FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kroeze, WK Hufeisen, SJ Popadak, BA Renock, SM Steinberg, S Ernsberger, P Jayathilake, K Meltzer, HY Roth, BL AF Kroeze, WK Hufeisen, SJ Popadak, BA Renock, SM Steinberg, S Ernsberger, P Jayathilake, K Meltzer, HY Roth, BL TI Reply: H-1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs SO NEUROPSYCHOPHARMACOLOGY LA English DT Letter ID HISTAMINE; RATS C1 Case Western Reserve Univ, Sch Med, Dept Biochem, RM W 463, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, NIMH, Psychoact Drug Screening Program, Cleveland, OH USA. Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH USA. Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. RP Kroeze, WK (reprint author), Case Western Reserve Univ, Sch Med, Dept Biochem, RM W 463, 10900 Euclid Ave, Cleveland, OH 44106 USA. RI Roth, Bryan/F-3928-2010; Ernsberger, Paul/O-2702-2014; Meltzer, Herbert/E-8131-2013 OI Ernsberger, Paul/0000-0003-2372-2500; NR 6 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2003 VL 28 IS 12 BP 2210 EP 2211 DI 10.1038/sj.npp.1300292 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 748ZD UT WOS:000186892200017 ER PT J AU Woodard, GE Zhao, J Rosado, JA Brown, J AF Woodard, GE Zhao, J Rosado, JA Brown, J TI Differences between natriuretic peptide receptors in the olfactory bulb and hypothalamus from spontaneously hypertensive and normotensive rat brain SO NEUROSCIENCE RESEARCH LA English DT Article DE ANP; NPR-A; hypertension; central nervous system; cGMP; olfactory bulb ID MESSENGER-RNA; CLEARANCE RECEPTOR; ANGIOTENSIN-II; BINDING-SITES; ANP RECEPTORS; ATRIAL; SYSTEM; SUBTYPES; LOCALIZATION; STIMULATION AB Natriuretic peptide receptor-A (NPR-A) functional characteristics in the hypothalamus and olfactory bulb (013) have been investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Autoradiographic studies demonstrate a decreased number of atrial natriuretic peptide (ANP) binding sites in the olfactory bulb and hypothalamus in SHR compared to WKY rats. We found that NPR-A showed a lower maximal binding capacity (B-max) and higher affinity in SHR than in WKY rats both in the olfactory bulb and hypothalamus. However, despite the lower B-max in SHR, both ANP(1-28) and ANP(5-25) stimulated similar or greater cGMP production than in WKY rats. These differences were found even before the development of hypertension. NPR-A in the olfactory bulb and hypothalamus from 3-week-old SHR showed a lower B-max and K-d and a higher cGMP production rate than in WKY rats, suggesting that these characteristics are intrinsic of NPR-A in SHR, instead of being a result of hypertension itself. The present study provides evidences for altered NPR-A receptor properties and function in the olfactory bulb and hypothalamus from SHR, which might be involved in the pathogenesis of hypertension. (C) 2003 Elsevier Ireland Ltd and The Japan Neuroscience Society. All rights reserved. C1 Univ Cambridge, Physiol Lab, Cambridge CB2 3EG, England. RP Woodard, GE (reprint author), NIDDKD, NIH, Bldg 10,Rm 8C-208,10 Ctr Dr,MSC 1752, Bethesda, MD 20892 USA. RI Woodard, Geoffrey/A-8608-2009; rosado, juan/H-3488-2015 OI rosado, juan/0000-0002-9749-2325 NR 43 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PD DEC PY 2003 VL 47 IS 4 BP 421 EP 429 DI 10.1016/j.neures.2003.08.002 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 750EB UT WOS:000186977400007 PM 14630346 ER PT J AU Gerfen, CR AF Gerfen, CR TI D1 dopamine receptor supersensitivity in the dopamine-depleted striatum animal model of Parkinson's disease SO NEUROSCIENTIST LA English DT Review DE dopamine; gene regulation; protein kinase; receptor supersensitivity; Parkinson's disease; dyskinesia ID ELEMENT-BINDING PROTEIN; EARLY GENE INDUCTION; LONG-TERM-MEMORY; C-FOS; MATRIX COMPARTMENTS; VENTRAL STRIATUM; KINASE CASCADE; MESSENGER-RNAS; RAT FOREBRAIN; BASAL GANGLIA AB Dopamine acts in the striatum principally through the D1 and D2 dopamine receptor subtypes, which are segregated to the direct and indirect striatal projection neurons, respectively. As a consequence, degeneration of the dopamine input to the striatum results in opposing affects in these pathways. The resulting functional imbalance is thought to be responsible for the bradykinesia of Parkinson's disease, which may be temporarily normalized by dopamine replacement therapy. However, direct striatal projection neurons become irreversibly supersensitive to D1 dopamine receptor activation, despite the fact that there is an actual decrease in receptor number. Recent studies show that this D1-supersensitive response results from a switch from the normal D1-mediated activation of protein-kinase A to an aberrant activation of ERK1/2/MAPkinase. This switch in D1-receptor-mediated regulation of protein kinase systems responsible for neuronal plasticity is suggested to underlie dyskinesia produced by L-DOPA treatment of Parkinson's disease. C1 NIMH, Lab Syst Neurosci, Neuroanat Sect, Bethesda, MD 20892 USA. RP Gerfen, CR (reprint author), Bldg 36,Room 2D-30,36 Convent Dr, Bethesda, MD 20817 USA. NR 42 TC 67 Z9 70 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD DEC PY 2003 VL 9 IS 6 BP 455 EP 462 DI 10.1177/1073858403255839 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 746AE UT WOS:000186723200015 PM 14678578 ER PT J AU Reeves, R Thiruchelvam, M Baggs, RB Cory-Slechta, DA AF Reeves, R Thiruchelvam, M Baggs, RB Cory-Slechta, DA TI Interactions of paraquat and triadimefon: Behavioral and neurochemical effects SO NEUROTOXICOLOGY LA English DT Article DE pesticides; neurotoxicity; combined exposures; paraquat; triadimefon; behavioral sensitization ID TRIAZOLE FUNGICIDE; PARKINSONS-DISEASE; RATS; TOXICITY; MICE; HYPERACTIVITY; MECHANISM; SYSTEM; MANEB AB Triadimefon (TDF), a triazole fungicide, and paraquat (PQ), a non-selective herbicide/dessicant, are both known to adversely impact brain dopaminergic function and are used in overlapping geographical areas of the US. Since real world situations indicate humans are exposed to a diverse mixture of chemicals, this study hypothesized that combined exposures to PQ + TDF could produce interactive effects by simultaneously attacking multiple target sites of dopamine systems. Thus, 10 mg/kg PQ (PQ10) and 25 or 50 mg/kg TDF(TDF25 and 50, respectively) were administered i.p. to male C57BL/6 mice, 2 per week for 12 weeks, either alone or in combination. Acutely, TDF50 increased horizontal and vertical activity with increased vertical activity still occurring 24 h later, indicative of sustained behavioral sensitization. Acutely, PQ decreased horizontal but not vertical activity with a lack of residual effects at 24 h. PQ prevented the increased levels of activity associated with TDF50. These interactions differed for horizontal and vertical activity, indicating their differential neurochemical mediation, and suggesting that they did not arise from simple additivity of PQ and TDF effects. Nor could the interactive effects be readily ascribed to corresponding neurochemical interactions, since all treatments generally increased levels of DA and metabolites acutely in striatum and were associated with general reductions in levels of DA and metabolites and turnover in striatum and frontal cortex 7 days after the final treatment. Thus, TDF and PQ both separately and through interactions may serve as environmental risk factors through different mechanisms for dopaminergically-mediated behavioral dysfunctions. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Univ Rochester, Sch Med & Dent, Dept Environm Med, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Div Lab Anim Med, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, NIEHS, Environm Hlth Sci Ctr, Rochester, NY 14642 USA. RP Reeves, R (reprint author), Univ Rochester, Sch Med & Dent, Dept Environm Med, Rochester, NY 14642 USA. NR 30 TC 13 Z9 16 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2003 VL 24 IS 6 BP 839 EP 850 DI 10.1016/S0161-813X(03)00057-3 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 751NV UT WOS:000187074600009 PM 14637379 ER PT J AU Caudle, RM Karai, L Mena, N Cooper, BY Mannes, AJ Perez, FM Iadarola, MJ Olah, Z AF Caudle, RM Karai, L Mena, N Cooper, BY Mannes, AJ Perez, FM Iadarola, MJ Olah, Z TI Resiniferatoxin-induced loss of plasma membrane in vanilloid receptor expressing cells SO NEUROTOXICOLOGY LA English DT Article DE vanilloid; nociceptors; neuroablation; resiniferatoxin; capsaicin; TRPV1 ID DORSAL-ROOT GANGLIA; SECONDARY HYPERALGESIA; CAPSAICIN RECEPTOR; URINARY-BLADDER; PAIN SENSATION; SPINAL-CORD; RAT DRG; NEURONS; VR1; DESENSITIZATION AB Resiniferatoxin (RTX), a potent analog of capsaicin, was evaluated electrophysiologically in dorsal root ganglion (DRG) cells and cell lines ectopically expressing the vanilloid receptor type 1 (VR1) to determine if cell phenotype influenced RTXs neurotoxic properties. Furthermore, capsaicin and heat activation of VR1 were evaluated in these cells to determine if cellular damage was unique to RTX activation of the receptors. RTX application to DRG cells identified as type 1, 2 or 5, cell types known to express VR1, induced large inward currents. RTX did not induce currents in DRG cells that do not express the receptor (type 4 cells). In cell lines ectopically expressing VR1, RTX-induced similar currents. RTX produced no effect in non-transfected cells. After exposure to RTX both DRG cells and transfected cells failed to respond to subsequent applications of the agonist. In addition, whole cell capacitance was reduced up to 70%. The decrease in capacitance was associated with the loss of plasma membrane, as determined by confocal microscopy. Cell phenotype, other than VR1 expression, did not influence the response to RTX. Interestingly, capsaicin and heat activation of vanilloid receptors also decreased cell capacitance, but the loss of membrane was not as great as with RTX and responses to these stimuli were not lost after the initial exposure. The loss of cell membrane required elevated intracellular levels of Ca2+ From these data it was concluded that the loss of cell membrane was dependent on the presence of both VR1 and intracellular Ca2+ accumulation, but not on cell phenotype. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Florida, Coll Dent, Dept Oral & Maxillofacial Surg, Gainesville, FL 32610 USA. Univ Florida, McKnight Brain Inst, Gainesville, FL 32610 USA. Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD USA. RP Caudle, RM (reprint author), Univ Florida, Coll Dent, Dept Oral & Maxillofacial Surg, 1600 Archer Rd,POB 100416, Gainesville, FL 32610 USA. OI Mannes, Andrew/0000-0001-5834-5667 NR 37 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2003 VL 24 IS 6 BP 895 EP 908 DI 10.1016/S0161-813X(03)00146-3 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 751NV UT WOS:000187074600014 PM 14637384 ER PT J AU Borrmann, L Schwanbeck, R Heyduk, T Seebeck, B Rogalla, P Bullerdiek, J Wisniewski, JR AF Borrmann, L Schwanbeck, R Heyduk, T Seebeck, B Rogalla, P Bullerdiek, J Wisniewski, JR TI High mobility group A2 protein and its derivatives bind a specific region of the promoter of DNA repair gene ERCC1 and modulate its activity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COLI RNA-POLYMERASE; PIGMENTOSUM GROUP-F; LUMINESCENCE ENERGY-TRANSFER; NUCLEOTIDE EXCISION-REPAIR; INTERSTRAND CROSS-LINKS; IFN-BETA GENE; HMGI-C; MOLECULAR CHARACTERIZATION; TRANSCRIPTION FACTORS; EXPRESSION PATTERNS AB High mobility group A2 (HMGA2) chromosomal non-histone protein and its derivatives play an important role in development and progression of benign and malignant tumors, obesity and arteriosclerosis, although the underlying mechanisms of these conditions are poorly understood. Therefore, we tried to identify target genes for this transcriptional regulator and to provide insights in the mechanism of interaction to its target. Multiple genes have been identified by microarray experiments as being transcriptionally regulated by HMGA2. Among these we chose the ERCC1 gene, encoding a DNA repair protein, for this study. DNA-binding studies were performed using HMGA2 and C-terminally truncated DeltaHMGA2, a derivative that is frequently observed in a variety of tumors. A unique high affinity HMGA2 binding site was mapped to a specific AT-rich region located -323 to -298 upstream of the ERCC1 transcription start site, distinguishing it from other potential AT-rich binding sites. The observed 1:1 stoichiometry for the binding of wild-type HMGA2 to this region was altered to 1:2 upon binding of truncated DeltaHMGA2, causing DNA bending. Furthermore, the regulatory effect of HMGA2 was confirmed by luciferase promoter assays showing that ERCC1 promoter activity is down-regulated by all investigated HMGA2 forms, with the most striking effect exerted by DeltaHMGA2. Our results provide the first insights into how HMGA2 and its aberrant forms bind and regulate the ERCC1 promoter. C1 Univ Bremen, Ctr Human Genet, D-28359 Bremen, Germany. Univ Gottingen, Zool Inst Entwicklungsbiol 3, D-37073 Gottingen, Germany. St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA. RP Schwanbeck, R (reprint author), NCI, NIH, Bldg 37,Room 6060B, Bethesda, MD 20892 USA. RI Schwanbeck, Ralf/A-2648-2008 OI Schwanbeck, Ralf/0000-0003-0925-929X NR 60 TC 35 Z9 40 U1 0 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 2003 VL 31 IS 23 BP 6841 EP 6851 DI 10.1093/nar/gkg884 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 747JY UT WOS:000186802500022 PM 14627817 ER PT J AU Mills, R Rozanov, M Lomsadze, A Tatusova, T Borodovsky, M AF Mills, R Rozanov, M Lomsadze, A Tatusova, T Borodovsky, M TI Improving gene annotation of complete viral genomes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COMPLETE DNA-SEQUENCE; LARGE VIRULENCE PLASMID; NUCLEOTIDE-SEQUENCE; PSI-BLAST; DATABASE; ALIGNMENT; PROTEINS AB Gene annotation in viruses often relies upon similarity search methods. These methods possess high specificity but some genes may be missed, either those unique to a particular genome or those highly divergent from known homologs. To identify potentially missing viral genes we have analyzed all complete viral genomes currently available in GenBank with a specialized and augmented version of the gene finding program GeneMarkS. In particular, by implementing genome-specific self-training protocols we have better adjusted the GeneMarkS statistical models to sequences of viral genomes. Hundreds of new genes were identified, some in well studied viral genomes. For example, a new gene predicted in the genome of the Epstein-Barr virus was shown to encode a protein similar to alpha-herpesvirus minor tegument protein UL14 with heat shock functions. Convincing evidence of this similarity was obtained after only 12 PSI-BLAST iterations. In another example, several iterations of PSI-BLAST were required to demonstrate that a gene predicted in the genome of Alcelaphine herpesvirus 1 encodes a BALF1-like protein which is thought to be involved in apoptosis regulation and, potentially, carcinogenesis. New predictions were used to refine annotations of viral genomes in the RefSeq collection curated by the National Center for Biotechnology Information. Importantly, even in those cases where no sequence similarities were detected, GeneMarkS significantly reduced the number of primary targets for experimental characterization by identifying the most probable candidate genes. The new genome annotations were stored in VIOLIN, an interactive database which provides access to similarity search tools for up-to-date analysis of predicted viral proteins. C1 Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. Georgia Inst Technol, Sch Biomed Engn, Atlanta, GA 30332 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Borodovsky, M (reprint author), Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. EM mark.borodovsky@biology.gatech.edu RI Mills, Ryan/F-4225-2010; Mills, Ryan/A-1979-2011 OI Mills, Ryan/0000-0003-3425-6998 FU NHGRI NIH HHS [HG00783, R01 HG000783] NR 38 TC 28 Z9 30 U1 0 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 2003 VL 31 IS 23 BP 7041 EP 7055 DI 10.1093/nar/gkg878 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 747JY UT WOS:000186802500042 PM 14627837 ER PT J AU Huss, K Travis, P Huss, RW AF Huss, K Travis, P Huss, RW TI General principles of asthma management: environmental control SO NURSING CLINICS OF NORTH AMERICA LA English DT Article ID HOUSE-DUST MITE; ALLERGIC DISEASE; BRONCHIAL HYPERREACTIVITY; HOME-ENVIRONMENT; EXPOSURE; CHILDREN; SENSITIZATION; TEMPERATURE; AVOIDANCE; CHILDHOOD AB House dust mites produce potent allergens that are a cause of asthma, nasal allergies, and skin allergies in sensitized individuals. This article educates nurses about house dust mites, factors influencing their growth, and methods to reduce allergic exposure in homes. The method used is an evidenced-based literature review. Nurses play an important role not only in educating patients about the major measures, but also in helping them to obtain high-quality products at an economical price. This article summarizes the most clinically important allergen reduction methods based on scientific review. C1 Johns Hopkins Univ, Sch Nursing, Baltimore, MD 21205 USA. Natl Inst Nursing Res, Div Extramural Activ, NIH, Bethesda, MD 20892 USA. Anne Arundel Med Ctr, Clin Efficiency, Annapolis, MD 21401 USA. Asthma Sinus & Allergy Ctr LLC, E Brunswick, NJ 08816 USA. RP Huss, K (reprint author), Johns Hopkins Univ, Sch Nursing, 525 N Wolfe St,Room 416, Baltimore, MD 21205 USA. NR 37 TC 3 Z9 5 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 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD DEC PY 2003 VL 38 IS 4 BP 609 EP + DI 10.1016/S0029-6465(03)00100-2 PG 13 WC Nursing SC Nursing GA 757VH UT WOS:000187581800006 PM 14763364 ER PT J AU North, KE Williams, K Williams, JT Best, LG T Lee, E Fabsitz, RR Howard, BV Gray, RS MacCluer, JW AF North, KE Williams, K Williams, JT Best, LG T Lee, E Fabsitz, RR Howard, BV Gray, RS MacCluer, JW TI Evidence for genetic factors underlying the insulin resistance syndrome in American Indians SO OBESITY RESEARCH LA English DT Article DE American Indians; insulin resistance; genetic; factors ID CORONARY-HEART-DISEASE; RISK-FACTORS; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; LINKAGE ANALYSIS; FAMILY; CHOLESTEROL; PEDIGREES; PLASMA; MEN AB Previous analyses of American Indians of the Strong Heart Study have demonstrated that various insulin-resistance variables cluster, although knowledge about the genetic determination of these clusters is unknown. In an effort to explore the influences on the aggregation of insulin-resistance phenotypes, we used principal component factor analysis to examine the clustering of these phenotypes in participants of the Strong Heart Family Study and evaluated the genetic and environmental contributions of such factors. Nine traits were chosen for principal component factor analysis: BMI, diastolic blood pressure, fasting glucose, high-density lipoprotein-cholesterol, natural log-transformed insulin, natural log-transformed triglycerides, percentage of body fat, systolic blood pressure, and waist-to-hip ratio. Analyses revealed three clusters: glucose/insulin/obesity, blood pressure, and dyslipidemia factors. Using a variance component approach and accounting for the effects of age, sex, center, and medication, we detected significant heritabilities (h(2)) for the three factors: h(2) = 0.67, h(2) = 0.33, and h(2) = 0.61, respectively. In multivariate analysis, no significant genetic correlations among factors were found. These results suggest that heredity explains a substantial proportion of the variability of the factors that underlie the insulin resistance syndrome in American Indians and that these factors are genetically independent. C1 Univ N Carolina, Dept Epidemiol, Bank Amer Ctr, Chapel Hill, NC 27514 USA. Univ Texas, Ctr Hlth Sci, San Antonio, TX USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. Missouri Breaks Ind Res Inc, Timber Lake, MO USA. Univ Oklahoma, Hlth Sci Ctr, Sch Publ Hlth, Amer Indian Hlth Res, Oklahoma City, OK USA. Natl Heart Lund & Blood Inst, Epidemiol & Biometry Program, NIH, Bethesda, MD USA. MedStar Res Inst, Washington, DC USA. RP North, KE (reprint author), Univ N Carolina, Dept Epidemiol, Bank Amer Ctr, 137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA. FU NHLBI NIH HHS [U01 HL65520, U01 HL41642, U01 HL65521, U01 HL41652, U01 HL41654] NR 23 TC 14 Z9 15 U1 0 U2 2 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 2003 VL 11 IS 12 BP 1444 EP 1448 DI 10.1038/oby.2003.193 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 759FF UT WOS:000187727100002 PM 14694207 ER PT J AU Hays, RD Mangione, CM Ellwein, L Lindblad, AS Spritzer, KL McDonnell, PJ AF Hays, RD Mangione, CM Ellwein, L Lindblad, AS Spritzer, KL McDonnell, PJ CA NEI RQL Res Grp TI Psychometric properties of the National Eye Institute-Refractive Error Quality of Life instrument SO OPHTHALMOLOGY LA English DT Article ID VISUAL FUNCTION QUESTIONNAIRE; VISION PROFILE; RADIAL KERATOTOMY; FUNCTIONAL STATUS; CATARACT-SURGERY; OUTCOMES; ACUITY; SF-36 AB Objective: To estimate the psychometric properties of a vision-targeted measure of health-related quality of life, the National Eye Institute-Refractive Error Quality of Life survey (NEI-RQL), which includes 13 scales designed to assess the impact of refractive error and its correction on day-to-day life. Design: Cross-sectional survey. Participants: The NEI-RQL was self-administered by 667 myopes, 380 hyperopes, and 114 emmetropes recruited from the practices of 6 medical centers. All participants had near and distance visual acuity of 20/32 or better in the worse eye while benefiting from their current method for correction of refractive error (glasses, contact lens, refractive surgery). Methods: Mean scores, standard deviations, internal consistency reliability, and test-retest intraclass correlations were estimated for the NEI-RQL scales. Item discrimination was assessed by item-scale correlations. Construct validity was evaluated by assessing the sensitivity of scale scores to type of refractive error, type of refractive error correction, and spherical equivalent. Construct validity of the NEI-RQL was compared to those of the Medical Outcomes Study 36-item short-form health survey (SF-36) and the National Eye Institute Vision Functioning Questionnaire (NEI VFQ-25) in a random subsample of respondents. Main Outcome Measures: The 13 NEI-RQL scales-clarity of vision, expectations, near vision, far vision, diurnal fluctuations, activity limitations, glare, symptoms, dependence on correction, worry, suboptimal correction, appearance, and satisfaction with correction. Results: Emmetropes tended to score significantly better on the NEI-RQL scales than myopes and hyperopes. The method of refractive error correction was also associated with NEI-RQL scores. In addition, the NEI-RQL multi-item scales accounted for 29% of the variance in the NEI-RQL satisfaction with correction item beyond that explained by the SF-36 and the NEI VFQ-25. Conclusion: These results support the reliability and construct validity of the NEI-RQL. The instrument appears to be useful for comparisons of people with different types of correction for refractive error. (C) 2003 by the American Academy of Ophthalmology. C1 Univ Calif Los Angeles, Sch Med, Div Gen Internal Med & Hlth Sci Res, Los Angeles, CA 90095 USA. RAND Corp, Santa Monica, CA 90406 USA. NEI, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Johns Hopkins Univ, Wilmer Ophthalmol Inst, Baltimore, MD 21218 USA. RP Hays, RD (reprint author), Univ Calif Los Angeles, Sch Med, Div Gen Internal Med & Hlth Sci Res, 911 Broxton Plaza,Room 110, Los Angeles, CA 90095 USA. RI Hays, Ronald/D-5629-2013 FU NEI NIH HHS [N01-EY-6-2112]; NIA NIH HHS [AG-02-004]; NIMHD NIH HHS [P20-MD00148-01] NR 28 TC 70 Z9 74 U1 1 U2 5 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 2003 VL 110 IS 12 BP 2292 EP 2301 DI 10.1016/j.ophtha.2002.07.001 PG 10 WC Ophthalmology SC Ophthalmology GA 748RT UT WOS:000186875400002 PM 14644710 ER PT J AU Klein, RC Schron, EB Renfroe, EG Hallstrom, A Kron, J Ocampo, C Leonen, A Tullo, N AF Klein, RC Schron, EB Renfroe, EG Hallstrom, A Kron, J Ocampo, C Leonen, A Tullo, N CA AVID Investigators TI Factors determining ICD implantation in drug therapy patients after termination of antiarrythmics versus implantable defibrillators trial SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE implantable cardioverter defibrillator; AVID Trial ID CARDIOVERTER-DEFIBRILLATORS; VENTRICULAR-ARRHYTHMIAS; CARDIAC-ARREST; PROGNOSIS; SURVIVORS AB Because of a significant survival benefit in the defibrillator arm of the Antiarrhythmics versus Implantable Defibrillator (AVID) Trial, patients in the antiarrhythmic drug (AAD) arm were advised to undergo IGD implantation. Despite this recommendation, ICD implantation in AAD patients was variable, with a large number of patients not undergoing ICD implantation. Patients were grouped by those who had been on AAD < 1 year (n = 111) and those on AAD > 1 year (n = 223). Multiple clinical and socioeconomic factors were evaluated to identify those who might be associated with a decision to implant an ICD. The primary reason for patients not undergoing ICD implantation was collected, as well as reasons for a delayed implantation, occurring later than 3 months from study termination. Of 111 patients on AAD for less than 1 year, 53 received an ICD within 3 months compared to 401223 patients on AAD for more than 1 year (P < 0.001). Patient refusal was the most common reason to not implant an ICD in patients on drug < 1 year, physician recommendation against implantation was the most common in patients on drug > 1 year. Multivariate analysis showed ICD recipients on AAD < 1 year were more likely to be working and have a history of myocardial infarction (MI), while those on AAD > 1 year were more likely to be working, have a history of MI and ventricular fibrillation, and less likely to have experienced syncope, as compared to those who did not get an ICD. Having private insurance may have played a role in younger patients receiving an ICD. C1 Univ Utah, Hlth Sci Ctr, Div Cardiol, Salt Lake City, UT 84132 USA. NHLBI, Seattle, WA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Oregon Hlth Sci Univ, Div Cardiol, Portland, OR 97201 USA. Univ Rochester, Sch Med & Dent, Dept Cardiol, Rochester, NY 14627 USA. St Josephs Hosp, Paterson, NJ USA. Med Ctr, Paterson, NJ USA. RP Klein, RC (reprint author), Univ Utah, Hlth Sci Ctr, Div Cardiol, 50 N Med Dr, Salt Lake City, UT 84132 USA. NR 12 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD DEC PY 2003 VL 26 IS 12 BP 2235 EP 2240 DI 10.1111/j.1540-8159.2003.00353.x PG 6 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 758EJ UT WOS:000187619900006 PM 14675006 ER PT J AU Turk, DC Dworkin, RH Allen, RR Bellamy, N Brandenburg, N Carr, DB Cleeland, C Dionne, R Farrar, JT Galer, BS Hewitt, DJ Jadad, AR Katz, NP Kramer, LD Manning, DC McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robinson, JP Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Witter, J AF Turk, DC Dworkin, RH Allen, RR Bellamy, N Brandenburg, N Carr, DB Cleeland, C Dionne, R Farrar, JT Galer, BS Hewitt, DJ Jadad, AR Katz, NP Kramer, LD Manning, DC McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robinson, JP Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Witter, J TI Core outcome domains for chronic pain clinical trials: IMMPACT recommendations SO PAIN LA English DT Article DE chronic pain; clinical trials; assessment; outcomes; quality of life; physical functioning; emotional functioning; adverse events; global ratings ID QUALITY-OF-LIFE; LOW-BACK-PAIN; CONSORT STATEMENT; HEALTH-STATUS; IMPACT; RESPONSIVENESS; OSTEOARTHRITIS; MANAGEMENT; DISTRESS; SOCIETY AB Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment. Methods. Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 27 specialists from academia. governmental agencies, and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered in clinical trials of treatments for chronic pain. Conclusions. There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Rochester, Rochester, NY USA. AstraZeneca, Wilmington, DE USA. Univ Queensland, St Lucia, Qld 4067, Australia. Pfizer Pharmaceut Grp, New York, NY USA. Tufts Univ, Dept Anesthesiol, Medford, MA 02155 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Endo Pharmaceut Inc, Chadds Ford, PA USA. Ortho McNeil Pharmaceut Inc, Raritan, NJ USA. Univ Toronto, Toronto, ON, Canada. Univ Hlth Network, Toronto, ON, Canada. Harvard Univ, Cambridge, MA 02138 USA. Purdue Pharma, Stamford, CT USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. NIH, Bethesda, MD 20892 USA. Dalhousie Univ, Dept Psychol, Halifax, NS, Canada. GlaxoSmithKline, Res Triangle Pk, NC USA. US FDA, Rockville, MD 20857 USA. Univ Washington, Dept Phys Med & Rehabil, Seattle, WA 98195 USA. Elan Pharmaceut, San Diego, CA USA. Abbott Labs, Lake Forest, IL USA. Univ Calif San Diego, La Jolla, CA 92093 USA. US Dept Vet Affairs, Washington, DC USA. RP Turk, DC (reprint author), Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. EM turkdc@u.washington.edu RI Farrar, John/A-1037-2007; Bellamy, Nicholas/G-3631-2010; OI Farrar, John/0000-0001-8656-5157; McGrath, Patrick/0000-0002-9568-2571 NR 48 TC 483 Z9 491 U1 4 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 2003 VL 106 IS 3 BP 337 EP 345 DI 10.1016/j.pain.2003.08.001 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 753AR UT WOS:000187209600014 PM 14659516 ER PT J AU Weiner, DK Haggerty, CL Kritchevsky, SB Harris, T Simonsick, EM Nevitt, M Newman, A AF Weiner, DK Haggerty, CL Kritchevsky, SB Harris, T Simonsick, EM Nevitt, M Newman, A CA Hlth Aging Body Composition Res Gr TI How does low back pain impact physical function in independent, well-functioning older adults? Evidence from the health ABC cohort and implications for the future SO PAIN MEDICINE LA English DT Article DE low back pain; older adults; disability; physical function ID SELF-RATED HEALTH; CHRONIC MUSCULOSKELETAL PAIN; DWELLING SENIOR-CITIZENS; LOWER-EXTREMITY FUNCTION; DEPRESSIVE SYMPTOMS; SUBSEQUENT DISABILITY; COMMUNITY; ASSOCIATION; PERFORMANCE; MORTALITY AB Objective. To determine the relationships between low back pain (LBP) frequency and intensity and self-reported and performance-based physical function in a large cohort of well-functioning older adults. Design. Cross-sectional survey and examination. Setting. Community-based cohort of the Health, Aging, and Body Composition (Health ABC) study. Participants. Participants were 2,766 community-dwelling adults, aged 70-79; 42% were African American, 52% were men. Outcome Measures. 1) Back pain-location, frequency, intensity; 2) Hip and/or knee pain; 3) Body mass index (BMI); 4) Self-reported difficulty doing functional tasks; 5) Lower extremity function, using the battery from the Established Populations for Epidemiologic Studies in the Elderly (EPESE); 6) Self-rated health; 7) Comorbidity; 8) Depressive symptoms, using the Center for Epidemiological Studies-Depression (CES-D) scale. Results. LBP was common (36%), and its frequency/intensity was significantly associated with other pain and comorbidities. In gender-specific models, LBP frequency/intensity was not significantly associated with EPESE performance score after adjusting for age, race, BMI, CES-D score, knee pain, hip pain, and other comorbidities. LBP frequency/intensity, however, was significantly associated with self-reported difficulty with most functional tasks after adjusting for important confounders. Conclusions. Among well-functioning community-dwelling older adults, LBP frequency/intensity was associated with perceived difficulty in performing important functional tasks, but not with observed physical performance. The demonstrated dose-response relationship between pain frequency/intensity and self-reported task performance difficulty underscores the importance of clinical efforts to treat pain without necessarily eradicating it. Additional work is needed to determine whether back pain is associated with a risk for progressive functional decline and loss of independence in older adults and whether therapeutic interventions can ameliorate decline and, therefore, preserve independence. C1 Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. NIA, Bethesda, MD 20892 USA. NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. NIA, Intramural Res Program, Baltimore, MD 21224 USA. Univ Calif San Francisco, Prevent Serv Grp, San Francisco, CA 94143 USA. RP Weiner, DK (reprint author), UPMC Pain Med, Ctr Commons,5750 Ctr Ave,Suite 400, Pittsburgh, PA 15206 USA. RI Agaliotis, Maria/G-5334-2012; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Haggerty, Catherine/0000-0002-9849-7865 FU NIA NIH HHS [N01-AG-6-2106, N01-AG-6-2101, N01-AG-6-2103] NR 57 TC 88 Z9 89 U1 3 U2 9 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD DEC PY 2003 VL 4 IS 4 BP 311 EP 320 DI 10.1111/j.1526-4637.2003.03042.x PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 748TH UT WOS:000186876800003 PM 14750907 ER PT J AU Pearl, JP Preston, E Kirk, AD AF Pearl, JP Preston, E Kirk, AD TI Tolerance: is it achievable in pediatric solid organ transplantation? SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID ANTI-CD154 MONOCLONAL-ANTIBODY; RENAL-ALLOGRAFT REJECTION; ALLOREACTIVE T-CELLS; DENDRITIC CELLS; LIVER-TRANSPLANTATION; MIXED CHIMERISM; ANTITHYMOCYTE GLOBULINS; COSTIMULATORY PATHWAY; IMMUNOLOGICAL MEMORY; NONHUMAN-PRIMATES AB Significant advances have been made in the understanding of allograft rejection. There is growing awareness that allograft acceptance, or tolerance, is also an active process rather than a passive absence of rejection. Mechanistic awareness of this process has spawned many preclinical strategies for the prevention of allograft rejection without the need for chronic immunosuppression. These therapies are currently entering clinical trials. This article reviews the prevailing therapies that hold promise for future clinical application. In particular, their application in children is discussed, as are biologic aspects of childhood immunity that may play a role in the success or failure of these strategies. C1 Natl Naval Med Res Inst, Dept Surg, Bethesda, MD 20889 USA. Georgetown Univ, Med Ctr, Dept Surg, Washington, DC 20057 USA. NIDDKD, Transplant Sect, Transplantat & Autoimmun Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Kirk, AD (reprint author), Room 11S-219,Bldg 10,Ctr Dr, Bethesda, MD 20892 USA. EM AllanK@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012 NR 107 TC 8 Z9 8 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 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD DEC PY 2003 VL 50 IS 6 BP 1261 EP + DI 10.1016/S0031-3955(03)00120-2 PG 22 WC Pediatrics SC Pediatrics GA 754MJ UT WOS:000187320700003 PM 14710780 ER PT J AU Abramson, JS Baker, CJ Baltimore, RS Bocchini, JA Long, SS McMillan, JA Meissner, HC Powell, KR Prober, CG Rennels, MB Saari, TN Weiner, LB Blackmon, L Batton, DG Bell, EF Denson, SE Engle, WA Kanto, WP Martin, GI Stark, AR AF Abramson, JS Baker, CJ Baltimore, RS Bocchini, JA Long, SS McMillan, JA Meissner, HC Powell, KR Prober, CG Rennels, MB Saari, TN Weiner, LB Blackmon, L Batton, DG Bell, EF Denson, SE Engle, WA Kanto, WP Martin, GI Stark, AR CA Comm Infect Dis Comm Fetus Newborn TI Revised indications for the use of Palivizumab and Respiratory Syncytial Virus Immune Globulin Intravenous for the prevention of respiratory syncytial virus infections SO PEDIATRICS LA English DT Article AB Palivizumab and Respiratory Syncytial Virus Immune Globulin Intravenous ( RSV- IGIV) are licensed by the Food and Drug Administration for use in preventing severe lower respiratory tract infections caused by respiratory syncytial virus ( RSV) in high- risk infants, children younger than 24 months with chronic lung disease ( formerly called bronchopulmonary dysplasia), and certain preterm infants. This statement provides revised recommendations for administering RSV prophylaxis to infants and children with congenital heart disease, for identifying infants with a history of preterm birth and chronic lung disease who are most likely to benefit from immunoprophylaxis, and for reducing the risk of RSV exposure and infection in high- risk children. On the basis of results of a recently completed clinical trial, prophylaxis with palivizumab is appropriate for infants and young children with hemodynamically significant congenital heart disease. RSV- IGIV should not be used in children with hemodynamically significant heart disease. Palivizumab is preferred for most high-risk infants and children because of ease of intramuscular administration. Monthly administration of palivizumab during the RSV season results in a 45% to 55% decrease in the rate of hospitalization attributable to RSV. Because of the large number of infants born after 32 to 35 weeks' gestation and because of the high cost, immunoprophylaxis should be considered for this category of preterm infants only if 2 or more risk factors are present. High- risk infants should not attend child care during the RSV season when feasible, and exposure to tobacco smoke should be eliminated. C1 Amer Acad Pediat, Comm Infect Dis, Elk Grove Village, IL 60007 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Natl Vaccine Program Off, Atlanta, GA USA. Amer Acad Pediat, Infect Dis Sect, Elk Grove Village, IL USA. Amer Acad Family Phys, Leawood, KS 66211 USA. NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Amer Thorac Soc, New York, NY 10019 USA. Amer Acad Pediat, Comm Fetus & Newborn, Elk Grove Village, IL USA. Amer Coll Obstetricians & Gynecologists, Washington, DC 20090 USA. Natl Assoc Neonatal Nurses, Glenview, IL 60025 USA. RP Abramson, JS (reprint author), Amer Acad Pediat, Comm Infect Dis, Elk Grove Village, IL 60007 USA. NR 5 TC 122 Z9 127 U1 0 U2 2 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 2003 VL 112 IS 6 BP 1442 EP 1446 PG 5 WC Pediatrics SC Pediatrics GA 749YK UT WOS:000186957500039 ER PT J AU Alexander, D AF Alexander, D TI The National Institute of Child Health and Human Development and phenylketonuria SO PEDIATRICS LA English DT Article DE phenylketonuria; PKU; NICHD; newborn screening; mental retardation; maternal PKU AB The National Institute of Child Health and Human Development ( NICHD) was established shortly after the Guthrie test for screening newborn infants for phenylketonuria ( PKU) was introduced. The NICHD supported the study demonstrating the longterm efficacy of screening and a low- phenylalanine diet in preventing mental retardation. With the identification of the adverse impact on fetal development of high intrauterine phenylalanine exposure from a mother with PKU, the NICHD organized and supported the study reported here, demonstrating the protective effect of phenylalanine restriction of the mother's diet during pregnancy. The study provides clear guidance for the management of pregnancy in women with PKU. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP NICHHD, NIH, Bldg 31,Rm 2 A03,31 Ctr Dr,MSC 2425, Bethesda, MD 20892 USA. EM da43w@nih.gov NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD DEC PY 2003 VL 112 IS 6 SU S BP 1514 EP 1515 PG 2 WC Pediatrics SC Pediatrics GA 749YN UT WOS:000186957800002 PM 14654655 ER PT J AU Koch, R Azen, C Friedman, E Hanley, W Levy, H Matalon, R Rouse, B Trefz, F Ning, JP de la Cruz, F AF Koch, R Azen, C Friedman, E Hanley, W Levy, H Matalon, R Rouse, B Trefz, F Ning, JP de la Cruz, F TI Research design, organization, and sample characteristics of the maternal PKU collaborative study SO PEDIATRICS LA English DT Article DE Maternal PKU Collaborative Study; phenylalanine; phenylalanine-restricted diet; hyperphenylalaninemic AB Objective. The Maternal PKU Collaborative Study ( MPKUCS) was initiated in 1984 by the National Institute of Child Health and Human Development ( NICHD). The purpose was to assess the efficacy of dietary restriction of phenylalanine in reducing morbidity in offspring of women with hyperphenylalaninemia ( HPA). A contract was awarded to Childrens Hospital Los Angeles as the Coordinating Center to provide implementation of the research protocol, data collection, and analysis. Methods. The Study included four regional contributing centers: Childrens Hospital Los Angeles ( Western Region), Boston Children's Hospital ( Northeast Region), University of Illinois ( Midwest Region), and University of Texas Medical Branch, Galveston ( Southeast Region). Within each region, many participating clinics were responsible for obstetric care, treatment, and monitoring protocols. In 1985, Canada joined the MPKUCS, and in 1992, Germany entered. They were selected because they provided dietary supplies and strong professional services. Acquisition began in 1984 and ended in October 1995. The study included 574 pregnancies in women with HPA and 100 control subjects matched on age, race, parity, and weeks of gestation. The sample included women with blood phenylalanine values > 240 mu mol/ L, 66% of whom had classical PKU, 22% had atypical PKU, and 12% had mild HPA. Informed consents were obtained on all participants. The women ranged in age from 15 to 36 years of age, with a mean age at conception of 23 years. Teenage pregnancies accounted for 19%. Seventy- five percent graduated from high school. Offspring included 416 newborns, 317 of whom were evaluated at 4 years of age and 289 at 6 to 7 years. Follow- up involved medical, nutritional, psychosocial, and psychological assessments. Conclusion. Women with PKU treated before conception and in control of their blood phenylalanine levels between 120 and 360 mu mol/ L ( 2 - 6 mg) exhibited normal pregnancies and neonatal outcome. Surprisingly, women who achieved control in the recommended range by 8 weeks of pregnancy also had a normal fetal outcome. C1 NICHHD, Bethesda, MD 20892 USA. Univ Tubingen, Childrens Hosp Reutlingen, Reutlingen, Germany. Univ Texas, Med Branch, Dept Pediat Genet, Galveston, TX 77550 USA. Childrens Hosp Boston, Boston, MA USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ So Calif, Dept Pediat, Keck Sch Med, Childrens Hosp Los Angeles,Div Med Genet, Los Angeles, CA 90089 USA. RP Koch, R (reprint author), Childrens Hosp Los Angeles, Maternal PKU Collaborat Study, PKU Program 73, 4650 Sunset Blvd, Los Angeles, CA 90027 USA. FU NICHD NIH HHS [N01-HD-2-3148] NR 2 TC 6 Z9 6 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2003 VL 112 IS 6 SU S BP 1519 EP 1522 PG 4 WC Pediatrics SC Pediatrics GA 749YN UT WOS:000186957800004 PM 14654657 ER PT J AU Koch, R Hanley, W Levy, H Matalon, K Matalon, R Rouse, B Trefz, F Guttler, F Azen, C Platt, L Waisbren, S Widaman, K Ning, JP Friedman, EG de la Cruz, F AF Koch, R Hanley, W Levy, H Matalon, K Matalon, R Rouse, B Trefz, F Guttler, F Azen, C Platt, L Waisbren, S Widaman, K Ning, JP Friedman, EG de la Cruz, F TI The maternal phenylketonuria international study: 1984-2002 SO PEDIATRICS LA English DT Article DE pregnancy; maternal phenylketonuria; offspring outcome; phenylalanine-restricted diet ID WOMEN AB Objective. The purpose of this report is to review the obstetric medical, psychological, and nutritional aspects and outcome of the women and offspring enrolled in the Maternal Phenylketonuria Study, which was established to assess the efficacy of a phenylalanine ( Phe)- restricted diet in preventing the morbidity associated with this disorder. Methods. A total of 382 women with hyperphenylalaninemia ( HPA) were enrolled in the study and completed 572 pregnancies. Outcome measures were analyzed with chi(2), Fisher exact text, analysis of variance, t test, Wilcoxon nonparametric test, and multiple logistic regression. Outcome measures were stratified according to maternal HPA classification and the time when dietary control was achieved. Results. Optimal birth outcomes occurred when maternal blood Phe levels between 120 and 360 mu mol/ L were achieved by 8 to 10 weeks of gestation and maintained throughout pregnancy ( trimester averages of 600 mu mol/ L). Mothers with mild HPA achieved similar birth outcomes as mothers who were in control preconceptually and those in control by 8 to 10 weeks of pregnancy. Conclusions. Before conception, counseling and early entrance into a prenatal care program is essential in achieving optimal fetal outcome in women with HPA. The achievement of pre- and periconceptional dietary control with a Phe- restricted diet significantly decreased morbidity in the offspring of women with HPA. C1 Childrens Hosp Los Angeles, Maternal PKU Collaborat Study, PKU Program 73, Los Angeles, CA 90027 USA. NICHHD, Bethesda, MD 20892 USA. Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. John F Kennedy Inst, DK-2600 Glostrup, Denmark. Univ Teubingen, Reutlingen, Germany. Univ Texas, Sch Med, Child Dev & Genet Div, Galveston, TX 77555 USA. Childrens Hosp & Med Ctr, Boston, MA USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ So Calif, Sch Med, Los Angeles, CA USA. RP Koch, R (reprint author), Childrens Hosp Los Angeles, Maternal PKU Collaborat Study, PKU Program 73, 4650 Sunset Blvd, Los Angeles, CA 90027 USA. FU NICHD NIH HHS [N01-HD-2-3148] NR 18 TC 53 Z9 56 U1 0 U2 4 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 2003 VL 112 IS 6 SU S BP 1523 EP 1529 PG 7 WC Pediatrics SC Pediatrics GA 749YN UT WOS:000186957800005 PM 14654658 ER PT J AU Guttler, F Azen, C Guldberg, P Romstad, A Hanley, WB Levy, HL Matalon, R Rouse, BM Trefz, F de la Cruz, F Koch, R AF Guttler, F Azen, C Guldberg, P Romstad, A Hanley, WB Levy, HL Matalon, R Rouse, BM Trefz, F de la Cruz, F Koch, R TI Impact of the phenylalanine hydroxylase gene on maternal phenylketonuria outcome SO PEDIATRICS LA English DT Article DE PKU; phenylalanine hydroxylase; mutation; maternal PKU; cognitive development ID MUTATIONS; DEFICIENCY; PHENOTYPE; GENOTYPE AB Objective. The aim of the present study was to examine to what extent maternal and offspring phenylalanine hydroxylase ( PAH) genotypes in conjunction with maternal IQ and dietary control during pregnancy are related to cognitive development in offspring of women with phenylketonuria ( PKU). Methods. PAH gene mutations were determined in 196 maternal PKU subjects and their offspring. The women were grouped according to PAH genotype, which predicts the metabolic phenotype ( severe PKU, mild PKU, and mild hyperphenylalaninemia [ MHP]). IQ was determined in both the mothers ( Wechsler Adult Intelligence Scale - Revised at > 18 years) and their children ( Wechsler Intelligence Scale for Children - Revised at > 6 - 7 years of age). Results. According to PAH genotypes, 62% of the women exhibited severe PKU, 19% exhibited mild PKU, and 19% exhibited MHP. Maternal IQ increased, and the assigned phenylalanine ( Phe) levels decreased with decreasing severity of PAH genotype. In offspring of mild maternal PKU, multiple regression analysis showed offspring IQ to be significantly related to maternal IQ but not to Phe exposure during pregnancy, which was < 750 μ mol/ L in all cases of mild PKU. In offspring of mothers with severe PKU and average Phe exposure during pregnancy of 360 to 750 μ mol/ L, multiple regression analysis revealed both maternal IQ and Phe exposure to be significant predictors of offspring IQ. When average Phe exposure was < 360 mu mol/ L, cognitive development was normal ( mean IQ: 105), whereas an average Phe exposure of > 750 mu mol/ L severely depressed offspring IQ ( mean IQ: 56) in this group regardless of maternal IQ. It could not be documented that the offspring PAH genotype affects cognitive development. Conclusion. Female individuals with severe PKU should be offered a diet for a lifetime. If good metabolic control is established, then women with PKU will have children with IQ scores that are not influenced by their disease. C1 John F Kennedy Inst, Dept Inherited Metab Dis & Mol Genet, DK-2600 Glostrup, Denmark. NICHHD, Bethesda, MD 20892 USA. Univ Tubingen, Reutlingen, Germany. Univ Texas, Med Branch, Childrens Hosp, Galveston, TX 77550 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ So Calif, Los Angeles, CA USA. Childrens Hosp, Div Med Genet, Los Angeles, CA 90027 USA. RP Guttler, F (reprint author), John F Kennedy Inst, Dept Inherited Metab Dis & Mol Genet, Gl Landevej 7, DK-2600 Glostrup, Denmark. FU NICHD NIH HHS [N01-HD-2-3148] NR 13 TC 11 Z9 12 U1 0 U2 3 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 2003 VL 112 IS 6 SU S BP 1530 EP 1533 PG 4 WC Pediatrics SC Pediatrics GA 749YN UT WOS:000186957800006 PM 14654659 ER PT J AU Levy, HL Waisbren, SE Guttler, F Hanley, WB Matalon, R Rouse, B Trefz, FK de la Cruz, F Azen, CG Koch, R AF Levy, HL Waisbren, SE Guttler, F Hanley, WB Matalon, R Rouse, B Trefz, FK de la Cruz, F Azen, CG Koch, R TI Pregnancy experiences in the woman with mild hyperphenylalaninemia SO PEDIATRICS LA English DT Article DE maternal phenylalanine; genotype; offspring; birth weight; birth length; birth head circumference; IQ ID CONGENITAL HEART-DISEASE; MATERNAL PHENYLKETONURIA; INTERNATIONAL SURVEY; TREATED PREGNANCIES; PHENYLALANINE AB Objective. A major issue in maternal phenylketonuria ( MPKU) has been whether maternal non- PKU mild hyperphenylalaninemia ( MHP) is teratogenic. Such untreated pregnancies and their outcomes are presented on this report. Methods. Enrolled pregnancies in which the untreated prepregnancy assigned phenylalanine level ( APL) was no more than 600 mu mol/ L were included in the Maternal PKU Collaborative Study and were followed according to protocol. Results. Forty- eight enrolled women with non- PKU MHP had mean APL 408 +/- 114 mu mol/ L. They had a total of 58 pregnancies that resulted in live births. Fifty were untreated. Maternal phenylalanine ( Phe) levels in the untreated pregnancies decreased during pregnancy for average Phe exposure of 270 +/- 84 mu mol/ L, virtually identical to the level of 269 +/- 136 mu mol/ L in the 8 treated pregnancies. Birth measurements in the 50 offspring from untreated pregnancies were within normal limits with z scores of - 0.25 for weight, 0.28 for length, and - 0.63 for head circumference, although birth head circumference was negatively correlated with maternal APL ( r = - 0.30). Only 1 offspring had congenital heart disease. Offspring IQ was 102 +/- 15 compared with 96 +/- 14 in the mothers with untreated pregnancies and with 109 +/- 21 in control offspring. Conclusion. Maternal non- PKU MHP no more than 600 mu mol/ L does not require dietary therapy. The naturally lower Phe level during pregnancy seems to protect against teratogenesis. C1 Childrens Hosp Boston, Div Genet, Boston, MA 02115 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. NICHHD, Bethesda, MD 20892 USA. Childrens Hosp Reutlingen, Reutlingen, Germany. Univ Texas, Med Branch, Galveston, TX 77550 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. John F Kennedy Inst, DK-2600 Glostrup, Denmark. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Childrens Hosp Boston, Div Genet, 300 Longwood Ave,IC-106, Boston, MA 02115 USA. EM harvey.levy@tch.harvard.edu FU NICHD NIH HHS [N01-HD-3149] NR 24 TC 21 Z9 21 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD DEC PY 2003 VL 112 IS 6 SU S BP 1548 EP 1552 PG 5 WC Pediatrics SC Pediatrics GA 749YN UT WOS:000186957800010 PM 14654663 ER PT J AU Terracciano, A AF Terracciano, A TI The Italian version of the NEO PI-R: conceptual and empirical support for the use of targeted rotation SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE procrustes rotation; NEO-PI-R; rotational variants; cross-cultural; validity; PANAS; CES-D ID COMREY PERSONALITY-SCALES; 5-FACTOR MODEL; VALIDATION; INVENTORY; TEMPERAMENT; CULTURES; TRAITS; GENERALIZABILITY; REPLICABILITY; DEPRESSION AB Earlier cross-cultural research on replicability of the Revised NEO Personality Inventory (NEO-PI-R) suggested that personality trait structure is universal, but a recent study using an Italian translation has challenged this position. The present article re-examines the psychometric properties of the Italian NEO-PI-R and discusses the importance of orthogonal Procrustes rotation when the replicability of complex factor structures is tested. The arguments are supported by data from a slightly modified translation of the NEO-PI-R, which was administered to 575 Italian subjects. These data show a close replication of the American normative factor structure when targeted rotation is used. Further, the validity of the Italian NEO-PI-R is supported by external correlates, such as demographic variables (age, sex, education), depression, and affect scales. (C) 2003 Elsevier Ltd. All rights reserved. C1 NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. RP Terracciano, A (reprint author), NIA, Lab Personal & Cognit, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI terracciano, antonio/B-1884-2008 FU Intramural NIH HHS [Z99 AG999999, ZIA AG000180-25, ZIA AG000180-26] NR 42 TC 36 Z9 37 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD DEC PY 2003 VL 35 IS 8 BP 1859 EP 1872 DI 10.1016/S0191-8869(03)00035-7 PG 14 WC Psychology, Social SC Psychology GA 747QN UT WOS:000186815900011 PM 19002272 ER PT J AU Tabacova, S Little, R Tsong, Y Vega, A Kimmel, CA AF Tabacova, S Little, R Tsong, Y Vega, A Kimmel, CA TI Adverse pregnancy outcomes associated with maternal enalapril antihypertensive treatment SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE anti-hypertensive drugs; ACE inhibitors; enalapril maternal exposure; adverse pregnancy outcomes; oligohydramnios; congenital abnormalities; neonatal renal failure ID CONVERTING ENZYME-INHIBITORS; NEONATAL RENAL-FAILURE; ACE-INHIBITORS; INDUCED HYPERTENSION; RISK-FACTORS; FETAL; PREECLAMPSIA; GROWTH; FETOPATHY; DISTRESS AB Background Adverse pregnancy outcomes following the use of angiotensin-converting enzyme (ACE) inhibitors, including enalapril, have been reported in descriptive studies. However, no analytical studies on the relationship between the adverse outcomes and enalapril gestational exposures are available. Objectives To explore the association between enalapril exposure and adverse outcomes in pregnancy, taking into account other possible risk factors. Methods We analyzed a series of all usable cases reported to the FDA between 1986 and 2000 in which enalapril was a suspect drug for the observed adverse outcomes (N = 110). Parameters of exposure and reported outcomes as well as information on potentially confounding variables were systematically abstracted from this series by a single physician. Because exposure to ACE inhibitors after the first trimester of pregnancy had been associated with adverse outcomes in the existing literature, we divided the cases into those exposed in the first trimester only (considered as the baseline group) and cases exposed beyond or after this time. Frequency of reported adverse outcomes in the second group was compared with those in the baseline group; odds ratios were computed, taking account of potentially confounding variables by logistic regression where appropriate. Results Exposure to enalapril after the first trimester of pregnancy was strongly associated with oligohydramnios and specific adverse outcomes thought to be secondary to reduced amniotic fluid volume (limb deformities, cranial ossification deficits, lung hypoplasia), as well as with neonatal renal failure. The relationship did not change after taking numerous potential confounders into account, including duration of exposure, concomitant drug use, maternal age, concurrent disease, neonatal gender, and gestational age at birth. Such a pattern of abnormalities is considered to be a consequence of the effect of ACE inhibition on fetal renal function that develops after the first trimester. Conclusion The specificity and temporality of the observed adverse manifestations suggest a causal relationship to enalapril exposure. Copyright (C) 2003 John Wiley Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. US EPA, Natl Ctr Environm Assesment, Off Res & Dev, Washington, DC 20460 USA. RP Tabacova, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Dndp,Hfd-120,5600 Fishers Lane, Rockville, MD 20857 USA. NR 42 TC 49 Z9 56 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD DEC PY 2003 VL 12 IS 8 BP 633 EP 646 DI 10.1002/pds.796 PG 14 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 757GH UT WOS:000187554300001 PM 14762979 ER PT J AU Catterall, WA Chandy, KG Clapham, DE Gutman, GA Hofmann, F Harmar, AJ Abernethy, DR Spedding, M AF Catterall, WA Chandy, KG Clapham, DE Gutman, GA Hofmann, F Harmar, AJ Abernethy, DR Spedding, M TI International Union of Pharmacology: Approaches to the nomenclature of voltage-gated ion channels SO PHARMACOLOGICAL REVIEWS LA English DT Editorial Material C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92717 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. Univ Edinburgh, Sch Biomed & Clin Lab Sci, Div Neurosci, Edinburgh, Midlothian, Scotland. Tech Univ Munich, Inst Pharmakol, D-8000 Munich, Germany. Inst Rech Int Servier, Neuilly Sur Seine, France. RP Abernethy, DR (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Harmar, Anthony/0000-0002-3838-9264 NR 4 TC 5 Z9 8 U1 1 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD DEC PY 2003 VL 55 IS 4 BP 573 EP 574 DI 10.1124/pr.55.4.5 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 749GG UT WOS:000186910700001 ER PT J AU Milhavet, O Gary, DS Mattson, MP AF Milhavet, O Gary, DS Mattson, MP TI RNA interference in biology and medicine SO PHARMACOLOGICAL REVIEWS LA English DT Review ID DOUBLE-STRANDED-RNA; MEDIATED GENETIC INTERFERENCE; CULTURED-MAMMALIAN-CELLS; DEPENDENT PROTEIN-KINASE; SMALL TEMPORAL RNAS; C-ELEGANS REQUIRES; CAENORHABDITIS-ELEGANS; MESSENGER-RNA; NEURODEGENERATIVE DISORDERS; MITOCHONDRIAL DYSFUNCTION AB First discovered in plants the nematode Caenorhabditis elegans, the production of small interfering RNAs (siRNAs) that bind to and induce the degradation of specific endogenous mRNAs is now recognized as a mechanism that is widely employed by eukaryotic cells to inhibit protein production at a post-transcriptional level. The endogenous siRNAs are typically 19- to 23-base double-stranded RNA oligonucleotides, produced from much larger RNAs that upon binding to target mRNAs recruit RNases to a protein complex that degrades the targeted mRNA. Methods for expressing siRNAs in cells in culture and in vivo using viral vectors, and for transfecting cells with synthetic siRNAs, have been developed and are being used to establish the functions of specific proteins in various cell types and organisms. RNA interference methods provide several major advantages over prior methods (antisense DNA or antibody-based techniques) for suppressing gene expression. Recent preclinical studies suggest that RNA interference technology holds promise for the treatment of various diseases. Pharmacologists have long dreamed of the ability to selectively antagonize or eliminate the function of individual proteins-RNAi technology may eventually make that dream a reality. C1 NIA, Gerontol Res Ctr, Neurosci Lab, 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. RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 176 TC 78 Z9 100 U1 0 U2 10 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD DEC PY 2003 VL 55 IS 4 BP 629 EP 648 DI 10.1124/pr.55.4.1 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 749GG UT WOS:000186910700009 PM 14657420 ER PT J AU Larralde, H Berezhkovskii, AM Weiss, GH AF Larralde, H Berezhkovskii, AM Weiss, GH TI Effects of an absorbing boundary on the average volume visited by N spherical Brownian particles SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article; Proceedings Paper CT International Workshop in honor of Shlomo Havlins 60th Birthday CY JAN 05-09, 2003 CL ELAT, ISRAEL DE reaction kinetics; optical measurements; Wiener sausage volume ID MODEL AB The number of distinct sites visited by a lattice random walk and its continuum analog, the volume swept out by a diffusing spherical particle are used to model different phenomena in physics, chemistry and biology. Therefore the problem of finding statistical properties of these random variables is of importance. There have been several studies of the more general problem of the volume of the region explored by N random walks or Brownian particles in an unbounded space. We here study the effects of a planar absorbing boundary on the average of this volume. The boundary breaks the translational invariance of the space, and introduces an additional spatial parameter, the initial distance of the Brownian particles from the surface. We derive expressions for the average volume visited in three dimensions and the average span in one dimension as functions of the time for given values of the initial distance to the absorbing boundary and N. The results can be transformed to those for N lattice random walks by appropriately choosing the radius and diffusion constant of the spheres. (C) 2003 Elsevier B.V. All rights reserved. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Nacl Autonoma Mexico, Ctr Ciencias Fis, Cuernavaca 62210, Morelos, Mexico. LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. RP Weiss, GH (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. EM ghw@helix.nih.gov NR 20 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD DEC 1 PY 2003 VL 330 IS 1-2 BP 167 EP 176 DI 10.1016/j.physa.2003.08.025 PG 10 WC Physics, Multidisciplinary SC Physics GA 753HH UT WOS:000187225600023 ER PT J AU Rouault, TA AF Rouault, TA TI How mammals acquire and distribute iron needed for oxygen-based metabolism SO PLOS BIOLOGY LA English DT Editorial Material ID HEMOCHROMATOSIS PROTEIN HFE; TRANSFERRIN RECEPTOR; HEREDITARY HEMOCHROMATOSIS; CRYSTAL-STRUCTURE; BINDING; GENE C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. EM trou@helix.nih.gov NR 19 TC 12 Z9 12 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD DEC PY 2003 VL 1 IS 3 BP 326 EP 328 AR e79 DI 10.1371/journal.pbio.0000079 PG 3 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 772HC UT WOS:000188835600007 PM 14691550 ER PT J AU Sharov, AA Piao, YL Matoba, R Dudekula, DB Qian, Y Vanburen, V Falco, G Martin, PR Stagg, CA Bassey, UC Wang, YX Carter, MG Hamatani, T Aiba, K Akutsu, H Sharova, L Tanaka, TS Kimber, WL Yoshikawa, T Jaradat, SA Pantano, S Nagaraja, R Boheler, KR Taub, D Hodes, RJ Longo, DL Schlessinger, D Keller, J Klotz, E Kelsoe, G Umezawa, A Vescovi, AL Rossant, J Kunath, T Hogan, BLM Curci, A D'Urso, M Kelso, J Hide, W Ko, MSH AF Sharov, AA Piao, YL Matoba, R Dudekula, DB Qian, Y Vanburen, V Falco, G Martin, PR Stagg, CA Bassey, UC Wang, YX Carter, MG Hamatani, T Aiba, K Akutsu, H Sharova, L Tanaka, TS Kimber, WL Yoshikawa, T Jaradat, SA Pantano, S Nagaraja, R Boheler, KR Taub, D Hodes, RJ Longo, DL Schlessinger, D Keller, J Klotz, E Kelsoe, G Umezawa, A Vescovi, AL Rossant, J Kunath, T Hogan, BLM Curci, A D'Urso, M Kelso, J Hide, W Ko, MSH TI Transcriptome analysis of mouse stem cells and early embryos SO PLOS BIOLOGY LA English DT Article ID GENE-EXPRESSION PATTERNS; PRIMORDIAL GERM-CELLS; CDNA CLONE SET; INITIAL ANNOTATION; SEQUENCE TAGS; GENOME; DATABASE; PROLIFERATION; VERIFICATION; DERIVATION AB Understanding and harnessing cellular potency are fundamental in biology and are also critical to the future therapeutic use of stem cells. Transcriptome analysis of these pluripotent cells is a first step towards such goals. Starting with sources that include oocytes, blastocysts, and embryonic and adult stem cells, we obtained 249,200 high-quality EST sequences and clustered them with public sequences to produce an index of approximately 30,000 total mouse genes that includes 977 previously unidentified genes. Analysis of gene expression levels by EST frequency identifies genes that characterize preimplantation embryos, embryonic stem cells, and adult stem cells, thus providing potential markers as well as clues to the functional features of these cells. Principal component analysis identified a set of 88 genes whose average expression levels decrease from oocytes to blastocysts, stem cells, postimplantation embryos, and finally to newborn tissues. This can be a first step towards a possible definition of a molecular scale of cellular potency. The sequences and cDNA clones recovered in this work provide a comprehensive resource for genes functioning in early mouse embryos and stem cells. The nonrestricted community access to the resource can accelerate a wide range of research, particularly in reproductive and regenerative medicine. C1 NIA, Baltimore, MD 21224 USA. NCI, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21701 USA. Duke Univ, Ctr Med, Durham, NC USA. Natl Res Inst Child Hlth & Dev, Tokyo, Japan. Osped San Raffaele, Inst Stem Cell Res, I-20127 Milan, Italy. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. CNR, Inst Genet & Biophys, I-80125 Naples, Italy. Univ Western Cape, S African Natl Bioinformat Inst, ZA-7535 Bellville, South Africa. RP Ko, MSH (reprint author), NIA, Baltimore, MD 21224 USA. EM KoM@grc.nia.nih.gov RI Hide, Winston Hide/C-7217-2009; Carter, Mark/B-5089-2010; Ko, Minoru/B-7969-2009; OI Kunath, Tilo/0000-0002-8805-7356; Hide, Winston Hide/0000-0002-8621-3271; Ko, Minoru/0000-0002-3530-3015; Dudekula, Dawood/0000-0002-4054-1827 FU NCI NIH HHS [N01-CO-5600] NR 41 TC 91 Z9 98 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD DEC PY 2003 VL 1 IS 3 BP 410 EP 419 AR e74 DI 10.1371/journal.pbio.0000074 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 772HC UT WOS:000188835600017 PM 14691545 ER PT J AU French, SA Stables, G AF French, SA Stables, G TI Environmental interventions to promote vegetable and fruit consumption among youth in school settings SO PREVENTIVE MEDICINE LA English DT Article DE fruits; vegetables; environment; schools; nutrition; adolescents; children ID CARDIOVASCULAR HEALTH CATCH; PHYSICAL-ACTIVITY; INTERDISCIPLINARY INTERVENTION; OUTCOME EVALUATION; SECONDARY-SCHOOLS; ADOLESCENT TRIAL; PRICING STRATEGY; FOOD ENVIRONMENT; INCREASE FRUIT; FAT FOODS AB Background. This paper reviews the available literature on the school food environment with a focus on identifying effective strategies to promote vegetable and fruit (VF) consumption among youth in school settings. Methods. Studies were identified through a search of electronic databases as well as references cited within published articles. Seven studies were identified that evaluated changes in VF intake and included a control group. Four additional school-based interventions were reviewed that focused on changes in VF intake as part of a multibehavior intervention. Results. Multicomponent school interventions have been effective in increasing F intake, with reported increases ranging from 0.2 to 0.6 servings per day. Impact on V intake has been less effective, with increases ranging from 0 to 0.3 servings per day. Total VF increases ranged from 0 to 0.6 servings per day. Results of environmental-only, school-based interventions have shown positive effects on students' choice of targeted foods. Conclusions. Environmental change interventions in schools show potential for positively affecting VF consumption among youth. (C) 2003 American Health Foundation and Elsevier Inc. All rights reserved. C1 Univ Minnesota, Div Epidemiol, Minneapolis, MN 55454 USA. NCI, Bethesda, MD 20892 USA. RP French, SA (reprint author), Univ Minnesota, Div Epidemiol, 1300 Sound 2nd St,Suite 300, Minneapolis, MN 55454 USA. NR 52 TC 122 Z9 123 U1 4 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD DEC PY 2003 VL 37 IS 6 BP 593 EP 610 DI 10.1016/j.ypmed.2003.09.007 PN 1 PG 18 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 749VX UT WOS:000186951100008 PM 14636793 ER PT J AU Going, S Thompson, J Cano, S Stewart, D Stone, E Harnack, L Hastings, C Norman, J Corbin, C AF Going, S Thompson, J Cano, S Stewart, D Stone, E Harnack, L Hastings, C Norman, J Corbin, C TI The effects of the Pathways Obesity Prevention Program on physical activity in American Indian children SO PREVENTIVE MEDICINE LA English DT Article DE American Indian children; physical activity; accelerometer; intervention ID TRITRAC-R3D ACTIVITY MONITOR; SELF-REPORT; SCHOOL; SCHOOLCHILDREN; ADOLESCENTS; OVERWEIGHT; YOUTH; ACCELEROMETER; DETERMINANTS; PREVALENCE AB Background. Inadequate opportunities for physical activity at school and overall low levels of activity contribute to the high prevalence of overweight and obesity in American-Indian children. Methods. A school-based physical activity intervention was implemented which emphasized increasing the frequency and quality of physical education (PE) classes and activity breaks. Changes in physical activity were assessed using the TriTrac-R3D accelerometer in a subsample of 580 of the students (34%) randomly selected from the Pathways study cohort. Baseline measures were completed with children in second grade. Follow-up measurements were obtained in the spring of the fifth grade. Results. Intervention schools were more active (+6.3 to +27.2%) than control schools at three of the four sites, although the overall difference between intervention and control schools (similar to10%) was not significant (P > 0.05). Boys were more active than girls by 17 to 21% (P less than or equal to .01) at both baseline and follow-up. Conclusions. Despite the trend for greater physical activity at three of four study sites, and an overall difference of similar to10% between intervention and control schools, high variability in accelerometer AVM and the opportunity to measure physical activity on only I day resulted in a the failure to detect the difference as significant. (C) 2003 American Health Foundation and Elsevier Science (USA). All rights reserved. C1 Univ Arizona, Dept Nutr Sci, Tucson, AZ 85721 USA. Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Ctr Hlth Promot & Dis Prevent, Albuquerque, NM 87131 USA. Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC 27514 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55454 USA. Johns Hopkins Univ, Baltimore, MD 21205 USA. Arizona State Univ, Tempe, AZ 85281 USA. RP Going, S (reprint author), Univ Arizona, Dept Nutr Sci, 238 Santz Bldg, Tucson, AZ 85721 USA. FU NHLBI NIH HHS [HL-50885, HL-50867, HL-50869, HL-50895, HL-50907] NR 35 TC 49 Z9 49 U1 3 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD DEC PY 2003 VL 37 IS 6 SU S BP S62 EP S69 DI 10.1016/j.ypmed.2003.08.005 PN 2 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 751XA UT WOS:000187114300008 PM 14636810 ER PT J AU Lohman, T Thompson, J Going, S Himes, JH Caballero, B Norman, J Cano, S Ring, K AF Lohman, T Thompson, J Going, S Himes, JH Caballero, B Norman, J Cano, S Ring, K TI Indices of changes in adiposity in American Indian children SO PREVENTIVE MEDICINE LA English DT Article DE American Indian children; native American; body composition changes; body fat; skinfolds; bioelectrical impedance; body mass index ID OVERWEIGHT PREVALENCE; ENERGY-EXPENDITURE; PHYSICAL-ACTIVITY; BODY-COMPOSITION; SCHOOLCHILDREN; OBESITY; WEIGHT; COMMUNITIES; ADOLESCENTS; HEIGHT AB Background. Pathways, a randomized trial, evaluated the effectiveness of a school-based obesity prevention program on body composition changes in American Indian children. Several body composition methods were compared in intervention and control schools for assessing body composition changes. Methods. Body composition methods, including skinfolds, bioelectric impedance analysis (BIA), body mass index (BMI), and using a combination of body composition methods were selected to assess 3-year changes in PBF in 705 children within 21 intervention schools and 663 children within 20 control schools. The study equation using skinfolds, BIA, and BMI was developed on a previous sample of American Indian children using deuterium oxide dilution as the criterion method. Results. Body fat changes among methods for the intervention sample ranged from 5.4% (BMI method) to 7.1% (combination of methods) and for the control sample, from 5.8% (BMI method) to 7.3% (combination of methods). The study equation estimates were significantly higher than the other methods and the BMI equation estimates were significantly lower than the other methods except by BIA. The BIA equation showed a significantly larger standard deviation of the difference over the 3-year intervention than each of the other methods indicating less reliability for detecting body composition changes. Conclusions. Within the Pathways large scale intervention trial with American Indian children, we found comparable yet significantly different mean PBF changes among methods. However, BIA was not as reliable as skinfolds and the combination of BIA, skinfolds, and body weight in assessing PBF changes. (C) 2003 American Health Foundation and Elsevier Science (USA). All rights reserved. C1 Univ Arizona, Dept Exercise & Sport Sci, Dept Physiol, Tucson, AZ 85721 USA. Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Ctr Hlth Promot & Dis Prevent, Albuquerque, NM 87131 USA. Univ Arizona, Dept Nutr Sci, Tucson, AZ 85721 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. Johns Hopkins Univ, Ctr Human Nutr, Baltimore, MD 21218 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. RP Lohman, T (reprint author), Univ Arizona, Dept Exercise & Sport Sci, Dept Physiol, Gittings Bldg,Room 93, Tucson, AZ 85721 USA. FU NHLBI NIH HHS [HL-50907, HL-50867, HL-50885, HL-50869] NR 18 TC 12 Z9 12 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 0091-7435 J9 PREV MED JI Prev. Med. PD DEC PY 2003 VL 37 IS 6 SU S BP S91 EP S96 DI 10.1016/j.ypmed.2003.08.004 PN 2 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 751XA UT WOS:000187114300011 PM 14636813 ER PT J AU Steckler, A Ethelbah, B Martin, CJ Stewart, D Pardilla, M Gittelsohn, J Stone, E Fenn, D Smyth, M Vu, M AF Steckler, A Ethelbah, B Martin, CJ Stewart, D Pardilla, M Gittelsohn, J Stone, E Fenn, D Smyth, M Vu, M TI Pathways process evaluation results: a school-based prevention trial to promote healthful diet and physical activity in American Indian third, fourth, and fifth grade students SO PREVENTIVE MEDICINE LA English DT Article DE process evaluation; American Indians; school health; Pathways; diet; physical activity ID ADOLESCENT TRIAL; OBESITY; SCHOOLCHILDREN; PROGRAM; INTERVENTION; MULTISITE; CATCH; CHILD AB Background. Pathways was a large-scale, multisite, 3-year, study testing a school-based intervention designed to lower percent body fat in American Indian children. Methods. At the 21 intervention schools process evaluation data were collected for training of school personnel; implementation of the classroom and physical activity curricula; implementation of the project's food service guidelines in the school cafeterias; adult participation in the family events; and, students' perceived exposure to the Pathways interventions. Results. Students received about 93% of the classroom curriculum lessons. The minimum requirement of physical education being taught three times per week for at least 30 minutes duration was achieved by the fifth grade. The implementation of the food service behavioral guidelines increased from 51% in the third grade to 87% in the fifth grade. The family events had lower than anticipated adult participation. The participation rates were 45% during the third grade, and 41 and 63% during the fourth and fifth grades, respectively. There was a significant difference between intervention and control students' perceived exposure to Pathways type interventions. Conclusion. The Pathways interventions were successfully implemented with good reach, high extent, and fidelity. (C) 2003 American Health Foundation and Elsevier Inc. All rights reserved. C1 Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27514 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Int Hlth, Div Human Nutr, Baltimore, MD USA. Univ Arizona, Dept Physiol, Tucson, AZ USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Collaborat Studies Coordinat Ctr, Chapel Hill, NC USA. Univ New Mexico, Sch Med, Natl Amer Diabetes Program, Dept Internal Med, Albuquerque, NM 87131 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Int Hlth, Div Human Nutr, Baltimore, MD USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ New Mexico, Hlth Sci Ctr, Ctr Hlth Promot & Dis Prevent, Albuquerque, NM 87131 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. RP Steckler, A (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27514 USA. FU NHLBI NIH HHS [HL50885, HL-50907, HL-50867, HL-50869, HL50905] NR 21 TC 49 Z9 50 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD DEC PY 2003 VL 37 IS 6 SU S BP S80 EP S90 DI 10.1016/j.ypmed.2003.08.002 PN 2 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 751XA UT WOS:000187114300010 PM 14636812 ER PT J AU Stone, EJ Norman, JE Davis, SM Stewart, D Clay, TE Caballero, B Lohman, TG Murray, DM AF Stone, EJ Norman, JE Davis, SM Stewart, D Clay, TE Caballero, B Lohman, TG Murray, DM TI Design, implementation, and quality control in the Pathways American-Indian multicenter trial SO PREVENTIVE MEDICINE LA English DT Article DE multicenter trial; quality control; American-Indian students; schools; diet; physical activity ID CARDIOVASCULAR HEALTH CATCH; PHYSICAL-ACTIVITY; ADOLESCENT TRIAL; OBESITY-PREVENTION; CHILD; YOUTH; PROGRAMS; INTERVENTIONS; COMMUNITIES; NUTRITION AB Background Pathways was the first multicenter American-Indian school-based study to test the effectiveness of an obesity prevention program promoting healthy eating and physical activity. Methods. Pathways employed a nested cohort design in which 41 schools were randomized to intervention or control conditions and students within these schools were followed as a cohort (1,704 third graders at baseline). The study's primary endpoint was percent body fat. Secondary endpoints were levels of fat in school lunches; time spent in physical activity; and knowledge, attitudes, and behaviors regarding diet and exercise. Quality control (QC) included design of data management systems which provided standardization and quality assurance of data collection and processing. Data QC procedures at study centers included manuals of operation, training and certification, and monitoring of performance. Process evaluation was conducted to monitor dose and fidelity of the interventions. Registration and tracking systems were used for students and schools. Results. No difference in mean percent body fat at fifth grade was found between the intervention and control schools. Percent of calories from fat and saturated fat in school lunches was significantly reduced in the intervention schools as was total energy intake from 24-hour recalls. Significant increases in self-reported physical activity levels and knowledge of healthy behaviors were found for the intervention school students. Conclusions. The Pathways study results provide evidence demonstrating the role schools can play in public health promotion. Its study design and QC systems and procedures provide useful models for other similar school based multi- or single-site studies. (C) 2003 American Health Foundation and Elsevier Science (USA). All rights reserved. C1 Univ New Mexico, Dept Phys Performance & Dev, Johnson Res Ctr, Albuquerque, NM 87131 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ New Mexico, Dept Pediat, Ctr Hlth Promot & Dis Prevent, Hlth Sci Ctr, Albuquerque, NM 87131 USA. Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Sch Publ Hlth, Chapel Hill, NC 27514 USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD 21205 USA. Univ Arizona, Dept Physiol, Tucson, AZ 85721 USA. Memphis State Univ, Dept Psychol, Memphis, TN 38152 USA. RP Stone, EJ (reprint author), Univ New Mexico, Dept Phys Performance & Dev, Johnson Res Ctr, Room 1150, Albuquerque, NM 87131 USA. FU NHLBI NIH HHS [U01 HL050867, U01 HL050885, U01 HL050905, U01 HL050907, U01-HL 50905]; PHS HHS [U01-H1-50869] NR 45 TC 23 Z9 23 U1 3 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD DEC PY 2003 VL 37 IS 6 SU S BP S13 EP S23 DI 10.1016/j.ypmed.2003.08.006 PN 2 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 751XA UT WOS:000187114300003 PM 14636805 ER PT J AU Story, M Snyder, MP Anliker, J Weber, JL Cunningham-Sabo, L Stone, EJ Chamberlain, A Ethelbah, B Suchindran, C Ring, K AF Story, M Snyder, MP Anliker, J Weber, JL Cunningham-Sabo, L Stone, EJ Chamberlain, A Ethelbah, B Suchindran, C Ring, K TI Changes in the nutrient content of school lunches: results from the Pathways study SO PREVENTIVE MEDICINE LA English DT Article DE American-Indian children; native American; obesity prevention; school food service; school lunch ID OBESITY-PREVENTION PROGRAMS; AMERICAN-INDIANS; ALASKA NATIVES; DIETARY-FAT; INTERVENTION; CHILDREN; AVAILABILITY; COMMUNITIES; MEALS; FOOD AB Background. Pathways, a randomized trial, evaluated the effectiveness of a school-based multicomponent intervention to reduce fatness in American-Indian schoolchildren. The goal of the Pathways food service intervention component was to reduce the fat in school lunches to no more than 30% of energy from fat while maintaining recommended levels of calories and key nutrients. Methods. The intervention was implemented by school food service staff in intervention schools over a 3-year period. Five consecutive days of school lunch menu items were collected from 20 control and 21 intervention schools at four time periods, and nutrient content was analyzed. Results. There was a significantly greater mean reduction in percent energy from fat and saturated fat in the intervention schools compared to the control schools. Mean percentages of energy from fat decreased from 33.1% at baseline to 28.3% at the end of the study in intervention schools compared to 33.2% at baseline and 32.2% at follow-up in the control schools (P < 0.003). There were no statistically significant differences for calories or nutrients between intervention and control schools. Conclusions. The Pathways school food lunch intervention documented the feasibility of successfully lowering the percent of energy from fat, as part of a coordinated obesity prevention program for American-Indian children. (C) 2003 American Health Foundation and Elsevier Science (USA). All rights reserved. C1 Univ Minnesota, Div Epidemiol, Sch Publ Hlth, Minneapolis, MN 55454 USA. Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Univ Arkansas, Dept Pediat, Little Rock, AR 72204 USA. Univ New Mexico, Ctr Hlth Promot & Dis Prevent, Albuquerque, NM 87131 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Todd Cty Sch District, Mission, SD USA. Johns Hopkins Univ, Baltimore, MD USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. RP Story, M (reprint author), Univ Minnesota, Div Epidemiol, Sch Publ Hlth, 1300 S 2nd St,Ste 300, Minneapolis, MN 55454 USA. FU NHLBI NIH HHS [HL-50907, HL-50867, HL-50885, HL-50905, HL-50869] NR 37 TC 28 Z9 28 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 0091-7435 J9 PREV MED JI Prev. Med. PD DEC PY 2003 VL 37 IS 6 SU S BP S35 EP S45 DI 10.1016/j.ypmed.2003.08.009 PN 2 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 751XA UT WOS:000187114300005 PM 14636807 ER PT J AU Story, M Stevens, J Himes, J Stone, E Rock, BH Ethelbah, B Davis, S AF Story, M Stevens, J Himes, J Stone, E Rock, BH Ethelbah, B Davis, S TI Obesity in American-Indian children: prevalence, consequences, and prevention SO PREVENTIVE MEDICINE LA English DT Article DE obesity; American Indian; native American; prevention; children; diet; physical activity; cardiovascular disease; Type 2 diabetes ID CARDIOVASCULAR RISK-FACTORS; NATIVE-CANADIAN COMMUNITY; WEIGHT CONTROL PRACTICES; CORONARY-HEART-DISEASE; BODY-IMAGE PERCEPTIONS; PHYSICAL-ACTIVITY; PIMA-INDIANS; ENERGY-EXPENDITURE; NAVAJO ADOLESCENTS; HUTCHINSON SMOKING AB Background. American Indians of all ages and both sexes have a high prevalence of obesity. The health risks associated with obesity are numerous and include Type 2 diabetes mellitus, hypertension, dyslipidemia, and respiratory problems. Obesity has become a major health problem in American Indians only in the past few generations and it is believed to be associated with the relative abundance of high-fat, high-calorie foods and the rapid change from active to sedentary lifestyles. Methods. The authors reviewed selected literature on prevalence of obesity in American-Indian children, and health consequences of obesity. Results. Obesity is now one of the most serious public health problems facing American-Indian children, and it has grave implications for the immediate and long-term health of American-Indian youth. Unless this pattern is reversed, American-Indian populations will be burdened by an increased incidence of chronic diseases. Intervention studies are urgently needed in American-Indian communities to develop and test effective strategies for obesity prevention and treatment. Conclusions. To be effective, educational and environmental interventions must be developed with full participation of the American-Indian communities. (C) 2003 American Health Foundation and Elsevier Inc. All rights reserved. C1 Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. NHLBI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA. RP Story, M (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. FU NHLBI NIH HHS [HL-50867, HL-50869, HL-50885, HL-50905, HL-50907] NR 89 TC 55 Z9 56 U1 3 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD DEC PY 2003 VL 37 IS 6 SU S BP S3 EP S12 DI 10.1016/j.ypmed.2003.08.008 PN 2 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 751XA UT WOS:000187114300002 PM 14636804 ER PT J AU Gao, AC Lou, W Dong, JT Barrett, JC Danielpour, D Isaacs, JT AF Gao, AC Lou, W Dong, JT Barrett, JC Danielpour, D Isaacs, JT TI Defining regulatory elements in the human KAI1 (CD 82) metastasis suppressor gene SO PROSTATE LA English DT Article DE KAI1; promoter; metastasis suppressor; prostate ID PROSTATE-CANCER CELLS; DOWN-REGULATION; TRANSMEMBRANE-4 SUPERFAMILY; MESSENGER-RNA; EXPRESSION; PROMOTER; LINES; OVEREXPRESSION; PROGRESSION; REGION AB The human KAI1 metastasis suppressor gene encodes for a 267 amino acid plasma membrane glycoprotein, which has four transmembrane domains and one large and one small extracellular domain. Plasma membrane expression of KAI1 is downregulated during the progression of several cancers to a metastatic state, including prostate, lung, and pancreatic cancers. To elucidate the mechanisms for this downregulation, an understanding of its transcriptional regulation is critical. Therefore, a set of luciferase reporter gene plasmid constructs were generated containing various 5' flanking regions to the transcription initiation site, with or without the first exon and a portion of the first intron of the KAI1 gene. These constructs were transfected into a series of normal and malignant prostate cell lines as well as fibroblasts and the resultant luciferase activities used to define the regulatory elements for expression of the KAI1 gene. Using this approach, the minimal KAI1 promoter was found to be 0.5 kb in size and contains two regions. The first region includes the 197 bp 5' to the transcription initiation site and the second region includes the first exon and a portion of first intron (i.e., +1 to +351 bp). This combined region result in positively regulated strong, but not epithelial specific, luciferase expression. In addition to this minimal promoter element from -197 to +351 bp, there is a second regulatory element further upstream (i.e., -735 to -197bp), which negatively regulates luciferase expression. Additional studies of Marreiros et al. (Gene 302:155, 2003) have documented that a third regulatory element even further 5' (i.e., -922 to -846 bp) encodes an enhancer for the KAI1 gene. C1 Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, James Buchanan Brady Urol Inst,Dept Urol, Baltimore, MD 21231 USA. Roswell Pk Canc Inst, Grace Canc Drug Ctr, Buffalo, NY 14263 USA. Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. RP Isaacs, JT (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, James Buchanan Brady Urol Inst,Dept Urol, Baltimore, MD 21231 USA. FU NCI NIH HHS [CA 58236] NR 36 TC 13 Z9 16 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 0270-4137 J9 PROSTATE JI Prostate PD DEC 1 PY 2003 VL 57 IS 4 BP 256 EP 260 DI 10.1002/pros.10309 PG 5 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 748QC UT WOS:000186871700001 PM 14601021 ER PT J AU Schleutker, J Baffoe-Bonnie, AB Gillanders, E Kainu, T Jones, MP Freas-Lutz, D Markey, C Gildea, D Riedesel, E Albertus, J Gibbs, KD Matikainen, M Koivisto, PA Tammela, T Bailey-Wilson, JE Trent, JM Kallioniemi, OP AF Schleutker, J Baffoe-Bonnie, AB Gillanders, E Kainu, T Jones, MP Freas-Lutz, D Markey, C Gildea, D Riedesel, E Albertus, J Gibbs, KD Matikainen, M Koivisto, PA Tammela, T Bailey-Wilson, JE Trent, JM Kallioniemi, OP TI Genome-wide scan for linkage in Finnish hereditary prostate cancer (HPC) families identifies novel susceptibility loci at 11q14 and 3p25-26 SO PROSTATE LA English DT Article DE genetic susceptibility; cancer predisposition; familiar cancer; homogeneous population ID CHROMOSOME 1Q42.2-43; GERMLINE MUTATIONS; HIGH-RISK; GENE; HPC2/ELAC2; FINLAND; SCREEN; BRCA2; POLYMORPHISMS; ASSOCIATION AB BACKGROUND. In order to identify predisposition loci to hereditary prostate cancer (HPC), we performed a genome-wide linkage analysis using samples from a genetically homogeneous population, with 13 Finnish multiplex prostate cancer families. METHODS. Altogether 87 DNA samples were genotyped from 13 families. Logarithm-of-odds (LOD) scores were calculated for all autosomes using FASTLINK and GENEHUNTER designating all unaffected men and all women as unknown. RESULTS. The highest LOD scores in the affected-only analyses were found at 11q14, where the two-point LOD score was 2.97 (0 = 0.0 at D11S901), GENEHUNTER heterogeneity LOD (HLOD) of 3.36, and a non-parametric-linkage (NPL) score of 2.67 (P = 0.008). A second positive site was at 3p25-26, with a two-point LOD score of 2.57 (theta = 0.01 at D3S1297), HLOD of 2.15, and NPL score of 2.27 (P = 0.02). CONCLUSIONS. The results suggest two HPC regions in the Finnish population, which have not been reported previously and warrant further study. C1 Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33014 Tampere, Finland. Tampere Univ Hosp, Dept Urol, FIN-33014 Tampere, Finland. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. NHGRI, Stat Genet Sect, NIH, Baltimore, MD USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. Univ Turku, Turku, Finland. VTT Tech Res Ctr Finland, Med Biotechnol Dept, Turku, Finland. RP Schleutker, J (reprint author), Univ Tampere, Inst Med Technol, Canc Genet Lab, Lenkkeilijankatu 6, 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; Bailey-Wilson, Joan/0000-0002-9153-2920; Gibbs, Kenneth/0000-0002-3532-5396 FU NCI NIH HHS [CA-06927, U01 CA89600]; NHGRI NIH HHS [N01-HG-55389]; NIGMS NIH HHS [GM 08663] NR 52 TC 36 Z9 36 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0270-4137 J9 PROSTATE JI Prostate PD DEC 1 PY 2003 VL 57 IS 4 BP 280 EP 289 DI 10.1002/pros.10302 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 748QC UT WOS:000186871700004 PM 14601024 ER PT J AU Wiklund, F Gillanders, EM Albertus, JA Bergh, A Damber, JE Emanuelsson, M Freas-Lutz, DL Gildea, DE Goransson, I Jones, MS Jonsson, BA Lindmark, F Markey, CJ Riedesel, EL Stenman, E Trent, JM Gronberg, H AF Wiklund, F Gillanders, EM Albertus, JA Bergh, A Damber, JE Emanuelsson, M Freas-Lutz, DL Gildea, DE Goransson, I Jones, MS Jonsson, BA Lindmark, F Markey, CJ Riedesel, EL Stenman, E Trent, JM Gronberg, H TI Genome-wide scan of Swedish families with hereditary prostate cancer: Suggestive evidence of linkage at 5q11.2 and 19p13.3 SO PROSTATE LA English DT Article DE hereditary prostate cancer; genome-wide scan; linkage analysis ID TUMOR-ASSOCIATED MACROPHAGES; SUSCEPTIBILITY LOCUS; ALLELIC IMBALANCE; CHROMOSOME 1Q; DOMINANT INHERITANCE; GENE; AGGRESSIVENESS; RISK; CONFIRMATION; PROGRESSION AB BACKGROUND. Prostate cancer (CaP) is a common disorder with multiple genetic and environmental factors contributing to the disease. CaP susceptibility loci can be identified through genome-wide scans of high-risk families. METHODS. Allele sharing at 405 markers, distributed across the genome, among 50 families with hereditary prostate cancer, ascertained throughout Sweden, was evaluated through linkage analyses. Genotype data were analyzed utilizing multipoint parametric and non-parametric methods. RESULTS. Two regions provided suggestive evidence for linkage: 19p13.3 (marker D19S209, LOD = 2.91, P = 0.0001) and 5q11.2 (marker D5S407, LOD = 2.24, P = 0.0007). Additional regions with moderate evidence for linkage in the complete set of families, or stratified subsets, were observed on chromosome 1, 4, 6, 7, 8, and X. CONCLUSIONS. Our results provide strong confirmatory evidence of linkage at 19q13.3 and 5q11.2. The lack of confirmation of linkage at several loci identified in other genome-wide scans emphasizes the need to combine linkage data between research groups. C1 Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Umea Univ, Dept Med Biosci, Umea, Sweden. Univ Gothenburg, Dept Surg Sci, Gothenburg, Sweden. Translat Genom Res Inst, Phoenix, AZ USA. RP Wiklund, F (reprint author), Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden. NR 44 TC 40 Z9 42 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 0270-4137 J9 PROSTATE JI Prostate PD DEC 1 PY 2003 VL 57 IS 4 BP 290 EP 297 DI 10.1002/pros.10303 PG 8 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 748QC UT WOS:000186871700005 PM 14601025 ER PT J AU Xu, JF Gillanders, EM Isaacs, SD Chang, BL Wiley, KE Zheng, SL Jones, M Gildea, D Riedesel, E Albertus, J Freas-Lutz, D Markey, C Meyers, DA Walsh, PC Trent, JM Isaacs, WB AF Xu, JF Gillanders, EM Isaacs, SD Chang, BL Wiley, KE Zheng, SL Jones, M Gildea, D Riedesel, E Albertus, J Freas-Lutz, D Markey, C Meyers, DA Walsh, PC Trent, JM Isaacs, WB TI Genome-wide scan for prostate cancer susceptibility genes in the Johns Hopkins hereditary prostate cancer families SO PROSTATE LA English DT Article DE CaP; linkage; genome-wide scan; hereditary ID LINKAGE ANALYSIS; GERMLINE MUTATIONS; LOCUS; CHROMOSOME; SCREEN; TESTS; RISK AB BACKGROUND. Although the subject of intensive study, the genetic influences responsible for familial clustering of prostate cancer remain largely unidentified. Genome-wide scans for linkage in prostate cancer families can be used to systematically search for genes capable of affecting risk for the disease. METHODS. All available family members from 188 families, each having at least three first-degree relatives affected with prostate cancer, were genotyped at 406 markers distributed across the genome at average intervals of less than 10 cM. Genotype data was analyzed using primarily a non-parametric, multipoint approach, although parametric analyses were performed as well. RESULTS. The strongest evidence for linkage was observed at D4S1615, at 4q21 (LOD of 2.8, P = 0.0002). Two other regions had LOD scores over 2.0: at 9q34 (marker D9S1826, LOD = 2.17, P = 0.0008) and at 2q23 (marker D2S151, LOD = 2.03, P = 0.001). An additional 12 regions had LOD scores over 1.0, including markers at 1q24-25 and 7q22 having scores >1.6. Stratifying the linkage results by age of diagnosis indicated that the linkages to chromosomes 2 and 4 were strongest in families with early and late ages of diagnosis, respectively. CONCLUSIONS. Our data implicate several new loci as harboring prostate cancer susceptibility genes, and provide confirmatory evidence of linkage at several loci identified previously in other genome-wide scans, including the three regions (4q21, 9q34, and 2q23) with strongest evidence for prostate cancer linkage. These data also emphasize the need to combine linkage data from large numbers of prostate cancer families in efforts to effectively address the extensive heterogeneity that characterizes genetic aspects of this disease. C1 Wake Forest Univ, Sch Med, Ctr Human Genom, Winston Salem, NC 27109 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. TGEN, Phoenix, AZ USA. RP Isaacs, WB (reprint author), Johns Hopkins Univ Hosp, Marburg 115,600 N Wolfe St, Baltimore, MD 21287 USA. NR 24 TC 56 Z9 58 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 0270-4137 J9 PROSTATE JI Prostate PD DEC 1 PY 2003 VL 57 IS 4 BP 320 EP 325 DI 10.1002/pros.10306 PG 6 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 748QC UT WOS:000186871700008 PM 14601028 ER PT J AU Lange, EM Gillanders, EM Davis, CC Brown, WM Campbell, JK Jones, M Gildea, D Riedesel, E Albertus, J Freas-Lutz, D Markey, C Giri, V Dimmer, JB Montie, JE Trent, JM Cooney, KA AF Lange, EM Gillanders, EM Davis, CC Brown, WM Campbell, JK Jones, M Gildea, D Riedesel, E Albertus, J Freas-Lutz, D Markey, C Giri, V Dimmer, JB Montie, JE Trent, JM Cooney, KA TI Genome-wide scan for prostate cancer susceptibility genes using families from the University of Michigan Prostate Cancer Genetics Project finds evidence for linkage on chromosome 17 near BRCA1 SO PROSTATE LA English DT Article DE prostate cancer; linkage analysis; BRCA1 ID DOMINANT INHERITANCE; GERMLINE MUTATIONS; LOCUS; PREDISPOSITION; HISTORY; RISK AB BACKGROUND. Previous linkage studies have suggested prostate cancer susceptibility genes located on chromosomes 1, 20, and X. Several putative prostate cancer candidate genes have also been identified including RNASEL, MSR1, and ELAC2. Presently, these linkage regions and candidate genes appear to explain only a small proportion of hereditary prostate cancer cases suggesting the need for additional whole genome analyses. METHODS. A genome-wide mode-of-inheritance-free linkage scan, using 405 genetic markers, was conducted on 175 pedigrees, the majority containing three or more affected individuals diagnosed with prostate cancer. Stratified linkage analyses were performed based on previously established criteria. RESULTS. Results based on the entire set of 175 pedigrees showed strong suggestive evidence for linkage on chromosome 17q (LOD = 2.36), with strongest evidence coming from the subset of pedigrees with four or more affected individuals (LOD = 3.27). Race specific analyses revealed strong suggestive evidence for linkage in our African-American pedigrees on chromosome 22q (LOD = 2.35). CONCLUSIONS. Genome-wide analysis of a large set of prostate cancer families indicates new areas of the genome that may harbor prostate cancer susceptibility genes. Specifically, our linkage results suggest that there is a prostate cancer susceptibility gene on chromosome 17 that is independent of ELAC2. Further research including combined analyses of independent genome-wide scan data may clarify the most important regions for future investigation. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Biostat Sect, Winston Salem, NC 27157 USA. NHGRI, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI USA. RP Lange, EM (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Biostat Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA. OI Giri, Veda/0000-0002-7268-5913 NR 30 TC 67 Z9 69 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 0270-4137 J9 PROSTATE JI Prostate PD DEC 1 PY 2003 VL 57 IS 4 BP 326 EP 334 DI 10.1002/pros.10307 PG 9 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 748QC UT WOS:000186871700009 PM 14601029 ER PT J AU Vise, PD Kodali, K Hoe, N Paszczynski, A Musser, JM Daughdrill, GW AF Vise, PD Kodali, K Hoe, N Paszczynski, A Musser, JM Daughdrill, GW TI Stable isotope labeling of a Group A Streptococcus virulence factor using a chemically defined growth medium SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID INVASIVE GROUP; PYOGENES; INHIBITOR; PROTEIN; SPECTROSCOPY; INFECTIONS; EXPRESSION; STRAINS AB A secreted, hypervariable virulence factor called the streptococcal inhibitor of complement (Sic) has been linked to the reemergence of epidemics due to the human pathogenic bacterium Group A Streptococcus. This paper describes a method for expressing and purifying Sic from an attenuated GAS strain using a chemically defined growth medium. This method was used to label specific amino acid residue types in Sic with forms containing the magnetically active isotope N-15, at the amide nitrogen. The N-15-labeling of Sic permits a detailed investigation of the structure and dynamics of the protein using nuclear magnetic resonance spectroscopy. The level of stable isotope incorporation was established using mass spectrometry and nuclear magnetic resonance spectroscopy. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Idaho, Dept Microbiol Mol Biol & Biochem, Moscow, ID 83844 USA. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RML Etc, Lab Human Bacterial Pathogenesis, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Daughdrill, GW (reprint author), Univ Idaho, Dept Microbiol Mol Biol & Biochem, POB 443052,Life Sci S Rm 142, Moscow, ID 83844 USA. FU NCRR NIH HHS [P20 RR16454-02, RR0631401, RR12948] NR 23 TC 8 Z9 8 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD DEC PY 2003 VL 32 IS 2 BP 232 EP 238 DI 10.1016/S1046-5928(03)00235-3 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 755FV UT WOS:000187393600008 PM 14965768 ER PT J AU Biesecker, BB Peay, HL AF Biesecker, BB Peay, HL TI Ethical issues in psychiatric genetics research: points to consider SO PSYCHOPHARMACOLOGY LA English DT Review DE psychiatric genetic disorders; genetic susceptibility; research ethics; points to consider ID SCHIZOPHRENIA SUSCEPTIBILITY LOCI; BIPOLAR-DISORDER; CLINICAL-PRACTICE; FAMILY ATTITUDES; INFORMED-CONSENT; 6P22.3 GENE; ASSOCIATION; CONSEQUENCES; NEUREGULIN-1; ADOLESCENTS AB Rationale. Psychiatric genetics research warrants ethical consideration because of the complex nature of conducting research among affected families. When researchers identify compelling reasons to offer susceptibility data to participants, they face challenges to identify an infrastructure to convey information and means to ensure that undue research risks are not encountered. Objectives. To outline ethical issues in conducting research in psychiatric genetics with the aim of considering how the identification of susceptibility genes for psychiatric disorders may shape future research; to provide points to consider for conducting psychiatric genetics research with the anticipation of offering susceptibility data to participants. Methods. Ethical issues that arise in psychiatric genetics research conducted with affected families are discussed along with reasons susceptibility data may be offered to participants in the future. Results. We suggest that all researchers, even those who have no intention of offering susceptibility genetic results, consider how advances in knowledge might affect the provision of research findings. Conclusions. Existing ethical issues are likely to become even more pressing as susceptibility genes are identified for major psychiatric disorders. It behooves researchers, mental health professionals, and geneticists to consider how to use our growing scientific knowledge to best help participants in ways that anticipate and prevent, rather than respond to, ethical conflicts. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Natl Coalit Hlth Profess Educ Genet, Lutherville Timonium, MD 21093 USA. RP Biesecker, BB (reprint author), NHGRI, Med Genet Branch, NIH, Bldg 10,Room 10C101,10 Ctr Dr,MSC 1852, Bethesda, MD 20892 USA. NR 61 TC 24 Z9 24 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2003 VL 171 IS 1 BP 27 EP 35 DI 10.1007/s00213-003-1502-2 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 750ET UT WOS:000186978900005 PM 13680086 ER PT J AU Vitiello, B AF Vitiello, B TI Ethical considerations in psychopharmacological research involving children and adolescents SO PSYCHOPHARMACOLOGY LA English DT Review DE ethics; psychopharmacology; children; research ID CONTROLLED-TRIAL; CLINICAL-TRIALS; MAJOR DEPRESSION; YOUNG-CHILDREN; MOOD DISORDERS; PLACEBO; PARTICIPATION; EFFICACY AB Rationale. Increased community utilization of psychotropic medications among children has brought attention to pediatric psychopharmacology research and associated ethical issues. Objectives. To discuss ethical aspects of child participation in psychopharmacology protocols. Methods. Selective review of relevant scientific and regulatory literature. Results. Efficacy and safety of psychotropics in children cannot be entirely inferred from adult data and direct participation of children in research is necessary. Child research must follow special regulations that are in addition to those common to all human research. For research with prospect of direct benefit, a critical factor is whether the risk/benefit ratio is favorable to the participating child. For research without such a prospect, the concepts of minimal risk and minor increase over minimal risk apply. However, the interpretation and application of these principles to specific protocols vary across settings and among ethics committees. Thus far, little empirical investigation has been conducted on children and parents' motivation for research participation, effectiveness of the informed consent and assent procedures, possibility of persistent consequences of exposure to experimental treatments and placebo, and validation of the concepts of minimal risk and minor increase over minimal risk.Conclusions. Research on human subject issues relevant to child participation is a promising approach to improving ethical methods and procedures of pediatric psychopharmacology. C1 NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Child & Adolescent Treatment & Prevent Intervent, 6001 Execut Blvd,Room 7149,MSC 9633, Bethesda, MD 20892 USA. NR 26 TC 16 Z9 16 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2003 VL 171 IS 1 BP 86 EP 91 DI 10.1007/s00213-003-1400-7 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 750ET UT WOS:000186978900013 PM 12677353 ER PT J AU Rosenstein, DL Miller, FG AF Rosenstein, DL Miller, FG TI Ethical considerations in psychopharmacological research involving decisionally impaired subjects SO PSYCHOPHARMACOLOGY LA English DT Review DE decisionally impaired; vulnerable; research ethics; federal regulations; protections; Institutional Review Board ID PLACEBO-CONTROLLED TRIALS; INFORMED-CONSENT; PSYCHIATRIC RESEARCH; ALZHEIMERS-DISEASE; CLINICAL-RESEARCH; COMPETENCE; SCHIZOPHRENIA; PARTICIPATION; CAPACITY; ISSUES AB Rationale. Research subjects who are unable to provide informed consent must be protected from exploitation. The federal regulations governing human subjects research mandate additional protections for 'mentally disabled' subjects but include neither a definition of this 'vulnerable' population nor any guidance on what safeguards should be employed or how they should be implemented. Objectives. This article begins with a definition of vulnerability due to a mental disorder in the context of the clinical research setting. It is organized along the following sequential phases of psychopharmacological research: study design and methodology; protocol review; subject recruitment and enrollment; conduct and monitoring of the study; and manuscript preparation and publication. Practical recommendations are then offered to clinical researchers and Institutional Review Boards (IRBs) for implementing additional protections for decisionally impaired subjects at each phase of the psychopharmacological research process.Methods. A computer-assisted literature review was performed to identify descriptions of safeguards for decisionally impaired subjects. Recommendations for additional protections were also drawn from the authors' experiences with the IRB review process and the conduct and monitoring of clinical research with decisionally impaired subjects. Results. The use of informed consent monitoring and the independent assessment of decision-making capacity are two feasible safeguards that IRBs can mandate for research with decisionally impaired subjects. There has been little systematic implementation of other safeguards such as research advance directives or prospective authorization for research participation. Conclusions. Clinical investigators and IRBs are under considerable scrutiny with respect to the protection of decisionally impaired research subjects. There is a pressing need for data-driven strategies for the optimal protection of decisionally impaired research subjects. C1 NIMH, Bethesda, MD 20892 USA. NIMH, Dept Clin Bioeth, NIH, Bethesda, MD 20892 USA. RP Rosenstein, DL (reprint author), NIMH, Bldg 10,Room 3N242,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA. NR 32 TC 15 Z9 16 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2003 VL 171 IS 1 BP 92 EP 97 DI 10.1007/s00213-003-1503-1 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 750ET UT WOS:000186978900014 PM 12774188 ER PT J AU Chen, DT AF Chen, DT TI Curricular approaches to research ethics training for psychiatric investigators SO PSYCHOPHARMACOLOGY LA English DT Review ID MORAL REASONING SKILLS; MEDICAL-EDUCATION; CLINICAL-RESEARCH; RESPONSIBLE CONDUCT; INFORMED-CONSENT; MENTAL-HEALTH; STUDENTS; PERFORMANCE; COMPETENCE; INTEGRITY AB Rationale. Training in research ethics is crucial for psychiatric investigators. Addressing ethical dimensions of human subjects research requires knowledge about the rules and norms governing research; sensitivity to ethical implications of actions; and skills in ethics problem solving. Investigators in training who are physicians have the additional challenge of developing identities as investigators that sometimes conflict with their identities as physicians. Objectives. To propose a curriculum for psychiatric research ethics training. Methods. Review of literature on ethics education and presentation of a curricular approach to research ethics training for psychiatric investigators.Results. Research ethics can be learned and should be taught. Involvement of active investigators in teaching research ethics is important. While core topics of psychiatric research ethics training have not yet been identified, there are available models from which to draw. Research ethics should be introduced early and integrated throughout the research training period. Lack of resources and institutional support can be obstacles to development of comprehensive research ethics curricula. Small-group, case-based discussion is best for teaching ethics problem-solving skills. Examples of teaching module ideas and a fully developed sample teaching module are presented. Conclusions. There is opportunity for creative models for teaching psychiatric research ethics. Work is needed to identify core topics, target pedagogical strategies to trainees at different levels, and develop evaluation methods. C1 NIMH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. RP Chen, DT (reprint author), Univ Virginia Hlth Syst, Dept Hlth Evaluat Sci, Box 800821,3rd Floor,W Complex,Room 3181, Charlottesville, VA 22908 USA. NR 47 TC 18 Z9 18 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2003 VL 171 IS 1 BP 112 EP 119 DI 10.1007/s00213-003-1500-4 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 750ET UT WOS:000186978900017 PM 12768270 ER PT J AU Abbott, D Doering, CR Caves, CM Lidar, DM Brandt, HE Hamilton, AR Ferry, DK Gea-Banacloche, J Bezrukov, SM Kish, LB AF Abbott, Derek Doering, Charles R. Caves, Carlton M. Lidar, Daniel M. Brandt, Howard E. Hamilton, Alex R. Ferry, David K. Gea-Banacloche, Julio Bezrukov, Sergey M. Kish, Laszlo B. TI Dreams versus Reality: Plenary Debate Session on Quantum Computing SO QUANTUM INFORMATION PROCESSING LA English DT Article DE Quantum Computing Debate; Quantum Computer Implementation C1 [Abbott, Derek] Univ Adelaide, Ctr Biomed Engn CBME, Adelaide, SA 5005, Australia. [Abbott, Derek] Univ Adelaide, Dept Elect & Elect Engn, Adelaide, SA 5005, Australia. [Doering, Charles R.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA. [Doering, Charles R.] Univ Michigan, Michigan Ctr Theoret Phys, Ann Arbor, MI 48109 USA. [Caves, Carlton M.] Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA. [Lidar, Daniel M.] Univ Toronto, Chem Phys Theory Grp, Dept Chem, Toronto, ON M5S 3H6, Canada. [Lidar, Daniel M.] Univ Toronto, Ctr Quantum Informat & Quantum Control, Toronto, ON M5S 3H6, Canada. [Hamilton, Alex R.] Univ New S Wales, Ctr Quantum Comp Technol, Sch Phys, Sydney, NSW 2052, Australia. [Brandt, Howard E.] USA, Res Lab, Adelphi, MD 20783 USA. [Ferry, David K.] Arizona State Univ, Dept Elect Engn, Tempe, AZ 85287 USA. [Gea-Banacloche, Julio] Univ Arkansas, Dept Phys, Fayetteville, AR 72701 USA. [Bezrukov, Sergey M.] NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. [Kish, Laszlo B.] Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. RP Abbott, D (reprint author), Univ Adelaide, Ctr Biomed Engn CBME, Adelaide, SA 5005, Australia. RI Caves, Carlton/K-8167-2014 OI Caves, Carlton/0000-0001-8876-1186 NR 0 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1570-0755 J9 QUANTUM INF PROCESS JI Quantum Inf. Process. PD DEC PY 2003 VL 2 IS 6 BP 449 EP 472 DI 10.1023/B:QINP.0000042203.24782.9a PG 24 WC Physics, Multidisciplinary; Physics, Mathematical SC Physics GA V25UK UT WOS:000208502700003 ER PT J AU Travis, LB Hauptmann, M Gaul, LK Storm, HH Goldman, MB Nyberg, U Berger, E Janower, ML Hall, P Monson, RR Holm, LE Land, CE Schottenfeld, D Boice, JD Andersson, M AF Travis, LB Hauptmann, M Gaul, LK Storm, HH Goldman, MB Nyberg, U Berger, E Janower, ML Hall, P Monson, RR Holm, LE Land, CE Schottenfeld, D Boice, JD Andersson, M TI Site-specific cancer incidence and mortality after cerebral angiography with radioactive thorotrast SO RADIATION RESEARCH LA English DT Article ID 2ND MALIGNANT NEOPLASMS; LONG-TERM SURVIVORS; ATOMIC-BOMB SURVIVORS; FOLLOW-UP SURVEY; HEPATIC ANGIOSARCOMA; HODGKINS-DISEASE; LUNG DOSIMETRY; PEPTIC-ULCER; UPDATED 1998; RADIATION AB Few opportunities exist to evaluate the carcinogenic effects of long-term internal exposure to a-particle-emitting radionuclides. Patients injected with Thorotrast (thorium-232) during radiographic procedures, beginning in the 1930s, provide one such valuable opportunity. We evaluated site-specific cancer incidence and mortality among an international cohort of 3,042 patients injected during cerebral angiography with either Thorotrast (n = 1,650) or a nonradioactive agent (n = 1,392) and who survived 2 or more years. Standardized incidence ratios (SIR) for Thorotrast and comparison patients (Denmark and Sweden) were estimated and relative risks (RR), adjusted for population, age and sex, were generated with multivariate statistical modeling. For U.S. patients, comparable procedures were used to estimate standardized mortality ratios (SMR) and RR, representing the first evaluation of long-term, site-specific cancer mortality in this group. Compared with nonexposed patients, significantly increased risks in Thorotrast patients were observed for all incident cancers combined (RR = 3.4, 95% CI 2.9-4.1, n = 480, Denmark and Sweden) and for cancer mortality (RR = 4.0, 95% CI 2.5-6.7, n = 114, U.S.). Approximately 335 incident cancers were above expectation, with large excesses seen for cancers of the liver, bile ducts and gallbladder (55% or 185 excess cancers) and leukemias other than CLL (8% or 26 excess cancers). The RR of all incident cancers increased with time since angiography (P < 0.001) and was threefold at 40 or more years; significant excesses (SIR = 4.0) persisted for 50 years. Increasing cumulative dose of radiation was associated with an increasing risk of all incident cancers taken together and with cancers of the liver, gallbladder, and peritoneum and other digestive sites; similar findings were observed for U.S. cancer mortality. A marginally significant dose response was observed for the incidence of pancreas cancer (P = 0.05) but not for lung cancer. Our study confirms the relationship between Thorotrast and increased cancer incidence at sites of Thorotrast deposition and suggests a possible association with pancreas cancer. After injection with >20 ml Thorotrast, the cumulative excess risk of cancer incidence remained elevated for up to 50 years and approached 97%. Caution is needed in interpreting the excess risks observed for site-specific cancers, however, because of the potential bias associated with the selection of cohort participants, noncomparability with respect to the internal or external comparison groups, and confounding by indication. Nonetheless, the substantial risks associated with liver cancer and leukemia indicate that unique and prolonged exposure to alpha-particle-emitting Thorotrast increased carcinogenic risks. (C) 2003 by Radiation Research Society. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Danish Canc Soc, DK-2100 Copenhagen, Denmark. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Karolinska Univ Hosp, Stockholm, Sweden. Informat Management Serv Inc, Rockville, MD USA. Worcester Med Ctr, Worcester, MA USA. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Swedish Radiat Protect Author, Stockholm, Sweden. Univ Michigan, Dept Epidemiol, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Int Epidemiol Inst, Rockville, MD USA. Vanderbilt Univ, Ctr Med, Nashville, TN USA. Rigshosp, Dept Oncol 5073, DK-2100 Copenhagen, Denmark. RP Travis, LB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Execut Plaza S,Suite 7086, Bethesda, MD 20892 USA. EM travis1@mail.nih.gov FU NCI NIH HHS [N01-CP-21152, N02-CP-81005, N01-CP-33059, N01-CP-21151] NR 71 TC 20 Z9 23 U1 0 U2 2 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2003 VL 160 IS 6 BP 691 EP 706 DI 10.1667/RR3095 PG 16 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 751QV UT WOS:000187079200011 PM 14640794 ER PT J AU Land, CE Tokunaga, M Koyama, K Soda, M Preston, DL Nishimori, I Tokuoka, S AF Land, CE Tokunaga, M Koyama, K Soda, M Preston, DL Nishimori, I Tokuoka, S TI Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1990 SO RADIATION RESEARCH LA English DT Article ID CASE-CONTROL INTERVIEW; MAMMARY CARCINOGENESIS; HODGKINS-DISEASE; RISK; INFANCY; RATS AB An incidence survey of the Life Span Study (LSS) population found 1093 breast cancers among 1059 breast cancer cases diagnosed during 1950-1990. As in earlier breast cancer surveys of this population, a linear and statistically highly significant radiation dose response was found. In the analysis, particular attention was paid to modification of radiation dose response by age at exposure (e) and attained age (a). Dose-specific excess relative risk (ERR1Sv) decreased with increasing values of e and a. A linear dose-response model analysis, with e and a as exponential age modifiers, did not conclusively discriminate between the two variables as modifiers of dose response. A modified isotonic regression approach, requiring only that ERR1Sv be monotonic in age, provides a fresh perspective indicating that both e and a are important modifiers of dose response. Exposure before age 20 was associated with higher ERR1Sv compared to exposure at older ages, with no evidence of consistent variation by exposure age for ages under 20. ERR1Sv was observed to decline with increasing attained age, with by far the largest drop around age 35. Possible explanations for these observations are discussed, along with research approaches that might provide more information. (C) 2003 by Radiation Research Society. C1 Natl Canc Inst, Radiat Epidemiol Branch, Bethesda, MD USA. Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima, Japan. Radiat Effects Res Fdn, Dept Epidemiol Pathol, Hiroshima, Japan. Radiat Effects Res Fdn, Dept Epidemiol, Nagasaki, Japan. Radiat Effects Res Fdn, Dept Biostat, Hiroshima, Japan. Radiat Effects Res Fdn, Dept Epidemiol Pathol, Nagasaki, Japan. RP Land, CE (reprint author), EPS 7046,6120 Execut Blvd,MS 7238, Bethesda, MD 20892 USA. NR 35 TC 186 Z9 192 U1 0 U2 10 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 2003 VL 160 IS 6 BP 707 EP 717 DI 10.1667/RR3082 PG 11 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 751QV UT WOS:000187079200012 PM 14640793 ER PT J AU Fee, CA Pettigrew, RI AF Fee, CA Pettigrew, RI TI National Institute of Biomedical Imaging and Bioengineering: Poised for the future SO RADIOLOGY LA English DT Editorial Material DE editorials; National Institute of Biomedical Imaging; and Bioengineering C1 US Dept Hlth & Human Serv, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA. RP Fee, CA (reprint author), US Dept Hlth & Human Serv, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, 6707 Democracy Blvd,Suite 202, Bethesda, MD 20892 USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2003 VL 229 IS 3 BP 636 EP 637 DI 10.1148/radiol.2293031004 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 745XZ UT WOS:000186717700004 PM 14657301 ER PT J AU Arbab, AS Bashaw, LA Miller, BR Jordan, EK Lewis, BK Kalish, H Frank, JA AF Arbab, AS Bashaw, LA Miller, BR Jordan, EK Lewis, BK Kalish, H Frank, JA TI Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging SO RADIOLOGY LA English DT Article DE cell labeling; contrast media, experimental studies; experimental study; iron; magnetic resonance (MR), contrast media; radiobiology, cell and tissue studies ID MESENCHYMAL STEM-CELLS; IN-VIVO TRACKING; CONTRAST AGENT; PHARMACOKINETICS; RADICALS; USPIO; VITRO AB PURPOSE: To evaluate the effect of using the ferumoxides-POlY-L-lysine (PLL) complex for magnetic cell labeling on the long-term viability, function, metabolism, and iron utilization of mammalian cells. MATERIALS AND METHODS: PLIL was incubated with ferumoxides for 60 minutes, incompletely coating the superparamagnetic iron oxide (SPIO) through electrostatic interactions. Cells were coincubated overnight with the ferumoxides-PLL complex, and iron uptake, cell viability, apoptosis indexes, and reactive oxygen species formation were evaluated. The disappearance or the life span of the detectable iron nanoparticles in cells was also evaluated. The iron concentrations in the media also were assessed at different time points. Data were expressed as the mean +/- 1 SD, and one-way analysis of variance and the unpaired Student t test were used to test for significant differences. RESULTS: Intracytoplasmic nanoparticles were stained with Prussian blue when the ferumoxides-PLL complex had magnetically labeled the human mesenchymal stem and HeLa cells. The long-term viability, growth rate, and apoptotic indexes of the labeled cells were unaffected by the enclosomal incorporation of SPIO, as compared with these characteristics of the nonlabeled cells. In nondividing human mesenchymal stem cells, enclosomal iron nanoparticles could be detected after 7 weeks; however, in rapidly dividing cells, intracellular iron had disappeared by five to eight divisions. A nonsignificant transient increase in reactive oxygen species production was seen in the human mesenchymal stem and HeLa cell lines. Labeled human mesenchymal stem cells did not differentiate to other lineage. A significant increase in iron concentration was observed in both the human mesenchymal stem and HeLa cell media at day 7. CONCLUSION: Magnetic cellular labeling with the ferumoxides-PLL complex had no short- or long-term toxic effects on tumor or stem cells. - RSNA, 2003. C1 NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. RP Arbab, AS (reprint author), NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, 10 Ctr Dr,Rm B1N256, Bethesda, MD 20892 USA. EM saali@cc.nih.gov NR 22 TC 373 Z9 453 U1 9 U2 56 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 2003 VL 229 IS 3 BP 838 EP 846 DI 10.1148/radiol.2293021215 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 745XZ UT WOS:000186717700031 PM 14657318 ER PT J AU Hirshberg, B Rother, KI Digon, BJ Venstrom, J Harlan, DM AF Hirshberg, B Rother, KI Digon, BJ Venstrom, J Harlan, DM TI State of the art: Islet transplantation for the cure of type 1 diabetes mellitus SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article DE diabetes; transplantation; islets of Langerhans; immunosuppression ID LONG-TERM SURVIVAL; MEDIATED INFLAMMATORY REACTION; RENAL-ALLOGRAFT REJECTION; BETA-CELL FUNCTION; PANCREAS TRANSPLANTATION; KIDNEY-TRANSPLANTATION; STEM-CELLS; INTERSTITIAL PNEUMONITIS; INSULIN INDEPENDENCE; HUMANIZED ANTI-CD154 C1 NIDDK, Transplantat & Autoimmun Branch, NIH, Ctr Clin,Dept Hlth & Human Serv, Bethesda, MD USA. RP Harlan, DM (reprint author), NIDDK, Transplantat & Autoimmun Branch, NIH, Ctr Clin,Dept Hlth & Human Serv, Bethesda, MD USA. EM DavidMH@intra.niddk.nih.gov NR 93 TC 13 Z9 13 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 EI 1573-2606 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD DEC PY 2003 VL 4 IS 4 BP 381 EP 389 DI 10.1023/A:1027358230402 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 756HX UT WOS:000187460600008 PM 14618023 ER PT J AU Ruperto, N Ravelli, A Murray, KJ Lovell, DJ Andersson-Gare, B Feldman, BM Garay, S Kuis, W Machado, C Pachman, L Prieur, AM Rider, LG Silverman, E Tsitsami, E Woo, P Giannini, EH Martini, A AF Ruperto, N Ravelli, A Murray, KJ Lovell, DJ Andersson-Gare, B Feldman, BM Garay, S Kuis, W Machado, C Pachman, L Prieur, AM Rider, LG Silverman, E Tsitsami, E Woo, P Giannini, EH Martini, A CA PRINTO PRCSG TI Preliminary core sets of measures for disease activity and damage assessment in juvenile systemic lupus erythematosus and juvenile dermatomyositis SO RHEUMATOLOGY LA English DT Article DE consensus; core set; disease activity assessment; disease damage assessment; juvenile dermatomyositis; juvenile systemic lupus erythematosus ID IDIOPATHIC INFLAMMATORY MYOPATHIES; HEALTH ASSESSMENT QUESTIONNAIRE; QUALITY-OF-LIFE; CLINICAL-TRIALS; PRELIMINARY DEFINITION; RHEUMATOID-ARTHRITIS; OUTCOME ASSESSMENT; ACTIVITY INDEX; 4 TOOLS; 2 PARTS AB Objective. To identify preliminary core sets of outcome variables for disease activity and damage assessment in juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). Methods. Two questionnaire surveys were mailed to 267 physicians from 46 different countries asking each member to select and rank the response variables used when assessing clinical response in patients with JSLE or JDM. Next, 40 paediatric rheumatologists from 34 countries met and, using the nominal group technique, selected the domains to be included in the disease activity and damage core sets for JSLE and JDM. Results. A total of 41 response variables for JSLE and 37 response variables for JDM were selected and ranked through the questionnaire surveys. In the consensus conference, domains selected for both JSLE and JDM activity or damage core sets included the physician and parent/patient subjective assessments and a global score tool. Domains specific for JSLE activity were the immunological tests and the kidney function parameters. Concerning JDM, functional ability and muscle strength assessments were indicated for both activity and damage core sets, whereas serum muscle enzymes were included only in the activity core set. A specific paediatric domain called 'growth and development' was introduced in the disease damage core set for both diseases and the evaluation of health-related quality of life was advised in order to capture the influence of the disease on the patient lifestyle. Conclusions. We developed preliminary core sets of measures for disease activity and damage assessment in JSLE and JDM. The prospective validation of the core sets is in progress. C1 IRCCS G Gaslini, PRINTO, I-16147 Genoa, Italy. Princess Margaret Hosp Children, Perth, WA, Australia. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Ryhovs Cty Hosp, Dept Pediat, Jonkoping, Sweden. Hosp Sick Children, Dept Rheumatol, Toronto, ON M5G 1X8, Canada. Hosp Sor Maria Ludovica, Unidad Reumatol, Buenos Aires, DF, Argentina. UMC Utrecht Wilhelmina Kinderziekenhuis, Dept Pediat Immunol & Rheumatol, Utrecht, Netherlands. Botucatu Med Sch, Dept Paediat, Sao Paulo, Brazil. Childrens Mem Hosp, Chicago, IL 60614 USA. Hop Necker Enfants Malad, Unite Immunol Hematol & Rhumatol Pediat, Paris, France. Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Aristotle Univ Thessaloniki, Dept Pediat, GR-54006 Thessaloniki, Greece. Great Ormond St Hosp Children, Dept Rheumatol, London WC1N 3JH, England. RP Ruperto, N (reprint author), IRCCS G Gaslini, PRINTO, Largo Gaslini 5, I-16147 Genoa, Italy. RI Feldman, Brian/A-8586-2011; Saad-Magalhaes, Claudia/C-3367-2013; RAVELLI, ANGELO/J-8161-2016; OI Saad-Magalhaes, Claudia/0000-0002-7631-7093; RAVELLI, ANGELO/0000-0001-9658-0385; Tsitsami, Elena/0000-0002-1573-7190; Rider, Lisa/0000-0002-6912-2458; De Inocencio, Jaime/0000-0002-0438-0245 FU NIAID NIH HHS [R03 AI 44046] NR 47 TC 117 Z9 120 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD DEC PY 2003 VL 42 IS 12 BP 1452 EP 1459 DI 10.1093/rheumatology/keg403 PG 8 WC Rheumatology SC Rheumatology GA 751VG UT WOS:000187109300003 PM 12832713 ER PT J AU Kimura, S AF Kimura, S TI Homeodomain transcription factor T/EBP/NKX2.1 in development and differentiation of the thyroid and lung SO SEIKAGAKU LA Japanese DT Review ID ENHANCER-BINDING PROTEIN; DEVELOPING MOUSE LUNG; FACTOR-I TTF-1; HEPATOCYTE NUCLEAR FACTOR-3-BETA; EPITHELIAL-CELL DIFFERENTIATION; GATA-6 ACTIVATES TRANSCRIPTION; THYROTROPIN RECEPTOR GENE; DOWNSTREAM TARGET GENE; HOMEOBOX GENE; BRANCHING MORPHOGENESIS C1 NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kimura, S (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Rm 3112B,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 87 TC 1 Z9 1 U1 0 U2 0 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F, 25-16 HONGO-5-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0037-1017 J9 SEIKAGAKU JI Seikagaku PD DEC PY 2003 VL 75 IS 12 BP 1493 EP 1504 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 760JQ UT WOS:000187808200003 PM 14748143 ER PT J AU Marincola, FM Ferrone, S AF Marincola, FM Ferrone, S TI Immunotherapy of melanoma: the good news, the bad ones and what to do next SO SEMINARS IN CANCER BIOLOGY LA English DT Editorial Material ID METASTATIC MELANOMA; TUMOR ESCAPE; CANCER C1 Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. NIH, Immunogenet Sect, Dept Transfus Med, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), Roswell Pk Canc Inst, Dept Immunol, Elm & Carlton St, Buffalo, NY 14263 USA. NR 17 TC 19 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD DEC PY 2003 VL 13 IS 6 BP 387 EP 389 DI 10.1016/j.semcancer.2003.09.002 PG 3 WC Oncology SC Oncology GA 755DK UT WOS:000187388300001 PM 15001156 ER PT J AU Monsurro, V Wang, E Panelli, MC Nagorsen, D Jin, P Katia, Z Smith, K Ngalame, Y Even, J Marincola, FM AF Monsurro, V Wang, E Panelli, MC Nagorsen, D Jin, P Katia, Z Smith, K Ngalame, Y Even, J Marincola, FM TI Active-specific immunization against melanoma: Is the problem at the receiving end? SO SEMINARS IN CANCER BIOLOGY LA English DT Article DE immunization; immunotherapy; interleukin-2; melanoma ID CD8(+) T-CELLS; TUMOR-INFILTRATING LYMPHOCYTES; CUTANEOUS MALIGNANT-MELANOMA; METASTATIC MELANOMA; IN-VIVO; ANTIGEN EXPRESSION; GENE-EXPRESSION; MESSENGER-RNA; PEPTIDE; MEMORY AB The recent progress in tumor immunology is a striking example of the successful application of modern biotechnology to understand the complex phenomenon of immune-mediated cancer rejection. Tumor antigens were identified and successfully utilized in active immunization trials to induce tumor antigen-specific T cells. This achievement has left, however, clinicians and researchers perplexed by the paradoxical observation that immunization-induced T cells can recognize tumor cells in standard assays but cannot induce tumor regression. A closer look at T cell physiology and tumor biology suggests that this observation is not so surprising. Here, we argue that successful immunization is one of several steps required for tumor clearance while more needs to be understood about how T cells localize and are effective within a tumor microenvironment impervious to the execution of their effector function. (C) 2003 Elsevier Ltd. All rights reserved. C1 NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10,R-1C711, Bethesda, MD 20892 USA. NR 66 TC 43 Z9 46 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD DEC PY 2003 VL 13 IS 6 BP 473 EP 480 DI 10.1016/j.semcancer.2003.09.011 PG 8 WC Oncology SC Oncology GA 755DK UT WOS:000187388300011 PM 15001166 ER PT J AU Goldstein, DS AF Goldstein, DS TI Imaging of the autonomic nervous system: Focus on cardiac sympathetic innervation SO SEMINARS IN NEUROLOGY LA English DT Review DE sympathetic; multiple system atrophy; Parkinson's disease; autonomic failure; norepinephrine; dysautonomia ID IDIOPATHIC DILATED CARDIOMYOPATHY; ACUTE MYOCARDIAL-INFARCTION; NEUROGENIC ORTHOSTATIC HYPOTENSION; HEART-RATE-VARIABILITY; PARKINSONS-DISEASE; I-123 METAIODOBENZYLGUANIDINE; ESSENTIAL-HYPERTENSION; NEURONAL FUNCTION; DIABETIC-PATIENTS; PLASMA-LEVELS AB Symptoms or signs of abnormal autonomic nervous system function occur commonly in several neurological disorders. Clinical evaluations have depended on physiological, pharmacological, and neurochemical approaches. Recently, imaging of sympathetic noradrenergic innervation has been introduced and applied especially in the heart. Most studies have used the radiolabeled sympathomimetic amine, I-123-metaiodobenzylguanidine. Decreased uptake or increased "washout" of I-123-metaiodobenzylguanidine-derived radioactivity is associated with worse prognosis or more severe disease in hypertension, congestive heart failure, arrhythmias, and diabetes mellitus. This pattern may reflect a high rate of postganglionic sympathetic nerve traffic to the heart. Many recent studies have agreed on the remarkable finding that all patients with Parkinson's disease and orthostatic hypotension have a loss of cardiac sympathetic innervation, whereas all patients with multiple system atrophy, often difficult to distinguish clinically from Parkinson's disease, have intact cardiac sympathetic innervation. Because Parkinson's disease entails a postganglionic sympathetic noradrenergic lesion, the disease appears to be not only a movement disorder, with dopamine loss in the nigrostriatal system of the brain, but also a dysautonomia, with noradrenaline loss in the sympathetic nervous system of the heart. As new ligands are developed, one may predict further, discoveries of involvement of components of the autonomic nervous system in neurological diseases. C1 NINDS, NIH, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, NIH, Clin Neurocardiol Sect, Bldg 10,Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. NR 115 TC 10 Z9 11 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD DEC PY 2003 VL 23 IS 4 BP 423 EP 433 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 809UI UT WOS:000220661200010 PM 15088263 ER PT J AU Menard, C Camphausen, K Muanza, T Sears-Crouse, N Smith, S Ben-Josef, E Coleman, CN AF Menard, C Camphausen, K Muanza, T Sears-Crouse, N Smith, S Ben-Josef, E Coleman, CN TI Clinical trial of endorectal amifostine for radioprotection in patients with prostate cancer: Rationale and early results SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT 3rd International Cytoprotection Investigators Congress CY MAY 15-18, 2003 CL NEVIS, W IND ASSOC ST ID CONFORMAL RADIATION-THERAPY; RADIOTHERAPY DOSE-ESCALATION; QUALITY-OF-LIFE; PHASE-II; TOPICAL APPLICATION; TOXICITY; CARCINOMA; WR-2721; INJURY; WR2721 C1 NCI, Radiat Oncol Branch, Ctr Canc Res, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Wayne State Univ, Detroit, MI 48202 USA. RP Menard, C (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, Dept Hlth & Human Serv,NIH, 9000 Rockville Pike,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. NR 23 TC 10 Z9 11 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 2003 VL 30 IS 6 SU 18 BP 63 EP 67 DI 10.1053/j.seminoncol.2003.11.016 PG 5 WC Oncology SC Oncology GA 767DK UT WOS:000188424800009 PM 14727242 ER PT J AU Rodriguez, AC Castle, PE Smith, JS Bratti, C Hildesheim, A Schiffman, M Viscidi, R Burk, RD Ashley, RL Castellsague, X Herrero, R AF Rodriguez, AC Castle, PE Smith, JS Bratti, C Hildesheim, A Schiffman, M Viscidi, R Burk, RD Ashley, RL Castellsague, X Herrero, R TI A population based study of herpes simplex virus 2 seroprevalence in rural Costa Rica SO SEXUALLY TRANSMITTED INFECTIONS LA English DT Article ID SIMPLEX-VIRUS TYPE-2; GENITAL HERPES; HUMAN-PAPILLOMAVIRUS; RISK-FACTORS; SEXUAL TRANSMISSION; HIGH PREVALENCE; PUBLIC-HEALTH; YOUNG-WOMEN; INFECTION; ANTIBODIES AB Objectives: To determine seroprevalence and determinants of herpes simplex virus 2 ( HSV- 2) seropositivity, in a random sample of a population based cohort of 10 049 women of Guanacaste, Costa Rica, using a highly sensitive and specific serological assay. Methods: Seroprevalence was determined by a type specific HSV- 2 ELISA assay in an age stratified random sample of 1100 women. Univariate and multivariate logistic regression was used to calculate odds ratios and 95% confidence intervals for risk factors of seropositivity. Results: Overall age adjusted HSV- 2 seroprevalence was 38.5% ( 95% CI, 37.5 to 39.5), and it was strongly associated with increasing age ( pT(rend <) (0.0001)), both among monogamous women and women with multiple sexual partners. A greater number of lifetime sexual partners increased the risk of seropositivity, with a 28.2% ( 95% CI, 24.4 to 32.2) seroprevalence among monogamous women and 75% ( 95% CI, 65.6 to 83.0) seroprevalence for those with four or more partners ( OR = 7.6 95% CI, 4.7 to 12.4 pTrend, 0.0001). Barrier contraceptive use was negatively associated with HSV- 2 seropositivity ( OR 0.54, 95% CI, 0.31 to 0.94). Women with antibodies against HPV 16, 18, or 31 were 1.6 times more likely to be HSV- 2 seropositive ( OR 1.6, 95% CI, 1.2 to 2.1). Conclusions: HSV- 2 infection is highly endemic in Guanacaste, even among lifetime monogamous women, suggesting a role of male behaviour in the transmission of the infection. Until vaccination against HSV- 2 is available, education to prevent high risk sexual behaviour and the use of condoms appear as preventive measures against HSV- 2. C1 Costa Rica Fdn Hlth Sci, Guanacaste Project, San Jose, Costa Rica. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Int Agcy Res Canc, F-69372 Lyon, France. Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA. Albert Einstein Coll Med, Canc Res Ctr, New York, NY USA. Univ Washington, Sch Med, Washington, DC USA. Inst Catala Oncol, Barcelona, Spain. RP Rodriguez, AC (reprint author), Proyecto Epidemiol Guancaste, Apdo 181-1250, Escazu, Costa Rica. RI Castellsague Pique, Xavier/N-5795-2014 OI Castellsague Pique, Xavier/0000-0002-0802-3595 FU NCI NIH HHS [N01-CP-21081, CA78527, N01-CP-11005, N01-CP-33061, N01-CP-40542, N01-CP-50535, N01-CP-81023] NR 25 TC 9 Z9 10 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1368-4973 J9 SEX TRANSM INFECT JI Sex. Transm. Infect. PD DEC 1 PY 2003 VL 79 IS 6 BP 460 EP 465 DI 10.1136/sti.79.6.460 PG 6 WC Infectious Diseases SC Infectious Diseases GA 751LX UT WOS:000187069500009 PM 14663121 ER PT J AU Yabroff, KR Gordis, L AF Yabroff, KR Gordis, L TI Does stage at diagnosis influence the observed relationship between socioeconomic status and breast cancer incidence, case-fatality, and mortality? SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE socioeconomic factors; breast neoplasms; incidence; mortality; survival; case-fatality ID SOCIAL-CLASS; CERVICAL-CANCER; RACIAL-DIFFERENCES; RANDOMIZED TRIALS; RISING INCIDENCE; INCIDENCE RATES; UNITED-STATES; FOLLOW-UP; FEMALE BREAST; BLACK-WOMEN AB Historically, lower socioeconomic status (SES) has been reported to be associated with decreased breast cancer incidence and mortality and increased case-fatality, although recent trends in breast cancer screening and treatment may alter these relationships. This study assessed the associations between SES and breast cancer incidence, case-fatality, and mortality by stage of disease at diagnosis using recent data in the United States. Breast cancer incidence and survival data from the Surveillance, Epidemiology, and End Results (SEER) tumor registry for black and white women aged 55 and above were linked to county level SES and population data based on place of residence. Poisson regression was used to calculate age-adjusted relative rates associated with SES levels and breast cancer incidence, case-fatality, and mortality. As SES decreased, localized breast cancer incidence rates decreased, while incidence rates of distant disease increased. Five-year localized and regional breast cancer case-fatality rates increased as SES decreased. Localized breast cancer mortality rates decreased as SES declined, whereas regional breast cancer mortality rates tended to increase. These results confirm some previously reported findings and suggest that associations between lower SES and lower localized breast cancer mortality rates are influenced mainly by underlying associations between SES and localized breast cancer incidence, whereas regional breast cancer mortality rates appear to reflect the underlying association between SES and regional case-fatality rates. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Yabroff, KR (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, Execut Pl N,Room 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. OI Yabroff, K. Robin/0000-0003-0644-5572 FU NCI NIH HHS [T32 CA09314] NR 78 TC 27 Z9 27 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 2003 VL 57 IS 12 BP 2265 EP 2279 DI 10.1016/S0277-9536(03)00100-X PG 15 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 749EH UT WOS:000186905400002 PM 14572836 ER PT J AU Beletsky, V Nadareishvili, Z Lynch, J Shuaib, A Woolfenden, A Norris, JW AF Beletsky, V Nadareishvili, Z Lynch, J Shuaib, A Woolfenden, A Norris, JW CA Canadian Stroke Consortium TI Cervical arterial dissection - Time for a therapeutic trial? SO STROKE LA English DT Article DE dissection; randomized controlled trials; stroke ID SECONDARY PREVENTION; ACETYLSALICYLIC-ACID; CAROTID DISSECTION; ISCHEMIC-STROKE; THROMBOLYSIS; STENOSIS; ASPIRIN; INJURY; DEATH AB Background and Purpose - Cervical arterial dissection is a major cause of stroke in young adults, yet despite standard treatment with anticoagulants or antiplatelet drugs, its management remains uncertain. The goal of this study was to assess the natural history of the disorder and to decide on the feasibility of a therapeutic trial. Methods - Collaborating members of the Canadian Stroke Consortium prospectively enrolled consecutively referred patients with angiographically proven acute vertebral or carotid arterial dissection. Data recorded included clinical and radiological details, recurrence of ischemic cerebral events, and medical or surgical treatment. Results - Of 116 patients, 67 had vertebral and 49 had carotid dissections, with no difference in age or sex. In 68 ( 59%), trauma occurred at the time of dissection. During the course of a 1- year follow- up, at least 17 patients ( 15%) had recurrent transient ischemic attacks, stroke, or death, mainly in the weeks immediately after the dissection. In 105 patients with complete follow- up, the event rate in those treated with anticoagulants was 8.3% and in those treated with aspirin was 12.4%, a nonsignificant difference of 4.1%. Using these data, we calculate that for a 2- arm trial ( aspirin versus anticoagulants) with 80% power and 5% significance, 913 patients are needed in each group. Conclusions - From our data indicating an initial relatively high recurrence rate, a multicenter trial of anticoagulants versus aspirin involving a total of 2000 patients is feasible. C1 Univ Western Ontario, London, ON, Canada. Univ Toronto, Toronto, ON, Canada. NIH, Bethesda, MD 20892 USA. Univ Alberta, Edmonton, AB, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Beletsky, V (reprint author), Univ Hosp, Dept Clin Neurol Sci, Room 7GE5,339 Windermere Rd, London, ON N6A 5A5, Canada. NR 33 TC 124 Z9 133 U1 0 U2 3 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 2003 VL 34 IS 12 BP 2856 EP 2860 DI 10.1161/01.STR.0000098649.39767.BC PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 750FP UT WOS:000186980900018 PM 14605328 ER PT J AU Kidwell, CS Warach, S AF Kidwell, CS Warach, S TI Acute ischemic cerebrovascular syndrome - Diagnostic criteria SO STROKE LA English DT Article DE brain imaging; classification; diagnosis ID MULTIPLE-SCLEROSIS; HUMAN STROKE; ATTACKS; RIND; MRI AB Background-Existing diagnostic classification systems for cerebrovascular disease are based primarily on clinical impression of temporal features, clinical syndrome, inferred localization, or ischemic mechanism. Diagnostic certainty of the ischemic pathology based on supportive or refuting laboratory or radiological evidence has been of secondary importance. Summary of Comment-Acute ischemic cerebrovascular syndrome (AICS) describes a spectrum of clinical presentations that share a similar underlying pathophysiology: cerebral ischemia. Diagnostic criteria for AICS incorporate prior classification systems and currently available information provided by neuroimaging and laboratory data to define 4 categories ranging from "definite AICS" to "not AICS," which define the degree of diagnostic certainty. Conclusions-Clinical trials testing new treatments for acute ischemic stroke or secondary stroke prevention should limit enrollment to patients with "definite" AICS whenever feasible. C1 Natl Inst Neurol Disorders & Stroke, NIH, Stroke Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Med Ctr, Dept Neurol, Los Angeles, CA 90024 USA. RP Warach, S (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Stroke Branch, 10 Ctr Dr,MSC 1063, Bethesda, MD 20892 USA. NR 23 TC 68 Z9 79 U1 0 U2 7 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 2003 VL 34 IS 12 BP 2995 EP 2998 DI 10.1161/01.STR.0000098902.69855.A9 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 750FP UT WOS:000186980900046 PM 14605325 ER PT J AU Radaev, S Kattah, M Rostro, B Colonna, M Sun, PD AF Radaev, S Kattah, M Rostro, B Colonna, M Sun, PD TI Crystal structure of the human myeloid cell activating receptor TREM-1 SO STRUCTURE LA English DT Article ID HEAVY-ATOM DERIVATIVES; QUICK-SOAK METHOD; 3-DIMENSIONAL STRUCTURE; MONOCLONAL-ANTIBODY; DOMAIN RECEPTORS; SEPTIC SHOCK; COMPLEX; RESPONSES; CLUSTER; SEPSIS AB Triggering receptors expressed on myeloid cells (TREM) are a family of recently discovered receptors that play important roles in innate immune responses, such as to activate inflammatory responses and to contribute to septic shock in response to microbial-mediated infections. To date, two TREM receptors in human and several homologs in mice have been identified. We report the 2.6 Angstrom resolution crystal structure of the extracellular domain of human TREM-1. The overall fold of the receptor resembles that of a V-type immunoglobulin domain with differences primarily located in the N-terminal strand. TREM-1 forms a "head-to-tail" dimer with 4100 Angstrom(2) interface area that is partially mediated by a domain swapping between the first strands. This mode of dimer formation is different from the "head-to-head" dimerization that existed in VHVL domains of antibodies or V domains of T cell receptors. As a result, the dimeric TREM-1 most likely contains two distinct ligand binding sites. 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 45 TC 32 Z9 39 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD DEC PY 2003 VL 11 IS 12 BP 1527 EP 1535 DI 10.1016/j.str.2003.11.001 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 752CG UT WOS:000187128900011 PM 14656437 ER PT J AU Elaraj, DM Skarulis, MC Libutti, SK Norton, JA Bartlett, DL Pingpank, JF Gibril, F Weinstein, LS Jensen, RT Marx, SJ Alexander, HR AF Elaraj, DM Skarulis, MC Libutti, SK Norton, JA Bartlett, DL Pingpank, JF Gibril, F Weinstein, LS Jensen, RT Marx, SJ Alexander, HR TI Results of initial operation for hyperparathyroidism in patients with multiple endocrine neoplasia type 1 SO SURGERY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY MAY 11-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Endocrine Surg ID TOTAL PARATHYROIDECTOMY; SERUM-CALCIUM; REOPERATION; EXPERIENCE; SURGERY AB Background. Hyperparathyroidism in patients with multiple endocrine neoplasia type I (MEN1) is characterized by multiglandular disease and a Propensity for recurrence after Parathyroidectomy (PTx). This study analyzes outcomes of a cohort of MEN1 patients undergoing initial PTx at one institution. Methods. Between April 1960 and September 2002, 92 patients with MEN1 underwent initial PTx. Outcomes were analyzed based on extent of parathyroid resection. Results. Fourteen percent had 2.5 or fewer glands resected, 69% had subtotal PTx, and 17% had total PTx (88% with immediate autotransplantation). The initial surgical cure rate was 98%. Excluding 6 patients lost to follow-up, 33% have developed recurrent hyperparathyroidism (in 46% after less than or equal to 2.5 PTx, in 33% after subtotal, and in 23% after total PTx). Median recurrence free survival was not statistically significantly different between subtotal versus total PTx, but it was longer for subtotal and total PTx compared with lesser resection (16.5 vs 7.0 years, respectively, P = .03). The incidence of severe hypoparathyroidism was 46% after total versus 26% after subtotal PTx. Conclusions. Subtotal and total PTx result. in durable control of MEN1-associated hyperparathyroidism and have longer recurrence free intervals compared with lesser resection. The high incidence of severe hypoparathyroidism after total PTx suggests that subtotal PTx is the initial operation of choice in this setting. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab & Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10,Room 2B07,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Weinstein, Lee/0000-0002-1899-5152 NR 16 TC 49 Z9 50 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 2003 VL 134 IS 6 BP 858 EP 864 DI 10.1016/S0039-6060(03)00406-9 PG 7 WC Surgery SC Surgery GA 755DU UT WOS:000187389100002 PM 14668715 ER PT J AU Kayton, ML Costouros, NG Lorang, D Alexander, HR Hewitt, SM Cochran, C Shalev, A Harlan, D Skarulis, MC Gorden, P Libutti, SK AF Kayton, ML Costouros, NG Lorang, D Alexander, HR Hewitt, SM Cochran, C Shalev, A Harlan, D Skarulis, MC Gorden, P Libutti, SK TI Peak stimulated insulin secretion is associated with specific changes in gene expression profiles in sporadic insulinomas SO SURGERY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY MAY 11-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Endocrine Surg ID HUMAN PANCREATIC-ISLETS; MICROARRAY ANALYSIS; IDENTIFICATION; LOCALIZATION; CALCIUM AB Background. The molecular pathways that are responsible for pathologic insulin secretion by insulinomas have not been characterized. We studied gene expression profiles from insulinomas and determined associations between these changes and preoperative peak serum insulin levels. Methods. Ten patients with insulinomas underwent calcium-stimulated arteriography and surgical resection. Tumor RNA was isolated; corresponding complementary DNA was hybridized to 10K human complementary DNA arrays. Pooled human islet cell complementary DNA served as the control. Cluster analysis of gene expression and analysis of expression ratios was performed. Results. Nineteen genes were up-regulated at least 3-fold in insulinomas compared with controls, which included the genes for islet amyloid polypeptide and proprotein convertase type 2. Cluster analysis revealed 2 groups of patients with insulinoma and with distinct Patterns of gene expression. Mean peak serum insulin values between groups were 196 and 1100 (U/mL (P < .05), which demonstrates a significant difference in insulin response to calcium stimulation between these 2 groups. Conclusion. We show that genes that are relevant to the Pathogenesis of hyperinsulinemia are expressed preferentially in insulinomas. In addition, patients with a distinct and common Pattern of gene expression had significantly higher stimulated insulin secretion levels. The study of these genes may help to identify the biochemical pathways that are responsible for pathologic insulin secretion. C1 NCI, Canc Res Ctr, Surg Branch, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Pathol Lab, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Canc Res Ctr, Surg Branch, Bldg 10,Room 2B07,10 Ctr Dr, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 13 TC 1 Z9 1 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 2003 VL 134 IS 6 BP 982 EP 987 DI 10.1016/S0039-6060(03)00482-3 PG 6 WC Surgery SC Surgery GA 755DU UT WOS:000187389100032 PM 14668731 ER PT J AU Norton, JA Warren, RS Kelly, MG Zuraek, MB Jensen, RT AF Norton, JA Warren, RS Kelly, MG Zuraek, MB Jensen, RT TI Aggressive surgery for metastatic liver neuroendocrine tumors SO SURGERY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY MAY 11-14, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Endocrine Surg ID ZOLLINGER-ELLISON SYNDROME; CARCINOID-TUMORS; ENDOCRINE TUMORS; LONG-TERM; GASTRINOMA; RESECTION; OCTREOTIDE; SURVIVAL; OUTCOMES; DISEASE AB Background. Neuroendocrine tumors of the gastrointestinal tract (carcinoids, pancreatic endocrine tumors) have low malignant potential but can decrease survival rates if they spread to the liver (LNET). Methods. The records of 16 patients with LNET primarily from gastrointestinal carcinoids treated surgically were retrospectively reviewed. Results. There were 12 women and 4 men. Median age was 56 years (range 25 to 75). Thirteen (81%) had a carcinoid tumor and 5 had gastrinoma. Two patients with multiple endocrine neoplasia type I had both a gastric carcinoid and a jejunal gastrinoma. Eight patients (50%) had the carcinoid syndrome. Each patient had all identifiable LNET either resected or ablated. Ten patients had liver wedge resections, 1 right trisegmentectomy, 5 left hepatic lobectomies, and 2 radiofrequency ablations. Thirteen (81%) patients had concomitant bowel resections. Two patients had concomitant total gastrectomies to remove stomach primaries. The final patient had an extraintestinal pelvic primary or a liver primary. There were no operative deaths, and all 8 (100%) patients with the carcinoid syndrome had amelioration of symptoms. The 5-year actuarial survival rate was 82% with a median follow-up of 32 months. Conclusions. This study demonstrates that liver and concomitant extrahepatic surgery can be performed safely in patients with liver metastases because of carcinoids or pancreatic endocrine tumors. It results in excellent long-term survival and amelioration of symptoms. Surgery should be the first-line therapy for patients with LNET. C1 NIDDKD, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Norton, JA (reprint author), Stanford Univ, 300 Pasteur Dr,Room H3591, Stanford, CA 94305 USA. NR 25 TC 142 Z9 146 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 2003 VL 134 IS 6 BP 1057 EP 1063 DI 10.1016/S0039-6060(03)00496-3 PG 7 WC Surgery SC Surgery GA 755DU UT WOS:000187389100052 PM 14668741 ER PT J AU Rothman, RB Jayanthi, S Wang, XY Dersch, CM Cadet, JL Prisinzano, T Rice, KC Baumann, MH AF Rothman, RB Jayanthi, S Wang, XY Dersch, CM Cadet, JL Prisinzano, T Rice, KC Baumann, MH TI High-dose fenfluramine administration decreases serotonin transporter binding, but not serotonin transporter protein levels, in rat forebrain SO SYNAPSE LA English DT Article DE serotonin transporter; fenfluramine; parachloroamphetamine; neurotoxicity; amphetamine ID BIOGENIC-AMINE TRANSPORTERS; P-CHLOROAMPHETAMINE; UPTAKE SITES; BRAIN; NEUROTOXICITY; INNERVATION; DEXFENFLURAMINE; HIPPOCAMPUS; COCAINE AB Administration of D-fenfluramine (D-FEN) or parachloroamphetamine (PCA) can produce long-lasting decreases in serotonin transporter (SERT) binding and tissue levels of serotonin (5-HT) in rat forebrain. These changes have been viewed as evidence for 5-HT neurotoxicity, but no studies have measured SERT protein levels. In the present study, we determined the effect of high-dose D-FEN or PCA, administered according to a "neurotoxic" dosing regimen, on the density of SERT sites using ligand binding methods and on SERT protein levels using Western blots. Rats were sacrificed 2 days and 2 weeks after administration of drug or saline. The density of SERT was determined in homogenates of caudate and whole brain minus caudate. D-FEN and PCA decreased SERT binding by 30-60% in both tissues and at both time points. Similarly, D-FEN and PCA administration profoundly decreased tissue 5-HT and 5-HIAA in frontal cortex. Despite the large decreases in SERT binding and depletion of tissue 5-HT that occurred with D-FEN administration, SERT protein expression, as determined by Western blot analysis, did not change in either tissue or time point. PCA administration decreased SERT protein by about 20% only at the 2-day point in the caudate. Drug treatments did not change expression of glial fibrillary acidic protein (GFAP), a hallmark indicator of neuronal damage, in whole brain minus candate in the 2-week group. These results support the hypothesis that decreases in tissue 5-HT and SERT binding sites induced by D-FEN and PCA reflect neuroadapative changes, rather than neurotoxic effects. Published 2003 Wiley-Liss, Inc.(dagger) C1 NIDA, CPS, DIR, NIH, Baltimore, MD 21224 USA. NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Rothman, RB (reprint author), NIDA, CPS, DIR, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Prisinzano, Thomas/B-7877-2010 NR 23 TC 39 Z9 41 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 0887-4476 J9 SYNAPSE JI Synapse PD DEC 1 PY 2003 VL 50 IS 3 BP 233 EP 239 DI 10.1002/syn.10266 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 734XH UT WOS:000186082900008 PM 14515341 ER PT J AU Clarke, LP Baker, H Kelloff, G AF Clarke, LP Baker, H Kelloff, G TI Foreword: Potential of optical imaging for early cancer detection, screening, diagnosis and image guided treatment SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Editorial Material AB This issue of the journal is dedicated to outline emerging optical technologies that have the potential to improve early cancer detection, screening, diagnosis, and treatment. The authors have briefly reviewed the progress of emerging technologies, described some of the emerging optical systems or methods in their laboratories, and then discuss the barriers for their translation to clinical applications. The scope of the manuscripts includes both endogenous and exogenous contrast agents, including molecular probes. The first four papers address early cancer detection, the remaining four papers address cancer diagnosis or image guided therapy, including either molecular or multi-modality imaging methods. C1 NCI, CIP, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Clarke, LP (reprint author), NCI, CIP, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD DEC PY 2003 VL 2 IS 6 BP 487 EP 489 PG 3 WC Oncology SC Oncology GA 759VQ UT WOS:000187757900001 ER PT J AU Gandjbakhche, AH Chernomordik, V Hattery, D Hassan, M Gannot, I AF Gandjbakhche, AH Chernomordik, V Hattery, D Hassan, M Gannot, I TI Tissue characterization by quantitative optical imaging methods SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article ID TUMORS IN-VIVO; BREAST-CANCER; FLUORESCENCE LIFETIME; EXTRACELLULAR PH; INTRACELLULAR PH; PHOTON MIGRATION; PATH-LENGTH; BLOOD-FLOW; TIME; MAMMOGRAPHY AB Optical methods have a long history in the field of medical diagnosis. The biomolecular specificity possible with optical methods has been particularly valuable in microscopy and histopathology while in vivo imaging of deep structures has traditionally been the domain of X-ray and MRI. The use of optical methods in deep tissue has been limited by multiple-scattering which blurs or distorts the optical signal. New stochastic methods which account for multiple scattering have been developed that are extending the usefulness of optical methods deep into tissue. In optical mammography, photons may travel through 10cm of tissue before arriving at the detector. We have developed a method for quantifying parameters of anomalous sites in breast tissue that may be used for functional characterization of tumors. In other work presented here, we are developing fluorescence based methods to detect and monitor tumor status. The immune response to a tumor is a target for fluorescently labeled specific antibodies. We have developed a method to localize the tumor site using CW fluorescence. Additionally, we have developed a method which uses time-resolved data and capitalizes on probe lifetime sensitivity to metabolic parameters such as pH and temperature to obtain functional information from the tumor site. C1 NICHD, LIMB, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Dept Biomed Engn, Fac Engn, IL-69978 Tel Aviv, Israel. RP Gandjbakhche, AH (reprint author), NICHD, LIMB, NIH, Bethesda, MD 20892 USA. NR 64 TC 12 Z9 12 U1 0 U2 0 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD DEC PY 2003 VL 2 IS 6 BP 537 EP 551 PG 15 WC Oncology SC Oncology GA 759VQ UT WOS:000187757900006 PM 14640765 ER PT J AU De Soyza, A Morris, K Perry, J Doherty, C Stock, F Holland, SM Gould, K Govan, JR Corris, PA AF De Soyza, A Morris, K Perry, J Doherty, C Stock, F Holland, SM Gould, K Govan, JR Corris, PA TI Divergent pro-inflammatory activity of B cepacia complex strains dependent on patient diagnosis: Cystic fibrosis vs chronic granulomatous disease SO THORAX LA English DT Meeting Abstract CT Winter Meeting of the British Thoracic-Society CY DEC 03-05, 2003 CL LONDON, ENGLAND SP British Thorac Soc C1 Univ Newcastle Upon Tyne, Freeman Hosp, Transplantat & Immunobiol Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Univ Newcastle Upon Tyne, Freeman Hosp, Dept Microbiol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Univ Edinburgh, Sch Med, Dept Med Microbiol, Edinburgh EH8 9AG, Midlothian, Scotland. NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2003 VL 58 SU 3 BP 2 EP 2 PG 1 WC Respiratory System SC Respiratory System GA 754RK UT WOS:000187345000006 ER PT J AU Fagan, P Stoddard, AM Hunt, MK Frazier, L Girod, K Sorensen, G AF Fagan, P Stoddard, AM Hunt, MK Frazier, L Girod, K Sorensen, G TI The feasibility of evaluating a tobacco control intervention for working youth SO TOBACCO CONTROL LA English DT Article ID SMOKING CESSATION; WORKPLACE SMOKING; CIGARETTE-SMOKING; ADOLESCENTS; HEALTH; CONSEQUENCES; ASSOCIATION AB Objectives: To describe the feasibility of implementing evaluation methods for a worksite tobacco control intervention for teens. Indicators of feasibility included employment stability, response rates to multiple surveys, and self reported 30 day smoking. Design: Grocery stores that were part of a single chain were randomised to four intervention stores and five control stores as part of the SMART project, a phase II methods development study designed to reduce smoking among working adolescents. Subjects: Data on smoking in the last 30 days and employment patterns were collected from working teens aged 15-18 years at seven data points over the 12 month intervention period using cross sectional surveys. Results: Data on employment stability indicate that employee turnover rates averaged 21% over the seven administrations. Response rates for the seven surveys ranged from 43-77% and were slightly greater in the control stores than the interventions stores (71% v 59%, p=0.06). Mean current smoking at the individual store level ranged from 9-32% and there was a negative correlation between smoking prevalence and response rate by survey and by store (-0.029, p=0.03). Among smokers who completed at least two surveys, there were no significant differences between intervention and control store on changes in the frequency of smoking. Conclusions: Evaluating a tobacco control intervention in the grocery store setting requires multiple survey assessments to monitor changes in smoking among adolescents. Strategies are needed to maintain high response rates and increase the number of multiple responses from eligible teens. C1 NCI, Div Canc Control & Populat Sci, Tobacco Control Res Branch, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Boston, MA 02125 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Frazier, L (reprint author), 6130 Execut Blvd,EPN 4042,MSC 7337, Bethesda, MD 20892 USA. NR 29 TC 4 Z9 4 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD DEC PY 2003 VL 12 SU 4 BP 34 EP 39 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 758LJ UT WOS:000187635600006 ER PT J AU Hunt, MK Fagan, P Lederman, R Stoddard, A Frazier, L Girod, K Sorensen, G AF Hunt, MK Fagan, P Lederman, R Stoddard, A Frazier, L Girod, K Sorensen, G TI Feasibility of implementing intervention methods in an adolescent worksite tobacco control study SO TOBACCO CONTROL LA English DT Article ID HEALTH PROMOTION PROGRAMS; SMOKING PREVENTION PROGRAMS; PEER EDUCATION; SOCIAL INFLUENCES; DRUG-ABUSE; PARTICIPATION; CRITIQUE; PROJECT; TRIAL AB Objective: To present feasibility data on SMART, the first teen worksite behavioural tobacco control intervention. Design: This phase II study was designed to estimate the efficacy and feasibility of a small scale, randomised, controlled intervention. Setting and subjects: This study, addressing youths aged 15-18 years, was implemented in four intervention and five control grocery stores that had an average of 44 eligible teens. Interventions: The tobacco use cessation and prevention interventions were based on social influences and peer leader models. Employee break rooms served as centres both for interactive activities including open houses, teen advisory boards, peer leader interviews, games and contests; and non-interactive interventions including bulletin boards and table tents with health messages and home mailings. Main process measures: Project staff collected process data on the extent of implementation of intervention activities, participation rates in activities, and contacts with peer leaders. On the final survey, teens reported on awareness of, participation in, and motivation for participating in project activities. Results: Indicators of feasibility were identified and discussed, including the number of activities implemented, teen participation, management support, cost, and barriers to and facilitators of implementation. During the 12 month intervention, a mean of 24.1 interactive activities and 55.3 non-interactive activities were implemented, and a mean 14.2% participation rate per activity per site was achieved. Eighty four per cent of teens reported being aware of SMART, and 39% reported participating in interactive and 67% in non-interactive activities. Conclusions: Teen smoking cessation rates in worksite programmes might be improved if they are conducted in companies where there is job stability and if teen programmes are part of worksite-wide tobacco control programmes that include both teens and adults. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. NCI, Tobacco Control Res Branch, Rockville, MD USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP Hunt, MK (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St,Room SM256, Boston, MA 02115 USA. NR 39 TC 11 Z9 11 U1 2 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD DEC PY 2003 VL 12 SU 4 BP 40 EP 45 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 758LJ UT WOS:000187635600007 ER PT J AU Backinger, CL Fagan, P Matthews, E Grana, R AF Backinger, CL Fagan, P Matthews, E Grana, R TI Adolescent and young adult tobacco prevention and cessation: current status and future directions SO TOBACCO CONTROL LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; NICOTINE PATCH THERAPY; HIGH-SCHOOL-STUDENTS; CIGARETTE-SMOKING; MASS-MEDIA; COLLEGE-STUDENTS; HUTCHINSON SMOKING; WORKPLACE SMOKING; BEHAVIOR OUTCOMES; MINORITY YOUTH AB Objective: To summarise the evidence on adolescent and young adult prevention and cessation, and provide future directions for research. Data sources: Data were collected from published literature. Searches for adolescent prevention were conducted using PubMed, PsycInfo, and ERIC; and for cessation, PubMed, and two major reviews that span January 1978 to May 2002. PubMed, PsychInfo, and SCCI were searched for young adults from January 1990 to May 2002. Study selection: Data included smoking prevention studies published from January 1990 to May 2002 and conducted in the USA; all identified smoking cessation studies for adolescents. Young adult data were limited to initiation and cessation studies. Data extraction: Extraction of data was by consensus of the authors. Data synthesis: Results of the review are qualitative in nature using a consensus approach of the authors. Conclusions: School based curricula alone have been generally ineffective in the long term in preventing adolescents from initiating tobacco use but are effective when combined with other approaches such media and smoke-free policies. Prevention research should consider multiple approaches and the social youth smoking cessation has been understudied to date, scientifically rigorous adolescent smoking cessation studies need to be conducted with attention to high risk smokers and less than daily smokers. Tobacco prevention and cessation for young adults needs focused attention. Prevention and cessation programmes need to address other tobacco products in addition to cigarettes. C1 NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. MasiMax Resources Inc, Rockville, MD USA. RP Backinger, CL (reprint author), 6130 Execut Blvd,EPN 4036, Rockville, MD 20852 USA. NR 99 TC 117 Z9 117 U1 3 U2 15 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD DEC PY 2003 VL 12 SU 4 BP 46 EP 53 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 758LJ UT WOS:000187635600008 ER PT J AU Heindel, JJ AF Heindel, JJ TI Endocrine disruptors and the obesity epidemic SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material C1 NIEHS, Cellular Organs & Syst Pathobiol Branch, Div Extramural Res & Training, NIH,DHHS, Res Triangle Pk, NC 27709 USA. RP Heindel, JJ (reprint author), NIEHS, Cellular Organs & Syst Pathobiol Branch, Div Extramural Res & Training, NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 6 TC 99 Z9 106 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2003 VL 76 IS 2 BP 247 EP 249 DI 10.1093/toxsci/kfg255 PG 3 WC Toxicology SC Toxicology GA 752NF UT WOS:000187173500001 PM 14677558 ER PT J AU Chanas, B Wang, HB Ghanayem, BI AF Chanas, B Wang, HB Ghanayem, BI TI Differential metabolism of acrylonitrile to cyanide is responsible for the greater sensitivity of male vs female mice: role of CYP2E1 and epoxide hydrolases SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID CYTOCHROME-P450 2E1; 2-CYANOETHYLENE OXIDE; IN-VIVO; SEX; TOXICITY; MOUSE; RATS; CARCINOGENICITY; DETOXIFICATION; NEPHROTOXICITY AB Acrylonitrile (AN) is a potent toxicant and a known rodent carcinogen. AN epoxidation to cyanoethylene oxide (CEO) via CYP2E1 and its subsequent metabolism via epoxide hydrolases (EH) to yield cyanide is thought to be responsible for the acute toxicity and mortality of AN. Recent reports showed that male mice are more sensitive than females to the acute toxicity/mortality of AN. The present work was undertaken to assess the metabolic and enzymatic basis for the greater sensitivity of male vs female mice to AN toxicity. Male and female wild-type and CYP2E1-null mice received AN at 0, 2.5, 10, 20, or 40 mg/kg by gavage. Cyanide concentrations were measured at 1 or 3 h after dosing. Current data demonstrated that cyanide levels in blood and tissues of AN-treated wild-type mice of both sexes were significantly greater than in vehicle-treated controls and increased in a dose-dependent manner. In contrast, cyanide levels in AN-treated CYP2E1-null mice were not statistically different from those measured in vehicle-treated controls. Furthermore, higher levels of cyanide were detected in male wild-type mice vs females in association with greater sensitivity of males to the acute toxicity/mortality of this chemical. Using Western blot analysis, negligible difference in CYP2E1 expression with higher levels of soluble and microsomal EH (sEH and mEH) was detected in the liver of male vs female mice. In kidneys, male mice exhibited higher expression of both renal CYP2E1 and sEH than did female mice. In conclusion, higher blood and tissue cyanide levels are responsible for the greater sensitivity of male vs female mice to AN. Further, higher expression of CYP2E1 and EH in male mice may contribute to greater formation of CEO and its subsequent metabolism to yield cyanide, respectively. (C) 2003 Elsevier Inc. All rights reserved. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Ghanayem, BI (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 38 TC 30 Z9 30 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 1 PY 2003 VL 193 IS 2 BP 293 EP 302 DI 10.1016/j.taap.2003.08.006 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 753GL UT WOS:000187223600014 PM 14644629 ER PT J AU Leitman, SF Tisdale, JF Bolan, CD Popovsky, MA Klippel, JH Balow, JE Boumpas, DT Illei, GG AF Leitman, SF Tisdale, JF Bolan, CD Popovsky, MA Klippel, JH Balow, JE Boumpas, DT Illei, GG TI Transfusion-associated GVHD after fludarabine therapy in a patient with systemic lupus erythematosus SO TRANSFUSION LA English DT Article ID VERSUS-HOST DISEASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; LOW-DOSE FLUDARABINE; RHEUMATOID-ARTHRITIS; CYCLOPHOSPHAMIDE; IRRADIATION AB BACKGROUND: Fludarabine, a purine antimetabolite with potent immunosuppressive properties, has previously been associated with the development of transfusion-associated GVHD (TA-GVHD) in patients with hematologic malignancies. Its role as a risk factor for TA-GVHD in patients without underlying leukemia or lymphoma is uncertain. STUDY DESIGN AND METHODS: A 42-year-old female with refractory lupus nephritis received three monthly cycles of fludarabine (30 mg/m(2)/day on Days 1-3) and cyclophosphamide (500 mg/m(2) on Day 1). Three months after the last dose of fludarabine, she received 2 units of packed RBCs and 6 units of pooled random platelets, none of which were irradiated. Two weeks later, fever, rash, aminotransferase elevations, hyperbilirubinemia, and pancytopenia developed. RESULTS: Marrow biopsy showed severe aplasia and skin biopsy was consistent with GVHD. Allele-level HLA typing on circulating lymphocytes revealed extra HLA alleles not present in her pretreatment sample, but identical to the HLA haplotypes of an unrelated platelet donor. Treatment with antithymocyte globulin, cyclosporine, and prednisone was followed by preparatory conditioning for a PBPC transplant from an HLA-identical sibling, but the patient died of disseminated candidiasis before transplant. CONCLUSIONS: Fludarabine and other purine analogs are increasingly used in the treatment of disorders other than hematologic malignancy, such as autoimmune disease. The occurence of TA-GVHD after fludarabine therapy in a patient with lupus strongly suggests that this drug is sufficiently immunoablative to be an independent risk factor for TA-GVHD. Irradiation of blood components should be considered in all patients who receive fludarabine therapy. C1 Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD USA. NIAMSD, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Leitman, SF (reprint author), NIH, Dept Transfus Med, Bldg 10,Room 1C-711, Bethesda, MD 20892 USA. NR 21 TC 24 Z9 28 U1 0 U2 2 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 2003 VL 43 IS 12 BP 1667 EP 1671 DI 10.1046/j.0041-1132.2003.00579.x PG 5 WC Hematology SC Hematology GA 750TT UT WOS:000187014900006 PM 14641861 ER PT J AU Cervenakova, L Yakovleva, O McKenzie, C Kolchinsky, S McShane, L Drohan, WN Brown, P AF Cervenakova, L Yakovleva, O McKenzie, C Kolchinsky, S McShane, L Drohan, WN Brown, P TI Similar levels of infectivity in the blood of mice infected with human-derived vCJD and GSS strains of transmissible spongiform encephalopathy SO TRANSFUSION LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; VARIANT CJD; PRION DISEASES; TONSIL BIOPSY; SMALL RODENTS; SAFETY; BSE; TRANSFUSION; COMPONENTS; PROTEIN AB BACKGROUND: The possible transmission of variant CJD (vCJD) through blood transfusion or use of plasma-derived products prompted this study comparing infectivity in murine models of vCJD and Gerstmann-Straussler-Scheinker (GSS) disease, a non-vCJD form of transmissible spongiform encephalopathy (TSE). STUDY DESIGN AND METHODS: RIII/Fa/Dk (RIII) or Swiss-Webster (Swiss) mice were inoculated intracerebrally (IC) with mouse-adapted strains of vCJD or GSS (Fukuoka-1) of similar infectivity. Groups of RIII mice were euthanized 17 weeks after inoculation (during the incubation period), and another 23 weeks after inoculation (when symptomatic). Blood was collected, separated into components, and inoculated into groups of healthy mice; brains and spleens from all mice were harvested and tested for the presence of PrPres by Western blot using 6H4 MoAb. RESULTS: Levels of 20-30 infectious doses per mL were present in buffy coat and plasma during both the incubation and symptomatic stages of disease; PLT pellet infectivity was lower (10 ID/mL) and RBCs were not infectious. The disease was transmitted more efficiently by IV than IC inoculation of plasma, but there was no difference observed with inoculation of buffy coat. The incubation period was shorter after IC inoculation of GSS- than vCJD-brain inocula. The amount of PrPres in spleens was similar for both TSE agents, but was slightly lower in brains of vCJD than GSS mice. CONCLUSION: Infectivity was detected in blood components of mice infected with a human-derived strain of vCJD during both the preclinical and clinical phases of disease in a similarly low range of concentrations as in mice infected with a human-derived nonvariant strain (GSS, Fukuoka-1). Other measures of virulence, including brain infectivity titers, incubation periods, and the accumulation of PrPres in spleens and brains, were also comparable in both experimental models. C1 Amer Red Cross, Jerome H Holland Lab Biomed Sci, Plasma Derivat Dept, Rockville, MD 20855 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NIH, Lab CNS Studies, Bethesda, MD 20892 USA. RP Cervenakova, L (reprint author), Amer Red Cross, Jerome H Holland Lab Biomed Sci, Plasma Derivat Dept, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. NR 26 TC 120 Z9 123 U1 0 U2 4 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 2003 VL 43 IS 12 BP 1687 EP 1694 DI 10.1046/j.0041-1132.2003.00586.x PG 8 WC Hematology SC Hematology GA 750TT UT WOS:000187014900010 PM 14641865 ER PT J AU Waldmann, TA AF Waldmann, TA TI IL-15 in the life and death of lymphocytes: immunotherapeutic implications SO TRENDS IN MOLECULAR MEDICINE LA English DT Article ID RECEPTOR-BETA-CHAIN; CD8(+) T-CELLS; ALPHA-CHAIN; INTERLEUKIN-2 RECEPTOR; RHEUMATOID-ARTHRITIS; PROLIFERATION; CYTOKINE; PROTEIN; MICE; HOMEOSTASIS AB Interleukin (IL)-2 and IL-15 play contrasting roles in the life and death of lymphocytes. IL-2 favors the death of self-reactive lymphocytes to yield self-tolerance, whereas IL-15 favors the survival of memory CD8(+) T cells. The actions of IL-15 on memory cell persistence and its inhibition of the immunological checkpoint, activation-induced cell death, enable the maintenance of long-lasting immune responses to vaccines. This supports our view that IL-15 should be used in lieu of IL-2 in the treatment of cancer and as a component of vaccines for cancer and AIDS. Furthermore, we suggest that IL-15 plays a major role in the pathogenesis of autoimmune diseases and propose that therapy involving monoclonal antibodies directed at the IL-15 receptor be evaluated in the treatment of such disorders. C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov NR 32 TC 31 Z9 35 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD DEC PY 2003 VL 9 IS 12 BP 517 EP 521 DI 10.1016/j.molmed.2003.10.005 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 757RK UT WOS:000187575100004 PM 14659465 ER PT J AU Martin, R AF Martin, R TI Interleukin 4 treatment of psoriasis: are pleiotropic cytokines suitable therapies for autoimmune diseases? SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID INTERFERON-GAMMA; TYPE-1 CYTOKINES; IL-4; CELLS; DIFFERENTIATION; MULTICENTER; MOUSE AB Many human autoimmune diseases are still treated by a combination of corticosteroids and general immunosuppression. A better understanding of the pathogenesis of these diseases has led to therapies that are more specific than current therapies of some of these disorders. In psoriasis, T helper (Th) cells with a pro-inflammatory phenotype (Th1) are considered essential to the disease process. A recent clinical trial of interleukin 4 in psoriasis has demonstrated that such pleiotropic cytokines can be used safely and effectively to correct imbalances in immune function. C1 NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Martin, R (reprint author), NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, 10 Ctr DR MSC 1400, Bethesda, MD 20892 USA. NR 23 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD DEC PY 2003 VL 24 IS 12 BP 613 EP 616 DI 10.1016/j.tips.2003.10.006 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 757TF UT WOS:000187577000003 PM 14654299 ER PT J AU Morgan, MA Schulkin, J LeDoux, JE AF Morgan, MA Schulkin, J LeDoux, JE TI Ventral medial prefrontal cortex and emotional perseveration: the memory for prior extinction training SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE MPFCv; fear conditioning; extinction; inhibition; context; reacquisition ID FEAR-POTENTIATED STARTLE; FRONTAL-CORTEX; CONDITIONED FEAR; DIFFERENTIAL CONTRIBUTION; EFFERENT PROJECTIONS; RAT; BRAIN; LESIONS; CONTEXT; DISSOCIATION AB Several years ago, we found that lesions of ventral medial prefrontal cortex (mPFCv) disrupted performance during the extinction component of a classical fear conditioning task without affecting acquisition performance. We called this emotional perseveration, hypothesizing that mPFCv may normally act to inhibit fear responses to a conditioned stimulus (CS) when the CS no longer signals danger. Subsequent studies have supported this hypothesis, showing that mPFCv is crucial for the memory of prior extinction training. The present study examined the effects of mPFCv lesions made after training. Such lesions resulted in reduced freezing to contextual stimuli and normal responding to the CS presented alone during a retention test. Rats were then subjected to extinction trials (CS without US) over multiple days. In contrast to pre-training lesions, post-training lesions had little effect on extinction rate. All rats were given additional training. Lesioned rats expressed greater fear reactions than controls, indicating that prior extinction was less effective in them. Lesioned rats also showed resistance to extinction during reextinction trials, confirming our earlier finding that lesions made before training weaken the effectiveness of extinction trials. These results suggest three conclusions. First, an intact mPFCv during acquisition may protect the animal from prolonged responding during extinction trials following brain insult. Second, changes in mPFCv may predispose subjects toward enhanced fear reactions that are difficult to extinguish when reexposed to fearful stimuli, due to a diminished capacity to benefit from the fear-reducing impact of prior extinction experience. Third, contextual cues processed by mPFCv may influence extinction performance. (C) 2003 Elsevier B.V. All rights reserved. C1 NYU, Dept Psychol, New York, NY 10003 USA. NYU, Ctr Neural Sci, New York, NY 10003 USA. Amer Coll Obstetricians & Gynecologists, Res Dept, Washington, DC 20024 USA. Georgetown Univ, Dept Physiol & Biophys, Washington, DC 20024 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Morgan, MA (reprint author), NYU, Dept Psychol, 6 Washington Pl, New York, NY 10003 USA. NR 56 TC 92 Z9 95 U1 4 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD NOV 30 PY 2003 VL 146 IS 1-2 BP 121 EP 130 DI 10.1016/j.bbr.2003.09.021 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 753PW UT WOS:000187240600012 PM 14643465 ER PT J AU Hiol, A Caron, JM Smith, CD Jones, TLZ AF Hiol, A Caron, JM Smith, CD Jones, TLZ TI Characterization and partial purification of protein fatty acyltransferase activity from rat liver SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE palmitoylation; protein fatty acyltransferase; heterotrimeric G protein; RGS protein; tubulin; liver ID ACYL-COENZYME-A; TERMINAL CYSTEINE RESIDUES; MYELIN PROTEOLIPID PROTEIN; ALPHA-SUBUNIT; S-ACYLATION; IN-VIVO; SACCHAROMYCES-CEREVISIAE; PALMITOYLATION; PALMITOYLTRANSFERASE; THIOLASE AB The acylation of proteins through the addition of palmitate to cysteine residues is a common posttranslational modification for a variety of proteins, but the enzymology of this reversible modification has resisted elucidation. We developed a strategy to purify protein fatty acyltransferase (PAT) activity from rat livers that took advantage of recent knowledge on the cellular location and inhibition of PAT activity. We determined that three different thiolases have PAT activity in the presence of imidazole and therefore started the purification with a plasma membrane fraction to minimize the contamination with these enzymes. After detergent extraction of the plasma membrane fraction, the PAT activity was enriched about 90-fold by sequential chromatography including affinity chromatography to a cerulenin-based inhibitor of palmitoylation. The partially purified PAT activity (1) was lost with treatments to degrade or denature proteins, (2) could acylate tubulin, Galpha and RGS16 and (3) showed a preference for palmitate and to a lesser degree other long-chain fatty acids. This purification procedure is a significant advance over previous efforts at PAT purification and a starting point for a proteomic approach for identification of mammalian PAT. Published by Elsevier B.V. C1 NIDDK, Div Endocrinol Diabet & Metab, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Dept Physiol, Farmington, CT USA. Penn State Univ, Dept Pharmacol, Hershey, PA 17033 USA. RP Jones, TLZ (reprint author), NIDDK, Div Endocrinol Diabet & Metab, Metab Dis Branch, NIH, 6707 Democracy Blvd,Room 651, Bethesda, MD 20892 USA. NR 39 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD NOV 30 PY 2003 VL 1635 IS 1 BP 10 EP 19 DI 10.1016/j.bbalip.2003.10.001 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 750JK UT WOS:000186987400002 PM 14642772 ER PT J AU Bonne, O Gilboa, A Louzoun, Y Kempf-Sherf, O Katz, M Fishman, Y Ben-Nahum, Z Krausz, Y Bocher, M Lester, H Chisin, R Lerer, B AF Bonne, O Gilboa, A Louzoun, Y Kempf-Sherf, O Katz, M Fishman, Y Ben-Nahum, Z Krausz, Y Bocher, M Lester, H Chisin, R Lerer, B TI Cerebral blood flow in chronic symptomatic mild traumatic brain injury SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE neuropsychological testing; SPECT; statistical parametric mapping; MTBI ID HEAD-INJURY; TECHNETIUM-99M-HMPAO SPECT; COMPUTED-TOMOGRAPHY; CONTUSION INDEX; CT; ABNORMALITIES; PERFORMANCE; MRI AB Patients with mild traumatic brain injury (MTBI) (journal of Head Trauma and Rehabilitation, 8, 1993, 83-84) challenge physicians' skills and test their patience. Their manifold symptomatology is often not supported by objective neurological findings. We sought to compare regional cerebral blood flow (rCBF) between symptomatic subjects with longstanding MTBI and healthy controls, and to examine the correspondence between neuropsychological deficit and rCBF compromise. Twenty-eight clinically symptomatic male subjects with MTBI and twenty matched controls underwent neuropsychological testing and Tc-99m-HMPAO brain SPECT imaging. Neuropsychological test data were used to categorize subjects into sub-groups according to the presumed location of lesions based on their neurobehavioral deficits. Image subtraction comparisons were made between controls, all MTBI subjects and sub-groups. MTBI patients demonstrated regions of hypoperfusion in frontal, pre-frontal and temporal cortices, and sub-cortical structures. Hypoperfusion in 'frontal', 'left posterior' and to a lesser extent 'sub-cortical' sub-groups was concordant with neuropsychological localization. This was not the case for the 'right posterior' group, where no concordance was found. The rCBF is reduced in symptomatic patients with longstanding MTBI and unremarkable structural brain imaging. Although group analysis is appropriate for the generation of statistically significant differences, the clinical application of brain SPECT imaging in MTBI calls for a capability to associate clinical examination, neuropsychological assessment and cerebral perfusion at the individual subject level. Such competence is still to be attained. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Dept Psychiat, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Dept Nucl Med, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel. Unit Treatment & Rehabil Head Trauma Victims, Jerusalem, Israel. RP Bonne, O (reprint author), NIMH, Mood & Anxiety Disorders Program, 15K North Dr,Room 200, Bethesda, MD 20892 USA. RI louzoun, yoram/F-5874-2011 OI louzoun, yoram/0000-0003-1714-6148 NR 50 TC 63 Z9 64 U1 2 U2 4 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 2003 VL 124 IS 3 BP 141 EP 152 DI 10.1016/S0925-4927(03)00109-4 PG 12 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 745VU UT WOS:000186711900002 PM 14623066 ER PT J AU Lee, M Petrovics, G Anderson, WB AF Lee, M Petrovics, G Anderson, WB TI The synergistic activation of Raf-1 kinase by phorbol myristate acetate and hydrogen peroxide in NIH3T3 cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Raf-1 kinase; PKC; Ras; hydrogen peroxide; PMA; phosphorylation ID SIGNAL-TRANSDUCTION PATHWAY; PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; C PHOSPHORYLATION; EGF RECEPTOR; PKC-EPSILON; IN-VIVO; RAS; H2O2; PHOSPHATASES AB We have previously demonstrated that a 33kDa C-terminal fragment of c-Raf-1 underwent a mobility shift in response to hydrogen peroxide (171202) and phorbol myristate acetate (PMA), respectively. In this study, we have demonstrated that H2O2 induced the activation of N-terminal deletion mutant as well as full length Raf-1 kinase. The pharmacological PKC activator PMA also induced a weak increase in Raf-1 kinase activity through PKC-epsilon activation as determined by the transient expression of dominant negative mutants of PKC-epsilon-K436R. Interestingly, H2O2 produced synergistic increase of PMA-stimulated Raf-1 kinase activation after simultaneous treatment of PMA and H2O2. This synergistic activation of Raf-1 kinase was further enhanced by cypermethrin (an inhibitor of protein phosphatase 213) and dephostatin (tyrosine kinase inhibitor) implying an inhibitory role for these phosphatases in the Raf-1 signaling pathway. Taken together, our data suggest that the synergistic activation of Raf-1 kinase in response to PMA and H2O2 occurs via mechanisms that involve an interaction of Raf-1 kinase and PKC-epsilon, along with a transient phosphorylation of both Raf-1 kinase and PKC. (C) 2003 Elsevier Inc. All rights reserved. C1 Korea Res Inst Chem Technol, Korea Inst Toxicol, Taejon 305600, South Korea. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Rockville, MD 20852 USA. RP Lee, M (reprint author), Korea Res Inst Chem Technol, Korea Inst Toxicol, POB 123, Taejon 305600, South Korea. NR 49 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 28 PY 2003 VL 311 IS 4 BP 1026 EP 1033 DI 10.1016/j.bbrc.2003.10.107 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 747KP UT WOS:000186803900035 PM 14623285 ER PT J AU Klee, C AF Klee, C TI Special section on calcineurin - Introduction SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Editorial Material C1 NCI, Biochem Lab, Bethesda, MD 20892 USA. RP Klee, C (reprint author), NCI, Biochem Lab, Natl Inst Hlth Bldg 37,Room 6106, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 28 PY 2003 VL 311 IS 4 BP 1087 EP 1088 DI 10.1016/j.bbrc.2003.10.132 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 747KP UT WOS:000186803900043 ER PT J AU Wakita, H Tomimoto, H Akiguchi, I Lin, JX Hara, M Ohtani, R Shibata, M AF Wakita, H Tomimoto, H Akiguchi, I Lin, JX Hara, M Ohtani, R Shibata, M TI Ibudilast, a phosphodiesterase inhibitor, protects against white matter damage under chronic cerebral hypoperfusion in the rat SO BRAIN RESEARCH LA English DT Article DE phosphodiesterase inhibitor; ibudilast; rat; white matter; microglia; ischemic cerebrovascular disease ID TUMOR-NECROSIS-FACTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; DISEASE PATIENTS; FACTOR-ALPHA; TNF-ALPHA; BRAIN; ISCHEMIA; MICROGLIA; MACROPHAGES AB Cerebrovascular white matter (WM) lesions, which are frequently observed in vascular cognitive impairment and vascular dementia, can be produced in rats by clipping the common carotid arteries bilaterally. Since TNF-alpha is known to cause the degeneration of myelin, we examined whether these lesions can be ameliorated by ibudilast, a cyclic AMP phosphodiesterase (PDE) inhibitor that suppresses tumor necrosis factor (TNF)-alpha production. After the ligation of both common carotid arteries in 29 rats, 21 rats received a daily oral administration of 10, 30 or 60 mg/kg ibudilast and 8 rats received vehicle for 14 days. The pathological changes in the white matter were quantified in terms of white matter lesions and the emergence of activated microglia immunoreactive for major histocompatibility complex (MHC) antigen. In the vehicle-treated animals, white matter lesions and microglial activation occurred in the optic tract, internal capsule and corpus callosum. A low dose (10 mg/kg) of ibudilast failed to suppress the white matter lesions and microglial activation, whereas a dose of either 30 or 60 mg/kg ibudilast ameliorated these lesions (p<0.001). Without an alterations in laboratory blood data, 60 mg/kg ibudilast exhibited percent reduction of the white matter lesions ranging between 50% and 70%, which was more effective than 30 mg/kg ibudilast (p<0.05). The TNF-alpha inummoreactive glia decreased in number in the 60 mg/kg ibudilast-treated group as compared to the vehicle-treated group (p<0.001). These results indicate a dose-dependent protective effect of ibudilast against cerebrovascular white matter lesions and suggest a potential use for ibudilast in the treatment of vascular dementia. (C) 2003 Elsevier B.V. All rights reserved. C1 Kyoto Univ, Fac Med, Dept Neurol, Sakyo Ku, Kyoto 6068507, Japan. RP Wakita, H (reprint author), Natl Inst Neurol Disorders & Stroke, Stroke Branch, NIH, Bldg 36,Room 4B22,36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. OI Ihara, Masafumi/0000-0002-7102-4048 NR 39 TC 45 Z9 51 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 28 PY 2003 VL 992 IS 1 BP 53 EP 59 DI 10.1016/j.brainres.2003.08.028 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 748DC UT WOS:000186846100006 PM 14604772 ER PT J AU Woo, HA Kang, SW Kim, HK Yang, KS Chae, HZ Rhee, SG AF Woo, HA Kang, SW Kim, HK Yang, KS Chae, HZ Rhee, SG TI Reversible oxidation of the active site cysteine of peroxiredoxins to cysteine sulfinic acid - Immunoblot detection with antibodies specific for the hyperoxidized cysteine-containing sequence SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THIOL-SPECIFIC ANTIOXIDANT; MAMMALIAN PEROXIREDOXIN; 2-CYS PEROXIREDOXIN; CRYSTAL-STRUCTURE; THIOREDOXIN; PROTEIN; FAMILY; OVEROXIDATION; INACTIVATION; REDUCTASE AB We previously suggested that oxidation of the active site cysteine of peroxiredoxin (Prx) I or Prx II to cysteine sulfinic acid in H2O2-treated cells is reversible (Woo, H. A., Chae, H. Z., Hwang, S. C., Yang, K.- S., Kang, S. W., Kim, K., and Rhee, S. G. (2003) Science 300, 653-656). In contrast, it was recently proposed that sulfinylation of Prx II, but not that of Prx I or Prx III, is reversible (Chevallet, M., Wagner, E., Luche, S., van Dorssealaer, A., Leize-Wagner, E., and Rabilloud, T. (2003) J. Biol. Chem. 278, 37146 - 37153). The detection of sulfinylated proteins in both of these previous studies relied on complex proteomics analysis. We now describe a simple immunoblot assay for the detection of sulfinylated Prx enzymes that is based on antibodies produced in response to a sulfonylated peptide modeled on the conserved active site sequence. These antibodies recognized both sulfinic and sulfonic forms of Prx equally well and allowed the detection of sulfinylated Prx enzymes in H2O2-treated cells with high sensitivity and specificity. With the use of these antibodies, we demonstrated that not only the cytosolic enzymes Prx I and Prx II but also the mitochondrial enzyme Prx III undergo reversible sulfinylation. The generation of antibodies specific for sulfonylated peptides should provide insight into protein function similar to that achieved with antibodies to peptides containing phosphoserine or phosphothreonine. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea. Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. Labfrontier Life Sci Inst, Suwon 442766, Kyunngi Do, South Korea. RP Rhee, SG (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 50,Rm 3523,South Dr,MSC 8015, Bethesda, MD 20892 USA. NR 21 TC 151 Z9 155 U1 1 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 28 PY 2003 VL 278 IS 48 BP 47361 EP 47364 DI 10.1074/jbc.C300428200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 746DM UT WOS:000186731400003 PM 14559909 ER PT J AU Missirlis, F Hu, JG Kirby, K Hilliker, AJ Rouault, TA Phillips, JP AF Missirlis, F Hu, JG Kirby, K Hilliker, AJ Rouault, TA Phillips, JP TI Compartment-specific protection of iron-sulfur proteins by superoxide dismutase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OXIDATIVE STRESS; DROSOPHILA-MELANOGASTER; SACCHAROMYCES-CEREVISIAE; REGULATORY PROTEIN; RESPONSIVE ELEMENT; MOTOR-NEURONS; CU,ZN-SUPEROXIDE DISMUTASE; CAENORHABDITIS-ELEGANS; ACONITASE ACTIVITY; MESSENGER-RNA AB Iron and oxygen are essential but potentially toxic constituents of most organisms, and their transport is meticulously regulated both at the cellular and systemic levels. Compartmentalization may be a homeostatic mechanism for isolating these biological reactants in cells. To investigate this hypothesis, we have undertaken a genetic analysis of the interaction between iron and oxygen metabolism in Drosophila. We show that Drosophila iron regulatory protein-1 (IRP1) registers cytosolic iron and oxidative stress through its labile iron sulfur cluster by switching between cytosolic aconitase and RNA-binding functions. IRP1 is strongly activated by silencing and genetic mutation of the cytosolic superoxide dismutase (Sod1), but is unaffected by silencing of mitochondrial Sod2. Conversely, mitochondrial aconitase activity is relatively insensitive to loss of Sod1 function, but drops dramatically if Sod2 activity is impaired. This strongly suggests that the mitochondrial boundary limits the range of superoxide reactivity in vivo. We also find that exposure of adults to paraquat converts cytosolic aconitase to IRP1 but has no affect on mitochondrial aconitase, indicating that paraquat generates superoxide in the cytosol but not in mitochondria. Accordingly, we find that transgene-mediated overexpression of Sod2 neither enhances paraquat resistance in Sod1(+) flies nor compensates for lack of SOD1 activity in Sod1-null mutants. We conclude that in vivo, superoxide is confined to the subcellular compartment in which it is formed, and that the mitochondrial and cytosolic SODs provide independent protection to compartment-specific protein iron-sulfur clusters against attack by superoxide generated under oxidative stress within those compartments. C1 Univ Guelph, Dept Mol Biol & Genet, Guelph, ON N1G 2W1, Canada. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. York Univ, Dept Biol, N York, ON M3J 1P3, Canada. RP Phillips, JP (reprint author), Univ Guelph, Dept Mol Biol & Genet, Guelph, ON N1G 2W1, Canada. RI Missirlis, Fanis/C-1137-2011 OI Missirlis, Fanis/0000-0003-0467-8444 NR 44 TC 65 Z9 66 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 28 PY 2003 VL 278 IS 48 BP 47365 EP 47369 DI 10.1074/jbc.M307700200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 746DM UT WOS:000186731400004 PM 12972424 ER PT J AU Ruan, H Zarnowski, MJ Cushman, SW Lodish, HF AF Ruan, H Zarnowski, MJ Cushman, SW Lodish, HF TI Standard isolation of primary adipose cells from mouse epididymal fat pads induces inflammatory mediators and down-regulates adipocyte genes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; TYPE-2 DIABETES-MELLITUS; NF-KAPPA-B; INSULIN-RESISTANCE; TRANSCRIPTION FACTORS; GLUT4 TRANSLOCATION; TNF-ALPHA; KINASE; PATHOGENESIS; EXPRESSION AB Isolation and subsequent in vitro culture of primary adipose cells are associated with down-regulation of GLUT4 mRNA and simultaneous induction of GLUT1 gene expression. Progressive loss of insulin-responsive GLUT4 contributes to the decrease in insulin-mediated glucose uptake in these cells when cultured in vitro. The mechanisms underlying these alterations are unknown. Here, we report that the standard procedure for isolating primary adipose cells from mouse adipose tissue triggers induction of many genes encoding inflammatory mediators including TNF-alpha, interleukin (IL)-1alpha, IL-6, multiple chemokines, cell adhesion molecules, acute-phase proteins, type I IL-1 receptor, and multiple transcription factors implicated in the cellular inflammatory response. Secretion of TNF-alpha protein was also significantly induced during the 2-h collagenase digestion of adipose tissue. Isolated primary adipose cells exhibit dramatic changes in expression of multiple mRNAs that are characteristic of TNF-alpha-treated 3T3-L1 adipocytes including down-regulation of many genes important for insulin action and triglyceride synthesis. Addition of TNF-alpha to primary adipose cells in culture did not change the kinetics or the extent of the repression of adipose cell- abundant genes. Moreover, TNF-alpha-neutralizing antibody failed to block the changes in gene transcription in isolated primary adipose cells. Also, the standard isolation procedure induced the expression of NF-kappaB family members and their target genes in primary adipose cells prepared from TNF-alpha-/- mice to the same extent as in cells isolated from wild-type mice and resulted in almost identical changes in global gene expression when these cells were cultured in vitro. Thus, these data suggest that the standard isolation procedure-triggered reprogramming of gene expression in primary adipose cells that results in decreased insulin sensitivity does not require TNF-alpha, at least in this in vitro model system, but may be dependent on other inflammatory cytokines produced by these cells. C1 MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. NIDDK, Expt Diabet Metab & Nutr Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Lodish, HF (reprint author), MIT, Whitehead Inst Biomed Res, 9 Cambridge Ctr,Rm 601, Cambridge, MA 02142 USA. NR 31 TC 100 Z9 104 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 28 PY 2003 VL 278 IS 48 BP 47585 EP 47593 DI 10.1074/jbc.M305257200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 746DM UT WOS:000186731400031 PM 12975378 ER PT J AU Hwang, M Morasso, MI AF Hwang, M Morasso, MI TI The novel murine Ca2+-binding protein, scarf, is differentially expressed during epidermal differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALMODULIN-LIKE PROTEIN; KERATINOCYTE DIFFERENTIATION; MULTIGENIC FAMILY; GENE-EXPRESSION; BINDING-SITES; SKIN PROTEIN; S100; IDENTIFICATION; LOCALIZATION; ENVELOPE AB Calcium (Ca2+) signaling-dependent systems, such as the epidermal differentiation process, must effectively respond to variations in Ca2+ concentration. Members of the Ca2+-binding proteins play a central function in the transduction of Ca2+ signals, exerting their roles through a Ca2+-dependent interaction with their target proteins, spatially and temporally. By performing a suppression subtractive hybridization screen we identified a novel mouse gene, Scarf (skin calmodulin-related factor), which has homology to calmodulin (CaM)- like Ca2+-binding protein genes and is exclusively expressed in differentiating keratinocytes in the epidermis. The Scarf open reading frame encodes a 148-amino acid protein that contains four conserved EF-hand motifs ( predicted to be Ca2+-binding domains) and has homology to mouse CaM, human CaM-like protein, hClp, and human CaM-like skin protein, hClsp. The functionality of Scarf EF-hand domains was assayed with a radioactive Ca2+-binding method. By Southern blot and computational genome sequence analysis, a highly related gene, Scarf2, was found 15 kb downstream of Scarf on mouse chromosome 13. The functional Scarf Ca2+-binding domains suggest a role in the regulation of epidermal differentiation through the control of Ca2+-mediated signaling. C1 NIAMS, Dev Skin Biol Unit, 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 29 TC 14 Z9 14 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 28 PY 2003 VL 278 IS 48 BP 47827 EP 47833 DI 10.1074/jbc.M306561200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 746DM UT WOS:000186731400059 PM 12970338 ER PT J AU Jiang, F Li, PF Fornace, AJ Nicosia, SV Bai, WL AF Jiang, F Li, PF Fornace, AJ Nicosia, SV Bai, WL TI G(2)/M arrest by 1,25-dihydroxyvitamin D-3 in ovarian cancer cells mediated through the induction of GADD45 via an exonic enhancer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VITAMIN-D-RECEPTOR; DECREASED DNA-REPAIR; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; ANDROGEN RECEPTOR; GENE-EXPRESSION; PROSTATE-CANCER; KINASE-ACTIVITY; ANALOG EB1089; GROWTH; PHOSPHORYLATION AB 1,25-Dihydroxyvitamin D-3 suppresses the growth of multiple human cancer cell lines by inhibiting cell cycle progression and inducing cell death. The present study showed that 1,25-dihydroxyvitamin D-3 causes cell cycle arrest at the G(2)/M transition through p53-independent induction of GADD45 in ovarian cancer cells. Detailed analyses have established GADD45 as a primary target gene for 1,25-dihydroxyvitamin D-3. A DR3-type vitamin D response element was identified in the fourth exon of GADD45 that forms a complex with the vitamin D receptor . retinoid X receptor heterodimer in electrophoresis mobility shift assays and mediates the dose-dependent induction of luciferase activity by 1,25-dihydroxyvitamin D-3 in reporter assays. Chromatin immunoprecipitation assays have shown that the vitamin D receptor is recruited in a ligand-dependent manner to the exonic enhancer but not to the GADD45 promoter regions. In ovarian cancer cells expressing GADD45 antisense cDNA or GADD45-null mouse embryo fibroblasts, 1,25-dihydroxyvitamin D-3 failed to induce G(2)/M arrest. Taken together, these results identify GADD45 as an important mediator for the tumor-suppressing activity of 1,25-dihydroxyvitamin D-3 in human ovarian cancer cells. C1 Univ S Florida, Coll Med, Dept Pathol, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA. H Lee Moffitt Canc Ctr, Program Mol Oncol, Tampa, FL 33612 USA. H Lee Moffitt Canc Ctr, Program Drug Discovery, Tampa, FL 33612 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Bai, WL (reprint author), Univ S Florida, Coll Med, Dept Pathol, 12901 Bruce B Downs Blvd,MDC 11, Tampa, FL 33612 USA. RI Fornace, Albert/A-7407-2008; Bai, Wenlong /A-8977-2013 OI Fornace, Albert/0000-0001-9695-085X; Bai, Wenlong /0000-0002-9536-0556 NR 56 TC 80 Z9 84 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 28 PY 2003 VL 278 IS 48 BP 48030 EP 48040 DI 10.1074/jbc.M308430200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 746DM UT WOS:000186731400082 PM 14506229 ER PT J AU Tkaczyk, C Beaven, MA Brachman, SM Metcalfe, DD Gilfillan, AM AF Tkaczyk, C Beaven, MA Brachman, SM Metcalfe, DD Gilfillan, AM TI The phospholipase C gamma(1)-dependent pathway of Fc epsilon RI-mediated mast cell activation is regulated independently of phosphatidylinositol 3-kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AFFINITY IGE RECEPTOR; PROTEIN-KINASE-C; INCREASED INSULIN SENSITIVITY; PHOSPHOINOSITIDE 3-KINASE; ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION; B-CELL; TYROSINE KINASE; CROSS-LINKING; RBL-2H3 CELLS AB Mast cell degranulation following FcepsilonRI aggregation is generally believed to be dependent on phosphatidylinositide 3-kinase (PI 3-kinase)-mediated phospholipase C (PLC) gamma activation. Here we report evidence that the PLCgamma(1)-dependent pathway of FcepsilonRI-mediated activation of mast cells is independent of PI 3-kinase activation. In primary cultures of human mast cells, FcepsilonRI aggregation induced a rapid translocation and phosphorylation of PLCgamma(1), and subsequent inositol trisphosphate (IP3) production, which preceded PI 3-kinase-related signals. In addition, although PI 3-kinase-mediated responses were completely inhibited by wortmannin, even at high concentrations, this PI 3-kinase inhibitor had no effect on parameters of FcepsilonRI-mediated PLCgamma activation, and had little effect on the initial increase in intracellular calcium levels that correlated with PLCgamma activation. Wortmannin, however, did produce a partial ( similar to 50%) concentration-dependent inhibition of FcepsilonRI-mediated degranulation in human mast cells and a partial inhibition of the later calcium response at higher concentrations. Further studies, conducted in mast cells derived from the bone marrow of mice deficient in the p85alpha and p85beta subunits of PI 3-kinase, also revealed no defects in FcepsilonRI-mediated PLCgamma(1) activation. These data are consistent with the conclusion that the PLCgamma-dependent component of FcepsilonRI-mediated calcium flux leading to degranulation of mast cells is independent of PI 3-kinase. However, PI 3-kinase may contribute to the later phase of FcepsilonRI-mediated degranulation in human mast cells. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Free Univ Berlin, Inst Biochem, D-1000 Berlin, Germany. RP Gilfillan, AM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Rm 11C206,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. NR 47 TC 75 Z9 75 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 28 PY 2003 VL 278 IS 48 BP 48474 EP 48484 DI 10.1074/jbc.M301350200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 746DM UT WOS:000186731400133 PM 13129935 ER PT J AU Suzuki, M Jeong, SY Karbowski, M Youle, RJ Tjandra, N AF Suzuki, M Jeong, SY Karbowski, M Youle, RJ Tjandra, N TI The solution structure of human mitochondria fission protein Fis1 reveals a novel TPR-like helix bundle SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE mitochondria; NMR; dynamin; tom20; tom70 ID DYNAMIN-RELATED GTPASE; IMPORT RECEPTOR TOM20; TRIPLE-RESONANCE NMR; WD REPEAT PROTEIN; OUTER-MEMBRANE; C-13-ENRICHED PROTEINS; CRYSTAL-STRUCTURE; TARGETING SIGNAL; DNM1P; SPECTROSCOPY AB Fis1 in yeast localizes to the outer mitochondrial membrane and facilitates mitochondrial fission by forming protein complexes with Dnm1 and Mdv1. Fis1 orthologs exist in higher eukaryotes, suggesting that they are functionally conserved. In the present study, we cloned the human Fis1 ortholog that was predicted in a database, and determined the protein structure using NMR spectroscopy. Following a flexible N-terminal tail, six alpha-helices connected with short loops construct a single core domain. The C-terminal tail containing a transmembrane segment appears to be disordered. In the core domain, each of two sequentially adjacent helices forms a hairpin-like conformation, resulting in a six helix assembly forming a slightly twisted slab similar to that of a tandem array of tetratricopeptide repeat (TPR) motif folds. Within this TPR-like core domain, no significant sequence similarity to the typical TPR motif is found. The structural analogy to the TPR-containing proteins suggests that Fis1 binds to other proteins at its concave hydrophobic surface. A simple composition of Fis1 comprised of a binding domain and a transmembrane segment indicates that the protein may function as a molecular adaptor on the mitochondrial outer membrane. In HeLa cells, however, increased levels in mitochondria-associated Fis1 did not result in mitochondrial translocation of Drp1, a potential binding partner of Fis1 implicated in the regulation of mitochondrial fission, suggesting that the interaction between Drp1 and Fis1 is regulated. (C) 2003 Elsevier Ltd. All rights reserved. C1 NHLBI, Biophys Chem Lab, Bethesda, MD 20892 USA. NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Biophys Chem Lab, Bldg 50,Room 3503,50 Ctr Dr, Bethesda, MD 20892 USA. NR 49 TC 100 Z9 105 U1 0 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 28 PY 2003 VL 334 IS 3 BP 445 EP 458 DI 10.1016/j.jmb.2003.09.064 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 745VF UT WOS:000186710600008 PM 14623186 ER PT J AU Mkrtchian, V Parsegian, VA Podgornik, R Saslow, WM AF Mkrtchian, V Parsegian, VA Podgornik, R Saslow, WM TI Universal thermal radiation drag on neutral objects SO PHYSICAL REVIEW LETTERS LA English DT Article ID ELECTRONIC FRICTION; SURFACE; VACUUM; FORCES; ATOM AB We compute the force on a small neutral polarizable object moving at velocity (ν) over right arrow relative to a photon gas equilibrated at a temperature T. We find a drag force linear in (ν) over right arrow. Its physical basis is related to that in recent formulations of the dissipative component of the Casimir force, i.e., the change in photon momentum in emission and absorption between the moving body and the stationary thermal bath. We estimate the strength of this universal drag force for different dielectric response functions and comment on its relevance in various contexts, especially to radiation-matter coupling in the cosmos. C1 Armenian Acad Sci, Inst Phys Res, Ashtarak 378410 2, Armenia. NIH, Lab Struct & Phys Biol, Bethesda, MD 20892 USA. Univ Ljubljana, Fac Math & Phys, SI-1000 Ljubljana, Slovenia. Texas A&M Univ, Dept Phys, College Stn, TX 77840 USA. RP Mkrtchian, V (reprint author), Armenian Acad Sci, Inst Phys Res, Ashtarak 378410 2, Armenia. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 17 TC 41 Z9 42 U1 0 U2 3 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD NOV 28 PY 2003 VL 91 IS 22 AR 220801 DI 10.1103/PhysRevLett.91.220801 PG 4 WC Physics, Multidisciplinary SC Physics GA 747JR UT WOS:000186801900003 PM 14683225 ER PT J AU Yu, L Lenardo, MJ AF Yu, L Lenardo, MJ TI The Paracaspase connection SO SCIENCE LA English DT Editorial Material ID NF-KAPPA-B; INDUCIBILITY; GENE C1 NIAID, Immunol Lab, Bethesda, MD 20892 USA. RP Yu, L (reprint author), NIAID, Immunol Lab, Bldg 10, Bethesda, MD 20892 USA. NR 8 TC 3 Z9 3 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 28 PY 2003 VL 302 IS 5650 BP 1515 EP 1516 DI 10.1126/science.1092951 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747JV UT WOS:000186802200027 PM 14645834 ER PT J AU Pommier, Y Redon, C Rao, VA Seiler, JA Sordet, O Takemura, H Antony, S Meng, LH Liao, ZY Kohlhagen, G Zhang, HL Kohn, KW AF Pommier, Y Redon, C Rao, VA Seiler, JA Sordet, O Takemura, H Antony, S Meng, LH Liao, ZY Kohlhagen, G Zhang, HL Kohn, KW TI Repair of and checkpoint response to topoisomerase I-mediated DNA damage SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE topoisomerase; homologous recombination; camptothecin; Tdp1; Mre11; ATM; ATR; BRCA1; BRCA2; RAD52; RAD51; RPA; DNA-PK; cell cycle checkpoints ID DOUBLE-STRAND BREAKS; S-PHASE CHECKPOINT; BLOOMS-SYNDROME PROTEIN; RNA-POLYMERASE-II; NF-KAPPA-B; CAMPTOTHECIN-INDUCED APOPTOSIS; ATM-DEPENDENT PHOSPHORYLATION; ATAXIA-TELANGIECTASIA CELLS; WERNER-SYNDROME PROTEIN; COLON-CARCINOMA CELLS AB Topoisomerase I (Top1) catalyzes two transesterification reactions: single-strand DNA cleavage and religation that are normally coupled for the relaxation of DNA supercoiling in transcribing and replicating chromatin. A variety of endogenous DNA modifications, potent anticancer drugs and carcinogens uncouple these two reactions, resulting in the accumulation of Top I cleavage complexes. Top I cleavage complexes damage DNA and kill cells by generating replication-mediated DNA double-strand breaks (DSBs) and by stalling transcription complexes. The repair of Top1-mediated DNA lesions involves integrated pathways that are conserved from yeasts to humans. Top1-mediated DNA damage and cell cycle checkpoint responses can be studied biochemically and genetically in yeast and human cells with known genetic defects. Defects in these repair/checkpoint pathways, which promote tumor development, explain, at least in part, the selectivity of camptothecins and other Top I inhibitors for cancer cells. (C) 2003 Elsevier B.V. All rights reserved. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Room 5068, Bethesda, MD 20892 USA. RI Sordet, Olivier/M-3271-2014 NR 284 TC 195 Z9 197 U1 0 U2 15 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 27 PY 2003 VL 532 IS 1-2 BP 173 EP 203 DI 10.1016/j.mrfmmm.2003.08.016 PG 31 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 754WK UT WOS:000187355500013 PM 14643436 ER PT J AU Mills, EM Banks, ML Sprague, JE Finkel, T AF Mills, EM Banks, ML Sprague, JE Finkel, T TI Pharmacology: Uncoupling the agony from ecstasy - A mitochondrial protein may mediate a dangerous side-effect of some recreational drugs SO NATURE LA English DT Editorial Material ID 3,4-METHYLENEDIOXYMETHAMPHETAMINE ECSTASY; MDMA; MICE; HYPERTHERMIA C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. Ohio No Univ, Dept Pharmaceut & Biomed Sci, Ada, OH 45810 USA. RP Mills, EM (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Banks, Matthew/K-4429-2014 OI Banks, Matthew/0000-0003-4949-5246 NR 11 TC 91 Z9 92 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 27 PY 2003 VL 426 IS 6965 BP 403 EP 404 DI 10.1038/426403a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747JE UT WOS:000186800800027 PM 14647371 ER PT J AU Collins, FS Guttmacher, AE AF Collins, FS Guttmacher, AE TI Genomic medicine - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NHGRI, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 27 PY 2003 VL 349 IS 22 BP 2170 EP 2171 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 746ZV UT WOS:000186779700029 ER PT J AU Nolan, MF Malleret, G Lee, KH Gibbs, E Dudman, JT Santoro, B Yin, DQ Thompson, RF Siegelbaum, SA Kandel, ER Morozov, A AF Nolan, MF Malleret, G Lee, KH Gibbs, E Dudman, JT Santoro, B Yin, DQ Thompson, RF Siegelbaum, SA Kandel, ER Morozov, A TI The hyperpolarization-activated HCN1 channel is important for motor learning and neuronal integration by cerebellar Purkinje cells SO CELL LA English DT Article ID LONG-TERM DEPRESSION; MUTANT MICE; NUCLEAR NEURONS; BASKET CELLS; COORDINATION; INHIBITION; RESPONSES; PACEMAKER; CURRENTS; CORTEX AB In contrast to our increasingly detailed understanding of how synaptic plasticity provides a cellular substrate for learning and memory, it is less clear how a neuron's voltage-gated ion channels interact with plastic changes in synaptic strength to influence behavior. We find, using generalized and regional knockout mice, that deletion of the HCN1 channel causes profound motor learning and memory deficits in swimming and rotarod tasks. In cerebellar Purkinje cells, which are a key component of the cerebellar circuit for learning of correctly timed movements, HCN1 mediates an inward current that stabilizes the integrative properties of Purkinje cells and ensures that their input-output function is independent of the previous history of their activity. We suggest that this nonsynaptic integrative function of HCN1 is required for accurate decoding of input patterns and thereby enables synaptic plasticity to appropriately influence the performance of motor activity. C1 Columbia Univ, Howard Hughes Med Inst, Ctr Neurobiol & Behav, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, Dept Pharmacol, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, Dept Physiol, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, Dept Biochem & Biophys, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, Dept Psychiat, New York, NY 10032 USA. Univ So Calif, Neurosci Program, Los Angeles, CA 90089 USA. NIMH, Unit Behav Genet, Bethesda, MD 20892 USA. RP Nolan, MF (reprint author), Columbia Univ, Howard Hughes Med Inst, Ctr Neurobiol & Behav, New York, NY 10032 USA. RI Nolan, Matthew/A-1356-2009 OI Nolan, Matthew/0000-0003-1062-6501 FU NIMH NIH HHS [MH045923]; NINDS NIH HHS [NS36658] NR 45 TC 178 Z9 182 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 26 PY 2003 VL 115 IS 5 BP 551 EP 564 DI 10.1016/S0092-8674(03)00884-5 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 748XE UT WOS:000186885600006 PM 14651847 ER PT J AU Iyer, MB Schleper, N Wassermann, EM AF Iyer, MB Schleper, N Wassermann, EM TI Priming stimulation enhances the depressant effect of low-frequency repetitive transcranial magnetic stimulation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE priming; transcranial magnetic stimulation; plasticity; motor cortex; long-term depression; treatment ID MOTOR CORTEX EXCITABILITY; LONG-TERM DEPRESSION; SYNAPTIC PLASTICITY; CORTICAL EXCITABILITY; PATTERNED STIMULATION; THETA-FREQUENCY; RTMS; METAPLASTICITY; HUMANS; POTENTIATION AB Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) can depress the excitability of the cortex locally and has been proposed for the treatment of disorders such as schizophrenia and epilepsy. Some have speculated that the depressant effect is related to long-term depression (LTD) of cortical synapses. Because in vitro LTD can be enhanced by pretreatment of synapses with higher-frequency stimulation, we hypothesized that if rTMS depression had mechanisms in common with LTD, higher-frequency priming would increase it also. In 25 healthy volunteers in two experiments, we measured motor-evoked potentials (MEPs) from TMS of the motor cortex to define the baseline response. Subthreshold rTMS (6 Hz, fixed rate or frequency modulated) was used to prime the motor cortex, followed by suprathreshold 1 Hz stimulation for 10 min at just above the MEP threshold. Over the next 60 min, we recorded MEPs every 10 sec and found significant increases in the amount of cortical depression with both types of 6 Hz priming rTMS relative to sham. The MEP depression from 6 Hz-primed 1 Hz rTMS showed no evidence of decay after 60 min. Pretreatment with 6 Hz primes both 1 Hz rTMS depression and LTD. Although not conclusive evidence, this strengthens the case for overlapping mechanisms and suggests a potent new technique for enhancing low-frequency rTMS depression that may have experimental and clinical applications. C1 NINDS, Brain Stimulat Unit, NIH, Bethesda, MD 20892 USA. RP Wassermann, EM (reprint author), Bldg 10,Room 5N254,10 Ctr Dr,MSC 1430, Bethesda, MD 20892 USA. NR 36 TC 195 Z9 199 U1 1 U2 11 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 NOV 26 PY 2003 VL 23 IS 34 BP 10867 EP 10872 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 749DC UT WOS:000186902500015 PM 14645480 ER PT J AU Singer, JH Diamond, JS AF Singer, JH Diamond, JS TI Sustained Ca2+ entry elicits transient postsynaptic currents at a retinal ribbon synapse SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ribbon synapse; rod bipolar cell; AII amacrine cell; retina; scotopic vision; AMPA receptor ID AII AMACRINE CELLS; ROD BIPOLAR CELLS; GLUTAMATE-RECEPTOR CHANNELS; RAT RETINA; RABBIT RETINA; CALCIUM-CHANNELS; CAT RETINA; NEUROTRANSMITTER RELEASE; MAMMALIAN RETINA; AFFERENT SYNAPSE AB Night (scotopic) vision is mediated by a distinct retinal circuit in which the light responses of rod-driven neurons are faster than those of the rods themselves. To investigate the dynamics of synaptic transmission at the second synapse in the rod pathway, we made paired voltage-clamp recordings from rod bipolar cells (RBCs) and postsynaptic AII and A17 amacrine cells in rat retinal slices. Depolarization of RBCs from -60 mV elicited sustained Ca2+ currents and evoked AMPA receptor (AMPAR)-mediated EPSCs in synaptically coupled amacrine cells that exhibited large, rapidly rising initial peaks that decayed rapidly to smaller, steady-state levels. The transient component persisted in the absence of feedback inhibition to the RBC terminal and when postsynaptic AMPA receptor desensitization was blocked with cyclothiazide, indicating that it reflects a time-dependent decrease in the rate of exocytosis from the presynaptic terminal. The EPSC waveform was similar when RBCs were recorded in perforated-patch or whole-cell configurations, but asynchronous release from RBCs was enhanced when the intraterminal Ca2+ buffer capacity was reduced. When RBCs were depolarized from -100 mV, inactivating, low voltage-activated (T-type channel-mediated) Ca2+ currents were evident. Although Ca2+ influx through T-type channels boosted vesicle release, as reflected by larger EPSCs, it did not make the EPSCs faster, indicating that activation of T-type channels is not necessary to generate a transient phase of exocytosis. We conclude that the time course of vesicle release from RBCs is inherently transient and, together with the fast kinetics of postsynaptic AMPARs, speeds transmission at this synapse. C1 NINDS, NIH, Synapt Physiol Unit, Bethesda, MD 20892 USA. RP Singer, JH (reprint author), NINDS, NIH, Synapt Physiol Unit, 36 Conent Dr,MSC-4066,Bldg 36,Room 2C09, Bethesda, MD 20892 USA. RI Diamond, Jeffrey/C-1835-2015 OI Diamond, Jeffrey/0000-0002-1770-2629 FU NINDS NIH HHS [K22 NS043365] NR 59 TC 135 Z9 135 U1 0 U2 7 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 NOV 26 PY 2003 VL 23 IS 34 BP 10923 EP 10933 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 749DC UT WOS:000186902500023 PM 14645488 ER PT J AU Hu, ZL Yue, X Shi, GF Yue, Y Crockett, DP Blair-Flynn, J Reuhl, K Tessarollo, L Zhou, RP AF Hu, ZL Yue, X Shi, GF Yue, Y Crockett, DP Blair-Flynn, J Reuhl, K Tessarollo, L Zhou, RP TI Corpus callosum deficiency in transgenic mice expressing a truncated ephrin-A receptor SO JOURNAL OF NEUROSCIENCE LA English DT Article DE corpus callosum; axon guidance; Eph receptors; ephrins; transgenic mice; neurite outgrowth ID GROWTH-FACTOR RECEPTOR; CENTRAL-NERVOUS-SYSTEM; TYROSINE KINASE; SIGNAL TRANSDUCTION; NEURITE OUTGROWTH; HIPPOCAMPAL AXONS; COMMISSURAL AXONS; CEREBRAL-CORTEX; GUIDANCE; BRAIN AB The A-class of the erythropoietin-producing hepatocellular carcinoma cell-derived (EphA) tyrosine kinase receptors and their ligands, the A-ephrins, play critical roles in the specification of topographic axon projection maps during development. In this study, the role of the EphA subfamily in callosal projections was investigated using transgenic mice expressing a kinase deletion mutant of EphA5. In approximately half of these transgenic mice, cerebral cortical neurons in various cortical regions (primary and secondary somatosensory cortices and frontal as well as visual areas) failed to project to the contralateral cortex. When commissural axons were examined with DiI labeling, few callosal fibers were found to traverse the midline in both the adult and neonatal transgenic mice. This defect in callosal development correlates with the expression of the transgene, because neurons in the superficial layers of the motor cortex, where transgene expression is low, show normal contralateral projection through the corpus callosum. In addition, multiple EphA receptors are expressed in callosal neurons and ephrin-A5 stimulates neurite outgrowth of callosal neurons in vitro. The midline glia structures important for callosal axon midline crossing appear normal in the transgenic mice, suggesting that the defects are unrelated to defective guidance structures at the midline. These observations suggest critical functions for EphA receptor in establishing callosal connections during brain development. C1 Rutgers State Univ, Coll Pharm, Canc Res Lab, Piscataway, NJ 08854 USA. Rutgers State Univ, Coll Pharm, Dept Pharmacol, Piscataway, NJ 08854 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Zhou, RP (reprint author), Rutgers State Univ, Coll Pharm, Canc Res Lab, Piscataway, NJ 08854 USA. NR 43 TC 28 Z9 29 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 NOV 26 PY 2003 VL 23 IS 34 BP 10963 EP 10970 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 749DC UT WOS:000186902500027 PM 14645492 ER PT J AU Paulson, EK Morcombe, CR Gaponenko, V Dancheck, B Byrd, RA Zilm, KW AF Paulson, EK Morcombe, CR Gaponenko, V Dancheck, B Byrd, RA Zilm, KW TI High-sensitivity observation of dipolar exchange and NOEs between exchangeable protons in proteins by 3D solid-state NMR spectroscopy SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SHIFT CORRELATION SPECTROSCOPY; ROTATING SOLIDS; ASSIGNMENT; POLYPEPTIDES; BACKBONE; SPECTRA; C-13; H-1 C1 Yale Univ, Dept Chem, New Haven, CT 06520 USA. NCI, Struct Biophys Lab, Frederick, MD 21702 USA. RP Zilm, KW (reprint author), Yale Univ, Dept Chem, POB 208107, New Haven, CT 06520 USA. RI Paulson, Eric/I-1816-2012; Byrd, R. Andrew/F-8042-2015 OI Byrd, R. Andrew/0000-0003-3625-4232 NR 19 TC 58 Z9 59 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 26 PY 2003 VL 125 IS 47 BP 14222 EP 14223 DI 10.1021/ja037559u PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 745ZU UT WOS:000186722200006 PM 14624539 ER PT J AU Ghribi, O Prammonjago, P Herman, MM Spaulding, NK Savory, J AF Ghribi, O Prammonjago, P Herman, MM Spaulding, NK Savory, J TI A beta(1-42)-induced JNK and ERK activation in rabbit hippocampus is differentially regulated by lithium but is not involved in the phosphorylation of tau SO MOLECULAR BRAIN RESEARCH LA English DT Article DE A beta; lithium; tau; JNK; EPK; caspase-3 ID GLYCOGEN-SYNTHASE KINASE-3-BETA; N-TERMINAL KINASE; ALZHEIMERS-DISEASE; IN-VITRO; PROTEIN-KINASES; INDUCED NEUROTOXICITY; NEURONS; P38; DEPOSITION; CASCADE AB Administration of Abeta(1-42) into the rabbit brain induces apoptosis and phosphorylation of tau. These Abeta effects correlate with the activation of JNK and ERK, but not of p38. Treatment with 7 mM lithium inhibits apoptosis, modulates JNK and ERK and does not affect the phosphorylation of tau. Our results demonstrate that lithium, at this dose, effectively inhibits the Abeta-induced apoptosis but has no effect on tau phosphorylation, and that MAP kinases are not involved in the phosphorylation of tau. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22908 USA. NIMH, IRP, NIH, Bethesda, MD USA. Univ Virginia, Hlth Sci Ctr, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. RP Ghribi, O (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Pathol, POB 800214, Charlottesville, VA 22908 USA. NR 26 TC 13 Z9 14 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 NOV 26 PY 2003 VL 119 IS 2 BP 201 EP 206 DI 10.1016/j.molbrainres.2003.09.001 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 748FV UT WOS:000186852600009 ER PT J AU Milner, M Patwardhan, V Bansode, A Nevagi, SA Kulkarni, S Kamakaka, R Modak, SP AF Milner, M Patwardhan, V Bansode, A Nevagi, SA Kulkarni, S Kamakaka, R Modak, SP TI Constructing 3D phylogenetic trees SO CURRENT SCIENCE LA English DT Article ID LENS PROTEINS; MOLECULAR EVOLUTION; VERTEBRATE LENS; CRYSTALLIN; BOOTSTRAP; MAMMALS AB Lens crystallins are highly conserved, tissue-specific proteins. Crystallins from eight vertebrates were compared on the basis of their isoelectric points, molecular weights and immuno-crossreactivity against polyclonal antibodies using 3D plots, to estimate 'star' and 'network' Euclidian distances between species. The phylogenetic trees obtained were tested by bootstrap and fixed in the 3D space by multidimensional scaling and a new sequential positioning method. 3D trees using 'network' distances give the best fits. C1 Karnatak Univ, Dept Zool, Dharwad 580003, Karnataka, India. Agharkar Res Inst, Pune 411004, Maharashtra, India. Ahmednagar Coll, Ahmednagar 414001, India. Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44195 USA. NICHHD, Bethesda, MD 20892 USA. Open Vis, Pune 411004, Maharashtra, India. RP Modak, SP (reprint author), Karnatak Univ, Dept Zool, Dharwad 580003, Karnataka, India. NR 35 TC 2 Z9 3 U1 0 U2 2 PU CURRENT SCIENCE ASSN PI BANGALORE PA C V RAMAN AVENUE, PO BOX 8005, BANGALORE 560 080, INDIA SN 0011-3891 J9 CURR SCI INDIA JI Curr. Sci. PD NOV 25 PY 2003 VL 85 IS 10 BP 1471 EP 1478 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 750TF UT WOS:000187013600024 ER PT J AU Jozwiak, K Hernandez, SC Kellar, KJ Wainer, IW AF Jozwiak, K Hernandez, SC Kellar, KJ Wainer, IW TI Enantioselective interactions of dextromethorphan and levomethorphan with the alpha 3 beta 4-nicotinic acetylcholine receptor: comparison of chromatographic and functional data SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Review DE reviews; enantiomer separation; dextromethorphan; levomethorphan; nicotinic acetylcholine receptor ID NONCOMPETITIVE INHIBITORS; NONLINEAR CHROMATOGRAPHY; STATIONARY-PHASE; KETAMINE; BINDING; SUBTYPES; AFFINITY; CELLS AB The enantioselectivity of the interaction of dextromethorphan (DM) and levomethorphan (LM) with an immobilized alpha3beta4 subtype of the nicotinic acetylcholine receptor (nAChR) liquid chromatographic stationary phase has been compared to DM- and LM-induced non-competitive blockade of nicotine-stimulated Rb-86(+) efflux from cells expressing the alpha3beta4-nAChR. The association rate constants (k(on)) and dissociation rate constants (k(off)) for the formation of the DM and LM complexes with the nAChR were determined using non-linear chromatographic techniques and the koff value for DM (1.01 +/- 0.01 s(-1)) was significantly lower than the k(off) for LM (1.55 +/- 0.002 s(-1)) while the k(on) values did not significantly differ (23.66 +/- 0.61 and 18.61 +/- 0.36 muM(-1) s(-1), respectively). In thermodynamic studies using the van't Hoff approach. the enthalpy change (DeltaHdegrees) of the DM-nAChR complex was 330 cal mol(-1) more stable than the LM-nAChR complex, while there was no significant difference in the entropy change (DeltaSdegrees). In the functional in vitro cell-based studies, there was no significant difference in the observed IC50 values for DM (10.1 +/- 1.01 muM) and LM (10.9 +/- 1.08 muM), but the recovery from the DM-induced blockade was slower than the recovery from LM-induced blockade; after 7 min: 38.25 +/- 15.46% recovery from DM blockade, 63.30 +/- 16.08% from LM blockade: after 4 h: 76.20 +/- 4.51% recovery from DM blockade and 93.12 +/- 8.76% from LM blockade. The enantioselective differences in the functional effects are consistent with the chromatographic and thermodynamic data and indicate that this difference is due to increased stability of the DM-nAChR complex. The results suggest that the chromatographic approach can be used to probe the interaction of non-competitive inhibitors (NCIs) with nAChRs and to predict relative duration of functional blockades. (C) 2003 Elsevier B.V. All rights reserved. C1 NIA, Bioanalyt & Drug Discovery Unit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. Med Univ Lublin, Dept Inorgan & Analyt Chem, Lublin, Poland. RP Wainer, IW (reprint author), NIA, Bioanalyt & Drug Discovery Unit, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 20 TC 27 Z9 27 U1 1 U2 6 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 2003 VL 797 IS 1-2 BP 373 EP 379 DI 10.1016/S1570-0232(03)00608-1 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 748CL UT WOS:000186844600025 PM 14630163 ER PT J AU Donati, D Akhyani, N Fogdell-Hahn, A Cermelli, C Cassiani-Ingoni, R Vortmeyer, A Heiss, JD Cogen, P Gaillard, WD Sato, S Theodore, WH Jacobson, S AF Donati, D Akhyani, N Fogdell-Hahn, A Cermelli, C Cassiani-Ingoni, R Vortmeyer, A Heiss, JD Cogen, P Gaillard, WD Sato, S Theodore, WH Jacobson, S TI Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections SO NEUROLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; LYMPHOPROLIFERATIVE DISORDERS; LATENT INFECTION; T-CELLS; HUMAN-HERPESVIRUS-6; VARIANT; VIRUS; ENCEPHALITIS AB Background: Human herpesvirus-6 (HHV-6), a ubiquitous beta-herpesvirus, is the causative agent of roseola infantum and has been associated with a number of neurologic disorders including seizures, encephalitis/meningitis, and multiple sclerosis. Although the role of HHV-6 in human CNS disease remains to be fully defined, a number of studies have suggested that the CNS can be a site for persistent HHV-6 infection. Objective: To characterize the extent and distribution of HHV-6 in human glial cells from surgical brain resections of patients with mesial temporal lobe epilepsy (MTLE). Method: Brain samples from eight patients with MTLE and seven patients with neocortical epilepsy (NE) undergoing surgical resection were quantitatively analyzed for the presence of HHV-6 DNA using a virus-specific real-time PCR assay. HHV-6 expression was also characterized by western blot analysis and in situ immunohistochemistry (IHC). In addition, HHV-6-reactive cells were analyzed for expression of glial fibrillary acidic protein (GFAP) by double immunofluorescence. Results: DNA obtained from four of eight patients with MTLE had significantly elevated levels of HHV-6 as quantified by real-time PCR. HHV-6 was not amplified in any of the seven patients with NE undergoing surgery. The highest levels of HHV-6 were demonstrated in hippocampal sections (up to 23,079 copies/10(6) cells) and subtyped as HHV-6B. Expression of HHV-6 was confirmed by western blot analysis and IHC. HHV-6 was co-localized to GFAP-positive cells that morphologically appeared to be astrocytes. Conclusions: HHV-6B is present in brain specimens from a subset of patients with MTLE and localized to astrocytes in the absence of inflammation. The amplification of HHV-6 from hippocampal and temporal lobe astrocytes of MTLE warrants further investigation into the possible role of HHV-6 in the development of MTLE. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20052 USA. George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Neurosurg, Washington, DC 20052 USA. Azienda Osped Univ Senese, Siena, Italy. Univ Modena & Reggio Emilia, Dipartimento Sci Ingn Microbiol & Biostat, Modena, Italy. RP Jacobson, S (reprint author), NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RI Cermelli, Claudio/L-1501-2016 OI Cermelli, Claudio/0000-0003-3396-0000 FU Intramural NIH HHS [Z99 NS999999] NR 45 TC 88 Z9 94 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 25 PY 2003 VL 61 IS 10 BP 1405 EP 1411 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 746VF UT WOS:000186767800019 PM 14638964 ER PT J AU Houlden, H Lincoln, S Farrer, M Cleland, PG Hardy, J Orrell, RW AF Houlden, H Lincoln, S Farrer, M Cleland, PG Hardy, J Orrell, RW TI Compound heterozygous PANK2 mutations confirm HARP and Hallervorden-Spatz syndromes are allelic SO NEUROLOGY LA English DT Article ID PALLIDAL DEGENERATION; RETINITIS-PIGMENTOSA; HYPOPREBETALIPOPROTEINEMIA; NEURODEGENERATION; ACANTHOCYTOSIS; DISEASE; MRI AB The authors describe a patient with hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration ( HARP) who has two compound heterozygote mutations of the PANK2 gene. IVS4-1 G > T segregates with the lipid and erythrocyte changes in the mother and sister. No other family members have the lipid, erythrocyte, or clinical abnormalities. The father and two brothers are heterozygous for Met327Thr. One other mutation has been found in this PANK2 region associated with the HARP phenotype, suggesting a local genotype effect. C1 UCL, Royal Free & Univ Coll Med Sch, Dept Clin Neurosci, London NW3 2PF, England. NIH, Dept Neurosci, Bethesda, MD 20892 USA. Newcastle Gen Hosp, Dept Neurol, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Mayo Clin Jacksonville, Dept Neurosci, Jacksonville, FL 32224 USA. RP Orrell, RW (reprint author), UCL, Royal Free & Univ Coll Med Sch, Dept Clin Neurosci, Royal Free Campus,Rowland Hill St, London NW3 2PF, England. EM r.orrell@rfc.ucl.ac.uk RI Houlden, Henry/C-1532-2008; Hardy, John/C-2451-2009; Orrell, Richard/L-2123-2013 OI Houlden, Henry/0000-0002-2866-7777; NR 10 TC 27 Z9 31 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 25 PY 2003 VL 61 IS 10 BP 1423 EP 1426 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 746VF UT WOS:000186767800024 PM 14638969 ER PT J AU Brenner, DJ Doll, R Goodhead, DT Hall, EJ Land, CE Little, JB Lubin, JH Preston, DL Preston, RJ Puskin, JS Ron, E Sachs, RK Samet, JM Setlow, RB Zaider, M AF Brenner, DJ Doll, R Goodhead, DT Hall, EJ Land, CE Little, JB Lubin, JH Preston, DL Preston, RJ Puskin, JS Ron, E Sachs, RK Samet, JM Setlow, RB Zaider, M TI Cancer risks attributable to low doses of ionizing radiation: Assessing what we really know SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ATOMIC-BOMB SURVIVORS; BREAST-CANCER; ADAPTIVE RESPONSE; 2ND MALIGNANCIES; CHILDHOOD-CANCER; X-RAYS; MORTALITY; EXPOSURE; CELLS; RATES AB High doses of ionizing radiation clearly produce deleterious consequences in humans, including, but not exclusively, cancer induction. At very low radiation doses the situation is much less clear, but the risks of low-dose radiation are of societal importance in relation to issues as varied as screening tests for cancer, the future of nuclear power, occupational radiation exposure, frequent-flyer risks, manned space exploration, and radiological terrorism. We review the difficulties involved in quantifying the risks of low-dose radiation and address two specific questions. First, what is the lowest dose of x- or gamma-radiation for which good evidence exists of increased cancer risks in humans? The epidemiological data suggest that it is approximate to10-50 mSv for an acute exposure and approximate to50-100 mSv for a protracted exposure. Second, what is the most appropriate way to extrapolate such cancer risk estimates to still lower doses? Given that it is supported by experimentally grounded, quantifiable, biophysical arguments, a linear extrapolation of cancer risks from intermediate to very low doses currently appears to be the most appropriate methodology. This linearity assumption is not necessarily the most conservative approach, and it is likely that it will result in an underestimate of some radiation-induced cancer risks and an overestimate of others. C1 Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA. Radcliffe Infirm, Clin Trial Serv Unit, Oxford OX2 6ME, England. MRC, Radiat & Genome Stabil Unit, Didcot OX11 0RD, Oxon, England. NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Radiobiol Lab, Boston, MA 02115 USA. NCI, Biostat Branch, Bethesda, MD 20892 USA. Radiat Effects Res Fdn, Hiroshima 7320815, Japan. US EPA, Div Environm Carcinogenesis, Res Triangle Pk, NC 27711 USA. US EPA, Off Radiat & Indoor Air, Washington, DC 20460 USA. Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. RP Brenner, DJ (reprint author), Columbia Univ, Ctr Radiol Res, 630 W 168th St, New York, NY 10032 USA. OI Zaider, Marco/0000-0002-5113-7862 NR 64 TC 770 Z9 804 U1 14 U2 73 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 25 PY 2003 VL 100 IS 24 BP 13761 EP 13766 DI 10.1073/pnas.2235592100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747KN UT WOS:000186803800007 PM 14610281 ER PT J AU Chattopadhyay, MK Tabor, CW Tabor, H AF Chattopadhyay, MK Tabor, CW Tabor, H TI Spermidine but not spermine is essential for hypusine biosynthesis and growth in Saccharomyces cerevisiae: Spermine is converted to spermidine in vivo by the FMS1-amine oxidase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE eIF5A; polyamine; polyamine oxidase ID INITIATION-FACTOR 5A; EUKARYOTIC CELL-PROLIFERATION; HUMAN POLYAMINE OXIDASE; DEOXYHYPUSINE SYNTHASE; PROTEIN-SYNTHESIS; AMINO-ACID; YEAST; GENE; IDENTIFICATION; VIABILITY AB In our earlier work we showed that either spermidine or spermine could support the growth of spe2Delta or spe3Delta polyamine-requiring mutants, but it was unclear whether the cells had a specific requirement for either of these amines. In the current work, we demonstrate that spermidine is specifically required for the growth of Saccharomyces cerevisiae. We were able to show this specificity by using a spe3Delta fms1Delta mutant that lacked both spermidine synthase and the FMS1-encoded amine oxidase that oxidizes spermine to spermidine. The polyamine requirement for the growth of this double mutant could only be satisfied by spermidine; i.e., spermine was not effective because it cannot be oxidized to spermidine in the absence of the FMS1 gene. We also showed that at least one of the reasons for the absolute requirement for spermidine for growth is the specificity of its function as a necessary substrate for the hypusine modification of eIF5A. Spermine itself cannot be used for the hypusine modification, unless it is oxidized to spermidine by the Fms1 amine oxidase. We have quantified the conversion of spermine in vivo and have shown that this conversion is markedly increased in a strain overexpressing the Fms1 protein. We have also shown this conversion in enzymatic studies by using the purified amine oxidase from yeast. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Tabor, H (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Rm 223, Bethesda, MD 20892 USA. NR 37 TC 52 Z9 53 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 2003 VL 100 IS 24 BP 13869 EP 13874 DI 10.1073/pnas.1835918100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747KN UT WOS:000186803800025 PM 14617780 ER PT J AU Belyantseva, IA Boger, ET Friedman, TB AF Belyantseva, IA Boger, ET Friedman, TB TI Myosin XVa localizes to the tips of inner ear sensory cell stereocilia and is essential for staircase formation of the hair bundle SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID UNCONVENTIONAL MYOSIN; MECHANOELECTRICAL TRANSDUCTION; HEARING-LOSS; ACTIN-FILAMENTS; DEAFNESS DFNB3; ADAPTATION; MUTATIONS; CHANNELS; MOUSE; LINKS AB Mutations of the gene encoding unconventional myosin XVa are associated with sensorineural deafness in humans (DFNB3) and shaker (Myo15(sh2)) mice. in deaf Myo15(sh2/sh2) mice, stereocilia are short, nearly equal in length, and lack myosin XVa immunoreactivity. We previously reported that myosin XVa mRNA and protein are expressed in cochlear hair cells. We now show that in the mouse, rat, and guinea pig, endogenous myosin XVa localizes to the tips of the stereocilia of the cochlear and vestibular hair cells. Myosin XVa localization overlaps with the barbed ends of actin filaments and extends to the apical plasma membrane of the stereocilia. Gene gun-mediated transfection of mouse inner ear sensory epithelia explants shows selective accumulation of myosin XVa-GFP at the tips of stereocilia, confirming the localization of native myosin XVa. Expression in COS7 cells also reveals targeting of myosin XVa-GFP to the dynamic actin region at the tips of filopodia. In a wild-type mouse, during auditory and vestibular hair cell development, myosin XVa appears at the tips of stereocilia at the time when the hair bundle begins to develop its characteristic staircase pattern. We propose that myosin XVa is essential for the graded elongation of stereocilia during their functional maturation. C1 Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA. RP Friedman, TB (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, 5 Res Court, Rockville, MD 20850 USA. NR 41 TC 101 Z9 107 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 2003 VL 100 IS 24 BP 13958 EP 13963 DI 10.1073/pnas.2334417100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747KN UT WOS:000186803800040 PM 14610277 ER PT J AU Dubois, S Shou, WN Haneline, LS Fleischer, S Waldmann, TA Muller, JR AF Dubois, S Shou, WN Haneline, LS Fleischer, S Waldmann, TA Muller, JR TI Distinct pathways involving the FK506-binding proteins 12 and 12.6 underlie IL-2-versus IL-15-mediated proliferation of T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INTERLEUKIN-2 IL-2 RECEPTOR; RETRACTED ARTICLE. SEE; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; CHAIN; MICE; FKBP12; DEATH; SHC; ASSOCIATION AB The molecular basis for the different roles of IL-2 and IL-15 in lymphocyte function has been poorly defined. Searching for differences that underlie the distinct T cell responses to the two cytokines, we observed a marked susceptibility of the IL-15-induced but not of the IL-2-induced proliferation to rapamycin despite a decrease of p70S6 kinase (p70(S6K)) activation by the drug in response to both cytokines. Activated splenic T lymphocytes deficient in the FK506-binding protein (FKBP) 12, a target of rapamycin activity, had reduced proliferation in response to IL-15 but not to IL-2. This decreased proliferation was accompanied by reduced activation of p70S6K and of the extracellular signal-regulated kinases (ERK) after IL-15 treatment. In contrast to FKBP12(-/-) cells, splenic FKBP12.6(-/-) T cells exhibited a decreased proliferative response to IL-2 in the presence of rapamycin without affecting p70S6K or ERK activation. Thus, IL-15 induces T cell proliferation mainly via FKBP12-mediated p70(S6K) activation. In contrast, IL-2 signaling involves multiple pathways that include at least one additional pathway that depends on FKBP12.6. C1 NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Dept Pediat, Riley Hosp Children,Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA. Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA. RP NCI, Metab Branch, Canc Res Ctr, NIH, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov NR 34 TC 28 Z9 29 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 2003 VL 100 IS 24 BP 14169 EP 14174 DI 10.1073/pnas.2335979100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747KN UT WOS:000186803800076 PM 14605212 ER PT J AU Bartosch, B Bukh, J Meunier, JC Granier, C Engle, RE Blackwelder, WC Emerson, SU Cosset, FL Purcell, RH AF Bartosch, B Bukh, J Meunier, JC Granier, C Engle, RE Blackwelder, WC Emerson, SU Cosset, FL Purcell, RH TI In vitro assay for neutralizing antibody to hepatitis C virus: Evidence for broadly conserved neutralization epitopes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HYPERVARIABLE REGION 1; HYPERIMMUNE SERUM; ENVELOPE PROTEIN; CELL ENTRY; INFECTION; CHIMPANZEES; GLYCOPROTEINS; TRANSMISSION; PREVENTION; EMERGENCE AB Our understanding of the humoral immune response to hepatitis C virus (HCV) is limited because the virus can be studied only in humans and chimpanzees and because previously described neutralization assays have not been robust or simple to perform. Nevertheless, epidemiologic and laboratory studies suggested that neutralizing Ab to HCV might be important in preventing infection. We have recently described a neutralization assay based on the neutralization of pseudotyped murine retrovirus constructs bearing HCV envelope glycoproteins on their surface. We have applied the assay to well characterized clinical samples from HCV-infected patients and chimpanzees, confirmed the existence of neutralizing Ab to HCV, and validated most previously reported neutralizations of the virus. We did not find neutralizing anti-HCV in resolving infections but did find relatively high titers (>1:320) of such Ab in chronic infections. Neutralizing Ab was directed not only to epitope(s) in the hypervariable region of the E2 envelope protein but also to one or more epitopes elsewhere in the envelope of the virus. Neutralizing Ab was broadly reactive and could neutralize pseudotype particles bearing the envelope glycoproteins of two different subgenotypes (1a and 1b). The ability to assay neutralizing anti-HCV should permit an assessment of the prospects for successful Ab-mediated passive and active immunoprophylaxis against hepatitis C. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Ecole Normale Super Lyon, INSERM U412, Lab Vectorol Retrovirale & Therapie Gen, F-69364 Lyon 07, France. RP Bartosch, B (reprint author), NIAID, Infect Dis Lab, NIH, 50 South Dr,MSC-8009, Bethesda, MD 20892 USA. NR 32 TC 232 Z9 250 U1 2 U2 11 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 25 PY 2003 VL 100 IS 24 BP 14199 EP 14204 DI 10.1073/pnas.2335981100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747KN UT WOS:000186803800081 PM 14617769 ER PT J AU Nishizuka, S Charboneau, L Young, L Major, S Reinhold, WC Waltham, M Kouros-Mehr, H Bussey, KJ Lee, JK Espina, V Munson, PJ Petricoin, E Liotta, LA Weinstein, JN AF Nishizuka, S Charboneau, L Young, L Major, S Reinhold, WC Waltham, M Kouros-Mehr, H Bussey, KJ Lee, JK Espina, V Munson, PJ Petricoin, E Liotta, LA Weinstein, JN TI Proteomic profiling of the NCI-60 cancer cell lines using new high-density reverse-phase lysate microarrays SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTICANCER DRUG SCREEN; MOLECULAR PHARMACOLOGY; MESSENGER-RNA; EXPRESSION DATABASE; PROTEIN MICROARRAYS; GENE; DIFFERENTIATION; FEASIBILITY; PATTERNS; VILLIN AB Because most potential molecular markers and targets are proteins, proteomic profiling is expected to yield more direct answers to functional and pharmacological questions than does transcriptional profiling. To aid in such studies, we have developed a protocol for making reverse-phase protein lysate microarrays with larger numbers of spots than previously feasible. Our first application of these arrays was to profiling of the 60 human cancer cell lines (NCl-60) used by the National Cancer Institute to screen compounds for anticancer activity. Each glass slide microarray included 648 lysate spots representing the NCl-60 cell lines plus controls, each at 10 two-fold serial dilutions to provide a wide dynamic range. Mouse monoclonal antibodies and the catalyzed signal amplification system were used for immunoquantitation. The signal levels from the >30,000 data points for our first 52 antibodies were analyzed by using P-SCAN and a quantitative dose interpolation method. Clustered image maps revealed biologically interpretable patterns of protein expression. Among the principal early findings from these arrays were two promising pathological markers for distinguishing colon from ovarian adenocarcinomas. When we compared the patterns of protein expression with those we had obtained for the same genes at the mRNA level by using both cDNA and oligonucleoticle arrays, a striking regularity appeared: cell-structure-related proteins almost invariably showed a high correlation between mRNA and protein levels across the NCl-60 cell lines, whereas non-cell-structure-related proteins showed poor correlation. C1 NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Virginia, Sch Med, Dept Hlth Evaluat Sci, Charlottesville, VA 22908 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Tissue Proteom Unit, Bethesda, MD 20892 USA. RP Weinstein, JN (reprint author), NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, NIH, Room 5056,Bldg 37,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Waltham, Mark/A-1728-2009; OI Bussey, Kimberly/0000-0003-1001-8207; Espina, Virginia/0000-0001-5080-5972 NR 31 TC 320 Z9 340 U1 4 U2 18 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 25 PY 2003 VL 100 IS 24 BP 14229 EP 14234 DI 10.1073/pnas.2331323100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747KN UT WOS:000186803800086 PM 14623978 ER PT J AU Wong, ML O'Kirwan, F Khan, N Hannestad, J Wu, KH Elashoff, D Lawson, G Gold, PW McCann, SM Licinio, J AF Wong, ML O'Kirwan, F Khan, N Hannestad, J Wu, KH Elashoff, D Lawson, G Gold, PW McCann, SM Licinio, J TI Identification, characterization, and gene expression profiling of endotoxin-induced myocarditis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NITRIC-OXIDE SYNTHASE; INFLAMMATORY RESPONSE SYNDROME; SEPTIC SHOCK; TIME-COURSE; VENTRICULAR DYSFUNCTION; SYSTEMIC INFLAMMATION; CARDIAC DYSFUNCTION; IN-VIVO; INJURY; RATS AB In septic shock, reversible cardiac dysfunction starts within 24 h. Myocardial depressant factors are thought to cause myocyte dysfunction, resulting in alterations of intrinsic cardiac function. Nitric oxide is a myocardial depressant factor candidate. Here we identify endotoxin-induced myocarditis (EIM) a previously uncharacterized pathophysiological entity. Features of EIM include differential patterns of inducible NO synthase (NOS2) mRNA induction in the left (LV) and right (RV) ventricles during the systemic response inflammatory syndrome (SIRS) and the presence of myocarditis with focal areas of aseptic necrosis in the RV 24 h after SIRS induction. Even though clinical data lead to the presumption of myocardial injury in sepsis, the underlying pathophysiological mechanisms have not been previously elucidated. Gene expression profiling was used to test the hypothesis of differential LV and RV responses in EIM, and revealed novel patterns of qualitative and quantitative expansion of transcription. Those genes are novel targets for drug development in SIRS and sepsis. Our results demonstrate spatial and temporal heterogeneity of myocardial responses in EIM. These findings justify the design of treatments to ameliorate tissue injury in the RV. Because the complexity of the inflammatory response increases substantially as time elapses, we suggest a stepwise and multitarget therapeutic approach for SIRS and sepsis. Our findings can help identify innate immune pathways that could become targets for immunotherapy in the treatment of disease caused by potential bioterrorism agents. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci,Conda Ctr 3357B, Ctr Pharmacogenom,Neuropsychiat Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Biostat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Lab Anim Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Endocrinol Diabet & Hypertens, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Gen Clin Res Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. NIMH, Clin Neuroendocrinol Branch, Intramural Res Program, Bethesda, MD 20892 USA. Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. RP Wong, ML (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci,Conda Ctr 3357B, Ctr Pharmacogenom,Neuropsychiat Inst, 695 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM mali@ucla.edu; mali@ucla.edu RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 FU NCRR NIH HHS [K12 RR017611, K24 RR016996, K24 RR017365, M01 RR000865, RR00865, RR016996, RR017365, RR017611]; NHGRI NIH HHS [HG002500, R03 HG002500]; NHLBI NIH HHS [HL004526, K30 HL004526]; NIDDK NIH HHS [DK058851, DK063240, R01 DK058851, R01 DK063240]; NIGMS NIH HHS [GM061394, U01 GM061394]; NIMH NIH HHS [MH062777] NR 39 TC 19 Z9 19 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 25 PY 2003 VL 100 IS 24 BP 14241 EP 14246 DI 10.1073/pnas.2336220100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747KN UT WOS:000186803800088 PM 14623955 ER PT J AU Srivastava, M Montagna, C Leighton, X Glasman, M Naga, S Eidelman, O Ried, T Pollard, HB AF Srivastava, M Montagna, C Leighton, X Glasman, M Naga, S Eidelman, O Ried, T Pollard, HB TI Haploinsufficiency of Anx7 tumor suppressor gene and consequent genomic instability promotes tumorigenesis in the Anx7(+/-) mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hepatocellular carcinoma; lymphosarcoma of the thymus; SKY analysis; cDNA microarray ID ANNEXIN-VII SYNEXIN; PROSTATE-CANCER; TRANSGENIC MICE; HEPATOCELLULAR-CARCINOMA; DICTYOSTELIUM-DISCOIDEUM; HAPLO-INSUFFICIENT; MUTATION; EXPRESSION; GROWTH; MUTANT AB Annexin 7 (ANX7) acts as a tumor suppressor gene in prostate cancer, where loss of heterozygosity and reduction of ANX7 protein expression is associated with aggressive metastatic tumors. To investigate the mechanism by which this gene controls tumor development, we have developed an Anx7(+/-) knockout mouse. As hypothesized, the Anx7(+/-) mouse has a cancer-prone phenotype. The emerging tumors express low levels of Anx7 protein. Nonetheless, the wild-type Anx7 allele is detectable in laser-capture microdissection-derived tumor tissue cells. Genome array analysis of hepatocellular carcinoma tissue indicates that the Anx7(+/-) genotype is accompanied by profound reductions of expression of several other tumor suppressor genes, DNA repair genes, and apoptosis-related genes. In situ analysis by tissue imprinting from chromosomes in the primary tumor and spectral karyotyping analysis of derived cell lines identify chromosomal instability and clonal chromosomal aberrations. Furthermore, whereas 23% of the mutant mice develop spontaneous neoplasms, all mice exhibit growth anomalies, including gender-specific gigantism and organomegaly. We conclude that haploinsufficiency of Anx7 expression appears to drive disease progression to cancer because of genomic instability through a discrete signaling pathway involving other tumor suppressor genes, DNA-repair genes, and apoptosis-related genes. C1 Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Sch Med, Inst Mol Med, Bethesda, MD 20814 USA. NCI, Ctr Canc Res, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Pollard, HB (reprint author), Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. NR 45 TC 54 Z9 62 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 25 PY 2003 VL 100 IS 24 BP 14287 EP 14292 DI 10.1073/pnas.2235927100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747KN UT WOS:000186803800096 PM 14608035 ER PT J AU Foerster, K Groner, F Matthes, J Koch, WJ Birnbaumer, L Herzig, S AF Foerster, K Groner, F Matthes, J Koch, WJ Birnbaumer, L Herzig, S TI Cardioprotection specific for the G protein G(i2) in chronic adrenergic signaling through beta(2)-adrenoceptors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE L-type calcium channel; single channel recording; mouse genetics; survival curve; pertussis toxin ID HEART-FAILURE; TRANSGENIC MICE; IN-VIVO; CARDIAC MYOCYTES; RECEPTOR OVEREXPRESSION; VENTRICULAR MYOCYTES; CALCIUM CHANNELS; MOUSE HEARTS; CA2+ CURRENT; INACTIVATION AB Two subtypes of beta-adrenoceptors, beta(1) and beta(2), mediate cardiac catecholamine effects. These two types differ qualitatively, e.g., regarding G protein coupling and calcium channel stimulation. Transgenic mice overexpressing human beta(2)-adrenoceptors survive high-expression levels, unlike mice overexpressing beta(1)-adrenoceptors. We examined the role of inhibitory G(i) proteins, known to be activated by beta(2)- but not beta(1)-adrenoceptors, on the chronic effects of human beta(2)-adrenoreceptor overexpression in transgenic mice. These mice were crossbred with mice where Galpha(i2), a functionally important cardiac G(i) alpha-subunit, was inactivated by targeted gene deletion. Survival of beta(2)-adrenoreceptor transgenic mice was reduced by heterozygous inactivation of Galpha(i2). Homozygous knockout/beta(2)-adrenoreceptor transgenic mice died within 4 days after birth. Heterozygous knockout/beta(2)-adrenoreceptor transgenic mice developed more pronounced cardiac hypertrophy and earlier heart failure compared with beta(2)-adrenoreceptor transgenic mice. Single calcium-channel activity was strongly suppressed in heterozygous knockout/beta(2)-adrenoreceptor transgenic mice. In cardiomyocytes from these mice, pertussis toxin treatment in vitro fully restored channel activity and enhanced channel activity in cells from homozygous Galpha(i2) knockout animals. Cardiac Galpha(i3) protein was increased in all Galpha(i2) knockout mouse strains. Our results demonstrate that Galpha(i2) takes an essential protective part in chronic signaling of overexpressed beta(2)-adrenoceptors, leading to prolonged survival and delayed cardiac pathology. However, reduction of calcium-channel activity by beta(2)-adrenoreceptor overexpression is due to a different pertussis-toxin-sensitive pathway, most likely by Galpha(i3). This result indicates that subtype-specific signaling of beta(2)-adrenoreceptor functionally bifurcates at the level of G(i), leading to different effects depending on the Galpha isoform. C1 Univ Cologne, Dept Pharmacol, D-50931 Cologne, Germany. Duke Univ, Med Ctr, Durham, NC 27710 USA. RP Birnbaumer, L (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, 111 T W Alexander Dr, Res Triangle Pk, NC 27709 USA. FU NIDDK NIH HHS [DK-19318] NR 42 TC 44 Z9 46 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 2003 VL 100 IS 24 BP 14475 EP 14480 DI 10.1073/pnas.1936026100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 747KN UT WOS:000186803800128 PM 14612574 ER PT J AU Schindler, CW Gilman, JP Graczyk, Z Wang, GF Gee, WL AF Schindler, CW Gilman, JP Graczyk, Z Wang, GF Gee, WL TI Reduced cardiovascular effects of methamphetamine following treatment with selegiline SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE methamphetamine; selegiline; cardiovascular; monkeys; pharmacotherapy; cocaine ID MONOAMINE-OXIDASE; SQUIRREL-MONKEYS; PHARMACOLOGICAL MECHANISMS; DOPAMINE METABOLISM; MAO-B; COCAINE; BRAIN; ADDICTION; TOXICITY; AGONISTS AB Selegiline is a specific MAO-B inhibitor. As MAO-B has been shown to be significantly involved in the metabolism of dopamine in certain regions of the primate brain, selegiline has been proposed for use in the treatment of drug addiction. Selegiline is also metabolized in vivo to I-methamphetamine. Therefore, when given in combination with psychostimulants such as d-methamphetamine, there is the potential for adverse effects. To study this possibility, squirrel monkeys were treated with chronic selegiline and tested with two doses of d-methamphetamine (0.1 and 1.0 mg/kg, i.v.). Following at least 7 days of treatment with once daily 0.3 mg/kg i.m. selegiline, the effects of methamphetamine on blood pressure and heart rate were no different than the effects of methamphetamine observed prior to selegiline treatment. However, following at least 10 days of treatment with 1.0 mg/kg i.m. selegiline, the effects of methamphetamine on blood pressure and heart rate were significantly reduced. Both methamphetamine and amphetamine were detected in plasma following chronic selegiline treatment. When monkeys were given an acute selegiline injection prior to methamphetamine, reduced cardiovascular effects were also seen. These results indicate that selegiline can be used safely even in combination with methamphetamine, as the cardiovascular effects of the drug combination were no greater than either drug alone, and were actually reduced at the higher selegiline dose. Published by Elsevier Ireland Ltd. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, DHHS,Intramural Res Program,NIH, Baltimore, MD 21224 USA. Univ Calif San Francisco, Sch Pharm, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. RP Schindler, CW (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, DHHS,Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 26 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD NOV 24 PY 2003 VL 72 IS 2 BP 133 EP 139 DI 10.1016/S0376-8716(03)00197-2 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 752XQ UT WOS:000187201800004 PM 14636968 ER PT J AU List, K Szabo, R Wertz, PW Segre, J Haudenschild, CC Kim, SY Bugge, TH AF List, K Szabo, R Wertz, PW Segre, J Haudenschild, CC Kim, SY Bugge, TH TI Loss of proteolytically processed filaggrin caused by epidermal deletion of matriptase/MT-SP1 SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CORNIFIED CELL ENVELOPES; HUMAN STRATUM-CORNEUM; SKIN BARRIER FUNCTION; SERINE-PROTEASE; ICHTHYOSIS VULGARIS; HARLEQUIN ICHTHYOSIS; PERMEABILITY BARRIER; STRUCTURAL PROTEINS; LAMELLAR GRANULES; IDENTIFICATION AB Profilaggrin is a large epidermal polyprotein that is proteolytically processed during keratinocyte differentiation to release multiple filaggrin monomer units as well as a calcium-binding regulatory NH2-terminal filaggrin S-100 protein. We show that epidermal deficiency of the transmembrane serine protease Matriptase/MT-SP1 perturbs lipid matrix formation, cornified envelope morphogenesis, and stratum corneum desquamation. Surprisingly, proteomic analysis of Matriptase/MT-SP1 -deficient epidermis revealed the selective loss of both proteolytically processed filaggrin monomer units and the NH2-terminal filaggrin S-100 regulatory protein. This was associated with a profound accumulation of profilaggrin and aberrant profilaggrin-processing products in the stratum corneum. The data identify keratinocyte Matriptase/MT-SP1 as an essential component of the profilaggrin-processing pathway and a key regulator of terminal epidermal differentiation. C1 Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Iowa, Coll Dent, Dows Inst, Iowa City, IA 52242 USA. Amer Red Cross, Dept Expt Pathol, Rockville, MD 20855 USA. Cornell Univ, Weill Med Coll, Dept Neurosci, White Plains, NY 10605 USA. Burke Med Res Inst, White Plains, NY 10605 USA. Finsen Lab, DK-2100 Copenhagen, Denmark. RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Room 211, Bethesda, MD 20892 USA. NR 56 TC 136 Z9 137 U1 0 U2 1 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 24 PY 2003 VL 163 IS 4 BP 901 EP 910 DI 10.1083/jcb.200304161 PG 10 WC Cell Biology SC Cell Biology GA 748EP UT WOS:000186849800022 PM 14638864 ER PT J AU Wallqvist, A Rabow, AA Shoemaker, RH Sausville, EA Covell, DG AF Wallqvist, A Rabow, AA Shoemaker, RH Sausville, EA Covell, DG TI Linking the growth inhibition response from the National Cancer Institute's anticancer screen to gene expression levels and other molecular target data SO BIOINFORMATICS LA English DT Article ID TRANSMEMBRANE CARBONIC-ANHYDRASES; RENAL-CELL CARCINOMA; DRUG SCREEN; DOWN-REGULATION; IN-VITRO; BETA-ADRENOCEPTOR; THYMOSIN BETA-4; CYCLIN-E; LINES; PROTEIN AB Motivation: Data mining tools are proposed to establish mechanistic connections between chemotypes and specific cellular functions. Drawing on a previous study that classified the cellular response patterns of growth inhibition measurements log(GI(50)) from the National Cancer Institute's (NCI's) anticancer screen, we have examined additional data for mRNA expression, sets of known molecular targets and mutational status against these same tumor cell lines to relate chemosensitivity more precisely to biochemical pathways. Results: Our analysis finds that gene expression levels do not, in general, correlate with log(GI(50)) measurements, instead they reflect a generic toxic condition. Within the remaining set of non-generic conditions, examples were found where a correlation suggesting a biochemical basis for cellular cytotoxicity could be supported. These included reconfirmation of previously observed associations between mutant and wild-type status of p53, and chemosensitivity to alkylating agents, while extending these results to reveal associations with gamma-induced expressions of MDM2, WAF1 and GADD45, signals that were not apparent in measurements of basal mRNA expression levels for any of these genes, Additional examinations revealed that mRNA expression levels directly correlated with paclitaxel chemosensitivity to mitosis, while also identifying additional chemotypes as P-glycoprotein substrates. Our analysis revealed well-known direct associations between p16 mutant status and chemotypes implicated in cell cycle control, and extended these results to include expression levels for three additional tyrosine kinase proteins (TEK, transgelin and hCdc4). Links were also found that suggested associations between chemosensitivity and the endocrine, paracrine ligand-receptor loops, via expression of the adrenergic receptor, calcium second messenger pathways via expression levels of carbonic anhydrase and cellular communication pathways via fibrillin. C1 Sci Applicat Int Corp, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Frederick, MD 21702 USA. RP Wallqvist, A (reprint author), Sci Applicat Int Corp, Frederick, MD 21702 USA. OI wallqvist, anders/0000-0002-9775-7469 FU NCI NIH HHS [N01-CO-56000] NR 65 TC 20 Z9 22 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 22 PY 2003 VL 19 IS 17 BP 2212 EP 2224 DI 10.1093/bioinformatics/btg302 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 749KN UT WOS:000186919200007 PM 14630650 ER PT J AU Miyamoto, T Hasuike, S Yogev, L Maduro, MR Ishikawa, M Westphal, H Lamb, DJ AF Miyamoto, T Hasuike, S Yogev, L Maduro, MR Ishikawa, M Westphal, H Lamb, DJ TI Azoospermia in patients heterozygous for a mutation in SYCP3 SO LANCET LA English DT Article ID SYNAPTONEMAL COMPLEX; PROTEIN SCP3; GENE; CHROMOSOMES; REGION AB Background Many cases of male infertility are diagnosed as idiopathic, reflecting poor understanding of the molecular defects underlying the abnormality. As more gene mutations causing male infertility in mice become known, there are improving prospects that knowledge about the genetic aetiology of human male infertility can be expanded. Sycp3 encodes a component of the synaptonemal complex. A null mutation of Sycp3 in mice causes azoospermia with meiotic arrest. We tested the hypothesis that mutation of the human testis-specific SYCP3 is associated with human nonobstructive azoospermia. Methods Human SYCP3 was isolated on the basis of homology between mouse Sycp3 cDNA and human genome sequences at the aminoacid level. Tissue-specific expression of SYCP3 was analysed by PCR of human cDNA. Samples of DNA from 19 azoospermic patients with maturation arrest and 75 normal fertile control men were screened for mutations in the SYCP3 gene by sequence analysis of the gene. The functional significance of the mutations found was analysed by a protein interaction study of the wild-type and truncated SYCP3 proteins. Findings We identified in two patients a 1 bp deletion (643delA) that results in a premature stop codon and truncation of the C-terminal, coiled-coil-forming region of the SYCP3 protein. The mutant protein showed greatly reduced interaction with the wild-type protein in vitro and interfered with SYCP3 fibre formation in cultured cells. Interpretation We suggest that SYCP3 has an essential meiotic function in human spermatogenesis that is compromised by the mutant protein via dominant negative interference. C1 Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Asahikawa Med Coll, Dept Obstet & Gynecol, Asahikawa, Hokkaido 078, Japan. Lis Matern Hosp, Tel Aviv Sourasky Med Ctr, Inst Study Fertil, Tel Aviv, Israel. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Lamb, DJ (reprint author), Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. FU NICHD NIH HHS [P01HD36289] NR 16 TC 115 Z9 136 U1 0 U2 4 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 22 PY 2003 VL 362 IS 9397 BP 1714 EP 1719 DI 10.1016/S0140-6736(03)14845-3 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 746VE UT WOS:000186767700010 PM 14643120 ER PT J AU Miller, FW Rider, LG Plotz, PH Isenberg, DA Oddis, CV AF Miller, FW Rider, LG Plotz, PH Isenberg, DA Oddis, CV TI Diagnostic criteria for polymyositis and dermatomyositis SO LANCET LA English DT Letter C1 NIEHS, Off Clin Res, Bethesda, MD 20892 USA. NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. UCL, London, England. Univ Pittsburgh, Sch Med, Div Rheumatol & Clin Immunol, Pittsburgh, PA USA. RP Miller, FW (reprint author), NIEHS, Off Clin Res, 9000 Rockville Pike,MSC 0958, Bethesda, MD 20892 USA. EM millerf@mail.nih.gov OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 3 TC 23 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD NOV 22 PY 2003 VL 362 IS 9397 BP 1762 EP 1763 DI 10.1016/S0140-6736(03)14862-3 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 746VE UT WOS:000186767700031 PM 14643132 ER PT J AU Dalakas, MC Hohlfeld, R AF Dalakas, MC Hohlfeld, R TI Diagnostic criteria for polymyositis and dermatomyositis - Reply SO LANCET LA English DT Letter ID INCLUSION-BODY MYOSITIS; MYOPATHIES; EXPRESSION C1 NINDS, Neuromuscular Dis Sect, Bethesda, MD 20892 USA. Univ Munich, Klinikum Grosshadern, Inst Clin Neuroimmunol, D-8000 Munich, Germany. Univ Munich, Klinikum Grosshadern, Max Planck Inst Neurobiol, D-8000 Munich, Germany. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, Bldg 10,Room 4N248, Bethesda, MD 20892 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 22 PY 2003 VL 362 IS 9397 BP 1763 EP 1763 DI 10.1016/S0140-6736(03)14863-5 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 746VE UT WOS:000186767700032 ER PT J AU Brodine, SK Starkey, MJ Shaffer, RA Ito, SI Tasker, SA Barile, AJ Tamminga, CL Stephan, KT Aronson, NE Fraser, SL Wallace, MR Wegner, SA Mascola, JR McCutchan, FE AF Brodine, SK Starkey, MJ Shaffer, RA Ito, SI Tasker, SA Barile, AJ Tamminga, CL Stephan, KT Aronson, NE Fraser, SL Wallace, MR Wegner, SA Mascola, JR McCutchan, FE TI Diverse HIV-1 subtypes and clinical, laboratory and behavioral factors in a recently infected US military cohort SO AIDS LA English DT Article DE HIV-1; HIV-1 subtypes; US military; cross-sectional study; risk factors; seroconversion; epidemiology ID IMMUNODEFICIENCY-VIRUS TYPE-1; NON-B SUBTYPES; GENETIC DIVERSITY; UNITED-STATES; SENTINEL SITE; VIRAL LOAD; RESISTANCE; POLYMORPHISMS; TRANSMISSION; PROGRESSION AB Objective: To describe the demographics, risk behaviors, and HIV-1 subtypes in a large cohort of recently HIV-infected military personnel. Design: Descriptive, cross-sectional study. Methods: US military personnel with recent HIV seroconversion from six medical referral centers were enrolled with a self-administered questionnaire, CD4 cell counts, syphilis and hepatitis B serologies, plasma viral RNA levels, and HIV-1 subtype nucleic acid sequencing. Results: Between February 1997 and May 2000, 520 patients were enrolled. Most [488 (94.3%)] were infected with HIV-1 subtype B. The most prevalent non-B subtype was a circulating recombinant form (CRF01_AE) [17 (61%)]; however, two pure subtypes (C and D), as well as CRF02_AG, CRF09_cpx and a BE recombinant were identified. The likely area of HIV-1 acquisition was the United States for 70% of the volunteers. At least three non-B subtype infections (two subtype C, one subtype CRF01_AE) were apparently acquired domestically. Risk behaviors and comorbid sexually transmitted diseases were reported during the seroconversion period. Volunteers with non-B subtype HIV infection were more likely to report heterosexual contacts [92% vs. 39%; odds ratio (OR), 10.0], including contacts with commercial sex workers (41% vs. 13%; OR, 4.9). The Roche Amplicor version 1.0 assay was less sensitive for non-B subtype infections than the Roche Amplicor version 1.5 assay. Conclusion: There is a high prevalence and diversity of non-B HIV subtypes in this large cohort. Efficient diagnosis of acute primary HIV-1 infection was identified as a goal for prevention programs. Modifiable risk behaviors and target populations for intervention were identified. (C) 2003 Lippincott Williams Wilkins. C1 San Diego State Univ, Coll Hlth & Human Serv, Grad Sch Publ Hlth, Dept Epidemiol & Biostat, San Diego, CA 92182 USA. USN, Hlth Res Ctr, San Diego, CA 92152 USA. Henry M Jackson Fdn Adv Mil Med, Rockville, MD USA. Geocenters Inc, Newton, MA USA. USN, Ctr Med, San Diego, CA 92152 USA. Walter Reed Army Inst Res, Rockville, MD USA. Natl Naval Med Res Inst, Bethesda, MD USA. USN, Med Ctr, Portsmouth, VA USA. Wilford Hall USAF Med Ctr, Lackland AFB, TX 78236 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Brodine, SK (reprint author), San Diego State Univ, Coll Hlth & Human Serv, Grad Sch Publ Hlth, Dept Epidemiol & Biostat, 5500 Campanile Dr, San Diego, CA 92182 USA. NR 30 TC 58 Z9 61 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 21 PY 2003 VL 17 IS 17 BP 2521 EP 2527 DI 10.1097/00002030-200311210-00016 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 809YR UT WOS:000220672500015 PM 14600525 ER PT J AU Cui, XZ Zeni, F Vodovitz, Y Correa-de-Araujo, R Quezado, M Roberts, A Wahl, S Danner, RL Banks, SM Gerstenberger, E Fitz, Y Natanson, C Eichacker, PQ AF Cui, XZ Zeni, F Vodovitz, Y Correa-de-Araujo, R Quezado, M Roberts, A Wahl, S Danner, RL Banks, SM Gerstenberger, E Fitz, Y Natanson, C Eichacker, PQ TI TGF-beta 1 increases microbial clearance but worsens lung injury during Escherichia coli pneumonia in rats SO CYTOKINE LA English DT Article DE acute lung injury; host defense; leukocyte; pneumonia; TGF-beta 1 ID GROWTH-FACTOR-BETA; TUMOR-NECROSIS-FACTOR; TRANSFORMING GROWTH-FACTOR-BETA-1; NITRIC-OXIDE; TGF-BETA; HUMAN-MONOCYTES; IMPROVES SURVIVAL; HUMAN-DISEASE; SEPTIC SHOCK; IFN-GAMMA AB We investigated the effects of either intravenous (IV) or intrabronchial (IB) treatment with transforming growth factor beta1 (TGF-beta1) during bacterial pneumonia in rats. Immediately following IB Escherichia coli inoculation (T0), animals (n = 270) were randomized to receive a single treatment with human recombinant TGF-beta1 either via IV or IB, or via both IV and IB routes, or to receive placebo (human serum albumin, HSA) only. Blood and lung analysis was done at 6 and 168 h after E. coli inoculation. Other animals (n = 40) were administered IV TGF-beta1 or HSA at T0 and 6, 12 and 24 h after E. coli inoculation to investigate the effects of multiple treatments also on survival rates alone. All animals received ceftriaxone daily. Route of administration did not influence TGF-beta1 (p = ns for the effect of TGF-beta1 comparing IV vs IB routes) and we averaged over this variable in analysis. The relative risk of death (mean +/- sem) was not altered by either single treatments administered at T0 (-0.18 +/- 0.25, p = 0.47) or multiple treatments (0.40 +/- 0.50, p = 0.66) of TGF-beta1. Single treatment with TGF-beta1 first decreased and then increased vascular leukocytes at 6 and 168 h, respectively, but increased alveolar leukocytes at both time points (p = 0.02 comparing the differing effects of TGF-beta1 on vascular and alveolar leukocytes at 6 and 168 h). Although TGF-beta1 decreased blood and lung bacteria counts at 6 and 168 h, it also increased serum tumor necrosis factor levels and lung injury scores at these time points (p < 0.05 for the effects of TGF-beta1 on each parameter at 6 and 168 h together). Thus, while increases in lung leukocyte recruitment with TGF-beta1 were associated with improved microbial clearance in this rat model of pneumonia, worsened lung injury may have negated these beneficial host defense effects, and overall survival was not significantly improved. Despite these harmful effects, additional studies may be warranted to better define the influence of exogenous TGF-beta1 on host defense during acute bacterial infections. Published by Elsevier Ltd. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. CHU St Etienne, Hop Bellevue, Serv Reanimat Polyvalente, F-42055 St Etienne 2, France. Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. NCI, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Cranial Res, NIH, Bethesda, MD 20892 USA. RP Cui, XZ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NR 55 TC 11 Z9 11 U1 1 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD NOV 21 PY 2003 VL 24 IS 4 BP 115 EP 127 DI 10.1016/j.cyto.2003.07.003 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 743WU UT WOS:000186597200001 PM 14572790 ER PT J AU Palena, C Arlen, P Zeytin, H Greiner, JW Schlom, J Tsang, KY AF Palena, C Arlen, P Zeytin, H Greiner, JW Schlom, J Tsang, KY TI Enhanced expression of lymphotactin by CD8(+) T cells is selectively induced by enhancer agonist peptides of tumor-associated antigens SO CYTOKINE LA English DT Article DE microarray; T-cell activation; tumor-associated antigens; agonist peptide ID HUMAN CARCINOEMBRYONIC ANTIGEN; DENDRITIC CELLS; PHASE-I; COSTIMULATORY MOLECULE; CHEMOKINE EXPRESSION; LYMPHOCYTE EPITOPE; IMMUNE-RESPONSES; REACTIVE CTL; CEA VACCINE; ACTIVATION AB Human tumor-associated antigens (TAAs) are weak immunogens. One strategy for increasing the immunogenicity of TAAs is to generate altered peptide ligands. In the studies reported here, microarray technology has been used to compare gene expression profiles of a human T cell line that was derived from the peripheral blood of a cancer patient vaccinated with a carcinoembryonic antigen (CEA)-based vaccine. We compared the gene expression profiles of this CEA-specific CD8 T cell line when (a) stimulated with the native peptide used to derive this line vs. no peptide, and (b) stimulated with its TCR enhancer agonist epitope vs. no peptide. The results demonstrate that the effect on the T cell line, when stimulated with the agonist peptide, is not an enhanced quantitative expression of the same genes or gene sets induced by the native peptide, but is rather a nearly reciprocal upregulation of different gene sets. The gene for the chemokine lymphotactin, which was overexpressed only in T cells stimulated with the agonist peptide, stood out above all others. This finding was extended using other T cell lines, and another set of agonist and native peptides from another TAA. ELISPOT and ELISA assays for lymphotactin confirmed and extended these findings. These studies suggest a potential role for lymphotactin in the T-cell activation processes and subsequent anti-tumor events. Published by Elsevier Ltd. C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. NR 34 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD NOV 21 PY 2003 VL 24 IS 4 BP 128 EP 142 DI 10.1016/j.cyto.2003.07.004 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 743WU UT WOS:000186597200002 PM 14572791 ER PT J AU McDonald, JP Woodgate, R AF McDonald, JP Woodgate, R TI Untitled SO DNA REPAIR LA English DT Letter C1 NICHHD, Lab Genom Integ, NIH, Bethesda, MD 20892 USA. RP Woodgate, R (reprint author), NICHHD, Lab Genom Integ, NIH, Bldg 6,Room 1A13 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD NOV 21 PY 2003 VL 2 IS 11 BP 1159 EP 1160 DI 10.1016/j.dnarep.2003.08.003 PG 2 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 743QJ UT WOS:000186584800001 ER PT J AU Yu, J Leibiger, B Yang, SN Caffery, JJ Shears, SB Leibiger, IB Barker, CJ Berggren, PO AF Yu, J Leibiger, B Yang, SN Caffery, JJ Shears, SB Leibiger, IB Barker, CJ Berggren, PO TI Cytosolic multiple inositol polyphosphate phosphatase in the regulation of cytoplasmic free Ca2+ concentration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PANCREATIC BETA-CELLS; ENDOPLASMIC-RETICULUM; TRISPHOSPHATE RECEPTOR; RYANODINE RECEPTOR; CALCIUM-CHANNEL; ACTIVATION; 1,4,5-TRISPHOSPHATE; 5-PHOSPHATASE; INHIBITION; RELEASE AB Multiple inositol polyphosphate phosphatase (MIPP) is an enzyme that, in vitro, has the interesting property of degrading higher inositol polyphosphates to the Ca2+ second messenger, inositol 1,4,5-trisphosphate (Ins(1,4,5)P-3), independently of inositol lipid breakdown. We hypothesized that a truncated cytosolic form of the largely endoplasmic reticulum-confined MIPP (cyt-MIPP) could represent an important new tool in the investigation of Ins( 1,4,5)P-3-dependent intracellular Ca2+ homeostasis. To optimize our ability to judge the impact of cyt-MIPP on intracellular Ca2+ concentration ([Ca2+](i)) we chose a poorly responsive beta-cell line (HIT M2.2.2) with an abnormally low [Ca2+](i). Our results show for the first time in an intact mammalian cell that cyt-MIPP expression leads to a significant enhancement of Ins(1,4,5)P-3 concentration. This is achieved without a significant interference from other cyt-MIPP-derived inositol phosphates. Furthermore, the low basal [Ca2+](i) of these cells was raised to normal levels (35 to 115 nM) when they expressed cyt-MIPP. Noteworthy is that the normal feeble glucose-induced Ca2+ response of HIT M2.2.2 cells was enhanced dramatically by mechanisms related to this increase in basal [Ca2+](i). These data support the use of cyt-MIPP as an important tool in investigating Ins(1,4,5)P-3-dependent Ca2+ homeostasis and suggest a close link between Ins(1,4,5)P-3 concentration and basal [Ca2+](i), the latter being an important modulator of Ca2+ signaling in the pancreatic beta-cell. C1 Karolinska Hosp, Karolinska Inst, Rolf Luft Ctr Diabet Res, Dept Mol Med, SE-17176 Stockholm, Sweden. NIEHS, Inositide Signaling Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Barker, CJ (reprint author), Karolinska Hosp, Karolinska Inst, Rolf Luft Ctr Diabet Res, Dept Mol Med, L3, SE-17176 Stockholm, Sweden. EM chris.barker@molmed.ki.se FU NIDDK NIH HHS [DK 58508] NR 44 TC 20 Z9 20 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 21 PY 2003 VL 278 IS 47 BP 46210 EP 46218 DI 10.1074/jbc.M303743200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743JV UT WOS:000186569400004 PM 12963730 ER PT J AU He, ML Gonzales-Iglesias, AE Stojilkovic, SS AF He, ML Gonzales-Iglesias, AE Stojilkovic, SS TI Role of nucleotide P2 receptors in calcium signaling and prolactin release in pituitary lactotrophs SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTRACELLULAR CALCIUM; ATP RECEPTORS; EXTRACELLULAR NUCLEOTIDES; PRIMARY CULTURES; PLASMA-MEMBRANE; CELLS; CHANNELS; ACTIVATION; DESENSITIZATION; MOBILIZATION AB Anterior pituitary cells express nucleotide-gated G protein-coupled P2 receptors (P2YRs) and cation-conducting channels (P2XRs). However, the identification of P2 receptors subtypes and their native ligands, and the distribution and function of these receptors within the secretory and non-secretory pituitary cells has been incompletely characterized. The focus in this study was on lactotroph subpopulation of cells. ATP and ADP, but not UTP and UDP, triggered calcium signaling in a majority (85%) of lactotrophs and prolactin release in mixed pituitary cells. Consistent with the role of P2 receptors in signaling and secretion, the actions of ATP and ADP were abolished in the presence of apyrase, an ectonucleotidase. Transcripts for G(q)-coupled calcium-mobilizing P2Y(1)R, P2Y(2)R, P2Y(4)R, and P2Y(6)R, as well as G(i)-coupled P2Y(12)R, were identified in mixed anterior pituitary cells. The ligand-selectivity profile of calcium mobilization-dependent signaling and prolactin secretion and the blockade of these responses by pyridoxal 5-phosphate 6-azophenyl-2', 4'-disulphonic acid indicated that P2Y(1)R mediates the stimulatory action of ATP and ADP. Within the channels expressed in anterior pituitary (P2X(2)R, P2X(3)R, P2X(4)R, and P2X(7)R), the P2X(4)R subtype provides a major pathway for calcium influx-dependent signaling and prolactin secretion. This conclusion was based on comparison of native to recombinant channels with respect to their ligand preference, sensitivity to pyridoxal 5-phosphate 6-azophenyl-2', 4'-disulphonic acid, and the rates of calcium signal desensitization. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHD, Sect Cellular Signaling, ERRB, NIH, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. NR 36 TC 24 Z9 24 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 21 PY 2003 VL 278 IS 47 BP 46270 EP 46277 DI 10.1074/jbc.M309005200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743JV UT WOS:000186569400010 PM 12970352 ER PT J AU Suzuki, N Khoo, KH Chen, CM Chen, HC Lee, YC AF Suzuki, N Khoo, KH Chen, CM Chen, HC Lee, YC TI N-glycan structures of pigeon IgG - A major serum glycoprotein containing Gal alpha 1-4Gal termini SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LINKED SUGAR CHAINS; IMMUNOGLOBULIN-G; FERTILIZED-EGGS; JAPANESE-QUAIL; BIOSYNTHETIC-PATHWAY; MAPPING TECHNIQUE; ESCHERICHIA-COLI; FANCIERS LUNG; CYST MEMBRANE; VH-GENE AB We had shown previously that all major glycoproteins of pigeon egg white contain Galalpha1-4Gal epitopes (Suzuki, N., Khoo, K.H., Chen, H.C., Johnson, J.R., and Lee, Y.C. (2001) J. Biol. Chem. 276, 23221-23229). We now report that Galalpha1-4Gal-bearing glycoproteins are also present in pigeon serum, lymphocytes, and liver, as probed by Western blot with Griffonia simplicifolia-I lectin (specific for terminal alpha-Gal) and anti-P-1 (specific for Galalpha1-4Galbeta1-4GlcNAcbeta1-) monoclonal antibody. One of the major glycoproteins from pigeon plasma was identified as IgG (also known as IgY), which has Galalpha1-4Gal in its heavy chains. High pressure liquid chromatography, mass spectrometric (MS), and MS/MS analyses revealed that N-glycans of pigeon serum IgG included (i) high mannose-type (33.3%), (ii) disialylated biantennary complex-type (19.2%), and (iii) alpha-galactosylated complex-type N-glycans (47.5%). Bi- and tri-antennary oligosaccharides with bisecting GlcNAc and alpha1-6 Fuc on the Asn-linked GlcNAc were abundant among N-glycans possessing terminal Galalpha1-4Gal sequences. Moreover, MS/MS analysis identified Galalpha1-4Galbeta1-4Galbeta1-4GlcNAc branch terminals, which are not found in pigeon egg white glycoproteins. An additional interesting aspect is that about two-thirds of high mannose-type N-glycans from pigeon IgG were monoglucosylated. Comparison of the N-glycan structures with chicken and quail IgG indicated that the presence of high mannose-type oligosaccharides may be a characteristic of these avian IgG. C1 Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Acad Sinica, Inst Biol Chem, Taipei 115, Taiwan. NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Lee, YC (reprint author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. FU NIDDK NIH HHS [DK 09970] NR 68 TC 35 Z9 36 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 21 PY 2003 VL 278 IS 47 BP 46293 EP 46306 DI 10.1074/jbc.M307132200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743JV UT WOS:000186569400013 PM 12966096 ER PT J AU Nagababu, E Ramasamy, S Abernethy, DR Rifkind, JM AF Nagababu, E Ramasamy, S Abernethy, DR Rifkind, JM TI Active nitric oxide produced in the red cell under hypoxic conditions by deoxyhemoglobin-mediated nitrite reduction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID S-NITROSOHEMOGLOBIN; PHYSIOLOGICAL CONDITIONS; BLOOD-CELLS; BIOCHEMICAL-CHARACTERIZATION; PLASMA NITRITE; HEMOGLOBIN; NO; OXIDATION; MECHANISM; BINDING AB Recent studies have generated a great deal of interest in a possible role for red blood cells in the transport of nitric oxide (NO) to the microcirculation and the vascular effect of this nitric oxide in facilitating the flow of blood through the microcirculation. Many questions have, however, been raised regarding such a mechanism. We have instead identified a completely new mechanism to explain the role of red cells in the delivery of NO to the microcirculation. This new mechanism results in the production of NO in the microcirculation where it is needed. Nitrite produced when NO reacts with oxygen in arterial blood is reutilized in the arterioles when the partial pressure of oxygen decreases and the deoxygenated hemoglobin formed reduces the nitrite regenerating NO. Nitrite reduction by hemoglobin results in a major fraction of the NO generated retained in the intermediate state where NO is bound to Hb(III) and in equilibrium with the nitrosonium cation bound to Hb(II). This pool of NO, unlike Hb(II) NO, is weakly bound and can be released from the heme. The instability of Hb(III) NO in oxygen and its displacement when flushed with argon requires that reliable determinations of red blood cell NO must be performed on freshly lysed samples without permitting the sample to be oxygenated. In fresh blood samples Hb(III) NO accounts for 75% of the red cell NO with appreciably higher values in venous blood than arterial blood. These findings confirm that nitrite reduction at reduced oxygen pressures is a major source for red cell NO. The formation and potential release from the red cell of this NO could have a major impact in regulating the flow of blood through the microcirculation. C1 NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. RP Rifkind, JM (reprint author), NIA, Mol Dynam Sect, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 39 TC 231 Z9 233 U1 1 U2 8 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 21 PY 2003 VL 278 IS 47 BP 46349 EP 46356 DI 10.1074/jbc.M307572200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743JV UT WOS:000186569400018 PM 12952953 ER PT J AU Olivera, A Rosenfeldt, HM Bektas, M Wang, F Ishii, I Chun, J Milstien, S Spiegel, S AF Olivera, A Rosenfeldt, HM Bektas, M Wang, F Ishii, I Chun, J Milstien, S Spiegel, S TI Sphingosine kinase type 1 induces G(12/13)-mediated stress fiber formation, yet promotes growth and survival independent of G protein-coupled receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL ADHESION KINASE; HETEROTRIMERIC G-PROTEINS; CELL-MIGRATION; DEPENDENT ACTIVATION; SIGNAL-TRANSDUCTION; ENDOTHELIAL-CELLS; INTRACELLULAR SPHINGOSINE-1-PHOSPHATE; SACCHAROMYCES-CEREVISIAE; TYROSINE PHOSPHORYLATION; LYSOPHOSPHATIDIC ACID AB Sphingosine 1- phosphate ( S1P) is the ligand for a family of specific G protein- coupled receptors ( GPCRs) that regulate a wide variety of important cellular functions, including growth, survival, cytoskeletal rearrangements, and cell motility. However, whether it also has an intracellular function is still a matter of great debate. Overexpression of sphingosine kinase type 1, which generated S1P, induced extensive stress fibers and impaired formation of the Src- focal adhesion kinase signaling complex, with consequent aberrant focal adhesion turnover, leading to inhibition of cell locomotion. We have dissected biological responses dependent on intracellular S1P from those that are receptor- mediated by specifically blocking signaling of Galpha(q), Galpha(i), Galpha(12/13), and Gbetagamma subunits, the G proteins that S1P receptors ( S1PRs) couple to and signal through. We found that intracellular S1P signaled " inside out" through its cell- surface receptors linked to G(12/ 13) -mediated stress fiber formation, important for cell motility. Remarkably, cell growth stimulation and suppression of apoptosis by endogenous S1P were independent of GPCRs and inside- out signaling. Using fibroblasts from embryonic mice devoid of functional S1PRs, we also demonstrated that, in contrast to exogenous S1P, intracellular S1P formed by overexpression of sphingosine kinase type 1 promoted growth and survival independent of its GPCRs. Hence, exogenous and intracellularly generated S1Ps affect cell growth and survival by divergent pathways. Our results demonstrate a receptor- independent intracellular function of S1P, reminiscent of its action in yeast cells that lack S1PRs. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. Natl Inst Neurosci, Dept Mol Genet, Tokyo 1878502, Japan. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem, Med Coll Virginia Campus, Richmond, VA 23298 USA. OI Ishii, Isao/0000-0002-5367-205X FU NCI NIH HHS [CA 61774]; NIMH NIH HHS [MH 01723] NR 75 TC 114 Z9 114 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 21 PY 2003 VL 278 IS 47 BP 46452 EP 46460 DI 10.1074/jbc.M308749200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743JV UT WOS:000186569400030 PM 12963721 ER PT J AU Hu, XQ Zhang, L Stewart, RR Weight, FF AF Hu, XQ Zhang, L Stewart, RR Weight, FF TI Arginine 222 in the pre-transmembrane domain 1 of 5-HT3A receptors links agonist binding to channel gating SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTORS; GATED ION-CHANNEL; FAST SYNAPTIC TRANSMISSION; AFFECTS DESENSITIZATION; MAJOR DETERMINANT; GABA(A) RECEPTOR; STRUCTURAL BASIS; MOLECULAR-BASIS; SUBUNIT; ACTIVATION AB Ligand- gated ion channels are integral membrane proteins that mediate fast synaptic transmission. Molecular biological techniques have been extensively used for determining the structure- function relationships of ligand- gated ion channels. However, the transduction mechanisms that link agonist binding to channel gating remain poorly understood. Arginine 222 ( Arg- 222), located at the distal end of the extracellular N- terminal domain immediately preceding the first transmembrane domain ( TM1), is conserved in all 5- HT3A receptors and alpha7- nicotinic acetylcholine receptors that have been cloned. To elucidate the possible role of Arg- 222 in the function of 5- HT3A receptors, we mutated the arginine residue to alanine ( Ala) and expressed both the wildtype and the mutant receptor in human embryonic kidney 293 cells. Functional studies of expressed wild- type and mutant receptors revealed that the R222A mutation increased the apparent potency of the full agonist, serotonin ( 5- HT), and the partial agonist, 2- Me- 5- HT, 5- and 12- fold, respectively. In addition, the mutation increased the efficacy of 2- Me- 5- HT and converted it from a partial agonist to a full agonist. Furthermore, this mutation also converted the 5- HT3 receptor antagonist/ very weak partial agonist, apomorphine, to a potent agonist. Kinetic analysis revealed that the R222A mutation increased the rate of receptor activation and desensitization but did not affect rate of deactivation. The results suggest that the pre- TM1 amino acid residue Arg- 222 may be involved in the transduction mechanism linking agonist binding to channel gating in 5- HT3A receptors. C1 NIAAA, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Hu, XQ (reprint author), NIAAA, Mol & Cellular Neurobiol Lab, NIH, Pk Bldg,Rm 150, Bethesda, MD 20892 USA. NR 41 TC 44 Z9 44 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 21 PY 2003 VL 278 IS 47 BP 46583 EP 46589 DI 10.1074/jbc.M308974200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743JV UT WOS:000186569400044 PM 12970351 ER PT J AU Canals, M Marcellino, D Fanelli, F Ciruela, F de Benedetti, P Goldberg, SR Neve, K Fuxe, K Agnati, LF Woods, AS Ferre, S Lluis, C Bouvier, M Franco, R AF Canals, M Marcellino, D Fanelli, F Ciruela, F de Benedetti, P Goldberg, SR Neve, K Fuxe, K Agnati, LF Woods, AS Ferre, S Lluis, C Bouvier, M Franco, R TI Adenosine A(2A)-dopamine D2 receptor-receptor heteromerization - Qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; FUNCTIONAL GABA(B) RECEPTOR; ADENOSINE A(2A) RECEPTORS; DOPAMINE D2 RECEPTORS; INTEGRATIVE MECHANISM; LIGAND-BINDING; TRANSFER BRET; LIVE CELLS; HETERODIMERIZATION; OLIGOMERIZATION AB There is evidence for strong functional antagonistic interactions between adenosine A(2A) receptors (A(2A)Rs) and dopamine D-2 receptors (D(2)Rs). Although a close physical interaction between both receptors has recently been shown using co-immunoprecipitation and co-localization assays, the existence of a A(2A)R-D2R protein-protein interaction still had to be demonstrated in intact living cells. In the present work, fluorescence resonance energy transfer ( FRET) and bioluminescence resonance energy transfer (BRET) techniques were used to confirm the occurrence of A(2A)R-D2R interactions in cotransfected cells. The degree of A(2A)R-D2R heteromerization, measured by BRET, did not vary after receptor activation with selective agonists, alone or in combination. BRET competition experiments were performed using a chimeric D2R-D1R in which helices 5 and 6, the third intracellular loop (I3), and the third extracellular loop (E3) of the D2R were replaced by those of the dopamine D-1 receptor (D1R). Although the wild type D2R was able to decrease the BRET signal, the chimera failed to achieve any effect. This suggests that the helix 5-I3-helix 6-E3 portion of D2R holds the site(s) for interaction with A(2A)R. Modeling of A(2A)R and D2R using a modified rhodopsin template followed by molecular dynamics and docking simulations gave essentially two different possible modes of interaction between D2R and A(2A)R. In the most probable one, helix 5 and/or helix 6 and the N-terminal portion of I3 from D2R approached helix 4 and the C-terminal portion of the C-tail from the A(2A)R, respectively. C1 Univ Barcelona, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. Univ Modena & Reggio Emilia, Dulbecco Telethon Inst, I-41100 Modena, Italy. Univ Modena & Reggio Emilia, Dept Chem, I-41100 Modena, Italy. Univ Modena & Reggio Emilia, Dept Biomed Sci, I-41100 Modena, Italy. NIDA, DHHS, NIH, Intramural Res Program, Baltimore, MD 21224 USA. Karolinska Inst, Dept Neurosci, Div Cellular & Mol Neurochem, S-17177 Stockholm, Sweden. Univ Montreal, Dept Biochem, Montreal, PQ H3C 3J7, Canada. Dept Vet Affairs Med Ctr, Portland, OR 97239 USA. RP Franco, R (reprint author), Univ Barcelona, Dept Biochem & Mol Biol, Marti & Franques 1, E-08028 Barcelona, Spain. RI Bouvier, Michel/H-2758-2014; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Fanelli, Francesca/O-8807-2014; OI Bouvier, Michel/0000-0003-1128-0100; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Fanelli, Francesca/0000-0002-7620-6895; Marcellino, Daniel/0000-0002-4618-7267; Canals, Meritxell/0000-0002-7942-5006 FU Telethon [TCP00068] NR 48 TC 282 Z9 284 U1 1 U2 23 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 21 PY 2003 VL 278 IS 47 BP 46741 EP 46749 DI 10.1074/jbc.M306451200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743JV UT WOS:000186569400065 PM 12933819 ER PT J AU Marinissen, MJ Servitja, JM Offermanns, S Simon, MI Gutkind, JS AF Marinissen, MJ Servitja, JM Offermanns, S Simon, MI Gutkind, JS TI Thrombin protease-activated receptor-1 signals through G(q)- and G(13)-initiated MAPK cascades regulating c-Jun expression to induce cell transformation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HETEROTRIMERIC G-PROTEINS; EARLY GENE-EXPRESSION; SMOOTH-MUSCLE-CELLS; NIH 3T3 CELLS; COUPLED RECEPTORS; ALPHA-SUBUNIT; BINDING PROTEINS; KINASE PATHWAY; MALIGNANT TRANSFORMATION; TYROSINE PHOSPHORYLATION AB Although the ability of G protein-coupled receptors to stimulate normal and aberrant cell growth has been intensely investigated, the precise nature of the molecular mechanisms underlying their transforming potential are still not fully understood. In this study, we have taken advantage of the potent mitogenic effect of thrombin and the focus-forming activity of one of its receptors, protease-activated receptor-1, to dissect how this receptor coupled to Galpha(i), Galpha(q/11), and Galpha(12/13) transduces signals from the membrane to the nucleus to initiate transcriptional events involved in cell transformation. Using endogenous and transfected thrombin receptors in NIH 3T3 cells, ectopic expression of muscarinic receptors coupled to Galpha(q) and Galpha(i), and chimeric G protein alpha subunits and murine fibroblasts deficient in Galpha(q/11), and Galpha(12/13), we show here that, although coupling to Galpha(i) is sufficient to induce ERK activation, the ability to couple to Galpha(q) and/or Galpha(13) is necessary to induce c-jun expression and cell transformation. Furthermore, we show that Galpha(q) and Galpha(13) can initiate the activation of MAPK cascades, including JNK, p38, and ERK5, which in turn regulate the activity of transcription factors controlling expression from the c-jun promoter. We also present evidence that c-Jun and the kinases regulating its expression are integral components of the transforming pathway initiated by protease-activated receptor-1. C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. CALTECH, Dept Biol, Pasadena, CA 91125 USA. CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA. Univ Heidelberg, Inst Pharmacol, Dept Mol Pharmacol, D-69120 Heidelberg, Germany. RP Gutkind, JS (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bldg 30,Rm 211,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; OI SERVITJA DUQUE, JOAN-MARC/0000-0002-1241-8004 NR 63 TC 65 Z9 66 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 21 PY 2003 VL 278 IS 47 BP 46814 EP 46825 DI 10.1074/jbc.M305709200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743JV UT WOS:000186569400073 PM 12954641 ER PT J AU Mohney, RP Das, M Bivona, TG Hanes, R Adams, AG Philips, MR O'Bryan, JP AF Mohney, RP Das, M Bivona, TG Hanes, R Adams, AG Philips, MR O'Bryan, JP TI Intersectin activates Ras but stimulates transcription through an independent pathway involving JNK SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOCYTIC PROTEIN INTERSECTIN; GROWTH-FACTOR RECEPTOR; PHOSPHOTYROSINE-BINDING DOMAINS; CLATHRIN-MEDIATED ENDOCYTOSIS; SRC HOMOLOGY 2; ADAPTER PROTEIN; EPS15 HOMOLOGY; DOWN-SYNDROME; KINASE; INHIBITOR AB Intersectin (ITSN) is a molecular scaffold involved in regulating endocytosis and mitogenic signaling. We previously demonstrated that ITSN transformed rodent fibroblasts, accelerated hormone-induced maturation of Xenopus oocytes, and activated the Elk-1 transcription factor through an MEK- and Erk-independent mechanism. We now demonstrate that ITSN complexes with the Ras guanine nucleotide exchange factor Sos1 leading to increased RasGTP levels. Using fluorescence resonant energy transfer analysis, we demonstrate that ITSN complexes with Ras in living cells leading to Ras activation on intracellular vesicles. These vesicles contain epidermal growth factor receptor but are distinct from transferrin-positive vesicles. However, Ras is not required for ITSN stimulation of transcription. Rather, we demonstrate that ITSN signals through JNK to activate Elk-1. Although ITSN activation of Elk-1 was Ras-independent, ITSN cooperates with Ras to synergistically activate JNK. These findings indicate that ITSN activates multiple intracellular signaling pathways and suggest that this adaptor protein may coordinately regulate the activity of these pathways in vivo. C1 NYU, Sch Med, Dept Med, New York, NY 10016 USA. NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA. RP O'Bryan, JP (reprint author), NIEHS, Lab Signal Transduct, NIH, US Dept HHS, Bldg 101,Rm F336,MD F3-06,POB 12233, Res Triangle Pk, NC 27709 USA. NR 47 TC 48 Z9 54 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 21 PY 2003 VL 278 IS 47 BP 47038 EP 47045 DI 10.1074/jbc.M303895200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743JV UT WOS:000186569400100 PM 12970366 ER PT J AU Shieh, JJ Pan, CJ Mansfield, BC Chou, JY AF Shieh, JJ Pan, CJ Mansfield, BC Chou, JY TI A glucose-6-phosphate hydrolase, widely expressed outside the liver, can explain age-dependent resolution of hypoglycemia in glycogen storage disease type Ia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUCOSE-PRODUCTION; IDENTIFICATION; TRANSPORTER; PROTEINS; 1B AB A fine control of the blood glucose level is essential to avoid hyper- or hypo- glycemic shocks associated with many metabolic disorders, including diabetes mellitus and type I glycogen storage disease. Between meals, the primary source of blood glucose is gluconeogenesis and glycogenolysis. In the final step of both pathways, glucose-6- phosphate ( G6P) is hydrolyzed to glucose by the glucose- 6- phosphatase ( G6Pase) complex. Because G6Pase ( renamed G6Pase-alpha) is primarily expressed only in the liver, kidney, and intestine, it has implied that most other tissues cannot contribute to interprandial blood glucose homeostasis. We demonstrate that a novel, widely expressed G6Pase- related protein, PAP2.8/ UGRP, renamed here G6Pase-beta, is an acid- labile, vanadate-sensitive, endoplasmic reticulum- associated phosphohydrolase, like G6Pase-alpha. Both enzymes have the same active site structure, exhibit a similar Km toward G6P, but the V-max of G6Pase-alpha is similar to6- fold greater than that of G6Pase-beta. Most importantly, G6Pase-beta couples with the G6P transporter to form an active G6Pase complex that can hydrolyze G6P to glucose. Our findings challenge the current dogma that only liver, kidney, and intestine can contribute to blood glucose homeostasis and explain why type Ia glycogen storage disease patients, lacking a functional liver/ kidney/ intestine G6Pase complex, are still capable of endogenous glucose production. 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 9S241,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Mansfield, Brian/0000-0002-8533-2789 NR 28 TC 54 Z9 59 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 21 PY 2003 VL 278 IS 47 BP 47098 EP 47103 DI 10.1074/jbc.M309472200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743JV UT WOS:000186569400107 PM 13129915 ER PT J AU Hwang, J Saha, A Boo, YC Sorescu, GP McNally, JS Holland, SM Dikalov, S Giddens, DP Griendling, KK Harrison, DG Jo, H AF Hwang, J Saha, A Boo, YC Sorescu, GP McNally, JS Holland, SM Dikalov, S Giddens, DP Griendling, KK Harrison, DG Jo, H TI Oscillatory shear stress stimulates endothelial production of O2- from p47(phox)-dependent NAD(P)H oxidases, leading to monocyte adhesion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE SYNTHASE; HUMAN CAROTID BIFURCATION; PROTEIN-KINASE-A; NADPH OXIDASE; SUPEROXIDE-DISMUTASE; UP-REGULATION; CELLS; ATHEROSCLEROSIS; EXPRESSION; FLOW AB Arterial regions exposed to oscillatory shear (OS) in branched arteries are lesion-prone sites of atherosclerosis, whereas those of laminar shear (LS) are relatively well protected. Here, we examined the hypothesis that OS and LS differentially regulate production of O-2(-) from the endothelial NAD(P)H oxidase, which, in turn, is responsible for their opposite effects on a critical atherogenic event, monocyte adhesion. We used aortic endothelial cells obtained from C57BL/6 (MAE-C57) and p47(phox-/-) (MAE- p47(-/-)) mice, which lack a component of NAD(P)H oxidase. O-2(-) production was determined by dihydroethidium staining and an electron spin resonance using an electron spin trap methoxycarbonyl-2,2,5,5- tetramethyl-pyrrolidine. Chronic exposure (18 h) to an arterial level of OS (+/- 5 dynes/cm(2)) increased O-2(-) (2-fold) and monocyte adhesion (3-fold) in MAE-C57 cells, whereas chronic LS (15 dynes/cm(2), 18 h) significantly decreased both monocyte adhesion and O-2(-) compared with static conditions. In contrast, neither LS nor OS were able to induce O-2(-) production and monocyte adhesion to MAE- p47(-/-). Treating MAE-C57 with a cell-permeable superoxide dismutase compound, polyethylene glycol-superoxide dismutase, also inhibited OS-induced monocyte adhesion. In addition, over-expressing p47(phox) in MAE-p47(-/-) restored OS-induced O-2(-) production and monocyte adhesion. These results suggest that chronic exposure of endothelial cells to OS stimulates O-2(-) and/or its derivatives produced from p47(phox)-dependent NAD(P) H oxidase, which, in turn, leads to monocyte adhesion, an early and critical atherogenic event. C1 Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30322 USA. Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Jo, H (reprint author), Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30322 USA. OI Boo, Yong Chool/0000-0001-9895-2066 FU NHLBI NIH HHS [HL 71014, HL 67413] NR 36 TC 177 Z9 180 U1 0 U2 8 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 21 PY 2003 VL 278 IS 47 BP 47291 EP 47298 DI 10.1074/jbc.M305150200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743JV UT WOS:000186569400131 PM 12958309 ER PT J AU Zhi, HJ Wang, XD Cabrera, JE Johnson, RC Jin, DJ AF Zhi, HJ Wang, XD Cabrera, JE Johnson, RC Jin, DJ TI Fis stabilizes the interaction between RNA polymerase and the ribosomal promoter rrnB P1, leading to transcriptional activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RATE-DEPENDENT REGULATION; BINDING PROTEIN FIS; ESCHERICHIA-COLI; DNA-BINDING; STRINGENT CONTROL; H-NS; UPSTREAM ACTIVATION; INITIATION COMPLEX; RPOB MUTANTS; GROWTH-PHASE AB It has been shown that Fis activates transcription of the ribosomal promoter rrnB P1; however, the mechanism by which Fis activates rrnB P1 transcription is not fully understood. Paradoxically, although Fis activates transcription of rrnB P1 in vitro, transcription from the promoter containing Fis sites ( as measured from rrnB P1-lacZ fusions) is not reduced in a fis null mutant strain. In this study, we further investigated the mechanism by which Fis activates transcription of the rrnB P1 promoter and the role of Fis in rRNA synthesis and cell growth in Escherichia coli. Like all other stringent promoters investigated so far, open complex of rrnB P1 has been shown to be intrinsically unstable, making open complex stability a potential regulatory step in transcription of this class of promoters. Our results show that Fis acts at this regulatory step by stabilizing the interaction between RNA polymerase and rrnB P1 in the absence of NTPs. Mutational analysis of the Fis protein demonstrates that there is a complete correlation between Fis-mediated transcriptional activation of rrnB P1 and Fis-mediated stabilization of preinitiation complexes of the promoter. Thus, our study indicates that Fis-mediated stabilization of RNA polymerase-rrnB P1 preinitiation complexes, presumably at the open complex step, contributes prominently to transcriptional activation. Furthermore, our in vivo results show that rRNA synthesis from the P1 promoters of several rRNA operons are reduced 2-fold in a fis null mutant compared with the wild type strain, indicating that Fis plays an important role in the establishment of robust rRNA synthesis when E. coli cells are emerging from a growth-arrested phase to a rapid growth phase. Thus, our results resolve an apparent paradox of the role of Fis in vitro and in vivo in the field. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. RP Jin, DJ (reprint author), NCI, Mol Biol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 69 TC 22 Z9 22 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 21 PY 2003 VL 278 IS 47 BP 47340 EP 47349 DI 10.1074/jbc.M305430200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743JV UT WOS:000186569400136 PM 13679374 ER PT J AU Modesti, M Junop, MS Ghirlando, R van de Rakt, M Gellert, M Yang, W Kanaar, R AF Modesti, M Junop, MS Ghirlando, R van de Rakt, M Gellert, M Yang, W Kanaar, R TI Tetramerization and DNA ligase IV interaction of the DNA double-strand break repair protein XRCC4 are mutually exclusive SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE DNA repair; non-homologous end joining; protein-protein interaction; V(D)J recombination ID V(D)J RECOMBINATION; CRYSTAL-STRUCTURE; BRCT DOMAIN; COMPLEX; CELLS; EXPRESSION; DISRUPTION; LETHALITY; STABILITY; MODULE AB The XRCC4 protein is of critical importance for the repair of broken chromosomal DNA by non-homologous end joining (NHEJ). The absence of XRCC4 abolishes chromosomal NHEJ almost completely. One reason for this severe phenotype is that XRCC4 binds and modulates the stability and activity of the NHEJ-specific ligase, DNA ligase IV. XRCC4 in solution is in equilibrium between the dimeric and tetrameric forms. Previous structural studies have shown that the interface between dimers is located in the same region as that implicated in DNA ligase IV interaction. With the use of equilibrium sedimentation analysis, we show here that only the XRCC4 dimer can associate with DNA ligase IV, forming a monodisperse complex of 2:1 stoichiometry in solution. In addition, physical analysis of XRCC4/DNA ligase IV complex formation, combined with mutational analysis of XRCC4, indicates that tetramerization and DNA ligase IV binding are mutually exclusive. We propose that the putative function of the XRCC4 tetramer is distinct from its DNA ligase IV-associated function. (C) 2003 Elsevier Ltd. All rights reserved. C1 Erasmus MC, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands. McMaster Univ, Dept Biochem, Hlth Sci Ctr, Hamilton, ON L8N 3Z5, Canada. NIDDKD, Lab Mol Biol, Dept Hlth & Huma Serv, NIH, Bethesda, MD 20892 USA. Erasmus MC Daniel, Dept Radiat Oncol, NL-3000 DR Rotterdam, Netherlands. RP Kanaar, R (reprint author), Erasmus MC, Dept Cell Biol & Genet, POB 1738, NL-3000 DR Rotterdam, Netherlands. EM r.kanaar@erasmusmc.nl RI Ghirlando, Rodolfo/A-8880-2009; Yang, Wei/D-4926-2011; Junop, Murray/E-4160-2015; OI Yang, Wei/0000-0002-3591-2195; Junop, Murray/0000-0001-6676-5717; Modesti, Mauro/0000-0002-4964-331X NR 39 TC 52 Z9 56 U1 0 U2 2 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 21 PY 2003 VL 334 IS 2 BP 215 EP 228 DI 10.1016/j.jmb.2003.09.031 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743LY UT WOS:000186574300005 PM 14607114 ER PT J AU Nolte, G AF Nolte, G TI The magnetic lead field theorem in the quasi-static approximation and its use for magnetoencephalography forward calculation in realistic volume conductors SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID PERTURBATIVE ANALYTICAL SOLUTIONS; HUMAN BRAIN; MODEL; HEAD; MEG; STIMULATION; EEG AB The equation for the magnetic lead field for a given magnetoencephalography (MEG) channel is well known for arbitrary frequencies omega but is not directly applicable to MEG in the quasi-static approximation. In this paper we derive an equation for omega = 0 starting from the very definition of the lead field instead of using Helmholtz's reciprocity theorems. The results are (a) the transpose of the conductivity times the lead field is divergence-free, and (b) the lead field differs from the one in any other volume conductor by a gradient of a scalar function. Consequently, for a piecewise homogeneous and isotropic volume conductor, the lead field is always tangential at the outermost surface. Based on this theoretical result, we formulated a simple and fast method for the MEG forward calculation for one shell of arbitrary shape: we correct the corresponding lead field for a spherical volume conductor by a superposition of basis functions, gradients of harmonic functions constructed here from spherical harmonics, with coefficients fitted to the boundary conditions. The algorithm was tested for a prolate spheroid of realistic shape for which the analytical solution is known. For high order in the expansion, we found the solutions to be essentially exact and for reasonable accuracies much fewer multiplications are needed than in typical implementations of the boundary element methods. The generalization to more shells is straightforward. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Nolte, G (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 24 TC 242 Z9 243 U1 1 U2 9 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 2003 VL 48 IS 22 BP 3637 EP 3652 DI 10.1088/0031-9155/48/22/002 PG 16 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 757ZP UT WOS:000187608300002 PM 14680264 ER PT J AU Grunewald, K Desai, P Winkler, DC Heymann, JB Belnap, DM Baumeister, W Steven, AC AF Grunewald, K Desai, P Winkler, DC Heymann, JB Belnap, DM Baumeister, W Steven, AC TI Three-dimensional structure of herpes simplex virus from cryo-electron tomography SO SCIENCE LA English DT Article ID CELLS; DNA; MICROSCOPY; VIRIONS; EGRESS; ENTRY AB Herpes simplex virus, a DNA virus of high complexity, consists of a nucleocapsid surrounded by the tegument-a protein compartment-and the envelope. The latter components, essential for infectivity, are pleiomorphic. Visualized in cryo-electron tomograms of isolated virions, the tegument was seen to form an asymmetric cap: On one side, the capsid closely approached the envelope; on the other side, they were separated by similar to35 nanometers of tegument. The tegument substructure was particulate, with some short actin-like. laments. The envelope contained 600 to 750 glycoprotein spikes that varied in length, spacing, and in the angles at which they emerge from the membrane. Their distribution was nonrandom, suggesting functional clustering. C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. Max Planck Inst Biochem, Dept Mol Struct Biol, D-82152 Martinsried, Germany. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RI Heymann, Bernard/F-6825-2011; OI Heymann, Bernard/0000-0002-8872-5326; Grunewald, Kay/0000-0002-4788-2691 FU NIAID NIH HHS [AI33077, R01 AI033077, R01 AI033077-10] NR 28 TC 295 Z9 304 U1 5 U2 37 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 21 PY 2003 VL 302 IS 5649 BP 1396 EP 1398 DI 10.1126/science.1090284 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 745HP UT WOS:000186683500052 PM 14631040 ER PT J AU Chowdhury, IH Farhadi, A Wang, XF Robb, ML Birx, DL Kim, JH AF Chowdhury, IH Farhadi, A Wang, XF Robb, ML Birx, DL Kim, JH TI Human T-cell leukemia virus type 1 tax activates cyclin-dependent kinase inhibitor p21/Waf1/Cip1 expression through a p53-independent mechanism: Inhibition of cdk2 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE HTLV-1; ATL; p21/Waf1/Cip1; p21 promoter; p53; CREB/ATF; cdk-2 ID LONG-TERMINAL-REPEAT; BINDING-PROTEIN-ALPHA; DNA-DAMAGE; HTLV-I; TRANSCRIPTION FACTORS; MOLECULAR-MECHANISM; P53; ARREST; P21; TRANSACTIVATION AB We investigated the possible involvement of HTLV-1 Tax in the transcriptional activation of p 21/Waf1/Cip1 (hereafter p21), a potent inhibitor of cyclin-dependent kinases and cell growth. Tax transfection resulted in enhanced expression of p21 protein in T and fibroblastoid cells. Similarly, Tax-expressing cells have higher amounts of endogenous p21 protein and RNA. However, neither Tax-negative, HTLV-1 transformed cells or HTLV-1-negative T cell lines had detectable levels of p21 protein and RNA. Cotransfection of Tax strongly activated the p21 promoter. CREB/ATF defective Tax mutant (M47) activated the p21 promoter significantly less efficiently. Tax activated wild type (wt) p21 promoter in p53-negative Jurkat and p53-positive A301 cells, irrespective of endogenous p53 status, and activated a mutant p21 promoter containing a p53 responsive element (p53RE) deletion as strongly as wit promoter. Of importance, cdk2 activity was almost completely abolished in Tax-induced p21-expressing MT-2 cells, suggesting that Tax-induced p21 predominantly affects the activity of cdk2, a late G I and S phase kinase. Taken together, these findings suggest that HTLV-1 Tax activates p21[Waf1/Cip1, a cell growth inhibitor, in a p53-independent mechanism through CREB/ATF-related transcription factors, and inhibits cdk2. Tax induction of p21 may balance the T-cell proliferation function of Tax and may contribute to the long clinical latency of HTLV-1 infection and the delayed development of adult T-cell leukemia. (C) 2003 Wiley-Liss, Inc. C1 Henry M Jackson Fdn Advancement Mil Med, Dept Vaccine Dev & Res, Rockville, MD USA. Walter Reed Army Inst Res, Rockville, MD USA. Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA. RP Chowdhury, IH (reprint author), NCI, CCR, HIV & AIDS Malignancy Branch, NIH, 10 Ctr Dr,Rm 10S255,MSC 1868, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI 00950] NR 67 TC 20 Z9 22 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 20 PY 2003 VL 107 IS 4 BP 603 EP 611 DI 10.1002/ijc.11316 PG 9 WC Oncology SC Oncology GA 734GT UT WOS:000186047200014 PM 14520699 ER PT J AU Alguacil, J Porta, M Kauppinen, T Malats, N Kogevinas, M Carrato, A AF Alguacil, J Porta, M Kauppinen, T Malats, N Kogevinas, M Carrato, A CA PANKRAS II Study Grp TI Occupational exposure to dyes, metals, polycyclic aromatic hydrocarbons and other agents and K-ras activation in human exocrine pancreatic cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE pancreas; ras genes; occupation; dyes; metals; case-case study; genotoxicology ID HUMAN-CELLS; ONCOGENE ACTIVATION; RISK-FACTORS; CARCINOGENIC METALS; MUTATIONAL SPECTRUM; LEATHER TANNERS; GENE-EXPRESSION; AMINO-ACIDS; DNA-REPAIR; MORTALITY AB ras genes are known critical DNA targets for chemical carcinogens. Exocrine pancreatic cancer (EPC) is the human tumor with the highest prevalence of K-ras mutations at diagnosis. We analyzed the relationship between past occupational exposure to dyes, metals, polycyclic aromatic hydrocarbons (PAHs) and other agents and mutations in codon 12 of the K-ras gene in 107 incident cases of EPC. Information on occupational and life-style factors was obtained from personal interviews conducted during hospital stay. Occupational exposures were examined using industrial hygienists (IH) assessment and the Finnish job-exposure matrix (Fin-jem). Specific occupational exposures among K-ras mutated EPC cases (n = 83) were compared to those of K-ras wildtype EPC cases (n = 24) (case-case analysis). Multivariate-adjusted odds ratios (OR) and their corresponding 95% confidence limits were estimated by unconditional logistic regression. Cases with K-ras mutations were significantly more likely than wild-type cases to have been exposed to dyes and organic pigments (OR 4.8;p<0.05). There was some indication of weaker associations between K-ras mutations and occupational exposure to lead, PAHs, benzo[a]pyrene, gasoline, nickel, inhalatory exposure to chromium and sedentary work. The association with chromium compounds was stronger for G to T transversions, a finding compatible with experimental studies on mutation spectra for chromium. Results lend moderate support to the hypothesis of indirect relationships between occupational exposure to dyes and organic pigments and the activation of the K-ras gene in the etiopathogenesis of human exocrine pancreatic cancer. (C) 2003 Wiley-Liss, Inc. C1 Univ Autonoma Barcelona, Inst Municipal Invest Med, Clin & Mol Epidemiol Canc Unit, E-08003 Barcelona, Spain. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Autonoma Barcelona, Catalonia, Spain. Finnish Inst Occupat Hlth, Dept Epidemiol & Biostat, Helsinki, Finland. Univ Autonoma Barcelona, Inst Municipal Invest Med, Resp & Environm Hlth Res Unit, E-08003 Barcelona, Spain. Hosp Univ Elx, Alacant, Spain. RP Univ Autonoma Barcelona, Inst Municipal Invest Med, Clin & Mol Epidemiol Canc Unit, Carrer Dr Aiguader 80, E-08003 Barcelona, Spain. EM rnporta@imim.es RI Porta, Miquel/B-5787-2008; Kogevinas, Manolis/C-3918-2017; OI Porta, Miquel/0000-0003-1684-7428; Malats, Nuria/0000-0003-2538-3784 NR 77 TC 28 Z9 30 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD NOV 20 PY 2003 VL 107 IS 4 BP 635 EP 641 DI 10.1002/ijc.11431 PG 7 WC Oncology SC Oncology GA 734GT UT WOS:000186047200018 PM 14520703 ER PT J AU Zhu, XX Giordano, T Yu, QS Holloway, HW Perry, TA Lahiri, DK Brossi, A Greig, NH AF Zhu, XX Giordano, T Yu, QS Holloway, HW Perry, TA Lahiri, DK Brossi, A Greig, NH TI Thiothalidomides: Novel isosteric analogues of thalidomide with enhanced TNF-alpha inhibitory activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; MESSENGER-RNA DEGRADATION; UA-RICH SEQUENCES; 5'-UNTRANSLATED REGION; RESPONSIVE ELEMENT; ANGIOGENESIS; TRANSLATION; INTERLEUKIN-1; METABOLITES; EXPRESSION AB Thalidomide is being increasingly used in the clinical management of a wide spectrum of immunologically-mediated and infectious diseases, and cancers. However, the mechanisms underlying its pharmacological action are still under investigation. In this regard, oral thalidomide is clinically valuable in the treatment of erythema nodosum leprosum (ENL) and mutiple myeloma and effectively reduces tumor necrosis factor-alpha (TNF-alpha) levels and angiogenesis in vivo. This contrasts with its relatively weak effects on TNF-alpha and angiogenesis in in vitro studies and implies that active metabolites contribute to its in vivo pharmacologic action and that specific analogues would be endowed with potent activity. Our focus in the structural modification of thalidomide is toward the discovery of novel isosteric active analogues. In this regard, a series of thiothalidomides and analogues were synthesized and evaluated for their TNF-alpha inhibitory activity against lipopolysacharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC), This was combined with a PBMC viability assay to differentiate reductions in TNF-alpha secretion from cellular toxicity. Two isosteric analogues of thalidomide, compounds 15 and 16, that mostly reflect the parent compound, together with the simple structure, dithioglutarimide 19, potently inhibited TNF-a secretion, compared to thalidomide, 1. The mechanism underpinning this most likely is posttranscriptional, as each of these compounds decreased TNF-alpha mRNA stability via its 3'-UTR. The potency of 19 warrants further study and suggests that replacement of the amide carbonyl with a thiocarbonyl may be beneficial for increased TNF-alpha inhibitory action. In addition, an intact phthalimido moiety appeared to be requisite for TNF-alpha inhibitory activity. C1 NIA, Drug Design & Dev Sect, Neurosci Lab, Gerontol Res Ctr 4E02,Intramural Res Program, Baltimore, MD 21224 USA. Message Pharmaceut, Malvern, PA 19355 USA. Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. NIH, Chapel Hill, NC 27599 USA. EM GreigN@vax.gre.nia.nih.gov NR 45 TC 51 Z9 55 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 20 PY 2003 VL 46 IS 24 BP 5222 EP 5229 DI 10.1021/jm030152f PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 743LG UT WOS:000186572800013 PM 14613324 ER PT J AU Kim, SJ Kim, YS Yuan, JP Petralia, RS Worley, PF Linden, DJ AF Kim, SJ Kim, YS Yuan, JP Petralia, RS Worley, PF Linden, DJ TI Activation of the TRPC1 cation channel by metabotropic glutamate receptor mGluR1 SO NATURE LA English DT Article ID LONG-TERM DEPRESSION; CEREBELLAR PURKINJE NEURONS; MUTANT MICE; SYNAPTIC PLASTICITY; CELLS; CONDUCTANCE; RESPONSES; DEFICIT; RELEASE; FAMILY AB Group I metabotropic glutamate receptors (consisting of mGluR1 and mGluR5) are G-protein-coupled neurotransmitter receptors(1) that are found in the perisynaptic region of the postsynaptic membrane(2). These receptors are not activated by single synaptic volleys but rather require bursts of activity(3-5). They are implicated in many forms of neural plasticity including hippocampal long-term potentiation and depression(6-8), cerebellar long-term depression(8-11), associative learning(7,11), and cocaine addiction(12). When activated, group I mGluRs engage two G-protein-dependent signalling mechanisms: stimulation of phospholipase C and activation of an unidentified, mixed-cation excitatory postsynaptic conductance (EPSC), displaying slow activation, in the plasma membrane(4,5,13-15). Here we report that the mGluR1-evoked slow EPSC is mediated by the TRPC1 cation channel. TRPC1 is expressed in perisynaptic regions of the cerebellar parallel fibre-Purkinje cell synapse and is physically associated with mGluR1. Manipulations that interfere with TRPC1 block the mGluR1-evoked slow EPSC in Purkinje cells; however, fast transmission mediated by AMPA-type glutamate receptors remains unaffected. Furthermore, co-expression of mGluR1 and TRPC1 in a heterologous system reconstituted a mGluR1-evoked conductance that closely resembles the slow EPSC in Purkinje cells. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Kangweon Natl Univ, Sch Med, Dept Physiol, Chunchon 20071, South Korea. NIDCD, NIH, Bethesda, MD 20892 USA. RP Worley, PF (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, 725 N Wolfe St, Baltimore, MD 21205 USA. RI Kim, Sang Jeong/J-2740-2012 NR 30 TC 241 Z9 249 U1 1 U2 9 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 20 PY 2003 VL 426 IS 6964 BP 285 EP 291 DI 10.1038/nature02162 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 744YQ UT WOS:000186660800043 PM 14614461 ER PT J AU Sklar, P Masur, H AF Sklar, P Masur, H TI HIV infection and cardiovascular disease - Is there really a link? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CORONARY-HEART-DISEASE; PROTEASE INHIBITORS; RISK C1 Drexel Univ, Coll Med, Div HIV AIDS Med, Philadelphia, PA 19104 USA. NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Sklar, P (reprint author), Drexel Univ, Coll Med, Div HIV AIDS Med, Philadelphia, PA 19104 USA. NR 11 TC 35 Z9 36 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 20 PY 2003 VL 349 IS 21 BP 2065 EP 2067 DI 10.1056/NEJMe038158 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 744QE UT WOS:000186642900012 PM 14627792 ER PT J AU Marini, JC AF Marini, JC TI Bisphosphonates in children with bone diseases - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID OSTEOGENESIS IMPERFECTA C1 NICHHD, Bethesda, MD 20892 USA. RP Marini, JC (reprint author), NICHHD, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 1 U2 2 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 20 PY 2003 VL 349 IS 21 BP 2071 EP 2071 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 744QE UT WOS:000186642900017 ER PT J AU Kopp, JB Schiffmann, R AF Kopp, JB Schiffmann, R TI Fabry's disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 20 PY 2003 VL 349 IS 21 BP E20 EP E20 DI 10.1056/ENEJMicm000011 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 744QE UT WOS:000186642900008 PM 14627801 ER PT J AU Mettus, RV Rane, SG AF Mettus, RV Rane, SG TI Characterization of the abnormal pancreatic development, reduced growth and infertility in Cdk4 mutant mice SO ONCOGENE LA English DT Article DE cyclin-dependent kinase 4; pancreas; fertility ID CYCLIN-DEPENDENT KINASE-4; DEFICIENT; DYSFUNCTION; MELANOMA; CANCER; FAMILY AB Cyclin-dependent kinase 4 (Cdk4) and Cdk6, and later Cdk2, in association with their specific cyclin partners, regulate the G1 to S phase cell cycle transition of mammalian cells by phosphorylation of retinoblastoma (Rb) family proteins. Phosphorylation of Rb results in the release of S-phase specific transcription factors; cell cycle-promoting gene expression, and advancement of the cell cycle. Loss of Cdk4 by homologous-targeted disruption leads to a delay in S-phase entry in serum-stimulated mouse embryo fibroblast (MEF) cultures. Homozygous Cdk4-deficient mice display defects in weight gain, fertility and hypoproliferation of specific endocrine cells of the pituitary and pancreas, the latter of which results in a diabetes-like phenotype. In contrast, inheritance of the p16(Ink4a)-insensitive Cdk4(R24C) mutation leads to spontaneous transformation of MEF cultures in vitro and, in vivo, hyperproliferative disorders that progress to cancer. In this manuscript, we report characterization of the abnormal pancreatic development, reduced growth and infertility in Cdk4 mutant mice. We observe that, whereas Cdk4 is dispensable for early pancreatic development, normal Cdk4 expression is critical for optimal growth of the organism. Also, we observe that loss of Cdk4 may result in insulin insensitivity, implicating an additional role of Cdk4 in beta-cell function, in addition to its role in beta-cell proliferation. Further, we demonstrate that loss of Cdk4 leads to an age-dependent defect in spermatogenesis and disruption in the timing of the estrus cycle. Taken together, our results indicate that the overall defects in growth, fertility and pancreatic development in Cdk4-deficient mice may be a combination of cell-type specific defects and altered glucose metabolism, as a result of defects in postnatal pancreatic development. C1 NCI, Cell Cycle & Human Dis Grp, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. RP Rane, SG (reprint author), NCI, Cell Cycle & Human Dis Grp, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. FU NCI NIH HHS [K22CA90790-01] NR 24 TC 62 Z9 63 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 20 PY 2003 VL 22 IS 52 BP 8413 EP 8421 DI 10.1038/sj.onc.1206888 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 744UB UT WOS:000186650300005 PM 14627982 ER PT J AU Whitmarsh, RJ Saginario, C Zhuo, Y Hilgenfeld, E Rappaport, EF Megonigal, MD Carroll, M Liu, M Osheroff, N Cheung, NKV Slater, DJ Ried, T Knutsen, T Blair, IA Felix, CA AF Whitmarsh, RJ Saginario, C Zhuo, Y Hilgenfeld, E Rappaport, EF Megonigal, MD Carroll, M Liu, M Osheroff, N Cheung, NKV Slater, DJ Ried, T Knutsen, T Blair, IA Felix, CA TI Reciprocal DNA topoisomerase II cleavage events at 5 '-TATTA-3 ' sequences in MLL and AF-9 create homologous single-stranded overhangs that anneal to form der(11) and der(9) genomic breakpoint junctions in treatment-related AML without further processing SO ONCOGENE LA English DT Article DE t(9;11) translocation; DNA topoisomerase II; secondary leukemia; etoposide; etoposide catechol; etoposide quinone ID ACUTE MYELOID-LEUKEMIA; BALANCED CHROMOSOME-ABERRATIONS; ACUTE LYMPHOBLASTIC-LEUKEMIA; SECONDARY ACUTE-LEUKEMIA; EUKARYOTIC TOPOISOMERASE; CLUSTER REGION; TRANSLOCATION BREAKPOINTS; MYELODYSPLASTIC SYNDROMES; INTERNATIONAL WORKSHOP; RELIGATION REACTION AB Few t(9;11) translocations in DNA topoisomerase II inhibitor-related leukemias have been studied in detail and the DNA damage mechanism remains controversial. We characterized the der(11) and der(9) genomic breakpoint junctions in a case of AML following etoposide and doxorubicin. Etoposide-, etoposide metabolite- and doxorubicin-induced DNA topoisomerase II cleavage was examined in normal homologues of the MLL and AF-9 breakpoint sequences using an in vitro assay. Induction of DNA topoisomerase II cleavage complexes in CEM and K562 cell lines was investigated using an in vivo complex of enzyme assay. The translocation occurred between identical 5'-TATTA-3' sequences in MLL intron 8 and AF-9 intron 5 without the gain or loss of bases. The 5'-TATTA-3' sequences were reciprocally cleaved by DNA topoisomerase II in the presence of etoposide, etoposide catechol or etoposide quinone, creating homologous 4-base 5' overhangs that would anneal to form both breakpoint junctions without any processing. der(11) and der(4) translocation breakpoints in a treatment-related ALL at the same site in MLL are consistent with a damage hotspot. Etoposide and both etoposide metabolites induced DNA topoisomerase II cleavage complexes in the hematopoietic cell lines. These results favor the model in which the chromosomal breakage leading to MLL translocations in DNA topoisomerase II inhibitor-related leukemias is a consequence of DNA topoisomerase II cleavage. C1 Childrens Hosp Philadelphia, Div Oncol, Abramson Res Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Canc Pharmacol, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. Hosp Univ Penn, Sch Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Josephy Stokes Jr Res Inst, Philadelphia, PA 19104 USA. NCI, Genet Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP Felix, CA (reprint author), Childrens Hosp Philadelphia, Div Oncol, Abramson Res Ctr, Rm 902B,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. RI Blair, Ian/B-3320-2010 FU NCI NIH HHS [CA77683, CA80175, CA85469]; NIGMS NIH HHS [GM33944] NR 69 TC 40 Z9 42 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 20 PY 2003 VL 22 IS 52 BP 8448 EP 8459 DI 10.1038/sj.onc.1207052 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 744UB UT WOS:000186650300009 PM 14627986 ER PT J AU Gallego, MI Bierie, B Hennighausen, L AF Gallego, MI Bierie, B Hennighausen, L TI Targeted expression of HGF/SF in mouse mammary epithelium leads to metastatic adenosquamous carcinomas through the activation of multiple signal transduction pathways SO ONCOGENE LA English DT Article DE breast cancer; transgenic mice; HGF; scatter factor; c-Met ID HEPATOCYTE GROWTH-FACTOR; MET TYROSINE KINASE; NEGATIVE BREAST-CANCER; FACTOR SCATTER FACTOR; C-MET; BETA-CATENIN; GLAND DEVELOPMENT; FACTOR/SCATTER FACTOR; RECEPTOR MET; COLORECTAL-CANCER AB Overexpression of hepatocyte growth factor (HGF), also called scatter factor (SIT), and its receptor c-Met are associated with poor prognosis for cancer patients. In particular, breast cancer cells can produce HGF that acts in a paracrine as well as in an autocrine manner. Therefore, HGF and c-Met are putative targets for cancer therapy. To explore HGF/c-Met signaling in breast cancer, we have generated transgenic mice expressing HGF specifically in mammary epithelium under the transcriptional control of the whey acidic protein (WAP) gene promoter. WAP-HGF transgenic females developed hyperplastic ductal trees and multifocal invasive tumors after several pregnancies, some of which progressed to lung metastases. Tumors produced HGF and displayed phosphorylated c-Met, which correlated with increased Akt as well as c-myc activation. A high growth rate, as demonstrated by Ki67 nuclear antigen staining, and a lack of progesterone receptor were characteristic of the tumors. Immunohistochemical analysis revealed areas of osteopontin (Opn) expression in WAP-HGF tumors and lung metastases in agreement with a previously reported role for Opn in invasive growth. We suggest that these mice may serve as a new breast cancer model for the evaluation of the effects of unscheduled HGF expression in breast cancer. C1 Fdn Marcelino Botin, Ctr Invest Energet Medioambientales & Tecnol, Project Breast Canc, Madrid 28042, Spain. NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Gallego, MI (reprint author), CIEMAT, Av Complutense 22,Edificio 7, E-28040 Madrid, Spain. NR 62 TC 72 Z9 76 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 20 PY 2003 VL 22 IS 52 BP 8498 EP 8508 DI 10.1038/sj.onc.1207063 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 744UB UT WOS:000186650300013 PM 14627990 ER PT J AU Bilski, P Burkhart, JG Chignell, CF AF Bilski, P Burkhart, JG Chignell, CF TI Photochemical characterization of water samples from Minnesota and Vermont sites with malformed frogs: potential influence of photosensitization by singlet molecular oxygen (O-1(2)) and free radicals on aquatic toxicity SO AQUATIC TOXICOLOGY LA English DT Article DE malformed frogs; UV radiation; photosensitization ID AMPHIBIAN POPULATION DECLINES; RANA-PIPIENS; HUMIC-ACID; PHOTOENHANCED TOXICITY; PHOTOINDUCED TOXICITY; LIMB MALFORMATIONS; AQUEOUS-SOLUTION; QUANTUM YIELDS; XENOPUS-LAEVIS; ROSE-BENGAL AB Environmental pollutants activated by UV sunlight may have contributed to the recent decline in frog populations and the concomitant increase in malformations in the USA and abroad. UV radiation is able to mutate DNA and to initiate photosensitization processes that generate mutagenic and biologically disruptive oxygen transients. We have examined water from selected sites in Minnesota and Vermont using singlet molecular oxygen (O-1(2)), detected by its phosphorescence and free radicals detected by spin trapping, as markers for photosensitization. Water from a pond in Minnesota with malformed frogs, which also causes malformations in the laboratory, photosensitized more O-1(2), even though it absorbed less UV light compared to water from a site that did not cause malformations. This suggested that unknown natural or pollutant agents were present, and that photosensitization may be involved. Although UV irradiation of the two Minnesota water samples in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) revealed the presence of the DMPO/(OH)-O-., DMPO/H-.(e(aq)(-)) and DMPO/C-.(unknown) adducts there were no qualitative or quantitative differences between them. We also examined water samples from several sites in Vermont, and compared them by measuring the quantum yield of O-1(2) photosensitization. While all the Vermont samples produced a small amount of O-1(2), there was no clear correlation with the incidence of frog malformations. However, the samples differed strongly in absorption spectra and the ability to quench O-1(2). These factors may determine how much UV light is absorbed and converted into chemical reactions. Our results show that photochemical characterization of O-1(2) photosensitization is possible in untreated natural water samples. Photosensitization falls into the category of global factors that may be closely associated with the effects of UV irradiation of the Earth's environments. Thus, photosensitization might be an important component in global amphibian malformation and decline. The observation of O-1(2) emission directly from natural water may also provide new opportunities to investigate the involvement of O-1(2) in other complex environmental processes. (C) 2003 Elsevier B.V. All rights reserved. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Toxicol Lab, ETP, Res Triangle Pk, NC 27709 USA. RP Bilski, P (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. NR 55 TC 9 Z9 10 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-445X J9 AQUAT TOXICOL JI Aquat. Toxicol. PD NOV 19 PY 2003 VL 65 IS 3 BP 229 EP 241 DI 10.1016/S0166-445X(03)00138-3 PG 13 WC Marine & Freshwater Biology; Toxicology SC Marine & Freshwater Biology; Toxicology GA 725LK UT WOS:000185544500001 PM 13678843 ER PT J AU Lowy, DR Gillison, ML AF Lowy, DR Gillison, ML TI A new link between Fanconi anemia and human papillomavirus-associated malignancies SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID SQUAMOUS-CELL CARCINOMA; EPIDERMODYSPLASIA-VERRUCIFORMIS; CERVICAL CARCINOGENESIS; P53 POLYMORPHISM; CANCER; HEAD; E6 C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Johns Hopkins Med Inst, Baltimore, MD USA. RP Lowy, DR (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 37,Rm 4106,MSC 4263, Bethesda, MD 20892 USA. NR 27 TC 30 Z9 32 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 19 PY 2003 VL 95 IS 22 BP 1648 EP 1650 DI 10.1093/jnci/djg125 PG 3 WC Oncology SC Oncology GA 747JF UT WOS:000186800900002 PM 14625250 ER PT J AU Cha, HJ Jeong, MJ Kleinman, HK AF Cha, HJ Jeong, MJ Kleinman, HK TI Role of thymosin beta(4) in tumor metastasis and angiogenesis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ENDOTHELIAL-CELLS; GROWTH-FACTOR; IN-VIVO; ACTIN; EXPRESSION; BINDING; CANCER; ADENOVIRUS; MEDIATORS; MIGRATION AB Background. Expression of the small peptide thymosin beta(4) is associated with angiogenesis induction, accelerated wound healing, and the metastatic potential of tumor cells. However, little is known about the mechanism(s) by which thymosin beta(4) promotes metastasis. Methods: Northern blot analysis and immunohistochemistry were used to examine thymosin beta(4) expression in mouse melanoma B16 cell lines and in B16-F10 cells derived from metastatic mouse lung tumors, respectively. B16-F10 cells infected with adenoviruses containing a thymosin beta(4) expression vector or an empty vector were injected subcutaneously and intravenously into C57BL/6 mice to evaluate tumor growth and metastatic potential, respectively. In vitro assays were used to study cell migration, invasion, matrix metalloproteinase activity, cell proliferation, and angiogenic activity of adenovirus-infected B16-F10 cells. Statistical significance of all results was analyzed by two-tailed Student's t tests. Results: Thymosin beta(4) mRNA was expressed in primary cultured B16-F10 cells derived from lung metastases and in B16-F10 cells that had formed lung tumors after being injected into mice but not in the B16-F1, B16-F10, or B16-BL6 cell lines. The mean tumor sizes in mice 20 days after injection with B16-F10 cells infected with thymosin beta(4)-expressing adenovirus and with control adenovirus were 21.7 min (95% confidence interval [CI] = 17.7 to 25.7 mm) and 13.3 mm, (95% CI = 11.1 to 15.3 mm), respectively (difference = 8.4 mm; P =.036). The mean numbers of metastatic lung nodules in mice (n = 20) 2 weeks after intravenous injection with thymosin beta(4)-expressing adenovirus and with control adenovirus were 46.7 (95 % CI = 35.0 to 57.7) and 10.9 (95 % CI = 6.2 to 15.6), respectively (difference = 35.8 metastatic lung nodules, P<.001). Thymosin 04 overexpression was associated with a mean 2.3-fold increase (95% CI = 1.9- to 2.7-fold increase; P<.001) in B16-F10 cell migration and a mean 4.4-fold increase (95% CI = 3.3- to 5.5-fold increase; P<.001) in the number of blood vessels in solid tumors derived from injected B16-F10 cells but had no effect on cell invasion, proliferation, or matrix metalloproteinase activity. This induction of angiogenesis by thymosin β(4) was associated with induction of vascular endothelial growth factor expression. Conclusion: Thymosin β(4) may stimulate tumor metastasis by activating cell migration and angiogenesis. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Chosun Univ, Coll Dent, Dept Oral Histol, Gwanju, South Korea. RP Kleinman, HK (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. NR 32 TC 152 Z9 168 U1 1 U2 9 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 19 PY 2003 VL 95 IS 22 BP 1674 EP 1680 DI 10.1093/jnci/djg100 PG 7 WC Oncology SC Oncology GA 747JF UT WOS:000186800900008 PM 14625258 ER PT J AU Stillman, FA Hartman, AM Graubard, BL Gilpin, EA Murray, DM Gibson, JT AF Stillman, FA Hartman, AM Graubard, BL Gilpin, EA Murray, DM Gibson, JT TI Evaluation of the American Stop Smoking Intervention Study (ASSIST): A report of outcomes SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ADULT CIGARETTE-SMOKING; TOBACCO CONTROL PROGRAM; HEART HEALTH-PROGRAM; COMMUNITY INTERVENTION; CESSATION COMMIT; PREVENTION; CALIFORNIA; ORDINANCES; INDUSTRY; DISEASE AB Background: The National Cancer Institute funded an 8-year, nonrandomized demonstration project for tobacco prevention and control, the American Stop Smoking Intervention Study (ASSIST). To evaluate ASSIST, we compared changes in adult smoking prevalence, per capita cigarette consumption, and tobacco control policies between the 17 ASSIST states and the 33 non-ASSIST states and the District of Columbia. Methods: The strength of tobacco control index was used to measure state-level program elements directed at tobacco control, and the initial outcomes index (IOI) was used to measure states' tobacco control policy outcomes. Prevalence data were obtained from the Tobacco Use Supplement to the Current Population Survey, and consumption data were obtained from the Tobacco Institute's bimonthly sales figures for cigarette packs moved from wholesale warehouses. Two-stage regression and mixed-effects linear modeling were used to analyze the various outcomes. Statistical analyses for testing individual regression coefficients were one-sided. Results: ASSIST states had a greater decrease in adult smoking prevalence than non-ASSIST states, with an adjusted difference of -0.63% (P =.049). Per capita cigarette consumption was not statistically significantly different between ASSIST and non-ASSIST states. However, an increase in the IOI of a state from the 25(th) to the 75(th) percentile was associated with a reduction in per capita cigarette consumption by 0.57 packs per person per month. State IOI was also inversely, albeit not statistically significantly, associated with smoking prevalence (regression coefficient = -0.11; P =.06). Conclusions: The reduction in adult smoking prevalence associated with ASSIST could have translated into approximately 278 700 fewer smokers nationwide if all states had implemented ASSIST. Investment in building state-level tobacco control capacity and promoting changes in tobacco control policies are effective strategies for reducing tobacco use. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Inst Global Tobacco Control, Baltimore, MD 21205 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Calif San Diego, Canc Prevent & Control Program, San Diego, CA 92103 USA. Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Stillman, FA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Inst Global Tobacco Control, 615 N Wolfe St,Rm W6027, Baltimore, MD 21205 USA. NR 52 TC 64 Z9 69 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 19 PY 2003 VL 95 IS 22 BP 1681 EP 1691 DI 10.1093/jnci/djg098 PG 11 WC Oncology SC Oncology GA 747JF UT WOS:000186800900009 PM 14625259 ER PT J AU Roth, MJ Baer, DJ Albert, PS Castonguay, TW Dorgan, JF Dawsey, SM Brown, ED Hartman, TJ Campbell, WS Giffen, CA Judd, JT Taylor, PR AF Roth, MJ Baer, DJ Albert, PS Castonguay, TW Dorgan, JF Dawsey, SM Brown, ED Hartman, TJ Campbell, WS Giffen, CA Judd, JT Taylor, PR TI Relationship between serum leptin levels and alcohol consumption in a controlled feeding and alcohol ingestion study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BREAST-CANCER; POSTMENOPAUSAL WOMEN; GROWTH-FACTOR; EPITHELIAL-CELLS; BODY-COMPOSITION; PROSTATE-CANCER; INSULIN; POPULATION; SECRETION; SMOKING AB We examined serum leptin levels in a controlled feeding and alcohol ingestion study to elucidate potential mechanisms by which alcohol may affect cancer and immunologically related health risks. A total of 53 healthy, nonsmoking postmenopausal women completed a random-order, three-period crossover design study in which each woman received zero (0 g of alcohol), one (15 g of alcohol), or two (30 g alcohol) drinks per day. After accounting for differences in body mass index, women who consumed 15 or 30 g of alcohol per day had 7.3% (95% confidence interval [CI] = 3.0% to 15.1%) and 8.9% (95% CI = 1.6% to 16.7%) higher serum leptin levels, respectively (P-trend =.018), than women who consumed 0 g of alcohol per day. Younger women (i.e., 49-54 years) demonstrated a statistically significantly larger association of alcohol consumption level with the increase in serum leptin levels than older women (i.e., 55-79 years) (24.4%, 95 % CI = 9.3 % to 42.0 % versus 3.7 %, 95 % CI = - 4.1 % to 12.1 % increase in serum leptin levels for 30 g of alcohol per day relative to 0 g of alcohol per day for the lowest age quartile compared with the three highest age quartiles combined; P =.022). These results indicate that moderate alcohol consumption (15-30 g of alcohol per day) increases serum leptin levels in postmenopausal women and may predispose moderate drinkers to the morbidities associated with chronic elevations of this hormone including cancer. C1 NCI, Canc Prevent Studies Branch, Ctr Canc Res, NIH, Rockville, MD USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Rockville, MD USA. ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Roth, MJ (reprint author), NCI, Canc Prevent Studies Branch, Ctr Canc Res, NIH, 6116 Execut Blvd,Ste 705,MSC 8314, Bethesda, MD 20892 USA. OI Castonguay, Thomas/0000-0003-1176-5095 NR 30 TC 22 Z9 22 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 19 PY 2003 VL 95 IS 22 BP 1722 EP 1725 DI 10.1093/jnci/djg090 PG 4 WC Oncology SC Oncology GA 747JF UT WOS:000186800900014 PM 14625264 ER PT J AU Harlan, LC Clegg, LX Warren, JL AF Harlan, LC Clegg, LX Warren, JL TI Chemotherapy in women with breast cancer SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NCI, Rockville, MD 20852 USA. RP Harlan, LC (reprint author), NCI, Rockville, MD 20852 USA. NR 3 TC 4 Z9 4 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 18 PY 2003 VL 139 IS 10 BP 868 EP 868 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 744ZV UT WOS:000186663500021 PM 14623632 ER PT J AU Phan, J Lee, K Cherry, S Tropea, JE Burke, TR Waugh, DS AF Phan, J Lee, K Cherry, S Tropea, JE Burke, TR Waugh, DS TI High-resolution structure of the Yersinia pestis protein tyrosine phosphatase YopH in complex with a phosphotyrosyl mimetic-containing hexapeptide SO BIOCHEMISTRY LA English DT Article ID N-TERMINAL DOMAIN; IMPORTANT VIRULENCE MECHANISM; SUBSTRATE-BINDING DOMAIN; CRYSTAL-STRUCTURE; CATALYTIC MECHANISM; FOCAL ADHESIONS; III SECRETION; IDENTIFICATION; SPECIFICITY; RECOGNITION AB Yersinia pestis, the causative agent of bubonic plague, secretes a eukaryotic-like protein tyrosine phosphatase (PTPase) termed Yersinia outer protein H (YopH) that is essential for virulence. We have determined, for the first time, the crystal structure of the YopH PTPase domain in complex with a nonhydrolyzable substrate analogue, the hexapeptide mimetic Ac-DADE-F(2)Pmp-L-NH2. As anticipated, the mode of ligand binding in the active site is similar to the way in which the corresponding phosphohexapeptide binds to the structurally homologous human PTP1B. Unexpectedly, however, the crystal structure also revealed a second substrate-binding site in YopH that is not present in PTP1B. The mode of binding and structural conformation of the hexapeptide analogue is quite different in the two sites. Although the biological function of the second substrate-binding site remains to be investigated, the structure of a substrate analogue in the active site of Y. pestis YopH opens the door for the structure-based design and optimization of therapeutic countermeasures to combat this potential agent of bioterrorism. C1 NCI, Macromol Crystallog Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. NCI, Med Chem Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. RI Burke, Terrence/N-2601-2014 NR 49 TC 39 Z9 39 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 18 PY 2003 VL 42 IS 45 BP 13113 EP 13121 DI 10.1021/bi030156m PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743ER UT WOS:000186559900003 PM 14609321 ER PT J AU Fuhrer, MJ Jutai, JW Scherer, MJ Deruyter, F AF Fuhrer, MJ Jutai, JW Scherer, MJ Deruyter, F TI A framework for the conceptual modelling of assistive technology device outcomes SO DISABILITY AND REHABILITATION LA English DT Review AB Purpose: A key step in planning assistive technology outcomes research is formulation of a conceptual model, specific to a particular type of device, that provides a rationale for the expected outcomes. This paper reflects the conviction that the development of device-specific causal models will be facilitated by having available an overarching framework that is potentially applicable to multifarious types of devices and their outcomes. Method: A literature review identified the critical, unmet needs for a conceptual framework. The assumptions underlying the framework were specified preparatory to describing it and discussing its implications. Results: The outcomes of assistive technology devices are depicted as resulting from the interaction among characteristics of a specific device-type, its users, and their environment. Initial junctures include procurement of a type of device and a period of introductory use that, interacting with various moderating co-factors, result in a variety of shorter-term outcomes, possible longer-term use, and its outcomes. Conclusions: The framework has the potential of facilitating the development of device-specific causal models. It also may contribute to developing a research agenda for assistive technology outcomes research by highlighting measures that need to be developed and by identifying testable hypotheses concerned, for example, with the manner and duration of devices' usage. C1 NICHHD, NIH, Damascus, MD 20872 USA. Univ Western Ontario, Dept Phys Med & Rehabil, London, ON, Canada. Inst Matching Person & Technol, Webster, NY USA. Duke Univ, Med Ctr, Div Speech Pathol & Audiol, Durham, NC USA. RP Fuhrer, MJ (reprint author), NICHHD, NIH, 13 Kings Valley Ct, Damascus, MD 20872 USA. OI Scherer, Marcia/0000-0001-8374-6526; Jutai, Jeffrey/0000-0002-7294-1323 NR 31 TC 73 Z9 73 U1 4 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1464-5165 J9 DISABIL REHABIL JI Disabil. Rehabil. PD NOV 18 PY 2003 VL 25 IS 22 BP 1243 EP 1251 DI 10.1080/09638280310001596207 PG 9 WC Rehabilitation SC Rehabilitation GA 742ZB UT WOS:000186547000001 PM 14617441 ER PT J AU Robey, RW Honjo, Y Morisaki, K Nadjem, TA Runge, S Risbood, M Poruchynsky, MS Bates, SE AF Robey, RW Honjo, Y Morisaki, K Nadjem, TA Runge, S Risbood, M Poruchynsky, MS Bates, SE TI Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity SO BRITISH JOURNAL OF CANCER LA English DT Article DE drug-resistance; BCRP/MXR/ABCP/ABCG2; mitoxantrone; flow cytometry; mutation ID CANCER RESISTANCE PROTEIN; MULTIDRUG-RESISTANCE; HALF-TRANSPORTER; P-GLYCOPROTEIN; FUMITREMORGIN C; CARCINOMA CELLS; STEM-CELLS; MXR ABCG2; OVEREXPRESSION; MITOXANTRONE AB Recent studies have shown that mutations at amino-acid 482 in the ABCG2 gene affect the substrate specificity of the protein. To delineate the effects of these mutations clearly, human embryonic kidney cells (HEK-293) were stably transfected with wild-type 482R or mutant 482G and 482T ABCG2. By flow cytometry, mitoxantrone, BODIPY-prazosin, and Hoechst 33342 were found to be substrates of all ABCG2 proteins, while rhodamine 123, daunorubicin, and LysoTracker Green were transported only by mutant ABCG2. In cytotoxicity assays, all ABCG2 proteins conferred high levels of resistance to mitoxantrone, SN-38, and topotecan, while mutant ABCG2 also exhibited a gain of function for mitoxantrone as they conferred a four-fold greater resistance compared to wild type. Cells transfected with mutant ABCG2 were 13- to 71-fold resistant to the P-glycoprotein substrates doxorubicin, daunorubicin, epirubicin, bisantrene, and rhodamine 123 compared to cells transfected with wild-type ABCG2, which were only three- to four-fold resistant to these compounds. ABCG2 did not confer appreciable resistance to etoposide, taxol or the histone deacetylase inhibitor depsipeptide. None of the transfected cell lines demonstrated resistance to flavopiridol despite our previous observation that ABCG2-overexpressing cell lines are cross-resistant to the drug. Recently reported inhibitors of ABCG2 were evaluated and 50 muM novobiocin was found to reverse wild-type ABCG2 completely, but only reverse mutant ABCG2 partially. The studies presented here serve to underscore the importance of amino-acid 482 in defining the substrate specificity of the ABCG2 protein and raise the possibility that amino-acid 482 mutations in human cancers could affect the clinical application of antagonists for ABCG2. C1 NIH, Ctr Canc Res, Canc Therapeut Branch, Bethesda, MD 20892 USA. RP Robey, RW (reprint author), NIH, Ctr Canc Res, Canc Therapeut Branch, 9000 Rockville Pike,Bldg 10,Rm 12C103, Bethesda, MD 20892 USA. NR 31 TC 210 Z9 218 U1 0 U2 10 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 17 PY 2003 VL 89 IS 10 BP 1971 EP 1978 DI 10.1038/sj.bjc.6601370 PG 8 WC Oncology SC Oncology GA 747DM UT WOS:000186790000029 PM 14612912 ER PT J AU Veazey, RS Klasse, PJ Ketas, TJ Reeves, JD Piatak, M Kunstman, K Kuhmann, SE Marx, PA Lifson, JD Dufour, J Mefford, M Pandrea, I Wolinsky, SM Doms, RW DeMartino, JA Siciliano, SJ Lyons, K Springer, MS Moore, JP AF Veazey, RS Klasse, PJ Ketas, TJ Reeves, JD Piatak, M Kunstman, K Kuhmann, SE Marx, PA Lifson, JD Dufour, J Mefford, M Pandrea, I Wolinsky, SM Doms, RW DeMartino, JA Siciliano, SJ Lyons, K Springer, MS Moore, JP TI Use of a small molecule CCR5 inhibitor in macaques to treat simian immunodeficiency virus infection or prevent simian-human immunodeficiency virus infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE HIV; AIDS; antiretroviral therapy; microbicide; chemokine receptor ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; ENTRY INHIBITORS; RHESUS MACAQUES; IN-VITRO; CHEMOKINE RECEPTORS; LANGERHANS CELLS; TYPE-1 ENTRY; T-CELLS; DC-SIGN AB Human immunodeficiency virus type 1 (HIV-1) fuses with cells after sequential interactions between its envelope glycoproteins, CD4 and a coreceptor, usually CC chemokine receptor 5 (CCR5) or CXC receptor 4 (CXCR4). CMPD 167 is a CCK5-specific small molecule with potent antiviral activity in vitro. We show that CMPD 167 caused a rapid and substantial (4200-fold) decrease in plasma viremia in six rhesus macaques chronically infected with simian immunodeficiency virus (SIV) strains SIVmac251 or SIVB670, but not in an animal infected with the X4 simian-human immunodeficiency virus (SHIV), SHIV-89.6P. In three of the SIV-infected animals, viremia reduction was sustained. In one, there was a rapid, but partial, rebound and in another, there was a rapid and complete rebound. There was a substantial delay (>21 d) between the end of therapy and the onset of full viremia rebound in two animals. We also evaluated whether vaginal administration of gel-formulated CMPD 167 could prevent vaginal transmission of the R5 virus, SHIV-162P4. Complete protection occurred in only 2 of 11 animals, but early viral replication was significantly less in the 11 CMPD 167-recipients than in 9 controls receiving carrier gel. These findings support the development of small molecule CCR5 inhibitors as antiviral therapies, and possibly as components of a topical microbicide to prevent HIV-1 sexual transmission. C1 Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. Tulane Univ, Hlth Sci Ctr, Tulane Natl Primate Res Ctr, Covington, LA 70433 USA. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. NCI, Sci Applicat Int Corp Frederick Inc, AIDS Vaccine Program, Retroviral Pathogenesis Lab, Frederick, MD 20702 USA. Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. Merck Res Labs, Dept Immunol & Rheumatol, Rahway, NJ 07065 USA. Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA. Merck Res Labs, Dept Atherosclerosis & Endocrinol, Rahway, NJ 07065 USA. RP Moore, JP (reprint author), Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, 1300 York Ave,W-805, New York, NY 10021 USA. RI Wolinsky, Steven/B-2893-2012; Reeves, Jacqueline/I-5379-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU NCI NIH HHS [N01-CO-124000]; NCRR NIH HHS [RR00164, P51 RR000164]; NIAID NIH HHS [AI41420, AI49080, AI52048, P01 AI052048, R01 AI041420, R01 AI049080]; NICHD NIH HHS [HD36310] NR 69 TC 117 Z9 122 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 17 PY 2003 VL 198 IS 10 BP 1551 EP 1562 DI 10.1084/jem.20031266 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 748CX UT WOS:000186845600010 PM 14623909 ER PT J AU Cesari, M Penninx, BWJH Lauretani, F Russo, CR Pahor, M Ferrucci, L AF Cesari, M Penninx, BWJH Lauretani, F Russo, CR Pahor, M Ferrucci, L TI Hemoglobin levels, skeletal muscle and disability in the elderly. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. INRCA Geriatr Dept, Lab Clin Epidemiol, Florence, Italy. NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 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 2003 VL 102 IS 11 MA 3719 BP 5B EP 5B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100010 ER PT J AU Liem, RI Seidel, NE Wong, C Cline, AP Gallagher, PG Bodine, DM AF Liem, RI Seidel, NE Wong, C Cline, AP Gallagher, PG Bodine, DM TI Hereditary spherocytosis mutations in an erythroid ankyrin insulator element are associated with gene silencing in vitro and promoter dysfunction in transgenic mice. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHGRI, Hematopoiesis Sect, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 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 2003 VL 102 IS 11 MA 9 BP 7A EP 7A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700010 ER PT J AU Schulze, H Korpal, M Bergmeier, W Italiano, JE Wahl, SM Wagner, DD Shivdasani, RA AF Schulze, H Korpal, M Bergmeier, W Italiano, JE Wahl, SM Wagner, DD Shivdasani, RA TI SLPI is a beta 1-tubulin binding protein that is expressed in megakaryocytes and platelets. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. NIH, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 2003 VL 102 IS 11 MA 31 BP 12A EP 12A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700032 ER PT J AU Alter, BP Peters, J Carr, A Lansdorp, PM Baerlocher, GM Willner, JP Weksler, BB AF Alter, BP Peters, J Carr, A Lansdorp, PM Baerlocher, GM Willner, JP Weksler, BB TI Dyskeratosis congenita (DC): Molecular diagnosis in a patient with no DC phenotype. Implications for future management. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. WESTAT Corp, Rockville, MD 20850 USA. British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. Univ British Columbia, Dept Med, Vancouver, BC, Canada. Univ Bern, Inselspital, Dept Hematol, CH-3010 Bern, Switzerland. Mt Sinai Sch Med, Dept Human Genet, New York, NY USA. Weill Cornell 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 2003 VL 102 IS 11 MA 3766 BP 16B EP 17B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537100057 ER PT J AU Alter, BP Huang, Y Rosenberg, PS AF Alter, BP Huang, Y Rosenberg, PS TI Individualized risk of adverse events in Fanconi's anemia (FA). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21218 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 2003 VL 102 IS 11 MA 3765 BP 16B EP 16B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100056 ER PT J AU Guralnik, JM Eisenstaedt, RS Ferrucci, L Klein, HG Woodman, RC AF Guralnik, JM Eisenstaedt, RS Ferrucci, L Klein, HG Woodman, RC TI The prevalence of anemia in persons age 65 and older in the United States: Evidence for a high rate of unexplained anemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Temple Univ, Sch Med, Dept Internal Med, Philadelphia, PA 19122 USA. NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. Ortho Biotech Prod LP, Bridgewater, NJ 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 2003 VL 102 IS 11 MA 3770 BP 17B EP 17B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100061 ER PT J AU Li, LH Zhang, JW Niu, C Ye, L Huang, HY He, X Tong, WG Ross, J Haug, J Johnson, T Feng, JQ Harris, SE Wiedemann, LM Mishina, Y AF Li, LH Zhang, JW Niu, C Ye, L Huang, HY He, X Tong, WG Ross, J Haug, J Johnson, T Feng, JQ Harris, SE Wiedemann, LM Mishina, Y TI Identification of the hematopoietic stem cell niche. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Missouri, Sch Dent, Kansas City, MO 64110 USA. Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC USA. Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA. Stowers Inst Med Res, Kansas City, MO 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 2003 VL 102 IS 11 MA 51 BP 18A EP 18A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700052 ER PT J AU Ferrucci, L Penninx, BW Lauretani, F Guralnik, JM Woodman, RC AF Ferrucci, L Penninx, BW Lauretani, F Guralnik, JM Woodman, RC TI Defining anemia using compensatory changes in serum erythropoietin (EPO): The InChianti study. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIA, NIH, Baltimore, MD 21224 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. INRCA, Florence, Italy. Ortho Biotech Prod LP, Bridgewater, NJ 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 2003 VL 102 IS 11 MA 3782 BP 20B EP 20B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100073 ER PT J AU Guasch, A Waqas, M Niaz, S Hsu, LL AF Guasch, A Waqas, M Niaz, S Hsu, LL TI Transgenic sickle cell mice develop a glomerular lesion similar to human sickle cell glomerulopathy. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Emory Univ, Dept Med, Div Renal, Atlanta, GA 30322 USA. NIH, Philadelphia, PA USA. St Christophers Hosp Children, Div Pediat Hematol Oncol, Philadelphia, PA 19133 USA. RI Hsu, Lewis/A-3360-2008 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 2003 VL 102 IS 11 MA 3820 BP 30B EP 30B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100111 ER PT J AU Rezvani, K Grube, M Brenchley, JM Price, DA Sconocchia, G Fujiwara, H Gostick, E Hensel, N Douek, DC Barrett, AJ AF Rezvani, K Grube, M Brenchley, JM Price, DA Sconocchia, G Fujiwara, H Gostick, E Hensel, N Douek, DC Barrett, AJ TI Four distinct HLA-A*0201-presented epitopes of the Wilms tumor antigen I (WT1) function as targets for leukemia-reactive CD8(+) T cells in patients with chronic myeloid leukemia (CML). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Nuffield Dept Med, Oxford, England. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 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 2003 VL 102 IS 11 MA 97 BP 31A EP 31A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700098 ER PT J AU Linden, MA Cheung, WCG Kim, JS Park, SS Kirchhof, N Carlson, CS Polakiewicz, R Janz, S Van Ness, BG AF Linden, MA Cheung, WCG Kim, JS Park, SS Kirchhof, N Carlson, CS Polakiewicz, R Janz, S Van Ness, BG TI Novel targeted deregulation of Bcl-X-L and c-Myc leads to accelerated plasma cell malignancies. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Minnesota, Sch Med, Ctr Canc, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Vet, Ctr Canc, Minneapolis, MN 55455 USA. Cell Signal Technol, Beverly, MA USA. NCI, 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 2003 VL 102 IS 11 MA 111 BP 35A EP 35A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700111 ER PT J AU Kato, GJ Martyr, S Wang, B Nichols, J Coles, WA Hunter, L Gladwin, MT AF Kato, GJ Martyr, S Wang, B Nichols, J Coles, WA Hunter, L Gladwin, MT TI Soluble VCAM-1 level in patients with sickle cell disease is a marker of endothelial dysfunction improved with hydroxyurea treatment, and associated with severity of hemolysis and pulmonary hypertension. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 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 2003 VL 102 IS 11 MA 141 BP 44A EP 44A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700141 ER PT J AU Inoue, A Kuroyanagi, Y Terui, K Cokic, VP Schechter, AN Ausenda, S Cappellini, MD Ikuta, T AF Inoue, A Kuroyanagi, Y Terui, K Cokic, VP Schechter, AN Ausenda, S Cappellini, MD Ikuta, T TI Intracellular signaling pathways that control fetal to beta-globin gene switching. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Milan, Maggiore Hosp, IRCCS, Hereditary Anemia Ctr, Milan, Italy. 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 2003 VL 102 IS 11 MA 151 BP 46A EP 47A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700151 ER PT J AU Wen, J Rogers, HM Noguchi, CT AF Wen, J Rogers, HM Noguchi, CT TI The involvement of SATB1 in the regulation of early-stage globin gene expression. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDKD, Biol Chem Lab, 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 2003 VL 102 IS 11 MA 150 BP 46A EP 46A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700150 ER PT J AU Bauer, TR Creevy, KE Gu, YC Donahue, RE Metzger, ME Tuschong, LM Embree, LJ Hickstein, DD AF Bauer, TR Creevy, KE Gu, YC Donahue, RE Metzger, ME Tuschong, LM Embree, LJ Hickstein, DD TI Very low-levels of CD18+neutrophils in the peripheral blood after non-myeloablative matched littermate transplant corrects the disease phenotype in dogs with canine leukocyte adhesion deficiency. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NHLBI, Hematol 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 2003 VL 102 IS 11 MA 153 BP 47A EP 47A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700153 ER PT J AU Trice, TA Bhanu, NV Lee, YT Schwartz, JD Miller, JL AF Trice, TA Bhanu, NV Lee, YT Schwartz, JD Miller, JL TI Ex vivo reversal of gamma-globin gene silencing and production of HbF-dominant, mature adult human erythroblasts using combinatorial signal transduction. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDK, Biol Chem Lab, NIH, 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 2003 VL 102 IS 11 MA 152 BP 47A EP 47A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700152 ER PT J AU Bernig, T Staats, B Yeager, M Taylor, JG Foster, CB Chanock, SJ AF Bernig, T Staats, B Yeager, M Taylor, JG Foster, CB Chanock, SJ TI Using haplotype-tagging SNPs (htSNPs) to detect locus wide haplotype diversity in the mannose-binding lectin gene, MBL2, for genetic association studies. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, NIH, Pediat Oncol Branch, Sect Genom Variat, Gaithersburg, MD USA. NCI, NIH, Core Genotyping Facil, Gaithersburg, MD USA. Johns Hopkins Univ, Dept Pediat, Div Infect Dis, Baltimore, MD 21218 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 2003 VL 102 IS 11 MA 3903 BP 50B EP 50B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100194 ER PT J AU Konno, A Wada, T Schurman, SH Garabedian, EK Kirby, M Anderson, SM Candotti, F AF Konno, A Wada, T Schurman, SH Garabedian, EK Kirby, M Anderson, SM Candotti, F TI Detection of revertant B lymphocytes in a patient with somatic mosaicism reveales differential contribution of Wiskott-Aldrich syndrome protein to selective advantage in T and B cell lineages. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet 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 2003 VL 102 IS 11 MA 3904 BP 50B EP 51B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537100195 ER PT J AU Wlodarski, M Howe, E Plasilova, M O'Keefe, C Risitano, A Rodriguez, A Maciejewski, JP AF Wlodarski, M Howe, E Plasilova, M O'Keefe, C Risitano, A Rodriguez, A Maciejewski, JP TI The role of epigenetic factors in shaping TCR repertoire of cytotoxic T cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Cleveland Clin Fdn, Ctr Canc, Expt Hematol & Hematopoiesis Sect, Cleveland, OH 44195 USA. 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 2003 VL 102 IS 11 MA 3939 BP 59B EP 59B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100230 ER PT J AU Goldfarb, AN Elagib, K Xiao, M Hussaini, IM Racke, FK Birrer, MJ Castellazzi, M AF Goldfarb, AN Elagib, K Xiao, M Hussaini, IM Racke, FK Birrer, MJ Castellazzi, M TI Jun blockade of erythropoiesis: Repression of GATA-1 by a novel transcriptional pathway involving the hairy-enhancer-of-split related factor HERP2. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. NCI, Mol Mech Sect, Rockville, MD USA. Ecole Normale Super Lyon, INSERM, U412, F-69364 Lyon, 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 2003 VL 102 IS 11 MA 200 BP 60A EP 60A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700200 ER PT J AU Takahashi, Y Aoki, I Chuang, KH Igarashi, T Silva, AC Tanaka, C Koretsky, AP Childs, RW AF Takahashi, Y Aoki, I Chuang, KH Igarashi, T Silva, AC Tanaka, C Koretsky, AP Childs, RW TI Labelling human lymphocytes for magnetic resonance imaging (MRI) using manganese chloride. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. Meiji Univ Oriental Med, Dept Med Informat, Kyoto, Japan. RI Aoki, Ichio/G-2529-2011 OI Aoki, Ichio/0000-0002-4429-5053 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 2003 VL 102 IS 11 MA 3947 BP 61B EP 61B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100238 ER PT J AU Rosenwald, A Wright, G Leroy, K Yu, X Gaulard, P Gascoyne, RD Chan, WC Zhao, T Haioun, C Greiner, TC Weisenburger, DD Lynch, JC Vose, JM Armitage, JO Smeland, EB Kvaloy, S Holte, H Delabie, J Campo, E Montserrat, E Lopez-Guillermo, A Ott, G Muller-Hermelink, HK Connors, JM Braziel, R Grogan, TM Fisher, RI Miller, TP LeBlanc, M Chiorazzi, M Zhao, H Yang, L Powell, J Wilson, WH Jaffe, ES Simon, R Klausner, RD Staudt, LM AF Rosenwald, A Wright, G Leroy, K Yu, X Gaulard, P Gascoyne, RD Chan, WC Zhao, T Haioun, C Greiner, TC Weisenburger, DD Lynch, JC Vose, JM Armitage, JO Smeland, EB Kvaloy, S Holte, H Delabie, J Campo, E Montserrat, E Lopez-Guillermo, A Ott, G Muller-Hermelink, HK Connors, JM Braziel, R Grogan, TM Fisher, RI Miller, TP LeBlanc, M Chiorazzi, M Zhao, H Yang, L Powell, J Wilson, WH Jaffe, ES Simon, R Klausner, RD Staudt, LM TI Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma for the LLMPP SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Metab Branch, Bethesda, MD USA. NCI, Med Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD USA. NCI, Biometr Res Branch, Bethesda, MD USA. Hop Henri Mondor, Dept Pathol, Creteil, France. Univ Nebraska, Dept Pathol & Microbiol, Omaha, NE USA. UNMC, Dept Societal & Prevent Med, Omaha, NE USA. UNMC, Dept Internal Med, Omaha, NE USA. Norwegian Radium Hosp, Dept Immunol, Oslo, Norway. Norwegian Radium Hosp, Dept Oncol, Oslo, Norway. Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. Univ Barcelona, Hosp Clin, Barcelona, Spain. Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. British Columbia Canc Ctr, Vancouver, BC, Canada. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Univ Arizona, Ctr Canc, Dept Pathol, Tucson, AZ 85721 USA. Univ Arizona, Ctr Canc, Dept Med, Tucson, AZ 85721 USA. Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. CIT, CBEL, Bioinformat & Mol Anal Sect, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 2003 VL 102 IS 11 MA 208 BP 62A EP 62A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700208 ER PT J AU Grever, MR Dewald, GW Lucas, DM Neuberg, DS Baird, ME Paternoster, SF Brockman, SR Lozanski, G Rizouli, V Gribben, JG Flinn, IW Tallman, MS Kitada, S Reed, JC Staudt, LM Paietta, E Byrd, JC AF Grever, MR Dewald, GW Lucas, DM Neuberg, DS Baird, ME Paternoster, SF Brockman, SR Lozanski, G Rizouli, V Gribben, JG Flinn, IW Tallman, MS Kitada, S Reed, JC Staudt, LM Paietta, E Byrd, JC TI ZAP-70 protein expression varies by interphase cytogenetic group and may predict disease progression to requirement of treatment among select genetic groups in patients with chronic lymphocytic leukemia (CLL). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Ohio State Univ, Columbus, OH 43210 USA. Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Burnham Inst, La Jolla, CA 92037 USA. Johns Hopkins Univ, Baltimore, MD USA. Our Lady Mercy Bronx, Bronx, NY USA. NIH, Bethesda, MD 20892 USA. Northwestern Univ, Chicago, IL 60611 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 2003 VL 102 IS 11 MA 244 BP 73A EP 73A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700244 ER PT J AU Calmels, B Kulka, M Metzger, M Keyvanfar, K Sellers, S Metcalfe, D Dunbar, C AF Calmels, B Kulka, M Metzger, M Keyvanfar, K Sellers, S Metcalfe, D Dunbar, C TI Genetic tracking of basophil and mast cell lineage relationships in vivo. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD USA. RI calmels, boris/R-2538-2016 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 2003 VL 102 IS 11 MA 279 BP 83A EP 83A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700279 ER PT J AU Fogarty, PF Seggewiss, R McCloskey, DJ Dunbar, CE Rick, ME AF Fogarty, PF Seggewiss, R McCloskey, DJ Dunbar, CE Rick, ME TI Depletion of CD25-expressing T cells and clinical responsiveness to daclizumab, an anti-IL-2 receptor antibody, in patients with immune thrombocytopenic purpura (ITP). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIH, Dept Lab Med, Hematol Serv, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 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 2003 VL 102 IS 11 MA 4042 BP 84B EP 84B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100333 ER PT J AU Berntorp, E Astermark, J Donfield, S Oldenburg, J Nelson, G Gomperts, E Winkler, C AF Berntorp, E Astermark, J Donfield, S Oldenburg, J Nelson, G Gomperts, E Winkler, C TI Genetic factors and inhibitor development: The Hemophilia Inhibitor Genetics Study (HIGS), design and methods. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Malmo Univ Hosp, Dept Coagulat Disorders, Malmo, Sweden. Rho Inc, Epidemiol & Biostat, Chapel Hill, NC USA. Inst Transfus Med & Immune Hematol, Frankfurt, Germany. NCI, Sci Applicat Int Corp, Lab Genom Divers, Frederick, MD 21701 USA. Baxter BioSci, Med Affairs, Westlake Village, CA 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 2003 VL 102 IS 11 MA 4105 BP 99B EP 99B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100396 ER PT J AU Wilson, WH Pittaluga, S Gutierrez, M Dunleavy, K Hegde, U Grant, N Steinberg, S Raffeld, M Grossbard, M Jaffe, E Janik, J AF Wilson, WH Pittaluga, S Gutierrez, M Dunleavy, K Hegde, U Grant, N Steinberg, S Raffeld, M Grossbard, M Jaffe, E Janik, J TI Dose-adjusted EPOCH-Rituximab in untreated diffuse large B-cell lymphoma: Benefit of rituximab appears restricted to tumors harboring anti-apoptotic mechanisms. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Canc Res Ctr, Bethesda, MD 20892 USA. St Lukes Roosevelt Hosp, New York, NY 10025 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 2003 VL 102 IS 11 MA 356 BP 105A EP 105A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700356 ER PT J AU Wilson, WH Neelapu, S Rosenwald, A White, T Dunleavy, K Pittaluga, S Hakim, F Stetler-Stevenson, M Steinberg, S Jaffe, ES Gress, R Wright, G Staudt, L Janik, J Kwak, L AF Wilson, WH Neelapu, S Rosenwald, A White, T Dunleavy, K Pittaluga, S Hakim, F Stetler-Stevenson, M Steinberg, S Jaffe, ES Gress, R Wright, G Staudt, L Janik, J Kwak, L TI Idiotype vaccine and dose-adjusted EPOCH-rituximab treatment untreated mantle cell lymphoma: Preliminary report on clinical outcome and analysis of immune response. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, 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 2003 VL 102 IS 11 MA 358 BP 105A EP 106A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700358 ER PT J AU Paz-Priel, I Long, L Mackall, CL Helman, LJ Wayne, AS AF Paz-Priel, I Long, L Mackall, CL Helman, LJ Wayne, AS TI Thromboembolic events (TEE) in children and young adults with sarcoma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Pediat Oncol 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 2003 VL 102 IS 11 MA 4184 BP 119B EP 119B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100475 ER PT J AU Hsu, LL Creary, M Jackson, E Gee, BE Buchanan, ID Hibbert, JM AF Hsu, LL Creary, M Jackson, E Gee, BE Buchanan, ID Hibbert, JM TI Increased cardiac output, protein and energy metabolism in children with sickle cell anemia (HbSS). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 St Christophers Hosp Children, Philadelphia, PA 19133 USA. NIH, Philadelphia, PA USA. Morehouse Sch Med, Atlanta, GA 30310 USA. RI Hsu, Lewis/A-3360-2008 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 2003 VL 102 IS 11 MA 410 BP 120A EP 121A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700410 ER PT J AU Tamura, T Kong, HJ Tailor, P Tsujimura, H Singh, H Ozato, K AF Tamura, T Kong, HJ Tailor, P Tsujimura, H Singh, H Ozato, K TI Essential roles of IRF-4 and IRF-8 in the development of dendritic cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 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 2003 VL 102 IS 11 MA 427 BP 125A EP 125A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700427 ER PT J AU Lacombe, J Krosl, G Herblot, S Martin, R Aplan, P Begley, GC Sauvageau, G Hoang, T AF Lacombe, J Krosl, G Herblot, S Martin, R Aplan, P Begley, GC Sauvageau, G Hoang, T TI Genetic interaction between SCL and c-Kit in hematopoietic cell survival. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Clin Res Inst Montreal, Montreal, PQ H2W 1R7, Canada. Univ Montreal, Dept Mol Biol & Pharmacol, Montreal, PQ, Canada. NCI, Dept Genet, Gaithersburg, MD USA. Univ Western Australia, Ctr Child Hlth Res, Perth, WA, Australia. 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 2003 VL 102 IS 11 MA 454 BP 132A EP 132A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700454 ER PT J AU Leeanansaksiri, W Wang, H Gooya, J Renn, K Keller, J AF Leeanansaksiri, W Wang, H Gooya, J Renn, K Keller, J TI Role of Id1 in proliferation and immortalization of stem cells and role of Id1 in myeloid versus lymphoid and erythroid cell fates. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, BRP, SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, LMI, CCR, Frederick, MD 21701 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 2003 VL 102 IS 11 MA 455 BP 133A EP 133A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700455 ER PT J AU Cattoretti, G Pasqualucci, L Ballon, G Tam, W Murty, VV Morse, HC Dalla-Favera, R AF Cattoretti, G Pasqualucci, L Ballon, G Tam, W Murty, VV Morse, HC Dalla-Favera, R TI A mouse model of diffuse large B-cell lymphoma induced by deregulated BCL6 expression. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Columbia Univ, Inst Canc Genet, New York, NY USA. NIAID, Immunopathol Lab, NIH, Rockville, MD USA. RI Cattoretti, Giorgio/H-2340-2011 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 2003 VL 102 IS 11 MA 466 BP 136A EP 136A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700466 ER PT J AU Yao, L Pike, SE Tosato, G AF Yao, L Pike, SE Tosato, G TI Vasostatin, an inhibitor of angiogenesis, promotes hematopoiesis in vivo. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Expt Translantat & Immunol 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 2003 VL 102 IS 11 MA 4266 BP 139B EP 140B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537100557 ER PT J AU Sloand, EM Mainwaring, LA Tarnowka, MK Barrett, AJ Young, NS AF Sloand, EM Mainwaring, LA Tarnowka, MK Barrett, AJ Young, NS TI CD34 cells from trisomy 8 patients express early apoptotic markers but do not undergo programmed cell death because of upregulation of anti-apoptotic proteins. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, 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 2003 VL 102 IS 11 MA 497 BP 145A EP 145A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700497 ER PT J AU Hu, J Anderson, S Orlic, D Dunbar, C AF Hu, J Anderson, S Orlic, D Dunbar, C TI Contrast in the mobilization of hematopoietic versus endothelial progenitors by AMD3100 in a rhesus macaque infarction model. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Mol Biol Branch, NIH, 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 2003 VL 102 IS 11 MA 4332 BP 155B EP 155B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100623 ER PT J AU Cokic, VP Jain, N Schechter, AN AF Cokic, VP Jain, N Schechter, AN TI Activation of human G protein-coupled receptor signaling pathway targeted genes by hydroxyurea in erythroid progenitor cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDKD, Biol Chem Lab, 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 2003 VL 102 IS 11 MA 4336 BP 156B EP 157B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537100627 ER PT J AU Chin, KL Drew, L Chen, L Liu, WL Rodgers, GP AF Chin, KL Drew, L Chen, L Liu, WL Rodgers, GP TI The control of hGC-1 in myelomonocytic cells relies on PU.1 and NF-kappa B binding. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDKD, Mol & Clin 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 2003 VL 102 IS 11 MA 4340 BP 157B EP 158B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537100631 ER PT J AU Yamaguchi, H Baerlocher, GM Chanock, SJ Lansdorp, PM Young, NS AF Yamaguchi, H Baerlocher, GM Chanock, SJ Lansdorp, PM Young, NS TI Telomerase reverse transcriptase enzyme gene (hTERT) mutations in patients with bone marrow failure. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 British Columbia Canc Res Ctr, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. Univ British Columbia, Dept Med, Vancouver, BC, Canada. NCI, Sect Genomic Variat, Pediat Oncol Branch, Ctr Adv Technol, Gaithersburg, MD USA. Univ Hosp Bern, Dept Hematol, CH-3010 Bern, Switzerland. NHLBI, Hematol Branch, NIH, 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 2003 VL 102 IS 11 MA 547 BP 158A EP 159A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700547 ER PT J AU Dower, NA Stang, SL Coughlin, J Zheng, Y Tiexiera, C Blumberg, P Stone, JC AF Dower, NA Stang, SL Coughlin, J Zheng, Y Tiexiera, C Blumberg, P Stone, JC TI The RasGRP family of Ras activators - a link between diacylglycerol and Ras signaling. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Alberta, Edmonton, AB T6G 2M7, Canada. NCI, Cellular Carcinogenesis & Tumor Promot Lab, 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 2003 VL 102 IS 11 MA 4367 BP 164B EP 164B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100658 ER PT J AU Klarmann, K Asefa, B Renn, K Keller, J AF Klarmann, K Asefa, B Renn, K Keller, J TI Tumor suppressors Ifi-204 and Ifi-205 inhibit primitive hematopoietic cell proliferation in vitro and in vivo and are regulated by notch. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 SAIC, BRP, Frederick, MD USA. NCI, LMI, Frederick, MD 21701 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 2003 VL 102 IS 11 MA 588 BP 169A EP 169A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700588 ER PT J AU Kim, KT Baird, K Ahn, JY Meltzer, P Small, D AF Kim, KT Baird, K Ahn, JY Meltzer, P Small, D TI Pim-1 is upregulated in constitutively activating FLT3 mutants and is one of components of the cell survival. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Johns Hopkins Med Inst, Sydney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. NHGRI, Canc Genet 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 2003 VL 102 IS 11 MA 600 BP 172A EP 172A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700600 ER PT J AU Lancet, JE Gojo, I Gotlib, J Greer, J Kaufmann, SH Liesveld, JL Adjei, A Messina, P Dugan, K Bruzek, L Lu, CH Thibault, A Rybak, ME Rackoff, W Wright, JJ Greenberg, PL Karp, JE AF Lancet, JE Gojo, I Gotlib, J Greer, J Kaufmann, SH Liesveld, JL Adjei, A Messina, P Dugan, K Bruzek, L Lu, CH Thibault, A Rybak, ME Rackoff, W Wright, JJ Greenberg, PL Karp, JE TI Tipifarnib (ZARNESTRA (TM)) in previously untreated poor-risk AML and MDS: Interim results of a phase 2 trial. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, IDB CTEP, Rockville, MD USA. Johnson & Johnson Consumer Prod Inc, PRD, Titusville, NJ USA. Mayo Clin, Rochester, MN USA. Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. Stanford Univ, Div Hematol, Stanford, CA 94305 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. NR 0 TC 11 Z9 12 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 2003 VL 102 IS 11 MA 613 BP 176A EP 176A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700613 ER PT J AU Dave, SS Wright, G Tan, B Rosenwald, A Chan, WC Gascoyne, RD Greiner, TC Weisenburger, DD Vose, J Armitage, JO Braziel, RM Miller, TP Grogan, TM Fisher, RI Smeland, EB Kvaloy, S Holte, H Delabie, J Connors, JM Muller-Hermelink, HK Ott, G Davies, AJ Norton, AJ Lister, TA Campo, E Montserrat, E Wilson, WH Jaffe, ES Chiorazzi, M Zhao, H Staudt, LM AF Dave, SS Wright, G Tan, B Rosenwald, A Chan, WC Gascoyne, RD Greiner, TC Weisenburger, DD Vose, J Armitage, JO Braziel, RM Miller, TP Grogan, TM Fisher, RI Smeland, EB Kvaloy, S Holte, H Delabie, J Connors, JM Muller-Hermelink, HK Ott, G Davies, AJ Norton, AJ Lister, TA Campo, E Montserrat, E Wilson, WH Jaffe, ES Chiorazzi, M Zhao, H Staudt, LM CA LLMPP TI A molecular predictor of survival following diagnosis of follicular lymphoma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Wurzburg, Wurzburg, Germany. St Bartholomews Hosp, London, England. Univ Barcelona, Barcelona, Spain. Univ Nebraska, Med Ctr, Lincoln, NE USA. NCI, 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 2003 VL 102 IS 11 MA 617 BP 177A EP 177A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700617 ER PT J AU Hans, CP Weisenburger, DD Greiner, TC Gascoyne, RD Delabie, J Ott, G Muller-Hermelink, HK Campo, E Braziel, R Jaffe, ES Pan, ZG Farinha, P Smith, LM Falini, B Banham, AH Rosenwald, A Staudt, LM Connors, JM Armitage, JO Chan, WC AF Hans, CP Weisenburger, DD Greiner, TC Gascoyne, RD Delabie, J Ott, G Muller-Hermelink, HK Campo, E Braziel, R Jaffe, ES Pan, ZG Farinha, P Smith, LM Falini, B Banham, AH Rosenwald, A Staudt, LM Connors, JM Armitage, JO Chan, WC TI Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Oxford, Dept Clin Lab Sci, Oxford, England. Univ Perugia, Inst Hematol, I-06100 Perugia, Italy. NCI, Hematopathol Sect, Bethesda, MD 20892 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. Univ Oregon, Hlth Sci Ctr, Dept Pathol, Portland, OR USA. Univ Barcelona, Dept Pathol, Barcelona, Spain. Univ Wurzburg, Dept Pathol, Wurzburg, Germany. Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Omaha, NE USA. RI Banham, Alison/B-2966-2009 NR 0 TC 1 Z9 1 U1 2 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 2003 VL 102 IS 11 MA 618 BP 177A EP 178A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700618 ER PT J AU Gascoyne, RD Dave, S Zettl, A Bea, S Chan, WC Rosenwald, A Jaffe, ES Campo, E Delabie, J Weisenburger, D Greiner, TC Ott, G Muller-Hermelink, K Rimsza, L Hans, C Connors, JM Wright, G Staudt, LM AF Gascoyne, RD Dave, S Zettl, A Bea, S Chan, WC Rosenwald, A Jaffe, ES Campo, E Delabie, J Weisenburger, D Greiner, TC Ott, G Muller-Hermelink, K Rimsza, L Hans, C Connors, JM Wright, G Staudt, LM TI Gene expression microarray analysis of de novo CD5(+) diffuse large B-cell lymphoma (LLMPP study): A distinct entity? SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Arizona, Ctr Canc, Tucson, AZ USA. Norwegian Radium Hosp, Oslo, Norway. NCI, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. Univ Barcelona, E-08007 Barcelona, Spain. Univ Wurzburg, Wurzburg, Germany. NCI, Metab Branch, Bethesda, MD 20892 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. NR 0 TC 5 Z9 5 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 2003 VL 102 IS 11 MA 621 BP 178A EP 179A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700621 ER PT J AU Rubio-Moscado, F Blesa, D Mestre, C Siebert, R Rosenwald, A Karran, L Martinez, JI Climent, J Marin, M Benet, I Albertson, DG Esteller, M Staudt, LM Pinkel, D Garcia-Conde, J Dyer, MJ Martinez-Climent, JA AF Rubio-Moscado, F Blesa, D Mestre, C Siebert, R Rosenwald, A Karran, L Martinez, JI Climent, J Marin, M Benet, I Albertson, DG Esteller, M Staudt, LM Pinkel, D Garcia-Conde, J Dyer, MJ Martinez-Climent, JA TI Parallel genome scanning and gene expression profiling pinpoint tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors TRAIL-DR4 and DR5 as candidate dosage-dependent tumor suppressor genes (TSGs) in B-cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 CNIO, Madrid, Spain. Univ Calif San Francisco, San Francisco, CA 94143 USA. FVIB, Valencia, Spain. Univ Leicester, Dept Haematol, Leicester, Leics, England. NCI, NIH, Bethesda, MD 20892 USA. Univ Hosp Schleswig, Kiel, Germany. Univ Valencia, Hosp Clin, Dept Hematol Oncol, Valencia, Spain. 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 2003 VL 102 IS 11 MA 620 BP 178A EP 178A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700620 ER PT J AU Zettl, A Bea, S Rosenwald, A Jehn, P Salaverria, I Ott, G Staudt, LM Chan, WC Jaffe, ES Weisenburger, DD Greiner, TC Gascoyne, RD Grogan, TM Delabie, J Mueller-Hermelink, HK Campo, E AF Zettl, A Bea, S Rosenwald, A Jehn, P Salaverria, I Ott, G Staudt, LM Chan, WC Jaffe, ES Weisenburger, DD Greiner, TC Gascoyne, RD Grogan, TM Delabie, J Mueller-Hermelink, HK Campo, E TI Different subtypes of diffuse large B-cell lymphoma defined by gene expression profiling are genetically distinct. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. Univ Arizona, Ctr Canc, SW Oncol Grp, Tucson, AZ USA. British Columbia Canc Ctr, Dept Pathol, Vancouver, BC, Canada. NCI, Hematopathol Sect, Bethesda, MD 20892 USA. Univ Nebraska, Dept Pathol, Omaha, NE 68182 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. Univ Barcelona, Hosp Clin, Anat Pathol Lab, Hematopathol Sect, Barcelona, Spain. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. NR 0 TC 2 Z9 2 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 2003 VL 102 IS 11 MA 619 BP 178A EP 178A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700619 ER PT J AU Lin, YW Zhang, ZH Apalan, PD AF Lin, YW Zhang, ZH Apalan, PD TI Distinct mechanisms lead to mutations at the HPRT locus in leukemic cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Genet Branch, Canc Res Ctr, NIH, Gaithersburg, MD USA. Kyoto Univ, Grad Sch Med, Dept Pediat, Kyoto, 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 2003 VL 102 IS 11 MA 4453 BP 184B EP 184B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100744 ER PT J AU Foley, JE Jung, U Mierra, A Eckhaus, M Bierer, BE Fowler, DH AF Foley, JE Jung, U Mierra, A Eckhaus, M Bierer, BE Fowler, DH TI Ex vivo rapamycin generates CD4(+) Th2 cells that potently abrogate murine GVHD. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, 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 2003 VL 102 IS 11 MA 668 BP 192A EP 192A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700668 ER PT J AU Shustik, C Duncan, A Ben Amor, H Turner, R Desjardins, P Ding, K Shepherd, L Sadura, A AF Shustik, C Duncan, A Ben Amor, H Turner, R Desjardins, P Ding, K Shepherd, L Sadura, A TI Cytogenetic abnormalities in untreated CLL. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 McGill Univ, Ctr Hlth, Montreal, PQ H3A 2T5, Canada. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Hop Charles LeMoyne, Greenfield Pk, PQ, Canada. NCI, Canada Clin Trials Grp, Kingston, ON, Canada. 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 2003 VL 102 IS 11 MA 4496 BP 194B EP 195B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537100787 ER PT J AU Walsh, T Patterson, T Langston, A van Burik, J Louie, A Herbrecht, R Hadley, S Perfect, J Hsu, C Gogate, J Hardalo, C Patino, H Pedicone, L Corcoran, G Raad, I AF Walsh, T Patterson, T Langston, A van Burik, J Louie, A Herbrecht, R Hadley, S Perfect, J Hsu, C Gogate, J Hardalo, C Patino, H Pedicone, L Corcoran, G Raad, I TI Posaconazole for treatment of invasive aspergillosis in patients who are refractory to or intolerant of conventional therapy: An externally controlled blinded trial. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Albany Med Ctr, Albany, NY USA. Hop Hautepierre, Strasbourg, France. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Duke Univ, Durham, NC 27706 USA. Schering Plough Res Inst, Kenilworth, NJ USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RI Young, Jo-Anne/G-2617-2013; Herbrecht, Raoul/D-3471-2013 OI Young, Jo-Anne/0000-0003-4182-341X; 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 2003 VL 102 IS 11 MA 682 BP 195A EP 196A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700682 ER PT J AU Calmels, B Kim, HJ Adler, R Laukkanen, MO Sellers, S Dunbar, CE AF Calmels, B Kim, HJ Adler, R Laukkanen, MO Sellers, S Dunbar, CE TI Retroviral vector integration into the genome of rhesus macaque long-term repopulating cells appears to be non-random, and recurrent integration loci include MDS1 and HIPK2. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Chonnam Univ Hosp, Kwangju, South Korea. RI calmels, boris/R-2538-2016 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 2003 VL 102 IS 11 MA 697 BP 199A EP 199A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700697 ER PT J AU Herblot, S Squire, JA Aplan, PD Hoang, T AF Herblot, S Squire, JA Aplan, PD Hoang, T TI The pre-TCR signal collaborates with the SCL and LMO1 oncogenes to induce T cell acute lymphoblastic leukemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Clin Res Inst Montreal, Montreal, PQ H2W 1R7, Canada. Ontario Canc Inst, Div Cellular & Mol Biol, Toronto, ON M4X 1K9, Canada. NCI, Med Branch, Dept Genet, Div Clin Sci, 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 2003 VL 102 IS 11 MA 4530 BP 203B EP 203B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100821 ER PT J AU Risitano, AM Plasilova, M O'Keefe, C Muranski, P Sloand, ES Maciejewski, JP Young, NS AF Risitano, AM Plasilova, M O'Keefe, C Muranski, P Sloand, ES Maciejewski, JP Young, NS TI Clonal T cell expansions in paroxysmal nocturnal hemoglobinuria (PNH) detected by T cell receptor analysis suggest a strong pathophysiologic relationship among PNH, aplastic anemia, and large granular lymphocytic syndrome. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Taussig Canc Ctr, Expt Hematol & Hematopoiesis Div, Cleveland, OH USA. RI Muranski, Pawel/E-5572-2010 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 2003 VL 102 IS 11 MA 719 BP 206A EP 206A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700719 ER PT J AU Gius, D Neckers, L Bradbury, M Harris, J AF Gius, D Neckers, L Bradbury, M Harris, J TI HSP90 inhibition with geldanamycin/17-AAG increases cytotoxicity, radiosensitization in cervical tumor cells: Implications for the radiation oncology. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. Rush Med Coll, Dept Internal Med, Chicago, IL 60612 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 2003 VL 102 IS 11 MA 4568 BP 212B EP 212B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100859 ER PT J AU Kang, EM Zickler, PP Burns, S Langemeijer, S Seufert, C Patterson, N Harlan, D Tisdale, JF AF Kang, EM Zickler, PP Burns, S Langemeijer, S Seufert, C Patterson, N Harlan, D Tisdale, JF TI Hematopoietic stem cell transplantation allows for tolerance of allogeneic islets but does not significantly contribute to organ regeneration. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDK, MCHB, NIH, DHHS, Bethesda, MD 20892 USA. NIDDK, ICBP, NIH, DHHS, Bethesda, MD 20892 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 2003 VL 102 IS 11 MA 746 BP 213A EP 213A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700746 ER PT J AU Berg, SL Blaney, SM Bernstein, M Kurtzberg, J Devidas, M Lampkin, T Murgo, AJ Harris, MB AF Berg, SL Blaney, SM Bernstein, M Kurtzberg, J Devidas, M Lampkin, T Murgo, AJ Harris, MB TI Activity of compound 506U78 in patients with refractory T-cell malignancies: A POG/CCG intergroup phase 2 study. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Duke Univ, Med Ctr, Durham, NC 27706 USA. Childrens Oncol Grp, Gainesville, FL USA. GlaxoSmithKline, Collegeville, PA USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Rockville, MD USA. Hackensack Univ, Tomorrow Childrens Inst, Med Ctr, Hackensack, NJ 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 2003 VL 102 IS 11 MA 792 BP 226A EP 226A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700792 ER PT J AU El Ouriaghli, F Mainwaring, L Sloand, E Fujiwara, H Keyvanfar, K Melenhorst, JJ Rezvani, K Solomon, S Sconocchia, G Hensel, N Barrett, JA AF El Ouriaghli, F Mainwaring, L Sloand, E Fujiwara, H Keyvanfar, K Melenhorst, JJ Rezvani, K Solomon, S Sconocchia, G Hensel, N Barrett, JA TI Neutrophil elastase production by leukemic cells confers a growth advantage for BCR-ABL positive stem cells in chronic myelogenous leukemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 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 2003 VL 102 IS 11 MA 807 BP 230A EP 230A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700807 ER PT J AU Erdmann, A Jung, U Hou, J Foley, J Levine, B June, C Fowler, D AF Erdmann, A Jung, U Hou, J Foley, J Levine, B June, C Fowler, D TI CD28 co-stimulation and cytokine polarization generates human Thl/Tcl and Th2/Tc2 populations: Potential application for allograft T cell engineering. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Penn, Abramson Family Canc Ctr, Philadelphia, PA 19104 USA. NCI, Expt Transplantat & Immunol Branch, 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 2003 VL 102 IS 11 MA 835 BP 238A EP 238A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700835 ER PT J AU Kogan, YL Hou, J Levine, B June, C Fowler, DH AF Kogan, YL Hou, J Levine, B June, C Fowler, DH TI Ex vivo rapamycin for GVHD prevention via Th2 cell graft engineering. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Penn, Abramson Family Canc Ctr, Philadelphia, PA 19104 USA. Duke Univ, Sch Med, Durham, NC USA. NIH, Expt Transplantat & Immunol Branch, 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 2003 VL 102 IS 11 MA 836 BP 238A EP 238A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700836 ER PT J AU Solomon, R Tran, T Carter, CS Hensel, N Wisch, L Childs, R Schindler, J Vitetta, ES Read, EJ Barrett, J AF Solomon, R Tran, T Carter, CS Hensel, N Wisch, L Childs, R Schindler, J Vitetta, ES Read, EJ Barrett, J TI Rapid engraftment and conserved graft-versus-leukemia effect without transplant-related mortality in elderly recipients of allografts selectively depleted of host-reactive lymphocytes. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIH, DTM, Cell Proc Sect, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75235 USA. 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 2003 VL 102 IS 11 MA 837 BP 238A EP 238A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700837 ER PT J AU Ting, SS Christopher, S Choi, U DeLeon, J Linton, G Whiting-Theobald, N Yamashita, K Harry, ML Felsburg, P AF Ting, SS Christopher, S Choi, U DeLeon, J Linton, G Whiting-Theobald, N Yamashita, K Harry, ML Felsburg, P TI In vivo gene transfer by intravenous injection of RD114-pseudotyped MFGS-gamma c-IRES-GFPhMGMT achieves myeloid and lymphoid marking in XSCID dogs. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. Univ Penn, Sch Vet Med, Dept Clin Studies, Philadelphia, PA 19104 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 2003 VL 102 IS 11 MA 876 BP 249A EP 250A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700876 ER PT J AU Dave, UP Suzuki, T Akagi, K Jenkins, NA Copeland, NG AF Dave, UP Suzuki, T Akagi, K Jenkins, NA Copeland, NG TI Lmo2 and Il2rg are frequent targets of retroviral insertion in AKXD T cell leukemias. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Mouse Canc Genet Program, Frederick, MD 21701 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 2003 VL 102 IS 11 MA 878 BP 250A EP 250A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700878 ER PT J AU Penninx, BW Pahor, M Woodman, RC Ferrucci, L Guralnik, JM AF Penninx, BW Pahor, M Woodman, RC Ferrucci, L Guralnik, JM TI Late-life anemia identifies persons at risk for mortality and hospitalization. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Ortho Biotech Prod, LP, Bridgewater, NJ USA. NIA, Baltimore, MD 21224 USA. NIA, 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 2003 VL 102 IS 11 MA 881 BP 251A EP 251A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700881 ER PT J AU Sung, L Nathan, PC Lange, B Beyene, J Buchanan, G AF Sung, L Nathan, PC Lange, B Beyene, J Buchanan, G TI Prophylactic G-CSF and GM-CSF decrease febrile neutropenia following chemotherapy in children with cancer: A meta-analysis of randomized controlled trials. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada. NCI, Pediat Branch, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Texas, SW Med Ctr, Dallas, TX 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 2003 VL 102 IS 11 MA 882 BP 251A EP 251A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700882 ER PT J AU Wong, EY Nilson, DG Lin, J Liem, RI Bodine, DM Gallagher, PG AF Wong, EY Nilson, DG Lin, J Liem, RI Bodine, DM Gallagher, PG TI Downstream sequences are required for full expression of the human alpha-spectrin gene promoter alpha. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Yale Univ, New Haven, CT 06520 USA. NHGRI, 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 2003 VL 102 IS 11 MA 889 BP 253A EP 253A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700889 ER PT J AU Gladwin, MT Cosby, K Partovi, KS Patel, RP Crawford, JH Kim-Shapiro, DB Schechter, AN Cannon, RO AF Gladwin, MT Cosby, K Partovi, KS Patel, RP Crawford, JH Kim-Shapiro, DB Schechter, AN Cannon, RO TI Novel function of human hemoglobin as a nitrite reductase regulates nitric oxide homeostasis and hypoxic vasodilation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Ctr Free Rad Biol, Birmingham, AL 35294 USA. Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NR 0 TC 3 Z9 3 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 2003 VL 102 IS 11 MA 898 BP 255A EP 255A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700898 ER PT J AU Goh, SH Lee, YT Robert, A Danner, R Miller, JL AF Goh, SH Lee, YT Robert, A Danner, R Miller, JL TI Detection and quantitation of nonglobin transcripts in circulating human reticulocytes with oligonucleotide arrays and real-time PCR. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NIH, Ctr Clin, Dept Crit Care 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 2003 VL 102 IS 11 MA 912 BP 259A EP 259A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700912 ER PT J AU Abdulmalik, O Safo, M Yang, JS Chen, QK Brugnara, C Evans, G Abraham, DJ Asakura, T AF Abdulmalik, O Safo, M Yang, JS Chen, QK Brugnara, C Evans, G Abraham, DJ Asakura, T TI In vitro and in vivo studies on 5-hydroxymethyl-2-furfural (5HMF): A new potent antisickling agent. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. Virginia Commonwealth Univ, Inst Struct Biol & Drug Discovery, Richmond, VA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NHLBI, Div Blood Dis & Resources, Bethesda, MD USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 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 2003 VL 102 IS 11 MA 922 BP 261A EP 261A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700922 ER PT J AU Asakura, T Abdulmalik, O Iyamu, EW Lian, LR Chen, QK Yang, JS Brugnara, C Safo, M Abraham, DJ Evans, G AF Asakura, T Abdulmalik, O Iyamu, EW Lian, LR Chen, QK Yang, JS Brugnara, C Safo, M Abraham, DJ Evans, G TI New screening protocol developed by the NHLBI SCD reference laboratory has significantly improved the discovery of new antisickling agents SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Virginia Commonwealth Univ, Inst Struct Biol & Drug Discovery, Richmond, VA USA. Natl Heart Lung & Blood Inst, Div Blood Dis & Resources, Bethesda, MD USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 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 2003 VL 102 IS 11 MA 932 BP 264A EP 264A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700932 ER PT J AU Schwartz, JD Lee, YT Trice, TA Gantt, NM Oneal, PA Gherman, RB Miller, JL AF Schwartz, JD Lee, YT Trice, TA Gantt, NM Oneal, PA Gherman, RB Miller, JL TI Single cell analysis of globin mRNA levels in circulating human reticulocytes. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDK, Lab Chem Biol, NIH, Bethesda, MD 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 2003 VL 102 IS 11 MA 937 BP 265A EP 265A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700937 ER PT J AU Gallagher, PG Wong, EY Pilon, AM Weiss, MJ Bodine, DM AF Gallagher, PG Wong, EY Pilon, AM Weiss, MJ Bodine, DM TI The human alpha hemoglobin stabilizing protein (AHSP) gene is regulated by GATA-1 and EKLF. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Yale Univ, New Haven, CT USA. NHGRI, NIH, Bethesda, MD USA. Childrens Hosp Philadelphia, Philadelphia, PA USA. RI Weiss, Mitchell/A-1245-2013 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 2003 VL 102 IS 11 MA 945 BP 267A EP 267A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700945 ER PT J AU Orem, J Otieno, MW Banura, C Mbidde, EK Fu, PF Johnson, J Ness, A Reynolds, S Black, J Whalen, C Remick, SC AF Orem, J Otieno, MW Banura, C Mbidde, EK Fu, PF Johnson, J Ness, A Reynolds, S Black, J Whalen, C Remick, SC TI Prospective screening for AIDS related non-Hodgkin's lymphoma (AR-NHL) patients(pts) in East Africa as part of a clinical trial. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Makerere Univ, Sch Med, Uganda Canc Inst, Kampala, Uganda. Univ Nairobi, Coll Hlth Sci, Kenyatta Natl Hosp, Nairobi, Kenya. Univ Hosp Cleveland, Ctr Comprehens Canc, Cleveland, OH 44106 USA. Case Western Reserve Univ, Ctr AIDS Res, Cleveland, OH 44106 USA. NCI, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 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 2003 VL 102 IS 11 MA 4810 BP 272B EP 272B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101101 ER PT J AU Bolyard, AA Pracht, G Schwinzer, B Zeidler, C Bonilla, MA Boxer, L Cham, B Donadieu, J Fier, C Freedman, M Kannourakis, G Kinsey, SE Winkelstein, J Alter, BP Reeves, L Welte, K Dale, DC AF Bolyard, AA Pracht, G Schwinzer, B Zeidler, C Bonilla, MA Boxer, L Cham, B Donadieu, J Fier, C Freedman, M Kannourakis, G Kinsey, SE Winkelstein, J Alter, BP Reeves, L Welte, K Dale, DC TI Severe chronic idiopathic neutropenia in adults: Long-term follow-up of 358 patients. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Washington, Seattle, WA 98195 USA. Kinderklin, Med Hsch, Hannover, Germany. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Ballarat, St John God Hosp, Canc Res Ctr, Ballarat, Vic, Australia. St Jamess Univ Hosp, Leeds, W Yorkshire, England. Hosp Trousseau, Serv Hematol & Oncol Pediat, Paris, France. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. NCI, Rockville, MD USA. St Joseph Childrens Hosp, Paterson, NJ USA. CancerCore Manitoba, Winnipeg, MB, Canada. Amgen Inc, Boulder, CO USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 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 2003 VL 102 IS 11 MA 966 BP 273A EP 273A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700966 ER PT J AU Aoki, Y Tosato, G AF Aoki, Y Tosato, G TI HIV Tat enhances Kaposi's sarcoma-associated herpesvirus infectivity. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, 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 2003 VL 102 IS 11 MA 994 BP 279A EP 279A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700994 ER PT J AU Wada, T Schurman, SH Garabedian, EK Nelson, DL Candotti, F AF Wada, T Schurman, SH Garabedian, EK Nelson, DL Candotti, F TI Multiple revertant patients in a single Wiskott-Aldrich syndrome family. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHGRI, NIH, Bethesda, MD 20892 USA. NCI, NIH, 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 2003 VL 102 IS 11 MA 1005 BP 282A EP 282A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701005 ER PT J AU Sconocchia, G Lau, M Fujiwara, H Barrett, AJ AF Sconocchia, G Lau, M Fujiwara, H Barrett, AJ TI Antileukemia effects of NK and NK-T cells on HLA-matched CD34+ CML cells of patients undergoing allogeneic hematopoietic stem cell transplantation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, NIH, 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 2003 VL 102 IS 11 MA 1007 BP 283A EP 283A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701007 ER PT J AU Rao, VK Dale, J Hurley, J Dugan, F Tretler, J Straus, SE AF Rao, VK Dale, J Hurley, J Dugan, F Tretler, J Straus, SE TI Use of mycophenolate mofetil in children with chronic, refractory immune cytopenias associated with autoimmune lymphoproliferative syndrome (ALPS). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIAID, Clin Invest Lab, 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 2003 VL 102 IS 11 MA 1015 BP 285A EP 285A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701015 ER PT J AU Washington, AV Quigley, L McVicar, DW AF Washington, AV Quigley, L McVicar, DW TI TREM family member, TLT-1, is expressed exclusively on peripheral blood platelets and megakaryocytes. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Expt Immunol Lab, Frederick, MD 21701 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 2003 VL 102 IS 11 MA 1042 BP 292A EP 292A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701042 ER PT J AU Neelapu, SS Gause, BL Nikcevich, DA Schuster, SJ Winter, J Gockerman, JP Sotomayor, E Inghirami, G Muggia, F Watson, T Snow, S Kubovic, P Ferraro, M Jaffe, ES Reynolds, CW Kwak, LW AF Neelapu, SS Gause, BL Nikcevich, DA Schuster, SJ Winter, J Gockerman, JP Sotomayor, E Inghirami, G Muggia, F Watson, T Snow, S Kubovic, P Ferraro, M Jaffe, ES Reynolds, CW Kwak, LW TI Vaccine therapy of follicular lymphoma in first remission: Long-term follow-up of phase II results and high rate of chemotherapy-induced complete remissions in a controlled, randomized phase III trial. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. St Marys Duluth Clin Hlth Syst, Duluth, MN USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Duke Univ, Ctr Comprehens Canc, Durham, NC 27706 USA. H Lee Moffit Canc Ctr & Res Inst, Tampa, FL USA. NYU, Sch Med, NYU Canc Inst, 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 2003 VL 102 IS 11 MA 4953 BP 307B EP 308B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537101244 ER PT J AU Cortes, J Giles, F O'Brien, S Beran, M McConkey, D Wright, J Schenkein, D Patel, G Verstovsek, S Pate, O Talpaz, M Kantarjian, H AF Cortes, J Giles, F O'Brien, S Beran, M McConkey, D Wright, J Schenkein, D Patel, G Verstovsek, S Pate, O Talpaz, M Kantarjian, H TI Phase II study of bortezomib (VELCADE (TM), formerly PS-341) for patients with imatinib-refractory chronic myeloid leukemia (CML) in chronic (CP) or accelerated phase (AP). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, CTEP, Bethesda, MD 20892 USA. Millennium Pharmaceut, Cambridge, MA 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 2003 VL 102 IS 11 MA 4971 BP 312B EP 313B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537101262 ER PT J AU Cortes, J O'Brien, S Verstovsek, S Thomas, D Giles, F Garcia-Manero, G Murgo, A Newman, R Rios, MB Talpaz, M Kantarjian, H AF Cortes, J O'Brien, S Verstovsek, S Thomas, D Giles, F Garcia-Manero, G Murgo, A Newman, R Rios, MB Talpaz, M Kantarjian, H TI Phase I study of subcutaneous (SC) homoharringtonine (HHT) for patients (pts) with chronic myelogenous leukemia (CML). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, CTEP, Bethesda, MD 20892 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 2003 VL 102 IS 11 MA 5010 BP 322B EP 322B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101301 ER PT J AU Ortiz, M Salcedo, R Tsai, S Collins, SJ Keller, J AF Ortiz, M Salcedo, R Tsai, S Collins, SJ Keller, J TI Stem cell factor dependent embryonic cell lines with hematopoietic and endothelial properties established from 10.5 dpc yolk sac and aorta gonad mesonephrous (AGM) region. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 SAIC Frederick Inc, BRP, NCI, Frederick, MD USA. NCI, LMI, Frederick, MD 21701 USA. Univ Utah, Dept Hematol, Salt Lake City, UT USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 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 2003 VL 102 IS 11 MA 1192 BP 331A EP 331A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701192 ER PT J AU Calado, RT Ellison, FM Young, NS Chen, JH AF Calado, RT Ellison, FM Young, NS Chen, JH TI Preferential Homing of Lin CD117(+) hematopoietic cells in irradiated and nonirradiated recipients. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RI Calado, Rodrigo/G-2619-2011 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 2003 VL 102 IS 11 MA 1198 BP 332A EP 333A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701198 ER PT J AU Ueda, T Brenner, S Malech, HL Langemeijer, S Phang, OA Donahue, RE Kang, EM Tisdale, JF AF Ueda, T Brenner, S Malech, HL Langemeijer, S Phang, OA Donahue, RE Kang, EM Tisdale, JF TI Cloning and functional analysis of the rhesus ABCG2 gene using an RD114-pseudotyped MFGS vector. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDK, MCHB, NIH, Bethesda, MD USA. NIAID, LHD, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RI Brenner, Sebastian/D-7456-2013 NR 0 TC 0 Z9 0 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 2003 VL 102 IS 11 MA 1201 BP 333A EP 333A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701201 ER PT J AU Suh, HC Ortiz, M Gooya, J Renn, K Friedman, AD Johnson, P Keller, J AF Suh, HC Ortiz, M Gooya, J Renn, K Friedman, AD Johnson, P Keller, J TI C/EBP alpha inhibits erythroid development and differentiation in vivo and in vitro. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 SAIC Frederick Inc, NCI, BRP, Frederick, MD USA. Johns Hopkins Univ, Div Pediat Oncol, Baltimore, MD USA. NCI Frederick, RCGL, DBS, 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 2003 VL 102 IS 11 MA 1235 BP 342A EP 342A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701235 ER PT J AU Wen, J Dickinson, LA Pack, SD Yu, XB Kohwi-Shigematsu, T Noguchi, CT AF Wen, J Dickinson, LA Pack, SD Yu, XB Kohwi-Shigematsu, T Noguchi, CT TI Tall/SCL represses transcription of target DNA via histone methylation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Pediat Oncol, Baltimore, MD USA. Univ Calif Berkeley, Dept Cell & Mol Biol, Berkeley, CA 94720 USA. RI Pack, Svetlana/C-2020-2014 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 2003 VL 102 IS 11 MA 1246 BP 345A EP 345A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701246 ER PT J AU Lennartsson, J Linnekin, D AF Lennartsson, J Linnekin, D TI The receptor tyrosine kinase c-Kit makes kinase independent and dependent contributions to synergistic proliferation induced by SCF in combination with GM-CSF. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Basic Res Lab, NCI, 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 2003 VL 102 IS 11 MA 1262 BP 349A EP 349A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701262 ER PT J AU Winterstein, D Linnekin, D AF Winterstein, D Linnekin, D TI Jak2 independent signaling through the IL3 receptor is sufficient to mediate synergistic growth in response to IL3 combined with SCF. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. NCI Frederick, Basic Res Lab CCR, 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 2003 VL 102 IS 11 MA 1263 BP 349A EP 349A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701263 ER PT J AU Fukuda, S Broxmeyer, HE Pelus, LM AF Fukuda, S Broxmeyer, HE Pelus, LM TI The Flt3 ligand/Flt3 axis regulates migration of normal and transformed hematopoietic cells by modulating SDF1 alpha (CXCL12)/CXCR4 signaling. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Washington, Dept Med, Seattle, WA USA. Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada. Med Hochsch, Hannover, Germany. Univ Michigan Hlth Syst, Div Pediat Hematol Oncol, Ann Arbor, MI 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 2003 VL 102 IS 11 MA 1268 BP 350A EP 350A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701267 ER PT J AU Aerbajinai, W Lee, YT Wojda, U Barr, V Miller, JL AF Aerbajinai, W Lee, YT Wojda, U Barr, V Miller, JL TI Cloning and characterization of a novel inhibitor of growth expressed during terminal erythroid differentiation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDK, Lab Chem Biol, NIH, 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 2003 VL 102 IS 11 MA 1277 BP 353A EP 353A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701277 ER PT J AU Asefa, B Dermott, JM Gooya, JM Garfinkel, DJ Stefanisko, K Vousden, K Keller, JR AF Asefa, B Dermott, JM Gooya, JM Garfinkel, DJ Stefanisko, K Vousden, K Keller, JR TI p205, a potential tumor suppressor, exerts its antiproliferative activity in an Rb- and p53-independent manner. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, LMI CCR, Frederick, MD USA. NCI, GRCBL CCR, Frederick, MD USA. NCI, BRP SAIC, Frederick, MD USA. NCI, RCGC CCR, 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 2003 VL 102 IS 11 MA 1296 BP 357A EP 358A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701296 ER PT J AU Greiner, TC Smith, LM Rosenwald, A Weisenburger, DW Gascoyne, R Connor, J Delabie, J Campo, E Ott, G Mueller-Hermelink, K Braziel, RM Jaffe, ES Armitage, JO Staudt, LM Chan, WC AF Greiner, TC Smith, LM Rosenwald, A Weisenburger, DW Gascoyne, R Connor, J Delabie, J Campo, E Ott, G Mueller-Hermelink, K Braziel, RM Jaffe, ES Armitage, JO Staudt, LM Chan, WC TI MRNA expression patterns in p53 mutant vs. WildType subgroups of diffuse large B-cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Nebraska, Med Ctr, Omaha, NE USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Natl Canc Inst, Metab Branch, NIH, Bethesda, MD USA. Univ Barcelona, Barcelona, Spain. Norwegian Radium Hosp, Oslo, Norway. Univ Wurzburg, Wurzburg, Germany. Univ Oregon, Ctr Hlth Sci, Portland, OR USA. Natl Canc Inst, Hematopathol Sect, NIH, Bethesda, MD 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 2003 VL 102 IS 11 MA 1338 BP 368A EP 368A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701338 ER PT J AU Hakansson, P Segal, D Lassen, C Gullberg, U Morse, H Meltzer, PS Fioretos, T AF Hakansson, P Segal, D Lassen, C Gullberg, U Morse, H Meltzer, PS Fioretos, T TI Identification of IFN-responsive genes as a result of inducible BCR/ABL expression using cDNA microarray analysis. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Lab Med, Lund, Sweden. NIAID, Immunopathol Lab, Bethesda, MD 20892 USA. NHGRI, Canc Genet 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 2003 VL 102 IS 11 MA 1339 BP 368A EP 368A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701339 ER PT J AU Lehrnbecher, T Fleischhack, G Hanisch, M Deinlein, F Simon, A Bernig, T Chanock, SJ Klingebiel, T AF Lehrnbecher, T Fleischhack, G Hanisch, M Deinlein, F Simon, A Bernig, T Chanock, SJ Klingebiel, T TI Circulating levels and promoter polymorphisms of IL-6 and IL-8 in pediatric cancer patients with fever and neutropenia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Childrens Hosp 3, Frankfurt, Germany. Childrens Hosp, Bonn, Germany. Childrens Hosp, Wurzburg, Germany. NCI, Pediat Oncol Branch, 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 2003 VL 102 IS 11 MA 1379 BP 380A EP 380A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701379 ER PT J AU Bernig, T Lehrnbecher, T Graubner, UB den Boer, ML Pieters, R Janka-Schaub, GE Chanock, SJ AF Bernig, T Lehrnbecher, T Graubner, UB den Boer, ML Pieters, R Janka-Schaub, GE Chanock, SJ TI Analysis of common genetic variants in MPO, CYP1A1, CYP2E1, NAT2 and NQO1 in childhood acute lymphoblastic leukemia: A common myeloperoxidase promoter polymorphism is associated with risk for childhood acute lmphoblastic leukemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Sect Genom Variat, Pediat Oncol Branch, Gaithersburg, MD USA. Childrens Univ Hosp 3, Frankfurt, Germany. Dr von Hauner Childrens Univ Hosp, Munich, Germany. Erasmus MC Sophia Childrens Hosp, Rotterdam, Netherlands. Childrens Univ Hosp, Hamburg, Germany. NR 0 TC 0 Z9 0 U1 2 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 2003 VL 102 IS 11 MA 1386 BP 382A EP 382A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701386 ER PT J AU Haining, WN Neuberg, D Keczkemethy, H Guenaga, J Silverman, LB Sallan, SE Cardoso, AA Douek, D Nadler, LM Guinan, EC AF Haining, WN Neuberg, D Keczkemethy, H Guenaga, J Silverman, LB Sallan, SE Cardoso, AA Douek, D Nadler, LM Guinan, EC TI T cell deficits at diagnosis and during therapy in children with ALL may preclude antigen specific vaccination. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NIAID, Vaccine Res Ctr, Human Immunol Sect, 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 2003 VL 102 IS 11 MA 1388 BP 382A EP 383A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701388 ER PT J AU Marcucci, G Stock, W Zwiebel, JA Cataland, SR Dai, G Moran, M Lucas, D Liu, S Klisovic, MI Kefauver, C Green, M Chan, KK Frankel, SR Grever, MR Byrd, JC AF Marcucci, G Stock, W Zwiebel, JA Cataland, SR Dai, G Moran, M Lucas, D Liu, S Klisovic, MI Kefauver, C Green, M Chan, KK Frankel, SR Grever, MR Byrd, JC TI Clinical activity of Genasense (TM) (GNS, oblimersen sodium), a pro-apoptotic to Bcl-2 oligonucleotide, in combination with daunorubicin and cytarabine: A phase I study in previously untreated elderly acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Ohio State Univ, Ctr Comprehens Canc, Columbus, OH USA. Ohio State Univ, Div Hematol, Chicago, IL USA. NCI, CTEP, Bethesda, MD 20892 USA. Genta Inc, Berkeley Hts, NJ USA. NR 0 TC 2 Z9 2 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 2003 VL 102 IS 11 MA 1398 BP 385A EP 385A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701398 ER PT J AU Frankel, AE Cohen, KA Hogge, DE Hall, PD Kreitman, RJ AF Frankel, AE Cohen, KA Hogge, DE Hall, PD Kreitman, RJ TI The AML recombinant toxin, DT(388)IL3, consisting of a truncated diphtheria toxin (DT388) linked to human interleukin 3 (IL3), shows safety at therapeutically active doses in cynomolgus monkeys. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Wake Forest Univ, Sch Med, Winston Salem, NC USA. British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 4E6, Canada. Med Univ S Carolina, Charleston, SC 29425 USA. NCI, Mol Biol Lab, 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 2003 VL 102 IS 11 MA 1399 BP 386A EP 386A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701399 ER PT J AU Gojo, I Gore, SD Jiemjit, A Greer, J Tidwell, ML Sparreboom, A Figg, WD Heyman, MR Rollins, S Trepel, J Sausville, EA Karp, JE AF Gojo, I Gore, SD Jiemjit, A Greer, J Tidwell, ML Sparreboom, A Figg, WD Heyman, MR Rollins, S Trepel, J Sausville, EA Karp, JE TI Phase I study of histone deacetylase inhibitor (HDI) MS-275 in adults with refractory or realpsed hematologic malignancies. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD USA. Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 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 2003 VL 102 IS 11 MA 1408 BP 388A EP 388A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701408 ER PT J AU Rimsza, L Roberts, R Miller, T Unger, J LeBlanc, M Braziel, R Weisenburger, D Chan, WC Greiner, T Hermelink, KM Jaffe, E Gascoyne, RD Campo, E Fuchs, D Spier, C Fisher, R Staudt, L Grogan, T AF Rimsza, L Roberts, R Miller, T Unger, J LeBlanc, M Braziel, R Weisenburger, D Chan, WC Greiner, T Hermelink, KM Jaffe, E Gascoyne, RD Campo, E Fuchs, D Spier, C Fisher, R Staudt, L Grogan, T TI Loss of MHC class II gene and protein expression in diffuse large B cell lymphoma is related to decreased tumor immumosurveillance and poor patient survival: A follow-up study to the NIH director's challenge leukemia and lymphoma molecular profiling project (LLMPP). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Arizona, Dept Pathol, Tucson, AZ USA. Arizona Canc Ctr, Tucson, AZ USA. Fred Hutchinson Canc Res Ctr, Ctr Stat, Seattle, WA 98104 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR USA. Univ Nebraska, Dept Pathol, Omaha, NE 68182 USA. Univ Wurzburg, Dept Pathol, D-97070 Wurzburg, Germany. NCI, Metab Branch, Bethesda, MD 20892 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Barcelona, Hosp Clin Prov, E-08007 Barcelona, Spain. Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY 14627 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 2003 VL 102 IS 11 MA 1417 BP 390A EP 391A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701417 ER PT J AU Larochelle, A Krouse, A Orlic, D Donahue, R Dunbar, C Hematti, P AF Larochelle, A Krouse, A Orlic, D Donahue, R Dunbar, C Hematti, P TI The use of AMD3100 mobilized peripheral blood stem cell CD34+targets for retroviral transduction results in high-level in vivo marking in rhesus macaques. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, NIH, 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 2003 VL 102 IS 11 MA 5315 BP 396B EP 397B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537101606 ER PT J AU Dunleavy, KM Little, RF Grant, N White, T Wright, G Janik, J Wilson, WH AF Dunleavy, KM Little, RF Grant, N White, T Wright, G Janik, J Wilson, WH TI Rituximab is associated with late onset neutropenia (LON) when administered with doxorubicin-based chemotherapy for the initial treatment of aggressive B-cell lymphomas. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, 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 2003 VL 102 IS 11 MA 1443 BP 397A EP 398A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701443 ER PT J AU Boyiadzis, M Carson, JM Memon, SA Dean, RM Castro, K Odom, J Pavletic, SZ Gea-Banacloche, J Kasten-Sportes, C Fowler, D Bishop, MR Gress, RE Hakim, FT AF Boyiadzis, M Carson, JM Memon, SA Dean, RM Castro, K Odom, J Pavletic, SZ Gea-Banacloche, J Kasten-Sportes, C Fowler, D Bishop, MR Gress, RE Hakim, FT TI Correlation of plasma interleukin-15 levels with natural killer cell reconstitution following allogeneic transplantation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RI Memon, Sarfraz/E-1198-2013 NR 0 TC 0 Z9 0 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 2003 VL 102 IS 11 MA 5363 BP 408B EP 409B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537101654 ER PT J AU Pro, B Smith, MR Younes, A Dang, NH Fayad, LE Goy, A Hagemeister, F McLaughlin, P Rodriguez, MA Samuels, B Arredondo, Y Frankel, SR Zwiebel, JA AF Pro, B Smith, MR Younes, A Dang, NH Fayad, LE Goy, A Hagemeister, F McLaughlin, P Rodriguez, MA Samuels, B Arredondo, Y Frankel, SR Zwiebel, JA TI Genasense (Bcl-2 antisense) plus rituximab is active in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 MD Anderson Canc Ctr, Houston, TX USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Genta Inc, Berkeley Hts, NJ USA. NCI, 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 2003 VL 102 IS 11 MA 1491 BP 410A EP 410A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701491 ER PT J AU Carvallo, CA Billings, EM Takahashi, Y Suffredini, D McCoy, P Igarashi, T Srinivasan, R Linehan, WM Childs, RW AF Carvallo, CA Billings, EM Takahashi, Y Suffredini, D McCoy, P Igarashi, T Srinivasan, R Linehan, WM Childs, RW TI Gene expression profiles in human T-lymphocytes during graft-versus-host disease (GVHD). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. 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 2003 VL 102 IS 11 MA 5373 BP 411B EP 411B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101664 ER PT J AU Little, R Dunleavy, K Grant, N Hegde, U Pittaluga, S Kumar, P Jaffe, E Steinberg, S Janik, J Wilson, WH AF Little, R Dunleavy, K Grant, N Hegde, U Pittaluga, S Kumar, P Jaffe, E Steinberg, S Janik, J Wilson, WH TI Phase II study of abbreviated treatment (short-Course) with EPOCH and rituximab (EPOCH-R) in AIDS-related lymphoma (ARL): Preliminary results on the role of rituximab in treatment. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Canc Res Ctr, 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 2003 VL 102 IS 11 MA 1494 BP 411A EP 411A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701494 ER PT J AU Battiwalla, M Saunthararajah, Y Nakamura, R Wisch, L Young, NS Sloand, EM Barrett, AJ AF Battiwalla, M Saunthararajah, Y Nakamura, R Wisch, L Young, NS Sloand, EM Barrett, AJ TI A simple scoring system defines a subgroup of myelodysplasia (MDS) patients with a high probability of hematological response to immunosuppression and identifies antithymocyte globulin (ATG) as the active immunosuppressive agent. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Univ Illinois, Hematol Oncol Sect, Chicago, IL USA. City Hope Natl Med Ctr, Div Hematol & Bone Marrow Transplantat, Duarte, CA 91010 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 2003 VL 102 IS 11 MA 1533 BP 422A EP 422A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701533 ER PT J AU Gotlib, J Jamieson, CHM List, A Cortes, J Albitar, M Sridhar, K Dugan, K Quesada, S Diaz, G Pate, O Novotny, W Chen, H Greenberg, PL AF Gotlib, J Jamieson, CHM List, A Cortes, J Albitar, M Sridhar, K Dugan, K Quesada, S Diaz, G Pate, O Novotny, W Chen, H Greenberg, PL TI Phase it study of Bevacizumab (anti-VEGF humanized monoclonal antibody) in patients with myelodysplastic syndrome (MDS): Preliminary results SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Stanford Univ, Sch Med, Stanford, CA USA. Arizona Canc Ctr, Tucson, AZ USA. MD Anderson Canc Ctr, Houston, TX USA. Palo Alto Vet Hlth Care Syst, Palo Alto, CA USA. Genentech Inc, San Francisco, CA 94080 USA. NCI, CTEP, Bethesda, MD USA. NR 0 TC 11 Z9 12 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 2003 VL 102 IS 11 MA 1545 BP 425A EP 425A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701545 ER PT J AU Wilson, DB Park, JR Andritsos, L Kulkarni, S Savage, SA Chanock, SJ Shannon, KM Monica, B AF Wilson, DB Park, JR Andritsos, L Kulkarni, S Savage, SA Chanock, SJ Shannon, KM Monica, B TI Monosomy 7 myelodysplastic-myeloproliferative syndrome in an infant with a germline mutation in the primer alignment region of the telomerase RNA (TERC) gene. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Washington Univ, Dept Pediat, St Louis, MO 63130 USA. Washington Univ, Dept Internal Med, St Louis, MO USA. Washington Univ, Dept Mol Biol & Pharmacol, St Louis, MO USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. NCI, Pediat Oncol Branch, Ctr Adv Technol, Gaithersburg, MD USA. UCSF, Dept Pediat, San Francisco, CA USA. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 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 2003 VL 102 IS 11 MA 1544 BP 425A EP 425A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701544 ER PT J AU Decker, T Oelsner, M Kreitman, RJ Salvatore, G Wang, QC Pastan, I Peschel, C Licht, T AF Decker, T Oelsner, M Kreitman, RJ Salvatore, G Wang, QC Pastan, I Peschel, C Licht, T TI Induction of caspase-dependent programmed cell death in B-CLL cells by recombinant anti-CD22 immunotoxins. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Naples Federico II, Sch Med, CNR, Ist Endocrinol & Oncol Sperimentale, Naples, Italy. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med Hematol Oncol 3, D-8000 Munich, 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 2003 VL 102 IS 11 MA 1602 BP 439A EP 439A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701602 ER PT J AU Seggewiss, R Lore, K Guenaga, FJ Metzger, ME Krouse, A Donahue, RE Douek, DC Dunbar, CE AF Seggewiss, R Lore, K Guenaga, FJ Metzger, ME Krouse, A Donahue, RE Douek, DC Dunbar, CE TI Superior immune reconstitution of in vitro expanded and retrovirally transduced CD34+cells compared to selected and unselected CD34+cells after autologous PBPC transplantation in rhesus macaques. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIAID, Vaccine Res Ctr, NIH, DHHS, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, DHHS, 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 2003 VL 102 IS 11 MA 1659 BP 455A EP 455A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701659 ER PT J AU Bauer, TR Creevy, KE Gu, YC Tuschong, LM Embree, LJ Hickstein, DD AF Bauer, TR Creevy, KE Gu, YC Tuschong, LM Embree, LJ Hickstein, DD TI Stable mixed chimerism following a non-myeloabative transplant regimen corrects the disease phenotype in dogs with the primary immunodeficiency disease canine leukocyte adhesion deficiency. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, NIH, 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 2003 VL 102 IS 11 MA 1663 BP 456A EP 456A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701663 ER PT J AU Bishop, MR Kasten-Sportes, C Dean, R Marchigiani, D Castro, K Chow, C Pavletic, S Gea-Banacloche, J Carter, C Read, E Leitman, S Gress, R Fowler, D AF Bishop, MR Kasten-Sportes, C Dean, R Marchigiani, D Castro, K Chow, C Pavletic, S Gea-Banacloche, J Carter, C Read, E Leitman, S Gress, R Fowler, D TI Preemptive DLI after T cell-depleted reduced-intensity allogeneic HSCT for metastatic breast cancer: Effect on engraftment, GVHD, and anti-tumor response. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. 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 2003 VL 102 IS 11 MA 5567 BP 460B EP 460B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101858 ER PT J AU Kurtzberg, J Wagner, EL Fraser, JK Cairo, MS Jensen, LA Cohen, G Carter, SL Kernan, NA AF Kurtzberg, J Wagner, EL Fraser, JK Cairo, MS Jensen, LA Cohen, G Carter, SL Kernan, NA TI Results of the cord blood transplantation study (COBLT) unrelated donor banking program from donor screening to characterization of banked units. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Duke Univ, Med Ctr, Durham, NC USA. Emmes Corp, Rockville, MD USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Georgetown Univ, Med Ctr, Washington, DC 20057 USA. NHLBI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 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 2003 VL 102 IS 11 MA 1680 BP 461A EP 461A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701680 ER PT J AU Chakrabarti, S Takahashi, Y Srinivasan, R Marquesen, M Shalabi, RA Goodwin, R Swanson, P Espinoza-Delgado, I Bolan, CD Leitman, SF Barren, AJ Young, NS Childs, R AF Chakrabarti, S Takahashi, Y Srinivasan, R Marquesen, M Shalabi, RA Goodwin, R Swanson, P Espinoza-Delgado, I Bolan, CD Leitman, SF Barren, AJ Young, NS Childs, R TI Durable engraftment and long-term survival following Fludarabine-based nonmyeloablative hematopoietic cell transplantation (HCT) in allo-immunized patients with ATG-refractory severe aplastic anemia (SAA) and paroxysmal nocturnal hemoglobinuria (PNH). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIH, DTM, Bethesda, MD 20892 USA. NIA, Baltimore, MD 21224 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 2003 VL 102 IS 11 MA 1711 BP 469A EP 469A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701711 ER PT J AU Gorak, E Geller, N Srinivasan, R Chakrabarti, S Suffredini, A Barrett, AJ Childs, R AF Gorak, E Geller, N Srinivasan, R Chakrabarti, S Suffredini, A Barrett, AJ Childs, R TI Decreased survival in patients with pulmonary engraftment syndrome following nonmyeloablative allogeneic hematopoietic cell transplantation (HCT). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NLBI, Hematol Branch, NIH, Bethesda, MD USA. NIH, Ctr Clin, 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 2003 VL 102 IS 11 MA 1714 BP 470A EP 470A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701714 ER PT J AU Beggs, KJ Campagnoli, C Sullivan, KE Johnson, MP Puck, JM Zanjani, ED Flake, AW AF Beggs, KJ Campagnoli, C Sullivan, KE Johnson, MP Puck, JM Zanjani, ED Flake, AW TI Eight years later: T and B-cell function in a patient transplanted in utero for X-linked severe combined immunodeficiency. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Childrens Hosp Philadelphia, Childrens Inst Surg Sci, Philadelphia, PA 19104 USA. Univ Nevada, Dept Anim Biotechnol, Reno, NV 89557 USA. Natl Human Genome Inst, Genet & Mol Biol Branch, 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 2003 VL 102 IS 11 MA 5648 BP 480B EP 480B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101939 ER PT J AU Confer, DL Leitman, SF Papadopoulos, EB Price, TH Stroncek, DF Robinett, P Braem, B AF Confer, DL Leitman, SF Papadopoulos, EB Price, TH Stroncek, DF Robinett, P Braem, B TI Serious complications following unrelated donor marrow collection: Experiences of the National Marrow Donor Program (R). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Natl Marrow Donor Program, Minneapolis, MN USA. NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Puget Sound Blood Ctr, Seattle, WA 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 2003 VL 102 IS 11 MA 1786 BP 490A EP 490A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701786 ER PT J AU Bosticardo, M Novelli, F Casanova, JL Candotti, F AF Bosticardo, M Novelli, F Casanova, JL Candotti, F TI IL-12 signaling pathway is restored in IL-12 receptor beta-1 (IL-12R beta 1) KO mice after retroviral-mediated gene transfer into hematopoietic stem cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. San Giovanni Battista Hosp, CeRMS, Ctr Expt Res & Clin Studies, Turin, Italy. Univ Paris 05, Lab Genet Humaine Malad Infect, INSERM, Fac Med Necker,U550, 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 2003 VL 102 IS 11 MA 1793 BP 492A EP 492A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701793 ER PT J AU Melenhorst, JJ Solomon, SR Zhao, L Hensel, NF Barrett, AJ AF Melenhorst, JJ Solomon, SR Zhao, L Hensel, NF Barrett, AJ TI Up to 45% transduction of human G-CSF mobilized peripheral blood CD34 cells following a single exposure to a retroviral vector facilitates efficient generation of gene-modified dendritic cells for immunotherapy. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Genet & Physiol, 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 2003 VL 102 IS 11 MA 5708 BP 494B EP 494B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101999 ER PT J AU Kang, EM Phang, OA Pule, M von Kalle, C Donahue, RE Vanin, EF Tisdale, JF AF Kang, EM Phang, OA Pule, M von Kalle, C Donahue, RE Vanin, EF Tisdale, JF TI LAM PCR mediated analysis of integration sites in rhesus recipients of replication competent retrovirus complicated by thymic lymphoma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Houston, TX 77030 USA. Cincinnato Childrens Hosp, Cincinnati, OH USA. NIDDK, DHHS, NIH, MCHB, Bethesda, MD USA. NHLBI, Hematol Branch, NIH, DHHS, 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 2003 VL 102 IS 11 MA 5726 BP 498B EP 499B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537102017 ER PT J AU Donahue, RE Morizono, K Ravasi, L Metzger, ME Bonifacino, A Krouse, A Mao, SH Szajek, LP Herscovitch, P Chen, ISY Eckelman, W AF Donahue, RE Morizono, K Ravasi, L Metzger, ME Bonifacino, A Krouse, A Mao, SH Szajek, LP Herscovitch, P Chen, ISY Eckelman, W TI Molecular imaging of CD34(+) cell progeny following transplant in non-human primates using positron emission tomography (PET). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Rockville, MD USA. Univ Calif Los Angeles, AIDS Inst, Los Angeles, CA 90024 USA. NIH, Ctr Clin, PET Dept, 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 2003 VL 102 IS 11 MA 5737 BP 501B EP 501B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537102028 ER PT J AU Taylor, JG Yamaguchi, H Young, NS Liu, JM Chancock, SJ AF Taylor, JG Yamaguchi, H Young, NS Liu, JM Chancock, SJ TI Common SNPs, haplotypes, and patterns of linkage disequilibrium in the FANCA gene. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIH, Sect Genom Variat, Pediat Branch, Gaithersburg, MD USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, 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 2003 VL 102 IS 11 MA 1845 BP 506A EP 506A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701844 ER PT J AU Alter, BP Leathwood, L Peters, J Carr, A Singer, D Aleck, K Wagner, L Greene, MH AF Alter, BP Leathwood, L Peters, J Carr, A Singer, D Aleck, K Wagner, L Greene, MH TI Diamond-Blackfan Anemia (DBA): Identification of nonpenetrant individuals in the molecular era SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Westat Corp, Rockville, MD USA. Univ Arizona, Phoeix Childrens Hosp, Dept Pediat, Phoenix, AZ 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 2003 VL 102 IS 11 MA 1847 BP 507A EP 507A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701846 ER PT J AU Chen, G Zeng, WH Green, S Young, NS AF Chen, G Zeng, WH Green, S Young, NS TI Hprt "mutations" in paroxysmal nocturnal hemoglobinuria (PNH) reflect T-cell clonal expansion, not genomic instability. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA 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 2003 VL 102 IS 11 MA 1850 BP 507A EP 508A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701849 ER PT J AU Brown, KE Lu, J Basu, A Melenhorst, JJ Young, NS AF Brown, KE Lu, J Basu, A Melenhorst, JJ Young, NS TI Analysis of inflammatory response and T cell repertoire in hepatitis-associated aplastic anemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 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 2003 VL 102 IS 11 MA 1866 BP 511A EP 512A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701865 ER PT J AU Ferrucci, L Woodman, RC Penninx, BW Chaves, PHM Lauretani, F Guralnik, JM AF Ferrucci, L Woodman, RC Penninx, BW Chaves, PHM Lauretani, F Guralnik, JM TI Unrecognized renal insufficiency and blunted EPO responses in the anemia of older persons: The inchianti study. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIA, NIH, Baltimore, MD 21224 USA. Ortho Biotech Prod LP, Clin Affairs, Bridgewater, MA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. John Hopkins Ctr Aging & Hlth, Baltimore, MD USA. INCRA, Florence, Italy. 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 2003 VL 102 IS 11 MA 1869 BP 512A EP 513A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701868 ER PT J AU Zeng, WH Chen, GB Kajigaya, S Risitano, AM Nunez, O Young, NS AF Zeng, WH Chen, GB Kajigaya, S Risitano, AM Nunez, O Young, NS TI Transcript profile of CD4 and CD8 T cells from the bone marrow of acquired aplastic anemia patients. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA 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 2003 VL 102 IS 11 MA 1867 BP 512A EP 512A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701866 ER PT J AU Chen, JC Calado, RT Ellison, FM Brandt, J Young, NS AF Chen, JC Calado, RT Ellison, FM Brandt, J Young, NS TI A mouse model of immune-mediated bone marrow failure reveals an "innocent bystander" mechanism of destruction of hematopoietic stem and stromal cells SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RI Calado, Rodrigo/G-2619-2011 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 2003 VL 102 IS 11 MA 1871 BP 513A EP 513A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701870 ER PT J AU Plasilova, M Risitano, A Rodriguez, A Wlodarski, M Howe, E Maciejewski, J AF Plasilova, M Risitano, A Rodriguez, A Wlodarski, M Howe, E Maciejewski, J TI Molecular T cell receptor repertoire analysis in immune mediated bone marrow failure syndromes-implications for the development of diagnostic tests SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Cleveland Clin Fdn, Expt Hematol & Hematopoiesis Sect, Taussig Canc Ctr, Cleveland, OH 44195 USA. NHLBI, 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 2003 VL 102 IS 11 MA 1872 BP 513A EP 513A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701871 ER PT J AU Rogers, HM Noguchi, CT AF Rogers, HM Noguchi, CT TI Select histone deacetylase inhibitors mimic induction of fetal hemoglobin by hypoxia in erythroid progenitor cells SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDK, Biol Chem Lab, NIH, 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 2003 VL 102 IS 11 MA 1885 BP 516A EP 517A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701884 ER PT J AU Little, JA Czechowicz, AD AF Little, JA Czechowicz, AD TI Short-chain fatty acids may act through acetyl transferase activity and HDAC inhibition at an embryonic globin gene promoter SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Minnesota, Minneapolis, MN USA. NIDDK, LCDB, NIH, 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 2003 VL 102 IS 11 MA 1890 BP 518A EP 518A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701889 ER PT J AU Sconocchia, G Keyvanfar, K El Ouriaghli, F Grube, M Rezvani, K Fujiwara, H Hensel, N Barrett, JA AF Sconocchia, G Keyvanfar, K El Ouriaghli, F Grube, M Rezvani, K Fujiwara, H Hensel, N Barrett, JA TI Phenotypic and functional characterization of a novel CD56+peripheral blood monocytes SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, 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 2003 VL 102 IS 11 MA 1905 BP 521A EP 521A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701904 ER PT J AU Tsujimura, H Tamura, T Kong, HJ Nishiyama, A Ishii, KJ Klinman, DM Ozato, K AF Tsujimura, H Tamura, T Kong, HJ Nishiyama, A Ishii, KJ Klinman, DM Ozato, K TI Cytokine induction by toll-like receptor 9 depends on the transcription factor IRF-8/ICSBP in dendritic cells SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 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 2003 VL 102 IS 11 MA 1914 BP 523A EP 523A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701913 ER PT J AU Nitto, T Mejia, RA Bystrom, J Dyer, KD Wynn, TA Rosenberg, HF AF Nitto, T Mejia, RA Bystrom, J Dyer, KD Wynn, TA Rosenberg, HF TI IL-5 dependent regulation of eosinophil ribonuclease gene expression SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 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 2003 VL 102 IS 11 MA 1920 BP 524A EP 524A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701919 ER PT J AU Shen, Y Iqbal, J Xiao, L Lynch, RC Rosenwald, A Staudt, LM Sherman, S Dybkaer, KS Zhou, G Eudy, JD Delabie, J McKeithan, TW Chan, WC AF Shen, Y Iqbal, J Xiao, L Lynch, RC Rosenwald, A Staudt, LM Sherman, S Dybkaer, KS Zhou, G Eudy, JD Delabie, J McKeithan, TW Chan, WC TI Identification of distinct gene expression profiles in different B-cell compartments in peripheral lymphoid organs. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Nebraska, Ctr Med, Munroe Meyer Inst, Ctr Human Mol Genet,Eppley Canc Inst,Dept Pathol, Omaha, NE 68198 USA. Univ Nebraska, Ctr Med, Munroe Meyer Inst,Dept Microbiol, Ctr Human Mol Genet,Eppley Canc Inst, Omaha, NE 68198 USA. Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. Univ Wurzburg, Dept Pathol, Wuerzburg, Ghana. NCI, Metab Branch, Ctr Canc Res, 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 2003 VL 102 IS 11 MA 1926 BP 526A EP 526A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701925 ER PT J AU Zhang, H Maus, MV June, CH Mackall, CL AF Zhang, H Maus, MV June, CH Mackall, CL TI Efficient expansion of human cytolytic CD8+T cells using anti-CD3/4-1BBL. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 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 2003 VL 102 IS 11 MA 1935 BP 528A EP 529A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701934 ER PT J AU Miera, A Jung, U Foley, JE Ullman, S Fowler, DH Hou, J AF Miera, A Jung, U Foley, JE Ullman, S Fowler, DH Hou, J TI CD28 co-stimulation of murine CD4(+)CD25(+) T regulatory cells: Flexible Th1/Th2 polarity and abrogation of T-reg function. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Natl Canc Inst, Natl Inst Hlth, 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 2003 VL 102 IS 11 MA 1937 BP 529A EP 529A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701936 ER PT J AU Taylor, JG Chen, RA Heller, SI Bernig, T Chanock, SJ AF Taylor, JG Chen, RA Heller, SI Bernig, T Chanock, SJ TI Common promoter haplotypes defined by SNPs in the vascular cell adhesion molecule 1 (VCAM1) gene modify basal and cytokine responsive reporter gene transcription. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Gaithersburg, 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 2003 VL 102 IS 11 MA 1951 BP 532A EP 532A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701950 ER PT J AU Beleslin-Cokic, BB Gojkovic-Bukarica, L Cokic, VP Noguchi, CT AF Beleslin-Cokic, BB Gojkovic-Bukarica, L Cokic, VP Noguchi, CT TI Erythropoietin stimulation of isolated human blood vessels and vascular smooth muscle cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDK, Biol Chem Lab, Natl Inst Hlth, Bethesda, MD USA. Univ Belgrade, Fac Med, Inst Clin Pharmacol Pharmacol & Toxicol, Belgrade, Serbia, Yugoslavia. 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 2003 VL 102 IS 11 MA 1953 BP 533A EP 533A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701952 ER PT J AU Aronson, DL Krizek, DM Rick, ME AF Aronson, DL Krizek, DM Rick, ME TI ADAMTS13 proteolysis of von Willebrand factor: What is bite-sized. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIH, Hematol Serv, Dept Lab Med, Ctr Clin, 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 2003 VL 102 IS 11 MA 1999 BP 544A EP 545A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701998 ER PT J AU Brown, KE Zhi, N Zadori, Z Wong, S Peter, T AF Brown, KE Zhi, N Zadori, Z Wong, S Peter, T TI Construction and sequencing of an infectious clone of the human parvovirus B19. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Univ Quebec, Inst Armand Frappier, INRS, Laval, PQ G1V 2M3, Canada. 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 2003 VL 102 IS 11 MA 2053 BP 559A EP 559A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702052 ER PT J AU El Kassar, N Lucas, PJ Merchant, M Bare, CV Mackall, C Mahmud, S Bhandoola, A Gress, RE AF El Kassar, N Lucas, PJ Merchant, M Bare, CV Mackall, C Mahmud, S Bhandoola, A Gress, RE TI Dose effect of IL-7 on TCR alpha beta and B cell development in the thymus. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 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 2003 VL 102 IS 11 MA 2073 BP 564A EP 564A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702071 ER PT J AU Nemeth, MJ Cline, AP Anderson, SM Garrett-Beal, LJ Bodine, DM AF Nemeth, MJ Cline, AP Anderson, SM Garrett-Beal, LJ Bodine, DM TI Decreased numbers of active primitive stem and progenitors in Hmgb3 knock-out mice correlate with delayed cell cycle progression. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NHGRI, Transgen Mouse Core, Bethesda, MD 20892 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 2003 VL 102 IS 11 MA 2092 BP 569A EP 569A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702090 ER PT J AU Jeon, JP Kundu, M Liu, P AF Jeon, JP Kundu, M Liu, P TI Role of c-Myc promoter binding protein, MBP-l, in hematopoiesis and leukemogenesis. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHGRI, Oncogenesis & Dev Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X 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 2003 VL 102 IS 11 MA 2157 BP 585A EP 586A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536702155 ER PT J AU Slape, CI Lowe, L Aplan, PD AF Slape, CI Lowe, L Aplan, PD TI Generation of immortal, IL3-dependent cell lines from embryonic stem (ES) cells expressing a NUP98-HOXD13 fusion gene. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Genet Branch, 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 2003 VL 102 IS 11 MA 2165 BP 587A EP 587A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702163 ER PT J AU Tomita, A Buchholz, DR Shi, YB AF Tomita, A Buchholz, DR Shi, YB TI PML-RAR and PLZF-RAR fusion proteins repress transcription by recruiting N-CoR-TBLR1 co-repressor complexes to target promoters in vivo. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NICHD, Lab Gene Regulat & Dev, NIH, 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 2003 VL 102 IS 11 MA 2177 BP 590A EP 591A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536702175 ER PT J AU Wlodarski, M O'Keefe, CL Plasilova, M Rodriguez, A Howe, E Risitano, A Young, NS Loughran, TP Karban, J Maciejewski, JP AF Wlodarski, M O'Keefe, CL Plasilova, M Rodriguez, A Howe, E Risitano, A Young, NS Loughran, TP Karban, J Maciejewski, JP TI Analysis of T cell receptor repertoire in LGL leukemia supports a non-random evolution of immunodominant CTL clones. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Cleveland Clin Fdn, Ctr Canc, Expt Hematol & Hematopoiesis Sect, Cleveland, OH USA. NIH, Hematol Branch, Bethesda, MD USA. Penn State Med Ctr, Inst Canc, Hershey, PA USA. Charles Univ, Fac Med 1, Prague, Czech Republic. 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 2003 VL 102 IS 11 MA 2218 BP 601A EP 601A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702216 ER PT J AU Shami, PJ Saavedra, JE Holubkov, R Wang, LY Keefer, LK AF Shami, PJ Saavedra, JE Holubkov, R Wang, LY Keefer, LK TI JS-K, a novel nitric oxide (NO) generator, shows potent anti-leukemic efficacy in a systemic human leukemia xenograft model. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Utah, Salt Lake City, UT USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 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 2003 VL 102 IS 11 MA 2310 BP 626A EP 626A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702308 ER PT J AU Dunleavy, KM Janik, J Grant, N White, T Pittaluga, S Jaffe, ES Staudt, L Wilson, WH AF Dunleavy, KM Janik, J Grant, N White, T Pittaluga, S Jaffe, ES Staudt, L Wilson, WH TI Phase I/II study of bortezomib combined with dose adjusted-EPOCH chemotherapy in relapsed or refractory diffuse large B-cell lymphomas SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Canc Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 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 2003 VL 102 IS 11 MA 2349 BP 636A EP 637A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536702347 ER PT J AU O'Connor, O Wright, J Moskowitz, CH Muzzy, J MacGregor-Cortelli, B Hamlin, P Straus, D Trehu, E Schenkein, DP Zelenetz, AD AF O'Connor, O Wright, J Moskowitz, CH Muzzy, J MacGregor-Cortelli, B Hamlin, P Straus, D Trehu, E Schenkein, DP Zelenetz, AD TI Promising activity of the proteasome inhibitor bortezomib (velcade) in the treatment of indolent non-Hodgkin's lymphoma and mantle cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Natl Canc Inst, Drug Dev Branch, Bethesda, MD USA. Millenium Pharmaceut, Cambridge, MA 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 2003 VL 102 IS 11 MA 2346 BP 636A EP 636A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702344 ER PT J AU Goy, A Bleyer, A Hagemeister, F Fayad, L Pro, B Romaguera, J Samaniego, F Sarris, AH Hart, S Cabanillas, F Murgo, A Duvic, M Rodriguez, MA AF Goy, A Bleyer, A Hagemeister, F Fayad, L Pro, B Romaguera, J Samaniego, F Sarris, AH Hart, S Cabanillas, F Murgo, A Duvic, M Rodriguez, MA TI Phase II study of compound GW506U78 (AraG) for patients with indolent B-cell or peripheral T-cell lymphoma previously treated with chemotherapy SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 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 2003 VL 102 IS 11 MA 2359 BP 639A EP 639A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702357 ER PT J AU Piekarz, RL Frye, R Zhan, ZR Turner, M Robey, RW Steadman, K Fojo, T Bates, SE AF Piekarz, RL Frye, R Zhan, ZR Turner, M Robey, RW Steadman, K Fojo, T Bates, SE TI Depsipeptide (FK228) in patients with cutaneous T cell lymphoma as a model for the use of histone deacetylase inhibitors in cancer therapy. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Canc Therapeut Branch, Bethesda, MD 20892 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RI Steadman, Kenneth/J-3883-2013 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 2003 VL 102 IS 11 MA 2366 BP 641A EP 641A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702364 ER PT J AU Courtenay-Luck, N Rybak, S Newton, D AF Courtenay-Luck, N Rybak, S Newton, D TI Treatment of human Daudi lymphoma with anti-MUC1 antibody-targeted RNase in SCID mice. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Antisoma Res Ltd, London, England. NCI, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 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 2003 VL 102 IS 11 MA 2387 BP 646A EP 646A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702385 ER PT J AU Janik, JE Morris, JC Quinn, C Gao, W Waldmann, TA Wilson, WH Kwak, LW Pittaluga, S Neelapu, S Streicher, H Berzofsky, LA Dahut, W Arlen, P Gulley, JL Schlom, J Davis, TA Lowy, I Nichol, G AF Janik, JE Morris, JC Quinn, C Gao, W Waldmann, TA Wilson, WH Kwak, LW Pittaluga, S Neelapu, S Streicher, H Berzofsky, LA Dahut, W Arlen, P Gulley, JL Schlom, J Davis, TA Lowy, I Nichol, G TI A pilot study of MDX-010 after vaccine failure in patients with advanced malignancy. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Medarex Inc, Clin Sci, Bloomsbury, NJ USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 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 2003 VL 102 IS 11 MA 2391 BP 647A EP 647A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702389 ER PT J AU Gupta, M Brynes, R Nathwani, B Nichols, P Raffeld, M Jaffe, ES Feinstein, D AF Gupta, M Brynes, R Nathwani, B Nichols, P Raffeld, M Jaffe, ES Feinstein, D TI Cyclosporine alone produces dramatic response and long-term progression free survival in patients with hemophagocytic syndrome and sulicuticular lymphoid dysplasia-subcutaneous panniculitis-like T-cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Los Angeles Cty & USC Med Ctr, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. NCI, Pathol 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 2003 VL 102 IS 11 MA 2398 BP 649A EP 649A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702396 ER PT J AU Caruccio, L Bettinotti, M Fraser, E Director-Myska, A Arthur, DC Stroncek, D AF Caruccio, L Bettinotti, M Fraser, E Director-Myska, A Arthur, DC Stroncek, D TI PRV-1 and NB1 are alleles of a single gene, CD177, at region 19q13.2 and PRV-1 is the most common allele in a normal population. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Dept Biol, Cambridge, MA 02138 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 2003 VL 102 IS 11 MA 2449 BP 661A EP 661A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702447 ER PT J AU Rassenti, LZ Toy, TL Huynh, L Greaves, A Gribben, JG Keating, MJ Rai, KR Flinn, IW Byrd, JC Kay, NE Goldin, LR Caporaso, NE Kipps, TJ AF Rassenti, LZ Toy, TL Huynh, L Greaves, A Gribben, JG Keating, MJ Rai, KR Flinn, IW Byrd, JC Kay, NE Goldin, LR Caporaso, NE Kipps, TJ TI High similarity between familial and sporadic cases of chroni lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Calif San Diego, La Jolla, CA 92093 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Long Isl Jewish Med Ctr, New York, NY USA. Johns Hopkins Univ, Ctr Canc, Baltimore, MD USA. Ohio State Univ, Columbus, OH 43210 USA. Mayo Clin, Rochester, MN USA. Natl Canc Inst, Rockville, MD USA. Univ Calif San Diego, CLL Res Consortium, La Jolla, CA 92093 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 2003 VL 102 IS 11 MA 2481 BP 670A EP 670A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702479 ER PT J AU Aurran-Schleinitz, TM Telford, W Perfetto, S Wilson, WH Marti, GE AF Aurran-Schleinitz, TM Telford, W Perfetto, S Wilson, WH Marti, GE TI Comparative multicolor flow cytometry of blood from normal donors and chronic lymphocytic leukemia to assess normal and aberrant B-cell subsets. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 US FDA, CBER, OCTGT, DCGT,Lab Stem Cell Biol, Bethesda, MD 20014 USA. NCI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. NIAIS, Vaccine Res Ctr, NIH, Bethesda, MD USA. NCI, MOCRU, NIH, 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 2003 VL 102 IS 11 MA 2489 BP 672A EP 672A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702487 ER PT J AU Gabrea, A Martelli, ML Qi, Y Barlogie, B Sawyer, JR Shaughnessy, JD Kuehl, MW AF Gabrea, A Martelli, ML Qi, Y Barlogie, B Sawyer, JR Shaughnessy, JD Kuehl, MW TI Different roles for IgH and Ig lambda translocations in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Bethesda, MD 20892 USA. Med Sch Catanzaro, Catanzaro, Italy. Univ Maryland, Baltimore, MD 21201 USA. Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 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 2003 VL 102 IS 11 MA 2508 BP 677A EP 677A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702506 ER PT J AU Badros, AZ Ratterree, B Natt, S Rapoport, AP Zeldis, JB Frankel, SR Meisenberg, B Takebe, N Zwiebel, JA Zhang, B Fenton, R AF Badros, AZ Ratterree, B Natt, S Rapoport, AP Zeldis, JB Frankel, SR Meisenberg, B Takebe, N Zwiebel, JA Zhang, B Fenton, R TI Phase I/II trial of oblimersen sodium (G3139), dexamethasone (Dex) and thalidomide (Thal) in patients with relapsed multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. NCI, CTEP, 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 2003 VL 102 IS 11 MA 2533 BP 684A EP 684A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702532 ER PT J AU Re, F Srinivasan, R Marincola, F Igarashi, T Barrett, J Childs, RW AF Re, F Srinivasan, R Marincola, F Igarashi, T Barrett, J Childs, RW TI Characterization of allogeneic leukemia specific CTL from HLA- matched siblings of leukemia patients using dendritic cells-tumor hybrids generated by electrofusion (EF) and polyethylene glycol (PEG) treatment. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 San Raffaele Sci Inst, Hematol Bone Marrow Transplant Unit, I-20132 Milan, Italy. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NIH, 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 2003 VL 102 IS 11 MA 2584 BP 698A EP 698A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702583 ER PT J AU Takahashi, Y Mena, O Srinivasan, R Igarashi, T Carvallo, C Rosenbaum, MG Linehan, WM Childs, RW AF Takahashi, Y Mena, O Srinivasan, R Igarashi, T Carvallo, C Rosenbaum, MG Linehan, WM Childs, RW TI Minor histocompatibility antigen (mHa) specific T-cells with cytotoxicity against autologous tumor cells can be isolated from patients with renal cell carcinoma having a GVT effect after nonmyeloablative hematopoietic cell transplantation (HCT). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIH, Hematol Branch, NHLBI, Bethesda, MD 20892 USA. NIH, NCI, Med Urolog Oncol 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 2003 VL 102 IS 11 MA 2594 BP 701A EP 701A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702593 ER PT J AU Reese, A Stevens, WT Donohue, T Chakrabarti, S Wesley, R Castro, K Fowler, D Bishop, MR Stroncek, D Leitman, S Childs, RW Bolan, CD AF Reese, A Stevens, WT Donohue, T Chakrabarti, S Wesley, R Castro, K Fowler, D Bishop, MR Stroncek, D Leitman, S Childs, RW Bolan, CD TI Clinical and laboratory features of minor ABO incompatible reduced intensity blood hematopoietic cell transplantation using cyclosporin (CsA) vs. CsA/mycophenolate mofetil (CsA/MMF) for graft-vs-host disease (GVHD) prophylaxis. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Natl Naval Med Res Inst, Dept Hematol Oncol, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Clin Ctr, Bethesda, MD 20892 USA. NIH, Bostat Serv, Bethesda, MD USA. NCI, Expt Transplantat & Immunol Branch, 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 2003 VL 102 IS 11 MA 2620 BP 708A EP 708A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702619 ER PT J AU Battiwalla, M Kurlander, R Solomon, SR Wehrlen, L Greene, A Barrett, AJ AF Battiwalla, M Kurlander, R Solomon, SR Wehrlen, L Greene, A Barrett, AJ TI Donor T lymphocyte engraftment is facilitated by higher CD34 cell doses in T cell depleted myeloablative allogeneic peripheral blood stem cell transplantation (PBSCT). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD USA. NIH, Ctr Clin, 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 2003 VL 102 IS 11 MA 2623 BP 709A EP 709A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702622 ER PT J AU Espinoza-Delgado, IJ Shetty, V Geller, N Bahceci, E Srinivasan, R Chakrabarti, S Solomon, S Marquesen, M Goodwin, R Swanson, P Barret, AJ Childs, RW AF Espinoza-Delgado, IJ Shetty, V Geller, N Bahceci, E Srinivasan, R Chakrabarti, S Solomon, S Marquesen, M Goodwin, R Swanson, P Barret, AJ Childs, RW TI Impact of age on transplant related mortality (TRM) following fludarabine and cyclophosphamide-based nonmyeloablative allogeneic hematopoietic cell transplantation (HCT). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIA, Hematol Oncol Sect, Baltimore, MD 21224 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Yale Univ, Ctr Canc, New Haven, CT 06520 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NCI, Urol Oncol 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 2003 VL 102 IS 11 MA 2656 BP 718A EP 718A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702655 ER PT J AU Yamashita, K Choi, U Woltz, PC Tamari, M Castro, K Hakim, FT Pavletic, SZ Malech, HL Horwitz, ME AF Yamashita, K Choi, U Woltz, PC Tamari, M Castro, K Hakim, FT Pavletic, SZ Malech, HL Horwitz, ME TI Severe chronic graft-versus-host-disease is characterized by an increase in CD4(+) effector memory cells relative to central memory cells that normalize following extracorporeal photopheresis. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 2003 VL 102 IS 11 MA 2663 BP 720A EP 720A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702662 ER PT J AU Bevans, M Marden, S Leidy, N Soeken, K Rivera, P Cusack, G Mayberry, H Bishop, M Barrett, J AF Bevans, M Marden, S Leidy, N Soeken, K Rivera, P Cusack, G Mayberry, H Bishop, M Barrett, J TI Quality of life in patients undergoing non-myeloablative (NST) versus myeloablative (MT) allogeneic peripheral blood stem cell transplantation (PBSCT). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIH, Bethesda, MD 20892 USA. MEDTAP Inc, Bethesda, MD USA. Univ Maryland, Baltimore, MD 21201 USA. NCI, Bethesda, MD 20892 USA. NHLBI, 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 2003 VL 102 IS 11 MA 2672 BP 722A EP 722A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702671 ER PT J AU Lim, JB Provenzano, M Bettinotti, M Caruccio, L Nalgosen, D Stroncek, D AF Lim, JB Provenzano, M Bettinotti, M Caruccio, L Nalgosen, D Stroncek, D TI Identification of a new HLA-A*3301 and HLA-A*3303 restricted cytomegalovirus-specific CD8+T lymphocyte epitope. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Yonsei Univ, Coll Med, Dept Lab Med, Seoul 120749, South Korea. NIH, 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 2003 VL 102 IS 11 MA 2677 BP 724A EP 724A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702676 ER PT J AU Chakrabarti, S Balow, JE Srinivasan, R Igarashi, T Takahashi, Y Carvallo, C Marquesen, M Goodwin, R Barrett, AJ Childs, R AF Chakrabarti, S Balow, JE Srinivasan, R Igarashi, T Takahashi, Y Carvallo, C Marquesen, M Goodwin, R Barrett, AJ Childs, R TI High-incidence of nephrotic syndrome associated with significant morbidity following nonmyeloablative allogeneic hematopoietic cell transplantation (HCT). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIDDK, 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 2003 VL 102 IS 11 MA 2687 BP 726A EP 727A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536702686 ER PT J AU Dean, RM Fowler, DH Wilson, W Odom, J Steinberg, S Chow, C Kasten-Sportes, C Gress, RE Bishop, MR AF Dean, RM Fowler, DH Wilson, W Odom, J Steinberg, S Chow, C Kasten-Sportes, C Gress, RE Bishop, MR TI Response to salvage chemotherapy influences outcome of reduced-intensity allogeneic stem cell transplantation for non-Hodgkin's lymphoma but does not preclude durable survival. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Canc Res Ctr, Expt Transplantat & Immunol 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 2003 VL 102 IS 11 MA 2691 BP 727A EP 728A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536702690 ER PT J AU Spitzer, TR Sykes, M Delmonico, F Tolkoff-Rubin, N McAfee, SL Dey, BR Ballen, K Sackstein, R Colby, C Saidman, S Ramos, EL Seyfert-Margolis, V Sachs, DH Cosimi, AB AF Spitzer, TR Sykes, M Delmonico, F Tolkoff-Rubin, N McAfee, SL Dey, BR Ballen, K Sackstein, R Colby, C Saidman, S Ramos, EL Seyfert-Margolis, V Sachs, DH Cosimi, AB TI Tolerance and antitumor responses following combined HLA-matched nonmyeloablative bone marrow and kidney transplantation for multiple myeloma with end-stage renal disease. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NIAID, Immune Tolerance Network, 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 2003 VL 102 IS 11 MA 2692 BP 728A EP 728A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702691 ER PT J AU Hawley, RG Moayeri, M Ramezani, A Morgan, RA Hawley, TS AF Hawley, RG Moayeri, M Ramezani, A Morgan, RA Hawley, TS TI Toward safe and efficient hemophilia A gene therapy. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Amer Red Cross, Holland Lab, Rockville, MD USA. George Washington Univ, Washington, DC USA. 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 2003 VL 102 IS 11 MA 2738 BP 742A EP 742A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702738 ER PT J AU Zhao, YB Zheng, ZL Robbins, PF Khong, HT Rosenberg, SA Morgan, RA AF Zhao, YB Zheng, ZL Robbins, PF Khong, HT Rosenberg, SA Morgan, RA TI Primary human lymphocytes retrovirally transduced with NY-ESO-1 antigen specific TCR genes recognize and kill NY-ESO-1 positive melanoma as well as other tumors. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Surg 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 2003 VL 102 IS 11 MA 2752 BP 746A EP 746A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702752 ER PT J AU Huang, Z Wong, AL Partovi, KS Schechter, AN Gladwin, MT AF Huang, Z Wong, AL Partovi, KS Schechter, AN Gladwin, MT TI The oxygen-dependent nitrite reductase/oxidase activity of hemoglobin. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Natl Inst Hlth, NIDDK, Biol Chem Lab, Bethesda, MD USA. Univ So Calif, Los Angeles, CA USA. Natl Inst Hlth, Dept Crit Care Med, Clin Ctr, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 2003 VL 102 IS 11 MA 2796 BP 758A EP 758A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702796 ER PT J AU Morris, CR Poljakovic, M Morris, SM Gladwin, MT AF Morris, CR Poljakovic, M Morris, SM Gladwin, MT TI Decreased L-arginine bioavailability and elevated arginase activity in sickle cell disease: A novel pathway towards pulmonary hypertension? SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Childrens Hosp Oakland, Res Ctr, Oakland, CA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NIDDK, Biol Chem Lab, Natl Inst Hlth, Bethesda, MD 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 2003 VL 102 IS 11 MA 2818 BP 763A EP 764A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536702818 ER PT J AU Seggewiss, R Dunbar, CE Magnusson, MK Wiestner, A AF Seggewiss, R Dunbar, CE Magnusson, MK Wiestner, A TI Imatinib inhibits T-cell activation and proliferation in a dose-dependent manner. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, DHHS, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, DHHS, Bethesda, MD USA. Landspitali Univ Hosp, Dept Lab Med, Reykjavik, Iceland. 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 2003 VL 102 IS 11 MA 2836 BP 768A EP 769A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536702836 ER PT J AU Fujiwara, H El Ouriaghli, F Kajigaya, S Melenhorst, J Rezvani, K Grube, M Sconocchia, G Hensel, N Barrett, AJ AF Fujiwara, H El Ouriaghli, F Kajigaya, S Melenhorst, J Rezvani, K Grube, M Sconocchia, G Hensel, N Barrett, AJ TI DNA loaded CD40-activated B cells (CD40-B) efficiently induce T-cell responses to diverse primary granule proteins (PGP) and CMV. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA 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 2003 VL 102 IS 11 MA 2839 BP 769A EP 769A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702839 ER PT J AU Aggarwal, A Grewal, R Green, RJ Boggio, L Green, D Wiestner, A Schechter, GP AF Aggarwal, A Grewal, R Green, RJ Boggio, L Green, D Wiestner, A Schechter, GP TI Rituximab for autoimmune hemophilia: A proposed treatment algorithm. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Washington Hosp Ctr, Washington, DC 20010 USA. Palm Beach Canc Inst, W Palm Beach, FL USA. Northwestern Univ, Chicago, IL 60611 USA. NCI, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. VA Med 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 2003 VL 102 IS 11 MA 2957 BP 799A EP 799A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702957 ER PT J AU Akel, S Bertolette, D Roberts, A Letterio, J Ruscetti, FW AF Akel, S Bertolette, D Roberts, A Letterio, J Ruscetti, FW TI Cross talk between the smad and the mitogen-activated protein kinase (MAPK) pathways regulates erythroid differentiation of erythroleukemic cells induced by TGF-beta, activin, hydroxyurea and butyrate. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, BRL, CCR, Frederick, MD 21701 USA. Hashemite Univ, Dept Med Lab Sci, Zarqa, Jordan. NCI, CCR, LCRC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 2003 VL 102 IS 11 MA 3093 BP 834A EP 834A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703093 ER PT J AU Jelacic, TM Linnekin, DM AF Jelacic, TM Linnekin, DM TI Protein kinase C delta plays opposite roles in growth mediated by wild type Kit and an oncogenic Kit mutant. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Basic Res Lab, Frederick, MD 21701 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 2003 VL 102 IS 11 MA 3094 BP 834A EP 834A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703094 ER PT J AU Khaldoyanidi, SK Matrosova, VY Orlovskaya, IA Scrobyan, N McClelland, M AF Khaldoyanidi, SK Matrosova, VY Orlovskaya, IA Scrobyan, N McClelland, M TI Hyaluronan, an essential component of the hematopoietic niche, facilitates recovery of ablated hematopoiesis by regulation of cytokine production. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 La Jolla Inst Mol Med, Dept Vasc Biol, San Diego, CA USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Inst Clin Immunol, Novosibirsk, Russia. Sidney Kimmel Canc Ctr, San Diego, CA USA. RI McClelland, Michael/A-8583-2011 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 2003 VL 102 IS 11 MA 3117 BP 839A EP 839A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703117 ER PT J AU Cokic, VP Beleslin-Cokic, BB Noguchi, CT Schechter, AN AF Cokic, VP Beleslin-Cokic, BB Noguchi, CT Schechter, AN TI Hydroxyurea induction of the eNOS - cGMP pathway in endothelial cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDKD, Biol Chem Lab, 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 2003 VL 102 IS 11 MA 3130 BP 842A EP 842A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703130 ER PT J AU Ho, LZ Davis, RE Conne, B Berczy, M Machweh-Fauceglia, P Staudt, LM Schwaller, J AF Ho, LZ Davis, RE Conne, B Berczy, M Machweh-Fauceglia, P Staudt, LM Schwaller, J TI The cIAP2/MALT1 fusion gene enhances CD40-mediated NF-kappa B activation in human germinal center B-cell lymphoma cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Geneva, Sch Med, Dept Pathol, CH-1211 Geneva, Switzerland. NCI, Metab Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 2003 VL 102 IS 11 MA 3150 BP 848A EP 848A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703150 ER PT J AU Varticovski, L Gandhi, BB Neckers, L Harris, CC Robles, AI AF Varticovski, L Gandhi, BB Neckers, L Harris, CC Robles, AI TI Hsp90 inhibitors reverse resistance to doxorubicin in p53-Null and mutant cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIH, Canc Res Ctr, 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 2003 VL 102 IS 11 MA 3212 BP 863A EP 863A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703212 ER PT J AU Marcucci, G Dai, GW Klisovic, MI Shen, TS Liu, SJ Sher, DA Lucas, D Whitman, SP Vukosavljevic, T Zwiebel, JA Frankel, SR Grever, MR Stock, W Chan, KK Byrd, JC AF Marcucci, G Dai, GW Klisovic, MI Shen, TS Liu, SJ Sher, DA Lucas, D Whitman, SP Vukosavljevic, T Zwiebel, JA Frankel, SR Grever, MR Stock, W Chan, KK Byrd, JC TI Pharmacologie and biologic assessment of Genasense (TM) (GNS, oblimersen sodium), a pro-apoptotic to Bcl-2 oligonucleotide, in combination with daunorubicin and cytarabine: A phase I study in previously untreated elderly acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Univ Chicago, Div Hematol Oncol, Chicago, IL 60637 USA. NCI, CTEP, Bethesda, MD 20892 USA. Genta Inc, Berkeley Hts, NJ 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 2003 VL 102 IS 11 MA 3254 BP 874A EP 874A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703254 ER PT J AU Iqbal, J Sanger, WG Horsman, DE Rosenwald, A Pickering, DL Dave, S Cao, K Zhu, Q Xiao, L Hans, CP Weisenburger, DD Greiner, TC Gascoyne, RD Ott, G Mueller-Hermelink, HK Delabie, J Braziel, RM Jaffe, ES Campo, E Lynch, JC Connors, JM Vose, JM Armitage, JO Grogan, T Staudt, LM Chan, WC AF Iqbal, J Sanger, WG Horsman, DE Rosenwald, A Pickering, DL Dave, S Cao, K Zhu, Q Xiao, L Hans, CP Weisenburger, DD Greiner, TC Gascoyne, RD Ott, G Mueller-Hermelink, HK Delabie, J Braziel, RM Jaffe, ES Campo, E Lynch, JC Connors, JM Vose, JM Armitage, JO Grogan, T Staudt, LM Chan, WC TI BCL2 translocation defines a subset of DLBCL with germinal center B-cell-like gene expression profiles and preferential expression of a set of genes. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Microbiol, Omaha, NE 68105 USA. Univ Nebraska, Med Ctr, Eppley Inst Res Canc, Omaha, NE 68105 USA. Univ Nebraska, Dept Comp Sci, Omaha, NE 68182 USA. British Columbia Canc Agcy, Dept Pathol & Med Oncol, Vancouver, BC V5Z 4E6, Canada. Univ Wurzburg, Dept Pathol, Wurzburg, Germany. Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. NCI, Canc Res Ctr, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Barcelona, Hosp Clin, Dept Pathol, Barcelona, Spain. Univ Arizona, SW Oncol Grp, Tucson, AZ 85721 USA. NR 0 TC 2 Z9 2 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 2003 VL 102 IS 11 MA 3289 BP 884A EP 884A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703289 ER PT J AU Zhao, SM Martinez, A Stetler-Stevenson, M Stetler-Stevenson, WG Guedez, L AF Zhao, SM Martinez, A Stetler-Stevenson, M Stetler-Stevenson, WG Guedez, L TI A role of tissue inhibitor of metalloproteinase(TIMP)-1 in regulating IL-10-autocrine signaling in B cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Pathol Lab, CCR, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012; Guedez, Liliana/H-4951-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808; 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 2003 VL 102 IS 11 MA 3296 BP 886A EP 886A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703296 ER PT J AU Rimsza, L Roberts, R Campo, E Grogan, T Bea, S Salaverria, I Zettl, A Fisher, R Unger, J LeBlanc, M Staudt, L Gascoyne, R Chan, W Weisenburger, D Greiner, T Jaffe, E Braziel, R Mueller-Hermelink, K AF Rimsza, L Roberts, R Campo, E Grogan, T Bea, S Salaverria, I Zettl, A Fisher, R Unger, J LeBlanc, M Staudt, L Gascoyne, R Chan, W Weisenburger, D Greiner, T Jaffe, E Braziel, R Mueller-Hermelink, K TI Loss of major histocompatibility class II (MHCII) expression in nodal diffuse large B cell lymphoma (DLBCL) is highly coordinated and unlikely related to chromosomal deletions. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Univ Arizona, Dept Pathol, Tucson, AZ USA. Univ Barcelona, Hosp Clin & Prov, Barcelona, Spain. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. Fred Hutchinson Canc Res Ctr, Stat Ctr, Seattle, WA 98104 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Nebraska, Dept Pathol, Omaha, NE 68182 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ 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 2003 VL 102 IS 11 MA 3321 BP 893A EP 893A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703321 ER PT J AU Grube, M Rezvani, K Wiestner, A Fujiwara, H Sconocchia, G Melenhorst, JJ Hensel, N Barrett, JA AF Grube, M Rezvani, K Wiestner, A Fujiwara, H Sconocchia, G Melenhorst, JJ Hensel, N Barrett, JA TI Detectable frequencies of cytotoxic T cells (CTL) recognizing peptide epitopes of CD19 and CD20 occur in healthy individuals and in patients with B cell malignancies. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. 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 2003 VL 102 IS 11 MA 3325 BP 894A EP 894A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703325 ER PT J AU Guedez, L Zhao, SM Martinez, A Kim, YS Stetler-Stevenson, M Stetler-Stevenson, WG AF Guedez, L Zhao, SM Martinez, A Kim, YS Stetler-Stevenson, M Stetler-Stevenson, WG TI Tissue inhibitor of metalloprotease (TIMP)-1 promotes a post-germinal center transcription program in a Burkitt's lymphoma cell line. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Pathol Lab, CCR, Bethesda, MD 20892 USA. RI Martinez, Antonio/D-8188-2012; Stetler-Stevenson, William/H-6956-2012 OI Martinez, Antonio/0000-0003-0790-9017; Stetler-Stevenson, William/0000-0002-5500-5808 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 2003 VL 102 IS 11 MA 3336 BP 897A EP 897A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703336 ER PT J AU Sloand, EM Mainwaring, LA Chen, GB Barrett, AJ Young, NS AF Sloand, EM Mainwaring, LA Chen, GB Barrett, AJ Young, NS TI Granulocyte-colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells but does not foster development of this abnormality in cells with normal karyotype. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA 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 2003 VL 102 IS 11 MA 3395 BP 912A EP 913A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536703395 ER PT J AU Gotlib, J Loh, M Lancet, JE Vattikuti, S Quesada, S Dugan, K Katamneni, U Sridhar, K Wright, J Thibault, A Rybak, ME Shannon, KM Greenberg, PL AF Gotlib, J Loh, M Lancet, JE Vattikuti, S Quesada, S Dugan, K Katamneni, U Sridhar, K Wright, J Thibault, A Rybak, ME Shannon, KM Greenberg, PL TI Phase I/II study of tipifarnib (ZARNESTRA (TM), farnesyltransferase inhibitor [FTI] R115777) in patients with myeloproliferative disorders (MPDs): Interim results. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. UCSF, Sch Med, San Francisco, CA USA. Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. Palo Alto Vet Hlth Care Syst, Palo Alto, CA USA. NCI, CTEP, Bethesda, MD 20892 USA. Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ 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 2003 VL 102 IS 11 MA 3425 BP 921A EP 921A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703425 ER PT J AU Robyn, J Akin, C Noel, P Brown, M Law, M Metcalfe, D Dunbar, C Nutman, T Klion, A AF Robyn, J Akin, C Noel, P Brown, M Law, M Metcalfe, D Dunbar, C Nutman, T Klion, A TI Clinical and molecular response to imatinib mesylate in myeloproliferative hypereosinophilic syndrome. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIH, NIAID, Hematol Branch, Bethesda, MD 20892 USA. NIH, NIAID, Lab Parasit Dis, Bethesda, MD 20892 USA. NIH, NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. NIH, Div Lab 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 2003 VL 102 IS 11 MA 3429 BP 922A EP 922A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703429 ER PT J AU Arons, E Stetler-Stevenson, M Raffeld, M Sorbara, L Kreitman, RJ AF Arons, E Stetler-Stevenson, M Raffeld, M Sorbara, L Kreitman, RJ TI Oligoclonal T cell receptor beta gene usage in hairy cell leukemia patients. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA 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 2003 VL 102 IS 11 MA 3439 BP 924A EP 924A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703439 ER PT J AU Qiang, YW Rudikoff, S Yao, L Tosato, G AF Qiang, YW Rudikoff, S Yao, L Tosato, G TI Wnt-3a induces migration of myeloma cells via activation of RhoA and PKC pathways. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. 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 2003 VL 102 IS 11 MA 3450 BP 927A EP 927A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703450 ER PT J AU Chu, YW Memon, SA Sharrow, SO Hakim, FT Gress, RE AF Chu, YW Memon, SA Sharrow, SO Hakim, FT Gress, RE TI IL-7 administration increases recent thymic emigrant populations in lymphoid tissue by altered lymphocyte trafficking and not by enhancement of thymic function. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIH, Expt Immunol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NIH, Expt Transplantat & Immunol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RI Memon, Sarfraz/E-1198-2013 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 2003 VL 102 IS 11 MA 3498 BP 939A EP 939A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703498 ER PT J AU Daniels, JT Fusaro, V Rosenblatt, K Ross, S Igarashi, T Srinivasan, R Petricoin, EF Liotta, L Childs, RW AF Daniels, JT Fusaro, V Rosenblatt, K Ross, S Igarashi, T Srinivasan, R Petricoin, EF Liotta, L Childs, RW TI Serologic methods to diagnose acute GVHD based on protein patterns using surface-enhanced-laser-desorption-ionization-time of flight (SELDI-TOF) mass spectrometry. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Walter Reed Army Med Ctr, Washington, DC 20307 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, NIH, Bethesda, MD 20014 USA. NCI, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol 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 2003 VL 102 IS 11 MA 3536 BP 949A EP 950A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536703536 ER PT J AU Kane, D Fu, PF Howard, M Robert, FM Cooper, BW Gerson, SL Mary, LJ Lazarus, HM Koc, ON AF Kane, D Fu, PF Howard, M Robert, FM Cooper, BW Gerson, SL Mary, LJ Lazarus, HM Koc, ON TI G-CSF-induced splenic enlargement in peripheral blood hematopoietic progenitor cell donors resolves within 10 days. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 2003 VL 102 IS 11 MA 3564 BP 957A EP 957A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703564 ER PT J AU Wayne, A Fowler, D Fry, T Hakim, F Love, C Miller, D Bishop, M Mackall, C Gress, R AF Wayne, A Fowler, D Fry, T Hakim, F Love, C Miller, D Bishop, M Mackall, C Gress, R TI Immune depletion prior to non-myeloablative (NM) allogeneic hematopoietic stem cell transplantation (alloSCT) results in rapid full donor engraftment in pediatric patients with malignancy. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NCI, NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Expt Transplantat Immunol Branch, NIH, Bethesda, MD 20892 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 2003 VL 102 IS 11 MA 3607 BP 968A EP 968A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703607 ER PT J AU Socie, G Rosenberg, PS Gluckman, E Alter, BP AF Socie, G Rosenberg, PS Gluckman, E Alter, BP TI How can we quantify the risk of squamous cell cancer (SCC) and death in transplanted versus non transplanted patients with Fanconi anemia (FA)? SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Hop St Louis, Paris, France. NCI, Div Canc Epidemiol & Genet, 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 2003 VL 102 IS 11 MA 3642 BP 979A EP 979A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703642 ER PT J AU Hematti, P Hanawa, H Keyvanfar, K Krouse, A Donahue, R Persons, D Dunbar, C Nienhuis, A AF Hematti, P Hanawa, H Keyvanfar, K Krouse, A Donahue, R Persons, D Dunbar, C Nienhuis, A TI Transduction of rhesus macaque hematopoietic stem cells with an SIV-based lentiviral vector results in high level in vivo marking SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting and Exhibition of the American-Society-of-Hematology CY DEC 06-09, 2003 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Div Expt Hematol, Memphis, TN 38105 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 2003 VL 102 IS 11 MA 3682 BP 989A EP 989A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703682 ER PT J AU Zhao, MF Chen, ZY Wen, J Yu, XB Beleslin-Cokic, B Rogers, H Noguchi, CT AF Zhao, MF Chen, ZY Wen, J Yu, XB Beleslin-Cokic, B Rogers, H Noguchi, CT TI Lentiviral-mediated modification of erythropoietin receptor on myoblasts confer survival privilege: Potential value for myoblasts transplantation therapy SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. Sidney Kimmel Comprehens Canc Johns Hopkins, Dept Oncol, Baltimore, 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 2003 VL 102 IS 11 MA 3688 BP 991A EP 991A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703688 ER PT J AU Chinen, J Zhu, SG Puck, JM AF Chinen, J Zhu, SG Puck, JM TI Retroviral vector insertion sites in human cord blood CD34 cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NHGRI, Immunogenet Sect, Genet & Mol Biol Branc, NIH, Bethesda, MD 20892 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 2003 VL 102 IS 11 MA 3707 BP 996A EP 997A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536703707 ER PT J AU Brenner, S Choi, U Whiting-Theobald, N Linton, GF Kang, E Rudikoff, AG Farese, AM MacVittie, TJ Horwitz, ME Malech, HL AF Brenner, S Choi, U Whiting-Theobald, N Linton, GF Kang, E Rudikoff, AG Farese, AM MacVittie, TJ Horwitz, ME Malech, HL TI Insertional analyses in rhesus monkey blood cells after non-myeloablative hematopoietic stem cell marking with a RD114-MFGS-gp91phox vector designed for treatment of X-linked chronic granulomatous disease: Pre-clinical safety study. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Clin Carl Gustav Carus, Dept Pediat, Dresden, Saxony, Germany. Univ Maryland, Greenbaum Canc Ctr, Baltimore, MD 21201 USA. RI Brenner, Sebastian/D-7456-2013 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 2003 VL 102 IS 11 MA 3709 BP 997A EP 997A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703709 ER PT J AU Lloyd-Jones, DM Camargo, CA Allen, LA Giugliano, RP O'Donnell, CJ AF Lloyd-Jones, DM Camargo, CA Allen, LA Giugliano, RP O'Donnell, CJ TI Predictors of long-term mortality after hospitalization for primary unstable angina pectoris and non-ST-elevation myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RISK STRATIFICATION; CORONARY SYNDROMES; FOLLOW-UP; MANAGEMENT; PROGNOSIS; CLASSIFICATION; ASSOCIATION; GUIDELINES AB Data are sparse regarding long-term outcomes after hospitalization for unstable angina pectoris (UAP) and non-ST-elevation myocardial infarction (NSTEMI), as defined by contemporary criteria. We extended follow-up in a preexisting database of unselected patients with primary UAP and NSTEMI admitted by way of the emergency department from 1991 to 1992. Stepwise Cox models were used to identify multivariate predictors of long-term mortality. There were 275 patients (mean age 66 +/- 12 years, 33% women) who survived to hospital discharge; 134 patients (49%) died during follow-up (median 9.4 years). Significant multivariate predictors of long-term mortality were: age (hazard ratio [HR] per decade 1.7, 95% confidence interval [CI] 1.4 to 1.9); prior MI (HR 1.7, 95% Cl 1.2 to 2.5); diabetes (HR 1.7, 95% CI 1.2 to 2.4); congestive heart failure (HR 2.2, 95% CI 1.5 to 3.4); elevated creatinine (HR 2.5, 95% CI 1.7 to 3.8); elevated leukocyte count (HR 1.7, 95% CI 1.1 to 2.5); systolic blood pressure <120 mm Hg at presentation (HR 2.0, 95% CI 1.1 to 3.6); lack of coronary revascularization during the index hospitalization (HR 2.0, 95% Cl 1.3 to 3.0); and lack of discharge beta-blocker therapy (HR 1.5, 95% CI 1.1 to 2.2). A clinical prediction rule was generated by assigning weighted point scores for the presence of each significant covariate. Long-term mortality increased markedly with each quintile of score; for quintiles 1 to 5, mortality rates were 8.5%, 29.4%, 47.6%, 75.0%, and 91.5%, respectively (p value for trend <0.001). These data are among the first assessments of long-term mortality after hospitalization for primary UAP and NSTEMI, as defined by contemporary guideline criteria. Easily obtained clinical covariates provide excellent prediction of long-term mortality up to 10 years after hospitalization for primary UAP and NSTEMI. (C)2003 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Lloyd-Jones, DM (reprint author), Massachusetts Gen Hosp, Div Cardiol, CIN 064, Boston, MA 02114 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 18 TC 20 Z9 20 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 2003 VL 92 IS 10 BP 1155 EP 1159 DI 10.1016/j.amjcard.2003.07.022 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 744NM UT WOS:000186638600003 PM 14609588 ER PT J AU Wegienka, G Baird, DD AF Wegienka, G Baird, DD TI Potential bias due to excluding oral contraceptive users when estimating menstrual cycle characteristics SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE bias (epidemiology); contraceptives, oral; menstrual cycle ID WOMEN AB Women take oral contraceptives for contraception but also for menstrual dysfunction treatment. This raises the question of whether or not women with menstrual dysfunction are underrepresented in analyses of menstrual function because oral contraceptive users are excluded. To explore this, the authors examined the history of oral contraceptive use among 1,322 Black women and White women, aged 35-49 years, who had been randomly selected from a large health plan's membership in Washington, DC, between 1996 and 1999. The women reported whether they took oral contraceptives during their teens, twenties, and thirties, and if so, the reason they took them (prevent pregnancy, medical problem, or both). They also reported their usual menstrual cycle length when not using oral contraceptives during these decades. The prevalence of oral contraceptive use strictly for medical problems was low for both Black women and White women (4-9% of women), and the distributions of usual cycle length were similar for women who did and did not take oral contraceptives. Thus, there was little evidence of substantial bias of estimates of cycle characteristics caused by excluding oral contraceptive users from analyses of menstrual function. However, our data indicate that, with only a few additional questions, information on usual menstrual cycle characteristics can be collected and used to evaluate bias in any given study. C1 Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA. NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Wegienka, G (reprint author), Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, 1 Ford Pl,3 E, Detroit, MI 48202 USA. OI Baird, Donna/0000-0002-5544-2653 NR 9 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2003 VL 158 IS 10 BP 947 EP 950 DI 10.1093/aje/kwg246 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 742XV UT WOS:000186544200005 PM 14607802 ER PT J AU London, SJ Pogoda, JM Hwang, KL Langholz, B Monroe, KR Kolonel, LN Kaune, WT Peters, JM Henderson, BE AF London, SJ Pogoda, JM Hwang, KL Langholz, B Monroe, KR Kolonel, LN Kaune, WT Peters, JM Henderson, BE TI Residential magnetic field exposure and breast cancer risk: A nested case-control study from a multiethnic cohort in Los Angeles County, California SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast neoplasms; electricity; electromagnetic fields; environmental exposure ID ELECTRIC BLANKET USE; VOLTAGE POWER-LINES; SPRAGUE-DAWLEY RATS; CHILDHOOD LEUKEMIA; WIRING CONFIGURATIONS; POOLED ANALYSIS; WIRE CODES; MELATONIN; PROLIFERATION; MORTALITY AB Some experimental and epidemiologic evidence suggests that residential exposure to power-frequency magnetic fields can increase breast cancer risk. This association was investigated in a nested case-control study of female breast cancer within a cohort of African Americans, Latinas, and Caucasians in Los Angeles County, California. Incident breast cancer was ascertained from 1993 to 1999 by linkage to county and state tumor registries. Controls were selected from a random sample of cohort members without breast cancer at baseline. Exposure was assessed in 1995-2001 by means of wiring configuration coding (an indirect measure of magnetic field exposure that has been associated with increased risk of childhood leukemia in Los Angeles and elsewhere in North America) in all homes occupied over the previous 10 years for 743 cases and 699 controls and by measurement of magnetic fields in the bedroom over a 7-day period for 347 cases and 286 controls. The estimated risk of breast cancer was not higher among women with wiring configuration codes associated with the highest magnetic fields (for a very high current configuration relative to very low, the adjusted odds ratio was 0.76 (95% confidence interval: 0.49, 1.18)). Stronger measured fields were not significantly associated with increased risk. These data suggest that residential magnetic field exposures commonly experienced by US women do not influence risk of breast cancer. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. Univ Hawaii, Canc Res Ctr Hawaii, Etiol Program, Honolulu, HI 96813 USA. EM Factors, Richland, WA USA. RP London, SJ (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. OI London, Stephanie/0000-0003-4911-5290 FU NCI NIH HHS [N01-CN-67010]; NIEHS NIH HHS [R01 ES06912, Z01 ES49018] NR 40 TC 24 Z9 27 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2003 VL 158 IS 10 BP 969 EP 980 DI 10.1093/aje/kwg254 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 742XV UT WOS:000186544200008 PM 14607805 ER PT J AU Viboud, C Boelle, PY Carrat, F Valleron, AJ Flahault, A AF Viboud, C Boelle, PY Carrat, F Valleron, AJ Flahault, A TI Prediction of the spread of influenza epidemics by the method of analogues SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE communicable disease control; diffusion; epidemiologic methods; forecasting; influenza; statistics, nonparametric ID TIME-SERIES ANALYSIS; DISEASE SURVEILLANCE; MORTALITY; FRANCE; CHAOS; PNEUMONIA; IMPACT; MODEL; ERROR; TOOL AB This study was designed to examine the performance of a nonparametric forecasting method first developed in meteorology, the "method of analogues," in predicting influenza activity. This method uses vectors selected from historical influenza time series that match current activity. The authors applied it to forecasting the incidences of influenza-like illnesses (ILI) in France and in the country's 21 administrative regions, using a series of data for 938 consecutive weeks of ILI surveillance between 1984 and 2002, and compared the results with those for autoregressive models. For 1- to 10-week-ahead predictions, the correlation coefficients between the observed and forecasted regional incidences ranged from 0.81 to 0.66 for the method of analogues and from 0.73 to -0.09 for the autoregressive models (p < 0.001). Similar results were obtained for national incidence forecasts. From the results of this method, maps of influenza epidemic forecasts can be made in countries in which national and regional data are available. C1 Univ Paris 06, INSERM, U444, Paris, France. WHO, Collaborating Ctr Elect Dis Surveillance, Paris, France. Assistance Publ Hop Paris, Paris, France. RP Viboud, C (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA. OI CARRAT, fabrice/0000-0002-8672-7918 NR 37 TC 35 Z9 38 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2003 VL 158 IS 10 BP 996 EP 1006 DI 10.1093/aje/kwg239 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 742XV UT WOS:000186544200011 PM 14607808 ER PT J AU Zubenko, GS Maher, B Hughes, HB Zubenko, WN Stiffler, JS Kaplan, BB Marazita, ML AF Zubenko, GS Maher, B Hughes, HB Zubenko, WN Stiffler, JS Kaplan, BB Marazita, ML TI Genome-wide linkage survey for genetic loci that influence the development of depressive disorders in families with recurrent, early-onset, major depression SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE genetic linkage; CREB1; depression; depression spectrum; sex-specificity; genome-wide scan ID RUBINSTEIN-TAYBI-SYNDROME; PSYCHIATRIC-DISORDERS; SUSCEPTIBILITY LOCUS; ALCOHOL DEPENDENCE; SCHIZOPHRENIA SUSCEPTIBILITY; ACETYLTRANSFERASE ACTIVITY; MOLECULAR NEUROBIOLOGY; GENDER DIFFERENCES; ESTROGEN-RECEPTOR; BINDING-PROTEIN AB In this report, we describe the results of the first genome-wide linkage survey for genetic loci that influence the development of unipolar Mood Disorders in 81 families identified by individuals with Recurrent, Early-Onset, Major Depressive Disorder (REMDD). Model-free linkage analysis was performed using genotypes for 392 highly informative polymorphisms with an average spacing of 9 cM. The highest maximum LOD score observed, 8.19 (genome-wide adjusted Pmuch less than0.0001), occurred for Recurrent Major Depressive Disorder (R-MDD) at D2S2321 (205 cM), located 121 kb proximal to CREB1. Nineteen chromosomal regions contained linkage peaks that reached genome-wide statistical significance (genome-wide adjusted P < 0.05) and ten of these were "highly significant" (adjusted P<0.001). Six of the 19 linkage peaks were revealed only when the analysis included covariates to control for the effects of sex and linkage to CREB1. Sex-specific susceptibility loci were common and preferentially affected the vulnerability of women to developing unipolar Mood Disorders. Five loci revealed evidence of interaction with the CREB1 locus in determining susceptibility (epistasis). A systematic candidate gene analysis is presented and potential overlaps of the linkage regions for unipolar Mood Disorders. with those reported for other psychiatric disorders are discussed. The findings suggest that genes whose products participate in cellular signaling pathways that converge on CREB, as well as the target genes whose expression they regulate, may also harbor alleles that affect the development of Mood Disorders and related conditions. (C) 2003 Wiley-Liss, Inc. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Carnegie Mellon Univ, Mellon Coll Sci, Dept Biol Sci, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial & Dent Genet, Pittsburgh, PA USA. NIMH, Mol Biol Lab, Intramural Res Program, Bethesda, MD 20892 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. RP Zubenko, GS (reprint author), Western Psychiat Inst & Clin, 3811 OHara St,room E-1230, Pittsburgh, PA 15213 USA. RI Maher, Brion/F-9185-2010 FU NCRR NIH HHS [1-P41-RR03655]; NHGRI NIH HHS [N01-HG-65403]; NIMH NIH HHS [MH48969, MH60866] NR 71 TC 129 Z9 137 U1 1 U2 9 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD NOV 15 PY 2003 VL 123B IS 1 BP 1 EP 18 DI 10.1002/ajmg.b.20073 PG 18 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 735ZU UT WOS:000186145800001 PM 14582139 ER PT J AU Schulze, TG McMahon, FJ AF Schulze, TG McMahon, FJ TI Genetic linkage and association studies in bipolar affective disorder: A time for optimism SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Review DE parametric and non-parametric linkage studies; linkage disequilibrium; LOD score; ascertainment; sample size; phenotype ID COMPLEX HUMAN-DISEASES; SINGLE-NUCLEOTIDE POLYMORPHISMS; DENSITY SCHIZOPHRENIA FAMILIES; PEDIGREE DISEQUILIBRIUM TEST; CASE-CONTROL DESIGNS; ACTIVATED PROTEIN-C; TRANSMISSION/DISEQUILIBRIUM TEST; MOLECULAR-GENETICS; DIABETES-MELLITUS; LOD SCORES AB Genetic research on complex diseases is beginning to bear fruit, with the successful identification of candidate susceptibility genes in diabetes, asthma, and other illnesses. Similar success is on the horizon for bipolar affective disorder (BPAD), but significant challenges remain. In this review, we outline the basic concepts of linkage and association mapping for complex phenotypes. We point out important caveats inherent in both approaches, and review guidelines on the interpretation of linkage statistics and significance thresholds. We then apply these concepts to an evaluation of the present status of genetic linkage and association studies in BPAD. The challenges posed by locus heterogeneity, phenotype definition, and sample size requirements are given a detailed treatment. Despite these challenges, we argue that the way ahead remains firmly rooted in linkage studies, complemented by association studies in linked regions. This is the only truly genome-wide approach currently available; it has succeeded in other complex phenotypes, and it is the surest strategy for mapping susceptibility genes in BPAD. Once these genes are identified, genetic mapping methods will yield to the other methods of 21st-century molecular biology as we begin to elucidate the pathophysiology of BPAD. (C) 2003 Wiley-Liss, Inc. C1 Psychiat Cent Inst Mental Hlth, Div Genet Epidemiol, D-68159 Mannheim, Germany. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. RP Schulze, TG (reprint author), Psychiat Cent Inst Mental Hlth, Div Genet Epidemiol, J5, D-68159 Mannheim, Germany. EM schulze@zi-mannheim.de RI McMahon, Francis/A-7290-2009; Schulze, Thomas/H-2157-2013; OI McMahon, Francis/0000-0002-9469-305X NR 115 TC 25 Z9 26 U1 3 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD NOV 15 PY 2003 VL 123C IS 1 BP 36 EP 47 DI 10.1002/ajmg.c.20012 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 738VR UT WOS:000186309000005 PM 14601035 ER PT J AU McWilliams, A Mayo, J MacDonald, S LeRiche, JC Palcic, B Szabo, E Lam, S AF McWilliams, A Mayo, J MacDonald, S LeRiche, JC Palcic, B Szabo, E Lam, S TI Lung cancer screening - A different paradigm SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE lung neoplasms; tomography; X-ray computed; bronchoscopy; diagnostic imaging; cytology ID ABERRANT PROMOTER METHYLATION; HELICAL COMPUTED-TOMOGRAPHY; COST-EFFECTIVENESS ANALYSIS; DOSE-RATE BRACHYTHERAPY; CARCINOMA IN-SITU; FOLLOW-UP; SPIRAL CT; FLUORESCENCE BRONCHOSCOPY; PHOTODYNAMIC THERAPY; SPUTUM CYTOLOGY AB Thoracic computed tomography (CT) is a sensitive method for detecting early lung cancer but has a high false-positive rate and is not sensitive for detecting central preinvasive and microinvasive cancer. Our hypothesis was that automated quantitative image cytometry (AQC) of sputum cells as the first screening method may improve detection rate by identifying individuals at highest risk for lung cancer. A total of 561 volunteer current or former smokers 50 years of age or older, with a smoking history of more than or equal to 30 pack/years, were studied. Among these, 423 were found to have sputum atypia defined as five cells or more with abnormal DNA content using AQC. Noncalcified pulmonary nodules were found in 46% (259/561). Of the 14 detected cancers, 13 were detected in subjects with sputum atypia-nine by CT and four carcinoma in situ/microinvasive cancers by autofluorescence bronchoscopy. One cancer was detected by CT alone. AQC of sputum cells improved the detection rate of lung cancer from 1.8 to 3.1%. CT scan alone would have missed 29% of the cancers. This screening paradigm shift has the additional potential of reducing the number of initial CT scans by at least 25% with further savings in follow-up investigations and treatment. C1 British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Vancouver Gen Hosp, Dept Radiol, Vancouver, BC, Canada. NCI DCP Lung & Upper Aerodigest Canc Res Grp, Bethesda, MD USA. RP McWilliams, A (reprint author), British Columbia Canc Agcy, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada. FU NCI NIH HHS [N01 CN 85188] NR 64 TC 88 Z9 91 U1 2 U2 13 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2003 VL 168 IS 10 BP 1167 EP 1173 DI 10.1164/rccm.2003010144OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 743FP UT WOS:000186562000010 PM 12882756 ER PT J AU David, GL Romieu, I Sienra-Monge, JJ Collins, WJ Ramirez-Aguilar, M del Rio-Navarro, BE Reyes-Ruiz, NI Morris, RW Marzec, JM London, SJ AF David, GL Romieu, I Sienra-Monge, JJ Collins, WJ Ramirez-Aguilar, M del Rio-Navarro, BE Reyes-Ruiz, NI Morris, RW Marzec, JM London, SJ TI Nicotinamide adenine dinucleotide (phosphate) reduced: Quinone oxidoreductase and glutathione S-transferase M1 polymorphisms and childhood asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE case-parent triad; oxidative stress; environmental tobacco smoke; GSTMI; NQO1 ID DIESEL-EXHAUST PARTICLES; PURIFIED NAD(P)H-QUINONE OXIDOREDUCTASE; INDUCED LUNG INJURY; CASE-PARENT TRIADS; OXIDATIVE STRESS; DT-DIAPHORASE; ANTIOXIDANT SUPPLEMENTATION; AIR-POLLUTION; OZONE; CHILDREN AB Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) M1 are phase 11 enzymes important in response to oxidative stress, such as occurs during exposure to ozone. We examined the relationship between functionally significant polymorphisms in NQO1 (Prol187Ser) and GSTM1 (homozygous deletion) and asthma risk in children with high lifetime exposure to ozone. We enrolled children with asthma from the allergy referral clinic at a public pediatric hospital in Mexico City, together with their parents. We assayed for the Pro187Ser polymorphism in NQO1 using a polymerase chain reaction-restriction fragment length polymorphism assay and for the presence of GSTM1 by polymerase chain reaction among 218 case-parent triads. We did not find strong evidence of an association between NQO1 genotype alone and asthma risk. However, among subjects with homozygous deletion of GSTM1, carriers of a serine allele were at significantly reduced risk of asthma compared with Pro/Pro homozygotes (relative risk = 0.4; 95% confidence interval, 0.2-0.8). The p value for difference in relative risk for NQO1 by GSTM1 genotype = 0.013. These data are consistent with a protective effect of the NQO1 Ser allele in this population of GSTM1-null children with high ozone exposure. C1 Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico. Hosp Infantil Mexico Frederico Gomez, Mexico City, DF, Mexico. RP David, GL (reprint author), Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, Dept Hlth & Human Serv, POB 12233,D2-01, Res Triangle Pk, NC 27709 USA. RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; London, Stephanie/0000-0003-4911-5290 FU NIEHS NIH HHS [Z01 ES 49019] NR 57 TC 70 Z9 72 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2003 VL 168 IS 10 BP 1199 EP 1204 DI 10.1164/rccm.200305-684OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 743FP UT WOS:000186562000014 PM 12969868 ER PT J AU Cheung, C Akiyama, TE Kudo, G Gonzalez, FJ AF Cheung, C Akiyama, TE Kudo, G Gonzalez, FJ TI Hepatic expression of cytochrome P450s in hepatocyte nuclear factor 1-alpha (HNF1 alpha)-deficient mice SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE hepatocyte nuclear factor 1 alpha; cytochrome P450; hepatic; gene expression; transcription factor; regulation ID ENRICHED TRANSCRIPTION FACTORS; RAT-LIVER CYTOCHROME-P-450; ACTIVATED RECEPTOR-ALPHA; MONOCLONAL-ANTIBODIES; BILE-ACID; DIABETES-MELLITUS; FACTOR 1-ALPHA; STEROL 27-HYDROXYLASE; XENOBIOTIC-METABOLISM; LIPID HOMEOSTASIS AB Hepatocyte nuclear factor I alpha (HNF1alpha) is a liver enriched homeodomain-containing transcription factor that has been shown to transactivate the promoters of several cytochrome P450 (CYP) genes, including CYP2E1, CYP1A2, CYP7A1, and CYP27, in vitro. In humans, mutations in HNF1alpha are linked to the occurrence of maturity onset diabetes of the young type 3, an autosomal dominant form of non-insulin-dependent diabetes mellitus in which afflicted subjects generally develop hyperglycemia before 25 years of age. Mice lacking HNF1alpha also develop similar phenotypes reminiscent of non-insulin-dependent diabetes mellitus. To investigate a potential role for HNF1alpha in the regulation of CYPs in vivo, the expression of major CYP genes from each family was examined in the livers of mice lacking HNF1alpha. Analysis of CYP gene expression revealed marked reductions in expression of Cyp1a2, Cyp2c29 and Cyp2e1, and a moderate reduction of Cyp3a11. In contrast Cyp2a5, Cyp2b10 and Cyp2d9 expression were elevated. There are also significant changes in the expression of genes encoding CYPs involved in fatty acid and bile acid metabolism characterized by a reduction in the expression of Cyp7b1, and Cyp27 as well as elevations in Cyp4a1/3, Cyp7a1, Cyp8b1, and Cyp39a1 expression. These results point to a critical role for HNF1alpha in the regulation of CYPs in vivo and suggest that this transcription factor may have an important influence on drug metabolism as well as lipid and bile acid homeostasis in maturity onset diabetes of the young type 3 diabetics. (C) 2003 Elsevier Inc. All rights reserved. C1 NIH, Lab Metab, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NIH, Lab Metab, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 64 TC 46 Z9 48 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 15 PY 2003 VL 66 IS 10 BP 2011 EP 2020 DI 10.1016/S0006-2952(03)00586-0 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 744QH UT WOS:000186643200015 PM 14599559 ER PT J AU Holmes, A Murphy, DL Crawley, JN AF Holmes, A Murphy, DL Crawley, JN TI Abnormal behavioral phenotypes of serotonin transporter knockout mice: Parallels with human anxiety and depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE serotonin transporter; gene; polymorphism; depression; anxiety; knockout ID 5-HT TRANSPORTER; PROMOTER POLYMORPHISM; OUT MICE; GENE; EXPRESSION; RECEPTORS; LACKING; BRAIN; ASSOCIATION; REGION AB Evidence of a link between genetic variation of the serotonin transporter and depression and anxiety prompted the generation of serotonin transporter knockout mice. Loss of serotonin reuptake function in knockouts causes reduced clearance of extracellular serotonin and associated alterations in serotonin neuronal firing and receptor function. Behavioral phenotyping function in knock-outs revealed genetic background-related abnormalities, including increased anxiety-like behaviors, reduced aggression, and exaggerated stress responses. Ongoing studies focus on identifying environmental, genetic, and developmental factors interacting with the htt mutation to produce these abnormalities. Serotonin transporter null mutant mice provide a model system to study how genetic variation in serotonin transporter function affects risk for neuropsychiatric disease. Biol Psychiatry 2003; 54:953-959 (C) 2003 Society of Biological Psychiatry C1 NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Bldg 10,Room 3C14, Bethesda, MD 20892 USA. NR 59 TC 191 Z9 200 U1 2 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2003 VL 54 IS 10 BP 953 EP 959 DI 10.1016/j.biopsych.2003.09.003 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 742RC UT WOS:000186531000001 PM 14625137 ER PT J AU Bonne, O Gilboa, A Louzoun, Y Brandes, D Yona, I Lester, H Barkai, G Freedman, N Chisin, R Shalev, AY AF Bonne, O Gilboa, A Louzoun, Y Brandes, D Yona, I Lester, H Barkai, G Freedman, N Chisin, R Shalev, AY TI Resting regional cerebral perfusion in recent posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 09-14, 2001 CL WAIKALOLA, HAWAII SP Amer Coll Neuropsychopharmacol DE SPECT; rCBF; PTSD; cerebellum; cortisol ID POSITRON-EMISSION-TOMOGRAPHY; SUBSTANCE-ABUSE HISTORIES; ACOUSTIC STARTLE RESPONSE; CHILDHOOD SEXUAL ABUSE; SCRIPT-DRIVEN IMAGERY; BRAIN BLOOD-FLOW; HIPPOCAMPAL VOLUME; PANIC DISORDER; RAT HIPPOCAMPUS; DEXAMETHASONE TREATMENT AB Background: Brain imaging research in posttraumatic stress disorder has been largely performed on patients with chronic disease, often heavily medicated, with current or past alcohol and substance abuse. Additionally, virtually only activation brain imaging paradigms have been done in posttraumatic stress disorder, whereas in other mental disorders both resting and activation studies have been performed. Methods: Twenty-eight (11 posttraumatic stress disorder) trauma survivors underwent resting state hexamethylpro-pyleneamineoxime single photon emission computed tomography and magnetic resonance imaging 6 months after trauma. Eleven nontraumatized subjects served as healthy controls. Results: Regional cerebral blood flow in the cerebellum was higher in posttraumatic stress disorder than in both control groups. Regional cerebral blood flow in right precentral, superior temporal, and fusiform gyri in posttraumatic stress disorder was higher than in healthy controls. Cerebellar and extrastriate regional cerebral blood flow were positively correlated with continuous measures of depression and posttraumatic stress disorder. Cortisol level in posttraumatic stress disorder was negatively correlated with medial temporal lobe perfusion. Anterior cingulate perfusion and cortisol level were positively correlated in posttraumatic stress disorder and negatively correlated in trauma survivors without posttraumatic stress disorder. Conclusions: Recent posttraumatic stress disorder is accompanied by elevated regional cerebral bloodflow, particularly in the cerebellum. This warrants attention because the cerebellum is often used as a reference region in regional cerebral bloodflow studies. The inverse correlation between plasma cortisol and medial temporal lobe perfusion may herald hippocampal damage. Biol Psychiatry 2003;54: 1077-1086 (C) 2003 Society of Biological Psychiatry C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Dept Psychiat, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Dept Nucl Med, IL-91120 Jerusalem, Israel. RP Bonne, O (reprint author), NIMH, Mood & Anxiety Disorders Program, 15K N Dr,Room 200, Bethesda, MD 20892 USA. RI louzoun, yoram/F-5874-2011 OI louzoun, yoram/0000-0003-1714-6148 NR 70 TC 70 Z9 75 U1 4 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2003 VL 54 IS 10 BP 1077 EP 1086 DI 10.1016/S0006-3223(03)00525-0 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 742RC UT WOS:000186531000014 PM 14625150 ER PT J AU Barlic, J Sechler, JM Murphy, PM AF Barlic, J Sechler, JM Murphy, PM TI IL-15 and IL-2 oppositely regulate expression of the chemokine receptor CX3CR1 SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; HUMAN INTERLEUKIN-8 RECEPTOR; MURINE BONE-MARROW; NK CELLS; IN-VIVO; FUNCTIONAL EXPRESSION; CHEMOTACTIC RECEPTOR; TARGETED DELETION; FRACTALKINE; CX(3)CR1 AB The chemokine receptor CX3CR1 (CX3C chemokine receptor 1) is expressed in mouse blood on natural killer (NK) cells and on monocytes. Because interleukin-15 (IL-15) is an essential cytokine for NK cell development and maintenance, we hypothesized that it may induce CX3CR1 expression on this cell type. In contrast, we found that in primary mouse bone marrow-derived NK cells IL-15 specifically inhibited CX3CR1 protein and mRNA accumulation, whereas the related cytokine IL-2 did not inhibit but instead increased CX3CR1 expression. Consistent with this finding, intravenous injection of a single dose of recombinant IL-15 into C57BL/6 mice decreased steady-state CX3CR1 levels 24 hours after injection in freshly isolated peripheral blood mononuclear cells (PBMCs), splenocytes, and bone marrow cells, and treatment of mouse PBMCs with IL-15 in vitro inhibited CX3CL1 (ligand for CX3CR1)-induced chemotaxis. These data suggest that IL-15 may be a negative regulator of innate immunity by inhibiting CX3CR1 expression. These data also suggest that IL-15 inhibition of CX3CR1 may subvert potential cell immunotherapy strategies in which IL-15 is used to expand NK cell populations in vivo or ex vivo. Finally, our results provide additional evidence for differential signaling by IL-2 and IL-15, despite usage of common betagamma(c) receptor chains. (C) 2003 by The American Society of Hematology. C1 NIAID, Mol Signaling Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Mol Signaling Sect, Host Def Lab, NIH, Bldg 10,Rm 11N113, Bethesda, MD 20892 USA. NR 59 TC 31 Z9 32 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 15 PY 2003 VL 102 IS 10 BP 3494 EP 3503 DI 10.1182/blood-2003-03-0946 PG 10 WC Hematology SC Hematology GA 741XT UT WOS:000186486200018 PM 12881312 ER PT J AU Maciejewski, JP Sloand, EM Nunez, O Boss, C Young, NS AF Maciejewski, JP Sloand, EM Nunez, O Boss, C Young, NS TI Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; ANTITHYMOCYTE GLOBULIN; GM-CSF; CHILDREN; CYCLOSPORINE; MULTICENTER; COMBINATION; IMMUNOSUPPRESSION; ERYTHROPOIETIN AB In contrast to severe aplastic anemia (sAA), the appropriate management of patients with moderate pancytopenia is unclear. In this study, we examined the efficacy of a humanized monoclonal antibody recognizing interleukin-2 receptor (daclizumab), which has proven to be a successful immunosuppressive agent in solid organ and bone marrow transplantation. We treated 17 patients with moderate aplastic anemia (mAA) with 1 mg/kg every 2 weeks for 3 months. mAA was defined as depression of 2 of the 3 blood counts: absolute neutrophil count 1200/mm(3) or less, platelet count 70 000/mm(3) or less, hemoglobin level 8.5 g/dL or lower, and absolute reticulocyte count 60 000/mm(3) or less. The primary end point of our protocol was a hematologic response in at least one affected peripheral blood value. Daclizumab had little toxicity. Six of the 16 (38%) evaluable patients responded to treatment. Two patients with previously chronic disease showed complete return of normal counts, which were sustained for more than 2 years following treatment. Four patients had single-lineage responses. Two previously transfusion-dependent patients became transfusion independent; one patient with many neutropenia-related infections had a normal neutrophil count following treatment. Daclizumab appears safe; its efficacy in this pilot protocol suggests that expanded study of this monoclonal antibody in immune-mediated bone marrow failure syndrome is warranted. (C) 2003 by The American Society of Hematology. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Sloand, EM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 7C108,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 33 Z9 42 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 15 PY 2003 VL 102 IS 10 BP 3584 EP 3586 DI 10.1182/blood-2003-04-1032 PG 3 WC Hematology SC Hematology GA 741XT UT WOS:000186486200029 PM 12881307 ER PT J AU Allende, ML Yamashita, T Proia, RL AF Allende, ML Yamashita, T Proia, RL TI G-protein-coupled receptor S1P(1) acts within endothelial cells to regulate vascular maturation SO BLOOD LA English DT Article ID BLOOD-VESSEL FORMATION; PDGF-B; TGF-BETA; MICE; ANGIOGENESIS; DIFFERENTIATION; GROWTH; MOUSE; SPHINGOSINE-1-PHOSPHATE; PROLIFERATION AB Sphingosine-1-phosphate (S1P) stimulates signaling pathways via G-protein-coupled receptors and triggers diverse cellular processes, including growth, survival, and migration. In S1P(1) receptor-deficient embryos, blood vessels were incompletely covered by vascular smooth muscle cells (VSMCs), indicating the S1P(1) receptor regulates vascular maturation. Because S1P(1) receptor expression is not restricted to a particular cell type, it was not known whether the S1P(1) receptor controlled VSMC coverage of vessels in a cell-autonomous fashion by functioning directly in VSMCs or indirectly through its activity in endothelial cells (ECs). By using the Cre/IoxP system, we disrupted the S1P(1) gene solely in ECs. The phenotype of the conditional mutant embryos mimicked the one obtained in the embryos globally deficient in S1P(1). Thus, vessel coverage by VSMCs is directed by the activity of the S1P(1) receptor in ECs. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Proia, RL (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, Bldg 10,Rm 9N-314,10 Ctr Dr MSC 1821, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012 NR 27 TC 210 Z9 217 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2003 VL 102 IS 10 BP 3665 EP 3667 DI 10.1182/blood-2003-02-0460 PG 3 WC Hematology SC Hematology GA 741XT UT WOS:000186486200041 PM 12869509 ER PT J AU El Ouriaghli, F Sioand, E Mainwaring, L Fujiwara, H Keyvanfar, K Melenhorst, JJ Rezvani, K Sconocchia, G Solomon, S Hensel, N Barrett, AJ AF El Ouriaghli, F Sioand, E Mainwaring, L Fujiwara, H Keyvanfar, K Melenhorst, JJ Rezvani, K Sconocchia, G Solomon, S Hensel, N Barrett, AJ TI Clonal dominance of chronic myelogenous leukemia is associated with diminished sensitivity to the antiproliferative effects of neutrophil elastase SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; COLONY-STIMULATING FACTOR; ABL TYROSINE KINASE; EARLY-CHRONIC PHASE; BCR-ABL; BONE-MARROW; PROGENITOR CELLS; INTERFERON-ALPHA; CML CELLS; IN-VITRO AB Clinical observations suggest that in chronic myelogenous leukemia (CIVIL), the Philadelphia chromosome (Ph+) clone has a growth advantage over normal hematopolesis. Patients with CML have high levels of neutrophil elastase, which has recently been shown to antagonize the action of granulocytecolony-stimulating factor (G-CSF) and other growth factors. We therefore compared the effect of elastase on the growth of normal and CML progenitor cells. In 10-day suspension cultures of normal or CML CD34(+) cells supplemented with G-CSF, stem cell factor (SCF), and granulocyte macrophage-colony-stimulating factor (GM-CSF), CML cells had diminished sensitivity to the growth inhibitory effect of elastase. When equal numbers of CML and normal CD34(+) cells were cocultured for 10 days, there was no change in the relative proportions of normal and leukemic cells (measured by fluorescence in situ hybridization [FISH] or flow cytometry). However, when elastase was added, CML cells predominated at the end of the culture period (78% vs 22% with 1 mug/mL and 80% vs; 20% with 5 mug/mL elastase). CML neutrophils substituted effectively for elastase in suppressing the proliferation of normal CD34(+) cells, but this effect was abrogated by serine protease inhibitors. These results suggest that elastase overproduction by the leukemic clone can change the growth environment by digesting growth factors, thereby giving advantage to Ph+ hematopoiesis. (C) 2003 by The American Society oi Hematology. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 45 TC 15 Z9 16 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 15 PY 2003 VL 102 IS 10 BP 3786 EP 3792 PG 7 WC Hematology SC Hematology GA 741XT UT WOS:000186486200056 PM 12893759 ER PT J AU Moir, S Donoghue, ET Pickeral, OK Malaspina, A Planta, MA Chun, TW Krishnan, SR Kottilil, S Birse, CE Leitman, SF Fauci, AS AF Moir, S Donoghue, ET Pickeral, OK Malaspina, A Planta, MA Chun, TW Krishnan, SR Kottilil, S Birse, CE Leitman, SF Fauci, AS TI Continuous flow leukapheresis induces expression of stress genes in lymphocytes: impact on microarray analyses SO BLOOD LA English DT Letter ID B-CELLS C1 NIH, Bethesda, MD 20892 USA. RP Moir, S (reprint author), NIH, Bldg 10,Rm 6A02,10 Ctr Dr,MSC-1576, Bethesda, MD 20892 USA. NR 6 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 15 PY 2003 VL 102 IS 10 BP 3852 EP 3853 DI 10.1182/blood-2003-08-2844 PG 2 WC Hematology SC Hematology GA 741XT UT WOS:000186486200073 PM 14597611 ER PT J AU Williams, JL Nath, N Chen, J Hundley, TR Gao, JJ Kopelovich, L Kashfi, K Rigas, B AF Williams, JL Nath, N Chen, J Hundley, TR Gao, JJ Kopelovich, L Kashfi, K Rigas, B TI Growth inhibition of human colon cancer cells by nitric oxide (NO)-donating aspirin is associated with cyclooxygenase-2 induction and beta-catenin/T-cell factor signaling, nuclear factor-kappa B, and NO synthase 2 inhibition: Implications for chemoprevention SO CANCER RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SODIUM-SALICYLATE; IN-VIVO; EXPRESSION; APOPTOSIS; CARCINOMA; PATHWAY; NSAIDS; PROLIFERATION; ACTIVATION AB Nitric oxide (NO)-releasing aspirin (ASA), consisting of a traditional ASA molecule to which a NO-donating moiety is covalently bound, is a promising colon cancer chemopreventive agent. NO-ASA inhibits colon cancer cell growth more potently than ASA by inhibiting cell proliferation and enhancing cell killing. We examined in cultured human colon cancer cells the effect of NO-ASA on the beta-catenin/T-cell factor signaling pathway, nuclear factor-kappaB, and NO synthase 2 and on cyclooxygenase (COX) expression, all presumed to participate in colon carcinogenesis. Besides inhibiting cell growth, NO-ASA inhibited the beta-catenin/T-cell factor signaling pathway (IC50, 1.1 muM), nuclear factor-kappabeta DNA binding (IC50, 7.5 muM), and NO synthase 2 expression (IC50, 2 muM). Interestingly, NO-ASA induced COX-2 expression, although it had no effect on COX-1. COX-2 induction was accompanied by increased prostaglandin E-2 production. These effects occurred at NO-ASA concentrations below or near its IC50 for cell growth (IC50, 2-50 muM). The metabolism of NO-ASA by these cells is characterized by a rapid deacetylation step and the formation of a conjugate with glutathione. NO-ASA had no effect on intracellular cyclic GMP concentrations. We propose a model incorporating the pleiotropic effects of NO-ASA on cell signaling and postulate that collectively these effects may contribute to its strong chemopreventive effect. C1 Amer Hlth Fdn, Ctr Canc, Inst Canc Prevent, Valhalla, NY 10595 USA. New York Med Coll, Sarah C Upham Div Gastroenterol, Valhalla, NY 10595 USA. CUNY, Sch Med, Dept Physiol & Pharmacol, New York, NY USA. NCI, Chemoprevent Branch, NIH, Bethesda, MD 20892 USA. RP Rigas, B (reprint author), Amer Hlth Fdn, Ctr Canc, Inst Canc Prevent, 1 Dana Rd, Valhalla, NY 10595 USA. FU NCI NIH HHS [CA 092423] NR 27 TC 86 Z9 94 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2003 VL 63 IS 22 BP 7613 EP 7618 PG 6 WC Oncology SC Oncology GA 746WM UT WOS:000186770700013 PM 14633677 ER PT J AU Tilli, MT Hudgins, SL Frech, MS Halama, ED Renou, JP Furth, PA AF Tilli, MT Hudgins, SL Frech, MS Halama, ED Renou, JP Furth, PA TI Loss of protein phosphatase 2A expression correlates with phosphorylation of DP-1 and reversal of dysplasia through differentiation in a conditional mouse model of cancer progression SO CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; MYC; TUMORIGENESIS; APOPTOSIS; INDUCTION; GLAND; CELLS; RAS; DP1 AB A conditional mouse model of time-dependent dysplasia reversal demonstrated that reversal and differentiation of dysplastic salivary gland tissue at the 4-month reversible stage was characterized by the appearance of a phosphorylated slower mobility form of Differentiation Related Transcription Factor 1-polypeptide-1 that was correlated with cellular differentiation. The phosphorylated form of DP-1 was not found at the 7-month irreversible stage or in adenocarcinomas. At the 4-month reversible stage, protein phosphatase 2A expression was down-regulated coincident with loss of oncogene expression, whereas PP2A expression persisted at the 7-month irreversible stage. Results are consistent with the hypothesis that persistent PP2A expression prevented the appearance of the phosphorylated form of DP-1 required for cellular differentiation and reversal of dysplasia after loss of oncogene expression. C1 Georgetown Univ, Lombardi Canc Ctr, Dept Oncol, Washington, DC 20057 USA. Univ Maryland, Grad Program Human Genet, Baltimore, MD USA. Univ Maryland, Sch Med, Baltimore, MD USA. NIDDK, Lab Genet & Physiol, Bethesda, MD USA. RP Furth, PA (reprint author), Georgetown Univ, Lombardi Canc Ctr, Dept Oncol, Res Bldg,Room E518,3970 Reservoir Rd, Washington, DC 20057 USA. FU NCI NIH HHS [R01 CA089041, R01 CA 89041, R01 CA089041-05] NR 22 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2003 VL 63 IS 22 BP 7668 EP 7673 PG 6 WC Oncology SC Oncology GA 746WM UT WOS:000186770700024 PM 14633688 ER PT J AU Liu, X Lee, J Cooley, M Bhogte, E Hartley, S Glick, A AF Liu, X Lee, J Cooley, M Bhogte, E Hartley, S Glick, A TI Smad7 but not Smad6 cooperates with oncogenic ras to cause malignant conversion in a mouse model for squamous cell carcinoma SO CANCER RESEARCH LA English DT Article ID EPIDERMAL GROWTH-FACTOR; HUMAN PANCREATIC-CANCER; TGF-BETA RECEPTOR; MAMMARY EPITHELIAL-CELLS; MAD-RELATED PROTEIN; BENIGN SKIN TUMORS; FACTOR-ALPHA; TRANSGENIC MICE; KERATINOCYTE DIFFERENTIATION; TERMINAL DIFFERENTIATION AB Smad7 and Smad6 are inhibitory Smads that block transforming growth factor-beta (TGF-beta) superfamily signal transduction. Smad7 is over-expressed in chemically induced mouse epidermal tumors, where oncogenic activation of c-ras is a frequent event. To test the role of Smad7 overexpression in tumor progression, we used retroviruses to transduce Smad7 or Smad6 and v-ras(Ha) into primary mouse keratinocytes. By itself, Smad7 transiently enhanced keratinocyte proliferation, blocked normal differentiation, and induced keratin 8, a marker of malignant conversion, but did not cause tumor formation. Smad7 extended the in vitro life span, suppressed senescence, and increased transformation frequency 3-fold of primary keratinocytes coexpressing v-ras(Ha). Smad7/v-ras(Ha) coinfected keratinocytes rapidly progressed to squamous cell carcinomas in vivo, whereas pBabe/v-ras(Ha)- or Smad6/v-ras(Ha)-transduced keratinocytes formed only benign papillomas. Smad7/v-ras(Ha) tumors had elevated proliferation and defective nuclear localizaton of Smad2, Smad3, and Smad5, whereas only Smad5 was altered in Smad6/v-ras(Ha) tumors. Smad7 overexpression in vitro induced epidermal growth factor (EGF)-like growth factors TGF-alpha, heparin binding-EGF, amphiregulin, and EGF receptor tyrosine phosphorylation as well as the EGF-CFC! growth factor cripto-1. TGF-alpha and cripto-1 were also overexpressed in Smad7/v-ras(Ha) tumors. These results suggest that Smad7 overexpression accelerates tumor progression through inhibition of TGF-beta superfamily signaling and up-regulation of the EGF-like superfamily of growth factors. This is the first demonstration that Smad7 overexpression can cause malignant conversion in a multistage cancer model and suggests that it may have an important role in the pathogenesis of human cancer. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. RP Glick, A (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bldg 37,Rm 4060C, Bethesda, MD 20892 USA. NR 59 TC 50 Z9 55 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2003 VL 63 IS 22 BP 7760 EP 7768 PG 9 WC Oncology SC Oncology GA 746WM UT WOS:000186770700037 PM 14633701 ER PT J AU Xu, WP Yuan, XT Jung, YJ Yang, YP Basso, A Rosen, N Chung, EJ Trepel, J Neckers, L AF Xu, WP Yuan, XT Jung, YJ Yang, YP Basso, A Rosen, N Chung, EJ Trepel, J Neckers, L TI The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-B; CATALYTIC SUBUNIT; INDUCED APOPTOSIS; PH DOMAIN; ACTIVATION; PHOSPHORYLATION; GROWTH; HSP90; 1-ALPHA; DEGRADATION AB AKT, a serine/threonine kinase that promotes cell survival, can be activated by overexpression of the receptor tyrosine kinase ErbB2. Conversely, down-regulation of ErbB2 inhibits AKT activation. Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells, and we show that ErbB2 inhibits PP1-dependent dephosphorylation of AKT. Inhibition of ErbB2 by either the HSP (heat shock protein) 90 inhibitor geldanamycin or the ErbB inhibitor ZD1839 in SKBR3 cells, a human breast cancer cell line overexpressing ErbB2 protein, induces a rapid and dramatic decrease in AKT activity. Decreased AKT activity occurs many hours before the HSP90-dependent decline of AKT protein but is correlated with loss of AKT phosphorylation. Decreased AKT phosphorylation is not due to blockade of AKT activation or to preferential HSP90-mediated degradation of phosphorylated AKT. Instead, it is caused by increased AKT dephosphorylation. Sensitivity to a panel of phosphatase inhibitors suggests involvement of the phosphatase PP1 in this process. In vitro phosphatase assay (using PP1 immunoprecipitated from COS7 cells transiently transfected with the wild-type protein, as well as purified PP1) confirmed that AKT is a substrate of PP1. Furthermore, endogenous PP1 and AKT associate with each other in SKBR3. However, the phosphatase is phosphorylated and its activity is suppressed (determined by in vitro assay). In contrast, ErbB2 inhibition abrogates PP1 phosphorylation and restores its activity (measured by its ability to dephosphorylate AKT in vitro). Finally, transient overexpression of constitutively active PP1 in SKBR3 cells promotes marked dephosphorylation of endogenous AKT protein. These data indicate that ErbB2 acts to preserve the phosphorylation, and hence to prolong the activation, of AKT kinase by repressing the activity of the phosphatase PP1. ErbB2 thus functions to regulate AKT kinase by simultaneously promoting its activation while inhibiting its inactivation. C1 Natl Canc Inst, Cell & Canc Biol Branch, Rockville, MD 20850 USA. Natl Canc Inst, Ctr Canc Res, Med Oncol Clin Res Unit, Rockville, MD 20850 USA. Beijing Union Med Coll Hosp, Div Chron Liver Dis, Beijing 100730, Peoples R China. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. RP Natl Canc Inst, Cell & Canc Biol Branch, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM len@helix.nih.gov NR 43 TC 80 Z9 81 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2003 VL 63 IS 22 BP 7777 EP 7784 PG 8 WC Oncology SC Oncology GA 746WM UT WOS:000186770700039 PM 14633703 ER PT J AU Fu, BJ Quintero, J Baker, CC AF Fu, BJ Quintero, J Baker, CC TI Keratinocyte growth conditions modulate telomerase expression, senescence, and immortalization by human papillomavirus type 16 E6 and E7 Oncogenes SO CANCER RESEARCH LA English DT Article ID HUMAN EPITHELIAL-CELLS; HTERT GENE-EXPRESSION; LIFE-SPAN; SERIAL CULTIVATION; DIFFERENTIATION; ONCOPROTEIN; ACTIVATION; AMPLIFICATION; INDUCTION; PRODUCT AB Keratinocytes undergo a finite number of divisions in culture before senescing. The high-risk human papillomavirus (HPV) E6 and E7 oncoproteins prevent keratinocyte senescence and extend life span by interacting with p53 and pRb, respectively, and also by transcriptionally activating the human telomerase reverse transcriptase (hTERT) gene, which encodes the catalytic subunit of telomerase. We correlated telomerase activity, which was measured by a highly sensitive and quantitative real-time quantitative-PCR-based telomeric repeat amplification protocol assay, with telomere length and the expression of hTERT, p16(INK4a), and RPV-16 E6 and E7 in keratinocytes grown under two culture conditions. Primary human foreskin keratinocytes (HFKs) cultured in keratinocyte serum-free medium on plastic senesced at similar to13 population doublings (PDs). Senescence was accompanied by a dramatic increase in p16(INK4A) levels, a marked decrease in telomerase, and only a slight decrease in telomere length. In contrast, HFKs grown in F medium on 3T3 fibroblast feeders maintained elevated telomerase and lower levels of p16(INK4A) for 60 PDs before senescing similar to81 PDs. E7 was shown to act synergistically with E6 to super induce telomerase expression in a feeder environment-dependent manner. Culture of both HFKs and HFK/16E6E7 cells in the feeder environment significantly increased the number of doublings that these cells could undergo without a significant reduction in telomere length. Finally, transfer of either HFKs or HFK/16E6E7 cells from plastic to the feeder fibroblast culture system significantly induced telomerase activity. This induction in telomerase was fully reversible and largely attributable to the medium. Our results suggest that the influence of keratinocyte culture conditions on the expression of telomerase and p16(INK4A) and on telomere maintenance is responsible, at least partially, for the differences in proliferative capacity, senescence, and HPV-keratinocyte interactions seen in the two culture systems. C1 NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Baker, CC (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, CRTS LCO Bldg 41,Room D804, Bethesda, MD 20892 USA. NR 51 TC 46 Z9 49 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2003 VL 63 IS 22 BP 7815 EP 7824 PG 10 WC Oncology SC Oncology GA 746WM UT WOS:000186770700044 PM 14633708 ER PT J AU Hodge, JW Poole, DJ Aarts, WM Yafal, AG Gritz, L Schlom, J AF Hodge, JW Poole, DJ Aarts, WM Yafal, AG Gritz, L Schlom, J TI Modified vaccinia virus Ankara recombinants are as potent as vaccinia recombinants in diversified prime and boost vaccine regimens to elicit therapeutic antitumor responses SO CANCER RESEARCH LA English DT Article ID HUMAN CARCINOEMBRYONIC ANTIGEN; COLONY-STIMULATING FACTOR; ATTENUATED MVA STRAIN; COSTIMULATORY MOLECULE B7; PROSTATE-SPECIFIC ANTIGEN; CEA TRANSGENIC MICE; T-CELL RESPONSES; IMMUNE-RESPONSES; SMALLPOX-VACCINATION; HOST-RANGE AB Cancer vaccine regimens use various strategies to enhance immune responses to specific tumor-associated antigens (TAAs), including the increasing use of recombinant poxviruses [vaccinia (rV) and fowlpox (rF)] for delivery of the TAA to the immune system. However, the use of replication competent vectors with the potential of adverse reactions have made attenuation a priority for next-generation vaccine strategies. Modified vaccinia Ankara (MVA) is a replication defective form of vaccinia virus. Here, we investigated the use of MVA encoding a tumor antigen gene, carcinoembryonic antigen (CEA), in addition to multiple costimulatory molecules (B7-1, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3 designated TRICOM). Vaccination of mice with MVA-CEA/TRICOM induced potent CD4(+) and CD8(+) T-cell responses specific for CEA. MVA-CEA/TRICOM could be administered twice in vaccinia naive mice and only a single time in vaccinia-immune mice before being inhibited by antivector-immune responses. The use of MVA-CEA/TRICOM in a diversified prime and boost vaccine regimen with rF-CEA/TRICOM, however, induced significantly greater levels of both CD4(+) and CD8(+) T-cell responses specific for CEA than that seen with rV-CEAfrRICOM prime and rF-CEA/TRICOM boost. In a self-antigen tumor model, the diversified MVA-CEA/TRICOWrF-CEA/ TRICOM vaccination regimen resulted in a significant therapeutic antitumor response as measured by increased survival, when compared with the diversified prime and boost regimen, rV-CEA/TRICONVrF-CEA/ TRICOM. The studies reported here demonstrate that MVA, when used as a prime in a diversified vaccination, is clearly comparable with the regimen using the recombinant vaccinia in both the induction of cellular immune responses specific for the "self"-TAA transgene and in antitumor activity. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Ther Biol Corp, Cambridge, MA USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 64 TC 56 Z9 57 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2003 VL 63 IS 22 BP 7942 EP 7949 PG 8 WC Oncology SC Oncology GA 746WM UT WOS:000186770700061 PM 14633725 ER PT J AU Libutti, SK Crabtree, JS Lorang, D Burns, AL Mazzanti, C Hewitt, SM O'Connor, S Ward, JM Emmert-Buck, MR Remaley, A Miller, M Turner, E Alexander, HR Arnold, A Marx, SJ Collins, FS Spiegel, AM AF Libutti, SK Crabtree, JS Lorang, D Burns, AL Mazzanti, C Hewitt, SM O'Connor, S Ward, JM Emmert-Buck, MR Remaley, A Miller, M Turner, E Alexander, HR Arnold, A Marx, SJ Collins, FS Spiegel, AM TI Parathyroid gland-specific deletion of the mouse Men1 gene results in parathyroid neoplasia and hypercalcemic hyperparathyroidism SO CANCER RESEARCH LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; SITE-SPECIFIC RECOMBINATION; TRANSGENIC MICE; TYPE-1; TUMORS; FEATURES; GENOME AB The inactivation of the MEN1 tumor suppressor gene in patients leads to a constellation of changes in endocrine tissues, including parathyroid neoplasia, pituitary adenomas, pancreatic neuroendocrine tumors, and carcinoids. To study the pathophysiological consequences of the deletion of the MEN1 gene, we set out to create a mouse model of hyperparathyroidism resulting from the deletion of the Men I gene in parathyroid tissue. We introduced a Men1 gene flanked by loxP sites into the mouse germ line and then used a parathyroid cell-specific promoter to drive the expression of Cre recombinase, resulting in the deletion of the Men1 gene. Here, we show that loss of Men1 gene function in the parathyroid glands of mice results in histological changes consistent with parathyroid neoplasia as well as systemic hypercalcemia. This model provides a means for dissecting the molecular basis of this familial cancer syndrome and may allow for the development of new strategies to treat related forms of hypercalcemia. C1 NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD USA. Univ Connecticut, Sch Med, Ctr Mol Med, Farmington, CT USA. Univ Connecticut, Sch Med, Div Endocrinol & Metab, Farmington, CT USA. Natl Inst Deafness & Commun Disorders, Mol Pathophysiol Sect, Bethesda, MD USA. RP Libutti, SK (reprint author), NCI, Surg Branch, Ctr Canc Res, 10 Ctr Dr,Room 2B07, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 16 TC 52 Z9 53 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2003 VL 63 IS 22 BP 8022 EP 8028 PG 7 WC Oncology SC Oncology GA 746WM UT WOS:000186770700071 PM 14633735 ER PT J AU Gorlick, R Anderson, P Andrulis, I Arndt, C Beardsley, GP Bernstein, M Bridge, J Cheung, NK Dome, JS Ebb, D Gardner, T Gebhardt, M Grier, H Hansen, M Healey, J Helman, L Hock, J Houghton, J Houghton, P Huvos, A Khanna, C Kieran, M Kleinerman, E Ladanyi, M Lau, C Malkin, D Marina, N Meltzer, P Meyers, P Schofield, D Schwartz, C Smith, MA Toretsky, J Tsokos, M Wexler, L Wigginton, J Withrow, S Schoenfeldt, M Anderson, B AF Gorlick, R Anderson, P Andrulis, I Arndt, C Beardsley, GP Bernstein, M Bridge, J Cheung, NK Dome, JS Ebb, D Gardner, T Gebhardt, M Grier, H Hansen, M Healey, J Helman, L Hock, J Houghton, J Houghton, P Huvos, A Khanna, C Kieran, M Kleinerman, E Ladanyi, M Lau, C Malkin, D Marina, N Meltzer, P Meyers, P Schofield, D Schwartz, C Smith, MA Toretsky, J Tsokos, M Wexler, L Wigginton, J Withrow, S Schoenfeldt, M Anderson, B TI Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: Meeting summary SO CLINICAL CANCER RESEARCH LA English DT Review ID COMPARATIVE GENOMIC HYBRIDIZATION; OSTEOSARCOMA LUNG METASTASES; SOFT-TISSUE SARCOMAS; P-GLYCOPROTEIN EXPRESSION; PARATHYROID-HORMONE 1-34; FAS-MEDIATED APOPTOSIS; MURINE OSTEOSARCOMA; GENE-EXPRESSION; CELL-LINES; CANINE OSTEOSARCOMA AB Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in adolescents. The North American pediatric cooperative groups have performed a series of clinical treatment trials in this disease over the past several decades, and biology studies of tumor tissue have been an important study component. A meeting was held in Bethesda, Maryland on November 29-30, 2001, sponsored by the NIH Office of Rare Diseases, the Children's Oncology Group, and the National Cancer Institute-Cancer Therapy Evaluation Program with the general objectives: (a) to review the current state of knowledge regarding OS biology; (b) to identify, prioritize, and support the development of biology studies of potential clinical relevance in OS; and (c) to discuss the available tissue resources and the appropriate methods for analysis of OS samples for the conduct of biology studies. This report summarizes the information presented and discussed by the meeting participants. C1 NCI, Clin Invest Branch, Pediat Sect, Canc Therapy Evaluat Program, Rockville, MD 20852 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Rochester, MN USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. Yale Univ, Sch Med, New Haven, CT USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Univ Nebraska, Med Ctr, Omaha, NE USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Indiana Univ, Med Ctr, Indianapolis, IN 46202 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Univ Connecticut, Ctr Hlth Sci, Farmington, CT USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. MD Anderson Canc Ctr, Houston, TX USA. Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Childrens Hosp, Los Angeles, CA 90027 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Colorado State Univ, Coll Vet Med & Biol Sci, Ft Collins, CO 80523 USA. EMMES Corp, Rockville, MD USA. RP Anderson, B (reprint author), NCI, Clin Invest Branch, Pediat Sect, Canc Therapy Evaluat Program, 6130 Execut Blvd,EPN 741, Rockville, MD 20852 USA. EM AndersonB@CTEP.NCI.NIH.gov RI Andrulis, Irene/E-7267-2013; OI Hock, Janet/0000-0001-8873-2545; Kieran, Mark/0000-0003-2184-7692 NR 126 TC 112 Z9 120 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2003 VL 9 IS 15 BP 5442 EP 5453 PG 12 WC Oncology SC Oncology GA 750TM UT WOS:000187014200004 PM 14654523 ER PT J AU De Pascalis, R Gonzales, NR Padlan, EA Schuck, P Batra, SK Schlom, J Kashmiri, SVS AF De Pascalis, R Gonzales, NR Padlan, EA Schuck, P Batra, SK Schlom, J Kashmiri, SVS TI In vitro affinity maturation of a specificity-determining region-grafted humanized anticarcinoma antibody: Isolation and characterization of minimally immunogenic high-afflnity variants SO CLINICAL CANCER RESEARCH LA English DT Article ID SURFACE-PLASMON RESONANCE; TUMOR-ASSOCIATED GLYCOPROTEIN-72; MURINE MONOCLONAL-ANTIBODY; METASTATIC COLON-CARCINOMA; PHASE-II; RADIOIMMUNOTHERAPY TRIAL; DETERMINING RESIDUES; COLORECTAL-CANCER; TAG-72 EXPRESSION; ALPHA-INTERFERON AB Purpose: HuCC49V10 (V10), a humanized anticarcinoma monoclonal antibody (Ab) CC49, was generated by grafting only the specificity-determining regions (SDRs) of CC49 onto the variable light and variable heavy frameworks of the human Abs LEN and 21/28'CL, respectively. SDRs are those residues of the complementarity-determining regions that are most critical for antigen (Ag) binding. Compared with HuCC49, which was developed by conventional complementarity-determining region grafting, V10 has lower reactivity to the sera from patients who were previously given murine CC49 in clinical trials, although its Ag-binding affinity is 2-3-fold lower than that of HuCC49. To generate variants of V10 with higher Ag-binding affinity and lower sera reactivity, in vitro affinity maturation of V10 was carried out using phage display technique. Experimental Design: A limited library of Fabs was generated by replacing some of the SDRs with all possible residues located at the corresponding positions in human Abs. The library was enriched, by several rounds of panning, in Fabs that have high affinity for the TAG-72 Ag. The clones encoding the best binders were expressed in insect cells as whole Abs that were purified and characterized. Results: Competition radioimmunoassay and surface plasmon resonance measurements showed that two of the isolates, V14 and V15, have higher binding affinity than that of V10. In addition, the surface plasmon resonance analysis showed that the variants V14 and V15, compared with the parental V10, have lower reactivity to the anti-V region Abs using sera from patients who received murine CC49. Conclusions: The two isolates, V14 and V15, which show higher Ag-binding reactivity and lower sera reactivity than the parental V10 Ab, are potentially more useful clinical reagents. These results demonstrate that phage display can be used to isolate variants of an Ab that are potentially less immunogenic in patients than the parental Ab from which they are derived. C1 NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Off Director, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68182 USA. RP Schlom, J (reprint author), NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NR 52 TC 16 Z9 17 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2003 VL 9 IS 15 BP 5521 EP 5531 PG 11 WC Oncology SC Oncology GA 750TM UT WOS:000187014200013 PM 14654532 ER PT J AU Augenbraun, M Goedert, JJ Thomas, D Feldman, J Seaberg, EC French, AL Robison, E Nowicki, M Terrault, N AF Augenbraun, M Goedert, JJ Thomas, D Feldman, J Seaberg, EC French, AL Robison, E Nowicki, M Terrault, N TI Incident hepatitis C virus in women with human immunodeficiency virus infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; INJECTION-DRUG USERS; UNITED-STATES; NATURAL-HISTORY; INTERAGENCY HIV; RISK; TRANSMISSION; PREVENTION; PREVALENCE; BALTIMORE AB Individuals infected with human immunodeficiency virus type 1 (HIV-1) are frequently coinfected with hepatitis C virus (HCV). Acute HCV infection is often asymptomatic and poorly understood. We conducted a historical prospective study of HCV antibody and viremia in plasma samples obtained during 1994-1999 from a cohort of initially HIV-1-infected, HCV-uninfected women and from HIV-1-HCV-uninfected women. Twenty-two (1.5%) of 1517 experienced seroconversion. Of these, 14 (64%) truly acquired a new infection as assessed by enzyme immunoassay response and new-onset viremia. The incidence rate in HIV-1-infected women was 2.7 cases per 1000 person-years; it was 3.3 cases per 1000 person-years in HIV-1-seronegative women (relative risk, 1.21; P = .75). Acquisition of HCV was associated with any history of drug use (P < .01). Five of 12 viremic, seroconverting individuals cleared viremia. Incident HCV infection among HIV-1-infected and HIV-1-uninfected women was low. It was linked to drug use and commonly resolved. C1 SUNY Downstate Med Ctr, Brooklyn, NY 11203 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. Rush Med Coll, CORE Ctr, Cook Cty Hosp, Chicago, IL 60612 USA. Univ So Calif, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Augenbraun, M (reprint author), SUNY Downstate Med Ctr, Box 1187,450 Clarkson Ave, Brooklyn, NY 11203 USA. FU NCRR NIH HHS [5-M01-RR00083, 5-MO1-RR00079]; NIAID NIH HHS [U01-AI-42590, U01-AI-35004, U01-AI-34989, U01-AI-31834, U01-AI-34994, U01-AI-34993]; NICHD NIH HHS [U01-HD-32632]; PHS HHS [5644201] NR 27 TC 15 Z9 15 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2003 VL 37 IS 10 BP 1357 EP 1364 DI 10.1086/379075 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 737HN UT WOS:000186224500012 PM 14583870 ER PT J AU Nguyen, DH Taub, DD AF Nguyen, DH Taub, DD TI Inhibition of chemokine receptor function by membrane cholesterol oxidation SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LIPID RAFTS; RHODOCOCCUS-EQUI; CELL-SURFACE; MICRODOMAINS; INFECTION; BINDING; TYPE-1; CAVEOLAE; PROTEIN AB Membrane cholesterol is required to maintain chemokine receptor conformation and function for CXCR4 and CCR5. We previously demonstrated that chemokines preferentially bind to receptors within lipid rafts, which are cholesterol- and sphingolipid-rich membrane microdomains. To further elucidate the role of cholesterol in chemokine receptor function, we examined the effects of membrane cholesterol oxidation by cholesterol oxidase (CO), which enzymatically converts cholesterol to 4-cholesten-3-one. Here, we demonstrate that CO treatment (0.25-2.0 U/ml) of human T cells inhibits CXCL12 (SDF-1alpha) and CCL4 (MIP-1beta) binding to cell surface CXCR4 and CCR5, respectively, resulting in the inhibition of chemokine-mediated intracellular calcium mobilization and chemotaxis. The effects were significantly enhanced by cotreatment with low-dose sphingomyelinase (SMase) (0.125 mU/ml), which produced little inhibitory effect by itself. CO and SMase treatment also inhibited HIV-1 infection through CXCR4, but not virus replication. Similar to the removal of membrane cholesterol, CO/SMase treatment induced conformation changes in the chemokine receptors as detected by differential loss in binding of epitope-specific monoclonal antibodies. We conclude that the native form of cholesterol with the hydroxyl group at C3 is critical to CXCR4 and CCR5 conformation and function. (C) 2003 Elsevier Inc. All rights reserved. C1 NIA, Immunol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Taub, DD (reprint author), NIA, Immunol Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 45 TC 43 Z9 45 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 15 PY 2003 VL 291 IS 1 BP 36 EP 45 DI 10.1016/S0014-4827(03)00345-8 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 744HJ UT WOS:000186621900004 PM 14597406 ER PT J AU Noth, U Tuli, R Seghatoleslami, R Howard, M Shah, A Hall, DJ Hickok, NJ Tuan, RS AF Noth, U Tuli, R Seghatoleslami, R Howard, M Shah, A Hall, DJ Hickok, NJ Tuan, RS TI Activation of p38 and Smads mediates BMP-2 effects on human trabecular bone-derived osteoblasts SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE osteogenic differentiation; BMP-2 signaling; p38 MAP kinase; Smad signaling; integrin; adhesion; p125(FAK) ID GROWTH-FACTOR-BETA; PROTEIN-KINASE CASCADES; TGF-BETA; MORPHOGENETIC PROTEIN-2; SIGNALING PATHWAYS; GENE-EXPRESSION; TRANSCRIPTION FACTORS; CELL-DIFFERENTIATION; ENDOTHELIAL-CELLS; FAMILY MEMBERS AB The bone morphogenetic proteins (BMPs) are potent osteoinductive factors that accelerate osteoblast maturation, accompanied by increased cell-substrate adhesion. BMP-2 treatment of osteoblastic cells increases phosphorylation of the cytoplasmic BMP-2 signaling molecules, Smad1 and Smad5. We have previously reported that BMP-2 treatment increase cytoskeletal organization of human trabecular bone-derived osteoblast-like cells (osteoblasts), which is also accompanied by an activation of the focal adhesion kinase p125(FAK). We report here that activation of p125(FAK) occurs with the same kinetics as the phosphorylation of Smad1, suggesting that BMP-2 initiates cross-talk between Smad signaling and the adhesion-mediated signaling pathway. As an adjunct to these effects, we examined activation of mitogen-activated protein (MAP) kinase family members in response to focal adhesion contact formation. Although phosphorylated forms of all three kinases were apparent, only SAPK2alpha/p38 (p38) was activated in response to BMP-2 treatment. Inhibition of p38 kinase activity suppressed BMP-2 induced Smad1 phosphorylation, as well as its translocation to the nucleus, suggesting the integration of p38 activation with Smad1 signaling. Finally, inhibition of p38 in osteoblasts also led to the complete abrogation of BMP-2 induced osteocalcin gene expression and matrix mineralization. These findings suggest that BMP-2 must activate p38 in order to mediate osteogenic differentiation and maturation. (C) 2003 Elsevier Inc. All rights reserved. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Grad Program Cell & Tissue Engn, Philadelphia, PA 19107 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, NIH, Bldg 50,Room 1503, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA 71602]; NIAMS NIH HHS [AR 39740, AR 44501]; NIDCR NIH HHS [DE 11327, DE 16865] NR 73 TC 80 Z9 82 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 15 PY 2003 VL 291 IS 1 BP 201 EP 211 DI 10.1016/S0014-4827(03)00386-0 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 744HJ UT WOS:000186621900018 PM 14597420 ER PT J AU Zigler, JS Qin, C Kamiya, T Krishna, MC Cheng, QF Tumminia, S Russell, P AF Zigler, JS Qin, C Kamiya, T Krishna, MC Cheng, QF Tumminia, S Russell, P TI Tempol-H inhibits opacification of lenses in organ culture SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE lens; cataract; cataract therapy; organ culture; oxidative stress; Tempol-H; free radicals ID OXIDATIVE STRESS; CHELATED IRON; MONKEY LENSES; CATARACT; DAMAGE; MODEL; TRANSPARENCY; MECHANISM; PROTECTS; RABBIT AB Cataract is the world's leading cause of blindness and a disease for which no efficacious medical therapy is available. To screen potential anti-cataract agents, a tens organ culture model system was used. Opacification of lenses maintained in culture was induced by specific insults including H2O2 or the cataractogenic sugar xylose. Potential anti-cataract agents were added to the culture medium and their ability to inhibit opacification and certain biochemical changes associated with the opacification were assessed. Among the compounds tested, Tempol-H, the hydroxylamine of the nitroxide Tempol, gave the most promising results. It significantly inhibited opacification of rat lenses in an H2O2-induced cataract system as well as opacification of rhesus monkey lenses induced by xylose. Tempol-H inhibited the loss of glutathione, the leakage of protein, and decreases in the ability of cultured lenses to accumulate H-3-choline from the medium, all of which were associated with the development of lens opacification. The antioxidative activity of Tempol-H and its ability to re-dox cycle make it an attractive candidate as a therapeutic agent for the prevention of aging-related cataract. (C) 2003 Elsevier Inc. C1 NEI, Lab Mechanism Ocular Dis, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Zigler, JS (reprint author), NEI, Lab Mechanism Ocular Dis, 6 Ctr Dr MSC-2735, Bethesda, MD 20892 USA. NR 25 TC 30 Z9 31 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 15 PY 2003 VL 35 IS 10 BP 1194 EP 1202 DI 10.1016/S0891-5849(03)00505-7 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 743UQ UT WOS:000186592300003 PM 14607518 ER PT J AU Towner, RA Qian, SY Kadiiska, MB Mason, RP AF Towner, RA Qian, SY Kadiiska, MB Mason, RP TI In vivo identification of aflatoxin-induced free radicals in rat bile SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE aflatoxin-B1; aflatoxin-M1; spin trapping; hydroxyl radicals; lipid radicals; desferoxamine mesylate; SKF525A; gadolinium chloride; HPLC-ESR; free radicals ID LIPID-PEROXIDATION; METABOLIC-ACTIVATION; NONPARENCHYMAL CELLS; SPIN-RESONANCE; KUPFFER CELLS; FATTY-ACIDS; HUMAN LIVER; GREEN TEA; B-1; CYTOCHROME-P-450 AB Aflatoxin B1 (AFB1) is a potent hepatocarcinogen. We have recently detected [via electron spin resonance (ESR) spectroscopy] free radicals in vivo in rat bile following AFB1 metabolism using the spin trapping [alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone (4-POBN)] technique. The aim of the present study was to identify the trapped free radical intermediates from the in vivo hepatic metabolism of AFB1. Rats were treated simultaneously with AFB1 (3 mg/kg i.p.) and the spin trapping agent 4-POBN (1 g/kg i.p.), and bile was collected over a period of I h at 20 min intervals. On-line high performance liquid chromatography (HPLC) coupled to ESR was used to identify an arachidonic acid-derived radical adduct of 4-POBN in rat bile, and a methyl adduct of 4-POBN from the reaction of hydroxyl radicals with carbon-13-labeled dimethyl sulfoxide (13 C-DMSO). The effect of metabolic inhibitors, such as desferoxamine mesylate (DFO), an iron chelator, 2-dimethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF) 525A, a cytochrome P-450 inhibitor, and gadolinium chloride (GdCl3), a Kupffer cell inactivator, on in vivo aflatoxin-induced free radical formation were also studied. It was found that there was a significant decrease in radical formation as a result of DFO, SKF525A and GdCl3 inhibition. Trapped 4-POBN radical adducts were also detected in rat bile following the in vivo metabolism of aflatoxin-M1, one of the hydroxylated metabolites of AFB1. (C) 2003 Elsevier Inc. C1 Oklahoma Med Res Fdn, Magnet Resonance Imaging Facil, Free Rad Biol & Aging Res Program, Oklahoma City, OK 73104 USA. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. RP Towner, RA (reprint author), Oklahoma Med Res Fdn, Magnet Resonance Imaging Facil, Free Rad Biol & Aging Res Program, Oklahoma City, OK 73104 USA. NR 51 TC 52 Z9 56 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 15 PY 2003 VL 35 IS 10 BP 1330 EP 1340 DI 10.1016/j.freeradbiomed.2003.08.002 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 743UQ UT WOS:000186592300017 PM 14607532 ER PT J AU Cui, CY Durmowicz, M Ottolenghi, C Hashimoto, T Griggs, B Srivastava, AK Schlessinger, D AF Cui, CY Durmowicz, M Ottolenghi, C Hashimoto, T Griggs, B Srivastava, AK Schlessinger, D TI Inducible mEDA-A1 transgene mediates sebaceous gland hyperplasia and differential formation of two types of mouse hair follicles SO HUMAN MOLECULAR GENETICS LA English DT Article ID HYPOHIDROTIC ECTODERMAL DYSPLASIA; ECTODYSPLASIN-A; BETA-CATENIN; GENE-EXPRESSION; SONIC-HEDGEHOG; SWEAT GLANDS; EDA GENE; MICE; TABBY; SKIN AB EDA splice isoforms EDA-A1 and EDA-A2 belong to the TNF ligand family and regulate skin appendage formation by activating NF-kB- and JNK- promoted transcription. To analyze their action further, we conditionally expressed the isoforms as tetracycline ('Tet')-regulated transgenes in Tabby (EDA-negative) and wild-type mice. Expression of only the mEDA-A1 transgene had two types of effects during embryogenesis: (1) determinative effects on sweat glands and hair follicles. In Tabby mice, one type of hair follicle ('guard hair') was restored, whereas a second type, the dominant undercoat hair follicle ('zigzag') was not; furthermore, the transgene sharply suppressed zigzag hair formation in wild-type mice, with the overall numbers of back hair follicles remaining the same; and (2) trophic effects on sebaceous and Meibomian glands. Marked hyperplasia resulted from expansion of the sebocyte-producing zone in sebaceous glands, with particularly high expression of the transgene and the replication marker PCNA, and correspondingly high production of sebum. The phenotypic effects of mEDA-A1 on sebaceous glands, but not on hair follicles, were reversed when the gene was repressed in adult animals. The results thus reveal both initiating and trophic isoform-specific effects of the EDA gene, and suggest a possible balance of isoform interactions in skin appendage formation. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Greenwood Genet Ctr, JC Self Res Inst Human Genet, Greenwood, SC 29646 USA. RP Schlessinger, D (reprint author), NIA, Genet Lab, NIH, 333 Cassell Dr,Suite 3000, Baltimore, MD 21224 USA. NR 39 TC 47 Z9 51 U1 0 U2 1 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 NOV 15 PY 2003 VL 12 IS 22 BP 2931 EP 2940 DI 10.1093/hmg/ddg325 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 741FL UT WOS:000186448000006 PM 14506134 ER PT J AU Cookson, MR Lockhart, PJ O'Farrell, C Schlossmacher, M Farrer, MJ AF Cookson, MR Lockhart, PJ O'Farrell, C Schlossmacher, M Farrer, MJ TI RING finger 1 mutations in Parkin produce altered localization of the protein SO HUMAN MOLECULAR GENETICS LA English DT Article ID RECESSIVE JUVENILE PARKINSONISM; ALPHA-SYNUCLEIN; LEWY BODIES; GENE; DISEASE; DEGRADATION; AGGRESOMES; BRAIN; UBIQUITINATION; ACCUMULATION AB The Parkin gene (PRKN) encodes an E3 protein-ubiquitin ligase for which loss of function is associated with autosomal-recessive juvenile (<20 years) and early-onset Parkinsonism (<45 years). Although detailed pathological reports are scarce, brains from patients with homozygous exonic deletions demonstrate neuronal loss in the substantia nigra, albeit without the Lewy body pathology characteristic of idiopathic Parkinson's disease. However, there are rare descriptions of more florid pathology, including Lewy bodies and tau positive astrocytes in individuals with compound heterozygous mutations. In the present study we examined whether PRKN point mutations, leading to amino acid substitutions, may alter the cellular distribution of the protein produced. Wild-type Parkin was homogeneously distributed throughout the cytoplasm with a small amount of protein in the nucleus after transfection into human embryonic kidney cells. Mutant isoforms with A82E, G328E and C431F amino acid substitutions were also normally distributed. However, two mutant isoforms, R256C and R275W, within RING finger 1 of the Parkin protein (238-293 amino acids), produced an unusual distribution of the protein, with large cytoplasmic and nuclear inclusions. We have replicated this observation in primary cultured neurons and demonstrate, by the accumulation/co-localization of cytoskeletal protein vimentin, that the inclusion bodies are aggresomes, a cellular response to misfolded protein. C1 Mayo Clin Jacksonville, Dept Neurosci, Jacksonville, FL 32224 USA. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Harvard Inst Med, Ctr Neurol Dis, Boston, MA 02115 USA. RP Farrer, MJ (reprint author), Mayo Clin Jacksonville, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. RI Lockhart, Paul/E-7753-2011 OI Lockhart, Paul/0000-0003-2531-8413 FU NINDS NIH HHS [P01-NS14540256, R01-NS541816-01] NR 46 TC 104 Z9 105 U1 1 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 NOV 15 PY 2003 VL 12 IS 22 BP 2957 EP 2965 DI 10.1093/hmg/ddg328 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 741FL UT WOS:000186448000009 PM 14519684 ER PT J AU Saleem, RA Banerjee-Basu, S Berry, FB Baxevanis, AD Walter, MA AF Saleem, RA Banerjee-Basu, S Berry, FB Baxevanis, AD Walter, MA TI Structural and functional analyses of disease-causing missense mutations in the forkhead domain of FOXC1 SO HUMAN MOLECULAR GENETICS LA English DT Article ID TRANSCRIPTION FACTOR GENE; DNA-BINDING DOMAIN; AXENFELD-RIEGER-SYNDROME; HELIX GENE; CARDIOVASCULAR DEVELOPMENT; CONGENITAL HYDROCEPHALUS; ANTERIOR-CHAMBER; FKHL7 GENE; MF1; PHENOTYPES AB Five missense mutations (P79L, P79T, I91S, I91T and R127H) within the forkhead DNA-binding domain of the FOXC1 transcription factor, identified in patients with Axenfeld-Rieger (AR) malformations, were studied to identify the effects of these mutations on FOXC1 structure and function. Molecular modeling and threading analyses predict that the I91S and T mutations may generate local disruptions to the structure of the forkhead domain while the R127H mutation alters the electrostatic charge of the DNA binding surface of the forkhead domain. The P79L and T mutations are not predicted to grossly perturb the structure of the forkhead domain. Biological analyses indicate that all of these missense mutations cause a range of FOXC1 perturbations, including nuclear localization defects, reduced or abolished DNA binding capacity, and a reduction in the transactivation capacity of FOXC1. These experiments extend our previous hypothesis that reduced transactivation of appropriate target genes by FOXC1, underlie AR malformations mapping to human chromosome 6p25. Importantly, these results can also be applied to predict the consequences of the molecular effects of mutations of other FOX genes that have analogous missense mutations, including FOXP2, FOXE3 and FOXC2. C1 Univ Alberta, Dept Med Genet, Edmonton, AB T6G 2H7, Canada. Univ Alberta, Dept Ophthalmol, Edmonton, AB T6G 2H7, Canada. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Walter, MA (reprint author), Univ Alberta, Dept Med Genet, 832 Med Sci Bldg, Edmonton, AB T6G 2H7, Canada. NR 40 TC 55 Z9 56 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 NOV 15 PY 2003 VL 12 IS 22 BP 2993 EP 3005 DI 10.1093/hmg/ddg324 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 741FL UT WOS:000186448000012 PM 14506133 ER PT J AU Fiorino, C Sanguineti, G Cozzarini, C Fellin, G Foppiano, F Menegotti, L Piazzolla, A Vavassori, V Valdagni, R AF Fiorino, C Sanguineti, G Cozzarini, C Fellin, G Foppiano, F Menegotti, L Piazzolla, A Vavassori, V Valdagni, R TI Rectal dose-volume constraints in high-dose radiotherapy of localized prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; conformal radiotherapy; rectal bleeding; dose-volume histograms ID CONFORMAL RADIATION-THERAPY; INTENSITY-MODULATED RADIOTHERAPY; CONVENTIONAL RADIOTHERAPY; SURFACE HISTOGRAMS; RANDOMIZED-TRIAL; 70 GY; IRRADIATION; ESCALATION; COMPLICATIONS; CARCINOMA AB Purpose: To investigate the relationship between rectal bleeding and dosimetric-clinical parameters in patients receiving three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. Methods: In a retrospective national study (AIROPROS01-01, AIRO: Associazione Italiana Radioterapia Oncologica), planning/clinical data for 245 consecutive patients with stage Tl-4N0-x prostate carcinoma who underwent 3D-CRT to 70-78 Gy (ICRU point) were pooled from four Italian institutions. The correlation between late rectal bleeding and rectal dose-volume data (the percentage of rectum receiving more than 50, 55, 60, 65, 70, and 75 Gy [V50-70]) and other dosimetric and clinical parameters were investigated in univariate (log-rank) and multivariate (Cox regression model) analyses. Median follow-up was 2 years. Results: Twenty-three patients were scored as late bleeders according to a modified RTOG definition (Grade 2: 16; Grade 3: 7); the actuarial 2-year rate was 9.2%. Excepting V75, all median and third quartile V50-70 values were found to be significantly correlated with late bleeding at univariate analysis. The smallest p value was seen for V-50 below/above the third quartile value (66%). The V70 (cut-off value: 30%) was found to be also predictive for late bleeding. In the high-dose subgroup (74-78 Gy), Grade 3 bleeding was highly correlated with this constraint. The predictive value of both V-50 and V-70 was confirmed by multivariate analyses. Conclusions: The present article provides evidence for correlation between rectal DVH parameters and late rectal bleeding in patients treated with curative intent with 3D-CRT. To keep the rate of moderate/severe rectal bleeding below 5-10%, it seems advisable to limit V-50 to 60-65%, V-60 to 45-50%, and V70 to 25-30%. (C) 2003 Elsevier Inc. C1 Hosp San Raffaele, Dept Med Phys & Radiotherapy, Serv Fis Sanit, I-20132 Milan, Italy. Natl Canc Inst, Dept Med Phys & Radiotherapy, Genoa, Italy. Osped S Chiara, Dept Med Phys & Radiotherapy, Trento, Italy. Osped Circolo Varese, Dept Med Phys & Radiotherapy, Varese, Italy. Casa Cura PioX, Dept Radiotherapy, Milan, Italy. RP Fiorino, C (reprint author), Hosp San Raffaele, Dept Med Phys & Radiotherapy, Serv Fis Sanit, Via Olgettina 60, I-20132 Milan, Italy. RI Valdagni, Riccardo/K-1361-2016; OI Valdagni, Riccardo/0000-0001-5140-9728; Cozzarini, Cesare/0000-0002-7006-8196 NR 49 TC 118 Z9 118 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2003 VL 57 IS 4 BP 953 EP 962 DI 10.1016/S0360-3016(03)00665-5 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 738NB UT WOS:000186293800007 PM 14575825 ER PT J AU Emanuel, EJ Schnipper, LE Kamin, DY Levinson, J Lichter, AS AF Emanuel, EJ Schnipper, LE Kamin, DY Levinson, J Lichter, AS TI The costs of conducting clinical research SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TRIALS AB Purpose: Physicians frequently receive payment for enrolling subjects onto clinical trials. Some view these payments as conflicts of interest. Others contend that these payments are necessary reimbursements for conducting clinical research. We evaluated the clinical and nonclinical hours and costs associated with conducting a mock phase III clinical research trial. Methods: We collected data from representatives of 21 clinical sites, on the numbers of hours associated with 13 activities necessary to the conduct of clinical research. The hours were based on enrolling 20 patients in a 12-month randomized placebo-controlled trial of a new chemotherapeutic agent. The outcome measures were disease progression and quality-of-life reports. These costs were evaluated for both government and pharmaceutical industry-sponsored trials. Results: On average, 4,012 hours (range, 1,512 to 13,319 hours) were required for a government-sponsored trial, and 3,998 hours (range: 1735 to 15,699) were required for a pharmaceutical industry-sponsored trial involving 20 subjects with 17 office visits, or approximately 200 hours per subject. Thirty-two percent of the hours were devoted to nonclinical activities, such as institutional review board submission and completion of clinical reporting forms. On average, excluding overhead expenses, it cost slightly more than $6,094 (range, $2,098 to $19,285) per enrolled subject for an industry-sponsored trial, including $1,999 devoted to nonclinical costs. Conclusion: Based on the results of our mock trial, the time required for nontreatment trial activities is considerable, and the associated costs are substantial. (C) 2003 by American Society of Clinical Oncology. C1 Lewin Grp, Falls Church, VA USA. Amer Soc Clin Oncol, Dept Publ Policy & Practice, Alexandria, VA USA. Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA 02215 USA. Natl Inst Hlth, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD USA. RP Lichter, AS (reprint author), Univ Michigan, Sch Med, 4101 Med Sci Bldg 1,1301 Catherine Rd, Ann Arbor, MI 48109 USA. NR 5 TC 66 Z9 67 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 15 PY 2003 VL 21 IS 22 BP 4145 EP 4150 DI 10.1200/JCO.2003.08.156 PG 6 WC Oncology SC Oncology GA 745BW UT WOS:000186669300014 PM 14559889 ER PT J AU Grimm, MC Newman, R Hassim, Z Cuan, N Connor, SJ Le, YY Wang, JM Oppenheim, JJ Lloyd, AR AF Grimm, MC Newman, R Hassim, Z Cuan, N Connor, SJ Le, YY Wang, JM Oppenheim, JJ Lloyd, AR TI Cutting edge: Vasoactive intestinal peptide acts as a potent suppressor of inflannnation in vivo by trans-deactivating chemokine receptors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN MONOCYTES; SUBSTANCE-P; DISEASE; CHEMOTAXIS; EXPRESSION; DESENSITIZATION; PHOSPHORYLATION; MACROPHAGES; ACTIVATION; ARTHRITIS AB Chemokines mediate trafficking of leukocytes to sites of inflammation and immune responses through activation of G protein-coupled receptors, which thereby provide appealing targets for novel anti-inflammatory agents. Vasoactive intestinal peptide (VIP) is an immunosuppressive neurotransmitter. We show that VIP inhibited the function of chemokine receptors on monocytes and CD4(+) T lymphocytes, with impaired chemotaxis and calcium flux in response to the cognate chemokine ligands CXCL12, CCL3, CCL4, and CCL5. This was mediated by VIP receptor type I and was not caused by chemokine receptor internalization. However, VIPcauseddose-dependentphosphorylation of the chemokine receptor CCR5. This trans-deactivation process was studied in a murine model of delayed-type hypersensitivity continuous infusion of VIP resulted in significant abrogation of monocyte and lymphocyte infiltration. Circulating mononuclear cells from VIP-infused mice were unable to respond to chemokines. VIP may provide a novel approach to treatment of inflammatory diseases through inhibition of chemokine-dependent leukocyte recruitment. C1 Univ New S Wales, Sch Med, Inflammat Res Unit, Sydney, NSW, Australia. NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. St Georges Clin Sch, Dept Med, Kogarah, NSW 2217, Australia. RP Grimm, MC (reprint author), St Georges Clin Sch, Dept Med, Kogarah, NSW 2217, Australia. NR 26 TC 37 Z9 38 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2003 VL 171 IS 10 BP 4990 EP 4994 PG 5 WC Immunology SC Immunology GA 744QJ UT WOS:000186643300008 PM 14607894 ER PT J AU Mongini, PKA Jackson, AE Tolani, S Fattah, RJ Inman, JK AF Mongini, PKA Jackson, AE Tolani, S Fattah, RJ Inman, JK TI Role of complement-binding CD21/CD19/CD81 in enhancing human B cell protection from fas-mediated apoptosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN RECEPTOR COMPLEX; FLICE-INHIBITORY PROTEIN; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HUMORAL IMMUNE-RESPONSES; CO-LIGATION; T-CELLS; AUTOANTIBODY PRODUCTION; CASPASE-8 ACTIVATION; LYMPHOCYTE RESPONSES; AFFINITY MATURATION AB Defective expression of Fas leads to B cell autoimmunity, indicating the importance of this apoptotic pathway in eliminating autoreactive B cells. However, B cells with anti-self specificities occasionally escape such regulation in individuals with intact Fas, suggesting ways of precluding this apoptosis. Here, we examine whether coligation of the B cell Ag receptor (BCR) with the complement (C3)-binding CD21/CD19/CD81 costimulatory complex can enhance the escape of human B cells from Fas-induced death. This was warranted given that BCR-initiated signals induce resistance to Fas apoptosis, some (albeit not all) BCR-triggered events are amplified by coligation of BCR and the co-stimulatory complex, and several self Ags targeted in autoimmune diseases effectively activate complement. Using a set of affinity-diverse surrogate Ags (receptor-specific mAb:dextran conjugates) with varying capacity to engage CD21, it was established that BCR:CD21 coligation lowers the BCR engagement necessary for inducing protection from Fas apoptosis. Enhanced protection was associated with altered expression of several molecules known to regulate Fas apoptosis, suggesting a unique molecular model for how BCR:CD21 coligation augments protection. BCR:CD21 coligation impairs the generation of active fragments of caspase-8 via dampened expression of membrane Fas and augmented expression of FLIPL. This, in turn, diminishes the generation of cells that would be directly triggered to apoptosis via caspase-8 cleavage of caspase 3 (type I cells). Any attempt to use the mitochondrial apoptotic protease-activating factor 1 (Apaf-1)-dependent pathway for apoptosis (as type II cells) is further blocked because BCR:CD21 coligation promotes up-regulation of the mitochondrial antiapoptotic molecule, Bcl-2. C1 NYU Med Ctr, Hosp Joint Dis, Dept Rheumatol, New York, NY 10003 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, Dept Pathol, New York, NY 10016 USA. NIH, Immunol Lab, Bethesda, MD 20892 USA. RP Mongini, PKA (reprint author), NYU Med Ctr, Hosp Joint Dis, Dept Rheumatol, 301 E 17th St, New York, NY 10003 USA. FU NIAID NIH HHS [R01AI052189] NR 84 TC 21 Z9 22 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 NOV 15 PY 2003 VL 171 IS 10 BP 5244 EP 5254 PG 11 WC Immunology SC Immunology GA 744QJ UT WOS:000186643300039 PM 14607925 ER PT J AU Lieto, LD Borrego, F You, CH Coligan, JE AF Lieto, LD Borrego, F You, CH Coligan, JE TI Human CD94 gene expression: Dual promoters differing in responsiveness to IL-2 or IL-15 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; CD8(+) T-CELLS; CLASS-I MOLECULES; INHIBITORY RECEPTORS; TRANSCRIPTION FACTORS; NK CELLS; LYMPHOID DEVELOPMENT; HLA-E; CD94/NKG2A; ACTIVATION AB CD94 is a C-type lectin required for the dimerization of the CD94/NKG2 family of receptors, which are expressed on NK cells and T cell subsets. Little is known about CD94 gene expression and the elements that regulate CD94 transcription. In this study, we report that CD94 gene expression is regulated by distal and proximal promoters that transcribe unique initial exons specific to each promoter. This results in two species of transcripts; the previously described CD94 mRNA and a novel CD94C mRNA. All NK cells and CD94(+), CD8(+) alphabeta T cells transcribe CD94 mRNA. Stimulation of NK and CD8(+) alphabeta T cells with IL-2 or IL-15 induced the transcription of CD94C mRNA. The distal and proximal promoters both contain elements with IFN-gamma-activated and Ets binding sites, known as GAS/EBS. Additionally, an unknown element, termed site A, was identified in the proximal promoter. EMSA analyses showed that constitutive factors could bind to oligonucleotide probes containing each element. After treatment of primary NK cells with IL-2 or IL-15, separate inducible complexes could be detected with oligonucleotide probes containing either the proximal or distal GAS/EBS elements. These elements are highly conserved between mice and humans, which suggests that both species regulate CD94 gene expression via mechanisms that predate their evolutionary divergence. C1 NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. RP Coligan, JE (reprint author), NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Twinbrook 2,Room 205,12441 Parklawn Dr, Rockville, MD 20852 USA. EM jcoligan@niaid.nih.gov NR 68 TC 23 Z9 23 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 NOV 15 PY 2003 VL 171 IS 10 BP 5277 EP 5286 PG 10 WC Immunology SC Immunology GA 744QJ UT WOS:000186643300043 PM 14607929 ER PT J AU Puri, N Kruhlak, MJ Whiteheart, SW Roche, PA AF Puri, N Kruhlak, MJ Whiteheart, SW Roche, PA TI Mast cell degranulation requires N-ethylmaleimide-sensitive factor-mediated SNARE disassembly SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FC-EPSILON-RI; MEMBRANE-FUSION; ALPHA-SNAP; CA2+-DEPENDENT EXOCYTOSIS; SYNAPTIC EXOCYTOSIS; GRANULE EXOCYTOSIS; ATPASE ACTIVITY; LEUKEMIA-CELLS; PC12 CELLS; NSF AB Mast cells possess specialized granules that, upon stimulation of surface FcR with IgE, fuse with the plasma membrane, thereby releasing inflammatory mediators. A family of membrane fusion proteins called SNAREs, which are present on both the granule and the plasma membrane, plays a role in the fusion of these granules with the plasma membrane of mast cells. In addition to the SNAREs themselves, it is likely that the SNARE accessory protein, N-ethylmaleimide-sensitive factor (NSF), affects the composition and structure of the SNARE complex. NSF is a cytoplasmic ATPase that disassembles the SNARE complexes. To investigate the role of NSF in mast cell degranulation, we developed an assay to measure secretion from transiently transfected RBL (rat basophilic leukemia)-2H3 mast cells (a tumor analog of mucosal mast cells). RBL-2H3 cells were cotransfected with a plasmid encoding a human growth hormone secretion reporter along with either wild-type NSF or an NSF mutant that lacks ATPase activity. Human growth hormone was targeted to and released from secretory granules in RBL-2H3 cells, and coexpression with mutant NSF dramatically inhibited regulated exocytosis from the transfected cells. Biochemical analysis of SNARE complexes in these cells revealed that overexpression of the NSF mutant decreased disassembly and resulted in an accumulation of SNARE complexes. These data reveal a role for NSF in mast cell exocytosis and highlight the importance of SNARE disassembly, or priming, in regulated exocytosis from mast cells. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. OI Whiteheart, Sidney/0000-0001-5577-0473 FU NHLBI NIH HHS [HL56652] NR 46 TC 51 Z9 51 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 NOV 15 PY 2003 VL 171 IS 10 BP 5345 EP 5352 PG 8 WC Immunology SC Immunology GA 744QJ UT WOS:000186643300051 PM 14607937 ER PT J AU Iribarren, P Cui, YH Le, Y Ying, GG Zhang, X Gong, WH Wang, JM AF Iribarren, P Cui, YH Le, Y Ying, GG Zhang, X Gong, WH Wang, JM TI IL-4 down-regulates lipopolysaccharide-induced formyl peptide receptor 2 in murine microglial cells by inhibiting the activation of mitogen-activated protein kinases SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; UP-REGULATION; EXPRESSION; PHOSPHATASE; MACROPHAGES; ASTROCYTES; CYTOKINE; TARGET; PATHWAYS AB Microglial cells actively participate in proinflammatory responses in the CNS. Upon stimulation with the bacterial LPS, microglial cells express a functional formyl peptide receptor 2 which mediates the chemotactic and activating effects of a variety of polypeptide agonists including amyloid beta (Abeta(1-42)), a critical pathogenic agent in Alzheimer's disease. In the present study, we found that LPS-induced expression and function of formyl peptide receptor 2 in microglial cells was markedly inhibited by IL-4, a Th2-type cytokine. Our effort to elucidate the mechanistic basis revealed that IL-4 attenuated LPS-stimulated activation of NF-kappaB, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase, and the effect of IL-4 was associated with a phosphoinositide 3-kinase pathway-dependent increase in serine/threonine phosphatase activity. These results suggest that IL-4 may play an important role in the maintenance of homeostasis of CNS and in the regulation of the disease process characterized by microglial activation in response to proinflammatory stimulants. C1 NCI, Canc Res Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. Lanzhou Mil Med Univ, Biochem Sect, Lanzhou, Peoples R China. Lanzhou Mil Med Univ, Mol Immunoregulat Lab, Lanzhou, Peoples R China. SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RP Wang, JM (reprint author), NCI, Canc Res Ctr, Lab Mol Immunoregulat, Bldg 560,Room 31-40, Frederick, MD 21702 USA. RI Zhang, Xia/B-8152-2008 OI Zhang, Xia/0000-0002-9040-1486 FU NCI NIH HHS [N01-CO-12400] NR 38 TC 23 Z9 23 U1 1 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 NOV 15 PY 2003 VL 171 IS 10 BP 5482 EP 5488 PG 7 WC Immunology SC Immunology GA 744QJ UT WOS:000186643300068 PM 14607954 ER PT J AU Chevillard, C Moukoko, CE Elwali, NEMA Bream, JH Kouriba, B Argiro, L Rahoud, S Mergani, A Henri, S Gaudart, J Mohamed-Ali, Q Young, HA Dessein, AJ AF Chevillard, C Moukoko, CE Elwali, NEMA Bream, JH Kouriba, B Argiro, L Rahoud, S Mergani, A Henri, S Gaudart, J Mohamed-Ali, Q Young, HA Dessein, AJ TI IFN-gamma polymorphisms (IFN-gamma+2109 and IFN-gamma+3810) are associated with severe hepatic fibrosis in human hepatic schistosomiasis (Schistosoma mansoni) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; NF-KAPPA-B; INTERFERON-GAMMA; HEPATOSPLENIC SCHISTOSOMIASIS; MOLECULAR REGULATION; PERIPORTAL FIBROSIS; GRANULOMA-FORMATION; CYTOKINE REGULATION; COLLAGEN-SYNTHESIS; GENE-EXPRESSION AB Schistosome infection is a major public health concern affecting millions of people living in tropical regions of Africa, Asia, and South America. Schistosomes cause mild clinical symptoms in most subjects, whereas a small proportion of individuals presents severe clinical disease (as periportal fibrosis (PPF)) that may lead to death. Severe PPF results from an abnormal deposition of extracellular matrix proteins in the periportal spaces due to a chronic inflammation triggered by eggs and schistosome Ags. Extracellular matrix protein production is regulated by a number of cytokines, including IFN-gamma. We have now screened putative polymorphic sites within this gene in a population living in an endemic area for Schistosoma mansoni. Two polymorphisms located in the third intron of the IFN-gamma gene are associated with PPF. The IFN-gamma +2109 A/G polymorphism is associated with a higher risk for developing PPF, whereas the IFN-gamma +3810 G/A polymorphism is associated with less PPF. The polymorphisms result in changes in nuclear protein interactions with the intronic regions of the gene, suggesting that they may modify IFN-gamma mRNA expression. These results are consistent with the results of previous studies. Indeed, PPF is controlled by a major locus located on chromosome 6q22-q23, closely linked to the gene encoding the alpha-chain of the IFN-gamma receptor, and low IFN-gamma producers have been shown to have an increased risk of severe PPF. Together, these observations support the view that IFN-gamma expression and subsequent signal transduction play a critical role in the control of PPF in human hepatic schistosome infection (S. mansoni). C1 Fac Med Marseille, INSERM, U399, Lab Parasitol Mycol, F-13385 Marseille, France. Al Zaiem Al Azhari Univ, Omdurman, Sudan. NCI, Expt Immunol Lab, Frederick, MD 21702 USA. Univ Gezira, Inst Nucl Med Mol Biol & Oncol, Wad Medani, Sudan. RP Chevillard, C (reprint author), Fac Med Marseille, INSERM, U399, Lab Parasitol Mycol, F-13385 Marseille, France. RI Young, Howard/A-6350-2008; Alain, Dessein/A-3142-2009; ARGIRO, LAURENT/A-7983-2010; chevillard, christophe/B-2732-2008; gaudart, jean/D-9071-2013; chevillard, christophe/A-7087-2015; Henri, Sandrine/O-3045-2016 OI Young, Howard/0000-0002-3118-5111; gaudart, jean/0000-0001-9006-5729; NR 45 TC 55 Z9 62 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2003 VL 171 IS 10 BP 5596 EP 5601 PG 6 WC Immunology SC Immunology GA 744QJ UT WOS:000186643300082 PM 14607968 ER PT J AU Landay, AL Spritzler, J Kessler, H Mildvan, D Pu, M Fox, L O'Neil, D Schock, B Kuritzkes, D Lederman, MM AF Landay, AL Spritzler, J Kessler, H Mildvan, D Pu, M Fox, L O'Neil, D Schock, B Kuritzkes, D Lederman, MM CA AIDS Clinical Trials Grp 5014 Team TI Immune reconstitution is comparable in antiretroviral-naive subjects after 1 year of successful therapy with a nucleoside reverse-transcriptase inhibitor- or protease inhibitor-containing antiretroviral regimen SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 6th International Congress on Drug Therapy in HIV Infection CY NOV 17-21, 2002 CL GLASGOW, SCOTLAND ID IMMUNODEFICIENCY-VIRUS-INFECTION; T-CELL DEATH; HIV-INFECTION; TREATMENT FAILURE; TYPE-1 INFECTION; IN-VIVO; CD4(+); ACTIVATION; APOPTOSIS; DISEASE AB We compared immune restoration in patients who suppressed human immunodeficiency virus type 1 replication after treatment with a protease inhibitor (PI) plus nevirapine or with 3 nucleoside reverse-transcriptase inhibitors (NRTIs) plus nevirapine. Changes in total and memory CD4 and CD8 cells were similar in the groups, as were decreases in immune activation (e. g., CD38 and HLA-DR) and increases in CD28 expression. Increases in naive CD4 and CD8 cells tended to be greater in the NRTI-treated group, with differences in naive CD4 cells significant at weeks 8 and 12 (P < .05) but not at week 48. Lymphocyte apoptosis decreased in both groups, but the week-1 decrease was greater in the PI-treated group (P < .02). Lymphocyte proliferation and skin- test responses were comparable. We find little evidence for differences in the major direct immunologic effect of PI versus NRTI regimens and propose that effects observed elsewhere were indirect, mediated through antiviral activity or adaptation of the virus to selection pressure. C1 Rush Med Coll, Dept Immunol Microbiol, Chicago, IL 60612 USA. Rush Med Coll, Dept Med, Chicago, IL 60612 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Div Infect Dis, New York, NY USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. Social & Sci Syst, Silver Spring, MD USA. Case Western Reserve Univ, Ctr AIDS Res, Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Landay, AL (reprint author), Rush Med Coll, Dept Immunol Microbiol, 1735 W Harrison St,Ste 616, Chicago, IL 60612 USA. FU NIAID NIH HHS [AI-25915, AI-32270, AI-38858, AI-46370, AI-27659, AI-38855] NR 53 TC 30 Z9 30 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 NOV 15 PY 2003 VL 188 IS 10 BP 1444 EP 1454 DI 10.1086/379041 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 745GW UT WOS:000186681800006 PM 14624369 ER PT J AU Serwadda, D Gray, RH Sewankambo, NK Wabwire-Mangen, F Chen, MZ Quinn, TC Lutalo, T Kiwanuka, N Kigozi, G Nalugoda, F Meehan, MP Morrow, RA Wawer, MJ AF Serwadda, D Gray, RH Sewankambo, NK Wabwire-Mangen, F Chen, MZ Quinn, TC Lutalo, T Kiwanuka, N Kigozi, G Nalugoda, F Meehan, MP Morrow, RA Wawer, MJ TI Human immunodeficiency virus acquisition associated with genital ulcer disease and herpes simplex virus type 2 infection: A nested case-control study in Rakai, Uganda SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED-DISEASES; HIV-INFECTION; TRANSMISSION; REACTIVATION; POPULATION; PLASMA; RNA AB To assess the timing of symptomatic genital ulcer disease ( GUD) relative to human immunodeficiency virus ( HIV) seroconversion, we studied 248 case subjects who underwent HIV seroconversion and 496 HIV- negative control subjects, at 3 interview visits conducted at 10- month intervals: visit 1, before HIV acquisition; visit 2, after seroconversion; and visit 3, 10 months after detection of seroconversion. Odds ratios ( ORs) and 95% confidence intervals ( CIs), for HIV acquisition, were estimated by logistic regression. HIV load was measured by RNA - polymerase chain reaction, and herpes simplex virus type 2 ( HSV- 2) serologic testing used HerpeSelect EIA with Western blot confirmation. The OR of HSV- 2 seropositivity associated with HIV acquisition was 1.7 ( 95% CI, 1.2 - 2.4). Prevalence of GUD was increased among case subjects, at visits 2 ( OR, 3.2; 95% CI, 1.9 - 5.3) and 3 ( OR, 2.1; 95% CI, 1.1 - 3.9). HIV load was increased in HSV- 2 - seropositive case subjects, compared with that in HSV- 2 - seronegative subjects, at 5 ( p = .04) and 15 (P = .02) months after seroconversion. HIV acquisition is associated with HSV- 2 seropositivity, and GUD is increased after seroconversion. HIV load is increased in HSV- 2 - positive subjects who seroconverted, suggesting a role for treatment of HSV- 2 infection in HSV- 2 - seropositive, dually infected individuals. C1 Johns Hopkins Univ, Bloomberg Sch Hyg & Publ Hlth, Dept Populat & Family Hlth Sci, Baltimore, MD 21205 USA. Makerere Univ, Inst Publ Hlth, Kampala, Uganda. Makerere Univ, Dept Med, Kampala, Uganda. Makerere Univ, Fac Med, Kampala, Uganda. Uganda Virus Res Inst, Rakai Project, Entebbe, Uganda. Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. Columbia Univ, Heilbrun Ctr Populat & Family Hlth, Joseph L Mailman Sch Publ Hlth, New York, NY USA. Univ Washington, Sch Med, Seattle, WA USA. RP Gray, RH (reprint author), Johns Hopkins Univ, Bloomberg Sch Hyg & Publ Hlth, Dept Populat & Family Hlth Sci, Ste 4030,615 N Wolfe St, Baltimore, MD 21205 USA. OI Sewankambo, Nelson/0000-0001-9362-053X FU FIC NIH HHS [5D43TW00010]; NIAID NIH HHS [AI30731, R01 AI3426S, R01 AI34826]; NICHD NIH HHS [5P30HD06826] NR 21 TC 123 Z9 125 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 NOV 15 PY 2003 VL 188 IS 10 BP 1492 EP 1497 DI 10.1086/379333 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 745GW UT WOS:000186681800011 PM 14624374 ER PT J AU Umemura, T Tanaka, E Ostapowicz, G Brown, KE Heringlake, S Tassopoulos, NC Wang, RYH Yeo, AET Shih, JWK Orii, K Young, NS Hatzakis, A Manns, MP Lee, WM Kiyosawa, K Alter, HJ AF Umemura, T Tanaka, E Ostapowicz, G Brown, KE Heringlake, S Tassopoulos, NC Wang, RYH Yeo, AET Shih, JWK Orii, K Young, NS Hatzakis, A Manns, MP Lee, WM Kiyosawa, K Alter, HJ TI Investigation of SEN virus infection in patients with cryptogenic acute liver failure, hepatitis-associated aplastic anemia, or acute and chronic non-A-E hepatitis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-NOV 01, 2000 CL DALLAS, TEXAS SP Amer Assoc Study Liver Dis ID NON-B-HEPATITIS; TRANSFUSION-ASSOCIATED HEPATITIS; UNITED-STATES; C VIRUS; UNKNOWN ETIOLOGY; DISEASE; TTV; GREECE AB SEN virus ( SENV) has been tentatively linked to transfusion- associated non - A - E hepatitis. We investigated SENV's role in unexplained hepatitis in other settings. Polymerase chain reaction amplification was used to detect 2 SENV variants ( SENV- D and SENV- H) in 1706 patients and control subjects. SENV was detected in 54 ( 22%) of 248 patients with acute or chronic non - A - E hepatitis, 9 ( 35%) of 26 patients with hepatitis-associated aplastic anemia, and 0 of 17 patients with cryptogenic acute liver failure, compared with 150 ( 24%) of 621 control subjects with liver disease and 76 ( 10%) of 794 healthy control subjects. When controlling for geographic region, the prevalence of SENV among case and control subjects was not significantly different. The severity of acute or chronic hepatitis A, B, or C was not influenced by coexisting SENV infection. No etiological role for SENV in the cause of cryptogenic hepatitis could be demonstrated. C1 NHLBI, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX USA. Shinshu Univ, Sch Med, Dept Med, Matsumoto, Nagano 390, Japan. Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany. Western Attica Gen Hosp, Dept Med 1, Athens, Greece. Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens, Greece. RP Alter, HJ (reprint author), NHLBI, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, NIH, Bldg 10,Rm 1C711, Bethesda, MD 20892 USA. NR 32 TC 46 Z9 51 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 NOV 15 PY 2003 VL 188 IS 10 BP 1545 EP 1552 DI 10.1086/379216 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 745GW UT WOS:000186681800018 PM 14624381 ER PT J AU Dunn, DT Gibb, DM Duong, T Babiker, AG Bulterys, M Gabiano, C Galli, L Giaquinto, C Gray, L Harris, DR Hughes, M McKinney, R Mofenson, L Moye, J Newell, ML Pahwa, S Palumbo, P Rudin, C Schluchter, M Sharland, M Shearer, W Thompson, B Tookey, P AF Dunn, DT Gibb, DM Duong, T Babiker, AG Bulterys, M Gabiano, C Galli, L Giaquinto, C Gray, L Harris, DR Hughes, M McKinney, R Mofenson, L Moye, J Newell, ML Pahwa, S Palumbo, P Rudin, C Schluchter, M Sharland, M Shearer, W Thompson, B Tookey, P CA HIV Paediat Prognostic Markers Col TI Short-term risk of disease progression in HIV-1-infected children receiving no antiretroviral therapy or zidovudine monotherapy: a meta-analysis SO LANCET LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; INTRAVENOUS IMMUNE GLOBULIN; BACTERIAL-INFECTIONS; CONTROLLED TRIAL; VIRAL LOAD; HIV; TYPE-1; TRANSMISSION; PREVENTION; MORTALITY AB Background Data on the short-term risk of disease progression in HIV-1-infected children are needed to address the question of when to begin combination antiretroviral therapy. We estimated 12-month risks of progression to AIDS and death, by age and most recent measurement of CD4 T-cell percentage (CD4%) or viral load, in children receiving no antiretroviral therapy or zidovudine monotherapy only. Methods We undertook a meta-analysis of individual longitudinal data for 3941 children from eight cohort studies and nine randomised trials in Europe and the USA. Estimates of risk were derived from parametric survival models. Findings 997 AIDS-defining events were recorded over 7297 person-years of follow-up in the analysis of CD4%, and 284 events over 2282 person-years in the viral load analysis, corresponding to 568 deaths (9087 person-years) and 129 deaths (2816 person-years), respectively. In children older than 2 years, risk of death increased sharply when CD4% was less than about 10%, or 15% for risk of AIDS, with a low and fairly stable risk at greater CD4%. Children younger than 2 years had worse outlook than older children with the same CD4%. Risk of progression increased when viral load exceeded about 10(5) copies per mL, although this association was more gradual compared with CD4%. Both markers had independent predictive value for disease progression; CD4% was the stronger predictor. Interpretation This information is important for paediatricians making decisions, and for researchers designing trials, about when to initiate or restart antiretroviral therapy. C1 MRC, Clin Trials Unit, London NW1 2DA, England. Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. Univ Turin, Dept Pediat, I-10124 Turin, Italy. Univ Florence, Dept Pediat, Florence, Italy. Univ Padua, Dept Pediat, Padua, Italy. UCL, Inst Child Hlth, London WC1E 6BT, England. WESTAT Corp, Rockville, MD 20850 USA. NICHD, Intravenous Immunoglobulin Study Gr, Bethesda, MD USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. NICHHD, NIH, Rockville, MD USA. N Shore LIJ Res Inst, Manhasset, NY USA. UMDNJ, Sch Med, Newark, NJ USA. Univ Childrens Hosp, Basel, Switzerland. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Baylor Coll Med, Houston, TX 77030 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. RP Dunn, DT (reprint author), MRC, Clin Trials Unit, 222 Euston Rd, London NW1 2DA, England. EM d.dunn@ctu.mrc.ac.uk RI Gray, Linsay/A-6741-2010; Tookey, Pat /G-2732-2010; SHCS, all/G-4072-2011; SHCS, int. coll. A/G-4083-2011; OI Tookey, Pat /0000-0001-6258-0387; Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586; Newell, Marie-Louise/0000-0002-1074-7699 NR 30 TC 139 Z9 143 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD NOV 15 PY 2003 VL 362 IS 9396 BP 1605 EP 1611 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 744MZ UT WOS:000186637400008 PM 14630440 ER PT J AU Mofenson, LM Harris, DR Moye, J Bethel, J Korelitz, J Read, JS Nugent, R Meyer, W AF Mofenson, LM Harris, DR Moye, J Bethel, J Korelitz, J Read, JS Nugent, R Meyer, W CA NICHD IVIG Clinical Trial Study Gr TI Alternatives to HIV-1 RNA concentration and CD4 count to predict mortality in HIV-1-infected children in resource-poor settings SO LANCET LA English DT Article AB Cheaper, simpler alternatives to CD4 lymphocyte count and HIV-1 RNA detection for assessing the prognosis of HIV-1 infection are needed for resource-poor settings. However, little is known about the predictive value of alternative assays, in particular in children. We assessed the prognostic value of total lymphocyte count, immune complex-dissociated p24 antigen, white blood cell count, packed-cell volume (haematocrit), and serum albumin for mortality in 376 HIV-1-infected, mainly African-American or Hispanic children enrolled during March, 1988 to January, 1991. In a Cox proportional hazards model, including all assay-alternatives to CD4 and RNA, total lymphocyte count (p<0.0001) and serum albumin (p=0.0107) independently predicted mortality. Further assessment of these markers is warranted in resource-poor settings. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD 20852 USA. WESTAT Corp, Rockville, MD 20850 USA. Quest Diagnost, Baltimore, MD USA. RP Mofenson, LM (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA. OI Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586 FU NICHD NIH HHS [HD-3-3162] NR 5 TC 30 Z9 31 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 15 PY 2003 VL 362 IS 9396 BP 1625 EP 1627 DI 10.1016/S0140-6736(03)14825-8 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 744MZ UT WOS:000186637400012 PM 14630444 ER PT J AU Fogarty, PF Yamaguchi, H Wiestner, A Baerlocher, GM Sloand, E Zeng, WHS Read, EJ Lansdorp, PM Young, NS AF Fogarty, PF Yamaguchi, H Wiestner, A Baerlocher, GM Sloand, E Zeng, WHS Read, EJ Lansdorp, PM Young, NS TI Late presentation of dyskeratosis congenita as apparently acquired aplastic anaemia due to mutations in telomerase RNA SO LANCET LA English DT Article ID GENE AB Aplastic anaemia In adults is usually acquired, but rarely constitutional types of bone marrow failure can occur late In life. We assessed two families with onset of pancytopenia in adults and detected two novel point mutations in the telomerase RNA gene (TERC) in each family. This gene Is abnormal in some kindreds with dyskeratosis congenita. Individuals in our families with mutated TERC did not have physical signs of dyskeratosis congenita, and their blood counts were nearly normal, but all had severely shortened telomeres, reduced haemopoietic function, and raised serum erythropoietin and thrombopoietin. Bone marrow failure of variable severity due to dyskeratosis congenita, historically characterised by associated physical anomalies and early pancytopenia, may be present in otherwise phenotypically normal adults, and can masquerade as acquired aplastic anaemia. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Univ British Columbia, Dept Med, Vancouver, BC, Canada. RP Young, NS (reprint author), NHLBI, Hematol Branch, 10 Ctr Dr,MSC 1652, Bethesda, MD 20892 USA. FU PHS HHS [R01A129524] NR 5 TC 141 Z9 147 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 15 PY 2003 VL 362 IS 9396 BP 1628 EP 1630 DI 10.1016/S0140-6736(03)14797-6 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 744MZ UT WOS:000186637400013 PM 14630445 ER PT J AU Hengen, PN Lyakhov, IG Stewart, LE Schneider, TD AF Hengen, PN Lyakhov, IG Stewart, LE Schneider, TD TI Molecular flip-flops formed by overlapping Fis sites SO NUCLEIC ACIDS RESEARCH LA English DT Review ID COLI CHROMOSOMAL ORIGIN; INVERSION STIMULATION FIS; HISTONE-LIKE PROTEINS; ESCHERICHIA-COLI; REPLICATION ORIGIN; DNA-REPLICATION; BINDING-SITES; SEQUENCE LOGOS; CRYSTAL-STRUCTURE; RNA-POLYMERASE AB The DNA-binding protein Fis frequently uses pairs of sites 7 or 11 base pairs (bp) apart. Two overlapping Fis sites separated by 11 bp are found in the Escherichia coli origin of chromosomal replication. Only one of these sites is bound by Fis at a time, so the structure is a molecular flip-flop that could direct alternative firing of replication complexes in opposite directions. Alternatively, the flip-flop could represent part of an on-off switch for replication. Because they can be used to create precise switched states, molecular flip-flops could be used as the basis of a novel molecular computer. C1 NCI, Intramural Res Support Program, SAIC, Frederick, MD 21702 USA. NCI, Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Schneider, TD (reprint author), NCI, Intramural Res Support Program, SAIC, POB B,Bldg 469,Room 144, Frederick, MD 21702 USA. OI Schneider, Thomas/0000-0002-9841-1531 FU PHS HHS [N01-C0-12400, N01-C0-56000] NR 108 TC 8 Z9 8 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 15 PY 2003 VL 31 IS 22 BP 6663 EP 6673 DI 10.1093/nar/gkg877 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743TX UT WOS:000186590600032 PM 14602927 ER PT J AU Li, XT Costantino, N Lu, LY Liu, DP Watt, RM Cheah, KSE Court, DL Huang, JD AF Li, XT Costantino, N Lu, LY Liu, DP Watt, RM Cheah, KSE Court, DL Huang, JD TI Identification of factors influencing strand bias in oligonucleotide-mediated recombination in Escherichia coli SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CHIMERIC RNA/DNA OLIGONUCLEOTIDES; EMBRYONIC STEM-CELLS; DNA MISMATCH-REPAIR; SYNTHETIC OLIGONUCLEOTIDES; GENE REPAIR; TRANSFORMATION; SYSTEM; YEAST; MUTS; REPLACEMENT AB Recombinogenic engineering methodology, also known as recombineering, utilizes homologous recombination to create targeted changes in cellular DNA with great specificity and flexibility. In Escherichia coli, the Red recombination system from bacteriophage lambda has been used successfully to modify both plasmid and chromosomal DNA in a highly efficient manner, using either a linear double-stranded DNA fragment or a synthetic single-stranded oligonucleotide (SSO). The current model for Red/SSO-mediated recombination involves the SSO first annealing to a transient, single-stranded region of DNA before being incorporated into the chromosome or plasmid target. It has been observed previously, in both eukaryotes and prokaryotes, that mutations in the two strands of the DNA double helix are 'corrected' by complementary SSOs with differing efficiencies. Here we investigate further the factors that influence the strand bias as well as the overall efficiency of Red/SSO-mediated recombination in E.coli. We show that the direction of DNA replication and the nature of the SSO-encoded mismatch are the main factors dictating the recombinational strand bias. However, the influence that the SSO-encoded mismatch exerts upon the recombinational strand bias is abolished in E.coli strains that are defective in mismatch repair (MMR). This reflects the fact that different base-base mispairs are corrected by the mutS/H/L-dependent MMR pathway with differing efficiencies. Furthermore, our data indicate that transcription has negligible influence on the strand bias. These results demonstrate for the first time that the interplay between DNA replication and MMR has a major effect on the efficiency and strand bias of Red/SSO-mediated recombination in E.coli. C1 Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100005, Peoples R China. Peking Union Med Coll, Beijing 100005, Peoples R China. NCI, Gene Regulat & Chromosome Biol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Huang, JD (reprint author), Univ Hong Kong, Dept Biochem, 3-F Lab Bloc,Fac Med Bldg,21 Sassoon Rd, Hong Kong, Hong Kong, Peoples R China. RI Watt, Rory/B-2177-2009 OI Watt, Rory/0000-0002-8718-1988 NR 37 TC 67 Z9 69 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 15 PY 2003 VL 31 IS 22 BP 6674 EP 6687 DI 10.1093/nar/gkg844 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743TX UT WOS:000186590600033 PM 14602928 ER PT J AU Butler, RN AF Butler, RN TI Sam Greenhouse's scholarly contributions to human aging studies SO STATISTICS IN MEDICINE LA English DT Article C1 Int Longevity Ctr USA, New York, NY 10028 USA. NIH, Lister Hill Auditorium, Bethesda, MD 20892 USA. RP Butler, RN (reprint author), Int Longevity Ctr USA, 60 E 86 St, New York, NY 10028 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 2003 VL 22 IS 21 BP 3281 EP 3284 DI 10.1002/sim.1628 PG 4 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 737RK UT WOS:000186245400004 PM 14566911 ER PT J AU Gail, MH AF Gail, MH TI Some of Sam Greenhouse's contributions to statistical methods SO STATISTICS IN MEDICINE LA English DT Article ID RELATIVE RISK; DISCRIMINANT; MODELS; DISEASE AB I briefly survey some areas of Sam Greenhouse's contributions to statistical methods before focusing on three examples. These examples illustrate Sam's ability to identify problems of practical importance and to make valuable contributions to their solutions. Many of his papers continue to provide important guidance and insight because he dealt with issues of enduring practical importance. Published in 2003 by John Wiley Sons, Ltd. C1 NCI, Biostat Branch, Div Canc Epidmeiol & Genet, Bethesda, MD 20892 USA. RP Gail, MH (reprint author), NCI, Biostat Branch, Div Canc Epidmeiol & Genet, 6120 Execut Blvd,Room EPS 8032, Bethesda, MD 20892 USA. NR 32 TC 0 Z9 0 U1 2 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 2003 VL 22 IS 21 BP 3301 EP 3308 DI 10.1002/sim.1631 PG 8 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 737RK UT WOS:000186245400007 PM 14566914 ER PT J AU Rosenberg, PS Katki, H Swanson, CA Brown, LM Wacholder, S Hoover, RN AF Rosenberg, PS Katki, H Swanson, CA Brown, LM Wacholder, S Hoover, RN TI Quantifying epidemologic risk factors using non-parametric regression: model selection remains the greatest challenge SO STATISTICS IN MEDICINE LA English DT Article DE epidemiologic methods; logistic models; oral cancer; alcohol drinking ID CROSS-VALIDATION; SPLINE FUNCTIONS; DOSE-RESPONSE; CHOICE AB Logistic regression is widely used to estimate relative risks (odds ratios) from case-control studies, but when the study exposure is continuous, standard parametric models may not accurately characterize the exposure-response curve. Semi-parametric generalized linear models provide a useful extension. In these models. the exposure of interest is modelled flexibly using a regression spline or a smoothing spline, while other variables are modelled using conventional methods. When coupled with a model-selection procedure based on minimizing a cross-validation score, this approach provides a non-parametric, objective, and reproducible method to characterize the exposure-response curve by one or several models with a favourable bias-variance trade-off. We applied this approach to case-control data to estimate the dose-response relationship between alcohol consumption and risk of oral cancer among African Americans. We did not find a uniquely 'best' model, but results using linear, cubic, and smoothing splines were consistent: there does not appear to be a risk-free threshold for alcohol consumption vis-a-vis the development of oral cancer. This finding was not apparent using a standard step-function model. In our analysis, the cross-validation curve had a global minimum and also a local minimum. In general, the phenomenon of multiple local minima makes it more difficult to interpret the results, and may present a computational roadblock to non-parametric generalized additive models of multiple continuous exposures. Nonetheless, the semi-parametric approach appears to be a practical advance. Published in 2003 by John Wiley Sons, Ltd. C1 NCI, Div Canc Epidmeiol & Genet, Biostat Branch, Rockville, MD 20852 USA. NCI, Epidemiol & Biostat Program, Rockville, MD 20852 USA. RP Rosenberg, PS (reprint author), NCI, Div Canc Epidmeiol & Genet, Biostat Branch, 6120 Execut Blvd,EPS 7006, Rockville, MD 20852 USA. RI Katki, Hormuzd/B-4003-2015 NR 20 TC 35 Z9 35 U1 1 U2 9 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 2003 VL 22 IS 21 BP 3369 EP 3381 DI 10.1002/sim.1638 PG 13 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 737RK UT WOS:000186245400014 PM 14566921 ER PT J AU Yu, BB Gastwirth, JL AF Yu, BB Gastwirth, JL TI The use of the 'reverse Cornfield inequality' to assess the sensitivity of a non-significant association to an omitted variable SO STATISTICS IN MEDICINE LA English DT Article ID SPERMICIDES; DEFECTS AB Unlike randomized experimental studies, investigators do not have control over the treatment assignment in observational studies. Hence, the treated and control (non-treated) groups may have widely different distributions of unobserved covariates. Thus, if observational data are analysed as if they had arisen from a controlled study, the analyses are subject to potential bias. Sensitivity analysis is a technique for assessing whether the inference drawn from a study could be altered by a moderate 'imbalance', between the distribution of the covariates in different groups. In this paper, we examine the sensitivity analysis of the test of proportions in 2 x 2 tables from a new perspective: 'could a non-significant result have occurred because the treated group has a higher prevalence of an unobserved risk factor?'. The study was motivated by an analysis of the studies concerning with the possible effect of spermicide use on birth defects that were cited in a legal decision. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Informat Management Serv Inc, Silver Spring, MD 20904 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. George Washington Univ, Dept Stat, Washington, DC 20052 USA. RP Yu, BB (reprint author), Informat Management Serv Inc, 12501 Prosper Dr,Suite 200, Silver Spring, MD 20904 USA. NR 19 TC 4 Z9 4 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 2003 VL 22 IS 21 BP 3383 EP 3401 DI 10.1002/sim.1639 PG 19 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 737RK UT WOS:000186245400015 PM 14566922 ER PT J AU Saksena, R Ma, XQ Kovac, P AF Saksena, R Ma, XQ Kovac, P TI One-pot preparation of a series of glycoconjugates with predetermined antigen-carrier ratio from oligosaccharides that mimic the O-PS of Vibrio cholerae O : 1, serotype Ogawa SO CARBOHYDRATE RESEARCH LA English DT Article DE vibrio cholerae O : 1; synthetic oligosaccharides; vaccine; neoglycoconjugate immunogens; SELDI-TOF ID VIBRIO-CHOLERAE O-1; STREPTOCOCCUS-PNEUMONIAE TYPE-3; METHYL ALPHA-GLYCOSIDES; SQUARIC ACID DIESTER; VACCINE DEVELOPMENT; DIETHYL SQUARATE; C-13-NMR SPECTRA; INABA; POLYSACCHARIDE; PROTEINS AB Di-through the pentasaccharide that mimic the upstream terminus of the O-specific polysaccharide of Vibrio cholerae 0:1, serotype Ogawa were synthesized in the form of 5-methoxycarbonylpentyl glycosides and linked to BSA using squaric acid diester chemistry. The conjugation reactions were monitored by surface-enhanced laser-desorption/ionization-time-of-flight mass spectrometry (SELDI-TOF MS), which allowed conducting the conjugation of the synthetic oligosaccharides in a controlled way and termination of the reaction when the desired molar hapten-BSA ratio had been reached. This made it possible to prepare, from one hapten in a one-pot reaction, a series of neoglycoconjugates having different, predetermined carbohydrate-carrier ratios. The accuracy of molecular mass determination in SELDI-TOF MS analysis could be increased by using the carrier protein as the internal standard. (C) 2003 Elsevier Ltd. All rights reserved. C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, Med Chem Lab, NIH, Bldg 8,Rm B1 A24, Bethesda, MD 20892 USA. EM kpn@helix.nih.gov NR 36 TC 16 Z9 16 U1 1 U2 3 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 14 PY 2003 VL 338 IS 23 BP 2591 EP 2603 DI 10.1016/S0008-6215(03)00273-8 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 748EE UT WOS:000186848900014 PM 14670719 ER PT J AU Wu, XW Brooks, BR AF Wu, XW Brooks, BR TI Self-guided Langevin dynamics simulation method SO CHEMICAL PHYSICS LETTERS LA English DT Article ID MOLECULAR-DYNAMICS; BROWNIAN DYNAMICS; AQUEOUS-SOLUTION; EXPLICIT WATER; PEPTIDE; ALGORITHMS; SYSTEM; MOTION AB This work presents a self-guided Langevin dynamics simulation method. The guiding force is calculated as a local average of the friction forces during a self-guided Langevin dynamics simulation. Three parameters, the local average time, t(L), the guiding factor, lambda, and the collision frequency, gamma, control a self-guided Langevin dynamics simulation. It is demonstrated through three model systems that this simulation method has an enhanced conformational search ability while has little alteration in conformational distribution when the guiding factor is chosen within the limit of lambdagamma < 1 ps(-1). This method is well suited for simulation studies where extensive conformational searching is required. Published by Elsevier B.V. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wu, XW (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Room 3308,50 South Dr, Bethesda, MD 20892 USA. NR 20 TC 196 Z9 198 U1 1 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD NOV 14 PY 2003 VL 381 IS 3-4 BP 512 EP 518 DI 10.1016/j.cplett.2003.10.013 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 743XE UT WOS:000186598200038 ER PT J AU Guo, GL Lambert, G Negishi, M Ward, JM Brewer, HB Kliewer, SA Gonzalez, FJ Sinal, CJ AF Guo, GL Lambert, G Negishi, M Ward, JM Brewer, HB Kliewer, SA Gonzalez, FJ Sinal, CJ TI Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FAMILIAL INTRAHEPATIC CHOLESTASIS; NUCLEAR RECEPTOR; GENE-EXPRESSION; PROTEIN GENE; IDENTIFICATION; HOMEOSTASIS; CAR; DETOXIFICATION; TRANSCRIPTION; ACTIVATION AB The nuclear receptors, farnesoid X receptor (FXR) and pregnane X receptor (PXR), are important in maintaining bile acid homeostasis. Deletion of both FXR and PXR in vivo by cross-breeding B6;129-Fxr(tm1Gonz) (FXR-null) and B6;129-Pxr(tm1Glaxo-Wellcome) (PXR-null) mice revealed a more severe disruption of bile acid, cholesterol, and lipid homeostasis in B6;129-Fxr(tm1Gonz) Pxr(tm1Glaxo-Wellcome) (FXR-PXR double null or FPXR-null) mice fed a 1% cholic acid (CA) diet. Hepatic expression of the constitutive androstane receptor (CAR) and its target genes was induced in FXR- and FPXR-null mice fed the CA diet. To test whether up-regulation of CAR represents a means of protection against bile acid toxicity to compensate for the loss of FXR and PXR, animals were pretreated with CAR activators, phenobarbital or 1,4- bis[2-(3,5-dichlorpyridyloxy)] benzene (TCPOBOP), followed by the CA diet. A role for CAR in protection against bile acid toxicity was confirmed by a marked reduction of serum bile acid and bilirubin concentrations, with an elevation of the expression of the hepatic genes involved in bile acid and/or bilirubin metabolism and excretion (CYP2B, CYP3A, MRP2, MRP3, UGT1A, and glutathione S-transferase alpha), following pretreatment with phenobarbital or TCPOBOP. In summary, the current study demonstrates a critical and combined role of FXR and PXR in maintaining not only bile acid but also cholesterol and lipid homeostasis in vivo. Furthermore, FXR, PXR, and CAR protect against hepatic bile acid toxicity in a complementary manner, suggesting that they serve as redundant but distinct layers of defense to prevent overt hepatic damage by bile acids during cholestasis. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. INSERM, U539, F-44035 Nantes, France. NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NCI, Vet & Tumor Pathol Sect, Ctr Canc Res, Frederick, MD 21702 USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Rm 2A19A,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 37 TC 197 Z9 203 U1 0 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 2003 VL 278 IS 46 BP 45062 EP 45071 DI 10.1074/jbc.M307145200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741HH UT WOS:000186452300005 PM 12923173 ER PT J AU Lee, JH Ghirlando, R Bhaskara, V Hoffmeyer, MR Gu, J Paull, TT AF Lee, JH Ghirlando, R Bhaskara, V Hoffmeyer, MR Gu, J Paull, TT TI Regulation of Mre11/Rad50 by Nbs1 - Effects on nucleotide-dependent DNA binding and association with ataxia-telangiectasia-like disorder mutant complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NIJMEGEN BREAKAGE SYNDROME; DOUBLE-STRAND BREAKS; FORKHEAD-ASSOCIATED DOMAIN; SACCHAROMYCES-CEREVISIAE; MEIOTIC RECOMBINATION; HUMAN RAD50/MRE11; DAMAGE RESPONSE; PROTEIN COMPLEX; FOCUS FORMATION; REPAIR COMPLEX AB The Mre11/Rad50 complex is a critical component of the cellular response to DNA double-strand breaks, in organisms ranging from archaebacteria to humans. In mammalian cells, Mre11/Rad50 (M/R) associates with a third component, Nbs1, that regulates its activities and is targeted by signaling pathways that initiate DNA damage-induced checkpoint responses. Mutations in the genes that encode Nbs1 and Mre11 are responsible for the human radiation sensitivity disorders Nijmegen breakage syndrome (NBS) and ataxia-telangiectasia-like disorder (ATLD), respectively, which are characterized by defective checkpoint responses and high levels of chromosomal abnormalities. Here we demonstrate nucleotide-dependent DNA binding by the human M/R complex that requires the Nbs1 protein and is specific for double-strand DNA duplexes. Efficient DNA binding is only observed with non-hydrolyzable analogs of ATP, suggesting that ATP hydrolysis normally effects DNA release. The alleles of MRE11 associated with ATLD and the C-terminal Nbs1 polypeptide associated with NBS were expressed with the other components and found to form triple complexes except in the case of ATLD 3/4, which exhibits variability in Nbs1 association. The ATLD 1/2, ATLD 3/4, and p70 M/R/N complexes exhibit nucleotide-dependent DNA binding and exonuclease activity equivalent to the wild-type enzyme, although the ATLD complexes both show reduced activity in endonuclease assays. Sedimentation equilibrium analysis of the recombinant human complexes indicates that Mre11 is a stable dimer, Mre11 and Nbs1 form a 1: 1 complex, and both M/R and M/R/N form large multimeric assemblies of similar to1.2 MDa. Models of M/R/N stoichiometry in light of this and previous data are discussed. C1 Univ Texas, Dept Mol Genet & Microbiol, Austin, TX 78712 USA. Univ Texas, Inst Cellular & Mol Biol, Austin, TX 78712 USA. Univ Texas, Dept Chem & Biochem, Austin, TX 78712 USA. NIDDK, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Paull, TT (reprint author), Univ Texas, Dept Mol Genet & Microbiol, 1 Univ Stn,A4800, Austin, TX 78712 USA. RI Ghirlando, Rodolfo/A-8880-2009 FU NCI NIH HHS [CA94000-01] NR 50 TC 71 Z9 72 U1 1 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 14 PY 2003 VL 278 IS 46 BP 45171 EP 45181 DI 10.1074/jbc.M308705200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741HH UT WOS:000186452300017 PM 12966088 ER PT J AU Zhou, M Zhang, YH Ardans, JA Wahl, LM AF Zhou, M Zhang, YH Ardans, JA Wahl, LM TI Interferon-gamma differentially regulates monocyte matrix metalloproteinase-1 and -9 through tumor necrosis factor-alpha and caspase 8 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROSTAGLANDIN-H SYNTHASE-2; IFN-GAMMA; INTERSTITIAL COLLAGENASE; HUMAN MACROPHAGES; INDUCED APOPTOSIS; TIMP-1 PRODUCTION; TNF-ALPHA; IN-VITRO; ACTIVATION; SUPPRESSION AB Tumor necrosis factor-alpha (TNFalpha) and granulocyte macrophage colony-stimulating factor (GM-CSF) individually enhance monocyte matrix metalloproteinase-9 (MMP-9) but induce MMP-1 only when added in combination. Because interferon-gamma (IFNgamma) is also found at inflammatory sites, we determined its effect on monocyte MMPs in the presence or absence of TNFalpha and GM-CSF. IFNgamma alone did not stimulate monocyte MMP-9 or MMP-1; however, in the presence of GM-CSF it induced MMP-1 and enhanced MMP-1 stimulated by GM-CSF and TNFalpha. IFNgamma induced MMP-1 in the presence of GM-CSF through the stimulation of TNFalpha production through a mechanism involving both p38 and ERK1/2 MAPKs, in which GM-CSF stimulated ERK1/2 whereas IFNgamma activated p38. In support of this conclusion TNFalpha neutralizing antibody and antibodies against TNF receptor I and -II blocked the induction of MMP-1 by GM-CSF and IFNgamma. In contrast to its effects on MMP-1, IFNgamma inhibited TNFalpha-induced MMP-9 through a caspase 8-dependent pathway as demonstrated by the restoration of MMP-9 with caspase 8 inhibitors. Moreover, the phosphorylation of STAT1 by IFNgamma was blocked by an inhibitor of caspase 8, indicating that STAT1 had a suppressive effect on MMP-9. Caspase 8-mediated phosphorylation of STAT1 through p38 MAPK as shown by the inhibition of IFNgamma-induced phosphorylation of p38 by caspase 8 inhibitors. Activation of caspase 8 by IFNgamma did not result in increased apoptosis. Thus IFNgamma in the presence of GM-CSF and/or TNFalpha differentially regulates monocyte MMPs through induction of TNFalpha and a novel mechanism involving caspase 8 that is independent of apoptosis. C1 NIDCR, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. RP Wahl, LM (reprint author), NIDCR, Immunopathol Sect, NIH, 30 Convent Dr,Bldg 30,Rm 325, Bethesda, MD 20892 USA. NR 29 TC 41 Z9 44 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 14 PY 2003 VL 278 IS 46 BP 45406 EP 45413 DI 10.1074/jbc.M309075200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741HH UT WOS:000186452300045 PM 12960156 ER PT J AU Ghirlando, R Trainor, CD AF Ghirlando, R Trainor, CD TI Determinants of GATA-1 binding to DNA - The role of non-finger residues SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; PROTEIN-PROTEIN INTERACTION; IN-VIVO; ZINC-FINGER; MEGAKARYOCYTIC CELLS; REGULATORY ELEMENT; SELF-ASSOCIATION; CUTTING EDGE; N-FINGER; COMPLEX AB Mammalian GATA transcription factors are expressed in various tissues in a temporally regulated manner. The prototypic member, GATA-1, is required for normal erythroid, megakaryocytic, and mast cell development. This family of DNA-binding proteins recognizes a consensus (A/T) GATA(A/G) motif and possesses homologous DNA binding domains consisting of two zinc fingers. The C-terminal finger of GATA-1 recognizes the consensus motif with nanomolar affinities, whereas the N-terminal finger shows a binding preference for a GATC motif, albeit with much reduced affinity (K(d)approximate tomuM). The N-terminal finger of GATA-2 also shows a preference for an AGATCT binding site, with an increased affinity attributed to N- and C-terminal flanking basic residues (K(d)approximate tonM). To understand the differences in the binding specificities of the N- and C-terminal zinc fingers of GATA-1, we have constructed a series of swapped domain peptides. We show that the specificity for AGATAA over AGATCT arises from the C-terminal non-finger basic domain. Thus, the N- terminal finger binds preferentially to AGATAA once appended to the C-terminal arm of the C-terminal finger. We further show that this specificity arises from the highly conserved QTRNRK residues. The converse is, however, untrue in the case of the C-terminal finger; swapping of QTRNRK with the corresponding LVSKRA does not switch the DNA binding specificity from AGATAA to AGATCT. These results highlight the important role of residues adjacent to the CXXCX(17)CNAC zinc finger motif (i.e. non-finger residues) in the specific recognition of DNA residues. C1 NIDDK, Mol Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ghirlando, R (reprint author), NIDDK, Mol Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RI Ghirlando, Rodolfo/A-8880-2009 NR 46 TC 20 Z9 20 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 14 PY 2003 VL 278 IS 46 BP 45620 EP 45628 DI 10.1074/jbc.M306410200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741HH UT WOS:000186452300071 PM 12941967 ER PT J AU Suzuki, N Nakatsuka, H Mochizuki, M Nishi, N Kadoya, Y Utani, A Oishi, S Fujii, N Kleinman, HK Nomizu, M AF Suzuki, N Nakatsuka, H Mochizuki, M Nishi, N Kadoya, Y Utani, A Oishi, S Fujii, N Kleinman, HK Nomizu, M TI Biological activities of homologous loop regions in the laminin alpha chain G domains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TERMINAL GLOBULAR DOMAIN; CELL-BINDING SEQUENCES; HEPARIN-BINDING; SYNTHETIC PEPTIDES; NEURITE OUTGROWTH; DEVELOPMENTAL EXPRESSION; BRANCHING MORPHOGENESIS; INTEGRIN-RECOGNITION; SUBMANDIBULAR-GLAND; MOLECULAR-CLONING AB Laminin alpha chains (alpha(1)-alpha(5) chains) have diverse chain-specific biological functions. The LG4 modules of laminin alpha chains consist of a 14-stranded beta-sheet (A-N) sandwich structure. Several biologically active sequences have been identified in the connecting loop regions. Here, we evaluated the biological activities of the loop regions of the E and F strands in the LG4 modules using five homologous peptides from each of the mouse alpha chains (EF-1: DYATLQLQEGRLHFMFDLG, alpha(1) chain 2747-2765; EF-2: DFGTVQLRNGFPFFSYDLG, alpha(2) chain 2808-2826; EF-3: RDSFVALYLSEGHVIFALG, alpha(3) chain 2266-2284; EF-4: DFMTLFLAHGRLVFMFNVG, alpha(4) chain 1511-1529; EF-5: SPSLVLFLNHGHFVAQTEGP, alpha(5) chain 3304-3323). These homologous peptides showed chain-specific cell attachment and neurite outgrowth activities. Well organized actin stress fibers and focal contacts with vinculin accumulation were observed in fibroblasts attached on EF-1, whereas fibroblasts on EF-2 and EF-4 showed filopodia with ruffling. Fibroblast attachment to EF-2 and EF-4 was mediated by syndecan-2. In contrast, EF-1 promoted alpha(2)beta(1) integrin-mediated fibroblast attachment and inhibited fibroblast attachment to a recombinant laminin alpha(1) chain LG4-5. The receptors for EF-3 and EF-5 are unknown. Further, when the active core sequence of EF-1 was cyclized, utilizing two additional cysteine residues at both the N and C termini through a disulfide bridge, the cyclic peptide significantly enhanced integrin-mediated cell attachment. These results indicate that integrin-mediated cell attachment to the EF-1 sequence is conformation-dependent and that the loop structure is important for the activity. The homologous peptides, which promote either integrin- or syndecan-mediated cell attachment, may be useful for understanding the cell type- and chain-specific biological activities of the laminins. C1 Hokkaido Univ, Grad Sch Environm Earth Sci, Kita Ku, Sapporo, Hokkaido 0600810, Japan. Kitasato Univ, Sch Med, Dept Anat, Sagamihara, Kanagawa 2288555, Japan. Chiba Univ, Sch Med, Dept Dermatol, Chiba 2608670, Japan. Kyoto Univ, Grad Sch Pharmaceut Sci, Kyoto 6068501, Japan. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Nomizu, M (reprint author), Hokkaido Univ, Grad Sch Environm Earth Sci, Kita Ku, Kita 10 Nishi 5, Sapporo, Hokkaido 0600810, Japan. RI Oishi, Shinya/C-1350-2011 OI Oishi, Shinya/0000-0002-2833-2539 NR 58 TC 54 Z9 54 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 14 PY 2003 VL 278 IS 46 BP 45697 EP 45705 DI 10.1074/jbc.M304667200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741HH UT WOS:000186452300079 PM 12933811 ER PT J AU Outten, FW Wood, MJ Munoz, FM Storz, G AF Outten, FW Wood, MJ Munoz, FM Storz, G TI The SufE protein and the SufBCD complex enhance SufS cysteine desulfurase activity as part of a sulfur transfer pathway for fe-s cluster assembly in Escherichia coli SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAMMALIAN SELENOCYSTEINE LYASE; NIFS-LIKE PROTEIN; AZOTOBACTER-VINELANDII; ERWINIA-CHRYSANTHEMI; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; GENE CLONING; ISCU; BIOSYNTHESIS; SCAFFOLD AB The sufABCDSE operon of the Gram-negative bacterium Escherichia coli is induced by oxidative stress and iron deprivation. To examine the biochemical roles of the Suf proteins, we purified all of the proteins and assayed their effect on SufS cysteine desulfurase activity. Here we report that the SufE protein can stimulate the cysteine desulfurase activity of the SufS enzyme up to 8-fold and accepts sulfane sulfur from SufS. This sulfur transfer process from SufS to SufE is sheltered from the environment based on its resistance to added reductants and on the analysis of available crystal structures of the proteins. We also found that the SufB, SufC, and SufD proteins associate in a stable complex and that, in the presence of SufE, the SufBCD complex further stimulates SufS activity up to 32-fold. Thus, the SufE protein and the SufBCD complex act synergistically to modulate the cysteine desulfurase activity of SufS. We propose that this sulfur transfer mechanism may be important for limiting sulfide release during oxidative stress conditions in vivo. C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Storz, G (reprint author), NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. OI Outten, Franklin/0000-0002-9095-0194; Storz, Gisela/0000-0001-6698-1241 NR 39 TC 155 Z9 168 U1 1 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 2003 VL 278 IS 46 BP 45713 EP 45719 DI 10.1074/jbc.M308004200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741HH UT WOS:000186452300081 PM 12941942 ER PT J AU Foster, CE Colonna, M Sun, PD AF Foster, CE Colonna, M Sun, PD TI Crystal structure of the human natural killer (NK) cell activating receptor NKp46 reveals structural relationship to other leukocyte receptor complex immunoreceptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FC-ALPHA-RI; MHC CLASS-I; H-2-DEFICIENT LYMPHOMA VARIANTS; IMMUNOGLOBULIN-LIKE RECEPTOR; HEAVY-ATOM DERIVATIVES; QUICK-SOAK METHOD; TRIGGERING RECEPTOR; INHIBITORY RECEPTOR; CYTOTOXICITY RECEPTORS; MEDIATED CYTOLYSIS AB Natural cytotoxicity receptors (NCR) mediate lysis of a variety of tumor and virus-infected cells by natural killer (NK) cells. Upon engagement, NCR trigger the cytolytic activity and cytokine release of NK cells through association with ITAM-containing signaling molecules. To further understand the function of these receptors in activation of natural cytotoxicity, we determined the crystal structure of the extracellular ligand binding domain of human NKp46, one of three known NCR, at 2.2-Angstrom resolution. The overall fold and disposition of the two C2-set immunoglobulin domains are similar to the D1D2 domains of inhibitory killer cell Ig-like receptor (KIR) and Ig-like transcript (ILT) receptors. As the cellular ligands of NKp46 have not yet been defined, the known ligand binding sites of KIR and ILT were compared with the corresponding structural regions of NKp46 in an effort to identify potential areas suitable for molecular recognition. A potential binding site for influenza hemagglutinin is located near the interdomain hinge, a region that mediates ligand binding in KIR. The structural similarity of NKp46 to inhibitory KIR receptors may have implications for how NK cells balance activating and inhibitory signals. 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 57 TC 38 Z9 39 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 14 PY 2003 VL 278 IS 46 BP 46081 EP 46086 DI 10.1074/jbc.M308491200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741HH UT WOS:000186452300125 PM 12960161 ER PT J AU Peterson, JH Woolhead, CA Bernstein, HD AF Peterson, JH Woolhead, CA Bernstein, HD TI Basic amino acids in a distinct subset of signal peptides promote interaction with the signal recognition particle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOPLASMIC-RETICULUM MEMBRANE; MALTOSE-BINDING PROTEIN; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; NASCENT PREPROLACTIN; TARGETING PATHWAYS; SECRETORY PROTEIN; ANCHOR SEQUENCES; TRIGGER FACTOR; IN-VITRO AB Previous studies have demonstrated that signal peptides bind to the signal recognition particle (SRP) primarily via hydrophobic interactions with the 54-kDa protein subunit. The crystal structure of the conserved SRP ribonucleoprotein core, however, raised the surprising possibility that electrostatic interactions between basic amino acids in signal peptides and the phosphate backbone of SRP RNA may also play a role in signal sequence recognition. To test this possibility we examined the degree to which basic amino acids in a signal peptide influence the targeting of two Escherichia coli proteins, maltose binding protein and OmpA. Whereas both proteins are normally targeted to the inner membrane by SecB, we found that replacement of their native signal peptides with another moderately hydrophobic but unusually basic signal peptide (DeltaEspP) rerouted them into the SRP pathway. Reduction in either the net positive charge or the hydrophobicity of the DeltaEspP signal peptide decreased the effectiveness of SRP recognition. A high degree of hydrophobicity, however, compensated for the loss of basic residues and restored SRP binding. Taken together, the data suggest that the formation of salt bridges between SRP RNA and basic amino acids facilitates the binding of a distinct subset of signal peptides whose hydrophobicity falls slightly below a threshold level. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 5,Rm 201, Bethesda, MD 20892 USA. NR 39 TC 52 Z9 53 U1 1 U2 11 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 14 PY 2003 VL 278 IS 46 BP 46155 EP 46162 DI 10.1074/jbc.M309082200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741HH UT WOS:000186452300133 PM 12949068 ER PT J AU Begg, M Mo, FM Offertaler, L Batkai, S Pacher, P Razdan, RK Lovinger, DM Kunos, G AF Begg, M Mo, FM Offertaler, L Batkai, S Pacher, P Razdan, RK Lovinger, DM Kunos, G TI G protein-coupled endothelial receptor for atypical cannabinoid ligands modulates a Ca2+-dependent K+ current SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POTASSIUM CHANNELS; EPOXYEICOSATRIENOIC ACIDS; CA2+-INDUCED RELAXATION; MESENTERIC-ARTERY; GUANYLYL CYCLASE; HIGH-CONDUCTANCE; CELLS; ANANDAMIDE; CALCIUM; INHIBITION AB The cannabinoid analog "abnormal cannabidiol" (abn-cbd) causes endothelium-dependent vasodilation in rat isolated mesenteric arteries through a G protein-coupled receptor distinct from CB1 or CB2. We examined the actions of abn-cbd on the electrophysiology of human umbilical vein endothelial cells (HUVEC), using the whole cell version of the patch clamp technique. Voltage steps produced noninactivating outward currents, which were abolished by iberiotoxin or by chelation of intracellular calcium. The presence of a BKCa channel in HUVEC was documented by reverse transcriptase-PCR. Abn-cbd concentration dependently potentiated the outward current produced by a single voltage step. This potentiation was abolished by the cannabidiol analog O-1918 or by pertussis toxin but was unaffected by CB1 or CB2 antagonists. HU-210, a CB1/CB2 receptor agonist, had no effect on the outward current. Clamping [Ca2+](i) did not prevent abn-cbd-induced increases in outward current. cGMP potentiated the outward current, and abn-cbd increased the cellular levels of cGMP. The increase in outward current produced by abn-cbd was blocked by KT-5823, an inhibitor of protein kinase G, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), an inhibitor of soluble guanylate cyclase. We conclude that a Ca2+-activated K+ current in HUVEC is potentiated by activation of a G(i)/G(o)-coupled receptor distinct from CB1 or CB2, which signals through cGMP and protein kinase G to increase channel availability or the sensitivity of the channel to voltage and/or Ca2+. Because iberiotoxin also inhibited abn-cbd-induced relaxation of intact, but not of endothelium-denuded, rat mesenteric artery segments, modulation of endothelial BKCa channels may underlie the mesenteric vasodilator action of abn-cbd. C1 NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. Organix Inc, Woburn, MA 01801 USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, NIH, 12420 Parklawn Dr,MSC-8115, Bethesda, MD 20892 USA. RI Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI Pacher, Pal/0000-0001-7036-8108; NR 49 TC 64 Z9 66 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 14 PY 2003 VL 278 IS 46 BP 46188 EP 46194 DI 10.1074/jbc.M307258200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741HH UT WOS:000186452300137 PM 12952947 ER PT J AU Virnik, K Lyubchenko, YL Karymov, MA Dahlgren, P Tolstorukov, MY Semsey, S Zhurkin, VB Adhya, S AF Virnik, K Lyubchenko, YL Karymov, MA Dahlgren, P Tolstorukov, MY Semsey, S Zhurkin, VB Adhya, S TI "Antiparallel" DNA loop in gal repressosome visualized by atomic force microscopy SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE transcription; DNA loop; repression; minicircles; AFM ID ESCHERICHIA-COLI; LAC REPRESSOR; CRYSTAL-STRUCTURE; RNA-POLYMERASE; POWERFUL TOOL; PROTEIN; OPERATORS; BINDING; HU; TRANSCRIPTION AB DNA looping is often involved in positive and negative regulation of gene transcription in both prokaryotes and eukaryotes. The transcription of the gal operon of Escherichia coli from two overlapping promoters P1 and P2 is negatively regulated via Gal repressosome assembly. It involves binding of two dimeric Gal repressor proteins (GalR) to two operators, O-E and O-I, flanking the two promoters, and formation of 113 bp DNA loop due to tetramerization of the two bound GalR dimers. The process requires negatively supercoiled DNA and the presence of the histone-like protein HU. Previous modeling of the repressosome based on evaluation of DNA elastic energy suggested a mutual antiparallel, rather than parallel, orientation of the two gal operators in an under-twisted DNA loop. To visualize the Gal loop by atomic force microscopy (AFM), plasmid DNA molecules were constructed with increased distance between the two operators. The AFM results demonstrated the formation of an antiparallel DNA loop in the Gal repressosome consistent with our earlier hypothesis. Importantly, the overall shape of the GalR mediated loop proved to be indistinguishable from that in the chimerical loop of the same size containing two lac operators (instead of two gal operators) and formed by Lacl. In addition, a possibility of the gal operon repression mediated by GalR in the absence of HU was shown in the new DNA constructs. Implications of these findings for the DNA structural organization in bacterial nucleoid are discussed. (C) 2003 Elsevier Ltd. All rights reserved. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Arizona State Univ, Dept Microbiol, Tempe, AZ 85287 USA. NCI, Lab Computat & Expt Biol, NIH, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Semsey, Szabolcs/L-6329-2013; OI Semsey, Szabolcs/0000-0002-4522-5495 NR 44 TC 33 Z9 33 U1 2 U2 3 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 14 PY 2003 VL 334 IS 1 BP 53 EP 63 DI 10.1016/j.jmb.2003.09.030 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741CG UT WOS:000186440700005 PM 14596799 ER PT J AU Markus, J Feikova, S Sramko, M Wolff, L Bies, J AF Markus, J Feikova, S Sramko, M Wolff, L Bies, J TI Proliferation-linked expression of the novel murine gene m4mbt encoding a nuclear zinc finger protein with four mbt domains SO GENE LA English DT Article DE polycomb group; transcription; differentiation; cell cycle; chromatin ID POLYCOMB GROUP PROTEIN; SEX COMB; DROSOPHILA-MELANOGASTER; BMI-1 PROTOONCOGENE; HUMAN HOMOLOG; CELLS; SIMILARITY; REPRESSOR; INTERACTS; COMPLEXES AB Here we describe the cloning and characterization of a novel murine gene named m4mbt that encodes a homolog of the lethal (3) malignant brain tumor (1(3)mbt) and Scm proteins. It is localized on mouse chromosome 15E2 and is organized into 17 exons. As demonstrated by Northern blot analysis, m4mbt mRNA is expressed in virtually all tested tissues and cell lines with the exception of stomach and muscle. The m4mbt transcript was most abundant in the testes. m4mbt expression was shown to initiate early during mouse embryonal development (before day 7) and continue until adulthood. The expression of m4mbt mRNA also appears to correlate with cellular proliferation, since we observed down-regulation of m4mbt expression during terminal monocytic differentiation and in contact-inhibited fibroblasts. Computer analysis of the amino acid (aa) sequence revealed that the M4mbt protein comprises an amino-terminally located atypical C2C2 zinc finger and four centrally located mbt repeats. Mbt repeats are also found in proteins of the Polycomb group (PcG) that associate with heterochromatin and function as long-term repressors of transcription. Using Western blot analysis and confocal fluorescent microscopy, we demonstrated that the M4mbt protein is localized in the nucleus. Since M4mbt has structural domains similar to chromatin-associated proteins, its expression is associated with proliferation, and it has a nuclear localization, it may have a regulatory role related to proliferation and/or differentiation. (C) 2003 Elsevier B.V. All rights reserved. C1 Slovak Acad Sci, Inst Canc Res, Mol Virol Lab, Bratislava 83391, Slovakia. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Bies, J (reprint author), Slovak Acad Sci, Inst Canc Res, Mol Virol Lab, Vlarska 7, Bratislava 83391, Slovakia. NR 27 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 13 PY 2003 VL 319 BP 117 EP 126 DI 10.1016/S0378-1119(03)00801-1 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 746FL UT WOS:000186736300011 PM 14597177 ER PT J AU Luo, Z Je, HS Wang, QA Yang, F Dobbins, GC Yang, ZH Xiong, WC Lu, B Mei, L AF Luo, Z Je, HS Wang, QA Yang, F Dobbins, GC Yang, ZH Xiong, WC Lu, B Mei, L TI Implication of geranylgeranyltransferase I in synapse formation SO NEURON LA English DT Article ID RECEPTOR GENE-EXPRESSION; ACETYLCHOLINE-RECEPTORS; NEUROMUSCULAR-JUNCTION; MUSCLE-CELLS; CARBOXYL METHYLATION; CDNA CLONING; PROTEIN; MUSK; DOMAIN; FARNESYLTRANSFERASE AB Agrin activates the transmembrane tyrosine kinase MuSK to mediate acetylcholine receptor (AChR) clustering at the neuromuscular junction (NMJ). However, the intracellular signaling mechanism downstream of MuSK is poorly characterized. This study provides evidence that geranylgeranyltransferase I (GGT) is an important signaling component in the Agrin/MuSK pathway. Agrin causes a rapid increase in tyrosine phosphorylation of the alpha(G/F) subunit of GGT and in GGT activity. Inhibition of GGT activity or expression prevents muscle cells from forming AChR clusters in response to Agrin and attenuates the formation of neuromuscular synapses in spinal neuron-muscle co-cultures. Importantly, transgenic mice expressing an alpha(G/F) mutant demonstrate NMJ defects with wider end-plate bands and smaller AChR plaques. These results support the notion that prenylation is necessary for AChR clustering and the NMJ formation and/or maintenance, revealing an active role of GGT in Agrin/MuSK signaling. C1 Univ Alabama, Civitan Int Res Ctr, Dept Neurobiol, Birmingham, AL 35294 USA. Univ Alabama, Civitan Int Res Ctr, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Civitan Int Res Ctr, Dept Phys Med, Birmingham, AL 35294 USA. Univ Alabama, Civitan Int Res Ctr, Dept Rehab, Birmingham, AL 35294 USA. NICHHD, Lab Cellular & Synapt Neurophysiol, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP Mei, L (reprint author), Univ Alabama, Civitan Int Res Ctr, Dept Neurobiol, Birmingham, AL 35294 USA. RI Yang, Feng/C-9530-2011; Lu, Bai/A-4018-2012; Mei, Lin/G-8755-2012; OI Je, hyunsoo/0000-0002-2924-5621 FU NINDS NIH HHS [T32NS07441] NR 55 TC 54 Z9 56 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 13 PY 2003 VL 40 IS 4 BP 703 EP 717 DI 10.1016/S0896-6273(03)00695-0 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 744UL UT WOS:000186651200007 PM 14622576 ER PT J AU Bamji, SX Shimazu, K Kimes, N Huelsken, J Birchmeier, W Lu, B Reichardt, LF AF Bamji, SX Shimazu, K Kimes, N Huelsken, J Birchmeier, W Lu, B Reichardt, LF TI Role of beta-catenin in synaptic vesicle localization and presynaptic assembly SO NEURON LA English DT Article ID LONG-TERM POTENTIATION; TYROSINE KINASE SUBSTRATE; CELL-CELL JUNCTIONS; E-CADHERIN; N-CADHERIN; EXCITATORY SYNAPSES; TRANSMITTER RELEASE; ADHESION MOLECULE; ALPHA-CATENIN; PHOSPHATIDYLINOSITOL 3-KINASE AB Cadherins and catenins are thought to promote adhesion between pre and postsynaptic elements in the brain. Here we show a role for beta-catenin in localizing the reserved pool of vesicles at presynaptic sites. Deletion of P-catenin in hippocampal pyramidal neurons in vivo resulted in a reduction in the number of reserved pool vesicles per synapse and an impaired response to prolonged repetitive stimulation. This corresponded to a dispersion of vesicles along the axon in cultured neurons. Interestingly, these effects are not due to beta-catenin's involvement in cadherin-mediated adhesion or wnt signaling. Instead, beta-catenin modulates vesicle localization via its PDZ binding domain to recruit PDZ proteins such as Veli to cadherin at synapses. This study defines a specific role for cadherins and catenins in synapse organization beyond their roles in mediating cell adhesion. C1 Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. NICHHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. Max Delbrueck Ctr Mol Med, D-13092 Berlin, Germany. RP Reichardt, LF (reprint author), Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. RI Lu, Bai/A-4018-2012; Huelsken, Joerg/C-3861-2009 FU NINDS NIH HHS [P01 NS016033, P01 NS016033-21] NR 87 TC 210 Z9 221 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 13 PY 2003 VL 40 IS 4 BP 719 EP 731 DI 10.1016/S0896-6273(03)00718-9 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 744UL UT WOS:000186651200008 PM 14622577 ER PT J AU Inagaki, K Chen, L Ikeno, F Lee, FH Imahashi, K Bouley, DM Rezaee, M Yock, PG Murphy, E Mochly-Rosen, D AF Inagaki, K Chen, L Ikeno, F Lee, FH Imahashi, K Bouley, DM Rezaee, M Yock, PG Murphy, E Mochly-Rosen, D TI Inhibition of delta-protein kinase C protects against reperfusion injury of the ischemic heart in vivo SO CIRCULATION LA English DT Article DE reperfusion; cardioprotection; kinases ID ACUTE MYOCARDIAL-INFARCTION; CARDIAC MYOCYTES; CELL-DEATH; EPSILON; APOPTOSIS; IDENTIFICATION; ACTIVATOR AB Background-Current treatment for acute myocardial infarction (AMI) focuses on reestablishing blood flow (reperfusion). Paradoxically, reperfusion itself may cause additional injury to the heart. We previously found that delta-protein kinase C (deltaPKC) inhibition during simulated ischemia/reperfusion in isolated rat hearts is cardioprotective. We focus here on the role for deltaPKC during reperfusion only, using an in vivo porcine model of AMI. Methods and Results-An intracoronary application of a selective deltaPKC inhibitor to the heart at the time of reperfusion reduced infarct size, improved cardiac function, inhibited troponin T release, and reduced apoptosis. Using P-31 NMR in isolated perfused mouse hearts, we found a faster recovery of ATP levels in hearts treated with the deltaPKC inhibitor during reperfusion only. Conclusions-Reperfusion injury after cardiac ischemia is mediated, at least in part, by deltaPKC activation. This study suggests that including a deltaPKC inhibitor at reperfusion may improve the outcome for patients with AMI. C1 Stanford Univ, Sch Med, Dept Mol Pharmacol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Cardiovasc Med, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Comparat Med, Stanford, CA 94305 USA. NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Mochly-Rosen, D (reprint author), Stanford Univ, Sch Med, Dept Mol Pharmacol, Stanford, CA 94305 USA. EM mochly@stanford.edu FU NHLBI NIH HHS [HL-52141] NR 17 TC 180 Z9 186 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 11 PY 2003 VL 108 IS 19 BP 2304 EP 2307 DI 10.1161/01.CIR.0000101682.24138.36 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 741TG UT WOS:000186475200003 PM 14597593 ER PT J AU Cesari, M Penninx, BWJH Newman, AB Kritchevsky, SB Nicklas, BJ Sutton-Tyrrell, K Rubin, SM Ding, JZ Simonsick, EM Harris, TB Pahor, M AF Cesari, M Penninx, BWJH Newman, AB Kritchevsky, SB Nicklas, BJ Sutton-Tyrrell, K Rubin, SM Ding, JZ Simonsick, EM Harris, TB Pahor, M TI Inflammatory markers and onset of cardiovascular events - Results from the Health ABC study SO CIRCULATION LA English DT Article DE cytokines; cardiovascular disease; inflammation ID C-REACTIVE PROTEIN; FUTURE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; NECROSIS-FACTOR-ALPHA; CAROTID ATHEROSCLEROSIS; RISK-FACTORS; INTERLEUKIN-6; CHOLESTEROL; FAILURE; MEN AB Background-Inflammation plays an important role in cardiovascular disease. The aim of this study is to investigate the predictive value of several inflammatory markers on the incidence of cardiovascular events in well-functioning older persons. Methods and Results-The subjects were 2225 participants 70 to 79 years old, without baseline cardiovascular disease, who were enrolled in the Health, Aging, and Body Composition study. Incident coronary heart disease (CHD), stroke, and congestive heart failure (CHF) events were detected during an average follow-up of 3.6 years. Blood levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha(TNF-alpha) were assessed. After adjustment for potential confounders, IL-6 was significantly associated with all outcomes (CHD events, per IL-6 SD increase: RR, 1.27; 95% CI, 1.10 to 1.48; stroke events, per IL-6 SD increase: RR, 1.45; 95% CI, 1.12 to 1.86; CHF events, per IL-6 SD increase: RR, 1.72; 95% CI, 1.40 to 2.12). TNF-alpha showed significant associations with CHD (per TNF-alpha SD increase: RR, 1.22; 95% CI, 1.04 to 1.43) and CHF (per TNF-alpha SD increase: RR, 1.59; 95% CI, 1.30 to 1.95) events. CRP was significantly associated with CHF events (per CRP SD increase: RR, 1.48; 95% CI, 1.23 to 1.78). A composite summary indicator of inflammation showed a strong association with incident cardiovascular events, with an especially high risk if all 3 inflammatory markers were in the highest tertile. Conclusions-Findings suggest that inflammatory markers are independent predictors of cardiovascular events in older persons. C1 Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC 27157 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Tennessee, Memphis, TN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Cesari, M (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Med Ctr Blvd, Winston Salem, NC 27157 USA. RI Cesari, Matteo/A-4649-2008; Newman, Anne/C-6408-2013; OI Cesari, Matteo/0000-0002-0348-3664; Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIA NIH HHS [N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106, P30-AG-021332-01] NR 31 TC 537 Z9 568 U1 5 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 11 PY 2003 VL 108 IS 19 BP 2317 EP 2322 DI 10.1161/01.CIR.0000097109.90783.FC PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 741TG UT WOS:000186475200006 PM 14568895 ER PT J AU Eichhorn, EJ Grayburn, PA Mayer, SA Sutton, MS Appleton, C Plehn, J Oh, J Greenberg, B DeMaria, A Frantz, R Krause-Steinrauf, H AF Eichhorn, EJ Grayburn, PA Mayer, SA Sutton, MS Appleton, C Plehn, J Oh, J Greenberg, B DeMaria, A Frantz, R Krause-Steinrauf, H CA BEST Investigators TI Myocardial contractile reserve by dobutamine stress echocardiography predicts improvement in ejection fraction with beta-blockade in patients with heart failure - The beta-Blocker Evaluation of Survival Trial (BEST) SO CIRCULATION LA English DT Article DE heart failure; receptors, adrenergic, beta; bucindolol; norepinephrine; contractility ID LEFT-VENTRICULAR FUNCTION; CARDIAC-INSUFFICIENCY BISOPROLOL; CORONARY-ARTERY-DISEASE; DILATED CARDIOMYOPATHY; ADRENERGIC-BLOCKADE; TIME-COURSE; METOPROLOL; REVASCULARIZATION; RECOVERY; THERAPY AB Background-beta-Blockers improve survival and reduce hospitalization in chronic heart failure (CHF) by biologically improving left ventricular ejection fraction (LVEF). However, a good predictor of improvement with this therapy has not been identified. This substudy of BEST examined whether myocardial contractile reserve, as determined by dobutamine stress echocardiography, predicts improvement in LVEF. Methods and Results-Seventy-nine patients with class III/IV CHF underwent dobutamine stress echocardiography before treatment with bucindolol (n=41) or placebo (n=38). Regional wall motion score index (WMSI) was calculated as the sum of the scores in each segment divided by the total number of segments visualized. WMSI was compared with change in LVEF after 3 months of therapy as determined by gated radionuclide scan. Change in WMSI correlated inversely with change in LVEF after 3 months of bucindolol (r=-0.72, P<0.0001) and was the most significant multivariate predictor of change in LVEF (P=0.0002). Patients with contractile reserve had demographics similar to those of patients without contractile reserve, including RVEF, LVEF, systolic blood pressure, and CHF duration. However, patients without contractile reserve had higher baseline plasma norepinephrine levels (687&PLUSMN;333 versus 420&PLUSMN;246 pg/mL, P<0.05) and greater decrease in plasma norepinephrine in response to bucindolol (-249+/-171 versus -35+/-277 pg/mL, P<0.05). Conclusions-This study suggests a direct relationship between contractile reserve and improvement in LVEF with β-blocker therapy in patients with advanced CHF. Patients without contractile reserve have higher resting adrenergic drive, as reflected by plasma norepinephrine, and may experience greater sympatholytic effects from bucindolol. C1 Univ Texas, SW Med Ctr, Cardiopulm Res Sci & Technol Inst, Dept Internal Med,Cardiol Div, Dallas, TX 75230 USA. Dallas VA Med Ctr, Dallas, TX USA. Univ Penn, Philadelphia, PA 19104 USA. Mayo Clin Scottsdale, Scottsdale, AZ USA. NIH, Cardiovasc Branch, Bethesda, MD USA. NHLBI, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. Univ Calif San Diego, San Diego, CA 92103 USA. Dept Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Eichhorn, EJ (reprint author), Univ Texas, SW Med Ctr, Cardiopulm Res Sci & Technol Inst, Dept Internal Med,Cardiol Div, 7777 forest Lane,Suite C-742, Dallas, TX 75230 USA. NR 26 TC 33 Z9 37 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 11 PY 2003 VL 108 IS 19 BP 2336 EP 2341 DI 10.1161/01.CIR.0000097111.00170.7B PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 741TG UT WOS:000186475200009 PM 14597587 ER PT J AU Altan-Bonnet, N Phair, RD Polishchuk, RS Weigert, R Lippincott-Schwartz, J AF Altan-Bonnet, N Phair, RD Polishchuk, RS Weigert, R Lippincott-Schwartz, J TI A role for Arf1 in mitotic Golgi disassembly, chromosome segregation, and cytokinesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLO-LIKE KINASE; ENDOPLASMIC-RETICULUM; PROTEIN; TRANSPORT; MITOSIS; FRAGMENTATION; INHERITANCE; COMPLEX; APPARATUS; PATHWAY AB In mitosis, chromosome, cytoskeleton, and organelle dynamics must be coordinated for successful cell division. Here, we present evidence for a role for Arf1, a small GTPase associated with the Golgi apparatus, in the orchestration of mitotic Golgi breakdown, chromosome segregation, and cytokinesis. We show that early in mitosis Arf1 becomes inactive and dissociates from Golgi membranes. This is followed by the dispersal of numerous Arf1-dependent peripheral Golgi proteins and subsequent Golgi disassembly. If Arf1 is kept in an active state by treatment with the small molecule H89 or expression of its GTP-locked form, intact Golgi membranes with bound peripheral proteins persist throughout mitosis. These cells enter mitosis but exhibit gross defects in chromosome segregation and cytokinetic furrow ingression. These findings suggest that mitotic Golgi disassembly depends on Arf1 inactivation and is used by the cell to disperse numerous peripheral Golgi proteins for coordinating the behavior of Golgi membranes, chromosomes, and cytoskeleton during mitosis. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. BioInformatics, Rockville, MD 20854 USA. Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, I-66030 Santa Maria Imbaro, Italy. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. FU Telethon [E.1249] NR 30 TC 67 Z9 72 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 11 PY 2003 VL 100 IS 23 BP 13314 EP 13319 DI 10.1073/pnas.2234055100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743LR UT WOS:000186573700038 PM 14585930 ER PT J AU Hernandez, L Kozlov, S Piras, G Stewart, CL AF Hernandez, L Kozlov, S Piras, G Stewart, CL TI Paternal and maternal genomes confer opposite effects on proliferation, cell-cycle length, senescence, and tumor formation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genomic imprinting; uniparental; igf2; p57(kip2); cloning ID EMBRYONIC STEM-CELLS; IMPRINTED GENES; IN-VITRO; P57(KIP2) EXPRESSION; MOUSE CHIMERAS; GROWTH; CANCER; LINES; DIFFERENTIATION; IDENTIFICATION AB Loss of imprinting is the silencing of active imprinted genes or the activation of silent imprinted genes, and it is one of the most common epigenetic changes associated with the development of a wide variety of tumors. Here, we have analyzed the effects that global imprinted gene expression has on cell proliferation and transformation. Primary mouse embryonic fibroblasts (MEFs), whose entire genome is either exclusively paternal (androgenetic) or maternal (parthenogenetic), exhibit dramatically contrasting patterns of growth. In comparison with biparental MEFs, androgenetic proliferation is characterized by a shorter cell cycle, increased saturation density, spontaneous transformation, and formation of tumors at low passage number. Parthenogenetic MEFs reach a lower saturation density, senesce, and die. The maternally expressed imprinted genes p57(kip2) and M6P/Igf2r retard proliferation and reduce the long-term growth of MEFs. In contrast, the paternally expressed growth factor Igf2 is essential for the long-term proliferation of all genotypes. Increased Igf2 expression in primary MEFs not only stimulates proliferation, but also results in their rapid conversion to malignancy with tumor formation of short latency. Our results reveal that paternally expressed imprinted genes, in the absence of maternal imprinted genes, predispose fibroblasts to rapid transformation. A potent factor in their transformation is IGF2, which on increased expression results in the rapid conversion of primary cells to malignancy. These results reveal a route by which malignant choriocarcinoma may arise from molar pregnancies. They also suggest that the derivation of stem cells from parthenogenetic embryos, for the purposes of therapeutic cloning, may be ineffective. C1 NCI, Canc & Dev Biol lab, Canc Res Ctr, Div Basic Sci, Frederick, MD 21702 USA. RP Stewart, CL (reprint author), NCI, Canc & Dev Biol lab, Canc Res Ctr, Div Basic Sci, Bldg 539 Room 121, Frederick, MD 21702 USA. NR 47 TC 64 Z9 68 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 11 PY 2003 VL 100 IS 23 BP 13344 EP 13349 DI 10.1073/pnas.2234026100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743LR UT WOS:000186573700043 PM 14581617 ER PT J AU Brentani, H Caballero, OL Camargo, AA da Silva, AM da Silva, WA Neto, ED Grivet, M Gruber, A Guimaraes, PEM Hide, W Iseli, C Jongeneel, CV Kelso, J Nagai, MA Ojopi, EPB Osorio, EC Reis, EMR Riggins, GJ Simpson, AJG de Souza, S Stevenson, BJ Strausberg, RL Tajara, EH Verjovski-Almeida, S Acencion, ML Bengtsono, MH Bettonip, F Bodmerq, WF Brionesr, MRS Camargos, LP Caveneet, W Ceruttiu, JM Coelho Andradev, LE Costa dos Santosn, PC Costaw, MCR da Silvaw, IT Esteciox, MRH Ferreiraw, KS Furnarit, FB Faria, M Galantep, PAF Guimaraesy, GS Holandaw, AJ Kimuraz, ET Leerkesp, MR Xin, LA Macielu, RMB Martinsbb, EAL Massirero, KB Melor, ASA Mestrinercc, CA Miraccan, EC Mirandas, LL Nobregadd, FG Oliveirap, PS Paquolaee, ACM Pandolficc, JRC Pardiniff, MIDC Passettip, F Quackenbushgg, J Schnabelr, B Sogayaro, MC Souzap, JE Valentinicc, SR Zaiatsp, AC Amaralx, EJ Arnaldiu, LAT de Araujow, AG de Bessan, SA Bicknellq, DC de Camaroy, MER Carrarop, DM Carrerhh, H Carvalhop, AF Colino, C Costaii, F Curcioz, C da Silvaw, IDCG da Silvav, NP Dellamanop, M El-Dorrykk, H Espreaficoll, EM Ferreirakk, AJS Ferreiraw, CA Fortesmm, MAHZ Gamann, AH Giannella-Netomm, D Giannellamm, MLCC Giorgimm, RR Goldmanoo, GH Goldmanpp, MHS Hackely, C Hobb, PL Kimuraqq, EM Kowalskirr, LP Kriegerss, JE Leitebb, LCC Lopesrr, A Lunamm, AMSC Mackaytt, A Marin, SKN Marquesw, AA Martins, WK Montagninirr, A Netorr, MM Nascimentobb, ALTO Nevilleuu, AM Nobregadd, MP O'Harett, MJ Otsukavv, AY de Melop, AIR Paco-Larsonww, ML Pereiraii, GG Pereira da Silvav, N Pesquerojj, JB Pessoajj, JG Rahalx, P Rainhoxx, CA Rodriguesyy, V Rogattoxx, SR Romanozz, CM Romeirox, JG Rossirr, BM Rusticcin, M de Sayy, RG Sant' Annaqq, SC Sarmazox, ML de Lima e Silvay, TC Soaresrr, FA Sonatiqq, MD Sousall, JD Queirozy, D Valenteww, V Vettorep, AL Villanovavv, FE Zagow, MA Zalcbergp, H AF Brentani, H Caballero, OL Camargo, AA da Silva, AM da Silva, WA Neto, ED Grivet, M Gruber, A Guimaraes, PEM Hide, W Iseli, C Jongeneel, CV Kelso, J Nagai, MA Ojopi, EPB Osorio, EC Reis, EMR Riggins, GJ Simpson, AJG de Souza, S Stevenson, BJ Strausberg, RL Tajara, EH Verjovski-Almeida, S Acencion, ML Bengtsono, MH Bettonip, F Bodmerq, WF Brionesr, MRS Camargos, LP Caveneet, W Ceruttiu, JM Coelho Andradev, LE Costa dos Santosn, PC Costaw, MCR da Silvaw, IT Esteciox, MRH Ferreiraw, KS Furnarit, FB Faria, M Galantep, PAF Guimaraesy, GS Holandaw, AJ Kimuraz, ET Leerkesp, MR Xin, LA Macielu, RMB Martinsbb, EAL Massirero, KB Melor, ASA Mestrinercc, CA Miraccan, EC Mirandas, LL Nobregadd, FG Oliveirap, PS Paquolaee, ACM Pandolficc, JRC Pardiniff, MIDC Passettip, F Quackenbushgg, J Schnabelr, B Sogayaro, MC Souzap, JE Valentinicc, SR Zaiatsp, AC Amaralx, EJ Arnaldiu, LAT de Araujow, AG de Bessan, SA Bicknellq, DC de Camaroy, MER Carrarop, DM Carrerhh, H Carvalhop, AF Colino, C Costaii, F Curcioz, C da Silvaw, IDCG da Silvav, NP Dellamanop, M El-Dorrykk, H Espreaficoll, EM Ferreirakk, AJS Ferreiraw, CA Fortesmm, MAHZ Gamann, AH Giannella-Netomm, D Giannellamm, MLCC Giorgimm, RR Goldmanoo, GH Goldmanpp, MHS Hackely, C Hobb, PL Kimuraqq, EM Kowalskirr, LP Kriegerss, JE Leitebb, LCC Lopesrr, A Lunamm, AMSC Mackaytt, A Marin, SKN Marquesw, AA Martins, WK Montagninirr, A Netorr, MM Nascimentobb, ALTO Nevilleuu, AM Nobregadd, MP O'Harett, MJ Otsukavv, AY de Melop, AIR Paco-Larsonww, ML Pereiraii, GG Pereira da Silvav, N Pesquerojj, JB Pessoajj, JG Rahalx, P Rainhoxx, CA Rodriguesyy, V Rogattoxx, SR Romanozz, CM Romeirox, JG Rossirr, BM Rusticcin, M de Sayy, RG Sant' Annaqq, SC Sarmazox, ML de Lima e Silvay, TC Soaresrr, FA Sonatiqq, MD Sousall, JD Queirozy, D Valenteww, V Vettorep, AL Villanovavv, FE Zagow, MA Zalcbergp, H CA Human Canc Genome Project Canc Genome Anatomy Project Annotation Consortiu Human Canc Genome Project Sequencing Consortium TI The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME ANATOMY PROJECT; GENE-EXPRESSION; WIDE DETECTION AB Whereas genome sequencing defines the genetic potential of an organism, transcript sequencing defines the utilization of this potential and links the genome with most areas of biology. To exploit the information within the human genome in the fight against cancer, we have deposited some two million expressed sequence tags (ESTs) from human tumors and their corresponding normal tissues in the public databases. The data currently define approximate to23,500 genes, of which only approximate to1,250 are still represented only by ESTs. Examination of the EST coverage of known cancer-related (CR) genes reveals that <1% do not have corresponding ESTs, indicating that the representation of genes associated with commonly studied tumors is high. The careful recording of the origin of all ESTs we have produced has enabled detailed definition of where the genes they represent are expressed in the human body. More than 100,000 ESTs are available for seven tissues, indicating a surprising variability of gene usage that has led to the discovery of a significant number of genes with restricted expression, and that may thus be therapeutically useful. The ESTs also reveal novel nonsynonymous germline variants (although the one-pass nature of the data necessitates careful validation) and many alternatively spliced transcripts. Although widely exploited by the scientific community, vindicating our totally open source policy, the EST data generated still provide extensive information that remains to be systematically explored, and that may further facilitate progress toward both the understanding and treatment of human cancers. C1 Univ Sao Paulo, Lab Genet Mol Canc, Dept Radiol, BR-05403010 Sao Paulo, Brazil. Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05508900 Sao Paulo, Brazil. Univ Estadual Paulista, Dept Biol, Inst Biociencias, BR-15054 Sao Jose Do Rio Preto, SP, Brazil. Ludwig Inst Canc Res, BR-01509010 Sao Paulo, Brazil. Univ Sao Paulo, Dept Patol, Fac Med Vet & Zootecn, BR-05508000 Sao Paulo, Brazil. Univ Sao Paulo, Fdn Hemocentro Ribeirao Preto, Fac Med Ribeirao Preto, BR-14051140 Ribeirao Preto, SP, Brazil. Univ Sao Paulo, Neurosci Lab, Inst Psiquiatria, Fac Med, BR-05403010 Sao Paulo, Brazil. NCI, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Univ Western Cape, S African Natl Bioinformat Inst, ZA-7535 Bellville, South Africa. Ludwig Inst Canc Res, Off Informat Technol, CH-1066 Epalinges, Switzerland. Ctr Estudo Telecomun PUC, BR-22453900 Rio De Janeiro, Brazil. RP Simpson, AJG (reprint author), Univ Sao Paulo, Lab Genet Mol Canc, Dept Radiol, Travessa Rua Dr Ovideo Pires Campos S-N 4 Andar, BR-05403010 Sao Paulo, Brazil. EM asimpson@licr.org RI Valente, Valeria/F-1301-2014; Correa-Giannella, Maria Lucia/D-2003-2012; Guimaraes, Pedro/A-9715-2008; Vettore, Andre/J-5168-2012; Gruber, Arthur/B-4711-2011; Romano, Camila/C-8185-2013; Paco-Larson, Maria/I-8613-2012; Passetti, Fabio/D-2422-2009; Oliveira, Paulo/D-5463-2011; de Bessa Garcia, Simone Aparecida/F-5334-2014; Mattoso Maia, Marco Antonio/J-8147-2014; Oliveira, Paulo/K-5588-2013; Lopes, Ademar/G-8526-2014; Ojopi, Elida/A-6773-2012; Camargo, Anamaria/E-9388-2012; Oliveira, Paulo/C-1275-2008; Hide, Winston Hide/C-7217-2009; Brentani, Helena/G-6839-2011; Jongeneel, Cornelis/B-2135-2012; Reis, Eduardo/H-2008-2011; Galante, Pedro/C-6564-2012; Nagai, Maria/C-6162-2012; Valentini, Sandro/C-4353-2012; Acencio, Marcio/D-9264-2012; Holanda, Adriano/E-2133-2012; Verjovski-Almeida, Sergio/E-4082-2012; Kowalski, Luiz/D-1701-2012; Rogatto, Silvia/E-6535-2012; Silva Jr, Wilson Araujo/E-9487-2011; Dias-Neto, Emmanuel/A-5869-2008; Silva, Israel/N-3858-2014; Tajara, Eloiza/G-7586-2012; da Silva, Aline/C-3649-2012; Pandolfi, Jose/I-6696-2013 OI Valente, Valeria/0000-0002-3942-7744; Iseli, Christian/0000-0002-2296-2863; Guimaraes, Pedro/0000-0002-7530-600X; Vettore, Andre/0000-0001-8526-5478; Passetti, Fabio/0000-0001-5672-7848; Oliveira, Paulo/0000-0002-1287-8019; de Bessa Garcia, Simone Aparecida/0000-0002-7122-7339; Mattoso Maia, Marco Antonio/0000-0001-5130-095X; Lopes, Ademar/0000-0002-8317-3817; Ojopi, Elida/0000-0001-5824-5199; Camargo, Anamaria/0000-0002-6076-9597; Hide, Winston Hide/0000-0002-8621-3271; Brentani, Helena/0000-0001-5192-4682; Galante, Pedro/0000-0002-4820-4155; Nagai, Maria/0000-0002-0728-4937; Acencio, Marcio/0000-0002-8278-240X; Holanda, Adriano/0000-0002-5409-6568; Verjovski-Almeida, Sergio/0000-0002-6356-2401; Kowalski, Luiz/0000-0001-5865-9308; Silva Jr, Wilson Araujo/0000-0001-9364-2886; Dias-Neto, Emmanuel/0000-0001-5670-8559; Silva, Israel/0000-0002-4687-1499; Tajara, Eloiza/0000-0002-2603-2057; da Silva, Aline/0000-0001-9249-4922; Pandolfi, Jose/0000-0002-7101-5803 NR 33 TC 74 Z9 80 U1 0 U2 11 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 11 PY 2003 VL 100 IS 23 BP 13418 EP 13423 DI 10.1073/pnas.1233632100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743LR UT WOS:000186573700056 PM 14593198 ER PT J AU Roessler, E Du, YZ Mullor, JL Casas, E Allen, WP Gillessen-Kaesbach, G Roeder, ER Ming, JE Altaba, ARI Muenke, M AF Roessler, E Du, YZ Mullor, JL Casas, E Allen, WP Gillessen-Kaesbach, G Roeder, ER Ming, JE Altaba, ARI Muenke, M TI Loss-of-function mutations in the human GL12 gene are associated with pituitary anomalies and holoprosencephaly-like features SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CUBITUS-INTERRUPTUS PROTEIN; BASAL-CELL CARCINOMAS; SONIC-HEDGEHOG; GLI PROTEINS; FLOOR PLATE; TRANSCRIPTION FACTOR; SIGNALING PATHWAY; MUTANT MICE; NEURAL-TUBE; ACTIVATION AB Diminished Sonic Hedgehog (Shh) signaling is associated with the most common forebrain defect in humans, holoprosencephaly (HPE), which includes cyclopia, a phenotype also seen in mice and other vertebrates with defective Shh signaling. The secreted protein Shh acts as a crucial factor that patterns the ventral forebrain and is required for the division of the primordial eye field and brain into two discrete halves. Gli2 is one of three vertebrate transcription factors implicated as obligatory mediators of Shh signal transduction. Here, we show that loss-of-function mutations in the human GLI2 gene are associated with a distinctive phenotype (within the HPE spectrum) whose primary features include defective anterior pituitary formation and pan-hypopituitarism, with or without overt forebrain cleavage abnormalities, and HPE-like mid-facial hypoplasia. We also demonstrate that these mutations lack GLI2 activity. We report on a functional association between GLI2 and human disease and highlight the role of GLI2 in human head development. C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. NYU, Sch Med, Skirball Inst Biomed Med, New York, NY 10016 USA. Fullerton Genet Ctr, Asheville, NC 28801 USA. Univ Klinikum Essen, Inst Humangenet Essen, D-45122 Essen, Germany. Valley Childrens Hosp, Dept Genet Med, Madera, CA 93638 USA. RP Muenke, M (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD01218, HD29862] NR 44 TC 177 Z9 181 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 11 PY 2003 VL 100 IS 23 BP 13424 EP 13429 DI 10.1073/pnas.2235734100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743LR UT WOS:000186573700057 PM 14581620 ER PT J AU Shoham, NG Centola, M Mansfield, E Hull, KM Wood, G Wise, CA Kastner, DL AF Shoham, NG Centola, M Mansfield, E Hull, KM Wood, G Wise, CA Kastner, DL TI Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ALDRICH-SYNDROME PROTEIN; CYTOSKELETAL-ASSOCIATED PROTEIN; NF-KAPPA-B; TYROSINE-PHOSPHATASE; ACTIVATING ADAPTER; PTP-PEST; GENE; MUTATIONS; DOMAIN; APOPTOSIS AB Pyrin, the familial Mediterranean fever protein, is found in association with the cytoskeleton in myeloid/monocytic cells and modulates IL-1beta processing, NF-kappabeta activation, and apoptosis. These effects are mediated in part through cognate interactions with the adaptor protein ASC, which shares an N-terminal motif with pyrin. We sought additional upstream regulators of inflammation by using pyrin as the bait in yeast two-hybrid assays. We now show that proline serine threonine phosphatase-interacting protein [PSTPIP1, or CD2-binding protein 1 (CD2BP1)], a tyrosine-phosphorylated protein involved in cytoskeletal organization, also interacts with pyrin. Recently, PSTPIP1/CD2BP1 mutations were shown to cause the syndrome of pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA), a dominantly inherited autoinflammatory disorder mediated predominantly by granulocytes. Endogenous PSTPIP1/CD2BP1 and pyrin are coexpressed in monocytes and granulocytes and can be coimmunoprecipitated from THP-1 cells. The B box segment of pyrin was necessary and the B box/coiled-coil segment sufficient for this interaction, whereas the SH3 and coiled-coil domains of PSTPIP1/CD2BP1 were both necessary, but neither was sufficient, for pyrin binding. The Y344F PSTPIP1/CD2BP1 mutation, which blocks tyrosine phosphorylation, was associated with a marked reduction in pyrin binding in pervanadate-treated cells. PAPA-associated A230T and E250Q PSTPIP1/CD2BP1 mutations markedly increased pyrin binding as assayed by immunoprecipitation and, relative to WT, these mutants were hyperphosphorylated when coexpressed with c-Abl kinase. Consistent with the hypothesis that these mutations exert a dominant-negative effect on the previously reported activity of pyrin, we found increased IL-1beta production by peripheral blood leukocytes from a clinically active PAPA patient with the A230T PSTPIP1/CD2BP1 mutation and in cell lines transfected with both PAPA-associated mutants. C1 NIAMSD, Genet & Genom Branch, Bethesda, MD 20892 USA. NIAMSD, Off Clin Director, Bethesda, MD 20892 USA. Texas Scottish Rite Hosp Children, Sarah M & Charles E Seay Ctr Musculoskeletal Res, Dallas, TX 75219 USA. RP Kastner, DL (reprint author), NIH, Bldg 10,Room 9N-214, Bethesda, MD 20892 USA. OI Wise, Carol/0000-0002-6790-2194 NR 35 TC 227 Z9 238 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 11 PY 2003 VL 100 IS 23 BP 13501 EP 13506 DI 10.1073/pnas.2135380100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743LR UT WOS:000186573700070 PM 14595024 ER PT J AU Li, F Goila-Gaur, R Salzwedel, K Kilgore, NR Reddick, M Matallana, C Castillo, A Zoumplis, D Martin, DE Orenstein, JM Allaway, GP Freed, EO Wild, CT AF Li, F Goila-Gaur, R Salzwedel, K Kilgore, NR Reddick, M Matallana, C Castillo, A Zoumplis, D Martin, DE Orenstein, JM Allaway, GP Freed, EO Wild, CT TI PA-457: A potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DIMERIZATION INITIATION SITE; TYPE-1 GAG; BETULINIC ACID; PARTICLE-PRODUCTION; PRECURSOR PROTEINS; DRUG-RESISTANCE; LATE DOMAIN; PROTEASE; TSG101 AB New HIV therapies are urgently needed to address the growing problem of drug resistance. In this article, we characterize the anti-HIV drug candidate 3-0-(3',3'-dimethylsuccinyl) betulinic acid (PA-457). We show that PA-457 potently inhibits replication of both WT and drug-resistant HIV-1 isolates and demonstrate that the compound acts by disrupting a late step in Gag processing involving conversion of the capsid precursor (p25) to mature capsid protein (p24). We find that virions from PA-457-treated cultures are noninfectious and exhibit an aberrant particle morphology characterized by a spherical, acentric core and a crescent-shaped, electron-dense shell lying just inside the viral membrane. To identify the determinants of compound activity we selected for PA-457-resistant virus in vitro. Consistent with the effect on Gag processing, we found that mutations conferring resistance to PA-457 map to the p25 to p24 cleavage site. PA-457 represents a unique class of anti-HIV compounds termed maturation inhibitors that exploit a previously unidentified viral target, providing additional opportunities for HIV drug discovery. C1 Panacos Pharmaceut Inc, Gaithersburg, MD 20877 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. RP Wild, CT (reprint author), Panacos Pharmaceut Inc, 209 Perry Pkwy, Gaithersburg, MD 20877 USA. FU NIAID NIH HHS [R43 AI051047, R43 AI51047] NR 36 TC 261 Z9 285 U1 2 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 11 PY 2003 VL 100 IS 23 BP 13555 EP 13560 DI 10.1073/pnas.2234683100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743LR UT WOS:000186573700079 PM 14573704 ER PT J AU Daviglus, ML Liu, K Pirzada, A Yan, LJL Garside, DB Feinglass, J Guralnik, JM Greenland, P Stamler, J AF Daviglus, ML Liu, K Pirzada, A Yan, LJL Garside, DB Feinglass, J Guralnik, JM Greenland, P Stamler, J TI Favorable cardiovascular risk profile in middle age and health-related quality of life in older age SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; ASSOCIATION DETECTION PROJECT; ALL-CAUSE MORTALITY; 25-YEAR FOLLOW-UP; BLOOD-PRESSURE; UNITED-STATES; CHRONIC DISABILITY; SERUM-CHOLESTEROL; CIGARETTE-SMOKING; NATURAL DEATH AB Background: Life expectancy is greater for people with favorable midlife cardiovascular risk profiles (ie, low risk). However, some speculate that increased longevity may lead to large numbers of ill, disabled, older persons with lower quality of life. Few data exist on this important issue. This study evaluates the relationship of midlife low-risk status to quality of life and illness in older age. Methods: Cohort of middle-aged adults from the Chicago Heart Association Detection Project in Industry (2692 women and 3650 men; baseline ages, 36-64 years [average age, 73.2 years in 1996]) without baseline (19671973) major electrocardiographic abnormalities or history of diabetes or myocardial infarction. Quality of life (12-item Health Status Questionnaire [HSQ-12] on physical, mental, and social well-being) and self-reported diseases were assessed after 26 years of follow-up. Baseline risk strata included low risk (favorable blood pressure and serum cholesterol levels, no smoking, and no minor electrocardiographic abnormalities); 0 risk factors (ie, no high risk factors but greater than or equal to1 risk factors not at favorable levels); or any 1, any 2, or 3 or more of the following 4 risk factors: high blood pressure, high serum cholesterol level, smoking, and minor electrocardiographic abnormalities. The HSQ-12 scores and disease outcomes for low risk were compared with other strata. Results: Adjusted scores for physical, mental, social functioning, and disease-free outcomes were highest for low-risk individuals and decreased significantly with number of risk factors (eg, 58% of low-risk women had excellent/very good health compared with 28% of women with greater than or equal to3 risk factors). Conclusions: Favorable cardiovascular risk profile in middle age is associated with better quality of life and lower risk of diseases in older age. Moreover, the fewer the risk factors, the higher the quality of life. C1 Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Div Geriatr, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Div Gen Internal Med, Chicago, IL 60611 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Daviglus, ML (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. FU NHLBI NIH HHS [R01 HL21010, R01 HL62684] NR 49 TC 75 Z9 76 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 10 PY 2003 VL 163 IS 20 BP 2460 EP 2468 DI 10.1001/archinte.163.20.2460 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 740YN UT WOS:000186431000010 PM 14609782 ER PT J AU De Sanjose, S Shah, K Engels, EA Viscidi, RP AF De Sanjose, S Shah, K Engels, EA Viscidi, RP TI Lack of serological evidence for an association between simian virus 40 and lymphoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Letter C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Inst Catala Oncol, Barcelona, Spain. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Stanley Div Dev Neurovirol, Baltimore, MD 21205 USA. RP De Sanjose, S (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8005, Rockville, MD 20852 USA. RI de Sanjose Llongueras, Silvia/H-6339-2014 NR 4 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 10 PY 2003 VL 107 IS 3 BP 507 EP 508 DI 10.1002/ijc.11326 PG 2 WC Oncology SC Oncology GA 733DK UT WOS:000185984500026 ER PT J AU Azuma, Y Arnaoutov, A Dasso, M AF Azuma, Y Arnaoutov, A Dasso, M TI SUMO-2/3 regulates topoisomerase II in mitosis SO JOURNAL OF CELL BIOLOGY LA English DT Article DE topoisomerase II; SUMO-1; SUMO-2; mitosis; chromosome segregation ID UBIQUITIN-CONJUGATING ENZYME; MITOTIC CHROMOSOMES; SACCHAROMYCES-CEREVISIAE; GENE ENCODES; ALPHA; CONDENSATION; PROTEASE; YEAST; POMBE; SMT4 AB We have analyzed the abundance of SUMO-conjugated species during the cell cycle in Xenopus egg extracts. The predominant SUMO conjugation products associated with mitotic chromosomes arose from SUMO conjugation of topoisomerase II. Topoisomerase II was modified exclusively by SUMO-2/3 during mitosis under normal circumstances, although we observed conjugation of topoisomerase II to SUMO-1 in extracts with exogenous SUMO-1 protein. Inhibition of SUMO modification by a dominant-negative mutant of the SUMO-conjugating enzyme Ubc9 (dnUbc9) did not detectably alter topoisomerase II activity, but it did increase the amount of unmodified topoisomerase II retained on mitotic chromosomes after high salt washing. dnUbc9 did not disrupt the assembly of condensed mitotic chromosomes or block progression of extracts through mitosis, but it did block the dissociation of sister chromatids at the metaphase-anaphase transition. Together, our results suggest that SUMO conjugation is important for chromosome segregation in metazoan systems, and that mobilization of topoisomerase II from mitotic chromatin may be a key target of this modification. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Dasso, M (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bldg 18,Room 106,18 Lib Dr,MSC-5431, Bethesda, MD 20892 USA. OI Dasso, Mary/0000-0002-5410-1371 NR 31 TC 133 Z9 137 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 10 PY 2003 VL 163 IS 3 BP 477 EP 487 DI 10.1083/jcb.200304088 PG 11 WC Cell Biology SC Cell Biology GA 743PZ UT WOS:000186583900008 PM 14597774 ER PT J AU Yang, F He, XP Russell, J Lu, B AF Yang, F He, XP Russell, J Lu, B TI Ca2+ influx-independent synaptic potentiation mediated by mitochondrial Na+-Ca2+ exchanger and protein kinase C SO JOURNAL OF CELL BIOLOGY LA English DT Article DE synaptic plasticity; neuromuscular junction; mitochondria; Na+-Ca2+ exchanger; Ca2+ influx ID DEVELOPING NEUROMUSCULAR SYNAPSES; MOTOR-NERVE TERMINALS; TRANSMITTER RELEASE; NEUROTRANSMITTER RELEASE; POSTTETANIC POTENTIATION; CALCIUM; RECEPTOR; NEUROTROPHINS; INHIBITION; PLASTICITY AB Activity-dependent modulation of synaptic transmission is an essential mechanism underlying many brain functions. Here we report an unusual form of synaptic modulation that depends on Na+ influx and mitochondrial Na+-Ca2+ exchanger, but not on Ca2+ influx. in Ca2+-free medium, tetanic stimulation of Xenopus motoneurons induced a striking potentiation of transmitter release at neuromuscular synapses. Inhibition of either Na+ influx or the rise of Ca2+ concentrations ([Ca2+](i)) at nerve terminals prevented the tetanus-induced synaptic potentiation (TISP). Blockade of Ca2+ release from mitochondrial Na+-Ca2+ exchanger, but not from ER Ca2+ stores, also inhibited TISP. Tetanic stimulation in Ca2+-free medium elicited an increase in [Ca2+](i), which was prevented by inhibition of Na+ influx or mitochondrial Ca2+ release. Inhibition of PKC blocked the TISP as well as mitochondrial Ca2+ release. These results reveal a novel form of synaptic plasticity and suggest a role of PKC in mitochondrial Ca2+ release during synaptic transmission. C1 NICHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. NICHD, Sect Cell Biol & Signal Transduct, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Lu, B (reprint author), NICHD, Sect Neural Dev & Plast, NIH, Bldg 49,Rm 6A80,49 Convent Dr, Bethesda, MD 20892 USA. RI Yang, Feng/C-9530-2011; Lu, Bai/A-4018-2012 NR 43 TC 76 Z9 78 U1 0 U2 1 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 10 PY 2003 VL 163 IS 3 BP 511 EP 523 DI 10.1083/jcb.200307027 PG 13 WC Cell Biology SC Cell Biology GA 743PZ UT WOS:000186583900011 PM 14610054 ER PT J AU Holmbeck, K Bianco, P Chrysovergis, K Yamada, S Birkedal-Hansen, H AF Holmbeck, K Bianco, P Chrysovergis, K Yamada, S Birkedal-Hansen, H TI MT1-MMP-dependent, apoptotic remodeling of unmineralized cartilage: a critical process in skeletal growth SO JOURNAL OF CELL BIOLOGY LA English DT Article DE cranial vault; Meckel's cartilage; matrix dissolution; chondrocyte apoptosis; metamorphosis; MT1-MMP ID HORMONE RESPONSE GENES; OSTEOBLAST-LIKE CELLS; MATRIX METALLOPROTEINASES; THYROID-HORMONE; BONE-FORMATION; HYPERTROPHIC CHONDROCYTES; EXTRACELLULAR-MATRIX; EXPRESSION PATTERN; MOLECULAR ANALYSIS; DEVELOP DWARFISM AB Skeletal tissues develop either by intramembranous ossification, where bone is formed within a soft connective tissue, or by endochondral ossification. The latter proceeds via cartilage anlagen, which through hypertrophy, mineralization, and partial resorption ultimately provides scaffolding for bone formation. Here, we describe a novel and essential mechanism governing remodeling of unmineralized cartilage anlagen into membranous bone, as well as tendons and ligaments. Membrane-type 1 matrix metalloproteinase (MT1-MMP)-dependent dissolution of unmineralized cartilages, coupled with apoptosis of non-hypertrophic chondrocytes, mediates remodeling of these cartilages into other tissues. The MT1-MMP deficiency disrupts this process and uncouples apoptotic demise of chondrocytes and cartilage degradation, resulting in the persistence of "ghost" cartilages with adverse effects on skeletal integrity. Some cells entrapped in these ghost cartilages escape apoptosis, maintain DNA synthesis, and assume phenotypes normally found in the tissues replacing unmineralized cartilages. The coordinated apoptosis and matrix metalloproteinase-directed cartilage dissolution is akin to metamorphosis and may thus represent its evolutionary legacy in mammals. C1 NIDCR, Matrix Metalloproteinase Unit, NIH, Bethesda, MD 20892 USA. Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, I-00161 Rome, Italy. RP Birkedal-Hansen, H (reprint author), NIDCR, Matrix Metalloproteinase Unit, NIH, Bldg 30,Rm 132,30 Convent Dr,MSC 4326, Bethesda, MD 20892 USA. FU NIDCR NIH HHS [Z01 DE000676] NR 47 TC 80 Z9 84 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 10 PY 2003 VL 163 IS 3 BP 661 EP 671 DI 10.1083/jcb.200307061 PG 11 WC Cell Biology SC Cell Biology GA 743PZ UT WOS:000186583900023 PM 14610065 ER PT J AU Hoshino, Y Jones, RW Ross, J Santos, N Kapikian, AZ AF Hoshino, Y Jones, RW Ross, J Santos, N Kapikian, AZ TI Human rotavirus strains bearing VP4 gene P[6] allele recovered from asymptomatic or symptomatic infections share similar, if not identical, VP4 neutralization specificities SO VIROLOGY LA English DT Article ID HOST-RANGE RESTRICTION; CAPSID PROTEINS VP4; PORCINE ROTAVIRUS; 4TH GENE; SEROTYPIC CHARACTERIZATION; MONOCLONAL-ANTIBODIES; NEONATAL INFECTIONS; VACCINE DEVELOPMENT; GOTTFRIED STRAIN; MATERNITY UNIT AB A rotavirus VP4 gene P[6] allele has been documented in a number of countries to be characteristically associated with an endemic predominantly asymptomatic infection in neonates in maternity hospital nurseries. The mechanisms underlying the endemicity and asymptomatic nature of such neonatal infections remain unknown. Rotavirus strains sharing this same P genotype, however, have more recently been recovered from an increasing number of symptomatic diarrheal episodes in infants and young children in various parts of the world. Previously, we have shown that an asymptomatic P[6] rotavirus neonatal infection is not associated with a unique VP7 (G) serotype but may occur in conjunction with various G types. Although amino acid sequence comparisons of the VP4 gene between selected "asymptomatic" and "symptomatic" P[6] rotavirus strains have been reported and yielded information concerning their VP4 genotypes, serotypic comparisons of the outer capsid spike protein VP4 of such viruses have not been studied systematically by two-way cross-neutralizations. We determined the VP4 neutralization specificities of four asymptomatic and four symptomatic P[6] strains: two each of asymptomatic and symptomatic strains by two-way tests, and two each of additional asymptomatic and symptomatic strains by one-way tests. Both asymptomatic and symptomatic P[6] strains were shown to bear similar, if not identical, VP4 neutralization specificities. Thus, P[6] rotavirus strains causing asymptomatic or symptomatic infections did not appear to belong to unique P (VP4) serotypes. In addition, a close VP4 serotypic relationship between human P[6] rotavirus strains and the porcine P[6] rotavirus Gottfried strain was confirmed. (C) 2003 Elsevier Inc. All rights reserved. C1 NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Hoshino, Y (reprint author), NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bldg 50,Room 6308,50 South Dr,MSC 8026, Bethesda, MD 20892 USA. RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 NR 74 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 2003 VL 316 IS 1 BP 1 EP 8 DI 10.1016/S0042-6822(03)00543-9 PG 8 WC Virology SC Virology GA 743WH UT WOS:000186596200001 PM 14599785 ER PT J AU Ivanic, J AF Ivanic, J TI Direct configuration interaction and multiconfigurational self-consistent-field method for multiple active spaces with variable occupations. I. Method SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MOLECULAR ELECTRONIC WAVEFUNCTIONS; UNITARY GROUP-APPROACH; CI CALCULATIONS; SCF METHOD; ENERGY EXTRAPOLATION; WAVE-FUNCTIONS; MCSCF THEORY; ALGORITHM; EFFICIENT; MATRIX AB In order to reduce the number of ineffective configurations in a priori generated configuration spaces, a direct configuration interaction method has been developed which limits the electron occupations of orbital groups making up a total active space. A wave function is specified by first partitioning an active space into an unrestricted number of orbital groups and second by providing limiting values, in the form of minima and maxima, for the electron occupancies of each group. The configuration interaction problem corresponding to all possible determinants satisfying these conditions is solved in a fully direct manner by the use of Slater-Condon expressions in conjunction with single and double replacements. This configuration interaction approach, termed occupation restricted multiple active space-configuration interaction, has also been linked with orbital optimization programs to produce the occupation restricted multiple active space-self consistent field method. (C) 2003 American Institute of Physics. C1 NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA. RP Ivanic, J (reprint author), NCI, Adv Biomed Comp Ctr, SAIC Frederick, Contract N01-CO-12400, Frederick, MD 21702 USA. NR 73 TC 130 Z9 132 U1 0 U2 9 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 8 PY 2003 VL 119 IS 18 BP 9364 EP 9376 DI 10.1063/1.1615954 PG 13 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 735WZ UT WOS:000186138700006 ER PT J AU Ivanic, J AF Ivanic, J TI Direct configuration interaction and multiconfigurational self-consistent-field method for multiple active spaces with variable occupations. II. Application to oxoMn(salen) and N2O4 SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MOLECULAR-ORBITAL METHODS; COMPACT EFFECTIVE POTENTIALS; EXPONENT BASIS-SETS; GAUSSIAN-TYPE BASIS; DINITROGEN TETROXIDE; ELECTRONIC WAVEFUNCTIONS; ORGANIC-MOLECULES; AB-INITIO; ATOMS; EPOXIDATION AB In a previous paper, a new direct configuration interaction method for multiple active spaces with variable occupations was described. The present article illustrates how this method may be applied to the oxoMn(salen) complex and the N2O4 molecule. In the first application it is shown how complete-active-space self-consistent-field wave functions of the oxoMn(salen) system may be approximated by a drastically reduced number of configurations with negligible loss of accuracy in terms of energetics. In the second application, to N2O4, it is demonstrated how the fully optimized reaction space wave function may be approximated and also how the recovery of dynamic correlation effects may be achieved. The best predictions of the structure (r(NN)=1.743 Angstrom, r(NO)=1.189 Angstrom, angle(ONO)=134.4degrees) and binding energy (D-e=16.0 kcal/mol) are both in very good agreement with experiment (r(NN)=1.756, r(NO)=1.191, angle(ONO)=134.46degrees, D-e=16.3 kcal/mol). (C) 2003 American Institute of Physics. C1 NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA. RP Ivanic, J (reprint author), NCI, Adv Biomed Comp Ctr, SAIC Frederick, Contract N01-CO-12400, Frederick, MD 21702 USA. NR 50 TC 52 Z9 52 U1 1 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 8 PY 2003 VL 119 IS 18 BP 9377 EP 9385 DI 10.1063/1.1615955 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 735WZ UT WOS:000186138700007 ER PT J AU Modi, WS Goedert, JJ Strathdee, S Buchbinder, S Detels, R Donfield, S O'Brien, SJ Winkler, C AF Modi, WS Goedert, JJ Strathdee, S Buchbinder, S Detels, R Donfield, S O'Brien, SJ Winkler, C TI MCP-1-MCP-3-eotaxin gene cluster influences HIV-1 transmission SO AIDS LA English DT Article DE HIV-1 transmission; MCP-1; MCP-3; eotaxin; immune system activation ID IMMUNODEFICIENCY-VIRUS TYPE-1; DENDRITIC CELL MATURATION; HUMAN MONOCYTES; CC CHEMOKINES; INFECTION; AIDS; EXPRESSION; PROGRESSION; COHORT; BETA AB Background: MCP-1 (CCL2), MCP-3 (CCL 7), and eotaxin (CCL 17) are genes for CC chemokines clustered on the long arm of chromosome 17. Previous studies have implicated these chemokines in monocyte recruitment, viral replication, and anti-HIV cytotoxic T cell responses. An epidemiological analysis identified genetic variants influencing HIV-1 transmission and disease progression. Methods: Genomic DNA from over 3000 participants enrolled in five natural history cohorts in the United States were analyzed. Nine single nucleotide polymorphisms (SNP) covering 33 kb containing these three genes were genotyped using the polymerase chain reaction. Distortions in allele, genotype, and haplotype frequencies were assessed with respect to HIV-1 transmission and rates of disease progression using categorical and survival analyses. Results: Extensive linkage disequilibrium was observed. Three SNP (-2136T located in the MCP-1 promoter region, 767G in intron 1 of MCP-1, and -1385A in the Eotaxin promoter) were nearly always found together on a 31 kb haplotype (H7) containing the three genes. Frequencies of the three variants and the H7 haplotype were significantly elevated (odds ratio, 0.6; P = 0.005-0.01) in uninfected European-Americans repeatedly exposed to HIV-1 through high-risk sexual behavior or contaminated blood products. Conclusions: Although the extensive linkage disequilibrium precludes positive identification of the causal variant, the results suggest that genetic variation in the H7 region influences susceptibility to HIV-1 infection. Since these chemokines do not bind the primary HIV-1 coreceptors CCR5 or CXCR4, the observed influence on transmission may result from activation of the immune system in response to infection rather than receptor blockage. (C) 2003 Lippincott Williams Wilkins. C1 NCI, SAIC Frederick, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Dept Publ Hlth, San Francisco, CA USA. Rho Inc, Chapel Hill, NC USA. RP Winkler, C (reprint author), NCI, SAIC Frederick, Frederick, MD 21702 USA. RI Strathdee, Steffanie/B-9042-2009 FU NCI NIH HHS [N01-CO-56000]; NIDA NIH HHS [DA12568] NR 37 TC 58 Z9 63 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 7 PY 2003 VL 17 IS 16 BP 2357 EP 2365 DI 10.1097/01.aids.0000076359.20434.44 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 809YO UT WOS:000220672200011 PM 14571188 ER PT J AU Alter-Koltunoff, M Ehrlich, S Dror, N Azriel, A Eilers, M Hauser, H Bowen, H Barton, CH Tamura, T Ozato, K Levi, BZ AF Alter-Koltunoff, M Ehrlich, S Dror, N Azriel, A Eilers, M Hauser, H Bowen, H Barton, CH Tamura, T Ozato, K Levi, BZ TI Nramp1-mediated innate resistance to intraphagosomal pathogens is regulated by IRF-8, PU.1, and Miz-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEQUENCE-BINDING-PROTEIN; IL-18 GENE-EXPRESSION; TRANSCRIPTION FACTOR; GP91(PHOX) EXPRESSION; NATURAL-RESISTANCE; COMPLEX-FORMATION; MYC REPRESSES; C-MYC; MACROPHAGES; ICSBP AB Natural resistance-associated macrophage protein 1 (Nramp1) is a proton/divalent cation antiporter exclusively expressed in monocyte/macrophage cells with a unique role in innate resistance to intraphagosomal pathogens. In humans, it is linked to several infectious diseases, including leprosy, pulmonary tuberculosis, visceral leishmaniasis, meningococcal meningitis, and human immunodeficiency virus as well as to autoimmune diseases such as rheumatoid arthritis and Crohn's disease. Here we demonstrate that the restricted expression of Nramp1 is mediated by the macrophage-specific transcription factor IRF-8. This factor exerts its activity via protein-protein interaction, which facilitates its binding to target DNA. Using yeast two-hybrid screen we identified Myc Interacting Zinc finger protein 1 (Miz-1) as new interacting partner. This interaction is restricted to immune cells and takes place on the promoter Nramp1 in association with PU.1, a transcription factor essential for myelopoiesis. Consistent with these data, IRF-8 knockout mice are sensitive to a repertoire of intracellular pathogens. Accordingly, IRF-8(-/-) mice express low levels of Nramp1 that can not be induced any further. Thus, our results explain in molecular terms the role of IRF-8 in conferring innate resistance to intracellular pathogens and point to its possible involvement in autoimmune diseases. C1 Technion Israel Inst Technol, Dept Food Engn & Biotechnol, IL-32000 Haifa, Israel. Univ Marburg, Inst Mol Biol & Tumour Res, D-35033 Marburg, Germany. GBF, Gesell Biotechnol Forsch GmbH, Dept Gene Regulat & Differentiat, D-38124 Braunschweig, Germany. Univ Southampton, Dept Biochem & Mol Biol, Southampton S016 7PX, Hants, England. NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Levi, BZ (reprint author), Technion Israel Inst Technol, Dept Food Engn & Biotechnol, IL-32000 Haifa, Israel. OI Eilers, Martin/0000-0002-0376-6533 NR 52 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 7 PY 2003 VL 278 IS 45 BP 44025 EP 44032 DI 10.1074/jbc.M307954200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 738UR UT WOS:000186306700018 PM 12904288 ER PT J AU Romero, N Radi, R Linares, E Augusto, O Detweiler, CD Mason, RP Denicola, A AF Romero, N Radi, R Linares, E Augusto, O Detweiler, CD Mason, RP Denicola, A TI Reaction of human hemoglobin with peroxynitrite Isomerization to nitrate and secondary formation of protein radicals SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYDROGEN-PEROXIDE; NITRIC-OXIDE; RELAXING FACTOR; CYTOCHROME-C; HORSERADISH-PEROXIDASE; MEDIATED OXIDATION; DIOXYGEN COMPLEXES; HUMAN MYOGLOBIN; OXYHEMOGLOBIN; SUPEROXIDE AB Peroxynitrite, a strong oxidant formed intravascularly in vivo, can diffuse onto erythrocytes and be largely consumed via a fast reaction (2x10(4) M-1 s(-1)) with oxyhemoglobin. The reaction mechanism of peroxynitrite with oxyhemoglobin that results in the formation of methemoglobin remains to be elucidated. In this work, we studied the reaction under biologically relevant conditions using millimolar oxyhemoglobin concentrations and a stoichiometric excess of oxyhemoglobin over peroxynitrite. The results support a reaction mechanism that involves the net one-electron oxidation of the ferrous heme, isomerization of peroxynitrite to nitrate, and production of superoxide radical and hydrogen peroxide. Homolytic cleavage of peroxynitrite within the heme iron allows the formation of ferrylhemoglobin in similar to10% yields, which can decay to methemoglobin at the expense of reducing equivalents of the globin moiety. Indeed, spin-trapping studies using 2-methyl-2-nitroso propane and 5,5 dimethyl-1-pyrroline-N-oxide ( DMPO) demonstrated the formation of tyrosyl- and cysteinyl-derived radicals. DMPO also inhibited covalently linked dimerization products and led to the formation of DMPO-hemoglobin adducts. Hemoglobin nitration was not observed unless an excess of peroxynitrite over oxyhemoglobin was used, in agreement with a marginal formation of nitrogen dioxide. The results obtained support a role of oxyhemoglobin as a relevant intravascular sink of peroxynitrite. C1 Fac Med, Dept Bioquim, Montevideo 11800, Uruguay. Fac Med, Ctr Free Rad & Biomed Res, Montevideo 11800, Uruguay. Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-0513970 Sao Paulo, Brazil. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Republica, Fac Ciencias, Inst Quim Biol, Montevideo 11400, Uruguay. RP Denicola, A (reprint author), Fac Med, Dept Bioquim, Avda Gral Flores 2125, Montevideo 11800, Uruguay. RI Augusto, Ohara/D-3839-2012; OI Augusto, Ohara/0000-0002-7220-4286; Linares, Edlaine/0000-0001-8164-3013 NR 61 TC 87 Z9 89 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 7 PY 2003 VL 278 IS 45 BP 44049 EP 44057 DI 10.1074/jbc.M305895200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 738UR UT WOS:000186306700021 PM 12920120 ER PT J AU Osborne, A Teng, QC Miles, EW Phillips, RS AF Osborne, A Teng, QC Miles, EW Phillips, RS TI Detection of open and closed conformations of tryptophan synthase by N-15-heteronuclear single-quantum coherence nuclear magnetic resonance of bound 1-N-15-L-tryptophan SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BIENZYME COMPLEX; BETA-SUBUNIT; ALPHA(2)BETA(2) COMPLEX; SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; 3-DIMENSIONAL STRUCTURE; SUBSTRATE-SPECIFICITY; ALLOSTERIC REGULATION; ALPHA-SUBUNIT; ACTIVE-SITES AB 1-N-15-L-Tryptophan (1-N-15-L-Trp) was synthesized from N-15-aniline by a Sandmeyer reaction, followed by cyclization to isatin, reduction to indole with LiAlH4, and condensation of the N-15-indole with L-serine, catalyzed by tryptophan synthase. 1-N-15-L-Trp was complexed with wild-type tryptophan synthase and beta-subunit mutants, betaK87T, betaD305A, and betaE109D, in the absence or presence of the allosteric ligands sodium chloride and disodium alpha-glycerophosphate. The enzyme complexes were observed by N-15-heteronuclear single-quantum coherence nuclear magnetic resonance (N-15-HSQC NMR) spectroscopy for the presence of 1-N-15-L-Trp bound to the beta- active site. No N-15-HSQC signal was detected for 1-N-15-L-Trp in 10 mM triethanolamine hydrochloride buffer at pH 8.1-N-15-L-Trp in the presence of wild-type tryptophan synthase in the absence or presence of 50 mM sodium chloride showed a cross peak at 10.25 ppm on the H-1 axis and 129 ppm on the N-15 axis as a result of reduced solvent exchange for the bound 1-N-15-L-Trp, consistent with formation of a closed conformation of the active site. The addition of disodium alpha-glycerophosphate produced a signal twice as intense, suggesting that the equilibrium favors the closed conformation. 15N-HSQC NMR spectra of betaK87T and betaE109D mutant Trp synthase with 1-N-15-L-Trp showed a similar cross peak either in the presence or absence of disodium alpha-glycerophosphate, indicating the preference for a closed conformation for these mutant proteins. In contrast, the betaD305A Trp synthase mutant only showed a N-15-HSQC signal in the presence of disodium alpha-glycerophosphate. Thus, this mutant Trp synthase favored an open conformation in the absence of disodium alpha-glycerophosphate but was able to form a closed conformation in the presence of disodium alpha-glycerophosphate. Our results demonstrate that the N-15-HSQC NMR spectra of 1-N-15-L-Trp bound to Trp synthase can be used to determine the conformational state of mutant forms in solution rapidly. In contrast, UV-visible spectra of wild-type and mutant Trp synthase in the presence of L-Trp with NaCl and/or disodium alpha-glycerophosphate are more difficult to interpret in terms of altered conformational equilibria. C1 Univ Georgia, Dept Chem, Athens, GA 30602 USA. Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. Univ Georgia, Ctr Metalloenzyme Studies, Athens, GA 30602 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Phillips, RS (reprint author), Univ Georgia, Dept Chem, Athens, GA 30602 USA. EM rsphillips@chem.uga.edu OI Phillips, Robert/0000-0001-8710-562X FU NIGMS NIH HHS [GM42588-13] NR 44 TC 20 Z9 20 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 7 PY 2003 VL 278 IS 45 BP 44083 EP 44090 DI 10.1074/jbc.M308276200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 738UR UT WOS:000186306700025 PM 12939261 ER PT J AU Bowman, EJ Gustafson, KR Bowman, BJ Boyd, MR AF Bowman, EJ Gustafson, KR Bowman, BJ Boyd, MR TI Identification of a new chondropsin class of antitumor compound that selectively inhibits V-ATPases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VACUOLAR H+-ATPASE; PROTON-TRANSLOCATING ATPASE; C-SUBUNIT; MACROLIDE LACTAMS; GENE ENCODES; EXPRESSION; ROTATION; MARINE; BAFILOMYCINS; CONCANAMYCIN AB We identify a new naturally occurring class of inhibitor of vacuolar H+-ATPases (V-ATPases) isolated from vacuolar membranes of Neurospora crassa and from chromaffin granule membranes of Bos taurus. To date, the new class includes six chondropsins and poecillastrin A, large polyketide-derived macrolide lactams with 33 - 37 membered rings. In the National Cancer Institute's 60-cell screen the chondropsin class showed a tumor cell growth inhibitory fingerprint essentially indistinguishable from that of the bafilomycin/concanamycin and the salicylihalamide/lobatamide classes of well-established V-ATPase inhibitors. Half-maximal inhibition of V-ATPase activity in vitro occurred at 0.04 - 0.7 muM for the fungal vacuolar V-ATPase and at 0.4 to > 10 muM for the chromaffin granule V-ATPase. Thus, the new inhibitors are somewhat less potent than the other two classes, which typically have K-i values of < 10 nM for V-ATPases, and the new inhibitors differ from the other two classes in their specificity. The bafilomycin class inhibits all eucaryotic V-ATPases, the salicylihalamide class inhibits mammalian V-ATPases but not fungal V-ATPases, and the new chondropsin class inhibits the N. crassa V-ATPase better than the chromaffin granule V-ATPase. Two mutations in the N. crassa V-ATPase that affect the binding of bafilomycin had small but reproducible effects on the affinity of chondropsins for the V-ATPase, suggesting the possibility of a similar mechanism of inhibition. C1 Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA. NCI, Mol Targets Dev Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. Univ S Alabama, USA Canc Res Inst, Mobile, AL 36688 USA. RP Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA. EM rbowman@biology.ucsc.edu NR 45 TC 37 Z9 42 U1 3 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 7 PY 2003 VL 278 IS 45 BP 44147 EP 44152 DI 10.1074/jbc.M306595200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 738UR UT WOS:000186306700033 PM 12944415 ER PT J AU Lee, KA Fuda, H Lee, YC Negishi, M Strott, CA Pedersen, LC AF Lee, KA Fuda, H Lee, YC Negishi, M Strott, CA Pedersen, LC TI Crystal structure of human cholesterol sulfotransferase (SULT2B1b) in the presence of pregnenolone and 3 '-phosphoadenosine 5 '-phosphate - Rationale for specificity differences between prototypical SULT2A1 and the SULT2B1 isoforms SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN HYDROXYSTEROID SULFOTRANSFERASE; ESTROGEN SULFOTRANSFERASE; MUTATIONAL ANALYSIS; NEUROSTEROIDS; SULFATE; COMPLEX; GENE; KERATINOCYTES; DIFFERENTIATION; TRANSCRIPTION AB The gene for human hydroxysteroid sulfotransferase (SULT2B1) encodes two peptides, SULT2B1a and SULT2B1b, that differ only at their amino termini. SULT2B1b has a predilection for cholesterol but is also capable of sulfonating pregnenolone, whereas SULT2B1a preferentially sulfonates pregnenolone and only minimally sulfonates cholesterol. We have determined the crystal structure of SULT2B1a and SULT2B1b bound to the substrate donor product 3'-phosphoadenosine 5'-phosphate at 2.9 and 2.4 Angstrom, respectively, as well as SULT2B1b in the presence of the acceptor substrate pregnenolone at 2.3 Angstrom. These structures reveal a different catalytic binding orientation for the substrate from a previously determined structure of hydroxysteroid sulfotransferase (SULT2A1) binding dehydroepiandrosterone. In addition, the amino-terminal helix comprising residues Asp(19) to Lys(26), which determines the specificity difference between the SULT2B1 isoforms, becomes ordered upon pregnenolone binding, covering the substrate binding pocket. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NICHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Pedersen, LC (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 32 TC 36 Z9 41 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 7 PY 2003 VL 278 IS 45 BP 44593 EP 44599 DI 10.1074/jbc.M308312200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 738UR UT WOS:000186306700089 PM 12923182 ER PT J AU Smith, SM Pentlicky, S Klase, Z Singh, M Neuveut, C Lu, CY Reitz, MS Yarchoan, R Marx, PA Jeang, KT AF Smith, SM Pentlicky, S Klase, Z Singh, M Neuveut, C Lu, CY Reitz, MS Yarchoan, R Marx, PA Jeang, KT TI An in vivo replication-important function in the second coding exon of Tat is constrained against mutation despite cytotoxic T lymphocyte selection SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELLULAR IMMUNE-RESPONSES; HIV-1 INFECTION; CYNOMOLGUS MONKEYS; VIRAL REPLICATION; RHESUS MACAQUES; VACCINE; PROTEIN; ESCAPE; DISEASE AB Human and simian immunodeficiency virus (HIV/SIV) Tat proteins are specified by two coding exons. Tat functions in the transcription of primate lentiviruses. A plethora of in vitro data currently suggests that the second coding exon of Tat is largely devoid of function. However, whether the second exon of Tat contributes functionally to viral pathogenesis in vivo remains unknown. To address this question directly, we compared infection of rhesus macaques with an SIV, engineered to express only the first coding exon of Tat (SIVtat1ex), to counterpart infection with wild-type SIVmac239 virus, which expresses the full 2-exon Tat. This comparison showed that the second coding exon of Tat contributes to chronic SIV replication in vivo. Interestingly, in macaques, we observed a cytotoxic T lymphocytes (CTL) response to the second coding exon of Tat, which appears to durably control SIV replication. When SIV mutated in an attempt to escape this second Tat-exon-CTL, the resulting virus was less replicatively fit and failed to populate the host in vivo. Our study provides the first evidence that the second coding exon in Tat embodies an important function for in vivo replication. We suggest the second coding exon of Tat as an example of a functionally constrained "epitope" whose elicited CTL response cannot be escaped by virus mutation without producing a virus that replicates poorly in vivo. C1 St Michaels Hosp, Newark, NJ 07102 USA. Univ Med & Dent New Jersey, Newark, NJ 07102 USA. Inst Pasteur, Unite Recombinaison & Express, F-75015 Paris, France. NIAID, Mol Virol Sect, NIH, Bethesda, MD 20892 USA. Univ Maryland, Inst Biotechnol, Inst Human Virol, Baltimore, MD 21201 USA. NCI, HIV & AIDS Malignancy Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, Dept Trop Med, Covington, LA 70433 USA. Tulane Natl Primate Res Ctr, Covington, LA 70433 USA. RP Smith, SM (reprint author), St Michaels Hosp, Newark, NJ 07102 USA. RI Jeang, Kuan-Teh/A-2424-2008; OI LU, CHUN-YI/0000-0002-5240-2808 NR 56 TC 38 Z9 38 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 7 PY 2003 VL 278 IS 45 BP 44816 EP 44825 DI 10.1074/jbc.M307546200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 738UR UT WOS:000186306700116 PM 12947089 ER PT J AU Chen, H Montagnani, M Funahashi, T Shimomura, I Quon, MJ AF Chen, H Montagnani, M Funahashi, T Shimomura, I Quon, MJ TI Adiponectin stimulates production of nitric oxide in vascular endothelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; FATTY-ACID OXIDATION; INSULIN-RESISTANCE; HORMONE ADIPONECTIN; MICROVASCULAR RECRUITMENT; GLOBULAR DOMAIN; PLASMA-PROTEIN; GLUCOSE-UPTAKE; BLOOD-FLOW; MUSCLE AB Adiponectin is secreted by adipose cells and mimics many metabolic actions of insulin. However, mechanisms by which adiponectin acts are poorly understood. The vascular action of insulin to stimulate endothelial production of nitric oxide ( NO), leading to vasodilation and increased blood flow is an important component of insulin-stimulated whole body glucose utilization. Therefore, we hypothesized that adiponectin may also stimulate production of NO in endothelium. Bovine aortic endothelial cells in primary culture loaded with the NO-specific fluorescent dye 4,5-diaminofluorescein diacetate (DAF-2 DA) were treated with lysophosphatidic acid (LPA) (a calcium-releasing agonist) or adiponectin (10 mug/ml bacterially produced full-length adiponectin). LPA treatment increased production of NO by similar to4-fold. Interestingly, adiponectin treatment significantly increased production of NO by similar to3-fold. Preincubation of cells with wortmannin ( phosphatidylinositol 3-kinase inhibitor) blocked only adiponectin- but not LPA-mediated production of NO. Using phospho-specific antibodies, we observed that either adiponectin or insulin treatment ( but not LPA treatment) caused phosphorylation of both Akt at Ser(473) and endothelial nitric-oxide synthase (eNOS) at Ser(1179) that was inhibitable by wortmannin. We next transfected bovine aortic endothelial cells with dominant-inhibitory mutants of Akt (Akt-AAA) or AMP-activated protein kinase (AMPK) (AMPK-K45R). Neither mutant affected production of NO in response to LPA treatment. Importantly, only AMPK-K45R, but not Akt-AAA, caused a significant partial inhibition of NO production in response to adiponectin. Moreover, AMPK-K45R inhibited phosphorylation of eNOS at Ser(1179) in response to adiponectin but not in response to insulin. We conclude that adiponectin has novel vascular actions to directly stimulate production of NO in endothelial cells using phosphatidylinositol 3-kinase-dependent pathways involving phosphorylation of eNOS at Ser(1179) by AMPK. Thus, the effects of adiponectin to augment metabolic actions of insulin in vivo may be due, in part, to vasodilator actions of adiponectin. C1 NCCAM, Diabet Unit, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Univ Bari, Sch Med, Dept Pharmacol & Human Physiol, I-70124 Bari, Italy. Osaka Univ, Grad Sch Med, Suita, Osaka 5650871, Japan. RP Quon, MJ (reprint author), NCCAM, Diabet Unit, Clin Invest Lab, NIH, Bldg 10,Rm 6C-205,10 Ctr Dr MSC 1632, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; montagnani, monica/0000-0002-5697-8185; Quon , Michael /0000-0002-5289-3707 NR 47 TC 627 Z9 669 U1 5 U2 30 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 7 PY 2003 VL 278 IS 45 BP 45021 EP 45026 DI 10.1074/jbc.M307878200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 738UR UT WOS:000186306700139 PM 12944390 ER PT J AU Agarwal, R Tang, ZY Yu, HT Cohen-Fix, O AF Agarwal, R Tang, ZY Yu, HT Cohen-Fix, O TI Two distinct pathways for inhibiting Pds1 ubiquitination in response to DNA damage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRAND BREAK; SACCHAROMYCES-CEREVISIAE; ANAPHASE INHIBITOR; BUDDING YEAST; CHECKPOINT PATHWAYS; MITOSIS; CDC20; PHOSPHORYLATION; PROTEOLYSIS; APC AB The presence of DNA damage activates a conserved cellular response known as the DNA damage checkpoint pathway. This pathway induces a cell cycle arrest that persists until the damage is repaired. Consequently, the failure to arrest in response to DNA damage is associated with genomic instability. In budding yeast, activation of the DNA damage checkpoint pathway leads to a mitotic cell cycle arrest. Following the detection of DNA damage, the checkpoint signal is transduced via the Mec1 kinase, which in turn activates two kinases, Rad53 and Chk1 that act in parallel pathways to bring about the cell cycle arrest. The downstream target of Rad53 is unknown. The target of Chk1 is Pds1, an inhibitor of anaphase initiation whose degradation is a prerequisite for mitotic progression. Pds1 degradation is dependent on its ubiquitination by the anaphase-promoting complex/ cyclosome ubiquitin ligase, acting in conjunction with the Cdc20 protein (APC/C-Cdc20). Previous studies showed that the Rad53 and Chk1 pathways independently lead to Pds1 stabilization but the mechanism for this was unknown. In the present study we show that both the Chk1 and the Rad53 pathways inhibit the APC/ C-Cdc20-dependent ubiquitination of Pds1 but they affect different steps of the process: the Rad53 pathway inhibits the Pds1-Cdc20 interaction whereas Chk1-dependent phosphorylation of Pds1 inhibits the ubiquitination reaction itself. Finally, we show that once the DNA damage is repaired, Pds1 dephosphorylation is involved in the recovery from the checkpoint induced cell cycle arrest. C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. RP Cohen-Fix, O (reprint author), NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM61542] NR 33 TC 66 Z9 66 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 7 PY 2003 VL 278 IS 45 BP 45027 EP 45033 DI 10.1074/jbc.M306783200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 738UR UT WOS:000186306700140 PM 12947083 ER PT J AU Liu, J Batkai, S Pacher, P Harvey-White, J Wagner, JA Cravatt, BF Gao, B Kunos, G AF Liu, J Batkai, S Pacher, P Harvey-White, J Wagner, JA Cravatt, BF Gao, B Kunos, G TI Lipopolysaccharide induces anandamide synthesis in macrophages via CD14/MAPK/phosphoinositide 3-kinase/NF-kappa B independently of platelet-activating factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR-KAPPA-B; CB1 CANNABINOID RECEPTORS; NECROSIS-FACTOR-ALPHA; ACID AMIDE HYDROLASE; ENDOGENOUS CANNABINOIDS; BACTERIAL LIPOPOLYSACCHARIDE; N-ARACHIDONOYLETHANOLAMINE; HEMORRHAGIC-SHOCK; HUMAN MONOCYTES; TNF-ALPHA AB Macrophage-derived endocannabinoids have been implicated in endotoxin (lipopolysaccharide (LPS))-induced hypotension, but the endocannabinoid involved and the mechanism of its regulation by LPS are unknown. In RAW264.7 mouse macrophages, LPS (10 ng/ ml) increases anandamide (AEA) levels > 10-fold via CD14-, NF-kappaB-, and p44/42-dependent, platelet-activating factor-independent activation of the AEA biosynthetic enzymes, N-acyltransferase and phospholipase D. LPS also induces the AEA-degrading enzyme fatty acid amidohydrolase ( FAAH), and inhibition of FAAH activity potentiates, whereas actinomycin D or cycloheximide blocks the LPS-induced increase in AEA levels and N-acyltransferase and phospholipase D activities. In contrast, cellular levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) are unaffected by LPS but increased by platelet-activating factor. LPS similarly induces AEA, but not 2-AG, in mouse peritoneal macrophages where basal AEA levels are higher, and the LPS-stimulated increase in AEA is potentiated in cells from FAAH(-/-) as compared with FAAH(+/+) mice. Intravenous administration of 10(7) LPS-treated mouse macrophages to anesthetized rats elicits hypotension, which is much greater in response to FAAH(-/-) than FAAH(+/+) cells and is susceptible to inhibition by SR141716, a cannabinoid CB1 receptor antagonist. We conclude that AEA and 2-AG synthesis are differentially regulated in macrophages, and AEA rather than 2-AG is a major contributor to LPS-induced hypotension. C1 NIAAA, Lab Physiol Sci, Bethesda, MD 20892 USA. Univ Wurzburg, Dept Med, D-97080 Wurzburg, Germany. Scripps Inst, La Jolla, CA 92037 USA. RP Kunos, G (reprint author), NIAAA, Lab Physiol Sci, 12420 Parklawn Dr,MSC-8115, Bethesda, MD 20892 USA. RI Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI Pacher, Pal/0000-0001-7036-8108; NR 50 TC 134 Z9 136 U1 0 U2 10 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 7 PY 2003 VL 278 IS 45 BP 45034 EP 45039 DI 10.1074/jbc.M306062200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 738UR UT WOS:000186306700141 PM 12949078 ER PT J AU Paugh, SW Payne, SG Barbour, SE Milstien, S Spiegel, S AF Paugh, SW Payne, SG Barbour, SE Milstien, S Spiegel, S TI The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2 SO FEBS LETTERS LA English DT Article DE FTY720; sphingosine kinase; sphingosine; sphingosine-1-phosphate; phosphorylation ID FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; 1-PHOSPHATE; RECEPTORS; PROTEIN; MICE; RATS AB The potent immunosuppressive drug FTY720, a sphingosine analog, induces redistribution of lymphocytes from circulation to secondary lymphoid tissues. FTY720 is phosphorylated in vivo and functions as an agonist for four G-protein-coupled sphingosine-1-phosphate receptors. The identity of the kinase that phosphorylates FTY720 is still not known. Here we report that although both sphingosine kinase type 1 (SphK1) and type 2 (SphK2) can phosphorylate FTY720 with low efficiency, SphK2 is much more effective than SphK1. FTY720 inhibited phosphorylation of sphingosine catalyzed by SphK2 to a greater extent than it inhibits SphK1. Thus, SphK2 may be the relevant enzyme that is responsible for in vivo phosphorylation of FTY720. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem, Med Coll Virginia Campus, Richmond, VA 23298 USA. RI Paugh, Steven/A-7739-2008 OI Paugh, Steven/0000-0001-5697-9228 FU NCI NIH HHS [CA61774]; NIAID NIH HHS [AI50094] NR 15 TC 168 Z9 178 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 6 PY 2003 VL 554 IS 1-2 BP 189 EP 193 DI 10.1016/S0014-5793(03)01168-2 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 741DT UT WOS:000186444000035 PM 14596938 ER PT J AU Kim, SK Gao, ZG Van Rompaey, P Gross, AS Chen, A Van Calenbergh, S Jacobson, KA AF Kim, SK Gao, ZG Van Rompaey, P Gross, AS Chen, A Van Calenbergh, S Jacobson, KA TI Modeling the adenosine receptors: Comparison of the binding domains of A(2A) agonists and antagonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTORS; LIGAND RECOGNITION; PYRAZOLO<4,3-E>-1,2,4-TRIAZOLO<1,5-C>PYRIMIDINE DERIVATIVES; HIGHLY POTENT; A(1); RESIDUES; ACTIVATION; RHODOPSIN; IDENTIFICATION AB A three-dimensional model of the human A(2A) adenosine receptor (AR) and its docked ligands was built by homology to rhodopsin and validated with site-directed mutagenesis and the synthesis of chemically complementary agonists. Different binding modes of A(2A)AR antagonists and agonists were compared by using the FlexiDock automated docking procedure, with manual adjustment. Putative binding regions for the 9H-purine ring in agonist NECA 3 and the 1H-[1,2,4]triazolo[1,5-c]quinazoline ring in antagonist CGS15943 1 overlapped, and the exocyclic amino groups of each were H-bonded to the side chain of N-6.55. For bound agonist, H-bonds formed between the ribose 3'- and 5'-substituents and the hydrophilic amino acids T-3.36, S-7.42, and H-7.43, and the terminal methyl group of the 5'-uronamide interacted with the hydrophobic side chain of F-6.44. Formation of the agonist complex destabilized the ground-state structure of the A(2A)AR, which was stabilized through a network of H-bonding and hydrophobic interactions in the transmembrane helical domain (TM) regions, facilitating a conformational change upon activation. Both flexibility of the ribose moiety, required for the movement of TM6, and its H-bonding to the receptor were important for agonism. Two sets of interhelical H-bonds involved residues conserved among ARs but not in rhodopsin: (1) E13(1.39) and H278(7.43) and (2) D52(2.50), with the highly conserved amino acids N280(7.45) and S281(7.46), and N284(7.49) with S91(3.39). Most Of the amino acid residues lining the putative binding site(s) were conserved among the four AR subtypes. The A(2A)AR/3 complex showed a preference for an intermediate conformation about the glycosidic bond, unlike in the A(3)AR/3 complex, which featured an anti-conformation. Hydrophilic amino acids of TMs 3 and 7 (ribose-binding region) were replaced with anionic residues for enhanced binding to amine-derivatized agonists. We identified new neoceptor (T88D)-neoligand pairs that were consistent with the model. C1 NIDDKD, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. Med Chem Lab, FFW, B-9000 Ghent, Belgium. RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, LBC, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Van Calenbergh, Serge/A-3167-2008; Jacobson, Kenneth/A-1530-2009 OI Van Calenbergh, Serge/0000-0002-4201-1264; Jacobson, Kenneth/0000-0001-8104-1493 NR 60 TC 108 Z9 109 U1 0 U2 6 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 6 PY 2003 VL 46 IS 23 BP 4847 EP 4859 DI 10.1021/jm0300431 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 739LJ UT WOS:000186347400008 PM 14584936 ER PT J AU Kim, HS Ohno, M Xu, B Kim, HO Choi, YS Ji, XD Maddileti, S Marquez, VE Harden, TK Jacobson, KA AF Kim, HS Ohno, M Xu, B Kim, HO Choi, YS Ji, XD Maddileti, S Marquez, VE Harden, TK Jacobson, KA TI 2-substitution of adenine nucleotide analogues containing a bicyclo[3.1.0]hexane ring system locked in a northern conformation: Enhanced potency as P2Y(1) receptor antagonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PURINERGIC RECEPTOR; BIOLOGICAL-ACTIVITY; PHOSPHOLIPASE-C; P-2Y-PURINOCEPTOR AGONISTS; PLATELET-AGGREGATION; P2X RECEPTORS; UDP-GLUCOSE; IN-VIVO; DERIVATIVES; IDENTIFICATION AB Preference for the northern (N) ring conformation of the ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of P2Y(1), receptors was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute (Nandanan et al. J. Med. Chem. 2000, 43, 829-842). We have now combined the ring-constrained (N)-methanocarba modification with other functionalities at the 2-position of the adenine moiety. A new synthetic route to this series of bisphosphate derivatives was introduced, consisting of phosphorylation of the pseudoribose moiety prior to coupling with the adenine base. The activity of the newly synthesized analogues was determined by measuring antagonism of 2-methylthio-ADP-stimulated phospholipase C (PLC) activity in 1321N1 human astrocytoma cells expressing the recombinant human P2Y(1), receptor and by using the radiolabeled antagonist [H-3](2)-chloro-N-6-methyl-(N)-methanocarba-2'-deoxyadenosine 3',5'-bisphosphate 5 in a newly developed binding assay in Sf9 cell membranes. Within the series of 2-halo analogues, the most potent molecule at the hP2Y(1) receptor was an (N)-methanocarba N-6-methyl-2-iodo analogue 12, which displayed a K-i value in competition for binding of [H-3]5 of 0.79 nM and a K-B value of 1.74 nM for inhibition of PLC. Thus, 12 is the most potent antagonist selective for the P2Y(1), receptor yet reported. The 2-iodo group was substituted with trimethyltin, thus providing a parallel synthetic route for the introduction of an iodo group in this high-affinity antagonist. The (N)-methanocarba-2-methylthio, 2-methylseleno, 2-hexyl, 2-(1-hexenyl), and 2-(l-hexynyl) analogues bound less well, exhibiting micromolar affinity at P2Y(1), receptors. An enzymatic method of synthesis of the 3',5'-bisphosphate from the corresponding 3'-monophosphate, suitable for the preparation of a radiophosphorylated analogue, was explored. C1 NIDDK, Bioorgan Chem Lab, Mol Recognit Sect, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Seoul Natl Univ, Div Chem & Mol Engn, Seoul 151742, South Korea. NCI, Med Chem Lab, Ctr Canc Res, NIH, Ft Detrick, MD 21702 USA. Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. RP Jacobson, KA (reprint author), NIDDK, Bioorgan Chem Lab, Mol Recognit Sect, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Choi, Yongseok/F-8375-2012 OI Jacobson, Kenneth/0000-0001-8104-1493; Choi, Yongseok/0000-0002-3622-3439 FU Intramural NIH HHS [Z01 DK031116-20]; NHLBI NIH HHS [HL54889, R01 HL054889, R29 HL054889]; NIGMS NIH HHS [GM38213, R01 GM038213] NR 48 TC 91 Z9 93 U1 0 U2 3 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 6 PY 2003 VL 46 IS 23 BP 4974 EP 4987 DI 10.1021/jm030127 PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 739LJ UT WOS:000186347400020 PM 14584948 ER PT J AU Russ, P Schelling, P Scapozza, L Folkers, G De Clercq, E Marquez, VE AF Russ, P Schelling, P Scapozza, L Folkers, G De Clercq, E Marquez, VE TI Synthesis and biological evaluation of 5-substituted derivatives of the potent antiherpes agent (north)-methanocarbathymine SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SIMPLEX-VIRUS TYPE-1; THYMIDINE KINASE GENE; PURINE NUCLEOSIDE ANALOGS; VARICELLA-ZOSTER VIRUS; ANTIVIRAL ACTIVITY; IN-VIVO; QUANTITATIVE-DETERMINATION; CYTOGENETIC GENOTOXICITY; HERPESVIRUS INFECTIONS; ENANTIOMERIC FORMS AB The conformationally locked nucleoside, (north)-methanocarbathymine (1a), is a potent and selective anti-herpes agent effective against herpes simplex type I (HSV1) and type 2 (HSV2) viruses. Hereby, we report on the synthesis and biological evaluation of a small set of 5-substituted pyrimidine nucleosides belonging to the same class of bicyclo[3.1.0]hexane nucleosides. Both the 5-bromovinyl (4) and the 5-bromo analogue (3) appeared to be exclusive substrates of HSV1 thymidine kinase (TK), contrasting with the 5-iodo analogue (2), which was significantly phosphorylated by the human cytosolic TK. The binding affinity constant and catalytic turnover for HSV1 TK were measured to assess the influence of the substitution on these parameters. In the plaque reduction and cytotoxicity assays, the 5-bromo analogue (3) showed good activity against HSV1 and HSV2 with less general toxicity than la. Against varicella-zoster virus (VZV), the north-locked 5-bromovinyl analogue (4) proved to be as potent as its conformationally unlocked 2'-deoxyriboside equivalent BVDU. The three compounds were also tested in vitro as prodrugs used in a gene therapy context on three osteosarcoma cell lines, either deficient in TK (TK-), nontransduced, or stably transduced with HSV1 TK. The 5-iodo compound (2, CC50 25 +/- 7 muM) was more efficient than ganciclovir (GCV, CC50 75+/-35 muM) in inhibiting growth of HSV1-TK transfected cells and less inhibitory than GCV toward TK- cells, whereas compound 3 inhibited transfected and nontransfected cell lines in a relatively similar dose-dependent manner. C1 NCI, Canc Res Ctr, Med Chem Lab, Frederick, MD 21702 USA. Swiss Fed Inst Technol, CH-8057 Zurich, Switzerland. Katholieke Univ Leuven, Rega Inst, B-3000 Louvain, Belgium. RP Marquez, VE (reprint author), NCI, Canc Res Ctr, Med Chem Lab, 376 Boyles St, Frederick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov NR 52 TC 45 Z9 47 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 6 PY 2003 VL 46 IS 23 BP 5045 EP 5054 DI 10.1021/jm030241s PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 739LJ UT WOS:000186347400026 PM 14584954 ER PT J AU Goss, PE Ingle, JN Martino, S Robert, NJ Muss, HB Piccart, MJ Castiglione, M Tu, D Shepherd, LE Pritchard, KI Livingston, RB Davidson, NE Norton, L Perez, EA Abrams, JS Therasse, P Palmer, MJ Pater, JL AF Goss, PE Ingle, JN Martino, S Robert, NJ Muss, HB Piccart, MJ Castiglione, M Tu, D Shepherd, LE Pritchard, KI Livingston, RB Davidson, NE Norton, L Perez, EA Abrams, JS Therasse, P Palmer, MJ Pater, JL TI A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ONCOLOGY TECHNOLOGY-ASSESSMENT; AROMATASE INHIBITOR LETROZOLE; RECEPTOR-POSITIVE TUMORS; SURGICAL-ADJUVANT-BREAST; BONE-MINERAL DENSITY; ESTROGEN-RECEPTOR; CELL-PROLIFERATION; AMERICAN-SOCIETY; PREVENTION; RESISTANCE AB BACKGROUND: In hormone-dependent breast cancer, five years of postoperative tamoxifen therapy -- but not tamoxifen therapy of longer duration -- prolongs disease-free and overall survival. The aromatase inhibitor letrozole, by suppressing estrogen production, might improve the outcome after the discontinuation of tamoxifen therapy. METHODS: We conducted a double-blind, placebo-controlled trial to test the effectiveness of five years of letrozole therapy in postmenopausal women with breast cancer who have completed five years of tamoxifen therapy. The primary end point was disease-free survival. RESULTS: A total of 5187 women were enrolled (median follow-up, 2.4 years). At the first interim analysis, there were 207 local or metastatic recurrences of breast cancer or new primary cancers in the contralateral breast -- 75 in the letrozole group and 132 in the placebo group -- with estimated four-year disease-free survival rates of 93 percent and 87 percent, respectively, in the two groups (P lessthan/equal 0.001 for the comparison of disease-free survival). A total of 42 women in the placebo group and 31 women in the letrozole group died (P=0.25 for the comparison of overall survival). Low-grade hot flashes, arthritis, arthralgia, and myalgia were more frequent in the letrozole group, but vaginal bleeding was less frequent. There were new diagnoses of osteoporosis in 5.8 percent of the women in the letrozole group and 4.5 percent of the women in the placebo group (P=0.07); the rates of fracture were similar. After the first interim analysis, the independent data and safety monitoring committee recommended termination of the trial and prompt communication of the results to the participants. CONCLUSIONS: As compared with placebo, letrozole therapy after the completion of standard tamoxifen treatment significantly improves disease-free survival. C1 Princess Margaret Hosp, Div Hematol Oncol, Toronto, ON M5G 2M9, Canada. Mayo Clin, Rochester, MN USA. John Wayne Canc Inst, Santa Monica, CA USA. Inova Fairfax Hosp, Falls Church, VA USA. Univ Vermont, Burlington, VT USA. Inst Jules Bordet, B-1000 Brussels, Belgium. Int Breast Canc Study Grp Coordinating Ctr, Bern, Switzerland. Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Univ Washington, Seattle, WA 98195 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Jacksonville, FL 32224 USA. NCI, Canc Therapy Evaluat Program, Clin Invest Branch, Rockville, MD USA. European Org Res Treatment Canc, Ctr Data, Brussels, Belgium. RP Goss, PE (reprint author), Princess Margaret Hosp, Div Hematol Oncol, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. FU NCI NIH HHS [CA21115, CA25224, CA31946, CA32102, CA38926] NR 42 TC 1104 Z9 1138 U1 1 U2 37 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 6 PY 2003 VL 349 IS 19 BP 1793 EP 1802 DI 10.1056/NEJMoa032312 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 739NR UT WOS:000186353800003 PM 14551341 ER PT J AU Bryant, J Wolmark, N AF Bryant, J Wolmark, N TI Letrozole after tamoxifen for breast cancer - What is the price of success? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Allegheny Gen Hosp, Dept Human Oncol, Pittsburgh, PA 15212 USA. RP Bryant, J (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. NR 4 TC 32 Z9 32 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 6 PY 2003 VL 349 IS 19 BP 1855 EP 1857 DI 10.1056/NEJMe038167 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 739NR UT WOS:000186353800012 PM 14551339 ER PT J AU Seminario, MC Precht, P Wersto, RP Gorospe, M Wange, RL AF Seminario, MC Precht, P Wersto, RP Gorospe, M Wange, RL TI PTEN expression in PTEN-null leukaemic T cell lines leads to reduced proliferation via slowed cell cycle progression SO ONCOGENE LA English DT Article DE PTEN; proliferation; cell cycle; apoptosis ID TUMOR-SUPPRESSOR PTEN; ANTIGEN RECEPTOR; CARCINOMA-CELLS; PHOSPHATASE-ACTIVITY; GROWTH ARREST; APOPTOSIS; ACTIVATION; PATHWAY; SIZE; STIMULATION AB The balance of activities between the proto-oncogene phosphoinositide 3-kinase (PI3K) and the tumour suppressor gene PTEN has been shown to affect cellular growth and proliferation, as well as tumorigenesis. Previously, PTEN expression in the PTEN-null Jurkat T cell leukaemia line was shown to cause reduced proliferation without cell cycle arrest. Here, we further these investigations by determining the basis for this phenomenon. By BrdU pulse-chase and cell cycle arrest and release assays, we find that PTEN expression reduced proliferation by slowing progression through all phases of the cell cycle. This was associated with reduced levels of cyclins A, B1 and B2, cdk4, and cdc25A and increased p27(KIP1) expression. Apoptosis played no role in the antiproliferative effect of PTEN, since only marginal increases in the rate of apoptosis were detected upon PTEN expression, and inhibitors of effector caspases did not restore proliferative capacity. Active Akt blocked the antiproliferative effects of PTEN, indicating that PTEN mediates its effects through conventional PI3K-linked signalling pathways. Similar results were obtained from a different PTEN-null leukaemia T cell line, CEM. Together, these results show that PTEN expression in leukaemic T cells leads to reduced proliferation via an apoptosis-independent mechanism involving slower passage through the cell cycle. C1 NIA, Cellular & Mol Biol Lab, IRP, NIH,DHHS, Baltimore, MD 21224 USA. NIA, Flow Cytometry Lab, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Wange, RL (reprint author), NIA, Cellular & Mol Biol Lab, IRP, NIH,DHHS, 5600 Nathan Shock Dr,MSC-12, Baltimore, MD 21224 USA. NR 47 TC 37 Z9 43 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 6 PY 2003 VL 22 IS 50 BP 8195 EP 8204 DI 10.1038/sj.onc.1206872 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 740LG UT WOS:000186403400014 PM 14603260 ER PT J AU Wan, XL Helman, LJ AF Wan, XL Helman, LJ TI Levels of PTEN protein modulate Akt phosphorylation on serine 473, but not on threonine 308, in IGF-II-overexpressing rhabdomyosarcomas cells SO ONCOGENE LA English DT Article DE Akt; phosphorylation; PTEN ID TUMOR-SUPPRESSOR PTEN; GROWTH-FACTOR-II; INTEGRIN-LINKED KINASE; SIGNAL-TRANSDUCTION; PROSTATE-CANCER; GLIOMA-CELLS; ACTIVATION; INSULIN; INHIBITION; EXPRESSION AB Constitutive activation of Akt has been found in many types of human cancer, and is believed to promote proliferation and increased cell survival thereby contributing to cancer progression. In this study, we examined Akt phosphorylation on Ser473 and Thr308 in seven IGF-II-overexpressing rhabdomyosarcomas (RMS) cells. All the RMS cell lines tested had high levels of Akt phosphorylation on Thr308, whereas three cell lines (Rh5, Rh18, and CTR) had a much lower level of Akt phosphorylation on Ser473. To determine whether the difference in Akt phosphorylation on Ser473, but not on Thr308, observed among cell lines is a cell-specific phenomenon or due to other factors, which possibly downregulate Akt phosphorylation, we examined expression of PTEN protein, which acts as a negative regulator of the PI3K/Akt signaling pathway through its ability to dephosphorylate phosphatidylinositol 3,4,5-triphosphate (PIP3). The levels of PTEN expression inversely correlate with Akt phosphorylation on Ser473, but not on Thr308. Consistent with this finding, transfection of wild-type PTEN into RMS and mouse myoblast C2C12 cells resulted in reduced Akt phosphorylation on Ser473, but not on Thr308. Our data suggest that Ser473 may be a key target residue for PTEN to modulate the effects of IGF-II on activating the PI3K/Akt pathway in RMS cells. A better understanding of the pathway in RMS will likely contribute to insights into the biology of the RMS tumorigenesis and hopefully lead to novel therapeutic options. C1 NCI, Mol Oncol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Helman, LJ (reprint author), NCI, Mol Oncol Sect, Pediat Oncol Branch, NIH, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. NR 53 TC 61 Z9 61 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 6 PY 2003 VL 22 IS 50 BP 8205 EP 8211 DI 10.1038/sj.onc.1206878 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 740LG UT WOS:000186403400015 PM 14603261 ER PT J AU Shearman, AM Cupples, LA Demissie, S Peter, I Schmid, CH Karas, RH Mendelsohn, ME Housman, DE Levy, D AF Shearman, AM Cupples, LA Demissie, S Peter, I Schmid, CH Karas, RH Mendelsohn, ME Housman, DE Levy, D TI Association between estrogen receptor alpha gene variation and cardiovascular disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-ARTERY-DISEASE; BONE-MINERAL DENSITY; HORMONE REPLACEMENT THERAPY; RANDOMIZED CONTROLLED TRIAL; VITAMIN-D-RECEPTOR; POSTMENOPAUSAL WOMEN; HEART-DISEASE; PLUS PROGESTIN; BREAST-CANCER; MYOCARDIAL-INFARCTION AB Context Estrogen and related hormone therapies activate estrogen receptors, which in turn regulate genes for several cardiovascular disease (CVD) risk factors. Relatively little is known, however, about the impact of genetic variation in estrogen receptor a (ESR1) on CVD risk. Objective To investigate whether the ESR1 c.454-397T>C polymorphism is associated with CVD risk. Design, Setting, and Participants Prospective study of 1739 unrelated men and women from the population-based offspring cohort of the Framingham Heart Study, who were followed up from 1971 to 1998. Main Outcome Measures Total atherosclerotic CVD events, defined as recognized or unrecognized myocardial infarction (MI), angina pectoris, coronary insufficiency, intermittent claudication, coronary heart disease death, or atherothrombotic stroke (n=178); major atherosclerotic CVD, defined as recognized acute MI, coronary insufficiency, coronary heart disease death, or atherothrombotic stroke (n=83); and recognized acute MI (n=59). Results Twenty percent of participants (n=352) were homozygous for the ESR1 c.454-397C allele. After adjustment for covariates (age, sex, body mass index, hypertension, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, and cigarette smoking), the CC genotype was significantly associated with major atherosclerotic CVD, with an odds ratio of 2.0 (95% confidence interval [CI], 1.3-3.2; P=.004) compared with individuals with the CT or TT genotypes. Participants with the CC genotype had 3.0-fold greater odds of MI (95% Cl, 1.7-5,2; P<.001) compared with those with the CT or TT genotype. The results remained significant when analyses were restricted to men; too few women had events to study them separately. Conclusions Individuals with the common ESR1 c.454-397CC genotype have a substantial increase in risk of MI. Whether ESR1 c.454-397T>C is causally related to MI risk or in linkage disequilibrium with 1 or more causal variants remains to be determined. These findings support the importance of estrogen receptors in CVD susceptibility, especially in men. Estrogen receptor variation also has potential to explain recent conflicting data regarding the effects of hormone therapy on CVD susceptibility in women. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Tufts New England Med Ctr, Dept Med, Div Clin Care Res, Biostat Res Ctr, Boston, MA USA. Tufts New England Med Ctr, Dept Med, Mol Cardiol Res Inst, Boston, MA USA. Tufts New England Med Ctr, Specialized Ctr Res Ischem Heart Dis, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Shearman, AM (reprint author), MIT, Ctr Canc Res, E17-536, Cambridge, MA 02139 USA. FU NHLBI NIH HHS [P50 HL63494, N01-HC-38038, R01-HL65230, N01-HC-25195, P50-HL63494] NR 43 TC 195 Z9 200 U1 1 U2 14 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 5 PY 2003 VL 290 IS 17 BP 2263 EP 2270 DI 10.1001/jama.290.17.2263 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 739PZ UT WOS:000186356800020 PM 14600184 ER PT J AU Rosas, MER Preston, KL Epstein, DH Moolchan, ET Wainer, IW AF Rosas, MER Preston, KL Epstein, DH Moolchan, ET Wainer, IW TI Quantitative determination of the enantiomers of methadone and its metabolite (EDDP) in human saliva by enantio selective liquid chromatography with mass spectrometric detection SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE enantiomer separation; chiral stationary phases, LC; methadone; 2-ethylene-1,5-dimethyl-3,3-diphenyl-pyrrolidine ID CHIRAL STATIONARY PHASE; ALPHA-1-ACID GLYCOPROTEIN; STEREOSELECTIVE DETERMINATION; ALPHA(1)-ACID GLYCOPROTEIN; MAIN METABOLITE; ENANTIOSELECTIVE ANALYSIS; DRUGS; PLASMA; COLUMN; SERUM AB A sensitive enantioselective liquid chromatographic assay with mass spectrometric detection (LC-MS) has been developed and validated for the simultaneous determination of saliva concentrations of (R)- and (S)-methadone (Met) and (R)- and (S)-2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine (EDDP, a primary metabolite of Met). Saliva specimens were collected using Salivette devices (Sarsedt), and centrifuged; collected saliva was then spiked with deuterated internal standards, D3-Met and D3-EDDP, and directly injected into the LC-MS. Enantioselective separations were achieved on a liquid chromatographic chiral stationary phase (CSP) based upon immobilized alpha(1)-acid glycoprotein (AGP) using a mobile phase composed of acetonitrile: ammonium acetate buffer (10 mM, pH 7.0) in a ratio of 18:82 (v/v), a flow rate of 0.9 ml/min and a temperature of 25 degreesC. Under these conditions, enantioselective separations were observed for methadone (alpha = 1.30) and EDDP (alpha = 1.17) within 15 min. Met, EDDP, D3-Met and D3-EDDP were detected using selected ion monitoring at m/z 310.20, 278.20, 313.20 and 281.20, respectively. Linear relationships between peak height ratio and drug-enantiomer concentrations were obtained for methadone in the range of 5.0-600.0 ng/ml, and for EDDP from 0.5 to 15.0 ng/ml per enantiomer with correlation coefficients better than 0.9994, where lower limit of quantification (LLOQ) for Met was 5 ng/ml and for EDDP 0.5 ng/ml. Acceptable intra- and inter-day precision of the method (CVs < 4.0%) and accuracy (CVs < 4.0%) were obtained. These findings demonstrate the accuracy and precision of the method used to successfully analyze saliva obtained from patients enrolled in a methadone-maintenance program. Published by Elsevier B.V. C1 NIA, Bioanalyt & Drug Discovery Unit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIDA, Intramural Res Program, Clin Pharmacol & Therapeut Res Branch, NIH, Baltimore, MD USA. RP Wainer, IW (reprint author), NIA, Bioanalyt & Drug Discovery Unit, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 41 TC 25 Z9 25 U1 0 U2 1 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 5 PY 2003 VL 796 IS 2 BP 355 EP 370 DI 10.1016/j.jchromb.2003.08.017 PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 740BQ UT WOS:000186381300014 PM 14581075 ER PT J AU Yadav, G Straume, M Heath, J Zatz, M AF Yadav, G Straume, M Heath, J Zatz, M TI Are changes in MAPK/ERK necessary or sufficient for entrainment in chick pineal cells? SO JOURNAL OF NEUROSCIENCE LA English DT Article DE MAPK; ERK; MEK inhibitor; circadian rhythms; clocks; entrainment; signal transduction; melatonin ID ACTIVATED PROTEIN-KINASE; MAP KINASE; CIRCADIAN CLOCK; SUPRACHIASMATIC NUCLEUS; GENE-EXPRESSION; LIGHT; PATHWAYS; INHIBITOR; GLAND; OSCILLATION AB Chick pineal cells in culture display a circadian rhythm of melatonin release. Light pulses can entrain (phase shift) the rhythm. One candidate for the photoentrainment pathway uses a mitogen-activated protein kinase (MAPK), also known as extracellular signal regulated kinase (ERK). We tested the hypothesis that activation of ERK (by phosphorylation to p-ERK) is necessary and/or sufficient for entrainment by measuring the ability of several drugs, light, and other perturbations to change levels of p-ERK and to induce phase shifts in the melatonin rhythm. If changes in the levels of p-ERK are sufficient for photoentrainment, then all perturbations that reduce its level must induce light-like phase shifts, and all those that increase its level must induce dark-like phase shifts. If such changes are necessary for photoentrainment, then light pulses must reduce p-ERK levels, and the duration of the light pulse, the magnitude and duration of the change in p-ERK, and the size of the phase shift must correlate. We found five perturbations that reduced p-ERK levels. Of these, two induced light-like phase shifts (PD 98059 and caffeine), one induced dark-like phase shifts (SB203580), and two did not induce phase shifts at all (U0126 and omitting a medium change). Serum increased p-ERK levels without inducing any phase shifts. Finally, light pulses did not elicit changes in p-ERK, nor was there a diurnal rhythm in p-ERK levels, nor could rapid changes in p-ERK levels have accounted for duration effects of light pulses on phase shifts. Taken together, these results argue strongly against the hypothesis that reduction (or increases) in MAPK/ERK activation is necessary or sufficient for entrainment in chick pineal cells. C1 NIMH, Lab Cellular & Mol Regulat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Virginia, Dept Internal Med, Ctr Biomath Technol, Charlottesville, VA 22903 USA. RP Zatz, M (reprint author), NIMH, Lab Cellular & Mol Regulat, NIH, Dept Hlth & Human Serv, Bldg 36,Room 2A-11, Bethesda, MD 20892 USA. NR 37 TC 8 Z9 10 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 5 PY 2003 VL 23 IS 31 BP 10021 EP 10031 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 741RZ UT WOS:000186474200008 PM 14602816 ER PT J AU Watanabe, K Lauwereyns, J Hikosaka, O AF Watanabe, K Lauwereyns, J Hikosaka, O TI Neural correlates of rewarded and unrewarded eye movements in the primate caudate nucleus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE caudate; motivation; reinforcement; saccade; monkey; latency ID PREFRONTAL CORTEX; NEURONAL-ACTIVITY; BASAL GANGLIA; STRIATUM; SIGNALS; EXPECTATION; NEUROPHYSIOLOGY; MOTIVATION; BEHAVIOR; GO AB The prospect of immediate reward elicits goal-oriented behavior. However, animals often have to perform actions that do not immediately lead to reward in the pursuit of a long-term goal. Here we identify neural activity in monkey caudate nucleus that specifically correlates with rewarded and unrewarded eye movements. The monkey performed a visually guided saccade task in which only one position was associated with positive reinforcement. To advance in the experimental session, however, the monkey had no choice but to complete a saccade to an unrewarded position as well as to a rewarded position. Some caudate saccadic neurons showed enhanced activity around the time of the saccade in rewarded trials ( rewarded-saccade neurons). Another subset of neurons discharged selectively around the execution of the saccade in unrewarded trials ( unrewarded-saccade neurons). In both rewarded and unrewarded trials, stronger activity of these neurons was associated with reduced saccade latency. These results suggest that both rewarded and unrewarded saccades are facilitated by caudate saccadic activity. The neuronal activity of unrewarded-saccade neurons might reflect the required execution of unrewarded eye movements on the way to future reward. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Adv Ind Sci & Technol, Inst Human Sci & Biomed Engn, Tsukuba, Ibaraki 3058566, Japan. Victoria Univ Wellington, Sch Psychol, Wellington 6006, New Zealand. RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA. NR 27 TC 74 Z9 78 U1 2 U2 9 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 NOV 5 PY 2003 VL 23 IS 31 BP 10052 EP 10057 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 741RZ UT WOS:000186474200011 PM 14602819 ER PT J AU Hashimoto, I Li, XK Bhat, AH Jones, M Zetts, AD Sahn, DJ AF Hashimoto, I Li, XK Bhat, AH Jones, M Zetts, AD Sahn, DJ TI Myocardial strain rate is a superior method for evaluation of left ventricular subendocardial function compared with tissue doppler imaging SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HYPERTROPHIC CARDIOMYOPATHY; VELOCITY-GRADIENT; SYSTOLIC FUNCTION; ISCHEMIC-MYOCARDIUM; DIASTOLIC FUNCTION; REGIONAL LEFT; RELAXATION ABNORMALITIES; STRESS ECHOCARDIOGRAPHY; SYSTEMIC HYPERTENSION; LONGITUDINAL FUNCTION AB OBJECTIVES This study was performed to evaluate subendocardial function using strain rate imaging (SRI). BACKGROUND The subendocardium and mid-wall of the left ventricle (LV) play important roles in ventricular function. Previous methods used for evaluating this function are either invasive or cumbersome. Strain rate imaging by ultrasound is a newly developed echocardiographic modality based on tissue Doppler imaging (TDI) that allows quantitative assessment of regional myocardial wall motion. METHODS We examined eight sheep using TDI in apical four-chamber views to evaluate the LV free wall. Peak strain rates (SRs) during isovolumic relaxation (IR), isovolumic contraction (IC), and myocardial strain were measured in the endocardial (End), mid-myocardial (Mid), and epicardial (Epi) layers. For four hemodynamic conditions (created after baseline by blood, dobutamine, and metoprolol infusion), we compared differences in SR of End, Mid, and Epi layers to peak positive and negative first derivative of LV pressure (dP/dt). RESULTS Strain rate during IC showed a good correlation with +dP/dt (r = 0.74, p < 0.001) and during IR with -dP/dt (r = 0.67, p = 0.0003). There was a significant difference in SR between the myocardial layers during both IC and IR (End: -3.4 +/- 2.2 s(-1), Mid: -1.8 +/- 1.5 s(-1), Epi: -0.63 +/- 1.0 s(-1), p < 0.0001 during IC; End: 2.2 +/- 1.5 s(-1) Mid: 1.0 +/- 0.8 s(-1), Epi: 0.47 +/- 0.64 s(-1), p < 0.0001. during IR). Also, SRs of the End and Mid layers during IC were significantly altered by different hemodynamic conditions (End at baseline: 1.7 +/- 0.7 s(-1); blood: 2.0 +/- 1.1 s(-1); dobutamine: 3.4 +/- 2.3 s(-1); metoprolol: 1.0 +/- 0.4 s(-1); p < 0.05). Myocardial strain showed differences in each layer (End: -34.3 +/- 12.6%; Mid: -22.6 +/- 12.1%; Epi: -11.4 +/- 7.9%; p < 0.0001) and changed significantly in different hemodynamic conditions (p < 0.0001). CONCLUSIONS Strain and SR appear useful and sensitive for evaluating myocardial function, especially for the subendocardial region. (C) 2003 by the American College of Cardiology Foundation. C1 Oregon Hlth Sci Univ, Clin Care Ctr Congenital Heart Dis, Portland, OR 97239 USA. NHLBI, Bethesda, MD 20892 USA. RP Sahn, DJ (reprint author), Oregon Hlth Sci Univ, Clin Care Ctr Congenital Heart Dis, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. NR 44 TC 89 Z9 118 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 5 PY 2003 VL 42 IS 9 BP 1574 EP 1583 DI 10.1016/S0735-1097(03)01074-X PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 739LU UT WOS:000186348600008 PM 14607441 ER PT J AU Hauptmann, M Lubin, JH Stewart, PA Hayes, RB Blair, A AF Hauptmann, M Lubin, JH Stewart, PA Hayes, RB Blair, A TI Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SISTER-CHROMATID EXCHANGES; CHROMOSOME-ABERRATIONS; CANCER MORTALITY; NASAL-MUCOSA; MARROW-CELLS; BONE-MARROW; CROSS-LINKS; IN-VITRO; RATS; LYMPHOCYTES AB Background: Many U.S. factory workers are exposed to formaldehyde. Although increased risks for leukemia have been found in medical workers and other professionals exposed to formaldehyde, studies in industrial workers, who are thought to have higher exposures, have shown inconsistent associations. We extended follow-up of a cohort of industrial workers to evaluate the association between formaldehyde exposure and lymphohematopoietic cancers. Methods: The cohort consisted of 25 619 workers (865 708 person-years) employed before January 1, 1966, at one of 10 U.S. industrial plants and followed through December 31, 1994. We analyzed formaldehyde exposure (peak exposure, average exposure intensity, cumulative exposure, and duration of exposure) and mortality from lymphohematopoietic malignancies using standardized mortality ratios and relative risks and 95% confidence intervals (CIs) based on Poisson regression. Statistical tests were two-sided. Results: Among the cohort, there were 178 deaths from lymphohematopoietic malignancies. Relative risks for leukemia (69 deaths), particularly for myeloid leukemia (30 deaths), increased with formaldehyde exposure. Compared with workers exposed to low peak levels of formaldehyde (0.1-1.9 ppm), relative risks for myeloid leukemia were 2.43 (95% CI = 0.81 to 7.25) and 3.46 (95% CI = 1.27 to 9.43) for workers exposed to peak levels of 2.0-3.9 ppm and greater than or equal to4.0 ppm, respectively (P-trend =.009). Compared with workers exposed to low levels of average exposure intensity of formaldehyde (0.1-0.4 ppm), workers exposed to 0.5-0.9 ppm and greater than or equal to1.0 ppm average intensity had relative risks of 1.15 (95% CI = 0.41 to 3.23) and 2.49 (95% CI = 1.03 to 6.03), respectively (P-trend =.088). The relative risk for leukemia was not associated with cumulative exposure but was weakly associated with duration of exposure. Relative risks for Hodgkin's disease also increased with formaldehyde exposure. Conclusions: Exposure to formaldehyde may cause leukemia, particularly myeloid leukemia, in humans. However, results from other investigations are mixed, suggesting caution in drawing definitive conclusions. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hauptmann, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd, Bethesda, MD 20892 USA. NR 49 TC 110 Z9 120 U1 0 U2 11 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 5 PY 2003 VL 95 IS 21 BP 1615 EP 1623 DI 10.1093/jnci/djg083 PG 9 WC Oncology SC Oncology GA 739DW UT WOS:000186327800012 PM 14600094 ER PT J AU Feng, HQ Takei, J Lipsitz, R Tjandra, N Bai, YW AF Feng, HQ Takei, J Lipsitz, R Tjandra, N Bai, YW TI Specific non-native hydrophobic interactions in a hidden folding intermediate: Implications for protein folding SO BIOCHEMISTRY LA English DT Article ID MOLTEN GLOBULE INTERMEDIATE; STATE HYDROGEN-EXCHANGE; STRUCTURAL CHARACTERIZATION; CYTOCHROME-C; NATIVE-STATE; PATHWAYS; APOMYOGLOBIN; MECHANISM; NMR; DENATURATION AB Structures of intermediates and transition states in protein folding are usually characterized by an-tide hydrogen exchange and protein engineering methods and interpreted on the basis of the assumption that they have native-like conformations. We were able to stabilize and determine the high-resolution structure of a partially unfolded intermediate that exists after the rate-limiting step of a four-helix bundle protein, Rd-apocyt b(562), by multidimensional NMR methods. The intermediate has partial native-like secondary structure and backbone topology, consistent with our earlier native state hydrogen exchange results. However, non-native hydrophobic interactions exist throughout the structure. These and other results in the literature suggest that non-native hydrophobic interactions may occur generally in partially folded states. This can alter the interpretation of mutational protein engineering results in terms of native-like side chain interactions. In addition, since the intermediate exists after the rate-limiting step and Rdapocyt b(562) folds very rapidly (k(f) similar to 10(4) s(-1)), these results suggest that non-native hydrophobic interactions, in the absence of topological misfolding, are repaired too rapidly to slow folding and cause the accumulation of folding intermediates. More generally, these results illustrate an approach for determining the high-resolution structure of folding intermediates. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 55 TC 57 Z9 57 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 4 PY 2003 VL 42 IS 43 BP 12461 EP 12465 DI 10.1021/bi035561s PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 742RD UT WOS:000186531100004 PM 14580191 ER PT J AU Hwang, KJ Xiang, BS Gruschus, JM Nam, KY No, KT Nirenberg, M Ferretti, JA AF Hwang, KJ Xiang, BS Gruschus, JM Nam, KY No, KT Nirenberg, M Ferretti, JA TI Distortion of the three-dimensional structure of the vnd/NK-2 homeodomain bound to DNA induced by an embryonically lethal A35T point mutation SO BIOCHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; NMR-SPECTROSCOPY; SECONDARY STRUCTURE; NK-2 HOMEODOMAIN; CHEMICAL-SHIFTS; GENE-EXPRESSION; HOMEOBOX GENES; NOESY-HMQC; HELIX-III; PROTEINS AB The three-dimensional solution structure obtained by NMR of the A35T mutant vnd/NK-2 homeodomain bound to the vnd/NK-2 consensus 16 bp DNA sequence was determined. This mutation to threonine from alanine in position 35 in helix 11 of the vnd/NK-2 homeodomain is associated with early embryonic lethality in Drosophila melanogaster. Although the unbound mutant protein is not structured, in the DNA-bound state it adopts the three-helix fold characteristic of all known homeodomains, but with alterations relative to the structure of the wild-type analogue. These structural modifications occur, and are accompanied by a 50-fold reduction in the DNA binding affinity, even though most of the protein-DNA interactions originally seen for the wild-type homeodomain are found likewise in the threonine analogue. Alterations include torsional angle changes in the loop between helix I and helix 11, and in the turn between helix 11 and helix 111, as well as in a distortion of the usual antiparallel orientation of helix I with respect to helix II. The alteration of the position of leucine 40 in the A35T mutant is proposed to explain the observed 1.27 ppm upfield shift of the corresponding amide proton resonance relative to the value observed for the wild-type analogue. A detailed comparison of the structures of the mutant A35T and wild-type vnd/NK-2 homeodomains bound to the cognate DNA is presented. The consequences of the structural alteration of the DNA-bound A35T mutant vnd/NK-2 protein may constitute the basis of the observed early embryonic lethality. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. Soong Sil Univ, Comp Aided Mol Design Res Ctr, Seoul 156743, South Korea. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ferretti, JA (reprint author), 50 South Dr, Bethesda, MD 20892 USA. NR 55 TC 1 Z9 1 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 4 PY 2003 VL 42 IS 43 BP 12522 EP 12531 DI 10.1021/bi030116i PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 742RD UT WOS:000186531100011 PM 14580198 ER PT J AU Ahmed, SA McPhie, P Smith, LA AF Ahmed, SA McPhie, P Smith, LA TI Autocatalytically fragmented light chain of botulinum A neurotoxin is enzymatically active SO BIOCHEMISTRY LA English DT Article ID CLOSTRIDIAL NEUROTOXINS; SPECTROSCOPIC ANALYSIS; TRYPTOPHAN SYNTHASE; STRUCTURAL-ANALYSIS; HEAVY-CHAIN; ACTIVATION; MECHANISM; TOXIN; TETANUS; SNAP-25 AB The zinc-endopeptidase light chain of botulinum A neurotoxin undergoes autocatalytic fragmentation that is accelerated by the presence of the metal cofactor, zinc [Ahmed, S. A. et al. (2001) J. Protein Chem. 20, 221-231]. We show in this paper that >95% fragmented light chain obtained in the absence of added zinc retained 100% of its original catalytic activity against a SNAP-25-derived synthetic peptide substrate. In the presence of zinc chloride, when >95% of the light chain had undergone autocatalytic fragmentation, the preparation retained 35% of its original catalytic activity. On the other hand, in the presence of glycerol, the light chain did not display autocatalysis and retained 100% of the original activity. These results suggest that the activity loss by incubation with zinc was not a direct consequence of autocatalysis and that the environment of the active site was not affected significantly by the fragmentation. The optimum pH 4.2-4.6 for autocatalysis was different than that (pH 7.3) for intrinsic catalytic activity. Inhibition of autocatalysis at low pH by a competitive inhibitor of catalytic activity rules out the presence of a contaminating protease but suggests a rate-limiting step of low pH-induced conformational change suitable for autocatalysis. Our results of LC concentration dependence of the fragmentation reaction indicate that the autocatalysis occurs by both intramolecular and intermolecular mechanisms. C1 USA, Med Res Inst Infect Dis, Dept Immunol & Mol Biol, Ft Detrick, MD 21702 USA. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Ahmed, SA (reprint author), USA, Med Res Inst Infect Dis, Dept Immunol & Mol Biol, 1425 Porter St, Ft Detrick, MD 21702 USA. NR 51 TC 18 Z9 18 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 4 PY 2003 VL 42 IS 43 BP 12539 EP 12549 DI 10.1021/bi030062c PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 742RD UT WOS:000186531100013 PM 14580200 ER PT J AU Pletnev, S Magracheva, E Kozlov, S Tobin, G Kotenko, SV Wlodawer, A Zdanov, A AF Pletnev, S Magracheva, E Kozlov, S Tobin, G Kotenko, SV Wlodawer, A Zdanov, A TI Characterization of the recombinant extracellular domains of human interleukin-20 receptors and their complexes with interleukin-19 and interleukin-20 SO BIOCHEMISTRY LA English DT Article ID FUNCTIONAL-CHARACTERIZATION; CRYSTAL-STRUCTURE; CUTTING EDGE; ORF VIRUS; CYTOKINE; HOMOLOG; IL-10; EXPRESSION; CLONING; FAMILY AB The soluble extracellular domains of human interleukin-20 (IL-20) receptors I and 11 (sIL-20R1 and sIL20R2), along with their ligands IL-19 and IL-20, were expressed in Drosophila S2 cells and purified to homogeneity. Formation of the receptor/receptor and ligand/receptor complexes was studied by size exclusion chromatography. Both ligands and soluble receptors were found to be monomeric in solution; homo- or heterodimers are not formed even at elevated concentrations. Under native conditions, both IL-19 and IL-20 form stable ternary 1:1:1 complexes with the sIL-20R1 and sIL20R2 receptors, as well as high-affinity binary complexes with sIL-20R2. Unexpectedly, sIL-20R1 does not bind on its own to either IL-19 or IL-20. Thus, one of the possible consecutive mechanisms of formation of the signaling ternary complex may involve two steps: first, the ligand binds to receptor II, creating a high-affinity binding site for the receptor I, and only then does receptor I complete the complex. C1 NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21701 USA. NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Biol Mimet Inc, Ft Detrick, MD 21702 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. RP Zdanov, A (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21701 USA. FU NCI NIH HHS [N01-CO-12400]; NIAID NIH HHS [R01 AI051139, R01 AI51139] NR 30 TC 35 Z9 44 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 4 PY 2003 VL 42 IS 43 BP 12617 EP 12624 DI 10.1021/bi0354583 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 742RD UT WOS:000186531100021 PM 14580208 ER PT J AU Suzuki, N Ichikawa, N Kasai, S Yamada, M Nishi, N Morioka, H Yamashita, H Kitagawa, Y Utani, A Hoffman, MP Nomizu, M AF Suzuki, N Ichikawa, N Kasai, S Yamada, M Nishi, N Morioka, H Yamashita, H Kitagawa, Y Utani, A Hoffman, MP Nomizu, M TI Syndecan binding sites in the laminin alpha 1 chain G domain SO BIOCHEMISTRY LA English DT Article ID TERMINAL GLOBULAR DOMAIN; HEPARIN-BINDING; MOUSE LAMININ; SYNTHETIC PEPTIDES; CELL-ADHESION; NEURITE OUTGROWTH; INTEGRIN-RECOGNITION; SUBMANDIBULAR-GLAND; GAMMA-1 CHAIN; BETA-1 CHAIN AB The laminin alpha1 chain G domain has multiple biological activities. Previously, we identified cell binding sequences in the laminin alpha1 chain G domain by screening 113 synthetic peptide-polystyrene beads for cell attachment activity. Here, we have used a recombinant protein of the laminin alpha1 G domain (rec-alpha1G) and a large set of synthetic peptides to further identify and characterize heparin, cell, and syndecan-4 binding sites in the laminin alpha1 chain G domain. The rec-alpha1G protein promoted both cell attachment and heparin binding (K-D = 19 nM). Cell attachment to the rec-alpha1G protein was inhibited 60% by heparin and 30% by EDTA. The heparin binding sites were identified by competing heparin binding to the rec-alpha1G protein with 110 synthetic peptides in solution. Only two peptides, AG73 (IC50 = 147 muM) and AG75 (IC50 = 206 muM), inhibited heparin binding to rec-alpha1G. When the peptides were compared in a solid-phase heparin binding assay, AG73 showed more heparin binding than AG75. AG73 also inhibited fibroblast attachment to the rec-alpha1G protein, but AG75 did not. Cell attachment to the peptides was studied using peptide-coated plates and peptide-conjugated sepharose beads. AG73 promoted cell attachment in both assays, but AG75 only showed cell attachment activity in the bead assay. Additionally, AG73, but not AG75, inhibited branching morphogenesis of mouse submandibular glands in organ culture. Furthermore, the rec-alpha1G protein bound syndecan-4, and both AG73 and AG75 inhibited this binding. These results suggest that the AG73 and AG75 sites are important for heparin and syndecan-4 binding in the laminin alpha1 chain G domain. These sites may play a critical role in the diverse biological activities involving heparin and syndecan-4 binding. C1 Hokkaido Univ, Grad Sch Environm Earth Sci, Sapporo, Hokkaido 0600810, Japan. Hokkaido Univ, Grad Sch Pharmaceut Sci, Sapporo, Hokkaido 0600810, Japan. Nagoya Univ, Grad Sch Bioagr Sci, Grad Course Regulat Biol Signals, Nagoya, Aichi 4648601, Japan. Chiba Univ, Sch Med, Dept Dermatol, Chiba 2608670, Japan. NIDCR, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. RP Nomizu, M (reprint author), Hokkaido Univ, Grad Sch Environm Earth Sci, Sapporo, Hokkaido 0600810, Japan. NR 50 TC 45 Z9 45 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 4 PY 2003 VL 42 IS 43 BP 12625 EP 12633 DI 10.1021/bi030014s PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 742RD UT WOS:000186531100022 PM 14580209 ER PT J AU Kim, IJ Ullrich, T Janetka, JW Furness, MS Jacobson, AE Rothman, RB Dersch, CM Flippen-Anderson, JL George, C Rice, KC AF Kim, IJ Ullrich, T Janetka, JW Furness, MS Jacobson, AE Rothman, RB Dersch, CM Flippen-Anderson, JL George, C Rice, KC TI Diaryldimethylpiperazine ligands with mu- and delta-opioid receptor affinity: Synthesis of (+)-4-[(alpha R)-alpha-(4-allyl-(2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenyl)methy l]-N-ethyl-N- phenylbenzamide and (-)-4-[(alpha R)-alpha-(2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenyl)methyl]-N-ethy l-N-phenylbenzamide SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID MESSAGE-ADDRESS CONCEPT; MEDIATED PHENOMENA; (+)-4-<(ALPHA-R)-ALPHA-((2S,5R)-4-ALLYL-2,5-DIMETHYL-1-PIPERAZINYL)-3-ME THOXYBE SNC-80; MORPHINE-TOLERANCE; ANTAGONISTS; AGONISTS; DEPENDENCE; POTENT; PROBES; NALTREXONE AB We have explored the synthesis of compounds that have good affinity for both mu- and delta-opioid receptors from the (alphaR,2S,5S) class of diaryldimethylpiperazines. These non-selective compounds were related to opioids that have been found to interact selectively with mu- or delta-opioid receptors as agonists or antagonists. In our initial survey, we found two compounds, (+)-4[(alphaR)-alpha-(4-allyl-(2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenyl)methyl]-N-ethyl-N-phenylbenzamide (14) and its N-H relative, (-)-4-[(alphaR)-alpha-(2S,5S)-dimethylpiperazin-1-yl)-(3-hydroxyphenylmethyl]-N-ethyl-N-phenylbenzamide (15), that interacted with delta-receptors with good affinity, and, as we hoped, with much higher affinity at p-receptors than SNC80. The relative configuration of the benzylic position in (+)-4-[(alphaR)-alpha-(4-allyl-(2S,5S)-dimethyl-1-piperazinyl)-(3-methoxyphenyl)methyl]-benzyl alcohol (10) was determined by X-ray crystallographic analysis of a crystal that was an unresolved twin. The absolute stereochemistry of that benzylic stereogenic center was unequivocally derived by the X-ray crystallographic analysis from the two other centers of asymmetry in the molecule that were known. Those were established from the synthesis via a dipeptide cyclo-L-Ala-L-Ala in which the absolute stereochemistry was established. Published by Elsevier Ltd. C1 NIDDKD, Med Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. RP Jacobson, AE (reprint author), NIDDKD, Med Chem Lab, NIH, Dept Hlth & Human Serv, Bldg 8,Room B1-23, Bethesda, MD 20892 USA. RI Janetka, James/A-8216-2011 OI Janetka, James/0000-0002-9888-5411 NR 27 TC 4 Z9 4 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD NOV 3 PY 2003 VL 11 IS 22 BP 4761 EP 4768 DI 10.1016/S0968-0896(03)00496-6 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 735VA UT WOS:000186134200008 PM 14556791 ER PT J AU Simon, R AF Simon, R TI Diagnostic and prognostic prediction using gene expression profiles in high-dimensional microarray data SO BRITISH JOURNAL OF CANCER LA English DT Review DE microarray; gene expression profiling; diagnostic classification; prognostic classification ID B-CELL LYMPHOMA; MOLECULAR CLASSIFICATION; BREAST-CANCER; ALGORITHMS; MELANOMA; SURVIVAL; SETS AB DNA microarrays are a potentially powerful technology for improving diagnostic classification, treatment selection and therapeutics development. There are, however, many potential pitfalls in the use of microarrays that result in false leads and erroneous conclusions. This paper provides a review of the key features to be observed in developing diagnostic and prognostic classification systems based on gene expression profiling and some of the pitfalls to be aware of in reading reports of microarray-based studies. C1 NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, 9000 Rockville Pike,MSC 7434, Bethesda, MD 20892 USA. NR 26 TC 102 Z9 109 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 3 PY 2003 VL 89 IS 9 BP 1599 EP 1604 DI 10.1038/sj.bjc.6601326 PG 6 WC Oncology SC Oncology GA 747DG UT WOS:000186789500001 PM 14583755 ER PT J AU Holick, CN Michaud, DS Leitzmann, MF Willett, WC Giovannucci, E AF Holick, CN Michaud, DS Leitzmann, MF Willett, WC Giovannucci, E TI Aspirin use and lung cancer in men SO BRITISH JOURNAL OF CANCER LA English DT Article DE aspirin; lung cancer; chemoprevention; prospective studies; epidemiology ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CHEMOPREVENTIVE EFFICACIES; UNITED-STATES; A/J MICE; RISK; TUMORIGENESIS; WOMEN; DISEASE; COX-2; PREVENTION AB We examined prospectively the relation between regular aspirin use and lung cancer risk in the Health Professionals Follow-Up Study. Of 49 383 US men aged 40 - 75 years who completed biennial self-administered questionnaires that assessed aspirin use beginning in 1986, 328 developed lung cancer during 601 453 person-years of follow-up through 31 December 2000. No information on aspirin dose was available. Controlling for current age, smoking status, and age at starting to smoke regularly, the relative risk (RR) of total lung cancer for regular users of aspirin ( twice or more per week) at baseline compared to nonusers was 1.13 (95% confidence interval (CI) = 0.89 - 1.43). Results were similar for non- small- cell lung cancer (RR = 1.16; 95% CI = 0.88 - 1.54). No apparent dose-dependent association was observed for the frequency of aspirin use and lung cancer risk ( P for trend = 0.64), and results remained null when consistent use of aspirin over time was examined. These findings do not suggest that regular aspirin use is associated with a reduced lung cancer risk. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Holick, CN (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 677 Huntington Ave, Boston, MA 02115 USA. RI Michaud, Dominique/I-5231-2014 FU NCI NIH HHS [CA55075, P01 CA055075] NR 22 TC 36 Z9 38 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 3 PY 2003 VL 89 IS 9 BP 1705 EP 1708 DI 10.1038/sj.bjc.6601343 PG 4 WC Oncology SC Oncology GA 747DG UT WOS:000186789500019 PM 14583773 ER PT J AU Murakami, T Cardones, AR Finkelstein, SE Restifo, NP Klaunberg, BA Nestle, FO Castillo, SS Dennis, PA Hwang, ST AF Murakami, T Cardones, AR Finkelstein, SE Restifo, NP Klaunberg, BA Nestle, FO Castillo, SS Dennis, PA Hwang, ST TI Immune evasion by murine melanoma mediated through CC chemokine receptor-10 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE metastasis; chemokine receptor; cancer; cell signaling ID PULSED DENDRITIC CELLS; LYMPH-NODE METASTASIS; T-CELLS; EPITHELIAL-CELLS; AKT ACTIVATION; CUTTING EDGE; FAS LIGAND; IFN-GAMMA; EXPRESSION; B16 AB Human melanoma cells frequently express CC chemokine receptor (CCR)10, a receptor whose ligand (CCL27) is constitutively produced by keratinocytes. Compared with B16 murine melanoma, cells rendered more immunogenic via overexpression of luciferase, B16 cells that overexpressed both luciferase and CCR10 resisted host immune responses and readily formed tumors. In vitro, exposure of tumor cells to CCL27 led to rapid activation of Akt, resistance to cell death induced by melanoma antigen-specific cytotoxic T cells, and phosphatidylinositol-3-kinase (PI3K)-dependent protection from apoptosis induced by Fas cross-linking. In vivo, cutaneous injection of neutralizing antibodies to endogenous CCL27 blocked growth of CCP10-expressing melanoma cells. We propose that CCR10 engagement by locally produced CCL27 allows melanoma cells to escape host immune antitumor killing mechanisms (possibly through activation of PI3K/Akt), thereby providing a means for tumor progression. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Therapeut Branch, CCR, NIH, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. RP Hwang, ST (reprint author), Bldg 10,Rm 12N246,10 Ctr Dr, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 44 TC 92 Z9 97 U1 1 U2 2 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 3 PY 2003 VL 198 IS 9 BP 1337 EP 1347 DI 10.1084/jem.20030593 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 740VY UT WOS:000186423700006 PM 14581607 ER PT J AU Schioppa, T Uranchimeg, B Saccani, A Biswas, SK Doni, A Rapisarda, A Bernasconi, S Saccani, S Nebuloni, M Vago, L Mantovani, A Melillo, G Sica, A AF Schioppa, T Uranchimeg, B Saccani, A Biswas, SK Doni, A Rapisarda, A Bernasconi, S Saccani, S Nebuloni, M Vago, L Mantovani, A Melillo, G Sica, A TI Regulation of the chemokine receptor CXCR4 by hypoxia SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE cell migration; SDF-1/CXCL12 receptor (CXCR4); low oxygen concentration; hypoxia-inducible factor 1 (HIF-1) ID TUMOR-ASSOCIATED MACROPHAGES; INDUCIBLE FACTOR-1; ENDOTHELIAL-CELLS; IN-VIVO; CARCINOMA; CANCER; ANGIOGENESIS; EXPRESSION; INFLAMMATION; METASTASIS AB Cell adaptation to hypoxia (Hyp) requires activation of transcriptional programs that coordinate expression of genes involved in oxygen delivery (via angiogenesis) and metabolic adaptation (via glycolysis). Here, we describe that oxygen availability is a determinant parameter in the setting of chemotactic responsiveness to stromal-derived factor 1 (CXCL12). Low oxygen concentration induces high expression of the CXCL12 receptor, CXC receptor 4 (CXCP4), in different cell types (monocytes, monocyte-derived macrophages, tumor-associated macrophages, endothelial cells, and cancer cells), which is paralleled by increased chemotactic responsiveness to its specific ligand. CXCR4 induction by Hyp is dependent on both activation of the Hyp-inducible factor 1 alpha and transcript stabilization. In a relay multistep navigation process, the Hyp-Hyp-inducible factor 1 alpha-CXCR4 pathway may regulate trafficking in and out of hypoxic tissue micro enviroriments. C1 Mario Negri Inst Pharmacol Res, I-20157 Milan, Italy. State Univ Milan, Inst Pathol, Ctr Eccellenza Innovaz Diangnost & Terapeut, I-20133 Milan, Italy. Biomed Res Inst, CH-6500 Bellinzona, Switzerland. Univ Milan, Dept Clin Sci L Sacco, Inst Pathol, I-20157 Milan, Italy. NCI, Sci Applicat Int Corp Frederick Inc, Tumor Hypoxia Lab, Dev Therapeut Program, Frederick, MD 21702 USA. RP Sica, A (reprint author), Mario Negri Inst Pharmacol Res, Via Eritrea 62, I-20157 Milan, Italy. OI Mantovani, Alberto/0000-0001-5578-236X; Saccani, Simona/0000-0001-7572-3308; Schioppa, Tiziana/0000-0002-6303-6065 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 55 TC 483 Z9 506 U1 7 U2 26 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 3 PY 2003 VL 198 IS 9 BP 1391 EP 1402 DI 10.1084/jem.20030267 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 740VY UT WOS:000186423700011 PM 14597738 ER PT J AU Dolensky, B Kirk, KL AF Dolensky, B Kirk, KL TI New approaches to side-chain fluorinated bioimidazoles: 4-alkynylimidazoles as substrates for fluorination SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE alkynes; "FBr" addition; urocanic acid ID STABILIZED PHOSPHORUS YLIDES; FLASH VACUUM PYROLYSIS; BUILDING-BLOCKS; REAGENTS; ESTERS; DERIVATIVES; ACETYLENES; HISTAMINE; ALKYNES AB 4-Alkynylimidazoles have been prepared and their behavior as substrates for "FBr" addition (NBS + (Et3N3HF)-H-.) have been studied. Facile Markownikov addition to ethylnylimidazole 2 gave fluorobromoolefin 9a, a potential synthon for the 2-imidazolyl-2-fluoro-1-ethenyl moiety. Reaction of the lithium salt of 2 with diethyl oxalate produced imidazolylpropynoic ester 3b. However, because of the deactivating effect of the ester functionality, all attempts to carry out addition of "FBr" to 3b met with failure. Reduction of the ester gave the hydroxymethyl-substituted acetylene 4. Addition of "FBr" to this substrate and reductive removal of bromine from the product produced fluoroolefins 12, precursors to E- and Z-beta-fluorourocanic acids. The same fluoroolefins can be used as intermediates in the synthesis of beta-fluorohistidinols. (C) 2003 Elsevier B.V. All rights reserved. C1 NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM kennethk@bdg8.niddk.nih.gov NR 18 TC 5 Z9 5 U1 2 U2 5 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD NOV 3 PY 2003 VL 124 IS 1 BP 105 EP 110 DI 10.1016/S0022-1139(03)00197-0 PG 6 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 743DF UT WOS:000186556600015 ER PT J AU Black, S AF Black, S TI Evolutionary role of left-handed proteins SO SCIENTIST LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Black, S (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU SCIENTIST INC PI PHILADELPHIA PA 3535 MARKET ST, SUITE 200, PHILADELPHIA, PA 19104-3385 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD NOV 3 PY 2003 VL 17 IS 21 BP 11 EP 11 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 738NL UT WOS:000186294700004 ER PT J AU Pandit, SD Bednarski, M Li, KCP AF Pandit, SD Bednarski, M Li, KCP TI A primer on molecular biology for imagers: 1. DNA, how does it work? SO ACADEMIC RADIOLOGY LA English DT Article C1 NIH, Mol Imaging Lab, Imaging Sci Program, Ctr Clin, Bethesda, MD 20892 USA. RP Pandit, SD (reprint author), NIH, Mol Imaging Lab, Imaging Sci Program, Ctr Clin, 10-1N306,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 8 Z9 8 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2003 VL 10 IS 11 BP 1215 EP 1223 DI 10.1016/S1076-6332(03)00379-9 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 738VA UT WOS:000186307500002 PM 14626296 ER PT J AU Iordanescu, G Summers, RM AF Iordanescu, G Summers, RM TI Automated centerline for computed tomography colonography SO ACADEMIC RADIOLOGY LA English DT Article DE computed tomography (CT); colon; computed tomography; 3D reconstruction; centerline detection; colon cancer; image processing ID CT COLONOGRAPHY; VIRTUAL ENDOSCOPY; COLON; PATH; FEASIBILITY; EXTRACTION; ALGORITHM; ROBUST AB Rationale and Objectives. A novel method to compute the centerline of the human colon obtained from computed tomography colonography is proposed. Two applications of this method are demonstrated: to compute local colonic distension (caliber), and to match polyps on supine and prone images. Materials and Methods. The centerline algorithm involves multiple steps including simplification of the colonic surface by decimation; thinning of the decimated colon to create a preliminary centerline; selection of equally spaced points on the preliminary centerline; grouping neighboring points; and mapping them back to rings in the original colon. This method was tested on 20 human computed tomography colonography datasets (supine and prone examinations of 10 patients) and on a computer-generated colon phantom. Results. Visual inspection of the colons and their centerlines showed the centerline to be accurate. For the colon phantom, the average error was only 1 mm. For 11 polyps visualized in both the supine and prone positions and found by computer-aided detection, the normalized distance along the centerline to each polyp was not significantly different on the supine and prone views (r = 0.999; P <.001). Conclusion. This method produces an accurate colon centerline that may be useful for flight path planning, matching detections on the supine and prone views, and computing local colonic distension. C1 NIH, Dept Radiol, Bethesda, MD 20892 USA. RP NIH, Dept Radiol, Bldg 10,Room 1C660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. NR 32 TC 22 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2003 VL 10 IS 11 BP 1291 EP 1301 DI 10.1016/S1076-6332(03)00464-1 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 738VA UT WOS:000186307500010 PM 14626304 ER PT J AU Dauter, Z AF Dauter, Z TI Twinned crystals and anomalous phasing SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID INTENSITY STATISTICS; PROTEIN CRYSTALS; ISOMORPHOUS REPLACEMENT; MOLECULAR-REPLACEMENT; STRUCTURE REFINEMENT; ANGSTROM-RESOLUTION; MEROHEDRY; DIFFRACTION; SIGNAL; HALF AB Merohedral or pseudomerohedral twinning of crystals cannot be identified from inspection of the diffraction patterns. Several methods for the identification of twinning and the estimation of the twin fraction are suitable for macromolecular crystals and all are based on the statistical properties of the measured diffraction intensities. If the crystal twin fraction is estimated and is not too close to 0.5, the diffraction data can be detwinned; that is, related to the individual crystal specimen. However, the detwinning procedure invariably introduces additional inaccuracies to the estimated intensities, which substantially increase when the twin fraction approaches 0.5. In some cases, a crystal structure can be solved with the original twinned data by standard techniques such as molecular replacement, multiple isomorphous replacement or multiwavelength anomalous diffraction. Test calculations on data collected from a twinned crystal of gpD, the bacteriophage lambda capsid protein, show that the single-wavelength anomalous diffraction (SAD) method can be used to solve its structure even if the data set corresponds to a perfectly twinned crystal with a twin fraction of 0.5. C1 NCI, Synchrotron Radiat Res Sect, Brookhaven Natl Lab, Upton, NY 11973 USA. RP Dauter, Z (reprint author), NCI, Synchrotron Radiat Res Sect, Brookhaven Natl Lab, Bldg 725A-X9, Upton, NY 11973 USA. NR 49 TC 42 Z9 42 U1 1 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD NOV PY 2003 VL 59 BP 2004 EP 2016 DI 10.1107/S0907444903021085 PN 11 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 735UN UT WOS:000186133100015 PM 14573956 ER PT J AU Fuller, R AF Fuller, R TI Conversation with Richard Fuller SO ADDICTION LA English DT Editorial Material ID DISULFIRAM TREATMENT; ALCOHOLISM; TRIAL; OUTCOMES C1 NIAAA, Clin & Prevent Res Program, Bethesda, MD USA. NR 13 TC 0 Z9 0 U1 3 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD NOV PY 2003 VL 98 IS 11 BP 1485 EP 1492 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 743GT UT WOS:000186564600003 PM 14616174 ER PT J AU Singleton, EG Anderson, LM Heishman, SJ AF Singleton, EG Anderson, LM Heishman, SJ TI Reliability and validity of the Tobacco Craving Questionnaire and validation of a craving-induction procedure using multiple measures of craving and mood SO ADDICTION LA English DT Article DE imagery; mood; reliability; smoking urge; tobacco craving; validity ID DRUG URGES; COEFFICIENT-ALPHA; IMAGERY SCRIPTS; ADDICTION; INSTRUMENT; ALCOHOL; MODEL AB Aims To determine the reliability and validity of the Tobacco Craving Questionnaire (TCQ) and the validity of imagery scripts to elicit self-reported tobacco craving. Design Active imagery of three auditory scripts that described no-. low- and high-intensity of smoking urge. Participants Current cigarette smokers (24 men, 24 women) not attempting to quit or reduce smoking. Measurements After each imagery condition, participants completed the 47-item TCQ, a Mood Form and Visual Analog Scale (VAS) questions. Findings Reliability of measures was demonstrated by internal consistency and unidimensionality of the four TCQ factors across imagery conditions. Criterion-related validity was demonstrated by an orderly increase in scores on the TCQ and VAS craving measures as a function of craving intensity of the imagery scripts. Increases in effect size parameters and parallel decreases in the stability of test-retest reliability for all craving measures indicated the validity of the imagery procedure. Convergent and discriminant validity were established by the craving scripts increasing self-reported craving, the no-craving (positive-affect) script increasing positive mood, the no-craving script not affecting craving and the craving scripts not affecting positive mood. Conclusions Findings further demonstrated the reliability and validity of the TCQ as a multi-factorial instrument to assess the construct of tobacco craving and suggested that the lability of craving, rather than inconsistency and instability in its measurement, was responsible for observed effects. C1 NIDA, Clin Pharmacol & Therapeut Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Heishman, SJ (reprint author), NIDA, Clin Pharmacol & Therapeut Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Singleton, Edward G./0000-0003-3442-877X NR 32 TC 27 Z9 31 U1 1 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD NOV PY 2003 VL 98 IS 11 BP 1537 EP 1546 DI 10.1046/j.1360-0443.2003.00449.x PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 743GT UT WOS:000186564600009 PM 14616180 ER PT J AU Melzer, D Lan, TY Guralnik, JM AF Melzer, D Lan, TY Guralnik, JM TI The predictive validity for mortality of the index of mobility-related limitation - results from the EPESE study SO AGE AND AGEING LA English DT Article DE disability; mobility limitation; mortality ID PEAK EXPIRATORY FLOW; ELDERLY POPULATION; OLDER PERSONS; DISABILITY; RISK; SURVIVAL; WOMEN AB Background: self-reported disability reflects physical, environmental and attitudinal factors. We have previously reported the empirical identification of three simple tests to provide an index of (ambulatory) mobility-related physiological limitations (MOBLI). Evidence of the MOBLI's responsiveness over time has been presented. Evidence of the predictive validity of the index is needed. Objective: we aimed to measure the predictive validity for future mortality of the MOBLI and of self-reported mobility disability in a longitudinal cohort study. Methods: data are from the sixth annual interview for two sites in the Established Populations for Epidemiologic Studies of the Elderly study. Included were 3,040 people, with information about self-reported walking difficulties, walking speed, time to complete five chair stands and peak expiratory flow. Age- and sex-adjusted death rates over a 4-year follow-up were computed, and proportional hazards regression models were used in the analysis. Results: the MOBLI score is associated with subsequent mortality over 4 years, with evidence of a 'dose-response' relationship. The predictive value for mortality of the MOBLI score is similar to that of self-reported mobility disability in the studied population. Conclusions: the 'objective' MOBLI index has predictive validity as a continuous or dichotomised measure of the physiological component of mobility limitation in older populations. Given its empirical basis and face validity, predictive validity and responsiveness to change, MOBLI should be considered for local validation and use in epidemiological comparisons of older populations across countries or over longer periods of time. C1 Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 2SR, England. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Melzer, D (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Forvie Site,Robinson Way, Cambridge CB2 2SR, England. RI Lan, Tzuo-Yun /E-3844-2010; OI Melzer, David/0000-0002-0170-3838 NR 29 TC 42 Z9 42 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0002-0729 J9 AGE AGEING JI Age Ageing PD NOV PY 2003 VL 32 IS 6 BP 619 EP 625 DI 10.1093/ageing/afg107 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 743PV UT WOS:000186583500011 PM 14600003 ER PT J AU Mierzejewski, P Rogowski, A Stefanski, R Goldberg, S Kostowski, W Bienkowski, P AF Mierzejewski, P Rogowski, A Stefanski, R Goldberg, S Kostowski, W Bienkowski, P TI Ethanol-reinforced behaviour predicts acquisition but not extinction of cocaine self-administration in the rat SO ALCOHOL AND ALCOHOLISM LA English DT Article ID ALCOHOL-PREFERRING AA; AVOIDING ANA RATS; SEEKING BEHAVIOR; FAMILIAL TRANSMISSION; DOPAMINERGIC SYSTEM; NOVELTY-SEEKING; ORAL ETHANOL; DRUG; PREEXPOSURE; AMPHETAMINE AB Aims: The aim of the present study was to evaluate the relationship between operant oral ethanol self-administration and intravenous (i.v.) cocaine self-administration in mate Wistar rats. Methods: Twenty-four rats were trained to lever press for 8% v/v ethanol in the sucrose-fading procedure. The subjects with the highest (high ethanol responders [HER], n = 7) and lowest (low ethanol responders [LER], n = 7) ethanol intakes were selected for further experiments. After a wash-out period, during which i.v. catheters were implanted. the HER and LER were trained to nose-poke for cocaine infusions (0.33 mg/kg/infusion, a FR1 schedule) for nine daily sessions. Results: The HER emitted more 'active' nose-pokes and obtained more cocaine infusions during sessions 2-4. Drug-seeking behaviour in the absence of cocaine reinforcement was then assessed for three consecutive extinction sessions. No between-group differences were found in terms of extinction of cocaine seeking. Locomotor responses to a novel environment were also similar in both groups. Conclusions: The present results suggest that a propensity to self-administer ethanol predicts more rapid acquisition of cocaine self-administration behaviour but does not influence subsequent behaviour during extinction. C1 Inst Psychiat & Neurol, Dept Pharmacol, PL-02957 Warsaw, Poland. Med Acad Warsaw, Dept Expt & Clin Pharmacol, Warsaw, Poland. NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD USA. RP Bienkowski, P (reprint author), Inst Psychiat & Neurol, Dept Pharmacol, 9 Sobieskiego St, PL-02957 Warsaw, Poland. NR 55 TC 13 Z9 13 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD NOV-DEC PY 2003 VL 38 IS 6 BP 543 EP 549 DI 10.1093/alcalc/agg114 PG 7 WC Substance Abuse SC Substance Abuse GA 754FR UT WOS:000187292500003 PM 14633641 ER PT J AU Flaker, G Greenspon, A Tardiff, B Schron, E Goldman, L Hellkamp, A Lee, K Lamas, G AF Flaker, G Greenspon, A Tardiff, B Schron, E Goldman, L Hellkamp, A Lee, K Lamas, G CA MOST Investigators TI Death in patients with permanent pacemakers for sick sinus syndrome SO AMERICAN HEART JOURNAL LA English DT Article ID LONG-TERM SURVIVAL; ATRIAL-FIBRILLATION; NODE DYSFUNCTION; CARDIAC DEATH; DUAL-CHAMBER; FOLLOW-UP; CLASSIFICATION; DISEASE; TRIAL; IMPLANTATION AB Background Although more than one million patients in the United States have permanent pacemakers, little is known about their cause of death. We evaluated the cause of death in 404 patients who died in the Mode Selection Trial (MOST). Methods In MOST, patients received a dual-chamber pacemaker randomly programmed to either dual-chamber or ventricular pacing. The circumstances surrounding each death were reviewed by a clinical events committee, which used prospectively defined criteria to adjudicate the cause of death. Results A total of 2010 patients with a median age of 74 years were included. After a median follow-up of 33 months, 404 (20%) patients died, including 198 (49%) of noncardiac causes and 143 (35.4%) of cardiac causes. In 63 patients, the cause of death was unknown. Independent predictors of death through the use of a multivariable analysis were (1) demographic factors including age, male sex, and weight; (2) clinical factors including prior myocardial infarction, cardiomyopathy, New York Heart Association class III/IV, and the Charlson Comorbidity Index; and (3) scores from two measures of functional status, the Karnofsky Score and the Mini-Mental State Examination. Independent predictors of cardiovascular death were similar. Conclusions Patients treated with permanent pacemakers for sinus node dysfunction are elderly and have a substantial mortality rate, with more than half the classifiable deaths being noncardiac. Baseline demographic variables and scores from quality-of-life measures can identify patients with the highest risk of death. C1 Univ Missouri, Div Cardiol, Columbia, MO 65212 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Duke Clin Res Inst, Durham, NC USA. NHLBI, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Miami, Mt Sinai Med Ctr, Sch Med, Miami Beach, FL 33140 USA. Univ Miami, Sch Med, Miami Heart Inst, Miami Beach, FL USA. RP Flaker, G (reprint author), Univ Missouri, Div Cardiol, Columbia, MO 65212 USA. FU NHLBI NIH HHS [U01-HL-49804, U01-HL-53973, U01-HL-55981] NR 25 TC 12 Z9 12 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2003 VL 146 IS 5 BP 887 EP 893 DI 10.1067/S0002-8703(03)00429-0 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 741ZW UT WOS:000186491100024 PM 14597940 ER PT J AU Caballero, B Clay, T Davis, SM Ethelbah, B Rock, BH Lohman, T Norman, J Story, M Stone, EJ Stephenson, L Stevens, J AF Caballero, B Clay, T Davis, SM Ethelbah, B Rock, BH Lohman, T Norman, J Story, M Stone, EJ Stephenson, L Stevens, J CA Pathways Study Res Grp TI Pathways: a school-based, randomized controlled trial for the prevention of obesity in American Indian schoolchildren SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE obesity; American Indians; schoolchildren; prevention programs; randomized trials ID CARDIOVASCULAR HEALTH CATCH; PHYSICAL-ACTIVITY PROGRAM; INTERDISCIPLINARY INTERVENTION; NUTRITION EDUCATION; ADOLESCENT TRIAL; CHILDREN; WEIGHT; OVERWEIGHT; PREVALENCE; HEIGHT AB Background: Childhood obesity is a major public health problem in the United States, particularly among American Indian communities. Objective: The objective was to evaluate the effectiveness of a school-based, multicomponent intervention for reducing percentage body fat in American Indian schoolchildren. Design: This study was a randomized, controlled, school-based trial involving 1704 children in 41 schools and was conducted over 3 consecutive years, from 3rd to 5th grades, in schools serving American Indian communities in Arizona, New Mexico, and South Dakota. The intervention had 4 components: 1) change in dietary intake, 2) increase in physical activity, 3) a classroom curriculum focused on healthy eating and lifestyle, and 4) a family-involvement program. The main outcome was percentage body fat; other outcomes included dietary intake, physical activity, and knowledge, attitudes, and behaviors. Results: The intervention resulted in no significant reduction in percentage body fat. However, a significant reduction in the percentage of energy from fat was observed in the intervention schools. Total energy intake (by 24-h dietary recall) was significantly reduced in the intervention schools but energy intake (by direct observation) was not. Motion sensor data showed similar activity levels in both the intervention and control schools. Several components of knowledge, attitudes, and behaviors were also positively and significantly changed by the intervention. Conclusions: These results document the feasibility of implementing a multicomponent program for obesity prevention in elementary schools serving American Indian communities. The program produced significant positive changes in fat intake and in food- and health-related knowledge and behaviors. More intense or longer interventions may be needed to significantly reduce adiposity in this population. C1 Johns Hopkins Univ, Baltimore, MD USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Arizona, Tucson, AZ 85721 USA. NHLBI, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Gila River Indian Community, Chapel Hill, NC USA. RP Caballero, B (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, 615 N Wolfe St, Baltimore, MD 21205 USA. FU NHLBI NIH HHS [U01 HL050869, U01 HL050867, U01-HL-50885, U01-HL-50905, U01-HL-50907] NR 35 TC 319 Z9 323 U1 4 U2 49 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2003 VL 78 IS 5 BP 1030 EP 1038 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 736AA UT WOS:000186146500021 PM 14594792 ER PT J AU Simons-Morton, BG Haynie, DL AF Simons-Morton, BG Haynie, DL TI Psychosocial predictors of increased smoking stage among sixth graders SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE substance use; parent-child relations; adolescence; attitudes ID ADOLESCENT SUBSTANCE USE; CIGARETTE-SMOKING; UNITED-STATES; PERCEIVED COMPETENCES; YOUNG ADOLESCENTS; PARENTAL SMOKING; NATURAL-HISTORY; INNER-CITY; PEER; INITIATION AB Objectives: To identify predictors of increases in smoking stage among sixth graders. Methods: At the beginning and end of sixth grade, 973 students completed surveys. Multivariate, partial proportional odds analyses were conducted. Results: Time 1 intenders were 4 times more likely than never users to smoke at Time 2. In adjusted analyses, female sex, white race, peers, and perceived prevalence were positively associated with an increase in smoking stage, and social competence, parental expectations, and parental monitoring were negatively associated with an increase in smoking stage. Conclusions: Early adolescent smoking advanced in stages; intent predicted initiation; peer and parent influences were independently associated with increases in smoking stage. C1 NICHD, DESPR, Prevent Res Branch, Rockville, MD 20852 USA. Natl Inst Child Hlth & Human Dev, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA. RP Simons-Morton, BG (reprint author), NICHD, DESPR, Prevent Res Branch, 6100 Execut Blvd,Rm 7B05, Rockville, MD 20852 USA. OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 FU NICHD NIH HHS [N01-HD-4-3207] NR 49 TC 22 Z9 22 U1 1 U2 1 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD NOV-DEC PY 2003 VL 27 IS 6 BP 592 EP 602 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 750EE UT WOS:000186977700002 PM 14672390 ER PT J AU Best, A Moor, G Holmes, B Clark, PI Bruce, T Leischow, S Buchholz, K Krajnak, J AF Best, A Moor, G Holmes, B Clark, PI Bruce, T Leischow, S Buchholz, K Krajnak, J TI Health promotion dissemination and systems thinking: Towards an integrative model SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article; Proceedings Paper CT 3rd Scientific Meeting of the American-Academy-of-Health-Behavior CY MAR 16-19, 2003 CL ST AUGUSTINE, FLORIDA SP Amer Acad Hlth Behavior DE systems thinking; dissemination; health promotion; community; planning AB Objective: To help close the gap between health promotion research and practice by using systems thinking. Methods: We reviewed 3 national US tobacco control initiatives and a project (ISIS) that had introduced systems thinking to tobacco control, speculating on ways in which systems thinking may add value to health promotion dissemination and implementation in general. Results: The diversity of disciplines involved in tobacco control have created disconnection in the field; systems thinking is necessary to increase the impact of strategies. Conclusion: Systems thinking has potential to improve synthesis, translation, and dissemination of research findings in other health promotion initiatives. C1 Vancouver Hosp & Hlth Sci Ctr, Ctr Clin Epidemiol & Evaluat, Vancouver, BC V5Z 1L8, Canada. Simon Fraser Univ, Sch Commun, Burnaby, BC V5A 1S6, Canada. Battelle Ctr Publ Hlth Res & Evaluat, Baltimore, MD USA. Vancouver Coastal Hlth Author, Hlth Syst Policy Dev & Community Involvement, Vancouver, BC, Canada. US NCI, Tobacco Control Res Branch, Bethesda, MD USA. RP Best, A (reprint author), Vancouver Hosp & Hlth Sci Ctr, Ctr Clin Epidemiol & Evaluat, 828 W 10th Ave,Room 718, Vancouver, BC V5Z 1L8, Canada. NR 44 TC 27 Z9 27 U1 2 U2 6 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD NOV-DEC PY 2003 VL 27 SU 3 BP S206 EP S216 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 751WY UT WOS:000187114100004 PM 14672381 ER PT J AU Best, A Stokols, D Green, LW Leischow, S Holmes, B Buchholz, K AF Best, A Stokols, D Green, LW Leischow, S Holmes, B Buchholz, K TI An integrative framework for community partnering to translate theory into effective health promotion strategy SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE community health promotion; health promotion theory; social ecology; PRECEDE-PROCEED; sytems thinking; transdisciplinary research; transdisciplinary collaboration ID INTERVENTIONS; PREVENTION; TOBACCO; DISEASE AB Introduction. Although there is general agreement about the complex interplay among individual-, family-, organizational-, and community-level factors as they influence health outcomes, there is still a gap between health promotion research and practice. The authors suggest that a disjuncture exists between the multiple theories and models of health promotion and the practitioners need for a more unified set of guidelines for comprehensive planning of programs. Therefore, we put forward in this paper an idea toward closing the gap between research and practice, a case for developing an overarching framework-with several health promotion models that could integrate existing theories-and applying it to comprehensive health promotion strategy. An Integrative Framework. We outline a theoretical foundation for future health promotion research and practice that integrates four models: the social ecology; the Life Course Health Development; the Predisposing, Reinforcing, and Enabling Constructs in Educational/Environmental Diagnosis and Evaluation-Policy, Regulatory and Organizational Constructs in Educational and Environmental Development; and the community partnering models. The first three models are well developed and complementary. There is little consensus on the latter model, community partnering. However, we suggest that such a model is a vital part of an overall framework, and we present an approach to reconciling theoretical tensions among researchers and practitioners involved in community health promotion. Integrating the Models: The Need for Systems Theory and Thinking. Systems theory has been relatively ignored both by the health promotion field and, more generally, by the health services. We make a case for greater use of systems theory in the development of an overall framework, both to improve integration and to incorporate key concepts from the diverse systems literatures of other disciplines. Vision for Healthy Communities. (1) Researchers and practitioners understand the complex interplay among individual-, family-, organizational-, and community-level factors as they influence population health; (2) health promotion researchers and practitioners collaborate effectively with others in the community to create integrated strategies that work as a system to address a wide array of health-related factors; (3) The Healthy People Objectives for the Nation includes balanced indicators to reflect health promotion realities and research-measures effects on all levels; (4) the gap between community health promotion "best practices" guidelines and the way things work in the everyday world of health promotion practice has been substantially closed. Conclusions and Recommendations. We suggest critical next steps toward closing the gap between health promotion research and practice: investing in networks that promote, support, and sustain ongoing dialogue and sharing of experience; finding common ground in an approach to community partnering; and gaining consensus on the proposed integrating framework. C1 Vancouver Hosp & Hlth Sci Ctr, Ctr Clin Epidemiol & Evaluat, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Hlth Care & Epidemiol, Vancouver, BC V6T 1W5, Canada. Univ Calif Irvine, Sch Social Ecol, Dept Planning Policy & Design, Irvine, CA USA. Ctr Dis Control & Prevent, Off Sci & Extramural Res, Publ Hlth Practice Program Off, Atlanta, GA USA. US Natl Canc Inst, Tobacco Control Res Branch, Bethesda, MD USA. Simon Fraser Univ, Sch Commun, Burnaby, BC V5A 1S6, Canada. RP Best, A (reprint author), Univ British Columbia, Dept Hlth Care & Epidemiol, Vancouver Hosp & Hlth Sci Ctr, 828 W 10th Ave,Room 718, Vancouver, BC V5Z 1L8, Canada. NR 53 TC 72 Z9 73 U1 4 U2 28 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD NOV-DEC PY 2003 VL 18 IS 2 BP 168 EP 176 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 741RC UT WOS:000186470200010 PM 14621414 ER EF