Fellowship Program, 6130 Execut Blvd,Suite 3109, Bethesda, MD 20892 USA. NR 89 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0021-1753 J9 ISIS JI Isis PD DEC PY 2002 VL 93 IS 4 BP 559 EP 584 DI 10.1086/375952 PG 26 WC History & Philosophy Of Science SC History & Philosophy of Science GA 657UR UT WOS:000181685200001 PM 12664791 ER PT J AU Sharabi, Y Reshef-Haran, I Burstein, M Eldad, A AF Sharabi, Y Reshef-Haran, I Burstein, M Eldad, A TI Cigarette smoking and hearing loss: Lessons from the young adult periodic examinations in Israel (YAPEIS) database SO ISRAEL MEDICAL ASSOCIATION JOURNAL LA English DT Article DE hearing loss; cigarette smoking; population study; young adults; periodic examination ID CARDIOVASCULAR RISK-FACTORS; MIDDLE-EAR EFFUSIONS; OTITIS-MEDIA; IMPAIRMENT; WORKERS AB Background: Some studies have indicated a possible link between cigarette smoking and hearing loss. Objectives: To analyze the association between smoking and hearing loss, other-than that induced by noise, and to characterize the type of HL impairment found in smokers. Methods: We conducted a retrospective cross-sectional study in 13,308 men aged 20-68 (median 34.6 years) who underwent a hearing test as part of a routine periodic examination. For each subject, age, smoking status (current, past or non-smokers) and number of cigarettes per day were noted and a hearing test was performed. The test was performed in a sealed, soundproof room by an experienced audiologist and included pure tone audiometry of 2508,000 Hz. The audiograms were analyzed and subjects were accordingly divided into two groups: those with HL and at least one of the following impairments in at least one ear: sensorineural, conductive or mixed; and those with no hearing loss (control). Audiograms showing HL typical to noise exposure were excluded. Results: The, prevalence of any type of HL among subjects < 35 years was 4.5%, compared to 1.0.5% among those > 35 years (P < 0.0001). A significantly higher incidence of any type of HL was found in current (11.8%) and past smokers (11.7%) than in non-smokers (8.1%) (P < 0.0001). The risk increment of the smoking status for developing HL among subjects under age 35 was 43%, and 17% among those above 35 years. Both, mild, flat, sensorineural impairment and conductive impairment were found to be associated particularly with smoking (odds ratio. 2.2 and 1.9, respectively). Conclusions. The incidence of HL unrelated to noise exposure is higher in smokers-than in non-smokers, and in young adults the effect is greater. C1 Israel Def Forces Med Corps, Tel Hashomer, Israel. RP Sharabi, Y (reprint author), NINDS, Natl Inst Hlth, CNCS, Bldg 10,Room 6N252,MSC 1620,10 Ctr Dr, Bethesda, MD 20892 USA. NR 18 TC 11 Z9 13 U1 0 U2 1 PU ISRAEL MEDICAL ASSOC JOURNAL PI RAMAT GAN PA 2 TWIN TOWERS, 11TH FL, 35 JABOTINSKY ST, PO BOX 3604, RAMAT GAN 52136, ISRAEL SN 1565-1088 J9 ISRAEL MED ASSOC J JI Isr. Med. Assoc. J. PD DEC PY 2002 VL 4 IS 12 BP 1118 EP 1120 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 673HP UT WOS:000182574900007 PM 12516904 ER PT J AU Hilton, C Sabundayo, BP Langan, SJ Hilton, M Henson, C Quinn, TC Margolick, JB Nelson, KE AF Hilton, C Sabundayo, BP Langan, SJ Hilton, M Henson, C Quinn, TC Margolick, JB Nelson, KE TI Screening for HIV infection in high-risk communities by urine antibody testing SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV test; urine testing; diagnosis of HIV infection ID PREVENTION; EPIDEMIC AB Objectives: To evaluate the effectiveness of urine screening to detect HIV-infected individuals in high-prevalence communities. Methods: Urine HIV testing was performed at 16 discrete events and four ongoing testing sites in Baltimore communities with a high incidence of HIV infection. When possible, positive urine test results were confirmed by blood testing. In addition, we attempted to obtain blood samples from subjects who reported a possible exposure to HIV but did not have a positive urine test. Results: From February 1998 to August 2001, we screened 1718 persons. Overall, 210 persons (12%) were HIV-positive, of whom 169 (80%) had never previously tested positive; 87% of those who tested positive received their results, and most were referred for medical care. Conclusions: Urine-based screening for HIV infection in high-prevalence inner city communities can be an effective tool for identifying and treating infected persons who are unaware of their infection. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Margolick, JB (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, 615 N Wolfe St E5153, Baltimore, MD 21205 USA. FU NCRR NIH HHS [M01-RR 00052]; NIAID NIH HHS [AI 41532] NR 17 TC 5 Z9 5 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS JI JAIDS PD DEC 1 PY 2002 VL 31 IS 4 BP 416 EP 421 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 618XZ UT WOS:000179444400008 PM 12447013 ER PT J AU Seage, GR Holte, S Gross, M Koblin, B Marmor, M Mayer, KH Lenderking, WR AF Seage, GR Holte, S Gross, M Koblin, B Marmor, M Mayer, KH Lenderking, WR TI Case-crossover study of partner and situational factors for unprotected sex SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV risk behaviors; case-crossover design; HIV epidemiologic methods ID HUMAN-IMMUNODEFICIENCY-VIRUS; AFRICAN-AMERICAN WOMEN; HIV-INFECTION; DRUG-USE; UNSAFE SEX; CONDOM USE; RISK; AIDS; GENDER; PREVENTION AB Objectives: To identify situational and partner characteristics associated with unprotected sex among women at risk for HIV infection. Methods: The most recent unprotected and protected sexual encounters were compared using a case-crossover design among 1,647 women enrolled in a prospective cohort study conducted in six U.S. cities. Information collected via audio computer-assisted self-interview included detailed situational and partner characteristics for participants most recent sexual encounters, with and without condom use. Paired odds ratios (ORs) and 95% confidence intervals were calculated for situational or partner characteristics that may differ between unprotected and protected sexual encounters, using conditional logistic regression. Results: In the adjusted analysis, partner age of older than 40 years (OR = 2.42), partner type (OR = 2.45 for a "steady" partner), partner use of alcohol (OR = 1.67) and drugs within 2 hours (OR = 1.42) of the sexual encounter, time since the encounters (OR = 0.41, 0.33, and 0.19), and exchange of sex for money or drugs (OR = 0.68) remained significantly associated with women's most recent unprotected sexual encounter. Conclusions: Considerations related to partner and relationship characteristics should provide information for the development of interventions for women. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY USA. Brown Univ, Mem Hosp, Providence, RI 02912 USA. RP Seage, GR (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. OI Marmor, Michael/0000-0001-6605-2661 FU NCRR NIH HHS [M01RR00096]; NIAID NIH HHS [AI27742, N01-AI-35176, N01-AI-45200] NR 46 TC 29 Z9 29 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS JI JAIDS PD DEC 1 PY 2002 VL 31 IS 4 BP 432 EP 439 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 618XZ UT WOS:000179444400010 PM 12447015 ER PT J AU Brooks, BP Simpson, JL Leber, SM Robertson, PL Archer, SM AF Brooks, BP Simpson, JL Leber, SM Robertson, PL Archer, SM TI Infantile spasms as a cause of acquired perinatal visual loss SO JOURNAL OF AAPOS LA English DT Article ID WEST SYNDROME; PROGNOSIS; BLINDNESS; CHILDREN; EEG AB Background. Visual abnormalities have been described in patients with infantile spasms (IS), an epileptic syndrome of early childhood. Methods: We report on 3 children who exhibited cortically mediated visual regression in association with the development of IS. Results: In 1 patient, loss of visual behavior was the presenting complaint. In all patients, visual behavior improved with treatment of seizures. Conclusions: IS are a potentially treatable cause of cortically impaired vision in early childhood. Because visual behavior might improve when the seizures are treated, patients should be referred appropriately. C1 Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol, Ann Arbor, MI 48105 USA. Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48105 USA. Univ Michigan, Dept Neurol, Ann Arbor, MI 48105 USA. Univ Michigan, Dept Ophthalmol, Ann Arbor, MI 48105 USA. RP Brooks, BP (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bldg 10,Room 10C101, Bethesda, MD 20892 USA. OI Archer, Steven/0000-0002-5539-4129 NR 21 TC 8 Z9 8 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD DEC PY 2002 VL 6 IS 6 BP 385 EP 388 DI 10.1067/mpa.2002.129796 PG 4 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 631BP UT WOS:000180147300009 PM 12506281 ER PT J AU Gil-Lamaignere, C Roilides, E Maloukou, A Georgopoulou, I Petrikkos, G Walsh, TJ AF Gil-Lamaignere, C Roilides, E Maloukou, A Georgopoulou, I Petrikkos, G Walsh, TJ TI Amphotericin B lipid complex exerts additive antifungal activity in combination with polymorphonuclear leucocytes against Scedosporium prolificans and Scedosporium apiospermum SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 07-11, 2000 CL NEW ORLEANS, LOUISIANA SP Infect Dis Soc Amer DE amphotericin B formulations; Scedosporium; polymorphonuclear leucocytes ID ASPERGILLUS-FUMIGATUS; NEUTROPHILS; INFECTIONS; AGENTS AB Scedosporium prolificans and Scedosporium apiospermum are resistant to most antifungal agents and cause refractory pulmonary and disseminated infections. The combined effects of deoxycholate amphotericin B, amphotericin B lipid complex and liposomal amphotericin B with human polymorphonuclear leucocytes (PMNs) in damaging hyphae of these fungi were evaluated by XTT assay. Amphotericin B lipid complex displayed a significant additive effect with PMNs against both Scedosporium species (22% for S. prolificans and 81% for S. apiospermum; P < 0.04). None of the formulations adversely affected the PMN antifungal activity. These findings may be important in designing better strategies for management of infections due to these organisms. C1 NCI, Immunocompromised Host Sect, Paediat Oncol Branch, Bethesda, MD 20892 USA. Aristotle Univ, Hippokratio Hosp, Paediat Dept 3, GR-54642 Thessaloniki, Greece. Univ Athens, Propedeut Dept Med 1, GR-11527 Athens, Greece. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Paediat Oncol Branch, Bldg 10,Room 13N240, Bethesda, MD 20892 USA. RI Gil-Lamaignere, Cristina/A-3866-2013 NR 11 TC 36 Z9 37 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD DEC PY 2002 VL 50 IS 6 BP 1027 EP 1030 DI 10.1093/jac/dkf198 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 622VY UT WOS:000179668900035 PM 12461027 ER PT J AU Radaev, S Sun, PD AF Radaev, S Sun, PD TI Crystallization of protein-protein complexes SO JOURNAL OF APPLIED CRYSTALLOGRAPHY LA English DT Article ID RECEPTOR; FC AB Crystallizing protein-protein complexes remains a rate-limiting step in their structure characterization. Crystallization conditions for the known protein - protein complexes have been surveyed in both the Protein Data Bank and the BMCD database. Compared with non-complexed proteins, crystallization conditions for protein - protein complexes are less diverse and heavily favor (71% versus 27%) polyethylene glycols (PEG) rather than ammonium sulfate or other high-salt crystallization conditions. The results suggest that the stability of protein complexes limits their available crystallization configuration space. Based on the survey, a set of sparse-matrix screen conditions was designed. C1 NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 11 TC 14 Z9 14 U1 0 U2 7 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0021-8898 J9 J APPL CRYSTALLOGR JI J. Appl. Crystallogr. PD DEC PY 2002 VL 35 BP 674 EP 676 DI 10.1107/S0021889802013973 PN 6 PG 3 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA 614FX UT WOS:000179178600004 ER PT J AU Ostberg, Y Pinne, M Benz, R Rosa, P Bergstrom, S AF Ostberg, Y Pinne, M Benz, R Rosa, P Bergstrom, S TI Elimination of channel-forming activity by insertional inactivation of the p13 gene in Borrelia burgdorferi SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; LYME-DISEASE SPIROCHETE; LIPID BILAYER-MEMBRANES; FRACTURE ELECTRON-MICROSCOPY; ESCHERICHIA-COLI; TREPONEMA-PALLIDUM; PORIN ACTIVITY; IDENTIFICATION; SEQUENCE; COMPLEX AB P13 is a chromosomally encoded 13-kDa integral outer membrane protein of the Lyme disease agent, Borrelia burgdorferi. The aim of this study was to investigate the function of the P13 protein. Here, we inactivated the p13 gene by targeted mutagenesis and investigated the porin activities of outer membrane proteins by using lipid bilayer experiments. Channel-forming activity was lost in the p13 mutant compared to wild-type B. burgdorferi, indicating that P13 may function as a porin. We purified native P13 to homogeneity by fast performance liquid chromatography and demonstrated that pure P13 has channel-forming activity with a single-channel conductance in 1 M KCl of 3.5 nS, the same as the porin activity that was lost in the p13 mutant. Further characterization of the channel formed by P13 suggested that it is cation selective and voltage independent. In addition, no major physiological effects of the inactivated p13 gene could be detected under normal growth conditions. The inactivation of p13 is the first reported inactivation of a gene encoding an integral outer membrane protein in B. burgdorferi. Here, we describe both genetic and biophysical experiments indicating that P13 in B. burgdorferi is an outer membrane protein with porin activity. C1 Umea Univ, Dept Biol Mol, SE-90187 Umea, Sweden. Univ Wurzburg, Lehrstuhl Biotechnol, Biozentrum, D-97074 Wurzburg, Germany. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Bergstrom, S (reprint author), Umea Univ, Dept Biol Mol, SE-90187 Umea, Sweden. OI Benz, Roland/0000-0002-9510-9265 NR 65 TC 28 Z9 28 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 2002 VL 184 IS 24 BP 6811 EP 6819 DI 10.1128/JB.184.24.6811-6819.2002 PG 9 WC Microbiology SC Microbiology GA 620JA UT WOS:000179529200008 PM 12446631 ER PT J AU Kuznetsov, VA Auffray, C AF Kuznetsov, VA Auffray, C TI Preface: Integrative statistical and computational methods for genomics studies SO JOURNAL OF BIOLOGICAL SYSTEMS LA English DT Editorial Material C1 NICHHD, Sect Med Biophys, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Genexpress CNRS, F-94801 Villejuif, France. RP Kuznetsov, VA (reprint author), NICHHD, Sect Med Biophys, Lab Integrat & Med Biophys, NIH, 13 S Dr,Bldg 13,Room 3W16, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA JOURNAL DEPT PO BOX 128 FARRER ROAD, SINGAPORE 912805, SINGAPORE SN 0218-3390 J9 J BIOL SYST JI J. Biol. Syst. PD DEC PY 2002 VL 10 IS 4 BP 281 EP 283 DI 10.1142/S0218339002000755 PG 3 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 630MM UT WOS:000180111800001 ER PT J AU Kim, S Li, H Dougherty, ER Cao, NW Chen, YD Bittner, M Suh, EB AF Kim, S Li, H Dougherty, ER Cao, NW Chen, YD Bittner, M Suh, EB TI Can Markov chain models mimic biological regulation? SO JOURNAL OF BIOLOGICAL SYSTEMS LA English DT Article DE gene selection; gene regulatory network; Markov chain simulation; steady-state analysis; melanoma ID EXPRESSION AB A fundamental question in biology is whether the network of interactions that regulate gene expression can be modeled by existing mathematical techniques. Studies of the ability to predict a gene's state based on the states of other genes suggest that it may be possible to abstract sufficient information to build models of the system that retain steady-state behavioral characteristics of the real system. This study tests this possibility by: (i) constructing a finite state homogeneous Markov chain model using a small set of interesting genes; (ii) estimating the model parameters based on the observed experimental data; (iii) exploring the dynamics of this small genetic regulatory network by analyzing its steady-state (long-run) behavior and comparing the resulting model behavior to the observed behavior of the original system. The data used in this study are from a survey of melanoma where predictive relationships (coefficient of determination, CoD) between 587 genes from 31 samples were examined. Ten genes with strong interactive connectivity were chosen to formulate a finite state Markov chain on the basis of their role as drivers in the acquisition of an invasive phenotype in melanoma cells. Simulations with different perturbation probabilities and different iteration times were run. Following convergence of the chain to steady-state behavior, millions of samples of the results of further transitions were collected to estimate the steady-state distribution of network. In these samples, only a limited number of states possessed significant probability of occurrence. This behavior is nicely congruent with biological behavior, as cells appear to occupy only a negligible portion of the state space available to them. The model produced both some of the exact state vectors observed in the data, and also a number of state vectors that were near neighbors of the state vectors from the original data. By combining these similar states, a good representation of the observed states in the original data could be achieved. From this study, we End that, in this limited context, Markov chain simulation emulates well the dynamic behavior of a small regulatory network. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. Texas A&M Univ, Dept Elect Engn, College Stn, TX 77840 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. RP Kim, S (reprint author), NHGRI, Canc Genet Branch, NIH, 50 S Dr MSC 8000, Bethesda, MD 20892 USA. NR 15 TC 66 Z9 68 U1 0 U2 2 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA JOURNAL DEPT PO BOX 128 FARRER ROAD, SINGAPORE 912805, SINGAPORE SN 0218-3390 J9 J BIOL SYST JI J. Biol. Syst. PD DEC PY 2002 VL 10 IS 4 BP 337 EP 357 DI 10.1142/S0218339002000676 PG 21 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 630MM UT WOS:000180111800005 ER PT J AU Kuznetsov, VA Pickalov, VV Senko, OV Knott, GD AF Kuznetsov, VA Pickalov, VV Senko, OV Knott, GD TI Analysis of the evolving proteomes: Predictions of the number of protein domains in nature and the number of genes in eukaryotic organisms SO JOURNAL OF BIOLOGICAL SYSTEMS LA English DT Article DE proteome complexity; evolution; number of genes; number of protein domains; Pareto-like distribution; stochastic process ID GENOME; SEQUENCE; STATISTICS; NETWORKS AB Motivation: Obtaining accurate estimates of the numbers of protein-coding genes and protein domains in a proteome, and the number of protein domains in nature is a daunting challenge. Computational analysis of the protein domain sets in the proteomes of many species allows us to estimate these numbers and to find their evolution relationships. Results: We have analyzed the distributions of the number of occurrences of protein domains in sample proteomes of the 70 fully sequenced genome organisms of three major kingdoms of life: Archaea, Bacteria and Eukaryota. We found that a large fraction of the identified distinct protein domains (i.e., unique domains and homologous domain families) in these 70 proteomes (1051 (23%) out of 4493) are found in at least one organism in each of these kingdoms of life and that 43 (1%) of these domains are common to all the 70 organisms. All the observed domain occurrence frequency distributions for these 70 proteomes are well fitted by a family of Pareto-like functions, associated with the steady state distributions of a linear Markov random process. We present explicit formulas that accurately predict the number of distinct protein domains and the number of protein-coding genes for a given organism as functions of the number of non-redundant domain-to-protein links in the proteomes. These functions allows us to predict that there are 42,740, 27,900, and 21,200 protein-coding genes/open reading frames in the human,A. thaliana, and mouse genomes, respectively. We also estimate that there are 5271, 2955, and 4915 distinct protein domains in the human, A. thaliana, and mouse proteomes, respectively, and about 5500 distinct protein domains in the entire "proteome world". C1 NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Theoret & Appl Mech, Novosibirsk 630090, Russia. Russian Acad Sci, Ctr Comp, Moscow 117967, Russia. Civilized Software Inc, Silver Spring, MD 20906 USA. RP Kuznetsov, VA (reprint author), NICHHD, Lab Integrat & Med Biophys, 13 South Dr, Bethesda, MD 20892 USA. EM vk28u@nih.gov; pickalov@itam.nsc.ru; senko@ccas.ru; knott@civilized.com RI Pickalov, Valery/K-3848-2012; Pickalov, Valery/B-7262-2008 OI Pickalov, Valery/0000-0001-9362-6966; Pickalov, Valery/0000-0001-9362-6966 NR 24 TC 11 Z9 12 U1 0 U2 3 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0218-3390 J9 J BIOL SYST JI J. Biol. Syst. PD DEC PY 2002 VL 10 IS 4 BP 381 EP 407 DI 10.1142/S0218339002000767 PG 27 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 630MM UT WOS:000180111800007 ER PT J AU Pattabiraman, N Martinez, HM Shapiro, BA AF Pattabiraman, N Martinez, HM Shapiro, BA TI Molecular modeling and dynamics studies of HIV-1 kissing loop structures SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article DE HIV-1 kissing loop structures; molecular modeling and dynamics; RNA dimerization; HIV-1 MAL and LAI isolates ID DIMERIZATION INITIATION SITE; IMMUNODEFICIENCY-VIRUS; GENOMIC RNA; MURINE LEUKEMIA; IN-VITRO; COMPLEX; DIMER; PROTEIN; IDENTIFICATION; RECOMBINATION AB Recognition of an RNA loop by another RNA loop is involved in several biological functions. The dimerization. of two copies of the HIV-1 genomic RNA is thought to be involved in several steps of the retroviral life cycle. It has been shown that the dimerization of the two HIV-1 RNA genomes is initiated by the so-called "kissing loop". The 9nt kissing loop consists of a palindromic 6nt sequence that forms Watson-Crick base-pairs at the kissing site in HIV-1. We report the results of our molecular modeling and dynamics studies on two major subtype isolates (MAL and LAI) of HIV-1 kissing loop structures. From our modeling studies, we conclude that the conformation of the loop in the monomer might be closer to the "A-RNA-like" conformation in order to form an initial kissing structure. This is achieved by the stacking interactions of the bases at the 3' end of the loop and by the intramolecular tertiary interactions of a single linker nucleotide. We discuss the effect of the loop size and the structural limitations on the formation of kissing loop structures. Also, we propose a possible mechanism to convert the kissing loop structure to a stable extended duplex structure without unwinding the stems. C1 NCI, SAIC, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. NCI, Ctr Canc Res, Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Pattabiraman, N (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, 3970 Reservoir Rd NW, Washington, DC 20057 USA. FU NCI NIH HHS [N01-CO-56000] NR 34 TC 16 Z9 18 U1 0 U2 2 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD DEC PY 2002 VL 20 IS 3 BP 397 EP 411 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 628RZ UT WOS:000180011500013 PM 12437378 ER PT J AU Williams-Brown, S Baldwin, DM Bakos, A AF Williams-Brown, S Baldwin, DM Bakos, A TI Storytelling as a method to teach African American women breast health information SO JOURNAL OF CANCER EDUCATION LA English DT Article ID BLACK-WOMEN; CANCER; MAMMOGRAPHY; PROJECT; PROGRAM AB Background. The purpose of this study was to explore the use of storytelling as a method to teach breast health information to older African American women. Methods. A qualitative design utilizing the focus-group method. Results. Six story types (categories) emerged from the focus-group data and were integrated into the breast health education class. Categories were: 1) loss, 2) pain, 3) Suffering, 4) fear and worry/stress, 5) death, and 6) faith in God and prayer. Three major outcomes resulted from the storytelling format: 1) peer teaching enhanced learning, 2) incorrect information was identified and clarified, and 3) personal experiences were validated. Conclusions. Integration of African American women's self-identified issues and concerns with breast health messages through storytelling resulted in a meaningful teaching-learning experience. C1 NCI, Div Canc Control & Populat Sci, Surveillance Res Program, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Georgia State Off Womens Hlth, Atlanta, GA USA. RP Williams-Brown, S (reprint author), NCI, Div Canc Control & Populat Sci, Surveillance Res Program, 6116 Execut Blvd,Suite 504, Bethesda, MD 20892 USA. NR 22 TC 24 Z9 24 U1 1 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD WIN PY 2002 VL 17 IS 4 BP 227 EP 230 PG 4 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 633VK UT WOS:000180305000012 PM 12556061 ER PT J AU Wu, YJ Carson, RE AF Wu, YJ Carson, RE TI Noise reduction in the simplified reference tissue model for neuroreceptor functional Imaging SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE simplified reference tissue model; receptors; functional images; positron emission tomography ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; C-11 RACLOPRIDE; HUMAN-BRAIN; CONTINUOUS-INFUSION; RECEPTOR-BINDING; PET; QUANTITATION; WAY-100635; KINETICS AB The Simplified Reference Tissue Model (SRTM) produces functional images of receptor binding parameters using an input function derived from a reference region and assuming a model with one tissue compartment. Three parameters are estimated: binding potential (BP), relative delivery (R-1), and the reference region clearance constant k(2)'. Since k(2)' should not vary across brain pixels, the authors developed a two-step method (SRTM2) using a global value of k(2)'. Whole-brain simulations were performed using human input functions and rate constants for [F-18]FCWAY, [C-11]flumazenil, and [C-11]raclopride, and parameter SD and bias were determined for SRTM and SRTM2. The global mean of k(2)' was slightly biased (2% to 6%), but the median was unbiased (<1%) and was used as the global value. Binding potential noise reductions with SRTM2 were 4% to 14%, 20% to 53%, and 10% to 30% for [F-18]FCWAY, [C-11]flumazenil, and [C-11]raclopride, respectively, with larger reductions for shorter scans. R, noise reduction was larger than that of BP. Simulations were also performed to assess bias when the reference and/or tissue regions followed a two-tissue compartment model. Owing to the constrained k(2)', SRTM2 showed somewhat larger biases due to violations of the one-compartment model assumption. These studies demonstrate that SRTM2 should be a useful method to improve the quality of neuroreceptor functional images. C1 NIH, PET Dept, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Carson, RE (reprint author), NIH, PET Dept, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C-401,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 26 TC 162 Z9 162 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD DEC PY 2002 VL 22 IS 12 BP 1440 EP 1452 DI 10.1097/01.WCB.0000033967.83623.34 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 622DT UT WOS:000179631800004 PM 12468889 ER PT J AU Giovacchini, G Chang, MCJ Channing, MA Toczek, M Mason, A Bokde, ALW Connolly, C Vuong, BK Ma, Y Der, MG Doudet, DJ Herscovitch, T Eckelman, TC Rapoport, SI Carson, RE AF Giovacchini, G Chang, MCJ Channing, MA Toczek, M Mason, A Bokde, ALW Connolly, C Vuong, BK Ma, Y Der, MG Doudet, DJ Herscovitch, T Eckelman, TC Rapoport, SI Carson, RE TI Brain incorporation of [C-11]arachidonic acid in young healthy humans measured with positron emission tomography SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE PET; arachidonic acid; second messenger; phospholipase A(2); phospholipids; modeling ID CEREBRAL BLOOD-VOLUME; PHOSPHOLIPASE A(2) ACTIVITY; ARACHIDONIC-ACID; FATTY-ACIDS; ALZHEIMERS-DISEASE; UNANESTHETIZED RATS; SIGNAL-TRANSDUCTION; AWAKE RATS; STIMULATION; PALMITATE AB Arachidonic acid (AA) is an important second messenger involved in signal transduction mediated by phospholipase A, The goal of this study was to establish an in vivo quantitative method to examine the role of AA in this signaling process in the human brain. A simple irreversible uptake model was derived from rat studies and modified for positron emission tomography (PET) to quantify the incorporation rate K* of [C-11]AA into brain. Dynamic 60-minute three-dimensional scans and arterial input functions were acquired in 8 young healthy adults studied at rest. Brain radioactivity was corrected for uptake of the metabolite [C-11]CO2. K* and cerebral blood volume (V-b) were estimated pixel-by-pixel and were calculated in regions of interest. K* equaled 5.6 +/- 1.2 and 2.6 +/- 0.5 muL . min(-1) . mL(-1) in gray and white matter, respectively. K* and V, values were found to be unchanged with data analysis periods from 20 to 60 minutes. Thus, PET can be used to obtain quantitative images of the incorporation rate K* of [C-11]AA in the human brain. As brain incorporation of labeled AA has been shown in awake rats to be increased by pharmacological activation associated with phospholipase A(2)-signaling, PET and [C-11]AA may be useful to measure signal transduction in the human brain. C1 NINDS, PET Dept, Ctr Clin, NIH, Bethesda, MD 20892 USA. NINDS, Clin Epilepsy Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NIA, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. Univ Pisa, Sch Med, Postgrad Specialty Sch Nucl Med, I-56100 Pisa, Italy. Univ British Columbia, Dept Neurol & Neurodegenerat Disorders, Vancouver, BC V5Z 1M9, Canada. RP Carson, RE (reprint author), NINDS, PET Dept, Ctr Clin, NIH, Bldg 10,Room 1C-401,10 Ctr DR MSC 1180, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 53 TC 52 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD DEC PY 2002 VL 22 IS 12 BP 1453 EP 1462 DI 10.1097/01.WCB.0000033209.60867.7A PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 622DT UT WOS:000179631800006 PM 12468890 ER PT J AU Cruz, NF Dienel, GA AF Cruz, NF Dienel, GA TI High glycogen levels in brains of rats with minimal environmental stimuli: Implications for metabolic contributions of working astrocytes SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain activation; glycogen; astrocytes; energy metabolism ID GLUCOSE-UTILIZATION; SENSORY STIMULATION; CEREBRAL-CORTEX; IN-VIVO; ENERGY-METABOLISM; MOUSE BRAIN; INVITRO; PHOSPHORYLASE; ISCHEMIA; ANAESTHESIA AB The concentration of glycogen, the major brain energy reserve localized mainly in astrocytes, is generally reported as about 2 or 3 mumol/g, but sometimes as high as 3.9 to 8 mumol/g, in normal rat brain. The authors found high but very different glycogen levels in two recent studies in which glycogen was determined by the routine amyloglucosidase procedure in 0.03N HCl digests either of frozen powders (4.8 to 6 mumol/g) or of ethanol-insoluble fractions (8 to 12 mumol/g). To evaluate the basis for these discrepant results, glycogen was assayed in parallel extracts of the same samples. Glycogen levels in ethanol extracts were twice those in 0.03N HCl digests, suggesting incomplete enzyme inactivation even with very careful thawing. The very high glycogen levels were biologically active and responsive to physiologic and pharmacological challenge. Glycogen levels fell after brief sensory stimulation, and metabolic labeling indicated its turnover under resting conditions. About 95% of the glycogen was degraded under in vitro ischemic conditions, and its "carbon equivalents" recovered mainly as glc, glc-P, and lactate. Resting glycogen stores were reduced by about 50% by chronic inhibition of nitric oxide synthase. Because neurotransmitters are known to stimulate glycogenolysis, stress or sensory activation due to animal handling and tissue-sampling procedures may stimulate glycogenolysis during an experiment, and glycogen lability during tissue sampling and extraction can further reduce glycogen levels. The very high glycogen levels in normal rat brain suggest an unrecognized role for astrocytic energy metabolism during brain activation. C1 Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Dienel, GA (reprint author), Univ Arkansas Med Sci, Dept Neurol, Slot 500,4301 W Markham St,Shorey Bldg,Room 7S-15, Little Rock, AR 72205 USA. EM dienelgeralda@uams.edu FU NINDS NIH HHS [NS36728] NR 84 TC 105 Z9 109 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD DEC PY 2002 VL 22 IS 12 BP 1476 EP 1489 DI 10.1097/01.WCB.0000034362.37277.C0 PG 14 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 622DT UT WOS:000179631800008 PM 12468892 ER PT J AU Dienel, GA Wang, RY Cruz, NF AF Dienel, GA Wang, RY Cruz, NF TI Generalized sensory stimulation of conscious rats increases labeling of oxidative pathways of glucose metabolism when the brain glucose-oxygen uptake ratio rises SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE aerobic glycolysis; sensory stimulation; metabolism; brain; [C-14]glucose; astrocytes ID C-13 NMR-SPECTROSCOPY; CEREBRAL BLOOD-FLOW; HUMAN VISUAL-CORTEX; IN-VIVO; PYRUVATE OXIDATION; PRIMARY CULTURES; ASTROCYTES; LACTATE; NEURONS; ACTIVATION AB Interpretation of functional metabolic brain images requires understanding of metabolic shifts in working brain. Because the disproportionately higher uptake of glucose compared with oxygen ("aerobic glycolysis") during sensory stimulation is not fully explained by changes in levels of lactate or glycogen, metabolic labeling by [6-C-14] glucose was used to evaluate utilization of glucose during brief brain activation. Increased labeling of tricarboxylic acid cycle-derived amino acids, mainly glutamate but also gamma-aminobutyric acid, reflects a rise in oxidative metabolism during aerobic glycolysis. The size of the glutamate, lactate, alanine, and aspartate pools changed during stimulation. Brain lactate was derived from blood-borne glucose and its specific activity was twice that of alanine, revealing pyruvate compartmentation. Glycogen labeling doubled during recovery compared with rest and activation; only 4% to 8% of the total C-14 was recovered in lactate plus glycogen. Restoration of glycogen levels was slow, and diversion of glucose from oxidative pathways to restore its level could cause a prolonged reduction of the global O-2/glucose uptake ratio. The rise in the brain glucose-oxygen uptake ratio during activation does not simply reflect an upward shift of glycolysis under aerobic conditions; instead, it involves altered fluxes into various (oxidative and biosynthetic) pathways with different time courses. C1 Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Dienel, GA (reprint author), Univ Arkansas Med Sci, Dept Neurol, Slot 500,4301 W Markham St,Shorey Bldg,Room 7S-15, Little Rock, AR 72205 USA. FU NINDS NIH HHS [NS36728] NR 69 TC 72 Z9 72 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD DEC PY 2002 VL 22 IS 12 BP 1490 EP 1502 DI 10.1097/01.WCB.0000034363.37277.89 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 622DT UT WOS:000179631800009 PM 12468893 ER PT J AU Saavedra, JE Keefer, LK AF Saavedra, JE Keefer, LK TI Nitrogen-based diazeniumdiolates: Versatile nitric oxide-releasing compounds in biomedical research and potential clinical applications SO JOURNAL OF CHEMICAL EDUCATION LA English DT Article ID CONTROLLED BIOLOGICAL RELEASE; RELAXING FACTOR; CEREBRAL VASOSPASM; POLYMERIC FILMS; DONOR; NO; AGENTS; THROMBORESISTANT; NUCLEOPHILES; CONVERSION C1 SAIC, NCI, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Chem Sect, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. RP Saavedra, JE (reprint author), SAIC, NCI, Intramural Res Support Program, Frederick, MD 21702 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 52 TC 17 Z9 17 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-9584 J9 J CHEM EDUC JI J. Chem. Educ. PD DEC PY 2002 VL 79 IS 12 BP 1427 EP 1434 PG 8 WC Chemistry, Multidisciplinary; Education, Scientific Disciplines SC Chemistry; Education & Educational Research GA 615DR UT WOS:000179231000005 ER PT J AU Gogtay, N Sporn, A Alfaro, CL Mulqueen, A Rapoport, JL AF Gogtay, N Sporn, A Alfaro, CL Mulqueen, A Rapoport, JL TI Clozapine-induced akathisia in children with schizophrenia SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID CONVENTIONAL ANTIPSYCHOTICS; RISPERIDONE; OLANZAPINE; PREVALENCE AB Akathisia is a relatively rare side effect with the newer atypical antipsychotic agents, particularly clozapine, and is easily misdiagnosed in children. As children are often unable to describe their symptoms verbally, their akathisia can be misdiagnosed as worsening of their psychosis, prompting an unnecessary increase in their neuroleptic dose. Two cases of childhood-onset schizophrenia associated with clozapine-induced akathisia responsive to beta-blocker treatment are described. Akathisia should be considered in all cases of apparent nonresponse to atypical antipsychotics. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Dept Pharm, Bethesda, MD 20892 USA. RP Rapoport, JL (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 3N202, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 12 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2002 VL 12 IS 4 BP 347 EP 349 DI 10.1089/104454602762599899 PG 3 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 644KD UT WOS:000180915700032 PM 12625995 ER PT J AU Koch, CA Pacak, K Chrousos, GP AF Koch, CA Pacak, K Chrousos, GP TI The molecular pathogenesis of hereditary and sporadic adrenocortical and adrenomedullary tumors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID MULTIPLE ENDOCRINE NEOPLASIA; VON-HIPPEL-LINDAU; MEDULLARY-THYROID CARCINOMA; MCCUNE-ALBRIGHT-SYNDROME; HUMAN ADRENAL-TUMORS; COMPARATIVE GENOMIC HYBRIDIZATION; BECKWITH-WIEDEMANN-SYNDROME; ANGIOTENSIN-II TYPE-1; RIBONUCLEIC-ACID EXPRESSION; FAMILIAL CARDIAC MYXOMAS AB Modern imaging modalities lead to frequent detection of adrenal masses, most of them incidental findings. Although the majority of adrenocortical and adrenomedullary tumors are benign, there are no reliable clinical and laboratory markers to distinguish most of them from malignant neoplasms. The molecular mechanisms underlying the pathogenesis of these tumors have recently begun to be unraveled. A fruitful avenue for the elucidation of tumorigenesis has been the study of adrenal tumors that are manifestations of hereditary or postzygotic genetic syndromes, because one knows the "first hit", i.e. the primary gene defect. In contrast, in sporadic adrenal tumors the first hit, possibly a somatic mutation of a tumor-related gene, is unknown, and therefore the sequence of genetic alterations is difficult to establish. In this article we review in addition to our own work the literature on molecular aspects of adrenocortical and adrenomedullary tumorigenesis. C1 Univ Leipzig, Dept Med 3, D-04103 Leipzig, Germany. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Koch, CA (reprint author), Univ Leipzig, Dept Med 3, Phil Rosenthalstr 27, D-04103 Leipzig, Germany. EM kochc@exchange.nih.gov RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 198 TC 106 Z9 111 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2002 VL 87 IS 12 BP 5367 EP 5384 DI 10.1210/jc.2002-021069 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 628DC UT WOS:000179976300004 PM 12466322 ER PT J AU Hirshberg, B Mog, S Patterson, N Leconte, J Harlan, DM AF Hirshberg, B Mog, S Patterson, N Leconte, J Harlan, DM TI Histopathological study of intrahepatic islets transplanted in the nonhuman primate model using Edmonton protocol immunosuppression SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID RENAL-ALLOGRAFT REJECTION; PANCREATIC-ISLETS; DIABETES-MELLITUS; BLOOD-FLOW; REVASCULARIZATION; VASCULARIZATION; MICROCIRCULATION; LANGERHANS; ISOGRAFTS; CD154 AB While islet cell transplantation is a promising way to restore insulin independence to patients with type I diabetes mellitus, a detailed histological analysis of the transplanted, intraportal islets has not yet been reported. Rhesus macaques underwent total pancreatectomy, then had allogeneic isolated islets infused into their portal vein, followed by daclizumab, tacrolimus, and sirolimus to prevent islet rejection. Islets were evenly distributed among the liver lobes. Liver sections from a primate given allogeneic islets 5 d earlier did not display any islet capillary formation, whereas intrahepatic islets transplanted 30 and 90 d before euthanasia showed an abundant capillary supply. Localized hepatocellular glycogenosis was observed surrounding the islets in a primate with functioning islets 7 months post transplant. Liver sections from a primate that rejected islets transplanted 2 months prior displayed only islet remnants with prominent local lymphohistiocytic inflammation and an occasional capillary. We conclude that islets develop an abundant vascular supply within 30 d following transplant and because capillaries persist even following rejection, that the vascular cells are likely from the recipient. While transplanted islets were not vascularized early post transplant, the primates remained insulin independent. The long-term consequence of islets in the liver, marked by the glycogenosis, remains unknown and warrants further study. C1 NIDDKD, Transplantat & Autoimmun Branch, NIH, Bethesda, MD 20892 USA. USN, Med Res Ctr, Dept Pathol, Silver Spring, MD 20910 USA. RP Harlan, DM (reprint author), NIDDK, Transplantat & Autoimmun Branch, NIH, Bldg 10,Room 11S210, Bethesda, MD 20892 USA. EM DavidMH@intra.niddk.nih.gov NR 25 TC 45 Z9 47 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2002 VL 87 IS 12 BP 5424 EP 5429 DI 10.1210/jc.2002-020684 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 628DC UT WOS:000179976300012 PM 12466330 ER PT J AU DelPparigi, A Tschop, M Heiman, ML Salbe, AD Vozarova, B Sell, SM Bunt, JC Tataranni, PA AF DelPparigi, A Tschop, M Heiman, ML Salbe, AD Vozarova, B Sell, SM Bunt, JC Tataranni, PA TI High circulating ghrelin: A potential cause for hyperphagia and obesity in Prader-Willi syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMANS AB Prader-Willi syndrome (PWS) is a genetic disorder occurring in 1 of 10,000-16,000 live births and is characterized by excessive appetite with progressive massive obesity as well as short stature and mental retardation. Most patients have GH deficiency and hypogonadotropic hypogonadism. The causes of the hyperphagia and abnormal GH secretion are unknown. To determine whether ghrelin, a novel GH secretagogue with orexigenic properties, is elevated in PWS, we measured fasting plasma ghrelin concentration; body composition (dual-energy x-ray absorptiometry); and subjective ratings of hunger (visual analog scale) in seven subjects (6 males and 1 female; age 26 +/- 7 yr; body fat, 39 +/- 11%, mean +/- SD) with PWS (diagnosis confirmed by genetic test) and 30 healthy subjects (reference population, 15 males and 15 females; age, 32 +/- 7 yr; body fat, 36 +/- 11%) fasted overnight. All subjects were weight stable for at least 6 months before admission to the study. The mean plasma ghrelin concentration was higher in PWS than in the reference population (307 +/- 164 vs. 109 +/- 24 fmol/ml; P < 0.001), and this difference remained significant after adjustment for percentage body fat (P < 0.001). Plasma ghrelin was also higher (P = 0.0004) in PWS than in five healthy subjects fasted for 36 h. A positive correlation was found between plasma ghrelin and subjective ratings of hunger (r = 0.71; P = 0.008). Furthermore, in subjects with PWS, the concentration of the hormone was not different before and after ingestion of 2 ml and a satiating amount of the same liquid meal (ghrelin concentrations: 307 +/- 164 vs. 306 +/- 205 vs. 260 +/- 134 fmol/ml, respectively; ANOVA for repeated measures, P = 0.56). This is the first evidence that ghrelin, a novel orexigenic hormone, is elevated in subjects with PWS. Our finding suggests that ghrelin may be responsible, at least in part, for the hyperphagia observed in PWS. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Eli Lilly & Co, Endocrine Res & Stat Dept, Indianapolis, IN 46285 USA. Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. RP DelPparigi, A (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Room 5-41A, Phoenix, AZ 85016 USA. EM adelpari@mail.nih.gov RI Tschoep, Matthias/I-5443-2014; OI Tschoep, Matthias/0000-0002-4744-371X; de Courten, Barbora/0000-0001-8760-2511 FU NIDDK NIH HHS [DK056336] NR 28 TC 209 Z9 215 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2002 VL 87 IS 12 BP 5461 EP 5464 DI 10.1210/jc.2002-020871 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 628DC UT WOS:000179976300018 PM 12466337 ER PT J AU Kindzelskii, AL Huang, JB Chaiworapongsa, T Fahmy, RM Kim, YM Romero, R Petty, HR AF Kindzelskii, AL Huang, JB Chaiworapongsa, T Fahmy, RM Kim, YM Romero, R Petty, HR TI Pregnancy alters glucose-6-phosphate dehydrogenase trafficking, cell metabolism, and oxidant release of maternal neutrophils SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RAT PERITONEAL-MACROPHAGES; PHORBOL-MYRISTATE ACETATE; COLONY-STIMULATING FACTOR; SUPEROXIDE PRODUCTION; GLYCOLYTIC-ENZYMES; BETA-CELLS; ACTIVATION; TRANSPORT; GAMMA; LEUKOCYTES AB Pregnancy is associated with changes in host susceptibility to infections and inflammatory disease. We hypothesize that metabolic enzyme trafficking affects maternal neutrophil activation. Specifically, immunofluorescence microscopy has shown that glucose-6-phosphate dehydrogenase (G-6-PDase), the rate-controlling step of the hexose monophosphate shunt (HMS), is located near the cell periphery in control neutrophils but is found near the microtubule-organizing centers in cells from pregnant women. Cytochemical studies confirmed that the distribution of the G-6-PDase antigen is coincident with functional G-6-PDase activity. Metabolic oscillations within activated pregnancy neutrophils are higher in amplitude, though lower in frequency, than activated control neutrophils, suggesting limited HMS activity. Analysis of radioisotope-labeled carbon flux from glucose to CO2 indicates that the HMS is intact in leukocytes from pregnant women, but its level is not enhanced by cell stimulation. Using extracellular fluorescent markers, activated pregnancy neutrophils were found to release reactive oxygen metabolites (ROMs) at a lower rate than activated control neutrophils. However, basal levels of ROM production in polarized pregnancy neutrophils were greater than in control neutrophils. Microtubule-disrupting agents reversed the observed changes in G-6-PDase trafficking, metabolic oscillations, and ROM production by maternal neutrophils. G-6-PDase trafficking appears to be one mechanism regulating ROM production by maternal neutrophils. C1 Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. Hutzel Hosp, NICHHD, Perinatol Res Branch, Detroit, MI 48201 USA. RP Petty, HR (reprint author), Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. NR 57 TC 38 Z9 40 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2002 VL 110 IS 12 BP 1801 EP 1811 DI 10.1172/JCI200215973 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 626YJ UT WOS:000179901100009 PM 12488430 ER PT J AU Tyrrell, GJ Lovgren, M Forwick, B Hoe, NP Musser, JM Talbot, JA AF Tyrrell, GJ Lovgren, M Forwick, B Hoe, NP Musser, JM Talbot, JA TI M types of group A streptococcal isolates submitted to the national centre for streptococcus (Canada) from 1993 to 1999 SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GROUP-A STREPTOCOCCI; CHANGING EPIDEMIOLOGY; M-PROTEIN; INFECTIONS; EMM; ONTARIO AB The National Centre for Streptococcus (NCS) (Canada) determined the group A streptococcal (GAS) M types of 4,760 Canadian isolates submitted between 1993 and 1999 by classic serotyping. The 10 most frequently identified M types were M1 (26.4%), M12 (9.8%), M28 (8.9%), M3 (6.8%), M4 (6.2%), M11 (4.8%), M89 (3.1%), M6 (3.0%), M2 (2.6%), and M77 (1.9%). Nontypeable isolates accounted for 15.4% of the collection. The province of Ontario submitted 51.1% of the isolates, followed by Quebec (21.2%) and Alberta (13.9%). Together, these three provinces constituted 71.3% of the Canadian population in 1996. The numbers of M types M1, M12, M28, and M3 occurred most frequently in subjects whose ages were <1 to 15 years and 25 to 45 years, as well as in the elderly (60 to 90 years). Further analysis found that the four most frequently identified M types from blood, brain, and cerebrospinal fluid were M1 (28.2%), M28 (9.2%), M12 (9.1%), and M3 (8.2%), with 13.4% of isolates being nontypeable. The four isolates from throats most frequently identified were M1 (19.5%), M12 (15.3%), M3 (8.6%), and M28 (5%) with 19.4% of isolates being nontypeable. The sic gene of a subset of M1 strains (9.5% of the M1 collection) was sequenced. Of 36 sic types identified, the four most common were sic1.01 (22.8%), sic1.02 (14.9%), sic1.135 (10.5%), and sic1.178 (9.6%). Together these four sic types further characterized nearly 60% of the M1 strains sequenced. In summary, from the years 1993 to 1999, the NCS detected 54 M types, of which 10 different M types constituted 73.5% of the collection. M1 was the most common GAS M type circulating in the Canadian population, responsible for more than a quarter of the isolates typed. The most common throat isolates differed in M-type and proportion from those of invasive isolates. Sequencing the sic gene further characterized the most common M-type serotype 1 in a fashion that may be useful for epidemiologic investigations. C1 Univ Alberta, Prov Lab Publ Hlth Alberta, Natl Ctr Streptococcus, Edmonton, AB T6G 2G2, Canada. Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB T6G 2G2, Canada. Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB T6G 2G2, Canada. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Tyrrell, GJ (reprint author), Walter Mackenzie Ctr, 2B3-13,8220-112 St, Edmonton, AB T6G 2J2, Canada. NR 24 TC 45 Z9 45 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2002 VL 40 IS 12 BP 4466 EP 4471 DI 10.1128/JCM.40.12.4466-4471.2002 PG 6 WC Microbiology SC Microbiology GA 622DP UT WOS:000179631500011 PM 12454137 ER PT J AU Engle, RE Yu, C Emerson, SU Meng, XJ Purcell, RH AF Engle, RE Yu, C Emerson, SU Meng, XJ Purcell, RH TI Hepatitis E virus (HEV) capsid antigens derived from viruses of human and swine origin are equally efficient for detecting anti-HEV by enzyme immunoassay SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID NON-B HEPATITIS; OPEN-READING FRAME-2; TRANSMITTED NON-A; UNITED-STATES; PHYLOGENETIC ANALYSIS; CYNOMOLGUS MACAQUES; INSECT CELLS; IDENTIFICATION; INFECTION; PROTEIN AB The recombinant truncated ORF2 (capsid) antigen derived from the Meng strain of swine hepatitis E virus (HEV) differs from that of the Sar-55 strain of human HEV by approximately 5% at the amino acid level. Serial serum samples from two chimpanzees and six rhesus monkeys experimentally infected with HEV were tested with one enzyme immunoassay (EIA) based on the Sar-55 antigen and with a second EIA based on the Meng antigen. We obtained 98% agreement (kappa = 0.952) by direct comparison. The virtually identical results obtained with these antigens in detecting seroconversion following infection with HEV suggests that they were reacting with antibodies that detect the same or very similar epitopes of HEV. We then tested human and swine serum samples for anti-HEV in EIAs that utilized one or the other of the two ORF2 antigens and showed that these results were also virtually identical. The specimens tested included swine sera from the United States, Canada, China, Korea, and Thailand and sera from veterinarians, U.S. and non-U.S. volunteer blood donors, and U.S. and non-U.S. animal handlers. We tested 792 swine sera and obtained 93% agreement (kappa = 0.839). We similarly tested 882 human sera and obtained 99% agreement (kappa = 0.938). Moreover, we found virtually no difference in the levels of prevalence of anti-HEV as measured by the two tests, again suggesting that the antigens derived from human and swine HEV contain the same immunodominant epitopes. C1 NIAID, Hepatitis Viruses Sect, LID, NIH, Rockville, MD 20852 USA. NIAID, Mol Hepatitis Sect, LID, NIH, Rockville, MD 20852 USA. Virginia Polytech Inst & State Univ, Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. RP Engle, RE (reprint author), NIAID, Hepatitis Viruses Sect, LID, NIH, Twinbrook I,Room 1505,5640 Fishers Lane, Rockville, MD 20852 USA. RI Meng, X.J./B-8769-2009 OI Meng, X.J./0000-0002-2739-1334 NR 43 TC 74 Z9 80 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2002 VL 40 IS 12 BP 4576 EP 4580 DI 10.1128/JCM.40.12.4576-4580.2002 PG 5 WC Microbiology SC Microbiology GA 622DP UT WOS:000179631500029 PM 12454155 ER PT J AU Hewitt, M Rowland, JH AF Hewitt, M Rowland, JH TI Mental health service use among adult cancer survivors: Analyses of the National Health Interview Survey SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER; RECOGNITION; DEPRESSION; PREVALENCE; BARRIERS; DISTRESS; SUPPORT AB Purpose: Analyses were conducted to obtain national estimates of mental health service use, unmet need for such services, and the prevalence of mental health problems among individuals reporting a cancer history. Methods: Of a nationally representative sample of 95,615 adults in the United States interviewed as part of the 1998, 1999, and 2000 National Health Interview Survey, 4,878 reported a history of cancer (excluding superficial skin cancer). Analyses assessed whether cancer survivors relative to those without a self-reported history of cancer had increased use of mental health services and had increased reports of unmet need for such services. Analyses were also conducted to ascertain demographic and health characteristics associated with service use and unmet need. Results: Compared with individuals without a cancer history, cancer survivors reported significantly greater contact in the past year with a mental health provider (7.2% v 5.7%). Cancer survivors were more likely to have used mental health services (odds ratio, 1.60 among those without other chronic illnesses and 3.04 among those with other chronic illnesses), and mental health service use was significantly greater among those who were under age 65 and diagnosed at younger ages, were formerly married, or had other comorbid chronic conditions. If all cancer survivors with mental health problems or who needed but could not access mental health services due to cost had received such care, mental health service use would have increased from 7.2% to 11.7%, a 62% increase in use. Conclusion: Cancer seems to be one of several chronic illnesses that precipitates the need for and use of mental health services. Improvements are needed in recognizing mental health problems among cancer survivors and reducing barriers to psychosocial service use. (C) 2002 by American Society of Clinical Oncology. C1 Natl Canc Policy Board, Inst Med, Washington, DC 20001 USA. NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA. RP Hewitt, M (reprint author), Natl Canc Policy Board, Inst Med, 500 5th St,NAS 308, Washington, DC 20001 USA. NR 38 TC 100 Z9 101 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2002 VL 20 IS 23 BP 4581 EP 4590 DI 10.1200/JCO.2002.03.077 PG 10 WC Oncology SC Oncology GA 622DX UT WOS:000179632200012 PM 12454116 ER PT J AU Muehrer, PR Salovey, P Afifi, AA Coyne, JC Kring, AM Merson, MH Prohaska, TR Rozensky, RH AF Muehrer, PR Salovey, P Afifi, AA Coyne, JC Kring, AM Merson, MH Prohaska, TR Rozensky, RH TI Overcoming barriers to collaboration between basic behavioral scientists and public health scientists in research on mental disorders SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE mental disorders; behavioral science; public health; prevention ID SCHIZOPHRENIC-PATIENTS SHOW; PRIMARY-CARE; DEPRESSIVE SYMPTOMS; RANDOMIZED TRIAL; UNITED-STATES; MYOCARDIAL-INFARCTION; PSYCHIATRIC-DISORDERS; MEDICAL-CARE; OLDER ADULTS; RISK FACTOR AB The behavioral and public health sciences both have a long and rich history supporting basic, translational, and applied research aimed at improving human lives and reducing human suffering. Through the complementary expertise of these disciplines, investigators have contributed to significant, worldwide improvements in mental and physical health. Further gains can be achieved through collaborative research among scientists in these 2 fields. Unfortunately, there are a number of barriers to such collaboration originating in different intellectual traditions, research methods, and the structure and values of academia. We identify these barriers and potential strategies for overcoming them. Several areas for future collaborative research appear promising, especially comorbid mental and physical disorders, adherence to interventions, stigma, and emotional processes. Theory-guided preventive interventions may represent especially fertile areas of collaborative effort. C1 NIMH, Hlth & Behav Sci Res Branch, Div Mental Disorders Behav Res & AIDS, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Psychol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Family Practice & Community Med, Philadelphia, PA 19104 USA. Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. Univ Illinois, Sch Publ Hlth, Chicago, IL USA. Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL 32611 USA. RP Muehrer, PR (reprint author), NIMH, Hlth & Behav Sci Res Branch, Div Mental Disorders Behav Res & AIDS, Room 6189,MSC 9615,6001 Execut Blvd, Bethesda, MD 20892 USA. NR 85 TC 5 Z9 5 U1 2 U2 6 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9583 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD DEC PY 2002 VL 9 IS 4 BP 253 EP 265 DI 10.1023/A:1020758416171 PG 13 WC Psychology, Clinical SC Psychology GA 606YW UT WOS:000178764500001 ER PT J AU Fuemmeler, BF Taylor, LAC Metz, AE Brown, RT AF Fuemmeler, BF Taylor, LAC Metz, AE Brown, RT TI Risk-taking and smoking tendency among primarily African American school children: Moderating influences of peer susceptibility SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE children; adolescent; smoking; risk-taking; peer influence ID PSYCHOSOCIAL PREDICTORS; ADOLESCENT; STUDENTS AB We examined the hypothesis that peer susceptibility would moderate the association between risk-taking and tendency to smoke in adolescents who were primarily African American. Participants were 88 preadolescents recruited from a 6th grade classroom in a public elementary school. We found an interaction of risk-taking and susceptibility to peer influence on smoking tendency. Specifically, a moderator effect was found for peer influence on the association between risk-taking and smoking tendency. The importance of examining peer susceptibility on health promotion and other health behaviors in children and adolescents was supported. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Hlth Profess, Charleston, SC USA. Med Univ S Carolina, Dept Clin Serv, Charleston, SC USA. RP Fuemmeler, BF (reprint author), NCI, Canc Prevent Fellowship Program, 6130 Execut Blvd EPN Suite 3109, Bethesda, MD 20892 USA. NR 31 TC 7 Z9 10 U1 1 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9583 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD DEC PY 2002 VL 9 IS 4 BP 323 EP 330 DI 10.1023/A:1020743102967 PG 8 WC Psychology, Clinical SC Psychology GA 606YW UT WOS:000178764500008 ER PT J AU Weinberger, DR AF Weinberger, DR TI Richard Jed Wyatt, MD (1939-2002) - In memoriam SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Biographical-Item C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, 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 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 2002 VL 22 IS 6 BP 543 EP 544 DI 10.1097/00004714-200212000-00002 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 622GW UT WOS:000179639500002 ER PT J AU Pratt, CB Ha, L Pratt, CA AF Pratt, CB Ha, L Pratt, CA TI Setting the public health agenda on major diseases in sub-Saharan Africa: African popular magazines and medical journals, 1981-1997 SO JOURNAL OF COMMUNICATION LA English DT Article ID AIDS AB This study investigates changes in the amount of media coverage and in the framing of 5 major infectious diseases in Africa in 4 sub-Sabaran African magazines and medical journals. During a 17-yearperiod (1981-1997), HIV/AIDS, a stigmal disease, dominated the coverage from the early to the mid-1990s; however, there was a paucity of such news items in the early 1980s. Nonstigmal diseases, such as malaria and tuberculosis, received much less coverage in proportion to their occurrences. In popular magazines, AIDS was framed as a homosexual, deadly, and lethal disease-but not as such in medical journals. This article presents implications and strategic lessons of those findings for the agenda-setting role of sub-Sabaran African media organizations and public health agencies. It also recommends norms for African media's reporting of health issues. C1 US Forest Serv, Off Commun, USDA, Washington, DC 20250 USA. Bowling Green State Univ, Dept Telecommun, Bowling Green, OH 43403 USA. Gallup Org Inc, Princeton, NJ 08542 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Michigan Publ Hlth Inst, Resource Ctr Cardiovasc Hlth, Okemos, MI USA. RP Pratt, CB (reprint author), US Forest Serv, Off Commun, USDA, Washington, DC 20250 USA. NR 23 TC 13 Z9 13 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0021-9916 J9 J COMMUN JI J. Commun. PD DEC PY 2002 VL 52 IS 4 BP 889 EP 904 DI 10.1093/joc/52.4.889 PG 16 WC Communication SC Communication GA 633WQ UT WOS:000180308000012 ER PT J AU Glantz, MD AF Glantz, MD TI Introduction to the special issue on the impact of childhood psychopathology interventions on subsequent substance abuse: Pieces of the puzzle SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Editorial Material ID MENTAL-DISORDERS; DRUG-ABUSE; PREVALENCE; COMORBIDITY; RISK AB Studies of adolescents and adults have reported high levels of co-occurrence of substance abuse with other psychiatric disorders, suggesting influence between the conditions. The comorbidity seems complex and variable, indicating that there may be more than I type of association between the comorbid disorders. When occurring in childhood, some of the frequently comorbid psychopathologies typically precede later drug and alcohol abuse and may have implications for substance abuse prevention as early risk indicators and as targets for intervention. Research discussed in this article and in this special issue provides a foundation for investigating the question of whether effective treatment of childhood psychopathologies can prevent or at least mitigate substance abuse for some adolescents. Clinical, research, and policy implications are discussed. C1 Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Glantz, MD (reprint author), Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, NIH, 6001 Execut Blvd,Suite 5153 MSC 9589, Bethesda, MD 20892 USA. NR 23 TC 19 Z9 19 U1 2 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2002 VL 70 IS 6 BP 1203 EP 1206 DI 10.1037//0022-006X.70.6.1203 PG 4 WC Psychology, Clinical SC Psychology GA 619WL UT WOS:000179500400001 PM 12472297 ER PT J AU Compton, SN Burns, BJ Egger, HL Robertson, E AF Compton, SN Burns, BJ Egger, HL Robertson, E TI Review of the evidence base for treatment of childhood psychopathology: Internalizing disorders SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Review ID RANDOMIZED CLINICAL-TRIAL; COGNITIVE-BEHAVIORAL TREATMENT; OBSESSIVE-COMPULSIVE DISORDER; 2-YEAR FOLLOW-UP; EMPIRICALLY SUPPORTED TREATMENTS; POSTTRAUMATIC STRESS SYMPTOMS; ADOLESCENT SUBSTANCE-ABUSERS; TREATING ANXIETY DISORDERS; DOUBLE-BLIND; PSYCHIATRIC COMORBIDITY AB This article reviews the empirical literature on psychosocial, psychopharmacological, and adjunctive treatments for children between the ages of 6 and 12 with internalizing disorders. The aim of this review was to identify interventions that have potential to prevent substance use disorders in adolescence by treating internalizing disorders in childhood. Results suggest that a variety of behavioral, cognitive-behavioral, and pharmacological interventions are effective in reducing symptoms of childhood depression, phobias, and anxiety disorders. None of the studies reviewed included substance abuse outcomes. Thus, little can be said about the relationship between early treatment and the prevention of later substance use. The importance of evaluating the generalizability of research-supported interventions to community settings is highlighted and recommendations for future research are offered. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Serv Effectiveness Res Program, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Dev Epidemiol Ctr, Durham, NC 27705 USA. Natl Inst Drug Abuse, Prevent Res Branch, Div Epidemiol Serv & Prevent Res, Bethesda, MD USA. RP Compton, SN (reprint author), Duke Univ, Med Ctr, Duke Child & Family Study Ctr, 718 Rutherford St, Durham, NC 27705 USA. FU PHS HHS [263-MJ-91952] NR 95 TC 75 Z9 75 U1 5 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2002 VL 70 IS 6 BP 1240 EP 1266 DI 10.1037//0022-0006X.70.6.1240 PG 27 WC Psychology, Clinical SC Psychology GA 619WL UT WOS:000179500400005 PM 12472300 ER PT J AU Farmer, EMZ Compton, SN Burns, BJ Robertson, E AF Farmer, EMZ Compton, SN Burns, BJ Robertson, E TI Review of the evidence base for treatment of childhood psychopathology: Externalizing disorders SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Review ID DEFICIT HYPERACTIVITY DISORDER; COGNITIVE BEHAVIORAL-THERAPY; CONDUCT-PROBLEM CHILDREN; SELF-CONTROL THERAPY; DOUBLE-BLIND; CLINICAL-SIGNIFICANCE; DISRUPTIVE BEHAVIOR; ANTISOCIAL-BEHAVIOR; CONTROLLED TRIAL; TIC DISORDER AB This article reviews controlled research on treatments for childhood externalizing behavior disorders. The review is organized around 2 subsets of such disorders: disruptive behavior disorders (i.e., conduct disorder, oppositional defiant disorder) and attention-deficit/hyperactivity disorder (ADHD). The review was based on a literature review of nonresidential treatments for youths ages 6-12. The pool of studies for this age group was limited, but results suggest positive outcomes for a variety of interventions (particularly parent training and community-based interventions for disruptive behavior disorders and medication for ADHD). The review also highlights the need for additional research examining effectiveness of treatments for this age range and strategies to enhance the implementation of effective practices. C1 Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Serv Effectiveness Res Program, Durham, NC 27710 USA. Natl Inst Drug Abuse, Prevent Res Branch, Div Epidemiol Serv & Prevent Res, Bethesda, MD USA. RP Farmer, EMZ (reprint author), Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Serv Effectiveness Res Program, Box 3454, Durham, NC 27710 USA. FU PHS HHS [263-MJ-919512] NR 109 TC 93 Z9 94 U1 7 U2 24 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2002 VL 70 IS 6 BP 1267 EP 1302 DI 10.1037//0022-006X.70.6.1267 PG 36 WC Psychology, Clinical SC Psychology GA 619WL UT WOS:000179500400006 PM 12472301 ER PT J AU Aframian, DJ Amit, D Baum, D Shai, BJ Panet, E Deutsch, A Palmon, D AF Aframian, DJ Amit, D Baum, D Shai, BJ Panet, E Deutsch, A Palmon, D TI Modifying vectorial secretion of reporter gene from salivary epithelial cells. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the International-Association-for-Dental-Research CY JUN 07-08, 2001 CL JERUSALEM, ISRAEL SP Int Assoc Dent Res C1 Hebrew Univ Jerusalem, Jerusalem, Israel. NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2002 VL 81 SI B BP B305 EP B305 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 632HM UT WOS:000180217902228 ER PT J AU Eliav, E Teich, S Benoliel, R Nahlieli, O Baruchin, A Gracely, RH AF Eliav, E Teich, S Benoliel, R Nahlieli, O Baruchin, A Gracely, RH TI Large myelinated nerve fiber hypersensitivity as an early sign in oral malignancy. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the International-Association-for-Dental-Research CY JUN 07-08, 2001 CL JERUSALEM, ISRAEL SP Int Assoc Dent Res C1 Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Dept Oral Diag Med & Radiol, IL-91010 Jerusalem, Israel. Barzilai Govt Hosp, Dept Maxillofacial Surg, Ashqelon, Israel. NICDR, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2002 VL 81 SI B BP B308 EP B308 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 632HM UT WOS:000180217902254 ER PT J AU Fermon, E Young, M Fisher, LW Kulkarni, AB Dafni, L Haze, A Leiser, Y Mao, Z Rosenfeld, E Shay, B Taylor, A Deutsch, D AF Fermon, E Young, M Fisher, LW Kulkarni, AB Dafni, L Haze, A Leiser, Y Mao, Z Rosenfeld, E Shay, B Taylor, A Deutsch, D TI Isolation and characterization of the mouse tuftelin gene and preparation of tuftelin targeting constructs for future generation of a tuftelin "knock-out" mouse. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the International-Association-for-Dental-Research CY JUN 07-08, 2001 CL JERUSALEM, ISRAEL SP Int Assoc Dent Res C1 Hebrew Univ Jerusalem, Dent Res Unit, Jerusalem, Israel. Hebrew Univ Jerusalem, Hadassah Fac Dent Med, Jerusalem, Israel. NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2002 VL 81 SI B BP B307 EP B307 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 632HM UT WOS:000180217902246 ER PT J AU Mao, Z Shay, B Hekmati, M Fermon, E Taylor, A Dafni, L Heikinheimo, K Rosenfeld, E Leiser, Y Fisher, LW Young, MF Deutsch, D AF Mao, Z Shay, B Hekmati, M Fermon, E Taylor, A Dafni, L Heikinheimo, K Rosenfeld, E Leiser, Y Fisher, LW Young, MF Deutsch, D TI Alternative splicing of the human and mouse tuftelin gene. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the International-Association-for-Dental-Research CY JUN 07-08, 2001 CL JERUSALEM, ISRAEL SP Int Assoc Dent Res C1 Hebrew Univ Jerusalem, Hadassah Fac Dent Med, IL-91010 Jerusalem, Israel. NIH, Bethesda, MD 20892 USA. Univ Turku, SF-20500 Turku, Finland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2002 VL 81 SI B BP B311 EP B311 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 632HM UT WOS:000180217902274 ER PT J AU Rapoport, O Ameve, I Septier, D Palmier, K Young, M Goldberg, M AF Rapoport, O Ameve, I Septier, D Palmier, K Young, M Goldberg, M TI Biglycan: a negative regulator of channel formation. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Meeting of the International-Association-for-Dental-Research CY SEP 05-08, 2001 CL ROME, ITALY SP Int Assoc Dent Res C1 Univ Paris 05, Fac Chir Dent, EA 2496, F-75270 Paris 06, France. CSDB, NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2002 VL 81 SI B BP B277 EP B277 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 632HM UT WOS:000180217902023 ER PT J AU Shay, B Young, M Fisher, LW Taylor, A Fermon, E Haze, A Mao, Z Rosenfeld, E Leiser, Y Daniell, T Dafni, L Deutsch, D AF Shay, B Young, M Fisher, LW Taylor, A Fermon, E Haze, A Mao, Z Rosenfeld, E Leiser, Y Daniell, T Dafni, L Deutsch, D TI Production of human and bovine recombinant tuftelin proteins. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the International-Association-for-Dental-Research CY JUN 07-08, 2001 CL JERUSALEM, ISRAEL SP Int Assoc Dent Res C1 Hebrew Univ Jerusalem, Hadassah Fac Dent Med, Jerusalem, Israel. Hebrew Univ Jerusalem, Inst Life Sci, IL-91904 Jerusalem, Israel. NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2002 VL 81 SI B BP B308 EP B308 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 632HM UT WOS:000180217902248 ER PT J AU Taylor, AL Shay, B Mao, ZK Daphni, L Rosenfeld, E Leiser, Y Fermon, E Haze, A Danieli, T Young, M Bernimoulin, JP Haegewald, S Zimmermann, B Deutsch, D AF Taylor, AL Shay, B Mao, ZK Daphni, L Rosenfeld, E Leiser, Y Fermon, E Haze, A Danieli, T Young, M Bernimoulin, JP Haegewald, S Zimmermann, B Deutsch, D TI Production and structural-functional characterization of recombinant human amelogenin proteins SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the International-Association-for-Dental-Research CY JUN 07-08, 2001 CL JERUSALEM, ISRAEL SP Int Assoc Dent Res C1 Hebrew Univ Jerusalem, Hadassah Fac Dent Med, IL-91010 Jerusalem, Israel. Hebrew Univ Jerusalem, Inst Life Sci, IL-91904 Jerusalem, Israel. NIDCR, NIH, Bethesda, MD USA. Humboldt Univ, D-1086 Berlin, Germany. Free Univ Berlin, D-1000 Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2002 VL 81 SI B BP B311 EP B311 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 632HM UT WOS:000180217902276 ER PT J AU Atella, GC Shahabuddin, M AF Atella, GC Shahabuddin, M TI Differential partitioning of maternal fatty acid and phospholipid in neonate mosquito larvae SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE malaria vector; mosquito; lipid metabolism; lipophorin; fatty acid; phospholipid; neonate ID RHODNIUS-PROLIXUS; PLASMODIUM-GALLINACEUM; AEDES-AEGYPTI; IN-VIVO; LIPOPHORIN; METABOLISM; MIDGUT; LIPOPROTEIN; HEMOLYMPH; INSECTS AB In animals, lipids are a source of energy, cell membrane components, signaling pathway modulators and emulsifying agents. In egg-laying animals, maternal yolk lipids, imported into the egg before laying, are metabolized or distributed in the developing embryo to serve these functions. Studies with birds, reptiles and insects have described lipid metabolism in adults and in eggs, but no studies have addressed how lipids are distributed in developing organs in the embryo. Here we show that maternal fatty acid and phospholipids segregate differently in tissues of newly hatched mosquito larvae. In the mother, both lipids are colocalized in yolk granules of developing oocytes and distributed evenly. In neonate larvae, however, the maternal fatty acid is stored along the side of the body, especially at the base of the body hair, and in the thorax, where the muscles are located, probably to provide energy for the rapid movements needed to find food immediately after birth. Most maternal phospholipids, however, are concentrated in the motile intestinal gastric caeca, from which they are released into the gut lumen where they may act as emulsifiers, probably to facilitate assimilation of the food the neonate ingests. Similar phenomena were observed in both Anopheles gambiae and Aedes aegypti mosquitoes, suggesting that such differential segregation of lipids is common to both insects. This study may lead to improved delivery of larvicidal agents and to efficient killing of newly hatched mosquito larvae as a control strategy for mosquito-borne diseases. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Shahabuddin, M (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 37 TC 13 Z9 13 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD DEC PY 2002 VL 205 IS 23 BP 3623 EP 3630 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 625VA UT WOS:000179835200005 PM 12409488 ER PT J AU Lindsey, EW MacKinnon-Lewis, C Campbell, J Frabutt, JM Lamb, ME AF Lindsey, EW MacKinnon-Lewis, C Campbell, J Frabutt, JM Lamb, ME TI Marital conflict and boys' peer relationships: The mediating role of mother-son emotional reciprocity SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article ID COGNITIVE-CONTEXTUAL FRAMEWORK; CHILD ADJUSTMENT; INTERPARENTAL CONFLICT; SOCIOMETRIC STATUS; SOCIAL COMPETENCE; ATTACHMENT RELATIONSHIPS; FAMILY; PRESCHOOLERS; PREDICTORS; AGGRESSION AB This study examined the role of mother-son emotional reciprocity in connections between marital conflict and the quality of boys' peer relationships. Parents from 84 intact families with preadolescent boys reported on the level of conflict in their marital relationship. Observations of mother-son interaction were coded for emotional reciprocity, and assessments of boys' peer relationships were obtained from both teachers and classmates. No direct connection between marital conflict and boys' peer relationships was observed. Rather, marital conflict affected boys' social competence indirectly, through its effect on the emotions expressed between mother and son. The findings support the proposal that emotional processes play an important role in connections between marital conflict and children's peer relationships and suggest that family emotional expressiveness deserves greater attention in both research and intervention. C1 Texas Tech Univ, Dept Human Dev & Family Studies, Lubbock, TX 79409 USA. Univ S Florida, Ctr Scholarship Act, Tampa, FL 33620 USA. NIDA, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Ctr Study Social Issues, Greensboro, NC 27412 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Lindsey, EW (reprint author), Texas Tech Univ, Dept Human Dev & Family Studies, POB 41162, Lubbock, TX 79409 USA. FU NIMH NIH HHS [MH49869] NR 75 TC 18 Z9 18 U1 1 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD DEC PY 2002 VL 16 IS 4 BP 466 EP 477 DI 10.1037//0893-3200.16.4.466 PG 12 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 630NE UT WOS:000180113800011 PM 12561292 ER PT J AU Howard, PC Sams, RL Bucher, JR Allaben, WT AF Howard, PC Sams, RL Bucher, JR Allaben, WT TI Phototoxicology and photocarcinogenesis at the US Food and Drug Administration's National Center for Toxicological Research SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Article DE phototoxicology; photocarcinogenesis; simulated solar light; SKH-1 hairless mice ID GLYCOLIC ACID; HAIRLESS MICE; PHOTOAGED SKIN; RADIATION; CANCER AB Ultraviolet radiation (UVR) causes skin cancer in humans and can induce skin cancer in test animals. The interaction of UVR with many drugs has been reported, however, there is a paucity of data concerning the carcinogenesis of cosmetic ingredients and environmental contaminants in combination with UVR. A research center has been developed at the U.S. Food and Drug Administration's National Center for Toxicological Research to quantify the potential carcinogenicity of combined exposure to chemicals and UVR. The chemicals tested in this facility are nominated to, and approved by, the National Toxicology Program. In this paper we describe the nomination of chemicals, test animals, source of UVR, dosimetry, and test paradigm that are used. This unique test facility is being used to protect public health through quantifying the photocarcinogenicity of chemicals to which the public is exposed. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Natl Toxicol Program Ctr Phototoxicol, Jefferson, AR 72079 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. NR 31 TC 8 Z9 8 U1 1 U2 1 PU NATL LABORATORIES FOODS DRUGS PI NANKANG, TAIPEI PA DEPT HEALTH, EXECUTIVE YUAN, 161-2 KUEN YANG ST DR. ERICK T. SUEN, DEPUTY DIR., NANKANG, TAIPEI, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2002 VL 10 IS 4 BP 252 EP 257 PG 6 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 643XP UT WOS:000180888900007 ER PT J AU Fu, PP Howard, PC Culp, SJ Xia, QS Webb, PJ Blankenship, LR Wamer, WG Bucher, JR AF Fu, PP Howard, PC Culp, SJ Xia, QS Webb, PJ Blankenship, LR Wamer, WG Bucher, JR TI Do topically applied skin creams containing retinyl palmitate affect the photocarcinogenecity of simulated solar light? SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Article DE retinyl palmitate; photocarcinogenicity; SKH-1 mice ID ALL-TRANS-RETINOL; MOUSE SKIN; VITAMIN-A; ACID; METABOLISM; INHIBITION AB Retinyl palmitate (all-trans-retinyl palmitate; RP) was nominated in 2001 by the U.S. Food and Drug Administration's Center for Food Safety and Applied Nutrition (CFSAN) to the National Toxicology Program (NTP) as a high priority compound for phototoxicity and photocarcinogenicity studies at the National Center for Toxicological Research (NCTR). Studies with SKH-1 hairless mice are required to test whether topical application of RP enhances the phototoxicity and photocarcinogenicity of simulated solar light and UV light. Mechanistic studies are needed to provide insight into the disposition of RP in vitro and on the skin of mice, and to test thoroughly whether genotoxic damage by UV-induced radicals may participate in any toxicity of topically applied RP in the presence of UV light. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. NR 43 TC 8 Z9 8 U1 0 U2 0 PU NATL LABORATORIES FOODS DRUGS PI NANKANG, TAIPEI PA DEPT HEALTH, EXECUTIVE YUAN, 161-2 KUEN YANG ST DR. ERICK T. SUEN, DEPUTY DIR., NANKANG, TAIPEI, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2002 VL 10 IS 4 BP 262 EP 268 PG 7 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 643XP UT WOS:000180888900009 ER PT J AU Marcy, TW Stefanek, M Thompson, KM AF Marcy, TW Stefanek, M Thompson, KM TI Genetic testing for lung cancer risk - If physicians can do it, should they? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE lung neoplasms; genetic screening; genetic counseling; smoking ID ENVIRONMENTAL TOBACCO-SMOKE; CESSATION TREATMENT; PARENTAL SMOKING; PASSIVE SMOKING; FOLLOW-UP; DISEASE; HEALTH; RECOMMENDATIONS; SUSCEPTIBILITY; PREDISPOSITION AB Advances in genetics have increased our ability to assess an individual's genetic risk for disease. There is a hypothesis that genetic test results will motivate high-risk individuals to reduce harmful exposures, to increase their surveillance for disease, or to seek preventive treatments. However, genetic testing for genes associated with an increased risk of lung cancer would not change physicians' recommendations regarding smoking cessation. Limited studies suggest that test results that demonstrate an increased risk of lung cancer do not improve smoking cessation success. These test results may even distort an individual's risk perceptions. Before recommending genetic testing to assess risk for disease, physicians need to consider whether knowledge about genetic susceptibility will alter patient management. C1 Univ Vermont, Coll Med, Off Hlth Promot Res, Burlington, VT 05401 USA. NCI, Div Canc Prevent, Off Prevent Oncol, Rockville, MD USA. NCI, Div Canc Control & Populat Sci, Basic Biobehav Res Branch, Rockville, MD USA. Univ Vermont, Vermont Canc Ctr, Burlington, VT USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Marcy, TW (reprint author), Univ Vermont, Coll Med, Off Hlth Promot Res, 1 S Prospect St, Burlington, VT 05401 USA. NR 36 TC 6 Z9 7 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2002 VL 17 IS 12 BP 946 EP 951 DI 10.1046/j.1525-1497.2002.20378.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 624ZH UT WOS:000179791800008 PM 12472931 ER PT J AU Gwinn-Hardy, K Singleton, AA AF Gwinn-Hardy, K Singleton, AA TI Familial Lewy body diseases SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article ID ALPHA-SYNUCLEIN GENE; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASE; CHROMOSOME 4P; BODIES DLB; DEMENTIA; MUTATIONS; SUSCEPTIBILITY; POLYMORPHISM AB Lewy body disease includes clinically and pathologically defined disorders in which Lewy bodies occur in the nervous system. In recent years, the molecular features of these disorders have been emerging. Several genetic loci have been identified in association with familial Lewy body disease; however, the genetic risks underlying most cases of familial Lewy body disease remain to be discovered. The fact that Lewy bodies stain strongly with antibodies to alpha-synuclein and that mutations in the a-synuclein gene lead to syndromes in which parkinsonism and dementia occur gives us important clues regarding the biologic processes leading to disease. Pursuit of additional mendelian causes of familial Lewy body disease and study of the factors contributing to the complex phenotypes associated with Lewy body disorders will elucidate underlying disease pathways and; thus, possible targets for therapeutic intervention. C1 NINDS, Div Intramural Res, Neurogenet Labs, NIH, Bethesda, MD 20892 USA. RP Gwinn-Hardy, K (reprint author), NINDS, Div Intramural Res, Neurogenet Labs, NIH, Bldg 10-3D, Bethesda, MD 20892 USA. RI Gwinn, Katrina/C-2508-2009; Singleton, Andrew/C-3010-2009 NR 74 TC 6 Z9 7 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD WIN PY 2002 VL 15 IS 4 BP 217 EP 223 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 621JC UT WOS:000179584400007 PM 12489918 ER PT J AU Chen, J Astle, CM Harrison, DE AF Chen, J Astle, CM Harrison, DE TI Hematopoietic stem cell functional failure in interleukin-2-deficient mice SO JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH LA English DT Article ID NAIVE T-CELLS; IL-2-DEFICIENT MICE; LYMPHOCYTE DEVELOPMENT; GAMMA PRODUCTION; NK CELLS; INFLAMMATION; INDUCTION; IL-2; CD19; PROLIFERATION AB The effects of interleukin-2 (IL-2) deficiency on hematopoiesis were tested by measuring cellular compositions in peripheral blood, spleen, thymus, and bone marrow of 3- to 5-month-old gene-targeted Il2 null (Il2(-/-)) mice using the Advia 120 Hematology system and fluorescence-activated cell staining (FACS). Il2(-/-) mice developed hematological failure and autoimmune responses, showing variable but significant degrees of anemia, lymphocytopenia, thrombocytopenia, splenomegaly, thymus involution, and weight loss. Surprisingly, Il2(-/-) mice had normal numbers of bone marrow cells (BMCs) with increased numbers of Lin(-)Kit(+)Sca1(+)CD34(-). and Lin(-)Kit(+)Sca1(+)CD34(+) cells that are normally associated with hematopoietic stem cells (HSCs) and progenitor cells. Day-12 colony-forming units-spleen cells were slightly reduced in Il2(-/-) mice. When Il2(-/-) and Il2(+/+) mice were compared for long-term HSC function in vivo in the competitive repopulation assay, BMCs from Il2(-/-) donors had 10- to 20-fold less HSC repopulating ability, which affected both myeloid and lymphoid cell lineages. Thus, HSCs from Il2(-/-) mice can proliferate normally but are functionally defective for reconstituting lethally irradiated recipients. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Chen, J (reprint author), NHLBI, Hematol Branch, Bldg 10,Room 7C118,10 Ctr Dr,MSC 1652, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA 34196]; NHLBI NIH HHS [R01 HL 63230, R01 HL 58820] NR 28 TC 10 Z9 10 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1525-8165 J9 J HEMATOTH STEM CELL JI J. Hematother. Stem Cell Res. PD DEC PY 2002 VL 11 IS 6 BP 905 EP 912 DI 10.1089/152581602321080565 PG 8 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA 639KF UT WOS:000180626900006 PM 12590705 ER PT J AU Borrego, F Kabat, J Sanni, TB Coligan, JE AF Borrego, F Kabat, J Sanni, TB Coligan, JE TI NK cell CD94/NKG2A inhibitory receptors are internalized and recycle independently of inhibitory signaling processes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HLA-E; ACTIVATING RECEPTORS; MEDIATED ENDOCYTOSIS; SURFACE EXPRESSION; ACTIN CYTOSKELETON; ANTIGEN RECEPTOR; MHC; RECOGNITION; PEPTIDE; MOLECULES AB Human CD94/NKG2A is an inhibitory receptor that recognizes HLA-E and is expressed by NK cells and a subset of T cells. We have analyzed the cellular trafficking of the CD94/NKG2A receptor using the NKL cell line and peripheral blood NK cells. Flow cytometric, confocal microscopic, and biochemical analyses show that CD94/NKG2A continuously recycles in an active process that requires the cytoskeleton between the cell surface and intracellular compartments that are distinguishable from recycling compartments used by well-characterized receptors, such as transferrin receptor (CD71). CD94/NKG2A, an inhibitory receptor, traffics differently from the closely related CD94/NKG2C molecule, an activating receptor. Using transfection/expression analyses of wild-type and mutant CD94/NKG2A molecules in the HLA-E negative rat basophilic cell line RBL-2H3, we demonstrate that CD94/NKG2A internalization is independent of ligand cross-linking or the presence of functional immunoreceptor tyrosine-based inhibition motifs. Thus, the mechanisms that control cell surface homeostasis of CD94/NKG2A are independent of functional signaling. C1 NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. RP Borrego, F (reprint author), NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Twinbrook 2,Room 205,12441 Parklawn Dr, Rockville, MD 20852 USA. NR 43 TC 27 Z9 27 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2002 VL 169 IS 11 BP 6102 EP 6111 PG 10 WC Immunology SC Immunology GA 619LX UT WOS:000179478400004 PM 12444112 ER PT J AU Chackerian, B Lenz, P Lowy, DR Schiller, JT AF Chackerian, B Lenz, P Lowy, DR Schiller, JT TI Determinants of autoantibody induction by conjugated papillomavirus virus-like particles SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REACTIVE LYMPHOCYTES-B; DENDRITIC CELLS; IMMUNE-RESPONSE; SELF-ANTIGEN; IN-VITRO; ACTIVATION; EXPRESSION; PROTECTION; ANTIBODIES; GENERATION AB Immunization of mice with self-Ag arrayed on the surface of papillomavirus-like particles induces long-lasting high-titer IgG production by autoreactive B cells. In contrast, immunization with disorganized self-Ag linked to foreign Th epitopes induces weak autoantibody responses that are predominantly of the IgM isotype. In this study, we evaluated the structural correlates of autoantibody induction to determine the basis of these disparate observations, using a system in which mice were vaccinated with a fusion protein containing self (TNF-alpha) and foreign (streptavidin) components, conjugated to biotinylated virus-like particles (VLPs). Similar titers of autoantibodies to TNF-alpha were elicited using conjugated polyomavirus VLPs and papillomavirus VLPs, indicating that acute activation of dendritic cells by the Ag is not required. Strong autoantibody responses were also induced by conjugated papillomavirus capsid pentamers, indicating that a higher order particulate structure is also not required. However, a reduction of self-Ag density on VLP surfaces dramatically reduced the efficiency of IgG autoantibody induction. In contrast, the negative effects of reductions in foreign Ag density were limited and could be overcome by dosage and adjuvant. These data suggest that the immune system has evolved to differentially recognize closely spaced repetitive Ags and that the signals generated upon interactions with high-density self-Ags can overwhelm the normal mechanisms for B cell tolerance. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 36,Room 1D-32, Bethesda, MD 20892 USA. NR 40 TC 103 Z9 105 U1 1 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2002 VL 169 IS 11 BP 6120 EP 6126 PG 7 WC Immunology SC Immunology GA 619LX UT WOS:000179478400006 PM 12444114 ER PT J AU Tatari-Calderone, Z Semnani, RT Nutman, TB Schlom, J Sabzevari, H AF Tatari-Calderone, Z Semnani, RT Nutman, TB Schlom, J Sabzevari, H TI Acquisition of CD80 by human T cells at early stages of activation: Functional involvement of CD80 acquisition in T cell to T cell interaction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN-PRESENTING CELLS; HIV-INFECTED INDIVIDUALS; PEPTIDE-MHC COMPLEXES; COSTIMULATORY MOLECULES; LYMPHOCYTES-T; EXPRESSION; CD28; B7; RECEPTORS; CTLA-4 AB The interaction between CD28 on T cells and CD80 on APCs intensifies the linkage between TCR and MHC at the site of contact between T cells and APCs. In this study, we demonstrate that during human T cell/human APC interaction, the autologous or allogeneic human CD4(+) T cells become positive for the detection of CD80 at an early stage of activation (24 h). This detection of CD80 is attributable to the acquisition of CD80 from APCs, as opposed to the up-regulation of endogenous CD80, as demonstrated by CD4(+) T cells treated with cyclohexamide. Furthermore, no CD80 mRNA could be detected at 24 h in T cells that had acquired CD80 from APCs. CD80 acquisition by T cells from APCs was enhanced upon TCR engagement. The amount of CD80 acquisition by CD4(+) T cells was shown to be related to the expression of CD80 on APCs. Using soluble fusion proteins (soluble CTLA-4, CD28, and CD80) to block either CD28 on the surface of T cells or CD80 on the surface of APCs, it was demonstrated that CD80 acquisition by T cells is mediated through its receptors, possibly CD28 interaction. Moreover, we demonstrate that T cells that have acquired CD80 have the ability to stimulate other T cells. These data thus suggest that CD80 acquisition by human T cells might play a role in the immunoregulation of T cell responses. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Center Dr,Room 8B09, Bethesda, MD 20892 USA. NR 37 TC 57 Z9 59 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2002 VL 169 IS 11 BP 6162 EP 6169 PG 8 WC Immunology SC Immunology GA 619LX UT WOS:000179478400012 PM 12444120 ER PT J AU D'Oro, U Munitic, I Chacko, G Karpova, T McNally, J Ashwell, JD AF D'Oro, U Munitic, I Chacko, G Karpova, T McNally, J Ashwell, JD TI Regulation of constitutive TCR internalization by the zeta-chain SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; ANTIGEN-RECEPTOR; ALPHA-BETA; TCR-CD3 COMPLEX; MONOCLONAL-ANTIBODY; SURFACE EXPRESSION; DOWN-MODULATION; TRANSGENIC MICE; CD3-ZETA CHAIN; ACTIVATION AB The ability of a T cell to be activated is critically regulated by the number of TCRs expressed on the plasma membrane. Cell surface TCR expression is influenced by dynamic processes such as synthesis and transport of newly assembled receptors, endocytosis of surface TCR, and recycling to the plasma membrane of internalized receptors. In this study, the internalization of fluorescently labeled anti-TCR Abs was used to analyze constitutive endocytosis of TCRs on T cells, and to investigate the role of the zeta-chain in this process. We found that cell surface TCRs lacking zeta were endocytosed more rapidly than completely assembled receptors, and that reexpression of full-length zeta led to a dose-dependent decrease in the rate of TCR internalization. Rapid TCR internalization was also observed with CD4(+)CD8(+) thymocytes from zeta-deficient mice, whereas TCR internalization on thymocytes from CD3-delta deficient animals was slow, similar to that of wild-type thymocytes. This identifies a specific role for zeta in the regulation of constitutive receptor internalization. Furthermore, chimeric molecules containing non-native intracellular amino acid sequences also led to high levels of TCR expression and reduced TCR cycling. These effects were dependent solely on the length of the intracellular tail, ruling out a role for intracellular zeta-specific interactions with other molecules as a mechanism for regulating TCR internalization. Rather, these findings strongly support a model in which the zeta-chain stabilizes TCR residency on the cell surface, and functions to maintain cell surface receptor expression by sterically blocking internalization sequences in other TCR components. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. NCI, Fluorescence Imaging Grp, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, Room 1B-40,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Chacko, George/I-4945-2014 OI Chacko, George/0000-0002-2127-1892 NR 39 TC 40 Z9 40 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2002 VL 169 IS 11 BP 6269 EP 6278 PG 10 WC Immunology SC Immunology GA 619LX UT WOS:000179478400025 PM 12444133 ER PT J AU Radaev, S Kattah, M Zou, ZC Colonna, M Sun, PD AF Radaev, S Kattah, M Zou, ZC Colonna, M Sun, PD TI Making sense of the diverse ligand recognition by NKG2D SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-INHIBITORY RECEPTOR; NATURAL-KILLER-CELLS; CLASS-I MOLECULES; COMPLEX CLASS-I; CRYSTAL-STRUCTURE; HLA-C; NK CELLS; BINDING; ACTIVATION; CD94/NKG2A AB NKG2D recognizes multiple diverse ligands. Despite recent efforts in determining the crystal structures of NKG2D-ligand complexes, the principle governing this receptor-ligand recognition and hence the criteria for identifying unknown ligands of NKG2D remain central issues to be resolved. Here we compared the molecular recognition between NKG2D and three of the known ligands, UL16 binding protein (ULBP), MHC class I-like molecule, and retinoic acid early inducible gene as observed in the ligand-complexed crystal structures. The comparison shows that while the receptor uses a common interface region to bind the three diverse ligands;, each ligand forms a distinct, but overlapping, set of hydrogen bonds, hydrophobic interactions, and salt bridges, illustrating the underlying principle of NKG2D-ligand recognition being the conservation in overall shape complementarity and binding energy while permitting variation in ligand sequence through induced fit recognition. To further test this hypothesis and to distinguish between diverse recognition and promiscuous ligand binding, four ULBP3 interface mutations, H21A, E76A, R82M, and D169A, were generated to each disrupt a single hydrogen bond or salt bridge. All mutant ULBP3 displayed reduced receptor binding, suggesting a specific, rather than promiscuous, receptor-ligand recognition. Mutants with severe loss of binding affect the receptor interactions that are mostly buried. Finally, a receptor-ligand recognition algorithm was developed to assist the identification of diverse NKG2D ligands based on evaluating the potential hydrogen bonds, hydrophobic interactions, and sail. bridges at the receptor-ligand interface. C1 NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. OI Colonna, Marco/0000-0001-5222-4987 NR 40 TC 21 Z9 23 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2002 VL 169 IS 11 BP 6279 EP 6285 PG 7 WC Immunology SC Immunology GA 619LX UT WOS:000179478400026 PM 12444134 ER PT J AU Greenwell-Wild, T Vazquez, N Sim, D Schito, M Chatterjee, D Orenstein, JM Wahl, SM AF Greenwell-Wild, T Vazquez, N Sim, D Schito, M Chatterjee, D Orenstein, JM Wahl, SM TI Mycobacterium avium infection and modulation of human macrophage gene expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-MEDIATED-IMMUNITY; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; FACTOR-KAPPA-B; HUMAN MONOCYTES; INTERFERON-GAMMA; MATRIX METALLOPROTEINASES; OPPORTUNISTIC INFECTIONS; ALVEOLAR MACROPHAGES; TNF-ALPHA AB Mycobacterium avium is a facultative intracellular pathogen cleared rapidly via intact host defense mechanisms. In the absence of adequate T cell function, as occurs in HIV-1-induced immunodeficiency, M. avium becomes an opportunistic infection with uncontrolled replication and reinfection of macrophage hosts. How M. avium infects, survives, and replicates in macrophages without signaling an effective microbicidal counterattack is unresolved. To address whether M. avium signals the expression of molecules, which influence mycobacterial survival or clearance, human monocyte-derived macrophage cultures were exposed to M. avium. Within minutes, M. avium, or its cell wall lipoarabinomannan, binds to the adherent macrophages and induces a spectrum of gene expression. In this innate response, the most abundant genes detected within 2 h by cDNA expression array involved proinflammatory chemokines, cytokines including TNF-alpha and IL-1, and adhesion molecules. Associated with this rapid initial up-regulation of recruitment and amplification molecules was enhanced expression of transcription factors and signaling molecules. By 24 h, this proinflammatory response subsided, and after 4 days, when some bacteria were being degraded, others escaped destruction to replicate within intracellular vacuoles. Under these conditions, inducible NO synthase was not up-regulated and increased transferrin receptors may facilitate iron-dependent mycobacterial growth. Sustained adhesion molecule and chemokine expression along with the formation of multinucleated giant cells appeared consistent with in vivo events. Thus, in the absence of T lymphocyte mediators, macrophages are insufficiently microbicidal and provide a nonhostile environment in which mycobacteria not only survive and replicate, but continue to promote recruitment of new macrophages to perpetuate the infection. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA. George Washington Univ, Dept Pathol, Washington, DC 20037 USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bldg 30,Room 320,30 Convent Dr, Bethesda, MD 20892 USA. NR 66 TC 32 Z9 33 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 DEC 1 PY 2002 VL 169 IS 11 BP 6286 EP 6297 PG 12 WC Immunology SC Immunology GA 619LX UT WOS:000179478400027 PM 12444135 ER PT J AU Mirani, M Elenkov, I Volpi, S Hiroi, N Chrousos, GP Kino, T AF Mirani, M Elenkov, I Volpi, S Hiroi, N Chrousos, GP Kino, T TI HIV-1 protein Vpr suppresses IL-12 production from human monocytes by enhancing glucocorticoid action: Potential implications of Vpr coactivator activity for the innate and cellular immunity deficits observed in HIV-1 infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FACTOR-KAPPA-B; TYPE-1 VPR; INTERFERON-GAMMA; CYCLE ARREST; NUCLEAR-LOCALIZATION; MUTATIONAL ANALYSIS; INTERLEUKIN-12 P35; MURINE IL-12; IN-VIVO AB The HIV-1 protein Vpr has glucocorticoid receptor coactivator activity, potently increasing the sensitivity of glucocorticoid target tissues to cortisol. Patients with AIDS and normal cortisol secretion have manifestations compatible with glucocorticoid hypersensitivity of the immune system, such as suppression of innate and cellular immunities. The latter can be explained by glucocorticoid-induced inhibition of cytokine networks regulating innate and Th1-driven cellular immunity. We demonstrated that extracellularly administered Vpr protein dose-dependently potentiated glucocorticoid-induced suppression of both mRNA expression and secretion of IL-12 subunit p35 and IL-12 holo-protein, but not IL-12 subunit p40 or IL-10, by human monocytes/macrophages stimulated with LPS or heat-killed, formalin-fixed Staphylococcus aureus (Cowan strain 1). This effect was inhibited by the glucocorticoid receptor antagonist RU 486. Also, Vpr changed the expression of an additional five glucocorticoid-responsive genes in the same direction as dexamethasone and was active in potentiating the trans-activation, but not the trans-repression, properties of the glucocorticoid receptor on nuclear factor kappaB- or activating protein 1-regulated simple promoters. Thus, extracellular Vpr enhances the suppressive actions of the ligand-activated glucocorticoid receptor on IL-12 secretion by human monocytes/macrophages. Through this effect, Vpr may contribute to the suppression of innate and cellular immunities of HIV-1-infected individuals and AIDS patients. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Div Rheumatol Allergy & Immunol, Washington, DC 20007 USA. RP Kino, T (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 9D42,10 Ctr Dr,MSC 1583, Bethesda, MD 20892 USA. NR 64 TC 67 Z9 69 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2002 VL 169 IS 11 BP 6361 EP 6368 PG 8 WC Immunology SC Immunology GA 619LX UT WOS:000179478400035 PM 12444143 ER PT J AU Chen, PL Li, J Barnes, J Kokkonen, GC Lee, JC Liu, YS AF Chen, PL Li, J Barnes, J Kokkonen, GC Lee, JC Liu, YS TI Restraint of proinflammatory cytokine biosynthesis by mitogen-activated protein kinase phosphatase-1 in lipopolysaccharide-stimulated macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR SYNTHESIS; MAP KINASE; SIGNALING PATHWAY; INNATE IMMUNITY; FACTOR-ALPHA; P38 MAPK; TNF; STRESS; PHOSPHORYLATION; INDUCTION AB Exposure of macrophages to LPS elicits the production of proinflammatory cytokines, such as TNF-alpha, through complex signaling mechanisms. Mitogen-activated protein (MAP) kinases play a critical role in this process. In the present study, we have addressed the role of MAP kinase phosphatase-1 (MKP-1) in regulating proinflammatory cytokine production using RAW264.7 macrophages. Analysis of MAP kinase activity revealed a transient activation of c-Jun N-terminal kinase (JNK) and p38 after LPS stimulation. Interestingly, MKP-1 was induced concurrently with the inactivation of JNK and p38, whereas blocking MKP-1 induction by triptolide prevented this inactivation. Ectopic expression of MKP-1 accelerated JNK and p38 inactivation and substantially inhibited the production of TNF-alpha and IL-6. Induction of MKP-1 by LPS was found to be extracellular signal-regulated kinase dependent and involved enhanced gene expression and increased protein stability. Finally, MKP-1 expression was also induced by glucocorticoids as well as cholera toxin B subunit, an agent capable of preventing autoimmune diseases in animal models. These findings highlight MKP-1 as a critical negative regulator of the macrophage inflammatory response, underscoring its premise as a potential target for developing novel anti-inflammatory drugs. C1 NIA, StressSignaling Unit, Cellular & Mol Biol Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. GlaxoSmithKline Pharmaceut, King Of Prussia, PA 19406 USA. RP Liu, YS (reprint author), NIA, StressSignaling Unit, Cellular & Mol Biol Lab, Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Liu, Yusen/E-3527-2011 NR 39 TC 209 Z9 216 U1 3 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2002 VL 169 IS 11 BP 6408 EP 6416 PG 9 WC Immunology SC Immunology GA 619LX UT WOS:000179478400041 PM 12444149 ER PT J AU Takahashi, M Osono, E Nakagawa, Y Wang, J Berzofsky, JA Margulies, DH Takahashi, H AF Takahashi, M Osono, E Nakagawa, Y Wang, J Berzofsky, JA Margulies, DH Takahashi, H TI Rapid induction of apoptosis in CD8(+) HIV-1 envelope-specific murine CTLs by short exposure to antigenic peptide SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; TUMOR-NECROSIS-FACTOR; EPSTEIN-BARR-VIRUS; CLASS-I; CELL-DEATH; MHC MOLECULE; ACTIVATION; COMPLEX; INFECTION; DELETION AB During primary viral infection, in vivo exposure to high doses of virus causes a loss of Ag-specific CD8(+) T cells. This phenomenon, termed clonal exhaustion, and other mechanisms by which CTLs are deleted are poorly understood. Here we show evidence for a novel form of cell death in which recently stimulated CD8(+) HIV-1 envelope gp160-specific murine CTLs become apoptotic in vitro after brief exposure to free antigenic peptide (P18-I10). Peak apoptosis occurred within 3 h of treatment with peptide, and the level of apoptosis was dependent on both the time after initial stimulation with target cells and the number of targets. Using T cell-specific H-2D(d)/PI8-110 tetramers, we observed that the apoptosis was induced by such complexes. Induction of apoptosis was blocked by cyclosporin A, a caspase 3 inhibitor, and a mitogen-activated protein kinase inhibitor, but not by Abs to either Fas ligand or to TNF-alpha. Thus, these observations suggest the existence of a Fas- or TNF-alpha-independent pathway initiated by TCR signaling that is involved in the rapid induction of CTL apoptosis. Such a pathway may prove important in the mechanism by which virus-specific CTLs are deleted in the presence of high viral burdens. C1 Nippon Med Coll, Dept Microbiol & Immunol, Bunkyo Ku, Tokyo 1138602, Japan. NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Takahashi, H (reprint author), Nippon Med Coll, Dept Microbiol & Immunol, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 1138602, Japan. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 37 TC 22 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 DEC 1 PY 2002 VL 169 IS 11 BP 6588 EP 6593 PG 6 WC Immunology SC Immunology GA 619LX UT WOS:000179478400063 PM 12444171 ER PT J AU Tuyet, DT Thiem, VD von Seidlein, L Chowdhury, A Park, E Canh, DG Chien, BT Tung, TV Naficy, A Rao, MR Ali, M Lee, H Sy, TH Nichibuchi, M Clemens, J Trach, DD AF Tuyet, DT Thiem, VD von Seidlein, L Chowdhury, A Park, E Canh, DG Chien, BT Tung, TV Naficy, A Rao, MR Ali, M Lee, H Sy, TH Nichibuchi, M Clemens, J Trach, DD TI Clinical, epidemiological, and socioeconomic analysis of an outbreak of Vibrio parahaemolyticus in Khanh Hoa Province, Vietnam SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BORNE DISEASE OUTBREAKS; PANDEMIC SPREAD; O3-K6 CLONE; STRAINS; GASTROENTERITIS; INFECTIONS; DIARRHEA; TAIWAN; DIVERSITY; EMERGENCE AB From 1996 onward, a pandemic spread of Vibrio parahaemolyticus infections due to one clone has been reported in several Asian countries. During a population-based study that relied on passive surveillance, 548 cases of V. parahaemolyticus infection were detected between 1997 and 1999 in the Khanh Hoa province of Vietnam. Detection of cases of V. parahaemolyticus infection abruptly stopped in November 1999, although Vibrio species other than V. parahaemolyticus continued to be isolated throughout 2000. Of the infections, 90% occurred in individuals >5 years old; 53% of the patients presented with watery stools, and 6% reported blood in their stools. All patients had recovered by the time of discharge. A surprising risk factor for V. parahaemolyticus infections was high socioeconomic status. Like the interruption of the transmission of V. cholerae infections that had been observed earlier, the transmission of V. parahaemolyticus came to a halt without meteorological changes or changes in water supply and sanitation. C1 Int Vaccine Inst, Seoul 151600, South Korea. Inst Pasteur, Nha Trang, Vietnam. Off Publ Hlth, Nha Trang, Vietnam. Natl Inst Hyg & Epidemiol, Hanoi, Vietnam. Kyoto Univ, Grad Sch Med, Kyoto, Japan. Kyoto Univ, Ctr SE Asian Studies, Kyoto, Japan. NIAID, NIH, Bethesda, MD 20892 USA. RP von Seidlein, L (reprint author), Int Vaccine Inst, POB 14, Seoul 151600, South Korea. NR 37 TC 23 Z9 24 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2002 VL 186 IS 11 BP 1615 EP 1620 DI 10.1086/345731 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 613RH UT WOS:000179144900011 PM 12447738 ER PT J AU Ma, L Kutty, G Jia, QY Imamichi, H Huang, L Atzori, C Beckers, P Groner, G Beard, CB Kovacs, JA AF Ma, L Kutty, G Jia, QY Imamichi, H Huang, L Atzori, C Beckers, P Groner, G Beard, CB Kovacs, JA TI Analysis of variation in tandem repeats in the intron of the major surface glycoprotein expression site of the human form of Pneumocystis carinii SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID DIHYDROPTEROATE SYNTHASE GENE; TRANSCRIBED SPACER REGIONS; F SP. HOMINIS; RIBOSOMAL-RNA GENES; RECURRENT PNEUMONIA; MULTIPLE LOCI; AIDS PATIENTS; MUTATIONS; DNA; HETEROGENEITY AB Variation in the tandem repeats in the expression site of the human-derived Pneumocystis carinii major surface glycoprotein gene was characterized by denaturing gel electrophoresis. The number of repeats in 147 isolates ranged from 2 to 6, with 2, 3, and 4 repeats being the most common. Sequence analysis identified 3 types of repeat units that differed by 1 nucleotide, which suggests a hierarchy of evolution of human-derived P. carinii. Examination of sequential samples obtained from 6 patients at an interval of 10-90 days showed an identical repeat pattern in each patient. However, in 2 of 4 patients with 2-3 different samples obtained within 4 days, different repeat patterns were observed among the samples. Quantifying the number of repeats by denaturing gel electrophoresis is a simple and rapid-typing method that can be used alone or in combination with other methods to study the epidemiology of P. carinii. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21701 USA. Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA USA. Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA USA. Luigi Sacco Hosp, Dept Infect Dis, Milan, Italy. Univ Nijmegen Hosp, Dept Med Microbiol, NL-6500 HB Nijmegen, Netherlands. RP Kovacs, JA (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Rm 7D43,MSC 1662, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-5600] NR 23 TC 22 Z9 23 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2002 VL 186 IS 11 BP 1647 EP 1654 DI 10.1086/345721 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 613RH UT WOS:000179144900015 PM 12447742 ER PT J AU Smith, HM Reporter, R Rood, MP Linscott, AJ Mascola, LM Hogrefe, W Purcell, RH AF Smith, HM Reporter, R Rood, MP Linscott, AJ Mascola, LM Hogrefe, W Purcell, RH TI Prevalence study of antibody to ratborne pathogens and other agents among patients using a free clinic in downtown Los Angeles SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 25-28, 2001 CL SAN FRANCISCO, CALIFORNIA SP Infect Dis Soc Amer ID HEPATITIS-E VIRUS; INSECT CELLS; DRUG-USERS; INFECTION; IDENTIFICATION; SEROREACTIVITY; HANTAVIRUS; BALTIMORE; DISEASE AB Norway rats (Rattus norvegicus) are hosts for various microbes. Homeless people who have contact with rats may be at risk of infection by them. The Los Angeles County Department of Health Services initiated a seroepidemiologic study among patients who used a free clinic in downtown Los Angeles; 200 serum specimens obtained for other routine assays were tested for antibodies to ratborne pathogens and other agents. The seroprevalence of antibody to hepatitis E virus in this population was 13.6%; to Bartonella elizabethae, 12.5%; to B. quintana, 9.5%; to B. henselae, 3.5%; to Seoul virus, 0.5%; and to Rickettsia typhi, 0.0%. This study found that patients and locally trapped rats had antibodies to some of the same agents. C1 Los Angeles Cty Dept Hlth Serv, Acute Communicable Dis Control Unit, Los Angeles, CA 90012 USA. Los Angeles Cty Dept Hlth Serv, Vector Management Program, Los Angeles, CA 90012 USA. Los Angeles Cty Dept Hlth Serv, Publ Hlth Lab, Los Angeles, CA 90012 USA. Focus Technol, Cypress, CA USA. NIAID, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. RP Smith, HM (reprint author), Los Angeles Cty Dept Hlth Serv, Acute Communicable Dis Control Unit, 313 N Figuroa St,Rm 212, Los Angeles, CA 90012 USA. OI Smith, Heather/0000-0002-7192-6180 NR 16 TC 33 Z9 36 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2002 VL 186 IS 11 BP 1673 EP 1676 DI 10.1086/345377 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 613RH UT WOS:000179144900019 PM 12447746 ER PT J AU Rothman, RE Majmudar, MD Kelen, GD Madico, G Gaydos, CA Walker, T Quinn, TC AF Rothman, RE Majmudar, MD Kelen, GD Madico, G Gaydos, CA Walker, T Quinn, TC TI Detection of bacteremia in emergency department patients at risk for infective endocarditis using universal 16S rRNA primers in a decontaminated polymerase chain reaction assay SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 07-11, 2000 CL NEW ORLEANS, LOUISIANA SP Infect Dis Soc Amer ID RIBOSOMAL-RNA GENES; BACTERIAL-ENDOCARDITIS; DIAGNOSIS; PCR; AMPLIFICATION; ELIMINATION; BLOOD; DNA AB Prompt definitive diagnosis of acute bacterial endocarditis in febrile injection drug users (IDUs) remains problematic because of delays associated with blood culture. Rapid detection of bacteremia by polymerase chain reaction (PCR) by use of "universal" primers has been hampered by background bacterial contamination. Broad-range eubacterial primers selected from the 16S rRNA gene were used in a PCR assay coupled with a simple pre-PCR decontamination step. All PCR reagents were pretreated with the restriction enzyme AluI, which has multiple digestion sites in the amplicon but none in the primer sets. When 4 different bacterial species were spiked into healthy human blood specimens, the assay identified each pathogen with an analytic sensitivity of 5 bacteria/PCR reaction. A clinical trial with 51 febrile IDUs revealed that PCR had a sensitivity and specificity of 86.7% and 86.9%, respectively, versus blood culture. Importantly, all (8/8) patients with blood culture-positive infective endocarditis were determined to be positive by PCR. This assay provides a promising diagnostic for rapid identification of bacteremia, particularly valuable in acute care settings. C1 Johns Hopkins Univ, Dept Emergency Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Rothman, RE (reprint author), Johns Hopkins Univ, Dept Emergency Med, 1830 E Monument St, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010; OI Rothman, Richard/0000-0002-1017-9505; Kelen, Gabor/0000-0002-3236-8286 FU NCRR NIH HHS [3M01RR00052-39-5[S1]] NR 15 TC 73 Z9 75 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2002 VL 186 IS 11 BP 1677 EP 1681 DI 10.1086/345367 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 613RH UT WOS:000179144900020 PM 12447747 ER PT J AU Jacobson, S AF Jacobson, S TI Immunopathogenesis of human T cell lymphotropic virus type I-associated neurologic disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 3rd Pfizer Symposium on Immunopathogenesis of Infections and Inflammatory Diseases of the Brain CY APR, 2002 CL CHARLESTON, SOUTH CAROLINA ID TROPICAL SPASTIC PARAPARESIS; CENTRAL-NERVOUS-SYSTEM; CYTOTOXIC LYMPHOCYTES-T; SPINAL-CORD LESIONS; BLOOD MONONUCLEAR-CELLS; HLA CLASS-I; HTLV-I; CEREBROSPINAL-FLUID; PERIPHERAL-BLOOD; PROVIRAL DNA AB This review focuses on current approaches to understanding the immunopathogenesis of human T cell lymphotropic virus (HTLV) type I-associated myelopathy/ tropical spastic paraparesis (HAM/TSP) based on newly developed molecular and immunologic techniques that have been adapted to studies of HTLV-I proviral load, HTLV-I mRNA, and HTLV- I tax-specific CD8 T cells. These methods enable researchers to study previously inaccessible aspects of this disease and allow a more detailed analysis of virus/host immune responses as they relate to disease specificity in this disorder. The role of HTLV- I-specific CD8 T cell immune responses is highlighted. The elucidation of the immunopathology of HAM/TSP will enhance our understanding of other HTLV- I-associated disorders plus other neurologic, hematologic, and inflammatory diseases for which viral etiologies have been suggested. C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bldg 10,Rm 5B-16,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 57 TC 64 Z9 66 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2002 VL 186 SU 2 BP S187 EP S192 DI 10.1086/344269 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 621KL UT WOS:000179587500009 PM 12424696 ER PT J AU Peterson, PK Major, E Oldstone, MBA Remington, JS AF Peterson, PK Major, E Oldstone, MBA Remington, JS TI Immunopathogenesis of infections and inflammatory diseases of the brain - Preface SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material C1 Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. NIH, Bethesda, MD 20892 USA. The Scripps Res Inst, La Jolla, CA USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. RP Peterson, PK (reprint author), Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2002 VL 186 SU 2 BP S139 EP S139 DI 10.1086/344940 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 621KL UT WOS:000179587500001 ER PT J AU Race, R Meade-White, K Raines, A Raymond, GJ Caughey, B Chesebro, B AF Race, R Meade-White, K Raines, A Raymond, GJ Caughey, B Chesebro, B TI Subclinical scrapie infection in a resistant species: Persistence, replication, and adaptation of infectivity during four passages SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 3rd Pfizer Symposium on Immunopathogenesis of Infections and Inflammatory Diseases of the Brain CY APR, 2002 CL CHARLESTON, SC ID BOVINE SPONGIFORM ENCEPHALOPATHY; TRANSMISSIBLE MINK ENCEPHALOPATHY; CHRONIC WASTING DISEASE; PRION PROTEIN; STRAIN VARIATION; AGENT; MICE; SHEEP; SUSCEPTIBILITY; HAMSTERS AB Cross-species infection with transmissible spongiform encephalopathy agents may lead to subclinical infection and to adaptation of the infection to new species. This is of particular concern for the millions of people possibly exposed to bovine spongiform encephalopathy (BSE) by consumption of BSE-infected beef. Subclinical infection was studied by making 4 serial passages of hamster scrapie agent (263K) in mice. At each step, infectivity was followed by inoculation of hamsters and mice. Subclinical infection was demonstrated either by detection of abnormal protease-resistant prion protein (PrP-res) or in the absence of PrP-res by detection of infectivity. Replication and adaptation of hamster infectivity in mice was shown in year 2 after initial mouse passage. In third and fourth passages, dual-tropic, mouse-tropic, and hamster-tropic infectivity was found in different animals. In some cases infectivity similar to the original 263K hamster scrapie strain was found after 2 or 3 serial mouse passages totaling 1200-1550 days. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Chesebro, B (reprint author), 903 S 4th St, Hamilton, MT 59840 USA. EM bchesebro@nih.gov NR 24 TC 45 Z9 45 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2002 VL 186 SU 2 BP S166 EP S170 DI 10.1086/344267 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 621KL UT WOS:000179587500006 PM 12424693 ER PT J AU Sabath, BF Major, EO AF Sabath, BF Major, EO TI Traffic of JC virus from sites of initial infection to the brain: The path to progressive multifocal leukoencephalopathy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 3rd Pfizer Symposium on Immunopathogenesis of Infections and Inflammatory Diseases of the Brain CY APR, 2002 CL CHARLESTON, SOUTH CAROLINA ID HUMAN POLYOMAVIRUS JC; HEMATOPOIETIC PROGENITOR CELLS; TONSILLAR STROMAL CELLS; HUMAN NEUROTROPIC VIRUS; HUMAN GLIAL-CELLS; NUCLEAR FACTOR-I; REGULATORY REGION; TRANSCRIPTIONAL REGULATION; MOLECULAR-BIOLOGY; B-LYMPHOCYTES AB Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the human brain caused by infection with the human polyomavirus, JC. Up to 80% of humans express serum antibodies to JC virus (JCV), yet considerably fewer people develop PML-predominantly those under immunosuppressive conditions. Recent research showed JCV infection in multiple tissues throughout the body, suggesting sites for viral latency. These observations allow the proposal of pathways that JCV may use from sites of initial infection to the brain. Results from investigations into cell-surface receptors, intracellular DNA-binding proteins, and variant viral regulatory regions also suggest mechanisms that may regulate cellular susceptibility to JCV infection. Together, these data elucidate how JCV may establish infection in various cell types, persist latently or become reactivated, and ultimately reach the brain to cause PML. C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, 36 Cnvent Dr,Bldg 36,Rm 5W21, Bethesda, MD 20892 USA. NR 53 TC 74 Z9 74 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2002 VL 186 SU 2 BP S180 EP S186 DI 10.1086/344280 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 621KL UT WOS:000179587500008 PM 12424695 ER PT J AU Kim, SZ Santamaria, E Jeong, TE Levy, HL Mato, JM Corrales, FJ Mudd, SH AF Kim, SZ Santamaria, E Jeong, TE Levy, HL Mato, JM Corrales, FJ Mudd, SH TI Methionine adenosyltransferase I/III deficiency: two Korean compound heterozygous siblings with a novel mutation SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID ISOLATED PERSISTENT HYPERMETHIONINEMIA; S-ADENOSYLMETHIONINE; DOMINANT INHERITANCE; TOTAL HOMOCYSTEINE; FOLATE-DEFICIENCY; MASS-SPECTROMETRY; INBORN-ERRORS; PLASMA; SERUM; ADENOSYLHOMOCYSTEINE AB Two Korean sisters, one detected during neonatal screening, the other ascertained at age 3 years during family screening, have persistent hypermethioninaemia without elevation of plasma tyrosine or severe liver disease. Plasma total homocysteine ( tHcy) is mildly elevated, but not so markedly as to establish a diagnosis of homocystinuria due to cystathionine beta-synthase (CBS) deficiency. CBS deficiency was ruled out by the presence of slightly elevated concentrations of plasma cystathionine. Although the plasma concentrations of methionine were markedly elevated, plasma S-adenosylmethionine ( AdoMet) was not. This pattern of metabolic abnormalities suggested that the patients have deficient activity of methionine adenosyltransferase ( MAT) in their livers ( MAT I/III deficiency). Molecular genetic studies demonstrate that each patient is a compound heterozygote for two mutations in MAT1A, the gene that encodes the catalytic subunit that composes MAT I and MAT III: a previously known inactivating G378S point mutation, and a novel W387X truncating mutation. W387X mutant protein, expressed in E. coli and purified, has about 75% of wild-type activity. Negative subunit interaction between the mutant subunits is suggested to explain the hypermethioninaemia of these sisters. They have had normal growth and development and have no mental retardation, neurological abnormalities, or other clinical problems. They are the first individuals of Korean descent proven to have MAT I/III deficiency. C1 NIMH, DIRP, LMB, Bethesda, MD 20892 USA. Korea Genet Res Ctr, Cheongju, South Korea. Univ Navarra, Div Hepatol & Gene Therapy, E-31080 Pamplona, Spain. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Mudd, SH (reprint author), NIMH, DIRP, LMB, Bldg 36,Room 1B-08,36 Convent Dr MSC 4034, Bethesda, MD 20892 USA. RI MATO, JOSE/A-5187-2011; SANTAMARIA, ENRIQUE/A-6012-2017 OI SANTAMARIA, ENRIQUE/0000-0001-8046-8102 NR 26 TC 12 Z9 12 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD FEB PY 2002 VL 25 IS 8 BP 661 EP 671 PG 11 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 656RA UT WOS:000181620300004 PM 12705496 ER PT J AU Lei, TC Virador, V Yasumoto, K Vieira, WD Toyofuku, K Hearing, VJ AF Lei, TC Virador, V Yasumoto, K Vieira, WD Toyofuku, K Hearing, VJ TI Stimulation of melanoblast pigmentation by 8-methoxypsoralen: The involvement of microphthalmia-associated transcription factor, the protein kinase A signal pathway, and proteasome-mediated degradation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE melanoblast; pigmentation; psoralens; Mitf ID MOUSE EPIDERMAL MELANOBLASTS; TYROSINASE-RELATED PROTEIN; ULTRAVIOLET-LIGHT; HUMAN MELANOCYTES; MELANOGENIC PROTEINS; GENE-EXPRESSION; HAIR-FOLLICLES; CYCLIC-AMP; VITILIGO; CELLS AB In this study, we used melb-a melanoblasts as a model to study mechanisms involved in stimulating melanocyte function in vitiliginous skin following exposure to 8-methoxypsoralen (8MOP). Melanin content and tyrosinase activity increased 3- and 7-fold, respectively, in melanoblasts treated with 8MOP for 6 d compared with untreated controls. The intracellular signal pathways involved in 8MOP-induced effects on melanoblasts were investigated, particularly the roles of protein kinase A and protein kinase C. Forskolin, a protein kinase A activator, mimicked and enhanced the 8MOP stimulation of melanoblast pigmentation whereas a protein kinase C activator, 1-oleoyl-2-acetylglycerol, had no effect, indicating that the protein kinase A pathway is involved rather than the protein kinase C pathway. Those observations were confirmed using inhibitors of the protein kinase A or protein kinase C pathways. Western blot and semiquantitative reverse transcriptase polymerase chain reaction were performed to assess the protein and mRNA expression levels of microphthalmia-associated transcription factor and tyrosinase in melanoblasts treated with 8MOP for 3 h, 6 h, 1 d, 3 d, or 6 d. Incubation with 8MOP stimulated microphthalmia-associated transcription factor protein and mRNA levels within 3 h, but, in contrast, tyrosinase mRNA and protein levels did not increase following 8MOP treatment until 1 d after treatment. The proteasome inhibitor lactacystin blocked the proteasome-mediated proteolysis of tyrosinase, and its effect on proteasomal function was enhanced by 8MOP. Taken together, these results show that 8MOP functions by initially stimulating levels of microphthalmia-associated transcription factor expression via activation of the protein kinase A pathway, which thereby stimulates tyrosinase expression and function and eventually leads to dramatic increases in melanin production by melanoblasts. C1 NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hearing, VJ (reprint author), NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bldg 37,Room 1B25, Bethesda, MD 20892 USA. NR 44 TC 16 Z9 19 U1 2 U2 12 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2002 VL 119 IS 6 BP 1341 EP 1349 DI 10.1046/j.1523-1747.2002.19607.x PG 9 WC Dermatology SC Dermatology GA 625ED UT WOS:000179803200019 PM 12485437 ER PT J AU Moshell, AN AF Moshell, AN TI The changing face of cutaneous biology as seen from the National Institutes of Health SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 50th Montagna Annual Symposium on the Biology of Skin CY JUL 27-31, 2001 CL SNOWMASS, COLORADO SP Avon Prod Inc, Fujisawa Healthcare Inc, F Hoffman La Roche Pharmaceut, Fdn Basic Cutaneous Res, Unilever PLC, Unilever NY, Dermik Labs, Johnson & Johnson Comsumer Prod Co, Merck & Co, Natl Psoriasis Fdn, Orentreich Fdn DE biology; dermatologist; scientist; qenomies; proteomics AB Over the past 50 y, research in skin biology and diseases has changed dramatically. These changes include (i) who is doing the research, from M.D. clinician dermatologists to predominantly Ph.D. research scientists and full-time or nearly full-time M.D. and M.D.-Ph.D. scientists, (ii) where, from small laboratories in the U.S.A. to large laboratories and multiinvestigator collaborations worldwide, (iii) what, from a focus on common skin diseases to an emphasis on understanding basic processes in skin, both in normal and disease states, and (iv) how, from patient observations, histology, and clinical immunology to cell and tissue culture, molecular biology and genetics, genomics and proteomics. Financing of this research has also changed, from the use of clinical surplus funds supplemented by U.S. government (National Institutes of Health, Veterans Administration, and other) monies to a greater dependence on government and private (pharmaceutical industry and philanthropy) funding. The future, funding issues aside, promises great advances with translation of basic knowledge to the diagnosis, prevention, and treatment of skin diseases. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Moshell, AN (reprint author), NIAMS, NIH, 45 Ctr Dr,Room 5AS25L, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD DEC PY 2002 VL 7 IS 1 BP 4 EP 5 DI 10.1046/j.1523-1747.2002.19640.x PG 2 WC Dermatology SC Dermatology GA 654YW UT WOS:000181525400003 PM 12518786 ER PT J AU Dlugosz, A Merlino, G Yuspa, SH AF Dlugosz, A Merlino, G Yuspa, SH TI Progress in cutaneous cancer research SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 50th Montagna Annual Symposium on the Biology of Skin CY JUL 27-31, 2001 CL SNOWMASS, COLORADO SP Avon Prod Inc, Fujisawa Healthcare Inc, F Hoffman La Roche Pharmaceut, Fdn Basic Cutaneous Res, Unilever PLC, Unilever NY, Dermik Labs, Johnson & Johnson Comsumer Prod Co, Merck & Co, Natl Psoriasis Fdn, Orentreich Fdn DE melanoma; basal cell carcinoma; carcinogenesis; skin ID BASAL-CELL CARCINOMAS; FACTOR SCATTER FACTOR; GROWTH-FACTOR-ALPHA; HEDGEHOG SIGNALING PATHWAY; MOUSE SKIN CARCINOGENESIS; TUMOR MODIFIER LOCI; N-RAS MUTATIONS; MALIGNANT-MELANOMA; TRANSGENIC MICE; SONIC HEDGEHOG AB Cutaneous cancers represent a major public health concern due to the very high incidence, associated medical costs, substantial mortality, and cosmetic deformities associated with treatment. Considerable progress in basic research has provided new insights into the underlying genetic basis of the major human cutaneous cancers, malignant melanoma, basal cell carcinoma, and squamous cell carcinoma. In turn, these genetic insights have illuminated biochemical pathways that promise to provide new approaches to the prevention and treatment of cutaneous neoplasms. This review will detail the evolving genetic information and indicate how this information is being used to refine experimental models that serve to both define the biochemistry of cancer pathogenesis and test novel approaches to cancer therapy. Combined with preventive measures to reduce exposure to sunlight, these advances are likely to reduce this major public health burden in the coming decade. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Dermatol, Ann Arbor, MI USA. Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI USA. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, 37 Convent Dr,MSC-4255,Bldg 37,Room 3B25, Bethesda, MD 20892 USA. FU NCI NIH HHS [R01 CA087837] NR 142 TC 50 Z9 52 U1 0 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD DEC PY 2002 VL 7 IS 1 BP 17 EP 26 DI 10.1046/j.1523-1747.2002.19631.x PG 10 WC Dermatology SC Dermatology GA 654YW UT WOS:000181525400005 PM 12518788 ER PT J AU Edghill-Smith, YY Aldrich, K Zhao, J Pinczewski, J Kalyanaraman, VS Johnson, M Heyliger, A Perrin, RP Woodward, R Robert-Guroff, M AF Edghill-Smith, YY Aldrich, K Zhao, J Pinczewski, J Kalyanaraman, VS Johnson, M Heyliger, A Perrin, RP Woodward, R Robert-Guroff, M TI Effects of intestinal survival surgery on systemic and mucosal immune responses in SIV-infected rhesus macaques SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE cellular immunity; IgA; IgG; lamina propria; neutralizing antibody; simian AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL DEPLETION; HIV-INFECTION; NEUTRALIZING ANTIBODIES; GASTROINTESTINAL-TRACT; LAMINA PROPRIA; VIRAL BURDEN; LYMPHOCYTES; CHIMPANZEES; CHALLENGE AB Evaluation of cellular immunity in the intestinal lamina propria of rhesus macaques has been used previously to assess protective immunity against mucosal simian immunodeficiency virus (SIV) challenges. As this technique requires survival surgery to obtain jejunal tissue, effects of surgical stress on the immune system were investigated. SIV-specific immune responses, including IgG and IgA binding antibodies in sera and mucosal secretions, IgG and IgA secreting cells in peripheral blood, IgG neutralizing antibodies, T-cell proliferative responses, and interferon-gamma secretion by peripheral blood mononuclear cells, were evaluated pre- and post-surgery in macaques immunized with adenovirus-SIV recombinant vaccines and SIV envelope protein and in SIV-infected macaques. No differences in these immune parameters were observed in SIV-naive, immunized macaques or healthy SIV-infected macaques with regard to surgery. A dramatic increase in total IgA antibody level following surgery in the rectal secretions of one SIV-infected macaque that was rapidly progressing to AIDS and failed to recover from surgery was attributed to an abscess that developed at the intestinal site. To date, nearly 30 other macaques have undergone the intestinal survival surgery, some on more than one occasion, without experiencing any clinical difficulty. Overall, our results suggest that in healthy macaques, intestinal resection survival surgery can be conducted safely. Further, the method can be used to reliably sample the intestinal mucosa without major or persistent impact on humoral or cellular immune responses. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Adv Biosci Labs Inc, Kensington, MD USA. RP Robert-Guroff, M (reprint author), NCI, Basic Res Lab, NIH, Bldg 41,Room D804,41 Lib Dr MSC 5055, Bethesda, MD 20892 USA. NR 30 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD DEC PY 2002 VL 31 IS 6 BP 313 EP 322 DI 10.1034/j.1600-0684.2002.01018.x PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 626FY UT WOS:000179847400001 PM 12519209 ER PT J AU Kos, M Denger, S Reid, G Korach, KS Gannon, F AF Kos, M. Denger, S. Reid, G. Korach, K. S. Gannon, F. TI Down but not out? A novel protein isoform of the estrogen receptor alpha is expressed in the estrogen receptor alpha knockout mouse SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article AB The mouse knockout of the estrogen receptor alpha (ER alpha) gene, known as alpha ERKO, has been extensively used for several years to study the role and function of ER alpha. Residual estradiol binding capacity in uterine tissue of 5-10% raised doubts if this knockout is a genuine null mutation of ER alpha. Although alternatively spliced ER alpha mRNA variants in the alpha ERKO mouse were reported previously, the corresponding protein isoforms have not been detected to date. Here we show that a variant ER alpha protein, 61 kDa in size, is expressed in the uterine tissue of alpha ERKO mice as a result of an alternative splicing. The transactivation capability of this protein is cell dependent and can be as high as 75% of the wild type ER alpha. C1 [Kos, M.; Denger, S.; Reid, G.; Gannon, F.] European Mol Biol Lab, D-69117 Heidelberg, Germany. [Korach, K. S.] NIEHS, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Gannon, F (reprint author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany. EM Frank.Gannon@embo.org RI Gannon, Frank/G-1194-2015; Kos, Martin/E-2534-2011; OI Kos, Martin/0000-0002-3337-9681; Korach, Kenneth/0000-0002-7765-418X NR 36 TC 57 Z9 58 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD DEC PY 2002 VL 29 IS 3 BP 281 EP 286 DI 10.1677/jme.0.0290281 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V40LS UT WOS:000209480700002 PM 12459030 ER PT J AU Bai, RL Bates, RB Hamel, E Moore, RE Nakkiew, P Pettit, GR Sufi, BA AF Bai, RL Bates, RB Hamel, E Moore, RE Nakkiew, P Pettit, GR Sufi, BA TI Lyngbyastatin 1 and Ibu-epilyngbyastatin 1: Synthesis, stereochemistry, and NMR line broadening SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID DOLASTATIN-11 AB The synthesis of a lyngbyastatin 1-Ibu-epilyngbyastatin 1 mixture combined with NMR and molecular modeling studies proved that natural lyngbyastatin 1 was only one Ibu epimer rather than a mixture of both and that the configuration of this epimer in the Ibu unit was R. The substance isolated with lyngbyastatin 1 was Ibu-epidolastatin 12. The extreme broadness in the proton NMR spectra of lyngbyastatin 1 and Ibu-epidolastatin 12 was exchange broadening due to rotation about the Ibu-Ala amide bond. It was a consequence of (1) a small energy difference between the cis and trans forms of this bond, (2) a substantial difference in conformation between these forms, and (3) a lowered barrier between them compared to most amide bonds (due to steric hindrance). The synthetic lyngbyastatin 1-Ibu-epilyngbyastatin 1 mixture had significant activities against cancer cells and in stimulating actin polymerization, but was less active than dolastatin 11 in all assays. C1 Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis,NIH, Frederick, MD 21702 USA. Univ Hawaii Manoa, Dept Chem, Honolulu, HI 96822 USA. Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem, Tempe, AZ 85287 USA. RP Bates, RB (reprint author), Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. EM batesr@u.arizona.edu FU NCI NIH HHS [R01 CA 78750] NR 8 TC 8 Z9 8 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD DEC PY 2002 VL 65 IS 12 BP 1824 EP 1829 DI 10.1021/np020117w PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 631WM UT WOS:000180190100016 PM 12502322 ER PT J AU Pettit, GR Numata, A Iwamoto, C Morito, H Yamada, T Goswami, A Clewlow, PJ Cragg, GM Schmidt, JM AF Pettit, GR Numata, A Iwamoto, C Morito, H Yamada, T Goswami, A Clewlow, PJ Cragg, GM Schmidt, JM TI Antineoplastic agents. 489. Isolation and structures of meliastatins 1-5 and related euphane triterpenes from the tree Melia dubia SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID VOLKENSII AB The bark of the giant neem tree Melia dubia was found to contain 11 euphane-type triterpenes. Five new compounds, meliastatins 1-5 (1-5), proved to inhibit growth of the P388 lymphocytic leukemia cell line (ED50 1.7-5.6,mug/mL). Four of the others, the previously known methyl kulonate (8), kulinone (9), 16-hydroxybutyrospermol (10), and kulactone (11), were also found to inhibit (ED50 2.5-6.2,mug/mL) the P388 cancer cell line. In addition, two new euphane triterpenes were isolated and named dubione A (6) and dubione B (7). Structures for each of the 11 euphane triterpenes were established by spectral techniques that included HRMS and 2D NMR. C1 Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Osaka Univ Pharmaceut Sci, Takatsuki, Osaka 5691094, Japan. Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Nat Prod Branch, Ft Detrick, MD 21702 USA. RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, POB 872404, Tempe, AZ 85287 USA. FU NCI NIH HHS [CA 44344-01A1-12, R01 CA 90441-01] NR 22 TC 27 Z9 28 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD DEC PY 2002 VL 65 IS 12 BP 1886 EP 1891 DI 10.1021/np020216+ PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 631WM UT WOS:000180190100027 PM 12502333 ER PT J AU Wang, XX Qin, ZH Leng, Y Wang, YM Jin, XN Chase, TN Bennett, MC AF Wang, XX Qin, ZH Leng, Y Wang, YM Jin, XN Chase, TN Bennett, MC TI Prostaglandin A(1) inhibits rotenone-induced apoptosis in SH-SY5Y cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE caspase-3; dopaminergic cell; mitochondrial complex I; nuclear factor-kappa B; Parkinson's disease; prostaglandin A1 ID NF-KAPPA-B; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; CYCLOPENTENONE PROSTAGLANDINS; ACTIVATION; HSP27; HSP70; PHOSPHORYLATION; MITOCHONDRIA; EFFECTOR AB The degeneration of nigral dopamine neurons in Parkinson's disease (PD) reportedly involves a defect in brain mitochondrial complex I in association with the activation of nuclear factor-kappaB (NF-kappaB) and caspase-3. To elucidate molecular mechanisms possibly linking these events, as well as to evaluate the neuroprotective potential of the cyclopentenone prostaglandin A(1) (PGA(1)), an inducer of heat shock proteins (HSPs), we exposed human dopaminergic SH-SY5Y cells to the complex I inhibitor rotenone. Dose-dependent apoptosis was preceded by the nuclear translocation of NF-kappaB and then the activation of caspase-3 over the ensuing 24 h. PGA(1) increased the expression of HSP70 and HSP27 and protected against rotenone-induced apoptosis, without increasing necrotic death. PGA(1) blocked the rotenone-induced nuclear translocation of NF-kappaB and attenuated, but did not abolish, the caspase-3 elevation. Unexpectedly, the caspase-3 inhibitor, Ac-DEVD.CHO (DEVD), at a concentration that completely prevented the caspase-3 elevation produced by rotenone, failed to protect against apoptosis. These results suggest that complex I deficiency in dopamine cells can induce apoptosis by a process involving early NF-kappaB nuclear translocation and caspase-3 activation. PGA, appears to protect against rotenone-induced cell death by inducing HSPs and blocking nuclear translocation of NF-kappaB in a process that attenuates caspase-3 activation, but is not mediated by its inhibition. C1 NINDS, Expt Therapeut Branch, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Lab Cellular & Neurobiol, Boston, MA USA. Walter Reed Army Inst Res, Dept Biol, Div Expt Therapeut, Silver Spring, MD USA. Blanchette Rockefeller Neurosci Inst, Rockville, MD USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, Bldg 10,Room 5C-103,10 Ctr Dr MSC 1604, Bethesda, MD 20892 USA. NR 48 TC 59 Z9 64 U1 1 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2002 VL 83 IS 5 BP 1094 EP 1102 DI 10.1046/j.1471-4159.2002.01224.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 621CR UT WOS:000179571400008 PM 12437580 ER PT J AU Vaudry, D Chen, Y Ravni, A Hamelink, C Elkahloun, AG Eiden, LE AF Vaudry, D Chen, Y Ravni, A Hamelink, C Elkahloun, AG Eiden, LE TI Analysis of the PC12 cell transcriptome after differentiation with pituitary adenylate cyclase-activating polypeptide (PACAP) SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE MAP kinase; microarray; neuritogenesis; proliferation ID NERVE GROWTH-FACTOR; NEURITE OUTGROWTH; GENE-EXPRESSION; PROTEIN-KINASE; MAP KINASE; SIGNALING PATHWAYS; MAMMALIAN-CELLS; SURVIVAL; INDUCTION; ARREST AB Pituitary adenylate cyclase-activating polypeptide (PACAP) promotes neurite outgrowth and inhibits proliferation of rat pheochromocytoma (PC12) cells. Characterizing the PACAP-differentiated PC12 cell transcriptome should provide genetic insight into how these processes occur in these cells, and in neuronal precursors in vivo . For this purpose, RNA samples were collected from PC12 cells before or after a 6-h treatment with PACAP, from which a labeled cDNA was hybridized to a high-density cDNA array containing 15 365 genes. The genomic response to PACAP involves at least 73 genes. Among the genes differentially expressed in the presence of PACAP, 71% were up regulated, and 29% down regulated, 2-fold or more. Sixty-six percent of the messages affected by PACAP code for functionally categorized proteins, most not previously known to be regulated during PC12 cell differentiation. PACAP has been shown to induce PC12 cell neurite outgrowth through the mitogen-activated protein kinase kinase (MEK) pathway independently of protein kinase A (PKA). Therefore treatments were conducted in the absence or presence of the PKA inhibitor H89, or the MEK inhibitor U0126 in order to identify subsets of genes involved in specific aspects of PC12 cell differentiation. Co-treatment of PC12 cells with PACAP plus H89 revealed a cluster of five genes specifically regulated through the PKA pathway and co-treatment of the cells with PACAP and U0126 revealed a cluster of 13 messages specifically activated through the MEK pathway. Many of the known genes regulated by PACAP have been associated with neuritogenesis (i.e. villin 2 or annexin A2) or cell growth (i.e. growth arrest specific 1 or cyclin B2). Thus, some of the expressed sequence tags (ESTs) that exhibit the same regulation pattern (i.e. AU016391 or AW552690) may also be involved in the neuritogenic and anti-mitogenic effects of PACAP in PC12 cells. Among the 73 PACAP regulated genes, 10 are disqualified on pharmacological grounds as actors in PACAP-mediated neurite outgrowth or growth arrest, leaving 63 new PACAP-regulated genes implicated in neuronal differentiation. Thirteen of these are candidates for mediating ERK-dependent neurite outgrowth, and 47 are possibly involved in the ERK-independent growth arrest induced by PACAP. C1 NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Eiden, LE (reprint author), NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bldg 36,Room 2 A-11, Bethesda, MD 20892 USA. OI Eiden, Lee/0000-0001-7524-944X FU Intramural NIH HHS [Z01 MH002386-21, Z01 MH002386-22, Z99 MH999999] NR 47 TC 50 Z9 51 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2002 VL 83 IS 6 BP 1272 EP 1284 DI 10.1046/j.1471-4159.2002.01242.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 624EE UT WOS:000179746700004 PM 12472882 ER PT J AU Luo, YQ Cai, JL Liu, Y Xue, HP Chrest, FJ Wersto, RP Rao, M AF Luo, YQ Cai, JL Liu, Y Xue, HP Chrest, FJ Wersto, RP Rao, M TI Microarray analysis of selected genes in neural stem and progenitor cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE astrocyte; differentiation; glial restricted precursor; neuroepithelial cells; neuronal restricted precursor; proliferation ID FIBROBLAST-GROWTH-FACTOR; SPINAL-CORD; NEURONAL DIFFERENTIATION; DOPAMINE NEURONS; TENASCIN-C; MICE; PRECURSORS; MIGRATION; LINEAGE; BRAIN AB To access and compare gene expression in fetal neuroepithelial cells (NEPs) and progenitor cells, we have used microarrays containing approximately 500 known genes related to cell cycle regulation, apoptosis, growth and differentiation. We have identified 152 genes that are expressed in NEPs and 209 genes expressed by progenitor cells. The majority of genes (141) detected in NEPs are also present in progenitor populations. There are 68 genes specifically expressed in progenitors with little or no expression in NEPs, and a few genes that appear to be present exclusively in NEPs. Using cell sorting, RT-PCR, in situ hybridization or immunocytochemistry, we have examined the segregation of expression to neuronal and glial progenitors, and identified several that appeared to be enriched in neuronal (e.g. CDK5, neuropilin, EphrinB2, FGF11) or glial (e.g. CXCR4, RhoC, CD44, tenascin C) precursors. Our data provide a first report of gene expression profiles of neural stem and progenitor cells at early stages of development, and provide evidence for the potential roles of specific cell cycle regulators, chemokines, cytokines and extracellular matrix molecules in neural development and lineage segregation. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. NIA, Res Resource Branch, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Rao, M (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, Room 4E02,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM raomah@grc.nia.nih.gov NR 61 TC 80 Z9 83 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2002 VL 83 IS 6 BP 1481 EP 1497 DI 10.1046/j.1471-4159.2002.01260.x PG 17 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 624EE UT WOS:000179746700024 PM 12472902 ER PT J AU Haughey, NJ Nath, A Chan, SL Borchard, AC Rao, MS Mattson, MP AF Haughey, NJ Nath, A Chan, SL Borchard, AC Rao, MS Mattson, MP TI Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE calpain; caspase; hippocampus; neurogenesis; learning and memory; stem cells ID CENTRAL-NERVOUS-SYSTEM; DENTATE GYRUS; NEURONAL DIFFERENTIATION; STEM-CELLS; HIPPOCAMPAL-NEURONS; PRECURSOR PROTEIN; TRANSGENIC MICE; PERFORANT PATH; ADULT-RAT; ENRICHED ENVIRONMENT AB Neurogenesis occurs in the adult mammalian brain and may play roles in learning and memory processes and recovery from injury, suggesting that abnormalities in neural progenitor cells (NPC) might contribute to the pathogenesis of disorders of learning and memory in humans. The objectives of this study were to determine whether NPC proliferation, survival and neuronal differentiation are impaired in a transgenic mouse model of Alzheimer's disease (AD), and to determine the effects of the pathogenic form of amyloid beta-peptide (Abeta) on the survival and neuronal differentiation of cultured NPC. The proliferation and survival of NPC in the dentate gyrus of the hippocampus was reduced in mice transgenic for a mutated form of amyloid precursor protein that causes early onset familial AD. Abeta impaired the proliferation and neuronal differentiation of cultured human and rodent NPC, and promoted apoptosis of neuron-restricted NPC by a mechanism involving dysregulation of cellular calcium homeostasis and the activation of calpains and caspases. Adverse effects of Abeta on NPC may contribute to the depletion of neurons and cognitive impairment in AD. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 4F02,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 89 TC 279 Z9 305 U1 1 U2 18 PU BLACKWELL PUBLISHING LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2002 VL 83 IS 6 BP 1509 EP 1524 DI 10.1046/j.1471-4159.2002.01267.x PG 16 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 624EE UT WOS:000179746700026 PM 12472904 ER PT J AU Li, Y Burke, RE AF Li, Y Burke, RE TI Developmental changes in short-term synaptic depression in the neonatal mouse spinal cord SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PURKINJE-CELL SYNAPSE; CALCIUM-CHANNEL TYPES; TRANSMITTER RELEASE; HIPPOCAMPAL SYNAPSES; NEUROTRANSMITTER RELEASE; PRESYNAPTIC DEPRESSION; FICTIVE LOCOMOTION; PYRAMIDAL NEURONS; MOTOR-NEURONS; BRAIN-STEM AB We examined age-dependent changes in short-term synaptic depression of monosynaptic excitatory postsynaptic potentials (EPSPs) recorded in lumbar motoneurons in hemisected spinal cords of neonatal Swiss-Webster mice between postnatal day 2 (P2) and 12 (P12). We used four paradigms that sample the input-output dependence on stimulation history in different but complementary ways: 1) paired-pulse depression; 2) steady-state depression during constant frequency trains; 3) modulation during irregular stimulation sequences; and 4) recovery after high-frequency conditioning trains. Paired-pulse synaptic depression declined more than steady-state depression during 10-pulse trains at frequencies from 0.125 to 8 Hz in this age range. Depression during sequences of irregular stimulations that more closely mimic physiological activation also declined with postnatal age. On the other hand, the overall rate of synaptic recovery after a 4-Hz conditioning train exhibited surprisingly little change between P2 and P12. Control experiments indicated that these observations depend primarily, if not exclusively, on changes in presynaptic transmitter release. The data were examined using quantitative models that incorporate factors that have been suggested to exist at more specialized central synapses. The model that best predicted the observations included two presynaptic compartments that are depleted during activation, plus two superimposed processes that enhance transmitter release by different mechanisms. One of the latter produced rapidly-decaying enhancement of transmitter release fraction. The other mechanism indirectly enhanced the rate of renewal of one of the depleted presynaptic compartments. This model successfully predicted the constant frequency and irregular sequence data from all age groups, as well as the recovery curves following short, high-frequency tetani. The results suggest that a reduction in release fraction accounts for much of the decline in synaptic depression during early postnatal development, although changes in both enhancement processes also contribute. The time constants of resource renewal showed surprisingly little change through the first 12 days of postnatal life. C1 NINDS, Lab Neural Control, NIH, Bethesda, MD 20892 USA. RP Burke, RE (reprint author), NINDS, Lab Neural Control, NIH, Bldg 49,Rm 3A50, Bethesda, MD 20892 USA. NR 62 TC 16 Z9 16 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2002 VL 88 IS 6 BP 3218 EP 3231 DI 10.1152/jn.00406.2002 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 626HK UT WOS:000179865600028 PM 12466442 ER PT J AU Toma, K Mima, T Matsuoka, T Gerloff, C Ohnishi, T Koshy, B Andres, F Hallett, M AF Toma, K Mima, T Matsuoka, T Gerloff, C Ohnishi, T Koshy, B Andres, F Hallett, M TI Movement rate effect on activation and functional coupling of motor cortical areas SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PARTIAL COHERENCE ANALYSIS; PACED FINGER MOVEMENTS; PARKINSONS-DISEASE; HUMAN BRAIN; CEREBRAL ACTIVATION; RHYTHMS; SYNCHRONIZATION; EEG; CORTEX; TIME AB We investigated changes in the activation and functional coupling of bilateral primary sensorimotor (SM1) and supplementary motor (SMA) areas with different movement rates in eight normal volunteers. An auditory-cued repetitive right-thumb movement was performed at rates of 0.5, 0.75, 1, 2, 3, and 4 Hz. As a control condition, subjects listened to pacing tones with no movements. Electroencephalogram (EEG) was recorded from 28 scalp electrodes and electromyogram was obtained from the hand muscles. The event-related changes in EEG band-power (ERpow: activation of each area) and correlation (ERcor: functional coupling between each pair of cortical areas) were computed every 32 ins. Modulations of ERpow and ERcor were inspected in alpha (8-12 Hz) and beta (16-20 Hz) bands. Motor cortical activation and coupling was greater for faster movements. With increasing movement rate, the timing relationship between movement and tone switched from synchronization (for 0.5-1 Hz) to syncopation (for 3-4 Hz). The results suggested that for slow repetitive movements (0.5-1 Hz), each individual movement is separately controlled, and EEG activation and coupling of the motor cortical areas were immediately followed by transient deactivation and decoupling, having clear temporal modulation locked to each movement. In contrast, for fast repetitive movements (3-4 Hz), it appears that the rhythm is controlled and the motor cortices showed sustained EEG activation and continuous coupling. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Rm 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. OI Mima, Tatsuya/0000-0001-7787-4855 NR 44 TC 55 Z9 56 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2002 VL 88 IS 6 BP 3377 EP 3385 DI 10.1152/jn.00281.2002 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 626HK UT WOS:000179865600040 PM 12466454 ER PT J AU Donchin, O Gribova, A Steinberg, O Mitz, AR Bergman, H Vaadia, E AF Donchin, O Gribova, A Steinberg, O Mitz, AR Bergman, H Vaadia, E TI Single-unit activity related to bimanual arm movements in the primary and supplementary motor cortices SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID NEURONAL-ACTIVITY; AREA; COORDINATION; CORTEX; MONKEYS; ACTIVATION; REPRESENTATIONS; DISCHARGE; LESIONS; VECTOR AB Single units were recorded from the primary motor (MI) and supplementary motor (SMA) areas of Rhesus monkeys performing one-arm (unimanual) and two-arm (bimanual) proximal reaching tasks. During execution of the bimanual movements, the task related activity of about one-half the neurons in each area (MI: 129/232, SMA: 107/206) differed from the activity during similar displacements of one arm while the other was stationary. The bulk of this "bimanual-related" activity could not be explained by any linear combination of activities during unimanual reaching or by differences in kinematics or recorded EMG activity. The bimanual-related activity was relatively insensitive to trial-to-trial variations in muscular activity or arm kinematics. For example, trials where bimanual arm movements differed the most from their unimanual controls did not correspond to the ones where the largest bimanual neural effects were observed. Cortical localization established by using a mixture of surface landmarks, electromyographic recordings, microstimulation, and sensory testing suggests that the recorded neurons were not limited to areas specifically involved with postural muscles. By rejecting this range of alternative explanations, we conclude that neural activity in MI as well as SMA can reflect specialized cortical processing associated with bimanual movements. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Physiol, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Hadassah Med Sch, Ctr Neural Computat, IL-91120 Jerusalem, Israel. NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Donchin, O (reprint author), Johns Hopkins Univ, Dept Biomed Engn, 720 Rutland Ave,Traylor 416, Baltimore, MD 21205 USA. RI Vaadia, Eilon/E-9347-2011; Donchin, Opher/A-4389-2008 OI Donchin, Opher/0000-0003-0963-4467 NR 45 TC 58 Z9 58 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2002 VL 88 IS 6 BP 3498 EP 3517 DI 10.1152/jn.00335.2001 PG 20 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 626HK UT WOS:000179865600050 PM 12466464 ER PT J AU Taber, KH Pierpaoli, C Rose, SE Rugg-Gunn, FJ Chalk, JB Jones, DK Hurley, RA AF Taber, KH Pierpaoli, C Rose, SE Rugg-Gunn, FJ Chalk, JB Jones, DK Hurley, RA TI The future for diffusion tensor imaging in neuropsychiatry SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID MATTER TRACT INTEGRITY; APPEARING WHITE-MATTER; HUMAN BRAIN; IN-VIVO; SCHIZOPHRENIA; MRI; CONNECTIVITY; ANISOTROPY; INJURY C1 Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Herbert J Frensley Ctr Imaging Res, Houston, TX 77030 USA. NINCDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. Univ Queensland, Ctr Magnet Resonance, Brisbane, Qld, Australia. Inst Neurol, Epilepsy Res Grp, London WC1N 3BG, England. Inst Psychiat, Dept Neuroimaging, London, England. Vet Affairs Med Ctr, Psychiat Serv, Houston, TX 77030 USA. RP Taber, KH (reprint author), Baylor Coll Med, Dept Radiol, 1 Baylor Plaza, Houston, TX 77030 USA. RI Rose, Stephen/C-8044-2009; Pierpaoli, Carlo/E-1672-2011; Jones, Derek/D-1460-2009; OI Jones, Derek/0000-0003-4409-8049 NR 31 TC 30 Z9 31 U1 0 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 2002 VL 14 IS 1 BP 1 EP 5 DI 10.1176/appi.neuropsych.14.1.1 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 517BD UT WOS:000173590500001 PM 11884647 ER PT J AU Bartoletti, A Cancedda, L Reid, SW Tessarollo, L Porciatti, V Pizzorusso, T Maffei, L AF Bartoletti, A Cancedda, L Reid, SW Tessarollo, L Porciatti, V Pizzorusso, T Maffei, L TI Heterozygous knock-out mice for brain-derived neurotrophic factor show a pathway-specific impairment of long-term potentiation but normal critical period for monocular deprivation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ocular dominance; neurotrophins; LTP; visual cortex; TrkB; visual deprivation ID RAT VISUAL-CORTEX; SYNAPTIC TRANSMISSION; BDNF; PLASTICITY; EXPERIENCE; HIPPOCAMPUS; INHIBITION; RESPONSES; BLOCKS; ALTERS AB Genetic deletion of a single allele of the BDNF gene affects hippocampal LTP and causes several behavioral phenotypes, including deficits in spatial learning. In the developing visual cortex, overexpression of BDNF accelerates the time course of the critical period for monocular deprivation (MD), and exogenous administration of BDNF alters the outcome of MD. We asked whether reduced levels of BDNF could affect visual cortex plasticity by studying long-term potentiation (LTP) induction and the effects of MD in heterozygous BDNF knock-out mice. We found that theta burst stimulation that induced LTP in the layer IV-III pathway of wild-type (wt) mice caused only a transient potentiation in BDNF+/- mice, and that this potentiation vanished in 25 min. In contrast, LTP elicited by stimulation of the white matter (WM), a form of LTP that can be induced only during the critical period, occurred normally in wt and BDNF+/- mice. The effects of MD during the critical period were similar in wt and BDNF+/- mice, indicating that layer IV-evoked, layer III LTP is not required for ocular dominance plasticity. We then asked whether reduction of cortical BDNF levels could prolong the critical period for MD and for the WM-evoked, layer III LTP induction. We found that in adult BDNF+/- mice, WM-evoked, layer III LTP was not inducible, and that the critical period for MD terminated normally. We conclude that deletion of one copy of the BDNF gene selectively impairs LTP of the layer IV-III pathway but does not alter ocular dominance plasticity. C1 Scuola Normale Super Pisa, Neurobiol Lab, Ist Neurosci, CNR, I-56100 Pisa, Italy. NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21701 USA. CNR, Ist Neurosci, Area Ric San Cataldo, I-56100 Pisa, Italy. RP Pizzorusso, T (reprint author), Scuola Normale Super Pisa, Neurobiol Lab, Ist Neurosci, CNR, Via Moruzzi 1, I-56100 Pisa, Italy. OI Pizzorusso, Tommaso/0000-0001-5614-0668 NR 26 TC 58 Z9 58 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 DEC 1 PY 2002 VL 22 IS 23 BP 10072 EP 10077 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 619DE UT WOS:000179458100002 PM 12451106 ER PT J AU Lu, CB Fu, WM Zhao, DH Mattson, MP AF Lu, CB Fu, WM Zhao, DH Mattson, MP TI The DNA damaging agent etoposide activates a cell survival pathway involving alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors and mitogen-activated protein kinases in hippocampal neurons SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Alzheimer's disease; apoptosis; cancer; glutamate; NMDA ID OXIDATIVE STRESS; NITRIC-OXIDE; MAP KINASE; NEURODEGENERATIVE DISORDERS; INCREASED VULNERABILITY; EXCITOTOXIC NECROSIS; ALZHEIMERS-DISEASE; PROMOTES APOPTOSIS; CORTICAL-NEURONS; STRAND BREAKS AB Etoposide, an inhibitor of topoisomerase II that induces DNA damage and can trigger cell death, is used as a chemotherapeutic agent. Because chemotherapies can result in neurological complications and because DNA damage in neurons is implicated in the pathogenesis of several neurodegenerative disorders, we studied the effects of etoposide on cultured hippocampal neurons. We found that etoposide induces neuronal apoptosis and that, prior to the cell death commitment point, there is an increase in whole-cell alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-induced current but no change in N-methyl-D-aspartate (NMDA)-induced current. Associated with the increase in AMPA-incluced current was an increase in the amounts of AMPA receptor subunits GluR1 and GluR4, whereas levels of the NMDA receptor subunit NR1 were unaffected by etoposide. AMPA receptor activation can result in excitotoxic cell death but can also activate signaling pathways that promote synaptic plasticity and cell survival. We found that etoposide increases the activation of p42 and p44 mitogen-activated protein (MAP) kinases, and that activation of the MAP kinases by etoposide requires AMPA receptor activation. Pharmacological blockade of AMPA receptors and p42/p44 MAP kinases, but not of NMDA receptors, exacerbated etoposide-induced cell death. These findings suggest that, although etoposide is neurotoxic, it also activates a cell survival pathway involving AMPA receptor-mediated activation of p42/p44 MAP kinases. Agents that selectively inhibit the cell life or death pathways triggered by DNA damage may prove useful in the settings of cancer and neurodegenerative disorders, respectively. Published 2002 Wiley-Liss, Inc. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Med Univ S Carolina, Sch Med, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, GRC 4F01,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 53 TC 6 Z9 9 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD DEC 1 PY 2002 VL 70 IS 5 BP 671 EP 679 DI 10.1002/jnr.10413 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 618GF UT WOS:000179409800007 PM 12424735 ER PT J AU Dickerman, RD Oldfield, EH AF Dickerman, RD Oldfield, EH TI Basis of persistent and recurrent Cushing disease: an analysis of findings at repeated pituitary surgery SO JOURNAL OF NEUROSURGERY LA English DT Article DE adrenocorticotropic hormone; dural invasion; pituitary adenoma; sella turcica; cavernous sinus; Cushing disease ID TRANS-SPHENOIDAL MICROSURGERY; CAVERNOUS SINUS; DURAL INVASION; TRANSSPHENOIDAL MICROSURGERY; SURGICAL-TREATMENT; ADENOMAS; HORMONE; CLASSIFICATION; THERAPY; TUMORS AB Object. The goal of this study was to establish the clinical importance of occult dural invasion-invasion of the dura mater or cavernous sinus that is not evident on imaging studies and is not obvious to the surgeon-as the basis of recurrent or persistent tumor and endocrinopathy. Methods. The authors retrospectively reviewed the case files of patients who underwent repeated transsphenoidal surgery for resection of an adrenocorticotropic hormone (ACTH)-producing pituitary adenoma. Patient selection required the availability of operative and pathology reports from the initial and repeated transsphenoidal surgeries. Because no determination of the cause of persistent or recurrent disease could be made if the tumor could not be localized during the repeated surgery, a pathology report confirming the presence of tumor from the second surgery was also required. Sixty-eight patients met these criteria. In 43 patients (63%) an ACTH-producing tumor was identified at the initial surgery, in 25 patients (37%) no tumor was found, and in three patients (4%) dural invasion was noted at surgery. In 49 (72%) of the 68 patients there was initial resolution of hypercortisolism and recurrent Cushing disease (CD), whereas in 19 patients (28%) there was persistent CD after the initial surgery. At repeated surgery (44 +/- 35 months after the initial surgery) in all 43 patients in whom tumor had been identified at the initial surgery, the tumor was found at the same site or contiguous to the same site. Dural invasion was noted by the surgeon in only three patients at the original surgery, whereas dural invasion by an ACTH-producing tumor was identified during repeated surgery in 42 (62%) of the 68 patients. In addition, 39 (93%) of the 42 invasive adenomas were located laterally and involved the cavernous sinus. Adenomatous invasion of the dura mater was found in 31 (54%) of the 57 microadenomas and in all 11 macroadenomas at repeated surgery. The presence of tumor was not detected in 28 of the 59 patients studied with magnetic resonance (MR) imaging and in none of these 59 patients was dural invasion evident on MR images. Conclusions. Recurrent and persistent CD consistently results from residual tumor. At repeated surgery the residual tumor can be found at or immediately contiguous to the site at which the tumor was found originally. Unappreciated dural invasion with growth of residual tumor within the cavernous sinus dura, which frequently occurs without residual tumor or dural invasion being evident on MR images or to the surgeon during surgery, is the basis of surgical failure in many patients with CD. Occult lateral dural invasion by tumor may also underlie recurrences of other types of pituitary adenomas. C1 Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM OldfielE@ninds.nih.gov NR 35 TC 52 Z9 54 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 2002 VL 97 IS 6 BP 1343 EP 1349 DI 10.3171/jns.2002.97.6.1343 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 626YG UT WOS:000179901000014 PM 12507132 ER PT J AU Lonser, RR Walbridge, S Vortmeyer, AO Pack, SD Nguyen, TT Gogate, N Olson, JJ Akbasak, A Bobo, RH Goffman, T Zhuang, ZP Oldfield, EH AF Lonser, RR Walbridge, S Vortmeyer, AO Pack, SD Nguyen, TT Gogate, N Olson, JJ Akbasak, A Bobo, RH Goffman, T Zhuang, ZP Oldfield, EH TI Induction of glioblastoma multiforme in nonhuman primates after therapeutic doses of fractionated whole-brain radiation therapy SO JOURNAL OF NEUROSURGERY LA English DT Article DE brain; glioblastoma multiforme; radiation-induced tumor; Macaca mulatta ID COMPARATIVE GENOMIC HYBRIDIZATION; SIMIAN IMMUNODEFICIENCY VIRUS; ACUTE LYMPHOBLASTIC-LEUKEMIA; NEURAL PROGENITOR CELLS; HUMAN GLIOMAS; IN-VITRO; MALIGNANT ASTROCYTOMA; CRANIAL IRRADIATION; GENETIC ALTERATIONS; NERVOUS-SYSTEM AB Object. To determine the acute and long-term effects of a therapeutic dose of brain radiation in a primate model, the authors studied the clinical, laboratory, neuroimaging, molecular, and histological outcomes in rhesus monkeys that had received fractionated whole-brain radiation therapy (WBRT). Methods. Twelve 3-year-old male primates (Macaca mulatta) underwent fractionated WBRT (350 cGy for 5 days/week for 2 weeks, total dose 3500 cGy). Animals were followed clinically and with laboratory studies and serial magnetic resonance (MR) imaging. They were killed when they developed medical problems or neurological symptoms, lesions appeared on MR imaging, or at study completion. Gross, histological, and molecular analyses were then performed. Nine (82%) of 11 animals that underwent long-term follow up (> 2.5 years) developed neurological symptoms and/or enhancing lesions on MR imaging, which were defined as glioblastoma multiforme (GBM), 2.9 to 8.3 years after radiation therapy. The GBMs were categorized as either unifocal (three) or multifocal (six), and were located in the supratentorial (six), infratentorial (two), or both (one) cranial regions. Histological examination revealed distant, noncontiguous tumor invasion within the white matter of all nine animals harboring GBMs. Novel interspecies comparative genomic hybridization (three animals) uniformly showed deletions in the GBMs that corresponded to chromosome 9 in humans. Conclusions. The high rate of GBM formation (82%) following a therapeutic dose of WBRT in nonhuman primates indicates that radioinduction of these neoplasms as a late complication of this therapy may occur more frequently than is currently recognized in human patients. The development of these tumors while monitoring the monkeys' conditions with clinical and serial MR imaging studies, and access to the tumor and the entire brain for histological and molecular analyses offers an opportunity to gather unique insights into the nature and development of GBMs. C1 Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008; Pack, Svetlana/C-2020-2014 NR 56 TC 20 Z9 20 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 2002 VL 97 IS 6 BP 1378 EP 1389 DI 10.3171/jns.2002.97.6.1378 PG 12 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 626YG UT WOS:000179901000019 PM 12507137 ER PT J AU Joseph, J Behar, T AF Joseph, J Behar, T TI 4th International Symposium on NeuroVirology - 10th International Conference on Neuroscience of HIV Infection SO JOURNAL OF NEUROVIROLOGY LA English DT Editorial Material C1 NIMH, NIH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. RP Joseph, J (reprint author), NIMH, NIH, Ctr Mental Hlth Res AIDS, 6001 Execut Blvd,Room 6202,MSC 9619, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 2002 VL 8 SU 2 BP 1 EP 2 DI 10.1080/13550280290101030 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 634ZG UT WOS:000180371900001 ER PT J AU Mattson, MP AF Mattson, MP TI Oxidative stress, perturbed calcium homeostasis, and immune dysfunction in Alzheimer's disease SO JOURNAL OF NEUROVIROLOGY LA English DT Review DE Alzheimer's disease; apoptosis; inositol trisphosphate; lymphocytes; ryanodine ID AMYLOID BETA-PEPTIDE; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; NECROSIS-FACTOR-ALPHA; HUMAN T-LYMPHOCYTES; NF-KAPPA-B; PRECURSOR PROTEIN; A-BETA; DIETARY RESTRICTION; MUTANT PRESENILIN-1; HIPPOCAMPAL-NEURONS AB Although Alzheimer's disease (AD) may not involve a transmissible agent, it does involve a pathogenic process similar to that of transmissible prion disorders (both involve a protein that adopts an abnormal pathogenic conformation in which it self-aggregates, forming amyloid deposits in and surrounding neurons) and viral dementias such as human immunodeficiency virus (HIV) encephalitis. The clinical presentation of patients with AD is dominated by cognitive deficits and emotional disturbances that result from dysfunction and degeneration of neurons in the limbic system and cerebral cortex. The pathogenic process in the brain involves deposition of insoluble aggregates of amyloid beta-peptide, oxidative stress and calcium dysregulation in neurons, and activation of inflammatory cytokine cascades involving microglia. However, AD patients also exhibit alterations in immune function. Studies of lymphocytes and lymphoblast cell lines from AD patients and age-matched normal control patients have documented alterations in cytokine and calcium signaling and increased levels of oxidative stress in immune cells from the AD patients. Studies of the pathogenic actions of mutations in presenilins and amyloid precursor protein that cause early-onset familial AD have established central roles for perturbed cellular calcium homeostasis and oxidative stress in the neurodegenerative process. Presenilin and amyloid precursor protein (APP) mutations also increase oxidative stress and perturb calcium signaling in lymphocytes in ways that alter their production of cytokines that are critical for proper immune responses. Immune dysfunction occurs prior to clinical symptoms in mouse models of AD, and brain cytokine responses to immune challenge are altered in presenilin mutant mice, suggesting a causal role for altered immune function in the disease process. Interestingly, immunization of AD mice with amyloid beta-peptide can stimulate the immune system to remove amyloid from the brain and can ameliorate memory deficits, suggesting that it may be possible to prevent AD by bolstering immune function. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 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 104 TC 91 Z9 100 U1 0 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 2002 VL 8 IS 6 BP 539 EP 550 DI 10.1080/13550280290100978 PG 12 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 633WB UT WOS:000180306600008 PM 12476348 ER PT J AU Ta, LE Phero, JC Pillemer, SR Hale-Donze, H McCartney-Francis, N Kingman, A Max, MB Gordon, SM Wahl, SM Dionne, RA AF Ta, LE Phero, JC Pillemer, SR Hale-Donze, H McCartney-Francis, N Kingman, A Max, MB Gordon, SM Wahl, SM Dionne, RA TI Clinical evaluation of patients with temporomandibular joint implants SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID CHRONIC-FATIGUE-SYNDROME; MULTIPLE CHEMICAL SENSITIVITIES; PITUITARY-ADRENAL AXIS; BACK-PAIN PATIENTS; GENERAL-POPULATION; SIGNAL-DETECTION; FIBROMYALGIA SYNDROME; RHEUMATOID-ARTHRITIS; THRESHOLD MEASURES; COHORT CONTROLS AB Purpose: An undetermined number of patients with temporomandibular joint (TMJ) symptoms have been treated with intra-articular disc implants composed of Teflon ethylene/propylene or Teflon polytetrafluoroethylene and aluminum oxide (Proplast-Teflon; Vitek, Houston, TX). These implants have shown the potential to fragment in situ resulting in nonbiodegradable particles that stimulate a giant cell reaction and lead to degeneration of local structures, pain, and limitation of mandibular opening. We examined the possible relationship between TMJ implants and persistent pain, responses to sensory stimuli, quality of life, and systemic immune dysfunction. Patients and Methods: This case series (32 patients) were referred from university-based orofacial pain centers and private practices from across the United States. Laboratory and clinical assessments evaluated orofacial pain symptoms, neurologic function, clinical signs and symptoms of rheumatologic disease, physical function, systemic measures of immune function, and behavioral measures. Results: We found that TMJ implant patients appeared to have altered sensitivity to sensory stimuli, a higher number of tender points with a diagnosis of fibromyalgia, increased self-report of chemical sensitivity, higher psychologic distress and significantly lower functional ability. Systemic illness or autoimmune disease was not evident in this series of TMJ implant patients. Conclusions: Significant problems were noted on clinical assessment of TMJ implant patients. This is a US government work. There are no restrictions on its use. C1 Univ Cincinnati, Med Ctr, Dept Anesthesia, Cincinnati, OH 45267 USA. NIH, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. NIH, Pain & Neurosensory Mech Branch, Bethesda, MD 20892 USA. NIH, Oral Infect & Immunity Branch, Bethesda, MD 20892 USA. RP Dionne, RA (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 10 Ctr Dr,Bldg 10,Room 1N-117, Bethesda, MD 20892 USA. EM raymond.dionne@nih.gov NR 70 TC 12 Z9 14 U1 4 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 2002 VL 60 IS 12 BP 1389 EP 1399 DI 10.1053/joms.2002.36089 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 620AG UT WOS:000179510100002 PM 12464999 ER PT J AU Patti, JW Neeman, Z Wood, BJ AF Patti, JW Neeman, Z Wood, BJ TI Radiofrequency ablation for cancer-associated pain SO JOURNAL OF PAIN LA English DT Article DE radiofrequency ablation; metastatic cancer pain AB Many treatment options are available for the management of cancer pain including drugs, local excision, radiation, brachytherapy, and nerve blocks. Percutaneous radiofrequency ablation has been used to treat painful neurologic and bone lesions and thus could potentially be used to treat cancer pain in other sites. Two superficial subcutaneous metastatic nodules were treated with percutaneous radiofrequency ablation. The patient received significant pain relief and improved quality of life. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Bethesda, MD USA. RP Wood, BJ (reprint author), NIH, Ctr Clin, Bldg 10,Room 1C660, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 10 TC 10 Z9 10 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD DEC PY 2002 VL 3 IS 6 BP 471 EP 473 DI 10.1054/jpai.2002.126785 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 629RJ UT WOS:000180062400007 PM 14622733 ER PT J AU Wang, SS O'Leary, LA FitzSimmons, SC Khoury, MJ AF Wang, SS O'Leary, LA FitzSimmons, SC Khoury, MJ TI The impact of early cystic fibrosis diagnosis on pulmonary function in children SO JOURNAL OF PEDIATRICS LA English DT Article ID PSEUDOMONAS-AERUGINOSA; PATIENT REGISTRY; GROWTH; MALNUTRITION; ACQUISITION; MORTALITY; RISK AB Objective: To investigate the impact of early diagnosis on pulmonary function in a large cohort of children with cystic fibrosis (CF). Study design: CF cases identified from the CF Foundation National Patient Registry and diagnosed between 1982 and 1990 were categorized as: early asymptomatic diagnosis (EAD; n = 157), early symptomatic diagnosis (ESD; n = 227), later asymptomatic diagnosis (LAD; n = 161), and later symptomatic diagnosis (LSD; n = 3080). Early CF diagnosis was diagnosis before 6 weeks of age; later diagnosis was diagnosis at 6 weeks to 36 months of age, inclusive. Asymptomatic diagnosis included diagnosis by either family history, genotype, prenatally, or neonatally. Pulmonary function was measured as percentage of predicted forced expiratory volume in one second (FEV1). Results: There were no overall differences in pulmonary function among the 4 diagnostic groups. However, EAD cases born more recently (1987 or later) had a higher mean FEV1 throughout the study, compared with the remaining diagnostic groups. For this later birth cohort, Cox regression analysis for those diagnosed later and/or symptomatically, demonstrated a 2-fold increase in risk (P = .06) for having moderate-to-severe pulmonary function (FEV1 < 70%) at ages 6 to 10 years, compared with EAD cases. Conclusions: Children diagnosed with CF early, asymptomatically and more recently may have better pulmonary function throughout early childhood, probably as a result of improved CF treatments in recent years. C1 Ctr Dis Control & Prevent, Off Genet & Dis Prevent, Atlanta, GA USA. Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. Cyst Fibrosis Fdn, Bethesda, MD USA. RP Wang, SS (reprint author), NCI, 6120 Execut blvd,Execut Plaza S,Room 7072, Rockville, MD 20852 USA. EM wangso@mail.nih.gov NR 24 TC 31 Z9 33 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2002 VL 141 IS 6 BP 804 EP 810 DI 10.1067/mpd.2002.129845 PG 7 WC Pediatrics SC Pediatrics GA 625UN UT WOS:000179834100014 PM 12461497 ER PT J AU Cascio, I Rapaka, RS AF Cascio, I Rapaka, RS TI Structural biology and structural genomics/proteomics SO JOURNAL OF PEPTIDE RESEARCH LA English DT Editorial Material C1 Natl Inst Drug Abuse, Div Neurosci & Behav Res, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Rapaka, RS (reprint author), Natl Inst Drug Abuse, Div Neurosci & Behav Res, 6001 Execut Blvd,Room 4282,MSC 9555, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-002X J9 J PEPT RES JI J. Pept. Res. PD DEC PY 2002 VL 60 IS 6 BP 307 EP 311 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 630AB UT WOS:000180084200002 ER PT J AU McCrae, RR Costa, PT Terracciano, A Parker, WD Mills, CJ De Fruyt, F Mervielde, I AF McCrae, RR Costa, PT Terracciano, A Parker, WD Mills, CJ De Fruyt, F Mervielde, I TI Personality trait development from age 12 to age 18: Longitudinal, cross-sectional, and cross-cultural analyses. SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT Inaugural Conference of the Association-for-Research-in-Personality CY FEB, 2001 CL SAN ANTONIO, TX SP Assoc Res Personality ID 5-FACTOR MODEL; LIFE-SPAN; TEMPERAMENT; CHILDHOOD; SELF; ADOLESCENTS; DEPRESSION; EXPERIENCE; PSYCHOLOGY; ADULTHOOD AB Three studies were conducted to assess mean level changes in personality traits during adolescence. Versions of the Revised NEO Personality Inventory (P. T. Costa, Jr., & R. R. McCrae, 1992a) were used to assess the 5 major personality factors. A 4-year longitudinal study of intellectually gifted students (N =. 230) was supplemented by cross-sectional studies of nonselected American (N = 1,959) and Flemish (N = 789) adolescents. Personality factors were reasonably invariant across ages, although rank-order stability of individual differences was low. Neuroticism appeared to increase in girls, and Openness to Experience increased in both boys and girls; mean levels of Extraversion, Agreeableness, and Conscientiousness were stable. Results extend knowledge of the developmental curve of personality traits backward from adulthood and help bridge the gap with child temperament studies. C1 NIA, Gerontol Res Ctr, Stress & Coping Sect, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Ctr Talented Youth, Baltimore, MD 21218 USA. State Univ Ghent, Dept Psychol, B-9000 Ghent, Belgium. RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, Stress & Coping Sect, NIH, 5600 Nathan Shock Dr,Box 3, Baltimore, MD 21224 USA. EM jeffm@lpc.grc.nia.nih.gov RI terracciano, antonio/B-1884-2008; Mervielde, Ivan/B-4655-2008; De Fruyt, Filip/A-3083-2009; Vollrath, Margarete/G-1297-2011; OI Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS [Z99 AG999999, ZIA AG000180-25, ZIA AG000180-26, ZIA AG000183-22, ZIA AG000183-23] NR 86 TC 177 Z9 182 U1 7 U2 59 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-3514 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD DEC PY 2002 VL 83 IS 6 BP 1456 EP 1468 DI 10.1037//0022-3514.83.6.1456 PG 13 WC Psychology, Social SC Psychology GA 622RY UT WOS:000179661800015 PM 12500824 ER PT J AU Takebayashi, M Hayashi, T Su, TP AF Takebayashi, M Hayashi, T Su, TP TI Nerve growth factor-induced neurite sprouting in PC12 cells involves sigma-1 receptors: Implications for antidepressants SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID FORCED SWIMMING TEST; GUINEA-PIG BRAIN; RAT-BRAIN; BINDING-SITES; NEUROACTIVE STEROIDS; OPIOID RECEPTOR; PROTEIN-KINASE; MESSENGER-RNA; SIGMA(1)-RECEPTORS; DEPRESSION AB One theory concerning the action of antidepressants relates to the drugs' ability to induce an adaptive plasticity in neurons such as neurite sprouting. Certain antidepressants are known to bind to sigma-1 receptors (Sig-1R) with high affinity. Sig-1R are dynamic endoplasmic reticulum proteins that are highly concentrated at the tip of growth cones in cultured cells. We therefore tested the hypotheses that Sig-1R might participate in the neurite sprouting and that antidepressants with Sig-1R affinity may promote the neuronal sprouting via Sig-1R. The prototypic Sig-1R agonist (+)pentazocine [(+)PTZ], as well as the Sig-1R-active antidepressants imipramine and fluvoxamine, although ineffective by themselves, were found to enhance the nerve growth factor (NGF)induced neurite sprouting in PC12 cells in a dose-dependent manner. A Sig-1R antagonist N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE100) blocked the enhancements caused by these Sig-1R agonists. In separate experiments, we found that NGF dose and time dependently increased Sig-1R in PC12 cells. Chronic treatment of cells with (+)PTZ, imipramine, or fluvoxamine also increased Sig-1R. These latter results suggested that NGF induces the neurite sprouting by increasing Sig-1R. Indeed, the overexpression of Sig-1R per se in PC12 cells enhanced the NGF-induced neurite sprouting. Furthermore, antisense deoxyoligonucleotides directed against Sig-1R attenuated the NGF-induced neurite sprouting. Thus, when taken together, our results indicate that Sig-1R play an important role in the NGF-induced neurite sprouting and that certain antidepressants may facilitate neuronal sprouting in the brain via Sig-1R. C1 NIDA, Cellular Pathobiol Unit, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Su, TP (reprint author), NIDA, Cellular Pathobiol Unit, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Hayashi, Teruo/A-9690-2008 NR 40 TC 89 Z9 95 U1 1 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2002 VL 303 IS 3 BP 1227 EP 1237 DI 10.1124/jpet.102.041970 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 616EN UT WOS:000179290500042 PM 12438547 ER PT J AU Ravi, N Mitra, A Hamilton, P Horkay, F AF Ravi, N Mitra, A Hamilton, P Horkay, F TI Characterization of the network properties of poly(ethylene glycol)-acrylate hydrogels prepared by variations in the ethanol-water solvent composition during crosslinking copolymerization SO JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS LA English DT Article; Proceedings Paper CT 222nd National Meeting of the American-Chemical-Society CY AUG 26-30, 2001 CL CHICAGO, ILLINOIS SP Amer Chem Soc DE poly(ethylene glycol)-acrylate hydrogels; crosslinking; copolymerization; mixed solvent; kinetics (polym.); mechanical properties ID OXIDE) MACROMONOMERS; POLYMERIZATION AB The characteristics of poly(ethylene glycol) (PEG)-acrylate hydrogel networks were investigated as a function of the ethanol-water solvent composition during free-radical crosslinking copolymerization. Macromonomer (88% omega-methoxy-PEG-acrylate and 10% omega-phenoxy-PEG-acrylate) and crosslinker (2% PEG-diacrylate) concentrations were kept constant. As the copolymerization progressed, the polymer solution in 100% ethanol became increasingly turbid, indicating the development of a heterogeneous network structure. In 100% water, however, the initially turbid polymer solution became increasingly transparent as the crosslinking copolymerization progressed. All the gels were optically clear upon equilibration in water. Kinetic studies, with attenuated total reflectance-infrared, showed a long induction period, along with a lowered reaction rate, in 100% ethanol, and a decrease in conversion with an increase in ethanol content. These results agree with the UV analysis of the Sol fractions, which indicated an increase in the amounts of unreacted PEG-acrylates with an increase in the ethanol content. The gels which were formed with a high ethanol concentration exhibited lower Young's modulus and higher swelling ability, suggesting that the network structure was significantly affected by the solvent composition during free-radical crosslinking copolymerization. From the stress-strain and swelling experiments, the Flory-Huggins interaction parameter was evaluated. The creep characteristics of the hydrogels were modeled with two Kelvin elements. (C) 2002 Wiley Periodicals, Inc. C1 Vet Affairs Med Ctr, Dept Surg, St Louis, MO 63125 USA. Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63130 USA. Washington Univ, Dept Chem Engn, St Louis, MO 63130 USA. Vet Affairs Med Ctr, Dept Med Res, St Louis, MO USA. NICHD, Lab Integrat & Med Phys, NIH, Bethesda, MD USA. RP Ravi, N (reprint author), Vet Affairs Med Ctr, Dept Surg, St Louis, MO 63125 USA. NR 24 TC 21 Z9 23 U1 0 U2 16 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-6266 J9 J POLYM SCI POL PHYS JI J. Polym. Sci. Pt. B-Polym. Phys. PD DEC 1 PY 2002 VL 40 IS 23 BP 2677 EP 2684 DI 10.1002/polb.10306 PG 8 WC Polymer Science SC Polymer Science GA 613UF UT WOS:000179149300009 ER PT J AU McClure, EB Lilienfeld, SO AF McClure, EB Lilienfeld, SO TI The dark side of Absorption: Empirical associations between an experiential response style and hypochondriacal concerns SO JOURNAL OF RESEARCH IN PERSONALITY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Personality CY 2002 CL SAVANNAH, GEORGIA SP Assoc Res Personal ID PERSONALITY; HYPNOTIZABILITY; VIVIDNESS; SYMPTOMS; IMAGERY AB We examined associations between hypochondriacal concerns and the personality dimensions of Absorption and Negative Emotionality (NE). On the basis of research suggesting that Absorption is associated with both negative and positive affective experiences, we hypothesized that participants with high levels of Absorption and NE would report higher levels of hypochondriacal concerns. A sample of 212 undergraduates completed a set of self-report measures assessing Absorption, NE, and aspects of hypochondriacal concerns. Results provide preliminary but mixed evidence that Absorption relates positively to certain hypochondriacal concerns, in some cases by means of interactions with NE. Published by Elsevier Science (USA). C1 Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. NIMH, Bethesda, MD 20892 USA. RP Lilienfeld, SO (reprint author), Emory Univ, Dept Psychol, 532 Kilgo Circle, Atlanta, GA 30322 USA. NR 26 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0092-6566 J9 J RES PERS JI J. Res. Pers. PD DEC PY 2002 VL 36 IS 6 BP 573 EP 579 AR PII S0092-6566(02)00507-X DI 10.1016/S0092-6566(02)00507-X PG 7 WC Psychology, Social SC Psychology GA 624TQ UT WOS:000179777900008 ER PT J AU Morf, CC AF Morf, CC TI Personality at the hub: Extending the conception of personality psychology SO JOURNAL OF RESEARCH IN PERSONALITY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Personality CY 2002 CL SAVANNAH, GEORGIA SP Assoc Res Personal ID REGULATORY PROCESSING MODEL; NEUROSCIENCE; NARCISSISM; BEHAVIOR AB Personality psychology has a focus on understanding the functioning of the person as a whole, and is thus located at the hub of the other sub-disciplines of psychology and related sciences devoted to the study of human nature. As such, personality is well situated to integrate work emerging from different levels of analysis related to the distinctive organization and operation of psychological processes that characterize individuals. Personality psychology can have an exciting future to the extent that it can cross arbitrary lines of sub-disciplines, and connect with relevant interdisciplinary work devoted to understanding psychological phenomena, regardless of traditional boundaries. Several important areas of connection are highlighted, including links to social psychology, biology, and psychopathology, but trying to set priorities in terms of substantive areas for the field seems a futile exercise. Also discussed is the pressing need to find the most fruitful levels of abstraction at which to conceptualize our constructs to maximize their yield. (C) 2002 Elsevier Science (USA). All rights reserved. C1 NIMH, Bethesda, MD 20892 USA. RP Morf, CC (reprint author), NIMH, 6001 Execut Blvd,Room 7216,MSC 9651, Bethesda, MD 20892 USA. NR 27 TC 9 Z9 9 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0092-6566 J9 J RES PERS JI J. Res. Pers. PD DEC PY 2002 VL 36 IS 6 BP 649 EP 660 AR PII S0092-6566(02)00517-2 DI 10.1016/S0092-6566(02)00517-2 PG 12 WC Psychology, Social SC Psychology GA 624TQ UT WOS:000179777900018 ER PT J AU Schaaf, MJM Cidlowski, JA AF Schaaf, MJM Cidlowski, JA TI Molecular mechanisms of glucocorticoid action and resistance SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 15th International Symposium of the Journal of Steroid Biochemistry and Molecular Biology CY MAY 17-20, 2002 CL MUNICH, GERMANY DE glucocorticoid; glucocorticoid receptor; homologous down-regulation; beta-isoform; NF-kappa B ID NF-KAPPA-B; RECEPTOR MESSENGER-RNA; HORMONE-BINDING DOMAIN; HEAT-SHOCK-PROTEIN; SITE-DIRECTED MUTAGENESIS; BETA-ISOFORM; NUCLEAR RECEPTORS; DOWN-REGULATION; TRANSCRIPTIONAL ACTIVATION; DNA-BINDING AB The actions of glucocorticoid hormones are mediated by an intracellular receptor, the glucocorticoid receptor (GR). The mechanism of action of this ligand-inducible transcription factor is discussed, focusing on mechanisms of glucocorticoid resistance. Three mechanisms are highlighted: ligand-induced down-regulation of the receptor, the dominant-negative inhibition by the beta-isoform of the receptor, and repression by the transcription factor NF-kappaB. It has been shown that these mechanisms can significantly inhibit glucocorticoid signaling, and could therefore seriously decrease the efficacy of glucocorticoids used clinically. (C) 2003 Published by Elsevier Science Ltd. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 149 TC 255 Z9 269 U1 3 U2 27 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD DEC PY 2002 VL 83 IS 1-5 BP 37 EP 48 DI 10.1016/S0960-0760(02)00263-7 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 670BM UT WOS:000182387400006 PM 12650700 ER PT J AU Ball, S Bachrach, K DeCarlo, J Farentinos, C Keen, M McSherry, T Polcin, D Snead, N Sockriter, R Wrigley, P Zammarelli, L Carroll, K AF Ball, S Bachrach, K DeCarlo, J Farentinos, C Keen, M McSherry, T Polcin, D Snead, N Sockriter, R Wrigley, P Zammarelli, L Carroll, K TI Characteristics, belief, and practices of community clinicians trained to provide manual-guided therapy for substance abusers SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE training; technology transfer; psychotherapy; substance abuse ID PSYCHOTHERAPY TREATMENT MANUALS; INTERPERSONAL PSYCHOTHERAPY; ALCOHOLISM; COUNSELORS; DISSEMINATION; PRACTITIONERS; DEPRESSION; CHALLENGE; SUCCESS; ISSUES AB The successful dissemination of empirically supported addiction therapies to community providers requires an appreciation. of the characteristics of those practitioners who might be willing participants in this process of technology transfer. Clinicians (N = 66) from I I community treatment programs associated with six research-clinic partnerships of the National Drug Abuse Clinical Trials Network volunteered to be trained in Motivational Interviewing or Motivational Enhancement Therapy (MET/MI) and were assessed prior to training. The sample of clinicians was heterogeneous in education and credentials, had a, high level of counseling experience, reported using a wide range of counseling techniques and orientations, but had limited prior exposure to MET/MI or to the use of treatment manuals of empirically supported therapies. In general, many of the clinicians reported beliefs and techniques that were consistent with their stated theoretical orientation and recovery status. Relatively few participants reported relying on one dominant orientation or set of techniques. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Yale Univ, Sch Med, VA CT Healthcare, Div Subst Abuse, West Haven, CT 06516 USA. Tarzana Treatment Ctr, Tarzana, CA 91356 USA. Lower E Side Serv Ctr, New York, NY 10002 USA. ChangePoint Inc, Portland, OR 97292 USA. Connecticut Renaissance Inc, Norwalk, CT 06852 USA. NE Treatment Ctr Inc, Philadelphia, PA 19123 USA. Haight Ashbury Free Clin Inc, San Francisco, CA 94117 USA. Chesterfield Subst Abuse Serv, Chesterfield, VA 23832 USA. Rehab Work, Philadelphia, PA 19301 USA. ADAPT Inc, Roseburg, OR 97470 USA. Willamette Family Treament Serv Inc, Eugene, OR 97402 USA. NIDA, Natl Drug Abuse Clin Trials Network, NIH, Bethesda, MD 20892 USA. RP Ball, S (reprint author), Yale Univ, Sch Med, VA CT Healthcare, Div Subst Abuse, 151D,950 Campbell Ave,Bldg 35, West Haven, CT 06516 USA. RI Carroll, Kathleen/A-7526-2009 FU NIDA NIH HHS [U10 DA013038, P50 DA009241, U10 DA13034, U10 DA13036, U10 DA13038, U10 DA13043, U10 DA13045, U10 DA13046] NR 46 TC 76 Z9 77 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD DEC PY 2002 VL 23 IS 4 BP 309 EP 318 AR PII S0740-5472(02)00281-7 DI 10.1016/S0740-5472(02)00281-7 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 631CV UT WOS:000180150500006 PM 12495792 ER PT J AU Thompson, FE Subar, AF Smith, AF Midthune, D Radimer, KL Kahle, LL Kipnis, V AF Thompson, FE Subar, AF Smith, AF Midthune, D Radimer, KL Kahle, LL Kipnis, V TI Fruit and vegetable assessment: Performance of 2 new short instruments and a food frequency questionnaire SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DOUBLY LABELED WATER; DIETARY ASSESSMENT METHODS; REPORTED ENERGY-INTAKE; CONSUMPTION; WOMEN; VALIDATION; VALIDITY; CANCER; HEALTH; RECALL AB Objective To evaluate the ability of 2 new short assessment instruments and a food frequency questionnaire (FFQ) to measure intake of fruit and vegetables. The "All-Day" screener asks frequency and portion size questions about 9 food items. The "By-Meal" screener is similar, except that it asks about 2 of those 9 food items in terms of mealtime. Design Survey participants completed 4 telephone-administered 24-hour dietary recalls over 1 year, a self-administered FFQ 1 to 2 months later, and 1 of 2 self-administered screeners after an additional 7 months. Subjects/setting Participating were 202 men and 260 women aged 20 to 70 years living throughout the United States. Statistical analyses Fruit and vegetable intakes measured by each screener and the FFQ were compared with true usual intake based on a measurement error model with 24-hour dietary recalls as the reference instrument. Results Estimates of median daily servings of fruit and vegetables were as follows: For men: True intake (5.8) vs All-Day screener (5.0), By-Meal screener (5.5), and FFQ (6.6); for women: true intake (4.2) vs All-Day screener (5.0), By-Meal screener (5.4), and FFQ (6.2). Estimated correlations between the test instruments and true intake were as follows: For men: All-Day screener (0.66), By-Meal screener (0.67), FFQ (0.68); for women: All-Day screener (0.51), By-Meal screener (0.53), and FFQ (0.54). Applications/conclusions Both screeners might be useful to estimate median intakes of fruit and vegetable servings in US populations, but they might be less useful in accurately ranking individuals. More research is needed before using the screeners in ethnic or low-literacy populations. C1 NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Cleveland State Univ, Dept Psychol, Cleveland, OH 44115 USA. Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Thompson, FE (reprint author), NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, EPN 4016,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. NR 29 TC 170 Z9 171 U1 3 U2 17 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD DEC PY 2002 VL 102 IS 12 BP 1764 EP 1772 DI 10.1016/S0002-8223(02)90379-2 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 623QM UT WOS:000179714400010 PM 12487538 ER PT J AU Ferrucci, L Penninx, BWJH Volpato, S Harris, TB Bandeen-Roche, K Balfour, J Leveille, SG Fried, LP Guralnik, JM AF Ferrucci, L Penninx, BWJH Volpato, S Harris, TB Bandeen-Roche, K Balfour, J Leveille, SG Fried, LP Guralnik, JM TI Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE IL-6; cytokines; disability; inflammation; aging; older women ID POPULATION; COMMUNITY; IL-6 AB OBJECTIVES: To test whether accelerated sarcopenia in older persons with high interleukin (IL)-6 serum levels plays a role in the prospective association between inflammation and disability found in many studies. DESIGN: Cohort study of older women with moderate to severe disability. PARTICIPANTS: Six hundred twenty older women from the Women's Health and Aging Study in whom information on baseline IL-6 serum level was available. MEASURMENTS: Self-report of functional status, objective measures of walking performance, and knee extensor strength were assessed at baseline and over six semiannual follow-up visits. Potential confounders were baseline age, race, body mass index, smoking, depression, and medical conditions. RESULTS: At baseline, women with high IL-6 were more often disabled and had lower walking speed. After adjusting for confounders, women in the highest IL-6 tertile (IL-6 > 3.10 pg/mL) were at higher risk of developing incident mobility disability (risk ratio (RR) = 1.50, 95% confidence interval (CI) = 1.01-2.27), disability in activities of daily living (RR = 1.41, 95% CI = 1.01-1.98), and severe limitation in walking (RR = 1.61, 95% CI = 1.09-2.38) and experienced steeper declines in walking speed (P < .001) than women in the lowest IL-6 tertile (IL-6 &LE;1.78 pg/mL). Decline in knee extensor strength was also steeper, but differences across IL-6 tertiles were not significant. After adjusting for change over time in knee extensor strength, the association between high IL-6 and accelerated decline of physical function was no longer statistically significant. CONCLUSIONS: Older women with high IL-6 serum levels have a higher risk of developing physical disability and experience a steeper decline in walking ability than those with lower levels, which are partially explained by a parallel decline in muscle strength. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. INRCA Geriatr Dept, Lab Clin Epidemiol, Florence, Italy. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA. RP Ferrucci, L (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C-309, Bethesda, MD 20892 USA. RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 FU NIA NIH HHS [N01-AG-0-2105] NR 19 TC 291 Z9 295 U1 1 U2 11 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2002 VL 50 IS 12 BP 1947 EP 1954 DI 10.1046/j.1532-5415.2002.50605.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 624EM UT WOS:000179747400005 PM 12473005 ER PT J AU Vaitkevicius, PV Ebersold, C Shah, MS Gill, NS Katz, RL Narrett, MJ Applebaum, GE Parrish, SM O'Connor, FC Fleg, JL AF Vaitkevicius, PV Ebersold, C Shah, MS Gill, NS Katz, RL Narrett, MJ Applebaum, GE Parrish, SM O'Connor, FC Fleg, JL TI Effects of aerobic exercise training in community-based subjects aged 80 and older: A pilot study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aerobic training; older people; exercise; oxygen consumption ID PHYSICAL-ACTIVITY; CARDIOVASCULAR-RESPONSES; ADULTS; MEN; VO2MAX; WOMEN; FITNESS AB OBJECTIVES: To assess the ability of sedentary, frail subjects aged 80 and older to train in a community-based exercise program and to evaluate clinical factors that predict improvements in peak oxygen consumption (VO(2)peak). DESIGN: Pretest, posttest. SETTING: Charlestown Retirement Community, Catonsville, Maryland PARTICIPANTS: Twenty-two (11 male, 11 female; mean age +/- standard deviation = 84 +/- 4.0, range 80-92) self-referred. INTERVENTION: Six months of moderate-intensity aerobic exercise training, two to three sessions/week, 20 to 30 minutes per session. Training modes included treadmill walking and/or stationary cycling. MEASUREMENTS: Baseline and follow-up maximal exercise treadmill tests (ETTs) with electrocardiogram monitoring and respiratory gas analysis. RESULTS: Six months of aerobic exercise training resulted in significant increases (mean +/- standard deviation) in ETT duration (11.9 +/- 3.3 vs 15.9 +/- 4.3 minutes; P = .01), VO(2)peak (1.23 +/- 0.37 vs 1.31 +/- 0.36 L/min; P = .04), and oxygen pulse (9.3 +/- 2.8 vs 10.1 +/- 3.2; P = .03). Mean heart rate was significantly lower during submaximal ETT stages 1 through 4 (P < .05), and resting systolic blood pressure decreased (146 +/- 18 vs 133 +/- 14 mmHg; P = .01) after training. Multiple regression analysis indicated that baseline VO(2)peak (r = 0.75, P = .002) and the total amount of time spent in exercise training (r = 0.55, P = .008) were independent predictors of the training-related improvements in VO(2)peak. CONCLUSIONS: Subjects aged 80 and older can increase aerobic capacity and reduce systolic blood pressure in a community-based exercise program of moderate intensity. The most important predictors of change in VO(2)peak were baseline VO(2)peak and the time spent in exercise training. Subjects with a lower baseline VO(2)peak had the greatest improvements in VO(2)peak after training. C1 Ctr Geriatr Res Educ & Clin, VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48105 USA. Univ Michigan, Div Geriatr & Cardiol, Ann Arbor, MI 48109 USA. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Ericksons Retirement Communities, Baltimore, MD USA. RP Vaitkevicius, PV (reprint author), Ctr Geriatr Res Educ & Clin, VA Ann Arbor Healthcare Syst, 11G,2215 Fuller Rd, Ann Arbor, MI 48105 USA. FU NIA NIH HHS [P0-1-AG-04402] NR 22 TC 29 Z9 29 U1 1 U2 8 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2002 VL 50 IS 12 BP 2009 EP 2013 DI 10.1046/j.1532-5415.2002.50613.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 624EM UT WOS:000179747400013 PM 12473013 ER PT J AU Slutsman, J Emanuel, LL Fairclough, D Bottorff, D Emanuel, EJ AF Slutsman, J Emanuel, LL Fairclough, D Bottorff, D Emanuel, EJ TI Managing end-of-life care: Comparing the experiences of terminally ill patients in managed care and fee for service SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE managed care; outcomes; terminally ill; end-of-life; empirical research ID MEDICAL-CARE; HEALTH-CARE; QUALITY; SATISFACTION; ENROLLEES; INSURANCE; BURDEN; NEEDS; HMO AB There have been no published empirical studies comparing the experiences of terminally ill patients in managed care organizations (MCOs) and those in fee for service (FFS). This investigation represents the first empirical study to systematically compare substantive outcomes between populations of terminally ill patients enrolled in MCO and FFS healthcare delivery systems. The investigators interviewed 988 patients whose physicians judged them to be terminally ill and 893 of their caregivers. Outcomes assessments were made in six domains: patient-physician relationship; access to care and use of health care; prevalence of symptoms; and planning for end-of-life care, care needs, and economic burdens. Overall, the two populations of terminally ill patients were found to have comparable outcomes, but several significant differences were present. MCO patients were more likely than their FFS counterparts to use an inconvenient hospital (P = .02), spend more than 10% of their income on medical care (P = .02), and have been bedridden more than 50% of the time during the last 4 weeks of life (P = .03). Caregivers of MCO patients were as likely as the caregivers of FFS patients to report a substantial caregiving burden (P = .59). Despite concerns about the threats of MCOs to the physician-patient relationship, few differences in the quality of the relationship between the two cohorts were found. Finally, terminally ill patients in MCOs did not show better experiences than those in FFS on any outcome measure. Additional research is required to explore how MCOs may improve upon the care available to dying patients. C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. Northwestern Univ, Feinberg Sch Med, Buehler Ctr Aging, Chicago, IL 60611 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometry, Colorado Hlth Outcomes Program, Denver, CO USA. Univ Kentucky, Canc Informat Serv, Lexington, KY USA. RP Emanuel, LL (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA. NR 42 TC 8 Z9 8 U1 1 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2002 VL 50 IS 12 BP 2077 EP 2083 DI 10.1046/j.1532-5415.2002.50622.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 624EM UT WOS:000179747400022 PM 12473022 ER PT J AU Bucci, JR Matsumoto, CS Swanson, SJ Agodoa, LYC Holtzmuller, KC Peters, TG Abbott, KC AF Bucci, JR Matsumoto, CS Swanson, SJ Agodoa, LYC Holtzmuller, KC Peters, TG Abbott, KC TI Donor hepatitis C seropositivity: Clinical correlates and effect on early graft and patient survival in adult cadaveric kidney transplantation SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ANTIBODY-POSITIVE DONORS; STAGE RENAL-DISEASE; VIRUS-INFECTION; ORGAN-TRANSPLANTATION; UNITED-STATES; RECIPIENTS; IMPACT; TRANSMISSION; CANDIDATES; DIALYSIS AB The impact of hepatitis C virus-positive donor kidneys on patient survival has not been analyzed in a national study. This study analyzed 20,111 adult (age, greater than or equal to16 yr) recipients having solitary cadaveric kidney transplants from adult donors with valid donor hepatitis C serologies from July 1, 1994, to June 30, 1998, in an historical cohort study (the 2000 United States Kidney Data System) of patient survival. Analysis was by the Cox proportional hazards models, which corrected for characteristics thought to affect outcomes. Of 484 kidneys positive for hepatitis C virus serology, 165 (34%) were given to recipients with confirmed negative hepatitis C serologies. Unadjusted 3-yr patient survival was 93% in all recipients of donor hepatitis C-negative kidneys versus 85% in all recipients of donor hepatitis C-positive kidneys (P = 0.01). Among hepatitis C-positive recipients, those who received hepatitis C-positive kidneys had worse survival than recipients of hepatitis C-negative kidneys. Among elderly hepatitis C-negative recipients, those who received hepatitis C-positive kidneys also had worse survival; in fact, all recipients of donor hepatitis C-positive kidneys had increased risk of mortality (P = 0.028). There were no significant interactions between donor hepatitis C positivity and either recipient hepatitis C positivity or older recipient age. The use of hepatitis C-positive kidneys in recipients who were hepatitis C-negative was fairly common and contrary to some current recommendations. Recipients of donor hepatitis C-positive kidneys were at independently increased risk of mortality, with no evidence that any subgroups were less affected. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Sch Hlth Sci, Bethesda, MD USA. WRAMC, Organ Transplant Serv, Washington, DC USA. NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. WRAMC, Gastroenterol Serv, Washington, DC USA. Jacksonville Transplant Ctr Shands, Jacksonville, FL USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 42 TC 48 Z9 48 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2002 VL 13 IS 12 BP 2974 EP 2982 DI 10.1097/01.ASN.0000034944.90425.75 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 618HT UT WOS:000179413200018 PM 12444217 ER PT J AU Hostetter, TH AF Hostetter, TH TI The next treatments of chronic kidney disease: If we find them, can we test them? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID RENAL-DISEASE; ACE-INHIBITION; NEPHROPATHY; BLOCKADE C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Hostetter, TH (reprint author), NIDDKD, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA. NR 14 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2002 VL 13 IS 12 BP 3024 EP 3026 DI 10.1097/01.ASN.0000042343.03375.1B PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 618HT UT WOS:000179413200024 PM 12444223 ER PT J AU Liu, Q Proschan, MA Pledger, GW AF Liu, Q Proschan, MA Pledger, GW TI A unified theory of two-stage adaptive designs SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE adaptive design; adaptive p value; conditional error function; confidence intervals; pivotal quantity; two-stage adaptive design; type I error rate; unbiased estimator ID CLINICAL-TRIALS; SAMPLE-SIZE; INTERIM ANALYSES AB Adaptation of a clinical trial occurs when there is a change from the planned course of action in design, sample size, or method of analysis. There are many proposed adaptations in the literature, but no comprehensive mathematical theory to support them. The standard Neyman-Pearson theory is not suitable for the setting, and its use may result in invalid inference. This article provides a general formulation of adaptation, under which its validity can be broadly and rigorously established. The basic theory on distribution, stochastic independence, point estimation, confidence intervals, hypothesis testing, and asymptotics is developed. Various examples are given to illustrate applications of the theory. The goal is to provide a solid theoretical foundation to aid the development of adaptive methods for clinical investigations. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NR 19 TC 53 Z9 53 U1 0 U2 3 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 2002 VL 97 IS 460 BP 1034 EP 1041 DI 10.1198/016214502388618852 PG 8 WC Statistics & Probability SC Mathematics GA 632TX UT WOS:000180239900014 ER PT J AU Dickerman, RD Stevens, QEJ Cohen, AJ Jaikumar, S AF Dickerman, RD Stevens, QEJ Cohen, AJ Jaikumar, S TI Radial tunnel syndrome in an elite power athlete: a case of direct compressive neuropathy SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Article DE palsy; peripheral nerve; posterior interosseous nerve; powerlifting; supinator muscle ID PRESSURE; TESTOSTERONE; CONTRACTION; MUSCLE; SIZE AB Radial tunnel syndrome (RTS) is thought to result from intermittent and dynamic compression of the posterior interosseous nerve (PIN) in the proximal part of the forearm associated with repeated supination and pronation. The diagnostic criteria encompassing RTS are purely clinical and the term "radial tunnel syndrome" has become controversial because of the lack of focal motor weakness in the majority of patients diagnosed with RTS. Retrospective cadaveric and surgical studies have revealed several areas within the forearm in which the PIN may become entrapped. Recent studies have suggested that the PIN is "fixed" in the supinator muscle and that wrist pronation is the actual movement that places the most stress on the PIN. The patients most often afflicted with RTS appear to be those who perform repetitive manual tasks involving rotation of the forearm and athletes involved in racket sports. Surgical exploration with decompression of the PIN is often required in patients with RTS. We present the first case of RTS occurring in an elite power athlete and believe this case represents a direct compressive sensory neuropathy. The optimum nonsurgical treatment plan for the elite athlete in training for competition and the cause of this compressive neuropathy in power athletes will be discussed. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Dickerman, RD (reprint author), Long Isl Jewish Med Ctr, Dept Surg, Div Neurosurg, 260-12 74th Ave, Glen Oaks, NY 11004 USA. NR 15 TC 13 Z9 14 U1 0 U2 1 PU WOODLAND PUBLICATIONS, INC PI NEW YORK PA 69 MURRAY ST, NEW YORK, NY 10007 USA SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD DEC PY 2002 VL 7 IS 4 BP 229 EP 232 DI 10.1046/j.1529-8027.2002.02030.x PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 620QA UT WOS:000179543000004 PM 12477169 ER PT J AU Pautler, SE Phillips, JL Walther, MM AF Pautler, SE Phillips, JL Walther, MM TI Assessment of risk for intra-abdominal adhesions at laparoscopy for urological tumors SO JOURNAL OF UROLOGY LA English DT Article DE urinary tract; laparoscopy; adhesions; risk factors; urologic neoplasms ID WALL ADHESIONS; SURGERY; TROCAR; ENTRY; PERITONEAL; INSERTION; INJURIES; ACCESS AB Purpose: Abdominal wall adhesions at laparoscopy may predispose patients to access related injuries and increase the complexity of the procedure. We have observed concern from referring physicians regarding the safety of laparoscopy in patients who previously underwent surgery because of the risk of abdominal adhesions. To assess the risk of adhesions at laparoscopy a retrospective cohort study was performed. Materials and Methods: All patients who underwent a transperitoneal urological laparoscopic procedure in a 6-year period at our institution were included in this study. A chart review was performed to obtain demographic/surgical data and identify preoperative risk factors for adhesions, such as previous abdominal or pelvic surgery, radiation and/or intra-abdominal inflammatory disease. Operative videotapes were reviewed to determine the presence and location of adhesions. Standard statistical analyses were performed. Results: During the study period 127 patients underwent transperitoneal laparoscopy and videotapes on 82 (65%) were available for review. A total of 44 patients (54%) were identified with preoperative risk factors for adhesions (group 1), while 38 (46%) had no risk factors (group 2). The relative risk of adhesions was 1.34 (95% CI 0.89 to 2.01, p = 0.18) when risk factors were identified. There were no differences in the groups in patient age, operative time, access technique, conversion to open surgery or complications. Estimated blood loss was significantly higher in group 2, likely due to the preponderance of cytoreductive laparoscopic nephrectomy in this group. Conclusions: There was no difference in the risk of intra-abdominal adhesions in patients with and without identifiable preoperative risk factors. Preoperative risk factors for adhesions should not contraindicate the transperitoneal laparoscopic approach for urological oncology procedures. C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Pautler, SE (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NR 25 TC 12 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2002 VL 168 IS 6 BP 2391 EP 2394 DI 10.1097/01.ju.0000035271.15152.b1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 618CE UT WOS:000179399900011 PM 12441924 ER PT J AU Linehan, WM AF Linehan, WM TI Editorial: Kidney cancer - A unique opportunity for the development of disease specific therapy SO JOURNAL OF UROLOGY LA English DT Editorial Material ID RENAL-CELL CARCINOMA; PARENCHYMAL SPARING SURGERY; TUMOR-SUPPRESSOR GENE; MET PROTOONCOGENE; MUTATIONS; FAMILIES; DOMAIN; VHL C1 NCI, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Bethesda, MD 20892 USA. NR 18 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2002 VL 168 IS 6 BP 2411 EP 2412 DI 10.1097/01.ju.0000038143.83146.59 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 618CE UT WOS:000179399900016 PM 12441928 ER PT J AU Balaji, KC Fair, WR Feleppa, EJ Porter, CR Tsai, H Liu, T Kalisz, A Urban, S Gillespie, J AF Balaji, KC Fair, WR Feleppa, EJ Porter, CR Tsai, H Liu, T Kalisz, A Urban, S Gillespie, J TI Role of advanced 2 and 3-dimensional ultrasound for detecting prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; imaging, three-dimensional; ultrasonography; spectrum analysis ID TRANSRECTAL ULTRASOUND; SEXTANT BIOPSIES; RADIOTHERAPY AB Purpose: We explored the clinical usefulness of spectrum analysis and neural networks for classifying prostate tissue and identifying prostate cancer in patients undergoing transrectal ultrasound for diagnostic or therapeutic reasons. Materials and Methods: Data on a cohort of 215 patients who underwent transrectal ultrasound guided prostate biopsies at Memorial-Sloan Kettering Cancer Center, New York, New York were included in this study. Radio frequency data necessary for 2 and 3-dimensional (D) computer reconstruction of the prostate were digitally recorded at transrectal ultrasound and prostate biopsy. The data were spectrally processed and 2-D tissue typing images were generated based on a pre-trained neural network classification. We used manually masked 2-D tissue images as building blocks for generating 3-D tissue images and the images were tissue type color coded using custom software. Radio frequency data on the study cohort were analyzed for cancer probability using the data set pre-trained by neural network methods and compared with conventional B-mode imaging. ROC curves were generated for the 2 methods using biopsy results as the gold standard. Results: The mean area under the ROC curve plus or minus SEM for detecting prostate cancer for the conventional B-mode and neural network methods was 0.66 +/- 0.03 and 0.80 +/- 0.05, respectively. Sensitivity and specificity for detecting prostate cancer by the neural network method were significantly increased compared with conventional B-mode imaging. In addition, the 2 and 3-D prostate images provided excellent visual identification of areas with a higher likelihood of cancer. Conclusions: Spectrum analysis could significantly improve the detection and evaluation of prostate cancer. Routine real-time application of spectrum analysis may significantly decrease the number of false-negative biopsies and improve the detection of prostate cancer at transrectal ultrasound guided prostate biopsy. It may also provide improved identification of prostate cancer foci during therapeutic intervention, such as brachytherapy, external beam radiotherapy or cryotherapy. In addition, 2 and 3-D images with prostate cancer foci specifically identified can help surgical planning and may in the distant future be an additional reliable noninvasive method of selecting patients for prostate biopsy. C1 Univ Nebraska, Med Ctr, Omaha, NE 68198 USA. Riverside Res Inst, New York, NY USA. New York Presbyterian Med Ctr, New York, NY USA. SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. Kaiser Permanente, Los Angeles, CA USA. NCI, Bethesda, MD 20892 USA. RP Balaji, KC (reprint author), Univ Nebraska, Med Ctr, 600 S 42nd St, Omaha, NE 68198 USA. FU NCI NIH HHS [CA53561] NR 20 TC 22 Z9 22 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2002 VL 168 IS 6 BP 2422 EP 2425 DI 10.1097/01.ju.0000036435.13421.57 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 618CE UT WOS:000179399900020 PM 12441931 ER PT J AU Krempl, C Murphy, BR Collins, PL AF Krempl, C Murphy, BR Collins, PL TI Recombinant respiratory syncytial virus with the G and F genes shifted to the promoter-proximal positions SO JOURNAL OF VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; TRANSCRIPTION ELONGATION-FACTOR; REPLICATION IN-VITRO; STRAND RNA VIRUS; VACCINE CANDIDATE; MESSENGER-RNA; RSV CHALLENGE; M2-2 PROTEIN; SH GENE; LIVE AB The genome of human respiratory syncytial virus (RSV) encodes 10 mRNAs and 11 proteins in the order 3'-NS1-NS2-N-P-M-SH-G-F-M2-1/A42-2-L-5'. The G and F glycoproteins are the major RSV neutralization and protective antigens. It seems likely that a high level of expression of G and F would be desirable for a live RSV vaccine. For mononegaviruses, the gene order is a major factor controlling the level of mRNA and protein expression due to the polar gradient of sequential transcription. In order to increase the expression of G and F, recombinant RSVs based on strain A2 were constructed in which the G or F gene was shifted from the sixth or seventh position (in a genome lacking the SH gene), respectively, to the first position (rRSV-G1/DeltaSH and rRSV-F1/DeltaSH, respectively). Another virus was made in which G and F were shifted together to the first and second positions, respectively (rRSV-G1F2/DeltaSH). Shifting one or two genes to the promoter-proximal position resulted in increased mRNA and protein expression of the shifted genes, with G and F expression increased up to 2.4-and 7.8-fold, respectively, at the mRNA level and approximately 2.5-fold at the protein level, compared to the parental virus. Interestingly, the transcription of downstream genes was not greatly affected even though shifting G or F, or G and F together, had the consequence of moving the block of genes NS1-NS2-N-P-M-(G) one or two positions further from the promoter. The efficiency of replication of the gene shift viruses in vitro was increased up to 10-fold. However, their efficiency of replication in the lower respiratory tracts of mice was statistically indistinguishable from that of the parental virus. In the upper respiratory tract, replication was slightly reduced on some days for viruses in which G was in the first position. The magnitude of the G-specific antibody response to the gene shift viruses was similar to that to the parental virus, whereas the F-specific response was increased up to fourfold, although this was not reflected in an increase of the neutralizing activity. Thus, shifting the G and F genes to the promoter-proximal position increased virus replication in vitro, had little effect on replication in the mouse, and increased the antigen-specific immunogenicity of the virus beyond that of parental RSV. C1 NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Collins, PL (reprint author), Bldg 50,Room 6503,50 S Dr MSC 8007, Bethesda, MD 20892 USA. RI Krempl, Christine/O-2081-2015 FU NIAID NIH HHS [AI-00087] NR 42 TC 23 Z9 26 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 23 BP 11931 EP 11942 DI 10.1128/JVI.76.23.11931-11942.2002 PG 12 WC Virology SC Virology GA 612PB UT WOS:000179083700016 PM 12414935 ER PT J AU Walter, BL Parsley, TB Ehrenfeld, E Semler, BL AF Walter, BL Parsley, TB Ehrenfeld, E Semler, BL TI Distinct poly(rC) binding protein KH domain determinants for poliovirus translation initiation and viral RNA replication SO JOURNAL OF VIROLOGY LA English DT Article ID GLOBIN MESSENGER-RNA; 5' NONCODING REGION; FRAGILE-X-SYNDROME; 3'-UNTRANSLATED REGION; ERYTHROID-DIFFERENTIATION; 5'-UNTRANSLATED REGION; 5'-NONCODING REGION; STABILITY COMPLEX; GROWTH-HORMONE; 3CD PROTEINASE AB The limited coding capacity of picornavirus genomic RNAs necessitates utilization of host cell factors in the completion of an infectious cycle. One host protein that plays a role in both translation initiation and viral RNA synthesis is poly(rC) binding protein 2 (PCBP2). For picornavirus RNAs containing type I internal ribosome entry site (IRES) elements, PCBP2 binds the major stem-loop structure (stem-loop M in the IRES and is essential for translation initiation. Additionally, the binding of PCBP2 to the 5'-terminal stem-loop structure (stem-loop I or cloverleaf) in concert with viral protein 3CD is required for initiation of RNA synthesis directed by poliovirus replication complexes. PCBP1, a highly homologous isoform of PCBP2, binds to poliovirus stem-loop I with an affinity similar to that of PCBP2; however, PCBP1 has reduced affinity for stem-loop IV. Using a dicistronic poliovirus RNA, we were able to functionally uncouple translation and RNA replication in PCBP-depleted extracts. Our results demonstrate that PCBP1 rescues RNA replication but is not able to rescue translation initiation. We have also generated mutated versions of PCBP2 containing site-directed lesions in each of the three RNA-binding domains. Specific defects in RNA binding to either stem-loop I and/or stem-loop IV suggest that these domains may have differential functions in translation and RNA replication. These predictions were confirmed in functional assays that allow separation of RNA replication activities from translation. Our data have implications for differential picornavirus template utilization during viral translation and RNA replication and suggest that specific PCBP2 domains may have distinct roles in these activities. C1 Univ Calif Irvine, Coll Med, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Semler, BL (reprint author), Univ Calif Irvine, Coll Med, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. FU NIAID NIH HHS [R56 AI026765, AI 26765, R01 AI026765] NR 63 TC 87 Z9 92 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 23 BP 12008 EP 12022 DI 10.1128/JVI.76.23.12008-12022.2002 PG 15 WC Virology SC Virology GA 612PB UT WOS:000179083700024 PM 12414943 ER PT J AU Hook, LM Jude, BA Ter-Grigorov, VS Hartley, JW Morse, HC Trainin, Z Toder, V Chervonsky, AV Golovkina, TV AF Hook, LM Jude, BA Ter-Grigorov, VS Hartley, JW Morse, HC Trainin, Z Toder, V Chervonsky, AV Golovkina, TV TI Characterization of a novel murine retrovirus mixture that facilitates hematopoiesis SO JOURNAL OF VIROLOGY LA English DT Article ID FOCUS-INDUCING VIRUSES; INDUCED IMMUNODEFICIENCY SYNDROME; LEUKEMIA-VIRUS; FORMING VIRUSES; MCF VIRUSES; STEM-CELLS; MICE; FRIEND; INFECTION; INDUCTION AB A new virus previously arose in BALB/c females mated repeatedly to C57BL/6 (116) males and then injected with fixed, activated B6 male spleen cells (V. S. Ter-Grigorov, O. Krifuks, E. Liubashevsky, A. Nyska, Z. Trainin, and V. Toder, Nat. Med. 3:31-41, 1997). In the present study, BAILB/cJ mice inoculated with virus-containing plasma from affected mice developed splenomegaly, which was caused by increased numbers of Sca-1(+) Lin(-) hematopoietic stem cells (HSC) and their differentiated progeny. Biological and molecular analyses of a new virus revealed a mixture of murine leukemia viruses (MuLVs). These MuLVs comprised ecotropic and mink lung cell focus-forming (MCF) virus classes and are termed Rauscher-like MuLVs because they bear numerous similarities to the ecotropic and MCF viruses of the Rauscher MuLV complex but do not include a spleen focus-forming virus. The ecotropic virus component alone transferred some disease characteristics, while MCF virus alone did not. Thus, we have described a novel virus mixture, termed Rauscher-like MuLV, that causes an increase in hematopoiesis due to activation of pluripotent HSC. Experiments using mice and a protocol that replicated the pregnancy and immunization strategy of the original experiment demonstrated that endogenous BALB/c mouse ecotropic and xenotropic MuLVs are activated by these treatments. Emv1 was expressed in the spleens of multiparous mice but not in those of virgin mice, and Bxv1Emv1-pseudotyped MuLVs were recovered following injection of fixed, activated B6 cells. Thus, multiple pregnancies and allostimuli appear to have provided the signals required for activation of and recombination among endogenous viruses and could have resulted in generation of the Rauscher-like MuLV mixture. C1 Jackson Lab, Bar Harbor, ME 04609 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. Kimron Vet Inst, Dept Pathol & Immunol, IL-50250 Bet Dagan, Israel. Tel Aviv Univ, Sackler Sch Med, Dept Embryol, IL-69978 Tel Aviv, Israel. RP Golovkina, TV (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. OI Morse, Herbert/0000-0002-9331-3705; Chervonsky, Alexander/0000-0001-7547-871X; Hook, Lauren/0000-0002-5540-2459 FU NCI NIH HHS [CA34196, CA65795, P30 CA034196] NR 52 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 23 BP 12112 EP 12122 DI 10.1128/JVI.76.23.12112-12122.2002 PG 11 WC Virology SC Virology GA 612PB UT WOS:000179083700033 PM 12414952 ER PT J AU Lee, BS Paulose-Murphy, M Chung, YH Connlole, M Zeichner, S Jung, JU AF Lee, BS Paulose-Murphy, M Chung, YH Connlole, M Zeichner, S Jung, JU TI Suppression of tetradecanoyl phorbol acetate-induced lytic reactivation of Kaposi's sarcoma-associated herpesvirus by K1 signal transduction SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; MICROVASCULAR ENDOTHELIAL-CELLS; INTERFERON REGULATORY FACTOR; CLASS-I MOLECULES; NF-KAPPA-B; GENE-EXPRESSION; NUCLEAR ANTIGEN; TRANSCRIPTIONAL ACTIVATION; DOWN-REGULATION; LYMPHOMA-CELLS AB The K1 protein of Kaposi's sarcoma-associated herpesvirus (KSHV) contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic region and elicits cellular signal transduction through this motif. To investigate the role of K1 signal transduction in KSHV replication, we expressed full-length K1 and CD8-K1 chimeras in BCBL1 cells. Unlike its strong signaling activity in uninfected B lymphocytes, K1 did not induce intracellular calcium mobilization or NF-AT activation at detectable levels in KSHV-infected BCBL1 cells. Instead, K1 signaling dramatically suppressed KSHV lytic reactivation induced by tetradecanoyl phorbol acetate (TPA) stimulation, but not by ORF50 ectopic expression. Mutational analysis showed that the cytoplasmic ITAM sequence of K1 was required for this suppression. Viral microarray and immunoblot analyses demonstrated that K1 signaling suppressed the TPA-mediated increase in the expression of a large subset of viral lytic genes in KSHV-infected BCBL1 cells. Furthermore, electrophoretic mobility shift assays demonstrated that TPA-induced activation of AP-1, NF-kappaB, and Oct-1 activities was severely diminished in BCBL1 cells expressing the K1 cytoplasmic domain. The reduced activities of these transcription factors may confer the observed reduction in viral lytic gene expression. These results demonstrate that K1-mediated signal transduction in KSHV-infected cells is profoundly different from that in KSHV-negative cells. Furthermore, K1 signal transduction efficiently suppresses TPA-mediated viral reactivation in an ITAM-dependent manner, and this suppression may contribute to the establishment and/or maintenance of KSHV latency in vivo. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Tumor Virol, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Immunol, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Jung, JU (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Tumor Virol, POB 9102,1 Pine Hill Dr, Southborough, MA 01772 USA. EM jae_jung@hms.harvard.edu FU NCI NIH HHS [CA82057, CA91819, R01 CA082057, R01 CA091819]; NCRR NIH HHS [K26 RR000168, P51 RR000168, RR00168] NR 75 TC 32 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 23 BP 12185 EP 12199 DI 10.1128/JVI.76.23.12185-12199.2002 PG 15 WC Virology SC Virology GA 612PB UT WOS:000179083700039 PM 12414958 ER PT J AU Race, RE Raines, A Baron, TGM Miller, MW Jenny, A Williams, ES AF Race, RE Raines, A Baron, TGM Miller, MW Jenny, A Williams, ES TI Comparison of abnormal prion protein glycoform patterns from transmissible spongiform encephalopathy agent-infected deer, elk, sheep, and cattle SO JOURNAL OF VIROLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; MOLECULAR ANALYSIS; STRAIN VARIATION; SCRAPIE; HUMANS AB Analysis of abnormal prion protein glycoform patterns from chronic wasting disease (CWD)-affected deer and elk, scrapie-affected sheep and cattle, and cattle with bovine spongiform encephalopathy failed to identify patterns capable of reliably distinguishing these transmissible spongiform encephalopathy diseases. However, PrP-res patterns sometimes differed among individual animals, suggesting infection by different or multiple CWD strains in some species. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. Agence Francaise Secur Sanitaire Aliments, Lyon, France. Colorado Div Wildlife, Wildlife Res Ctr, Ft Collins, CO 80526 USA. USDA, Vet Sci Labs, Anim & Plant Hlth Inspect Serv, Ames, IA USA. Univ Wyoming, Dept Vet Sci, Laramie, WY 82071 USA. RP Race, RE (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. NR 15 TC 47 Z9 48 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 23 BP 12365 EP 12368 DI 10.1128/JVI.76.23.12365-1268.2002 PG 4 WC Virology SC Virology GA 612PB UT WOS:000179083700060 PM 12414979 ER PT J AU Faix, PH Feldman, SA Overbaugh, J Eiden, MV AF Faix, PH Feldman, SA Overbaugh, J Eiden, MV TI Host range and receptor binding properties of vectors bearing feline leukemia virus subgroup B envelopes can be modulated by envelope sequences outside of the receptor binding domain SO JOURNAL OF VIROLOGY LA English DT Article ID ENDOTHELIAL-CELL TROPISM; SARCOMA-ASSOCIATED VIRUS; CHINESE-HAMSTER CELLS; GIBBON APE; SURFACE GLYCOPROTEIN; GENE; DETERMINANTS; INFECTION; PROTEIN; PVC-211 AB To evaluate host range differences between two different strains of feline leukemia virus subgroup B (FeLV-B), we compared the binding and infectivity patterns of retrovirus vectors bearing either FeLV-B-90Z or FeLV-B-GA envelopes. We report here that the ability of these envelopes to utilize different Pit1 orthologs is mediated primarily by the receptor binding domain; however, in the case of FeLV-B-90Z, the C terminus also contributes to the recognition of certain Pit1 orthologs. C1 NIMH, Sect Mol Virol, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA. RP Eiden, MV (reprint author), NIMH, Sect Mol Virol, Lab Cellular & Mol Regulat, Bldg 36,Room 2A11,36 Convent Dr,MSC 4068, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA51080, R01 CA051080] NR 48 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 23 BP 12369 EP 12375 DI 10.1128/JVI.76.23.12369-12375.2002 PG 7 WC Virology SC Virology GA 612PB UT WOS:000179083700061 PM 12414980 ER PT J AU Suzuki, Y Craigie, R AF Suzuki, Y Craigie, R TI Regulatory mechanisms by which barrier-to-autointegration factor locks autointegration and stimulates intermolecular integration of Moloney murine leukemia virus preintegration complexes SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRAL DNA INTEGRATION; REVERSE TRANSCRIPTION COMPLEXES; VIRAL-DNA; NUCLEOPROTEIN COMPLEX; IN-VITRO; PROTEIN; INVITRO; TYPE-1; REQUIREMENT; MODULATION AB Retroviral integration is mediated by a preintegration complex (PIC) which contains the viral DNA made by reverse transcription together with associated protein factors. Prior to association with target DNA, the PIC must avoid suicidal intramolecular integration of its viral DNA (autointegration). We have demonstrated that barrier-to-autointegration factor (BAF) blocks the autointegration of Moloney murine leukemia virus (MoMLV) PICs in vitro. In this study, we show that BAF is an authentic component of MoMLV. Analysis of the sedimentation properties of initial, salt-stripped, and BAF-reconstituted PICs reveals that the viral DNA within the PIC is reversibly compacted by BAF, consistent with the functional role of BAF in protecting the viral DNA from autointegration. Furthermore, we find that BAF can promote the association of PICs with target DNA. Thus, our data suggest that BAF plays critical roles in promoting preferential intermolecular integration by both blocking autointegration and stimulating the capture of target DNA. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Craigie, R (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 5,Room 301,5 Ctr Dr,MSC 0560, Bethesda, MD 20892 USA. NR 31 TC 53 Z9 55 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 23 BP 12376 EP 12380 DI 10.1128/JVI.76.23.12376-12380.2002 PG 5 WC Virology SC Virology GA 612PB UT WOS:000179083700062 PM 12414981 ER PT J AU Mauser, A Saito, S Appella, E Anderson, CW Seaman, WT Kenney, S AF Mauser, A Saito, S Appella, E Anderson, CW Seaman, WT Kenney, S TI The Epstein-Barr virus immediate-early protein BZLF1 regulates p53 function through multiple mechanisms SO JOURNAL OF VIROLOGY LA English DT Article ID TATA-BINDING PROTEIN; TUMOR-SUPPRESSOR GENE; CELL-CYCLE ARREST; HUMAN CYTOMEGALOVIRUS; IN-VIVO; DNA-BINDING; TRANSCRIPTIONAL ACTIVATION; WILD-TYPE; P53-MEDIATED APOPTOSIS; MAMMALIAN-CELLS AB The Epstein-Barr virus (EBV) immediate-early protein BZLF1 is a transcriptional activator that mediates the switch between the latent and the lytic forms of EBV infection. It was previously reported that BZLF1 inhibits p53 transcriptional function in reporter gene assays. Here we further examined the effects of BZLF1 on p53 function by using a BZLF1-expres sing adenovirus vector (AdBZLF1). Infection of cells with the AdBZLF1 vector increased the level of cellular p53 but prevented the induction of p53-dependent cellular target genes, such as p21 and MDM2. BZLF1-expressing cells had increased p53-specific DNA binding activity in electrophoretic mobility shift assays, increased p53 phosphorylation at multiple residues (including serines 6, 9, 15, 33, 46, 315, and 392), and increased acetylation at lysine 320 and lysine 382. Thus, the inhibitory effects of BZLF1 on p53 transcriptional function cannot be explained by its effects on p53 phosphorylation, acetylation, or DNA binding activity. BZLF1 substantially reduced the level of cellular TATA binding protein (TBP) in both normal human fibroblasts and A549 cells, and the inhibitory effects of BZLF1 on p53 transcriptional function could be partially rescued by the overexpression of TBP. Thus, BZLF1 has numerous effects on p53 posttranslational modification but may inhibit p53 transcriptional function in part through an indirect mechanism involving the suppression of TBP expression. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Kenney, S (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [R01 CA058853, R01 CA 58853, CA 64852] NR 95 TC 76 Z9 80 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 24 BP 12503 EP 12512 DI 10.1128/JVI.76.24.12503-12512.2002 PG 10 WC Virology SC Virology GA 617DE UT WOS:000179344800011 PM 12438576 ER PT J AU Okada, M Jeang, KT AF Okada, M Jeang, KT TI Differential requirements for activation of integrated and transiently transfected human T-cell leukemia virus type 1 long terminal repeat SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; TRANSCRIPTIONAL COACTIVATORS P300; I TAX GENE; HTLV-I; BINDING-PROTEIN; HISTONE ACETYLTRANSFERASE; 21-BASE-PAIR REPEATS; BASAL TRANSCRIPTION; TRANS-ACTIVATION; STRESS-RESPONSE AB Adult T-cell leukemia (ATL) cells contain integrated human T-cell leukemia virus type 1 (HTLV-1) proviruses. Although the exact sequence of events leading to the development of ATL remains incompletely resolved, expression of the integrated HTLV-1 long terminal repeat (LTR) is likely required at some point during the process of T-cell transformation. While much has been learned about the regulated expression of transiently transfected LTR reporter plasmids, an analysis of factors required for expression of chromosomally integrated HTLV-1 LTR has not been done. Here, we have constructed CHOK1 and HeLa cells that contain an integrated HTLV-1 LTR-luciferase gene. Using these cells, we have compared the requirements for activation of transiently transfected versus stably integrated HTLV-1 LTR. We observed different requirements for CREB, p300, and P/CAF in the expression of transiently transfected versus stably integrated HTLV-1 LTR. Furthermore, with dominant-negative mutants of CREB, p300, and P/CAF, we found that activation of integrated HTLV-1 LTR by an ambient stress signal, UV-C, proceeds through a path mechanistically distinct from that used by viral oncoprotein, Tax. Our findings point to additional complexities in the regulated expression of HTLV-1 proviruses compared with those hitherto revealed through transfection studies. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bldg 4,Rm 306,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 57 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 24 BP 12564 EP 12573 DI 10.1128/JVI.76.24.12564-12573.2002 PG 10 WC Virology SC Virology GA 617DE UT WOS:000179344800017 PM 12438582 ER PT J AU Jin, X Gao, XJ Ramanathan, M Deschenes, GR Nelson, GW O'Brien, SJ Goedert, JJ Ho, DD O'Brien, TR Carrington, M AF Jin, X Gao, XJ Ramanathan, M Deschenes, GR Nelson, GW O'Brien, SJ Goedert, JJ Ho, DD O'Brien, TR Carrington, M TI Human immunodeficiency virus type 1 (HIV-1)-specific CD8(+)-T-cell responses for groups of HIV-1-infected individuals with different HLA-B*35 genotypes SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; LONG-TERM NONPROGRESSORS; HIV-1 RNA LEVELS; VIRAL LOAD; DISEASE PROGRESSION; CELL RESPONSES; INFECTION; AIDS; ESCAPE; VARIANTS AB Human immunodeficiency virus type 1 (HIV-1) -infected individuals with HLA-B*35 allelic variants B*3502/ 35031350415301 (B*35-Px) progress more rapidly to AIDS than do those with B*3501 (B*35-PY). The mechanisms responsible for this phenomenon are not clear. To examine whether cellular immune responses may differ according to HLA-B*35 genotype, we quantified HIV-1-specific CD8(+)-T-cell (CTL) responses using an intracellular cytokine-staining assay with specimens from 32 HIV-1-positive individuals who have B*35 alleles. Among them, 75% had CTL responses to Poll, 69% had CTL responses to Gag, 50% had CTL responses to Nef, and 41% had CTL responses to Env. The overall magnitude of CTL responses did not differ between patients bearing B*35-Px genotypes and those bearing B*35-PY genotypes. A higher percentage of Gag-specific CTL was associated with lower HIV-1 RNA levels (P = 0.009) in individuals with B*35-PY. A negative association between CTL activity for each of the four HIV antigens and viral load was observed among individuals with B*35-PY, and the association reached significance for Gag. No significant relationship between CTL activity and viral load was observed in the B*35-Px group. The relationship between total CTL activity and HIV RNA among B*35-Px carriers differed significantly from that among B*35-PY carriers (P < 0.05). The data are consistent with the hypothesis that higher levels of virus-specific CTL contribute to protection against HIV disease progression in infected individuals with B*35-PY, but not in those with B*35-Px. C1 Univ Rochester, Med Ctr, Infect Dis Unit, Rochester, NY 14642 USA. NCI, Intramural Res Support Program, SAIC, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Jin, X (reprint author), Univ Rochester, Med Ctr, Infect Dis Unit, 601 Elmwood Ave,Box 689, Rochester, NY 14642 USA. FU NCI NIH HHS [N01 CO 12400, N01CO12400] NR 41 TC 43 Z9 44 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 24 BP 12603 EP 12610 DI 10.1128/JVI.76.24.12603-12610.2002 PG 8 WC Virology SC Virology GA 617DE UT WOS:000179344800021 PM 12438586 ER PT J AU Jones, KS Nath, M Petrow-Sadowski, C Baines, AC Dambach, M Huang, Y Ruscetti, FW AF Jones, KS Nath, M Petrow-Sadowski, C Baines, AC Dambach, M Huang, Y Ruscetti, FW TI Similar regulation of cell surface human T-cell leukemia virus type 1 (HTLV-1) surface binding proteins in cells highly and poorly transduced by HTLV-1-pseudotyped virions SO JOURNAL OF VIROLOGY LA English DT Article ID AVIAN-LEUKOSIS VIRUS; MURINE LEUKEMIA; RECEPTOR EXPRESSION; SYNCYTIUM FORMATION; TRANSMEMBRANE GLYCOPROTEIN; ENVELOPE GLYCOPROTEINS; MONOCLONAL-ANTIBODIES; RETROVIRUS INFECTION; SARCOMA-VIRUSES; SU GLYCOPROTEIN AB Little is known about the requirements for human T-cell leukemia virus type 1 (HTLV-1) entry, including the identity of the cellular receptor(s). Previous studies have shown that although the HTLV receptor(s) are widely expressed on cell lines of various cell types from different species, cell lines differ dramatically in their susceptibility to HTLV-Env-mediated fusion. Human cells (293, HeLa, and primary CD4(+) T cells) showed higher levels of binding at saturation than rodent (NIH 3T3 and NRK) cells to an HTLV-1 SU immunoadhesin. A direct comparison of the binding of the HTLV-1 surface glycoprotein (SU) immunoadhesin and transduction by HTLV-1 pseudotyped virus revealed parallels between the level of binding and the titer for various cell lines. When cells were treated with phorbol myristate acetate (PMA), which down-modulates a number of cell surface molecules, the level of SU binding was markedly reduced. However, PMA treatment only slightly reduced the titer of murine leukemia virus(HTLV-1) on both highly susceptible and poorly susceptible cells. Treatment of target cells with trypsin greatly reduced binding, indicating that the majority of HTLV SU binding is to proteins. Polycations, which enhance the infectivity of several other retroviruses, inhibited HTLV-1 Env-mediated binding and entry on both human and rodent cells. These results suggest that factors other than the number of primary binding receptors are responsible for the differences in the titers of HTLV-1 pseudotypes between highly susceptible cells and poorly susceptible cells. C1 Natl Canc Inst, Basic Res Lab, Canc Res Ctr, Frederick, MD 21702 USA. SAIC, Basic Res Program, Frederick, MD USA. RP Ruscetti, FW (reprint author), Natl Canc Inst, Basic Res Lab, Canc Res Ctr, Bldg 567,Rm 253, Frederick, MD 21702 USA. FU NCI NIH HHS [N01 CO 124000] NR 78 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 24 BP 12723 EP 12734 DI 10.1128/JVI.76.24.12723-12734.2002 PG 12 WC Virology SC Virology GA 617DE UT WOS:000179344800033 PM 12438598 ER PT J AU Heidecker, G Hill, S Lloyd, PA Derse, D AF Heidecker, G Hill, S Lloyd, PA Derse, D TI A novel protease processing site in the transframe protein of human T-cell leukemia virus type 1 PR76(gag-pro) defines the N terminus of RT SO JOURNAL OF VIROLOGY LA English DT Article ID OPEN READING FRAMES; I PROTEASE; HTLV-I; REVERSE-TRANSCRIPTASE; SPECIFICITY; REPLICATION; RETROVIRUS; CLEAVAGE; LINES; VIVO AB The genomic RNA of human T-cell leukemia virus type I encodes three polyproteins, Gag, Gag-Pro, and Gag-Pro-Pol, which are translated as a result of no, one, and two frameshifts, respectively. In this report we demonstrate that the 77 residues encoded at the C terminus of the Gag-Pro precursor can be collectively detected as an 8-kDa transframe protein (TFP) in virions. Mutant viruses with a C-terminally truncated TFP (19, 32, or 50 residues) had essentially a wild-type phenotype in vitro. However, a virus mutant that encoded only the Gag and Gag-Pro-Pol polyproteins due to a mutation in the second frameshift site, and hence did not produce TFP, was noninfectious. Mutation analysis of the proteolytic cleavage site between PR and TFP revealed the presence of an additional site and the existence of a p1 peptide separating protease and TFP. While removal of the cleavage site at the PR-p1 junction had a modest effect on virus replication, mutation of the p1-TFP cleavage site led to noninfectious virus and the loss of reverse transcriptase activity. Determination of the amino-terminal sequence of a hemagglutinin-tagged RT demonstrated that the same site is used in processing the Gag-Pro-Pol precursor and thus defines the start of mature RT. Neither mutation alone or in combination caused changes in the amounts or processing patterns of the Gag polyprotein, indicating that protease is active independent of its C terminus. C1 NCI Frederick, Basic Res Lab, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. RP Heidecker, G (reprint author), NCI Frederick, Basic Res Lab, Bldg 567,Rm 154, Frederick, MD 21702 USA. FU NCI NIH HHS [N01 CO 12400, N01CO12400] NR 18 TC 14 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 24 BP 13101 EP 13105 DI 10.1128/JVI.76.24.13101-13105.2002 PG 5 WC Virology SC Virology GA 617DE UT WOS:000179344800074 PM 12438640 ER PT J AU Cen, S Javanbakht, H Kim, S Shiba, K Craven, R Rein, A Ewalt, K Schimmel, P Musier-Forsyth, K Kleiman, L AF Cen, S Javanbakht, H Kim, S Shiba, K Craven, R Rein, A Ewalt, K Schimmel, P Musier-Forsyth, K Kleiman, L TI Retrovirus-specific packaging of aminoacyl-tRNA synthetases with cognate primer tRNAs SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSFER-RNA-SYNTHETASE; IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE; GAG PROTEIN; PARTICLES; MUTANT; PR160(GAG-POL); MUTATIONS; BINDING; COMPLEX AB The tRNAs used to prime reverse transcription in human immunodeficiency virus type 1 (HIV-1), Rous sarcoma virus (RSV), and Moloney murine leukemia virus (Mo-MuLV) are tRNA(3)(Lys), tRNA(TrP), and tRNA(Pro), respectively. Using antibodies to the three cognate human aminoacyl-tRNA synthetases, we found that only lysyl-tRNA synthetase (LysRS) is present in HIV-1, only tryptophanyl-tRNA synthetase (TrpRS) is present in RSV, and neither these two synthetases nor prolyl-tRNA synthetase (ProRS) is present in Mo-MuLV. LysRS and TrpRS are present in HIV-1 and RSV at approximately 25 and 12 molecules/virion, respectively. These results support the hypothesis that, in HIV-1 and RSV, the cognate aminoacyl-tRNA synthetase may be used as the signal for targeting the selective packaging of primer tRNAs into retroviruses. The absence of ProRS in Mo-MuLV is consistent with reports that selective packaging of tRNA(Pro) in this virus is less important for achieving optimum annealing of the primer to Mo-MuLV genomic RNA. C1 McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. McGill Univ, Jewish Gen Hosp, McGill AIDS Ctr, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3T 1E2, Canada. Sungkyunkwan Univ, Natl Creat Res Initiat Ctr ARS Network, Suwon 440746, Kyunggido, South Korea. Japanese Fdn Canc Res, Dept Cell Biol, Toshima Ku, Tokyo 170, Japan. Penn State Univ, Milton S Hershey Med Ctr, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. NCI, HIVDRP, NIH, Frederick, MD 21702 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. RP Kleiman, L (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, 3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM lawrence.kleiman@mcgill.ca NR 25 TC 54 Z9 56 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2002 VL 76 IS 24 BP 13111 EP 13115 DI 10.1128/JVI.76.24.13111-13115.2002 PG 5 WC Virology SC Virology GA 617DE UT WOS:000179344800076 PM 12438642 ER PT J AU Liu, J Periyasamy, SM Gunning, W Fedorova, OV Bagrov, AY Malhotra, D Xie, ZJ Shapiro, JI AF Liu, J Periyasamy, SM Gunning, W Fedorova, OV Bagrov, AY Malhotra, D Xie, ZJ Shapiro, JI TI Effects of cardiac glycosides on sodium pump expression and function in LLC-PK1 and MDCK cells SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT ASN/ISN World Congress of Nephrology CY OCT 10-17, 2001 CL SAN FRANCISCO, CA SP ASN, ISN DE proximal tubule sodium reabsorption; Na,K-ATPase; kidney; trafficking; inhibition; digitalis-like substance; chronic renal failure; volume expansion ID NA-K-ATPASE; OUABAIN-LIKE IMMUNOREACTIVITY; PLASMA MARINOBUFAGENIN-LIKE; ALPHA-SUBUNIT; ENDOGENOUS OUABAIN; VOLUME EXPANSION; KIDNEY-CELLS; NA+,K+-ATPASE; HYPERTENSION; ENDOCYTOSIS AB Background. The decreases in proximal tubule sodium reabsorption seen with chronic renal failure and volume expansion have been ascribed to circulating digitalis-like substances (DLS). However, the circulating concentrations of DLS do not acutely inhibit the sodium pump to a degree consistent with the observed changes in proximal tubule sodium reabsorption. Methods. We examined how cell lines that simulated proximal (LLC-PK1) and distal tubule (MDCK) cells responded to acute (30 min) and long-term (up to 12 hours) Na(+),K(+)-ATPase inhibition with DLS. Results. In LLC-PK1, but not MDCK cells, low concentrations of ouabain decreased (86)Rb uptake profoundly in a time and dose dependent manner. In LLC-PK1 cells grown to confluence, transcellular (22)Na flux was markedly reduced in concert with the decreases in (86)Rb uptake. Similar findings were observed with marinobufagenin (MBG) and deproteinated extract of serum derived from patients with chronic renal failure. However, inhibition of the Na(+),K(+)-ATPase with low extracellular potassium concentrations did not produce any of these effects. Western and Northern blots detected no change in alphal Na(+),K(+)-ATPase protein and message RNA, respectively, in LLC-PK1 cells treated with ouabain for 12 hours. However, the decrease in enzymatic activity of Na(+),K(+)-ATPase of these cells was comparable to observed decreases in (86)Rb uptake. Differential centrifugation as well as biotinylation experiments demonstrated a shift of the Na(+),K(+)-ATPase from the plasmalemma with prolonged ouabain treatment. Conclusions. The results show that binding of cardiac glycosides by proximal (but not distal) tubular cells results in internalization of Na(+),K(+)-ATPase with the net effect to amplify inhibition of the Na(+),K(+)-ATPase. As the circulating concentrations of DLS increase with chronic renal failure and volume expansion, we suggest that this phenomenon explains some of the decreased sodium reabsorption by the proximal tubule seen in these conditions. C1 Med Coll Ohio, Dept Med, Toledo, OH 43614 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43699 USA. Med Coll Ohio, Dept Pharmacol, Toledo, OH 43699 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Shapiro, JI (reprint author), Med Coll Ohio, Dept Med, 3120 Glendale Ave, Toledo, OH 43614 USA. EM jshapiro@mco.edu RI Gunning, William/E-4681-2010 FU NHLBI NIH HHS [HL57144, HL63238] NR 36 TC 48 Z9 49 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2002 VL 62 IS 6 BP 2118 EP 2125 DI 10.1046/j.1523-1755.2002.00672.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 617DV UT WOS:000179346600020 PM 12427136 ER PT J AU Vardarli, I Baier, LJ Hanson, RL Akkoyun, M Fischer, C Rohmeiss, P Basci, A Bartram, CR van der Woude, FJ Janssen, B AF Vardarli, I Baier, LJ Hanson, RL Akkoyun, M Fischer, C Rohmeiss, P Basci, A Bartram, CR van der Woude, FJ Janssen, B TI Gene for susceptibility to diabetic nephropathy in type 2 diabetes maps to 18q22.3-23 SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT ASN/ISN World Congress of Nephrology CY OCT 10-17, 2001 CL SAN FRANCISCO, CALIFORNIA DE genetics; diabetes mellitus; linkage analysis; end-stage renal disease; insulin dependency; proteinuria; type 2 diabetes in Turkey; Pima Indian study ID PIMA-INDIANS; LINKAGE ANALYSIS; ALBUMIN EXCRETION; KIDNEY-DISEASE; RENAL-DISEASE; MELLITUS; COMPLICATIONS; PREDISPOSITION; LOCI; RISK AB Background. Diabetic nephropathy is the major cause of end-stage renal failure in patients with diabetes mellitus types I and 2. Epidemiological studies have suggested a genetic susceptibility to diabetic nephropathy. The aim of this study was to localize the gene(s) responsible for susceptibility to diabetic nephropathy. Methods. A genetic linkage analysis was performed in 18 large Turkish families with type 2 diabetes mellitus and diabetic nephropathy. The result was checked in 101 affected sibling pairs of Pima Indians. Results. A highly significant LOD score of 6.1 on chromosome 18q22.3-23 between the markers D18S469 and D18S58 was obtained in multipoint analysis. There was no indication for locus heterogeneity. In Pima Indians, linkage to the markers D18S469 and D18S58 was confirmed (P = 0.033), using the affected sib-pair method. The genetic model that fit best was a dominant mode of inheritance with an almost complete penetration in the Turkish population. Conclusions. There is strong evidence for the localization of a gene responsible for diabetic nephropathy in Turkish type 2 diabetes mellitus patients. This locus maps to chromosome 18q22.3-23, between D18S43 and D18S50, an interval of 8.5 cM. C1 Univ Heidelberg, Univ Hosp Mannheim, Med Dept Nephrol Endocrinol Rheumatol 5, D-6800 Mannheim, Germany. Univ Heidelberg, Univ Hosp Mannheim, Eye Clin, D-6800 Mannheim, Germany. NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. Ege Univ, Sch Med, Dept Med, Div Nephrol, Bornova, Turkey. RP Vardarli, I (reprint author), Univ Heidelberg, Klinikum Mannheim, Fak Klin Med, Med Klin, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 29 TC 101 Z9 106 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2002 VL 62 IS 6 BP 2176 EP 2183 DI 10.1046/j.1523-1755.2002.00663.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 617DV UT WOS:000179346600027 PM 12427143 ER PT J AU Sarnak, MJ Poindexter, A Wang, SR Beck, GJ Kusek, JW Marcovina, SM Greene, T Levey, AS AF Sarnak, MJ Poindexter, A Wang, SR Beck, GJ Kusek, JW Marcovina, SM Greene, T Levey, AS TI Serum C-reactive protein and leptin as predictors of kidney disease progression in the Modification of Diet in Renal Disease Study SO KIDNEY INTERNATIONAL LA English DT Article DE progressive renal disease; chronic kidney disease; MDRD Study; inflammation; nutritional status; hyperleptinemia; glomerulosclerosis ID CARDIOVASCULAR RISK-FACTORS; HEMODIALYSIS-PATIENTS; DIABETIC NEPHROPATHY; ENDOTHELIAL-CELLS; GLOMERULOSCLEROSIS; INFLAMMATION; EXPRESSION; MORTALITY; URINARY; MARKERS AB Background. In vitro and in vivo data suggest that markers of inflammation and nutritional status may be risk factors for the progression of chronic kidney disease. Methods. We investigated whether higher levels of C-reactive protein (CRP) and leptin were risk factors for progression of chronic kidney disease in the Modification of Diet in Renal Disease (MDRD) Study. Frozen samples were assayed for high sensitivity C-reactive protein (CRP) or leptin in 804 patients. CRP and leptin were then evaluated as risk factors for glomerular filtration rate (GFR) decline using univariate and multivariable analyses. Results. At baseline, the mean (median) CRP in Study A (GFR between 25 and 55 mL/min/1.73 m(2)) and Study B (GFR between 13 and 24 mL/min/1.73 m(2)) were 0.48 (0.25) and 0.46 (0.20) mg/dL, respectively, while the mean (median) leptin in Study A and Study B were 15.2 (9.80) and 15.1 (7.80) ng/mL, respectively. Mean follow-up time was 2.2 years. The mean GFR decline was -4.33 and -3.65 mL/min/year in Study A and 13, respectively. There was no significant association between the rate of GFR decline with the level of CRP or leptin in multivariable analysis in Study A [0.08 (-0.14, 0.30) mL/min/year slower GFR decline per twofold increase in CRP level; and 0.14 (-0.13, 0.40) mL/min/year slower GFR decline per twofold increase in leptin level], or in multivariable analysis in Study B [-0.05 (-0.28, 0.18) mL/min/year faster GFR decline per twofold increase in CRP level; and -0.12 (-0.42, 0.19) mL/min/year faster GFR decline per twofold increase in leptin level]. Conclusions. Higher serum levels of CRP and leptin are not independent risk factors for progression of non-diabetic kidney disease. C1 Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Sarnak, MJ (reprint author), Tufts Univ New England Med Ctr, Box 391,750 Washington St, Boston, MA 02111 USA. FU NIDDK NIH HHS [1K23 DK02904-02] NR 38 TC 59 Z9 59 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2002 VL 62 IS 6 BP 2208 EP 2215 DI 10.1046/j.1523-1755.2002.00677.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 617DV UT WOS:000179346600031 PM 12427147 ER PT J AU Abbott, KC Oglesby, RJ Agodoa, LY AF Abbott, KC Oglesby, RJ Agodoa, LY TI Hospitalized avascular necrosis after renal transplantation in the United States SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT AST 2000 Meeting CY 2000 CL CHICAGO, ILLINOIS SP AST DE osteonecrosis; hip; total hip arthroplasty; kidney rejection; year of transplant; complications; USRDS; bone pain post-transplant ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PROSPECTIVE-PAYMENT SYSTEM; ASEPTIC NECROSIS; RISK-FACTORS; CORTICOSTEROID-THERAPY; BONE NECROSIS; FEMORAL-HEAD; OSTEONECROSIS; RECIPIENTS; HYPERPARATHYROIDISM AB Background. The national incidence of and risk factors for hospitalized avascular necrosis (AVN) in renal transplant recipients has not been reported. Methods. This historical cohort study consisted of 42,096 renal transplant recipients enrolled in the United States Renal Data System (USRDS) between 1 July 1994 and 30 June 1998. The data source was USRDS files through May 2000. Associations with hospitalizations for a primary diagnosis of AVN (ICD-9 codes 733.4x) within three years after renal transplant were assessed in an intention-to-treat design by Cox regression analysis. Results. Recipients had a cumulative incidence of 7.1 episodes/1000 person-years from 1994 to 1998. The two-year incidence of AVN did not change significantly over time. Eighty-nine percent of the cases of AVN were due to AVN of the hip (733.42) and 60.2% of patients with AVN underwent total hip arthroplasty (THA); these percentages did not change significantly over time. In the Cox regression analysis, an earlier year of transplant, African American race [adjusted hazard ratio (AHR), 1.65, 95% confidence interval (CI) 1.33 to 2.03], allograft rejection (AHR 1.67, 95% CI 1.35 to 2.07), peritoneal dialysis (vs. hemodialysis; AHR 1.44, 95% CI 1.15 to 1.81), and diabetes (AHR 0.41, 95% CI 0.27 to 0.64) were the only factors independently associated with hospitalizations for AVN. Conclusions. The incidence of AVN did not decline significantly over time in the renal transplant population. Patients with allograft rejection, African American race, peritoneal dialysis and earlier date of transplant were at the highest risk of AVN, while diabetic recipients were at a decreased risk. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Rheumatol Serv, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Dial Nephrol Serv, Washington, DC 20307 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 46 TC 22 Z9 24 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2002 VL 62 IS 6 BP 2250 EP 2256 DI 10.1046/j.1523-1755.2002.00667.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 617DV UT WOS:000179346600037 PM 12427153 ER PT J AU Kaserer, K Knezevic, V Pichlofer, B Scheuba, C Passler, C Worth, J Niederle, B Krizman, D AF Kaserer, K Knezevic, V Pichlofer, B Scheuba, C Passler, C Worth, J Niederle, B Krizman, D TI Construction of cDNA libraries from microdissected benign and malignant thyroid tissue SO LABORATORY INVESTIGATION LA English DT Article ID LASER CAPTURE MICRODISSECTION; PREOPERATIVE DIAGNOSIS; CELLS; EXPRESSION; CARCINOMA; TUMORS; RNA AB cDNA libraries were constructed from thyroid epithelial cells gained by laser capture microdissection for gene expression analysis of the progression of thyroid cancer. Six histologically diverse thyroid tissue specimens were used. A mean of 93 ng of total RNA was gained per tissue sample from a mean estimated number of 25,000 microdissected cells per sample. Analysis of randomly selected clones from six libraries showed an average insert size of 600 (range, 300-1500) bp. Preliminary sequencing of clones selected from the six libraries indicates a range of 46% to 62% known genes per library, 4% to 25% anonymous expressed sequence tags per library, and 15% to 43% novel expressed sequence tags per library. Thyroglobulin was found in normal thyroid epithelium and follicular thyroid adenoma, whereas calcitonin precursor transcripts were found in medullary thyroid carcinoma. We demonstrate production of high-quality cDNA libraries of microdissected tissue of the thyroid, which should prove useful for gene expression analysis of human thyroid tumors. C1 Univ Vienna, Sch Med, Dept Clin Pathol, A-1090 Vienna, Austria. Univ Vienna, Sch Med, Dept Surg, A-1090 Vienna, Austria. 20 20 Gene Syst Inc, Rockville, MD USA. NCI, Off Director, NIH, Bethesda, MD 20892 USA. NCI, Canc Genome Anat Project, NIH, Bethesda, MD 20892 USA. RP Kaserer, K (reprint author), Univ Vienna, Sch Med, Dept Clin Pathol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. FU NCI NIH HHS [N01-CO-56000] NR 13 TC 6 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 2002 VL 82 IS 12 BP 1707 EP 1714 DI 10.1097/01.LAB.0000043121.48152.79 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 628CG UT WOS:000179974100010 PM 12480920 ER PT J AU Verma, M Srivastava, S AF Verma, M Srivastava, S TI Epigenetics in cancer: implications for early detection and prevention SO LANCET ONCOLOGY LA English DT Review ID EPSTEIN-BARR-VIRUS; CELL LUNG-CANCER; DNA METHYLATION; PROMOTER HYPERMETHYLATION; HISTONE DEACETYLATION; COLORECTAL-CANCER; GENE-EXPRESSION; NATURAL-SELECTION; EPITHELIAL-CELLS; DOWN-REGULATION AB Knowledge of the molecular events that occur during the early stages of cancer has advanced rapidly. The initiation and development of cancer involves several molecular changes, which include epigenetic alterations. Epigenetics is the study of modifications in gene expression that do not involve changes in DNA nucleotide sequences. Modifications in gene expression through methylation of DNA and remodelling of chromatin via histone proteins are believed to be the most important of the epigenetic changes. The study of epigenetics offers great potential for the identification of biomarkers that can be used to detect and diagnose cancer in its earliest stages and to accurately assess individual risk. There has been a recent surge of interest among researchers as variations in the methylation of DNA have been shown to be the most consistent molecular changes in many neoplasms. An important distinction between a genetic and an epigenetic change in cancer is that epigenetic changes can be reversed more easily by use of therapeutic interventions. The discovery of these basic premises should stimulate much future research on epigenetics. C1 NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Verma, M (reprint author), NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Execut Plaza N,Room 3144,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. NR 74 TC 86 Z9 93 U1 0 U2 6 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2002 VL 3 IS 12 BP 755 EP 763 DI 10.1016/S1470-2045(02)00932-4 PG 9 WC Oncology SC Oncology GA 623UC UT WOS:000179720400025 PM 12473517 ER PT J AU van Klaveren, RJ de Koning, HJ Mulshine, J Hirsch, FR AF van Klaveren, RJ de Koning, HJ Mulshine, J Hirsch, FR TI Lung cancer screening by spiral CT. What is the optimal target population for screening trials? SO LUNG CANCER LA English DT Article DE lung cancer; spiral CT; screening; selection criteria; co-morbidity; risk assessment; age cut-off levels ID CIGARETTE-SMOKING; FOLLOW-UP; ADMINISTRATIVE DATA; COMORBIDITY INDEX; FORMER SMOKERS; UNITED-STATES; CO-MORBIDITY; RISK; MORTALITY; AGE AB The purpose of this document is to provide recommendations for the selection of the optimal target population for lung cancer screening trials with Spiral Computer Tomography based on an analysis of risk factors and high-risk populations. Our recommendations are to include current or ex-smokers ( < 5 years) with a smoking history of at least 30 years and an average consumption of at least 20 cigarettes a day. When these selection criteria are applied there is no need for a lower age cut-off. Elderly people can be included as long as their life expectancy is more than 10 years. Participants should be fit enough to undergo thoracic surgery. They may have a history of previous cancer, provided that the cancer has been curatively treated at least 5 years ago without evidence of relapse, except for,breast cancer, melanoma and hypernephroma. People with an inability to lie flat, who are unable to hold their breath for 20 s, with a body weight above 140 kg, a chest CT scan within 1 year before enrolment or a previous pneumonectomy should not be invited. The inadequacy of the unit 'Pack-Years' (PY) to estimate the individual lung cancer risk is recognised, and future initiatives to develop an appropriate lung cancer risk model are encouraged. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Rotterdam Hosp, Erasmus Med Ctr, Dept Pulmonol, NL-3015 GD Rotterdam, Netherlands. Erasmus Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands. NCI, Intervent Sect, Med Branch, Bethesda, MD 20892 USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. RP van Klaveren, RJ (reprint author), Univ Rotterdam Hosp, Erasmus Med Ctr, Dept Pulmonol, Dr Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands. NR 66 TC 34 Z9 34 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD DEC PY 2002 VL 38 IS 3 BP 243 EP 252 AR PII S0169-5002(02)00222-2 DI 10.1016/S0169-5002(02)00222-2 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 630BK UT WOS:000180087500004 PM 12445745 ER PT J AU Aoki, I Tanaka, C Takegami, T Ebisu, T Umeda, M Fukunaga, M Fukuda, K Silva, AC Koretsky, AP Naruse, S AF Aoki, I Tanaka, C Takegami, T Ebisu, T Umeda, M Fukunaga, M Fukuda, K Silva, AC Koretsky, AP Naruse, S TI Dynamic activity-induced manganese-dependent contrast magnetic resonance imaging (DAIM MRI) SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE functional MRI; manganese; brain activity; somatosensory stimulation; calcium channels ID FUNCTIONAL MRI; CA CHANNELS; HUMAN BRAIN; RAT-BRAIN; STIMULATION; COMPLEXES; FREQUENCY; FLUXES; AGENTS; HEART AB Activity-induced manganese-dependent contrast (AIM) MRI is a hemodynamic-independent functional MRI method that used manganese ion as an MR-detectable contrast agent. In AIM, MnCl2 is infused intra-arterially after the blood-brain barrier (BBB) is opened with a hyperosmolar agent. Upon functional stimulation of the brain, Mn2+ accumulates in the active region(s) by entering active cells through voltage-gated Ca2+ channels, causing local signal increases in T-1-weighted images. The contrast of AIM MRI depends strongly on the depth of anesthesia, and the low levels used in somatosensory stimulation studies can lead to significant nonspecific accumulation of manganese ion throughout the brain. The purpose of this study was to produce an AIM functional map of somatosensory stimulation, which separates the stimulation-specific signal increase from the nonspecific activation due to light anesthesia. A dynamic AIM (DAIM) paradigm was developed, which used sequential MR scans during MnCl2 infusion, prior to and following functional stimulation of the brain. Stimulation-specific functional maps were produced using time-course analysis. The new method was tested during glutamate administration and electric stimulation of the rat forepaw. It was shown that DAIM maps are better confined to the specific region of brain activated by somatosensory stimulation as compared to AIM MRI. C1 Meiji Univ Oriental Med, Dept Neurosurg, Kyoto, Japan. Kyoto Prefectural Univ Med, Dept Neurosurg, Kyoto 602, Japan. Meiji Univ Oriental Med, Dept Physiol, Kyoto, Japan. NINDS, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. Kyoto Prefectural Univ Med, Dept Radiol, Kyoto, Japan. RP Aoki, I (reprint author), Meiji Univ Oriental Med, Med MR Ctr, Dept Med Informat, Hiyoshi, Kyoto 6290392, Japan. RI Silva, Afonso/A-7129-2009; Aoki, Ichio/G-2529-2011; Fukunaga, Masaki/F-6441-2013; Koretsky, Alan/C-7940-2015 OI Aoki, Ichio/0000-0002-4429-5053; Fukunaga, Masaki/0000-0003-1010-2644; Koretsky, Alan/0000-0002-8085-4756 NR 30 TC 91 Z9 94 U1 2 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2002 VL 48 IS 6 BP 927 EP 933 DI 10.1002/mrm.10320 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 620FW UT WOS:000179524200001 PM 12465100 ER PT J AU de Zwart, JA van Gelderen, P Kellman, P Duyn, JH AF de Zwart, JA van Gelderen, P Kellman, P Duyn, JH TI Application of sensitivity-encoded echo-planar imaging for blood oxygen level-dependent functional brain imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; accelerated imaging; SENSE; brain imaging; fMRI; BOLD ID MULTIPLE DETECTORS; COIL ARRAYS; FAST MRI; SENSE; EPI; FMRI; ACQUISITION; SMASH; NOISE; TESLA AB The benefits of sensitivity-encoded (SENSE) echo-planar imaging (EPI) for functional MRI (fMRI) based on blood oxygen level-dependent (BOLD) contrast were quantitatively investigated at 1.5 T. For experiments with 3.4 x 3.4 x 4.0 mm(3) resolution, SENSE allowed the single-shot EPI image acquisition duration to be shortened from 24.1 to 12.4 ms, resulting in a reduced sensitivity to geometric distortions and T-2* blurring. Finger-tapping fMRI experiments, performed on eight normal volunteers, showed an overall 18% loss in t-score in the activated area, which was substantially smaller than expected based on the image signal-to-noise ratio (SNR) and g-factor, but similar to the loss predicted by a model that takes physiologic noise into account. C1 NINDS, Adv MRI, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP de Zwart, JA (reprint author), NINDS, Adv MRI, Lab Funct & Mol Imaging, NIH, Bldg 10,Rm B1D-118,10 Ctr Dr, Bethesda, MD 20892 USA. EM Jacco.deZwart@nih.gov RI Duyn, Jozef/F-2483-2010 NR 28 TC 104 Z9 105 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2002 VL 48 IS 6 BP 1011 EP 1020 DI 10.1002/mrm.10303 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 620FW UT WOS:000179524200013 PM 12465111 ER PT J AU Cohen, DM Wei, JN Smith, EO Gao, XL Quast, MJ Sokoloff, L AF Cohen, DM Wei, JN Smith, EO Gao, XL Quast, MJ Sokoloff, L TI A method for measuring cerebral glucose metabolism in vivo by C-13-NMR spectroscopy SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE 2-deoxyglucose; NMR spectroscopy; bicuculline; glucose utilization; metabolism; cerebral; brain ID RAT-BRAIN; DEOXYGLUCOSE METHOD; INVIVO; 2-DEOXY-D-GLUCOSE; 2-DEOXYGLUCOSE AB Current methods for estimating the rate of cerebral glucose utilization (CMRglc) typically measure metabolic activity for 40 min or longer subsequent to administration of [C-13]glucose, 2-[C-14]deoxyglucose, or 2-[F-18]deoxyglucose. We report preliminary findings on estimating CMRglc for a period of 15 min by use of 2-[6-C-13]deoxyglucose. After a 24-hr fast, rats were anesthetized, infused with [1-C-13]glucose for 50 min, and injected with 2-[6-C-13]deoxyglucose (500 mg/kg). During the subsequent 12.95 min the estimated value of CMRglc was 0.6 +/- 0.4 micromol/min/g (mean +/- SD, N = 7), in agreement with values reported for anesthetized rats studied with the 2-[C-14]deoxyglucose method and other C-13-NMR methods that measure CMRglc. In rats injected with bicuculline methiodide (a known stimulant of CMRglc), CMRglc increased by more than 75% during 12.95 min following injection of bicuculline (Wilcoxon signed rank test, P = 0.042, N = 8). C1 Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Houston, Houston, TX USA. NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. RP Cohen, DM (reprint author), Baylor Coll Med, Childrens Nutr Res Ctr, 1100 Bates St, Houston, TX 77030 USA. NR 19 TC 12 Z9 12 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2002 VL 48 IS 6 BP 1063 EP 1067 DI 10.1002/mrm.10284 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 620FW UT WOS:000179524200020 PM 12465118 ER PT J AU Kellman, P Guttman, MA Herzka, DA McVeigh, ER AF Kellman, P Guttman, MA Herzka, DA McVeigh, ER TI Phased array ghost elimination (PAGE) for segmented SSFP imaging with interrupted steady-state SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE FISP; SSFP; SENSE; ghost cancellation; myocardial tagging; cardiac imaging AB Steady-state free precession (SSFP) has recently proven to be valuable for cardiac imaging due to its high signal-to-noise ratio and blood-myocardium contrast. Data acquired using ECG-triggered, segmented sequences during the approach to steady-state, or return to steady-state after interruption, may have ghost artifacts due to periodic k-space distortion. Schemes involving several preparatory RF pulses have been proposed to restore steady-state, but these consume imaging time during early systole. Alternatively, the phased-array ghost elimination (PAGE) method may be used to remove ghost artifacts from the first several frames. PAGE was demonstrated for cardiac cine SSFP imaging with interrupted steady-state using a simple alpha/2 magnetization preparation and storage scheme and a spatial tagging preparation. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,MSC-1061,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. OI Herzka, Daniel/0000-0002-9400-7814 FU Intramural NIH HHS [Z01 HL004608-08] NR 9 TC 8 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2002 VL 48 IS 6 BP 1076 EP 1080 DI 10.1002/mrm.10309 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 620FW UT WOS:000179524200023 PM 12465121 ER PT J AU Kramer, I Shearer, GM AF Kramer, I Shearer, GM TI Quantifying the strength and durability of induced immunity to HIV infection in women engaging in unprotected sexual contacts with infected men SO MATHEMATICAL AND COMPUTER MODELLING LA English DT Article DE HIV infection; mucosal barriers; innate immunity; cellular immunity; induced immunity; seroprevalence; AIDS ID IMMUNODEFICIENCY-VIRUS TRANSMISSION; SERONEGATIVE PARTNERS; TYPE-1 INFECTION; IFN-ALPHA; T-CELLS; REPLICATION; LYMPHOCYTES; PROSTITUTES; RESISTANCE; MUCOSAL AB Evidence is accumulating that exposure to human immunodeficiency virus (HIV) can lead to an increased resistance or immunity to subsequent infection. A multirisk model that permits either induced immunity or infection to develop after heterosexual inoculation with HIV is shown to be compatible with a wide spectrum of disparate male-to-female transmission data. When the model is applied to time-dependent, HIV-seroprevalence data, the probability that an unexposed woman would remain unexposed after an unprotected contact with an infected man was estimated to be greater than 0.95 on the average. Thus, it would require at least 14 unprotected sexual contacts with HIV-infected men for 50% of an unexposed cohort of women to become exposed to the virus. This suggests that there is a low probability that HIV virions will be found to have penetrated the mucosal barriers of the reproductive tract after a contact. The model also predicts, that the average woman whose mucosal barriers have been breached by HIV has a significant probability of developing immunity to the virus rather than infection. Modelling data for a cohort of unexposed Nairobi women leads to the prediction that the probability of acquiring induced immunity per contact is about 60% of the probability of acquiring the disease per contact. The modelling results also predict that those who had developed resistance to HIV run the small, but significant risk of becoming infected nonetheless by continuing high-risk behavior. For the common contact rate of ten per month, the modelling predicts that the HIV-transmission risk per contact for unexposed women in the Nairobi cohort is 1/178 while the transmission risk for the cohort's immunized women is 1/1548. These numbers suggest that HIV infection is difficult to transmit through heterosexual intercourse on the average and that male-to-female HIV-transmission risk per contact for African women lies between 1/178 and 1/1548. Direct confirmation of the predictions in the last paragraph has been subsequently observed in two completely independent studies. The Nairobi research team recently reported that a notable number of Nairobi prostitutes previously identified to be members of the HIV-resistant group became infected nonetheless. Second, in a study of 174 sexually monogamous, discordant couples in Rakai, Uganda reporting contacts rates of nine to ten per month, the male-to-female HIV-transmission risk per contact was found to be 1/769 by direct measurement, a value that falls between the above limits of 1/178 and 1/1548 predicted by the modelling. Thus, a second major prediction of this paper has been directly confirmed, and induced immunity to HIV is limited and not absolutely protective. Circumstantial evidence suggests that the induced immunity to HIV predicted by the model could be generated and/or initiated by nonspecific innate immune responses, specific immunological responses, including IgA-mediated mucosal immunity and cytotoxic T lymphocytes (CTL) immunity, or some combination of the above. It is suggested here, that a decrease in the ability of HIV virions to penetrate the protective mucus layer of the reproductive tract may be a prerequisite, cofactor, or the principle cause of the induced immunity or resistance demonstrated to exist in this paper. The value of the probability that induced immunity to HIV will develop after a contact is shown to be a sensitive function of the woman's human leucocyte antigen (HLA) supertype profile. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Maryland, Dept Phys, Catonsville, MD 21250 USA. NCI, Expt Immunol Branch, Cell Mediated Immun Sect, NIH, Bethesda, MD 20892 USA. RP Kramer, I (reprint author), Univ Maryland, Dept Phys, 1000 Hilltop Circle, Catonsville, MD 21250 USA. NR 27 TC 4 Z9 4 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-7177 J9 MATH COMPUT MODEL JI Math. Comput. Model. PD DEC PY 2002 VL 36 IS 11-13 BP 1435 EP 1458 AR PII S0895-7177(02)00299-6 DI 10.1016/S0895-7177(02)00299-6 PG 24 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering; Mathematics, Applied SC Computer Science; Mathematics GA 625TH UT WOS:000179831300020 ER PT J AU McNeil, DE Cote, TR Clegg, L Mauer, A AF McNeil, DE Cote, TR Clegg, L Mauer, A TI SEER update of incidence and trends in pediatric malignancies: Acute lymphoblastic leukemia SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE acute lymphoblastic leukemia (ALL); epidemiology; SEER ID CHILDREN; FEATURES AB Background. Acute lymphoblastic leukemia (ALL) represents the most common malignancy of childhood. its incidence peaks in children just before school entry age; i.e., in 2-3 year olds. It is known to be more common in white children in the USA; the incidence is also higher in boys than girls. Procedure. We reviewed the 5,379 cases of ALL among persons under 20 years of age in the National Cancer Institute's Surveillance Epidemiology and End Results SEER) database. Results. The overall incidence of ALL was 26/10(6) person-years between 1973 and 1998, but increased from 19/10(6) person-years in 1973-77 to 28/10(6) person-years in 1993-98 P < 0.0001). Rates were 44% higher among Whites compared to Blacks (27/10(6) person-years vs. 15/10(6) person-years, P < 0.0001). In 1992-1998, the incidence rate for Hispanics was 43/10(6) person-year, significantly higher than non-Hispanics (28/10(6), P < 0.0001). White children with ALL had better 5-year survival rates than Black children with ALL (71% vs. 58%, P < 0.0001), and 5-year surival was poorest among black males. Conclusions. ALL incidence has increased over the examined 25-year period. The rate in US whites is higher than that of US Blacks, mid the rates in the Hispanic subgroup are the highest of all. While the median survival period is now more than 10 years overall, the 5-year survival rate remains poor for Black males under 4 guar, of age. Socioeconomic factors do not account for this difference, which may relate to ALL subtype distribution. (C) 2002 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Rockville, MD USA. NCI, Div Canc Control & Populat Sci, Canc Stat Branch, Rockville, MD USA. Univ Tennessee, Div Hematol Oncol, Memphis, TN USA. RP McNeil, DE (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, EPS Room 7125,6120 Execut Blvd,MSC 7236, Bethesda, MD 20892 USA. NR 18 TC 53 Z9 54 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD DEC PY 2002 VL 39 IS 6 BP 554 EP 557 DI 10.1002/mpo.10161 PG 4 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 606LC UT WOS:000178734600004 PM 12376977 ER PT J AU Clarke, LP Baker, H Kelloff, G Sullivan, D AF Clarke, LP Baker, H Kelloff, G Sullivan, D TI RFA : CA-03-002: Network for translational research: Optical imaging SO MEDICAL PHYSICS LA English DT Editorial Material C1 NCI, Biomed Imaging Program, Rockville, MD 20852 USA. RP Clarke, LP (reprint author), NCI, Biomed Imaging Program, 6130 Execut Blvd, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2002 VL 29 IS 12 BP 2959 EP 2959 DI 10.1118/1.1525010 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 628BA UT WOS:000179970900027 PM 12512733 ER PT J AU Pollock, PM Walker, GJ Glendening, JM Noy, TQ Bloch, NC Fountain, JW Hayward, NK AF Pollock, PM Walker, GJ Glendening, JM Noy, TQ Bloch, NC Fountain, JW Hayward, NK TI PTEN inactivation is rare in melanoma tumours but occurs frequently in melanoma cell lines SO MELANOMA RESEARCH LA English DT Article DE PTEN; melanoma; mutation; deletion; loss of heterozygosity ID MALIGNANT-MELANOMA; PTEN/MMAC1 GENE; SUPPRESSOR GENE; ALLELIC LOSSES; CHROMOSOME 9P; MUTATIONS; IDENTIFICATION; HETEROZYGOSITY; TUMORIGENESIS; SPECIMENS AB Deletions detected in cytogenetic and loss of heterozygosity (LOH) studies indicate that at least one tumour suppressor gene maps to the long arm of chromosome 10. Previous deletion mapping studies have observed LOH on 10q in about 30% of melanomas analysed. The PTEN gene, mapping to chromosome band 10q23.3, encodes a protein with both lipid and protein phosphatase activity. Somatic mutations and deletions in PTEN have been detected in a variety of cell lines and tumours, including melanoma samples. We performed mutation analyses and extensive allelic loss studies to investigate the role this gene plays in melanoma pathogenesis. We found that a total of 34 out of 57 (60%) melanoma cell lines carried hemizygous deletions of chromosome 10q encompassing the PTEN locus. A further three cell lines carried smaller deletions excluding PTEN. Inactivation of both PTEN alleles by exon-specific homozygous deletion or mutation was observed in 13 out of 57 (23%) melanoma cell lines. The mutation spectrum observed does not indicate an important role for ultraviolet radiation in the genesis of these mutations, and evidence from three cell lines supports the acquisition of PTEN aberrations in culture. Ten out of 49 (20%) matched melanoma tumour/normal samples harboured hemizygous deletions of either the whole chromosome or most of the long arm. Mutations within PTEN were detected in only one of the 10 tumours demonstrating LOH at 10q23 that were analysed. These results suggest that PTEN inactivation may be important for the propagation of melanoma cells in culture, and that another chromosome 10 tumour suppressor gene may be important for melanoma pathogenesis in vivo. (C) 2002 Lippincott Williams Wilkins. C1 Univ Queensland, Queensland Inst Med Res, Joint Expt Oncol Program, Brisbane, Qld 4029, Australia. PO Royal Brisbane Hosp, Queensland Canc Fund, Brisbane, Qld 4029, Australia. Univ So Calif, Inst Med Genet, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. RP Pollock, PM (reprint author), NHGRI, Canc Genet Branch, NIH, 50 South Dr,Bldg 50,Room 5139, Bethesda, MD 20892 USA. RI Walker, Graeme/C-2548-2012; hayward, nicholas/C-1367-2015 OI Walker, Graeme/0000-0002-9392-8769; hayward, nicholas/0000-0003-4760-1033 NR 38 TC 39 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD DEC PY 2002 VL 12 IS 6 BP 565 EP 575 DI 10.1097/00008390-200212000-00006 PG 11 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 635FK UT WOS:000180388100006 PM 12459646 ER PT J AU Consolandi, C Bordoni, R Castiglioni, B Frosini, A Mezzelani, A Rizzi, E Battaglia, C Pera, C Ferrara, GB Zatta, P Zambenedetti, P Bernardi, LR De Bellis, G AF Consolandi, C Bordoni, R Castiglioni, B Frosini, A Mezzelani, A Rizzi, E Battaglia, C Pera, C Ferrara, GB Zatta, P Zambenedetti, P Bernardi, LR De Bellis, G TI Investigation of a subset of human polymorphisms by ligase detection reaction and universal array SO MINERVA BIOTECNOLOGICA LA English DT Article; Proceedings Paper CT Microarray Meeting 2002 CY APR 12, 2002 CL SEGRATE, ITALY DE polymorphism; ligase detection reaction; universal array ID DENSITY OLIGONUCLEOTIDE ARRAYS; SEQUENCE-ANALYSIS; IDENTIFICATION; HYBRIDIZATION; MUTATIONS AB We present our results in the identification of human polymorphisms within the 2(nd) exon of the HLA-A region, in the exon 4 of apolipoprotein E and in the exon 15 of the transferrin gene. Allele specific detection was performed by PCR followed by ligase detection reaction (LDR) in combination with a universal array, a powerful method for high throughput DNA sequence analysis. This work confirmed the results previously obtained by sequence or enzymatic analysis thus demonstrating the feasibility of genotyping studies by LDR using a universal DNA array. C1 Univ Milan, Dept Biomed Sci & Technol, I-20133 Milan, Italy. CNR, Inst Biomed Technol, Milan, Italy. Natl Canc Inst, Inst Agr Biol & Biotechnol, Genoa, Italy. Natl Canc Inst, Adv Biotechnol Ctr, Genoa, Italy. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. Gen Hosp, Encephalon Bank, Dolo Venice, Italy. RI Mezzelani, Alessandra/B-3355-2014; Battaglia, Cristina /E-5166-2017; Rizzi, Ermanno/J-7448-2012; Castiglioni, Bianca/G-9856-2013; De Bellis, Gianluca/H-9725-2013 OI Battaglia, Cristina /0000-0003-3025-9657; Castiglioni, Bianca/0000-0003-2326-6701; rizzi, ermanno/0000-0002-9898-2326; MEZZELANI, ALESSANDRA/0000-0001-7563-5869; De Bellis, Gianluca/0000-0002-1622-4477 NR 11 TC 0 Z9 0 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 1120-4826 J9 MINERVA BIOTECNOL JI Minerva Biotechnol. PD DEC PY 2002 VL 14 IS 3-4 BP 259 EP 263 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 672GE UT WOS:000182512200007 ER PT J AU Hoang, MP Murakata, LA Katabi, N Henson, DE Albores-Saavedra, J AF Hoang, MP Murakata, LA Katabi, N Henson, DE Albores-Saavedra, J TI Invasive papillary carcinomas of the extrahepatic bile ducts: a clinicopathologic and immunohistochemical study of 13 cases SO MODERN PATHOLOGY LA English DT Article DE extrahepatic bile ducts; immunohistochemistry; papillary carcinoma ID TUMOR-SUPPRESSOR GENE; DPC4/SMAD4 GENE; BILIARY-TRACT; P53 PROTEIN; GALLBLADDER; EXPRESSION; CANCER; DPC4; MUTATIONS; SURVIVAL AB Carcinomas of the extrahepatic bile ducts are uncommon neoplasms that are morphologically heterogeneous and associated with a poor prognosis. We have previously shown that the noninvasive and minimally invasive papillary carcinomas of the extrahepatic bile ducts behave as in situ carcinomas and are associated with a better prognosis. We reviewed the clinical records of 13 patients with invasive papillary carcinomas of the extrahepatic bile ducts and analyzed the microscopic features and selected immunohistochemical reactivity (p53, Mib-1, and Dpc4) that might correlate with patient survival. In addition, we present the updated SEER (Surveillance, Epidemiology, and End Results) data of the National Cancer Institute for the invasive extrahepatic bile duct carcinomas compiled from 1975 to 1998. The 13 patients with papillary carcinoma had a male to female ratio of 1:1, and their ages ranged from 33 to 89 years. Painless jaundice and abdominal pain were the most common complaints. Five tumors were located in the distal portion, one in the mid portion, and six in the proximal portion of the common bile duct. One papillary carcinoma arose in the right hepatic duct. The Whipple procedure was performed in six patients, common bile duct resection in six, and right hepatic lobectomy in one. The cell phenotype of the papillary carcinomas was biliary in nine and intestinal in three. One tumor had both biliary and intestinal phenotypes. Four tumors dedifferentiated (two to undifferentiated small cell carcinomas, one to small [oat] cell carcinoma, and one to giant cell carcinoma). Two papillary carcinomas extended into the pancreas and three into the liver. Only one patient had lymph node metastases at presentation. Follow-up was available in 10 patients. Six patients died of disease from 2 weeks to 2 years and I month after surgery. Four patients are alive with no evidence of disease from 4 months to 8 years and 8 months after surgery. Of 174 invasive papillary carcinomas compiled by the SEER program, 71 were confined to the ductal wall, and 61 had regional lymph node metastases. Papillary carcinomas confined to the ductal wall have better 10-year relative survival rates than adenocarcinomas limited to the wall (21% versus 12%). Likewise papillary carcinomas with lymph node metastasis have better prognosis than adenocarcinoma with nodal metastases (10-y survival rate of 12% versus 5%). Currently, the histologic type and the stage of the disease are the most important prognostic factors in these papillary carcinomas. Separation of invasive and noninvasive or minimally invasive papillary carcinoma is critical in estimating the patient outcome. Our findings suggest that there is no correlation between p53, Ki-67, and Dpc4 expression in these tumors and survival of the patients. C1 Univ Texas, SW Med Ctr, Div Anat Patol, Dallas, TX USA. Baylor Med Ctr, Div Anat Patol, Dallas, TX USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Albores-Saavedra, J (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Pathol, POB 33932, Shreveport, LA 71130 USA. NR 22 TC 39 Z9 40 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 2002 VL 15 IS 12 BP 1251 EP 1258 DI 10.1097/01.MP.0000036450.61830.8E PG 8 WC Pathology SC Pathology GA 629DC UT WOS:000180034300002 PM 12481004 ER PT J AU Clark, BD Vezza, PR Copeland, C Wilder, AM Abati, A AF Clark, BD Vezza, PR Copeland, C Wilder, AM Abati, A TI Diagnostic sensitivity of bronchoalveolar lavage versus lung fine needle aspirate SO MODERN PATHOLOGY LA English DT Article DE bronchoalveolar lavage; immunosuppression; lung fine needle aspiration; respiratory cytopathology ID CHRONIC GRANULOMATOUS-DISEASE; PULMONARY ASPERGILLOSIS; INVASIVE ASPERGILLOSIS; RESPIRATORY CYTOLOGY; CANCER; COMPLICATIONS; ACCURACY; BIOPSY; HOST; CT AB Bronchoalveolar lavage (BAL) and lung fine-needle aspirate (LFNA) are commonly performed as the first line of investigation for a myriad of pulmonary problems associated with abnormal imaging findings (mass, cavitary lesion, infiltrates, etc.). The relative sensitivities of these two procedures are not well established for cytologic diagnosis of lesions for any single disease event. Records were searched for single pulmonary disease events with closely timed BAL and LFNA, as defined by both procedures occurring within less than or equal to8 days of each other. No samples with "unsatisfactory" diagnoses were considered for the analyses. Success of identifying malignancy and/or an infectious agent was recorded for both procedures. Between January 1989 and June 2000, 52 episodes of closely timed (65% within 3 d) BAL and LFNA procedures were identified in 45 patients for a single disease event. The clinical scenarios as per the sample requisitions were as follows: consolidation/infiltrate (60%), mass/nodule (23%), cavitary lesion (5.7%), pneumonia (5.7%), or not specified (5.7%). For all cases examined (n=52), in 18 (35%) of the episodes, LFNA uniquely identified either malignancy, 6/18 (12%), or infectious agents such as Aspergillus and acid-fast bacteria, 12/18 (23%), with a corresponding nondiagnostic BAL In one episode with a clinical diagnosis of infiltrates, the BAL was positive for acid-fast bacteria, whereas the LFNA was negative. Chi-square analysis of the data revealed statistical significance with P<.0001 with 2 degrees of freedom, indicating LFNA to be a superior method for the diagnosis of pulmonary pathology over BAL. Based on our data, LFNA is the superior method for the cytologic diagnosis of pulmonary pathology amenable to cytologic examination. C1 NCI, Cytopathol Serv, Cytopathol Sect, Lab Pathol,NIH, Bethesda, MD 20892 USA. Our Lady Fatima Hosp, Dept Pathol, Providence, RI USA. RP Abati, A (reprint author), NCI, Cytopathol Serv, Cytopathol Sect, Lab Pathol,NIH, Bldg 10,Room 2A19, Bethesda, MD 20892 USA. NR 30 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 2002 VL 15 IS 12 BP 1259 EP 1265 DI 10.1097/01.MP.0000036456.45865.A9 PG 7 WC Pathology SC Pathology GA 629DC UT WOS:000180034300003 PM 12481005 ER PT J AU Zhang, J Berenstein, E Siraganian, RP AF Zhang, J Berenstein, E Siraganian, RP TI Phosphorylation of Tyr342 in the linker region of Syk is critical for Fc epsilon RI signaling in mast cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; AFFINITY IGE RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; ACTIVATION LOOP TYROSINES; B-CELL; PHOSPHOLIPASE C-GAMMA-1; FAMILY KINASES; NEGATIVE REGULATION; INTERDOMAIN-B; BINDING-SITE AB The linker region of Syk and ZAP70 tyrosine kinases plays an important role in regulating their function. There are three conserved tyrosines in this linker region; Tyr317 of Syk and its equivalent residue in ZAP70 were previously shown to negatively regulate the function of Syk and ZAP70. Here we studied the roles of the other two tyrosines, Tyr342 and Tyr346 of Syk, in FcepsilonRI-mediated signaling. Antigen stimulation resulted in Tyr342 phosphorylation in mast cells. Syk with Y342F mutation failed to reconstitute FcepsilonRI-initiated histamine release. In the Syk Y34217-expressing cells there was dramatically impaired receptor-induced phosphorylation of multiple signaling molecules, including LAT, SLP-76, phospholipase C-gamma2, but not Vav. Compared to wild-type Syk, Y342F Syk had decreased binding to phosphorylated immunoreceptor tyrosine-based activation motifs and reduced kinase activity. Surprisingly, mutation of Tyr346 had much less effect on FcepsilonR1-dependent mast cell degranulation. An anti-Syk-phospho-346 tyrosine antibody indicated that antigen stimulation induced only a very minor increase in the phosphorylation of this tyrosine. Therefore, Tyr342, but not Tyr346, is critical for regulating Syk in mast cells and the function of these tyrosines in immune receptor signaling appears to be different from what has been previously reported for the equivalent residues of ZAP70. C1 NIDCR, RAST Sect, OIIB, NIH, Bethesda, MD 20892 USA. RP Zhang, J (reprint author), NIDCR, RAST Sect, OIIB, NIH, Bldg 10,Rm 1N106, Bethesda, MD 20892 USA. FU NIDCR NIH HHS [N01-DE-62614] NR 61 TC 44 Z9 45 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2002 VL 22 IS 23 BP 8144 EP 8154 DI 10.1128/MCB.22.23.8144-8154.2002 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 614LH UT WOS:000179190600005 PM 12417718 ER PT J AU Marcu, MG Doyle, M Bertolotti, A Ron, D Hendershot, L Neckers, L AF Marcu, MG Doyle, M Bertolotti, A Ron, D Hendershot, L Neckers, L TI Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1 alpha SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; TRANSCRIPTION FACTOR ATF6; KAR2 BIP GENE; ER STRESS; MESSENGER-RNA; TRANSMEMBRANE PROTEIN; KINASE-ACTIVITY; ALPHA-SUBUNIT; HSP90; IRE1 AB The molecular chaperone HSP90 regulates stability and function of multiple protein kinases. The HSP90-binding drug geldanamycin interferes with this activity and promotes proteasome-dependent degradation of most HSP90 client proteins. Geldanamycin also binds to GRP94, the HSP90 parallog located in the endoplasmic reticulum (ER). Because two of three ER stress sensors are transmembrane kinases, namely IRE1alpha and PERK, we investigated whether HSP90 is necessary for the stability and function of these proteins. We found that HSP90 associates with the cytoplasmic domains of both kinases. Both geldanamycin and the HSP90-specific inhibitor, 514, led to the dissociation of HSP90 from the kinases and a concomitant turnover of newly synthesized and existing pools of these proteins, demonstrating that the continued association of HSP90 with the kinases was required to maintain their stability. Further, the previously reported ability of geldanamycin to stimulate ER stress-dependent transcription apparently depends on its interaction with GRP94, not HSP90, since geldanamycin but not 514 led to up-regulation of BiP. However, this effect is eventually superseded by HSP90-dependent destabilization of unfolded protein response signaling. These data establish a role for HSP90 in the cellular transcriptional response to ER stress and demonstrate that chaperone systems on both sides of the ER membrane serve to integrate this signal transduction cascade. C1 NCI, Cell & Canc Biol Branch, NIH, Rockville, MD 20850 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NYU, Skirball Inst, New York, NY 10016 USA. RP Neckers, L (reprint author), 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM len@helix.nih.gov OI Ron, David/0000-0002-3014-5636 NR 46 TC 119 Z9 122 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2002 VL 22 IS 24 BP 8506 EP 8513 DI 10.1128/MCB.22.24.8506-8513.2002 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 620HF UT WOS:000179527400012 PM 12446770 ER PT J AU Sachs, LM Jones, PL Havis, E Rouse, N Demeneix, BA Shi, YB AF Sachs, LM Jones, PL Havis, E Rouse, N Demeneix, BA Shi, YB TI Nuclear receptor corepressor recruitment by unliganded thyroid hormone receptor in gene repression during Xenopus laevis development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BETA-A GENE; N-COR; TRANSCRIPTIONAL REPRESSION; HISTONE DEACETYLASE; IN-VIVO; TR-BETA; AMPHIBIAN METAMORPHOSIS; INTESTINAL DEVELOPMENT; MEDIATED REPRESSION; EXPRESSION AB Thyroid hormone receptors (TR) act as activators of transcription in the presence of the thyroid hormone (T-3) and as repressors in its absence. While many in vitro approaches have been used to study the molecular mechanisms of TR action, their physiological relevance has not been addressed. Here we investigate how TR regulates gene expression during vertebrate postembryonic development by using T-3-dependent amphibian metamorphosis as a model. Earlier studies suggest that TR acts as a repressor during premetamorphosis when T3 is absent. We hypothesize that corepressor complexes containing the nuclear receptor corepressor (N-CoR) are key factors in this TR-dependent gene repression, which is important for premetamorphic tadpole growth. To test this hypothesis, we isolated Xenopus laevis N-CoR (xN-CoR) and showed that it was present in pre- and metamorphic tadpoles. Using a chromatin immunoprecipitation assay, we demonstrated that xN-CoR was recruited to the promoters of T, response genes during premetamorphosis and released upon T3 treatment, accompanied by a local increase in histone acetylation. Furthermore, overexpression of a dominant-negative N-CoR in tadpole tail muscle led to increased transcription from a T-3-dependent promoter. Our data indicate that N-CoR is recruited by unliganded TR to repress target gene expression during premetamorphic animal growth, an important process that prepares the tadpole for metamorphosis. C1 NICHD, Unit Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Museum Natl Hist Nat, UMR 8572 CNRS, Lab Physiol Gen & Comparee, F-75231 Paris 05, France. RP Sachs, LM (reprint author), NICHD, Unit Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. OI Havis, Emmanuelle/0000-0001-5634-3174 NR 64 TC 65 Z9 67 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2002 VL 22 IS 24 BP 8527 EP 8538 DI 10.1128/MCB.22.24.8527-8538.2002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 620HF UT WOS:000179527400014 PM 12446772 ER PT J AU Heffernan, TP Simpson, DA Frank, AR Heinloth, AN Paules, RS Cordeiro-Stone, M Kaufmann, WK AF Heffernan, TP Simpson, DA Frank, AR Heinloth, AN Paules, RS Cordeiro-Stone, M Kaufmann, WK TI An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CYCLE CHECKPOINTS; XERODERMA-PIGMENTOSUM VARIANT; IRRADIATED HUMAN FIBROBLASTS; NIJMEGEN BREAKAGE SYNDROME; EARLY EMBRYONIC LETHALITY; DIPLOID HUMAN FIBROBLASTS; DOUBLE-STRAND BREAKS; ATAXIA-TELANGIECTASIA; DEPENDENT PHOSPHORYLATION; PROTEIN-KINASE AB Inhibition of replicon initiation is a stereotypic DNA damage response mediated through S checkpoint mechanisms not yet fully understood. Studies were undertaken to elucidate the function of checkpoint proteins in the inhibition of replicon initiation following irradiation with 254 nm UV light (UVC) of diploid human fibroblasts immortalized by the ectopic expression of telomerase. Velocity sedimentation analysis of nascent DNA molecules revealed a 50% inhibition of replicon initiation when normal human fibroblasts were treated with a low dose of UVC (1 J/m(2)). Ataxia telangiectasia (AT), Nijmegen breakage syndrome (NBS), and AT-like disorder fibroblasts, which lack an S checkpoint response when exposed to ionizing radiation, responded normally when exposed to UVC and inhibited replicon initiation. Pretreatment of normal and AT fibroblasts with caffeine or UCN-01, inhibitors of ATR (AT mutated and Rad3 related) and Chk1, respectively, abolished the S checkpoint response to UVC. Moreover, overexpression of kinase-inactive ATR in U20S cells severely attenuated UVC-induced Chk1 phosphorylation and reversed the UVC-induced inhibition of replicon initiation, as did overexpression of kinase-inactive Chk1. Taken together, these data suggest that the UVC-induced S checkpoint response of inhibition of replicon initiation is mediated by ATR signaling through Chk-1 and is independent of ATM, Nbs1, and Well. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Ctr Environm Hlth & Susceptibil, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. NIEHS, Growth Control & Canc Grp, Res Triangle Pk, NC 27709 USA. RP Kaufmann, WK (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, CB 7295, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [CA55065, CA81343, P30 CA016086, P30-CA16086, R01 CA055065, R01 CA081343]; NIEHS NIH HHS [P30 ES010126, P30-ES10126, R01 ES011012, T32 ES007017] NR 68 TC 166 Z9 171 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2002 VL 22 IS 24 BP 8552 EP 8561 DI 10.1128/MCB.22.24.8552-8561.2002 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 620HF UT WOS:000179527400016 PM 12446774 ER PT J AU Inga, A Storici, F Darden, TA Resnick, MA AF Inga, A Storici, F Darden, TA Resnick, MA TI Differential transactivation by the p53 transcription factor is highly dependent on p53 level and promoter target sequence SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; DNA-BINDING SITES; CELL-CYCLE CHECKPOINT; MUTANT P53; FUNCTIONAL ASSAY; GENOMIC DNA; IN-VIVO; APOPTOTIC FUNCTION; INDUCE APOPTOSIS; BREAST-CANCER AB Little is known about the mechanisms that regulate differential transactivation by p53. We developed a system in the yeast Saccharomyces cerevisiae that addresses p53 transactivation capacity from 26 different p53 response elements (REs) under conditions where all other factors, such as chromatin, are kept constant. The system relies on a tightly regulated promoter (rheostatable) that can provide for a broad range of p53 expression. The p53 transactivation capacity toward each 20- to 22-bp-long RE could be ranked by using a simple phenotypic assay. Surprisingly, there was as much as a 1,000-fold difference in transactivation. There was no correlation between the functional rank and statistical predictions of binding energy of the REs. Instead we found that the central sequence element in an RE greatly affects p53 transactivation capacity, possibly because of DNA structural properties. Our results suggest that intrinsic DNA binding affinity and p53 protein levels are important contributors to p53-induced differential transactivation. These results are also relevant to understanding the regulation by other families of transcription factors that recognize several sequence-related response elements and/or have tightly regulated expression. We found that p53 had weak activity towards half the apoptotic REs. In addition, p53 alleles associated with familial breast cancer, previously classified as wild type, showed subtle differences in transactivation capacity towards several REs. C1 NIEHS, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Resnick, MA (reprint author), NIEHS, Genet Mol Lab, NIH, Mail Drop D3-01,TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. NR 89 TC 124 Z9 125 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2002 VL 22 IS 24 BP 8612 EP 8625 DI 10.1128/MCB.22.8612-8625.2002 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 620HF UT WOS:000179527400022 PM 12446780 ER PT J AU Kuprash, DV Alimzhanov, MB Tumanov, AV Grivennikov, SI Shakhov, AN Drutskaya, LN Marino, MW Turetskaya, RL Anderson, AO Rajewsky, K Pfeffer, M Nedospasov, SA AF Kuprash, DV Alimzhanov, MB Tumanov, AV Grivennikov, SI Shakhov, AN Drutskaya, LN Marino, MW Turetskaya, RL Anderson, AO Rajewsky, K Pfeffer, M Nedospasov, SA TI Redundancy in tumor necrosis factor (TNF) and lymphotoxin (LT) signaling in vivo: Mice with inactivation of the entire TNF/LT locus versus single-knockout mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PERIPHERAL LYMPHOID ORGANS; ALPHA-DEFICIENT MICE; NATURAL-KILLER-CELLS; T-CELL; B-CELL; SALMONELLA-TYPHIMURIUM; DENDRITIC CELLS; IMMUNE RESPONSIVENESS; ABNORMAL-DEVELOPMENT; SCAVENGER RECEPTORS AB Homologous genes and gene products often have redundant physiological functions. Members of the tumor necrosis factor (TNF) family of cytokines can signal activation, proliferation, differentiation, costimulation, inhibition, or cell death, depending on the type and status of the target cell. TNF, lymphotoxin alpha (LTalpha), and LTbeta form a subfamily of a larger family of TNF-related ligands with their genes being linked within a compact 12-kb cluster inside the major histocompatibility complex locus. Singly TNF-, LTalpha-, and LTbeta-deficient mice share several phenotypic features, suggesting that TNF/LT signaling pathways may regulate overlapping sets of target genes. In order to directly address the issue of redundancy of TNF/LT signaling, we used the Cre-loxP recombination system to create mice with a deletion of the entire TNF/LT locus. Mice with a triple LTO/TNF/LTalpha deficiency essentially manifest a combination of LT and TNF single-knockout phenotypes, except for microarchitecture of the spleen, where the disorder of lymphoid cell positioning and functional T- and B-cell compartmentalization is severer than that found in TNF or LT single-knockout mice. Thus, our data support the notion that TNF and LT have largely nonredundant functions in vivo. C1 Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Mol Immunol, Moscow 319991, Russia. Moscow MV Lomonosov State Univ, Belozersky Inst Physico Chem Biol, Moscow, Russia. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany. Univ Cologne, Inst Genet, D-50931 Cologne, Germany. Mem Sloan Kettering Canc Ctr, New York Branch, Ludwig Inst Canc Res, New York, NY 10021 USA. USA, Med Res Inst Infect Dis, Dept Clin Pathol, Frederick, MD 21702 USA. RP Nedospasov, SA (reprint author), Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Mol Immunol, 32 Vavilov St, Moscow 319991, Russia. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016; OI Kuprash, Dmitry/0000-0002-1488-4148; Pfeffer, Klaus/0000-0002-5652-6330 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 70 TC 47 Z9 49 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2002 VL 22 IS 24 BP 8626 EP 8634 DI 10.1128/MCB.22.24.8626-8634.2002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 620HF UT WOS:000179527400023 PM 12446781 ER PT J AU Prochazka, A Farook, VS Ossowski, V Wolford, JK Bogardus, C AF Prochazka, A Farook, VS Ossowski, V Wolford, JK Bogardus, C TI Variant screening of PRKAB2, a type 2 diabetes mellitus susceptibility candidate gene on 1q in Pima Indians SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE AMP-activated protein kinase; beta 2 subunit gene; chromosome 1q; association; type 2 diabetes mellitus; Pima Indians ID ACTIVATED PROTEIN-KINASE; SKELETAL-MUSCLE; INDEPENDENT REPLICATION; SUBUNIT; EXPRESSION; SCAN; LOCI; GLUCOSE; SEARCH AB The AMP-activated protein kinase (AMPK) is a key enzyme involved in the regulation of lipid and glucose metabolism. There are multiple isoforms of the three subunits of this enzymatic complex, each encoded by a different gene in humans. We have investigated the PRKAB2 gene encoding the beta2 subunit, which is located on chromosome 1q within a region linked with type 2 diabetes mellitus (T2DM) in the Pima Indians and four different Caucasian populations. The gene consists of eight exons spanning about 15 kb, and we detected nine variants in the introns and 3' UTR, including eight informative single nucleotide polymorphisms (SNPs) and one rare 4 bp insertion/deletion. In an analysis of representative markers in selected Pima Indians including 149 diabetic cases (onset age <25 years) and 150 controls (at least 45 years old, with normal glucose tolerance), we found no evidence for association of this locus with T2DM. We conclude that variants in PRKAB2 are unlikely to contribute to the disease susceptibility in Pima Indians. Published by Elsevier Science Ltd C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Res Branch, NIH, Phoenix, AZ 85016 USA. RP Prochazka, A (reprint author), NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Res Branch, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. EM mprochazka@phx.niddk.nih.gov NR 23 TC 0 Z9 0 U1 1 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD DEC PY 2002 VL 16 IS 6 BP 421 EP 427 DI 10.1006/mcpr.2002.0439 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 626LU UT WOS:000179874600004 ER PT J AU Kim, HC Bing, GY Kim, SJ Jhoo, WK Shin, EJ Wie, MB Ko, KH Kim, WK Flanders, KC Choi, SG Hong, JS AF Kim, HC Bing, GY Kim, SJ Jhoo, WK Shin, EJ Wie, MB Ko, KH Kim, WK Flanders, KC Choi, SG Hong, JS TI Kainate treatment alters TGF-beta 3 gene expression in the rat hippocampus SO MOLECULAR BRAIN RESEARCH LA English DT Article DE hippocampus; kainic acid; neurodegeneration; transforming growth factor-beta 3; astrocyte; exogenous TGF-beta 3 ID GROWTH-FACTOR-BETA; KAINIC ACID; MESSENGER-RNA; CEREBRAL-ISCHEMIA; ADULT TISSUES; SUPEROXIDE DISMUTASE; FACTOR-BETA-1 GENE; MICROGLIAL CELLS; NERVOUS-SYSTEM; INFARCT SIZE AB In order to evaluate the role of transforming growth factor (TGF)-beta3 in the neurodegenerative process, we examined the levels of mRNA and immunocytochemical distribution for TGF-beta3 in the rat hippocampus after systemic kainic acid (KA) administration. Hippocampal TGF-beta3 mRNA level was reduced 3 h after KA injection. However, the levels of TGF-beta3 mRNA were elevated 1 day post-KA and lasted for at least 30 days. A mild TGF-beta3 immunoreactivity (TGF-beta3-IR) in the Ammon's horn and a moderate TGF-beta3-IR in the dentate granule cells were observed in the normal hippocampus. The CA1 and CA3 neurons lost their TGF-beta3-IR, while TGF-beta3-positive glia-like cells proliferated mainly throughout the CA1 sector and had an intense immunoreactivity at 7, 15 and 30 days after KA. This immunocytochemical distribution of TGF-beta3-positive non-neuronal populations was similar to that of glial fibrillary acidic protein (GFAP)-positive cells. Double labeling immunocytochemical analysis demonstrated colocalization of TGF-beta3- and GFAP-immunoreactivity in the same cells. These findings suggest a compensatory mechanism of astrocytes for the synthesis of TGF-beta3 protein in response to KA-induced neurodegeneration. In addition, exogenous TGF-beta3 (5 or 10 ng/i.c.v.) significantly attenuated KA-induced seizures and neuronal damages in a dose-related manner. Therefore, our results suggest that TGF-beta3 plays an important role in protective mechanisms against KA-induced neurodegeneration. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Kangweon Natl Univ, Korea Inst Drug Abuse, Coll Pharm, Neurotoxicol Program, Chunchon 200701, South Korea. Univ Kentucky, Med Ctr, Dept Anat & Neurobiol, Lexington, KY 40536 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Kangweon Natl Univ, Dept Vet Med, Chunchon 200701, South Korea. Seoul Natl Univ, Coll Pharm, Seoul, South Korea. Ewha Univ, Sch Med, Inst Neurosci, Dept Pharmacol, Seoul, South Korea. Kangwon Natl Univ, Div Environm & Biol Engn, Chunchon 200701, South Korea. NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Kim, HC (reprint author), Kangweon Natl Univ, Korea Inst Drug Abuse, Coll Pharm, Neurotoxicol Program, Chunchon 200701, South Korea. RI bing, guoying/F-7084-2012 NR 56 TC 9 Z9 10 U1 0 U2 0 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 DEC PY 2002 VL 108 IS 1-2 BP 60 EP 70 AR PII S0169-328X(02)00514-4 DI 10.1016/S0169-328X(02)00514-4 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 630CF UT WOS:000180089400007 ER PT J AU Itokawa, M Lin, ZC Uhl, GR AF Itokawa, M Lin, ZC Uhl, GR TI Dopamine efflux via wild-type and mutant dopamine transporters: alanine substitution for proline-572 enhances efflux and reduces dependence on extracellular dopamine, sodium and chloride concentrations SO MOLECULAR BRAIN RESEARCH LA English DT Article DE neurotransmitters; modulators; transporters; and receptors; uptake and transporters ID CALCIUM-INDEPENDENT RELEASE; FACILITATED EXCHANGE DIFFUSION; TRANSMEMBRANE ALPHA-HELICES; SEROTONIN TRANSPORTER; OUTWARD TRANSPORT; MEDIATED EFFLUX; CELL-LINES; AMPHETAMINE; COCAINE; HYPOTHESIS AB The dopamine transporter (DAT) can mediate not only inward uptake of dopamine, but also its outward efflux by mechanisms that have been only partially elucidated. DAT-dependent dopamine efflux can be studied kinetically and apparent substrate affinity and V-max values determined. We now report that wild-type DAT displays apparent affinities for efflux more than 300-fold lower than those for uptake. Efflux rates are enhanced by increased extracellular concentrations of dopamine or amphetamine and by lowered extracellular concentrations of Na+ or Cl-. Alanine substitutions for six proline residues located in or near DAT transmembrane domains increase apparent affinity and decrease V-max values for dopamine efflux mediated by these mutant transporters. Mutant 12P572A displays increased DAT efflux with reduced dependence on ion or dopamine concentrations. These data add to evidence for the specificity of transporter-mediated efflux processes and begin to elucidate DAT candidate domains that may be preferentially involved with efflux activities. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD 21224 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, IRP, NIH, 5500 Nathan Shock Dr,POB 5180, Baltimore, MD 21224 USA. NR 31 TC 2 Z9 2 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 DEC PY 2002 VL 108 IS 1-2 BP 71 EP 80 AR PII S0169-328X(02)00515-6 DI 10.1016/S0169-328X(02)00515-6 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 630CF UT WOS:000180089400008 ER PT J AU Sutter, TR He, XR Dimitrov, P Xu, LJ Narasimhan, G George, EO Sutter, CH Grubbs, C Savory, R Stephan-Gueldner, M Kreder, D Taylor, MJ Lubet, R Patterson, TA Kensler, TW AF Sutter, TR He, XR Dimitrov, P Xu, LJ Narasimhan, G George, EO Sutter, CH Grubbs, C Savory, R Stephan-Gueldner, M Kreder, D Taylor, MJ Lubet, R Patterson, TA Kensler, TW TI Multiple comparisons model-based clustering and ternary pattern tree numerical display of gene response to treatment: Procedure and application to the preclinical evaluation of chemopreventive agents SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID EXPRESSION PATTERNS; MICROARRAY; OLTIPRAZ; CYTOCHROME-P450; CARCINOGENS; INDUCTION; GENOMICS; ENZYMES; STRESS; DIOXIN AB Microarray technology has greatly aided the identification of genes that are expressed differentially. Statistical analysis of such data by multiple comparisons procedures has been slow to develop, in part, because methods to cluster the results of such comparisons in biologically meaningful ways have not been available. We isolated and analyzed, by Northern blot and GeneChip, replicate liver RNA samples (n = 4/group) from rats fed with control diet or diet containing one of three chemopreventive compounds, selected because their pharmacological activities, including RNA expression response, are relatively well understood. We report on a classification tree, based on the results of nonparametric multiple comparisons, which results in the bipolar hierarchical clustering of genes in relation to their response to treatment. In addition to identifying treatment-responsive genes, application of this procedure to our test study identified the known pharmacological relationships among the treatment groups without supervision. Also, small treatment-specific subsets of genes were identified that may be indicative of additional pharmacophores present in the test compounds. C1 Univ Memphis, W Harry Feinstone Ctr Genom Res, Memphis, TN 38152 USA. Univ Memphis, Dept Math Sci, Memphis, TN 38152 USA. Univ Alabama, Chemoprevent Ctr, Birmingham, AL 35294 USA. Roche, Welwyn Garden City, Herts, England. F Hoffman La Roche AG, Basel, Switzerland. Roche Biosci, Palo Alto, CA 94304 USA. NCI, Div Canc Prevent, Rockville, MD 20852 USA. Johns Hopkins Sch hyg & Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. RP Sutter, TR (reprint author), Univ Memphis, W Harry Feinstone Ctr Genom Res, 201 life Sci Bldg, Memphis, TN 38152 USA. RI Kensler, Thomas/D-8686-2014 OI Kensler, Thomas/0000-0002-6676-261X FU NCI NIH HHS [R01 CA39416, N01-CN-95114-MAO]; NIAAA NIH HHS [U01 AA13515]; NIEHS NIH HHS [R01 ES08148] NR 32 TC 6 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2002 VL 1 IS 14 BP 1283 EP 1292 PG 10 WC Oncology SC Oncology GA 630CU UT WOS:000180090600005 PM 12516961 ER PT J AU Kanzaki, A Takebayashi, Y Ren, XQ Miyashita, H Mori, S Akiyama, S Pommier, Y AF Kanzaki, A Takebayashi, Y Ren, XQ Miyashita, H Mori, S Akiyama, S Pommier, Y TI Overcoming multidrug drug resistance in P-glycoprotein/MDR1-overexpressing cell lines by ecteinascidin 743 SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID MINOR-GROOVE; GLYCOPROTEIN EXPRESSION; CARIBBEAN TUNICATE; ANTITUMOR-ACTIVITY; MARINE COMPOUND; TOPOISOMERASE-I; P-GLYCOPROTEIN; LEUKEMIA-CELLS; CANCER-CELLS; PHASE-I AB Ecteinascidin 743 (Et-743) is a novel anticancer agent forming covalent guanine adducts at specific sites in the DNA minor groove. Et-743 has a unique mechanism of action because it kills cancer cells by poisoning transcription-coupled nucleotide excision repair. Recent studies suggested a complex relationship between P-glycoprotein (P-gp)/MDR1 and Et-743. On one hand, Et-743 was reported to down-regulate the MDR1 promoter in vitro. On the other hand, P-gp overexpression was hypothesized to contribute to Et-743 resistance in an ovarian cell line. The present study was performed to further investigate the relationship between P-gp/MDR1 and the activity of Et-743. First, we found no P-gp/MDR1 overexpression (mRNA and protein levels) in two independently generated Et-743 resistant human colon carcinoma cell lines (HCT116/ER5 and SW480/ER0.5). Secondly, we found no cross-resistance to Et-743 in two well-characterized P-gp/MDR1-overexpressing cell lines (KB-8-5 and KB-C-2). Third, Et-743 pretreatment enhanced the cytotoxicity and the cellular accumulation of doxorubicin and vincristine in P-gp/MDR1-overexpressing KB-8-5/KB-C2 cell lines. Fourth, we observed P-gp/MDR1 down-regulation by Et-743 in KB-C-2 cells. These results indicate that Et-743 does not select for the emergence of a P-gp phenotype in all cell lines made resistant to Et-743 and that P-gp overexpression is not sufficient to confer resistance to Et-743. Furthermore, Et-743 is an effective agent in P-gp-overexpressing cells. Et-743 can potentiate the activity of other chemotherapeutic agents by down-regulating P-gp/MDR1, suggesting that the combination of Et-743 and chemotherapeutic agents that are substrates for P-gp/MDR1 may be valuable in the clinic. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Tohoku Univ, Dept Pathol, Inst Dev Aging & Canc, Sendai, Miyagi 9808575, Japan. Tohoku Univ, Grad Sch Dent, Dept Oral & Maxillofacial Surg, Aoba Ku, Sendai, Miyagi 9808575, Japan. Kagoshima Univ, Fac Med, Dept Canc Chemotherapy, Canc Res Inst, Kagoshima 890, Japan. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Room 5068, Bethesda, MD 20892 USA. NR 42 TC 55 Z9 64 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2002 VL 1 IS 14 BP 1327 EP 1334 PG 8 WC Oncology SC Oncology GA 630CU UT WOS:000180090600010 PM 12516966 ER PT J AU Weisberg, RA Storz, G AF Weisberg, RA Storz, G TI Take your vitamins with a pinch of RNA SO MOLECULAR CELL LA English DT Article AB RNA "aptamers" capable of binding and discriminating among structurally related small molecules can be concocted in the laboratory. Two groups have now discovered that conserved domains in the 5' ends of some mRNAs bind specific metabolites and respond by changing their shape in biologically useful ways, demonstrating that aptamers; also are present in the natural world. C1 NICHHD, Genet Mol Lab, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Weisberg, RA (reprint author), NICHHD, Genet Mol Lab, Bethesda, MD 20892 USA. OI Storz, Gisela/0000-0001-6698-1241 NR 9 TC 5 Z9 5 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC PY 2002 VL 10 IS 6 BP 1266 EP 1268 DI 10.1016/S1097-2765(02)00788-8 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 628BE UT WOS:000179971300007 PM 12504003 ER PT J AU Greene, EC Mizuuchi, K AF Greene, EC Mizuuchi, K TI Target immunity during Mu DNA transposition: Transpososome assembly and DNA looping enhance MuA-mediated disassembly of the MuB target complex SO MOLECULAR CELL LA English DT Article ID BACTERIOPHAGE-MU; B-PROTEIN; STRAND-TRANSFER; ACTIVE-SITE; RECOGNITION; TETRAMER; ATPASE; FORM AB The Mu transpososome can distinguish between proximal and distal DNA during the selection of a site for transposition. This phenomenon, termed target immunity, involves MuA-stimulated removal of MuB oligomers from sites near the Mu genome. Using a combination of ensemble and single-molecule fluorescence methods, we show that the MuA tetramer can stably associate with the DNA-bound MuB oligomer and is more efficient than monomeric MuA at stimulating the dissociation of MuB from DNA. In addition, we demonstrate that DNA looping is essential for efficient disassembly of the MuB oligomer. We propose a model in which the MuA tetramer forms a multivalent complex with the MuB oligomer and catalyzes the processive removal of MuB from DNA. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mizuuchi, K (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 29 TC 19 Z9 19 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC PY 2002 VL 10 IS 6 BP 1367 EP 1378 DI 10.1016/S1097-2765(02)00733-5 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 628BE UT WOS:000179971300016 PM 12504012 ER PT J AU Comstock, KE Georgiadis, N Pecon-Slattery, J Roca, AL Ostrander, EA O'Brien, SJ Wasser, SK AF Comstock, KE Georgiadis, N Pecon-Slattery, J Roca, AL Ostrander, EA O'Brien, SJ Wasser, SK TI Patterns of molecular genetic variation among African elephant populations SO MOLECULAR ECOLOGY LA English DT Article DE African elephant; microsatellites; phylogeography ID LOXODONTA-AFRICANA; MICROSATELLITE; LOCI AB The highly threatened African elephants have recently been subdivided into two species, Loxodonta africana (savannah or bush elephant) and L. cyclotis (forest elephant) based on morphological and molecular studies. A molecular genetic assessment of 16 microsatellite loci across 20 populations (189 individuals) affirms species level genetic differentiation and provides robust genotypic assessment of species affiliation. Savannah elephant populations show modest levels of phylogeographic subdivision based on composite microsatellite genotype, an indication of recent population isolation and restricted gene flow between locales. The savannah elephants show significantly lower genetic diversity than forest elephants, probably reflecting a founder effect in the recent history of the savannah species. C1 Univ Washington, Dept Zool, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Mpala Res Ctr, Nanyuki, Kenya. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Wasser, SK (reprint author), Univ Washington, Dept Zool, Seattle, WA 98195 USA. OI Ostrander, Elaine/0000-0001-6075-9738 FU NHGRI NIH HHS [T32 HG0035] NR 37 TC 76 Z9 78 U1 5 U2 38 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0962-1083 J9 MOL ECOL JI Mol. Ecol. PD DEC PY 2002 VL 11 IS 12 BP 2489 EP 2498 DI 10.1046/j.1365-294X.2002.01615.x PG 10 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 619TD UT WOS:000179492800004 PM 12453234 ER PT J AU Grimm, SL Seagroves, TN Kabotyanski, EB Hovey, RC Vonderhaar, BK Lydon, JP Miyoshi, K Hennighausen, L Ormandy, CJ Lee, AV Stull, MA Wood, TL Rosen, JM AF Grimm, SL Seagroves, TN Kabotyanski, EB Hovey, RC Vonderhaar, BK Lydon, JP Miyoshi, K Hennighausen, L Ormandy, CJ Lee, AV Stull, MA Wood, TL Rosen, JM TI Disruption of steroid and prolactin receptor patterning in the mammary gland correlates with a block in lobuloalveolar development SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; BREAST-CANCER-CELLS; PROGESTERONE-RECEPTOR; C/EBP-BETA; GENE-EXPRESSION; POSTNATAL-DEVELOPMENT; SIGNAL TRANSDUCER; BINDING-PROTEINS; TYROSINE KINASE; DEFICIENT MICE AB Targeted deletion of the bZIP transcription factor, CCAAT/enhancer binding protein-beta (C/EBPbeta), was shown previously to result in aberrant ductal morphogenesis and decreased lobuloalveolar development, accompanied by an altered pattern of progesterone receptor (PR) expression. Here, similar changes in the level and pattern of prolactin receptor (PrIR) expression were observed while screening for differentially expressed genes in C/EBPbeta(null) mice. PR patterning was also altered in PrIRnull mice, as well as in mammary tissue transplants from both PrIRnull and signal transducer and activator of transcription (Stat) 5a/b-deficient mice, with concomitant defects in hormone-induced proliferation. Down-regulation of PR and activation of Stat5 phosphorylation were seen after estrogen and progesterone treatment in. both C/EBPbeta(null) and wild-type mice, indicating that these signaling pathways were functional, despite the failure of steroid hormones to induce proliferation. IGF binding protein-5, IGF-II, and insulin receptor substrate-1 all displayed altered patterns and levels of expression in C/EBPbeta(null) mice, suggestive of a change in the IGF signaling axis. In addition, small proline-rich protein (SPRR2A), a marker of epidermal differentiation, and keratin 6 were misexpressed in the mammary epithelium of C/EBPbeta(null) mice. Together, these data suggest that C/EBPbeta is a master regulator of mammary epithelial cell fate and that the correct spatial pattern of PR and PrIR expression is a critical determinant of hormone-regulated cell proliferation. C1 Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Coll Med, Breast Ctr, Dept Med, Houston, TX 77030 USA. NCI, Mol & Cellular Endocrinol Sect, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Garvan Inst Med Res, Canc Res Program, Darlinghurst, NSW, Australia. Penn State Univ, Coll Med, Dept Neurosci & Anat, Hershey, PA 17033 USA. RP Rosen, JM (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. EM jrosen@bcm.tmc.edu RI Ormandy, Chris/G-4165-2014 NR 57 TC 83 Z9 85 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2002 VL 16 IS 12 BP 2675 EP 2691 DI 10.1210/me.2002-0239 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623EE UT WOS:000179689700001 PM 12456789 ER PT J AU Miyoshi, K Meyer, B Gruss, P Cui, YZ Renou, JP Morgan, FV Smith, GH Reichenstein, M Shani, M Hennighausen, L Robinson, GW AF Miyoshi, K Meyer, B Gruss, P Cui, YZ Renou, JP Morgan, FV Smith, GH Reichenstein, M Shani, M Hennighausen, L Robinson, GW TI Mammary epithelial cells are not able to undergo pregnancy-dependent differentiation in the absence of the helix-loop-helix inhibitor Id2 SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GLAND DEVELOPMENT; GENE-EXPRESSION; PROLIFERATION; PROTEINS; MOUSE; COTRANSPORTER; LOCALIZATION; PROLACTIN; HORMONE; TISSUE AB Mammary alveolar development during pregnancy is triggered by hormone signals. The prolactin receptor/Jak2/signal transducer and activator of transcription (Stat) 5 signal transduction pathway is the principal mediator of these cues and alveolar development is abrogated in its absence. The loss of the basic helix-loop-helix protein inhibitor of differentiation (Id)2 results in a similar defect. To investigate the role of Id2 in mammary epithelium, we performed structural and molecular analyses. Id2-null mammary epithelial cells were unable to form alveoli; the epithelial architecture was disorganized and dissimilar from early stages of alveologenesis in wild-type glands. The epithelial cells retained the ductal marker Na-K-Cl cotransporter (NKCC)1. Nuclear localization of Stat5a and down-regulation of NKCC1 was observed in some areas, indicating a limited response to pregnancy signals. The differentiation status of Id2-null tissue at term was further characterized with cDNA microarrays enriched in mammary specific sequences (mammochip). Some of the early differentiation markers for mammary epithelium were expressed in the Id2-null tissue, whereas genes that are expressed at later stages of pregnancy were not induced. From these results, we conclude that, in the absence of Id2, mammary epithelial development is arrested at an early stage of pregnancy. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Labs, NIH, Bethesda, MD 20892 USA. Univ Tokushima, Sch Dent, Dept Biochem, Tokushima 7708504, Japan. Max Planck Inst Biophys Chem, Dept Mol Cell Biol, D-37077 Gottingen, Germany. INRA, F-78280 Jouy En Josas, France. Agr Res Org, Volcani Ctr, IL-50250 Bet Dagan, Israel. RP Robinson, GW (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Room 101,8 Ctr Dr, Bethesda, MD 20892 USA. EM traudl@nih.gov RI Robinson, Gertraud/I-2136-2012 NR 24 TC 35 Z9 35 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2002 VL 16 IS 12 BP 2892 EP 2901 DI 10.1210/me.2002-0128 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623EE UT WOS:000179689700018 PM 12456807 ER PT J AU Zhao, L Melenhorst, JJ Hennighausen, L AF Zhao, L Melenhorst, JJ Hennighausen, L TI Loss of interleukin 6 results in delayed mammary gland involution: A possible role for mitogen-activated protein kinase and not signal transducer and activator of transcription 3 SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; JAK STAT PATHWAY; EPITHELIAL-CELLS; TYROSINE PHOSPHORYLATION; CYTOKINE RECEPTORS; BREAST-CANCER; APOPTOSIS; DIFFERENTIATION; FAMILY; BCL-2 AB We have investigated the role of IL-6 in the initiation and progression of mouse mammary gland involution in IL-6-null mice. This study was based on the hypothesis that IL-6 is the activating cytokine for signal transducer and activator of transcription 3 (Stat), the transcription factor whose presence is required for controlled mammary gland involution. We now show that expression of IL-6 is low during lactation but increases at the onset of involution in parallel with the activation of Stat3 and p44/42 MAPK. Moreover, we demonstrated that injection of IL-6 into virgin and lactating mice activates Stat3 in mammary epithelium. The in vivo role of IL-6 was investigated using mutant mice. Involution of mammary tissue in IL-6-null mice was delayed similar to that seen in mammary conditional Stat3- and Bax-null mice. However, Stat3 activation during involution was independent of the IL-6 status. This suggests that either IL-6 does not induce Stat3 in vivo or its absence is compensated for by other cytokines, such as leukemia-inhibitory factor (LIF). In contrast, the increase of p44/42 MAPK (ERK1/2) phosphorylation at the onset of involution was dependent on the presence of IL-6. Delayed involution corresponded with a decrease of epithelial cell death, and a delayed induction of Bax and sulfated glycoprotein 2 (SGP2, or clusterin) expression. Our experiments demonstrate on a genetic level that IL-6 contributes to the induction of the controlled remodeling of mammary tissue during involution, possibly through the MAPK pathway and by mediating the expression of the cell death protein Bax. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Zhao, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Room 101, Bethesda, MD 20892 USA. EM LingZ@intra.niddk.nih.gov; hennighausen@nih.gov NR 33 TC 39 Z9 40 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2002 VL 16 IS 12 BP 2902 EP 2912 DI 10.1210/me.2001-0330 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 623EE UT WOS:000179689700019 PM 12456808 ER PT J AU Trincavelli, ML Tuscano, D Marroni, M Falleni, A Gremigni, V Ceruti, S Abbracchio, MP Jacobson, KA Cattabeni, F Martini, C AF Trincavelli, ML Tuscano, D Marroni, M Falleni, A Gremigni, V Ceruti, S Abbracchio, MP Jacobson, KA Cattabeni, F Martini, C TI A(3) adenosine receptors in human astrocytoma cells: Agonist-mediated desensitization, internalization, and down-regulation SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; PHARMACOLOGICAL CHARACTERIZATION; BIOCHEMICAL-CHARACTERIZATION; DEPENDENT PHOSPHORYLATION; ENDOCYTOSIS; SUBTYPE; CYTOSKELETON; DERIVATIVES; ACTIVATION; INDUCTION AB A(3) adenosine receptor activation has been previously demonstrated to result in both neuroprotective and neurodegenerative effects, depending upon specific pathophysiological conditions. This dual effect may depend on receptor regulation mechanisms that are able to change receptor availability and/or function. In the present study, we investigated desensitization, internalization, and down-regulation of native A(3) adenosine receptors in human astrocytoma cells after exposure to the agonist 2-chloro-N6-(3-iodobenzyl)-N-methyl-5'-carbamoyladenosine (CI-IBMECA). CI-IBMECA induced a concentration-dependent inhibition of adenylyl cyclase activity with an EC50 value of 2.9 +/- 0.1 nM. The effect was suggested to be mediated by A(3) adenosine receptor subtype by the use of selective adenosine receptor antagonists. Cell treatment with pertussis toxin abolished CI-IBMECA-mediated inhibition of adenylyl cyclase activity, evidencing an A(3) receptor coupling to inhibitory G protein. Short-term exposure to the agonist CI-IBMECA (100 nM) caused rapid receptor desensitization, within 15 min. Agonist-induced desensitization was accompanied by receptor internalization: A(3) adenosine receptor internalized with rapid kinetics, within 30 min, after cell exposure to 100 nM CI-IBMECA. The localization of A(3) adenosine receptors on the plasma membrane and in intracellular compartments was directly revealed by immunogold electron microscopy. After desensitization, the removal of agonist led to the restoration of A(3) adenosine receptor functioning through receptor recycling to the cell surface within 120 min. Prolonged agonist exposure (1-24 h) resulted in a marked down-regulation of A(3) adenosine receptors that reached 21.9 +/- 2.88% of control value after 24 h. After down-regulation, the recovery of receptor functioning was slow (24 h) and associated with the restoration of receptor levels close to control values. In conclusion, our results demonstrated that A(3) receptors, in astrocytoma cells, are regulated after short- and long-term agonist exposure. C1 Univ Pisa, Dipartimento Psichiat Neurobiol Farmacol & Biotec, I-56126 Pisa, Italy. Univ Pisa, Dipartimento Morphol Umana & Biol Applicata, I-56126 Pisa, Italy. Univ Milan, Dipartimento Sci Farmacol, Milan, Italy. NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Martini, C (reprint author), Univ Pisa, Dipartimento Psichiat Neurobiol Farmacol & Biotec, Via Bonanno 6, I-56126 Pisa, Italy. RI Ceruti, Stefania/A-6376-2008; Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014; OI Ceruti, Stefania/0000-0003-1663-4211; Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388; Trincavelli, Maria Letizia/0000-0001-8124-977X; Martini, Claudia/0000-0001-9379-3027 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 40 TC 48 Z9 48 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2002 VL 62 IS 6 BP 1373 EP 1384 DI 10.1124/mol.62.6.1373 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 615VY UT WOS:000179268900013 PM 12435805 ER PT J AU Fant, M Weisoly, DL Cocchia, M Huber, R Khan, S Lunt, T Schlessinger, D AF Fant, M Weisoly, DL Cocchia, M Huber, R Khan, S Lunt, T Schlessinger, D TI PLAC1, a trophoblast-specific gene, is expressed throughout pregnancy in the human placenta and modulated by keratinocyte growth factor SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE fetal growth; placentation; gene expression; reproduction ID CELL; DIFFERENTIATION; RECEPTOR; SYNCYTIOTROPHOBLAST; LOCUS; MICE AB Plac1, a placenta-specific gene, is expressed exclusively by cells of trophoblastic line-age in the mouse, and maps to a region of the X chromosome known to be important in placental growth. These studies were undertaken to define the cellular location of the mRNA for the human orthologue, PLAC1, within the human placenta, and to examine its expression throughout gestation. By Northern analysis, PLAC1 mRNA was detected in term human placenta, migrating as a single 1.7 kb transcript, but in no other fetal or adult tissues tested. Expression was observed throughout gestation, whereas mouse Plac1 is significantly reduced after 12.5 dpc. Using an S-35-labeled riboprobe, PLAC1 expression was trophoblast-specific at all stages of gestation (8-41 weeks); no expression was seen in cells within the stromal compartment or decidua. Using BeWo choriocarcinoma cells as a trophoblast model, keratinocyte growth factor (KGF) stimulated steady-state PLAC1 mRNA expression approximately twofold by Northern analysis and quantitative real-time PCR. Stimulation was observed only after 24 hr of exposure, suggesting that the stimulatory effect of KGF is secondary to the promotion of trophoblast growth or differentiation. No change in mRNA levels resulted from exposure to insulin-like growth factor II (IGF-II). Trophoblast-specific expression throughout gestation and responsiveness to KGF are consistent with a fundamental role for PLAC1 at the maternal-fetal interface. (C) 2002 Wiley-Liss, Inc. C1 Univ Texas, Sch Med, Dept Pediat, Houston, TX 77030 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Fant, M (reprint author), Univ Texas, Sch Med, Dept Pediat, MSB 3236A,6431 Fannin, Houston, TX 77030 USA. FU NICHD NIH HHS [HD-041404] NR 25 TC 30 Z9 36 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 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD DEC PY 2002 VL 63 IS 4 BP 430 EP 436 DI 10.1002/mrd.10200 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA 607UK UT WOS:000178809000003 PM 12412044 ER PT J AU Chan, JMK Villarreal, G Jin, WW Stepan, T Burstein, H Wahl, SM AF Chan, JMK Villarreal, G Jin, WW Stepan, T Burstein, H Wahl, SM TI Intraarticular gene transfer of TNFR : Fc suppresses experimental arthritis with reduced systemic distribution of the gene product SO MOLECULAR THERAPY LA English DT Article DE inflammation; arthritis; TNFR; gene therapy; rAAV ID TUMOR-NECROSIS-FACTOR; RECOMBINANT ADENOASSOCIATED VIRUS; COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; FACTOR-ALPHA; FACTOR RECEPTOR; IMMUNE-RESPONSE; VIRAL VECTORS; THERAPY; EXPRESSION AB Tumor necrosis factor et (TNFalpha) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). Blockage of TNFalpha actions by systemic administration of TNF antagonists has recently been shown to ameliorate joint symptoms in RA patients. In the present study, a streptococcal cell wall (SCW)-induced rat arthritis model was used to evaluate the effect of different gene transfer routes of a TNF antagonist on the development and severity of arthritis. Successful delivery of a plasmid DNA encoding a rat TNF receptor-immunoglobulin Fc (TNFR:Fc) fusion gene prompted the subsequent administration of a recombinant adeno-associated virus (rAAV) vector encoding the antagonist, either locally (intraarticular) or systemically (intramuscular). The TNFR:Fc gene, delivered by either route, resulted in profound suppression of the arthritis as reflected in decreased inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and mRNA expression of joint proinflammatory cytokines. Increased bioactive serum TNFR levels were detected as a result of rAAV-ratTNFR:Fc administration, concomitant with a decrease in circulating TNFalpha. Administration of the rAAV-ratTNFR:Fc vector to one joint also suppressed arthritis in the contralateral joint. Importantly, intraarticular administration resulted in significantly lower systemic distribution of the gene product. Hence, the use of rAAV as the delivery vector for TNFR:Fc effectively suppressed SCW-induced arthritis and may provide an approach for local delivery of antiarthritic therapy. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Targeted Genet Corp, Seattle, WA 98101 USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bldg 30,Room 320,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. NR 57 TC 63 Z9 72 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD DEC PY 2002 VL 6 IS 6 BP 727 EP 736 DI 10.1006/mthe.2002.0808 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 628ZN UT WOS:000180026100007 PM 12498769 ER PT J AU Lu, HZ Zhang, YF Roberts, DD Osborne, CK Templeton, NS AF Lu, HZ Zhang, YF Roberts, DD Osborne, CK Templeton, NS TI Enhanced gene expression in breast cancer cells in vitro and tumors in vivo SO MOLECULAR THERAPY LA English DT Article DE breast cancer; gene expression; gene therapy; SAGE; liposome; nonviral delivery; GAPDH; promoter; enhancer; hypoxia ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE GENE; SYSTEMIC DELIVERY; THERAPY; VECTOR; IDENTIFICATION; PROMOTER; MICE; DNA AB Gene therapy clinical trials for cancer frequently produce inconsistent results. Some of this variability could result from differences in transcriptional regulation that limit expression of therapeutic genes in specific cancers. Systemic liposomal delivery of a nonviral plasmid DNA showed efficacy in animal models for several cancers. However, we observed large differences in the levels of gene expression from a CMV promoter-enhancer between lung and breast cancers. To optimize gene expression in breast cancer cells in vitro and in vivo, we created a new promoter-enhancer chimera to regulate gene expression. Serial analyses of gene expression data from a panel of breast carcinomas and normal breast cells predicted that the glyceraidehyde-3-phosphate dehydrogenase (GAPDH) promoter is highly active in breast cancers. Furthermore, GAPDH is up-regulated by hypoxia, which is common in tumors. We added the GAPDH promoter, including the hypoxia enhancer sequences, to our in vivo gene expression plasmid. The novel CMV-GAPDH promoter-enhancer showed up to 70-fold increased gene expression in breast tumors compared to the optimized CMV promoter-enhancer alone. No significant increase in gene expression was observed in other tissues. These data demonstrate tissue-specific effects on gene expression after nonviral delivery and suggest that gene delivery systems may require plasmid modifications for the treatment of different tumor types. Furthermore, expression profiling can facilitate the design of optimal expression plasmids for use in specific cancers. C1 NCI, Ctr Cell & Gene Therapy, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Templeton, NS (reprint author), NCI, Ctr Cell & Gene Therapy, NIH, Bldg 10,Room 2A27, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU NCI NIH HHS [P50CA58183] NR 27 TC 27 Z9 27 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD DEC PY 2002 VL 6 IS 6 BP 783 EP 792 DI 10.1006/mthe.2002.0813 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 628ZN UT WOS:000180026100012 PM 12498774 ER PT J AU Kershaw, MH Westwood, JA Hwu, P AF Kershaw, MH Westwood, JA Hwu, P TI Dual-specific T cells combine proliferation and antitumor activity SO NATURE BIOTECHNOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; MOLECULAR-BASIS; GENE; ANTIGEN; IMMUNOTHERAPY; CANCER; VIVO; INTERLEUKIN-2; ANTIBODIES AB An effective immune response against cancer requires the activation and expansion of specific T cells. Tumor antigens, however, are generally poor immunogens. To achieve expansion of tumor-reactive T cells in vivo, we used a strategy of generating dual-specific T cells that could respond to a powerful immunogen while also possessing tumor reactivity. We generated dual-specific T cells by genetic modification of alloreactive T cells with a chimeric receptor recognizing folate-binding protein, an ovarian cancer-associated antigen. Mouse dual-specific T cells responded in vitro to both allogeneic antigen and tumor cells expressing folate-binding protein, and expanded in number in vivo in response to immunization with allogeneic cells. Most importantly, the combination of dual-specific T cells and immunization had an antitumor effect in vivo. We also generated human dual-specific T cells and characterized the dual-specific nature of individual clones. Assigning the tasks of expansion and tumor reactivity to different receptors within the same lymphocyte may help to overcome the problem of poor immunogenicity of tumor antigens. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hwu, P (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. OI Kershaw, Michael/0000-0002-2697-487X NR 33 TC 76 Z9 77 U1 2 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2002 VL 20 IS 12 BP 1221 EP 1227 DI 10.1038/nbt756 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 620VF UT WOS:000179552600041 PM 12415288 ER PT J AU Fernandez-Capetillo, O Chen, HT Celeste, A Ward, I Romanienko, PJ Morales, JC Naka, K Xia, ZF Camerini-Otero, RD Motoyama, N Carpenter, PB Bonner, WM Chen, JJ Nussenzweig, A AF Fernandez-Capetillo, O Chen, HT Celeste, A Ward, I Romanienko, PJ Morales, JC Naka, K Xia, ZF Camerini-Otero, RD Motoyama, N Carpenter, PB Bonner, WM Chen, JJ Nussenzweig, A TI DNA damage-induced G(2)-M checkpoint activation by histone H2AX and 53BP1 SO NATURE CELL BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; NUCLEAR FOCI; ATM; PHOSPHORYLATION; KINASE; BRCA1; P53 AB Activation of the ataxia telangiectasia mutated (ATM) kinase triggers diverse cellular responses to ionizing radiation (IR), including the initiation of cell cycle checkpoints(1). Histone H2AX, p53 binding-protein 1 (53BP1) and Chk2 are targets of ATM-mediated phosphorylation(2-5), but little is known about their roles in signalling the presence of DNA damage. Here, we show that mice lacking either H2AX or 53BP1, but not Chk2, manifest a G2-M checkpoint defect close to that observed in ATM(-/-) cells after exposure to low, but not high, doses of IR. Moreover, H2AX regulates the ability of 53BP1 to efficiently accumulate into IR-induced foci. We propose that at threshold levels of DNA damage, H2AX-mediated concentration of 53BP1 at double-strand breaks is essential for the amplification of signals that might otherwise be insufficient to prevent entry of damaged cells into mitosis. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Div Oncol Res, Rochester, MN 55905 USA. NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. NILS, Dept Geriatr Res, Aichi 4748522, Japan. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Fernandez-Capetillo, O (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RI Fernandez-Capetillo, Oscar/H-3508-2015 OI Fernandez-Capetillo, Oscar/0000-0002-2690-6885 NR 28 TC 427 Z9 446 U1 3 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD DEC PY 2002 VL 4 IS 12 BP 993 EP 997 DI 10.1038/ncb884 PG 5 WC Cell Biology SC Cell Biology GA 621CW UT WOS:000179571800021 PM 12447390 ER PT J AU Putney, JW AF Putney, JW TI PLC-gamma: an old player has a new role SO NATURE CELL BIOLOGY LA English DT Editorial Material ID CAPACITATIVE CALCIUM-ENTRY; PHOSPHOLIPASE-C; INOSITOL TRISPHOSPHATE; INSP(3) RECEPTOR; ACTIVATION; RELEASE; STORE; CELLS; CHANNELS AB The pivotal role of phospholipase C (PLC) in calcium signalling is well established. A product of PLC, inositol 1,4,5-trisphosphate (InsP(3)), is an important and almost ubiquitous signal for the release of calcium from intracellular endoplasmic reticulum stores. Recent work has demonstrated that the PLC-gamma isoform is essential for activating calcium entry into cells through channels in the plasma membrane. C1 Natl Inst Environm Hlth Studies, Calcium Regulat Sect, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), Natl Inst Environm Hlth Studies, Calcium Regulat Sect, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NR 16 TC 12 Z9 13 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD DEC PY 2002 VL 4 IS 12 BP E280 EP E281 DI 10.1038/ncb1202-e280 PG 2 WC Cell Biology SC Cell Biology GA 621CW UT WOS:000179571800005 PM 12461531 ER PT J AU Trent, JM Baxevanis, AD AF Trent, JM Baxevanis, AD TI Chipping away at genomic medicine SO NATURE GENETICS LA English DT Editorial Material C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Trent, JM (reprint author), NHGRI, NIH, 50 South Dr, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 1 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2002 VL 32 SU S BP 462 EP 462 DI 10.1038/ng1025 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 624CN UT WOS:000179742900002 ER PT J AU Chuaqui, RF Bonner, RF Best, CJM Gillespie, JW Flaig, MJ Hewitt, SM Phillips, JL Krizman, DB Tangrea, MA Ahram, M Linehan, WM Knezevic, V Emmert-Buck, MR AF Chuaqui, RF Bonner, RF Best, CJM Gillespie, JW Flaig, MJ Hewitt, SM Phillips, JL Krizman, DB Tangrea, MA Ahram, M Linehan, WM Knezevic, V Emmert-Buck, MR TI Post-analysis follow-up and validation of microarray experiments SO NATURE GENETICS LA English DT Review ID LASER CAPTURE MICRODISSECTION; HUMAN PROSTATE-CANCER; GENE-EXPRESSION PATTERNS; CELL-LINES; PROTEOMIC ANALYSIS; TISSUE; CDNA; SPECIMENS; CARCINOMA; BENIGN AB Measurement of gene-expression profiles using microarray technology is becoming increasingly popular among the biomedical research community. Although there has been great progress in this field, investigators are still confronted with a difficult question after completing their experiments: how to validate the large data sets that are generated? This review summarizes current approaches to verifying global expression results, discusses the caveats that must be considered, and describes some methods that are being developed to address outstanding problems. C1 NCI, Pathogenet Unit, Pathol Lab, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, Bethesda, MD 20892 USA. RI Bonner, Robert/C-6783-2015; OI Hewitt, Stephen/0000-0001-8283-1788 NR 70 TC 298 Z9 316 U1 2 U2 12 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2002 VL 32 SU S BP 509 EP 514 DI 10.1038/ng1034 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 624CN UT WOS:000179742900011 PM 12454646 ER PT J AU Casey, G Neville, PJ Plummer, SJ Xiang, Y Krumroy, LM Klein, EA Catalona, WJ Nupponen, N Carpten, JD Trent, JM Silverman, RH Witte, JS AF Casey, G Neville, PJ Plummer, SJ Xiang, Y Krumroy, LM Klein, EA Catalona, WJ Nupponen, N Carpten, JD Trent, JM Silverman, RH Witte, JS TI RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases SO NATURE GENETICS LA English DT Article ID INTERFERON; ARMS AB RNASEL (encoding ribonuclease L) has recently been proposed as a candidate for the hereditary prostate cancer (HPC1) gene. We determined that the RNASEL variant Arg462Gln has three times less enzymatic activity than the wildtype and is significantly associated with prostate cancer risk (P=0.007). At least one copy of the mutated allele that causes this substitution is carried by nearly 60% of the men in our study. Men that are heterozygous with respect to the mutated allele have 50% greater risk of prostate cancer than non-carriers, and homozygotes have more than double the risk. C1 Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Cleveland Clin Fdn, Inst Urol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. Washington Univ, Dept Urol Surg, St Louis, MO USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Casey, G (reprint author), Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. NR 12 TC 8 Z9 8 U1 0 U2 7 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2002 VL 32 IS 4 BP 582 EP 583 DI 10.1038/ng1021 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 621MH UT WOS:000179593000009 ER PT J AU Kundu, M Javed, A Jeon, JP Horner, A Shum, L Eckhaus, M Muenke, M Lian, JB Yang, YZ Nuckolls, GH Stein, GS Liu, PP AF Kundu, M Javed, A Jeon, JP Horner, A Shum, L Eckhaus, M Muenke, M Lian, JB Yang, YZ Nuckolls, GH Stein, GS Liu, PP TI Cbf beta interacts with Runx2 and has a critical role in bone development SO NATURE GENETICS LA English DT Article ID BINDING-FACTOR-BETA; MYOSIN HEAVY-CHAIN; CLEIDOCRANIAL DYSPLASIA; OSTEOBLAST DIFFERENTIATION; ACUTE-LEUKEMIA; TRANSCRIPTION; PROTEINS; TRANSACTIVATION; HEMATOPOIESIS; CBF-ALPHA-2 AB Runx2 (runt-related transcription factor 2, also known as Cbfa1, Osf2 and AML3) is essential for bone development in mice, and mutations in RUNX2 are found in 65-80% of individuals with cleidocranial dysplasia(1,2). Although all Runx family members can interact with Cbfbeta (core-binding factor b, encoded by Cbfb), a role for Cbfbeta in bone development has not been demonstrated owing to lethality in Cbfb(-/-) mouse embryos at 12.5 days post coitum (d.p.c.)from hemorrhages and lack of definitive hematopoiesis(3,4). Using a 'knock-in' strategy, we generated mouse embryonic stem (ES) cells that express Cbfb fused in-frame to a cDNA encoding green fluorescent protein (GFP)(5). Cbfb(+/GFP) mice had normal life spans and appeared normal, but Cbfb(GFP/GFP) pups died within the first day after birth. The Cbfb(GFP/GFP) mice exhibited a delay in endochondral and intramembranous ossification as well as in chondrocyte differentiation, similar to but less severe than delays observed in Runx2(-/-) mice(6,7). We demonstrate that Cbfbeta is expressed in developing bone and forms a functional interaction with Runx2, and that Cbfb(GFP) is a hypomorphic allele. The fusion allele maintains sufficient function in hematopoietic cells to bypass the early embryonic lethality, and identifies a new role for Cbfb in bone development. Our findings raise the possibility that mutations in CBFB may be responsible for some cases of cleidocranial dysplasia that are not linked to mutations in RUNX2. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Dept Cell Biol, Worcester, MA 01605 USA. NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Vet Resources Program, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Liu, PP (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Bldg 49,Room 3A26, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012; OI Liu, Paul/0000-0002-6779-025X; Javed, Amjad/0000-0002-0847-8266 NR 32 TC 144 Z9 152 U1 1 U2 7 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2002 VL 32 IS 4 BP 639 EP 644 DI 10.1038/ng1050 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 621MH UT WOS:000179593000017 PM 12434156 ER PT J AU Miller, J Horner, A Stacy, T Lowrey, C Lian, JB Stein, G Nuckolls, GH Speck, NA AF Miller, J Horner, A Stacy, T Lowrey, C Lian, JB Stein, G Nuckolls, GH Speck, NA TI The core-binding factor beta subunit is required for bone formation and hematopoietic maturation SO NATURE GENETICS LA English DT Article ID FETAL LIVER HEMATOPOIESIS; RECEPTOR TYROSINE KINASES; CLEIDOCRANIAL DYSPLASIA; CBFA1-DEFICIENT MICE; ENDOTHELIAL-CELLS; DNA RECOGNITION; RUNT DOMAIN; CBF-BETA; GENE; AML1 AB Core-binding factor beta (Cbfbeta) is the common non-DNA-binding subunit of the Cbf family of heterodimeric transcription factors. Mice deficient in Cbfbeta have a severe block in fetal liver hematopoiesis at the stage of hematopoietic stem cell (HSC) emergence(1,2). Here we show that by providing Cbfbeta function in endothelial cells and hematopoietic progenitors we can rescue fetal liver hematopoiesis in Cbfbeta-deficient embryos. The rescued mice die at birth, however, with severe defects in skeletal development, though intramembranous ossification occurs to some extent. Fetal liver hematopoiesis is restored at embryonic day (E) 12.5, but by E17.5 significant impairments in lymphopoiesis and myelopoiesis are observed. Thus, we conclude that the Cbfbeta subunit is required for HSC emergence, bone formation and normal differentiation of lymphoid and myeloid lineage cells. C1 Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03755 USA. NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Dept Med, Hanover, NH USA. Dartmouth Coll Sch Med, Dept Pharmacol & Toxicol, Hanover, NH USA. Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA USA. RP Speck, NA (reprint author), Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03755 USA. NR 29 TC 108 Z9 110 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2002 VL 32 IS 4 BP 645 EP 649 DI 10.1038/ng1049 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 621MH UT WOS:000179593000018 PM 12434155 ER PT J AU Carpten, JD Robbins, CM Villablanca, A Forsberg, L Presciuttini, S Bailey-Wilson, J Simonds, WF Gillanders, EM Kennedy, AM Chen, JD Agarwal, SK Sood, R Jones, MP Moses, TY Haven, C Petillo, D Leotlela, PD Harding, B Cameron, D Pannett, AA Hoog, A Heath, H James-Newton, LA Robinson, B Zarbo, RJ Cavaco, BM Wassif, W Perrier, ND Rosen, IB Kristoffersson, U Turnpenny, PD Farnebo, LO Besser, GM Jackson, CE Morreau, H Trent, JM Thakker, RV Marx, SJ Teh, BT Larsson, C Hobbs, MR AF Carpten, JD Robbins, CM Villablanca, A Forsberg, L Presciuttini, S Bailey-Wilson, J Simonds, WF Gillanders, EM Kennedy, AM Chen, JD Agarwal, SK Sood, R Jones, MP Moses, TY Haven, C Petillo, D Leotlela, PD Harding, B Cameron, D Pannett, AA Hoog, A Heath, H James-Newton, LA Robinson, B Zarbo, RJ Cavaco, BM Wassif, W Perrier, ND Rosen, IB Kristoffersson, U Turnpenny, PD Farnebo, LO Besser, GM Jackson, CE Morreau, H Trent, JM Thakker, RV Marx, SJ Teh, BT Larsson, C Hobbs, MR TI HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome SO NATURE GENETICS LA English DT Article ID HEREDITARY HYPERPARATHYROIDISM; FAMILIAL HYPERPARATHYROIDISM; PARATHYROID TUMORS; GENE; REGION; LOCUS; CHROMOSOME-11; DISTINCT; 1Q21-Q32; LINKAGE AB We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors. C1 Karolinska Hosp, Dept Mol Med, S-10401 Stockholm, Sweden. Karolinska Hosp, Dept Pathol & Oncol, S-10401 Stockholm, Sweden. Karolinska Hosp, Dept Surg Sci, S-10401 Stockholm, Sweden. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Inherited Dis Res Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA. Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Mol Endocrinol Grp, Oxford OX3 9DU, England. Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI USA. Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RA Leiden, Netherlands. Princess Alexandra Hosp, Dept Endocrinol & Diabet, Brisbane, Qld 4102, Australia. Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. Univ Sydney, Royal N Shore Hosp, Kolling Inst Med Res, Sydney, NSW 2006, Australia. Henry Ford Hosp, Dept Pathol, Detroit, MI 48202 USA. Inst Portugues Oncol Francisco Gentil, Ctr Invest Patobiol Mol, Lisbon, Portugal. Univ London Kings Coll, Sch Med & Dent, Dept Clin Biochem, London, England. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden. Royal Devon & Exeter Hosp Wonford, Dept Clin Genet, Exeter, Devon, England. St Bartholomews Hosp, Dept Endocrinol, London, England. Henry Ford Hosp, Dept Med Genet, Detroit, MI 48202 USA. Univ Utah, Div Endocrinol, Salt Lake City, UT USA. Univ Utah, Dept Infect Dis, Salt Lake City, UT USA. RP Carpten, JD (reprint author), Karolinska Hosp, Dept Mol Med, S-10401 Stockholm, Sweden. RI Agarwal, Sunita/D-1428-2016; OI Agarwal, Sunita/0000-0002-7557-3191; Thakker, Rajesh/0000-0002-1438-3220; Cavaco, Branca/0000-0001-8946-8635 FU NCI NIH HHS [R01 CA075177] NR 26 TC 346 Z9 358 U1 1 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2002 VL 32 IS 4 BP 676 EP 680 DI 10.1038/ng1048 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 621MH UT WOS:000179593000024 PM 12434154 ER PT J AU Long, EO AF Long, EO TI Versatile signaling through NKG2D SO NATURE IMMUNOLOGY LA English DT Editorial Material ID T-CELLS; DAP12 AB Receptors in the immune system usually specialize in transmitting specific types of signals. However, by associating with two different signaling subunits, the receptor NKG2D can transmit distinct signals for either costimulation or full-fledged activation. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 12 TC 31 Z9 38 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2002 VL 3 IS 12 BP 1119 EP 1120 DI 10.1038/ni1202-1119 PG 2 WC Immunology SC Immunology GA 619GP UT WOS:000179467800004 PM 12447364 ER PT J AU Naramura, M Jang, IK Kole, H Huang, F Haines, D Gu, H AF Naramura, M Jang, IK Kole, H Huang, F Haines, D Gu, H TI c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation SO NATURE IMMUNOLOGY LA English DT Article ID RECEPTOR SIGNAL-TRANSDUCTION; ADAPTER PROTEIN SLP-76; NEGATIVE REGULATOR; UBIQUITIN LIGASE; TYROSINE KINASES; RING-TYPE; COMPLEX; ZAP-70; MICE; PHOSPHORYLATION AB How Cbl family proteins regulate T cell responses is unclear. We found that c-Cbl Cbl-b double knockout (dKO) T cells became hyperresponsive upon anti-CD3 stimulation, even though the major T cell antigen receptor (TCR) signaling pathways were not enhanced. The dKO T cells did not down-modulate surface TCR after ligand engagement, which resulted in sustained TCR signaling. However, these cells showed normal ligand-independent TCR internalization, and trafficking of internalized TCR to the lysosome compartment after ligand engagement was reduced. These findings show that Cbl family proteins negatively regulate T cell activation by promoting clearance of engaged TCR from the cell surface, a process that is apparently essential for the termination of TCR signals. C1 NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA. NCI, Pathol Histotechnol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Gu, H (reprint author), NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA. OI Naramura, Mayumi/0000-0003-3658-0767 FU NCI NIH HHS [N01-CO-56000] NR 40 TC 239 Z9 249 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2002 VL 3 IS 12 BP 1192 EP 1199 DI 10.1038/ni855 PG 8 WC Immunology SC Immunology GA 619GP UT WOS:000179467800018 PM 12415267 ER PT J AU Hallenbeck, JM AF Hallenbeck, JM TI The many faces of tumor necrosis factor in stroke SO NATURE MEDICINE LA English DT Review ID ACUTE CORONARY SYNDROMES; FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; FACTOR-ALPHA; TNF-ALPHA; ENDOTHELIAL-CELLS; BRAIN INJURY; RAT-BRAIN; SUPEROXIDE-DISMUTASE; REPERFUSION INJURY C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Hallenbeck, JM (reprint author), NINDS, Stroke Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 78 TC 281 Z9 291 U1 1 U2 10 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2002 VL 8 IS 12 BP 1363 EP 1368 DI 10.1038/nm1202-1363 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 620UZ UT WOS:000179552000031 PM 12457181 ER PT J AU Reiter, CD Wang, XD Tanus-Santos, JE Hogg, N Cannon, RO Schechter, AN Gladwin, MT AF Reiter, CD Wang, XD Tanus-Santos, JE Hogg, N Cannon, RO Schechter, AN Gladwin, MT TI Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease SO NATURE MEDICINE LA English DT Article ID REGIONAL BLOOD-FLOW; PULMONARY-HYPERTENSION; MEDIATED VASODILATION; ERYTHROCYTES; ERYTHROPOIETIN; AUTOXIDATION; INSTABILITY; CONSUMPTION; ENDOTHELIUM; DETERMINES AB Although the deleterious vasoconstrictive effects of cell-free, hemoglobin-based blood substitutes have been appreciated, the systemic effects of chronic hemolysis on nitric oxide bioavailability have not been considered or quantified. Central to this investigation is the understanding that nitric oxide reacts at least 1,000 times more rapidly with free hemoglobin solutions than with erythrocytes. We hypothesized that decompartmentalization of hemoglobin into plasma would divert nitric oxide from homeostatic vascular function. We demonstrate here that plasma from patients with sickle-cell disease contains cell-free ferrous hemoglobin, which stoichiometrically consumes micromolar quantities of nitric oxide and abrogates forearm blood flow responses to nitric oxide donor infusions. Therapies that inactivate plasma hemoglobin by oxidation or nitric oxide ligation restore nitric oxide bioavailability. Decompartmentalization of hemoglobin and subsequent dioxygenation of nitric oxide may explain the vascular complications shared by acute and chronic hemolytic disorders. C1 NIDDK, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. Med Coll Wisconsin, Biophys Res Inst, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Free Rad Res Ctr, Milwaukee, WI 53226 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NIDDK, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. RI Tanus-Santos, Jose/A-4451-2008; OI Schechter, Alan N/0000-0002-5235-9408 FU NCRR NIH HHS [RR01008]; NIGMS NIH HHS [GM55792] NR 48 TC 664 Z9 676 U1 0 U2 20 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2002 VL 8 IS 12 BP 1383 EP 1389 DI 10.1038/nm799 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 620UZ UT WOS:000179552000034 PM 12426562 ER PT J AU Carro, E Trejo, JL Gomez-Isla, T LeRoith, D Torres-Aleman, I AF Carro, E Trejo, JL Gomez-Isla, T LeRoith, D Torres-Aleman, I TI Serum insulin-like growth factor I regulates brain amyloid-levels SO NATURE MEDICINE LA English DT Article ID CHOROID-PLEXUS; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; BETA-PEPTIDE; CEREBROSPINAL-FLUID; BINDING-PROTEINS; MESSENGER-RNA; RECEPTOR; PLASMA; NEURODEGENERATION AB Levels of insulin-like growth factor I (IGF-I), a neuroprotective hormone, decrease in serum during aging, whereas amyloid-beta(Abeta), which is involved in the pathogenesis of Alzheimer disease, accumulates in the brain. High brain Abeta levels are found at an early age in mutant mice with low circulating IGF-I, and Abeta burden can be reduced in aging rats by increasing serum IGF-I. This opposing relationship between serum IGF-I and brain Abeta levels reflects the ability of IGF-I to induce clearance of brain Abeta, probably by enhancing transport of Abeta carrier proteins such as albumin and transthyretin into the brain. This effect is antagonized by tumor necrosis factor-alpha, a proinflammatory cytokine putatively involved in dementia and aging. Because IGF-I treatment of mice overexpressing mutant amyloid markedly reduces their brain Abeta burden, we consider that circulating IGF-I is a physiological regulator of brain amyloid levels with therapeutic potential. C1 CSIC, Inst Cajal, Neuroendocrinol Lab, E-28002 Madrid, Spain. Univ Navarra, Univ Navarra Clin, E-31080 Pamplona, Spain. NIH, Clin Endocrinol Branch, Bethesda, MD USA. RP Torres-Aleman, I (reprint author), CSIC, Inst Cajal, Neuroendocrinol Lab, E-28002 Madrid, Spain. RI Trejo, Jose Luis/F-5518-2016 NR 45 TC 332 Z9 349 U1 1 U2 7 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2002 VL 8 IS 12 BP 1390 EP 1397 DI 10.1038/nm793 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 620UZ UT WOS:000179552000035 PM 12415260 ER PT J AU Shaffer, AL Rosenwald, A Staudt, LM AF Shaffer, AL Rosenwald, A Staudt, LM TI Lymphoid malignancies: The dark side of B-cell differentiation SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NF-KAPPA-B; GERMINAL-CENTER FORMATION; HELICOBACTER-PYLORI INFECTION; NON-HODGKIN-LYMPHOMA; TRANSCRIPTION FACTOR; C-MYC; SOMATIC HYPERMUTATION; GENE-EXPRESSION; MALT LYMPHOMA AB When the regulation of B-cell differentiation and activation is disrupted, lymphomas and leukaemias can occur. The processes that normally create immunoglobulin diversity might be misdirected, resulting in oncogenic chromosomal translocations; that block differentiation, prevent apoptosis and/or promote proliferation. Prolonged or unregulated antigenic stimulation might contribute further to the development and progression of some malignancies. Lymphoid malignancies often resemble normal stages of B-cell differentiation, as shown by molecular techniques such as gene-expression profiling. The similarities and differences between malignant and normal B cells indicate strategies for the treatment of these, cancers. C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 120 TC 234 Z9 241 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD DEC PY 2002 VL 2 IS 12 BP 920 EP 932 DI 10.1038/nri953 PG 13 WC Immunology SC Immunology GA 636DT UT WOS:000180439800013 PM 12461565 ER PT J AU Vicario-Abejon, C Owens, D McKay, R Segal, M AF Vicario-Abejon, C Owens, D McKay, R Segal, M TI Role of neurotrophins in central synapse formation and stabilization SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID HIPPOCAMPAL EXCITATORY SYNAPSES; CULTURED CORTICAL-NEURONS; BDNF KNOCKOUT MICE; CELLS IN-VITRO; TRKB RECEPTORS; NEUROTRANSMITTER RELEASE; DENDRITIC GROWTH; DEFICIENT MICE; FULL-LENGTH; ANTEROGRADE TRANSPORT AB The neurotrophins are best known for their ability to support neuronal survival and differentiation, but a role in synapse formation and plasticity has recently emerged. For central neurons, brain-derived neurotrophic factor can increase the number of excitatory and inhibitory synapses by regulating axonal morphology or by directly promoting synapse formation. In addition, neurotrophins promote the maturation and stabilization of the cellular and molecular components that are responsible for neurotransmitter release, and this ultimately leads to an increase in the number of functional synapses. These long-term structural and molecular changes are likely to be crucial not only during development, but also during synaptic plasticity in the adult. C1 CSIC, Ctr Invest Biol, Grp Growth Factors Vertebrate Dev, E-28006 Madrid, Spain. Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. RP Vicario-Abejon, C (reprint author), CSIC, Ctr Invest Biol, Grp Growth Factors Vertebrate Dev, E-28006 Madrid, Spain. NR 130 TC 134 Z9 138 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD DEC PY 2002 VL 3 IS 12 BP 965 EP 974 DI 10.1038/nrn988 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 621QC UT WOS:000179600100015 PM 12461553 ER PT J AU Schwarz, MJ Offenbaecher, M Neumeister, A Ewert, T Willeit, M Praschak-Rieder, N Zach, J Zacherl, M Lossau, K Weisser, R Stucki, G Ackenheil, M AF Schwarz, MJ Offenbaecher, M Neumeister, A Ewert, T Willeit, M Praschak-Rieder, N Zach, J Zacherl, M Lossau, K Weisser, R Stucki, G Ackenheil, M TI Evidence for an altered tryptophan metabolism in fibromyalgia SO NEUROBIOLOGY OF DISEASE LA English DT Article ID NECROSIS-FACTOR-ALPHA; PSYCHOLOGICAL STRESS; GENERAL-POPULATION; PLASMA INTERLEUKIN-6; RHEUMATOID-ARTHRITIS; FIBROSITIS SYNDROME; NORMAL VOLUNTEERS; SEROTONIN LEVELS; PAIN THRESHOLD; DEPLETION AB Fibromyalgia (FM) is a prevalent syndrome with chronic pain and a hypothesized underlying disturbance of the tryptophan (TRP) metabolism. We performed a tryptophan depletion (TD) test in 17 FM patients and 17 controls. TRP, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and interleukin-6 (IL-6) were measured. Additionally pain perception was monitored in the FM patients. FM patients and controls exhibited a decrease of TRP and KYN during TD. 5-HIAA levels also decreased in all controls and in 11 FM patients, but showed a marked increase in 6 FM patients. IL-6 significantly increased during TD in the patients, but not in the controls. Pain perception was not affected in the FM patients. These data demonstrate an altered TRP metabolism in a subgroup of FM patients, where the TD seems to activate 5-HT metabolism. Our findings may have diagnostic as well as therapeutic implications in the field of fibromyalgia. (C) 2003 Elsevier Science (USA). C1 Univ Munich, Hosp Psychiat, D-80336 Munich, Germany. Univ Munich, Dept Phys Med & Rehabil, D-80336 Munich, Germany. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Vienna, Hosp Psychiat, Vienna, Austria. RP Schwarz, MJ (reprint author), Univ Munich, Hosp Psychiat, D-80336 Munich, Germany. NR 36 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD DEC PY 2002 VL 11 IS 3 BP 434 EP 442 DI 10.1006/nbdi.2002.0563 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 643NC UT WOS:000180866500007 PM 12586552 ER PT J AU Deutsch, J Rapoport, SI Rosenberger, TA AF Deutsch, J Rapoport, SI Rosenberger, TA TI Coenzyme A and short-chain acyl-CoA species in control and ischemic rat brain SO NEUROCHEMICAL RESEARCH LA English DT Article DE acyl-CoA; acetyl-CoA; 3-hydroxy-3-methylglutaryl-CoA; butyryl-CoA; brain; ischemia; rat; mitochondria; energy ID NITRIC-OXIDE SYNTHASE; FATTY-ACID; CEREBRAL-ISCHEMIA; A ESTERS; METABOLISM; STROKE; PHOSPHOLIPIDS; HYPOXIA; STATINS; SLICES AB A rapid and reliable method was developed to quantify brain concentrations of coenzyme A (CoA) and short-chain acyl-CoAs having chain length less than or equal to 4 carbon atoms. The method employs tissue extraction and isolation using an oligonucleotide purification cartridge and quantifies concentrations by peak area analysis following high-performance liquid chromatography (HPLC). In adult anesthetized rats subjected to 4-s high-energy microwave irradiation to stop brain metabolism, the brain concentrations of CoA, 3-hydroxy-3-methylglutaryl- CoA (HMGCoA), acetyl-CoA, and butyryl-CoA equaled 68.7 +/- 18.5, 2.7 +/- 1.5, 7.6 +/- 2.3, and 30.6 +/- 15.9 nmol.g(-1), respectively. After 5 min of complete ischemia, the brain concentrations of CoA and HMG-CoA increased 2- and 12-fold compared to controls, whereas acetyl-CoA and butyryl-CoA concentrations did not change. Markedly elevated levels of CoA and HMG-CoA following cerebral ischemia may reflect disturbed energy metabolism and altered formation of cholesterol and isoprenoids. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Sch Pharm, Dept Med Chem, David R Bloom Ctr Pharm, IL-91120 Jerusalem, Israel. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 10,Room 6N202, Bethesda, MD 20892 USA. NR 38 TC 16 Z9 16 U1 0 U2 6 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD DEC PY 2002 VL 27 IS 12 BP 1577 EP 1582 DI 10.1023/A:1021614422668 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 626GE UT WOS:000179862800002 PM 12515307 ER PT J AU Yu, ZY Ono, S Spatz, M McCarron, RM AF Yu, ZY Ono, S Spatz, M McCarron, RM TI Effect of hemorrhagic shock on apoptosis and energy-dependent efflux system in the brain SO NEUROCHEMICAL RESEARCH LA English DT Article DE programmed cell death; P-glycoprotein; bcl-2 gene; mdr1 gene; in situ hybridization; hemorrhagic shock ID MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN EXPRESSION; PROGRAMMED CELL-DEATH; RAT-BRAIN; ENDOTHELIAL-CELLS; GLOBAL-ISCHEMIA; TRANSGENIC MICE; TRANSPORT PROTEINS; BCL-2; INJURY AB Recent findings suggest that apoptosis, which contributes to neuronal damage after ischemic injury, may play a role in sequelae associated with severe blood loss. This study examined the effect of hemorrhage and resuscitation on the expression (in situ hybridization and computerized image analysis) of bcl-2 mRNA, which codes for a protein that inhibits apoptosis, and mdr1 mRNA, which codes for a glycoprotein marker for drug efflux from the brain. Anaesthetized rats were subjected to volume-controlled (15 mL/kg) hemorrhage followed by resuscitation with shed blood (BR) or nonresuscitated (NR); control animals had femoral artery cannulation only (SHAM). Following 24 hr blood loss, distinctly lower levels of bcl-2 gene expression were observed in dentate gyrus of NR rats (0.25 +/- 0.04) as compared to SHAM rats (0.52 +/- 0.07); suscitation with shed blood prevented this reduction (0.58 +/- 0.05). Similar results were observed in cortex, striatum, and hypothalamus. Also, mdr1 mRNA levels were significantly reduced in all brain areas of the NR group as compared to the BR and SHAM groups. The findings suggest that blood resuscitation suppressed apoptosis and protected against loss of energy-dependent efflux system in the brain in response to hemorrhage. C1 USN, Resusciat Med Dept, Combat Casualty Care Directorate, Med Res Ctr, Silver Spring, MD 20910 USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. RP McCarron, RM (reprint author), USN, Resusciat Med Dept, Combat Casualty Care Directorate, Med Res Ctr, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM McCarronR@nnmc.navy.mil NR 51 TC 13 Z9 17 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD DEC PY 2002 VL 27 IS 12 BP 1625 EP 1632 DI 10.1023/A:1021630926302 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 626GE UT WOS:000179862800010 PM 12515315 ER PT J AU Purdon, AD Rosenberger, TA Shetty, HU Rapoport, SI AF Purdon, AD Rosenberger, TA Shetty, HU Rapoport, SI TI Energy consumption by phospholipid metabolism in mammalian brain SO NEUROCHEMICAL RESEARCH LA English DT Article DE brain; phospholipids; phosphatidylinositide cycle; ether phospholipids; de novo synthesis; turnover; signaling; phospholipase C; myo-inositol; rat; human; energy; ATP; phosphatidylinositol ID ARACHIDONIC-ACID; RAT-BRAIN; PHOSPHOINOSITIDE TURNOVER; SIGNAL-TRANSDUCTION; HUMAN-PLATELETS; IN-VIVO; LIPIDS; BIOSYNTHESIS; NEURONS; SYSTEM AB Until recently, brain phospholipid metabolism was thought to consume only 2% of the ATP consumed by the mammalian brain as a whole. In this paper, however, we calculate that 1.4% of total brain ATP consumption is consumed for the de novo synthesis of ether phospholipids and that another 5% is allocated to the phosphatidylinositide cycle. When added to previous estimates that fatty acid recycling within brain phospholipids and maintenance of membrane lipid asymmetries of acidic phospholipids consume, respectively, 5% and 8% of net brain ATP consumption, it appears that phospholipid metabolism can consume up to 20% of net brain ATP consumption. This new estimate is consistent with recent evidence that phospholipids actively participate in brain signaling and membrane remodeling, among other processes. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 10,Room 6N202, Bethesda, MD 20892 USA. NR 60 TC 23 Z9 26 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD DEC PY 2002 VL 27 IS 12 BP 1641 EP 1647 DI 10.1023/A:1021635027211 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 626GE UT WOS:000179862800012 PM 12515317 ER PT J AU Ishai, A Haxby, JV Ungerleider, LG AF Ishai, A Haxby, JV Ungerleider, LG TI Visual imagery of famous faces: Effects of memory and attention revealed by fMRI SO NEUROIMAGE LA English DT Article DE face perception; functional MRI; visual imagery ID POSITRON EMISSION TOMOGRAPHY; PRIMATE TEMPORAL CORTEX; CEREBRAL BLOOD-FLOW; HUMAN NEURAL SYSTEM; SHORT-TERM-MEMORY; MENTAL-IMAGERY; FUNCTIONAL-ANATOMY; WORKING-MEMORY; DIRECTED ATTENTION; NEURONAL CORRELATE AB Complex pictorial information can be represented and retrieved from memory as mental visual images. Functional brain imaging studies have shown that visual perception and visual imagery share common neural substrates. The type of memory (short- or long-term) that mediates the generation of mental images, however, has not been addressed previously. The purpose of this study was to investigate the neural correlates underlying imagery generated from short- and long-term memory (STM and LTM). We used famous faces to localize the visual response during perception and to compare the responses during visual imagery generated from STM (subjects memorized specific pictures of celebrities before the imagery task) and imagery from LTM (subjects imagined famous faces without seeing specific pictures during the experimental session). We found that visual perception of famous faces activated the inferior occipital gyri, lateral fusiform gyri, the superior temporal sulcus, and the amygdala. Small subsets of these face-selective regions were activated during imagery. Additionally, visual imagery of famous faces activated a network of regions composed of bilateral calcarine, hippocampus, precuneus, intraparietal sulcus (IPS), and the inferior frontal gyrus (IFG). In all these regions, imagery generated from STM evoked more activation than imagery from LTM. Regardless of memory type, focusing attention on features of the imagined faces (e.g., eyes, lips, or nose) resulted in increased activation in the right IPS and right IFG. Our results suggest differential effects of memory and attention during the generation faces. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Ishai, A (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. NR 83 TC 177 Z9 185 U1 3 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2002 VL 17 IS 4 BP 1729 EP 1741 DI 10.1006/nimg.2002.1330 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 628AP UT WOS:000179969800007 PM 12498747 ER PT J AU Patterson, JC Ungerleider, LG Bandettini, PA AF Patterson, JC Ungerleider, LG Bandettini, PA TI Task-independent functional brain activity correlation with skin conductance changes: an fMRI study SO NEUROIMAGE LA English DT Article ID PREFRONTAL CORTEX; HUMAN AMYGDALA; VISUAL-CORTEX; DAMAGE; REWARD; MRI AB Lesions of the ventromedial prefrontal cortex cause a loss of skin conductance response (SCR) to stimuli with affective content and an inability to integrate information with social consequences into decisions. Previous behavioral studies using a gambling task were able to differentiate patients with lesions in this region from normal subjects. In the present imaging study, this region, among others, was shown to be "spontaneously" activated during three different cognitive states: a gambling task, a working memory task, and resting state. SCR data were simultaneously collected during the scanning process. Six subjects were scanned at 1.5 T during all three states, and one subject was scanned at 3 T during the resting state only. SCR data were used as a reference function for correlation analysis with the fMRI time series during each of the three tasks. SCR changes were evident during the gambling and two-back tasks as well as during rest. SCR activity was not observed to be specifically related to reward-based decisions in the gambling task. Correlation of the fMRI time series directly with the SCR data revealed a consistent set of activated regions. The activity of these regions showing correlation with the SCR appeared independent of the cognitive state. Further, the subject scanned only at rest (without the possible confound of task-related carryover activity) replicated the findings in the original six subjects. From these data, SCR appears to be a marker of a network that is active during, but independent of, the task being studied. (C) 2002 Elsevier Science (USA). C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Patterson, JC (reprint author), Louisiana State Univ, Ctr Hlth Sci, Inst Biomed Res, PET Imaging Ctr, 1505 Kings Highway, Shreveport, LA 71130 USA. NR 23 TC 78 Z9 78 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2002 VL 17 IS 4 BP 1797 EP 1806 DI 10.1006/nimg.2002.1306 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 628AP UT WOS:000179969800013 PM 12498753 ER PT J AU Wrenn, CC Marriott, LK Kinney, JW Holmes, A Wenk, GL Crawley, JN AF Wrenn, CC Marriott, LK Kinney, JW Holmes, A Wenk, GL Crawley, JN TI Galanin peptide levels in hippocampus and cortex of galanin-overexpressing transgenic mice evaluated for cognitive performance SO NEUROPEPTIDES LA English DT Article ID CHOLINERGIC BASAL FOREBRAIN; LOCUS-COERULEUS NEURONS; ALZHEIMERS-DISEASE; RETROGRADE-AMNESIA; CEREBRAL-CORTEX; MEMORY TASKS; FEAR; AMYGDALA; LESIONS; RATS AB Galanin-overexpressing transgenic mice (GAL-tg) generated on a dopamine P-hydroxylase promoter were previously shown to express high levels of galanin mRNA in the locus coeruleus, and to perform poorly on challenging cognitive tasks. The present study employed radioimmunoassay to quantitate the level of galanin peptide overexpression in two brain regions relevant to learning and memory, the hippocampus and cerebral cortex. Approximately 4-fold higher levels of galanin were detected in the hippocampus of GAL-tg as compared to WT. Approximately 10-fold higher levels of galanin were detected in the frontal cortex of GAL-tg as compared to WT. A second cohort of GAL-tg and WT again showed high levels of galanin overexpression in GAL-tg as compared to WT in both brain regions. Correlation analyses were conducted between galanin peptide concentrations and behavioral scores on four learning and memory tasks: the Morris water maze, social transmission of food preference, standard delay fear conditioning, and trace fear conditioning. While some significant correlations were detected, neither hippocampal nor cortical galanin levels in the two cohorts of GAL-tg consistently correlated with performance across these diverse cognitive tasks. Several interpretations of these findings are discussed, including the possibility that a threshold level of galanin overexpression is sufficient to impair performance on learning and memory tasks in mice. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NIMH, Sect Behav Genom, Bethesda, MD 20892 USA. Univ Arizona, Div Neural Syst Memory & Aging, Dept Psychol, Tucson, AZ USA. Univ Arizona, Div Neural Syst Memory & Aging, Dept Neurol, Tucson, AZ USA. RP Crawley, JN (reprint author), NIMH, Sect Behav Genom, Bethesda, MD 20892 USA. FU NIA NIH HHS [R01 AG10546] NR 56 TC 21 Z9 22 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD DEC PY 2002 VL 36 IS 6 BP 413 EP 426 DI 10.1016/S0143-4179(02)00111-7 PG 14 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 637HH UT WOS:000180505300005 PM 12507436 ER PT J AU Hashimoto, R Takei, N Shimazu, K Christ, L Lu, B Chuang, DM AF Hashimoto, R Takei, N Shimazu, K Christ, L Lu, B Chuang, DM TI Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: An essential step for neuroprotection against glutamate excitotoxicity SO NEUROPHARMACOLOGY LA English DT Article DE lithium; BDNF; TrkB; excitotoxicity; neuroprotection; cerebral cortical neuron ID GLYCOGEN-SYNTHASE KINASE-3-BETA; LONG-TERM POTENTIATION; BDNF KNOCKOUT MICE; RAT-BRAIN; TRANSCRIPTION FACTOR; INDUCED APOPTOSIS; CULTURED NEURONS; NEUROFILAMENT-L; MESSENGER-RNA; KINASE AB Mechanisms underlying the therapeutic effects of lithium for bipolar mood disorder remain poorly understood. Recent studies demonstrate that lithium has neuroprotective actions against a variety of insults in vitro and in vivo. This study was undertaken to investigate the role of the brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway in mediating neuroprotection of lithium against glutamate excitotoxicity in cortical neurons. Pretreatment with either lithium or BDNF protected rat cerebral cortical neurons from glutamate excitotoxicity. The duration of treatment required to elicit maximal neuroprotection by BDNF (1 day) was much shorter than that by lithium (6 days). K252a, an inhibitor of Trk tyrosine kinases, and a BDNF neutralizing antibody suppressed the neuroprotective effect of lithium. Treatment of cortical neurons with lithium increased the cellular BDNF content in 3 days and the phosphorylation of TrkB at Tyr490 in 5 days, suggesting that long-term lithium administration enhances BDNF expression/secretion, leading to the activation of TrkB receptor. Lithium failed to protect against glutamate excitotoxicity in cortical neurons derived from homozygous and heterozygous BDNF knockout mice, although lithium fully protected cortical neurons prepared from wild type mice littermates. Taken together, these data suggest that the BDNF/TrkB pathway plays an essential role in mediating the neuroprotective effect of lithium. Published by Elsevier Science Ltd. C1 NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Niigata Univ, Brain Res Inst, Dept Mol Neurobiol, Niigata 9518585, Japan. NICHHD, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RI Lu, Bai/A-4018-2012; Hashimoto, Ryota/P-8572-2014 OI Hashimoto, Ryota/0000-0002-5941-4238 NR 46 TC 167 Z9 177 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD DEC PY 2002 VL 43 IS 7 BP 1173 EP 1179 DI 10.1016/S0028-3908(02)00217-4 PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 639DY UT WOS:000180613400015 PM 12504924 ER PT J AU Holmes, A Yang, RJ Murphy, DL Crawley, JN AF Holmes, A Yang, RJ Murphy, DL Crawley, JN TI Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin transporter; fluoxetine; desipramine; antidepressant; gene knockout mouse; depression ID FORCED SWIMMING TEST; TAIL SUSPENSION TEST; MAJOR DEPRESSION; REUPTAKE INHIBITORS; AFFECTIVE-DISORDERS; 5-HT1B RECEPTORS; DEFICIENT MICE; ANIMAL-MODELS; GENE; SYSTEM AB Inhibition of the serotonin transporter (5-HTT) is a principal initial target of many antidepressants. However, the contribution of the 5-HTT to their therapeutic efficacy is incompletely understood. We utilized a targeted gene mutation approach to examine the role of the 5-HTT in the behavioral actions of antidepressants. The 5-HTT mutation was bred onto two separate genetic backgrounds, C57BL/6J and 129S6. On a preliminary screen for gross physical, neurological and behavioral functions, all measures were normal with the exception that 5-HTT -/- mice on the C57BL16J background showed increased body weight and poor rotarod performance, and 5-HTT -/- mice on the 129S6 background showed reduced neuromuscular strength. On the tail suspension test, 5-HTT -/- mice on the 129S6 background showed a baseline antidepressant-like reduction in immobility. In contrast, the same mice showed increased immobility in the forced swim test, possibly due to compromised neuromuscular strength. 5-HTT -/- mice on the C57BL16J background showed no baseline antidepressant-related phenotype on either test. The behavioral effects of three antidepressants were tested in 5-HTT mutant mice (C57BL16J background) in the tail suspension test. The anti-immobility effects of the serotonin reuptake inhibitor, fluoxetine (30 mg/kg), were abolished in 5-HTT -/- mice, confirming that the 5-HTT gene is required for the behavioral effects of fluoxetine. In contrast, 5-HTT -/- mice retained sensitivity to the anti-immobility effects of the norcpinephrine reuptake inhibitor, desipramine (20 mg/kg), and the mixed serotonin/norepinephrine reuptake inhibitor, imipramine (25 mg/kg). 5-HTT knockout mice provide a valuable tool for delineating the neuropsychopharmacological actions of antidepressants. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 NIMH, Sect Behav Genomics, NIH, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Holmes, A (reprint author), NIMH, Sect Behav Genomics, NIH, Bldg 10,Room 4D11, Bethesda, MD 20892 USA. NR 81 TC 184 Z9 185 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2002 VL 27 IS 6 BP 914 EP 923 AR PII S0893-133X(02)00374-3 DI 10.1016/S0893-133X(02)00374-3 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 613XM UT WOS:000179156900003 PM 12464448 ER PT J AU Crombag, HS Grimm, JW Shaham, Y AF Crombag, HS Grimm, JW Shaham, Y TI Effect of dopamine receptor antagonists on renewal of cocaine seeking by reexposure to drug-associated contextual cues SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE conditioning; occasion setting; context; drug self-administration; raclopride; reinstatement; relapse; SCH 23390 ID SELF-ADMINISTERED COCAINE; TIME-DEPENDENT CHANGES; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; CONDITIONED REWARD; INDUCED REINSTATEMENT; INTRAVENOUS COCAINE; INVIVO BINDING; BEHAVIOR; RATS AB We recently found that in rats trained to self-administer a heroin-cocaine mixture, exposure to the drug self-administration environment, after extinction of the drug-reinforced behavior in a different context, leads to renewal of drug seeking. Here we further explored the role of contextual stimuli in drug seeking by characterizing the effect of drug-associated environmental stimuli on renewal of cocaine seeking. We also investigated whether activation of dopamine receptors contributes to context-induced renewal of cocaine seeking by testing the effects of selective D1-like (SCH 23390) and D2-like (raclopride) receptor antagonists. Rats were trained for 10 days to self-administer cocaine by pressing a lever. Next, lever pressing was extinguished in the presence of the discrete cues associated with cocaine infusions for 10 days in a context that was distinctively different from the drug-taking context. On the test days, rats were pretreated with SCH 23390 (0, 5 or 10 mug/kg) or raclopride (0, 50 or 100 mug/kg) and nonreinforced lever-pressing behavior was determined either in the extinction context (Control group) or the cocaine-associated context (Renewal group). Consistent with our previous report, cocaine seeking was renewed when rats were exposed to the drug-associated context after extinction in a different context. Furthermore, pretreatment with the D1-like or the D2-like receptor antagonists attenuated context-induced renewal of cocaine seeking. These data suggest that activation of dopamine receptors is involved in reinstatement of cocaine seeking induced by exposure to the drug self-administration context. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI shaham, yavin/G-1306-2014 NR 70 TC 94 Z9 95 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2002 VL 27 IS 6 BP 1006 EP 1015 AR PII S0893-133X(02)00356-1 DI 10.1016/S0893-133X(02)00356-1 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 613XM UT WOS:000179156900012 PM 12464457 ER PT J AU Hariri, AR Mattay, VS Tessitore, A Fera, F Smith, WG Weinberger, DR AF Hariri, AR Mattay, VS Tessitore, A Fera, F Smith, WG Weinberger, DR TI Dextroamphetamine modulates the response of the human amygdala SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE fear; anxiety; amygdala; monoamines; dopamine; amphetamine ID REPEATED D-AMPHETAMINE; BASOLATERAL AMYGDALA; DOPAMINE; SENSITIZATION; INHIBITION; EXPRESSION; ACTIVATION; NETWORK; SIGNALS; STRESS AB Amphetamine, a potent monoaminergic agonist, has pronounced effects on emotional behavior in humans, including the generation of fear and anxiety. Recent animal studies have demonstrated the importance of monoamines, especially dopamine, in modulating the response of the amygdala, a key brain region involved in the perception of fearful and threatening stimuli, and the generation of appropriate physiological and behavioral responses. We have explored the possibility that the anxiogenic effect of amphetamine in humans reflects the drug's influence on the activity of the amygdala. In a double-blind placebo controlled study, fMRI revealed that dextroamphetamine potentiated the response of the amygdala during the perceptual processing of angry and fearful facial expressions. Our results provide the first evidence of a specific neural substrate for the anxiogenic effects of amphetamine and are consistent with animal models of dopaminergic activation of the amygdala. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Hariri, AR (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, 10 Ctr Dr,Room 3C108, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011 NR 25 TC 110 Z9 111 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2002 VL 27 IS 6 BP 1036 EP 1040 AR PII S0893-133X(02)00373-1 DI 10.1016/S0893-133X(02)00373-1 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 613XM UT WOS:000179156900015 PM 12464460 ER PT J AU Frascella, J Pilotte, N Thomas, D AF Frascella, J Pilotte, N Thomas, D TI In memoriam - Roger M. Brown, 1941-2002 SO NEUROPSYCHOPHARMACOLOGY LA English DT Biographical-Item C1 NIDA, NIH, Bethesda, MD USA. RP Frascella, J (reprint author), NIDA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2002 VL 27 IS 6 BP 1086 EP 1087 AR PII S0893-133X(02)00413-X DI 10.1016/S0893-133X(02)00413-X PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 613XM UT WOS:000179156900022 ER PT J AU Decking, UKM AF Decking, UKM TI Spatial heterogeneity in the heart: Recent insights and open questions SO NEWS IN PHYSIOLOGICAL SCIENCES LA English DT Article ID MYOCARDIAL BLOOD-FLOW; CORONARY RESERVE; GLUCOSE-UPTAKE; DOG HEART; PATTERNS; REGIONS AB Within the left ventricular myocardium and despite its rather homogeneous structure, local myocardial perfusion varies substantially. Areas of low and high local flow differ with regard to substrate uptake, energy turnover, and demand. This spatial heterogeneity is related to distinct differences in local protein expression, forming the basis of a novel homeostatic mechanism. C1 Univ Dusseldorf, Inst Herz & Kreislaufphysiol, D-40001 Dusseldorf, Germany. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Decking, UKM (reprint author), Univ Dusseldorf, Inst Herz & Kreislaufphysiol, D-40001 Dusseldorf, Germany. NR 20 TC 18 Z9 19 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0886-1714 J9 NEWS PHYSIOL SCI JI News Physiol. Sci. PD DEC PY 2002 VL 17 BP 246 EP 250 DI 10.1152/nips.01393.2002 PG 5 WC Physiology SC Physiology GA 618YF UT WOS:000179445200007 PM 12433979 ER PT J AU Otsuka, C Sanadai, S Hata, Y Okuto, H Noskov, VN Loakes, D Negishi, K AF Otsuka, C Sanadai, S Hata, Y Okuto, H Noskov, VN Loakes, D Negishi, K TI Difference between deoxyribose- and tetrahydrofuran-type abasic sites in the in vivo mutagenic responses in yeast SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MAJOR APURINIC ENDONUCLEASE; STRUCTURAL GENE APN1; DNA-POLYMERASE-KAPPA; SACCHAROMYCES-CEREVISIAE; APYRIMIDINIC SITES; SYNTHETIC OLIGONUCLEOTIDES; MAMMALIAN-CELLS; REPAIR ENZYMES; A-RULE; BYPASS AB We have analyzed the mutagenic specificity of an abasic site in DNA using the yeast oligonucleotide transformation assay. Oligonucleotides containing an abasic site or its analog were introduced into B7528 or its derivatives, and nucleotide incorporation opposite abasic sites was analyzed. Cytosine was most frequently incorporated opposite a natural abasic site (O) ('C-rule'), followed by thymine. Deletion of REV1 decreased the transformation efficiency and the incorporation of cytosine nearly to a background level. In contrast, deletion of RAD30 did not affect them. We compared the mutagenic specificity with that of a tetrahydrofuran abasic site (F), an abasic analog used widely. Its mutation spectrum was clearly different from that of O. Adenine, not cytosine, was most favorably incorporated. However, deletion of REV1 decreased the transformation efficiency with F-containing oligonucleotide as in the case of O. These results suggest that the bypass mechanism of F is different from that of O, although the bypasses in both cases are dependent on REV1. We also found that the mutagenic specificity of F can be affected by not only the adjacent bases, but also a base located two positions away from F. C1 Okayama Univ, Ctr Gene Res, Okayama 7008530, Japan. NCI, Bethesda, MD 20892 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. RP Negishi, K (reprint author), Okayama Univ, Ctr Gene Res, Okayama 7008530, Japan. NR 42 TC 36 Z9 36 U1 1 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 DEC 1 PY 2002 VL 30 IS 23 BP 5129 EP 5135 DI 10.1093/nar/gkf666 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 622WX UT WOS:000179671500020 PM 12466536 ER PT J AU Zhang, JH Rowe, WL Struewing, JP Buetow, KH AF Zhang, JH Rowe, WL Struewing, JP Buetow, KH TI HapScope: a software system for automated and visual analysis of functionally annotated haplotypes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN LIPOPROTEIN-LIPASE; HUMAN GENOME; APOLIPOPROTEIN-E; ALZHEIMERS-DISEASE; SEQUENCE VARIATION; CROHNS-DISEASE; GENE; SUSCEPTIBILITY; IDENTIFICATION; POLYMORPHISM AB We have developed a software analysis package, HapScope, which includes a comprehensive analysis pipeline and a sophisticated visualization tool for analyzing functionally annotated haplotypes. The HapScope analysis pipeline supports: (i) computational haplotype construction with an expectation-maximization or Bayesian statistical algorithm; (ii) SNP classification by protein coding change, homology to model organisms or putative regulatory regions; and (iii) minimum SNP subset selection by either a Brute Force Algorithm or a Greedy Partition Algorithm. The HapScope viewer displays genomic structure with haplotype information in an integrated environment, providing eight alternative views for assessing genetic and functional correlation. It has a user-friendly interface for: (i) haplotype block visualization; (ii) SNP subset selection; (iii) haplotype consolidation with subset SNP markers; (iv) incorporation of both experimentally determined haplotypes and computational results; and (v) data export for additional analysis. Comparison of haplotypes constructed by the statistical algorithms with those determined experimentally shows variation in haplotype prediction accuracies in genomic regions with different levels of nucleotide diversity. We have applied HapScope in analyzing haplotypes for candidate genes and genomic regions with extensive SNP and genotype data. We envision that the systematic approach of integrating functional genomic analysis with population haplotypes, supported by HapScope, will greatly facilitate current genetic disease research. C1 NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. RP Zhang, JH (reprint author), NCI, Lab Populat Genet, NIH, 8424 Helgerman Court,Room 101,MSC 8302, Bethesda, MD 20892 USA. EM jinghuiz@mail.nih.gov RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 29 TC 22 Z9 25 U1 1 U2 2 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 DEC 1 PY 2002 VL 30 IS 23 BP 5213 EP 5221 DI 10.1093/nar/gkf654 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 622WX UT WOS:000179671500030 PM 12466546 ER PT J AU Mazumder, R Iyer, LM Vasudevan, S Aravind, L AF Mazumder, R Iyer, LM Vasudevan, S Aravind, L TI Detection of novel members, structure-function analysis and evolutionary classification of the 2H phosphoesterase superfamily SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RIBOSE 1'',2''-CYCLIC PHOSPHATE; 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE; TRANSFER-RNA LIGASE; ESCHERICHIA-COLI; CYCLIC PHOSPHODIESTERASE; SACCHAROMYCES-CEREVISIAE; PHOSPHOLIPID SYNTHASES; POLYNUCLEOTIDE KINASE; SECONDARY STRUCTURE; DATABASE SEARCH AB 2',3' Cyclic nucleotide phosphodiesterases are enzymes that catalyze at least two distinct steps in the splicing of tRNA introns in eukaryotes. Recently, the biochemistry and structure of these enzymes, from yeast and the plant Arabidopsis thaliana, have been extensively studied. They were found to share a common active site, characterized by two conserved histidines, with the bacterial tRNA-ligating enzyme LigT and the vertebrate myelin-associated 2',3' phosphodiesterases. Using sensitive sequence profile analysis methods, we show that these enzymes define a large superfamily of predicted phosphoesterases with two conserved histidines (hence 2H phosphoesterase superfamily). We identify several new families of 2H phosphoesterases and present a complete evolutionary classification of this superfamily. We also carry out a structure- function analysis of these proteins and present evidence for diverse interactions for different families, within this superfamily, with RNA substrates and protein partners. In particular, we show that eukaryotes contain two ancient families of these proteins that might be involved in RNA processing, transcriptional co-activation and post-transcriptional gene silencing. Another eukaryotic family restricted to vertebrates and insects is combined with UBA and SH3 domains suggesting a role in signal transduction. We detect these phosphoesterase modules in polyproteins of certain retroviruses, rotaviruses and coronaviruses, where they could function in capping and processing of viral RNAs. Furthermore, we present evidence for multiple families of 2H phosphoesterases in bacteria, which might be involved in the processing of small molecules with the 2',3' cyclic phosphoester linkages. The evolutionary analysis suggests that the 2H domain emerged through a duplication of a simple structural unit containing a single catalytic histidine prior to the last common ancestor of all life forms. Initially, this domain appears to have been involved in RNA processing and it appears to have been recruited to perform various other functions in later stages of evolution. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 82 TC 90 Z9 90 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 1 PY 2002 VL 30 IS 23 BP 5229 EP 5243 DI 10.1093/nar/gkf645 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 622WX UT WOS:000179671500032 PM 12466548 ER PT J AU Frank, EG Sayer, JM Kroth, H Ohashi, E Ohmori, H Jerina, DM Woodgate, R AF Frank, EG Sayer, JM Kroth, H Ohashi, E Ohmori, H Jerina, DM Woodgate, R TI Translesion replication of benzo[a]pyrene and benzo[c]phenanthrene diol epoxide adducts of deoxyadenosine and deoxyguanosine by human DNA polymerase iota SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DOSE-DEPENDENT DIFFERENCES; GUANINE PHOSPHORIBOSYLTRANSFERASE GENE; HUMAN DINB1 GENE; NUCLEOTIDE MISINSERTION; MUTATIONAL CONSEQUENCES; M13MP7L2 CONSTRUCTS; NUCLEOSIDE ADDUCTS; ESCHERICHIA-COLI; SEQUENCE CONTEXT; UV-MUTAGENESIS AB Human DNA polymerase iota (poliota) is a Y-family polymerase whose cellular function is presently unknown. Here, we report on the ability of poliota to bypass various stereoisomers of benzo[a]pyrene (BaP) diol epoxide (DE) and benzo[c]phenanthrene (BcPh) DE adducts at deoxyadenosine (dA) or deoxyguanosine (dG) bases in four different template sequence contexts in vitro. We find that the BaP DE dG adducts pose a strong block to poliota-dependent replication and result in a high frequency of base misincorporations. In contrast, misincorporations opposite BaP DE and BcPh DE dA adducts generally occurred with a frequency ranging between 2 x 10(-3) and 6 x 10(-4). Although dTMP was inserted efficiently opposite all dA adducts, further extension was relatively poor, with one exception (a cis opened adduct derived from BcPh DE) where up to 58% extension past the lesion was observed. Interestingly, another human Y-family polymerase, polkappa, was able to extend dTMP inserted opposite a BaP DE dA adduct. We suggest that poliota might therefore participate in the error-free bypass of DE-adducted dA in vivo by predominantly incorporating dTMP opposite the damaged base. In many cases, elongation would, however, require the participation of another polymerase more specialized in extension, such as polkappa. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bldg 6,Room 1A13,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 62 TC 53 Z9 56 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 DEC 1 PY 2002 VL 30 IS 23 BP 5284 EP 5292 DI 10.1093/nar/gkf643 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 622WX UT WOS:000179671500038 PM 12466554 ER PT J AU Jackson, Y Dietz, WH Sanders, C Kolbe, LJ Whyte, JJ Wechsler, H Schneider, BS McNally, LA Charles-Azure, J Vogel-Taylor, M Starke-Reed, P Hubbard, VS Johnson-Taylor, WL Troiano, RP Donato, K Yanovski, S Kuczmarski, RJ Haverkos, L McMurry, K Wykoff, RF Woo, V Noonan, AS Rowe, J McCarty, K Spain, CB AF Jackson, Y Dietz, WH Sanders, C Kolbe, LJ Whyte, JJ Wechsler, H Schneider, BS McNally, LA Charles-Azure, J Vogel-Taylor, M Starke-Reed, P Hubbard, VS Johnson-Taylor, WL Troiano, RP Donato, K Yanovski, S Kuczmarski, RJ Haverkos, L McMurry, K Wykoff, RF Woo, V Noonan, AS Rowe, J McCarty, K Spain, CB TI Summary of the 2000 Surgeon General's listening session: Toward a national action plan on overweight and obesity SO OBESITY RESEARCH LA English DT Article DE schools; worksites; media; family and community; health care ID UNITED-STATES AB Objective: To provide insight into discussions at the Surgeon General's Listening Session, "Toward a National Action Plan on Overweight and Obesity," and to complement The Surgeon General's Call to Action to Prevent and Decrease Overweight and Obesity. Research Methods and Procedures: On December 7 and 8, 2000, representatives from federal, state, academic, and private sectors attended the Surgeon General's Listening Session and were given an opportunity to recommend what to include in a national plan to address overweight and obesity. The public was invited to comment during a corresponding public comment period. The Surgeon General's Listening Session was also broadcast on the Internet, allowing others to view the deliberations live or access the archived files. Significant discussion points from the Listening Session have been reviewed by representatives of the federal agencies and are the basis of this complementary document. Results: Examples of issues, strategies, and barriers to change are discussed within five thematic areas: schools, health care, family and community, worksite, and media. Suggested cooperative or collaborative actions for preventing and decreasing overweight and obesity are described. An annotated list of some programmatic partnerships is included. Discussion: The Surgeon General's Listening Session provided an opportunity for representatives from family and community groups, schools, the media, the health-care environment, and worksites to become partners and to unite around the common goal of preventing and decreasing overweight and obesity. The combination of approaches from these perspectives offers a rich resource of opportunity to combat the public health epidemic of overweight and obesity. C1 NIH, Div Nutr Res Coordinat, DHHS, Bethesda, MD 20892 USA. Adm Aging, US Dept HHS, Washington, DC USA. Ctr Dis Control & Prevent, Div Nutr & Phys Act, DHHS, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Adolescent & Sch Hlth, DHHS, Atlanta, GA USA. Ctr Medicare & Medicaid Serv, Agcy Healthcare Res & Qual, DHHS, Baltimore, MD USA. US FDA, DHHS, Rockville, MD 20857 USA. US Hlth Resources & Serv Adm, DHHS, Rockville, MD 20857 USA. Indian Hlth Serv, US Dept HHS, Rockville, MD USA. NIH, Off Director, DHHS, Bethesda, MD 20892 USA. NCI, NIH, DHHS, Bethesda, MD 20892 USA. NHLBI, NIH, DHHS, Bethesda, MD 20892 USA. NIDDKD, NIH, DHHS, Bethesda, MD 20892 USA. NICHHD, NIH, DHHS, Bethesda, MD 20892 USA. Off Dis Prevent & Hlth Promot, DHHS, Washington, DC USA. Off Surg Gen, DHHS, Washington, DC USA. Off Womens Hlth, DHHS, Washington, DC USA. Presidents Council Phys Fitness & Sports, Off Publ Hlth & Sci, DHHS, Washington, DC USA. RP Johnson-Taylor, WL (reprint author), NIH, Div Nutr Res Coordinat, DHHS, 2 Democracy Plaza,Room 640,6707 Democracy Blvd,MS, Bethesda, MD 20892 USA. OI Troiano, Richard/0000-0002-6807-989X NR 12 TC 22 Z9 22 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD DEC PY 2002 VL 10 IS 12 BP 1299 EP 1305 DI 10.1038/oby.2002.176 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 625MY UT WOS:000179821300014 PM 12490675 ER PT J AU Horchner, R Tuinebreijer, WE Kelder, H van Urk, E AF Horchner, R Tuinebreijer, WE Kelder, H van Urk, E TI Coping behavior and loneliness among obese patients SO OBESITY SURGERY LA English DT Article DE morbid obesity; obesity; loneliness; coping behavior AB Background: Morbid obesity can be accompanied by physical and social problems that may influence interpersonal relationships and the recruitment of social support. The problems can be tackled with a variety of coping strategies. Methods: 104 patients with a body mass index (BMI) 32-64 kg/m(2) and mean age 36 yr were presented with the Utrecht Coping List (UCL) and the Loneliness Scale. Of these patients, 94 were female, and this cohort was analyzed more extensively. Results: Patients exhibited elevated values on the Loneliness Scale and in the UCL sub-scales palliative response, avoidance/wait-and-see, passive/depressive response pattern and expression of emotions/anger. The active approach UCL sub-scale scored lower than in a control group. Conclusion: Obese female patients displayed avoidance, wait-and-see and passive response pattern as coping behavior, experiencing their intimate relationships as relatively unreliable and not very intimate. More research is needed to determine the effect of coping behavior on therapeutic effect. C1 NINR, Beverwijk, Netherlands. RP Horchner, R (reprint author), Prof Ten Doesschatestr 65, NL-1963 AR Heemskerk, Netherlands. NR 6 TC 12 Z9 13 U1 0 U2 4 PU F D-COMMUNICATIONS INC PI TORONTO PA 3100 BAYVIEW AVE, UNIT 4, TORONTO, ONTARIO M2N 5L3, CANADA SN 0960-8923 J9 OBES SURG JI Obes. Surg. PD DEC PY 2002 VL 12 IS 6 BP 864 EP 868 DI 10.1381/096089202320995718 PG 5 WC Surgery SC Surgery GA 637HL UT WOS:000180505600027 PM 12568196 ER PT J AU Weiss, LK Burkman, RT Cushing-Haugen, KL Voigt, LF Simon, MS Daling, JR Norman, SA Bernstein, L Ursin, G Marchbanks, PA Strom, BL Berlin, JA Weber, AL Doody, DR Wingo, PA McDonald, JA Malone, KE Folger, SG Spirtas, R AF Weiss, LK Burkman, RT Cushing-Haugen, KL Voigt, LF Simon, MS Daling, JR Norman, SA Bernstein, L Ursin, G Marchbanks, PA Strom, BL Berlin, JA Weber, AL Doody, DR Wingo, PA McDonald, JA Malone, KE Folger, SG Spirtas, R TI Hormone replacement therapy regimens and breast cancer risk SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ESTROGEN-PROGESTIN-REPLACEMENT; MENOPAUSAL ESTROGEN; POSTMENOPAUSAL WOMEN; UNITED-STATES; PLUS PROGESTIN; MAMMARY-GLAND; PROLIFERATION; MEDROXYPROGESTERONE; COMBINATION; POPULATION AB OBJECTIVE: Hormone replacement therapy (HRT) has increased in the United States over the past 2 decades in response to reports of long-term health benefits. A relationship between HRT and breast cancer risk has been observed in a number of epidemiological studies. In 2002, the Women's Health Initiative Randomized Controlled Trial reported an association between continuous combined HRT and breast cancer risk. The objective of this study was to examine die association between breast cancer risk and HRT according to regimen and duration and recency of use. METHODS: A multicenter, population-based, case-control study was conducted in five United States metropolitan areas from 1994 to 1998. Analyzed were data from 3823 postmenopausal white and black women (1,870 cases and 1953 con-trols) aged 35-64 years. Odds ratios (ORs) were calculated as estimates of breast cancer risk using standard, unconditional, multivariable logistic regression analysis. Potential confounders were included in the final model if they altered ORs by 10% or more. Two-sided P values for trend were computed from the likelihood ratio statistic. RESULTS: Continuous combined HRT was associated with increased breast cancer risk among current users of 5 or more years (1.54; 95% confidence interval 1.10, 2.17). Additionally, a statistically significant trend indicating increasing breast cancer risk with longer duration of continuous combined HRT was observed among current users (P=.01). There were no positive associations between breast cancer risk and other HRT regimens. CONCLUSION: Our data suggest a positive association between continuous combined HRT and breast cancer risk among current, longer term users. Progestin administered in an uninterrupted regimen may be a contributing factor. Risk dissipates once use is discontinued. (C) 2002 by The American College of Obstetricians and Gynecologists. C1 Wayne State Univ, Populat Studies & Prevent Program, Karmanos Canc Inst, Detroit, MI USA. Henry Ford Hlth Syst, Dept Obstet & Gynecol, Detroit, MI USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Wayne State Univ, Karmanos Canc Inst, Dept Internal Med, Detroit, MI USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. NICHHD, Contracept & Reprod Hlth Branch, Populat Res Ctr, Bethesda, MD 20892 USA. RP Weiss, LK (reprint author), NCI, Canc Ctr Branch, Off Ctr Training & Resources, 6116 Execut Blvd,Suite 700, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-PC-67010, N01-CN-0532, N01-CN-65064, N01-PC-67006]; NICHD NIH HHS [N01-HD-2-3166, N01-HD-3-3168, N01-HD-3-3174, N01-HD-3-3175, N01-HD-3-3176, Y01-HD-7022] NR 42 TC 140 Z9 142 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2002 VL 100 IS 6 BP 1148 EP 1158 AR PII S0029-7844(02)02502-4 DI 10.1016/S0029-7844(02)02502-4 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 620GX UT WOS:000179526600003 PM 12468157 ER PT J AU Tewari, KS DiSaia, PJ AF Tewari, KS DiSaia, PJ TI Primary prevention of uterine cervix cancer: focus on vaccine history and current strategy SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID HUMAN PAPILLOMAVIRUS TYPE-16; VIRUS-LIKE PARTICLES; INTRAEPITHELIAL NEOPLASIA; NATURAL-HISTORY; INNATE IMMUNITY; SMALLPOX ERADICATION; SCREENING PROGRAMS; FOLATE-DEFICIENCY; DENDRITIC CELLS; E7 ONCOPROTEIN AB Primary prevention of uterine cervix cancer spans the gamut of human papillomavirus; vaccine development, dietary adjustment, chemoprevention, and risk reduction. Lifestyle and social behaviors impact on risk for cervical cancer. Before examining the growing body of molecular evidence, animal studies, and phase I clinical trials that suggest that a virus-based vaccine for cervical cancer may soon become a reality, one must reflect on what has gone before in the vaccine -based battle with viral disease. C1 Univ Calif Irvine, Chao Family NCI Designated Comprehens Canc Ctr, Div Gynecol Oncol, Irvine Med Ctr, Orange, CA 92868 USA. RP DiSaia, PJ (reprint author), Univ Calif Irvine, Chao Family NCI Designated Comprehens Canc Ctr, Div Gynecol Oncol, Irvine Med Ctr, 101 City Dr, Orange, CA 92868 USA. NR 132 TC 1 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 0889-8545 J9 OBSTET GYN CLIN N AM JI Obstet. Gynecol. Clin. N. Am. PD DEC PY 2002 VL 29 IS 4 BP 843 EP + AR PII S0889-8545(02)00046-3 DI 10.1016/S0889-8545(02)00046-3 PG 27 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 627HQ UT WOS:000179928100013 PM 12509098 ER PT J AU Trimble, EL Schoenfeldt, M Cornelison, TL Wright, J Kolker, A Christian, M AF Trimble, EL Schoenfeldt, M Cornelison, TL Wright, J Kolker, A Christian, M TI Clinical trials - Referral resource SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD USA. Ovarian Canc Natl Alliance, Washington, DC USA. RP Trimble, EL (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2002 VL 16 IS 12 BP 1660 EP 1660 PG 1 WC Oncology SC Oncology GA 631ZA UT WOS:000180197100011 PM 12520641 ER PT J AU Thulasiraj, RD Rahamathulla, R Saraswati, A Selvaraj, S Ellwein, LB AF Thulasiraj, RD Rahamathulla, R Saraswati, A Selvaraj, S Ellwein, LB TI The Sivaganga Eye Survey: I. Blindness and cataract surgery SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE blindness prevalence; visual impairment; cataract surgery; aphakia; population-based study; India ID QUALITY-OF-LIFE; VISUAL-ACUITY; DOUMEN COUNTY; SHUNYI COUNTY; CHINA; PREVALENCE; OUTCOMES; NEPAL AB PURPOSE To assess the prevalence of visual acuity impairment, blindness, and cataract surgery among older adults in rural southern India. METHODS Random selection of village- and urban-based clusters was used to identify a cross-sectional sample of persons 50 years of age or older from the Sivaganga district of Tamil Nadu. Subjects in 25 selected clusters were enumerated through a door-to-door survey and invited to examination sites for measurement of uncorrected, presenting, and best-corrected visual acuity and ocular examination in 1999. The principal cause was identified for eyes with presenting visual acuity worse than 6/18. Quality assurance monitoring of visual acuity measurements took place in five of the study clusters. RESULTS A total of 5081 persons in 3517 households were enumerated, and 4642 (91.4%) were examined. Thirty-six percent presented with visual acuity worse than 6/18 in the better eye. The prevalence of blindness, based on visual acuity worse than 6/60 in both eyes, was 6.0% (95% confidence interval [CI]: 5.1% to 6.9%) with presenting vision, and 2.5% (95 % CI: 1.8% to 3.1%) with best correction. Blindness with presenting visual acuity was associated with older age and illiteracy. Cataract was the principal cause of blindness in one or both eyes in 69.4% of those presenting blind, and uncorrected aphakia and other refractive error affected 35.6% in at least one eye. The prevalence of cataract surgery was 14.7% (95% CL 13.0% to 16.4%); low surgical coverage among the cataract blind was associated with illiteracy. CONCLUSIONS It appears that much has been done in the prevention of blindness in Sivaganga. Nevertheless, blindness remains an important public health problem, mainly because of cataract and refractive error. Prevention of blindness programs in the area should target these two causes. C1 NEI, Bethesda, MD 20892 USA. Aravind Eye Hosp, Madurai, Tamil Nadu, India. RP Ellwein, LB (reprint author), NEI, 31 Ctr Dr, Bethesda, MD 20892 USA. NR 15 TC 37 Z9 42 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0928-6586 J9 OPHTHALMIC EPIDEMIOL JI Ophthalmic Epidemiol. PD DEC PY 2002 VL 9 IS 5 BP 299 EP 312 DI 10.1076/opep.9.5.299.10334 PG 14 WC Ophthalmology SC Ophthalmology GA 625AM UT WOS:000179794600001 PM 12528915 ER PT J AU Thulasiraj, RD Reddy, A Selvaraj, S Munoz, SR Ellwein, LB AF Thulasiraj, RD Reddy, A Selvaraj, S Munoz, SR Ellwein, LB TI The Sivaganga Eye Survey: II. Outcomes of cataract surgery SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE cataract surgery; visual impairment; surgical complications; blindness; aphakia; population-based study; India ID MADURAI INTRAOCULAR-LENS; QUALITY-OF-LIFE; RURAL DISTRICT; VISUAL-ACUITY; DOUMEN COUNTY; SHUNYI COUNTY; OLDER ADULTS; BLINDNESS; CHINA; POPULATION AB PURPOSE To assess the clinical outcomes of cataract surgery in rural southern India. METHODS Cluster sampling was used in randomly selecting a cross-sectional sample of persons 50 years of age or older for visual acuity measurement, refraction, and ocular examination in 1999. Subjects were queried as to the date and place of surgery for each cataract-operated eye. Surgical complications were noted and the principal cause of reduced vision was identified for eyes with presenting visual acuity worse than 6/18. RESULTS Within the cataract-operated sample of 682 persons, 13.8% had presenting visual acuity worse than 6/60 in both eyes, 25.2% better than or equal to 6/18 in both eyes, and 37.8% were bilaterally operated on. For aphakic eyes, 50.5% presented with visual acuity better than or equal to 6/18; 82.6% with best-correction. For pseudophakic eyes, the corresponding percentages were 78.0% and 94.5%. Over one-third of all eyes were pseudophakic, and nearly three-fourths had been operated on in non-governmental facilities. Uncorrected aphakia and other refractive error were the main causes of vision impairment. In multiple logistic regression modeling, poor presenting visual acuity in aphakic eyes was associated with illiteracy, rural residence, and surgery in government facilities; gender and time period of surgery were not predictors of vision outcomes. None of these variables were associated with best-corrected outcomes in aphakic eyes, nor with presenting and best-corrected outcomes in pseudophakic eyes. CONCLUSIONS Visual acuity outcomes in pseudophakic eyes were good. More attention must be given to needless vision impairment among the cataract-operated because of inadequate aphakic correction, especially among those operated on in government facilities, the illiterate, and those living in rural villages. C1 NEI, Bethesda, MD 20892 USA. Aravind Eye Hosp, Madurai, Tamil Nadu, India. Univ La Frontera, Unidad Epidemiol Clin, Temuco, Chile. RP Ellwein, LB (reprint author), NEI, 31 Ctr Dr, Bethesda, MD 20892 USA. NR 22 TC 32 Z9 33 U1 0 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0928-6586 J9 OPHTHALMIC EPIDEMIOL JI Ophthalmic Epidemiol. PD DEC PY 2002 VL 9 IS 5 BP 313 EP 324 DI 10.1076/opep.9.5.313.10339 PG 12 WC Ophthalmology SC Ophthalmology GA 625AM UT WOS:000179794600002 PM 12528916 ER PT J AU Jampol, LM Moy, CS Murray, TG Reynolds, SM Albert, DM Schachat, AP Diddie, KR Engstrom, RE Finger, PT Hovland, KR Joffe, L Olsen, KR Wells, CG AF Jampol, LM Moy, CS Murray, TG Reynolds, SM Albert, DM Schachat, AP Diddie, KR Engstrom, RE Finger, PT Hovland, KR Joffe, L Olsen, KR Wells, CG CA COMS Follow Plaqued Eyes Wkng Grp TI The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma - IV. Local treatment failure and enucleation in the first 5 years after brachytherapy. COMS report No. 19 SO OPHTHALMOLOGY LA English DT Article ID UVEAL MELANOMA; MALIGNANT-MELANOMA; RADIATION-THERAPY; I-125 PLAQUE; RADIOTHERAPY; RECOMMENDATIONS; IRRADIATION; MANAGEMENT; REGRESSION; DOSIMETRY AB Objective: To describe the frequency and predictors of local treatment failure and enucleation after iodine 125 (I-125) brachytherapy in patients with choroidal melanoma treated and followed up in a large randomized clinical trial. Design: Prospective, noncomparative, interventional case series within a randomized, multicenter clinical trial. Participants: Patients enrolled in the Collaborative Ocular Melanoma Study (COMS) trial of enucleation versus brachytherapy between February 1987 and July 1998; tumors measured 2.5 to 10.0 mm in apical height and no more than 16.0 mm in longest basal dimension. Methods: 1125 brachytherapy was administered via episcleral plaque according to a standard protocol. Follow-up ophthalmic evaluations, including ophthalmic ultrasound and fundus photography, were performed according to a standard protocol at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Survival analysis methods were used to estimate the cumulative risk of postirradiation treatment failure and enucleation. Factors associated with treatment failure and enucleation of plaqued eyes were evaluated using Cox proportional hazards analysis. Main Outcome Measures: Reports of enucleation and of local treatment failure, defined as tumor growth, recurrence, or extrascleral extension, derived from clinical reports based on echographic and photographic documentation. Results: As of September 30, 2000, 638 of the 650 patients randomized to brachytherapy and so treated had been followed up for 1 year or longer, and 411 had been followed up for at least 5 years. Sixty-nine eyes were enucleated during the first 5 years after brachytherapy, and treatment failure was reported for 57 eyes. The Kaplan-Meier estimate of proportion of patients undergoing enucleation by 5 years was 12.5% (95% confidence interval [Cl], 10.0%-15.6%); the risk of treatment failure was 10.3% (95% Cl, 8.0%-13.2%). Treatment failure was the most common reason for enucleation within 3 years of treatment; beyond 3 years, ocular pain was most common. Risk factors for enucleation were greater tumor thickness, closer proximity of the posterior tumor border to the foveal avascular zone, and poorer baseline visual acuity in the affected eye. Risk factors for treatment failure were older age, greater tumor thickness, and proximity of the tumor to the foveal avascular zone. Local treatment failure was associated weakly with reduced survival after controlling for baseline tumor and personal characteristics (adjusted risk ratio, 1.5; P = 0.08). 1125 Conclusions. Local treatment failure and enucleation were relatively infrequent events after brachytherapy within the COMS. Treatment failure typically occurred early and was associated weakly with poorer survival. The COMS randomized trial documented the absence of a clinically or statistically significant difference in survival for patients randomly assigned to enucleation versus brachytherapy. This analysis documents the efficacy of brachytherapy to achieve sustained local tumor control and to conserve the globe. Ophthalmology 2002,109:2197-2206 (C) 2002 by the American Academy of Ophthalmology. C1 Northwestern Univ, Sch Med, Dept Ophthalmol, Chicago, IL 60611 USA. Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Baltimore, MD 21205 USA. Univ Miami, Sch Med, Bascom Palmer Eye Inst, Miami, FL USA. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. Univ So Calif, Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, Med Ctr, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. New York Eye Canc Ctr, New York, NY USA. Porter Adventist Hosp, Denver, CO USA. Retina Associates SW, Tucson, AZ USA. Retina Vitreous Consultants, Pittsburgh, PA USA. Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA. RP Jampol, LM (reprint author), NINDS, COMS Coordinating Ctr, Ctr Neurosci, NIH, Room 2214,6001 Execut Blvd,MSC 9520, Bethesda, MD 20892 USA. OI Finger, Paul T/0000-0002-8111-3896 FU NEI NIH HHS [EY 06282, EY 06253, EY 06257, EY 06258, EY 06260, EY 06264, EY 06265, EY 06266, EY 06269, EY 06270, EY 06274, EY 06275, EY 06276, EY 06280, EY 06284, EY 06287, EY 06288, EY 06289, EY 06291, EY 06839, EY 06843, EY 06844, EY 06848, EY 06858, EY 06899, EY06279, EY06283] NR 33 TC 129 Z9 135 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2002 VL 109 IS 12 BP 2197 EP 2206 AR PII S0161-6420(02)01277-0 DI 10.1016/S0161-6420(02)01277-0 PG 10 WC Ophthalmology SC Ophthalmology GA 622MZ UT WOS:000179652000007 PM 12466159 ER PT J AU Walker, RH Friedman, J Wiener, J Hobler, R Gwinn-Hardy, K Adam, A DeWolfe, J Gibbs, R Baker, M Farrer, M Hutton, M Hardy, J AF Walker, RH Friedman, J Wiener, J Hobler, R Gwinn-Hardy, K Adam, A DeWolfe, J Gibbs, R Baker, M Farrer, M Hutton, M Hardy, J TI A family with a tau P301L mutation presenting with parkinsonism SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE genetics; parkinsonism; progressive supranuclear palsy; dementia; tau ID FRONTOTEMPORAL DEMENTIA; EXTENDED HAPLOTYPE; GENE; DISEASE; CHROMOSOME-17; ASSOCIATION; POLYMORPHISMS; PHENOTYPE; MISSENSE; INSOMNIA AB We report a sib-pair with a tau P301L mutation. Unlike most previous cases with this mutation, parkinsonism, rather than dementing features were the predominant and presenting feature. We have also observed that the P301L mutation has occurred on the HI tau haplotype background. The haplotype background may influence the disease phenotype since in many previous Caucasian families with the P301L mutation, the haplotype background has been H2. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Mayo Clin Jacksonville, Labs Neurogenet, Dept Neurosci, Jacksonville, FL 32224 USA. Bronx Vet Adm Med Ctr, Dept Neurol, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Brown Univ, Sch Med, Dept Clin Neurosci, Providence, RI 02912 USA. Mem Hosp Rhode Isl, Div Neurol, Pawtucket, RI 02860 USA. VA Hudson Valley Healthcare Syst, Dept Psychol, Castle Point, NY 12511 USA. NINDS, Neurogenet Lab, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), Mayo Clin Jacksonville, Labs Neurogenet, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. RI Gwinn, Katrina/C-2508-2009; Hardy, John/C-2451-2009 NR 20 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD DEC PY 2002 VL 9 IS 2 BP 121 EP 123 AR PII S1353-8020(02)00003-2 DI 10.1016/S1353-8020(02)00003-2 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 619LM UT WOS:000179477500010 PM 12473404 ER PT J AU Bastian, LA McBride, CM Fish, L Lyna, P Farrell, D Lipkus, IM Rimer, BK Siegler, IC AF Bastian, LA McBride, CM Fish, L Lyna, P Farrell, D Lipkus, IM Rimer, BK Siegler, IC TI Evaluating participants' use of a hormone replacement therapy decision-making intervention SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE tailored; HRT; decision-making; menopause ID BREAST-CANCER; TAILORED INTERVENTIONS; RANDOMIZED TRIAL; MENOPAUSE SURVEY; HEALTH BEHAVIOR; WOMEN; MAMMOGRAPHY; RISK; MESSAGES; SUPPORT AB Background: Associations between optimal use of a tailored decision-aid and levels of accuracy of perceived breast cancer risk, confidence in decision-making, and satisfaction with decisions about HRT were evaluated in a randomized intervention trial with a community sample of women aged 45-54. Methods: Data are from 289 women randomized to receive a computer-tailored three-step decision-aid. Results: Forty-seven percent of participants reported optimal use of the intervention materials. African American women and those with low confidence in decision-making were less likely to use the intervention optimally than white women and those with higher confidence (P < 0.05). Optimal use of the decision-aid was associated with increased accuracy of perceived risk and confidence to make a decision. Discussion: When used optimally, self-directed decision-aids can improve women's ability to make decisions about HRT. Additional refinement of these aids is needed. For some subgroups of women, adjuncts such as telephone counseling also might be considered. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Detect & Control Res Program, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Internal Med, Durham, NC 27710 USA. RP Bastian, LA (reprint author), Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, 508 Fulton St 152, Durham, NC 27705 USA. FU NCI NIH HHS [P01-CA-72099-05] NR 35 TC 23 Z9 23 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD DEC PY 2002 VL 48 IS 3 BP 283 EP 291 AR PII S0738-3991(02)00048-4 DI 10.1016/S0738-3991(02)00048-4 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 635TT UT WOS:000180416000011 PM 12477613 ER PT J AU Ronckers, CM Land, CE Hayes, RB Verduijn, PG Stovall, M Van Leeuwen, FE AF Ronckers, CM Land, CE Hayes, RB Verduijn, PG Stovall, M Van Leeuwen, FE TI Late health effects of childhood nasopharyngeal radium irradiation: Nonmelanoma skin cancers, benign tumors, and hormonal disorders SO PEDIATRIC RESEARCH LA English DT Article ID SALIVARY-GLAND TUMORS; LYMPHOID HYPERPLASIA; RADIATION TREATMENT; EXTERNAL RADIATION; COMMON OUTCOMES; ODDS RATIO; SURVIVORS; RISK; NETHERLANDS; COHORT AB Nasopharyngeal radium irradiation (NRI) was widely used from 1940 through 1970 to treat otitis serosa in children and barotrauma in airmen and submariners. We assessed whether NRI-exposed individuals were at higher risk for benign tumors, nonmelanoma skin cancer, thyroid disorders, and conditions related to regulatory control of anterior pituitary hormones, such as growth and reproductive characteristics. We conducted a retrospective cohort study in 3440 NRI-exposed and 3088 non-exposed subjects, who as children were treated at nine ear, nose and throat clinics in The Netherlands between 1945 and 1981. Based on information from original medical records, we traced vital status through follow-up at municipal population registries. Disease status (including medical confirmation) and indicators of pituitary gland radiation damage were assessed from a self-administered questionnaire in 1997. The average radiation doses were 11, 7, and 1.5 cGy for pituitary, parotid, and thyroid gland, respectively, and 3.2 cGy for the facial skin. Among exposed subjects, 23 benign head and neck tumors were observed, compared with 21 among nonexposed subjects. Elevated risk of basal cell carcinoma of the head and neck area was observed in exposed subjects (odds ratio = 2.6; 95% confidence interval: 1.0-6.7). Exposed and nonexposed groups did not differ substantially with regard to thyroid disorders, height, and reproductive characteristics, although exposed males more frequently reported a history of fertility problems compared with nonexposed males (odds ratio = 1.4; 95% confidence interval: 1.0-2.1). We found no evidence of highly elevated risk of benign head and neck tumors, nonmelanoma skin cancer, thyroid disorders, or indicators of pituitary radiation damage after childhood NRI in The Netherlands. C1 NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Rockville, MD 20852 USA. Reinaert Kliniek, Dept Ear Nose & Throat Med, Maastricht, Netherlands. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. RP Ronckers, CM (reprint author), NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, 6120 Execut Blvd, Rockville, MD 20852 USA. FU NCI NIH HHS [Y3CP0012-01, N01CP330103] NR 46 TC 4 Z9 4 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 DEC PY 2002 VL 52 IS 6 BP 850 EP 858 DI 10.1203/01.PDR.0000034232.09928.77 PG 9 WC Pediatrics SC Pediatrics GA 618NK UT WOS:000179424000004 PM 12438660 ER PT J AU Lester, BM Tronick, EZ LaGasse, L Seifer, R Bauer, CR Shankaran, S Bada, HS Wright, LL Smeriglio, VL Lu, J Finnegan, LP Maza, PL AF Lester, BM Tronick, EZ LaGasse, L Seifer, R Bauer, CR Shankaran, S Bada, HS Wright, LL Smeriglio, VL Lu, J Finnegan, LP Maza, PL TI The maternal lifestyle study: Effects of substance exposure during pregnancy on neurodevelopmental outcome in 1-month-old infants SO PEDIATRICS LA English DT Article DE infants; cocaine; opiates; polydrug use; pregnancy substance abuse; prenatal drug exposure; neurobehavior; NICU Network Neurobehavioral Scale; cry; multisite; heavy exposure; threshold effects; low birth weight; meconium ID PRENATAL COCAINE EXPOSURE; BRAZELTON SCALE; ALCOHOL-USE; BEHAVIORAL-CHARACTERISTICS; NEUROBEHAVIORAL STATUS; CRY CHARACTERISTICS; CIGARETTE-SMOKING; CRACK/COCAINE USE; NEWBORN-INFANTS; GROWTH AB Objective. This was a prospective longitudinal multisite study of the effects of prenatal cocaine and/or opiate exposure on neurodevelopmental outcome in term and preterm infants at 1 month of age. Methods. The sample included 658 exposed and 730 comparison infants matched on race, gender, and gestational age (11.7% born <33 weeks' gestational age). Mothers were recruited at 4 urban university-based centers and were mostly black and on public assistance. Exposure was determined by meconium assay and self-report with alcohol, marijuana, and tobacco present in both groups. At I month corrected age, infants were tested by masked examiners with the NICU Network Neurobehavioral Scale and acoustical cry analysis. Exposed and comparison groups were compared adjusting for covariates (alcohol, marijuana, tobacco, birth weight, social class, and site). Separate analyses were conducted for level of cocaine exposure. Results. On the NICU Network Neurobehavioral Scale, cocaine exposure was related to lower arousal, poorer quality of movement and self-regulation, higher excitability, more hypertonia, and more nonoptimal reflexes with most effects maintained after adjustment for covariates. Some effects were associated with heavy cocaine exposure, and effects were also found for opiates, alcohol, marijuana, and birth weight. Acoustic cry characteristics that reflect reactivity, respiratory, and neural control of the cry sound were also compromised by prenatal drug exposure, including cocaine, opiates, alcohol, and marijuana and by birth weight. Fewer cry effects remained after adjustment for covariates. Conclusions. Cocaine effects are subtle and can be detected when studied in the context of polydrug use and level of cocaine exposure. Effects of other drugs even at low thresholds can also be observed in the context of a polydrug model. The ability to detect these drug effects requires a large sample and neurobehavioral tests that are differentially sensitive to drug effects. Long-term follow-up is necessary to determine whether these differences develop into clinically significant deficits. C1 Brown Univ, Women & Infants Hosp, Infant Dev Ctr, Sch Med, Providence, RI 02905 USA. Bradley Hosp, Providence, RI USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Univ Miami, Sch Med, Miami, FL USA. Wayne State Univ, Sch Med, Detroit, MI USA. Univ Tennessee, Ctr Hlth Sci, Sch Med, Memphis, TN 38163 USA. NICHHD, Bethesda, MD 20892 USA. NIDA, Bethesda, MD 20892 USA. NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. Adm Children Youth & Families, Washington, DC USA. RP Lester, BM (reprint author), Brown Univ, Women & Infants Hosp, Infant Dev Ctr, Sch Med, 101 Dudley St, Providence, RI 02905 USA. OI Seifer, Ronald/0000-0003-4879-2839 FU NICHD NIH HHS [U10 HD 21385, U10 HD 27904, U10 HD 27856, U10 HD 21397, N01-HD-2-3159] NR 77 TC 164 Z9 169 U1 6 U2 19 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2002 VL 110 IS 6 BP 1182 EP 1192 DI 10.1542/peds.110.6.1182 PG 11 WC Pediatrics SC Pediatrics GA 620TU UT WOS:000179549200035 PM 12456917 ER PT J AU Rothman, RB Vu, N Xu, H Baumann, MH Lu, YF AF Rothman, RB Vu, N Xu, H Baumann, MH Lu, YF TI Endogenous corticotropin releasing factor regulates adrenergic and opioid receptors SO PEPTIDES LA English DT Article DE corticotropin releasing factor (CRF); adrenergic receptors; opioid receptors ID ANTI-OPIATE PEPTIDES; MU-BINDING-SITES; ALPHA(2)-ADRENOCEPTOR SUBTYPES; LOCUS-COERULEUS; HUMAN BRAIN; MORPHINE; MEMBRANES; RATS AB Previous work from this laboratory demonstrated that intracerebroventricular (i.c.v.) administration of IgG antibodies directed against selected neuropeptides changed the density of opioid receptors, suggesting that neuropeptides in the CNS can perform a regulatory role. To further test this hypothesis, we administered anticorticotropin (CRF) IgG to rats via the i.c.v. route and measured the density of opioid mu and delta receptors and also beta- and alpha(2)-adrenergic receptors. The results demonstrated that anti-CR-F IgG upregulates mu and beta-adrenergic receptors. We conclude that CRF in the cerebrospinal fluid may exert regulatory effects throughout the brain. (C) 2002 Elsevier Science Inc. All rights. reserved. C1 NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NR 22 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 2002 VL 23 IS 12 BP 2177 EP 2180 AR PII S0196-9781(02)00245-0 DI 10.1016/S0196-9781(02)00245-0 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 641WJ UT WOS:000180769800012 PM 12535696 ER PT J AU Lin, L Wisor, J Shiba, T Taheri, S Yanai, K Wurts, S Lin, X Vitaterna, M Takahashi, J Lovenberg, TW Koehl, M Uhl, G Nishino, S Mignot, E AF Lin, L Wisor, J Shiba, T Taheri, S Yanai, K Wurts, S Lin, X Vitaterna, M Takahashi, J Lovenberg, TW Koehl, M Uhl, G Nishino, S Mignot, E TI Measurement of hypocretin/orexin content in the mouse brain using an enzyme immunoassay: the effect of circadian time, age and genetic background SO PEPTIDES LA English DT Article DE hypocretin; orexin; narcolepsy; enzyme immunoassay; histamine receptor; knockout ID VESICULAR MONOAMINE TRANSPORTER; OREXIN-A LEVELS; HUMAN NARCOLEPSY; BEHAVIORAL CHARACTERIZATION; DOWN-REGULATION; OBESE MICE; NEURONS; EXPRESSION; SLEEP; RAT AB The hypocretins (1 and 2) have emerged as key regulators of sleep and wakefulness. We developed a high-throughput enzyme immunoassay (EIA) to measure total brain hypocretin levels from large numbers of mice. Hypocretin levels were not altered by circadian time or age. However, significant differences in one or both hypocretin peptides were observed between different mouse strains. We studied hypocretin levels in knockout and transgenic mouse models with obesity, circadian gene mutations or monoaminergic defects. Compared to controls, only histamine receptor knockouts had lower hypocretin levels. This was most pronounced in H1 receptor knockouts suggesting the existence of a positive feedback loop between hypocretin and histaminergic neurons. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Stanford Univ, Ctr Narcolepsy & Sleep Disorders, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. Tohoku Univ, Sch Med, Dept Pharmacol, Sendai, Miyagi 980, Japan. Northwestern Univ, Ctr Funct Genom, Evanston, IL USA. RW Johnson Pharmaceut Res Inst, San Diego, CA 92121 USA. NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD USA. RP Mignot, E (reprint author), Stanford Univ, Ctr Narcolepsy & Sleep Disorders, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. RI Takahashi, Joseph/E-8482-2012; Koehl, Muriel/C-3698-2011; OI Takahashi, Joseph/0000-0003-0384-8878; Taheri, Shahrad/0000-0001-8314-1500 FU NINDS NIH HHS [NS23724] NR 52 TC 31 Z9 33 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 2002 VL 23 IS 12 BP 2203 EP 2211 AR PII S0196-9781(02)00251-6 DI 10.1016/S0196-9781(02)00251-6 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 641WJ UT WOS:000180769800016 PM 12535700 ER PT J AU Preusch, PC AF Preusch, PC TI News from the National Institute of General Medical Sciences: What IS training in the pharmacological sciences? SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material C1 NIGMS, Pharmacol Sci Training Grant Program, Physiol & Biol Chem Div, Bethesda, MD 20892 USA. RP Preusch, PC (reprint author), NIGMS, Pharmacol Sci Training Grant Program, Physiol & Biol Chem Div, 45 Ctr Dr,MSC 6200, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD DEC PY 2002 VL 19 IS 12 BP 1771 EP 1772 DI 10.1023/A:1021472920194 PG 2 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 624ED UT WOS:000179746600001 PM 12523653 ER PT J AU Blaisdell, J Mohrenweiser, H Jackson, J Ferguson, S Coulter, S Chanas, B Xi, T Ghanayem, B Goldstein, JA AF Blaisdell, J Mohrenweiser, H Jackson, J Ferguson, S Coulter, S Chanas, B Xi, T Ghanayem, B Goldstein, JA TI Identification and functional characterization of new potentially defective alleles of human CYP2C19 SO PHARMACOGENETICS LA English DT Article DE CYP2C19; polymorphisms; mephenytoin; cytochrome P450; drug metabolism ID S-MEPHENYTOIN 4'-HYDROXYLATION; POOR METABOLIZER PHENOTYPE; GENETIC-POLYMORPHISM; DOSE REQUIREMENT; HYDROXYLATION; PHARMACOKINETICS; CYTOCHROME-P450; DEBRISOQUIN; SUBFAMILY AB CYP2C19 is a clinically important enzyme responsible for the metabolism of a number of therapeutic drugs, such as S-mephenytoin, omeprazole, diazepam, proguanil, propranolol and certain antidepressants. Genetic polymorphisms in this enzyme result in poor metabolizers of these drugs. There are racial differences in the incidence of the poor metabolizer trait, which represents 13-23% of Asians but only 3-5% of Caucasians. In this study, single nucleotide polymorphisms (SNPs) in CYP2C19 were identified by direct sequencing of genomic DNA from 92 individuals from three different racial groups of varied ethnic background, including Caucasians, Asians and blacks. Several new alleles were identified containing the coding changes Arg(144)His (CYP2C19*9), Pro(227)Leu (CYP2C19* 10), Arg(150)His (Cyp2C19* 11), stop(491)Cys (CYP2C19* 12), Arg(410)Cys (CYP2C19* 13), Leu(17)Pro (CYP2C19* 14) and Ile(19)Leu (CYP2C19* 15). When expressed in a bacterial cDNA expression system, CYP2C19*9 exhibited a modest decrease in the V-max. for 4'-hydroxylation of S-mephenytoin, and no alteration in its affinity for reductase. CYP2C19* 10 exhibited a dramatically higher K-m and lower V-max for mephenytoin. CYP2C19* 12 was unstable and expressed poorly in a bacterial cDNA expression system. Clinical studies will be required to confirm whether this allele is defective in vivo. CYP2C19*9, CYP2C19*10 and CYP2C19*12 all occurred in African-Americans, or individuals of African descent, and represent new potentially defective alleles of CYP2C19 which are predicted to alter risk of these populations to clinically important drugs. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Lawrence Livermore Natl Lab, Livermore, CA USA. RP Goldstein, JA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. RI Goldstein, Joyce/A-6681-2012; OI Coulter, Sherry/0000-0002-2732-3470 FU NIEHS NIH HHS [Y1-ES-8054-05] NR 33 TC 80 Z9 88 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 2002 VL 12 IS 9 BP 703 EP 711 DI 10.1097/00008571-200212000-00004 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 631MN UT WOS:000180171700004 PM 12464799 ER PT J AU Jensen, RT AF Jensen, RT TI Involvement of cholecystokinin/gastrin-related peptides and their receptors in clinical gastrointestinal disorders SO PHARMACOLOGY & TOXICOLOGY LA English DT Review ID ZOLLINGER-ELLISON-SYNDROME; CCK-A RECEPTOR; IRRITABLE-BOWEL-SYNDROME; ENTEROCHROMAFFIN-LIKE-CELL; MESSENGER-RNA EXPRESSION; HUMAN PANCREATIC-CANCER; DUODENAL-ULCER DISEASE; GASTRIC-ACID SECRETION; CHRONIC ACALCULOUS CHOLECYSTITIS; HELICOBACTER-PYLORI INFECTION AB In this paper the possible roles of cholecystokinin (CCK), gastrin, or gastrin-related peptides and their receptors in human gastrointestinal diseases are reviewed. For CCK/CCKA receptors (CCKA-R), the evidence for their proposed involvement in diseases caused by impaired CCK release or CCKA-R mutations, pancreatic disorders (acute/chronic pancreatitis), gastrointestinal motility disorders (gallbladder disease. irritable bowel syndrome), pancreatic tumor growth and satiety disorders, is briefly reviewed. The evidence that has established the involvement of gastrin/CCKB-R in mediating the action of hypergastrinaemic disorders. mediating lipergastrinaemic effects on the gastric mucosa (ECL hyperplasia, carcinoids. parietal cell mass). and acid-peptic diseases. is reviewed. The evidence for their possible involvement in mediating growth of gastric and pancreatic tumours and possible involvement of gastrin-related peptides in colon cancers. is reviewed briefly. C1 NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. NR 283 TC 53 Z9 54 U1 0 U2 5 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0901-9928 J9 PHARMACOL TOXICOL JI Pharmacol. Toxicol. PD DEC PY 2002 VL 91 IS 6 BP 333 EP 350 DI 10.1034/j.1600-0773.2002.910611.x PG 18 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 632NV UT WOS:000180230200010 PM 12688377 ER PT J AU Xu, H Fabricant, DS Piersen, CE Bolton, JL Pezzuto, JA Fong, H Totura, S Farnsworth, NR Constantinou, AI AF Xu, H Fabricant, DS Piersen, CE Bolton, JL Pezzuto, JA Fong, H Totura, S Farnsworth, NR Constantinou, AI TI A preliminary RAPD-PCR analysis of Cimicifuga species and other botanicals used for women's health SO PHYTOMEDICINE LA English DT Review DE RAPD; DNA profiles; Trifolium pratense; Cimicifuga racemosa; species identification ID MENOPAUSAL WOMEN; RACEMOSA; ISOFLAVONES; EXTRACTS AB Traditional taxonomic methods of botanical identification that rely primarily on morphological observations cannot be used efficiently when only powdered plant materials are available. Thus, our objectives were to determine if we could apply a molecular approach to: a) produce unique DNA profiles that are characteristic of the species, and b) determine if the geographical area or time of collection influences these DNA profiles. Towards this end, random amplified polymorphic DNA (RAPD) analyses were performed on a number of botanicals currently used for women's health. The test materials included samples from three species each of the genera Cimicifuga (Actaea) and Trifolium, as well as samples of Vitex agnus-castus L., Glycyrrhiza glabra L., Gingko biloba L., Valeriana officinalis L., Angelica sinensis (Oliv.) Diels, Viburnum prunifolium L., Humulus lupulus L., Vaccinium macrocarpon Ait., Panax ginseng C.A. Mey. Cimicifuga racemosa (L.) Nutt. and Trifolium pratense L. are currently under clinical investigation in our basic research laboratories and medical clinic for the relief of post-menopausal symptoms. Characteristic profiles produced with the OPC-15 primer could distinguish the three Cimicifuga species: C racemosa, C americana and C. rubifolia. Similar results were obtained with the three Trifiblium species: Trifoliumpratense L., Trifolium incarnatum L., and Trifolium repens L. Accessions of cultivated T pratense collected from the same field at different times, produced identical profiles. Accessions of Cimicifuga species collected from different geographical areas produced similar but not identical DNA profiles; however, species-specific DNA fragments were identified. These results demonstrate that RAPD analysis can be applied to distinguish species when only powdered material is available for testing. This methodology can be applied to identify species of commercial value regardless of collection time or geographic area. C1 Univ Illinois, Coll Med, Dept Surg Oncol, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Program Collaborat Res Pharmaceut Sci, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. UIC, Ctr Bot Dietary Supplement Res, NIH, Chicago, IL USA. RP Constantinou, AI (reprint author), Univ Illinois, Coll Med, Dept Surg Oncol, M-C 820,840 S Wood St, Chicago, IL 60612 USA. OI Constantinou, Andreas/0000-0003-0365-1821 FU NCCIH NIH HHS [P50 AT00155] NR 13 TC 27 Z9 28 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0944-7113 J9 PHYTOMEDICINE JI Phytomedicine PD DEC PY 2002 VL 9 IS 8 BP 757 EP 762 DI 10.1078/094471102321621403 PG 6 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 653NB UT WOS:000181441700015 PM 12587700 ER PT J AU Huizing, M Boissy, RE Gahl, WA AF Huizing, M Boissy, RE Gahl, WA TI Hermansky-Pudlak syndrome: Vesicle formation from yeast to man SO PIGMENT CELL RESEARCH LA English DT Review DE yeast vacuole; Drosophila pigment granule; lysosome biogenesis; protein trafficking; oculocutaneous albinism; dense body; vesicle ID STORAGE-POOL DEFICIENCY; CHEDIAK-HIGASHI-SYNDROME; AP-3 ADAPTER COMPLEX; PALE EAR EP; PROTEIN COMPLEX; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER; LATE-GOLGI; INHERITED ABNORMALITIES; GRANULOMATOUS COLITIS AB The disorders known as Hermansky Pudlak syndrome ( HPS) are a group of genetic diseases resulting from abnormal formation of intracellular vesicles. In HPS, dysfunction of melanosomes results in oculocutaneous albinism, and absence of platelet dense bodies causes a bleeding diathesis. In addition, some HPS patients suffer granulomatous colitis or fatal pulmonary fibrosis, perhaps due to mistrafficking of a subset of lysosomes. The impaired function of specific organelles indicates that the causative genes encode proteins operative in the formation of certain vesicles. Four such genes, HPS1, ADTB3A, HPS3, and HPS4, are associated with the four known subtypes of HPS, i.e. HPS-1, HPS-2, HPS-3, and HPS-4. ADTB3A codes for the beta3A subunit of adaptor complex-3, known to assist in vesicle formation from the trans Golgi network or late endosome. However, the functions of the HPS1, HPS3, and HPS4 gene products remain unknown. These three genes arose with the evolution of mammals and have no homologs in yeast, reflecting their specialized function. In contrast, all four known HPS-causing genes have homologs in mice, a species with 14 different models of HPS, i.e. hypopigmentation and a platelet storage pool deficiency. Pursuit of the mechanism of mammalian vesicle formation and trafficking, impaired in HPS, relies upon investigation of these mouse models as well as studies of protein complexes involved in yeast vacuole formation. C1 NHGRI, Med Genet Branch, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Dermatol, Cincinnati, OH USA. RP Huizing, M (reprint author), NHGRI, Med Genet Branch, Sect Human Biochem Genet, NIH, 10 Ctr Dr,MSC 1851,Bldg 10,Room 10C-103B, Bethesda, MD 20892 USA. NR 137 TC 81 Z9 82 U1 1 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD DEC PY 2002 VL 15 IS 6 BP 405 EP 419 DI 10.1034/j.1600-0749.2002.02074.x PG 15 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 618HE UT WOS:000179412000003 PM 12453182 ER PT J AU Lei, TC Vieira, WD Hearing, VJ AF Lei, TC Vieira, WD Hearing, VJ TI In vitro migration of melanoblasts requires matrix metalloproteinase-2: Implications to vitiligo therapy by photochemotherapy SO PIGMENT CELL RESEARCH LA English DT Article DE melanoblast migration; MMP2; psoralens; ECM ID MELANOCYTE-STIMULATING HORMONE; HAIR-FOLLICLES; KERATINOCYTES; INHIBITOR; REPIGMENTATION; INDUCTION; LAMININ-5; RECEPTOR; PEPTIDES; MMP-2 AB It is known that the migration of melanocyte precursors (melanoblasts) from the outer root sheath of hair follicles into clinically depigmented epidermis is crucial to the repigmentation of vitiliginous skin treated with photochemotherapy (PUVA), but such migratory cells must penetrate extracellular matrix tissue barriers in vivo. To test the hypothesis that matrix metalloproteinases (MMPs) are required for this process, we determined whether cultured melb-a cells, an immortal line of melanoblasts isolated from neonatal mouse epidermis, express and secrete MMPs and whether a synthetic metalloproteinase inhibitor, GM6001 (Galardin), inhibits their migratory behavior in vitro. Reverse transcriptase-polymerase chain reaction and Western blotting were used to determine the patterns of MMP expression by melanoblasts at the mRNA and protein levels, respectively. The proteolytic activities of MMPs secreted into the culture medium were assessed by gelatin zymography. The capacity of melanoblasts to migrate on bronectin, laminin or laminin-5 substrates was estimated using Transwell migration assays. The results show that MMP2, MMP9 and MT1-MMP transcripts are expressed by these melanoblasts, but only MMP2 is secreted and activated in the extracellular environment. Although the therapeutic efficacy of PUVA in stimulating repigmentation of vitiliginous skin might derive from direct effects of UVA and/or 8-methoxypsoralen (8MOP), recent studies have shown that keratinocyte-derived factors induced by ultraviolet radiation, especially alpha-melanocyte stimulating hormone (alphaMSH), play a major role in regulating melanocyte function. Therefore, we also examined whether 8MOP and/or alphaMSH are involved in the up-regulation of MMP2 expression in melanoblasts. Western blotting and zymographic analyses revealed that MMP2 synthesis and secretion were induced by 8MOP and or by a This induction of MMP2 resulted in significant increases of migration by melanoblasts on laminin or on laminin-5 substrates, while concomitant treatment with GM6001 blocked that induced migration. Taken together, these results suggest the importance of MMP2 in melanoblast migration and in the response to PUVA therapy. C1 NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hearing, VJ (reprint author), NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bldg 37,Room 1B25, Bethesda, MD 20892 USA. NR 25 TC 33 Z9 41 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD DEC PY 2002 VL 15 IS 6 BP 426 EP 432 DI 10.1034/j.1600-0749.2002.02044.x PG 7 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 618HE UT WOS:000179412000005 PM 12453184 ER PT J AU Jiang, N Jordan, IK Wessler, SR AF Jiang, N Jordan, IK Wessler, SR TI Dasheng and RIRE2. A nonautonomous long terminal repeat element and its putative autonomous partner in the rice genome SO PLANT PHYSIOLOGY LA English DT Article ID BACTERIAL ARTIFICIAL CHROMOSOMES; TRANSPOSABLE ELEMENTS; MAIZE; RETROTRANSPOSONS; SEQUENCES; GENE; RETROVIRUS; REVEALS; IDENTIFICATION; RECOMBINATION AB Dasheng is one of the highest copy number long terminal repeat elements and one of the most recent elements to amplify in the rice (Oryza sativa) genome. However, the absence of any significant coding capacity for retroviral proteins, including gag and pol, suggests that Dasheng is a nonautonomous element. Here, we have exploited the availability of 360 Mb of rice genomic sequence to identify a candidate autonomous element. RIRE2 is a previously described gypsy-like long terminal repeat retrotransposon with significant sequence similarity to Dasheng in the regions where putative cis factors for retrotransposition are thought to be located. Dasheng and RIRE2 elements have similar chromosomal distribution patterns and similar target site sequences, suggesting that they use the same transposition machinery. In addition, the presence of several RIRE2-Dasheng element chimeras in the genome is consistent with the copackaging of element mRNAs in the same virus-like particle. Finally, both families have recently amplified members, suggesting that they could have been coexpressed, a necessary prerequisite for RIRE2 to serve as the source of transposition machinery for Dasheng. Consistent with this hypothesis, transcripts from both elements were found in the same expressed sequence tag library. C1 Univ Georgia, Dept Plant Biol, Athens, GA 30602 USA. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Wessler, SR (reprint author), Univ Georgia, Dept Plant Biol, Athens, GA 30602 USA. EM sue@dogwood.botany.uga.edu RI Jiang, Ning/G-6546-2012 NR 40 TC 40 Z9 41 U1 1 U2 1 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD DEC PY 2002 VL 130 IS 4 BP 1697 EP 1705 DI 10.1104/pp.015412 PG 9 WC Plant Sciences SC Plant Sciences GA 628JL UT WOS:000179990100013 PM 12481052 ER PT J AU Diemert, DJ AF Diemert, DJ TI Prevention and self-treatment of travelers' diarrhea SO PRIMARY CARE LA English DT Article ID PEACE CORPS VOLUNTEERS; BISMUTH SUBSALICYLATE; DOUBLE-BLIND; TRIMETHOPRIM-SULFAMETHOXAZOLE; PROPHYLACTIC DOXYCYCLINE; EPIDEMIOLOGY; LOPERAMIDE; THAILAND; THERAPY; CIPROFLOXACIN AB Of the 50 million people who travel from the industrialized world to developing countries every year, between 20% and 50% will develop at least one episode of diarrhea, making it the most common ailment of travel. Although usually a mild illness, travelers' diarrhea can result in significant morbidity and hardship while overseas. Precautions can be taken to minimize the risk of developing diarrhea. If diarrhea does develop despite precautions, effective treatment, usually a combination of an antibiotic and an antimotility agent, can be taken along and started by the traveler at the onset of symptoms. C1 NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD 20852 USA. RP Diemert, DJ (reprint author), NIAID, Malaria Vaccine Dev Unit, NIH, Twinbrook 1,Room 1123,5640 Fishers Lane, Rockville, MD 20852 USA. NR 61 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 0095-4543 J9 PRIMARY CARE JI Primary Care PD DEC PY 2002 VL 29 IS 4 BP 843 EP + AR PII S0095-4543(02)00034-9 DI 10.1016/S0095-4543(02)00034-9 PG 14 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 628CT UT WOS:000179975300005 PM 12687896 ER PT J AU Sasahara, K Demura, M Nitta, K AF Sasahara, K Demura, M Nitta, K TI Equilibrium and kinetic folding of hen egg-white lysozyme under acidic conditions SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE hen egg-white lysozyme; protein folding; stopped flow; folding intermediate ID MOLTEN GLOBULE STATE; CIRCULAR-DICHROISM SPECTROSCOPY; X-RAY-SCATTERING; ALPHA-LACTALBUMIN; EQUINE LYSOZYME; 3-STATE MODEL; ON-PATHWAY; PROTEIN; INTERMEDIATE; THERMODYNAMICS AB The equilibrium and kinetic folding of hen egg-white lysozyme was studied by means of circular dichroism spectra in the far- and near-ultraviolet (UV) regions at 25degreesC under the acidic pH conditions. In equilibrium condition at pH 2.2, hen lysozyme shows a single cooperative transition in the GdnCl-induced unfolding experiment. However, in the GdnCl-induced unfolding process at lower pH 0.9, a distinct intermediate state with molten globule characteristics was observed. The time-dependent unfolding and refolding of the protein were induced by concentration jumps of the denaturant and measured by using stopped-flow circular dichroism at pH 2.2. Immediately after the dilution of denaturant, the kinetics of refolding shows evidence of a major unresolved far-UV CD change during the dead time (< 10 ms) of the stopped-flow experiment (burst phase). The observed refolding and unfolding curves were both fitted well to a single-exponential function, and the rate constants obtained in the far- and near-UV regions coincided with each other. The dependence on denaturant concentration of amplitudes of burst phase and both rate constants was modeled quantitatively by a sequential three-state mechanism, U<---->I<---->N, in which the burst-phase intermediate (I) in rapid equilibrium with the unfolded state (U) precedes the rate-determining formation of the native state (N). The role of folding intermediate state of hen lysozyme was discussed. (C) 2002 Wiley-Liss, Inc. C1 Hokkaido Univ, Grad Sch Sci, Div Biol Sci, Sapporo, Hokkaido, Japan. RP NIH, Bldg 8,Room 220, Bethesda, MD 20892 USA. EM Kenjisa@intra.niddk.nih.gov RI Demura, Makoto/F-5272-2011 NR 55 TC 33 Z9 34 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-3585 EI 1097-0134 J9 PROTEINS JI Proteins PD DEC 1 PY 2002 VL 49 IS 4 BP 472 EP 482 DI 10.1002/prot.10215 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 619KU UT WOS:000179475800006 PM 12402357 ER PT J AU Vondrasek, J Wlodawer, A AF Vondrasek, J Wlodawer, A TI HIVdb: A database of the structures of human immunodeficiency virus protease SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Editorial Material ID SYNTHETIC HIV-1 PROTEASE; INHIBITOR C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. Acad Sci Czech Republ, Inst Organ Chem & Biochem, Prague 6, Czech Republic. RP Vondrasek, J (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RI Vondrasek, JIri/A-4244-2008 NR 12 TC 47 Z9 49 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 0887-3585 J9 PROTEINS JI Proteins PD DEC 1 PY 2002 VL 49 IS 4 BP 429 EP 431 DI 10.1002/prot.10246 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 619KU UT WOS:000179475800001 PM 12402352 ER PT J AU Kipnis, V Midthune, D Freedman, L Bingham, S Day, NE Riboli, E Ferrari, P Carroll, RJ AF Kipnis, V Midthune, D Freedman, L Bingham, S Day, NE Riboli, E Ferrari, P Carroll, RJ TI Bias in dietary-report instruments and its implications for nutritional epidemiology SO PUBLIC HEALTH NUTRITION LA English DT Article; Proceedings Paper CT 4th International Conference on Dietary Assessment Methods CY SEP 17-20, 2000 CL TUCSON, ARIZONA DE dietary assessment methods; measurement error; biological markers ID DOUBLY LABELED WATER; ISOLATED SOY PROTEIN; NITROGEN-BALANCE; MEASUREMENT ERROR; LONG-TERM; ENERGY-EXPENDITURE; METABOLIC BALANCE; ELDERLY PEOPLE; BREAST-CANCER; RELATIVE RISK AB Objective: To evaluate measurement error structure in dietary assessment instruments and to investigate its implications for nutritional studies, using urinary nitrogen excretion as a reference biomarker for protein intake. Design: The dietary assessment methods included different food-frequency questionnaires (FFQs) and such conventional dietary-report reference instruments as a series of 24-hour recalls, 4-day weighed food records or 7-day diaries. Setting: Six original pilot validation studies within the European Prospective Investigation of Cancer (EPIC), and two validation studies conducted by the British Medical Research Council (MRC) within the Norfolk cohort that later joined as a collaborative component cohort of EPIC. Subjects: A sample of approximately 100 to 200 women and men, aged 35-74 years, from each of eight validation studies. Results: In assessing protein intake, all conventional dietary-report reference methods violated the critical requirements for a valid reference instrument for evaluating, and adjusting for, dietary measurement error in an FFQ. They displayed systematic bias that depended partly on true intake and partly was person-specific, correlated with person-specific bias in the FFQ. Using the dietary-report methods as reference instruments produced substantial overestimation (up to 230%) of the FFQ correlation with true usual intake and serious underestimation (up to 240%) of the degree of attenuation of FFQ-based log relative risks. Conclusion: The impact of measurement error in dietary assessment instruments on the design, analysis and interpretation of nutritional studies may be much greater than has been previously estimated, at least regarding protein intake. C1 NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. Bar Ilan Univ, Ramat Gan, Israel. Gertner Inst Epidemiol & Hlth Policy Res, Tel Hashomer, Israel. MRC, Dunn Human Nutr Unit, Cambridge, England. Univ Cambridge, Strangeways Res Lab, Cambridge, England. Int Agcy Res Canc, Unit Nutr & Canc, F-69372 Lyon, France. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RP Kipnis, V (reprint author), NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA-57030]; PHS HHS [P30-E509106] NR 42 TC 135 Z9 139 U1 1 U2 16 PU C A B I PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 1368-9800 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD DEC PY 2002 VL 5 IS 6A SI SI BP 915 EP 923 DI 10.1079/PHN2002383 PG 9 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA 652VT UT WOS:000181402100016 PM 12633516 ER PT J AU Parshall, GW Pearson, GS Inch, TD Becker, ED AF Parshall, GW Pearson, GS Inch, TD Becker, ED TI Impact of scientific developments on the chemical weapons convention (IUPAC Technical Report) SO PURE AND APPLIED CHEMISTRY LA English DT Article AB This document was prepared as a report from IUPAC to the Organisation for the Prohibition of Chemical Weapons (OPCW) to provide an evaluation of scientific and technological advances in the chemical sciences relevant to the Chemical Weapons Convention (CWC). The report is intended to assist OPCW and its Member States in preparation for the First Review Conference to be held on 28 April 2003. The CWC, now ratified by 145 nations and in effect since 1997, totally prohibits the production, storage, or use of toxic chemicals as weapons of war. This report is based on an IUPAC Workshop held in Bergen, Norway, 30 June to 3 July 2002. The report highlights developments in organic synthesis and changes in chemical plant design that will pose new challenges to the Convention, but it also describes recent and probable future developments in analytical chemistry that should assist in implementation of the Convention. The key issues identified at the Workshop are listed, and the findings and observations are summarized in 18 points. C1 NIH, Bethesda, MD 20892 USA. DuPont Co Inc, Wilmington, DE 19806 USA. Univ Bradford, Dept Peace Studies, Bradford BD7 1DP, W Yorkshire, England. Royal Soc Chem, London, England. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU INT UNION PURE APPLIED CHEMISTRY PI RES TRIANGLE PK PA 104 TW ALEXANDER DR, PO BOX 13757, RES TRIANGLE PK, NC 27709-3757 USA SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD DEC PY 2002 VL 74 IS 12 BP 2323 EP 2352 DI 10.1351/pac200274122323 PG 30 WC Chemistry, Multidisciplinary SC Chemistry GA 652EU UT WOS:000181367500016 ER PT J AU Belgrave, LL Zablotsky, D Guadagno, MA AF Belgrave, LL Zablotsky, D Guadagno, MA TI How do we talk to each other? Writing qualitative research for quantitative readers SO QUALITATIVE HEALTH RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Sociological-Association CY AUG 11-16, 2000 CL WASHINGTON, D.C. SP Amer Sociol Assoc AB The growth of qualitative research holds the potential for vastly enriching our understanding of phenomena in the health sciences. However, the potential of this trend is hampered by a widespread inability of quantitative and qualitative researchers to talk to each other. The authors' concern in this area grows out of our experience reviewing small grant applications for the National Institute on Aging, where they frequently find qualitative research proposals scoring worse than do those using quantitative approaches. This article addresses practical problems in communicating qualitative research to readers whose training and experience is primarily quantitative. Two themes running through the discussion are the need for detail and the explicit tying of methodological strategies to research goals. C1 Univ Miami, Dept Sociol, Coral Gables, FL 33124 USA. Univ N Carolina, Dept Sociol, Charlotte, NC USA. Inst Aging, NIH, Ctr Sci Review, Bethesda, MD USA. RP Belgrave, LL (reprint author), Univ Miami, Dept Sociol, POB 248162, Coral Gables, FL 33124 USA. NR 22 TC 15 Z9 15 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 J9 QUAL HEALTH RES JI Qual. Health Res. PD DEC PY 2002 VL 12 IS 10 BP 1427 EP 1439 DI 10.1177/1049732302238753 PG 13 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA 616XH UT WOS:000179328400010 PM 12474913 ER PT J AU Gilbert, ES AF Gilbert, ES TI The risk of cancer from exposure to plutonium SO RADIATION RESEARCH LA English DT Meeting Abstract CT American-Statistical-Association Conference on Radiation and Health CY JUN 23-26, 2002 CL DEERFIELD BEACH, FLORIDA SP American Statist Assoc ID MAYAK WORKERS C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NR 7 TC 0 Z9 1 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2002 VL 158 IS 6 BP 783 EP 784 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 622YQ UT WOS:000179676000015 ER PT J AU Lubin, JH Wang, ZY Kleinerman, RA AF Lubin, JH Wang, ZY Kleinerman, RA TI Residential radon and lung cancer in a high radon area of Gansu Province, China SO RADIATION RESEARCH LA English DT Meeting Abstract CT American-Statistical-Association Conference on Radiation and Health CY JUN 23-26, 2002 CL DEERFIELD BEACH, FLORIDA SP American Statist Assoc ID EXPOSURE; RISK; ERROR C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2002 VL 158 IS 6 BP 784 EP 785 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 622YQ UT WOS:000179676000017 ER PT J AU Krewski, D Lubin, JH Zielinski, JM Alavanja, M Catalan, VS Field, RW Klotz, JB Letourneau, EG Lynch, CF Lyon, JL Sandler, DP Schoenberg, JB Steck, DJ Stolwijk, JA Weinberg, C Wilcox, HB AF Krewski, D Lubin, JH Zielinski, JM Alavanja, M Catalan, VS Field, RW Klotz, JB Letourneau, EG Lynch, CF Lyon, JL Sandler, DP Schoenberg, JB Steck, DJ Stolwijk, JA Weinberg, C Wilcox, HB TI A combined analysis of North American case-control studies of residential radon and lung cancer: An update SO RADIATION RESEARCH LA English DT Meeting Abstract CT American-Statistical-Association Conference on Radiation and Health CY JUN 23-26, 2002 CL DEERFIELD BEACH, FLORIDA SP American Statist Assoc ID INDOOR RADON; EXPOSURE; RISK; FINLAND; WOMEN C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Washington, DC USA. Hlth Canada, Healthy Environm & Consumer Safety Branch, Ottawa, ON K1A 0L2, Canada. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Washington, DC USA. Lakehead Univ, Ctr Excellence Children & Adolescents Special Nee, Thunder Bay, ON P7B 5E1, Canada. Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. Univ Iowa, Dept Occupat & Environm Hlth, Iowa City, IA 52242 USA. Canc Epidemiol, Dept Hlth & Senior Serv, Trenton, NJ USA. Hlth Canada, Radiat Protect Bur, Hlth Protect Branch, Ottawa, ON K1A 0L2, Canada. Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT 84112 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. St Johns Univ, Dept Phys, Collegeville, MN 56321 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Univ Ottawa, McLaughlin Ctr Populat Hlth Risk Assessment, Ottawa, ON K1N 6N5, Canada. NR 25 TC 3 Z9 3 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2002 VL 158 IS 6 BP 785 EP 790 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 622YQ UT WOS:000179676000018 ER PT J AU Amundson, SA Bittner, M Fornace, AJ AF Amundson, SA Bittner, M Fornace, AJ TI Genome-wide transcriptional responses at low doses: The power of microarray technology SO RADIATION RESEARCH LA English DT Meeting Abstract CT American-Statistical-Association Conference on Radiation and Health CY JUN 23-26, 2002 CL DEERFIELD BEACH, FLORIDA SP American Statist Assoc ID STRESS C1 NHGRI, NIH, Bethesda, MD 20892 USA. NCI, Gene Response Sect, NIH, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 3 TC 1 Z9 1 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2002 VL 158 IS 6 BP 791 EP 791 PG 1 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 622YQ UT WOS:000179676000021 ER PT J AU Linet, MS AF Linet, MS TI Children's exposure to diagnostic medical radiation and cancer risk: An epidemiologist's perspective SO RADIATION RESEARCH LA English DT Meeting Abstract CT American-Statistical-Association Conference on Radiation and Health CY JUN 23-26, 2002 CL DEERFIELD BEACH, FLORIDA SP American Statist Assoc ID CHILDHOOD-CANCER C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Linet, MS (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 1 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2002 VL 158 IS 6 BP 796 EP 797 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 622YQ UT WOS:000179676000027 ER PT J AU Mabuchi, K Yoshinaga, S Ron, E AF Mabuchi, K Yoshinaga, S Ron, E TI Overview of occupational medical exposure SO RADIATION RESEARCH LA English DT Meeting Abstract CT American-Statistical-Association Conference on Radiation and Health CY JUN 23-26, 2002 CL DEERFIELD BEACH, FLORIDA SP American Statist Assoc ID MORTALITY; RADIOLOGISTS; CANCER C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Inst Radiol Sci, Chiba 260, Japan. RP Mabuchi, K (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 2 U2 2 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2002 VL 158 IS 6 BP 803 EP 804 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 622YQ UT WOS:000179676000035 ER PT J AU Sigurdson, A Yoshinaga, S Doody, M Mabuchi, K AF Sigurdson, A Yoshinaga, S Doody, M Mabuchi, K TI Cancer risks associated with employment as a radiological technologist SO RADIATION RESEARCH LA English DT Meeting Abstract CT American-Statistical-Association Conference on Radiation and Health CY JUN 23-26, 2002 CL DEERFIELD BEACH, FLORIDA SP American Statist Assoc C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Natl Inst Radiol Sci, Chiba 260, Japan. RP Sigurdson, A (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2002 VL 158 IS 6 BP 805 EP 807 PG 3 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 622YQ UT WOS:000179676000037 ER PT J AU Marcos, HB Libutti, SK Alexander, HR Lubensky, IA Bartlett, DL Walther, MM Linehan, WM Glenn, GM Choyke, PL AF Marcos, HB Libutti, SK Alexander, HR Lubensky, IA Bartlett, DL Walther, MM Linehan, WM Glenn, GM Choyke, PL TI Neuroendocrine tumors of the pancreas in von Hippel-Lindau disease: Spectrum of appearances at CT and MR imaging with histopathologic comparison SO RADIOLOGY LA English DT Article DE pancreas, neoplasms; pancreas, CT; pancreas, cysts; pancreas, MR; pheochromocytorna; von Hippel-Linclau disease ID ISLET-CELL TUMORS; GASTROINTESTINAL-TRACT; GENETIC-ANALYSIS; IDENTIFICATION; LOCALIZATION; PREVALENCE; FEATURES AB PURPOSE: To demonstrate the imaging characteristics of neuroendocrine tumors (NETs) of the pancreas in patients with von Hippel-Linclau (VHL) disease to establish diagnostic criteria. MATERIALS AND METHODS: Twenty-five patients with VHL disease and 29 surgically confirmed pancreatic NETs were included. Screening computed tomographic (CT) and/or magnetic resonance (MR) imaging findings were reviewed, and tumor number, diameter, growth rates (doubling time), location, presence of metastatic disease, and attenuation or enhancement properties were determined. RESULTS: Eighteen of 29 (62%) pancreatic NETs were smaller than 3.0 cm in diameter and enhanced homogeneously on contrast material-enhanced CT and MR images. No tumor smaller than 3.0 cm metastasized. Tumors 3.0 cm or larger (111 [38%] of 29) more often enhanced heterogeneously, and two of 11 were associated with hepatic metastases. Smaller (<3.0 cm) tumors displayed longer mean doubling times (mean, 927 vs 351 days) than did larger (greater than or equal to3.0 cm) tumors; however, there was considerable overlap. Fifteen (52%) tumors were located in the pancreatic head; eight (28%), in the tail; and six (21%), in the body. Ten (40%) patients with pancreatic NETs had associated pheochromocytomas, and 22 (88%) had no or mild pancreatic cystic disease, which is substantially more than the general population of patients with VHL disease. CONCLUSION: Pancreatic NETs in VHL have characteristic features at CT and MR imaging: Most are small, located in the pancreatic head, and enhance homogeneously. Tumors larger than 3.0 cm are prone to metastasize and enhance heterogeneously. (C) RSNA 2002,. C1 NCI, Dept Diagnost Radiol, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Dept Diagnost Radiol, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Rm 1C660, Bethesda, MD 20892 USA. NR 19 TC 44 Z9 53 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2002 VL 225 IS 3 BP 751 EP 758 DI 10.1148/radiol.2253011297 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 618MA UT WOS:000179420800019 PM 12461257 ER PT J AU Kim, AH Kohn, MC Portier, CJ Walker, NJ AF Kim, AH Kohn, MC Portier, CJ Walker, NJ TI Impact of physiologically based pharmacokinetic modeling on benchmark dose calculations for TCDD-induced biochemical responses SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE benchmark dose; PBPK modeling; TCDD; biochemical responses; risk assessment ID SPRAGUE-DAWLEY RATS; GROWTH-FACTOR RECEPTOR; DIBENZO-P-DIOXINS; CELL-PROLIFERATION; CHRONIC EXPOSURE; TUMOR PROMOTION; END-POINTS; LIVER; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; INDUCTION AB In risk assessment, noncancer risk is currently estimated using a no observed adverse effect level (NOAEL) from an experimental dose-response study, divided by uncertainty factors, to estimate a presumably safe level of human exposure. A benchmark dose approach, in which an effective dose (ED) resulting in a specified percentage increase over background for effects is estimated by empirical modeling, has been proposed as a replacement for the NOAEL methodology. The aim of this analysis is to compare methods for estimation of body burden resulting in a 1 or 10% maximum increase over background (BB01 or BB10) for biochemical responses following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in female Sprague-Dawley rats. In one method, an ED resulting in a prespecified increase in response over background was estimated using average daily doses and an empirical Hill model. The ED was then converted to an equivalent body burden by a simple kinetic model assuming steady-state conditions, half-life of TCDD in the rat, and 100% absorption of TCDD. Alternatively, a mechanistic physiologically based pharmacokinetic (PBPK) model of TCDD in the rat was used to predict body burdens for administered doses. These PBPK-modeled body burdens were then used directly by the Hill model to calculate a BB01 or BB10. In general, the body burden values derived from EDs were within five-fold of BB01 or BB10 calculated from the PBPK model. BB01 and BB10 values from both methods were within two orders of magnitude of current human general population exposure to all dioxin-like compounds. (C) 2002 Elsevier Science (USA). C1 NIEHS, Lab Computat Biol & Risk Assessment, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. RP Walker, NJ (reprint author), NIEHS, Lab Computat Biol & Risk Assessment, POB 12233,MD D4-01, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010; Walker, Nigel/D-6583-2012 OI Portier, Christopher/0000-0002-0954-0279; Walker, Nigel/0000-0002-9111-6855 NR 33 TC 10 Z9 11 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 2002 VL 36 IS 3 BP 287 EP 296 DI 10.1006/rtph.2002.1590 PG 10 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 622BR UT WOS:000179627100007 PM 12473413 ER PT J AU Vermeulen, R Stewart, P Kromhout, H AF Vermeulen, R Stewart, P Kromhout, H TI Dermal exposure assessment in occupational epidemiologic research SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Review DE epidemiology; exposure assessment; exposure variability; dermal uptake; review; skin exposure ID RUBBER-MANUFACTURING-INDUSTRY; POLYCYCLIC AROMATIC-HYDROCARBONS; POLYCHLORINATED-BIPHENYLS PCBS; PERCUTANEOUS-ABSORPTION; HAND DERMATITIS; INHALATION EXPOSURE; PESTICIDE EXPOSURE; URINARY-EXCRETION; MEASUREMENT ERROR; ORGANIC-COMPOUNDS AB Recognition of the importance of skin exposure in industrial settings has steadily increased over the last few decades. Unfortunately, the growing attention to dermal exposure in industrial hygiene has often not been reflected in the field of occupational epidemiology. An extensive literature survey was conducted to identify dermal exposure assessment methods that have been applied in epidemiologic studies. Subsequently, methodologies are postulated that could be applied to epidemiologic research. Attention is given to intensity, frequency, and duration of exposure, the exposed surface area, and personal, temporal and spatial variability in dermal exposure and uptake. It is anticipated that, in the near future, dermal exposure assessment in epidemiologic research will be based generally on expert judgment and to some degree on process-specific exposure models. Field studies collecting quantitative dermal exposure data and statistical modeling to identify exposure determinants will, however, be imperative if progress is to be made in the field of dermal exposure assessment for epidemiologic purposes. C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. Univ Utrecht, Inst Risk Assessment Sci, Environm & Occupat Hlth Grp, Utrecht, Netherlands. RP Vermeulen, R (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Executive Blvd, Rockville, MD 20892 USA. RI Kromhout, Hans/A-9159-2008; Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 110 TC 20 Z9 20 U1 0 U2 2 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PD DEC PY 2002 VL 28 IS 6 BP 371 EP 385 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 633NM UT WOS:000180289400002 PM 12539797 ER PT J AU Weinstein, BM AF Weinstein, BM TI Plumbing the mysteries of vascular development using the zebrafish SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE zebrafish; blood vessels; vascular endothelium; vascular smooth muscle ID GROWTH-FACTOR VEGF; CARDIOVASCULAR DEVELOPMENT; ARTERIAL VESSELS; DANIO-RERIO; GENE CLOCHE; EXPRESSION; DIFFERENTIATION; VASCULOGENESIS; ANGIOGENESIS; ENDOTHELIUM AB The zebrafish has recently emerged as an advantageous model organism for studying how the stereotypic and evolutionarily conserved network of vertebrate blood vessels arises during development. The ability to screen for vascular-specific mutants and to image and experimentally manipulate blood vessels throughout living embryos has already yielded new insights into the anatomy of the early vasculature, the dynamics of growing blood vessels, the specification of early vascular progenitors, and arterial-venous differentiation of blood vessels. C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Weinstein, BM (reprint author), NICHHD, Genet Mol Lab, NIH, Bldg 6B,Room 309,6 Ctr Dr, Bethesda, MD 20892 USA. NR 57 TC 40 Z9 42 U1 1 U2 7 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD DEC PY 2002 VL 13 IS 6 BP 515 EP 522 DI 10.1016/S1084-9521(02)00105-2 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 627HM UT WOS:000179927800019 PM 12468255 ER PT J AU Curt, GA AF Curt, GA TI Introduction: Complementary and alternative medicine in cancer treatment SO SEMINARS IN ONCOLOGY LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Curt, GA (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2002 VL 29 IS 6 BP 529 EP 530 DI 10.1053/sonc.2002.50001 PG 2 WC Oncology SC Oncology GA 627UD UT WOS:000179953800001 ER PT J AU Richardson, MA Straus, SE AF Richardson, MA Straus, SE TI Complementary and alternative medicine: Opportunities and challenges for cancer management and research SO SEMINARS IN ONCOLOGY LA English DT Review ID CELL LUNG-CANCER; GALACTOSIDE-SPECIFIC LECTIN; LEUKEMIA GROUP-B; QUALITY-OF-LIFE; DOSE VITAMIN-C; BREAST-CANCER; PROSTATE-CANCER; UNCONVENTIONAL THERAPIES; PC-SPES; DIETARY-SUPPLEMENT C1 NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Richardson, MA (reprint author), NIH, Ctr Alternat & Complementary Med, 6707 Democracy Blvd,Suite 106, Bethesda, MD 20892 USA. NR 115 TC 45 Z9 45 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2002 VL 29 IS 6 BP 531 EP 545 DI 10.1053/sonc.2002.50002 PG 15 WC Oncology SC Oncology GA 627UD UT WOS:000179953800002 PM 12516036 ER PT J AU White, JD AF White, JD TI Complementary and alternative medicine research: A National Cancer Institute perspective SO SEMINARS IN ONCOLOGY LA English DT Review ID CELL LUNG-CANCER; DOSE VITAMIN-C; HYDRAZINE SULFATE; ANTINEOPLASTONS A10; CONTROLLED TRIAL; PLACEBO; THERAPIES; PROGRAM; AS2-1 C1 NCI, Off Canc Complementary & Alternat Med, NIH, Bethesda, MD 20892 USA. NCI, Off Deputy Director Extramural Sci, NIH, Bethesda, MD 20892 USA. RP White, JD (reprint author), NCI, Off Canc Complementary & Alternat Med, NIH, Execut Plaza N,Suite 102, Bethesda, MD 20892 USA. NR 24 TC 21 Z9 21 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2002 VL 29 IS 6 BP 546 EP 551 DI 10.1053/sonc.2002.50003 PG 6 WC Oncology SC Oncology GA 627UD UT WOS:000179953800003 PM 12516037 ER PT J AU Nahin, RL AF Nahin, RL TI Use of the best case series to evaluate complementary and alternative therapies for cancer: A systematic review SO SEMINARS IN ONCOLOGY LA English DT Review ID DOSE VITAMIN-C; COLORECTAL-CANCER; ANTINEOPLASTONS A10; PHASE-II; CHEMOTHERAPY; TRIAL; MANAGEMENT; SURVIVAL; MEDICINE; PLACEBO C1 NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Nahin, RL (reprint author), 9000 Rockville Pike,Bldg 31,Room 2B11, Bethesda, MD 20892 USA. OI Nahin, Richard/0000-0002-3682-4816 NR 60 TC 13 Z9 13 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2002 VL 29 IS 6 BP 552 EP 562 DI 10.1053/sonc.2002.50004 PG 11 WC Oncology SC Oncology GA 627UD UT WOS:000179953800004 PM 12516038 ER PT J AU Mansky, PJ AF Mansky, PJ TI Mistletoe and cancer: Controversies and perspectives SO SEMINARS IN ONCOLOGY LA English DT Review ID VISCUM-ALBUM L; GALACTOSIDE-SPECIFIC LECTIN; BLOOD MONONUCLEAR-CELLS; CORONARY HEART-DISEASE; NECROSIS FACTOR-ALPHA; INDUCED APOPTOSIS; IN-VITRO; EUROPEAN MISTLETOE; HUMAN MONOCYTES; EXTRACT C1 NIH, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Mansky, PJ (reprint author), NIH, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, 8 West Dr,Quarters 15-B1,MSC 2669, Bethesda, MD 20892 USA. NR 49 TC 17 Z9 17 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2002 VL 29 IS 6 BP 589 EP 594 DI 10.1053/sonc.2002.50006 PG 6 WC Oncology SC Oncology GA 627UD UT WOS:000179953800008 PM 12516042 ER PT J AU Ziran, N Hill, S Wright, ME Kovacs, J Robey, PG Wientroub, S Collins, MT AF Ziran, N Hill, S Wright, ME Kovacs, J Robey, PG Wientroub, S Collins, MT TI Ribbing disease: radiographic and biochemical characterization, lack of response to pamidronate SO SKELETAL RADIOLOGY LA English DT Article DE diaphyseal dysplasia; tibiae; bisphosphonates; radiographs; CT; MRI ID MULTIPLE DIAPHYSEAL SCLEROSIS; FIBROUS DYSPLASIA; ENGELMANN-DISEASE; PAGETS-DISEASE; BONE; DIAGNOSIS; THERAPY AB Ribbing disease is a rare form of sclerosing dysplasia characterized by benign endosteal and periosteal bone growth confined to the diaphyses of the long bones, usually the tibiae and femora. The onset is usually after puberty and the most common presentation is pain that is usually self-limited, but may progress. The etiology and optimal treatment for the disease are unknown. We present the case of a 39-year-old Hispanic man with clinical and radiological manifestations of Ribbing disease. Radiographs and CT imaging demonstrated typical cortical thickening in the mid-diaphyses of the tibiae bilaterally that correlated with intense tracer uptake on Tc-99m-MDP bone scans. MRI demonstrated cortical thickening and abnormal marrow signal consistent with marrow edema. Bone marrow edema may explain the pain frequently associated with the disease. Multiple serum and urine markers of bone metabolism were within normal limits. In an effort to ameliorate pain, the patient was treated with the bisphosphonate, pamidronate. In spite of treatment, pain increased, requiring additional and larger doses of analgesics. Serial radiographs, CT, bone scans, and MRI all demonstrated disease progression with pamidronate treatment. In this report we present for the first time the finding of bone marrow edema with MRI as well as disease progression during intravenous pamidronate treatment. C1 NIDCR, CSDB, NIH, Bethesda, MD 20892 USA. Univ Rochester, Dept Orthoped Surg, Rochester, NY 14642 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. Tel Aviv Med Ctr & Sch Med, Dana Childrens Hosp, Dept Pediat Orthoped Surg, IL-64239 Tel Aviv, Israel. RP Collins, MT (reprint author), NIDCR, CSDB, NIH, Bldg 30,Room 228,MSC 4320, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 20 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD DEC PY 2002 VL 31 IS 12 BP 714 EP 719 DI 10.1007/s00256-002-0552-6 PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 629JA UT WOS:000180045500008 PM 12483434 ER PT J AU Davalos, A Castillo, J Alvarez-Sabin, J Secades, JJ Mercadal, J Lopez, S Cobo, E Warach, S Sherman, D Clark, WM Lozano, R AF Davalos, A Castillo, J Alvarez-Sabin, J Secades, JJ Mercadal, J Lopez, S Cobo, E Warach, S Sherman, D Clark, WM Lozano, R TI Oral citicoline in acute ischemic stroke - An individual patient data pooling analysis of clinical trials SO STROKE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Neurological-Association CY SEP 30-OCT 01, 2001 CL CHICAGO, ILLINOIS SP Amer Neurolog Assoc DE cytidine diphosphate choline; neuroprotection; stroke, acute; stroke, ischemic ID RANDOMIZED EFFICACY TRIAL; NEUROLOGICAL-DISORDERS; NATIONAL-INSTITUTE AB Background and Purpose-No single neuroprotective agent has been shown to influence outcome after acute stroke. Citicoline has been studied worldwide in many clinical trials with positive findings, but only 1 trial has obtained significant results in the primary efficacy variables. Our objective was to evaluate the effects of oral citicoline in patients with acute ischemic stroke by a data pooling analysis of clinical trials. The primary efficacy end point chosen was the common evaluation of recovery, combining National Institutes of Health Stroke Scale less than or equal to1, modified Rankin Scale score less than or equal to1, and Barthel Index less than or equal to95 at 3 months using the generalized estimating equations analysis. Methods-A systematic search of all prospective, randomized, placebo-controlled, double-blind clinical trials with oral citicoline (MEDLINE, Cochrane, and Ferrer Group bibliographic databases) was undertaken. Individual patient data were extracted from each study and pooled in a single data file. The main inclusion criteria included compatible neuroimaging with ischemic stroke, National Institutes of Health Stroke Scale greater than or equal to8, and prior modified Rankin Scale score less than or equal to1. Four clinical trials using various doses of oral citicoline (500, 1000, and 2000 mg) were identified. Results-Of 1652 randomized patients, 1372 fulfilled the inclusion criteria (583 received placebo, 789 received citicoline). Recovery at 3 months was 25.2% in citicoline-treated patients and 20.2% in placebo-treated patients (odds ratio [OR], 1.33; 95% CI, 1.10 to 1.62; P=0.0034). The dose showing the largest difference with placebo was 2000 mg, with 27.9% of patients achieving recovery (OR, 1.38; 95% CI, 1.10 to 1.72; P=0.0043). The overall safety of citicoline was similar to placebo. Conclusions-Treatment with oral citicoline within the first 24 hours after onset in patients with moderate to severe stroke increases the probability of complete recovery at 3 months. C1 Hosp Univ Girona Doctor Josep Trueta, Dept Neurol, Girona 17007, Spain. Hosp Clin Univ, Dept Neurol, Santiago De Compostela, Spain. Hosp Gen Valle Hebron, Dept Neurol, Barcelona, Spain. Grp Ferrer SA, Dept Med, Barcelona, Spain. Univ Politecn Catalunya, Dept Stat & Operat Res, Barcelona, Spain. NINDS, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Oregon Hlth Sci Univ, Oregon Stroke Ctr, Portland, OR 97201 USA. RP Davalos, A (reprint author), Hosp Univ Girona Doctor Josep Trueta, Dept Neurol, Av Franca S-N, Girona 17007, Spain. RI Cobo, Erik/H-6230-2011; OI Cobo, Erik/0000-0002-3534-5602; Castillo, Jose/0000-0002-6685-3001 NR 20 TC 121 Z9 138 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2002 VL 33 IS 12 BP 2850 EP 2857 DI 10.1161/01.STR.0000038691.03334.71 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 625QL UT WOS:000179827100028 PM 12468781 ER PT J AU Gryk, MR Marintchev, A Maciejewski, MW Robertson, A Wilson, SH Mullen, GP AF Gryk, MR Marintchev, A Maciejewski, MW Robertson, A Wilson, SH Mullen, GP TI Mapping of the interaction interface of DNA polymerase beta with XRCC1 SO STRUCTURE LA English DT Article DE chemical shift mapping; deuteration; DNA base excision repair; multidimensional NMR; structure-based mutants ID PROTEIN SECONDARY STRUCTURE; N-TERMINAL DOMAIN; CHEMICAL-SHIFT; REPAIR POLYMERASE; NMR-SPECTROSCOPY; BINDING; ASSIGNMENTS; RESONANCE; COMPLEX; C-13 AB Residues of DNA polymerase beta (beta-Pol) that interact with the DNA repair protein XRCC1 have been determined by NMR chemical shift mapping (CSM) and mutagenesis. N-15/C-13/H-2/H-1,C-13-methyl(Leu,Ile,Val)-labeled beta-Pol palm-thumb domain was used for assignments of the H-1, N-15, and C-13 resonances used for CSM of the palm-thumb on forming the 40 kDa complex with the XRCC1 N-terminal domain (NTD). Large chemical shift changes were observed in the thumb on complexation. N-15 relaxation data indicate reduction in high-frequency motion for a thumb loop and three palm turn/loops, which showed concomitant chemical shift changes on complexation. A DeltaV303-V306 deletion and an L301R/V303R/V306R triple mutation abolished complex formation due to loss in hydrophobicity. In an updated model, the thumb-loop of beta-Pol contacts an edge/face region of the beta sheet of the XRCC1 NTD, while the beta-Pol palm weakly contacts the alpha2 helix. C1 Univ Connecticut, Ctr Hlth, Dept Biochem, Farmington, CT 06030 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Gryk, MR (reprint author), Univ Connecticut, Ctr Hlth, Dept Biochem, Farmington, CT 06030 USA. FU NIEHS NIH HHS [ES09847]; NIGMS NIH HHS [GM52738] NR 28 TC 31 Z9 34 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD DEC PY 2002 VL 10 IS 12 BP 1709 EP 1720 AR PII S0969-2126(02)00908-5 DI 10.1016/S0969-2126(02)00908-5 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 664AL UT WOS:000182039500014 PM 12467578 ER PT J AU Elaraj, DM Remaley, AT Simonds, WF Skarulis, MC Libutti, SY Bartlett, DL Venzon, DJ Marx, SJ Alexander, HR AF Elaraj, DM Remaley, AT Simonds, WF Skarulis, MC Libutti, SY Bartlett, DL Venzon, DJ Marx, SJ Alexander, HR TI Utility of rapid intraoperative parathyroid hormone assay to predict severe postoperative hypocalcemia after reoperation for hyperparathyroidism SO SURGERY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 07-09, 2002 CL BANFF, CANADA SP American Assoc Endocrine Surg ID RECURRENT HYPERPARATHYROIDISM; EXPLORATION; PERSISTENT AB Background. Patients undergoing reoperative parathyroidectomy may develop severe transient or permanent hypoparathyroidism. This study's purpose was to determine the utility of intraoperative parathyroid hormone (IO-PTH) values in predicting the development of severe hypocalcemia for patients undergoing reoperation for primary hyperparathyroidism. Methods. Between March 1999 and October 2001, 68 patients with persistent or recurrent hyperparathyroidism underwent reoperation using IO-PTH measurements. The maximum percent decrease and lowest actual PTH value obtained at surgery were compared to determine any correlation with the development of postoperative hypocalcemia requiring, supplementation. Results. Of 68 patients, 25 required calcium and calcitriol postoperatively and 43 did not. There was a significant difference between the 2 groups with respect to lowest IO-PTH value (18.4 +/- 2.6 vs 28.0 +/- 3.9 pg/mL; P = .02), percent decrease in IO-PTH (89% +/- 1% vs 80% +/- 3%; P = .03), and lowest postoperative ionized calcium (1.06 +/- 0.01 vs 1.19 +/- 0.01 mmol/L; P < .001). A percent decrease in IO-PTH of 84% or greater was found to be predictive of patients experiencing hypocalcemia requiring supplementation with a positive predictive value of 46% and a negative predictive value of 82%. Conclusions. Although a maximum percent decrease in IO-PTH of 84% or greater was associated with an increased incidence of postoperative hypocalcemia requiring supplementation in the 68-patient cohort, on further analysis the association was significant only for patients with multiglandular disease and not those with single adenomas. This value may be useful for identifying patients who will need closer postoperative monitoring or prophylactic supplementation. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B07,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 11 TC 18 Z9 18 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2002 VL 132 IS 6 BP 1028 EP 1033 DI 10.1067/msy.2002.128480 PG 6 WC Surgery SC Surgery GA 630RQ UT WOS:000180123000032 PM 12490851 ER PT J AU Ferris, FL AF Ferris, FL TI Foreword: Evaluation of new treatment paradigms for diabetic retinopathy and macular edema SO SURVEY OF OPHTHALMOLOGY LA English DT Editorial Material C1 NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. RP Ferris, FL (reprint author), NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD DEC PY 2002 VL 47 SU 2 BP S237 EP S237 AR PII S0039-6257(02)00385-5 DI 10.1016/S0039-6257(02)00385-5 PG 1 WC Ophthalmology SC Ophthalmology GA 627LT UT WOS:000179935200001 PM 12507624 ER PT J AU Oz, M Zhang, L Morales, M AF Oz, M Zhang, L Morales, M TI Endogenous cannabinoid, anandamide, acts as a noncompetitive inhibitor on 5-HT3 receptor-mediated responses in Xenopus oocytes SO SYNAPSE LA English DT Article DE anandamide; 5-HT3 receptor; Xenopus oocytes ID LAEVIS OOCYTES; ION CHANNELS; RAT-BRAIN; NEURONS; ACTIVATION; SUBUNIT; PROGESTERONE; FORSKOLIN; MEMBRANES; GANGLION AB The cloned 5-HT3 receptor from NCB-20 neuroblastoma cells was expressed in Xenopus oocytes and the effect of the endogenous cannabinoid ligand, anandamide, was investigated on the function of this receptor. The oocytes expressing the cloned 5-HT3 receptors were voltage-clamped at -70 mV. Anandamide, at the concentration range of 0.1-100 muM, reversibly inhibited 1 muM 5-HT induced currents. The inhibition of 5-HT induced currents by anandamide was concentration-dependent with an EC50 of 3.7 muM and slope value of 0.94. This inhibitory effect was not dependent on the membrane potential and anandamide did not have an effect on the reversal potential of 5-HT-induced currents. In the presence of 10 muM anandamide, the maximum 5-HT-induced response was also inhibited and the respective EC50 values were 3.4 muM and 3.1 muM in the absence and presence of anandamide, indicating that anandamide acts as a noncompetitive antagonist on 5-HT, receptors. CB, receptor antagonist SR-141716A (1 V,M) and pertussis toxin (5 mug/ml) did not cause a significant change on the inhibition of 5-HT responses by anandamide. The effect of anandamide was not changed by preincubating the oocytes with 0.2 mM 8-Br-cAMP, a membrane-permeable analog of cAMP, or Sp-cAMPS (0.1 mM), a membrane-permeable protein kinase A activator. These results suggest that the effect of anandamide is independent of the activation of CAMP pathway and not mediated by the activation of PTX sensitive G-proteins. In conclusion, we demonstrated that the endogenous cannabinioid anandamide inhibits the function of 5-HT3 receptors expressed in Xenopus oocytes in a cannabinoid-receptor independent and noncompetitive manner. Published 2002 Wiley-Liss Inc.' C1 Natl Inst Drug Abuse, IRP, Cellular Neurobiol Sect, Baltimore, MD 21224 USA. NIAAA, Mol & Cellular Neurobiol Lab, Bethesda, MD USA. Cellular Neurophysiol Sect, Baltimore, MD 21224 USA. RP Oz, M (reprint author), Natl Inst Drug Abuse, IRP, Cellular Neurobiol Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Oz, Murat/E-2148-2012 NR 36 TC 43 Z9 44 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 0887-4476 J9 SYNAPSE JI Synapse PD DEC 1 PY 2002 VL 46 IS 3 BP 150 EP 156 DI 10.1002/syn.10121 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 604KH UT WOS:000178619500003 PM 12325042 ER PT J AU Nalcioglu, O Clarke, L AF Nalcioglu, Orhan Clarke, Laurence TI Foreword SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Editorial Material C1 [Nalcioglu, Orhan] Univ Calif Irvine, John Tu & Thomas Yuen Ctr Funct Oncoimaging, Irvine, CA 92697 USA. [Clarke, Laurence] NCI, Biomed Imaging Program, NIH, Bethesda, MD 20892 USA. RP Nalcioglu, O (reprint author), Univ Calif Irvine, John Tu & Thomas Yuen Ctr Funct Oncoimaging, Irvine, CA 92697 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD DEC PY 2002 VL 1 IS 6 BP 417 EP 417 PG 1 WC Oncology SC Oncology GA V28FZ UT WOS:000208668000001 ER PT J AU Sullivan, DC AF Sullivan, Daniel C. TI Challenges and Opportunities for In Vivo Imaging in Oncology SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Editorial Material C1 NCI, Biomed Imaging Program, EPN, Bethesda, MD 20892 USA. RP Sullivan, DC (reprint author), NCI, Biomed Imaging Program, EPN, Room 6070,6130 Execut Blvd, Bethesda, MD 20892 USA. EM ds274k@nih.gov NR 4 TC 10 Z9 10 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD DEC PY 2002 VL 1 IS 6 BP 419 EP 422 PG 4 WC Oncology SC Oncology GA V28FZ UT WOS:000208668000002 PM 12625769 ER PT J AU Mulshine, JL Smith, RA AF Mulshine, JL Smith, RA TI Lung cancer. 2: Screening and early diagnosis of lung cancer SO THORAX LA English DT Review ID 2ND PRIMARY TUMORS; ACTION PROJECT; BREAST-CANCER; RETINOIC ACID; ISOTRETINOIN; CARCINOMA; TOBACCO; RISK; TIME; MAMMOGRAPHY AB Technical developments in spiral CT scanning mean that considerably smaller lung cancers can now be identified than with previous methods of detection. Only time will tell whether this enhanced capability will result in a reduction in the number of deaths from lung cancer. The implications and problems of screening for lung cancer are discussed. Screening implies a careful refinement of a range of clinical activities that must be routinely delivered in a carefully coordinated fashion to allow for the possibility of improved outcome. Critical analyses of the nuances of this process are essential if the field is to move forward. C1 NCI, Intervent Sect, Ctr Canc Res, Bethesda, MD 20892 USA. Amer Canc Soc, Atlanta, GA 30329 USA. RP Mulshine, JL (reprint author), NCI, Intervent Sect, Ctr Canc Res, Bethesda, MD 20892 USA. EM mulshinej@bprb.nci.nih.gov NR 49 TC 14 Z9 16 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD DEC PY 2002 VL 57 IS 12 BP 1071 EP 1078 DI 10.1136/thorax.57.12.1071 PG 8 WC Respiratory System SC Respiratory System GA 622QC UT WOS:000179656900015 PM 12454304 ER PT J AU Griesenbach, U Escudero-Garcia, S Farley, R Cheng, S Geddes, DM Caplen, NJ Alton, EWFW AF Griesenbach, U Escudero-Garcia, S Farley, R Cheng, S Geddes, DM Caplen, NJ Alton, EWFW TI Gene silencing through RNA interference as putative therapy for CF SO THORAX LA English DT Meeting Abstract CT Winter Meeting of the British-Thoracic-Society CY DEC 04-06, 2002 CL LONDON, ENGLAND SP British Thorac Soc C1 Univ London Imperial Coll Sci Technol & Med, Fac Med, Natl Heart & Lung Inst, Dept Gene Therapy, London, England. Genzyme Corp, Framingham, MA 01701 USA. NHGRI, NIH, Med Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD DEC PY 2002 VL 57 SU 3 MA P124 PG 1 WC Respiratory System SC Respiratory System GA 624PM UT WOS:000179768600288 ER PT J AU Lorand, L Velasco, PT Hill, JM Hoffmeister, KJ Kaye, FJ AF Lorand, L Velasco, PT Hill, JM Hoffmeister, KJ Kaye, FJ TI Intracranial hemorrhage in systemic lupus erythematosus associated with an autoantibody against factor XIII SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE lupus; factor XIII autoantibody ID ANTICOAGULANT-HYPOPROTHROMBINEMIA SYNDROME; FIBRIN-STABILIZING FACTOR; FACTOR-VIII INHIBITOR; ANTIPHOSPHOLIPID SYNDROME; PATIENT; ANTIBODIES; PROTHROMBIN; ACTIVATION; DEFICIENCY; THERAPY AB Intracranial hemorrhage in a young woman with systemic lupus erythematosus necessitated two surgical evacuations. In the absence of a family history of bleeding, clot solubility in urea suggested a factor XIII (FXIII) inhibitor. The patient's IgG bound well to the virgin and the thrombin-modified zymogen ensemble (A(2)B(2) and A(2)'B-2) and to the free rA(2) but reacted poorly with the thrombin-modified rA(2)'. Since the IgG did not block the thrombin-catalyzed proteolysis of A subunits nor the dissociation of the A(2)'B-2, its action might be to interfere with the release of activation peptides from the thrombin-cleaved zymogen, hindering the conformational change necessary for generating FXIIIa. Treatment with cryoprecipitate and cyclophosphamide arrested the hemorrhage and almost neutralized the antibody so that the patient's clot became insoluble in urea and showed a. close to normally crosslinked gamma-gamma and alpha(n) fibrin chain profile. Nevertheless, she still has detectable anti-FXIII antibody and may be at risk for hemorrhage. C1 Northwestern Univ, Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA. Natl Naval Med Res Inst, Dept Hematol & Med Oncol, Bethesda, MD USA. NCI, Ctr Canc Res, NIH, Natl Naval Med Ctr, Bethesda, MD 20892 USA. RP Lorand, L (reprint author), Northwestern Univ, Sch Med, Dept Cell & Mol Biol, Searle 4-555,303 E Chicago Ave, Chicago, IL 60611 USA. EM l-lorand@northwestern.edu RI kaye, frederic/E-2437-2011 FU NHLBI NIH HHS [HL-16346] NR 36 TC 18 Z9 22 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD DEC PY 2002 VL 88 IS 6 BP 919 EP 923 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 630FD UT WOS:000180096100007 PM 12529739 ER PT J AU Cunningham, ML AF Cunningham, ML TI A mouse is not a rat is not a human: Species differences exist SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material C1 NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. RP Cunningham, ML (reprint author), NIEHS, Natl Toxicol Program, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 10 TC 18 Z9 19 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2002 VL 70 IS 2 BP 157 EP 158 DI 10.1093/toxsci/70.2.157 PG 2 WC Toxicology SC Toxicology GA 621XB UT WOS:000179615300001 PM 12441359 ER PT J AU Huff, J AF Huff, J TI Carcinogenicity of bisphenol A revisited SO TOXICOLOGICAL SCIENCES LA English DT Letter ID CANCER C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 14 TC 11 Z9 11 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2002 VL 70 IS 2 BP 281 EP 283 DI 10.1093/toxsci/70.2.281 PG 3 WC Toxicology SC Toxicology GA 621XB UT WOS:000179615300015 PM 12441373 ER PT J AU Wu, GG Su, YQ Yu, Q Jin, SZ Zhao, TM AF Wu, GG Su, YQ Yu, Q Jin, SZ Zhao, TM TI Development of a DNA-based genotyping method for the Diego blood group system SO TRANSFUSION LA English DT Article ID CELL SURFACE-ANTIGENS; ISBT WORKING PARTY; TERMINOLOGY; BAND-3 AB BACKGROUND: The paucity of appropriate reagents for serologic typing of the Diego blood group has hindered the identification of the rare Di(b-) blood donors needed to transfuse a Di(b) antigen-negative patient who presented with anti-Di(b). Development of an alternative Di typing approach as a supplement to the current serologic typing method is an important and necessary goal. STUDY DESIGN AND METHODS: DI1 and DI2 alleles result from a single C to T substitution at nucleotide 2561 in exon 19 of the human anion exchanger gene causing a proline (DI1) to leucine (DI2) change at amino acid position 854. Allele-specific primers were designed to specifically amplify the DI1 and DI2 alleles using a PCR-based assay system. RESULTS: A PCR sequence-specific primer (SSP) method for Di genotyping was developed, and the specificity and reproducibility of the method were assessed in a blind control study using serologic tests, family segregation, and DNA sequencing analyses. A total of 1766 DNA samples from unrelated blood donors were typed for DI1 and DI2 alleles and a single Di(b-) donor was identified. The frequency of DI1 and DI2 alleles among Chinese blood donors was 0.0357 and 0.9643, respectively. CONCLUSION: A simple, accurate, and inexpensive DNA-based PCR-SSP method was established for Di genotyping. The typing results can be visualized on a single photograph within 3 hours, making this reliable method suitable for large-scale typing of potential blood donors without serologic backup. C1 Shen Zhen Inst Transfus Med, Shen Zhen 518035, Peoples R China. NIH, Bethesda, MD 20892 USA. RP Wu, GG (reprint author), Shen Zhen Inst Transfus Med, Ni Gang Xi Rd,Mei Gang Nan St, Shen Zhen 518035, Peoples R China. NR 12 TC 9 Z9 12 U1 0 U2 3 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2002 VL 42 IS 12 BP 1553 EP 1556 DI 10.1046/j.1537-2995.2002.00248.x PG 4 WC Hematology SC Hematology GA 626TF UT WOS:000179888700006 PM 12473133 ER PT J AU Haddad, SA Winer, KK Gupta, A Chakrabarti, S Noel, P Klein, HG AF Haddad, SA Winer, KK Gupta, A Chakrabarti, S Noel, P Klein, HG TI A puzzling case of anemia SO TRANSFUSION LA English DT Article AB BACKGROUND: Iron deficiency anemia in adults is most frequently due to chronic blood loss. When the clinical course is complicated by sudden, severe declines in Hb concentration, the cause, nature, and location of bleeding may require an extensive clinical evaluation. CASE REPORT: A 39-year-old woman was admitted for management of refractory hypoparathyroidism related to total thyroidectomy for Graves' disease. Two weeks before admission, her Hb level was 7.0 g per dL. Despite transfusion with four units of RBCs during this interval, her admission Hb level was 5.7 g per dL. There was no evidence of blood loss or hemolysis. Laboratory values were consistent with an iron-deficient state. The patient's hospital course included repeated instances of sharp Hb drop and appropriate but unsustained response to RBC transfusion. Extensive work-up identified no occult source of bleeding. Clinical suspicion raised the possibility of self-inflicted blood loss. The patient subsequently admitted to repeatedly drawing blood from her indwelling catheter and discarding it in the lavatory. CONCLUSION: Munchausen syndrome should be considered in cases of unexplained anemia, especially in the target demographic group: young, female, healthcare professionals. Early diagnosis may prevent morbidity, multiple hospitalizations, and the risk of invasive diagnostic procedures. C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Haddad, SA (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bldg 10,Room 1C 711, Bethesda, MD 20892 USA. NR 10 TC 3 Z9 4 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2002 VL 42 IS 12 BP 1610 EP 1613 DI 10.1046/j.1537-2995.2002.00269.x PG 4 WC Hematology SC Hematology GA 626TF UT WOS:000179888700016 PM 12473143 ER PT J AU Kavanaugh, CJ Desai, KV Calvo, A Brown, PH Couldrey, C Lubet, R Green, JE AF Kavanaugh, CJ Desai, KV Calvo, A Brown, PH Couldrey, C Lubet, R Green, JE TI Pre-clinical applications of transgenic mouse mammary cancer models SO TRANSGENIC RESEARCH LA English DT Review DE animal models; breast cancer; breast cancer classification; gene expression profiling; microarray ID HUMAN-BREAST-CANCER; GROWTH-FACTOR-ALPHA; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROTEIN TRANSFERASE INHIBITOR; ESTROGEN-RECEPTOR-ALPHA; TUMOR DEVELOPMENT; C-MYC; GLAND HYPERPLASIA; GENE-EXPRESSION; MICE BEARING AB Breast cancer is a leading cause of cancer morbidity and mortality. Given that the majority of human breast cancers appear to be due to non- genetic factors, identifying agents and mechanisms of prevention is key to lowering the incidence of cancer. Genetically engineered mouse models of mammary cancer have been important in elucidating molecular pathways and signaling events associated with the initiation, promotion, and the progression of cancer. Since several transgenic mammary models of human breast cancer progress through well- defined cancer stages, they are useful pre- clinical systems to test the efficacy of chemopreventive and chemotherapeutic agents. This review outlines several oncogenic pathways through which mammary cancer can be induced in transgenic models and describes several types of preventive and therapeutic agents that have been tested in transgenic models of mammary cancer. The effectiveness of farnesyl inhibitors, aromatase inhibitors, differentiating agents, polyamine inhibitors, anti- angiogenic inhibitors, and immunotherapeutic compounds including vaccines have been evaluated in reducing mammary cancer and tumor progression in transgenic models. C1 NCI, Lab Cellular Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Green, JE (reprint author), NCI, Lab Cellular Regulat & Carcinogenesis, Bldg 41, Bethesda, MD 20892 USA. NR 131 TC 10 Z9 11 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD DEC PY 2002 VL 11 IS 6 BP 617 EP 633 DI 10.1023/A:1021159705363 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 617RC UT WOS:000179373800011 PM 12509137 ER PT J AU Green, JE Cardiff, R Hennighausen, L Wakefield, L Wagner, U Lee, E Rosen, J Medina, D Nitkin, A Liu, E AF Green, JE Cardiff, R Hennighausen, L Wakefield, L Wagner, U Lee, E Rosen, J Medina, D Nitkin, A Liu, E TI Validation of transgenic mammary cancer models: goals of the NCI Mouse Models of Human Cancer Consortium and the mammary cancer CD-ROM SO TRANSGENIC RESEARCH LA English DT Editorial Material C1 NCI, Lab Cellular Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. Baylor Coll Med, Houston, TX 77030 USA. Cornell Univ, Sch Med, New York, NY 10021 USA. Genome Inst Singapore, Singapore, Singapore. RP Green, JE (reprint author), NCI, Lab Cellular Regulat & Carcinogenesis, Bldg 41, Bethesda, MD 20892 USA. RI Liu, Edison/C-4141-2008; Wagner, Ulrike/B-6039-2009 NR 0 TC 3 Z9 3 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD DEC PY 2002 VL 11 IS 6 BP 635 EP 636 DI 10.1023/A:1021140606271 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 617RC UT WOS:000179373800012 PM 12509138 ER PT J AU Sakurai, K Zou, JP Torres, NI Tschetter, JR Kim, HS Shearer, GM AF Sakurai, K Zou, JP Torres, NI Tschetter, JR Kim, HS Shearer, GM TI Study of the effect of indoleamine 2,3-dioxygenase on murine mixed lymphocyte reactions and skin allograft rejection SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID T-CELL PROLIFERATION; TRYPTOPHAN CATABOLISM; INTERFERON-GAMMA; IFN-GAMMA; HEART ALLOGRAFTS; INHIBITION; EXPRESSION; ACTIVATION; CHLAMYDIA; GROWTH C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Shearer, GM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Tschetter, Jolynne/0000-0003-1743-1221 NR 22 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 2002 VL 34 IS 8 BP 3271 EP 3273 AR PII S0041-1345(02)03560-1 DI 10.1016/S0041-1345(02)03560-1 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 628FW UT WOS:000179983100077 PM 12493443 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI Proteomic analysis at the bedside: early detection of cancer SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID LASER CAPTURE MICRODISSECTION; IMMOBILIZED PH GRADIENTS; OVARIAN-CANCER; 2-DIMENSIONAL ELECTROPHORESIS; PROTEIN BIOCHIP; PROSTATE; EXPRESSION; TECHNOLOGY; DISCOVERY; TISSUE AB Proteomic technologies promise to accelerate rapidly a new era in molecular medicine, especially in the detection and discovery of disease-related biomarkers. These technologies have no bigger impact than in the field of human cancer research. Beyond lifestyle-associated prevention strategies, early detection of cancer has the most profound impact on the ultimate course of the disease: the earlier the cancer is detected, the better the prognosis. Today, new proteomic technologies are being used to discover new diagnostic and prognostic biomarkers for the early detection and treatment of cancer that will have important implications at the bedside. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, FDA NCI Clin Prote Program, Bethesda, MD 20892 USA. NCI, CCr, Pathol Lab, FDA NCI Clin Prote Program,NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, FDA NCI Clin Prote Program, Bethesda, MD 20892 USA. NR 40 TC 5 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD DEC PY 2002 VL 20 IS 12 SU S BP S30 EP S34 AR PII S0167-7799(02)02092-9 DI 10.1016/S1471-1931(02)00204-5 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 617HT UT WOS:000179356800007 PM 12570157 ER PT J AU Driggers, PH Segars, JH AF Driggers, PH Segars, JH TI Estrogen action and cytoplasmic signaling pathways. Part II: the role of growth factors and phosphorylation in estrogen signaling SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID PROTEIN-KINASE-C; ELEMENT-BINDING PROTEIN; BREAST-CANCER CELLS; RECEPTOR-MEDIATED TRANSCRIPTION; LIGAND-INDEPENDENT ACTIVATION; PROGESTERONE-RECEPTOR; CROSS-TALK; CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE; SYNERGISTIC ACTIVATION; GENE-EXPRESSION AB In recent years, distinct signaling pathways involving specific complexes of cytoplasmic proteins have been shown to orchestrate estrogen action. These pathways might supplement or augment genomic effects of estrogen that are attributable to transcriptional activation by liganded receptor. Signals might be transduced through phosphorylation of the estrogen receptors (ERs), or indirectly through effects upon transcriptional coactivators or cell receptors. Estrogen signaling is coupled to growth factor signaling with feedback mechanisms directly impacting function of growth factor receptors. These signaling pathways regulate important physiological processes, such as cell growth and apoptosis. Here, we focus on cytoplasmic signaling pathways leading to activation of ERs. C1 Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. RP Driggers, PH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, 4301 JOnes Bridge Rd, Bethesda, MD 20814 USA. FU Intramural NIH HHS [Z99 HD999999] NR 72 TC 148 Z9 156 U1 0 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD DEC PY 2002 VL 13 IS 10 BP 422 EP 428 AR PII S1043-2760(02)00634-3 DI 10.1016/S1043-2760(02)00634-3 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 615GV UT WOS:000179238200004 PM 12431838 ER PT J AU Grammatopoulos, DK Chrousos, GP AF Grammatopoulos, DK Chrousos, GP TI Functional characteristics of CRH receptors and potential clinical applications of CRH-receptor antagonists SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; ACTIVATED PROTEIN-KINASE; MAST-CELL DEGRANULATION; PITUITARY-ADRENAL AXIS; HORMONE-RECEPTOR; TYPE-1 RECEPTOR; BINDING-PROTEIN; CRF2 RECEPTOR; HIGH-AFFINITY; UROTENSIN-I AB Corticotropin-releasing hormone (CRH) plays a major role in coordinating the behavioral, endocrine, autonomic and immune responses to stress. CRH and CRH-related peptides and their receptors are present in the central nervous system and in a wide variety of peripheral tissues, including the immune, cardiovascular and reproductive systems, and have been associated with the pathophysiology of many disease states. These observations have led to the development of several CRH receptor type-selective antagonists, which have been used experimentally to elucidate the role of CRH and related peptides in physiological and disease processes, such as anxiety and depression, sleep disorders, addictive behavior, inflammatory and allergic disorders, neurological diseases and pre-term labor. Because of the complex network of multiple CRH receptor subtypes and their tissue- and agonist-specific signaling diversity, antagonists need to be developed that can target specific CRH receptor isoform-driven signaling pathways. C1 Univ Warwick, Dept Biol Sci, Sir Quinton Hazell Mol Med Res Ctr, Coventry CV4 7AL, W Midlands, England. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Grammatopoulos, DK (reprint author), Univ Warwick, Dept Biol Sci, Sir Quinton Hazell Mol Med Res Ctr, Coventry CV4 7AL, W Midlands, England. OI grammatopoulos, dimitris/0000-0002-6296-8290 NR 84 TC 165 Z9 171 U1 0 U2 10 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD DEC PY 2002 VL 13 IS 10 BP 436 EP 444 AR PII S1043-2760(02)00670-7 DI 10.1016/S1043-2760(02)00670-7 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 615GV UT WOS:000179238200006 PM 12431840 ER PT J AU Sonnhammer, ELL Koonin, EV AF Sonnhammer, ELL Koonin, EV TI Orthology, paralogy and proposed classification for paralog subtypes SO TRENDS IN GENETICS LA English DT Letter C1 Karolinska Inst, Ctr Genom & Bioinformat, S-17177 Stockholm, Sweden. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Sonnhammer, ELL (reprint author), Karolinska Inst, Ctr Genom & Bioinformat, S-17177 Stockholm, Sweden. NR 12 TC 219 Z9 241 U1 1 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD DEC PY 2002 VL 18 IS 12 BP 619 EP 620 AR PII S0168-9525(02)02793-2 DI 10.1016/S0168-9525(02)02793-2 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 618TL UT WOS:000179433300008 PM 12446146 ER PT J AU Jan, MH Thomas, TL Hooper, TI AF Jan, MH Thomas, TL Hooper, TI TI Prescription medication, use aboard US submarines during periods underway. SO UNDERSEA & HYPERBARIC MEDICINE LA English DT Article DE submarine medicine; undersea medicine; submarine; undersea ID APPROPRIATENESS INDEX AB Jan MH, Thomas TL, Hooper TI, Prescription medication use aboard US submarines during periods underway. Undersea Hyperb Med 2002; 29(4): 294-306 - Since January 1997, automated medical records fom U.S. submarines have been stored in a centralized database as part of a descriptive epidemiology study. 200 medical encounter notes were randomly selected from 1,017 initial health visits during submarine underway periods between April 1996 and January 1998. Medication prescription appropriateness was assessed using a modified Medication Appropriateness Index (MAI) described in the literature. Seven diagnostic categories accounted for 51.4% of all diagnoses: acute upper respiratory infections (17.6%), superficial wounds (9.7%), elevated blood pressure without the diagnosis of hypertension (7.9%), sprain/strains (4.7%), skin infections (4.3%), eye disorders (3.6%), and ear disorders (3.6%). Prescribed medications were consistent with the care of minor health problems. Mean number of medications prescribed per encounter was 1.4 +/- 1.1 (S.D.). 84% of prescribed medications were assigned a modified MAI summary score of 0, indicating the prescription was appropriate in all aspects. However, anti-infective medication prescriptions demonstrated a significant proportion of non-zero summary scores suggesting some room for improvement in the prescribing practices for this specific medication category. C1 USN, Ctr Med, Med Corps, Portsmouth, VA 23701 USA. NCI, Radiat Epidemiol Branch, NIH, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. RP Jan, MH (reprint author), USN, Ctr Med, Med Corps, 620 John Paul Jones Circle, Portsmouth, VA 23701 USA. NR 11 TC 3 Z9 3 U1 0 U2 1 PU UNDERSEA & HYPERBARIC MEDICAL SOC INC PI KENSINGTON PA 10531 METROPOLITAN AVE, KENSINGTON, MD 20895 USA SN 1066-2936 J9 UNDERSEA HYPERBAR M JI Undersea Hyperb. Med. PD WIN PY 2002 VL 29 IS 4 BP 294 EP 306 PG 13 WC Marine & Freshwater Biology; Medicine, Research & Experimental SC Marine & Freshwater Biology; Research & Experimental Medicine GA 685CV UT WOS:000183244000011 PM 12797671 ER PT J AU Berndt, SI Carter, HB Landis, PK Tucker, KL Hsieh, LJ Metter, EJ Platz, EA AF Berndt, SI Carter, HB Landis, PK Tucker, KL Hsieh, LJ Metter, EJ Platz, EA TI Calcium intake and prostate cancer risk in a long-term aging study: The Baltimore Longitudinal Study of Aging SO UROLOGY LA English DT Article ID VITAMIN-D; DAIRY-PRODUCTS; UNITED-STATES; PHOSPHORUS; DIET; HYPOTHESIS; COHORT AB Objectives. To investigate the association between prostate cancer and calcium and other nutrients thought to influence the synthesis of 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. Methods. We included in the analysis 454 male participants in the Baltimore Longitudinal Study of Aging who were 46 to 92 years old at the time of completion of a food frequency questionnaire. Among them, 69 men were diagnosed with prostate cancer during their lifetime. In 68% of the cases, the food frequency questionnaire was completed after the diagnosis of cancer. Multiple logistic regression analysis was used to calculate the odds ratio and 95% confidence interval of prostate cancer. Results. The median calcium intake was 788 mg/day. The adjusted odds ratio of prostate cancer for the highest tertile compared with the lowest tertile of calcium intake was 0.92 (95% confidence interval 0.48 to 1.77; P-trend = 0.89). Likewise, no significant trends were found for phosphorus, vitamin D, fructose, or animal protein intake. Dairy products, including milk, were not associated with an increased risk of prostate cancer. The adjusted odds ratio of prostate cancer was 1.26 (95% confidence interval 0.57 to 2.79; P-trend = 0.73) for men with high dairy intakes compared with those with low dairy intakes. Conclusions. The results of this study suggest that calcium intake within moderate limits is not associated with a notably increased risk of prostate cancer. (C) 2002, Elsevier Science Inc. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NIA, Clin Invest Lab, Baltimore, MD 21224 USA. Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. RP Platz, EA (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. RI Tucker, Katherine/A-4545-2010; OI Tucker, Katherine/0000-0001-7640-662X FU NCI NIH HHS [T32-CA09312, CA58236] NR 30 TC 42 Z9 43 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD DEC PY 2002 VL 60 IS 6 BP 1118 EP 1123 AR PII S0090-4295(02)01991-X DI 10.1016/S0090-4295(02)01991-X PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 626TC UT WOS:000179888500039 PM 12475694 ER PT J AU Santos, N Volotao, EM Soares, CC Carolina, M Albuquerque, M da Silva, FM Chizhikov, V Hoshino, Y AF Santos, N Volotao, EM Soares, CC Carolina, M Albuquerque, M da Silva, FM Chizhikov, V Hoshino, Y TI VP7 gene polymorphism of serotype G9 rotavirus strains and its impact on G genotype determination by PCR SO VIRUS RESEARCH LA English DT Article DE rotavirus; PCR G genotyping; VP7 gene polymorphism; gastroenteritis ID POLYMERASE CHAIN-REACTION; GROUP-A ROTAVIRUS; MOLECULAR CHARACTERIZATION; REVERSE TRANSCRIPTION; ACUTE GASTROENTERITIS; VACCINE DEVELOPMENT; BRAZILIAN CHILDREN; UNITED-STATES; NUCLEIC-ACID; IDENTIFICATION AB Rotaviruses are the single most important etiologic agents of severe diarrhea of infants and young children worldwide. Surveillance of rotavirus serotypes/genotypes (both VP7[G] and VP4[P]) is in progress globally in which polymerase chain reaction (PCR) has been the assay of choice. We investigated polymorphism of the VP7 gene of serotype G9 rotavirus strains and its impact on the determination of VP7 gene genotype by PCR assay. By VP7 gene sequence analysis, we and others have previously shown that the G9 rotavirus strains belong to one of three VP7 gene lineages. By PCR assay using three different sets of commonly used primers specific for G1-4, 8 and 9, 23 Brazilian G9 strains and 5 well-characterized prototype G9 strains which collectively represented all three VP7 gene lineages were typed as: (i) G3; (ii) G4; (iii) G9; (iv) G3 and G9; or (v) G9 and G4 depending on a primer pool employed. This phenomenon appeared to be due to: (i) a VP7 gene lineage-specific polymorphism, more specifically mutation(s) in the primer binding region of the VP7 gene of G9 strain; and (ii) the magnitude of difference in nucleotide homology at respective primer binding site between homotypic (G9) and heterotypic (G3 or G4) primers present in a primer pool employed. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Fed Rio de Janeiro, Inst Microbiol, Dept Virol, Ilha Fdn, BR-21941590 Rio De Janeiro, Brazil. US FDA, Ctr Biol Evaluat & Res, Kensington, MD 20895 USA. NIH, Infect Dis Lab, Bethesda, MD 20892 USA. RP Santos, N (reprint author), Univ Fed Rio de Janeiro, Inst Microbiol, Dept Virol, Ilha Fdn, Cidade Univ,CCS Bl 1, BR-21941590 Rio De Janeiro, Brazil. RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 NR 61 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD DEC PY 2002 VL 90 IS 1-2 BP 1 EP 14 AR PII S0168-1702(02)00106-5 DI 10.1016/S0168-1702(02)00106-5 PG 14 WC Virology SC Virology GA 629QL UT WOS:000180060300001 PM 12457958 ER PT J AU Brooks, PJ AF Brooks, PJ TI DNA repair in neural cells: basic science and clinical implications SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE neurodegeneration; recombination; mismatch repair; oxidative damage; neurogenesis; oxytocin ID NIJMEGEN BREAKAGE SYNDROME; CENTRAL-NERVOUS-SYSTEM; TRANSCRIPTION-COUPLED REPAIR; ATAXIA-TELANGIECTASIA GENE; A XERODERMA-PIGMENTOSUM; NUCLEOTIDE EXCISION-REPAIR; ADULT MAMMALIAN BRAIN; DOUBLE-STRAND BREAKS; RNA-POLYMERASE-II; COCKAYNE-SYNDROME AB As one part of a distinguished scientific career, Dr. Bryn Bridges focused his attention on the issue of DNA damage and repair in stationary phase bacteria. His work in this area led to his interest in DNA repair and mutagenesis in another non-dividing cell population, the neurons in the mammalian nervous system. He has specifically taken an interest in the magnocellular neurons of the central nervous system, and the possibility that somatic mutations may be occurring in these neurons. As part of this special issue dedicated to Bryn Bridges upon his retirement, I will discuss the various DNA repair pathways known to be active in the nervous system. The importance of DNA repair to the nervous system is most graphically illustrated by the neurological abnormalities observed in patients with hereditary diseases associated with defects in DNA repair. I will consider the mechanisms underlying the neurological abnormalities observed in patients with four of these diseases: xeroderma pigmentosum (XP), Cockayne's syndrome (CS), ataxia telangectasia (AT) and AT-like disorder (ATLD). I will also propose a mechanism for one of the observations indicating that somatic mutation can occur in the magnocellular neurons of the aging rat brain. Finally, as a parallel to Bridges inquiry into how much DNA synthesis is going on in stationary phase bacteria, I will address the question of how much DNA synthesis in going on in neurons, and the implications of the answer to this question for recent studies of neurogenesis in adult mammals. Published by Elsevier Science B.V. C1 NIAAA, Neurogenet Lab, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Brooks, PJ (reprint author), NIAAA, Neurogenet Lab, Mol Neurobiol Sect, NIH, 12420 Parklawn Dr,MSC 8110, Bethesda, MD 20892 USA. NR 148 TC 65 Z9 65 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD NOV 30 PY 2002 VL 509 IS 1-2 BP 93 EP 108 AR PII S0027-5107(02)00222-1 DI 10.1016/S0027-5107(02)00222-1 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 618FD UT WOS:000179407300008 PM 12427533 ER PT J AU Mandavilli, BS Santos, JH Van Houten, B AF Mandavilli, BS Santos, JH Van Houten, B TI Mitochondrial DNA repair and aging SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE mitochondria; DNA damage; DNA repair; animal models; C. elegans; Drosophila; yeast ID BASE-EXCISION-REPAIR; NEMATODE CAENORHABDITIS-ELEGANS; AMYOTROPHIC-LATERAL-SCLEROSIS; ADENINE-NUCLEOTIDE TRANSLOCATOR; MANGANESE SUPEROXIDE-DISMUTASE; POLYMERASE-CHAIN-REACTION; PROTEIN OXIDATIVE DAMAGE; GENE-EXPRESSION PROFILE; MOTOR-NEURON DISEASE; COENZYME-Q SYNTHESIS AB The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell. Oxidative damage to the mitochondrial DNA is implicated in various degenerative diseases, cancer and aging. The importance of mitochondrial ROS in age-related degenerative diseases is further strengthened by studies using animal models, Caenorhabditis elegans, Drosophila and yeast. Research in the last several years shows that mitochondrial DNA is more susceptible to various carcinogens and ROS when compared to nuclear DNA. DNA damage in mammalian mitochondria is repaired by base excision repair (BER). Studies have shown that mitochondria contain all the enzymes required for BER. Mitochondrial DNA damage, if not repaired, leads to disruption of electron transport chain and production of more ROS. This vicious cycle of ROS production and mtDNA damage ultimately leads to energy depletion in the cell and apoptosis. Published by Elsevier Science B.V. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Van Houten, B (reprint author), NIEHS, Mol Genet Lab, NIH, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. NR 247 TC 212 Z9 221 U1 1 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD NOV 30 PY 2002 VL 509 IS 1-2 BP 127 EP 151 AR PII S0027-5107(02)00220-8 DI 10.1016/S0027-5107(02)00220-8 PG 25 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 618FD UT WOS:000179407300010 PM 12427535 ER PT J AU Qiao, YW Spitz, MR Guo, ZZ Hadeyati, M Grossman, L Kraemer, KH Wei, QY AF Qiao, YW Spitz, MR Guo, ZZ Hadeyati, M Grossman, L Kraemer, KH Wei, QY TI Rapid assessment of repair of ultraviolet DNA damage with a modified host-cell reactivation assay using a luciferase reporter gene and correlation with polymorphisms of DNA repair genes in normal human lymphocytes SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE host-cell reactivation; DNA repair; genetic susceptibility; genotype; molecular epidemiology ID XERODERMA-PIGMENTOSUM; CANCER PATIENTS; NECK-CANCER; SKIN-CANCER; CAPACITY; HEAD; RISK AB As DNA repair plays an important role in genetic susceptibility to cancer, assessment of the DNA repair phenotype is critical for molecular epidemiological studies of cancer. In this report, we compared use of the luciferase (luc) reporter gene in a host-cell reactivation (HCR) (LUC) assay of repair of ultraviolet (UV) damage to DNA to use of the chloramphenicol (cat) gene-based HCR (CAT) assay we used previously for case-control studies. We performed both the assays on cryopreserved lymphocytes from 102 healthy non-Hispanic white subjects. There was a close correlation between DNA repair capacity (DRC) as measured by the LUC and CAT assays. Although these two assays had similar variation, the LUC assay was faster and more sensitive. We also analyzed the relationship between DRC and the subjects' previously determined genotypes for four polymorphisms of two nucleotide-excision repair (NER) genes (in intron 9 of xeroderma pigmentosum (XP) C and exons 6, 10 and 23 of XPD) and one polymorphism of a base-excision repair gene in exon 10 of X-ray complementing group 1 (XRCC1). The DRC was significantly lower in subjects homozygous for one or more polymorphisms of the two NER genes than in subjects with other genotypes (P = 0.010). In contrast, the polymorphic XRCC1 allele had no significant effect on DRC. These results suggest that the post-UV LUC assay measures NER phenotype and that polymorphisms of XPC and XPD genes modulate DRC. For population studies of the DNA repair phenotype, many samples need to be evaluated, and so the LUC assay has several advantages over the CAT assay: the LUC assay was more sensitive, had less variation, was not radioactive, was easier to perform, and required fewer cryopreserved cells. These features make the LUC-based HCR assay suitable for molecular epidemiological studies. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem, Baltimore, MD 21205 USA. NCI, Basic Res Lab, Bethesda, MD 20892 USA. RP Wei, QY (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, 1515 Holcombe Blvd,Box 189, Houston, TX 77030 USA. FU Intramural NIH HHS [Z01 BC004517-31]; NCI NIH HHS [CA 16672, R01 CA100264, R29 CA070334, CA 70334]; NIEHS NIH HHS [ES11740]; NIGMS NIH HHS [GM 22846] NR 17 TC 125 Z9 130 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD NOV 30 PY 2002 VL 509 IS 1-2 BP 165 EP 174 AR PII S0027-5107(02)00219-1 DI 10.1016/S0027-5107(02)00219-1 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 618FD UT WOS:000179407300012 PM 12427537 ER PT J AU Mientus, S Gallinat, J Wuebben, Y Pascual-Marqui, RD Mulert, C Frick, K Dorn, H Herrmann, WM Winterer, G AF Mientus, S Gallinat, J Wuebben, Y Pascual-Marqui, RD Mulert, C Frick, K Dorn, H Herrmann, WM Winterer, G TI Cortical hypoactivation during resting EEG in schizophrenics but not in depressives and schizotypal subjects as revealed by low resolution electromagnetic tomography (LORETA) SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE schizophrenia; schizotypal personality; depression; hypofrontality; EEG; LORETA ID CEREBRAL BLOOD-FLOW; CONTINGENT NEGATIVE-VARIATION; POSITRON EMISSION TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; BRAIN GLUCOSE-METABOLISM; TO-NOISE RATIO; COGNITIVE ACTIVATION; NEUROLEPTIC-NAIVE; SPECTRAL-ANALYSIS; MAJOR DEPRESSION AB This study was performed in order to address the question whether the newly introduced technique of low-resolution electromagnetic tomography (LORETA) is able to detect hypofrontality in schizophrenic patients. We investigated resting EEGs of 19 unmedicated schizophrenics and 20 normal subjects. For comparison, we also investigated 19 subjects with schizotypal personality and 30 unmedicated depressive patients. A significant increase of delta activity was found in schizophrenic patients over the whole cortex, most strongly in the anterior cingulate gyrus and temporal lobe (fusiform gyrus). Both schizotypal subjects and depressive subjects showed significantly less delta, theta and beta activity in the anterior cingulum, a decrease of alphal activity in the right temporal lobe and a decrease of alpha2 activity in the left temporal lobe. The results suggest general cortical hypoactivation, most pronounced in the anterior cingulate and temporal lobe in schizophrenics, whereas there is evidence for a complex, frequency-dependent spatial pattern of hyperactivation in schizotypal subjects and depressive patients. The results are discussed within a neurophysiological and methodological framework. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Free Univ Berlin, Dept Psychiat, D-14050 Berlin, Germany. Univ Hosp Psychiat Zurich, KEY Inst Brain Mind Res, Zurich, Switzerland. NIMH, NIH, Bethesda, MD 20892 USA. RP Gallinat, J (reprint author), Free Univ Berlin, Dept Psychiat, Eschenallee 3, D-14050 Berlin, Germany. RI Mulert, Christoph/F-2576-2012; Pascual-Marqui, Roberto/A-2012-2008 OI Pascual-Marqui, Roberto/0000-0002-5029-4065 NR 80 TC 54 Z9 56 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD NOV 30 PY 2002 VL 116 IS 1-2 BP 95 EP 111 AR PII S0925-4927(02)00043-4 DI 10.1016/S0925-4927(02)00043-4 PG 17 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 621QT UT WOS:000179601500008 PM 12426037 ER PT J AU Follmann, DA AF Follmann, DA TI Regression analysis based on pairwise ordering of patients' clinical histories SO STATISTICS IN MEDICINE LA English DT Article DE clinical trials; subjective rankings; logistic regression; pairwise ordering regression; utility ID MULTIPLE END-POINTS; SUBJECTIVE RANKINGS; TRIALS; ENDPOINTS; OUTCOMES; EXAMPLE; MODELS AB When a medical treatment influences a variety of outcomes, describing the global effect of treatment can be difficult. Traditional approaches specify how treatment affects each separate outcome. This can be done with separate models for each outcome, or by using a combined multivariate model. Describing the overall effect of a treatment thus requires combining these separate effects in some fashion and can be difficult to explain. In this paper, I specify a regression model for use with multiple outcomes where the outcome histories for each pair of patients are ranked. Pairs of patients with different lengths of follow-up are evaluated solely over the common follow-up interval. The logit of the probability that the outcome for patient i is better than that of patient j is assumed to depend on a linear function of the difference of the covariate vectors (for example, treatment indicators) for persons i and j. Thus covariates directly affect the entire clinical history, rather than directly affecting specific outcomes that comprise the history. The idea is that ranking outcomes is more relevant and interpretable than statistically combining separate effects. An estimating equations approach for estimation is described and an example of a clinical trial involving patients with heart failure is provided. Published in 2002 by John Wiley Sons, Ltd. C1 NHLBI, Off Biostat Res, Rockledge Ctr 2, Bethesda, MD 20892 USA. RP Follmann, DA (reprint author), NHLBI, Off Biostat Res, Rockledge Ctr 2, Bethesda, MD 20892 USA. NR 20 TC 5 Z9 5 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 30 PY 2002 VL 21 IS 22 BP 3353 EP 3367 DI 10.1002/sim.1272 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 610KQ UT WOS:000178959600004 PM 12407677 ER PT J AU Pfeiffer, RM Bura, E Smith, A Rutter, JL AF Pfeiffer, RM Bura, E Smith, A Rutter, JL TI Two approaches to mutation detection based on functional data SO STATISTICS IN MEDICINE LA English DT Article DE classification; mode; non-linear regression; superpopulation model; bootstrap ID CURVES; MISMATCHES; REGRESSION; DHPLC; DNA AB A new technique, denaturing high-performance liquid chromatography (dHPLC), allows for detection of any heterozygous sequence variation in a gene without prior knowledge of the precise location of the sequence change. The results of a dHPLC analysis are recorded in real-time in the form of a chromatogram that is sequence-specific. In this paper we present methods to classify an individual, based on the observed chromatogram, as a homozygous wild-type or a carrier of a specific variant for the given DNA segment by comparison to representative chromatograms that are obtained from the training set of individuals with known variant status. The first approach consists of finding a parsimonious parametric model and then classifying each newly observed curve based on comparing the most discriminating characteristic, the main mode, to the main mode of the training curves. The second approach consists of finding empirical estimates of the modes of each chromatogram and using a bootstrap test for equality with the corresponding estimates of the training curves. We apply both methods to data on the breast cancer susceptibility gene BRCAl and test the performance of the methods on independent samples. Published in 2002 by John Wiley Sons, Ltd. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. George Washington Univ, Dept Stat, Washington, DC 20052 USA. RP Pfeiffer, RM (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8030, Bethesda, MD 20892 USA. RI Pfeiffer, Ruth /F-4748-2011; OI Rutter, Joni/0000-0002-6502-2361 NR 13 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 30 PY 2002 VL 21 IS 22 BP 3447 EP 3464 DI 10.1002/sim.1269 PG 18 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 610KQ UT WOS:000178959600010 PM 12407683 ER PT J AU Borlongan, CV Emerich, DF Hoffer, BJ Bartus, RT AF Borlongan, CV Emerich, DF Hoffer, BJ Bartus, RT TI Bradykinin receptor agonist facilitates low-dose Cyclosporine-A protection against 6-hydroxydopamine neurotoxicity SO BRAIN RESEARCH LA English DT Article DE neuroprotection; Parkinson's disease; immunosuppression; calcineurin; striatum; substantia nigra ID BLOOD-BRAIN-BARRIER; DEVELOPING DOPAMINE NEURONS; PARKINSONS-DISEASE; CEREPORT(TM) RMP-7; CELL-DEATH; IMMUNOPHILIN LIGANDS; NEUROTROPHIC ACTIONS; IN-VIVO; RATS; SURVIVAL AB Cyclosporine-A (CsA) is neuroprotective in animal models of Parkinson's disease (PD), Huntington's disease and stroke. Because CsA does not easily cross the blood-brain barrier (BBB), high doses (i.e. >10 mg/kg in rats) and chronic administration may be necessary to produce beneficial effects. However, immumosuppressant side effects (including nephrotoxicity and hepatotoxicity) are associated with such CsA dosing regimens. The bradykinin B2 receptor agonist, Cereport(R) (labradimil and formerly called RMP-7), transiently increases the permeability of the BBB to facilitate delivery of drugs to the CNS. Here we examined the effects of co-administration of CsA and Cereport in the unilateral 6-OHDA model of PD. Animals were pretreated with vehicle, CsA alone (1 mg/kg, a low dose without either immunosuppressive or neuroprotective effects, or 10 mg/kg, a high dose that produces both immunosuppression and neuroprotection), or CsA (1 mg/kg) in combination with Cereport (9 mug/kg). Behavioral analyses, using elevated body swing and amphetamine-induced rotational tests, revealed that a low dose of CsA was neuroprotective when combined with Cereport, but not when given alone. Tyrosine hydroxylase immunohistochemistry demonstrated that while near complete (>90%) depletions of nigral TH-ir neurons were noted in lesioned animals that received vehicle infusion or low-dose CsA alone, lesioned animals that received low-dose CsA+Cereport exhibited a significant sparing of nigral TH-ir neurons and a marked reduction in the loss of striatal TH-ir fibers. The safer and effective administration of lower doses of CsA combined with enhanced BBB permeability using Cereport, offers a novel way of producing protective effects in the CNS without the toxic liabilities of high-dose CsA. Published by Elsevier Science B.V. C1 NIDA, Cellular Neurobiol Branch, IRP, NIH, Baltimore, MD 21224 USA. Alkermes Inc, Life Sci R&D, Cambridge, MA 02139 USA. RP Hoffer, BJ (reprint author), NIDA, Cellular Neurobiol Branch, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Borlongan, Cesar/0000-0002-2966-9782 NR 48 TC 25 Z9 25 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 NOV 29 PY 2002 VL 956 IS 2 BP 211 EP 220 AR PII S0006-8993(02)03474-1 DI 10.1016/S0006-8993(02)03474-1 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 621ZH UT WOS:000179621000004 PM 12445688 ER PT J AU Liao, XM Poirot, E Chang, AHC Zhang, XD Zhang, JA Nato, F Fournier, JM Kovac, P Glaudemans, CPJ AF Liao, XM Poirot, E Chang, AHC Zhang, XD Zhang, JA Nato, F Fournier, JM Kovac, P Glaudemans, CPJ TI The binding of synthetic analogs of the upstream, terminal residue of the O-polysaccharides (O-PS) of Vibrio cholerae O : 1 serotypes Ogawa and Inaba to two murine monoclonal antibodies (MAbs) specific for the Ogawa lipopolysaccharide (LPS) SO CARBOHYDRATE RESEARCH LA English DT Article ID ANTIGENIC DETERMINANTS; SUBSITES; HOMOPOLYMER; CHAIN; O76 AB The binding of nineteen analogues of the upstream, terminal, monosaccharide residue of each of the O-polysaccharide (O-PS) of Vibrio, cholerae O:1, serotype Ogawa and Inaba, with two murine monoclonal IgG antibodies both specific for the Ogawa LPS were measured using fluorescence spectroscopy. The use of the deoxy and the deoxyfluoro analogs allowed further refinement of the hydrogen-bonding pattern involved in the binding. Based on the binding characteristics observed for some of the ligands in the Inaba series, the binding of the monosaccharide that represents the upstream, terminal unit of the O-PS of V. cholerae O:1 serotype Inaba was redefined. We show for the first time that the upstream, terminal monosaccharide of the Inaba O-PS shows weak binding with these two anti-Ogawa antibodies. The results obtained allow further rationalization of the structural basis for the binding of V. cholerae O:1 antigens to their homologous antibodies. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NIDDK, Lab Med Chem, NIH, Bethesda, MD 20892 USA. Ctr Natl Ref Vibr & Cholera, Unite Cholera & Vibr, F-75724 Paris 15, France. Inst Pasteur, Lab Ingn Anticorps, F-75724 Paris 15, France. RP Glaudemans, CPJ (reprint author), NIDDK, Lab Med Chem, NIH, Bethesda, MD 20892 USA. NR 20 TC 14 Z9 15 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD NOV 29 PY 2002 VL 337 IS 24 BP 2437 EP 2442 AR PII S0008-6215(02)00278-1 DI 10.1016/S0008-6215(02)00278-1 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 623DW UT WOS:000179688900008 PM 12493228 ER PT J AU Lavine, N Ethier, N Oak, JN Pei, L Liu, F Trieu, P Rebois, RV Bouvier, M Hebert, TE Van Tol, HHM AF Lavine, N Ethier, N Oak, JN Pei, L Liu, F Trieu, P Rebois, RV Bouvier, M Hebert, TE Van Tol, HHM TI G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HETEROTRIMERIC G-PROTEINS; BETA-GAMMA-SUBUNITS; BETA(2)-ADRENERGIC RECEPTOR; SIGNALING COMPLEXES; XENOPUS OOCYTES; K+ CHANNELS; KINASE; TRAFFICKING; ACTIVATION; MEMBRANES AB A large number of studies have demonstrated co-purification or co-immunoprecipitation of receptors with G proteins. We have begun to look for the presence of effector molecules in these receptor complexes. Co-expression of different channel and receptor permutations in COS-7 and HEK 293 cells in combination with co-immunoprecipitation experiments established that the dopamine D-2 and D-4, and beta(2)-adrenergic receptors (beta(2)-AR) form stable complexes with Kir3 channels. The D-4/ Kir3 and D-2 receptor/Kir3 interaction does not occur when the channel and receptor are expressed separately and mixed prior to immunoprecipitation, indicating that the interaction is not an artifact of the experimental protocol and reflects a biosynthetic event. The observed complexes are stable in that they are not disrupted by receptor activation or modulation of G protein a subunit function. However, using a peptide that binds Gbetagamma (betaARKct), we show that Gbetagamma is critical for dopamine receptor-Kir3 complex formation, but not for maintenance of the complex. We also provide evidence that Kir3 channels and another effector, adenylyl cyclase, are stably associated with the beta(2)-adrenergic receptor and can be co-immunoprecipitated by anti-receptor antibodies. Using bioluminescence resonance energy transfer, we have shown that in living cells under physiological conditions, beta(2)AR interacts directly with Kir3.1/3.4 and Kir3.1/3.2c heterotetramers as well as with adenylyl cyclase. All of these interactions are stable in the presence of receptor agonists, suggesting that these signaling complexes persist during signal transduction. In addition, we provide evidence that the receptor-effector complexes are also found in vivo. The observation that several G protein-coupled receptors form stable complexes with their effectors suggests that this arrangement might be a general feature of G protein-coupled signal transduction. C1 Univ Toronto, Ctr Addict & Mental Hlth, Mol Neurobiol Lab, Dept Pharmacol, Toronto, ON M5T 1R8, Canada. Univ Toronto, Inst Med Sci, Dept Psychiat, Toronto, ON M5T 1R8, Canada. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. NINDS, NIH, Bethesda, MD 20892 USA. Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada. RP Van Tol, HHM (reprint author), Univ Toronto, Ctr Addict & Mental Hlth, Mol Neurobiol Lab, Dept Pharmacol, 250 Coll St, Toronto, ON M5T 1R8, Canada. RI Bouvier, Michel/H-2758-2014 OI Bouvier, Michel/0000-0003-1128-0100 NR 41 TC 133 Z9 135 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 29 PY 2002 VL 277 IS 48 BP 46010 EP 46019 DI 10.1074/jbc.M205035200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 620JB UT WOS:000179529300041 PM 12297500 ER PT J AU Zhang, L Hosoi, M Fukuzawa, M Sun, H Rawlings, RR Weight, FF AF Zhang, L Hosoi, M Fukuzawa, M Sun, H Rawlings, RR Weight, FF TI Distinct molecular basis for differential sensitivity of the serotonin type 3A receptor to ethanol in the absence and presence of agonist SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NCB-20 NEUROBLASTOMA-CELLS; MEDIATED ION CURRENT; 5-HT3 RECEPTORS; FUNCTIONAL EXPRESSION; ALCOHOLS POTENTIATE; PROTEIN; SUBUNIT; CHANNEL; RELEASE; NEURONS AB Ethanol can potentiate serotonin type 3 (5-HT3) receptor-mediated responses in various neurons and in cells expressing 5-HT3A receptors. However, the molecular basis for alcohol modulation of 5-HT3 receptor function has not been determined. Here we report that point mutations of the arginine at amino acid 222 in the N-terminal domain of the 5-HT3A receptor can alter the EC50 value of the 5-HT concentration-response curve. Some point mutations at amino acid 222 resulted in spontaneous opening of the 5-HT3A receptor channel and an inward current activated by ethanol in the absence of agonist. Among these mutant receptors, the amplitude of the current activated by ethanol in the absence of agonist was correlated with the amplitude of the current resulting from spontaneous channel openings, suggesting that the sensitivity of the receptor to ethanol in the absence of agonist is, at least in part, dependent on the preexisting conformational equilibrium of the receptor protein. On the other hand, point mutations that conferred greater sensitivity to ethanol potentiation of agonist-activated responses were less sensitive or insensitive to ethanol in the absence of agonist. For these receptors, the magnitude of the potentiation of agonist-activated responses by ethanol was inversely correlated with the EC50 values of the 5-HT concentration-response curves, suggesting that these mutations may modulate ethanol sensitivity of the receptor by altering the EC50 value of the receptor. Thus, distinct molecular processes may determine the sensitivity of 5-HT3A receptors to ethanol in the absence and presence of agonist. C1 NIAAA, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NIAAA, Clin Sci Lab, Bethesda, MD 20892 USA. RP Zhang, L (reprint author), NIAAA, Mol & Cellular Neurobiol Lab, NIH, Pk Bldg,Rm 150, Bethesda, MD 20892 USA. NR 41 TC 17 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 29 PY 2002 VL 277 IS 48 BP 46256 EP 46264 DI 10.1074/jbc.M207683200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 620JB UT WOS:000179529300074 PM 12368287 ER PT J AU Desai, A Turetsky, D Vasudevan, K Buonanno, A AF Desai, A Turetsky, D Vasudevan, K Buonanno, A TI Analysis of transcriptional regulatory sequences of the N-methyl-D-aspartate receptor 2A subunit gene in cultured cortical neurons and transgenic mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESTRICTIVE SILENCER FACTOR; HETEROMERIC NMDA RECEPTORS; EXCITATORY AMINO-ACIDS; RNAS ENCODING SUBUNITS; CENTRAL-NERVOUS-SYSTEM; SODIUM-CHANNEL GENE; SPINAL-CORD NEURONS; MESSENGER-RNAS; RAT-BRAIN; DEVELOPMENTAL-CHANGES AB The postnatal appearance and up-regulation of the NR2A subunit of the N-methyl-D-aspartate receptor contributes to the functional heterogeneity of the receptor during development. To elucidate the molecular mechanisms that regulate the neural and developmental specific expression of NR2A, an upstream similar to9-kb region of the gene harboring the promoter was isolated and characterized in transgenic mice and transfected cortical neurons. Transgenic mouse lines generated with luciferase reporter constructs driven by either 9 or 1 kb of upstream sequence selectively transcribe the transgene in brain, as compared with other non-neural tissues. Reporter luciferase levels in dissociated cultures made from these mice are over 100-fold greater in neuronal/glial co-cultures than in pure glial cultures. Analysis of NR2A 5'-nested deletions in transfected cultures of cortical neurons and glia indicate that while sequences residing upstream of - 1079 bp augment NR2A neuronal expression, sequences between -486 and -447 bp are sufficient to maintain neuronal preference. An RE1/NRSE element is not necessary for NR2A neuron specificity. Furthermore, comparison of the 5'-deletion constructs in cortical neurons grown for 5, 8, 11, or 14 days in vitro indicate that sequences between -1253 and -1180 bp are necessary for maturational up-regulation of NR2A. Thus, different cis-acting sequences control the regional and temporal expression of NR2A, implicating distinct regulatory pathways. C1 NICHD, LDN, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Buonanno, A (reprint author), NICHD, LDN, Mol Neurobiol Sect, NIH, Bldg 49,Rm 5A38,49 Convent Dr, Bethesda, MD 20892 USA. NR 78 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 29 PY 2002 VL 277 IS 48 BP 46374 EP 46384 DI 10.1074/jbc.M203032200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 620JB UT WOS:000179529300088 PM 12356765 ER PT J AU Hu, AH Wang, F Sellers, JR AF Hu, AH Wang, F Sellers, JR TI Mutations in human nonmuscle myosin IIA found in patients with May-Hegglin anomaly and Fechtner syndrome result in impaired enzymatic function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE MYOSIN; HEAVY-CHAINS; LIGHT-CHAIN; IN-VITRO; STATE; ACTIN; EXPRESSION; FRAGMENTS; PLATELET; COMPLEX AB A family of autosomal-dominant diseases including May-Hegglin anomaly, Fechtner syndrome, Sebastian syndrome, Alport syndrome, and Epstein syndrome are commonly characterized by giant platelets and thrombocytopenia. In addition, there may be leukocyte inclusions, deafness, cataracts, and nephritis, depending on the syndrome. Mutations in the human nonmuscle myosin IIA heavy chain gene (WYH9) have been linked to these diseases. Two of the recently described mutations, N93K and R702C, are conserved in smooth and nonmuscle myosins from vertebrates and lie in the head domain of myosin. Interestingly, the two mutations lie within close proximity in the three-dimensional structure of myosin. These two mutations were engineered into a heavy meromyosin-like recombinant fragment of nonmuscle myosin IIA which was expressed in baculovirus along with the appropriate light chains. The R702C mutant displays 25% of the maximal MgATPase activity of wild type heavy meromyosin and moves actin filaments at half the wild type rate. The effects of the N93K mutation are more dramatic. This heavy meromyosin has only 4% of the maximal MgATPase activity of wild type and does not translocate actin filaments in an in vitro motility assay. Biochemical characterization of the mutant is consistent with this mutant being unable to fully adopt the "on" conformation. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Sellers, JR (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Rm 8N202, Bethesda, MD 20892 USA. NR 30 TC 54 Z9 62 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 29 PY 2002 VL 277 IS 48 BP 46512 EP 46517 DI 10.1074/jbc.M208506200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 620JB UT WOS:000179529300105 PM 12237319 ER PT J AU Hu, JX Reyes-Cruz, G Chen, WZ Jacobson, KA Spiegel, AM AF Hu, JX Reyes-Cruz, G Chen, WZ Jacobson, KA Spiegel, AM TI Identification of acidic residues in the extracellular loops of the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+ and a positive allosteric modulator SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCIUM-SENSING RECEPTOR; CELL-SURFACE EXPRESSION; CA2+-SENSING RECEPTOR; SIGNAL-TRANSDUCTION; ACTIVATING MUTATIONS; CHIMERIC RECEPTORS; ACID(B) RECEPTORS; TERMINAL DOMAIN; BINDING; ANTAGONIST AB We investigated the role of the eight acidic residues in the extracellular loops (exo-loops) of the seven-transmembrane domain of the human Ca2+ receptor (hCaR) in receptor activation by Ca2+ and in response to a positive allosteric modulator, NPS R-568. Both in the context of the full-length receptor and of a truncated receptor lacking the extracellular domain (Rho-C-hCaR), we mutated each acidic residue to. alanine, singly and in combination, and tested the effect on expression of the receptor, on activation by Ca2+, and on NPS R-568 augmentation of sensitivity to Ca2+. Of the eight acidic residues, mutation of any of three in exo-loop 2, Asp(758), Glu(759), and Glu(767), increased the sensitivity of both the full-length hCaR and of Rho-C-hCaR to activation by Ca2+. Mutation of all five acidic residues in exo-loop 2, whether in the full-length receptor or in Rho-C-hCaR, impaired cell surface expression of the mutant receptor and thereby largely abolished response to Ca2+. Mutation of Glu(837) in exo-loop 3 to alanine did not alter Ca2+ sensitivity of the full-length receptor, but in both the latter context and in Rho-C-hCaR, alanine substitution of Glu(837) drastically reduced sensitivity to NPS R-568. Our data point to a key role of three specific acidic residues in exo-loop 2 in Wall activation and to Glu(837) at the junction between exo-loop 3 and transmembrane helix seven in response to NPS R-568. We speculate on the basis of these results that the three acidic residues we identified in exo-loop 2 help maintain an inactive conformation of the seven-transmembrane domain of the hCaR. C1 NIDCD, Mol Pathophysiol Sect, NIH, Bethesda, MD 20892 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Hu, JX (reprint author), NIDCD, Mol Pathophysiol Sect, NIH, Bldg 10,Rm 8C-101,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031126-01, Z99 DK999999] NR 31 TC 61 Z9 64 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 29 PY 2002 VL 277 IS 48 BP 46622 EP 46631 DI 10.1074/jbc.M207100200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 620JB UT WOS:000179529300119 PM 12297503 ER PT J AU Guo, FS Maurizi, MR Esser, L Xia, D AF Guo, FS Maurizi, MR Esser, L Xia, D TI Crystal structure of ClpA, an Hsp100 chaperone and regulator of ClpAP protease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ATP-DEPENDENT PROTEOLYSIS; SENSITIVE FUSION PROTEIN; DNA-POLYMERASE-III; ESCHERICHIA-COLI; CONFORMATIONAL-CHANGES; MIGRATION MOTOR; BINDING SITES; COMPLEX; TRANSPORT; DOMAIN AB Escherichia coli ClpA, an Hsp100/Clp chaperone and an integral component of the ATP-dependent ClpAP protease, participates in regulatory protein degradation and the dissolution and degradation of protein aggregates. The crystal structure of the ClpA subunit reveals an N-terminal domain with pseudo-twofold symmetry and two AAA(+) modules (D1 and D2) each consisting of a large and a small sub-domain with ADP bound in the sub-domain junction. The N-terminal domain interacts with the D1 domain in a manner similar to adaptor-binding domains of other AAA(+) proteins. D1 and D2 are connected head-to-tail consistent with a cooperative and vectorial translocation of protein substrates. In a planar hexamer model of ClpA, built by assembling ClpA D1 and D2 into homohexameric rings of known structures of AAA(+) modules, the differences in D1-D1 and D2-D2 interfaces correlate with their respective contributions to hexamer stability and ATPase activity. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Xia, D (reprint author), 37 Convent Dr,Bldg 37,Rm 1B22, Bethesda, MD 20892 USA. NR 52 TC 146 Z9 149 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 29 PY 2002 VL 277 IS 48 BP 46743 EP 46752 DI 10.1074/jbc.M207796200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 620JB UT WOS:000179529300134 PM 12205096 ER PT J AU Guo, FS Esser, L Singh, SK Maurizi, MR Xia, D AF Guo, FS Esser, L Singh, SK Maurizi, MR Xia, D TI Crystal structure of the heterodimeric complex of the adaptor, ClpS, with the N-domain of the AAA(+) chaperone, ClpA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; SUBSTRATE-RECOGNITION; DENSITY-MODIFICATION; PROTEIN STRUCTURES; RIBOSOMAL-PROTEIN; PROTEOLYSIS; PROTEASES; IDENTIFICATION; DEGRADATION; RESOLUTION AB Substrate selectivity and proteolytic activity for the E. coli ATP-dependent protease, ClpAP, is modulated by an adaptor protein, ClpS. ClpS binds to ClpA, the regulatory component of the ClpAP complex. We report the crystal structure of ClpS in complex with the isolated N-terminal domain of CIpA in two different crystal forms at 2.3- and 3.3-Angstrom resolution. The ClpS structure forms an alpha/beta-sandwich and is topologically analogous to the C-terminal domain of the ribosomal protein L7/L12. ClpS contacts two surfaces on the N-terminal domain in both crystal forms; the more extensive interface was shown to be favored in solution by protease protection experiments. The N-terminal 20 residues of ClpS are not visible in the crystal structures; the removal of the first 17 residues produces ClpSDeltaN, which binds to the CIpA N-domain but no longer inhibits CIpA activity. A zinc binding site involving two His and one Glu residue was identified crystallographically in the N-terminal domain of ClpA. In a model of ClpS bound to hexameric ClpA, ClpS is oriented with its N terminus directed toward the distal surface of ClpA, suggesting that the N-terminal region of ClpS may affect productive substrate interactions at the apical surface or substrate entry into the CIpA translocation channel. C1 NCI, Ctr Canc Res, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Xia, D (reprint author), NCI, Ctr Canc Res, Cell Biol Lab, NIH, 37 Convent Dr,MSC 4255,Bldg 37,Rm 1B22, Bethesda, MD 20892 USA. NR 49 TC 74 Z9 76 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 29 PY 2002 VL 277 IS 48 BP 46753 EP 46762 DI 10.1074/jbc.M208104200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 620JB UT WOS:000179529300135 PM 12235156 ER PT J AU Westphal, H AF Westphal, H TI Genes that fashion the pituitary gland SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT Symposium on Comparative Clinical and Molecular Endocrinology CY AUG 30-31, 2001 CL ZEIST, NETHERLANDS SP Intervet Int, Utrecht Univ DE knockout (mouse); molecular genetics AB The pituitary gland with its distinct populations of hormone-producing cells is formed from precursor cells that are created when epithelial cells from the prospective diencephalon about the roof of the oral cavity during early development of the mammalian embryo. Successive steps of assembly during development lead from a rudimentary pouch to a definitive structure called Ratlike's pouch, and finally to the pituitary gland with its anterior, intermediate and posterior lobes. The proliferation and differentiation of highly specialized cells from their precursors is directed by signaling cascades and transcriptional events that are being dissected by genetic and molecular approaches. Our current state of knowledge in this regard allows us to use the pituitary as a paradigm to delineate general principles of organogenesis in the mammalian organism. Published by Elsevier Science Ireland Ltd. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Westphal, H (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD NOV 29 PY 2002 VL 197 IS 1-2 BP 45 EP 46 AR PII S0303-7207(02)00277-0 DI 10.1016/S0303-7207(02)00277-0 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 620FY UT WOS:000179524400006 PM 12431794 ER PT J AU Kelly, PA Bachelot, A Kedzia, C Hennighausen, L Ormandy, CJ Kopchick, JJ Binart, N AF Kelly, PA Bachelot, A Kedzia, C Hennighausen, L Ormandy, CJ Kopchick, JJ Binart, N TI The role of prolactin and growth hormone in mammary gland development SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT Symposium on Comparative Clinical and Molecular Endocrinology CY AUG 30-31, 2001 CL ZEIST, NETHERLANDS SP Intervet Int, Utrecht Univ DE epithelial cells; stroma; receptor knockout; transplantation; differentiation ID RECEPTOR-DEFICIENT MICE; GENE-EXPRESSION; TARGETED DISRUPTION; MOUSE; DEFECTS; IMPLANTATION; MECHANISMS AB Development and differentiation of the mammary gland occur primarily during pregnancy. Females homozygous (-/-) for the null mutation of the PRL receptor (PRLR) gene are sterile due to a complete failure of blastocysts to implant. In progesterone-treated mice pregnancy is rescued but the mammary gland is severely underdeveloped. Interestingly, females hemizygous for the PRLR (+/-) in their first lactation show an almost complete failure to lactate. This phenotype. disappears in the second and subsequent pregnancies in inbred 129/Sv mice but is maintained in inbred C57BL/6 mice. In GH receptor (GHR) KO mice litter size is markedly decreased, probably due to an ovarian defect. To assess the relevance of the GH and PRLRs in the mammary gland development, GHR and PRLR null epithelia were transplanted into cleared fat pads of wild-type mice. Such studies show that epithelial GHR is not required for functional mammary development. In contrast, epithelial PRLRs are required for mammary development and milk protein gene expression during pregnancy. Since ductal development is impaired in GHR -/- mice, it appears that GH signals through the stromal compartment. In summary, it is now established that GH and PRL activate Stat5 in separate compartments, reflecting their specific roles in ductal and alveolar development and differentiation. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Fac Med Necker Enfants Malad, INSERM, Unit 344 Endocrinol Mol, F-75730 Paris 15, France. NIH, Lab Genet & Physiol, Bethesda, MD USA. Garvan Inst Med Res, Darlinghurst, NSW, Australia. Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA. RP Kelly, PA (reprint author), Fac Med Necker Enfants Malad, INSERM, Unit 344 Endocrinol Mol, 156 Rue Vaugirard, F-75730 Paris 15, France. EM kelly@necker.fr RI Kelly, Paul/A-7951-2008; Ormandy, Chris/G-4165-2014 NR 24 TC 71 Z9 80 U1 2 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD NOV 29 PY 2002 VL 197 IS 1-2 BP 127 EP 131 AR PII S0303-7207(02)00286-1 DI 10.1016/S0303-7207(02)00286-1 PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 620FY UT WOS:000179524400017 PM 12431805 ER PT J AU Stefanova, I Dorfman, JR Germain, RN AF Stefanova, I Dorfman, JR Germain, RN TI Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes SO NATURE LA English DT Article ID SINGLE-CELL ANALYSIS; TRANSGENIC MICE; DEFICIENT MICE; RECEPTOR; CD4; MOLECULES; RESPONSES; THRESHOLDS; ACTIVATION; SURVIVAL AB Major histocompatibility complex (MHC) class I and II molecules are highly polymorphic proteins that bind and present foreign peptides to the clonally distributed alphabeta receptors (TCR) of T lymphocytes. As a population, the immature T lymphocytes generated in the thymus express a very diverse set of TCR specificities. A process of positive selection filters this broad repertoire to optimize peripheral T cells for antigen recognition in the context of available MHC products. Only those precursor T cells whose TCRs generate an adequate but not excessive signalling response to self-peptides bound to the expressed MHC proteins undergo successful maturation(1). Here we show that post-thymic self-recognition facilitates the antigen reactivity of mature T cells. Both experimental and physiological interruption of T-cell contact with self-peptide MHC ligands leads to a rapid decline in signalling and response sensitivity to foreign stimuli. Because the adaptive immune system must be recruited early in an infectious process when antigen is limiting(2), these findings suggest that positive selection ensures predictable T-cell recognition of available self-ligands, which in turn promotes efficient responses to pathogens. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Dorfman, Jeffrey/B-4854-2011 OI Dorfman, Jeffrey/0000-0001-9938-8911 NR 30 TC 247 Z9 249 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 28 PY 2002 VL 420 IS 6914 BP 429 EP 434 DI 10.1038/nature01146 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 619TZ UT WOS:000179494700043 PM 12459785 ER PT J AU Sundar, S Jha, TK Thakur, CP Engel, J Sindermann, H Fischer, C Junge, K Bryceson, A Berman, J AF Sundar, S Jha, TK Thakur, CP Engel, J Sindermann, H Fischer, C Junge, K Bryceson, A Berman, J TI Oral miltefosine for Indian visceral leishmaniasis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID AMPHOTERICIN-B; KALA-AZAR; TRIAL; DONOVANI AB Background: There are 500,000 cases per year of visceral leishmaniasis, which occurs primarily in the Indian subcontinent. Almost all untreated patients die, and all the effective agents have been parenteral. Miltefosine is an oral agent that has been shown in small numbers of patients to have a favorable therapeutic index for Indian visceral leishmaniasis. We performed a clinical trial in India comparing miltefosine with the most effective standard treatment, amphotericin B. Methods: The study was a randomized, open-label comparison, in which 299 patients 12 years of age or older received orally administered miltefosine (50 or 100 mg [approximately 2.5 mg per kilogram of body weight] daily for 28 days) and 99 patients received intravenously administered amphotericin B (1 mg per kilogram every other day for a total of 15 injections). Results: The groups were well matched in terms of age, weight, proportion with previous failure of treatment for leishmaniasis, parasitologic grade of splenic aspirate, and splenomegaly. At the end of treatment, splenic aspirates were obtained from 293 patients in the miltefosine group and 98 patients in the amphotericin B group. No parasites were identified, for an initial cure rate of 100 percent. By six months after the completion of treatment, 282 of the 299 patients in the miltefosine group (94 percent [95 percent confidence interval, 91 to 97]) and 96 of the 99 patients in the amphotericin B group (97 percent) had not had a relapse; these patients were classified as cured. Vomiting and diarrhea, generally lasting one to two days, occurred in 38 percent and 20 percent of the patients in the miltefosine group, respectively. Conclusions: Oral miltefosine is an effective and safe treatment for Indian visceral leishmaniasis. Miltefosine may be particularly advantageous because it can be administered orally. It may also be helpful in regions where parasites are resistant to current agents. C1 Kala Azar Res Ctr, Brahmpura, Muzaffarpur, India. Banaras Hindu Univ, Inst Med Sci, Varanasi 221005, Uttar Pradesh, India. Balaji Utthan Sanastan, Patna, Bihar, India. Zentaris Asta Med, Frankfurt, Germany. London Sch Hyg & Trop Med, London WC1, England. Walter Reed Army Inst Res, Silver Spring, MD USA. RP Berman, J (reprint author), Natl Ctr Complementary & Alternat Med, 6707 Democracy Blvd,Ste 401, Bethesda, MD 20892 USA. NR 20 TC 401 Z9 413 U1 3 U2 9 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 28 PY 2002 VL 347 IS 22 BP 1739 EP 1746 DI 10.1056/NEJMoa021556 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 619GU UT WOS:000179468600003 PM 12456849 ER PT J AU Boehm, M Nabel, EG AF Boehm, M Nabel, EG TI Angiotensin-converting enzyme 2 - A new cardiac regulator SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CARBOXYPEPTIDASE C1 NHLBI, Bethesda, MD 20892 USA. RP Boehm, M (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 43 Z9 59 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 28 PY 2002 VL 347 IS 22 BP 1795 EP 1797 DI 10.1056/NEJMcibr022472 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 619GU UT WOS:000179468600011 PM 12456857 ER PT J AU Knapp, S Gonzalez, S Myers, DS Eckman, LL Bewley, CA AF Knapp, S Gonzalez, S Myers, DS Eckman, LL Bewley, CA TI Shortcut to mycothiol analogues SO ORGANIC LETTERS LA English DT Article ID DEPENDENT FORMALDEHYDE DEHYDROGENASE; MYCOBACTERIUM-SMEGMATIS; THIOLS; TUBERCULOSIS; BIOSYNTHESIS; DETOXIFICATION; REDUCTASE AB graphic The synthesis of a simplified thioglycosidic analogue (2) of mycothiol (1) is described. Evaluation of 2 against mycothiol S-conjugate amidase from Mycobacterium tuberculosis reveals good specific activity (7500 nmol min(-1) mg-protein(-1), vs 14 200 for 1), indicating that 2 can serve as a starting point for antitubercular drug design. C1 Rutgers State Univ, Dept Chem & Biol Chem, Piscataway, NJ 08854 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Knapp, S (reprint author), Rutgers State Univ, Dept Chem & Biol Chem, 610 Taylor Rd, Piscataway, NJ 08854 USA. EM knapp@rutchem.rutgers.edu NR 28 TC 33 Z9 36 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD NOV 28 PY 2002 VL 4 IS 24 BP 4337 EP 4339 DI 10.1021/ol0269796 PG 3 WC Chemistry, Organic SC Chemistry GA 618RG UT WOS:000179430600039 PM 12443092 ER PT J AU Rottbauer, W Saurin, AJ Lickert, H Shen, XT Burns, CG Wo, ZG Kemler, R Kingston, R Wu, C Fishman, M AF Rottbauer, W Saurin, AJ Lickert, H Shen, XT Burns, CG Wo, ZG Kemler, R Kingston, R Wu, C Fishman, M TI Reptin and pontin antagonistically regulate heart growth in zebrafish embryos SO CELL LA English DT Article ID CHROMATIN REMODELING COMPLEX; BETA-CATENIN; BRANCH MIGRATION; BINDING-PROTEIN; COLON-CARCINOMA; RUVB PROTEINS; DNA HELICASE; CYCLIN D1; C-MYC; EXPRESSION AB Organ size is precisely regulated during development, but the control mechanisms remain obscure. We have isolated a mutation in zebrafish, liebeskummer (lik), which causes development of hyperplastic embryonic hearts. lik encodes Reptin, a component of a DNA-stimulated ATPase complex. The mutation activates ATPase activity of Reptin complexes and causes a cell-autonomous proliferation of cardiomyocytes to begin well after progenitors have fashioned the primitive heart tube. With regard to heart growth, beta-catenin and Pontin, a DNA-stimulated ATPase that is often part of complexes with Reptin, are in the same genetic pathways. Pontin reduction phenocopies the cardiac hyperplasia of the lik mutation. Thus, the Reptin/Pontin ratio serves to regulate heart growth during development, at least in part via the beta-catenin pathway. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Max Planck Inst Immunbiol, Dept Mol Embryol, D-79108 Freiburg, Germany. NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Fishman, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. RI Lickert, Heiko/K-9045-2013 FU NHLBI NIH HHS [5R01HL49579, T32 HL007208, 1R01HL63206]; NIDDK NIH HHS [5R01DK55383] NR 40 TC 112 Z9 115 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 27 PY 2002 VL 111 IS 5 BP 661 EP 672 DI 10.1016/S0092-8674(02)01112-1 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 621MV UT WOS:000179594500008 PM 12464178 ER PT J AU Lacey, JV Mink, R Lubin, JH Sherman, ME Troisi, R Hartge, P Schatzkin, A Schairer, C AF Lacey, JV Mink, R Lubin, JH Sherman, ME Troisi, R Hartge, P Schatzkin, A Schairer, C TI Estrogen replacement therapy and risk of ovarian cancer in postmenopausal women - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Lacey, JV (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NR 5 TC 1 Z9 2 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 NOV 27 PY 2002 VL 288 IS 20 BP 2539 EP 2539 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 618AL UT WOS:000179394500011 ER PT J AU Montgomery, SP Xu, H Tadaki, DK Celniker, A Burkly, LC Berning, JD Cruzata, F Elster, EA Gray, G Kampen, RL Swanson, SJ Harlan, DM Kirk, AD AF Montgomery, SP Xu, H Tadaki, DK Celniker, A Burkly, LC Berning, JD Cruzata, F Elster, EA Gray, G Kampen, RL Swanson, SJ Harlan, DM Kirk, AD TI Combination induction therapy with monoclonal antibodies specific for CD80, CD86, and CD154 in nonhuman primate renal transplantation SO TRANSPLANTATION LA English DT Article ID INTRAHEPATIC ISLET ALLOGRAFTS; DONOR-SPECIFIC TRANSFUSION; LONG-TERM SURVIVAL; HUMANIZED ANTI-CD154; REJECTION; SKIN; ACCEPTANCE; BLOCKING; PATHWAYS; MODEL AB Background. Antibodies and fusion proteins specific for CD80, CD86, and CD154 have shown promise as agents capable of inducing donor-specific tolerance in rodents. These agents have also been shown to be synergistic with one another in many settings of counter-adaptive immunity. In the nonhuman primate, monoclonal antibodies specific for CD80 and CD86 have prolonged the time to rejection of renal allografts but have not resulted in tolerance. A monoclonal antibody specific for CD154 has resulted in markedly prolonged survival of kidney, islet, cardiac, and skin allografts, but again most animals have eventually developed rejection after prolonged periods of rejection-free survival off therapy. Methods. A combination of monoclonal antibodies specific for CD80, CD86, and CD154 were used in a mismatched nonhuman primate renal-allograft model. Doses used were based on optimized treatment protocols for each agent individually. Results. Treatment of four rhesus macaques with this combination yielded a mean rejection-free survival of 565 days (311-911 days), significantly greater than untreated controls (mean survival = 7.0 days, P = 0.001) and animals treated with only a combination of anti-CD80 and CD86 (mean survival = 191 days, P = 0.01). The survival of animals treated with this combination of monoclonal antibodies was not significantly greater than those treated with anti-CD154 alone, but the production of alloantibody was delayed compared with monotherapy anti-CD154. C1 NIDDK, Transplantat & Autoimmun Branch, Bethesda, MD 20889 USA. Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. Wyeth, Andover, MA USA. Biogen Inc, Cambridge, MA USA. RP Kirk, AD (reprint author), NIDDK, Transplantat & Autoimmun Branch, Room 11-S-219,Bldg 10,Ctr Dr, Bethesda, MD 20889 USA. RI Kirk, Allan/B-6905-2012 FU NIAID NIH HHS [AI43900-01] NR 18 TC 42 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 2002 VL 74 IS 10 BP 1365 EP 1369 DI 10.1097/01.TP.0000040001.25099.D3 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 618TG UT WOS:000179432900002 PM 12451232 ER PT J AU Sauna, ZE Muller, M Peng, XH Ambudkar, SV AF Sauna, ZE Muller, M Peng, XH Ambudkar, SV TI Importance of the conserved Walker B glutamate residues, 556 and 1201, for the completion of the catalytic cycle of ATP hydrolysis by human P-glycoprotein (ABCB1) SO BIOCHEMISTRY LA English DT Article ID MULTIDRUG-RESISTANCE PROTEIN; NUCLEOTIDE-BINDING SITES; HAMSTER OVARY CELLS; CRYSTAL-STRUCTURE; TRANSITION-STATE; FUNCTIONAL-CHARACTERIZATION; MONOCLONAL-ANTIBODIES; EXPRESSION SYSTEM; TRANSPORTER; SUBUNIT AB The human MDR1 (ABCB1) gene product, P-glycoprotein (Pgp), functions as an ATP-dependent efflux pump for a variety of chemotherapeutic drugs. In this study, we assessed the role of conserved glutamate residues in the Walker B domain of the two ATP sites (E556 and E1201, respectively) during the catalytic cycle of human Pgp. The mutant Pgps (E556Q, E556A, E1201Q, E1201A, E556/1201Q, and E556/1201A) were characterized using a vaccinia virus based expression system. Although steady-state ATP hydrolysis and drug transport activities were abrogated in both E556Q and E1201Q mutant Pgps, [alpha-P-32]-8-azidoADP was trapped in the presence of vanadate (Vi), and the release of trapped [alpha-P-32]-8-azidoADP occurred to a similar extent as in wild-type Pgp. This indicates that these mutations do not affect either the first hydrolysis event or the ADP release step. Similar results were also obtained when Glu residues were replaced with Ala (E556A and E1201A). Following the first hydrolysis event and release of [alpha-P-32]-8-azidoADP, both E556Q and E1201Q mutant Pgps failed to undergo another cycle of Vi-induced [alpha-P-32]-8-azidoADP trapping. Interestingly, the double mutants E556/1201Q and E556/1201A trapped [alpha-P-32]-8-azidoADP even in the absence of Vi, and the occluded nucleotide was not released after incubation at 37 degreesC for an extended period. In addition, the properties of transition state conformation of the double mutants generated in the absence of Vi were found to be similar to that of the wild-type protein trapped in the presence of Vi (Pgp.[alpha-P-32]-8-azidoADP.Vi). Thus, in contrast to the single mutants, the double mutants appear to be defective in the ADP release step. In aggregate, these data suggest that E556 and E1201 residues in the Walker B domains may not be critical as catalytic carboxylates for the cleavage of the bond between the gamma-P and the beta-P of ATP during hydrolysis but are essential for the second ATP hydrolysis step and completion of the catalytic cycle. C1 NCI, NIH, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, NIH, Cell Biol Lab, Ctr Canc Res, Bldg 37,Room 1B-22,37 Convent Dr, Bethesda, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 65 TC 72 Z9 73 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 26 PY 2002 VL 41 IS 47 BP 13989 EP 14000 DI 10.1021/bi026626e PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 617RT UT WOS:000179375200016 PM 12437356 ER PT J AU Rywik, TM O'Connor, FC Gittings, NS Wright, JG Khan, AA Fleg, JL AF Rywik, TM O'Connor, FC Gittings, NS Wright, JG Khan, AA Fleg, JL TI Role of nondiagnostic exercise-induced ST-Segment abnormalities in predicting future coronary events in asymptomatic volunteers SO CIRCULATION LA English DT Article DE exercise; coronary disease; prognosis ID SILENT-MYOCARDIAL-ISCHEMIA; TREADMILL STRESS TEST; 5-YEAR FOLLOW-UP; PROGNOSTIC-SIGNIFICANCE; HEALTHY-MEN; ELECTROCARDIOGRAPHY; DISEASE; ARTERIOGRAPHY; HEMODYNAMICS; DEPRESSION AB Background-Whether exercise-induced ST-segment depression <1 mm is an independent predictor of future coronary events (CEs) in asymptomatic subjects is unknown. Methods and Results-We performed maximal treadmill exercise tests on 1083 volunteers from the Baltimore Longitudinal Study of. Aging who were free from clinical coronary heart disease. Exercise ST-segment changes were stratified by Minnesota code criteria: 11:1 (n=213), flat or downsloping ST depression greater than or equal to1 mm; 11:2 (n=66), flat or downsloping ST depression greater than or equal to0.5 mm and <1 mm; 11:4 (n=124), ST-J depression greater than or equal to1 mm with slowly rising ST segments; and 11:5 (n=69), minor ST depression (<0.5 mm) before exercise that worsened to flat or downsloping ST depression greater than or equal to1 mm during or after exercise. Risk of CE was compared with subjects with normal exercise ECG (n=611). Over a mean follow-up of 7.9 years, 76 subjects developed CEs (angina pectoris, myocardial infarction, or coronary death). On univariate analysis, age (relative risk [RR]=1.07/year, P<0.0001), male sex (RR=1.98, P=0.009), plasma cholesterol (RR=1.02/mg per dL, P<0.0001), hypertension (RR=2.23, P=0.002), duration of exercise (RR=0.71/min, P=0.0001), and systolic blood pressure at peak effort (RR=1.02/mm Hg, P=0.002) were associated with CE. By Cox proportional hazards analysis, age (RR=1.06/year, P<0.0001), male sex (RR=2.76, P=0.0002), plasma cholesterol (RR=1.02 per 1 mg/dL, P<0.0001), duration of exercise (RR=0.87/min, P=0.004), and ST-segment changes coded as either 11:1 (RR=2.70, P=0.0005) or 11:5 (RR=2.73, P=0.04) were independent predictors of CE. Conclusions-Both a classic ischemic ST-segment exercise response and intensification of minor preexercise ST-segment depression to levels 22:1 mm independently predicted future CE in this asymptomatic population. Neither slowly rising ST depression nor horizontal ST depression <1 mm was prognostic. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Fleg, JL (reprint author), NHLBI, DECA, 6701 Rockledge Dr,Room 8112,MSC 7936, Bethesda, MD 20892 USA. NR 29 TC 24 Z9 26 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 NOV 26 PY 2002 VL 106 IS 22 BP 2787 EP 2792 DI 10.1167/01.CIR.0000039329.47437.3B PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 621GY UT WOS:000179581700017 PM 12451004 ER PT J AU Holland, NT Duramad, P Rothman, N Figgs, LW Blair, A Hubbard, A Smith, MT AF Holland, NT Duramad, P Rothman, N Figgs, LW Blair, A Hubbard, A Smith, MT TI Micronucleus frequency and proliferation in human lymphocytes after exposure to herbicide 2,4-dichlorophenoxyacetic acid in vitro and in vivo SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE 2,4-D; human lymphocytes; applicators; replicative index; micronucleus frequency ID SISTER-CHROMATID EXCHANGES; NON-HODGKINS-LYMPHOMA; CHROMOSOME-ABERRATIONS; PHENOXY HERBICIDES; CELL-PROLIFERATION; PERIPHERAL-BLOOD; IN-VITRO; PESTICIDES; 2,4-D; WORKERS AB Widespread use of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and its association with non-Hodgkin's lymphoma (NHL) and other cancers has raised public concern. Here, micronucleus (MN) formation has been used as a biomarker of genotoxicity, and replicative and mitotic indices (MIs) as biomarkers of cell cycle kinetics in human lymphocytes. Cells were cultured either as whole blood or isolated lymphocytes and treated with pure or commercial forms of 2,4-D at doses between 0.001 and 1 mM for 48 h. Exposure to 2,4-D produced a minimal increase in MN in whole blood and even smaller one in isolated lymphocyte cultures. This induction took place only at levels approaching cytotoxicity and was accompanied by a significant inhibition of replicative index (RI). At a low (0.005 mM) dose of commercial 2,4-D, a small, marginally significant increase in RI (12-15%) was found in two independent sets of experiments (P = 0.052). Additionally, we found that lymphocyte RI was more affected by commercial 2,4-D containing 9.4% of the chemically pure 2,4-D, than with an equal concentration of the latter suggesting that other ingredients present in the commercial pesticide may be responsible or may enhance the effect of 2,4-D. Mitotic index, however, did not show any significant change with either commercial or pure 2,4-D. The lymphocytes of 12 male applicators exposed solely to 2,4-D during a 3-month period had a significantly higher RI than the same group prior to exposure and than a control group (P < 0.01), in accordance with the in vitro finding of increased RI at low doses. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. NCI, Bethesda, MD 20892 USA. St Louis Univ, St Louis, MO 63108 USA. Univ Calif Berkeley, Sch Publ Hlth, Div Biostat, Berkeley, CA 94720 USA. RP Holland, NT (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. FU NIEHS NIH HHS [P42ES04705] NR 61 TC 49 Z9 52 U1 1 U2 5 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 NOV 26 PY 2002 VL 521 IS 1-2 BP 165 EP 178 DI 10.1016/S1383-5718(02)00237-1 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 619QK UT WOS:000179487500016 PM 12438013 ER PT J AU Ress, NB Witt, KL Xu, J Haseman, JK Bucher, JR AF Ress, NB Witt, KL Xu, J Haseman, JK Bucher, JR TI Micronucleus induction in mice exposed to diazoaminobenzene or its metabolites, benzene and aniline: implications for diazoaminobenzene carcinogenicity SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE bone marrow; chromosome damage; carcinogenicity; erythrocyte; mixtures ID BONE-MARROW; PERIPHERAL-BLOOD; 1,3-DIPHENYL-1-TRIAZENE; ANEUPLOIDY; INTERPHASE; BIOASSAY; TOXICITY; WORKERS; DAMAGE; ASSAY AB Diazoaminobenzene (DAAB), a manufacturing intermediate metabolized primarily to the known carcinogens benzene and aniline, has been identified as an impurity in a number of dyes and coloring agents that are components of cosmetics, food products, and pharmaceuticals. Several structural analogs of DAAB are carcinogenic as well. DAAB was selected for metabolism and toxicity studies by the National Toxicology Program (NTP) based on the potential for human exposure, positive Salmonella data, and lack of adequate toxicological data. In the toxicology studies in mice, DAAB exhibited properties similar to benzene and aniline. Because both these metabolites induce micronuclei (MN) in rodent bone marrow erythrocytes, DAAB was tested for induction of micronuclei in male B6C3F(1) mice. DAAB was administered twice by corn oil gavage at 24 h intervals, at doses of 25, 50, and 100 mg/kg per day. In addition, comparative micronucleus tests were conducted with benzene, aniline, and a mixture of benzene plus aniline; doses were based on the respective molar equivalents of each metabolite to DAAB. It was hypothesized that any observed increase in micronuclei seen in DAAB-treated mice would be due primarily to the effects of the benzene metabolite, as benzene is a more potent inducer of chromosomal damage than aniline. Results of this study showed that DAAB and benzene were effective inducers of micronuclei, with stronger responses noted for DAAB at higher doses. Positive results were also obtained with the mixture of benzene and aniline, although the magnitude of the response was lower than for DAAB. Aniline gave a weak positive response at doses exceeding its molar equivalent to 100 mg/kg DAAB. Overall, the data indicated that DAAB is a potent inducer of micronuclei in mice, and its activity appears to be closely related to the activity of benzene, one of its primary metabolites. The results. are consistent with a prediction of carcinogenicity for DAAB. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved. C1 NIEHS, Res Triangle Pk, NC 27709 USA. ILS, Res Triangle Pk, NC 27709 USA. SITEK Res Labs, Rockville, MD 20850 USA. RP Bucher, JR (reprint author), NIEHS, 79 Alexander Dr,Mail Drop EC-34, Res Triangle Pk, NC 27709 USA. NR 30 TC 12 Z9 12 U1 0 U2 1 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 NOV 26 PY 2002 VL 521 IS 1-2 BP 201 EP 208 AR PII S1383-5718(02)00241-3 DI 10.1016/S1383-5718(02)00241-3 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 619QK UT WOS:000179487500019 PM 12438016 ER PT J AU Kim, Y Clark, DJ AF Kim, Y Clark, DJ TI SWI/SNF-dependent long-range remodeling of yeast HIS3 chromatin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL ACTIVATION; REGULATORY SEQUENCES; SWI-SNF; IN-VIVO; NUCLEOSOME; COMPLEX; DNA; PROMOTER; RECRUITMENT AB Current models for the role of the SWI/SNF chromatin remodeling complex in gene regulation are focused on promoters, where the most obvious changes in chromatin structure occur. Here we present evidence that the SWI/SNF complex is involved in the remodeling of the chromatin structure of an entire gene in vivo. We compared the native chromatin structures of a small yeast plasmid containing the HIS3 gene purified from uninduced and induced cells. Relative to uninduced chromatin, induced chromatin displayed a large reduction in negative supercoiling, a large reduction in sedimentation rate, and increased accessibility to restriction enzymes with sites located both near and far from the HIS3 promoter. These observations indicate that the entire plasmid was remodeled as a result of induction. Loss of supercoiling required the presence of the SWI/SNF remodeling complex and the activator Gcn4p in vivo. The TATA boxes were not required, suggesting that remodeling was not the result of transcription. The induction-dependent loss of negative supercoiling was not apparent in cells, indicating that the supercoils were lost preferentially from induced chromatin during purification. Thus, induced HIS3 chromatin has a highly labile structure that is revealed as a result of purification. It is concluded that induction of HIS3 creates a domain of labile chromatin structure that extends far beyond the promoter to include the entire gene. We propose that the SWI/SNF complex is recruited to the HIS3 promoter by Gcn4p and then directs remodeling of a chromatin domain, with important implications for transcription. C1 NIH, Natl Inst Diabet & Digest & Kidney Dis, Lab Cellular & Dev Biol, Bethesda, MD 20892 USA. RP Clark, DJ (reprint author), NIH, Natl Inst Diabet & Digest & Kidney Dis, Lab Cellular & Dev Biol, Bldg 50,Rm 3148, Bethesda, MD 20892 USA. NR 37 TC 32 Z9 32 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 NOV 26 PY 2002 VL 99 IS 24 BP 15381 EP 15386 DI 10.1073/pnas.242536699 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000026 PM 12432091 ER PT J AU Goldsby, RE Hays, LE Chen, X Olmsted, EA Slayton, WB Spangrude, GJ Preston, BD AF Goldsby, RE Hays, LE Chen, X Olmsted, EA Slayton, WB Spangrude, GJ Preston, BD TI High incidence of epithelial cancers in mice deficient for DNA polymerase delta proofreading SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MISMATCH REPAIR; STEM-CELLS; SACCHAROMYCES-CEREVISIAE; XERODERMA-PIGMENTOSUM; REPLICATION ERRORS; 3'->5' EXONUCLEASE; COLORECTAL-CANCER; MUTATOR PHENOTYPE; COLON-CANCER; MOUSE AB Mutations are a hallmark of cancer. Normal cells minimize spontaneous mutations through the combined actions of polymerase base selectivity, 3' --> 5' exonucleolytic proofreading, mismatch correction, and DNA damage repair. To determine the consequences of defective proofreading in mammals, we created mice with a point mutation (D400A) in the proofreading domain of DNA polymerase delta (poldelta, encoded by the Pold1 gene). We show that this mutation inactivates the 3' --> 5' exonuclease of poldelta and causes a mutator and cancer phenotype in a recessive manner. By 18 months of age, 94% of homozygous Pold1(D400A/D400A) mice developed cancer and died (median survival = 10 months). In contrast, only 3-4% of Pold1(+/D400A) and Pold1(+/+) mice developed cancer in this time frame. Of the 66 tumors arising in 49 Pold1(D400A/D400A) mice, 40 were epithelial in origin (carcinomas), 24 were mesenchymal (lymphomas and sarcomas), and two were composite (teratomas); one-third of these animals developed tumors in more than one tissue. Skin squamous cell carcinoma was the most common tumor type, occurring in 60% of all Pold1(D400A/D400A) mice and in 90% of those surviving beyond 8 months of age. These data show that poldelta proofreading suppresses spontaneous tumor development and strongly suggest that unrepaired DNA polymerase errors contribute to carcinogenesis. Mice deficient in poldelta proofreading provide a tractable model to study mechanisms of epithelial tumorigenesis initiated by a mutator phenotype. C1 Univ Utah, Sch Med, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA. Univ Utah, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, Salt Lake City, UT 84112 USA. Univ Utah, Sch Med, Dept Oncol Sci, Salt Lake City, UT 84112 USA. Univ Utah, Sch Med, Dept Biochem, Salt Lake City, UT 84112 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, NIEHS, Comparat Mouse Genom Ctr, Seattle, WA 98195 USA. RP Preston, BD (reprint author), Univ Utah, Sch Med, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA. FU NCI NIH HHS [K08 CA72731]; NIEHS NIH HHS [R01 ES09927, U01 ES11045, R01 ES09927-S1, U01 ES011045] NR 47 TC 97 Z9 108 U1 2 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 NOV 26 PY 2002 VL 99 IS 24 BP 15560 EP 15565 DI 10.1073/pnas.232340999 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000057 PM 12429860 ER PT J AU Tanaka, Y Hanada, K Mizokami, M Yeo, AET Shih, JWK Gojobori, T Alter, HJ AF Tanaka, Y Hanada, K Mizokami, M Yeo, AET Shih, JWK Gojobori, T Alter, HJ TI A comparison of the molecular clock of hepatitis C virus in the United States and Japan predicts that hepatocellular carcinoma incidence in the United States will increase over the next two decades SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NON-B-HEPATITIS; NON-A; LIVER-DISEASE; MUTATION-RATE; FOLLOW-UP; INFECTION; EPIDEMIOLOGY; EVOLUTION; ANTIBODY; TRANSFUSION AB The prevalence of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is considerably lower in the U.S. than in Japan. To elucidate this difference, we determined the time origin of the HCV epidemic in each country by using molecularly clocked long-term serial samples obtained from HCV carriers of genotypes 1a and 1b. The molecular clock estimated that HCV genotype 1 first appeared in Japan in around 1882, whereas emergence in the U.S. was delayed until around 1910. In addition, by statistical analysis using coalescent theory, the major spread time for HCV infection in Japan occurred in the 1930s, whereas widespread dissemination of HCV in the U.S. occurred in the 1960s. These estimates of viral spread time are consistent with epidemiologic observations and predict that the burden of HCC in the U.S. will increase in the next two to three decades, possibly to equal that currently experienced in Japan. C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. Nagoya City Univ, Grad Sch Med Sci, Dept Clin Mol Informat Med, Nagoya, Aichi 4678601, Japan. Natl Inst Genet, Ctr Informat Biol, Mishima, Shizuoka 4118540, Japan. Jacobus Pharmaceut Co Inc, Princeton, NJ 08540 USA. RP Tanaka, Y (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NR 33 TC 227 Z9 234 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 NOV 26 PY 2002 VL 99 IS 24 BP 15584 EP 15589 DI 10.1073/pnas.242608099 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000061 PM 12438687 ER PT J AU Kipnis, J Mizrahi, T Hauben, E Shaked, I Shevach, E Schwartz, M AF Kipnis, J Mizrahi, T Hauben, E Shaked, I Shevach, E Schwartz, M TI Neuroprotective autoimmunity: Naturally occurring CD4(+)CD25(+) regulatory T cells suppress the ability to withstand injury to the central nervous system SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MYELIN BASIC-PROTEIN; NEONATAL TOLERANCE; PROTECTIVE AUTOIMMUNITY; OPTIC-NERVE; ADULT LIFE; NEUROPATHIES; DEGENERATION; VACCINATION; EXPANSION; EXPOSURE AB The ability of rats or mice to withstand the consequences of injury to myelinated axons in the CNS was previously shown to depend on the ability to manifest a T cell-mediated protective immune response, which is amenable to boosting by myelin-specific T cells. Here we show that this ability, assessed by retinal ganglion cell survival after optic nerve injury or locomotor activity after spinal cord contusion, is decreased if the animals were immunized as neonates with myelin proteins (resulting in their non responsiveness as adults to myelin proteins) or injected with naturally occurring regulatory CD4(+)CD25(+) T cells immediately after the injury, and is improved by elimination of these regulatory T cells. In nude BALB/c mice replenished with a splenocyte population lacking CD4(+)CD25(+) regulatory T cells, significantly more neurons survived after optic nerve injury than in nude mice replenished with a complete splenocyte population or in matched wild-type controls. In contrast, neuronal survival in wildtype BALB/c mice injected with CD4(+)CD25(+) regulatory T cells immediately after injury was significantly worse than in noninjected controls. These findings suggest that the ability to cope with the sequelae of a CNS insult is affected unfavorably by non responsiveness to myelin self-antigens and favorably by conditions allowing rapid expression of an autoimmune response. The regulatory T cells might represent an evolutionary compromise between the need to avoid autoimmune diseases and the need for autoimmunity on alert for the purpose of tissue maintenance. C1 Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. NIAID, Immunol Lab, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Schwartz, M (reprint author), Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. NR 26 TC 174 Z9 184 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 NOV 26 PY 2002 VL 99 IS 24 BP 15620 EP 15625 DI 10.1073/pnas.232565399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000067 PM 12429857 ER PT J AU Cho, YS Kim, MK Cheadle, C Neary, C Park, YG Becker, KG Cho-Chung, YS AF Cho, YS Kim, MK Cheadle, C Neary, C Park, YG Becker, KG Cho-Chung, YS TI A genomic-scale view of the cAMP response element-enhancer decoy: A tumor target-based genetic tool SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTION FACTOR AP-2; BREAST-CANCER CELLS; RI-ALPHA SUBUNIT; GROWTH ARREST; CYCLIC-AMP; EXPRESSION PATTERNS; ANTISENSE DEPLETION; NUCLEAR-PROTEIN; DNA MICROARRAY; OLIGONUCLEOTIDE AB Enhancer DNA decoy oligodeoxynucleotides (ODNs) inhibit transcription by competing for transcription factors. A decoy ODN composed of the cAMP response element (CRE) inhibits CRE-directed gene transcription and tumor growth without affecting normal cell growth. Here, we use DNA microarrays to analyze the global effects of the CRE-decoy ODN in cancer cell lines and in tumors grown in nude mice. The CRE-decoy up-regulates the AP-2beta transcription factor gene in tumors but not in the livers of host animals. The up-regulated expression of AP-2beta is clustered with the up-regulation of other genes involved in development and cell differentiation. Concomitantly, another cluster of genes involved in cell proliferation and transformation is down-regulated. The observed alterations indicate that CRE-directed transcription favors tumor growth. The CRE-decoy ODN, therefore, may serve as a target-based genetic tool to treat cancer and other diseases in which CRE-directed transcription is abnormally used. C1 NCI, Canc Res Ctr, Basic Res Lab, Cellular Biochem Sect, Bethesda, MD 20892 USA. NIA, DNA Array Unit, NIH, Baltimore, MD 21224 USA. RP Cho-Chung, YS (reprint author), NCI, Canc Res Ctr, Basic Res Lab, Cellular Biochem Sect, Bldg 10,Room 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Becker, Kevin/0000-0002-6794-6656 NR 33 TC 22 Z9 22 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 NOV 26 PY 2002 VL 99 IS 24 BP 15626 EP 15631 DI 10.1073/pnas.242617799 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000068 PM 12438686 ER PT J AU Thimme, R Bukh, J Spangenberg, HC Wieland, S Pemberton, J Steiger, C Govindarajan, S Purcell, RH Chisari, FV AF Thimme, R Bukh, J Spangenberg, HC Wieland, S Pemberton, J Steiger, C Govindarajan, S Purcell, RH Chisari, FV TI Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; PERIPHERAL-BLOOD; CELL RESPONSE; IMMUNE-RESPONSE; CDNA CLONE; B VIRUS; INFECTION; CHIMPANZEES; LIVER; HCV AB To define the early events that determine the outcome of acute hepatitis C virus (HCV) infection, we compared the course of viremia with the peripheral and intrahepatic T cell response and intrahepatic cytokine profile in six acutely infected chimpanzees. Three different outcomes were observed after peak viral titers were reached: sustained viral clearance, transient viral clearance followed by chronic infection, and chronic infection that persisted at initial peak titers. The results indicate that HCV spread outpaces the T cell response and that HCV rapidly induces but is not controlled by IFN-alpha/beta; that viral clearance follows the entry and accumulation of HCV-specific IFN-gamma-producing T cells in the liver; and that it may not require the destruction of infected cells. C1 The Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. Univ Hosp Freiburg, Dept Med 2, D-79106 Freiburg, Germany. NIH, Infect Dis Lab, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. Univ So Calif, Rancho Los Amigos Med Ctr, Liver Res Lab, Downey, CA 90242 USA. RP Chisari, FV (reprint author), The Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. RI Chisari, Francis/A-3086-2008; OI Chisari, Francis/0000-0002-4832-1044 FU NCI NIH HHS [N01-CO-56000, R01 CA076403]; NIAID NIH HHS [N01-AI-45180, N01-AI-52705, R01 AI020001, R21 AI052705] NR 45 TC 439 Z9 460 U1 3 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 NOV 26 PY 2002 VL 99 IS 24 BP 15661 EP 15668 DI 10.1073/pnas.202608299 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000074 PM 12441397 ER PT J AU Su, AI Pezacki, JP Wodicka, L Brideau, AD Supekova, L Thimme, R Wieland, S Bukh, J Purcell, RH Schultz, PG Chisari, FV AF Su, AI Pezacki, JP Wodicka, L Brideau, AD Supekova, L Thimme, R Wieland, S Bukh, J Purcell, RH Schultz, PG Chisari, FV TI Genomic analysis of the host response to hepatitis C virus infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL-CULTURE; MICROARRAY ANALYSIS; RNA REPLICATION; IMMUNE-RESPONSE; CHIMPANZEE; PROTEIN; LIVER; GENES; ENTRY; ALPHA AB We have examined the progression of hepatitis C virus (HCV) infections by gene expression analysis of liver biopsies in acutely infected chimpanzees that developed persistent infection, transient viral clearance, or sustained clearance. Both common responses and outcome-specific changes in expression were observed. All chimpanzees showed gene expression patterns consistent with an IFN-alpha response that correlated with the magnitude and duration of infection. Transient and sustained viral clearance were uniquely associated with induction of IFN-gamma-induced genes and other genes involved in antigen processing and presentation and the adaptive immune response. During the early stages of infection, host genes involved in lipid metabolism were also differentially regulated. We also show that drugs that affect these biosynthetic pathways can regulate HCV replication in HCV replicon systems. Our results reveal genome-wide transcriptional changes that reflect the establishment, spread, and control of infection, and they reveal potentially unique antiviral programs associated with clearance of HCV infection. C1 The Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. The Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. Novartis Res Fdn, Genomics Inst, San Diego, CA 92121 USA. Natl Res Council Canada, Steacie Inst Mol Sci, Ottawa, ON K1A 0R6, Canada. NIH, Hepatitis Viruses Sect, Infect Dis Lab, Bethesda, MD 20892 USA. RP Chisari, FV (reprint author), The Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. RI Chisari, Francis/A-3086-2008; OI Chisari, Francis/0000-0002-4832-1044; Su, Andrew I./0000-0002-9859-4104 FU NCI NIH HHS [CA 76403, R01 CA076403]; NIAID NIH HHS [AI20001, R01 AI020001] NR 31 TC 438 Z9 460 U1 3 U2 27 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 NOV 26 PY 2002 VL 99 IS 24 BP 15669 EP 15674 DI 10.1073/pnas.202608199 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000075 PM 12441396 ER PT J AU Strome, EM Wheler, GHT Higley, JD Loriaux, DL Suomi, SJ Doudet, DJ AF Strome, EM Wheler, GHT Higley, JD Loriaux, DL Suomi, SJ Doudet, DJ TI Intracerebroventricular corticotropin-releasing factor increases limbic glucose metabolism and has social context-dependent behavioral effects in nonhuman primates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; CEREBROSPINAL-FLUID; MAJOR DEPRESSION; BETA-ENDORPHIN; RHESUS-MONKEYS; BLOOD-FLOW; BRAIN; AMYGDALA; PET AB Corticotropin-releasing factor (CRF) is a neuropeptide involved in integrating the behavioral, autonomic, and hormonal responses to stress within the central nervous system. Patients suffering from depression have abnormal activity in stress responsive brain regions and elevated cerebrospinal fluid CRF. The DSM-IV criteria for major depressive disorder include behavioral changes such as depressed mood, anhedonia, and psychomotor agitation/retardation. We studied the effects of 434 mug of CRF given intracerebroventricularly over 40 min in group and individually housed monkeys to examine the role of elevated levels of central CRF on behavior. CRF elicited a wide range of behaviors, which fell into three broad categories: anxiety-like, depressive-like, and externally oriented. Externally oriented behaviors decreased, and anxiety-like behaviors increased regardless of how the animals were housed. Interestingly, increased depressive-like behaviors were only observed when the animals were socially housed. In a separate experiment, we examined the effects of the same dose of CRF on the regional cerebral glucose metabolism of lightly anesthetized monkeys by using positron emission tomography and [F-18]fluorodeoxyglucose. CRF infusion increased glucose metabolism in the pituitary/infundibulum, the amygdala, and hippocampus. These results indicate that increased central CRF tone affects primate behavior in a context-dependent manner, and that it activates limbic and stress-responsive regions. The fact that intracerebroventricular CRF increases depressive-like behavior in socially housed animals and increases activity in limbic brain regions may help explain the behavioral and metabolic alterations in humans with affective disorders, and this model could therefore have significant value in the development of novel antidepressant treatments. C1 Univ British Columbia, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada. Univ British Columbia, Dept Med, Vancouver, BC V6T 2B5, Canada. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. NIAAA, Clin Studies Lab, Primate Unit, Intramural Res Program, Poolesville, MD 20837 USA. NICHHD, Lab Comparat Ethol, Intramural Res Program, Anim Ctr,NIH, Poolesville, MD 20837 USA. RP Strome, EM (reprint author), Univ British Columbia, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada. EM strome@interchange.ubc.ca NR 37 TC 52 Z9 57 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 NOV 26 PY 2002 VL 99 IS 24 BP 15749 EP 15754 DI 10.1073/pnas.232480899 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000088 PM 12438692 ER PT J AU Qin, M Kang, J Smith, CB AF Qin, M Kang, J Smith, CB TI Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FMR1 KNOCKOUT MICE; PROTEIN-SYNTHESIS; TRANSLATION; RIBOSOMES; FOLLICLES; STIMULI; MEMORY; GENE; RNA AB in humans, failure to express the fragile X mental retardation protein (FMRP) gives rise to fragile X syndrome, the most common form of inherited mental retardation. A fragile X knockout (fmr1 KO) mouse has been described that has some of the characteristics of patients with fragile X syndrome, including immature dendritic spines and subtle behavioral deficits. In our behavioral studies, fmr1 KO mice exhibited hyperactivity and a higher rate of entrance into the center of an open field compared with controls, suggesting decreased levels of anxiety. our finding of impaired performance of fmr1 KO mice on a passive avoidance task is suggestive of a deficit in learning and memory. In an effort to understand what brain regions are involved in the behavioral abnormalities, we applied the [C-14]deoxyglucose method for the determination of cerebral metabolic rates for glucose (CMRglc). We measured CMRglc in 38 regions in adult male fmr1 KO and WT littermates. We found CMRglc, was higher in all 38 regions in fmr1 KO mice, and in 26 of the regions, differences were statistically significant. Differences in CMRglc ranged from 12% to 46%, and the greatest differences occurred in regions of the limbic system and primary sensory and posterior parietal cortical areas. Regions most affected are consistent with behavioral deficiencies and regions in which FMRP expression is highest. Higher CMRglc in fragile X mice may be a function of abnormalities found in dendritic spines. C1 NIMH, Unit Neurobiol, Lab Cerebral Metab, United State Publ Hlth Serv,Dept Hlth & Human Ser, Bethesda, MD 20892 USA. RP Smith, CB (reprint author), NIMH, Unit Neurobiol, Lab Cerebral Metab, United State Publ Hlth Serv,Dept Hlth & Human Ser, Bethesda, MD 20892 USA. NR 52 TC 53 Z9 56 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 NOV 26 PY 2002 VL 99 IS 24 BP 15758 EP 15763 DI 10.1073/pnas.242377399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000090 PM 12427968 ER PT J AU Czubayko, U Plenz, D AF Czubayko, U Plenz, D TI Fast synaptic transmission between striatal spiny projection neurons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BASAL GANGLIA; RAT STRIATUM; NIGROSTRIATAL PATHWAY; INHIBITORY SYNAPSES; NEURAL-NETWORK; IN-VITRO; NEOSTRIATUM; INTERNEURONS; MODEL; CONNECTIONS AB Striatal inhibition plays an important role in models of cortex-basal ganglia function and is altered in many basal ganglia diseases. The,gamma-aminobutyric acid ergic spiny projection neuron comprises >95% of striatal neurons, but despite strong anatomical evidence, the electrophysiological properties and functions of their local axon collaterals are unknown. We simultaneously recorded from adjacent spiny projection neurons (<5-10 mum) in whole-cell patch mode and demonstrated a fast synaptic connection between 26/69 pairs in cortex-striatum-substantia nigra organcitypic cultures and 5/38 pairs in acute striatal slices. The synapse, which was blocked by gamma-aminobutyric acid type A antagonists, displayed a wide range of failure rates, was depolarizing at rest, and reversed above -60 mV. Presynaptic bursts of action potentials were highly correlated with total postsynaptic depolarization at rest. Synaptic transmission was optimized for burst discharge >14 Hz and showed considerable short-term plasticity, including paired-pulse depression at intervals <25 ms, intraburst facilitation, and interburst augmentation. This activity-dependent collateral interaction provides the basis for a new class of basal ganglia models in which striatal neurons cooperate as well as compete during processing of cortical inputs. C1 NIMH, Unit Neural Network Physiol, Lab Syst Neurosci, Bethesda, MD 20892 USA. Univ Tennessee, Coll Med, Dept Anat & Neurobiol, Memphis, TN 38163 USA. RP Plenz, D (reprint author), NIMH, Unit Neural Network Physiol, Lab Syst Neurosci, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU NINDS NIH HHS [NS-26473-11] NR 36 TC 120 Z9 121 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 26 PY 2002 VL 99 IS 24 BP 15764 EP 15769 DI 10.1073/pnas.242428599 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 620JJ UT WOS:000179530000091 PM 12438690 ER PT J AU Galbraith, CG Yamada, KM Sheetz, MP AF Galbraith, CG Yamada, KM Sheetz, MP TI The relationship between force and focal complex development SO JOURNAL OF CELL BIOLOGY LA English DT Article DE focal adhesion; vinculin; laser tweezers; migration; force-dependent signaling ID ACTIN STRESS FIBERS; CELL-MIGRATION; CYTOSKELETAL REORGANIZATION; TRACTION FORCES; FIBROBLASTS; CONTACTS; DYNAMICS; BINDING; MATRIX; FIBRONECTIN AB To adhere and migrate, cells must be capable of applying cytoskeletal force to the extracellular matrix (ECM) through integrin receptors. However, it is unclear if connections between integrins and the ECM are immediately capable of transducing cytoskeletal contraction into migration force, or whether engagement of force transmission requires maturation of the adhesion. Here, we show that initial integrin-ECM adhesions become capable of exerting migration force with the recruitment of vinculin, a marker for focal complexes, which are precursors of focal adhesions. We are able to induce the development of focal complexes by the application of mechanical force to fibronectin receptors from inside or outside the cell, and we are able to extend focal complex formation to vitronectin receptors by the removal of c-Src. These results indicate that cells use mechanical force as a signal to strengthen initial integrin-ECM adhesions into focal complexes and regulate the amount of migration force applied to individual adhesions at localized regions of the advancing lamella. C1 Columbia Univ, Dept Biol Sci, Sherman Fairchild Ctr, New York, NY 10027 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Sheetz, MP (reprint author), Columbia Univ, Dept Biol Sci, Sherman Fairchild Ctr, POB 2408,Rm 713,1212 Amsterdam Ave, New York, NY 10027 USA. OI Yamada, Kenneth/0000-0003-1512-6805 FU NIGMS NIH HHS [GM 36277-15, R01 GM036277] NR 41 TC 544 Z9 553 U1 6 U2 64 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 NOV 25 PY 2002 VL 159 IS 4 BP 695 EP 705 DI 10.1083/jcb.200204153 PG 11 WC Cell Biology SC Cell Biology GA 620HR UT WOS:000179528400016 PM 12446745 ER PT J AU Xu, X Ziegler, RG Waterhouse, DJ Saavedra, JE Keefer, LK AF Xu, X Ziegler, RG Waterhouse, DJ Saavedra, JE Keefer, LK TI Stable isotope dilution high-performance liquid chromatography-electrospray ionization mass spectrometry method for endogenous 2-and 4-hydroxyestrones in human urine SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE stable isotope dilution LC-MS; hormonal carcinogenesis; hydroxyestrones; p-toluenesulfonhydrazide ID CATECHOL ESTROGENS; BREAST-CANCER; RADIOIMMUNOASSAY; 2-HYDROXYESTRONE; STEROIDS; 16-ALPHA-HYDROXYESTRONE; IDENTIFICATION; NEUROSTEROIDS; QUANTITATION; METABOLITES AB A sensitive, precise and accurate stable isotope dilution high-performance liquid chromatography-electrospray ionization mass spectrometry method has been developed for measuring endogenous 2- and 4-hydroxyestrones, the main catechol estrogens in human urine. Compared to the published methods using gas chromatography-mass spectrometry, this approach simplifies sample preparation and increases the throughput of analysis. The unique part of our method is the use of a simple and rapid derivatization step that forms a hydrazone at the C-17 carbonyl group of catechol estrogens. This derivatization step has greatly enhanced method sensitivity as well as HPLC separability of 2- and 4-hydroxyestrones. Standard curves were linear over a 100-fold calibration range with correlation coefficients for the linear regression curves typically greater than 0.996. The lower limit of quantitation for each catechol estrogen is 1 ng per 10-ml urine sample, with an accuracy of 97-99% and overall precision, including the hydrolysis, extraction and derivatization steps, of 1-3% for samples prepared concurrently and 2-11% for samples prepared in several batches. This method is adequate for measuring the low endogenous levels of catechol estrogens in urine from postmenopausal women. Published by Elsevier Science B.V. C1 NCI, Off Director, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. RP Ziegler, RG (reprint author), NCI, Off Director, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Execut Plaza S,Room 8098,6120 Execut Blvd,MSC 724, Rockville, MD 20852 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-56000] NR 29 TC 29 Z9 32 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD NOV 25 PY 2002 VL 780 IS 2 BP 315 EP 330 AR PII S1570-0232(02)00539-1 DI 10.1016/S1570-0232(02)00539-1 PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 613KT UT WOS:000179132000014 PM 12401358 ER PT J AU Mannes, AJ Brown, DC Perkowski, SZ Keller, J Caudle, RM Iadarola, MJ Mengc, QC AF Mannes, AJ Brown, DC Perkowski, SZ Keller, J Caudle, RM Iadarola, MJ Mengc, QC TI Measurement of resiniferatoxin in cerebrospinal fluid by high-performance liquid chromatography SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE resiniferatoxin ID CAPSAICIN AB A sensitive and simple high-performance liquid chromatographic (HPLC) assay was developed for the quantification of resiniferatoxin (RTX) in canine cerebrospinal fluid (CSF). A reversed-phase C-18 column and acetonitrile in 0.02 M NaH2PO4 as mobile phase provided satisfactory resolution for RTX analysis. Direct HPLC analysis of the CSF samples without sample extraction or preparation improves the accuracy and detection limits of this assay. This assay was applied to measure CSF RTX content to test this method for research and clinical applications related to studies examining its analgesia effects. Published by Elsevier Science B.V. C1 NIDCR, PPCS, DASS, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Anesthesia, Philadelphia, PA 19104 USA. Univ Florida, Coll Dent, Dept Oral & Maxillofacial Surg, Gainesville, FL USA. NIDCR, PNMB, NIH, Bethesda, MD USA. RP Mannes, AJ (reprint author), NIDCR, PPCS, DASS, NIH, Bldg 10,Room 1N117,Rockville Pike, Bethesda, MD 20892 USA. OI Mannes, Andrew/0000-0001-5834-5667 FU NIDA NIH HHS [K08DA00422] NR 8 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD NOV 25 PY 2002 VL 780 IS 2 BP 475 EP 479 AR PII S1570-0232(02)00626-8 DI 10.1016/S1570-0232(02)00626-8 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 613KT UT WOS:000179132000032 PM 12401376 ER PT J AU Ishii, K Moss, B AF Ishii, K Moss, B TI Mapping interaction sites of the A20R protein component of the vaccinia virus DNA replication complex SO VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; TO-ALANINE MUTAGENESIS; POLYMERASE GENE; PROCESSIVE FORM; ENCODES; GLYCOSYLASE; KINASE; H5R; PURIFICATION; POXVIRUSES AB The vaccinia virus A20R protein is required for DNA replication, is associated with the processive form of the viral DNA polymerase, and directly interacts with the viral proteins encoded by the D4R, D5R, and H5R open reading frames as determined by a genome-wide yeast two-hybrid analysis. The purpose of the present study was to further analyze the latter protein-protein interactions. Association of an epitope-tagged A20R protein with an epitope-tagged D4R or H5R protein, expressed in vaccinia virus-infected cells, was demonstrated by binding the complex to one mAb followed by Western blotting with another. Interaction between the A20R and D5R proteins, which was weakest in the yeast two-hybrid analysis, could not be demonstrated by this method. A panel of N- and C-terminal truncated forms of the A20R protein was tested for interaction with the D4R, H5R, and D5R proteins using the yeast two-hybrid system. These studies revealed that nonoverlapping regions of A20R comprising amino acids 1 to 25, 26 to 76, and 201 to 251 were required for binding of D4R, H5R, and D5R, respectively. By contrast, no interaction of A20R with D4R could be detected after deletion of only 25 codons from either end of the latter open reading frame. A fusion protein containing either full-length A20R or only the N-terminal 25 amino acids of A20R was sufficient to capture the D4R protein, whereas the fusion protein containing A20R amino acids 26 to 426 was not, confirming the results of the yeast two-hybrid analysis. The distinct protein binding domains of the A20R protein may contribute to the assembly or stability of the multiprotein DNA replication complex. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 045, Bethesda, MD 20892 USA. NR 34 TC 36 Z9 41 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 25 PY 2002 VL 303 IS 2 BP 232 EP 239 DI 10.1006/viro.2002.1721 PG 8 WC Virology SC Virology GA 628GL UT WOS:000179984700003 PM 12490386 ER PT J AU Swanson, SJ Hale, DA Mannon, RB Kleiner, DE Cendales, LC Chamberlain, CE Polly, SM Harlan, DM Kirk, AD AF Swanson, SJ Hale, DA Mannon, RB Kleiner, DE Cendales, LC Chamberlain, CE Polly, SM Harlan, DM Kirk, AD TI Kidney transplantation with rabbit antithymocyte globulin induction and sirolimus monotherapy SO LANCET LA English DT Article ID TOLERANCE AB Renal allograft recipients generally need to take several immunosuppressive agents for life. Calcineurin inhibitors and glucocorticosteroids are the mainstays of most regimens but have undesirable chronic effects. We postulated that aggressive T-cell depletion combined with the newer immunosuppressant sirolimus would permit transplantation without multidrug treatment. We therefore tested T-cell depletion with rabbit antithymocyte globulin followed by sirolimus monotherapy in 12 patients in an open-label study. This approach was tolerated well, and all patients achieved excellent renal function, and most did not need chronic steroid treatment or calcineurin inhibitors. Rejection was typically correlated with low concentrations of sirolimus, indicating continued dependence on maintenance immunosuppression. C1 Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20307 USA. NIDDKD, Transplantat & Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Pharm, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Kirk, AD (reprint author), Room 11S-219,Bldg 10,Ctr Dr, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012; OI Kleiner, David/0000-0003-3442-4453 NR 5 TC 90 Z9 91 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 23 PY 2002 VL 360 IS 9346 BP 1662 EP 1664 DI 10.1016/S0140-6736(02)11606-0 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 618AE UT WOS:000179393900014 PM 12457792 ER PT J AU Mouton, PR Long, JM Lei, DL Howard, V Jucker, M Calhoun, ME Ingram, DK AF Mouton, PR Long, JM Lei, DL Howard, V Jucker, M Calhoun, ME Ingram, DK TI Age and gender effects on microglia and astrocyte numbers in brains of mice SO BRAIN RESEARCH LA English DT Article DE unbiased stereology; design-based stereology; neuroglia; astroglia; dentate gyrus; CA1 ID FIBRILLARY ACIDIC PROTEIN; MESSENGER-RNA INCREASES; STEREOLOGICAL ANALYSIS; CEREBRAL-CORTEX; MOUSE-BRAIN; HIPPOCAMPUS; NEURONS; RATS; EXPRESSION AB The morphological changes that occur during normal brain aging are not well understood. This study used modem stereology to assess the effects of age and gender on total numbers of astrocytes and microglia in the hippocampal formation in C57B1/6NNIA (136) mice. Astrocytes and microglia were visualized using immunocytochemistry for glial fibrillary acidic protein (GFAP) and complement receptor 3 (Mac-1), respectively, and numbers of each cell type in dentate gyrus (DG) and CA1 regions were estimated using the optical fractionator method. The results reveal significantly greater (similar to20%) numbers of microglia and astrocytes in aged females compared to young female 136 mice. We also report that on average female B6 mice have 25-40% more astrocytes and microglia in DG and CA1 regions than age-matched male C57B1/6J mice. Since astrocytes and microglia are thought to be targets of gonadal hormones, the effects of sex hormones and reproductive aging may be responsible for these findings. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIA, Gerontol Res Ctr, Neurosci Lab, NIH, Baltimore, MD 21224 USA. Univ Basel, Inst Pathol, Basel, Switzerland. Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, Kastor Neurobiol Aging Labs, New York, NY USA. RP Mouton, PR (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, NIH, Room 4E05,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 36 TC 132 Z9 134 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 22 PY 2002 VL 956 IS 1 BP 30 EP 35 AR PII S0006-8993(02)03475-3 DI 10.1016/S0006-8993(02)03475-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 620DB UT WOS:000179517200004 PM 12426043 ER PT J AU Kim, SY Sharma, S Hoskins, JR Wickner, S AF Kim, SY Sharma, S Hoskins, JR Wickner, S TI Interaction of the DnaK and DnaJ chaperone system with a native substrate, p1 RepA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK PROTEINS; MOLECULAR CHAPERONE; ESCHERICHIA-COLI; ATP HYDROLYSIS; BINDING-SPECIFICITY; NUCLEOTIDE EXCHANGE; REPLICATION ORIGIN; INITIATOR PROTEIN; PEPTIDE-BINDING; CLPA CHAPERONE AB DnaK, the Hsp70 chaperone of Escherichia coli interacts with protein substrates in an ATP-dependent manner, in conjunction with DnaJ and GrpE co-chaperones, to carry out protein folding, protein remodeling, and assembly and disassembly of multisubunit protein complexes. To understand how DnaJ targets specific proteins for recognition by the DnaK chaperone system, we investigated the interaction of DnaJ and DnaK with a known natural substrate, bacteriophage PI RepA protein. By characterizing RepA deletion derivatives, we found that DnaJ interacts with a region of RepA located between amino acids 180 and 200 of the 286-amino acid protein. A peptide corresponding to amino acids 180195 inhibited the interaction of RepA and DnaJ. Two site-directed RepA mutants with alanine substitutions in this region were about 4-fold less efficiently activated for oriP1 DNA binding by DnaJ and DnaK than wild type RepA. We also identified by deletion analysis a site in RepA, in the region of amino acids 35-49, which interacts with DnaK. An alanine substitution mutant in amino acids 36-39 was constructed and found defective in activation by DnaJ and DnaK. Taken together the results suggest that DnaJ and DnaK interact with separate sites on RepA. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wickner, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Rm 5144,37 Convent Dr,MSC37-4264, Bethesda, MD 20892 USA. NR 40 TC 31 Z9 33 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 22 PY 2002 VL 277 IS 47 BP 44778 EP 44783 DI 10.1074/jbc.M206176200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 618EE UT WOS:000179404800026 PM 12237299 ER PT J AU Bowen, C Birrer, M Gelmann, EP AF Bowen, C Birrer, M Gelmann, EP TI Retinoblastoma protein-mediated apoptosis after gamma-irradiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ABL TYROSINE KINASE; RADIATION-INDUCED APOPTOSIS; N-TERMINAL KINASE; ETOPOSIDE-INDUCED APOPTOSIS; TUMOR-SUPPRESSOR PROTEIN; CELL-CYCLE ARREST; LARGE T-ANTIGEN; C-ABL; GENE-PRODUCT; DNA-DAMAGE AB Restoration of expression of the retinoblastoma gene to DU-145 prostate-cancer cells sensitizes them to apoptosis induced by y-irradiation. In contrast, RB expression-protected cells from UV-induced cell death. RB, a caspase substrate, remained intact during apoptosis in y-irradiated DU-145 cells because serine proteases, but not caspases, were activated. In DU-145 cells, RB-mediated apoptosis involved biphasic activation of ABL kinase. ABL kinase was activated within minutes of irradiation, but in the presence of RB expression ABL kinase activation was enhanced 48 It after irradiation, coincident with the onset of cell death. Apoptosis was inhibited by RB mutants with constitutive ABL binding, but ABL overexpression overcame the effect of the RB mutant constructs. Expression of kinase-dead ABL had a dominant-negative effect on RB-mediated cell death. Activation of JUN N-terminal kinase depended on the presence of RB and occurred within 8 h of irradiation. Mutant JUN proteins that lacked the N-terminal transactivation domain and serine substrates for JUN N-terminal kinase inhibited cell death in a dominant-negative manner. Irradiation of DU-145 cells caused activation of p38 MAPK independent of the expression of RB. Inhibitors of p38 MAPK blocked apoptosis after irradiation of RB-expressing cells. The data show that after y-irradiation, intact RB mediates transcriptional activation that leads to activation of JNK and late activation of ABL kinase. In addition, p38 MAPK activation occurred independent of RB. ABL kinase, JUN N-terminal kinase, and p38 MAPK activity were all required for RB-mediated DU-145 cell death after y-irradiation. C1 NCI, NIH, Rockville, MD 20850 USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Dept Med, Washington, DC 20007 USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Dept Oncol, Washington, DC 20007 USA. RP Gelmann, EP (reprint author), NCI, NIH, Ste 300,9610 Med Ctr Dr, Rockville, MD 20850 USA. FU NCI NIH HHS [CA79912] NR 92 TC 36 Z9 37 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 22 PY 2002 VL 277 IS 47 BP 44969 EP 44979 DI 10.1074/jbc.M202000200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 618EE UT WOS:000179404800050 PM 12297496 ER PT J AU Netzel-Arnett, S Mitola, DJ Yamada, SS Chrysovergis, K Holmbeck, K Birkedal-Hansen, H Bugge, TH AF Netzel-Arnett, S Mitola, DJ Yamada, SS Chrysovergis, K Holmbeck, K Birkedal-Hansen, H Bugge, TH TI Collagen dissolution by keratinocytes requires cell surface plasminogen activation and matrix metalloproteinase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-BOUND UROKINASE; SMOOTH-MUSCLE CELLS; I COLLAGEN; DEFICIENT MICE; INTERSTITIAL COLLAGENASE; DEGRADING PROTEASES; GROWTH-FACTOR; SYSTEM; INVASION; INHIBITION AB Matrix metalloproteinase-14 is required for degradation of fibrillar collagen by mesenchymal cells. Here we show that keratinocytes use an alternative plasminogen and matrix metalloproteinase-13-dependent pathway for dissolution of collagen fibrils. Primary keratinocytes displayed an absolute requirement for serum to dissolve collagen. Dissolution of collagen was abolished in plasminogen-depleted serum and could be restored by the exogenous addition of plasminogen. Both plasminogen activator inhibitor-1 and tissue inhibitor of metalloproteinase blocked collagen dissolution, demonstrating the requirement of both plasminogen activation and matrix metalloproteinase activity for degradation. Cell surface plasmin activity was critical for the degradation process as aprotinin, but not alpha(2)-antiplasmin, prevented collagen dissolution. Keratinocytes with single deficiencies in either urokinase or tissue plasminogen activator retained the ability to dissolve collagen. However, collagen fibril dissolution was abolished in keratinocytes with a combined deficiency in both urokinase and tissue plasminogen activator. Combined, but not single, urokinase and tissue plasminogen activator deficiency also completely blocked the activation of the fibrillar collagenase, matrix metalloproteinase-13, by keratinocytes. The activation of matrix metalloproteinase-13 in normal keratinocytes was prevented by plasminogen activator inhibitor-1 and aprotinin but not by tissue inhibitor of metalloproteinase-1 and -2, suggesting that plasmin activates matrix metalloproteinase-13 directly. We propose that plasminogen activation facilitates keratinocyte-mediated collagen breakdown via the direct activation of matrix metalloproteinase-13 and possibly other fibrillar collagenases. C1 NIDCR, Matrix Metalloprot Unit, NIH, Bethesda, MD 20892 USA. NIDCR, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA. RP Birkedal-Hansen, H (reprint author), NIDCR, Matrix Metalloprot Unit, NIH, Rm 30-132,30 Convent Dr, Bethesda, MD 20892 USA. NR 77 TC 62 Z9 62 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 22 PY 2002 VL 277 IS 47 BP 45154 EP 45161 DI 10.1074/jbc.M206354200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 618EE UT WOS:000179404800073 PM 12192005 ER PT J AU Park, GT Lim, SE Jang, SI Morasso, MI AF Park, GT Lim, SE Jang, SI Morasso, MI TI Suprabasin, a novel epidermal differentiation marker and potential cornified envelope precursor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUPPRESSION SUBTRACTIVE HYBRIDIZATION; PROTEIN-KINASE-C; GENE-EXPRESSION; CELL-ENVELOPE; CDNA CLONING; CALCIUM; INVOLUCRIN; COMPLEX; KERATINOCYTES; ENVOPLAKIN AB The suprabasin gene is a novel gene expressed in mouse and human differentiating keratinocytes. We identified a partial cDNA encoding suprabasin using a suppression subtractive hybridization method between the proliferative basal and differentiating suprabasal populations of the mouse epidermis. A 3' gene-specific probe hybridized to transcripts of 0.7- and 2.2-kb pairs on Northern blots with specific detection in differentiated keratinocytes of stratified epithelia. The mouse gene was mapped to chromosome 7 by fluorescence in situ hybridization. This region is syntenic to human chromosome band 19q13.1, which contained the only region in the data bases with homology to the mouse suprabasin sequence. During embryonic mouse development, suprabasin mRNA was detected at day 15.5, coinciding with epidermal stratification. Suprabasin was detected in the suprabasal layers of the epithelia in the tongue, stomach, and epidermis. Differentiation of cultured primary epidermal keratinocytes with 0.12 mm Ca2+ or 12-O-tetradecanoylphorbol-13-acetate treatment resulted in the induction of suprabasin. The 2.2-kb cDNA transcript encodes a protein of 72 kDa with a predicted isoelectric point of 6.85. The translated sequence has an amino-terminal domain, a central domain composed of repeats rich in glycine and alanine, and a carboxyl-terminal domain. The alternatively spliced 0.7-kb transcript encodes a smaller protein that shares the NH2- and COOH-terminal regions but lacks the repeat domain region. Cross-linking experiments indicate that suprabasin is a substrate for transglutaminase 2 and 3 activity. Altogether, these results indicate that the suprabasin protein potentially plays a role in the process of epidermal differentiation. C1 NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD 20892 USA. NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Morasso, MI (reprint author), NIAMS, Dev Skin Biol Unit, NIH, Bldg 50,Rm 1525, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [Z01 AR041124-06] NR 34 TC 31 Z9 33 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 22 PY 2002 VL 277 IS 47 BP 45195 EP 45202 DI 10.1074/jbc.M205380200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 618EE UT WOS:000179404800078 PM 12228223 ER PT J AU Meyer, C Notari, L Becerra, SP AF Meyer, C Notari, L Becerra, SP TI Mapping the type I collagen-binding site on pigment epithelium-derived factor - Implications for its antiangiogenic activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CEREBELLAR GRANULE NEURONS; FACTOR PEDF; NEUROTROPHIC ACTIVITY; NONINHIBITORY SERPIN; INDUCED RETINOPATHY; SELECTIN BINDING; KINETIC-ANALYSIS; CELL-ADHESION; BOVINE EYES; INHIBITOR AB Pigment epithelium-derived factor (PEDF), a neurotrophic and antiangiogenic serpin, is identified in tissues rich in collagen, e.g. cornea, vitreous, bone, and cartilage. We show that recombinant human PEDF formed complexes with collagens from the bovine cornea and vitreous. We have examined the direct binding of PEDF to collagen I and found that interactions were ionic in nature and occurred when PEDF and collagen I were both in solution, when either one was immobilized, or even when collagen I was denatured under reducing conditions. 125 I-PEDF bound to immobilized collagen I in a saturable fashion (K-D = 123 nm). Compared with neurotrophic PEDF-derived peptides, ovalbumin and angiogenic inhibitors, only full-length PEDF competed efficiently with I-125-PEDF for the binding to immobilized collagen I (EC50 = 3 mug/ml). The collagen-binding region was analyzed using controlled proteolysis and chemically modified PEDF. Cleavage of the serpin exposed loop did not prevent binding to collagen 1. Conjugation of lysines with fluorescein increased the collagen binding affinity. However, treatment of PEDF with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide abolished it, implicating the PEDF aspartic and/or glutamic acid residues in its interaction with collagen 1. A negatively charged region on the surface of the PEDF molecule is rich in acidic residues (Glu(41), Glu(42), Glu(43) Asp(44) Asp(64), Asp(256), Asp(258), Glu(290), Glu(291), Glu(296) Asp(300), Glu(304)) available to interact directly with positively charged areas of collagen. This represents the first collagen-binding site described for a serpin, which in PEDF, is distinct from its heparin-binding region, neurotrophic active site, and its serpin exposed loop. The collagen-binding property of PEDF may play a role in surface localization and modulation of its antiangiogenic effects in the eye and bone. C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Becerra, SP (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bldg 6,Rm 308,6 Ctr Dr,MSC 2740, Bethesda, MD 20892 USA. NR 42 TC 91 Z9 91 U1 2 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 22 PY 2002 VL 277 IS 47 BP 45400 EP 45407 DI 10.1074/jbc.M208339200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 618EE UT WOS:000179404800103 PM 12237317 ER PT J AU Horkay, F Hecht, AM Grillo, I Basser, PJ Geissler, E AF Horkay, F Hecht, AM Grillo, I Basser, PJ Geissler, E TI Experimental evidence for two thermodynamic length scales in neutralized polyacrylate gels SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PHYSIOLOGICAL SALT-SOLUTIONS; POLYELECTROLYTE SOLUTIONS; NONINTEGER DIMENSIONS; SCATTERING; CHEMISTRY; HYDROGELS; SURFACES; EXCHANGE; CATIONS AB The small angle neutron scattering (SANS) behavior of fully neutralized sodium polyacrylate gels is investigated in the presence of calcium ions. Analysis of the SANS response reveals the existence of three characteristic length scales, two of which are of thermodynamic origin, while the third length is associated with the frozen-in structural inhomogeneities. This latter contribution exhibits power law behavior with a slope of about -3.6, reflecting the presence of interfaces. The osmotically active component of the scattering signal is defined by two characteristic length scales, a correlation length xi and a persistence length L. (C) 2002 American Institute of Physics. C1 NIH, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Univ Grenoble 1, Spectrometrie Phys Lab, CNRS, UMR 5588, F-38402 St Martin Dheres, France. Inst Max Von Laue Paul Langevin, F-38052 Grenoble, France. RP Horkay, F (reprint author), NIH, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, Bldg 10, Bethesda, MD 20892 USA. RI Basser, Peter/H-5477-2011 NR 23 TC 30 Z9 30 U1 0 U2 4 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD NOV 22 PY 2002 VL 117 IS 20 BP 9103 EP 9106 DI 10.1063/1.1522399 PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 611XC UT WOS:000179042300003 ER PT J AU Sergueev, K Court, D Reaves, L Austin, S AF Sergueev, K Court, D Reaves, L Austin, S TI E-coli cell-cycle regulation by bacteriophage lambda SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE cell division; p(L) operon; initiation of replication; flow cytometry; recombineering ID ESCHERICHIA-COLI; REPLICATION; GENES AB We re-examined the old but surprising claim of Kourilsky and Knapp that transient expression of genes located downstream of the p, promoter of bacteriophage lambda can induce cell-cycle synchrony in a population of Escherichia coli cells. Although we were unable to reproduce a lasting synchrony, a cessation of division, followed by one or two fairly synchronous cell divisions was observed. This line up of the cell cycle was found to be due to two genetically separable events: a temporary block of cell division and, at the same time, a block to the initiation of new rounds of DNA replication. These blocks then release after about one mass doubling so that chromosome replication and cell division occur during a short time interval in all the cells in the population. The cell division block is a result of the transient expression of the lambda kil gene. The block to initiation of DNA replication requires a region that we term bin (blocks initiation) immediately upstream of the xis gene. The region consists of ea22 and ea8.5 and two small open reading frames (ORFs) that flank them. Deletion-substitution mutagenesis suggests that all four ORFs may be required for the initiation block. The ability of the phage to modify two aspects of the host cell cycle presumably reflects a stratagem that provides the phage with an advantage for lysogeny or lytic growth. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NCI, FCRDC, Gene Regulat & Chromosome Biol Lab, Ft Detrick, MD 21702 USA. RP Austin, S (reprint author), NCI, FCRDC, Gene Regulat & Chromosome Biol Lab, POB B,Bldg 539, Ft Detrick, MD 21702 USA. NR 22 TC 25 Z9 25 U1 2 U2 13 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 22 PY 2002 VL 324 IS 2 BP 297 EP 307 DI 10.1016/S0022-2836(02)01037-9 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 621JU UT WOS:000179585900010 PM 12441108 ER PT J AU Dundr, M Hoffmann-Rohrer, U Hu, QY Grummt, I Rothblum, LI Phair, RD Misteli, T AF Dundr, M Hoffmann-Rohrer, U Hu, QY Grummt, I Rothblum, LI Phair, RD Misteli, T TI A kinetic framework for a mammalian RNA polymerase in vivo SO SCIENCE LA English DT Article ID TRANSCRIPTION; NUCLEOLUS; COMPONENTS; PROMOTER; NUCLEUS; CYCLE; CELLS AB We have analyzed the kinetics of assembly and elongation of the mammalian RNA polymerase I complex on endogenous ribosomal genes in the nuclei of living cells with the use of in vivo microscopy. We show that components of the RNA polymerase I machinery are brought to ribosomal genes as distinct subunits and that assembly occurs via metastable intermediates. With the use of computational modeling of imaging data, we have determined the in vivo elongation time of the polymerase, and measurements of recruitment and incorporation frequencies show that incorporation of components into the assembling polymerase is inefficient. Our data provide a kinetic and mechanistic framework for the function of a mammalian RNA polymerase in living cells. C1 NCI, NIH, Bethesda, MD 20892 USA. German Canc Res Ctr, D-69120 Heidelberg, Germany. Weis Ctr Res, Danville, PA 17821 USA. BioInformat Serv, Rockville, MD 20854 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 22 TC 291 Z9 297 U1 1 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 22 PY 2002 VL 298 IS 5598 BP 1623 EP 1626 DI 10.1126/science.1076164 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 617KV UT WOS:000179361600050 PM 12446911 ER PT J AU Ozaki, K Spolski, R Feng, CG Qi, CF Cheng, J Sher, A Morse, HC Liu, CY Schwartzberg, PL Leonard, WJ AF Ozaki, K Spolski, R Feng, CG Qi, CF Cheng, J Sher, A Morse, HC Liu, CY Schwartzberg, PL Leonard, WJ TI A critical role for IL-21 in regulating immunoglobulin production SO SCIENCE LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; RECEPTOR-GAMMA CHAIN; B-CELL FUNCTION; LYMPHOID DEVELOPMENT; CYTOKINE RECEPTOR; NATURAL-KILLER; MICE; EXPRESSION; MEMORY; TRANSPLANTATION AB The cytokine interleukin-21 (IL-21) is closely related to IL-2 and IL-15, and their receptors all share the common cytokine receptor gamma chain, gamma(c), which is mutated in humans with X-linked severe combined immunodeficiency disease (XSCID). We demonstrate that, although mice deficient in the receptor for IL-21 (IL-21R) have normal lymphoid development, after immunization, these animals have higher production of the immunoglobulin IgE, but lower IgG1, than wild-type animals. Mice lacking both IL-4 and IL-21R exhibited a significantly more pronounced phenotype, with dysgammaglobulinemia, characterized primarily by a severely impaired IgG response. Thus, IL-21 has a significant influence on the regulation of B cell function in vivo and cooperates with IL-4. This suggests that these gamma(c)-dependent cytokines may be those whose inactivation is primarily responsible for the B cell defect in humans with XSCID. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NHLBI, Transgen Facil, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 49,Room 4A38, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 NR 32 TC 571 Z9 593 U1 0 U2 23 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 NOV 22 PY 2002 VL 298 IS 5598 BP 1630 EP 1634 DI 10.1126/science.1077002 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 617KV UT WOS:000179361600052 PM 12446913 ER PT J AU Schutz, J Dersch, CM Horel, R Spetea, M Koch, M Meditz, R Greiner, E Rothman, RB Schmidhammer, H AF Schutz, J Dersch, CM Horel, R Spetea, M Koch, M Meditz, R Greiner, E Rothman, RB Schmidhammer, H TI Synthesis and biological evaluation of 14-alkoxymorphinans. 17. Highly delta opioid receptor selective 14-alkoxy-substituted indolo- and benzofuromorphinans SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTAGONIST ACTIVITY; IMMUNE-SYSTEM; NALTRINDOLE; BINDING; AGONIST; KAPPA; AFFINITY; ANALOGS; SERIES; CELLS AB 14-Alkoxy analogues of naltrindole and naltriben differently substituted in positions 5 and 17 and at the indole nitrogen (compounds 28-44) have been synthesized in an effort to enhance the delta potency and/or delta selectivity and in order to further elaborate on structure-activity relationships of this class of compounds. Introduction of a 14-alkoxy instead of the 14-hydroxy group present in naltrindole resulted in somewhat lower delta binding affinity, while in many cases (compounds 31, 34, 37, 40, 41, 44, HS 378) the (5 receptor selectivity was considerably increased. An ethoxy group in position 14 is superior to other alkoxy groups concerning delta affinity and selectivity (34, 41, 42, 44, HS 378). In [35S]GTPgammaS binding, compounds 34,41, and HS 378 exhibited about one-tenth the antagonist potency of naltrindole at delta opioid receptors while their delta antagonist selectivity was considerably higher. 17-Methyl-substituted compounds 35 and 44 were found to be pure delta receptor agonists in this test. C1 NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, Baltimore, MD 21244 USA. Univ Innsbruck, Inst Pharm, Dept Pharmaceut Chem, A-6020 Innsbruck, Austria. RP Rothman, RB (reprint author), NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, Baltimore, MD 21244 USA. EM rrothman@belite.com; Helmut.Schmidhammer@uibk.ac.at NR 44 TC 21 Z9 21 U1 0 U2 1 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 NOV 21 PY 2002 VL 45 IS 24 BP 5378 EP 5383 DI 10.1021/jm020940p PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 617DC UT WOS:000179344400020 PM 12431065 ER PT J AU Lee, YS Worthington, SE Krauss, M Brooks, BR AF Lee, YS Worthington, SE Krauss, M Brooks, BR TI Reaction mechanism of chorismate mutase studied by the combined potentials of quantum mechanics and molecular mechanics SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID CLAISEN REARRANGEMENT; BACILLUS-SUBTILIS; CATALYTIC MECHANISM; TRANSITION-STATE; ACTIVE-SITE; ELECTROSTATIC CATALYSIS; PREPHENATE; ENZYME; QM/MM; SELECTION AB The reaction path for the rearrangement of chorismate to prephenate in B.subtilis has been determined in a QM/MM study including the entire protein environment while treating the reaction with ab initio quantum chemistry. In addition to the reactant, chorismate, the side-chains of glu78 and arg90 are included in the quantum region to explore whether the strong ionic hydrogen bonding of the side chains to the substrate has a catalytic effect. The hydrogen bonds from glu78 and arg90 induce electronic effects that activate the substrate. The energetic residue analysis finds that the binding from arg7, arg63, and arg90 are all catalytic due to a differential stabilization along the reaction path of the transition state with respect to the reactant by the local environment. A global QM/MM optimization including the entire protein environment shows only slight changes in the protein environment around the active site along the reaction path. The rearrangement reaction occurs with almost a complete break in the C-O ether bond in chorismate before the C-C bond forms to create prephenate. In this study, the reacting complex forms a hydrogen bond to arg63 that stabilizes the region near the protein surface where the substrate may enter the active site. C1 Natl Inst Stand & Technol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. NIH, Ctr Informat Technol, Ctr Mol Modeling, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Krauss, M (reprint author), Natl Inst Stand & Technol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. NR 27 TC 51 Z9 52 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD NOV 21 PY 2002 VL 106 IS 46 BP 12059 EP 12065 DI 10.1021/jp0268718 PG 7 WC Chemistry, Physical SC Chemistry GA 617AE UT WOS:000179336200023 ER PT J AU Sidorov, IA Hirsch, KS Harley, CB Dimitrov, DS AF Sidorov, IA Hirsch, KS Harley, CB Dimitrov, DS TI Cancer cell dynamics in presence of telomerase inhibitors: Analysis of in vitro data SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article ID PEPTIDE NUCLEIC-ACIDS; IMMORTAL CELLS; LENGTH; PROLIFERATION; HETEROGENEITY; ASSOCIATION; SEQUENCES; LEUKEMIA; GROWTH; MODELS AB The inhibition of telomerase activity in actively dividing cells leads to suppression of cell growth after a time delay (inhibitory delay) required to reach a threshold telomeric DNA size. We developed a mathematical model of the dynamics of telomere size distribution and cell growth in the presence of telomere inhibitors that allowed quantification of the inhibitory delay. The model based on the solution of a system of differential equations described quantitatively recent experimental data on dynamics of cultured cells in presence of telomerase inhibitors. The analysis of the data by this model suggested the existence of at least two distinct subpopulations of cells with different proliferative activity. Size distribution of telomeres. fraction of proliferating cells, and tumor doubling times are of critical importance for the dynamics of cancer cells growth in presence of telomerase inhibitors. Rapidly growing cells with large telomeric DNA heterogeneity and small proliferating fractions as well as those with very short homogeneous telomeres would be the most sensitive to telomerase inhibitors. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NCI, NIH, Ft Detrick, MD 21702 USA. Emergent Biotechnol LLC, Redwood City, CA 94608 USA. Geron Corp, Menlo Pk, CA 94025 USA. RP Dimitrov, DS (reprint author), NCI, NIH, Bldg 469,POB B, Ft Detrick, MD 21702 USA. NR 45 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD NOV 21 PY 2002 VL 219 IS 2 BP 225 EP 233 DI 10.1006/yjtbi.3117 PG 9 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 630YF UT WOS:000180138700006 PM 12413877 ER PT J AU Lee, JS FitzGibbon, E Butman, JA Dufresne, CR Kushner, H Wientroub, S Robey, PG Collins, MT AF Lee, JS FitzGibbon, E Butman, JA Dufresne, CR Kushner, H Wientroub, S Robey, PG Collins, MT TI Normal vision despite narrowing of the optic canal in fibrous dysplasia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MCCUNE-ALBRIGHT-SYNDROME; ACTIVATING G(S)ALPHA MUTATION; REVERSIBLE VISUAL-LOSS; STIMULATORY G-PROTEIN; NERVE DECOMPRESSION; SKULL BASE; BONE; GENE; BLINDNESS; CHILDHOOD AB Background: Fibrous dysplasia of bone frequently involves the anterior base of the cranium and results in encasement of the optic-nerve canals. It has been assumed that such encasement leads to constriction and eventual blindness. There is controversy about whether patients should be regularly monitored or whether they should undergo prophylactic decompression of the optic nerve. This question is of particular concern in patients with normal vision, since the risks associated with surgical decompression include blindness. Methods: We studied 38 patients with fibrous dysplasia of the lesser wing of the sphenoid bone. The patients underwent a detailed neuro-ophthalmologic examination and computed tomography of the face and skull, reformatted to measure the extent of involvement of the optic canal and the area of the canals. The results were compared with those of 38 age- and sex-matched controls. Results: Of the 38 patients, 15 were male and 23 female, and their mean age was 26 years. Twelve had polyostotic fibrous dysplasia, and 26 had the McCune-Albright syndrome. Sixty-seven optic canals were affected by fibrous dysplasia; in 49 of them (73 percent) there was complete encasement. The mean (+/-SD) areas of the right and left canals were 9.6+/-3.8 mm(sup 2) and 9.9+/-3.6 mm(sup 2), respectively, in the patients, as compared with 12.0+/-2.9 mm(sup 2) and 11.9+/-2.7 mm(sup 2) in the controls (P=0.009 for the comparison of the right areas and P=0.03 for the comparison of the left areas by the paired t-test). In all but two of the patients, the results of neuro-ophthalmologic examination were normal. In the two patients with monocular visual impairment, the areas of the optic canals were similar on the normal and abnormal sides. Conclusions: Encasement of the optic canal in fibrous dysplasia causes narrowing of the canal, but that in itself does not result in visual loss. Therefore, prophylactic decompression of the optic nerve does not appear to be indicated on the basis of the presence of fibrous dysplasia on diagnostic images alone, since it does not correlate with visual loss. C1 NEI, Vraniofacial & Skeleton Dis Branch, Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Div Plast Surg, Washington, DC 20007 USA. Biomed Comp Res Inst, Philadelphia, PA USA. Tel Aviv Med Ctr & Sch Med, Dana Childrens Hosp, Dept Pediat Orthoped Surg, IL-64239 Tel Aviv, Israel. RP Lee, JS (reprint author), Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, 521 Parnassus Ave,C-522, San Francisco, CA 94143 USA. RI Butman, John/A-2694-2008; Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; Butman, John/0000-0002-1547-9195 NR 26 TC 79 Z9 88 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 21 PY 2002 VL 347 IS 21 BP 1670 EP 1676 DI 10.1056/NEJMoa020742 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 617BL UT WOS:000179339900005 PM 12444181 ER PT J AU Horng, S Miller, FG AF Horng, S Miller, FG TI Arthroscopic surgery for osteoarthritis of the knee SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Horng, S (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 21 PY 2002 VL 347 IS 21 BP 1719 EP 1719 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 617BL UT WOS:000179339900022 ER PT J AU Eidsath, A Chernomordik, V Gandjbakhche, A Smith, P Russo, A AF Eidsath, A Chernomordik, V Gandjbakhche, A Smith, P Russo, A TI Three-dimensional localization of fluorescent masses deeply embedded in tissue SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID IN-VIVO FLUORESCENCE; BREAST-CANCER; IMAGE-RECONSTRUCTION; NODE LOCALIZATION; CONTRAST AGENTS; NANOSPHERES; MEDIA; SPECTROSCOPY; DRAINAGE; PHOTON AB In this paper we present preliminary results obtained for tissue-like phantoms and ex vivo tissue slabs using a prototype system for CW infrared fluorescence imaging of fluorescent markers. Besides the design of the experimental system itself, we have developed a theoretical model of photon migration under experimental conditions and associated 3D reconstruction algorithms to estimate the distribution of fluorescent markers. Application of the developed algorithms in the analysis of 2D intensity distributions of the fluorescent light demonstrated their ability to reconstruct positions of the markers (including their depths) with good accuracy (error less than or equal to 10%) both for the Intralipid phantoms and ex vivo tissue slabs. C1 NIH, DBEPS, ORS, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD 20892 USA. NCI, ROB, NIH, Bethesda, MD 20892 USA. RP Eidsath, A (reprint author), NIH, DBEPS, ORS, Bldg 10, Bethesda, MD 20892 USA. NR 23 TC 18 Z9 18 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD NOV 21 PY 2002 VL 47 IS 22 BP 4079 EP 4092 AR PII S0031-9155(02)37207-5 DI 10.1088/0031-9155/47/22/311 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 628DK UT WOS:000179977000012 PM 12476983 ER PT J AU Presciuttini, S Toni, C Tempestini, E Verdiani, S Casarino, L Spinetti, I De Stefano, F Domenici, R Bailey-Wilson, JE AF Presciuttini, S Toni, C Tempestini, E Verdiani, S Casarino, L Spinetti, I De Stefano, F Domenici, R Bailey-Wilson, JE TI Inferring relationships between pairs of individuals from locus heterozygosities SO BMC GENETICS LA English DT Article ID MISSPECIFIED RELATIONSHIPS; DNA; PATERNITY; INFERENCE; IDENTIFICATION; RELATEDNESS; GENOTYPES; KINSHIP; PROGRAM AB Background: The traditional exact method for inferring relationships between individuals from genetic data is not easily applicable in all situations that may be encountered in several fields of applied genetics. This study describes an approach that gives affordable results and is easily applicable; it is based on the probabilities that two individuals share 0, 1 or both alleles at a locus identical by state. Results: We show that these probabilities (z(i)) depend on locus heterozygosity ( H), and are scarcely affected by variation of the distribution of allele frequencies. This allows us to obtain empirical curves relating z(i)'s to H for a series of common relationships, so that the likelihood ratio of a pair of relationships between any two individuals, given their genotypes at a locus, is a function of a single parameter, H. Application to large samples of mother-child and full-sib pairs shows that the statistical power of this method to infer the correct relationship is not much lower than the exact method. Analysis of a large database of STR data proves that locus heterozygosity does not vary significantly among Caucasian populations, apart from special cases, so that the likelihood ratio of the more common relationships between pairs of individuals may be obtained by looking at tabulated z(i) values. Conclusions: A simple method is provided, which may be used by any scientist with the help of a calculator or a spreadsheet to compute the likelihood ratios of common alternative relationships between pairs of individuals. C1 Univ Pisa, Dipartimento Biomed, Pisa, Italy. Univ Genoa, Dipartimento Med Legale Lavoro Psicol Med & Crimi, Genoa, Italy. Univ Cagliari, Ist Med Legale & Anat & Istol Patol, Cagliari, Italy. NHGRI, Baltimore, MD USA. RP Presciuttini, S (reprint author), Univ Pisa, Dipartimento Biomed, Pisa, Italy. NR 28 TC 12 Z9 13 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD NOV 20 PY 2002 VL 3 AR 23 DI 10.1186/1471-2156-3-23 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 632KL UT WOS:000180222400001 PM 12441003 ER PT J AU Wright, JT Bakris, G Greene, T Agodoa, LY Appel, LJ Charleston, J Cheek, D Douglas-Baltimore, JG Gassman, J Glassock, R Hebert, L Jamerson, K Lewis, J Phillips, RA Toto, RD Middleton, JP Rostand, SG AF Wright, JT Bakris, G Greene, T Agodoa, LY Appel, LJ Charleston, J Cheek, D Douglas-Baltimore, JG Gassman, J Glassock, R Hebert, L Jamerson, K Lewis, J Phillips, RA Toto, RD Middleton, JP Rostand, SG CA African Amer Study Kidney Dis Hype TI Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease - Results from the AASK trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 74th Annual Scientific Sessions of the American-Heart-Association CY NOV 11-14, 2001 CL ANAHEIM, CALIFORNIA SP Amer Heart Assoc ID CONVERTING-ENZYME-INHIBITION; GLOMERULAR-FILTRATION RATE; CALCIUM-CHANNEL BLOCKERS; CHRONIC RENAL-DISEASE; AFRICAN-AMERICANS; RISK-FACTOR; NONDIABETIC NEPHROPATHIES; DIABETIC NEPHROPATHY; NEPHROSCLEROSIS; INSUFFICIENCY AB Context Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD. Objective To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension. Design Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998. Setting and Participants A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years. Interventions Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n=554) or 92 mm Hg or less (lower; n=540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n=441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n=436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n=217). Open-label agents were added to achieve the assigned BP goals. Main Outcome Measures Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or greater than or equal to25 mL/min per 1.73 m(2)) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol. Results Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m(2) per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 ml per year; P=.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group=2%; 95% confidence interval [CI], -22% to 21 %; P=.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P=.04) and 38% (95% CI, 14%-56%; P=.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups. Conclusions No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline. C1 Case Western Reserve Univ, Univ Hosp Cleveland, Dept Med, Cleveland, OH 44106 USA. Louis Stokes Cleveland Dept Vet Affairs Med Ctr, Dept Med, Cleveland, OH 44106 USA. Cleveland Clin Fdn, Dept Biostat, Cleveland, OH 44195 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA. NIDDKD, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Prevent Med, Baltimore, MD USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Ohio State Univ, Dept Med, Columbus, OH 43210 USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. Mt Sinai Sch Med, New York, NY USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Alabama, Birmingham, AL USA. RP Wright, JT (reprint author), Case Western Reserve Univ, Univ Hosp Cleveland, Dept Med, 11000 Euclid Ave,Horwitz Tower,Suite 7311, Cleveland, OH 44106 USA. FU NCRR NIH HHS [2P20 RR11104, 5M01 RR-00071, M01 RR-00080, M01 RR00052, M01 RR00827, P20-RR11145]; NIDDK NIH HHS [U01 DK048643, DK 2818-02]; PHS HHS [M01 00032] NR 50 TC 1001 Z9 1028 U1 6 U2 46 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 NOV 20 PY 2002 VL 288 IS 19 BP 2421 EP 2431 DI 10.1001/jama.288.19.2421 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 616FB UT WOS:000179292300025 PM 12435255 ER PT J AU Waters, DD Alderman, EL Hsia, J Howard, BV Cobb, FR Rogers, WJ Ouyang, P Thompson, P Tardif, JC Higginson, L Bittner, V Steffes, M Gordon, DJ Proschan, M Younes, N Verter, JI AF Waters, DD Alderman, EL Hsia, J Howard, BV Cobb, FR Rogers, WJ Ouyang, P Thompson, P Tardif, JC Higginson, L Bittner, V Steffes, M Gordon, DJ Proschan, M Younes, N Verter, JI TI Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ESTROGEN-REPLACEMENT; HEART-DISEASE; ARTERY DISEASE; CARDIOVASCULAR-DISEASE; E CONSUMPTION; PROGRESSION; RISK; PREVENTION; SIMVASTATIN; PROGESTIN AB Context Hormone replacement therapy (HRT) and antioxidant vitamins are widely used for secondary prevention in postmenopausal women with coronary disease, but no clinical trials have demonstrated benefit to support their use. Objective To determine whether HRT or antioxidant vitamin supplements, alone or in combination, influence the progression of coronary artery disease in postmenopausal women, as measured by serial quantitative coronary angiography. Design, Setting, and Patients The Women's Angiographic Vitamin and Estrogen (WAVE) Trial, a randomized, double-blind trial of 423 postmenopausal women with at least one 15% to 75% coronary stenosis at baseline coronary angiography. The trial was conducted from July 1997 to January 2002 in 7 clinical centers in the United States and Canada. Interventions Patients were randomly assigned in a 2 x 2 factorial design to receive either 0.625 mg/d of conjugated equine estrogen (plus 2.5 mg/d of medroxyprogesterone acetate for women who had not had a hysterectomy), or matching placebo, and 400 IU of vitamin E twice daily plus 500 mg of vitamin C twice daily, or placebo. Main Outcome Measure Annualized mean (SD) change in minimum lumen diameter (MLD) from baseline to concluding angiogram of all qualifying coronary lesions averaged for each patient. Patients with intercurrent death or myocardial infarction (MI) were imputed the worst rank of angiographic outcome. Results The mean (SD) interval between angiograms was 2.8 (0.9) years. Coronary progression, measured in mean (SD) change, worsened with HRT by 0.047 (015) mm/y and by 0.024 (0.15) mm/y with HRT placebo (P=.17); and for antioxidant vitamins by 0.044 (0.15) mm/y and with vitamin placebo by 0.028 (0.15) mm/y (P=32). When patients with intercurrent death or MI were included, the primary outcome showed an increased risk for women in the active HRT group (P=.045), and suggested an increased risk in the active vitamin group (P=.09). Fourteen patients died in the HRT group and 8 in the HRT placebo group (hazard ratio [HR], 1.8; 95% confidence interval [CI], 0.75-4.3), and 16 in the vitamin group and 6 in the vitamin placebo group (HR, 2.8; 95% CI, 1.1-7.2). Death, nonfatal MI, or stroke occurred in 26 HRT patients vs 15 HRT controls (HR, 1.9; 95% CI, 0.97-3.6) and in 26 vitamin patients and 18 vitamin controls (HR, 1.5; 95% CI, 0.80-2.9). There was no interaction between the 2 treatment interventions. Conclusion In postmenopausal women with coronary disease, neither HRT nor antioxidant vitamin supplements provide cardiovascular benefit. Instead, a potential for harm was suggested with each treatment. C1 San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Stanford Univ, Div Cardiovasc Med, Stanford, CA 94305 USA. George Washington Univ, Dept Med, Washington, DC USA. George Washington Univ, Dept Stat, Washington, DC 20052 USA. Medstar Res Inst, Dept Cardiol, Washington, DC USA. Duke Univ, Duke Ctr Living, Durham, NC USA. Univ Alabama, Div Cardiol, Birmingham, AL USA. Johns Hopkins Bayview Med Ctr, Div Cardiol, Baltimore, MD USA. Hartford Hosp, Div Cardiol, Hartford, CT 06115 USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Univ Ottawa, Inst Heart, Ottawa, ON, Canada. Univ Minnesota, Cent Biochem Lab, Minneapolis, MN USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Waters, DD (reprint author), San Francisco Gen Hosp, Div Cardiol, Room 5G1,1001 Potrero Ave, San Francisco, CA 94110 USA. FU NCRR NIH HHS [M01 RR02715]; NHLBI NIH HHS [N01-HV-68170, N01-HV-68165] NR 34 TC 352 Z9 365 U1 2 U2 9 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 NOV 20 PY 2002 VL 288 IS 19 BP 2432 EP 2440 DI 10.1001/jama.288.19.2432 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 616FB UT WOS:000179292300026 PM 12435256 ER PT J AU Burdette, JE Chen, SN Lu, ZZ Xu, HY White, BEP Fabricant, DS Liu, JH Fong, HHS Farnsworth, NR Constantinou, AI van Breemen, RB Pezzuto, JM Bolton, JL AF Burdette, JE Chen, SN Lu, ZZ Xu, HY White, BEP Fabricant, DS Liu, JH Fong, HHS Farnsworth, NR Constantinou, AI van Breemen, RB Pezzuto, JM Bolton, JL TI Black cohosh (Cimicifuga racemosa L.) protects against menadione-induced DNA damage through scavenging of reactive oxygen species: Bioassay-directed isolation and characterization of active principles SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Cimicifuga racemosa (black cohosh, Actaea racemosa); single-cell gel electrophoresis assay (comet assay); menadione; antioxidant; reactive oxygen species ID ACID PHENETHYL ESTER; CAFFEIC ACID; IN-VITRO; OXIDATIVE STRESS; FERULIC ACID; PISCIDIC ACID; METABOLISM; CANCER; ANTIOXIDANTS; HEPATOCYTES AB The roots/rhizomes of Cimicifuga racemosa L. (Nutt.) (black cohosh) have traditionally been used to treat menopausal symptoms through an unknown mechanism of action. In an effort to determine if black cohosh had additional health benefits, methanol extracts were investigated for their potential to scavenge reactive oxygen species and to protect against menadione-induced DNA damage. These extracts effectively scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals. In addition, the extracts showed dose-dependent decreases in DNA single-strand breaks and oxidized bases induced by the quinone menadione using the comet (single-cell gel electrophoresis assay) and fragment length associated repair enzyme assays, respectively. Bioassay-directed fractionation of the methanolic extracts using the DPPH assay as a monitor led to the isolation of nine antioxidant active compounds: caffeic acid (1), methyl caffeate (2), ferulic acid (3), isoferulic acid (4), fukinolic acid (5), cimicifugic acid A (6), cimicifugic acid B (7), cimicifugic acid F (8), cimiracemate A (9), and cimiracemate B (10). Six of these antioxidants were found to reduce menadione-induced DNA damage in cultured S30 breast cancer cells with the following order of potency: methyl caffeate (2) > caffeic acid (1) > ferulic acid (3) > cimiracemate A (9) > cimiracemate B (10) > fukinolic acid (5). These data suggest that black cohosh can protect against cellular DNA damage caused by reactive oxygen species by acting as antioxidants. C1 Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, UIC,NIH, Ctr Bot & Dietary Supplements Res, Chicago, IL 60612 USA. Univ Illinois, Dept Surg, Chicago, IL 60612 USA. RP Bolton, JL (reprint author), Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, 833 S Wood St, Chicago, IL 60612 USA. OI Constantinou, Andreas/0000-0003-0365-1821 FU NCCIH NIH HHS [P50 AT00155] NR 45 TC 57 Z9 61 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD NOV 20 PY 2002 VL 50 IS 24 BP 7022 EP 7028 DI 10.1021/jf020725h PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 615UU UT WOS:000179266000015 PM 12428954 ER PT J AU Merchant, MS Woo, CW Mackall, CL Thiele, CJ AF Merchant, MS Woo, CW Mackall, CL Thiele, CJ TI Potential use of imatinib in Ewing's sarcoma: Evidence for in vitro and in vivo activity SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID KINASE INHIBITOR STI571; ABL TYROSINE KINASE; STEM-CELL FACTOR; GROWTH-FACTOR; C-KIT; POSITIVE CELLS; IN-VITRO; PDGF-C; APOPTOSIS; RECEPTOR AB Background: Ewing's sarcoma cells express c-kit, a receptor tyrosine kinase, and its ligand, stem cell factor (SCF), creating a potential autocrine loop that may promote tumor survival. We thus examined whether the specific tyrosine kinase inhibitor imatinib mesylate (hereafter imatinib; formerly ST1571) could inhibit the proliferation of Ewing's sarcoma cells in vitro and in vivo. Methods: The effect of imatinib on e-kit expression and phosphorylation in Ewing's sarcoma cells was examined by immunoblotting. The effect of imatinib on cell growth and apoptosis was examined with an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay and with a morphologic test and Annexin V staining, respectively. The effect of imatinib oral therapy (every 12 hours for 5-7 days) on primary tumor growth was assessed in Ewing's sarcoma xenografts in SCID/bg mice (5 or 10 mice per group). Results: All Ewing's sarcoma cell lines tested were sensitive to imatinib-mediated apoptosis with a concentration inhibiting growth by 50% (IC50) of 10-12 muM. Imatinib inhibited SCF-mediated e-kit phosphorylation (IC50 = 0.1-0.5 muM). In the xenograft model, imatinib treatment resulted in the regression or control of primary Ewing's sarcomas. After 6 days of treatment, the mean lower extremity volume including xenograft tumor was 3744 mm(3) (95% confidence interval [CI] = 3050 to 4437 mm(3)), 1442 mm(3) (95% Cl = 931 to 1758 mm(3)), and 346 mm(3) (95% CI = 131 to 622 mm 3) in mice treated with carrier alone or with imatinib at 50 mg/kg or at 100 mg/kg, respectively. Conclusions: Imatinib interferes with growth of all Ewing's sarcoma cell lines tested in vitro and in vivo. Targeted inhibition of tyrosine kinase-dependent autocrine loops, therefore, may be a viable therapeutic strategy for Ewing's sarcoma. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Merchant, MS (reprint author), 10 Ctr Dr,MSC 1298,Bldg 10-13N240, Bethesda, MD 20892 USA. NR 29 TC 79 Z9 81 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 20 PY 2002 VL 94 IS 22 BP 1673 EP 1679 PG 7 WC Oncology SC Oncology GA 615UJ UT WOS:000179265000007 PM 12441322 ER PT J AU Moore, LE Smith, AH Eng, C Kalman, D DeVries, S Bhargava, V Chew, K Moore, D Ferreccio, C Rey, OA Waldman, FM AF Moore, LE Smith, AH Eng, C Kalman, D DeVries, S Bhargava, V Chew, K Moore, D Ferreccio, C Rey, OA Waldman, FM TI Arsenic-related chromosomal alterations in bladder cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; TRANSITIONAL-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; DISEASE ENDEMIC AREA; ARTESIAN WELL WATER; DRINKING-WATER; BLACKFOOT-DISEASE; MALIGNANT NEOPLASMS; POLY(ADP-RIBOSE) POLYMERASE; CYTOGENETIC ANALYSIS AB Background: Previous studies have demonstrated that ingestion of arsenic in drinking water is a strong risk factor for several forms of cancer, including bladder cancer. It is not known whether arsenic-related cancers are genetically similar to cancers in unexposed individuals or what mechanisms of carcinogenesis may underlie their formation. This study was designed to compare chromosomal alterations in bladder cancers of arsenic-exposed individuals to provide insight into the mechanism of how arsenic may induce or promote cancer. Methods: A case-case study was conducted in Argentina and Chile examining chromosomal alterations in bladder tumor DNA in 123 patients who had been exposed to arsenic in their drinking water. Patients were placed into one of four arsenic exposure categories according to their average 5-year peak arsenic exposure. Patients were also classified as ever smokers or never smokers. Comparative genomic hybridization was used to identify chromosomal alterations throughout the genome. All statistical tests were two-sided. Results: The total number of chromosomal alterations was higher in individuals exposed to higher arsenic levels (5.7 +/- 5.1, 5.6 +/- 5.1, 7.3 +/- 7.4, and 9.1 +/- 6.5 [mean standard deviation] chromosomal alterations per tumor with increasing arsenic exposure; P-trend = .02, adjusted for stage and grade). The trend was stronger in high-grade (G2-G3) tumors (6.3 +/- 5.5, 8.3 +/- 4.7, 10.3 +/- 7.8, and 10.5 +/- 6.4 alterations per tumor; P-trend = .01) than it was in low-grade (G1) tumors (3.5 +/- 3.1, 1.1 +/- 1.1, 2.5 +/- 2.5, and 3.6 +/- 3.2 alterations per tumor; P-trend = .79). The mean number of chromosomal alterations also increased with tumor stage and grade (P-trend<.001) independently of arsenic exposure but was not associated with smoking history. Deletion of part or all of chromosome 17p (P-trend<.001) showed the strongest association with arsenic exposure. Conclusions: Bladder tumors in patients with higher levels of arsenic exposure showed higher levels of chromosomal instability. Most of the chromosomal alterations associated with arsenic exposure were also associated with tumor stage and grade, raising the possibility that bladder tumors from arsenic-exposed patients may behave more aggressively than tumors from unexposed patients. C1 Pontificia Univ Catolica Chile, Santiago, Chile. Univ Washington, Seattle, WA 98195 USA. Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Moore, LE (reprint author), NCI, Occupat Epidemiol Branch, 6120 Execut Blvd,EPS 8118,MSC 7240, Bethesda, MD 20892 USA. RI Smith, Allan/F-9249-2011 FU NCI NIH HHS [CA47537, CA89715]; NIEHS NIH HHS [P30-ES01896, P42-ES04705] NR 65 TC 48 Z9 50 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 20 PY 2002 VL 94 IS 22 BP 1688 EP 1696 PG 9 WC Oncology SC Oncology GA 615UJ UT WOS:000179265000009 PM 12441324 ER PT J AU Goedert, JJ Vitale, F Lauria, C Serraino, D Tainburini, M Montella, M Messina, A Brown, EE Rezza, G Gafa, L Romano, N AF Goedert, JJ Vitale, F Lauria, C Serraino, D Tainburini, M Montella, M Messina, A Brown, EE Rezza, G Gafa, L Romano, N CA Classical Kaposi Sarcoma Working G TI Risk factors for classical Kaposi's sarcoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HOMOSEXUAL MEN; HERPES-VIRUS; HUMAN-HERPESVIRUS-8; TRANSMISSION; ANTIBODIES; SMOKING AB Background: Classical Kaposi's sarcoma (KS) is a malignancy of lymphatic endothelial skin cells. Although all forms of KS are associated with the KS-associated herpesvirus (KSHV), classical KS occurs in a small fraction of KSHV-infected people. We sought to identify risk factors for classical KS in KSHV-infected individuals. Methods: Lifestyle and medical history data from case patients with biopsy-proven non-AIDS (non-acquired immunodeficiency syndrome) KS in Italy were compared by logistic regression analysis with data from population-based KSHV-seropositive control subjects of comparable age and sex. After KSHV immunofluorescence testing, randomly selected patients on the rosters of local physicians were identified as control subjects. Risk of KS was estimated by odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: From April 13, 1998, through October 8, 2001, we enrolled 141 classical KS case patients and 192 KSHV-seropositive control subjects of similar age (mean = 72 years for case patients and 73 years for control subjects) and sex (30% female case patients and 35% female control subjects). The strongest association was a reduced risk of KS with cigarette smoking (OR = 0.25, 95% CI = 0.14 to 0.45). Cigarette smoking intensity and duration could be evaluated for men, among whom the risk for KS was inversely related to the amount of cumulative smoking (P-trend<.001). KS risk decreased approximately 20% (OR = 0.81, 95% CI = 0.74 to 0.89) for each 10 pack-years reported, and it was decreased sevenfold (OR = 0.14, 95% CI = 0.07 to 0.30) with more than 40 pack-years. In multivariable analysis, a decreased KS risk was associated with smoking (OR = 0.23, 95% CI = 0.12 to 0.44); but an increased KS risk was associated with topical corticosteroid use (OR = 2.73, 95% CI = 1.35 to 5.51), infrequent bathing (OR = 1.85, 95% CI = 1.04 to 3.33), and a history of asthma (OR = 2.18, 95% CI = 0.95 to 4.97) or of allergy among men (OR = 2.59, 95% CI = 1.15 to 5.83) but not among women (OR = 0.09, 95% CI = 0.003 to 2.76). KS was not related to other exposures or illnesses examined. Conclusion: Risk for classical KS was approximately fourfold lower in cigarette smokers, a result that requires confirmation by other studies. Identification of how smoking affects KS risk may lead to a better understanding of the pathogenesis of this malignancy and interventions for its prevention. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. Ist Super Sanita, Epidemiol & Biostat Lab, I-00161 Rome, Italy. Univ Catania, Dipartimento Sci Biomed, Catania, Italy. Ist Tumori Fdn G Pascale, Serv Epidemiol & Prevenz, Naples, Italy. IRCCS, Ist Nazl Malattie Infett Lazzaro Spallanzani, Dipartimento Epidemiol, Rome, Italy. Lega Italiana Lotta Contro & Tumori, Sez Ragusa, Ragusa, Italy. Univ Palermo, Dipartimento Igiene & Microbiol Giuseppe DAlessan, Palermo, Italy. RP Goedert, JJ (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 8012, Rockville, MD 20892 USA. RI REZZA, GIOVANNI/D-4393-2016 OI REZZA, GIOVANNI/0000-0003-0268-6790 FU NCI NIH HHS [N02-CP-91027] NR 32 TC 67 Z9 68 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 20 PY 2002 VL 94 IS 22 BP 1712 EP 1718 PG 7 WC Oncology SC Oncology GA 615UJ UT WOS:000179265000012 PM 12441327 ER PT J AU El Khadem, HS Coxon, B AF El Khadem, HS Coxon, B TI Resonance-stabilized phenylazo-ene-phenylimine cations of cyclobutanetetraone derivatives SO CARBOHYDRATE RESEARCH LA English DT Article DE anions; bathochromic shift; cations; chiral shift reagents; cyclobutenedione phenylazo-phenylamines; enolization; hypsochromic shift; NMR spectroscopy; UV-Vis spectrophotometry ID SQUARIC ACID; POLY(PHENYLHYDRAZONES); PHENYLHYDRAZINE; SPECTROSCOPY; PROTEIN AB Cyclobutenedione phenylazo-phenylamines A,ere found to exhibit bathochromic shifts in acidic media and hypsochromic shifts in basic media, like phenylazo-phenylhydrazones. The bathochromic shifts are due to the formation of resonance-stabilized cations and the hypsochromic shifts to enolization. The phenylazo-phenylamines and their cations and anions have been studied by NMR spectroscopy. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 American Univ, Dept Chem, Washington, DC 20016 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP El Khadem, HS (reprint author), American Univ, Dept Chem, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD NOV 19 PY 2002 VL 337 IS 21-23 BP 2161 EP 2170 AR PII S0008-6215(02)00119-2 DI 10.1016/S0008-6215(02)00119-2 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 618PB UT WOS:000179425500024 PM 12433479 ER PT J AU Nossal, R Zimmerberg, J AF Nossal, R Zimmerberg, J TI Endocytosis: Curvature to the ENTH degree SO CURRENT BIOLOGY LA English DT Editorial Material ID CLATHRIN; MEMBRANE; NUCLEATION; VESICLES; AP180 C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Nossal, R (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 20 TC 17 Z9 17 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 19 PY 2002 VL 12 IS 22 BP R770 EP R772 AR PII S0960-9822(02)01289-7 DI 10.1016/S0960-9822(02)01289-7 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 619QC UT WOS:000179486700008 PM 12445401 ER PT J AU Beral, V Hamajima, N Hirose, K Rohan, T Calle, EE Heath, CW Coates, RJ Liff, JM Talamini, R Chantarakul, N Koetsawang, S Rachawat, D Morabia, A Schuman, L Stewart, W Szklo, M Bain, C Schofield, F Siskind, V Band, P Coldman, AJ Gallagher, RP Hislop, TG Yang, P Kolonel, LM Nomura, AMY Hu, J Johnson, KC Mao, Y De Sanjose, S Lee, N Marchbanks, P Ory, HW Peterson, HB Wilson, HG Wingo, PA Ebeling, K Kunde, D Nishan, P Hopper, JL Colditz, G Gajalakshmi, V Martin, N Pardthaisong, T Solpisornkosol, S Theetranont, C Boosiri, B Chutivongse, S Jimakorn, P Virutamasen, P Wongsrichanalai, C Ewertz, M Adami, HO Bergkvist, L Magnusson, C Persson, I Chang-Claude, J Paul, C Skegg, DCG Spears, GFS Boyle, P Evstifeeva, T Daling, JR Hutchinson, WB Malone, K Noonan, EA Stanford, JL Thomas, DB Weiss, NS White, E Andrieu, N Bremond, A Clavel, F Gairard, B Lansac, J Piana, L Renaud, R Izquierdo, A Viladiu, P Cuevas, HR Ontiveros, P Palet, A Salazar, SB Arsitizabal, N Cuadros, A Tryggvadottir, L Tulinius, H Bachelot, A Le, MG Peto, J Franceschi, S Lubin, F Modan, B Ron, E Wax, Y Friedman, GD Hiatt, RA Levi, F Bishop, T Kosmelj, K Primic-Zakelj, M Ravnihar, B Stare, J Beeson, WL Fraser, G Bulbrook, RD Cuzick, J Duffy, SW Fentiman, IS Hayward, JL Wang, DY McMichael, AJ McPherson, K Hanson, RL Leske, MC Mahoney, MC Nasca, PC Varma, AO Weinstein, AL Moller, TR Olsson, H Ranstam, J Goldbohm, RA van den Brandt, PA Apelo, RA Baens, J de la Cruz, JR Javier, B Lacaya, LB Ngelangel, CA La Vecchia, C Negri, E Marubini, E Ferraroni, M Gerber, M Richardson, S Segala, C Gatei, D Kenya, P Kungu, A Mati, JG Brinton, LA Hoover, R Schairer, C Spirtas, R Lee, HP Rookus, MA van Leeuwen, FE Schoenberg, JA McCredie, M Gammon, MD Clarke, EA Jones, L Neil, A Vessey, M Yeates, D Appleby, P Banks, E Bull, D Crossley, B Goodill, A Green, J Hermon, C Key, T Langston, N Lewis, C Reeves, G Collins, R Doll, R Peto, R Mabuchi, K Preston, D Hannaford, P Kay, C Rosero-Bixby, L Gao, YT Jin, F Yuan, JM Wei, HY Yun, T Zhiheng, C Berry, G Cooper Booth, J Jelihovsky, T MacLennan, R Shearman, R Wang, QS Baines, CJ Miller, AB Wall, C Lund, E Stalsberg, H Shu, XO Zheng, W Katsouyanni, K Trichopoulou, A Trichopoulos, D Dabancens, A Martinez, L Molina, R Salas, O Alexander, XE Anderson, K Folsom, AR Hulka, BS Bernstein, L Enger, S Haile, RW Paganini-Hill, A Pike, MC Ross, RK Ursin, G Yu, MC Longnecker, MP Newcomb, P Bergkvist, L Kalache, A Farley, TMM Holck, S Meirik, O AF Beral, V Hamajima, N Hirose, K Rohan, T Calle, EE Heath, CW Coates, RJ Liff, JM Talamini, R Chantarakul, N Koetsawang, S Rachawat, D Morabia, A Schuman, L Stewart, W Szklo, M Bain, C Schofield, F Siskind, V Band, P Coldman, AJ Gallagher, RP Hislop, TG Yang, P Kolonel, LM Nomura, AMY Hu, J Johnson, KC Mao, Y De Sanjose, S Lee, N Marchbanks, P Ory, HW Peterson, HB Wilson, HG Wingo, PA Ebeling, K Kunde, D Nishan, P Hopper, JL Colditz, G Gajalakshmi, V Martin, N Pardthaisong, T Solpisornkosol, S Theetranont, C Boosiri, B Chutivongse, S Jimakorn, P Virutamasen, P Wongsrichanalai, C Ewertz, M Adami, HO Bergkvist, L Magnusson, C Persson, I Chang-Claude, J Paul, C Skegg, DCG Spears, GFS Boyle, P Evstifeeva, T Daling, JR Hutchinson, WB Malone, K Noonan, EA Stanford, JL Thomas, DB Weiss, NS White, E Andrieu, N Bremond, A Clavel, F Gairard, B Lansac, J Piana, L Renaud, R Izquierdo, A Viladiu, P Cuevas, HR Ontiveros, P Palet, A Salazar, SB Arsitizabal, N Cuadros, A Tryggvadottir, L Tulinius, H Bachelot, A Le, MG Peto, J Franceschi, S Lubin, F Modan, B Ron, E Wax, Y Friedman, GD Hiatt, RA Levi, F Bishop, T Kosmelj, K Primic-Zakelj, M Ravnihar, B Stare, J Beeson, WL Fraser, G Bulbrook, RD Cuzick, J Duffy, SW Fentiman, IS Hayward, JL Wang, DY McMichael, AJ McPherson, K Hanson, RL Leske, MC Mahoney, MC Nasca, PC Varma, AO Weinstein, AL Moller, TR Olsson, H Ranstam, J Goldbohm, RA van den Brandt, PA Apelo, RA Baens, J de la Cruz, JR Javier, B Lacaya, LB Ngelangel, CA La Vecchia, C Negri, E Marubini, E Ferraroni, M Gerber, M Richardson, S Segala, C Gatei, D Kenya, P Kungu, A Mati, JG Brinton, LA Hoover, R Schairer, C Spirtas, R Lee, HP Rookus, MA van Leeuwen, FE Schoenberg, JA McCredie, M Gammon, MD Clarke, EA Jones, L Neil, A Vessey, M Yeates, D Appleby, P Banks, E Bull, D Crossley, B Goodill, A Green, J Hermon, C Key, T Langston, N Lewis, C Reeves, G Collins, R Doll, R Peto, R Mabuchi, K Preston, D Hannaford, P Kay, C Rosero-Bixby, L Gao, YT Jin, F Yuan, JM Wei, HY Yun, T Zhiheng, C Berry, G Cooper Booth, J Jelihovsky, T MacLennan, R Shearman, R Wang, QS Baines, CJ Miller, AB Wall, C Lund, E Stalsberg, H Shu, XO Zheng, W Katsouyanni, K Trichopoulou, A Trichopoulos, D Dabancens, A Martinez, L Molina, R Salas, O Alexander, XE Anderson, K Folsom, AR Hulka, BS Bernstein, L Enger, S Haile, RW Paganini-Hill, A Pike, MC Ross, RK Ursin, G Yu, MC Longnecker, MP Newcomb, P Bergkvist, L Kalache, A Farley, TMM Holck, S Meirik, O CA Collaborative Group on Hormonal Factors in Breast Cancer TI Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58515 women with breast cancer and 95067 women without the disease SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; alcohol; tobacco; smoking; collaborative analysis ID ORAL-CONTRACEPTIVE USE; ITALIAN CASE-CONTROL; POSTMENOPAUSAL WOMEN; CIGARETTE-SMOKING; RISK-FACTORS; YOUNG-WOMEN; BEVERAGE CONSUMPTION; MENOPAUSAL STATUS; SOUTHERN FRANCE; HORMONE USE AB Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1 % per 10 g per day, P < 0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers= 1.03, 95% CI 0.98 - 1.07, and for current smokers=0.99, 0.92 - 1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. (C) 2002 Cancer Research UK. C1 Radcliffe Infirm, Canc Res UK Epidemiol Unit, Oxford OX2 6HE, England. Aichi Res Inst, Nagoya, Japan. Emory Univ, Atlanta, GA USA. Aviano Cancer Ctr, Pordenone, Italy. Mahidol Univ, Bangkok, Thailand. Johns Hopkins Univ, Breast Tumor Collaborat Stud, Baltimore, MD USA. Univ Queensland, Brisbane, Australia. Central Inst Cancer Res, Berlin, Germany. Catalan Inst Oncol, Barcelona, Spain. Univ Melbourne, Ctr Genet Epidemiol, Melbourne, Australia. Chennai Cancer Inst, Madras, India. Chiang Mai Univ, Chiang Mai, Thailand. Chulalongkorn Univ, Bangkok, Thailand. Danish Cancer Soc, Aalborg, Denmark. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. Deutches Krebsforschungszentr, Heidelberg, Germany. Univ Otago, Dunedin, New Zealand. Eur Inst Oncol, Milan, Italy. INSERM, French Multictr Breast Stud, Villejuif, France. Girona Cancer Registry, Girona, Spain. Hosp Gen Mexico City, Mexico City, Mexico. Hosp Univ, Cali, Colombia. Icelandic Cancer Soc, Reykjavik, Iceland. INSERM, Inst Gustav Roussey, Villejuif, France. Internatl Agcy Res Cancer, Lyon, France. Israel Chaim Sheba Med Ctr, Tel Hashomer, Israel. Inst Univ Med Soc Prevent, Lausanne, Switzerland. Cancer Res UK Genet Epidemiol Lab, Leeds, England. Inst Oncol, Ljubljana, Slovenia. Cancer Res UK Dept Math Statist Epidemiol, London, England. London Sch Hygeine Trop Med, London, England. Univ Hosp, Lund, Sweden. Maastricht Univ, Maastricht, Netherlands. Univ Philippines, Manila, Philippines. Ist Mario Negri, Milan, Italy. Ist Nazionale Tumor, Div Statist Med Biometria, Milan, Italy. Ist Statist Med Biometria, Milan, Italy. Montpellier Cancer Ctr, Montpellier, France. INSERM, Montpellier, France. Nairobi Ctr Res Reproduct, Nairobi, Kenya. Natl Univ Singapore, Singapore, Singapore. Netherlands Cancer Inst, Amsterdam, Netherlands. NSW Cancer Council, Sydney, NSW, Australia. Dpt Publ Health & Primary Care, Oxford, England. Cancer Res UK Epidemiol Unit, Oxford, England. Radiat Effects Res Fdn, Hiroshima, Japan. Royal Coll Gen Practitioners, Oral Contracept Study, London, England. Univ Costa Rica, San Jose, Costa Rica. Shanghai Cancer Inst, Shanghai, Peoples R China. Shanghai Inst Planned Parenthood Res, Shanghai, Peoples R China. Dept Publ Health, Sydney, Australia. Tianjin Cancer Inst, Tianjin, Peoples R China. Dept Publ Health Sci, Toronto, ON, Canada. Tromso Univ, Tromso, Norway. Univ Athens, Sch Med, Athens, Greece. Univ Chile, Santiago, Chile. Univ Edinburgh, Edinburgh, Midlothian, Scotland. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. Univ Nottingham, Nottingham, England. Univ So Calif, Los Angeles, CA USA. WHO, Geneva, Switzerland. Albert Einstein Coll Med, New York, NY USA. Amer Canc Soc, Atlanta, GA 30329 USA. Univ Hawaii Manoa, Canc Res Ctr, Honolulu, HI 96822 USA. Brigham & Womens Hosp, Channing Lab, Harvard Med Sch, Boston, MA USA. Loma Linda Univ, Loma Linda, CA 92350 USA. NCI, Bethesda, MD 20892 USA. New Jersey State Dept Hlth, Trenton, NJ 08625 USA. Columbia Univ, Sch Publ Hlth, New York, NY USA. Vanderbilt Univ, Nashville, TN USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA. Univ Wisconsin, Comprehens Canc Ctr, Madison, WI 53706 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Canc Res UK MRC BHF, Epidemiol Studies Unit, Oxford, England. Canc Res UK MRC BHF, Clin Trial Serv Unit, Oxford, England. RP Beral, V (reprint author), Radcliffe Infirm, Canc Res UK Epidemiol Unit, Gibson Bldg,Woodstock Rd, Oxford OX2 6HE, England. RI Ranstam, Jonas/A-4386-2009; de Sanjose Llongueras, Silvia/H-6339-2014; Beral, Valerie/B-2979-2013; Katsouyanni, Klea/D-4856-2014; Negri, Eva/B-7244-2013; Clavel-Chapelon, Francoise/G-6733-2014; Brinton, Louise/G-7486-2015; Hamajima, Nobuyuki/I-7237-2014; IBIS, GENICA/O-1906-2015; ANDRIEU, Nadine/H-4255-2014; Colditz, Graham/A-3963-2009; Ferraroni, Monica/D-6548-2017; OI Ranstam, Jonas/0000-0002-8287-7273; Katsouyanni, Klea/0000-0002-0132-9575; Negri, Eva/0000-0001-9712-8526; Brinton, Louise/0000-0003-3853-8562; Colditz, Graham/0000-0002-7307-0291; Ferraroni, Monica/0000-0002-4542-4996; Magnusson, Cecilia/0000-0002-8567-6725; Tryggvadottir, Laufey/0000-0001-8067-9030; La Vecchia, Carlo/0000-0003-1441-897X; Longnecker, Matthew/0000-0001-6073-5322 NR 73 TC 500 Z9 507 U1 4 U2 42 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 18 PY 2002 VL 87 IS 11 BP 1234 EP 1245 DI 10.1038/sj.bjc.6600596 PG 12 WC Oncology SC Oncology GA 625MH UT WOS:000179819900009 PM 12439712 ER PT J AU Hayes, SM Laky, K El-Khoury, D Kappes, DJ Fowlkes, BJ Love, PE AF Hayes, SM Laky, K El-Khoury, D Kappes, DJ Fowlkes, BJ Love, PE TI Activation-induced modification in the CD3 complex of the gamma delta T cell receptor SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE T cell receptor; structure; glycosylation; CD3; activation ID ANTIGEN RECEPTOR; ALPHA-BETA; INTRAEPITHELIAL LYMPHOCYTES; TCR-BETA; GLYCOSYLATION; SUBUNIT; MICE; AUTOIMMUNITY; EXPRESSION; PATHWAYS AB The T cell antigen receptor complexes expressed on alphabeta and gammadelta T cells differ not only in their respective clonotypic heterodimers but also in the subunit composition of their CD3 complexes. The gammadelta T cell receptors (TCRs) expressed on ex vivo gammadelta T cells lack CD3delta, whereas alphabeta TCRs contain CD3delta. While this result correlates with the phenotype of CD3delta(-/-) mice, in which gammadelta T cell development is unaffected, it is inconsistent with the results of previous studies reporting that CD3delta is a component of the gammadelta TCR. Since earlier studies examined the subunit composition of gammadelta TCRs expressed on activated and expanded peripheral gammadelta T cells or gammadelta TCR+ intestinal intraepithelial lymphocytes, we hypothesized that activation and expansion may lead to changes in the CD3 subunit composition of the gammadelta TCR. Here, we report that activation and expansion do in fact result in the inclusion of a protein, comparable in mass and mobility to CD3delta, in the gammadelta TCR. Further analyses revealed that this protein is not CD3delta, but instead is a differentially glycosylated form of CD3gamma. These results provide further evidence for a major difference in the subunit composition of alphabeta- and gammadelta TCR complexes and raise the possibility that modification of CD3gamma may have important functional consequences in activated gammadelta T cells. C1 NICHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. NIAID, Cellular & Mol Immunol Lab, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA. RP Love, PE (reprint author), NICHD, Lab Mammalian Genes & Dev, NIH Bldg 6B,Rm 2B-210,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 17 Z9 18 U1 0 U2 4 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 NOV 18 PY 2002 VL 196 IS 10 BP 1355 EP 1361 DI 10.1084/jem.20021196 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 618HL UT WOS:000179412600008 PM 12438426 ER PT J AU Molldrem, JJ Kant, S Lu, SJ Rios, R Streicher, H Wang, CQ Giralt, S O'Brien, S Cortes, J Champlin, R Martin, T Wieder, E AF Molldrem, JJ Kant, S Lu, SJ Rios, R Streicher, H Wang, CQ Giralt, S O'Brien, S Cortes, J Champlin, R Martin, T Wieder, E TI Peptide vaccination with PR1 elicits active T cell immunity that induces cytogenetic remission in acute myelogenous leukemia. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Dept Bone Marrow Transplant, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Leukemia Dept, Houston, TX 77030 USA. NCI, CTEP, Bethesda, MD 20892 USA. RI Kanodia, Shreya/E-5169-2010 NR 0 TC 6 Z9 7 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 NOV 16 PY 2002 VL 100 IS 11 MA 8 BP 6A EP 6A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700009 ER PT J AU Takahashi, Y McCoy, JP Carvallo, C Rivera, C Igarashi, T Srinivasan, R Young, N Childs, R AF Takahashi, Y McCoy, JP Carvallo, C Rivera, C Igarashi, T Srinivasan, R Young, N Childs, R TI PNH cells are not resistant to allogeneic immune attack and can be eradicated following nonmyeloablative allogeneic stem cell transplantation (NST). SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, DLM, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 21 BP 9A EP 9A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700022 ER PT J AU Gladwin, MT Jison, ML Sachdev, V Nichols, JS Coles, W Ernst, IR Ognibene, FP Rodgers, GP Schechter, AN Castro, O AF Gladwin, MT Jison, ML Sachdev, V Nichols, JS Coles, W Ernst, IR Ognibene, FP Rodgers, GP Schechter, AN Castro, O TI A prospective clinical study of the prevalence and etiology of secondary pulmonary hypertension in sickle cell disease. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. NHLBI, NIH, Cardiovasc Branch, Bethesda, MD 20892 USA. NIDDK, NIH, Mol & Clin Hematol Branch, Bethesda, MD USA. NIDDK, NIH, Biol Chem Lab, Bethesda, MD USA. Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2002 VL 100 IS 11 MA 23 BP 10A EP 10A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700024 ER PT J AU Tsujimura, H Tamura, T Ozato, K AF Tsujimura, H Tamura, T Ozato, K TI ICSBP/IRF-8 is a transcription factor critical for the development of B220(+) plasmacytoid dendritic cells. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NICHHD, NIH, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 34 BP 12A EP 13A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700035 ER PT J AU Syed, HP Castro, O Gladwin, M Palestine, A AF Syed, HP Castro, O Gladwin, M Palestine, A TI Central retinal vein occlusion in sickle cell disease SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Howard Univ Hosp, Ctr Sickle Cell Dis, Washington, DC USA. NIH, Bethesda, MD 20892 USA. Metropolitan Retina Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3545 BP 23B EP 23B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800088 ER PT J AU Ostera, GR Schechter, AN Moore, LR Milliron, S Chalmers, JJ Zborowski, M AF Ostera, GR Schechter, AN Moore, LR Milliron, S Chalmers, JJ Zborowski, M TI Cell magnetophoresis: Separation of red cells based on hemoglobin magnetic susceptibility. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIDDK, NIH, Biol Chem Lab, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Biomed Engn, Cleveland, OH 44195 USA. Ohio State Univ, Dept Chem Engn, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV 16 PY 2002 VL 100 IS 11 MA 84 BP 26A EP 26A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700085 ER PT J AU Asakura, T Lian, LR Chen, QK Iyamu, WE Abdulmalik, O Bulgnara, C Evans, G AF Asakura, T Lian, LR Chen, QK Iyamu, WE Abdulmalik, O Bulgnara, C Evans, G TI Screening of new therapeutic agents for the treatment of sickle cell disease: Five-year summary of the NIH Sickle Cell Disease Reference Laboratory SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Hosp, Boston, MA 02115 USA. NHLBI, Blood Div, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV 16 PY 2002 VL 100 IS 11 MA 3564 BP 27B EP 27B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800107 ER PT J AU Orlic, D Arai, AE Sheikh, FH Agyeman, KO McGehee, J Hoyt, RF Sachdev, V Yu, ZX Hong, S Metzger, ME Dunbar, CE AF Orlic, D Arai, AE Sheikh, FH Agyeman, KO McGehee, J Hoyt, RF Sachdev, V Yu, ZX Hong, S Metzger, ME Dunbar, CE TI Cytokine mobilized CD34+cells do not benefit rhesus monkeys following induced myocardial infarction. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHGRI, NIH, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NHLBI, NIH, Cardiac Energet Lab, Bethesda, MD 20892 USA. NHLBI, Lab Anim Med & Surg, Bethesda, MD 20892 USA. NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. NHLBI, Pathol Branch, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, Bethesda, MD 20892 USA. NR 0 TC 10 Z9 11 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 NOV 16 PY 2002 VL 100 IS 11 MA 94 BP 28A EP 29A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700095 ER PT J AU Gao, CJ Kang, EM Kuramoto, K Agricola, B von Kalle, C Donahue, RE Tisdale, JF AF Gao, CJ Kang, EM Kuramoto, K Agricola, B von Kalle, C Donahue, RE Tisdale, JF TI Retrovirally-transduced muscle derived cells possess both myogenic and hematopoietic potential: Direct evidence at a clonal level in the non-human primate model. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Childrens Hosp, Cincinnati, OH 45229 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIDDK, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 98 BP 29A EP 30A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700099 ER PT J AU Nakamura, T Iwasaki, M Osato, M Ito, Y Jenkins, NA Copeland, NG AF Nakamura, T Iwasaki, M Osato, M Ito, Y Jenkins, NA Copeland, NG TI Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PA SP Amer Soc Hematol C1 Japanese Fdn Canc Res, Tokyo 117548, Japan. Natl Univ Singapore, Inst Mol & Cell Biol, Singapore, Singapore. Natl Canc Inst, Mouse Canc Genet Program, Frederick, MD USA. RI Osato, Motomi/N-5056-2014 OI Osato, Motomi/0000-0003-3982-9054 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 109 BP 32A EP 32A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700110 ER PT J AU El Ouriaghli, FJD Fujiwara, H Melenhorst, JJ Sconnochia, G Hensel, N Barrett, J AF El Ouriaghli, FJD Fujiwara, H Melenhorst, JJ Sconnochia, G Hensel, N Barrett, J TI Neutrophil elastase enzymatically antagonizes the in vitro action of G-CSF: Implication for the regulation of granulopoiesis. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3603 BP 36B EP 36B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800146 ER PT J AU Caruccio, L Bettinotti, M Matsuo, K Sharon, V Stroncek, D AF Caruccio, L Bettinotti, M Matsuo, K Sharon, V Stroncek, D TI Expression of neutrophil membrane glycoprotein CD177 increases during pregnancy. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Kurume Univ, Dept Internal Med 1, Fukuoka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3610 BP 38B EP 38B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800153 ER PT J AU Cornetta, K Laughlin, M Carter, S Wall, D Weinthal, J Sievers, E Wagner, J Sweetman, R McCarthy, P Jensen, L Chao, N AF Cornetta, K Laughlin, M Carter, S Wall, D Weinthal, J Sievers, E Wagner, J Sweetman, R McCarthy, P Jensen, L Chao, N TI Umbilical Cord Blood Transplantation in adults: Results of a prospective, multi-institutional, NHBLI sponsored trial. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Indiana Univ, Indianapolis, IN 46204 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. EMMES Corp, Bethesda, MD USA. Texas Transplant Inst, San Antonio, TX USA. N Texas Childrens Hosp, Dallas, TX USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Minnesota, Minneapolis, MN 55455 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Duke Univ, Durham, NC 27706 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 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 NOV 16 PY 2002 VL 100 IS 11 MA 146 BP 42A EP 42A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700147 ER PT J AU Risitano, AM Green, S Sharpe, S O'Keefe, C Zeng, WH Maciejewski, JP Young, NS AF Risitano, AM Green, S Sharpe, S O'Keefe, C Zeng, WH Maciejewski, JP Young, NS TI TCR sequencing: The molecular signature of autoimmunity in aplastic anemia. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. Taussig Canc Ctr, Expt Hematol & Hematopoiesis Div, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 155 BP 44A EP 44A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700156 ER PT J AU Gallagher, PG Pilon, AM Nilson, DG Orkin, SH Bodine, DM AF Gallagher, PG Pilon, AM Nilson, DG Orkin, SH Bodine, DM TI Decreased mRNA expression and altered chromatin configuration of non-globin Erythroid Krupple-Like Factor (EKLF) target genes in EKLF-deficient mice. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Yale Univ, New Haven, CT 06520 USA. NHGRI, NIH, GMBB, Bethesda, MD 20892 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 165 BP 47A EP 47A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700166 ER PT J AU Safford, MG Allen, ANL Schwartz, RH Powell, J AF Safford, MG Allen, ANL Schwartz, RH Powell, J TI Egr2 and Egr3 are upregulated in anergic T cells and negatively regulate T cell activation. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. NIH, LCMI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 170 BP 48A EP 48A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700171 ER PT J AU Vance, BA Schenk, AS Erdmann, A Fowler, D Gress, RE AF Vance, BA Schenk, AS Erdmann, A Fowler, D Gress, RE TI NK receptor diversity analysis of freshly isolated and cultured lymphocytes. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3672 BP 52B EP 52B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800215 ER PT J AU Simak, J Holada, K Risitano, AM Zivny, JH Young, NS Vostal, JG AF Simak, J Holada, K Risitano, AM Zivny, JH Young, NS Vostal, JG TI Elevated counts of circulating endothelial membrane microparticles in patients with paroxysmal nocturnal hemoglobinuria. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD USA. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 202 BP 56A EP 57A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700203 ER PT J AU Iwasaki-Arai, J Pu, Z Huettner, CS Fenyus, M Lekstrom-Himes, J Tenen, DG Akashi, K AF Iwasaki-Arai, J Pu, Z Huettner, CS Fenyus, M Lekstrom-Himes, J Tenen, DG Akashi, K TI C/EBP alpha deficiency in hematopoiesis induces accumulation of non-malignant myeloblasts mimicking acute myelogenous leukemia. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA USA. NIAID, LHD, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 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 NOV 16 PY 2002 VL 100 IS 11 MA 218 BP 61A EP 61A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700219 ER PT J AU Licht, T Bukki, J Gotze, K Prettin, S Ambudkar, SV Gottesman, MM Peschel, C AF Licht, T Bukki, J Gotze, K Prettin, S Ambudkar, SV Gottesman, MM Peschel, C TI Role of histone deacetylation in coordinate regulation of multidrug resistance genes in human hematopoietic cells. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Tech Univ Munich, Klinikum Rechts Isar, Med Klin 3, D-8000 Munich, Germany. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 241 BP 66A EP 67A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700242 ER PT J AU Rothwell, SW Chen, WK Krishnamurti, C AF Rothwell, SW Chen, WK Krishnamurti, C TI Gene expression profile of human pulmonary endothelial cells subjected to hypoxic conditions. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Walter Reed Army Inst Res, Dept Blood Res, Silver Spring, MD USA. NHLBI, Div Extramural Affairs, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3748 BP 69B EP 69B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800291 ER PT J AU Caruccio, L Walkovich, K Bettinotti, M Stroncek, D AF Caruccio, L Walkovich, K Bettinotti, M Stroncek, D TI PRV-1 (CD177) polymorphisms: Correlation between high frequency single nucleotide substitutions and neutrophil surface protein expression. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 259 BP 71A EP 71A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700260 ER PT J AU Beleslin-Cokic, BB Cokic, VP Yu, XB Weksler, BB Schechter, AN Noguchi, CT AF Beleslin-Cokic, BB Cokic, VP Yu, XB Weksler, BB Schechter, AN Noguchi, CT TI Erythropoietin stimulates a nitric oxide response in vascular endothelial SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. Johns Hopkins Univ, Sydney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3760 BP 72B EP 72B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800303 ER PT J AU Igarashi, T Srinivasan, R Wynberg, J Takahashi, Y Becknell, B Caligiuri, M Linehan, WM Childs, R AF Igarashi, T Srinivasan, R Wynberg, J Takahashi, Y Becknell, B Caligiuri, M Linehan, WM Childs, R TI Generation of allogeneic NK cells with selective cytotoxicity to melanoma and renal cell carcinoma based on KIR-ligand incompatibility. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NCI, UOB, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 4 Z9 4 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 NOV 16 PY 2002 VL 100 IS 11 MA 264 BP 73A EP 73A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700265 ER PT J AU Wagner, JE Thompson, JS Carter, S Jensen, L Kernan, NA AF Wagner, JE Thompson, JS Carter, S Jensen, L Kernan, NA TI Impact of graft-versus-host disease (GVHD) prophylaxis on 3-year disease-free survival (DFS): Results of a multi-center, randomized phase II-III trial comparing T cell depletion/cyclosporine (TCD) and methotrexate/cyclosporine (M/C) in 410 recipients of unrelated donor bone marrow (BM). SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Bethesda, MD 20892 USA. Unrelated Donor Marrow Transplantat Trial, Bethesda, MD USA. NR 0 TC 5 Z9 5 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 NOV 16 PY 2002 VL 100 IS 11 MA 274 BP 75A EP 76A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700275 ER PT J AU Gallagher, PG Nilson, DG Wong, C Garrett, LJ Cline, AP Bodine, DM AF Gallagher, PG Nilson, DG Wong, C Garrett, LJ Cline, AP Bodine, DM TI A two base pair deletion at position-72/-73 of the ankyrin-1 promoter associated with hereditary spherocytosis disrupts TFIID complex binding and decreases transcription of a linked reporter gene. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Yale Univ, New Haven, CT 06520 USA. NHGRI, NIH, GMMB, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 281 BP 77A EP 78A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700282 ER PT J AU Weisbein, JL Wong, C Cline, AP Garrett, LJ Felsenfeld, G Gallagher, PG Bodine, DM AF Weisbein, JL Wong, C Cline, AP Garrett, LJ Felsenfeld, G Gallagher, PG Bodine, DM TI Mutations at positions-108 and-153 of the erythroid ankyrin promoter decrease expression in transgenic mice by disrupting insulator function. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHGRI, Hematopoiesis Sect, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 282 BP 78A EP 78A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700283 ER PT J AU Kobayashi, T Yamaguchi, M Kim, S Morikawa, J Ogawa, S Ueno, S Suh, E Dougherty, E Shmulevich, I Shiku, H Wei, Z AF Kobayashi, T Yamaguchi, M Kim, S Morikawa, J Ogawa, S Ueno, S Suh, E Dougherty, E Shmulevich, I Shiku, H Wei, Z TI Gene expression profiling and immunohistochemistry revealed differences in both lymphoma cells and vascular specific gene expression in de novo CD5+ and CD5- diffuse large B-cell lymphomas. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Mie Univ, Sch Med, Dept Internal Med 2, Tsu, Mie 514, Japan. Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Div Computat Biol, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Canc Genom Core Lab, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 335 BP 91A EP 91A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700336 ER PT J AU Kuramoto, K Sellers, S Agricola, B Metzger, M Donahue, R von Kalle, C Dunbar, CE AF Kuramoto, K Sellers, S Agricola, B Metzger, M Donahue, R von Kalle, C Dunbar, CE TI A genetic tracking approach to studying in vivo hematopoiesis and response to cytokines in non-human primates. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Mol Hematopoiesis Sect, Bethesda, MD 20892 USA. Univ Freiburg, D-7800 Freiburg, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 406 BP 110A EP 110A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700407 ER PT J AU Candotti, F Podsakoff, GM Schurman, SH Muul, LM Engel, BC Carbonaro, DA Jagadeesh, GJ Tuschong, LM Carter, CS Ramsey, WJ Choi, C Smogorzweska, T Hershfield, MS Read, EJ Tisdale, JF Dunbar, CE Kohn, DB AF Candotti, F Podsakoff, GM Schurman, SH Muul, LM Engel, BC Carbonaro, DA Jagadeesh, GJ Tuschong, LM Carter, CS Ramsey, WJ Choi, C Smogorzweska, T Hershfield, MS Read, EJ Tisdale, JF Dunbar, CE Kohn, DB TI Clinical evaluation of retroviral vectors for corrective gene transfer of adenosine deaminase (ADA) deficiency. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, Bethesda, MD 20892 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 428 BP 116A EP 116A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700429 ER PT J AU Ting, SS Hartnett, BJ Linton, GF Malech, HL Felsburg, PJ AF Ting, SS Hartnett, BJ Linton, GF Malech, HL Felsburg, PJ TI Gene therapy in canine X-linked severe combined immunodeficiency by RD114 pseudotyped oncoretroviral vector. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, Dept Host Def, Bethesda, MD 20892 USA. Univ Penn, Sch Vet Med, Dept Clin Studies, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 427 BP 116A EP 116A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700428 ER PT J AU Bhanu, NV Trice, TA Lee, YWT Miller, JL AF Bhanu, NV Trice, TA Lee, YWT Miller, JL TI Stem cell factor increases fetal hemoglobin production through activation of MEK and p44 MAPK. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIDDK, NIH, Biol Chem Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 438 BP 118A EP 119A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700439 ER PT J AU Peters, LL Moriyama, K Huizing, M Gahl, WA Bonifacino, JS Ciciotte, SL Gwynn, B AF Peters, LL Moriyama, K Huizing, M Gahl, WA Bonifacino, JS Ciciotte, SL Gwynn, B TI Cappuccino, a mouse model of Hermansky-Pudlak syndrome, encodes a novel protein that is part of the pallidin-muted (BLOC-1) complex. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Jackson Lab, Bar Harbor, ME 04609 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 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 NOV 16 PY 2002 VL 100 IS 11 MA 464 BP 125A EP 125A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700465 ER PT J AU Levantini, E Giorgetti, A Cerisoli, F Bertolotti, F Guidi, A Traggiai, E Martin, R Iscove, NM Keller, G Aplan, P Hoang, T Magli, CM AF Levantini, E Giorgetti, A Cerisoli, F Bertolotti, F Guidi, A Traggiai, E Martin, R Iscove, NM Keller, G Aplan, P Hoang, T Magli, CM TI A novel role of the homeobox gene OTX1 in hematopoiesis. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Ist Tecnol Biomed, Area Ric Pisa, Pisa, Italy. Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada. Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. Mt Sinai Sch Med, Inst Gene Therapy & Mol Med, New York, NY USA. NCI, Div Clin Sci, Gaithersburg, MD USA. RI traggiai, elisabetta/A-2316-2009; Cerisoli, Francesco/C-9711-2009; Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 490 BP 131A EP 131A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700491 ER PT J AU Fellowes, VS Husebekk, A Gress, RE Vance, BA AF Fellowes, VS Husebekk, A Gress, RE Vance, BA TI Detection of breast cancer tumor cell contamination in peripheral blood mononuclear cell concentrates. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Hosp No Norway, Dept Immunol & Transfus Med, Tromso, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 4024 BP 135B EP 135B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800567 ER PT J AU Gurevich, RM Pineault, N Aplan, PD Humphries, RK AF Gurevich, RM Pineault, N Aplan, PD Humphries, RK TI The NUP98-Topoisomerase I (NUP98-TOP1) fusion associated with t(11;20) can induce marked myeloproliferation independent of a mutation designed to block TOP1 catalytic activity. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. NIH, Ctr Canc Res, Genet Branch, Gaithersburg, MD USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 506 BP 135A EP 135A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700507 ER PT J AU Husebekk, A Fellowes, VS Vance, BA Gress, RE Lynghaug, GM Dormanen, K Virijevic, I Skogen, B AF Husebekk, A Fellowes, VS Vance, BA Gress, RE Lynghaug, GM Dormanen, K Virijevic, I Skogen, B TI A sensitive and specific test for detection of breast cancer cells in peripheral blood. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Hosp No Norway, Dept Immunol & Transfus Med, Tromso, Norway. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 4023 BP 135B EP 135B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800566 ER PT J AU Pineault, N Ohta, H Abramovich, C Buske, C Aplan, PD Feuring-Buske, M Hogge, DE Humphries, KR AF Pineault, N Ohta, H Abramovich, C Buske, C Aplan, PD Feuring-Buske, M Hogge, DE Humphries, KR TI The homeodomain (HD) of HOXD13 is necessary and sufficient for the myeloproliferative activity of the AML-associated fusion protein NUP98-HOXD13 (NUPD13). SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. Univ Munich, Natl Res Ctr Environm & Hlth, D-80539 Munich, Germany. NCI, Ctr Canc Res, Gaithersburg, MD USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 516 BP 137A EP 138A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700517 ER PT J AU Kim, KT Baird, K Allebach, J Meltzer, P Small, D AF Kim, KT Baird, K Allebach, J Meltzer, P Small, D TI Pim-1 and Myc expressions are remarkably decreased in response to FLT3 inhibitor in FLT3-expressing leukemia cells. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. NHGRI, NIH, Canc Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2002 VL 100 IS 11 MA 520 BP 138A EP 138A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700521 ER PT J AU Oscier, DG Rosenwald, A Orchard, JA Ibbotson, RE Henrickson, SE Staudt, LM AF Oscier, DG Rosenwald, A Orchard, JA Ibbotson, RE Henrickson, SE Staudt, LM TI DNA microarray analysis distinguishes t(11;14) lymphocytosis from chronic lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Royal Bournemouth Hosp, Bournemouth, Dorset, England. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 526 BP 140A EP 140A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700527 ER PT J AU Robyn, JA Madariaga, MLL Hu, J Bamji, N Adler, R Dunbar, CE Magnusson, MK AF Robyn, JA Madariaga, MLL Hu, J Bamji, N Adler, R Dunbar, CE Magnusson, MK TI In vivo functional characterizations of Rabaptin-5, a leukemia fusion partner to platelet-derived growth factor beta receptor in a patient with CMML. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 532 BP 141A EP 142A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700533 ER PT J AU Shin, MG Kajigaya, S McCoy, JP Levin, BC Young, NS AF Shin, MG Kajigaya, S McCoy, JP Levin, BC Young, NS TI Unexpected mitochondrial DNA heterogeneity in single CD34+cell clones from normal bone marrow SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. NIST, Div Biotechnol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 4105 BP 154B EP 155B PN 2 PG 2 WC Hematology SC Hematology GA 614JL UT WOS:000179184800648 ER PT J AU Wilson, WH Neelapu, S White, T Hegde, U Pittaluga, S Hakim, F Stetler-Stevenson, M Frye, R Steinberg, S Jaffe, ES Gress, R Staudt, L Janik, J Kwak, L AF Wilson, WH Neelapu, S White, T Hegde, U Pittaluga, S Hakim, F Stetler-Stevenson, M Frye, R Steinberg, S Jaffe, ES Gress, R Staudt, L Janik, J Kwak, L TI Idiotype vaccine following EPOCH-rituximab treatment in untreated mantle cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 608 BP 162A EP 162A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700609 ER PT J AU Sloand, EM Fuhrer, M Johnson, S Basu, A Maciejewski, JP Risatano, A Barrett, J Young, NS AF Sloand, EM Fuhrer, M Johnson, S Basu, A Maciejewski, JP Risatano, A Barrett, J Young, NS TI Preferential inhibition of trisomy 8 progenitor cell growth by autologons CD8+ V-beta-restricted T cells in pateints with trisomy 8 myelodysplasia. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Div Intramural Res, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2002 VL 100 IS 11 MA 620 BP 166A EP 166A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700621 ER PT J AU Plasilova, M O'Keefe, CL Rodriguez, A Risitano, AM Kalaycio, M Young, NS Maciejewski, JP AF Plasilova, M O'Keefe, CL Rodriguez, A Risitano, AM Kalaycio, M Young, NS Maciejewski, JP TI Comparison of TCR VB and CDR3 region repertoire in myelodysplastic syndrome and its similarity to other bone marrow failure states. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Cleveland Clin Fdn, Hematopoiesis & Leukemia Program, Cleveland, OH 44195 USA. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 625 BP 167A EP 167A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700626 ER PT J AU Wiestner, A Rosenwald, A Barry, T Ibbotson, RE Stetler-Stevenson, M Orchard, JA Wilson, WH Hamblin, TJ Oscier, DG Staudt, LM AF Wiestner, A Rosenwald, A Barry, T Ibbotson, RE Stetler-Stevenson, M Orchard, JA Wilson, WH Hamblin, TJ Oscier, DG Staudt, LM TI Zap70 expression identifies B-CLL with unmutated immunoglobulin genes, worse clinical outcome and a distinct gene expression profile. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. Royal Bournemouth Hosp, Dept Hematol, Bournemouth, Dorset, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 631 BP 168A EP 169A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700632 ER PT J AU Fowler, DH Hou, J Fellowes, V Vance, B Bishop, MR Gress, RE Levine, B June, C Leitman, S Read, EJ Carter, C AF Fowler, DH Hou, J Fellowes, V Vance, B Bishop, MR Gress, RE Levine, B June, C Leitman, S Read, EJ Carter, C TI Donor Th2 cells for GVHD modulation: Clinical scale and grade generation using CD3, CD28 co-stimulation. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. Univ Penn, Ctr Canc, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. RI Levine, Bruce/D-1688-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 648 BP 173A EP 173A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700649 ER PT J AU Srinivasan, R Geller, N Chakrabarti, S Donohue, T Marquesen, M Sloand, E Dunbar, C Barrett, AJ Young, N Childs, R AF Srinivasan, R Geller, N Chakrabarti, S Donohue, T Marquesen, M Sloand, E Dunbar, C Barrett, AJ Young, N Childs, R TI High response rate and improved survival in patients with steroid-refractory acute graft-vs-host disease (SRGVHD) treated with Daclizumab with or without Infliximab. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 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 NOV 16 PY 2002 VL 100 IS 11 MA 651 BP 173A EP 174A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700652 ER PT J AU Cokic, VP Beleslin-Cokic, BB Slade, MA Noguchi, CT Schechter, AN AF Cokic, VP Beleslin-Cokic, BB Slade, MA Noguchi, CT Schechter, AN TI Stimulation of nitric oxide production by hydroxyurea in endothelial cells and macrophages SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIDDK, Biol Chem Lab, Bethesda, MD USA. Xavier Univ, New Orleans, LA 70125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 4227 BP 182B EP 182B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800770 ER PT J AU Lucas, ML Seidel, NE Porada, CD Anderson, SM Malech, HM Quigley, JG Abkowitz, JL Zanjani, ED Bodine, DM AF Lucas, ML Seidel, NE Porada, CD Anderson, SM Malech, HM Quigley, JG Abkowitz, JL Zanjani, ED Bodine, DM TI Increased transduction of human HSC with retroviruses pseudotyped with FeLV or RD114 envelopes in a sheep/human chimeric model. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHGRI, NIH, GMBB, Bethesda, MD 20892 USA. Univ Nevada, Reno, NV 89557 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 685 BP 183A EP 184A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184700686 ER PT J AU Brenner, S Whiting-Theobald, NL Malech, HL AF Brenner, S Whiting-Theobald, NL Malech, HL TI Relationship between length of cell culture, cell division, transduction efficiency and engraftment in NOD/SCID mice of human mobilized CD34(+) peripheral blood stem cells. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIAID, NIH, Host Def Lab, Bethesda, MD 20892 USA. RI Brenner, Sebastian/D-7456-2013 NR 0 TC 2 Z9 2 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 NOV 16 PY 2002 VL 100 IS 11 MA 686 BP 184A EP 184A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700687 ER PT J AU Linnekin, D Krupa, S AF Linnekin, D Krupa, S TI PI3 kinase as a therapeutic target for diseases associated with mutations in the catalytic domain of Kit. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Frederick Canc Res Facil, Basic Res Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 712 BP 190A EP 190A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700713 ER PT J AU Hung, JL DeGraff, W Steinberg, S Stein, WD Nussenzweig, A Fojo, T Rao, VK AF Hung, JL DeGraff, W Steinberg, S Stein, WD Nussenzweig, A Fojo, T Rao, VK TI Study of ionizing radiation-induced chromosomal aberrations in bone marrow cells of Ku-deficient mice. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 4271 BP 192B EP 193B PN 2 PG 2 WC Hematology SC Hematology GA 614JL UT WOS:000179184800814 ER PT J AU Fumo, G Neckers, L AF Fumo, G Neckers, L TI Constitutively activated tyrosine kinase KIT protein in human mast cell lines is de-stabilized and the mast cells undergo apoptosis following treatment with 17-allylamino-17-demethoxygeldanamycin. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Cell & Canc Biol Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 724 BP 193A EP 193A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700725 ER PT J AU Lauchle, JO Bonifas, JM Curtiss, NP Green, ED Le Beau, MM Shannon, KM AF Lauchle, JO Bonifas, JM Curtiss, NP Green, ED Le Beau, MM Shannon, KM TI Development of a fully sequenced contig spanning a 2.5 Mb deleted segment of 7q22 implicated in myeloid leukemia and candidate gene discovery. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 4272 BP 193B EP 193B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800815 ER PT J AU Karp, JE Gojo, I Gocke, CD Greer, J Tidwell, M Sarkodee-Adoo, C Passaniti, A Chen, H Zwiebel, JA AF Karp, JE Gojo, I Gocke, CD Greer, J Tidwell, M Sarkodee-Adoo, C Passaniti, A Chen, H Zwiebel, JA TI Timed sequential therapy (TST) of relapsed and refractory adult acute myelogenous leukemia (AML) with the anti-vascular endothelial growth factor (VEGF) monoclonal antibody Bevacizumab. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. NCI, Invest Drug Branch, Rockville, MD USA. NR 0 TC 8 Z9 8 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 NOV 16 PY 2002 VL 100 IS 11 MA 744 BP 198A EP 198A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700745 ER PT J AU Zha, HB Raffeld, M Charboneau, L Pittaluga, S Liotta, LA Petricoin, E Kwak, L Jaffe, ES AF Zha, HB Raffeld, M Charboneau, L Pittaluga, S Liotta, LA Petricoin, E Kwak, L Jaffe, ES TI Phosphorylation of Akt and Bad in follicular lymphomas (FL) analyzed by reverse phase protein microarrays. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 747 BP 199A EP 199A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700748 ER PT J AU Tamura, T Kong, HJ Tunyaplin, C Tsujimura, H Thotakura, P Calame, K Ozato, K AF Tamura, T Kong, HJ Tunyaplin, C Tsujimura, H Thotakura, P Calame, K Ozato, K TI ICSBP overrides the activity of p210 bcr/abl in myeloid progenitor cells. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NICHHD, NIH, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. Columbia Univ, Coll Phys & Surg, Dept Microbiol, New York, NY 10027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 769 BP 205A EP 205A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700770 ER PT J AU Fowler, DH Odom, D Castro, K Kasten-Sportes, C Gea-Banacloche, J Dean, RM Wilson, W Foley, J Hou, J Hakim, F Leitman, S Read, EJ Carter, C Levine, B June, CH Gress, RE Bishop, MR AF Fowler, DH Odom, D Castro, K Kasten-Sportes, C Gea-Banacloche, J Dean, RM Wilson, W Foley, J Hou, J Hakim, F Leitman, S Read, EJ Carter, C Levine, B June, CH Gress, RE Bishop, MR TI Co-stimulated Th2 cells for modulation of acute GVHD: Phase I clinical trial results. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Penn, Ctr Canc, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RI Levine, Bruce/D-1688-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 804 BP 214A EP 214A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700805 ER PT J AU Nasr, R Rosenwald, A El-Sabban, ME Amulf, B Hermine, O Staudt, L de The, H Bazarbachi, A AF Nasr, R Rosenwald, A El-Sabban, ME Amulf, B Hermine, O Staudt, L de The, H Bazarbachi, A TI Arsenic/interferon specifically reverses two distinct gene networks critical for the survival of HTLV-I infected leukemic cells SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Amer Univ Beirut, Beirut, Lebanon. Natl Canc Inst, Ctr Canc Res, Metab Branch, Bethesda, MD USA. Hop Necker Enfants Malad, CNRS, URA 1461, Paris, France. Hop Necker Enfants Malad, Dept Hematol, Paris, France. St Louis Hosp, CNRS, UPR 9051, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 4370 BP 215B EP 215B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800913 ER PT J AU Plasschaert, SL van der Kolk, DM Eveline, SDBT Kamps, WA Scheffer, GL Scheper, RL Bates, SE Vellenga, E de Vries, EG AF Plasschaert, SL van der Kolk, DM Eveline, SDBT Kamps, WA Scheffer, GL Scheper, RL Bates, SE Vellenga, E de Vries, EG TI Expression and activity of breast cancer resistance protein (BCRP) in acute lymphoblastic leukemia. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Groningen Hosp, Groningen, Netherlands. Free Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Univ Groningen Hosp, Groningen, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 4395 BP 220B EP 220B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184800938 ER PT J AU Baerlocher, GM Sloand, EM Vulto, IM Young, NS Lansdorp, PM AF Baerlocher, GM Sloand, EM Vulto, IM Young, NS Lansdorp, PM TI Short telomere length in GPI-negative blood cells from patients with paroxysmal nocturnal hemoglobinuria. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 860 BP 228A EP 228A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700861 ER PT J AU Chen, GB Zeng, WH Keyvanfar, K Bilings, E Young, NS AF Chen, GB Zeng, WH Keyvanfar, K Bilings, E Young, NS TI Differential gene expression profile in hematopoietic progenitor cells form paroxysmal nocturnal hemoglobinuria (PNH) patients. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 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 NOV 16 PY 2002 VL 100 IS 11 MA 861 BP 228A EP 228A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700862 ER PT J AU Baerlocher, GM Sloand, EM Alter, BP Wagner, JE Vulto, IM Leathwood, L Young, NS Lansdorp, PM AF Baerlocher, GM Sloand, EM Alter, BP Wagner, JE Vulto, IM Leathwood, L Young, NS Lansdorp, PM TI Subset specific telomere length to distinguish patients with bone marrow failure syndromes? SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NCI, Clin Genet Branch, Bethesda, MD 20892 USA. Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 863 BP 229A EP 229A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700864 ER EF