FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Pressel, S Davis, BR Louis, GT Whelton, P Adrogue, H Egan, D Farber, M Payne, G Probstfield, J Ward, H AF Pressel, S Davis, BR Louis, GT Whelton, P Adrogue, H Egan, D Farber, M Payne, G Probstfield, J Ward, H CA ALLHAT Res Grp TI Participant recruitment in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) SO CONTROLLED CLINICAL TRIALS LA English DT Article DE clinical trial; patient recruitment; antihypertensive drug treatment; lipid-lowering treatment ID PRAVASTATIN AB The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a practice-based, randomized, multicenter clinical trial in 42,419 high-risk hypertensive patients aged 55 years and older; 10,356 of these patients are also in a lipid-lowering trial component. The purpose of the antihypertensive component is to determine whether the occurrence of fatal coronary heart disease and/or nonfatal myocardial infarction differs between patients randomized to diuretic (chlorthalidone) and those randomized to either calcium antagonist (amlodipine), angiotensin-converting enzyme inhibitor (lisinopril), or alpha-adrenergic blocker (doxazosin) therapy. (The doxazosin arm has been discontinued.) The purpose of the lipid-lowering component is to determine whether lowering low-density lipoprotein cholesterol with a 3-hydroxymethyl-glutaryl coenzyme A reductase inhibitor (pravastatin) in moderately hypercholesterolemic patients will reduce all-cause mortality compared to a control group receiving "usual care." ALLHAT recruited patients from a variety of practice settings from February 1994 through January 1998. Sites were paid for randomizations and are paid for completed follow-up visits and documented study events. Communication and monitoring were facilitated by nine regional coordinator teams. It was recognized from the outset that patient recruitment would be a very large task because of the number of participants (> 40,000) needed, the ambitious nature of the goal for recruitment of African-Americans (> 55%), and the knowledge that many investigators had limited experience recruiting participants for clinical trials. Multiple adjustments in the initial ALLHAT overall recruitment plan facilitated achievement of sample size goals for both components of the trial. The experience obtained from this large trial should be valuable for the planning and implementation of successful recruitment in future trials. (C) Elsevier Science Inc. 2001. C1 Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX 77030 USA. Tulane Univ, New Orleans, LA 70118 USA. Vet Affairs Med Ctr, Houston, TX 77030 USA. NHLBI, Bethesda, MD 20892 USA. Pitman Internal Med Associates, Pitman, NJ USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif Los Angeles, King Drew Med Ctr, Los Angeles, CA 90059 USA. RP Pressel, S (reprint author), Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, 1200 Herman Pressler St,Suite E801, Houston, TX 77030 USA. FU NHLBI NIH HHS [N01-HC-35130] NR 12 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 2001 VL 22 IS 6 BP 674 EP 686 DI 10.1016/S0197-2456(01)00177-5 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 502QF UT WOS:000172753700006 PM 11738123 ER PT J AU Cui, XL Goldberg, IG Meyers, DE Cintron, AD Ashe, RE Ma, PL Danner, RL AF Cui, XL Goldberg, IG Meyers, DE Cintron, AD Ashe, RE Ma, PL Danner, RL TI Nitric oxide (NO)-responsive genes identified using oligonucleotide microarrays SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2001 VL 29 IS 12 SU S MA 59 BP A20 EP A20 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 505PJ UT WOS:000172920900060 ER PT J AU Danis, M Linde-Zwirble, WT Lidicker, J Angus, DC AF Danis, M Linde-Zwirble, WT Lidicker, J Angus, DC TI Access to ICU care by the uninsured in the United States SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. Hlth Proc Management LLC, Doylestown, PA USA. NIH, Bethesda, MD 20892 USA. RI Angus, Derek/E-9671-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2001 VL 29 IS 12 SU S MA 2 BP A1 EP A1 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 505PJ UT WOS:000172920900004 ER PT J AU Ma, PL Cui, XL Nishanian, EV Wang, WH Danner, RL AF Ma, PL Cui, XL Nishanian, EV Wang, WH Danner, RL TI Nitric oxide (NO) regulates tumor necrosis factor (TNF alpha) and interleukin-8 (IL-8) in human phagocytes by distinct mechanisms SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Columbia Univ, Med Ctr, New York, NY USA. Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2001 VL 29 IS 12 SU S MA 60 BP A20 EP A20 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 505PJ UT WOS:000172920900062 ER PT J AU McDonald, CT Flibotte, J Rosand, J Lee, ME Greer, D Ougorets, I Ezzeddine, M Oliveira, J Buonanno, F Rordorf, G Schwamm, L Koroshetz, W AF McDonald, CT Flibotte, J Rosand, J Lee, ME Greer, D Ougorets, I Ezzeddine, M Oliveira, J Buonanno, F Rordorf, G Schwamm, L Koroshetz, W TI Prophylactic antibiotics for ventriculostomy in the neuro intensive care unit: Relationships between CSF infection, initial diagnosis, and need for permanent ventriculoperitoneal shunt SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Cornell Med Sch, Boston, MA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2001 VL 29 IS 12 SU S MA 111 BP A35 EP A35 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 505PJ UT WOS:000172920900111 ER PT J AU Panigada, M Berra, L Greco, G De Marchi, L Kolobow, T AF Panigada, M Berra, L Greco, G De Marchi, L Kolobow, T TI Effect of horizontal tracheal tube orientation on bacterial colonization of the lower respiratory tract in sheep intubated and mechanically ventilated SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Osped San Gerardo, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2001 VL 29 IS 12 SU S MA 351 BP A107 EP A107 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 505PJ UT WOS:000172920900351 ER PT J AU Grossman, Z Paul, WE AF Grossman, Z Paul, WE TI Autoreactivity, dynamic tuning and selectivity - Opinion SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material ID T-CELL RECEPTOR; HETEROCLITIC ANTIGEN ANALOGS; POSITIVE SELECTION; DENDRITIC CELLS; IN-VIVO; ACTIVATION THRESHOLD; EFFECTOR FUNCTION; PERIPHERAL TOLERANCE; SIGNALING THRESHOLDS; TYROSINE PHOSPHATASE AB The immune system adjusts its response to the context in which antigens, including self-antigens, are recognized. Recent observations support a conceptual framework for understanding how this may be achieved at the cellular and cell-population levels. At both levels, 'perturbations' elicit competition between excitation and de-excitation, resulting either in adaptation or in various responses. The responsiveness of individual cells is dynamically tuned, reflecting their recent experience. The tuning of T-cell activation thresholds by self-ligands facilitates positive selection and continuously regulates the level of autoreactivity in the periphery. Autoreactivity appears to be involved in regulation of the immune response, homeostasis, maintaining of the functional integrity of naive and memory cells, and in other physiological functions. C1 Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Grossman, Z (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. RI Grossman, Zvi/A-9643-2008 NR 104 TC 93 Z9 95 U1 0 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 2001 VL 13 IS 6 BP 687 EP 698 DI 10.1016/S0952-7915(01)00280-1 PG 12 WC Immunology SC Immunology GA 486BB UT WOS:000171797600010 PM 11677091 ER PT J AU Schiffmann, R Boespflug-Tanguy, O AF Schiffmann, R Boespflug-Tanguy, O TI An update on the leukodsytrophies SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID PELIZAEUS-MERZBACHER-DISEASE; PROTEOLIPID PROTEIN GENE; NERVOUS-SYSTEM HYPOMYELINATION; VANISHING WHITE-MATTER; CHILDHOOD ATAXIA; POINT MUTATIONS; LEUKOENCEPHALOPATHY; MYELIN; CHROMOSOME; PHENOTYPE AB This review centers on important recent advances in the understanding of the role of glial fibrillary acidic protein in Alexander disease and of proteolipid protein in hypomyelinating disorders such as Pelizaeus-Merzbacher and spastic paraplegia. We also describe seven novel leukodystrophies. These include childhood ataxia with central nervous system hypomyelination, a relatively common leukodystrophy syndrome with linkage to chromosome 3 in some patients, and megalencephalic leukoencephalopathy with subcortical cysts whose gene has recently been cloned. These, along with five other disorders, including leukodystrophy with polyol metabolism abnormality, demonstrate that an increasing number of protein and metabolic abnormalities can cause primary myelin disorders. Curr Opin Neurol 14:789-794. (C) 2001 Lippincott Williams Wilkins. C1 NIH, Bethesda, MD 20892 USA. INSERM, U384, Clermont Ferrand, France. RP Schiffmann, R (reprint author), NIH, Bldg 10,Room 3D03,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 47 TC 36 Z9 36 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2001 VL 14 IS 6 BP 789 EP 794 DI 10.1097/00019052-200112000-00018 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 510NG UT WOS:000173213700018 PM 11723390 ER PT J AU Kobe, B Kajava, AV AF Kobe, B Kajava, AV TI The leucine-rich repeat as a protein recognition motif SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID PORCINE RIBONUCLEASE INHIBITOR; 2.0 ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; CHORIONIC-GONADOTROPIN; SIGNAL-TRANSDUCTION; DOMAIN; BINDING; RECEPTOR; FAMILY; SITE AB Leucine-rich repeats (LRRs) are 20-29-residue sequence motifs present in a number of proteins with diverse functions. The primary function of these motifs appears to be to provide a versatile structural framework for the formation of protein-protein interactions. The past two years have seen an explosion of new structural information on proteins with LRRs. The new structures represent different LRR subfamilies and proteins with diverse functions, including GTPase-activating protein rna 1 p from the ribonuclease-inhibitor-like subfamily; spliceosomal protein U2A', Rab geranylgeranyltransferase, internalin B, dynein light chain 1 and nuclear export protein TAP from the SDS22-like subfamily; Skp2 from the cysteine-containing subfamily; and YopM from the bacterial subfamily. The new structural information has increased our understanding of the structural determinants of LRR proteins and our ability to model such proteins with unknown structures, and has shed new light on how these proteins participate in protein-protein interactions. C1 Univ Queensland, Dept Biochem & Mol Biol, Inst Mol Biosci, Brisbane, Qld 4072, Australia. NIH, Ctr Informat Technol, Ctr Mol Modeling, Bethesda, MD 20892 USA. RP Kobe, B (reprint author), Univ Queensland, Dept Biochem & Mol Biol, Inst Mol Biosci, Brisbane, Qld 4072, Australia. RI Kobe, Bostjan/D-1292-2009; Kajava, Andrey/E-1107-2014 OI Kobe, Bostjan/0000-0001-9413-9166; Kajava, Andrey/0000-0002-2342-6886 NR 48 TC 915 Z9 963 U1 16 U2 90 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD DEC PY 2001 VL 11 IS 6 BP 725 EP 732 DI 10.1016/S0959-440X(01)00266-4 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 501BV UT WOS:000172663900011 PM 11751054 ER PT J AU Giacoia, GP AF Giacoia, GP TI Adverse drug effects and adverse drug reactions in pediatric patients: Workshop summary and recommendations SO CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material C1 Natl Inst Child Hlth & Human Dev, NIH, Rockville, MD 20852 USA. RP Giacoia, GP (reprint author), Natl Inst Child Hlth & Human Dev, NIH, 6100 Execut Blvd,Rm 4B-11, Rockville, MD 20852 USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0011-393X J9 CURR THER RES CLIN E JI Curr. Ther. Res.-Clin. Exp. PD DEC PY 2001 VL 62 IS 12 BP 942 EP 950 DI 10.1016/S0011-393X(01)80097-7 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 515MK UT WOS:000173499500009 ER PT J AU Duggal, S Carlson, EA Sroufe, LA Egeland, B AF Duggal, S Carlson, EA Sroufe, LA Egeland, B TI Depressive symptomatology in childhood and adolescence SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID LIFE EVENTS; DEVELOPMENTAL PSYCHOPATHOLOGY; MALTREATED CHILDREN; GENDER DIFFERENCES; YOUNG ADOLESCENTS; SEXUAL ABUSE; RATING-SCALE; FOLLOW-UP; DISORDERS; RISK AB Antecedents of depressive symptomatology in childhood and adolescence were examined in a prospective longitudinal study of at-risk youth (n = 168) from families of lower socioeconomic status. Relations between family context factors, maternal depressive symptoms, and depressive symptoms in childhood and adolescence were examined, with a focus on early family relationship factors rarely available for analysis in longitudinal data sets. Results suggest the possibility of etiological differences between depressive symptoms in childhood and in adolescence. Depressive symptomatology in childhood was predicted by the overall family context. Cumulative effects of maternal depressive symptomatology, early care lacking in emotional supportiveness, abuse, and family stressors were observed. Depressive symptomatology in adolescence, on the other hand, was specifically associated with maternal depression and early care lacking in emotional supportiveness. Moreover, an intriguing sex difference emerged: maternal depressive symptomatology was strongly associated with depressive symptomatology in adolescence for females, but for males supportive early care appeared more relevant. C1 Univ Minnesota, Minneapolis, MN 55455 USA. RP Duggal, S (reprint author), NIMH, Sect Dev Psychopathol, Suite 106C,5413 W Cedar Lane, Bethesda, MD 20892 USA. FU NIMH NIH HHS [MH 40864] NR 81 TC 90 Z9 92 U1 1 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD WIN PY 2001 VL 13 IS 1 BP 143 EP 164 DI 10.1017/S0954579401001109 PG 22 WC Psychology, Developmental SC Psychology GA 411MX UT WOS:000167504800010 PM 11346049 ER PT J AU Lechleider, RJ Ryan, JL Garrett, L Eng, C Deng, CX Wynshaw-Boris, A Roberts, AB AF Lechleider, RJ Ryan, JL Garrett, L Eng, C Deng, CX Wynshaw-Boris, A Roberts, AB TI Targeted mutagenesis of Smad1 reveals an essential role in chorioallantoic fusion SO DEVELOPMENTAL BIOLOGY LA English DT Article DE TGF-beta; Smads; allantois; BMP; targeted mutagenesis; VCAM-1; placenta ID TGF-BETA-SUPERFAMILY; CARDIAC DEVELOPMENT; MURINE ALLANTOIS; AXIAL ROTATION; RAT EMBRYOS; MICE; DISRUPTION; RECEPTOR; DEFECTS; GROWTH AB The Smad family of intracellular signaling intermediates transduce signals downstream from the transforming growth factor beta (TGF-beta) family of receptor serine threonine kinases. The original member of this family, Smad1, has been shown to mediate signals from receptors for the bone morphogenetic proteins (BMPs), a large group of ligands in the TGF-beta superfamily that mediate important developmental events. We have targeted the Smad1 gene in mice and created mutants null at this locus. Smad1 mutant mice die at approximately 9.5 days postcoitum due to defects in allantois formation. In Smad1 mutant mice, the allantois fails to fuse to the chorion, resulting in a lack of placenta and failure to establish a definitive embryonic circulation. Although vasculogenesis is initiated in the mutant allantois, the vessels formed are disorganized, and VCAM-1 protein, a marker for distal allantois development, is not expressed. Smad1 null fibroblasts are still able to respond to BMP2, however, suggesting that the defect observed in the developing extraembryonic tissue is caused by a very specific loss of transcriptional activity regulated by Smad1. Our data further demonstrate that although highly similar structurally, Smad proteins are not functionally homologous. C1 Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. NHGRI, Lab Genet Dis Res, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NIDDK, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. RP Lechleider, RJ (reprint author), Georgetown Univ, Sch Med, Dept Cell Biol, 3900 Reservoir Rd NW, Washington, DC 20007 USA. RI deng, chuxia/N-6713-2016 FU NCI NIH HHS [CO75GA] NR 43 TC 119 Z9 130 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2001 VL 240 IS 1 BP 157 EP 167 DI 10.1006/dbio.2001.0469 PG 11 WC Developmental Biology SC Developmental Biology GA 502BF UT WOS:000172723300011 PM 11784053 ER PT J AU Belair, CD Peterson, RE Heideman, W AF Belair, CD Peterson, RE Heideman, W TI Disruption of erythropoiesis by dioxin in the zebrafish SO DEVELOPMENTAL DYNAMICS LA English DT Article DE TCDD; zebrafish; development; cardiovascular toxicity; hematopoiesis; erythropoiesis ID ARYL-HYDROCARBON RECEPTOR; DIBENZO-P-DIOXINS; LIFE-STAGE DEVELOPMENT; DANIO-RERIO; LAKE TROUT; COMPARATIVE TOXICITY; GFP REPORTER; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; GENE; EXPRESSION AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) causes early life stage mortality in a variety of fish species. We have used the zebrafish (Danio rerio) to study the cardiovascular effects of TCDD treatment over the time course of zebrafish development. Early TCDD exposure (6 ng/ml) starting at 4 hr postfertilization (hpf) produced reductions in blood flow and in the number of circulating erythrocytes. These defects were consistently observable by 72 hpf. However, these responses were not observed when TCDD exposure was delayed until 96 hpf or later. These results suggest a model in which TCDD interferes with cardiovascular and erythropoietic developmental processes that are normally completed by 96 hpf. This model is strengthened by the finding that TCDD exposure blocks the step in hematopoiesis in which developing zebrafish switch from the primitive phase to the definitive phase of erythropoiesis. We observed no effect of TCDD on the levels of circulating primitive erythrocytes before 72 hpf and the expression of markers for early hematopoiesis, GATA-1 and GATA-2. However, early TCDD exposure prevented the appearance of definitive phase erythrocytes. TCDD produced a small delay in the migration of blood cells expressing SCL from the intermediate cell mass to the dorsal mesentery and dorsal aorta. Despite the decrease in blood flow produced by TCDD, confocal microscopy of the trunk vasculature by using a Tie2/green fluorescence protein endothelial marker at 48, 60, 72, and 96 hpf of TCDD-exposed (4 hpf) revealed no apparent defects in blood vessel structure. (C) 2001 Wiley-Liss, Inc. C1 Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. Univ Wisconsin, NIEHS, Dev & Mol Toxicol Ctr, Madison, WI USA. RP Heideman, W (reprint author), Univ Wisconsin, Sch Pharm, 777 Highland Ave, Madison, WI 53705 USA. FU NIEHS NIH HHS [5 F32 ES05862-03, P30ES09090] NR 32 TC 75 Z9 77 U1 0 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2001 VL 222 IS 4 BP 581 EP 594 DI 10.1002/dvdy.1213 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 497WH UT WOS:000172478100005 PM 11748828 ER PT J AU Lu, MM Yang, HH Zhang, LL Shu, WG Blair, DG Morrisey, EE AF Lu, MM Yang, HH Zhang, LL Shu, WG Blair, DG Morrisey, EE TI The bone morphogenic protein antagonist gremlin regulates proximal-distal patterning of the lung SO DEVELOPMENTAL DYNAMICS LA English DT Article DE gremlin; BMP; lung epithelium; lung development; proximal-distal patterning ID TRANSCRIPTION FACTOR; MOUSE LUNG; GENE; EXPRESSION; BMP; CERBERUS; FAMILY; LIMB; EPITHELIUM; OUTGROWTH AB The proximal-distal patterning of lung epithelium involves a complex series of signaling and transcriptional events resulting in the programmed differentiation of highly specialized cells for gas exchange and surfactant protein expression essential for postnatal lung function. The BMP signaling pathway has been shown to regulate cellular differentiation in the lung as well as other tissues. In this report, we show that the can family of related BMP antagonists, including gremlin, cer-1, PRDC, and Dan are expressed in the lung during embryonic development with gremlin expression observed in the proximal airway epithelium. The role of gremlin in lung development was explored by overexpressing it in the distal. lung epithelium of transgenic mice using the human SP-C promoter. SP-C/gremlin transgenic mice exhibited a disruption of the proximal-distal patterning found in the airways of the mammalian lung. Expanded expression of the proximal epithelial cell markers CC10 and HFH-4 (Foxj1) was observed in the distal regions of transgenic lungs. Furthermore, smooth muscle alpha -actin expression was observed surrounding the distal airways of SP-C/gremlin mice, indicating a proximalization of distal lung tubules. These data suggest that gremlin plays an important role in lung morphogenesis by regulating the proximal-distal patterning of the lung during development. (C) 2001 Wiley-Liss, Inc. C1 Univ Penn, Dept Med, Philadelphia, PA 19104 USA. NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Frederick, MD USA. RP Morrisey, EE (reprint author), Univ Penn, Dept Med, 953 BRB II-III,421 Curie Blvd, Philadelphia, PA 19104 USA. FU NHLBI NIH HHS [HL64632-01] NR 32 TC 62 Z9 62 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2001 VL 222 IS 4 BP 667 EP 680 DI 10.1002/dvdy.1231 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 497WH UT WOS:000172478100012 PM 11748835 ER PT J AU Guerre-Millo, M Rouault, C Poulain, P Andre, J Poitout, V Peters, JM Gonzalez, FJ Fruchart, JC Reach, G Staels, B AF Guerre-Millo, M Rouault, C Poulain, P Andre, J Poitout, V Peters, JM Gonzalez, FJ Fruchart, JC Reach, G Staels, B TI PPAR-alpha-null mice are protected from high-fat diet-induced insulin resistance SO DIABETES LA English DT Article ID ACTIVATED RECEPTOR-ALPHA; TARGETED DISRUPTION; LIPID-METABOLISM; DEFICIENT MICE; ACID OXIDATION; OBESE MICE; BETA-CELL; EXPRESSION; GLUCOSE; GENE AB Peroxisome proliferator-activated receptor (PPAR)-alpha controls the expression of genes involved in lipid metabolism. PPAR-alpha furthermore participates to maintain blood glucose during acute metabolic stress, as shown in PPAR-alpha -null mice, which develop severe hypoglycemia when fasted. Here, we assessed a potential role for PPAR-alpha in glucose homeostasis in response to long-term high-fat feeding. When subjected to this nutritional challenge, PPAR-alpha -null mice remained normoglycemic and normoinsulinemic, whereas wild-type mice became hyperinsulinemic (190%; P<0.05) and slightly hyperglycemic (120%; NS). Insulin tolerance tests (ITTs) and glucose tolerance tests (GTTs) were performed to evaluate insulin resistance (IR). Under standard diet, the response to both tests was similar in wild-type and PPAR--null mice. Under high-fat diet, however, the efficiency of insulin in ITT was reduced and the amount of hyperglycemia in GTT was increased only in wild-type and not in PPAR-alpha -null mice. The IR index, calculated as the product of the areas under glucose and insulin curves in GTT, increased fourfold in high-fat-fed wildtype mice, whereas it remained unchanged in PPAR-alpha -null mice. In contrast, PPAR-alpha deficiency allowed the twofold rise in adiposity and blood leptin levels elicited by the diet. Thus, the absence of PPAR-alpha dissociates IR from high-fat diet-induced increase in adiposity. The effects of PPAR-alpha deficiency on glucose homeostasis seem not to occur via the pancreas, because glucose-stimulated insulin secretion of islets was not influenced by the PPAR-alpha genotype. These data suggest that PPAR-alpha plays a role for the development of IR in response to a Western-type high-fat diet. C1 Inst Pasteur, Dept Atherosclerose, INSERM, U545, F-59019 Lille, France. INSERM, U465, Paris, France. Hop Hotel Dieu, INSERM, U311, Paris, France. Univ Lille 2, Fac Pharm, Lille, France. Univ Washington, Pacific NW Res Inst, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Staels, B (reprint author), Inst Pasteur, Dept Atherosclerose, INSERM, U545, F-59019 Lille, France. RI Peters, Jeffrey/D-8847-2011; Staels, Bart/N-9497-2016 OI Staels, Bart/0000-0002-3784-1503 NR 35 TC 148 Z9 154 U1 1 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2001 VL 50 IS 12 BP 2809 EP 2814 DI 10.2337/diabetes.50.12.2809 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 507CT UT WOS:000173009900021 PM 11723064 ER PT J AU Lindsay, RS Kobes, S Knowler, WC Bennett, PH Hanson, RL AF Lindsay, RS Kobes, S Knowler, WC Bennett, PH Hanson, RL TI Genome-wide linkage analysis assessing parent-of-origin effects in the inheritance of type 2 diabetes and BMI in Pima Indians SO DIABETES LA English DT Article ID QUANTITATIVE-TRAIT LOCI; BIRTH-WEIGHT; METHYLMALONIC ACIDEMIA; SUSCEPTIBILITY LOCUS; SIB PAIRS; MELLITUS; GENE; ASSOCIATION; ISODISOMY; INTERVAL AB We examined the hypothesis that imprinted genes may affect the propensity to type 2 diabetes and obesity in Pima Indians. Multipoint variance component methods were used to assess linkage of BMI (kg/m(2)) and age-adjusted diabetes to loci derived from either father (LODFA) or mother (LODMO) in a genome-wide scan. Tentative evidence of loci where imprinted genes might be acting was found for diabetes with maternally derived alleles on chromosomes 5 (LODMO = 1.5) and 14 (LODMO = 1.6). Evidence of linkage of BMI to maternally derived alleles was found on chromosome 5 (LODMO = 1.7) and to paternally derived alleles on chromosome 10p (LODFA = 1.7). Additional analyses of sibling pairs who were affected by diabetes and younger than 25 years of age showed an increase of sharing of maternally derived alleles on chromosome 6 (LODMO = 3.0). We also examined sites of a priori interest where action of imprinted genes has been proposed in diabetes or obesity. We found no evidence of parent-specific linkage (of either diabetes or BMI) on chromosome 11p, a region that contains several imprinted genes, but observed weak evidence of linkage of diabetes to paternally derived alleles (LODFA = 0.9) in the region of chromosome 6q, believed to contain an exclusively paternally expressed gene or genes that cause transient neonatal diabetes mellitus. In conclusion, we determined regions of interest on chromosomes 5, 6, and 10 where imprinted genes might be affecting the risk of type 2 diabetes or obesity in Pima Indians. C1 NIDDKD, NIH, Phoenix, AZ 85014 USA. RP Lindsay, RS (reprint author), NIDDKD, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 33 TC 76 Z9 76 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2001 VL 50 IS 12 BP 2850 EP 2857 DI 10.2337/diabetes.50.12.2850 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 507CT UT WOS:000173009900027 PM 11723070 ER PT J AU Ishizuya-Oka, A Ueda, S Inokuchi, T Amano, T Damjanovski, S Stolow, M Shi, YB AF Ishizuya-Oka, A Ueda, S Inokuchi, T Amano, T Damjanovski, S Stolow, M Shi, YB TI Thyroid hormone-induced expression of Sonic hedgehog correlates with adult epithelial development during remodeling of the Xenopus stomach and intestine SO DIFFERENTIATION LA English DT Article DE Sonic hedgehog; thyroid hormone; digestive tract; remodeling; Xenopus laevis ID ACID-BINDING-PROTEIN; CELLULAR-DIFFERENTIATION; MESENCHYMAL INTERACTIONS; CONNECTIVE-TISSUE; DIGESTIVE ORGANS; GENE-EXPRESSION; IN-VITRO; METAMORPHOSIS; LAEVIS; GUT AB Sonic hedgehog (Shh) was isolated from the Xenopus laevis intestine as an early thyroid hormone (TH) response gene. To investigate possible roles of TH-upregulated expression of Shh during metamorphosis, we raised a polyclonal antibody against Xenopus Shh and immunohistochemically examined the relationship between Shh expression and the larval-to-adult intestinal remodeling at the cellular level. Our results indicate that the epithelial-specific expression of Shh in the intestine spatiotemporally correlates well with active proliferation and/or initial differentiation of the secondary (adult) epithelial primordia that originate from stem cells, but not with apoptosis of the primary (larval) epithelium. Given the similar transformations of the stomach during metamorphosis, we also analyzed Shh expression in this organ and found similar correlations in the stomach, although the position of the adult epithelial primordia and their final differentiation in the stomach are different from those in the intestine. Furthermore, we show here that Shh expression is organ-autonomously induced by TH and its correlation with the adult epithelial development is reproduced in vitro in both the intestine and the stomach. More importantly, addition of recombinant Shh protein to the culture medium results in developmental anomalies of both organs. However, differentiation of the adult epithelium is more severely inhibited by exogenous Shh in the intestine than in the stomach. These results suggest that TH-upregulated expression of Shh plays important roles in the postembryonic gastrointestinal remodeling, but its roles are at least partially different between the intestine and the stomach. C1 Dokkyo Univ, Sch Med, Dept Histol & Neurobiol, Mibu, Tochigi 3210293, Japan. NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Utsunomiya Univ, Fac Educ, Dept Biol, Utsunomiya, Tochigi 321, Japan. RP Ishizuya-Oka, A (reprint author), Dokkyo Univ, Sch Med, Dept Histol & Neurobiol, Mibu, Tochigi 3210293, Japan. RI Damjanovski, Sashko/N-8728-2015 NR 41 TC 42 Z9 42 U1 0 U2 5 PU BLACKWELL WISSENSCHAFTS-VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 57, D-10707 BERLIN, GERMANY SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD DEC PY 2001 VL 69 IS 1 BP 27 EP 37 DI 10.1046/j.1432-0436.2001.690103.x PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 502BE UT WOS:000172723200003 PM 11776392 ER PT J AU Chen, LJ Lebetkin, EH Burka, LT AF Chen, LJ Lebetkin, EH Burka, LT TI Metabolism of (R)-(+)-Pulegone in F344 rats SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID MONOTERPENE KETONE; ALLYLIC REARRANGEMENT; MENTHOFURAN; HEPATOTOXICITY; PULEGONE; MOUSE; CYTOCHROME-P-450; R-(+)-PULEGONE; DISPOSITION; GLUTATHIONE AB (R)-(+)-Pulegone, a monoterpene ketone, is a major component of pennyroyal oil. Ingestion of high doses of pennyroyal oil has caused severe toxicity and occasionally death. Studies have shown that metabolites of pulegone were responsible for the toxicity. Previous metabolism studies have used high, near lethal doses and isolation and analysis techniques that may cause degradation of some metabolites. To clarify these issues and further explore the metabolic pathways, a study of C-14-labeled pulegone in F344 rats at doses from 0.8 to 80 mg/kg has been conducted. High-pressure liquid chromatography (HPLC) analysis of the collected urine showed the metabolism of pulegone to be extensive and complex. Fourteen metabolites were isolated by HPLC and characterized by NMR, UV, and mass spectroscopy. The results demonstrated that pulegone was metabolized by three major pathways: 1) hydroxylation to give monohydroxylated pulegones, followed by glucuronidation or further metabolism; 2) reduction of the carbon-carbon double bond to give diastereomeric menthone/isomenthone, followed by hydroxylation and glucuronidation; and 3) Michael addition of glutathione to pulegone, followed by further metabolism to give diastereomeric 8-(N-acetylcystein-S-yl)menthone/isomenthone. This 1,4-addition not only took place in vivo but also in vitro under catalysis of glutathione S-transferase or mild base. Several hydroxylated products of the two mercapturic acids were also observed. Contrary to the previous study, all but one of the major metabolites characterized in the present study are phase II metabolites, and most of the metabolites in free forms are structurally different from those previously identified phase I metabolites. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Chen, LJ (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. NR 25 TC 24 Z9 24 U1 2 U2 10 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD DEC PY 2001 VL 29 IS 12 BP 1567 EP 1577 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 497ZB UT WOS:000172484400009 PM 11717176 ER PT J AU Mann, CL Bortner, CD Jewell, CM Cidlowski, JA AF Mann, CL Bortner, CD Jewell, CM Cidlowski, JA TI Glucocorticoid-induced plasma membrane depolarization during thymocyte apoptosis: association with cell shrinkage and degradation of the Na+/K+ adenosine triphosphatase SO ENDOCRINOLOGY LA English DT Article ID DEOXYRIBONUCLEIC-ACID; RIBONUCLEIC-ACID; CATION-TRANSPORT; FLOW-CYTOMETRY; ACTIVATION; LYMPHOCYTES; DEATH; VOLUME; K+; PROLIFERATION AB Multiple signaling pathways are known to induce apoptosis in thymocytes through mechanisms that include the loss of mitochondrial membrane potential, cell shrinkage, caspase activation, and DNA degradation but little is known about the consequences of apoptosis on the properties of the plasma membrane. We have previously shown that apoptotic signals, including survival factor withdrawal and glucocorticoids, induce plasma membrane depolarization during rat thymocyte apoptosis, but the mechanisms involved in this process are unknown. We report here that inhibition of the Na+/K+-adenosine triphosphatase (Na+/K+-ATPase) with ouabain similarly depolarized control thymocytes and enhanced glucocorticoid-induced membrane depolarization, suggesting a link between Na+/K+-ATPase and plasma membrane depolarization of thymocytes. To determine whether repression of Na+/K+-ATPase levels within cells can account for the loss of plasma membrane potential, we assessed protein levels of the Na+/K+-ATPase in apoptotic thymocytes. Spontaneously dying thymocytes had decreased levels of both catalytic and regulatory subunits of Na+/K+-ATPase, and glucocorticoid. treatment enhanced the loss of Na+/K+-ATPase protein. The pan caspase inhibitor (z-VAD) blocked both cellular depolarization and repression of Na+/K+-ATPase in both spontaneously dying and glucocorticoid-treated thymocytes; however, specific inhibitors of caspase 8, 9, and caspase 3 did not. Interestingly, glucocorticoid treatment simultaneously induced cell shrinkage and depolarization. Furthermore, depolarization and the loss of Na+/K+-ATPase protein were limited to the shrunken population of cells. The data indicate an important role for Na+/K+-ATPase in both spontaneous and glucocorticoid-induced apoptosis of rat thymocytes. C1 Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), POB 12233,MD F3-07,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 43 TC 56 Z9 57 U1 1 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2001 VL 142 IS 12 BP 5059 EP 5068 DI 10.1210/en.142.12.5059 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 497JX UT WOS:000172452700004 PM 11713198 ER PT J AU Nethrapalli, IS Singh, M Guan, XP Guo, QF Lubahn, DB Korach, KS Toran-Allerand, CD AF Nethrapalli, IS Singh, M Guan, XP Guo, QF Lubahn, DB Korach, KS Toran-Allerand, CD TI Estradiol (E2) elicits Src phosphorylation in the mouse neocortex: The initial event in E2 activation of the MAPK cascade? SO ENDOCRINOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; ESTROGEN-INDUCED ACTIVATION; PROTEIN-KINASE CASCADE; TYROSINE PHOSPHORYLATION; FAMILY KINASES; SH2 DOMAIN; DIFFERENTIATION; COMPLEX; CELLS; INVITRO AB In neocortical explants, E2 activates various signaling components of the MAPK cascade, including E-Raf and MAPK kinase-dependent ERK, suggesting a possible role in the differentiative actions of E2 in the brain. To further characterize the signaling pathways activated by E2, we determined whether c-Src, a member of the Src family of nonreceptor tyrosine kinases and an important modulator of both the MAPK cascade and neuronal differentiation, may play a role in E2 signaling. The present studies show for the first time in the brain that E2 elicits phosphorylation of c-Src on three functionally critical tyrosine residues (Y220, Y423, and Y534), and that this phosphorylation occurs despite disruption of Ella (in ER knockout mice). PP2, a Src family kinase inhibitor, suppressed not only E2-induced phosphorylation of c-Src, but ERK phosphorylation as well, suggesting that c-Src may be an upstream regulator of E2 signaling. E2-induced phosphorylation of c-Src is associated with increased tyrosine phosphorylation of She, increased association of She with Grb2, and induction of Ras, but not Rap1, activation. Together, these data provide evidence that E2 activates a novel c-Src-dependent signal transduction pathway in the developing brain. C1 Columbia Univ Coll Phys & Surg, Dept Anat & Cell Biol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Ctr Neurobiol & Behav, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Ctr Reprod Sci, New York, NY 10032 USA. Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. Univ Missouri, Dept Child Hlth, Columbia, MO 65211 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Toran-Allerand, CD (reprint author), Columbia Univ Coll Phys & Surg, Dept Anat & Cell Biol, 630 W 168th St,Black Bldg 1615, New York, NY 10032 USA. OI Korach, Kenneth/0000-0002-7765-418X; Singh, Meharvan/0000-0002-8072-1769 NR 20 TC 44 Z9 45 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2001 VL 142 IS 12 BP 5145 EP 5148 DI 10.1210/en.142.12.5145 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 497JX UT WOS:000172452700014 PM 11713208 ER PT J AU Longnecker, MP Daniels, JL AF Longnecker, MP Daniels, JL TI Environmental contaminants as etiologic factors for diabetes SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Methodologies for Community Health Assesment for Areas of Concern CY OCT 04-05, 2000 CL ONTARIO, CANADA DE arsenic; diabetes mellitus; epidemiology; nitrates; nitrites; nitroso compounds; occupations; polychlorinated biphenyls; tetrachlorodibenzodioxin ID DRY CLEANING WORKERS; PAPER-MILL WORKERS; ART GLASS WORKERS; ARSENIC EXPOSURE; DRINKING-WATER; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; ECOLOGICAL ANALYSIS; INSULIN-RESISTANCE; CANCER MORTALITY; TANNERY WORKERS AB For both type 1 and type 2 diabetes mellitus, the rates have been increasing in the United States and elsewhere; rates vary widely by country, and genetic factors account for less than half of new cases. These observations suggest environmental factors cause both type 1 and type 2 diabetes. Occupational exposures have been associated with increased risk of diabetes, In addition, recent data suggest that toxic substances in the environment, other than infectious agents or exposures that stimulate an immune response, are associated with the occurrence of these diseases. We reviewed the epidemiologic data that addressed whether environmental contaminants might cause type 1 or type 2 diabetes. For type 1 diabetes, higher intake of nitrates, nitrites, and N-nitroso compounds, as well as higher serum levels of polychlorinated biphenyls have been associated with increased risk, Overall, however, the data were limited or inconsistent. With respect to type 2 diabetes, data on arsenic and 2,3,7,8-tetrachlorodibenzo-p-dioxin relative to risk were suggestive of a direct association but were inconclusive. The occupational data suggested that more data on exposure to N-nitroso compounds, arsenic, dioxins, talc, and straight oil machining fluids in relation to diabetes would be useful. Although environmental factors other than contaminants may account for the majority of type 1 and type 2 diabetes, the etiologic role of several contaminants and occupational exposures deserves further study. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 90 TC 125 Z9 133 U1 2 U2 14 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2001 VL 109 SU 6 BP 871 EP 876 DI 10.2307/3454649 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 538BU UT WOS:000174794800008 PM 11744505 ER PT J AU Ahlbom, A Cardis, E Green, A Linet, M Savitz, D Swerdlow, A AF Ahlbom, A Cardis, E Green, A Linet, M Savitz, D Swerdlow, A CA ICNIRP Standing Comm Epidemiology TI Review of the epidemiologic literature on EMF and health SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE cancer; chronic disease; epidemiology; extremely low-frequency EMF; review ID MAGNETIC-FIELD EXPOSURE; ELECTRIC UTILITY WORKERS; VOLTAGE POWER-LINES; ACUTE LYMPHOBLASTIC-LEUKEMIA; AMYOTROPHIC-LATERAL-SCLEROSIS; VIDEO DISPLAY TERMINALS; ELF ELECTROMAGNETIC-FIELDS; BREAST-CANCER RISK; CARDIOVASCULAR-DISEASE MORTALITY; AUTONOMIC CONTROL MECHANISMS AB Exposures to extremely low-frequency electric and magnetic fields (EMF) emanating from the generation, transmission, and use of electricity are a ubiquitous part of modern life. Concern about potential adverse health effects was initially brought to prominence by an epidemiologic report two decades ago from Denver on childhood cancer. We reviewed the now voluminous epidemiologic literature on EMF and risks of chronic disease and conclude the following: a) The quality of epidemiologic studies on this topic has improved over time and several of the recent studies on childhood leukemia and on cancer associated with occupational exposure are close to the limit of what can realistically be achieved in terms of size of study and methodological rigor. b) Exposure assessment is a particular difficulty of EMF epidemiology, in several respects: i) The exposure is imperceptible, ubiquitous, has multiple sources, and can vary greatly over time and short distances, ii) The exposure period of relevance is before the date at which measurements can realistically be obtained and of unknown duration and induction period. iii) The appropriate exposure metric is not known and there are no biological data from which to impute it. c) In the absence of experimental evidence and given the methodological uncertainties in the epidemiologic literature, there is no chronic disease for which an etiological relation to EMF can be regarded as established. d) There has been a large body of high quality data for childhood cancer, and also for adult leukemia and brain tumor in relation to occupational exposure, Among all the outcomes evaluated in epidemiologic studies of EMF, childhood leukemia in relation to postnatal exposures above 0.4 muT is the one for which there is most evidence of an association. The relative risk has been estimated at 2.0 (95% confidence limit: 1.27-3.13) in a large pooled analysis, This is unlikely to be due to chance but, may be, in part, due to bias, This is difficult to interpret in the absence of a known mechanism or reproducible experimental support. In the large pooled analysis only 0.8% of all children were exposed above 0.4 muT. Further studies need to be designed to test specific hypotheses such as aspects of selection bias or exposure, On the basis of epidemiologic findings, evidence shows an association of amyotrophic lateral sclerosis with occupational EMF exposure although confounding is a potential explanation. Breast cancer, cardiovascular disease, and suicide and depression remain unresolved. C1 Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden. Int Agcy Res Canc, F-69372 Lyon, France. Queensland Inst Med Res, Epidemiol & Populat Hlth Unit, Brisbane, Qld 4006, Australia. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Inst Canc Res, Epidemiol Sect, Sutton, Surrey, England. RP Ahlbom, A (reprint author), Karolinska Inst, Inst Environm Med, Box 210, S-17177 Stockholm, Sweden. RI Cardis, Elisabeth/C-3904-2017; OI Green, Adele/0000-0002-2753-4841 NR 219 TC 92 Z9 99 U1 3 U2 24 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2001 VL 109 SU 6 BP 911 EP 933 DI 10.2307/3454653 PG 23 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 538BU UT WOS:000174794800012 PM 11744509 ER PT J AU Newbold, RR Jefferson, WN Padilla-Banks, E AF Newbold, RR Jefferson, WN Padilla-Banks, E TI The mouse uterotrophic assay: Other end points SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Newbold, RR (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 5 TC 10 Z9 11 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2001 VL 109 IS 12 BP A569 EP A569 DI 10.1289/ehp.109-a569a PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 526NL UT WOS:000174136500003 PM 11776952 ER PT J AU Haupt, R Romanengo, M Fears, T Viscoli, C Castagnola, E AF Haupt, R Romanengo, M Fears, T Viscoli, C Castagnola, E TI Incidence of septicaemias and invasive mycoses in children undergoing treatment for solid tumours: a 12-year experience at a single Italian institution SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE bacterial infections; mycoses; paediatrics; solid tumour ID BONE-MARROW TRANSPLANTATION; CEFTAZIDIME PLUS AMIKACIN; COLONY-STIMULATING FACTOR; BLOOD-STREAM INFECTIONS; CANCER-PATIENTS; GRANULOCYTOPENIC PATIENTS; MULTICENTER SURVEILLANCE; ANTIMICROBIAL THERAPY; NEUTROPENIC PATIENTS; FUNGAL-INFECTIONS AB We carried out a retrospective study on the infection rate-in episodes per 100 person months at risk (p/m/r)-of septicaemia and invasive mycoses in children with solid tumours treated at a single institution between 1985 and 1996. Among 982 patients, accounting for 8108 p/m/r, 257 infectious episodes were documented, for an infection rate of 3.2. The infection rate for 'intensive' treatment was greater than that for 'less intensive' treatments, 3.7 compared with 0.5, respectively; P <0.001. 58% of infectious episodes were associated with neutropenia, 22% were megatherapy-related, and 39% were related to central venous catheter (CVC), while in 13% of the episodes no risk factor was identified. Of the episodes, single organism Gram-positive bacteraemias accounted for 62%, single organism Gram-negative for 23%, multiple organism bacteraemias for 7%, invasive mycoses for 4%, and isolated fungaemias for 4%. The infection rate for Gram-positive organisms decreased significantly over time (-5.9% per year; P <0.01), but increased for the Gram-negative organisms (+3.4% per year; P = 0.4). This study demonstrates that the risk of bacteraemia increases in parallel with the treatment intensity, and that a considerable number of children with solid tumours develop bacteraemia in the absence of an identifiable risk factor. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 G Gaslini Childrens Hosp, Infect Dis Unit, Genoa, Italy. G Gaslini Childrens Hosp, Sci Directorate, Clin Epidemiol & Biostat Sect, Genoa, Italy. Gaslini Childrens Hosp, Hematol Oncol Unit, Genoa, Italy. NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA. Univ Genoa, Genoa, Italy. Natl Inst Canc Res, Immunocompromised Host Dis Unit, Genoa, Italy. RP Castagnola, E (reprint author), G Gaslini Childrens Hosp, Infect Dis Unit, Genoa, Italy. RI Haupt, Riccardo/C-2237-2012; Castagnola, Elio/C-1865-2012; Castagnola, Elio/J-4454-2016 OI Castagnola, Elio/0000-0002-5336-8429; Castagnola, Elio/0000-0002-5336-8429 NR 42 TC 46 Z9 48 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD DEC PY 2001 VL 37 IS 18 BP 2413 EP 2419 DI 10.1016/S0959-8049(01)00274-X PG 7 WC Oncology SC Oncology GA 500MK UT WOS:000172631200022 PM 11720836 ER PT J AU Belyakov, IM Wang, J Koka, R Ahlers, JD Snyder, JT Tse, R Cox, J Gibbs, JS Margulies, DH Berzofsky, JA AF Belyakov, IM Wang, J Koka, R Ahlers, JD Snyder, JT Tse, R Cox, J Gibbs, JS Margulies, DH Berzofsky, JA TI Activating CTL precursors to reveal CTL function without skewing the repertoire by in vitro expansion SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CTL; T cell receptor; flow cytometry; cellular activation; T lymphocyte ID CYTOTOXIC T-LYMPHOCYTES; RECOMBINANT VACCINIA VIRUS; CELL RESPONSES; IMMUNE-RESPONSE; PEPTIDE; MUCOSAL; IMMUNIZATION; ANTIGEN; SPECIFICITY; INDUCTION AB Detection of the functional CD8(+) CTL response usually requires in vitro restimulation. The differences between the CD8+ CTL repertoire in freshly isolated precursor cells and CD8+ CTL after short-term in vitro expansion have been generally assumed to be minimal, but have never been defined experimentally. Using staining with P18-110/H-2D(d) tetramers; and monoclonal antibodies (mAb) against V beta, we show the surprising result that there was significant skewing of the CD8+ CTL repertoire after just 7 days of stimulation. In contrast, we found that overnight incubation of precursor cells with peptide allows the functional assessment of CD8+ CTL (which cannot be detected ex vivo from freshly isolated cells) without changing the absolute number of antigen-specific CTL as measured by tetramer staining or the repertoire of TCR analyzed with mAb. This study affords a better understanding of the differences between the ex vivo and in vitro stimulated CTL repertoire, and provides an approach to reveal a more faithful representation of the functional in vivo CTL response without skewing of the repertoire of T cells detected. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. NIAID, Mol Biol Sect, Immunol Lab, Rockville, MD USA. Henry M Jackson Fdn, Rockville, MD USA. NIAID, Viral Dis Lab, Viral Immunol Sect, Bethesda, MD USA. RP Belyakov, IM (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bldg O,Rm 6B-09, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 30 TC 22 Z9 22 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 2001 VL 31 IS 12 BP 3557 EP 3566 DI 10.1002/1521-4141(200112)31:12<3557::AID-IMMU3557>3.0.CO;2-O PG 10 WC Immunology SC Immunology GA 505HZ UT WOS:000172908500016 PM 11745375 ER PT J AU Powell, JD Bruniquel, D Schwartz, RH AF Powell, JD Bruniquel, D Schwartz, RH TI TCR engagement in the absence of cell cycle progression leads to T cell anergy independent of p27(Kip1) SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T lymphocyte; anergy; p27(Kip1); IL-2; cell cycle ID CLONAL ANERGY; STIMULATION; COSTIMULATION; INDUCTION; MICE; EXPRESSION; INHIBITION; EXPANSION; RAPAMYCIN; INVITRO AB We have proposed a model in which the prevention of anergy by costimulation is the result of IL-2-induced G1 to S phase cell cycle progression. Here we demonstrate that the reversal of anergy by exogenous IL-2 also occurs during this window of the cell cycle. Recently, it has been proposed that the cell cycle inhibitor p27(Kip1) is an anergic factor. In contrast, our data demonstrate that during the induction, maintenance and rechallenge phases of anergy, P27(Kip1) levels do not correlate with the anergic phenotype. Although p27(Kip1) levels were down-regulated by IL-2 during the G1 to S phase transition, the amount of IL-2 required to produce this effect was far lower than that required to prevent the induction of anergy. Furthermore, T cell lines from P27(Kip1) knockout mice were anergized as well as T cells from mice that were heterozygous for p27(Kip1). Interestingly, the forced overexpression of p27(Kip1) was able to decrease IL-2 promoter-induced transcription, suggesting that the cell cycle machinery may be involved in T cell activation; however, physiological levels of p27(KIP1) did not prevent IL-2 transcription. Overall, our data serve to disassociate the ability of IL-2 to downregulate p27(KIP1) and its ability to prevent or reverse anergy. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, 9000 Rockville Pike,Bldg 4,Room 1111,MSC-0420, Bethesda, MD 20892 USA. NR 22 TC 38 Z9 40 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 2001 VL 31 IS 12 BP 3737 EP 3746 DI 10.1002/1521-4141(200112)31:12<3737::AID-IMMU3737>3.0.CO;2-G PG 10 WC Immunology SC Immunology GA 505HZ UT WOS:000172908500035 PM 11745394 ER PT J AU Koski, GK Lyakh, LA Rice, NR AF Koski, GK Lyakh, LA Rice, NR TI Rapid lipopolysaccharide-induced differentiation of CD14(+) monocytes into CD83(+) dendritic cells is modulated under serum-free conditions by exogenously added IFN-gamma and endogenously produced IL-10 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE dendritic cell; monocyte/macrophage; lipoplysaccharide; immunomodulator; transcription factor ID CALCIUM IONOPHORE; INTERFERON-GAMMA; TNF-ALPHA; KAPPA-B; IN-VIVO; RELB; MICE; INTERLEUKIN-10; MACROPHAGES; MATURATION AB We showed previously that about half of purified CD14(+) peripheral blood monocytes cultured under serum-free conditions and treated with GM-CSF and bacterial LIPS rapidly (2-4 day) differentiate into CD83(+) dendritic cells (DC). The remaining cells retain the CD14(+)/CD83(-) monocyte/macrophage phenotype. In order to identify factors that influence whether monocytes differentiate into DC or remain on the monocyte/macrophage developmental pathway, we evaluated the effects of exogenously added IFN-gamma and endogenously produced IL-10 on the proportion and function of CD14(+) monocytes that adopt DC characteristics in response to LIPS. IFN-gamma priming dramatically increased the proportion of monocytes that adopted stable DC characteristics in response to LIPS, improved their T cell allosensitizing capacity, and enhanced levels of secreted IL-12 heterodimer. IFN-gamma priming also suppressed the production of IL-10, a cytokine known to have inhibitory effects on DC differentiation. When monocytes were treated with LIPS plus IL-10-neutralizing antibodies, dramatically enhanced DC differentiation, IL-12 secretion, and T cell allosensitizing capacity were observed, mimicking in many respects the effects of IFN-gamma priming. IFN-gamma primed cells still displayed appreciable sensitivity to exogenously added IL-10, suggesting that attenuated IL-10 secretion is partially responsible for the enhancing effects of IFN-gamma. These studies therefore identify IFN-gamma as a DC differentiation co-factor for CD14(+) monocytes, and IL-10 as an autocrine/paracrine inhibitor of DC differentiation, linking these agents for the first time as mutually opposed regulators that govern whether CD14(+) cells differentiate into DC upon contact with LIPS or remain on the monocyte/macrophage developmental pathway. C1 NCI, Regulat Cell Growth Lab, Canc Res Ctr, Frederick, MD 21701 USA. RP Koski, GK (reprint author), Univ Penn, Dept Surg, 364 Stemmler Hall, Philadelphia, PA 19104 USA. NR 27 TC 28 Z9 29 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 2001 VL 31 IS 12 BP 3773 EP 3781 DI 10.1002/1521-4141(200112)31:12<3773::AID-IMMU3773>3.0.CO;2-W PG 9 WC Immunology SC Immunology GA 505HZ UT WOS:000172908500039 PM 11745398 ER PT J AU Malapati, S Pierce, SK AF Malapati, S Pierce, SK TI The influence of CD40 on the association of the B cell antigen receptor with lipid rafts in mature and immature cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE B lymphocyte; CD40; lipid raft; B cell antigen receptor ID DENDRITIC CELLS; CROSS-LINKING; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; MEMBRANE RAFTS; APOPTOSIS; LYMPHOCYTES; ACTIVATION; PATHWAY; ENTRY AB Cholesterol- and sphingolipid-rich membrane microdomains termed lipid rafts appear to play a central role in B cell activation. In mature B cells, signaling through the B cell antigen receptor (BCR) is initiated from within rafts and leads to activation. In immature B cells, the BCR is excluded from rafts and signaling leads to apoptosis. CD40, a member of the tumor necrosis receptor family, is expressed by B cells throughout development and has been shown to influence the results of the engagement of antigen by the BCR in both mature B and immature B cells. Here evidence is provided that CD40 is excluded from the lipid rafts of both mature and immature B cells and remains excluded from rafts even after cross-linking. Nevertheless, in mature B cells CD40 signaling influences the association of the BCR with rafts resulting in an increase in the amount of BCR that translocates; into rafts following ligand binding and a subsequent acceleration of the movement of the BCR from rafts. In immature B cells, the cross-linked BCR remains excluded from rafts in the presence of CD40 signaling, conditions under which BCR-induced apoptosis is blocked. These results indicate that CD40 functions outside lipid rafts to influence raft-dependent events in mature B cells and raft-independent events in immature B cells. C1 NIAID, NIH, Immunogenet Lab, Rockville, MD 20852 USA. Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL USA. RP Pierce, SK (reprint author), NIAID, NIH, Immunogenet Lab, Twinbrook 2,12441 Parklawn Dr,Room 200B,MSC 8180, Rockville, MD 20852 USA. NR 35 TC 14 Z9 14 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 2001 VL 31 IS 12 BP 3789 EP 3797 DI 10.1002/1521-4141(200112)31:12<3789::AID-IMMU3789>3.0.CO;2-V PG 9 WC Immunology SC Immunology GA 505HZ UT WOS:000172908500041 PM 11745400 ER PT J AU Hess, S Teubert, U Ortwein, J Eger, K AF Hess, S Teubert, U Ortwein, J Eger, K TI Profiling indomethacin impurities using high-performance liquid chromatography and nuclear magnetic resonance SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE reversed-phase chromatography; indomethacin; impurities; validation; nuclear magnetic resonance ID MASS-SPECTROMETRY; DRUG SUBSTANCE; IDENTIFICATION; PHOLCODINE AB The anti-inflammatory drug indomethacin was investigated regarding new related impurities. Therefore, related substances 2-9 were prepared by independent synthesis and physicochemically characterized. To determine indomethacin and its related substances, a new HPLC-UV method was developed and validated. Indomethacin and its impurities were eluted on a C-18 column with a mobile phase consisting of methanol and an aqueous solution of 0.2% phosphoric acid at a flow rate of 1.5 ml/min and were quantified by UV detection at 320 nm. Overall, the HPLC-UV method was simple and reliable for the detection of eight impurities in indomethacin. In addition to the HPLC-UV method, H-1 nuclear magnetic resonance (NMR) was used to investigate indomethacin regarding impurities. For that purpose, related substances 2-9 were systematically added to indomethacin and investigated. The NMR method was found to be very useful for the identification of impurities in bulk substance without prior separation. Both HPLC-UV and NMR were used to analyze 38 batches of indomethacin available on the European market. The outcome was that 42% of the batches did not meet the compendial requirements although they met the specifications of current compendial methods. Some batches contained the previously undescribed impurity 8, while other batches contained by-products from two distinct synthetic routes. The methods presented herein are important contributions to the ongoing efforts to reduce impurities and therefore the risk of adverse side-effects in drugs that are no longer under patent protection. (C) 2001 Published by Elsevier Science B.V. C1 Univ Leipzig, Inst Pharm, D-04103 Leipzig, Germany. RP Hess, S (reprint author), NIDDK, LBC, NIH, Bldg 8,Rm B2A27, Bethesda, MD 20892 USA. RI Hess, Sonja/K-4842-2013 OI Hess, Sonja/0000-0002-5904-9816 NR 21 TC 13 Z9 15 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD DEC PY 2001 VL 14 IS 4 BP 301 EP 311 DI 10.1016/S0928-0987(01)00198-1 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 491NV UT WOS:000172115500005 PM 11684404 ER PT J AU Hwang, YC Sato, SN Tsai, JY Yan, SD Bakr, S Zhang, HP Oates, PJ Ramasamy, R AF Hwang, YC Sato, SN Tsai, JY Yan, SD Bakr, S Zhang, HP Oates, PJ Ramasamy, R TI Aldose reductase activation is a key component of myocardial response to ischemia SO FASEB JOURNAL LA English DT Article DE aldose reductase; ischemia-reperfusion; myocardial metabolism ID LIPID-PEROXIDATION PRODUCT; PERFUSED RAT-HEART; MUSCLE CELL-GROWTH; DIABETIC COMPLICATIONS; GLUCOSE-OXIDATION; NITRIC-OXIDE; ALDEHYDE REDUCTASE; IN-VITRO; METABOLISM; INJURY AB Aldose reductase, a member of the aldo-keto reductase family, has been implicated in the development of vascular and neurological complications in diabetes. Despite recent studies from our laboratory demonstrating protection of ischemic hearts by an aldose reductase inhibitor, the presence and influence of aldose reductase in cardiac tissue remain unknown. Our goal in this study was to isolate and characterize the kinetic properties of cardiac aldose reductase, as well as to study the impact of flux via this enzyme on glucose metabolism and contractile function in hearts subjected to ischemia-reperfusion. Results demonstrate that ischemia increases myocardial aldose reductase activity and that these increases are, in part, due to activation by nitric oxide. The kinetic parameter of cardiac aldose reductase (K-cat) was significantly higher in ischemic tissues. Aldose reductase inhibition increased glycolysis and glucose oxidation. Aldose reductase inhibited hearts, when subjected to ischemia/reperfusion, exhibited less ischemic injury and was associated with lower lactate/pyruvate ratios (a measure of cytosolic NADH/NAD(+)), greater tissue content of adenosine triphosphate, and improved cardiac function. These findings indicate that aldose reductase is a component of ischemic injury and that pharmacological inhibitors of aldose reductase present a novel adjunctive approach for protecting ischemic hearts. C1 Columbia Univ Coll Phys & Surg, Dept Med, Div Cardiol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20892 USA. Pfizer Global Res & Dev, Dept Cardiovasc & Metab Dis, Groton, CT USA. RP Ramasamy, R (reprint author), Columbia Univ Coll Phys & Surg, Dept Med, Div Cardiol, PH 10-403,630 W 168th St, New York, NY 10032 USA. EM rr260@columbia.edu NR 47 TC 2 Z9 2 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD DEC PY 2001 VL 15 IS 14 BP 243 EP + DI 10.1096/fj.01-0368fje PG 22 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 506HT UT WOS:000172964800004 ER PT J AU Karymov, MA Tomschik, M Leuba, SH Caiafa, P Zlatanova, J AF Karymov, MA Tomschik, M Leuba, SH Caiafa, P Zlatanova, J TI DNA methylation-dependent chromatin fiber compaction in vivo and in vitro: requirement for linker histone SO FASEB JOURNAL LA English DT Article DE histone H1; chromatin fibers; atomic force microscopy ID SCANNING FORCE MICROSCOPY; CPG METHYLATION; CORE PARTICLES; H1 HISTONE; RNA GENE; NUCLEOSOME; POLY(ADP-RIBOSYL)ATION; BINDING; TRANSCRIPTION; REPRESSION AB Dynamic alterations in chromatin structure mediated by postsynthetic histone modifications and DNA methylation constitute a major regulatory mechanism in DNA functioning. DNA methylation has been implicated in transcriptional silencing, in part by inducing chromatin condensation. To understand the methylation-dependent chromatin structure, we performed atomic force microscope (AFM) studies of fibers isolated from cultured cells containing normal or elevated levels of m(5)C. Chromatin fibers were reconstituted on control or methylated DNA templates in the presence or absence of linker histone. Visual inspection of AFM images, combined with quantitative analysis of fiber structural parameters, suggested that DNA methylation induced fiber compaction only in the presence of linker histones. This conclusion was further substantiated by biochemical results. C1 Polytech Univ, Dept Chem & Chem Engn, Brooklyn, NY 11201 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. Univ Roma La Sapienza, Dept Cellular Biotechnol & Haematol, I-00161 Rome, Italy. RP Zlatanova, J (reprint author), Polytech Univ, Dept Chem & Chem Engn, 6 Metrotech Ctr, Brooklyn, NY 11201 USA. EM leuba@nih.gov; jzlatano@duke.poly.edu RI Zlatanova, Jordanka/B-3273-2009 NR 60 TC 43 Z9 46 U1 1 U2 12 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD DEC PY 2001 VL 15 IS 14 BP 2631 EP 2641 DI 10.1096/fj.01-0345com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 506HT UT WOS:000172964800033 PM 11726539 ER PT J AU Rosenfeldt, HM Hobson, JP Maceyka, M Olivera, A Nava, VE Milstien, S Spiegel, S AF Rosenfeldt, HM Hobson, JP Maceyka, M Olivera, A Nava, VE Milstien, S Spiegel, S TI EDG-1 links the PDGF receptor to Src and focal adhesion kinase activation leading to lamellipodia formation and cell migration SO FASEB JOURNAL LA English DT Article DE sphingosine-1-phosphate; motility; Src; FAK ID PROTEIN-COUPLED RECEPTORS; HUMAN ENDOTHELIAL-CELLS; AIRWAY SMOOTH-MUSCLE; SPHINGOSINE 1-PHOSPHATE; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; LYSOPHOSPHATIDIC ACID; FAMILY KINASES; DEFICIENT MICE AB Sphingosine-1-phosphate (SPP), formed by sphingosine kinase, is the ligand for EDG-1, a GPCR important for cell migration and vascular maturation. Here we show that cytoskeletal rearrangements, lamel-lipodia extensions, and cell motility induced by platelet-derived growth factor (PDGF) are abrogated in EDG-1 null fibroblasts. However, EDG-1 appears to be dispensable for mitogenicity and survival effects, even those induced by its ligand SPP and by PDGF. Furthermore, PDGF induced focal adhesion formation and activation of FAK, Src, and stress-activated protein kinase 2, p38, were dysregulated in the absence of EDG-1. In contrast, tyrosine phosphorylation of the PDGFR and activation of extracellular signal regulated kinase (ERK1/2), important for growth and survival, were unaltered. Our results suggest that EDG-1 functions as an integrator linking the PDGFR to lamel-lipodia extension and cell migration. PDGF, which stimulates sphingosine kinase, leading to increased SPP levels in many cell types, also induces translocation of sphingosine kinase to membrane ruffles. Hence, recruitment of sphingosine kinase to the cell's leading edge and localized formation of SPP may spatially and temporally stimulate EDG-1, resulting in activation and integration of downstream signals important for directional movement toward chemoattractants, such as PDGF. These results may also shed light on the vital role of EDG-1 in vascular maturation. C1 Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, W226A Res Bldg,3970 Reservoir Rd NW, Washington, DC 20007 USA. EM spiegel@bc.georgetown.edu RI Maceyka, Michael/B-9277-2008 FU NCI NIH HHS [2P30-CA-51008]; NIGMS NIH HHS [GM43880] NR 64 TC 127 Z9 130 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD DEC PY 2001 VL 15 IS 14 BP 2649 EP 2659 DI 10.1096/fj.01-0523com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 506HT UT WOS:000172964800035 PM 11726541 ER PT J AU Ye, WM Chow, WH Lagergren, J Yin, L Nyren, O AF Ye, WM Chow, WH Lagergren, J Yin, L Nyren, O TI Risk of adenocarcinomas of the esophagus and gastric cardia in patients with gastroesophageal reflux diseases and after antireflux surgery SO GASTROENTEROLOGY LA English DT Article ID BARRETTS-ESOPHAGUS; INCREASING INCIDENCE; CANCER; REGRESSION; EPITHELIUM; CARCINOMA; TOBACCO; ALCOHOL; DIFFERENTIATION; FUNDOPLICATION AB Background & Aims: Gastroesophageal reflux has been proposed as an important risk factor for esophageal and gastric cardia adenocarcinoma, but prospective data are lacking. Furthermore, the effect of antireflux surgery has not yet been studied. We conducted a population-based retrospective cohort study to fill these gaps. Methods: A cohort of 35,274 male and 31,691 female patients with a discharge diagnosis of gastroesophageal reflux diseases, and another cohort of 6406 male and 4671 female patients who underwent antireflux surgery, were identified in the Swedish Inpatient Register. Follow-up was attained through record linkage with several nationwide registers. Standardized incidence ratio (SIR) was used to estimate relative risk of upper gastrointestinal cancers, using the general Swedish population as reference. Results: After exclusion of the first year follow-up, 37 esophageal and 36 gastric cardia adenocarcinomas were observed among male patients who did not have surgery (SIR, 6.3, 95% confidence interval [CI], 4.5-8.7; SIR, 2.4, 95% CI, 1.7-3.3, respectively). SIR for esophageal adenocarcinoma increased with follow-up time (P = 0.03 for trend). Among male patients who had undergone antireflux surgeries, risks were also elevated (16 esophageal adenocarcinoma, SIR, 14.1, 95% CI, 8.0-22.8; 15 gastric cardia adenocarcinomas, SIR, 5.3, 95% CI, 3.0-8.7) and remained elevated with time after surgery. The cancer risk pattern in women was similar to that for men, but the number of cases were much smaller. Conclusions: Gastroesophageal reflux is strongly associated with the risk of esophageal adenocarcinoma, and to a lesser extent, with gastric cardia adenocarcinoma. The risk of developing adenocarcinomas of the esophagus and gastric cardia remains increased after antireflux surgery. C1 Karolinska Inst, Dept Med Epidemiol, SE-17177 Stockholm, Sweden. Karolinska Inst, Dept Sodersjukhuset, SE-17177 Stockholm, Sweden. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Karolinska Hosp, Dept Surg, S-10401 Stockholm, Sweden. RP Ye, WM (reprint author), Karolinska Inst, Dept Med Epidemiol, Box 281, SE-17177 Stockholm, Sweden. RI Ye, Weimin/A-5939-2008 NR 41 TC 161 Z9 162 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2001 VL 121 IS 6 BP 1286 EP 1293 DI 10.1053/gast.2001.29569 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 497TN UT WOS:000172471700006 PM 11729107 ER PT J AU Frucht, DM Gadina, M Jagadeesh, GJ Aksentijevich, I Takada, K Bleesing, JJH Nelson, J Muul, LM Perham, G Morgan, G Gerritsen, EJA Schumacher, RF Mella, P Veys, PA Fleisher, TA Kaminski, ER Notarangelo, LD O'Shea, JJ Candotti, F AF Frucht, DM Gadina, M Jagadeesh, GJ Aksentijevich, I Takada, K Bleesing, JJH Nelson, J Muul, LM Perham, G Morgan, G Gerritsen, EJA Schumacher, RF Mella, P Veys, PA Fleisher, TA Kaminski, ER Notarangelo, LD O'Shea, JJ Candotti, F TI Unexpected and variable phenotypes in a family with JAK3 deficiency SO GENES AND IMMUNITY LA English DT Article DE JAK3; SCID; IL-2; Fas ligand; lymphoproliferation ID SEVERE COMBINED IMMUNODEFICIENCY; MICE LACKING JAK3; COMBINED IMMUNE-DEFICIENCY; COMMON GAMMA-CHAIN; T-CELLS; INTERLEUKIN-2 RECEPTOR; JAK3-DEFICIENT MICE; LYMPHOCYTE APOPTOSIS; TYROSINE KINASE; NATURAL-KILLER AB Mutations of the Janus kinase 3 (JAK3) have been previously described to cause an autosomal recessive variant of severe combined immunodeficiency (SCID) usually characterized by the near absence of T and NK cells, but preserved numbers of B lymphocytes (T-B+SCID). We now report a family whose JAK3 mutations are associated with the persistence of circulating T cells, resulting in previously undescribed clinical presentations, ranging from a nearly unaffected 18-year-old subject to an 8-year-old sibling with a severe lymphoproliferative disorder. Both siblings were found to be compound heterozygotes for the same deleterious JAK3 mutations: an A96G initiation start site mutation, resulting in a dysfunctional, truncated protein product and a G2775(+3)C mutation in the splice donor site sequence of intron 18, resulting in a splicing defect and a predicted premature stop. These mutations were compatible with minimal amounts of functional JAK3 expression, leading to defective cytokine-dependent signaling. Activated T cells in these patients failed to express Fas ligand (FasL) in response to IL-2, which may explain the accumulation of T cells with an activated phenotype and a skewed T cell receptor (TcR) V beta family distribution. We speculate that residual JAK3 activity accounted for the maturation of thymocytes, but was insufficient to sustain IL-2-mediated homeostasis of peripheral T cells via Fas/FasL interactions. These data demonstrate that the clinical spectrum of JAK3 deficiency is quite broad and includes immunodeficient patients with accumulation of activated T cells, and indicate an essential role for JAK3 in the homeostasis of peripheral T cells in humans. C1 NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Lab Med, Bethesda, MD USA. Derriford Hosp, Plymouth PL6 8DH, Devon, England. Great Ormond St Hosp Children, London WC1N 3JH, England. Univ Brescia, Dept Pediat, I-25121 Brescia, Italy. RP Frucht, DM (reprint author), Cell Biol Lab, Bldg 29B,Room 3NN22, Bethesda, MD 20892 USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 46 TC 31 Z9 33 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD DEC PY 2001 VL 2 IS 8 BP 422 EP 432 DI 10.1038/sj.gene.6363802 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 497ET UT WOS:000172443000002 PM 11781709 ER PT J AU Zhao, JM Moch, H Scheidweiler, AF Baer, A Schaffer, AA Speel, EJM Roth, J Heitz, PU Komminoth, P AF Zhao, JM Moch, H Scheidweiler, AF Baer, A Schaffer, AA Speel, EJM Roth, J Heitz, PU Komminoth, P TI Genomic imbalances in the progression of endocrine pancreatic tumors SO GENES CHROMOSOMES & CANCER LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; VONHIPPEL-LINDAU-DISEASE; NEUROENDOCRINE TUMORS; SUPPRESSOR GENE; CHROMOSOMAL ALTERATIONS; HYBRIDIZATION; GASTRINOMAS; MANAGEMENT; MUTATIONS; METASTASES AB Endocrine pancreatic tumors (EPTs) are neoplasms with malignant potential. To explore the molecular basis of metastatic progression in human El we analyzed 17 paired specimens of primary EPTs and their metastases and 28 nonmetastatic EPTs using comparative genomic hybridization (CGH). Genomic alterations were detected in all of the matched primary/metastatic tumors and 19 (58%) nonmetastatic EPTs. The mean number of genomic changes was 17.3 in metastases, 12.5 in their primary tumors, and 4.5 in nonmetastatic EPTs. Statistical analysis of shared genomic changes in matched pairs of primary tumors and metastases showed a high probability (>95%) of a clonal relationship in 15 of the 17 cases. A closely related genetic pattern was also demonstrated on the basis of concordance analysis of the two groups. The most striking genomic changes which were enriched in metastases included gains of chromosomes 4 and 7 and losses of 21q. Other common regions of frequent losses (>40%) identified in metastases and/or their primary tumors involved 2p, 2q, 3p, 3q, 6q, 10p, and 11p, whereas frequently detected gains (>40%) in the paired tumors involved 5p, 5q, 12q, 14q, 17q, 18q, and 20q. These chromosomal aberrations were found in significantly fewer nonmetastatic EPTs. Some of these chromosomal loci may harbor genes contributing to the progression of El (C) 2001 Wiley-Liss, Inc. C1 Univ Zurich, Inst Pathol, Dept Pathol, CH-8091 Zurich, Switzerland. Univ Basel, Inst Pathol, Basel, Switzerland. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. Univ Zurich, Div Cell & Mol Pathol, Zurich, Switzerland. RP Zhao, JM (reprint author), Univ Zurich, Inst Pathol, Dept Pathol, Schmelzbergstr 12, CH-8091 Zurich, Switzerland. RI Schaffer, Alejandro/F-2902-2012 NR 28 TC 71 Z9 72 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 2001 VL 32 IS 4 BP 364 EP 372 DI 10.1002/gcc.1201 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 489WQ UT WOS:000172015800008 PM 11746977 ER PT J AU Kudoh, T Tsang, M Hukriede, NA Chen, XF Dedekian, M Clarke, CJ Kiang, A Schultz, S Epstein, JA Toyama, R Dawid, IB AF Kudoh, T Tsang, M Hukriede, NA Chen, XF Dedekian, M Clarke, CJ Kiang, A Schultz, S Epstein, JA Toyama, R Dawid, IB TI A gene expression screen in zebrafish embryogenesis SO GENOME RESEARCH LA English DT Article ID MOUSE EMBRYOS; SPEMANNS ORGANIZER; XENOPUS EMBRYOS; HOMEOBOX GENES; CDNA LIBRARY; PROTEIN; ENDODERM; CONSTRUCTION; INDUCTION; PATTERN AB A screen for developmentally regulated genes was conducted in the zebrafish, a system offering substantial advantages for the study of the molecular genetics of vertebrate embryogenesis. Clones from a normalized cDNA library from early somitogenesis stages were picked randomly and tested by high-throughput in situ hybridization for restricted expression in at least one of four stages of development. Among 2765 clones that were screened, a total of 347 genes with patterns judged to be restricted were selected. These clones were subjected to partial sequence analysis, allowing recognition of functional motifs in 163 among them. In addition, a portion of the clones were mapped with the aid of the LN54 radiation hybrid panel. The usefulness of the in situ hybridization screening approach is illustrated by describing several new markers for the characteristic structure in the fish embryo named the yolk syncytial layer, and for different regions of the developing brain. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Unit Biol Computat, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RI TSANG, Michael/E-2758-2013; Tsang, Michael/I-9305-2014 OI TSANG, Michael/0000-0001-6384-2422; Tsang, Michael/0000-0001-7123-0063 NR 47 TC 139 Z9 141 U1 2 U2 19 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD DEC PY 2001 VL 11 IS 12 BP 1979 EP 1987 DI 10.1101/gr.209601 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 497VF UT WOS:000172475600003 PM 11731487 ER PT J AU Hukriede, N Fisher, D Epstein, J Joly, L Tellis, P Zhou, Y Barbazuk, B Cox, K Fenton-Noriega, L Hersey, C Miles, J Sheng, XM Song, A Waterman, R Johnson, SL Dawid, IB Chevrette, M Zon, LI McPherson, J Ekker, M AF Hukriede, N Fisher, D Epstein, J Joly, L Tellis, P Zhou, Y Barbazuk, B Cox, K Fenton-Noriega, L Hersey, C Miles, J Sheng, XM Song, A Waterman, R Johnson, SL Dawid, IB Chevrette, M Zon, LI McPherson, J Ekker, M TI The LN54 radiation hybrid map of zebrafish expressed sequences SO GENOME RESEARCH LA English DT Article ID VERTEBRATE GENOME EVOLUTION; DANIO-RERIO; CHROMOSOMES; GENES AB To increase the density of a gene map of the zebrafish, Danio rerio, we have placed 3119 expressed sequence tags (ESTs) and cDNA sequences oil the LN54 radiation hybrid (RH) panel. The ESTs and genes mapped here join 748 SSLp markers and 459 previously mapped genes and ESTs, bringing the total number of markers on the LN54 RH panel to 4226. Addition of these new markers brings the total LN54 map size to 14,372 cR, with 118 kb/cR. The distribution of ESTs according to linkage groups shows relatively little variation (minimum, 73; maximum, 201). This observation, combined with a relatively uniform size for zebrafish chromosomes, as previously indicated by karyotyping, indicates that there are no especially gene-rich or gene-poor chromosomes in this species. We developed an algorithm to provide a semiautomatic method for the selection of additional framework markers for the LN54 map. This algorithm increased the total number of framework markers to 1150 and permitted the mapping of a high percentage of sequences that could not be placed on a previous version of the LN54 map. The increased concentration of expressed sequences on the LN54 map of the zebrafish genome will facilitate the molecular characterization of mutations in this species. C1 Ottawa Civic Hosp, Res Inst, Ottawa, ON K1Y 4E9, Canada. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Unit Biol Computat, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada. McGill Univ, Dept Surg, Montreal, PQ H3G 1A4, Canada. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Dept Hematol, Boston, MA 02115 USA. Univ Ottawa, Dept Med, Ottawa, ON K1Y 4E9, Canada. Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1Y 4E9, Canada. RP Ekker, M (reprint author), Ottawa Civic Hosp, Res Inst, Ottawa, ON K1Y 4E9, Canada. FU NIDDK NIH HHS [R01 DK055381, R01 DK55379, R01 DK55381] NR 27 TC 61 Z9 62 U1 1 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD DEC PY 2001 VL 11 IS 12 BP 2127 EP 2132 DI 10.1101/gr.210601 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 497VF UT WOS:000172475600020 PM 11731504 ER PT J AU Cui, YZ Li, ML Walton, KD Sun, KL Hanover, JA Furth, PA Hennighausen, L AF Cui, YZ Li, ML Walton, KD Sun, KL Hanover, JA Furth, PA Hennighausen, L TI The Stat3/5 locus encodes novel endoplasmic reticulum and helicase-like proteins that are preferentially expressed in normal and neoplastic mammary tissue SO GENOMICS LA English DT Article ID METASTATIC-DISEASE; GLAND DEVELOPMENT; GENE-EXPRESSION; MOUSE; APOPTOSIS; STAT5B; AUXIN; INVOLUTION; INDUCTION; FAMILY AB The signal transducers and activators of transcription (STAT) 5 and 3 are critical for mammary alveolar development during pregnancy and remodeling during involution. In the mouse, STAT3, STAT5a, and STAT5b are encoded by adjacent genes on chromosome 11 (60.5 cM). To identify additional genes in the Stat3/5 locus that may participate in: normal and neoplastic development of the mammary gland, we have cloned and sequenced 500 kb and searched for genes preferentially expressed in mammary tissue. We identified six known genes and cloned two new genes, termed D11Lgp1 and D11Lgp2. Both genes are most highly expressed in normal mammary tissue and mammary tumors from several transgenic mouse models. LGP1 consists of 532 and 530 amino acids in mouse and human, respectively (88% similarity). A region in the carboxy-terminal half of LGP1 has limited homology with Arabidopsis thaliana GH3-like proteins. Immunofluorescence studies demonstrated that LGP1 is located in the nuclear envelope and the endoplasmic reticulum. LGP2 is a cytoplasmic protein of 678 amino acids. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. China Med Univ, Dept Med Genet, Shenyang 110001, Peoples R China. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. EM Yongzhic@intra.niddk.nih.gov; hennighausen@nih.gov OI Walton, Katherine/0000-0001-9108-5617 NR 19 TC 27 Z9 31 U1 3 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 2001 VL 78 IS 3 BP 129 EP 134 DI 10.1006/geno.2001.6661 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 501CW UT WOS:000172666200005 PM 11735219 ER PT J AU Jaworski, CJ Moreira, E Li, AG Lee, R Rodriguez, IR AF Jaworski, CJ Moreira, E Li, AG Lee, R Rodriguez, IR TI A family of 12 human genes containing oxysterol-binding domains SO GENOMICS LA English DT Article DE oxysterols; oxysterol-binding protein; multi-gene family; bioinformatics ID CHOLESTEROL-METABOLISM; OXYGENATED STEROLS; PROTEIN OSBP; CDNA CLONING; PATHWAY; CELLS; APOPTOSIS; IDENTIFICATION; TRANSCRIPTION; HOMOLOGY AB Oxysterol-binding proteins (OSBPs) have been described in a wide range of eukaryotes, and are often found to be part of a multi-gene family. We have used bioinformatics and data mining as a starting point for identifying new family members in humans based on the presence of the OSBP signature EQVSHHPP. In addition to OSBP and the recently reported OSBP2, we have found 10 other genes encoding oxysterol-binding domains. Here, we report cDNA and deduced peptide sequences of the previously unknown OSBPs and compare the peptides and genes. All of the genes encode a pleckstrin homology domain, except OSBPL2. However, two of the peptides, OSBPL2 and OSBPL1A, consist of the OSBP domain only. A second OSBPL1 transcript (OSBPL1B) contains 15 additional upstream exons, with a deduced peptide containing a pleckstrin homology domain. Cladistic analysis divides the human OSBP genes into five groups, whose members share similarities in sequence and gene structure; RT-PCR analysis indicates that expression patterns among group members vary widely. C1 NEI, NIH, Bethesda, MD 20892 USA. RP NEI, NIH, Bethesda, MD 20892 USA. EM jaworski@helix.nih.gov NR 37 TC 76 Z9 85 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 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD DEC PY 2001 VL 78 IS 3 BP 185 EP 196 DI 10.1006/geno.2001.6663 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 501CW UT WOS:000172666200011 PM 11735225 ER PT J AU Shaywitz, SE Holahan, JM Freudenheim, DA Fletcher, JM Makuch, RW Shaywitz, BA AF Shaywitz, SE Holahan, JM Freudenheim, DA Fletcher, JM Makuch, RW Shaywitz, BA TI Heterogeneity within the gifted: Higher IQ boys exhibit behaviors resembling boys with learning disabilities SO GIFTED CHILD QUARTERLY LA English DT Article ID YALE CHILDRENS INVENTORY; EMOTIONAL ADJUSTMENT; ATTENTIONAL DEFICITS; READING-DISABILITY; ADOLESCENTS; INSTRUMENT; STUDENTS AB Previous studies of the gifted have been inconsistent, portraying them as both more and less well adjusted than the nongifted or less gifted. We examined behavioral, cognitive, attentional, and family history dimensions among four groups of 87 boys: High Gifted (IQ 140-154), Low Gifted (IQ 124-139), Learning Disabled, and a Normal control group. Findings indicated that High Gifted boys exhibit levels of behavior problems similar to the Learning Disabled, whereas Low Gifted boys demonstrate significantly lower levels of behavioral problems than do the Learning Disabled boys. These data provide support for the view of the gifted population as heterogeneous, with the High Gifted exhibiting more behavioral problems than the Low Gifted. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Univ Texas, Sch Med, Houston, TX USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NICHD Yale Ctr Study Learning & Attent, New Haven, CT 06520 USA. RP Shaywitz, SE (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. NR 34 TC 7 Z9 7 U1 3 U2 4 PU NATL ASSOC GIFTED CHILDREN PI WASHINGTON PA 1707 L ST, NW, STE 550, WASHINGTON, DC 20006 USA SN 0016-9862 J9 GIFTED CHILD QUART JI Gifted Child Q. PD WIN PY 2001 VL 45 IS 1 BP 16 EP 23 DI 10.1177/001698620104500103 PG 8 WC Education, Special SC Education & Educational Research GA 398DU UT WOS:000166742000003 ER PT J AU Maurer, M Trajanoski, Z Frey, G Hiroi, N Galon, J Willenberg, HS Gold, PW Chrousos, GP Scherbaum, WA Bornstein, SR AF Maurer, M Trajanoski, Z Frey, G Hiroi, N Galon, J Willenberg, HS Gold, PW Chrousos, GP Scherbaum, WA Bornstein, SR TI Differential gene expression profile of glucocorticoids, testosterone, and dehydroepiandrosterone in human cells SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE microarray; gene expression profile; dehydroepiandrosterone (DHEA); glucocorticoids; testosterone; Principal Component Analysis (PCA); online PCR ID TRAUMA-HEMORRHAGE AB Glucocorticoids are the major immunomodulating hormones in the human body. Recently, increasing interest in androgens as immunomodulators has emerged. In particular, Dehydroepiandrosterone (DHEA) has been suggested as beneficial in the treatment of some autoimmune disorders. However, the action and role of testicular and adrenal androgens on human immune cells remains unclear. This is the first study to provide large-scale gene expression data on the action of different steroids (DHEA, glucocorticoids, and testosterone) on human peripheral blood mononuclear cells using the recently developed genomic-scale technology of microarrays. Novel computational tools and techniques such as Principal Component Analysis (PCA) were used for analysis, clustering and visualization. We have demonstrated that each steroid has its distinct gene expression profile, although DHEA and testosterone co-regulated most genes in a similar direction while glucocorticoids frequently regulated the same genes in an opposite direction. Our data suggest an important and a complex regulatory role for androgens on human immune cells that should be considered in androgen replacement or treatment strategies. C1 Graz Univ Technol, Inst Biomed Engn, Graz, Austria. NICHHD, Bethesda, MD USA. Univ Dusseldorf, Dept Endocrinol, Dusseldorf, Germany. Inst Curie Lab Immunol Cellulaire & Clin, Paris, France. NIMH, Bethesda, MD USA. RP Bornstein, SR (reprint author), Graz Univ Technol, Inst Biomed Engn, Graz, Austria. NR 16 TC 28 Z9 32 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD DEC PY 2001 VL 33 IS 12 BP 691 EP 695 DI 10.1055/s-2001-19142 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 510FV UT WOS:000173198800001 PM 11753752 ER PT J AU Fauth, C Zhang, HG Harabacz, S Brown, J Saracoglu, K Lederer, G Rittinger, O Rost, I Eils, R Kearney, L Speicher, MR AF Fauth, C Zhang, HG Harabacz, S Brown, J Saracoglu, K Lederer, G Rittinger, O Rost, I Eils, R Kearney, L Speicher, MR TI A new strategy for the detection of subtelomeric rearrangements SO HUMAN GENETICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; IN-SITU HYBRIDIZATION; MENTAL-RETARDATION; CHROMOSOMAL REARRANGEMENTS; RECURRENT TRANSLOCATION; TELOMERE INTEGRITY; MULTIPLEX-FISH; 24-COLOR FISH; LEUKEMIA; PROBES AB We present a new strategy for the detection of subtelomeric rearrangements. This approach is based on two hybridizations with different probe sets. The first set consists of microdissected subtelomeric probes (each 5-10 megabases in size) labeled combinatorially employing 7 different fluorochromes. With this set, subtelomeric interchromosomal exchanges can be detected in a 24-color experiment. The second set comprises a second generation of subtelomeric PAC-, P1- and BAC-clones. Probes for p- and q-arms are labeled with two different colors. This second set detects small deletions; in addition it provides regional information, so that translocated material identified by the first probe set can be assigned to the p- or q-arm of a chromosome. The test has been evaluated in a blind study on a series of subtle translocations and deletions. C1 Tech Univ Munich, Inst Human Genet, D-81675 Munich, Germany. LMU Munchen, Inst Anthropol & Human Genet, Munich, Germany. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Inst Mol Med, MRC, Mol Haematol Unit, Oxford, England. German Canc Res Ctr, D-6900 Heidelberg, Germany. St Johanns Spital, Klin Genet, Salzburg, Austria. LMU Munchen, Kinderklin, Abt Med Genet, Munich, Germany. RP Fauth, C (reprint author), Tech Univ Munich, Inst Human Genet, Trogerstr 32, D-81675 Munich, Germany. RI Speicher, Michael/B-5362-2013; Eils, Roland/B-6121-2009 OI Speicher, Michael/0000-0003-0105-955X; Eils, Roland/0000-0002-0034-4036 NR 37 TC 23 Z9 24 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 2001 VL 109 IS 6 BP 576 EP 583 DI 10.1007/s00439-001-0629-7 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 510FD UT WOS:000173197300002 PM 11810269 ER PT J AU Hodges, AK Li, SW Maynard, J Parry, L Braverman, R Cheadle, JP DeClue, JE Sampson, JR AF Hodges, AK Li, SW Maynard, J Parry, L Braverman, R Cheadle, JP DeClue, JE Sampson, JR TI Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin SO HUMAN MOLECULAR GENETICS LA English DT Article ID EKER RAT MODEL; GENE-PRODUCTS; SCLEROSIS GENE; ALLELIC LOSS; RENAL CARCINOMAS; CHROMOSOME 9Q34; CELL-CYCLE; COMPLEX; PROTEIN; EXPRESSION AB Critical functions of hamartin and tuberin, encoded by the TSC1 and TSC2 genes, are likely to be closely linked. The proteins interact directly with one another and mutations affecting either gene result in the tuberous sclerosis phenotype. However, the regions of hamartin and tuberin that interact have not been well defined, and the relationship between their interaction and the pathogenesis of tuberous sclerosis has not been explored. To address these issues a series of hamartin and tuberin constructs were used to assay for interaction in the yeast two-hybrid system. Hamartin (amino acids 302-430) and tuberin (amino acids 1-418) interacted strongly with one another. A region of tuberin encoding a putative coiled-coil (amino acids 346-371) was necessary but not sufficient to mediate the interaction with hamartin, as more N-terminal residues were also required. A region of hamartin (amino acids 719-998) predicted to encode coiled-coils was capable of oligermerization but was not important for the interaction with tuberin. Subtle, non-truncating mutations identified in patients with tuberous sclerosis and located within the putative binding regions of hamartin (N198_F199delinsI;593-595delACT) or tuberin (G294E and I365del), abolished or dramatically reduced interaction of the proteins as assessed by yeast two-hybrid assays and by co-immunoprecipitation of the full-length proteins from Cos7 cells. In contrast, three non-pathogenic missense polymorphisms of tuberin (R261W, M286V, R367Q) in the same region as the disease-causing TSC2 mutations did not. These results indicate a requirement for interaction in critical growth suppressing functions of hamartin and tuberin. C1 Univ Wales Coll Med, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales. NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Hodges, AK (reprint author), Univ Wales Coll Med, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales. RI Parry, Lee/A-9623-2011; Hodges, Angela/C-5676-2011; OI Parry, Lee/0000-0002-4467-9196 NR 48 TC 72 Z9 73 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 1 PY 2001 VL 10 IS 25 BP 2899 EP 2905 DI 10.1093/hmg/10.25.2899 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 504QW UT WOS:000172868200006 PM 11741833 ER PT J AU Caldwell, J Wainer, IW AF Caldwell, J Wainer, IW TI Stereochemistry: definitions and a note on nomenclature SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE enantiomer; stereochemistry; isomer; chiral; racemate AB The impact of stereochemistry in medicine is increasingly being felt with the realisation of the therapeutic potential offered by single enantiomers. Consequently, a basic comprehension of the terminology and nomenclature used in stereochemistry is becoming a requirement for many researchers and clinicians. The first aim of this article is to familiarise readers with some of the well-established terms used to define key principles in stereochemistry. The issue of nomenclature in stereochemistry can be confusing to the uninitiated. A search through the literature reveals a number of different designation systems, some of which may not be interchangeable or may be obsolete. The second aim of this article is, therefore, to clarify this issue. It is hoped that this article will assist the reader of this supplement, as well as facilitate the interpretation of both new and existing literature concerning enantiomeric drugs. Copyright (C) 2001 John Wiley Sons, Ltd. C1 NIA, Gerontol Res Ctr, Bioanalyt & Drug Discovery Unit, NIH, Baltimore, MD 21224 USA. Univ London Imperial Coll Sci Technol & Med, Sch Med, Div Biomed Sci, London, England. RP Wainer, IW (reprint author), NIA, Gerontol Res Ctr, Bioanalyt & Drug Discovery Unit, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 2 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD DEC PY 2001 VL 16 SU 2 BP S105 EP S107 DI 10.1002/hup.334 PG 3 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 508CX UT WOS:000173070900008 ER PT J AU Wainer, IW AF Wainer, IW TI The therapeutic promise of single enantiomers: introduction SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE enantiomer; stereochemistry; chiral ID STEREOISOMERS; LEUCOVORIN; IFOSFAMIDE AB This review uses several examples drawn from the literature to show how using active enantiomers as therapeutic agents may yield several benefits, including more predictable pharmacokinetics, more accurate drug monitoring and enhanced tolerability. As a result of these benefits, the therapeutic use of single enantiomers will become increasingly important not only in psychopharmacology, but in medicine generally. Indeed, over the early years of the new millennium, the therapeutic use of single active enantiomers is set to redefine the benefit-risk ratio in the management of many common conditions. Copyright (C) 2001 John Wiley Sons, Ltd. C1 NIA, Gerontol Res Ctr, Bioanalyt & Drug Discovery Unit, NIH, Baltimore, MD 21224 USA. RP Wainer, IW (reprint author), NIA, Gerontol Res Ctr, Bioanalyt & Drug Discovery Unit, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 18 TC 4 Z9 4 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD DEC PY 2001 VL 16 SU 2 BP S73 EP S77 DI 10.1002/hup.333 PG 5 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 508CX UT WOS:000173070900003 ER PT J AU Levi, AJ Segars, JH Miller, BT Leondires, MP AF Levi, AJ Segars, JH Miller, BT Leondires, MP TI Endometrial cavity fluid is associated with poor ovarian response and increased cancellation rates in ART cycles SO HUMAN REPRODUCTION LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-26, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Soc Reprod Med DE cancellation rates; endometrium; fluid; hydrosalpinx; IVF ID IN-VITRO FERTILIZATION; CHLAMYDIA-TRACHOMATIS INFECTION; GONADOTROPIN-RELEASING-HORMONE; HEAT-SHOCK PROTEINS; HYDROSALPINX FLUID; PREGNANCY RATES; ADVERSELY AFFECT; EMBRYO-TRANSFER; INFERTILE WOMEN; IGG ANTIBODIES AB BACKGROUND: Endometrial cavity fluid (ECF) is occasionally observed during assisted reproductive technology (ART) cycles. However, few reports have described its prevalence or significance. METHODS AND RESULTS: We examined the relationships between ECF, clinical pregnancy rate (CPR), tubal factor infertility and ultrasound-visible (USV) hydrosalpinges. In 843 ART cycles involving 721 patients, ECF was observed during stimulation in 57 cycles and after human chorionic gonadotrophin (HCG) administration in 12 cycles, with an overall incidence of 8.2% (69/843). When ECF was observed during stimulation, the cancellation rate due to poor ovarian response was significantly higher (29.8 versus 16.9%, P <0.05) and the CPR per started cycle was significantly lower (26.3 versus 42.4%, P <0.05) than cycles without ECF. When ECF developed after HCG administration, the CPR was similar compared with that of the group for which ECF was not observed. In the 327 cycles involving tubal factor infertility patients, USV hydrosalpinges were noted in 71 cycles (71/327; 21.7%), and ECF developed in five of those cycles (5/71; 7.0%). A total of 27 cycles during which ECF developed (27/57, 47.4%) involved non-tubal factor patients. CONCLUSIONS: ECF during stimulation was associated with increased cancellation rates and lower CPRs per started cycle, and was not associated with USV hydrosalpinges. Furthermore, ECF observed after HCG administration did not impact CPR and may represent a different clinical entity. C1 Walter Reed Army Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol, Washington, DC 20307 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Reprod Med Associates New Jersey, Morristown, NJ USA. RP Leondires, MP (reprint author), Walter Reed Army Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol, Room 2J06,Bldg 2,6900 Georgia Ave NW, Washington, DC 20307 USA. NR 44 TC 19 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD DEC PY 2001 VL 16 IS 12 BP 2610 EP 2615 DI 10.1093/humrep/16.12.2610 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 501FP UT WOS:000172673200023 PM 11726583 ER PT J AU Scuteri, A Chen, CH Yin, FCP Chih-Tai, T Spurgeon, HA Lakatta, EG AF Scuteri, A Chen, CH Yin, FCP Chih-Tai, T Spurgeon, HA Lakatta, EG TI Functional correlates of central arterial geometric phenotypes SO HYPERTENSION LA English DT Article; Proceedings Paper CT 4th International Workshop on Structure and Function on Large Arteries CY APR 27-28, 2001 CL PARIS, FRANCE DE blood flow velocity; blood pressure; carotid arteries; hypertension; arterial remodeling; ultrasonography ID ISOLATED SYSTOLIC HYPERTENSION; CAROTID-ARTERY; ASSOCIATION; HYPERTROPHY; THICKNESS; FORCES; STRESS; MASS AB We have assessed the functional correlates of common carotid artery (CCA) arterial geometry, derived by combining a measure of vascular mass (VM) with the wall-to-lumen (W/L) ratio in both untreated hypertensive (HT) and normotensive (NT: blood pressure < 140/90 mm Hg) subjects of a broad age span (30 to 79 years) of both genders. Brachial systolic, diastolic, and pulse (SBP, DBP, PP) pressures; CCA SBP and PP. CCA diameter (D); intima-media thickness (IMT); relative distensibility, circumferential wall stress (MBP X W/L). fluid shear stress (FSS); strain, augmentation index (AGIh); and aortic pulse wave velocity (PWV) were measured in 680 NT and 635 untreated HT Taiwanese men and women. Carotid geometric phenotypes (CGPs) were derived from ultrasonographic measures of VM and W/L ratio. A normal CGP (CGPI) was defined as that within the 95th NT percentile of age- and gender-specific VM and W/L means. Three "deviant" CGPs were defined as follows: CGP2 or remodeling. ie, a normal VM coupled with an increased W/L; CGP3 or hypertrophy, ie, an increase in both VM and W/L; and CGP4 or hypertrophy with dilation, ie, an increased VM with normal W/L. The prevalence of specific CGPs in the total sample was 83.4% . for CGPI, 5.5% for CGP2, 2.2% for CGP3, and 8.9% for CGP4. Compared with CGPI, all deviant CGPs had increased carotid resistance, had higher CCA circumferential wall stress, and varied in blood flow velocity. Compared with CGP I CGP2 subjects were more likely to be women (69.3% versus 45.9%), were on average 10 years older, and had similar central and brachial BP levels. PWV, and AGIh but had increased strain, higher distensibility, lower flow, and a higher FSS. CGP3 subjects did not differ in age or gender but had a higher prevalence of HT; higher circumferential stress, PWV, and distensibility: and lower flow, as well as a trend toward higher SBP PP, and AGIh and lower FSS. CGP4 subjects did not differ in age or gender but exhibited higher AGIh and aortic PWV. lower distensibility and FSS, and unchanged strain and flow. CGP4 was the only deviant CGP in which the average brachial or central arterial pressures were significantly increased. CGP4 subjects also had the highest prevalence of HT among all the CGPs (77.8% versus 45% in CGPI). CGPs exhibit some common mechanical or functional proper-ties but each also exhibits a unique profile. Although differing quantitatively in NT and HT and at young and older age, the characteristic functional profile of a given CGP is preserved, regardless of age or BP status. A normal CGP is characterized by a low circumferential wall stress and high FSS. Each deviant CGP is characterized by a unique combination of increased circumferential wall stress, with variable FSS, strain, distensibility, central BP. and late pressure augmentation. The interplay among these factors, particularly circumferential wall and FSS, likely determines the CGP: conversely, the resultant CGP may modulate the FSS and wall stress for a given pressure and flow. C1 NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. Natl Yang Ming Univ, Div Cardiol, Taipei Vet Gen Hosp, Dept Social Med, Taipei, Taiwan. Washington Univ, Dept Biomed Engn, St Louis, MO USA. Taichung Vet Gen Hosp, Div Cardiol, Taichung, Taiwan. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 20 TC 31 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2001 VL 38 IS 6 BP 1471 EP 1475 DI 10.1161/hy1201.099291 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 509HT UT WOS:000173141500045 PM 11751738 ER PT J AU Butera, RJ Wilson, CG DelNegro, CA Smith, JC AF Butera, RJ Wilson, CG DelNegro, CA Smith, JC TI A methodology for achieving high-speed rates for artificial conductance injection in electrically excitable biological cells SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE computational instrumentation; electrophysiology; neurophysiology ID PRE-BOTZINGER COMPLEX; RESPIRATORY RHYTHM GENERATION; PACEMAKER NEURONS; VENTRICULAR CELLS; DYNAMIC CLAMP; MODELS; CIRCUITS AB We present a novel approach to implementing the dynamic clamp protocol (Sharp et al., 1993), commonly used in neurophysiology and cardiac electrophysiology experiments. Our approach is based on real-time extensions to the Linux operating system. Conventional PC-based approaches have typically utilized single-cycle computational rates of 10 kHz or slower. In this paper, we demonstrate reliable cycle-to-cycle rates as fast as 50 kHz. Our system, which we call model reference current injection (MRCI); pronounced merci is also capable of episodic logging of internal state variables and interactive manipulation of model parameters. The limiting factor in achieving high speeds was not processor speed or model complexity, but cycle jitter inherent in the CPU/motherboard performance. We demonstrate these high speeds and flexibility with two examples: 1) adding action-potential ionic currents to a mammalian neuron under whole-cell patch-clamp and 2) altering a cell's intrinsic dynamics via MRCI while simultaneously coupling it via artificial synapses to an internal computational model cell. These higher rates greatly extend the applicability of this technique to the study of fast electrophysiological currents such fast Na+ currents and fast excitatory/inhibitory synapses. C1 Georgia Inst Technol, Sch Elect & Comp Engn, Atlanta, GA 30332 USA. NINCDS, Cellular & Syst Neurobiol Sect, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP Butera, RJ (reprint author), Georgia Inst Technol, Sch Elect & Comp Engn, Atlanta, GA 30332 USA. NR 35 TC 29 Z9 33 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD DEC PY 2001 VL 48 IS 12 BP 1460 EP 1470 DI 10.1109/10.966605 PG 11 WC Engineering, Biomedical SC Engineering GA 493NW UT WOS:000172230400011 PM 11759927 ER PT J AU Yim, PJ Cebral, JJ Mullick, R Marcos, HB Choyke, PL AF Yim, PJ Cebral, JJ Mullick, R Marcos, HB Choyke, PL TI Vessel surface reconstruction with a tubular deformable model SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE atherosclerosis; deformable model; magnetic resonance angiography; surface reconstruction ID COMPUTATIONAL HEMODYNAMICS; ANGIOGRAPHIC IMAGES; MR-ANGIOGRAPHY; MEDICAL IMAGES; BLOOD-FLOW; SEGMENTATION; VISUALIZATION; CONTRAST; ULTRASOUND; ANEURYSMS AB Three-dimensional (3-D) angiographic methods are gaining acceptance for evaluation of atherosclerotic disease. However, measurement of vessel stenosis from 3-D angiographic methods can be problematic due to limited image resolution and contrast. We present a method for reconstructing vessel surfaces from 3-D angiographic methods that allows for objective measurement of vessel stenosis. The method is a deformable model that employs a tubular coordinate system. Vertex merging is incorporated into the coordinate system to maintain even vertex spacing and to avoid problems of self-intersection of the surface. The deformable model was evaluated on clinical magnetic resonance (MR) images of the carotid (n = 6) and renal (n = 2) arteries, on an MR image of a physical vascular phantom and on a digital vascular phantom. Only one gross error occurred for all clinical images. All reconstructed surfaces had a realistic, smooth appearance. For all segments of the physical vascular phantom, vessel radii from the surface reconstruction had an error of less than 0.2 of the average voxel dimension. Variability of manual initialization of the deformable model had negligible effect on the measurement of the degree of stenosis of the digital vascular phantom. C1 NIH, Imaging Sci Program, Bethesda, MD 20892 USA. George Mason Univ, Sch Computat Sci, Fairfax, VA 22030 USA. GE John F Welch Technol Ctr, Bangalore, Karnataka, India. NIH, Imaging Sci Program, Bethesda, MD 20892 USA. RP Yim, PJ (reprint author), NIH, Imaging Sci Program, Bldg 10,Room 1C660, Bethesda, MD 20892 USA. NR 30 TC 75 Z9 80 U1 1 U2 9 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD DEC PY 2001 VL 20 IS 12 BP 1411 EP 1421 DI 10.1109/42.974935 PG 11 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 511ZM UT WOS:000173296700021 PM 11811840 ER PT J AU Mueller, YM De Rosa, SC Hutton, JA Witek, J Roederer, M Altman, JD Katsikis, PD AF Mueller, YM De Rosa, SC Hutton, JA Witek, J Roederer, M Altman, JD Katsikis, PD TI Increased CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells SO IMMUNITY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTED RHESUS-MONKEYS; FAS LIGAND EXPRESSION; LYMPH-NODES; PERIPHERAL-BLOOD; CROSS-LINKING; UP-REGULATION; TAT PROTEIN; VIRAL-RNA; LYMPHOCYTES AB Why HIV-specific CD8(+) T cells ultimately fail to clear or control HIV infection is not known. We show here that HIV-specific CD8(+) T cells exhibit increased sensitivity to CD95/Fas-induced apoptosis. This apoptosis is 3-fold higher compared to CMV-specific CD8(+) T cells from the same patients. HIV-specific CD8+ T cells express the CD45RA(-)CD62L(-) but lack the CD45RA(+)CD62L- T cell effector memory (T-EM) phenotype. This skewing is not found in CMV- and EBV-specific CD8(+) T cells in HIV-infected individuals. CD95/Fas-induced apoptosis is much higher in the CD45RA-CD62L- T-EM cells. However, cytotoxicity and IFN gamma production by HIV-specific CD8(+) T cells is not impaired. Our data suggest that the survival and differentiation of HIV-specific CDW T cells may be compromised by CD95/Fas apoptosis induced by FasL-expressing HIV-infected cells. C1 Med Coll Penn & Hahnemann Univ, Dept Microbiol & Immunol, Philadelphia, PA 19129 USA. Med Coll Penn & Hahnemann Univ, Dept Med, Philadelphia, PA 19129 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30329 USA. RP Katsikis, PD (reprint author), Med Coll Penn & Hahnemann Univ, Dept Microbiol & Immunol, 3300 Henry Ave, Philadelphia, PA 19129 USA. RI Roederer, Mario/G-1887-2011 FU NIAID NIH HHS [R01 AI46719] NR 47 TC 108 Z9 108 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2001 VL 15 IS 6 BP 871 EP 882 DI 10.1016/S1074-7613(01)00246-1 PG 12 WC Immunology SC Immunology GA 506GK UT WOS:000172961400003 PM 11754810 ER PT J AU Radaev, S Rostro, B Brooks, AG Colonna, M Sun, PD AF Radaev, S Rostro, B Brooks, AG Colonna, M Sun, PD TI Conformational plasticity revealed by the cocrystal structure of NKG2D and its class I MHC-like ligand ULBP3 SO IMMUNITY LA English DT Article ID T-CELL RECEPTOR; CRYSTAL-STRUCTURE; PROTEIN STRUCTURES; NK CELLS; COMPLEX; PEPTIDE; RECOGNITION; ACTIVATION; INTERFACES; MOLECULES AB wNKG2D is known to trigger the natural killer (NK) cell lysis of various tumor and virally infected cells. In the NKG2D/ULBP3 complex, the structure of ULBP3 resembles the alpha1 and alpha2 domains of classical MHC molecules without a bound peptide. The lack of alpha3 and beta 2m domains is compensated by replacing two hydrophobic patches at the underside of the class I MHC-like beta sheet floor with a group of hydrophilic and charged residues in ULBP3. NKG2D binds diagonally across the ULBP3 a helices, creating a complementary interface, an asymmetrical subunit orientation, and local conformational adjustments in the receptor. The interface is stabilized primarily by hydrogen bonds and hydrophobic interactions. Unlike the KIR receptors that recognize a conserved HLA region by a lock-and-key mechanism, NKG2D recognizes diverse ligands by an induced-fit mechanism. C1 NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Sun, PD (reprint author), NIAID, Struct Biol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. OI Colonna, Marco/0000-0001-5222-4987 NR 51 TC 101 Z9 107 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2001 VL 15 IS 6 BP 1039 EP 1049 DI 10.1016/S1074-7613(01)00241-2 PG 11 WC Immunology SC Immunology GA 506GK UT WOS:000172961400016 PM 11754823 ER PT J AU Udey, MC von Stebut, E Mendez, S Sacks, DL Belkaid, Y AF Udey, MC von Stebut, E Mendez, S Sacks, DL Belkaid, Y TI Skin dendritic cells in murine cutaneous leishmaniasis SO IMMUNOBIOLOGY LA English DT Article ID EPIDERMAL LANGERHANS CELLS; MAJOR INFECTION; NATURAL MODEL; T-CELLS; IMMUNITY; MICE; MACROPHAGES; VACCINATION; INDUCTION AB Studies of the immuno pathogenesis of Leishmania major-induced murine cutaneous leishmaniasis provide a framework for understanding the evolution of L. major infection of skin in humans and the foundation for rationale vaccine design. Experiments in which infection is initiated with "supraphysiologic" numbers of parasites clearly identify Th-derived type I cytokines as essential participants in macrophage activation and macrophage nitric oxide production as prerequisite for parasite control. Dendritic cells, rather than macrophages, appear to be responsible for L. major-specific Th priming in these studies. Recent studies of murine cutaneous leishmaniasis in a model system in which infection is initiated with lower, more physiologic numbers of parasites confirm many of the important findings obtained in "high dose" inoculation models, but important differences have been noted. The low dose inoculation model should ultimately provide insights into mechanisms that are responsible for dendritic cell recruitment into leishmania lesions, mechanisms that facilitate parasite acquisition by skin dendritic cells and cellular interactions that eventuate in T cell priming and lesion involution. C1 NCI, Ctr Canc Res, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Mainz, Dept Dermatol, D-6500 Mainz, Germany. RP Udey, MC (reprint author), NCI, Ctr Canc Res, Dermatol Branch, NIH, Bldg 10,Rm 12N238, Bethesda, MD 20892 USA. NR 22 TC 9 Z9 10 U1 0 U2 1 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD DEC PY 2001 VL 204 IS 5 BP 590 EP 594 DI 10.1078/0171-2985-00096 PG 5 WC Immunology SC Immunology GA 521ZG UT WOS:000173870800009 PM 11846222 ER PT J AU Griffiths, MM Remmers, EF AF Griffiths, MM Remmers, EF TI Genetic analysis of collagen-induced arthritis in rats: a polygenic model for rheumatoid arthritis predicts a common framework of cross-species inflammatory autoimmune disease loci SO IMMUNOLOGICAL REVIEWS LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; QUANTITATIVE TRAIT LOCUS; GENOME-WIDE LINKAGE; T-CELL; II COLLAGEN; SUSCEPTIBILITY LOCUS; AUTOANTIBODY PRODUCTION; ADJUVANT ARTHRITIS; DNA-POLYMORPHISM; IMMUNE-RESPONSE AB Collagen-induced arthritis (CIA) is a useful model for dissecting the genetic patterns underlying susceptibility to rheumatoid arthritis (RA) and related chronic/inflammatory autoimmune diseases. CIA exhibits three phenotypes characteristic of autoimmune disease pathogenesis: abnormal levels of immune reactivity to self antigens; chronic inflammation of target organs expressing that specific autoantigen; activation and direct participation of invading mononuclear cells and resident tissue fibroblasts in organ damage. Over 25 different quantitative trait loci (QTL) regulating arthritis severity and autoantibody in rats with CIA are mapped. QTL-congenic strains show that certain CIA-QTLs can modulate arthritis independently. These monogenic models are proving to be highly informative for fine mapping and function studies, revealing gender effects and evidence of gene clusters. Recent genome scans of RA populations identified RA-susceptibility loci in chromosome regions homologous to rat chromosomal segments housing CIA-QTLs. Also, CIA-QTLs frequently co-localize with susceptibility QTLs mapped in other rat arthritis models induced with non-immunogenic adjuvant oils and/or in rat autoimmune models of multiple sclerosis and diabetes. Common autoimmunity genes and inflammation genes important to several human diseases are likely being detected in the various rat disease models. Continued dissection of the genetic underpinnings of rat arthritis models should provide candidate genes for investigation in human patients and lead to a clearer understanding of the complex genetics of RA. C1 Univ Utah, Med Ctr, Dept Med, Div Rheumatol,Sch Med, Salt Lake City, UT 84132 USA. Salt Lake City Vet Affairs, Salt Lake City Hlth Care Syst, Res Serv, Salt Lake City, UT USA. NIAMSD, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Griffiths, MM (reprint author), Univ Utah, Med Ctr, Dept Med, Div Rheumatol,Sch Med, 30 N 1990 E 4B200, Salt Lake City, UT 84132 USA. NR 96 TC 28 Z9 33 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 2001 VL 184 BP 172 EP 183 DI 10.1034/j.1600-065x.2001.1840116.x PG 12 WC Immunology SC Immunology GA 519RH UT WOS:000173738900015 PM 12086311 ER PT J AU Tonelli, L Webster, JI Rapp, KL Sternberg, E AF Tonelli, L Webster, JI Rapp, KL Sternberg, E TI Neuroendocrine responses regulating susceptibility and resistance to autoimmune/inflammatory disease in inbred rat strains SO IMMUNOLOGICAL REVIEWS LA English DT Review ID PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING-FACTOR; NECROSIS-FACTOR SYNTHESIS; LEWIS RATS; ARGININE-VASOPRESSIN; GLUCOCORTICOID RECEPTOR; INFLAMMATORY DISEASE; INDUCED ARTHRITIS; BLOOD-PRESSURE; NERVOUS-SYSTEM AB Rodent animal models of inflammatory and autoimmune disease have been important tools in the study of the interaction between neuroendocrine physiology and the immune responses. The rat has been particularly useful in part because, in contrast to other species, most rat models of autoimmune/inflammatory disease are induced rather than spontaneous. This allows for systematic and controlled manipulations of the neuroendocrine system in relation to exposure to the antigen or pro-inflammatory trigger, The most frequently used immune challenges include lipopolysaccharide-induced septic shock, carrageenan-induced local inflammation and adjuvant or bacterial cell wall-induced arthritis. By analyzing the responses to these challenges in different strains of rats and mice it has been possible to define the relationships between the neuroendocrine and immune systems and to identify some mechanisms through which these connections confer susceptibility and resistance to autoimmune and inflammatory diseases. The present review will discuss data obtained from rodent physiology, indicating that an important component in the susceptibility or resistance to development of these diseases is due to dysfunctional regulation of the immune response by the neuroendocrine hypothalamic-pituitary-adrenal axis. In particular, the importance of neurons of the paraventricular hypothalamic nucleus in determining susceptibility or resistance to autoimmune and inflammatory disease will be discussed. C1 NIMH, Sect Neuroendocrine Immunol & Behav, Bethesda, MD USA. RP Sternberg, E (reprint author), 10 Ctr Dr MSC-1284,Bldg 10,Room 2D46, Bethesda, MD 20892 USA. RI Webster Marketon, Jeanette/H-5613-2011 OI Webster Marketon, Jeanette/0000-0002-3627-1094 NR 68 TC 28 Z9 29 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 2001 VL 184 BP 203 EP 211 DI 10.1034/j.1600-065x.2001.1840118.x PG 9 WC Immunology SC Immunology GA 519RH UT WOS:000173738900017 PM 11918683 ER PT J AU Ramsey, KH Sigar, IM Rana, SV Gupta, J Holland, SM Byrne, GI AF Ramsey, KH Sigar, IM Rana, SV Gupta, J Holland, SM Byrne, GI TI Role for inducible nitric oxide synthase in protection from chronic Chlamydia trachomatis urogenital disease in mice and its regulation by oxygen free radicals SO INFECTION AND IMMUNITY LA English DT Article ID GENITAL-TRACT INFECTION; OUTER-MEMBRANE PROTEIN; GENE KNOCKOUT MICE; CELL-CULTURE; GUINEA-PIGS; IN-VITRO; MACROPHAGES; ACTIVATION; IMMUNIZATION; SUPEROXIDE AB has been previously reported that although inducible nitric oxide synthase (MOS) gene knockout (NOS2(-/-)) mice resolve Chlamydia trachomatis genital infection, the production of reactive nitrogen species (RNS) via iNOS protects a significant proportion of mice from hydrosalpinx formation and infertility. We now report that higher in vivo RNS production correlates with mouse strain-related innate resistance to hydrosalpinx formation. We also show that mice with a deletion of a key component of phagocyte NADPH oxidase (p47(phox-/-)) resolve infection, produce greater amounts of RNS in vivo, and sustain lower rates of hydrosalpinx formation than both wild-type (WT) NOS2(+/+) and NOS2(-/-) controls. When we induced an in vivo chemical block in iNOS activity in p47(phox-/-) mice using NG-monomethyl-L-arginine (L-NMMA), a large proportion of these mice eventually succumbed to opportunistic infections, but not before they resolved their chlamydial infections. Interestingly, when compared to WT and untreated p47(phox-/-) controls, L-NMMA-treated p47(phox-/-) mice resolved their infections more rapidly. However, L-NMMA-treated p47(phox-/-) mice lost resistance to chronic chlamydial disease, as evidenced by an increased rate of hydrosalpinx formation that was comparable to that for NOS2(-/-) mice. We conclude that phagocyte oxidase-derived reactive oxygen species (ROS) regulate RNS during chlamydial urogenital infection in the mouse. We further conclude that while neither phagocyte oxidase-derived ROS nor iNOS-derived RNS are essential for resolution of infection, RNS protect from chronic chlamydial disease in this model. C1 Midwestern Univ, Chicago Coll Osteopath Med, Dept Microbiol, Downers Grove, IL 60515 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Sch Med, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. RP Ramsey, KH (reprint author), Midwestern Univ, Chicago Coll Osteopath Med, Dept Microbiol, Downers Grove, IL 60515 USA. FU NIAID NIH HHS [R01 AI019782, AI19782, AI37807, R15 AI037807, R15 AI037807-01A1] NR 43 TC 39 Z9 42 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2001 VL 69 IS 12 BP 7374 EP 7379 DI 10.1128/IAI.69.12.7374-7379.2001 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 494QP UT WOS:000172297600023 PM 11705910 ER PT J AU Egland, PG Du, LD Kolenbrander, PE AF Egland, PG Du, LD Kolenbrander, PE TI Identification of independent Streptococcus gordonii SspA and SspB functions in coaggregation with Actinomyces naeslundii SO INFECTION AND IMMUNITY LA English DT Article ID PORPHYROMONAS-GINGIVALIS; CELL-SURFACE; POLYPEPTIDES; BACTERIA; FUSOBACTERIUM; MOLECULES; ADHESION; BIOFILMS; GENES; DL1 AB The initial stages of dental plaque formation involve the adherence of early colonizing organisms such as Streptococcus gordonii and Actinomyces naeslundii to the saliva-coated tooth surface and to each other. The S. gordonii surface proteins SspA and SspB are known to play a role in adherence to salivary proteins and mediate coaggregation with other bacteria. Coaggregation is the adhesin receptor-mediated interaction between genetically distinct cell types and appears to be ubiquitous among oral isolates. To define the function of SspA and SspB separately on the surface of their natural host, we constructed and analyzed the coaggregation properties of an isogenic sspB mutant of S. gordonii DL1, an sspAB double mutant, and a previously described sspA mutant. A. naeslundii strains have been previously classified into six coaggregation groups based on the nature of their coaggregations with S. gordonii DL1 and other oral streptococci. Coaggregation assays with the ssp and sspB mutants showed that SspA and SspB are the streptococcal proteins primarily responsible for defining these coaggregation groups and, thus, are highly significant in the establishment of early dental plaque. SspA exhibited two coaggregation-specific functions. It participated in lactose-inhibitable and -noninhibitable interactions, while SspB mediated only lactose-noninhibitable coaggregations. Accordingly, the sspAB double mutant lacked these functions and allowed us to detect a third coaggregation interaction with one of these organisms. These proteins may play an important role in development of S. gordonii-A. naeslundii communities in early dental plaque. Understanding these adhesin proteins will aid investigations of complex microbial communities that characterize periodontal diseases. C1 NIDCR, NIH, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. RP Kolenbrander, PE (reprint author), NIDCR, NIH, Oral Infect & Immun Branch, Bldg 30,Room 310,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. NR 21 TC 42 Z9 44 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2001 VL 69 IS 12 BP 7512 EP 7516 DI 10.1128/IAI.69.12.7512-7516.2001 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 494QP UT WOS:000172297600040 PM 11705927 ER PT J AU Loukinova, E Chen, Z Van Waes, C Dong, G AF Loukinova, E Chen, Z Van Waes, C Dong, G TI Expression of proangiogenic chemokine Gro 1 in low and high metastatic variants of Pam murine squamous cell carcinoma is differentially regulated by IL-1 alpha, EGF and TGF-beta 1 through NF-kappa B dependent and independent mechanisms SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE chemokine; Gro 1 (KC); growth factors; IL-1 alpha; EGF; TGF-beta 1; transcription factors; NF-kappa B; squamous cell carcinoma ID PROINFLAMMATORY CYTOKINE EXPRESSION; HOST ENVIRONMENT PROMOTES; TUMOR-NECROSIS-FACTOR; HUMAN-MELANOMA CELLS; GENE-EXPRESSION; FACTOR-BETA; CONSTITUTIVE ACTIVATION; BREAST-CANCER; TGF-BETA; INTERLEUKIN-8 EXPRESSION AB We previously reported that chemokine Growth Regulated Oncogene 1 (Gro 1) is over-expressed in murine squamous cell carcinoma (SCC) with metastatic tumor progression. The enhanced expression of Gro-1 gene by SCC is regulated by activation of nuclear factor-kappaB (NF-kappaB), leading to accelerated tumor growth, angiogenesis and metastasis in vivo. In our study, we investigated the effect of the regulatory cytokines, IL-1 alpha, EGF and TGF-beta1 on activation of NF-kappaB and Gro 1 in primary and metastatic sublines of the murine SCC Pam 212. We found that Gro 1 expression could be induced by IL-1 alpha or EGF in the low cytokine producing Pam 212 cells, but no significant induction was observed in high cytokine producing and metastatic LY-2 cells. Conditioned medium from LY-2 containing functional IL-1 alpha induced Gro 1 expression in Pam 212 cells, which can be blocked by IL-1 receptor antagonist (IL-1 RA).IL-1 RA, however, had a minimal effect on constitutive Gro 1 production by LY-2 cells. TGF-beta1 suppressed constitutive as well as IL-1 alpha and EGF-inducible Gro 1 production in both Pam 212 and LY-2 cells. IL-1 alpha and EGF, but not TGF-beta1, were found to activate NF-kappaB in Pam 212, whereas none of the stimulants showed a significant effect on constitutive activation of NF-kappaB in LY-2 cells. Overexpression of a super repressor I kappaB alphaM in Pam 212 inhibited NF-kappaB binding activity, which led to impaired Gro 1 induction by IL-1 alpha and EGF. These results demonstrate that IL-1 alpha, EGF, and TGF-beta1 are important modulators of Gro 1 expression in SCC. Different responses to these modulators observed along with SCC metastatic progression may suggest a transition mechanism(s) for Gro 1 expression from host factor dependent to an independent stage involving NF-kappaB activation. C1 Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA. RP Dong, G (reprint author), NIDCD, NIH, Bldg 10,Rm 5D55,10 Ctr Dr, Bethesda, MD 20892 USA. FU NIDCD NIH HHS [Z01-DC-00016] NR 50 TC 36 Z9 38 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 DEC 1 PY 2001 VL 94 IS 5 BP 637 EP 644 DI 10.1002/ijc.1514 PG 8 WC Oncology SC Oncology GA 489BR UT WOS:000171972600005 PM 11745457 ER PT J AU Striegel-Moore, RH McMahon, RP Biro, FM Schreiber, G Crawford, PB Voorhees, C AF Striegel-Moore, RH McMahon, RP Biro, FM Schreiber, G Crawford, PB Voorhees, C TI Exploring the relationship between timing of menarche and eating disorder symptoms in black and white adolescent girls SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE sexual maturation; adolescent girls; early-onset menarche ID BODY-IMAGE; PUBERTY; FATNESS; ONSET AB Objective: This study examined the relationship between timing of sexual maturation and eating disorders symptoms in adolescent girls. Method: Data were collected over 10 years for a cohort of 1,213 Black girls and 1,166 White girls who were either 9 or 10 years old at study entry. Annually, girls' height and weight were measured and, biannually, girls completed self-report measures of eating disorders symptoms. Results: Early-onset menarche is a risk factor for the development of body image and dieting concerns, but the effect of timing is due to the impact of early and late maturation on body weight. Discussion: Findings underscore the importance of adiposity as a risk factor for poor mental health. (C) 2001 by John Wiley & Sons, Inc. C1 Wesleyan Univ, Middletown, CT USA. Maryland Med Res Inst, Baltimore, MD USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Westat Corp, Rockville, MD USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. NHLBI, Bethesda, MD 20892 USA. RP Striegel-Moore, RH (reprint author), Dept Psychol, 207 High St, Middletown, CT 06459 USA. RI McMahon, Robert/C-5462-2009 FU NHLBI NIH HHS [N01-HC55026, N01-HC-55023, N01-HC-55024, N01-HC-55025]; NIMH NIH HHS [R01 MH57897] NR 23 TC 50 Z9 52 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD DEC PY 2001 VL 30 IS 4 BP 421 EP 433 DI 10.1002/eat.1103 PG 13 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 489QP UT WOS:000172003200006 PM 11746303 ER PT J AU Wilcox, AJ AF Wilcox, AJ TI On the importance - and the unimportance - of birthweight SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE birthweight; fetal growth; gestational age; low birthweight; intrauterine growth retardation; small for gestational age; infant mortality; analytical methods ID LOW-BIRTH-WEIGHT; INTRAUTERINE GROWTH-RETARDATION; LOWER MORTALITY-RATE; PERINATAL-MORTALITY; PRETERM DELIVERY; UNITED-STATES; FETAL GROWTH; ASSOCIATION; FREQUENCY; PREGNANCY AB Birthweight is one of the most accessible and most misunderstood variables in epidemiology. A baby's weight at birth is strongly associated with mortality risk during the first! year and, to a. lesser degree, with developmental problems in childhood and the risk of various diseases in adulthood. Epidemiological analyses often regard birthweight as on the causal pathway to these health outcomes. Under this assumption of causality, birthweight is used to explain variations in infant mortality and later morbidity, and is also used as an intermediate health endpoint in itself. Evidence presented here suggests the link between birthweight and health outcomes may not be causal. Methods of analysis that assume causality are unreliable at best, and biased at worst. The category of 'low birthweight' in particular is uninformative and seldom justified. The main utility of the birthweight distribution is to provide an estimate of the proportion of small preterm births in a population (although even this requires special analytical methods). While the ordinary approaches to birthweight are not well grounded, the links between birthweight and a range of health outcomes may nonetheless reflect the workings of biological mechanisms with implications for human health. C1 Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Wilcox, AJ (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 46 TC 354 Z9 366 U1 4 U2 29 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 2001 VL 30 IS 6 BP 1233 EP 1241 DI 10.1093/ije/30.6.1233 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 520NC UT WOS:000173787100003 PM 11821313 ER PT J AU Matthews, JR AF Matthews, JR TI Commentary: The Paris Academy of Science report on Jean Civiale's statistical research and the 19th century background to evidence-based medicine SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Matthews, JR (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 2001 VL 30 IS 6 BP 1249 EP 1250 DI 10.1093/ije/30.6.1249 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 520NC UT WOS:000173787100008 PM 11821318 ER PT J AU Sachs, LM Amano, T Shi, YB AF Sachs, LM Amano, T Shi, YB TI An essential role of histone deacetylases in postembryonic organ transformations in Xenopus laevis SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE amphibian metamorphosis; histones acetylation; thyroid hormone receptor ID TRANSCRIPTIONAL REPRESSION; TRICHOSTATIN-A; AMPHIBIAN METAMORPHOSIS; RECEPTOR SUPERFAMILY; GENE-EXPRESSION; THYROID-HORMONE; N-COR; ACETYLATION; CHROMATIN; DIFFERENTIATION AB Amphibian metamorphosis is the result of thyroid hormone (TH)-induced organ transformations including de novo morphogenesis, tissue remodeling and resorption through programmed cell death (apoptosis). All chances during metamorphosis are presumed to be mediated through gene regulation cascades initiated by TH. Numerous studies have implicated important roles of chromatin remodeling in transcriptional regulation. In particular, several lines of evidence support the view that histone acetylation is associated with transcriptional activation and histone deacetylation leads to gene repression. Here we address the physiological roles of histone deacetylases during vertebrate postembryonic development by using amphibian metamorphosis as a model. We first demonstrate that Xenopus laevis Rpd3 (a histone deacetylase) and Sin3 (a corepressor associated to Rpd3) are expressed in premetamorphic and metamorphic tadpole tissues, suggesting their involvement in these postembryonic processes. To test this possibility, we use a histone deacetylase inhibitor, trichostatin A, to block histone deacetylases and examine the development of the tadpoles. Our results indicate both natural and T,-induced metamorphosis are blocked by the inhibitor. We further show that this drug inhibits metamorphosis in different tissues, whether they involve de novo development or resorption through apoptosis, and that it functions in a stage-dependent but organ-autonomous manner. The data thus support an important role of histone deacetylases in the gene regulation cascades induced by T-3 during metamorphosis. C1 NICHHD, Lab Gene Regulat & Dev, Unit Mol Morphogenesis, NIH, Bethesda, MD 20892 USA. Museum Natl Hist Nat, UMR 8572 CNRS, Lab Physiol Gen & Comparee, F-75231 Paris 05, France. RP Shi, YB (reprint author), NICHHD, Lab Gene Regulat & Dev, Unit Mol Morphogenesis, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. NR 41 TC 25 Z9 26 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD DEC PY 2001 VL 8 IS 6 BP 595 EP 601 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 495ER UT WOS:000172327700001 PM 11712071 ER PT J AU Neumeister, A Konstantinidis, A Praschak-Rieder, N Willeit, M Hilger, E Stastny, J Kasper, S AF Neumeister, A Konstantinidis, A Praschak-Rieder, N Willeit, M Hilger, E Stastny, J Kasper, S TI Monoaminergic function in the pathogenesis of seasonal affective disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Review DE catecholamines; pathogenesis; seasonal affective disorder; serotonin (5-HT) ID ACUTE TRYPTOPHAN DEPLETION; PLATELET H-3-IMIPRAMINE BINDING; FREE DEPRESSED-PATIENTS; MAJOR AFFECTIVE-DISORDERS; HEALTHY CONTROL SUBJECTS; EYE-BLINK RATES; I-123 BETA-CIT; LIGHT THERAPY; WINTER DEPRESSION; NORMAL MALES AB Seasonal affective disorder/winter type (SAD) is characterized by recurrent depressive episodes during autumn and winter alternating with non-depressive episodes during spring and summer. Light therapy with full-spectrum, bright white light has been shown to be effective for this condition. Several hypotheses have been discussed in the literature about the pathogenesis of SAD, The most prominent includes disturbances in central monoaminergic transmission. Evidence can be inferred from studies showing a seasonal rhythm of central and peripheral serotonergic functioning which may be a predisposing factor for SAD. Some of the symptoms of SAD are believed to represent an attempt to overcome a putative deficit in brain serotonergic transmission. Moreover, 5-HT receptor challenge studies suggest altered activity at or downstream to central 5-HT receptors. Monoamine depletion studies support hypotheses about serotonergic and catecholaminergic dysfunctions in SAD and suggest that light therapy may well compensate for this underlying deficit. Further, albeit indirect, support for the importance of monoaminergic mechanisms in SAD and its involvement in the mechanism of the action of light therapy comes from studies showing antidepressant efficacy of serotonergic and noradrenergic antidepressants in the treatment of SAD. Altogether, disturbances in brain monoaminergic transmission seem to play a key role in the pathogenesis of SAD; monoaminergic systems may also play an important role in the mechanisms of the action of light therapy. C1 NIMH, NIH, Mood Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Neumeister, A (reprint author), NIMH, NIH, Mood Anxiety Disorders Program, North Dr,Bldg 15K Room 200, Bethesda, MD 20892 USA. NR 109 TC 31 Z9 31 U1 2 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD DEC PY 2001 VL 4 IS 4 BP 409 EP 420 PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 513UT UT WOS:000173399200010 PM 11806867 ER PT J AU Ahmed, F Torrado, M Johnson, E Morrison, J Tomarev, SI AF Ahmed, F Torrado, M Johnson, E Morrison, J Tomarev, SI TI Changes in mRNA levels of the Myoc/Tigr gene in the rat eye after experimental elevation of intraocular pressure or optic nerve transection SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPEN-ANGLE GLAUCOMA; GLUCOCORTICOID RESPONSE PROTEIN; HEAD EXTRACELLULAR-MATRIX; TRABECULAR MESHWORK CELLS; OUTFLOW OBSTRUCTION; MOLECULAR-CLONING; RHESUS-MONKEY; EXPRESSION; TIGR; MYOCILIN AB PURPOSE. To isolate the rat Myoc/Tigr gene and investigate changes in its expression pattern in normal eyes and in eyes with either pressure-induced optic nerve damage or optic nerve transection. METHODS. Expression pattern of the rat Myoc/Tigr gene was investigated by Northern blot hybridization. Optic nerve damage and death of ganglion cells in the retina were induced unilaterally, by injection of hyper-tonic saline solution, episcleral vein cauterization, or optic nerve transection. The levels of mRNA for Myoc/Tigr were compared between several tissues of the control and surgically altered eyes, by using semiquantitative RT-PCR. real-time PCR, and Northern blot analysis. RESULTS. The rat Myoc/Tigr gene is 10 kb long and contains three exons. Among the eye tissues analyzed, Myoc/Tigr mRNA was detected in the combined tissues of the eye angle, sclera, cornea, retina, and optic nerve head. With pressure-induced optic nerve degeneration, the level of Myoc/Tigr mRNA decreased in the retina and the combined tissues of the eye angle, but increased in the optic nerve head. After optic nerve transection, the level of Myoc/Tigr mRNA increased in the retina, but did not change in the combined tissues of the eve angle. CONCLUSIONS. The decreased level of Myoc/Tigr mRNA in the retina after induction of elevated intraocular pressure compared with that in the control retina cannot be explained by ganglion cell death alone. Differences in Myoc/Tigr mRNA levels in eye tissues after elevation of intraocular pressure or optic nerve transection may reflect the activation of different signaling pathways involved in regulation of this gene. C1 NEI, LMDB, NIH, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Kenneth C Swan Ocular Neurobiol Lab, Casey Eye Inst, Portland, OR 97201 USA. RP Tomarev, SI (reprint author), NEI, LMDB, NIH, Bldg 6,Room 2A04,6 Ctr Dr,MSC 2730, Bethesda, MD 20892 USA. RI Torrado, Mario/A-4889-2010 OI Torrado, Mario/0000-0001-9762-7018 NR 41 TC 23 Z9 25 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2001 VL 42 IS 13 BP 3165 EP 3172 PG 8 WC Ophthalmology SC Ophthalmology GA 498GL UT WOS:000172501400013 PM 11726618 ER PT J AU de Smet, MD Bitar, G Mainigi, S Nussenblatt, RB AF de Smet, MD Bitar, G Mainigi, S Nussenblatt, RB TI Human S-antigen determinant recognition in uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MHC CLASS-II; MULTIPLE-SCLEROSIS; BETA-ARRESTIN; CRYSTAL-STRUCTURE; BEHCETS-DISEASE; T-CELLS; PEPTIDE; EXPRESSION; RESPONSES AB PURPOSE. Soluble antigen (S-Ag) is a member of the arrestin family of protein with which it shares a high level of homology. It is an immunologically privileged retinal antigen that can elicit experimental autoimmune uveitis (EAU) and is thought to be a target for ocular inflammatory diseases. This study was conducted to identify in humans, the immunogenic determinants of human S-Ag and to establish whether a specific response profile occurs in particular ocular inflammatory conditions. METHODS. Peripheral blood lymphocyte responses were measured against a panel of 40 overlapping synthetic peptides of human S-Ag in patients with chronic uveitis and compared with control subjects. Patients with Behcet disease, sarcoidosis, Vogt-Koyanagi-Harada, and sympathetic ophthalmia were tested. RESULTS. A limited number of immunodominant determinants were identified for Behcet disease and sarcoidosis. These were all located at sites of limited homology with other known arrestins. In addition, several individual patients had prominent proliferative responses to multiple determinants well above that of control subjects. This determinant spread was observed in all disease entities except sympathetic ophthalmia, which did not show any immunoreactivity to S-Ag. Significant response shifts were also noted over time in two patients. CONCLUSIONS. The results indicate that there are specific immunodominant determinants to human S-Ag in patients with certain forms of uveitis. However, in individual patients, response is not limited to these determinants. In the chronic stage of disease, response is spread over many determinants. C1 Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands. NEI, Clin Immunol Sect, Bethesda, MD 20892 USA. NEI, Immunol Lab, Bethesda, MD 20892 USA. RP de Smet, MD (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, Rm G2-217,Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. OI de Smet, Marc/0000-0002-9217-5603 NR 38 TC 53 Z9 55 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2001 VL 42 IS 13 BP 3233 EP 3238 PG 6 WC Ophthalmology SC Ophthalmology GA 498GL UT WOS:000172501400023 PM 11726628 ER PT J AU Seth, RK Haque, MSR Zelenka, PS AF Seth, RK Haque, MSR Zelenka, PS TI Regulation of c-fos induction in lens epithelial cells by 12(S)HETE-dependent activation of PKC SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PROTEIN-KINASE-C; EPIDERMAL GROWTH-FACTOR; SERUM RESPONSE ELEMENT; UNSATURATED FATTY-ACIDS; 12(S)-HYDROXYEICOSATETRAENOIC ACID; PHOSPHATIDYLINOSITOL 3-KINASE; INTERCELLULAR COMMUNICATION; LIPOXYGENASE METABOLITES; TYROSINE PHOSPHORYLATION; SELECTIVE ACTIVATION AB PURPOSE. 12(S)-Hydroxreicosatetraenoic acid (12(S)HETE), a 12-lipoxygenase metabolite of arachidonic acid, is required for epidermal growth factor (EGF)- dependent DNA synthesis and c-fos induction in lens epithelial cells. The present study was undertaken to identify signal transduction events upstream of c-fos induction that may be regulated by 12(S)HETE. METHODS. The rabbit lens epithelial cell line. N/N1003A, was cultured in serum-free medium, with or without EGF. Activation of PKC and other selected enzymes was examined in the presence of the lipoxygenase inhibitor baicalein and/or exogenous 12(S)HETE. Relative abundance of PKC isoforms in subcellular fractions was determined by immunoblot analysis with isoform-specific antibodies. PKC activity in subcellular fractions was measured by peptide substrate phosphorylation, with and without pseudosubstrate peptide inhibitor. Phosphorylated enzymes were detected by immunoblot analysis. Relative levels of c-fos mRNA were determined by RT/PCR with internal standard. RESULTS. Baicalein blocked EGF-dependent translocation and activation of PKC, without affecting phosphorylation of Erk1/2. Of several PKC isoforms investigated (alpha, betaI, beta II, and gamma), only PKC alpha and beta II were significantly activated by EGF and inhibited by baicalein. 12(S)HETE, in combination with EGF, countered the effect of lipoxygenase inhibitors on PKC activation, and 12(S)HETE in the absence of EGF stimulated PKC translocation. Also of note, 12(S)HETE alone activated PKC gamma, an isoform that was not significantly activated by EGF. Inhibiting PKC activation with GF109203X blocked induction of c-fos by EGF but did not affect EGF-stimulated phosphorylation of Erk1/2, indicating that the effect of PKC on c-fos; induction is independent of the Erk1/2 pathway. CONCLUSIONS. In lens epithelial cells, 12(S)HETE-dependent activation of PKC alpha and beta II acts in concert with other EGF-dependent signals to induce c-fos mRNA. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Zelenka, PS (reprint author), Bldg 6,Rm 214,6 Ctr Dr,MSC 2730, Bethesda, MD 20892 USA. NR 70 TC 21 Z9 23 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2001 VL 42 IS 13 BP 3239 EP 3246 PG 8 WC Ophthalmology SC Ophthalmology GA 498GL UT WOS:000172501400024 PM 11726629 ER PT J AU Aymerich, MS Alberdi, EM Martinez, A Becerra, SP AF Aymerich, MS Alberdi, EM Martinez, A Becerra, SP TI Evidence for pigment epithelium-derived factor receptors in the neural retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CILIARY NEUROTROPHIC FACTOR; CEREBELLAR GRANULE CELLS; FACTOR PEDF; NONINHIBITORY SERPIN; MOTOR-NEURONS; GENE-TRANSFER; BOVINE EYES; EXPRESSION; PHOTORECEPTORS; MOUSE AB PURPOSE. The neurotrophic activity of pigment epithelium-derived factor (PEDF), an extracellular factor present in the retina, is mediated by binding to cell-surface receptors in responsive cell cultures. In the present study, the expression of PEDF receptors in native neural retinas from adult steers was examined. METHODS. Binding reactions were performed with I-125-PEDF and fluoresceinated PEDF using plasma membranes, detergent-soluble membrane proteins, or cryosections of retina from adult bovine eves. Radioligand-binding and competition analyses were performed with a computer-assisted program. Ligand blot analysis of detergent-soluble membrane proteins was performed with I-125-PEDF followed by autoradiography. Ligand-affinity column chromatography of detergent-soluble membrane proteins was performed with PEDF-coupled resin followed by SDS-PAGE. Binding of fluoresceinated PEDF to retina cryosections was detected by confocal microscopy. RESULTS. Radioligand-binding assays showed that I-125-PEDF bound in a specific and saturable fashion to one class of sites on retina membranes (K-d = 2.5-6.5 nM: maximum binding [B-max] = 1-48 X 10(10) sites/retina). A peptide of 44 amino acids (44-mer), identified as the receptor-binding region of PEDF, competed efficiently for I-125-PEDF binding to retina membranes with kinetics similar to the full-length PEDF. Ligand blot analysis and ligand-affinity chromatography revealed a specific and high-affinity PEDF-binding protein of similar to 85 kDa in retina plasma membranes. Confocal microscopy showed that fluorescein-conjugated PEDF stained exclusively the inner segments of photoreceptors and cells of the ganglion cell layer in retinal cryosections. CONCLUSIONS. Altogether, these data conclusively demonstrate the existence of PEDF receptors discretely distributed on the surface of cells from the adult neural retina of bovine eyes. Furthermore, they provide evidence for the direct action of PEDF on photoreceptor and ganglion cell neurons and an anatomic basis for studies to assess PEDF neurotrophic effects on the adult retina. C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. NCI, Dept Cell & Canc Biol, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Becerra, SP (reprint author), NEI, LRCMB, NIH, Bldg 6,Room 308,6 Ctr Dr,MSC 2740, Bethesda, MD 20892 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 39 TC 79 Z9 85 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2001 VL 42 IS 13 BP 3287 EP 3293 PG 7 WC Ophthalmology SC Ophthalmology GA 498GL UT WOS:000172501400030 PM 11726635 ER PT J AU Leverich, GS Nolen, WA Rush, AJ McElroy, SL Keck, PE Denicoff, KD Suppes, T Altshuler, LL Kupka, R Kramlinger, KG Post, RM AF Leverich, GS Nolen, WA Rush, AJ McElroy, SL Keck, PE Denicoff, KD Suppes, T Altshuler, LL Kupka, R Kramlinger, KG Post, RM TI The Stanley Foundation Bipolar Treatment Outcome Network I. Longitudinal methodology SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; methodology; longitudinal; clinical trials; treatment; life chart; CGI-BP; Stanley Foundation Bipolar Network; NIMH ID AFFECTIVE-DISORDER; UNITED-STATES; DOUBLE-BLIND; WORKSHOP REPORT; LAMOTRIGINE; PLACEBO; ILLNESS; SCALE; DEPRESSION; PREVALENCE AB The NIMH-Stanley Foundation Bipolar Treatment Outcome Network, a multisite clinical trials network, has been established to address many of the neglected areas of research in bipolar illness. The Network was designed so that it would be able to conduct randomized clinical trials at several different levels of methodologic rigor (blinded and open-label) both in academic and community practice settings in order to better assess long-term efficacy of existing treatments and develop new ones. In this fashion, large numbers of representative patients with bipolar disorder have been enrolled with an additional focus of elucidating possible clinical and biological predictors of treatment response. The unique focus of the Network is its systematic longitudinal approach to illness so that patients can be assessed comprehensively over the long-term in sequential randomized clinical trials at critical clinical decision points where data on relative efficacy are inadequate. Bipolar I and bipolar II patients with a range of illness variants and comorbidities are included. Daily prospective ratings of severity of mania and depression and associated degree of functional impairment are completed on the NIMH-Life Chart Method(TM) and a modified Clinical Global Impressions Scale for Bipolar Illness (CGI-BP) is utilized. More detailed cross-sectional ratings for depression (Inventory of Depressive Symptomatology), mania (Young Mania Rating Scale), and psychosis (Positive and Negative Syndrome Scale) are additionally used at academic centers. This article describes the rationale for the Network, its guiding principles, methods, and study design to systematically assess the highly variable course of bipolar illness and its response to current and future treatments. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Willem Arntsz Huis & Acad Hosp, HC Rumke Grp, Utrecht, Netherlands. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Cincinnati, Coll Med, Dept Psychiat, Biol Psychiat Program, Cincinnati, OH USA. Univ Calif Los Angeles, Los Angeles, CA USA. VA Med Ctr, Los Angeles, CA USA. Mayo Clin, Dept Psychiat, Rochester, MN USA. RP NIH, Bldg 10,10 Ctr Dr,MSC 1272,Room 35239, Bethesda, MD 20892 USA. EM levericg@inta.nimh.nih.gov RI Nolen, Willem/E-9006-2014; OI Rush, Augustus/0000-0003-2004-2382 NR 64 TC 110 Z9 110 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC PY 2001 VL 67 IS 1-3 BP 33 EP 44 AR PII S0165-0327(01)00430-X DI 10.1016/S0165-0327(01)00430-X PG 12 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 535FD UT WOS:000174633800004 PM 11869751 ER PT J AU Suppes, T Leverich, GS Keck, PE Nolen, WA Denicoff, KD Altshuler, LL McElroy, SL Rush, AJ Kupka, R Frye, MA Bickel, M Post, RM AF Suppes, T Leverich, GS Keck, PE Nolen, WA Denicoff, KD Altshuler, LL McElroy, SL Rush, AJ Kupka, R Frye, MA Bickel, M Post, RM TI The Stanley Foundation Bipolar Treatment Outcome Network II. Demographics and illness characteristics of the first 261 patients SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; depression; illness course; family history; comorbidity; suicide; Treatment Outcome Network; Stanley Foundation ID EPIDEMIOLOGIC CATCHMENT-AREA; IMPULSE-CONTROL DISORDERS; MANIC-DEPRESSIVE ILLNESS; ONE-MONTH PREVALENCE; PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS; UNITED-STATES; IOWA 500; WORKSHOP REPORT; FOLLOW-UP AB Background: Since recent NIMH Bipolar Disorder Workshops highlighted the dearth of longitudinal and controlled studies of bipolar illness. the Stanley Foundation Bipolar Network (SFBN) has recruited a large cohort of patients with bipolar disorder to begin to address these issues. This report describes the demographics and course of illness characteristics of this study population. Methods: The first 261 outpatients to be diagnosed by the Structured Clinical Interview for DSM-IV (SCID) and complete a detailed patient and a brief clinician questionnaire are described. All patients met DSM-IV criteria for bipolar I (n = 211), bipolar II (n = 42), or NOS (n = 5) or schizoaffective (n = 3), bipolar type. Chi-square and t-tests were used to examine statistically significant associations among important demographic and descriptive items. Results: The general demographic and illness characteristics were similar to those in many bipolar clinical samples and not dissimilar from those reported in epidemiological surveys. The majority of patients had been hospitalized, with almost half reporting a worsening of illness over time, and two-thirds were not asymptomatic between episodes. First treatment for patients had been delayed by an average of (0 years from illness onset (by SCID). Almost a third of patients had attempted suicide at least once, and 30% reported current suicidal ideation at study entry. A total of 62% reported moderate to severe impact of the illness on occupational functioning. Early onset bipolar illness (less than or equal to17 years old) was associated with increased frequency of mood switches, worsening course of illness, and history of early abuse (physical, verbal, or sexual). Conclusion: The SFBN represents a sample of predominantly BPI patients largely recruited from the community who will be followed in detail longitudinally, participate in clinical trials, and thus help advance our understanding and treatment of this life-threatening medical disorder. While there is a broad range of illness characteristics and severity, the majority of patients have been severely impacted by their illness despite the availability of multiple conventional treatment approaches in the community. These data further underscore the need for development of new and earlier treatment interventions. Limitation: The SFBN population is limited by the lack of random selection and represents a cohort willing to be treated and followed intensively in academic tertiary referral centers. While its characteristics are similar to many clinical study populations, the generalizability to non-clinic populations remains uncertain. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Stanley Fdn Biopolar Network, Bethesda, MD 20814 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Biopolar Disorder Clin, Dallas, TX 75247 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Res Program, Dallas, TX 75247 USA. NIMH, Biol Psychiat Program, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Biol Psychiat Program, Cincinnati, OH 45267 USA. VA Med Ctr, Los Angeles, CA 90073 USA. Willem Arntsz Huis & Accad Hosp Utrecht, HC Rumke Grp, NL-6512 PZ Utrecht, Netherlands. RP Suppes, T (reprint author), Stanley Fdn Biopolar Network, 5430 Grosvenor Lane,Suite 200, Bethesda, MD 20814 USA. RI Nolen, Willem/E-9006-2014; OI Rush, Augustus/0000-0003-2004-2382 NR 55 TC 282 Z9 284 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC PY 2001 VL 67 IS 1-3 BP 45 EP 59 AR PII S0165-0327(01)00432-3 DI 10.1016/S0165-0327(01)00432-3 PG 15 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 535FD UT WOS:000174633800005 PM 11869752 ER PT J AU Pickard, JG Brown, GW AF Pickard, JG Brown, GW TI Developing and evaluating cam services SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Letter C1 Washington Univ, George Warren Brown Sch Social Work, NIMH, St Louis, MO 63130 USA. RP Pickard, JG (reprint author), Washington Univ, George Warren Brown Sch Social Work, NIMH, Campus Box 1196,1 Brookings Dr, St Louis, MO 63130 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD DEC PY 2001 VL 7 IS 6 BP 613 EP 613 PG 1 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 515WJ UT WOS:000173519400003 PM 11822608 ER PT J AU Wootton, JC Sparber, A AF Wootton, JC Sparber, A TI Surveys of complementary and alternative medicine: part IV. Use of alternative and complementary therapies for rheumatologic and other diseases SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID ARTHRITIS; CARE; COMMUNITY; ADULTS AB This fourth review in the series covers eight recent U.S. surveys on complementary and alternative medicine (CAM) use by patients with rheumatologic and other autoimmune conditions, and summarizes seven studies of other disease categories. Regarding the previous reviews, the acronym CAM is used unless it is possible to refine the concepts. This reflects the problem that most survey questionnaires do not differentiate between adjunct or complementary therapies and alternative approaches to treatment. C1 Alternat Med Fdn Inc, Bethesda, MD 20814 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Wootton, JC (reprint author), Alternat Med Fdn Inc, 5411 W Cedar Lane 205A, Bethesda, MD 20814 USA. NR 21 TC 14 Z9 15 U1 3 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD DEC PY 2001 VL 7 IS 6 BP 715 EP 721 DI 10.1089/10755530152755270 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 515WJ UT WOS:000173519400017 PM 11822620 ER PT J AU Gottesman, MM Ambudkar, SV AF Gottesman, MM Ambudkar, SV TI Overview: ABC transporters and human disease SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE ATP hydrolysis; diseases; multidrug resistance; nucleotide-binding domains; transmembrane domains; transport proteins; substrates; structure ID FAMILIAL INTRAHEPATIC CHOLESTASIS; REPAIR PROTEIN MUTS; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; CRYSTAL-STRUCTURE; TANGIER-DISEASE; ATP HYDROLYSIS; CELL-LINE; GENE; MUTATIONS AB ABC transporters are found in all known organisms, and approximately 1,100 different transporters belonging to this family have been described in the literature. The family is defined by homology within the ATP-binding cassette (ABC) region, which extends outside of the more typical Walker motifs found in all ATP-binding proteins. Most family members also contain transmembrane domains involved in recognition of substrates, which are transported across, into, and out of cell membranes, but some members utilize ABCs as engines to regulate ion channels. There are approximately 50 known ABC transporters in the human, and there are currently 13 genetic diseases associated with defects in 14 of these transporters. The most common genetic disease conditions include cystic fibrosis, Stargardt disease, age-related macular degeneration, adrenoleukodystrophy, Tangier disease, Dubin-Johnson syndrome and progressive familial intrahepatic cholestasis. At least 8 members of this family are involved in the transport of a variety of amphipathic compounds, including anticancer drugs, and some appear to contribute to the resistance of cancer cells to chemotherapy. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37,Room 1A09,37 Convent Dr, Bethesda, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 45 TC 207 Z9 216 U1 3 U2 28 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD DEC PY 2001 VL 33 IS 6 BP 453 EP 458 DI 10.1023/A:1012866803188 PG 6 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 511TE UT WOS:000173281000002 PM 11804186 ER PT J AU Dean, M Allikmets, R AF Dean, M Allikmets, R TI Complete characterization of the human ABC gene family SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE ATP-binding cassette; transporter; ABC genes ID BINDING CASSETTE TRANSPORTER-1; CYSTIC-FIBROSIS GENE; RECESSIVE RETINITIS-PIGMENTOSA; DROSOPHILA WHITE GENE; TANGIER-DISEASE; MACULAR DEGENERATION; STARGARDT-DISEASE; HUMAN HOMOLOG; MUTATIONS; CLONING AB The human ATP-binding cassette (ABC) transporters comprise a large family of membrane transport proteins and play a vital role in many cellular processes. The genes provide functions as diverse as peptide transport, cholesterol and sterol transport, bile acid, retinoid, and iron transport. In addition some ABC genes play a role as regulatory elements. Many ABC genes play a role in human genetic diseases, and several are critical drug transport proteins overexpressed in drug resistant cells. Analysis of the gene products allows the genes to be grouped into seven different subfamilies. C1 NCI, Human Genet Sect, Lab Genom Divers, Frederick, MD 21701 USA. Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. Columbia Univ, Dept Pathol, New York, NY USA. RP Dean, M (reprint author), NCI, Human Genet Sect, Lab Genom Divers, Frederick, MD 21701 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 31 TC 170 Z9 178 U1 0 U2 9 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD DEC PY 2001 VL 33 IS 6 BP 475 EP 479 DI 10.1023/A:1012823120935 PG 5 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 511TE UT WOS:000173281000005 PM 11804189 ER PT J AU Sauna, ZE Smith, MM Muller, M Kerr, KM Ambudkar, SV AF Sauna, ZE Smith, MM Muller, M Kerr, KM Ambudkar, SV TI The mechanism of action of multidrug-resistance-linked P-glycoprotein SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE ABC transporter; ATP hydrolysis; cancer chemotherapy; catalytic cycle; multidrug resistance; P-glycoprotein ID CATALYTIC TRANSITION-STATE; NUCLEOTIDE-BINDING DOMAINS; STIMULATED ATPASE ACTIVITY; ACUTE MYELOID-LEUKEMIA; REPAIR PROTEIN MUTS; HAMSTER OVARY CELLS; CRYSTAL-STRUCTURE; ABC TRANSPORTER; LABELING SITES; DRUG TRANSPORT AB P-glycoprotein (Pgp), the ATP-binding cassette (ABC) transporter, confers multidrug resistance to cancer cells by extruding cytotoxic natural product amphipathic drugs using the energy of ATP hydrolysis. Our studies are directed toward understanding the mechanism of action of Pgp and recent work deals with the assessment of interaction between substrate and ATP sites and elucidation of the catalytic cycle of ATP hydrolysis. The kinetic analyses of ATP hydrolysis by reconstituted purified Pgp suggest that ADP release is the rate-limiting step in the catalytic cycle and the substrates exert their effect by modulating ADP release. In addition, we provide evidence for two distinct roles for ATP hydrolysis in a single turnover of Pgp, one in the transport of drug and the other in effecting conformational changes so as to reset the transporter for the next catalytic cycle. Detailed kinetic measurements determined that both nucleotide-binding domains behave symmetrically and during individual hydrolysis events the ATP sites are recruited in a random manner. Furthermore, only one nucleotide site hydrolyzes ATP at,my given time, causing (in this site) a conformational change that drastically decreases (>30-fold) the affinity of the second site for ATP-binding. Thus, the blocking of ATP-binding to the second site while the first one is in catalytic conformation appears to be the basis for the alternate catalytic cycle of ATP hydrolysis by Pgp, and this may be applicable as well to other ABC transporters linked with the development of multidrug resistance. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 91 TC 125 Z9 133 U1 0 U2 17 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD DEC PY 2001 VL 33 IS 6 BP 481 EP 491 DI 10.1023/A:1012875105006 PG 11 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 511TE UT WOS:000173281000006 PM 11804190 ER PT J AU Bates, SE Robey, R Miyake, K Rao, K Ross, DD Litman, T AF Bates, SE Robey, R Miyake, K Rao, K Ross, DD Litman, T TI The role of half-transporters in multidrug resistance SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE ABCG2; mitoxantrone; ABC transporter; drug resistance gene ID CARCINOMA CELL-LINE; BREAST-CANCER CELLS; MITOXANTRONE-RESISTANT; P-GLYCOPROTEIN; DRUG ACCUMULATION; FUMITREMORGIN-C; PLASMA-MEMBRANE; GENE; ABC; OVEREXPRESSION AB ATP-binding cassette proteins comprise a superfamily of transporter proteins, a subset of which have been implicated in multidrug resistance. Although P-glycoprotein was described over 15 years ago, the recent expansion in the number of transporters identified has prompted renewed interest in the role of drug transporters in clinical drug resistance. These newly identified transporters include additional members of the MRP family, ABC2, and a new half-transporter, MXR/BCRP/ABCP1. This half-transporter confers high levels of resistance to mitoxantrone, anthracyclines, and the camptothecins SN-38 and topotecan. At 72 kDa, MXR localizes to the plasma membrane in cells which highly overexpress the protein either through gene amplification or though gene rearrangement. Future studies will be aimed at identifying an inhibitor, and attempting to translate recognition of this new transporter into a target for anticancer treatment. C1 NCI, Med Branch, Bethesda, MD 20892 USA. Univ Maryland, Greenebaum Canc Ctr, College Pk, MD 20742 USA. Univ Maryland, Sch Med, Dept Med, Div Hematol Oncol, Baltimore, MD 21201 USA. Vet Adm Med Ctr, Baltimore, MD 21218 USA. Herlev Univ Hosp, Lab Oncol, DK-2730 Herlev, Denmark. RP Bates, SE (reprint author), NCI, Med Branch, Bldg 10, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov NR 49 TC 107 Z9 111 U1 2 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X EI 1573-6881 J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD DEC PY 2001 VL 33 IS 6 BP 503 EP 511 DI 10.1023/A:1012879205914 PG 9 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 511TE UT WOS:000173281000008 PM 11804192 ER PT J AU Baler, R AF Baler, R TI Clockless yeast and the gears of the clock: How do they mesh? SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Review DE yeast two hybrid; circadian interactome; clock genes ID PROTEIN-PROTEIN INTERACTIONS; CIRCADIAN CLOCK; IN-VIVO; 2-HYBRID SYSTEM; PERIOD PROTEIN; HYBRID SYSTEM; TIMELESS; DROSOPHILA; COMPLEX; GENE AB In spite of its apparent weakness as a clock model, the budding yeast has spawned a technique that has revolutionized our ability to study specific protein-protein interactions like those at the core of the molecular timekeeping mechanisms. Here, the author will summarize the evolution, power, and limitations of this technique and highlight its potential and actual contributions to the field of chronobiology. C1 NIMH, Lab Cellular & Mol Regulat, Unit Temporal Gene Express, NIH, Bethesda, MD 20892 USA. RP Baler, R (reprint author), NIMH, Lab Cellular & Mol Regulat, Unit Temporal Gene Express, NIH, Bldg 36,Room 2A-09, Bethesda, MD 20892 USA. RI Jelinek, Milan/C-8515-2011 NR 57 TC 1 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD DEC PY 2001 VL 16 IS 6 BP 516 EP 522 DI 10.1177/074873001129002204 PG 7 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 495PX UT WOS:000172350500002 PM 11760009 ER PT J AU Chou, JJ Gaemers, S Howder, B Louis, JM Bax, A AF Chou, JJ Gaemers, S Howder, B Louis, JM Bax, A TI A simple apparatus for generating stretched polyacrylamide gels, yielding uniform alignment of proteins and detergent micelles SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE detergent micelle; dipolar coupling; liquid crystal; polyacrylamide gels; protein NMR ID LIQUID-CRYSTALLINE MEDIUM; RESIDUAL DIPOLAR COUPLINGS; SOLUTION NMR; MACROMOLECULES; PHASE; N-15; C-13 AB Compressed and stretched polyacrylamide hydrogels previously have been shown to offer a robust method for aligning proteins. A simple, funnel-like apparatus is described for generating uniformly stretched hydrogels. For prolate-shaped proteins, gels stretched in the direction of the magnetic field yield two-fold larger alignment than gels compressed to the same aspect ratio in this direction. Empirically, protein alignment is found to be proportional to (c-2.3)(2) [(d(o)/d(N))(3)-1], where d(o) and d(N) are the diameters of the cylindrical gels before and after stretching, respectively, and c is the polyacrylamide weight fraction in percent. Low gel densities, in the 4-7% range, are found to have minimal effects on macromolecular rotational correlation times, tau (c), and no effect of the compression ratio on tau (c) could be discerned over the range studied (d(o)/d(N) less than or equal to 1.4). Application is demonstrated for a sample containing the first Ig-binding domain of protein G, and for a detergent-solubilized peptide. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Chou, James/N-9840-2013 NR 25 TC 186 Z9 189 U1 0 U2 27 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD DEC PY 2001 VL 21 IS 4 BP 377 EP 382 DI 10.1023/A:1013336502594 PG 6 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 504MP UT WOS:000172860700009 PM 11824758 ER PT J AU Sinha, N Tsai, CJ Nussinov, R AF Sinha, N Tsai, CJ Nussinov, R TI Building blocks, hinge-bending motions and protein topology SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID HIV-1 PROTEASE; BACTERIOPHAGE-T4 LYSOZYME; STRUCTURAL-CHANGES; ADENYLATE KINASE; T4 LYSOZYME; CALMODULIN; RESOLUTION; MUTANT; DYNAMICS; CRYSTAL AB Here we show that the locations of molecular hinges in protein structures fall between building block elements. Building blocks are fragments of the protein chain which constitute local minima. These elements fold first. In the next stop they associate through a combinatorial assembly process. While chain-linked building blocks may be expected to trial-associate first, if unstable, alternate more stable associations will take place, Hence, we would expect, that molecular hinges will be at such inter-building block locations, or at the less stable, 'unassigned' regions, On the other hand, hinge-bonding motions are well known to be critical for protein function. Hence, protein folding and protein function are evolutionarily related. Further, the pathways through which proteins attain their three dimensional folds are determined by protein topology. However, at the same time the locations of the hinges, and hinge-bonding motions are also an outcome of protein topology. Thus, protein folding and function appear coupled, and relate to protein topology, Here we provide some results illustrating such a relationship. C1 NCI Frederick, Intramural Res Support Program, SAIC Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Sinha, N (reprint author), NCI Frederick, Intramural Res Support Program, SAIC Lab Expt & Computat Biol, Bldg 469,Rm 151, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 41 TC 10 Z9 10 U1 0 U2 2 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD DEC PY 2001 VL 19 IS 3 BP 369 EP 380 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 513ZT UT WOS:000173411900004 PM 11790137 ER PT J AU Li, W Ma, BY Shapiro, BA AF Li, W Ma, BY Shapiro, BA TI Molecular dynamics simulations of the denaturation and refolding of an RNA tetraloop SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID RIBOSOMAL-PROTEIN S15; IMPLICIT SOLVATION MODEL; STRUCTURE PREDICTION; SECONDARY STRUCTURE; GNRA TETRALOOPS; FORCE-FIELD; FREE-ENERGY; STABLE RNA; HAIRPIN; STABILITY AB Tetraloops are very abundant structural elements of RNA that are formed by four nucleotides in a hairpin loop which is closed by a double stranded helical stein with some Watson-Crick base pairs. A tetraloop r(GCGAAGGC) was identified from the crystal structure of the central domain of 16S rRNA (727-730) in the Thermus thermophilus 30S ribosomal complex (1). The crystal structure of the 30S complex includes a total of 104 nucleotides from the central domain of the 16S rRNA and three ribosomal proteins S6, S15 and S18. Independent biochemical experiments have demonstrated that protein S 15 plays the role in initiating the formation of the central domain of this complex. In the crystal, the tetraloop interacts with the protein S15 at two sites: one of them is associated with hydrogen bond interactions between residue His50 and nucleotide G730, and the other is associated with the occurrence of residue Arg53 beside A728. This paper uses molecular dynamics (MID) simulations to investigate the protein-dependent structural stability of the tetraloop and demonstrates the folding pathway of this tetraloop via melting denaturation and its subsequent refolding. Three important results are derived from these simulations: (i) The stability of nucleotide A728 appears to be protein dependent. Without the interaction with S15, A728 flips away from stacking with A729. (ii) The melting temperature demonstrated by the simulations is analogous to the results of thermodynamic experiments. In addition, the simulated folding of the tetraloop is stepwise: the native shape of the backbone is formed firsts this is then followed by the formation of the Watson-Crick base pairs in the stem; and finally the hydrogen bonds and base stacking in the loop are formed. (iii) The tetraloop structure is similar to the crystal structure at salt concentrations of 0.1 M and 1.0 M used for the simulations, but the refolded structure at 0.1 M salt is more comparable to the crystal structure than at 1.0 M. The results from the simulations using both the Generalized Born continuum model and explicit solvent model (Particle Mesh Ewald) generate a similar pathway for unfolding/refolding of the tetraloop. C1 NCI, Lab Expt & Computat Biol, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Shapiro, BA (reprint author), NCI, Lab Expt & Computat Biol, Ctr Canc Res, NIH, Bldg 469,Room 150, Frederick, MD 21702 USA. RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X NR 48 TC 15 Z9 17 U1 0 U2 1 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD DEC PY 2001 VL 19 IS 3 BP 381 EP 396 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 513ZT UT WOS:000173411900005 PM 11790138 ER PT J AU Crosson, K Eisner, E Brown, C Ter Maat, J AF Crosson, K Eisner, E Brown, C Ter Maat, J TI Primary care physicians' attitudes, knowledge, and practices related to cancer clinical trials SO JOURNAL OF CANCER EDUCATION LA English DT Article ID ENROLLMENT; BARRIERS AB Background. Participation of patients in cancer clinical trials is disappointingly low and several physician-based factors are thought to be responsible. Methods, In 1998-1999, the National Cancer Institute (NCI) conducted a probability survey of three primary care physician groups to gain a better understanding of the barriers to clinical-trial patient accrual from their perspective. Results. Findings from this survey of 706 primary care physicians indicate that the vast majority (98%) refer their patients with cancer to a specialist for cancer treatment and rarely bring up the topic of cancer clinical trials. Frequently cited reasons for not mentioning clinical trials are preferring to leave that discussion to the oncologist (41%) and being unaware of any clinical trials that may be available for the patient (37%). Conclusion. Primary care physicians may represent an important untapped resource for introducing the concept of clinical trials as an option to newly diagnosed cancer patients. C1 NCI, Off Commun, Bethesda, MD 20892 USA. NCI, Off Educ & Special Initiat, Bethesda, MD 20892 USA. CODA Res Inc, Silver Spring, MD USA. RP Eisner, E (reprint author), NCI, Off Commun, Bldg 31,Room 10A-03, Bethesda, MD 20892 USA. NR 14 TC 19 Z9 19 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD WIN PY 2001 VL 16 IS 4 BP 188 EP 192 PG 5 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 544FZ UT WOS:000175148700005 PM 11848665 ER PT J AU Carroll, SL Herrera, AH Horowits, R AF Carroll, SL Herrera, AH Horowits, R TI Targeting and functional role of N-RAP, a nebulin-related LIM protein, during myofibril assembly in cultured chick cardiomyocytes SO JOURNAL OF CELL SCIENCE LA English DT Article DE chick; cardiomyocyte; N-RAP; LIM protein; myofibril assembly ID ACTIN-FILAMENTS; CARDIAC MYOFIBRILLOGENESIS; FOCAL ADHESIONS; STRIATED-MUSCLE; LOCALIZATION; ANTIBODIES; SEQUENCE; BINDING; TROPOMYOSIN; REPEATS AB Targeting and functional effects of N-RAP domains were studied by expression as GFP-tagged fusion proteins in cultured embryonic chick cardiomyocytes. GFP-tagged N-RAP was targeted to myofibril precursors, myofibril ends and cell contacts, expression patterns that are similar to endogenous N-RAP. The GFP-tagged N-RAP LIM domain (GFP-N-RAP-LIM) was targeted to the membrane in cells with myofibril precursors and cell-cell contacts. The GFP-tagged super repeats (N-RAP-SR) and the GFP-tagged domain normally found in between the super repeats and the LIM domain (N-RAP-IB) were each observed at sites of myofibril assembly, incorporating into myofibril precursors in a manner similar to full length N-RAP. However, unlike full-length N-RAP, N-RAP-SR and N-RAP-IB were also found in mature myofibrils, associating with the sarcomeric actin filaments and the Z-lines, respectively. N-RAP-IB was also colocalized with oc-actinin at cell contacts. Each of the N-RAP constructs could inhibit the formation of mature myofibrils in cultured cardiomyocytes, with the effects of N-RAP-SR and N-RAP-IB depending on the time of transfection. The results show that each region of N-RAP is crucial for myofibril assembly. Combining the targeting and functional effects of N-RAP domains with information in the literature, we propose a new model for initiation of myofibrillogenesis. C1 NIAMSD, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. RP Horowits, R (reprint author), NIAMSD, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. NR 26 TC 15 Z9 15 U1 1 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD DEC PY 2001 VL 114 IS 23 BP 4229 EP 4238 PG 10 WC Cell Biology SC Cell Biology GA 503AD UT WOS:000172774200010 PM 11739655 ER PT J AU Raharjo, WH Enarson, P Sullivan, T Stewart, CL Burke, B AF Raharjo, WH Enarson, P Sullivan, T Stewart, CL Burke, B TI Nuclear envelope defects associated with LMNA mutations cause dilated cardiomyopathy and Emery-Dreifuss muscular dystrophy SO JOURNAL OF CELL SCIENCE LA English DT Article DE nuclear lamin; nuclear envelope; muscular dystrophy; cardiomyopathy; lipodystrophy; emerin ID INTERMEDIATE FILAMENT PROTEINS; ENCODING LAMIN A/C; SACCHAROMYCES-CEREVISIAE; PARTIAL LIPODYSTROPHY; MEMBRANE PROTEIN; PORE COMPLEXES; CAAX MOTIF; GENE; CELLS; IDENTIFICATION AB Nuclear lamin A and C alleles that are linked to three distinct human diseases have been expressed both in HeLa cells and in fibroblasts derived from Lmna null mice. Point mutations that cause dilated cardiomyopathy (L85R and N195K) and autosomal dominant Emery-Dreifuss muscular dystrophy (L530P) modify the assembly properties of lamins A and C and cause partial mislocalization of emerin, an inner nuclear membrane protein, in HeLa cells. At the same time, these mutant lamins interfere with the targeting and assembly of endogenous lamins and in this way may cause significant changes in the molecular organization of the nuclear periphery. By contrast, lamin A and C molecules harboring a point mutation (R482W), which gives rise to a dominant form of familial partial lipodystrophy, behave in a manner that is indistinguishable from wild-type lamins A and C, at least with respect to targeting and assembly within the nuclear lamina. Taken together, these results suggest that nuclear structural defects could contribute to the etiology of both dilated cardiomyopathy and autosomal dominant Emery-Dreifuss muscular dystrophy. C1 Univ Calgary, Dept Cell Biol & Anat, Calgary, AB T2N 4N1, Canada. NCI, Lab Canc & Dev Biol, FCRDC, Frederick, MD 21702 USA. RP Burke, B (reprint author), Univ Florida, Dept Anat & Cell Biol, Box 100235, Gainesville, FL 32610 USA. NR 51 TC 157 Z9 161 U1 2 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD DEC PY 2001 VL 114 IS 24 BP 4447 EP 4457 PG 11 WC Cell Biology SC Cell Biology GA 510TM UT WOS:000173223400011 PM 11792810 ER PT J AU Scahill, L McCracken, J McDougle, CJ Aman, M Arnold, LE Tierney, E Cronin, P Davies, M Ghuman, J Gonzalez, N Koenig, K Lindsay, R Martin, A McGough, J Posey, DJ Swiezy, N Volkmar, F Ritz, L Vitiello, B AF Scahill, L McCracken, J McDougle, CJ Aman, M Arnold, LE Tierney, E Cronin, P Davies, M Ghuman, J Gonzalez, N Koenig, K Lindsay, R Martin, A McGough, J Posey, DJ Swiezy, N Volkmar, F Ritz, L Vitiello, B TI Methodological issues in designing a multisite trial of risperidone in children and adolescents with autism SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID PEDIATRIC PSYCHOPHARMACOLOGY; DISORDER; NETWORK; DRUGS AB Objective: To describe the methodological challenges and decisions made in developing a multisite, controlled study of risperidone in children and adolescents with autism. Methods: Review the design considerations for clinical trials in children with autistic disorder accompanied by severe tantrums, aggressive and/or self-injurious behaviors. These design considerations include the definition of inclusion criteria that are relevant to clinical practice and matching study design to the goal of evaluating short- and long-term effects. Additional ethical and scientific issues concern the length of trial and sample size. Results: We undertook a short-term, placebo-controlled study to evaluate the efficacy and safety of risperidone in children and adolescents with autistic disorder. This trial design was followed by an extended open-label maintenance on risperidone to confirm durability of treatment effects and to monitor safety. Finally, a placebo-controlled discontinuation study tested the need for continuous treatment. Conclusions: In the absence of standard pharmacological treatment for children with autistic disorder, a placebo-controlled study remains the most appropriate method of testing efficacy and safety. The clinical relevance of this study is enhanced by the addition of an extended maintenance phase followed by a placebo discontinuation. C1 NIMH, Res Unit Pediat Psychopharmacol, Bethesda, MD 20892 USA. Columbia Univ, Res Unit Pediat Psychopharmacol, New York, NY USA. Kennedy Krieger Inst, Res Unit Pediat Psychopharmacol, Baltimore, MD USA. Ohio State Univ, Res Unit Pediat Psychopharmacol, Columbus, OH 43210 USA. Indiana Univ, Res Unit Pediat Psychopharmacol, Bloomington, IN USA. Univ Calif Los Angeles, Res Unit Pediat Psychopharmacol, Los Angeles, CA USA. Yale Univ, Res Unit Pediat Psychopharmacol, Autism Network, New Haven, CT USA. RP Scahill, L (reprint author), Yale Child Study Ctr, POB 207900, New Haven, CT 06520 USA. OI Scahill, Lawrence/0000-0001-5073-1707 FU NCRR NIH HHS [M01-RR00865, M01-RR00052, M01-RR00750, M01-RR00034, M01-RR06022]; NIMH NIH HHS [K23 MH001883-01A1, N0MH70009, K01 MH0179201, K23 MH01966, N01MH80011, N01MH70010, N01MH70001] NR 23 TC 28 Z9 28 U1 2 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2001 VL 11 IS 4 BP 377 EP 388 DI 10.1089/104454601317261555 PG 12 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 518VU UT WOS:000173689200003 PM 11838820 ER PT J AU Garvey, MA Kaczynski, KJ Becker, DA Bartko, JJ AF Garvey, MA Kaczynski, KJ Becker, DA Bartko, JJ TI Subjective reactions of children to single-pulse transcranial magnetic stimulation SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID MOTOR CORTEX; MATURATION; PAIN; ADOLESCENTS; DISORDER; NERVE AB Single-pulse transcranial magnetic stimulation is a useful tool to investigate cortical function in childhood neuropsychiatric disorders. Magnetic stimulation is associated with a shock-like sensation that is considered painless in adults. Little is known about how children perceive the procedure. We used a self-report questionnaire to assess children's subjective experience with transcranial magnetic stimulation. Normal children and children with attention-deficit hyperactivity disorder (ADHD) underwent transcranial magnetic stimulation in a study of cortical function in ADHD. Subjects were asked to rate transcranial magnetic stimulation on a 1 to 10 scale (most disagreeable = 1, most enjoyable = 10) and to rank it among common childhood events. Thirty-eight subjects completed transcranial magnetic stimulation; 34 said that they would repeat it. The overall rating for transcranial magnetic stimulation was 6.13, and transcranial magnetic stimulation was ranked fourth highest among the common childhood events. These results suggest that, although a few children find transcranial magnetic stimulation uncomfortable, most consider transcranial magnetic stimulation painless. Further studies are necessary to confirm these findings. C1 NIMH, Pediat & Dev Neuropsychiat Branch, Pediat Movement Disorders Unit, NIH, Bethesda, MD 20892 USA. RP Garvey, MA (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, Pediat Movement Disorders Unit, NIH, 10 Ctr Dr,Room 4N208,MSC 1255, Bethesda, MD 20892 USA. NR 23 TC 34 Z9 34 U1 0 U2 2 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD DEC PY 2001 VL 16 IS 12 BP 891 EP 894 DI 10.1177/088307380101601205 PG 4 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 505ZU UT WOS:000172946100005 PM 11785502 ER PT J AU Brandi, ML Gagel, RF Angeli, A Bilezikian, JP Beck-Peccoz, P Bordi, C Conte-Devolx, B Falchetti, A Gheri, RG Libroia, A Lips, CJM Lombardi, G Mannelli, M Pacini, F Pondder, BAJ Raue, F Skogseid, B Tamburrano, G Thakker, RV Thompson, NW Tomassetti, P Tonelli, F Wells, SA Marx, SJ AF Brandi, ML Gagel, RF Angeli, A Bilezikian, JP Beck-Peccoz, P Bordi, C Conte-Devolx, B Falchetti, A Gheri, RG Libroia, A Lips, CJM Lombardi, G Mannelli, M Pacini, F Pondder, BAJ Raue, F Skogseid, B Tamburrano, G Thakker, RV Thompson, NW Tomassetti, P Tonelli, F Wells, SA Marx, SJ TI Guidelines for diagnosis and therapy of MEN type 1 and type 2 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID MULTIPLE ENDOCRINE NEOPLASIA; MEDULLARY-THYROID CARCINOMA; ZOLLINGER-ELLISON-SYNDROME; FAMILIAL ISOLATED HYPERPARATHYROIDISM; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; GERM-LINE MUTATIONS; RET PROTOONCOGENE; PROGNOSTIC FACTORS; PROPHYLACTIC THYROIDECTOMY; NEUROENDOCRINE TUMORS AB This is a consensus statement from an international group, mostly of clinical endocrinologists. MEN1 and MEN2 are hereditary cancer syndromes. The commonest tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2. Management strategies improved after the discoveries of their genes. MEN1 has no clear syndromic variants. Tumor monitoring in MEN1 carriers includes biochemical tests yearly and imaging tests less often. Neck surgery includes subtotal or total parathyroidectomy, parathyroid cryopreservation, and thymectomy. Proton pump inhibitors or somatostatin analogs are the main management for oversecretion of entero-pancreatic hormones, except insulin. The roles for surgery of most entero-pancreatic tumors present several controversies: exclusion of most operations on gastrinomas and indications for surgery on other tumors. Each MEN1 family probably has an inactivating MEN1 germline mutation. Testing for a germline MEN1 mutation gives useful information, but rarely mandates an intervention. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial medullary thyroid cancer (MTC). They vary in aggressiveness of MTC and spectrum of disturbed organs. Mortality in MEN2 is greater from MTC than from pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an activating germline RET mutation. RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy. C1 Univ Florence, Dept Internal Med, I-50139 Florence, Italy. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Turin, Dipartimento Sci Clin & Biol, I-10100 Turin, Italy. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Univ Milan, Inst Endocrine Sci, Osped Maggiore, IRCCS, I-20100 Milan, Italy. Univ Parma, Dept Pathol & Lab Med, I-43100 Parma, Italy. Timone Hosp, F-13385 Marseille, France. Azienda Osped Careggi, Unita Endocrinol, Florence, Italy. Osped Niguarda Ca Granda, Div Endocrinol, Milan, Italy. Univ Utrecht, Med Ctr, Dept Internal Med, NL-3508 GA Utrecht, Netherlands. Univ Naples Federico II, Dept Mol & Clin Endocrinol, I-80100 Naples, Italy. Univ Florence, Dept Clin Physiopathol, I-50121 Florence, Italy. Univ Pisa, Dept Endocrinol & Metab, Endocrinol Sect, I-56100 Pisa, Italy. Univ Cambridge, Dept Genet, Cambridge CB2 2XZ, England. Endokrinol Gemeinschaftspraxis, D-69111 Heidelberg, Germany. Univ Uppsala Hosp, Endocrine Oncol Unit, S-75185 Uppsala, Sweden. Univ Roma La Sapienza, Dept Clin Sci, Endocrine Sect, I-00100 Rome, Italy. Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England. Univ Michigan, Med Ctr, Div Endocrine Surg, Ann Arbor, MI 48109 USA. Univ Bologna, Dept Int Med & Gastroenterol, I-40100 Bologna, Italy. Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20862 USA. RP Brandi, ML (reprint author), Univ Florence, Dept Internal Med, Viale G Pieraccini 6, I-50139 Florence, Italy. EM m.brandi@dmi.unifi.it RI FALCHETTI, ALBERTO/Q-1787-2016; OI FALCHETTI, ALBERTO/0000-0002-6739-4417; Mannelli, Massimo/0000-0002-8001-9857; Thakker, Rajesh/0000-0002-1438-3220 FU NIDDK NIH HHS [R01 DK032333] NR 143 TC 1017 Z9 1086 U1 8 U2 41 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2001 VL 86 IS 12 BP 5658 EP 5671 DI 10.1210/jc.86.12.5658 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 502DJ UT WOS:000172728200002 PM 11739416 ER PT J AU Zuckerman-Levin, N Tiosano, D Eisenhofer, G Bornstein, S Hochberg, Z AF Zuckerman-Levin, N Tiosano, D Eisenhofer, G Bornstein, S Hochberg, Z TI The importance of adrenocortical glucocorticoids for adrenomedullary and physiological response to stress: A study in isolated glucocorticoid deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ADDISONS-DISEASE; CHROMAFFIN CELLS; CATECHOLAMINES; PLASMA; METABOLISM; RECEPTOR; RELEASE; ACTH AB Glucocorticoids are required for the normal functioning of chromaffin cells and their capacity to produce epinephrine. This was modeled in a unique clinical syndrome of isolated glucocorticoid deficiency due to unresponsiveness to ACTH. The working hypotheses were that in patients with isolated glucocorticoid. deficiency, adrenomedullary epinephrine would be suppressed despite replacement therapy; that norepinephrine might show a compensatory response; and that the physiological response to stress would reflect these changes. Toward these hypotheses, patients with ACTH unresponsiveness on glucocorticoid replacement were subjected to three levels of acute stress: assumption of upright posture, cold pressor, and exercise. Their catecholamine and physiological response were monitored. Patients with isolated glucocorticoid deficiency of this study had severe adrenomedullary dysfunction, characterized by a minimal resting production of epinephrine (6 +/- 2 pg/ml compared with 64 +/- 22 pg/ml of the controls) and a minimal response to stress. A slight compensatory increase of norepinephrine was found in response to cold pressor test (754 +/- 200 pg/ml compared with 431 +/- 73 pg/ml of the control). The physiological response is characterized by low systolic blood pressure and high pulse rate in rest and mild stress and in a pressor response to exercise (diastolic 87 +/- 5 mm Hg, compared with 73 +/- 2 mm Hg of the control). It is concluded that intra-adrenal glucocorticoids are essential for epinephrine secretion, that norepinephrine may be compensatory, and that these result in a distinct physiological response. The implications of the pressor response to exercise, the declining pulse pressure, and the increased pulse response insinuate a lower physical fitness in patients with adrenal insufficiency. C1 Rambam Med Ctr, Dept Pediat, IL-31096 Haifa, Israel. NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. NINCDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. RP Hochberg, Z (reprint author), Rambam Med Ctr, Dept Pediat, POB 9602, IL-31096 Haifa, Israel. EM z_hochberg@rambam.health.gov.il NR 24 TC 38 Z9 39 U1 2 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2001 VL 86 IS 12 BP 5920 EP 5924 DI 10.1210/jc.86.12.5920 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 502DJ UT WOS:000172728200043 PM 11739465 ER PT J AU Engels, EA AF Engels, EA TI Human immunodeficiency virus infection, aging, and cancer SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE human immunodeficiency virus (HIV); acquired immunodeficiency syndrome (AIDS); aging; Kaposi's sarcoma; non-Hodgkin's lymphoma; lung cancer ID SARCOMA-ASSOCIATED HERPESVIRUS; CLASSIC KAPOSIS-SARCOMA; HUMAN-HERPESVIRUS-8 INFECTION; NATURAL-HISTORY; HOMOSEXUAL MEN; RISK-FACTORS; AIDS; POPULATION; CARCINOMA AB HIV infection increases non-Hodgkin's lymphoma and Kaposi's sarcoma risk. Among HIV-uninfected persons, risk for these malignancies and others increases with age. As HIV-infected persons age, new patterns in cancer incidence may emerge. In this article, data from the AIDS-Cancer Registry Match study are presented on risk for Kaposi's sarcoma and lung cancer among persons with AIDS. For 132,346 homosexual men with AIDS, Kaposi's sarcoma incidence was highest for men 30-39 years old (5.0 cases/100 person-years) and declined with age (P-trend < .0001). This trend likely arises from variation in Kaposi's sarcoma herpesvirus prevalence among homosexual men. For 239,257 adults with A-IDS (all risk groups), lung cancer incidence increased with age, and was higher than in the general population (P < .0001), probably reflecting heavy smoking among HIV-infected adults. Identifying separate effects of HIV and aging on cancer risk will require detailed data on individuals' HIV infection status and exposures to known carcinogens. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Engels, EA (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8005, Rockville, MD 20852 USA. NR 26 TC 23 Z9 25 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2001 VL 54 SU 1 BP S29 EP S34 DI 10.1016/S0895-4356(01)00444-9 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 503QK UT WOS:000172811300007 PM 11750207 ER PT J AU MacKay, CR AF MacKay, CR TI Commentary on "genetic testing for hereditary disease" SO JOURNAL OF CLINICAL ETHICS LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP MacKay, CR (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 17100 COLE RD #312, HAGERSTOWN, MD 21740-6901 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD WIN PY 2001 VL 12 IS 4 BP 373 EP 374 PG 2 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 551DB UT WOS:000175543300004 PM 12026742 ER PT J AU Ahlers, JD Belyakov, IM Thomas, EK Berzofsky, JA AF Ahlers, JD Belyakov, IM Thomas, EK Berzofsky, JA TI High-affinity T helper epitope induces complementary helper and APC polarization, increased CTL, and protection against viral infection SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ALTERED PEPTIDE LIGANDS; IMMUNODEFICIENCY-VIRUS ENVELOPE; DENDRITIC CELLS; IN-VIVO; VACCINE CONSTRUCTS; NEUTRALIZING ANTIBODY; ANTITUMOR IMMUNITY; LYMPHOCYTE; RESPONSES; INDUCTION AB Natural viral proteins do not always make optimal vaccines. We have found that sequence modification to increase epitope affinity for class II MHC molecules (epitope enhancement) can improve immunogenicity. Here we show first that a higher-affinity helper epitope-enhanced HIV vaccine not only induces more cytotoxic T lymphocytes (CTLs), but also skews helper cells toward Th1 cytokine production and protects against HIV-1 recombinant vaccinia viral challenge. Furthermore, we elucidate a novel mechanism in which the higher-affinity vaccine induces dramatically more effective helper cells with a higher level of CD40L per helper cell and more positive cells, which in turn more effectively conditions dendritic cells (DCs) for CTL activation in a second culture. The improved helper cells also induce much greater IL-12 production by DCs, accounting for the reciprocal T helper polarization to Th1, and increase costimulatory molecule expression. Thus, increasing affinity for class Il MHC results in a complementary interaction in which T helper and antigen-presenting cells polarize each other, as well as increase CTL, and provide greater vaccine efficacy against viral infection. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. Immunex Corp, Seattle, WA USA. RP Berzofsky, JA (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bldg 10,Room 6B-12,MSC 1578, Bethesda, MD 20892 USA. NR 46 TC 67 Z9 68 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2001 VL 108 IS 11 BP 1677 EP 1685 DI 10.1172/JCI13463 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 498YQ UT WOS:000172541500017 PM 11733563 ER PT J AU Mazzoni, A Young, HA Spitzer, JH Visintin, A Segal, DM AF Mazzoni, A Young, HA Spitzer, JH Visintin, A Segal, DM TI Histamine regulates cytokine production in maturing dendritic cells, resulting in altered T cell polarization SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NF-KAPPA-B; MAST-CELLS; HELPER CELLS; IN-VIVO; PROSTAGLANDIN E-2; IMMUNE-RESPONSE; TH1 DEVELOPMENT; IL-12; MATURATION; ACTIVATION AB Atopic diseases such as allergy and asthma are characterized by increases in Th2 cells and serum IgE antibodies. The binding of allergens to IgE on mast cells triggers the release of several mediators, of which histamine is the most prevalent. Here we show that histamine, together with a maturation signal, acts directly upon immature dendritic cells (iDCs), profoundly altering their T cell polarizing capacity. We demonstrate that iDCs express two active histamine receptors, H1 and H2. Histamine did not significantly affect the LPS-driven maturation of iDCs with regard to phenotypic changes or capacity to prime naive T cells, but it dramatically altered the repertoire of cytokines and chemokines secreted by mature DCs. In particular, histamine, acting upon the H2 receptor for a short period of time, increased IL-10 production and reduced IL-12 secretion. As a result, histamine-matured I)Cs polarized naive CD4(+)T cells toward a Th2 phenotype, as compared with DCs that had matured in the absence of histamine. We propose that the Th2 cells favor IgE production, leading to increased histamine secretion by mast cells, thus creating a positive feedback loop that could contribute to the severity of atopic diseases. C1 Natl Canc Inst, Expt Immunol Branch, Bethesda, MD USA. Natl Canc Inst, Expt Immunol Lab, Frederick, MD USA. RP Segal, DM (reprint author), NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. NR 54 TC 230 Z9 246 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2001 VL 108 IS 12 BP 1865 EP 1873 DI 10.1172/JCI13930 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 503WC UT WOS:000172823700018 PM 11748270 ER PT J AU Livneh, A Shtrasburg, S Martin, BM Baniel, J Gal, R Pras, M AF Livneh, A Shtrasburg, S Martin, BM Baniel, J Gal, R Pras, M TI Light chain amyloidosis of the urinary bladder. A site restricted deposition of an externally produced immunoglobulin SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE primary amyloidosis; urinary bladder; lambda light chain; amino acid sequence ID PRIMARY LOCALIZED AMYLOIDOSIS; GENITOURINARY TRACT; AL AMYLOIDOSIS; TISSUES; EXTRACTION AB Aims-To identify the amyloid protein in a patient with amyloidosis localised to the urinary bladder, and to see whether subtyping of the protein by sequence analysis increases the understanding of the selection of the urinary bladder as the site of amyloid deposition. Methods-A patient with gross haematuria and a congophilic mass in his urinary bladder was evaluated further. Characterisation of the amyloid protein was performed using conventional histological and immunohistochemical methods. Determination of the N-terminal amino acid sequence of the amyloid protein was performed using protein sequencers. Results-The patient's history, physical examination, and laboratory evaluation excluded the involvement of other organs, justifying a diagnosis of amyloidosis localised to the urinary bladder. Histological and immunological studies showed that the amyloid protein deposited in the urinary bladder of the patient was probably of the amyloid light chain type. No plasma cells or lymphocytes were seen in sections of the urinary bladder and lower ureter adjacent to the amyloid deposits. Molecular analysis showed the sequence NFMLTQPHSISGSPG, which assigned the amyloid protein to either the V lambda (I) or the V lambda (VI) immunoglobulin (Ig) light chain families. Conclusions-The findings suggest that the amyloid protein in this patient originated outside the urinary bladder. The heterogeneity of the Ig proteins in known cases of amyloidosis of the lower urinary tract suggests that the amino acid residues, which determine the V lambda subtyping, have no major role in restricting the deposited protein to the urinary bladder. C1 Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Rabin Med Ctr, Dept Urol, IL-49100 Petah Tiqwa, Israel. Rabin Med Ctr, Dept Pathol, IL-49372 Petah Tiqwa, Israel. RP Livneh, A (reprint author), Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel. NR 19 TC 8 Z9 9 U1 1 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 J9 J CLIN PATHOL JI J. Clin. Pathol. PD DEC PY 2001 VL 54 IS 12 BP 920 EP 923 PG 4 WC Pathology SC Pathology GA 501ZR UT WOS:000172718300003 PM 11729210 ER PT J AU Gill, S Peston, D Vonderhaar, BK Shousha, S AF Gill, S Peston, D Vonderhaar, BK Shousha, S TI Expression of prolactin receptors in normal, benign, and malignant breast tissue: an immunohistological study SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article; Proceedings Paper CT Winter Meeting of the Pathological-Society-of-Great-Britain-and-Ireland CY JAN, 1999 CL CAMBRIDGE, ENGLAND SP Pathol Soc Great Britain & Ireland DE breast; breast carcinoma; male breast; prolactin receptors; oestrogen receptors ID PROGNOSTIC-SIGNIFICANCE; PROGESTERONE RECEPTORS; GROWTH-HORMONE; CARCINOMA; CANCER; ESTROGEN; MICE AB Aims-Prolactin plays an important role in the proliferation and differentiation of normal breast epithelium, and possibly in the development of breast carcinoma. The effects of prolactin are mediated by its receptor; thus, alteration in the expression of this receptor could be important in studying the biology of breast cancer. This investigation was aimed at comparing the expression of prolactin receptors in normal, benign, and malignant breast tissue. Material/Methods-The expression of prolactin receptors was studied in paraffin wax embedded sections of 102 breast biopsies (93 female and nine male), using the monoclonal antibody B6.2, and the avidin-biotin immunoperoxidase technique. Six biopsies were normal, 34 had benign lesions, and 62 were malignant. Results-In normal cases, prolactin receptor positivity was seen only on the luminal borders of the epithelial cells lining ducts and acini. In most benign lesions, variable degrees of luminal and cytoplasmic staining were seen. Cells showing apocrine metaplasia and florid regular ductal epithelial hyperplasia were mostly negative. In malignant cases, the staining pattern was mostly cytoplasmic and heterogeneous. Forty one of the 59 carcinomas in women showed a degree of positivity involving 10-100% of the tumour cells. A significant direct correlation was found between prolactin receptor and oestrogen receptor staining when only cases that scored more than 100/300 for the latter receptor, using the H scoring system, were considered (p = 0.0207). No correlation was found between prolactin receptors and progesterone receptors, patient's age, tumour size, tumour grade, or axillary lymph node status. Conclusions-Prolactin receptors seem to be expressed at different cellular sites in normal, benign, and malignant breast epithelial cells. The receptor is expressed in more than two thirds of female breast carcinomas, suggesting that it may play a role in the pathogenesis of the disease. The positivity is correlated with moderate and strong staining for oestrogen receptors in tissue sections, but not with other prognostic factors. C1 Univ London Imperial Coll Sci Technol & Med, Charing Cross Hosp, Sch Med, Dept Histopathol, London W6 8RF, England. NCI, Bethesda, MD 20892 USA. RP Shousha, S (reprint author), Univ London Imperial Coll Sci Technol & Med, Charing Cross Hosp, Sch Med, Dept Histopathol, Fulham Palace Rd, London W6 8RF, England. NR 26 TC 77 Z9 81 U1 1 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 J9 J CLIN PATHOL JI J. Clin. Pathol. PD DEC PY 2001 VL 54 IS 12 BP 956 EP 960 PG 5 WC Pathology SC Pathology GA 501ZR UT WOS:000172718300010 PM 11729217 ER PT J AU Thompson, JL Davis, SM Gittelsohn, J Going, S Becenti, A Metcalfe, L Stone, E Harnack, L Ring, K AF Thompson, JL Davis, SM Gittelsohn, J Going, S Becenti, A Metcalfe, L Stone, E Harnack, L Ring, K TI Patterns of physical activity among American Indian children: An assessment of barriers and support SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE obesity prevention; American Indian; physical activity; formative assessment ID PRIMARY PREVENTION PROGRAM; CARDIOVASCULAR HEALTH; ADOLESCENT TRIAL; SCHOOL-CHILDREN; OBESITY; ELEMENTARY; EDUCATION; WEIGHT; YOUTH; SCHOOLCHILDREN AB Estimates indicate that 10% to 50% of American Indian and non-Indian children in the U.S. are obese, defined as a body-mass index greater than or equal to 95(th) percentile of the NHANES II reference data. Pathways is a two-phase, multi-site study to develop and test a school-based obesity prevention program in American Indian schoolchildren in grades three through five. During Phase I feasibility prior to initiation of the Pathways trial, data were collected related to physical activity patterns, and the supports of, and barriers to, physical activity. Nine schools from communities representing six different tribal groups participated in this study. Multiple measures were used for data collection including direct observation, paired child interviews, and in-depth interviews and focus groups with adults. Students completed the self-administered Knowledge, Attitudes, and Behaviors (KAB) survey, and a Physical Activity Questionnaire (PAQ). Barriers to physical activity at schools included a lack of facilities, equipment, and trained staff persons for PE. Adults were not consistently active with their children, but they were highly supportive of their children's activity level. Children reported a strong enjoyment of physical activity and strong peer support to be physically active. Weather conditions, safety concerns, and homework/chores were common barriers to physical activity reported by children and adult caregivers. The information was used to design culturally and age-appropriate; practical interventions including the five physical activity programs for schoolchildren in the Pathways study. C1 Univ New Mexico, Hlth Sci Ctr, Ctr Hlth Promot & Dis Prevent, Albuquerque, NM 87131 USA. Johns Hopkins Univ, Ctr Human Nutr, Dept Int Hlth, Sch Publ Hlth, Baltimore, MD USA. Univ Arizona, Dept Nutr Sci, Intervent Program, Tucson, AZ USA. Indian Hlth Serv, Crownpoint Healthcare Facil, Dept Community & Prevent Hlth, Hlth Promot & Dis Prevent Program, Crownpoint, NM USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. RP Thompson, JL (reprint author), Univ New Mexico, Hlth Sci Ctr, Ctr Hlth Promot & Dis Prevent, 2701 Frontier NE,Suite 251, Albuquerque, NM 87131 USA. FU NHLBI NIH HHS [HL-50867, HL-50869, HL-50885, U01 HL050905, U01 HL050907, HL-50905, U01 HL050867, U01 HL050869, U01 HL050885] NR 38 TC 30 Z9 31 U1 1 U2 8 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD DEC PY 2001 VL 26 IS 6 BP 423 EP 445 DI 10.1023/A:1012507323784 PG 23 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 496RJ UT WOS:000172409700002 PM 11759094 ER PT J AU McCauley, E Feuillan, P Kushner, H Ross, JL AF McCauley, E Feuillan, P Kushner, H Ross, JL TI Psychosocial development in adolescents with Turner syndrome SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE psychosocial development; Turner syndrome; self-image ID CHILDRENS MANIFEST ANXIETY; REVISED MEASURE; I THINK; BEHAVIOR; GIRLS; DEPRESSION; CANCER; STYLE; WOMEN; FEEL AB Turner syndrome is a genetic condition in which part or all of the second X chromosome is missing. Our goal in this study was to examine the psychosocial adjustment of a sample of adolescent girls with Turner syndrome. Subjects included 122 girls with a diagnosis of Turner syndrome (TS) and a control group of 108 girls with no genetic disorder or chronic illness. Subjects were 13 to 18 years of age. A battery of questionnaires assessing social, academic, school, and behavioral functioning was administered. TS girls were seen as having significantly more problems in terms of social relationships and school progress and were more likely to meet criteria for attention-deficit hyperactivity disorder than control girls, The TS girls were also rated by a parent as less socially competent (e.g., fewer friends, less time with friends) than the control group. Social difficulties appear to be an area of vulnerability for TS girls. Counseling individuals with Turner syndrome and their families about the need to carefully develop and nurture social skills and relationships may prove useful in advancing the social adaptation of these young women. C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Pediat, Philadelphia, PA 19107 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Biomed Res Comp Inst, Philadelphia, PA USA. RP Ross, JL (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Pediat, 1025 Walnut St, Philadelphia, PA 19107 USA. FU NINDS NIH HHS [NS-29857, NS-32531] NR 26 TC 56 Z9 61 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD DEC PY 2001 VL 22 IS 6 BP 360 EP 365 PG 6 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 502LU UT WOS:000172745700002 PM 11773800 ER PT J AU Speer, AM Repella, JD Figueras, S Demian, NK Kimbrell, TA Wasserman, EM Post, RM AF Speer, AM Repella, JD Figueras, S Demian, NK Kimbrell, TA Wasserman, EM Post, RM TI Lack of adverse cognitive effects of 1 Hz and 20 Hz repetitive transcranial magnetic stimulation at 100% of motor threshold over left prefrontal cortex in depression SO JOURNAL OF ECT LA English DT Article DE repetitive transcranial magnetic stimulation bipolar disorder; memory ID ELECTROCONVULSIVE-THERAPY; STIMULUS PARAMETERS; MAJOR DEPRESSION; MOOD; RTMS; ANTIDEPRESSANT; SUPPRESSION; INDUCTION; EFFICACY; SPEECH AB Objective: The potential therapeutic effects of repetative transcranial magnetic stimulation (rTMS) are being examined in various neuropsychiatric illnesses. This study assesses the Cognitive performance of depressed patients receiving high or ow frequency rTMS for 10 days. Methods: 18 depressed patients participated in a randomized double-blind cross-over study exploring the antidepressant effects of 2 weeks (10 daily) of sham, 1 Hz, or 20 Hz rTMS administered over the left dorsolateral prefrontal cortex at 100% of motor threshold (MT). A subgroup completed a battery of cognitive tests at baseline and following each 2-week phase of treatment, and differences in performance were assessed using paired t-tests and were correlated with the degree of clinical improvement using Hamilton Depression Rating Scale scores. Results: There were no major changes in cognitive test scores as a result of 10 days of either 1 Hz or 20 Hz rTMS. Moreover, any minor attenuations in cognition were not related to the degree of clinical improvement. Conclusions: Cognitive functioning in many domains following 2 weeks of 1 Hz or 20 Hz rTMS at 100% MT over the left dorsolateral prefrontal cortex in depressed patients is not disrupted. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. N Little Rock VA Med Ctr, N Little Rock, AK USA. NINCDS, Brain Stimulat Unit, NIH, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, 10 Ctr Dr,Room 3N212, Bethesda, MD 20892 USA. NR 31 TC 31 Z9 32 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 J9 J ECT JI J. ECT PD DEC PY 2001 VL 17 IS 4 BP 259 EP 263 DI 10.1097/00124509-200112000-00005 PG 5 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 501BK UT WOS:000172663000005 PM 11731727 ER PT J AU Pandiani, JA Banks, SM Schacht, LM AF Pandiani, JA Banks, SM Schacht, LM TI Caseload segregation/integration and service delivery outcomes for children and adolescents SO JOURNAL OF EMOTIONAL AND BEHAVIORAL DISORDERS LA English DT Article; Proceedings Paper CT 12th Annual Research Conference: A System of Care for Childrens Mental Health: Expanding the Research Base CY FEB 21-24, 1999 CL TAMPA, FLORIDA ID SYSTEM INTEGRATION; CARE; PROGRAM AB In this article we explore the relationship between the degree to which local systems of care share responsibility for children and adolescents (measured by the Caseload Segregation/integration Ratio) and four service delivery outcomes in one state over a 4-year period. Caseload segregation/integration is measured for community mental health agencies, child protection and juvenile justice programs, and special education programs for emotional and behavioral disorders. Service outcomes under examination include referral for intensive residential treatment and hospitalization for behavioral health care (for all children), incarceration (for boys), and maternity (for girls). Results indicate that greater caseload integration is associated with less referral for residential treatment and higher rates of incarceration. The interpretation of these findings is discussed, and further research is suggested. C1 Vermont Dept Dev & Mental Hlth Serv, Waterbury, VT 05671 USA. Bristol Observ, Bristol, RI USA. Univ Massachusetts, Dept Psychiat, Worcester, MA 01605 USA. NIH, Bethesda, MD 20892 USA. NASMHPD Res Inst, Alexandria, VA USA. RP Pandiani, JA (reprint author), Vermont Dept Dev & Mental Hlth Serv, 103 S Main St,Weeks 1, Waterbury, VT 05671 USA. NR 27 TC 1 Z9 1 U1 1 U2 1 PU PRO-ED INC PI AUSTIN PA 8700 SHOAL CREEK BLVD, AUSTIN, TX 78757-6897 USA SN 1063-4266 J9 J EMOT BEHAV DISORD JI J. Emot. Behav. Disord. PD WIN PY 2001 VL 9 IS 4 BP 232 EP + DI 10.1177/106342660100900403 PG 8 WC Education, Special; Psychology, Educational; Psychology, Multidisciplinary SC Education & Educational Research; Psychology GA 496JC UT WOS:000172391600003 ER PT J AU Weed, DL McKeown, RE AF Weed, DL McKeown, RE TI Ethics in epidemiology and public health I. Technical terms SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID SPECIFIED PRINCIPLISM; BIOETHICS; CASUISTRY C1 NCI, Off Prevent Oncol, Div Canc Prevent, Bethesda, MD 20892 USA. RP Weed, DL (reprint author), NCI, Off Prevent Oncol, Div Canc Prevent, EPS T-41,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 25 TC 6 Z9 6 U1 0 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD DEC PY 2001 VL 55 IS 12 BP 855 EP 857 DI 10.1136/jech.55.12.855 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 495NF UT WOS:000172346700008 PM 11707476 ER PT J AU Parascandola, M Weed, DL AF Parascandola, M Weed, DL TI Causation in epidemiology SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID BLACK-BOX EPIDEMIOLOGY; PUBLIC-HEALTH; DISEASE; MODELS; FUTURE AB Causation is an essential concept in epidemiology, yet there is no single, clearly articulated definition for the discipline. From a systematic review of the literature, five categories can be delineated: production, necessary and sufficient, sufficient-component, counterfactual, and probabilistic. Strengths and weaknesses of these categories are examined in terms of proposed characteristics of a useful scientific definition of causation: it must be specific enough to distinguish causation from mere correlation, but not so narrow as to eliminate apparent causal phenomena from consideration. Two categories-production and counterfactual-are present in any definition of causation but are not themselves sufficient as definitions. The necessary and sufficient cause definition assumes that all causes are deterministic. The sufficient-component cause definition attempts to explain probabilistic phenomena via unknown component causes. Thus, on both of these views, heavy smoking can be cited as a cause of lung cancer only when the existence of unknown deterministic variables is assumed. The probabilistic definition, however, avoids these assumptions and appears to best fit the characteristics of a useful definition of causation. It is also concluded that the probabilistic definition is consistent with scientific and public health goals of epidemiology. In debates in the literature over these goals, proponents of epidemiology as pure science tend to favour a narrower deterministic notion of causation models while proponents of epidemiology as public health tend to favour a probabilistic view. The authors argue that a single definition of causation for the discipline should be and is consistent with both of these aims. It is concluded that a counterfactually-based probabilistic definition is more amenable to the quantitative tools of epidemiology, is consistent with both deterministic and probabilistic phenomena, and serves equally well for the acquisition and the application of scientific knowledge. C1 NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA. RP Parascandola, M (reprint author), NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Execut Plaza S,Suite T-41,6120 Execut Blvd,MSC 71, Bethesda, MD 20892 USA. NR 73 TC 73 Z9 78 U1 1 U2 7 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD DEC PY 2001 VL 55 IS 12 BP 905 EP 912 DI 10.1136/jech.55.12.905 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 495NF UT WOS:000172346700017 PM 11707485 ER PT J AU Zieler, H Keister, DB Dvorak, JA Ribeiro, JMC AF Zieler, H Keister, DB Dvorak, JA Ribeiro, JMC TI A snake venom phospholipase A(2) blocks malaria parasite development in the mosquito midgut by inhibiting ookinete association with the midgut surface SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE malaria; ookinete; transmission blocking; phospholipase; p-bromophenacyl bromide; eastern diamondback rattlesnake; Crotalus adamanteus; Plasmodium gallinaceum; Plasmodium falciparum; Aedes aegypti ID AEDES-AEGYPTI MIDGUT; YELLOW-FEVER MOSQUITO; PLASMODIUM-GALLINACEUM; CRYSTAL-STRUCTURE; ANNEXIN-V; PANCREATIC PHOSPHOLIPASE-A2; DIMERIC PHOSPHOLIPASE-A2; PHOSPHATIDYLCHOLINE; BINDING; INTERFACES AB Oocyst formation is a critical stage in the development of the malaria parasite in the mosquito. We have discovered that the phospholipase A(2) (PLA2) from the venom of the eastern diamondback rattlesnake (Crotalus adamanteus) inhibits oocyst formation when added to infected chicken blood and fed to mosquitoes. A similar transmission-blocking activity was demonstrated for PLA2s from the venom of other snakes and from the honeybee. This effect is seen both with the avian malaria parasite Plasmodium gallinaceum and with the human parasite Plasmodium falciparum developing in their respective mosquito hosts. The inhibition occurs even in the presence of an irreversible inhibitor of the active site of PLA2, indicating that the hydrolytic activity of the enzyme is not required for the antiparasitic effect. Inhibition is also seen when the enzyme is fed to mosquitoes together with ookinetes, suggesting that the inhibition occurs after ookinete maturation. PLA2 has no direct effect on the parasite. However, pretreatment of midguts with PLA2 (catalytically active or inactive) dramatically lowers the level of ookinete/midgut association in vitro. It appears, therefore, that PLA2 is acting by associating with the midgut surface and preventing ookinete attachment to this surface. Thus, PLA2 is an excellent candidate for expression in transgenic mosquitoes as a means of inhibiting the transmission of malaria. C1 NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Malaria Vaccines Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Biophys Parasitol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Chromatin Inc, 2201 W Campbell Pk Dr, Chicago, IL 60612 USA. EM zieler@chromatininc.com OI Ribeiro, Jose/0000-0002-9107-0818 NR 62 TC 54 Z9 58 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 EI 1477-9145 J9 J EXP BIOL JI J. Exp. Biol. PD DEC PY 2001 VL 204 IS 23 BP 4157 EP 4167 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 502NB UT WOS:000172748700015 PM 11809789 ER PT J AU Arterberry, ME Bornstein, MH AF Arterberry, ME Bornstein, MH TI Three-month-old infants' categorization of animals and vehicles based on static and dynamic attributes SO JOURNAL OF EXPERIMENTAL CHILD PSYCHOLOGY LA English DT Article DE categorization; infants; static information; dymanic or motion-carried information ID POINT-LIGHT DISPLAYS; VISUAL-PERCEPTION; GENDER RECOGNITION; BIOLOGICAL MOTION; GAIT PERCEPTION; FORM CATEGORIES; LINE JUNCTIONS; REPRESENTATIONS; ORIENTATION; SENSITIVITY AB Three-month-old infants' categorization of animals and vehicles based on static and dynamic attributes was investigated using a multiple-exemplar habituation-test paradigm. Half of the infants viewed static color images of animals and vehicles, and the other half viewed dynamic point-light displays of the same animals and vehicles. Following habituation, infants viewed a novel exemplar from the habituation category and an exemplar from a novel category. Regardless of whether they viewed static or dynamic displays, infants showed habituation to varying exemplars from the same category generalized habituation to a novel exemplar from the habituation category, dishabituated to an exemplar from a novel category, and showed a significant novelty preference for a novel-category exemplar. These findings suggest that infants categorize animals and vehicles using either static or dynamic information. (C) 2001 Academic Press. C1 NICHHD, Bethesda, MD 20892 USA. Gettysburg Coll, Gettysburg, PA 17325 USA. RP Arterberry, ME (reprint author), NICHHD, Suite 8030,Rockledge Dr, Bethesda, MD 20892 USA. NR 59 TC 33 Z9 35 U1 2 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-0965 J9 J EXP CHILD PSYCHOL JI J. Exp. Child Psychol. PD DEC PY 2001 VL 80 IS 4 BP 333 EP 346 DI 10.1006/jecp.2001.2637 PG 14 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 493FB UT WOS:000172210400002 PM 11689034 ER PT J AU Bornstein, MH Cote, LR Venuti, P AF Bornstein, MH Cote, LR Venuti, P TI Parenting beliefs and behaviors in northern and southern groups of Italian mothers of young infants SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article ID UNITED-STATES; MATERNAL-BEHAVIOR; RICAN MOTHERS; CHILD; SELF; ARGENTINA; CULTURE; IDEAS; JAPAN; COMPETENCE AB Similarities and differences in northern and southern Italian mothers' social and didactic parenting beliefs and behaviors, and relations between their beliefs and behaviors, are reported. Both groups of mothers reported that they engaged more in social than didactic interactions with their infants, whereas in actuality both groups engaged in didactic behaviors with their infants for longer periods of time than they engaged in social behaviors. In addition, northern mothers engaged in more social interactions with their infants than did southern mothers. No correlations between beliefs and behaviors emerged in either group. These data speak to issues of intracultural variation and cross-cultural similarities in family psychology and parenting, belief-behavior relations in parenting, and the importance of methodology (parental report or observation) in the study of parenting and family functioning. C1 NICHHD, Bethesda, MD 20892 USA. Univ Naples 2, Dept Psychol, Naples, Italy. RP Bornstein, MH (reprint author), NICHHD, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. NR 87 TC 31 Z9 31 U1 2 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD DEC PY 2001 VL 15 IS 4 BP 663 EP 675 DI 10.1037//1893.3200.15.4.663 PG 13 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 502BH UT WOS:000172723500009 PM 11770473 ER PT J AU Mizukoshi, E Rehermann, B AF Mizukoshi, E Rehermann, B TI Immune responses and immunity in hepatitis C virus infection SO JOURNAL OF GASTROENTEROLOGY LA English DT Review DE HCV; immune response; innate; helper T cell; CTL ID T-CELL-RECEPTOR; HYPERVARIABLE REGION-1; ANTIBODY-RESPONSE; HYPERIMMUNE SERUM; I INTERFERON; CORE PROTEIN; ADULT MICE; ACTIVATION; CHIMPANZEES; LYMPHOCYTES C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr,Room 9B16, Bethesda, MD 20892 USA. NR 96 TC 17 Z9 20 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0944-1174 J9 J GASTROENTEROL JI J. Gastroenterol. PD DEC PY 2001 VL 36 IS 12 BP 799 EP 808 DI 10.1007/s005350170001 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 505AY UT WOS:000172889800001 PM 11777207 ER PT J AU Chouljenko, VN Lin, XQ Storz, J Kousoulas, KG Gorbalenya, AE AF Chouljenko, VN Lin, XQ Storz, J Kousoulas, KG Gorbalenya, AE TI Comparison of genomic and predicted amino acid sequences of respiratory and enteric bovine coronaviruses isolated from the same animal with fatal shipping pneumonia SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID TRANSMISSIBLE GASTROENTERITIS CORONAVIRUS; INFECTIOUS-BRONCHITIS VIRUS; INDUCED CELL-FUSION; OPEN READING FRAME; POLYMERASE GENE; RNA-POLYMERASE; MONOCLONAL-ANTIBODIES; SPIKE GLYCOPROTEIN; IDENTIFICATION; POLYPROTEIN AB The complete genome sequences are reported here of two field isolates of bovine coronavirus (BCoV), which were isolated from respiratory and intestinal samples of the same animal experiencing fatal pneumonia during a bovine shipping fever epizootic. Both genomes contained 31028 nucleotides and included 13 open reading frames (ORFs) flanked by 5'- and 3'-untranslated regions (UTRs). ORF1a and ORF1 b encode replicative polyproteins pp1a and pp1ab, respectively, that contain all of the putative functional domains documented previously for the closest relative, mouse hepatitis virus. The genomes of the BCoV isolates differed in 107 positions, scattered throughout the genome except the 5'-UTR. Differences in 25 positions were non-synonymous and were located in all proteins except pp 1 b. Six replicase mutations were identified within or immediately downstream of the predicted largest pp1a-derived protein, p195/p210. Single amino acid changes within p195/p210 as well as within the S glycoprotein might contribute to the different phenotypes of the BCoV isolates. C1 Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA. Sci Applicat Int Corp, Adv Biomed Comp Ctr, NCI, Frederick, MD 21702 USA. RP Kousoulas, KG (reprint author), Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA. RI Gorbalenya, Alexander/J-4818-2012 OI Gorbalenya, Alexander/0000-0002-4967-7341 FU NCI NIH HHS [N01-CO-56000] NR 45 TC 48 Z9 72 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD DEC PY 2001 VL 82 BP 2927 EP 2933 PN 12 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 497EJ UT WOS:000172442200011 PM 11714968 ER PT J AU Feolo, M Fuller, TC Taylor, M Zone, JJ Neuhausen, SL AF Feolo, M Fuller, TC Taylor, M Zone, JJ Neuhausen, SL TI A strategy for high throughput HLA-DQ typing SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE HLA associations; HLA-DQA1; HLA-DQB1; histocompatibility testing ID CELIAC-DISEASE; OLIGONUCLEOTIDE PROBES; GENETIC-HETEROGENEITY; CONFORMATION ANALYSIS; DNA AB We have developed a high throughput HLA typing methodology that is a modification of the standard sequence-specific primer method. This approach is distinct from other methods using an automated DNA analyzer, as more than one gene is typed in a single lane. We have optimized the method for use on an ABI 373 automated genotyping machine. Primers were designed to preferentially amplify DNA fragments of the generic allelic groups of the DQA1 and DQB1 loci. PCR products representing alleles at the DQA 1 locus were amplified using a different fluorescent dye than the PCR products from the DQB1 locus. Only three PCR reactions are required for low resolution typing of DQA1 and DQB1. Use of different labeled primers enables genotyping for both loci in a single gel lane, allowing for 64 samples to be typed at low resolution for both DQA1 and DQB1 on a single gel. Automated allele assignments were determined based on DNA migration distance through a polyacrylamide gel using a standard genotype allele-calling program. Accuracy of this method is greater than 98% for both loci. The strategy described here may be adapted to include more loci or to produce higher resolution typing of alleles encoded by these loci. It can be readily optimized for use on other slab gel or capillary electrophoresis systems. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Med Informat, Salt Lake City, UT USA. RP Neuhausen, SL (reprint author), Univ Utah, Div Genet Epidemiol, 391 Chipeta Way,Suite D-2, Salt Lake City, UT 84108 USA. FU NIDDK NIH HHS [R01 DK-50678]; NLM NIH HHS [5 T15 LM07124] NR 18 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 1 PY 2001 VL 258 IS 1-2 BP 65 EP 71 DI 10.1016/S0022-1759(01)00473-2 PG 7 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 493TP UT WOS:000172239800007 PM 11684124 ER PT J AU Huang, JQ Durum, SK Muegge, K AF Huang, JQ Durum, SK Muegge, K TI Cutting edge: Histone acetylation and recombination at the TCR gamma locus follows IL-7 induction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR-DEFICIENT MICE; T-CELL DEVELOPMENT; INTERLEUKIN-7 RECEPTOR; ACCESSIBILITY CONTROL; V(D)J RECOMBINATION; GENE REARRANGEMENT; TRANSCRIPTION; CLEAVAGE; ENHANCER; STAT5 AB IL-7 signaling is required for V(D)J recombination at the TCR gamma locus. We have recently reported that IL-7 controls chromatin accessibility for RAG-mediated cleavage. Inhibition of histone deacetylase substituted for the IL-7 signal, indicating a role for histone acetylation in altering chromatin accessibility. We found a greatly reduced histone 3 and histone 4 acetylation level in IL-7R alpha (-/-) thymocytes in comparison with RAG(-/-) thymocytes or fetal thymocytes. Sterile transcripts, indicating an open chromatin configuration, were suppressed in IL-7R alpha (-/-) and IL-7(-/-)RAG(-/-) thymocytes. Moreover, exogenously added IL-7 induced sterile transcripts from the TCR gamma constant region in cultured thymocytes from IL-7(-/-)RAG(-/-) mice. This induction correlated with increased histone acetylation at the J-promoter and C-enhancer regulatory elements at the TCR gamma locus. These results suggest that IL-7 regulates chromatin accessibility for V(D)J recombination by specifically altering histone acetylation within the TCR gamma locus. C1 NCI, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. NCI, Sci Applicat Int Corp, Ft Detrick, MD 21702 USA. RP Muegge, K (reprint author), NCI, Mol Immunoregulat Lab, Bldg 469,Room 243, Ft Detrick, MD 21702 USA. NR 23 TC 39 Z9 40 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2001 VL 167 IS 11 BP 6073 EP 6077 PG 5 WC Immunology SC Immunology GA 494WU UT WOS:000172309500002 PM 11714763 ER PT J AU Urban, JF Noben-Trauth, N Schopf, L Madden, KB Finkelman, FD AF Urban, JF Noben-Trauth, N Schopf, L Madden, KB Finkelman, FD TI Cutting edge: IL-4 receptor expression by non-bone marrow-derived cells is required to expel gastrointestinal nematode parasites SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; PROTECTIVE IMMUNITY; NIPPOSTRONGYLUS-BRASILIENSIS; TRICHINELLA-SPIRALIS; CYTOKINE PRODUCTION; MICE; GAMMA; MASTOCYTOSIS; INFECTIONS; EXPULSION AB Expulsion of two gastrointestinal nematode parasites, Nippostrongylus brasiliensis and Trichinella spiralis, is similar in that both require IL-4R alpha expression, but different in that T cells and mast cells are required for IL-4-induced expulsion of T. spiralis but not N. brasiliensis. To examine the role of IL-4R alpha signaling in immunity to these parasites, we studied worm expulsion in chimeric mice that selectively expressed IL-4R alpha on bone marrow-derived or non-bone marrow-derived cells. N. brasiliensis was expelled by mice that expressed IL-4R alpha only on non-bone marrow-derived cells, but not by mice that expressed IL-4R alpha only on bone marrow-derived cells. Although T. spiralis expulsion required IL-4R alpha expression by both bone marrow and non-bone marrow-derived cells, IL-4 stimulation eliminated the requirement for IL-4R alpha expression by bone marrow-derived cells. Thus, direct IL-4R alpha signaling of nonimmune gastrointestinal cells may be generally required to induce worm expulsion, even when mast cell and T cell responses are also required. C1 USDA ARS, Anim & Nat Resources Inst, Immunol & Dis Resistance Lab, Beltsville, MD 20705 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. Univ Cincinnati, Coll Med, Dept Internal Med, Div Immunol, Cincinnati, OH 45267 USA. RP Finkelman, FD (reprint author), Cincinnati Vet Adm Med Ctr, Res Serv 151, 3200 Vine St, Cincinnati, OH 45220 USA. OI Urban, Joseph/0000-0002-1590-8869 FU NIAID NIH HHS [R01 AI44971, R01 AI35987, R21 AI46972] NR 23 TC 73 Z9 74 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2001 VL 167 IS 11 BP 6078 EP 6081 PG 4 WC Immunology SC Immunology GA 494WU UT WOS:000172309500003 PM 11714764 ER PT J AU Blanca, IR Bere, EW Young, HA Ortaldo, JR AF Blanca, IR Bere, EW Young, HA Ortaldo, JR TI Human B cell activation by autologous NK cells is regulated by CD40-CD40 ligand interaction: Role of memory B cells and CD5(+) B cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; LARGE GRANULAR LYMPHOCYTES; BONE-MARROW TRANSPLANTATION; TUMOR-NECROSIS-FACTOR; T-CELL; IMMUNOGLOBULIN-SYNTHESIS; ANTIBODY-PRODUCTION; DIFFERENTIATION; EXPRESSION; CYTOKINE AB NK cells are a subpopulation of lymphocytes characterized primarily by their cytolytic activity. They are recognized as an important component of the immune response against virus infection and tumors. In addition to their cytolytic activity, NK cells also participate either directly or indirectly in the regulation of the ongoing Ab response. More recently, it has been suggested that NK cells have an important role in the outcome of autoimmune diseases. Here, we demonstrate that human NK cells can induce autologous resting B cells to synthesize Ig, including switching to IgG and IgA, reminiscent of a secondary Ab response. B cell activation by the NK cell is contact-dependent and rapid, suggesting an autocrine B cell-regulated process. This NK cell function is T cell-independent, requires an active cytoplasmic membrane, and is blocked by anti-CD40 ligand (anti-CD154) or CD40-mIg fusion protein, indicating a critical role for CD40-CD40 ligand interaction. Depletion studies also demonstrate that CD5(+) B cells (autoreactive B-1 cells) and a heterogeneous population of CD27(+) memory B cells play a critical role in the Ig response induced by NK cells. The existence of this novel mechanism of B cell activation has important implications in innate immunity, B cell-mediated autoimmunity, and B cell neoplasia. C1 NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. Cent Univ Venezuela, Fac Med, Inst Inmunol, Caracas, Venezuela. RP Ortaldo, JR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Bldg 560,Room 31-93, Frederick, MD 21702 USA. NR 45 TC 52 Z9 54 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2001 VL 167 IS 11 BP 6132 EP 6139 PG 8 WC Immunology SC Immunology GA 494WU UT WOS:000172309500011 PM 11714772 ER PT J AU Caldwell, CC Kojima, H Lukashev, D Armstrong, J Farber, M Apasov, SG Sitkovsky, MV AF Caldwell, CC Kojima, H Lukashev, D Armstrong, J Farber, M Apasov, SG Sitkovsky, MV TI Differential effects of physiologically relevant hypoxic conditions on T lymphocyte development and effector functions SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCIBLE FACTOR 1-ALPHA; CELL ACTIVATION; O-2 HOMEOSTASIS; BLOOD-FLOW; OXYGEN; ADENOSINE; RELEASE; TUMOR; CYTOTOXICITY; MICROENVIRONMENT AB Direct measurements revealed low oxygen tensions (0.5-4.5% oxygen) in murine lymphoid organs in vivo. To test whether adaptation to changes in oxygen tension may have an effect on lymphocyte functions, T cell differentiation and functions at varying oxygen tensions were studied. These studies show: 1) differentiated CTL deliver Fas ligand- and perforin-dependent lethal hit equally well at all redox conditions; 2) CTL development is delayed at 2.5% oxygen as compared with 20% oxygen. Remarkably, development of CTL at 2.5% oxygen is more sustained and the CTL much more lytic; and 3) hypoxic exposure and TCR-mediated activation are additive in enhancing levels of hypoxia response element-containing gene products in lymphocyte supernatants. In contrast, hypoxia inhibited the accumulation of nonhypoxia response element-containing gene products (e.g., IL-2 and IEFN-gamma) in the same cultures. This suggests that T cell activation in hypoxic conditions in vivo may lead to different patterns of lymphokine secretion and accumulation of cytokines (e.g., vascular endothelial growth factor) affecting endothelial cells and vascular permeabilization. Thus, although higher numbers of cells survive and are activated during 20% oxygen incubation in vitro, the CTL which develop at 2.5% oxygen are more lytic with higher levels of activation markers. It is concluded that the ambient 20 % oxygen tension (plus 2-ME) is remarkably well suited for immunologic specificity and cytotoxicity studies, but oxygen dependence should be taken into account during the design and interpretation of results of in vitro T cell development assays and gene expression studies in vivo. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sitkovsky, MV (reprint author), NIAID, Immunol Lab, NIH, 10-11N311,10 Ctr Dr, Bethesda, MD 20892 USA. RI Lukashev, Dmitriy/F-8133-2010 NR 52 TC 185 Z9 197 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2001 VL 167 IS 11 BP 6140 EP 6149 PG 10 WC Immunology SC Immunology GA 494WU UT WOS:000172309500012 PM 11714773 ER PT J AU Liu, K Rosenberg, SA AF Liu, K Rosenberg, SA TI Transduction of an IL-2 gene into human melanoma-reactive lymphocytes results in their continued growth in the absence of exogenous IL-2 and maintenance of specific antitumor activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; T-LYMPHOCYTES; RETROVIRAL TRANSDUCTION; METASTATIC MELANOMA; CANCER-PATIENTS; ANTIGEN; CELLS; INTERLEUKIN-2; IMMUNOTHERAPY; THERAPY AB IL-2-dependent activated cells undergo apoptotic death when IL-2 is withdrawn either in vitro or after in vivo cell transfer. To attempt to sustain their survival after IL-2 withdrawal, melanoma reactive human T lymphocytes were retrovirally transduced with an exogenous human IL-2 gene. Transduced PBMC and cloned CD8(+) T cells produced IL-2 and maintained viability after IL-2 withdrawal. Upon restimulation, IL-2 transductants proliferated in the absence of exogenous IL-2 and could be actively grown, and their survival could be maintained without added IL-2 for over 8 wk. PBMCs similarly transduced with a control vector did not produce IL-2 and failed to proliferate in the absence of IL-2. A CD8(+) T cell clone, when transduced with an IL-2 gene, manifested the same phenotypes as PBMCs in the absence of exogenous IL-2. Furthermore, an Ab reactive with the alpha -chain of IL-2R complex reduced the viability mediated by IL-2 secretion of the IL-2 transductants. Moreover, transduction of an IL-2 gene did not affect the high degree of recognition and specificity of transductants against melanoma targets. These tumor-reactive IL-2 transductants may be valuable for in vitro studies and for improved adoptive transfer therapies for patients with metastatic melanoma. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Liu, K (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 2B08, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC003811-33] NR 31 TC 77 Z9 81 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2001 VL 167 IS 11 BP 6356 EP 6365 PG 10 WC Immunology SC Immunology GA 494WU UT WOS:000172309500039 PM 11714800 ER PT J AU Hesse, M Modolell, M La Flamme, AC Schito, M Fuentes, JM Cheever, AW Pearce, EJ Wynn, TA AF Hesse, M Modolell, M La Flamme, AC Schito, M Fuentes, JM Cheever, AW Pearce, EJ Wynn, TA TI Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: Granulomatous pathology is shaped by the pattern of L-arginine metabolism SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYCOBACTERIUM-AVIUM INFECTION; MARROW-DERIVED MACROPHAGES; SCHISTOSOMA-MANSONI EGGS; HYDROXY-L-ARGININE; MURINE SCHISTOSOMIASIS; HEPATIC-FIBROSIS; HEALING WOUNDS; LIVER ARGINASE; TH2 CYTOKINES; T-CELLS AB Type 2 cytokines regulate fibrotic liver pathology in mice infected with Schistosoma mansoni. Switching the immune response to a type 1-dominant reaction has proven highly effective at reducing the pathologic response. Activation of NOS-2 is critical, because type 1-deviated/NO synthase 2 (NOS-2) -deficient mice completely fail to control their response. Here, we demonstrate the differential regulation of NOS-2 and arginase type 1 (Arg-1) by type 1/type 2 cytokines in vivo and for the first time show a critical role for arginase in the pathogenesis of schistosomiasis. Using cytokine-deficient mice and two granuloma models, we show that induction of Arg-1 is type 2 cytokine dependent. Schistosome eggs induce Arg-1, while Mycobacterium avium-infected mice develop a dominant NOS-2 response. IFN-gamma suppresses Arg-1 activity, because type 1 polarized IL-4/IL-10-deficient, IL-4/IL-13-deficient, and egg/IL-12-sensitized animals fail to up-regulate Arg-1 following egg exposure. Notably, granuloma size decreases in these type-1-deviated/Arg-1-unresponsive mice, suggesting an important regulatory role for Arg-1 in schistosome egg-induced pathology. To test this hypothesis, we administered difluoromethylornithine to block ornithine-aminodecarboxylase, which uses the product of arginine metabolism, L-ornithine, to generate polyamines. Strikingly, granuloma size and hepatic fibrosis increased in the ornithine-aminodecarboxylase-inhibited mice. Furthermore, we show that type 2 cytokine-stimulated macrophages produce proline under strict arginase control. Together, these data reveal an important regulatory role for the arginase biosynthetic pathway in the regulation of inflammation and demonstrate that differential activation of Arg-1/NOS-2 is a critical determinant in the pathogenesis of granuloma formation. C1 NIAID, Parasit Dis Lab, NIH, Immunobiol Sect, Bethesda, MD 20892 USA. Schistosomiasis Immunol & Pathol Unit, Freiburg, Germany. Max Planck Inst Immunbiol, D-7800 Freiburg, Germany. Cornell Univ, Dept Immunol Microbiol, Ithaca, NY 14853 USA. Biomed Res Inst, Rockville, MD 20852 USA. Univ Extremadura, Dept Biochem, Caceres, Spain. RP Wynn, TA (reprint author), NIAID, Parasit Dis Lab, NIH, Immunobiol Sect, 7 Ctr Dr,Room 7-318, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011; Fuentes, Jose/H-9490-2014 OI Fuentes, Jose/0000-0001-6910-2089 NR 52 TC 412 Z9 433 U1 2 U2 36 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2001 VL 167 IS 11 BP 6533 EP 6544 PG 12 WC Immunology SC Immunology GA 494WU UT WOS:000172309500061 PM 11714822 ER PT J AU Liang, TS Gao, JL Fatemi, O Lavigne, M Leto, TL Murphy, PM AF Liang, TS Gao, JL Fatemi, O Lavigne, M Leto, TL Murphy, PM TI The endogenous opioid spinorphin blocks fMet-leu-phe-induced neutrophil chemotaxis by acting as a specific antagonist at the N-formylpeptide receptor subtype FPR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANGIOTENSIN-CONVERTING ENZYME; FORMYL PEPTIDE RECEPTOR; ENKEPHALIN-DEGRADING ENZYMES; SERUM AMYLOID-A; NEUTRAL ENDOPEPTIDASE; AMINOPEPTIDASE-N; CEREBROSPINAL-FLUID; INHIBITORY-ACTION; GENE-CLUSTER; HEMOGLOBIN AB Spinorphin is an endogenous heptapeptide (leucylvalylvalyltyrosylprolyltryptophylthreonine), first isolated from bovine spinal cord, whose sequence matches a conserved region of beta -hemoglobin. Also referred to as LVV-hemorphin-4 and a member of the nonclassical opioid hemorphin family, spinorphin inhibits enkephalin-degrading enzymes and is analgesic. Recently, spinorphin was reported to block neutrophil activation induced by the chemotactic N-formylpeptide N-formylmethionylleucylphenylalanine (fMLF), suggesting a potential role as an endogenous negative regulator of inflammation. Here we use both gain- and loss-of-function genetic tests to identify the specific mechanism of spinorphin action on neutrophils. Spinorphin induced calcium flux in normal mouse neutrophils, but was inactive in neutrophils from mice genetically deficient in the fMLF receptor subtype FPR (N-formylpeptide receptor). Consistent with this, spinorphin induced calcium flux in human embryonic kidney 293 cells transfected with mouse FPR, but had no effect on cells expressing the closely related fMLF receptor subtype FPR2. Despite acting as a calcium-mobilizing agonist at FPR, spinorphin was a weak chemotactic agonist and effectively blocked neutrophil chemotaxis induced by fMLF at concentrations selective for FPR. Spinorphin did not affect mouse neutrophil chemotaxis induced by concentrations of fMLF that selectively activate FPR2. Thus, spinorphin blocks fMLF-induced neutrophil chemotaxis by acting as a specific antagonist at the fMLF receptor subtype FPR. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N113, Bethesda, MD 20892 USA. NR 49 TC 32 Z9 33 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2001 VL 167 IS 11 BP 6609 EP 6614 PG 6 WC Immunology SC Immunology GA 494WU UT WOS:000172309500070 PM 11714831 ER PT J AU Goulet, JL Griffiths, RC Ruiz, P Mannon, RB Flannery, P Platt, JL Koller, BH Coffman, TM AF Goulet, JL Griffiths, RC Ruiz, P Mannon, RB Flannery, P Platt, JL Koller, BH Coffman, TM TI Deficiency of 5-lipoxygenase accelerates renal allograft rejection in mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUKOTRIENE B-4 RECEPTOR; GLOMERULAR MESANGIAL CELLS; INFLAMMATORY RESPONSES; HEMODYNAMIC-RESPONSES; TARGETED DISRUPTION; INTERFERON-GAMMA; RAT; INHIBITION; ROLES; PROSTAGLANDIN AB Acute renal allograft rejection is associated with alterations in renal arachidonic acid metabolism, including enhanced synthesis of leukotrienes (LTs). LTs, the products of the 5-lipoxygenase (5-LO) pathway, are potent lipid mediators with a broad range of biologic activities. Previous studies, using pharmacological agents to inhibit LT synthesis or activity, have implicated these eicosanoids in transplant rejection. To further investigate the role of LTs in acute graft rejection, we transplanted kidneys from CByD2F(1) mice into fully allogeneic 129 mice that carry a targeted mutation in the 5lo gene. Unexpectedly, allograft rejection was significantly accelerated in 5-LO-deficient mice compared with mild-type animals. Despite the marked reduction in graft survival, the 5lo mutation had no effect on the hemodynamics or morphology of the allografts. Although LTB4 levels were reduced, renal thromboxane B, production and cytokine expression were not altered in 5-LO-deficient allograft recipients. These findings suggest that, along with their proinflammatory actions, metabolites of 5-LO can act to enhance allograft survival. C1 Vet Affairs Med Ctr, Durham, NC 27705 USA. Duke Univ, Dept Med, Div Nephrol, Durham, NC 27705 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL 33101 USA. NIDDK, Transplantat & Autoimmun Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin, Dept Immunol, Rochester, MN 55905 USA. Mayo Clin, Dept Surg, Rochester, MN 55905 USA. Mayo Clin, Dept Pediat, Rochester, MN 55905 USA. RP Coffman, TM (reprint author), Vet Affairs Med Ctr, Bldg 6,Room 1100,508 Fulton St, Durham, NC 27705 USA. FU NIDDK NIH HHS [5-T32-DK07731, P01-DK38108] NR 50 TC 17 Z9 17 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2001 VL 167 IS 11 BP 6631 EP 6636 PG 6 WC Immunology SC Immunology GA 494WU UT WOS:000172309500073 PM 11714834 ER PT J AU Biragyn, A Surenhu, M Yang, D Ruffini, PA Haines, BA Klyushnenkova, E Oppenheim, JJ Kwak, LW AF Biragyn, A Surenhu, M Yang, D Ruffini, PA Haines, BA Klyushnenkova, E Oppenheim, JJ Kwak, LW TI Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; DNA VACCINES; SELECTIVE RECRUITMENT; ADAPTIVE IMMUNITY; FUSION PROTEINS; CHEMOKINE; LYMPHOMA; RECEPTOR; VACCINATION; ACTIVATION AB Chemokine receptors are differentially expressed on immature and mature dendritic cells (DQ. Herein, we demonstrate for the first time that murine antimicrobial peptides beta -defensins 2 and 3 bind murine CCR6, similarly to inflammatory chemokine macrophage-inflammatory protein 3 alpha, and they chemoattract bone marrow-derived immature, but not mature DC. Using various chemokines or defensins fused with nonimmunogenic tumor Ags, we studied their capacity to delivery Ags to subsets of immune cells to elicit antitumor immunity. We demonstrate that DNA immunizations with fusion constructs with beta -defensin 2 or inflammatory chemokines that target immature DC, but not homeostatic chemokines secondary lymphoid tissue chemokine, CCL21, or stromal cell-derived factor 1, CXCL12, which chemoattract mature DC, elicit Immoral, protective, and therapeutic immunity against two different syngeneic lymphomas. C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Sci Applicat Int Corp, Mclean, VA 22102 USA. RP Biragyn, A (reprint author), NCI, Mol Immunoregulat Lab, Bldg 567,Room 213, Frederick, MD 21702 USA. NR 43 TC 212 Z9 239 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2001 VL 167 IS 11 BP 6644 EP 6653 PG 10 WC Immunology SC Immunology GA 494WU UT WOS:000172309500075 PM 11714836 ER PT J AU Douek, DC Betts, MR Hill, BJ Little, SJ Lempicki, R Metcalf, JA Casazza, J Yoder, C Adelsberger, JW Stevens, RA Baseler, MW Keiser, P Richman, DD Davey, RT Koup, RA AF Douek, DC Betts, MR Hill, BJ Little, SJ Lempicki, R Metcalf, JA Casazza, J Yoder, C Adelsberger, JW Stevens, RA Baseler, MW Keiser, P Richman, DD Davey, RT Koup, RA TI Evidence for increased T cell turnover and decreased thymic output in HIV infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; SIMIAN IMMUNODEFICIENCY VIRUS; BONE-MARROW TRANSPLANTATION; LYMPHOID-TISSUES; RHESUS MACAQUES; RAPID TURNOVER; IN-VIVO; CD4(+); LYMPHOCYTES; KINETICS AB The effects of HIV infection upon the thymus and peripheral T cell turnover have been implicated in the pathogenesis of AIDS. In this study, we investigated whether decreased thymic output, increased T cell proliferation, or both can occur in HIV infection. We measured peripheral blood levels of TCR rearrangement excision circles (TREC) and parameters of cell proliferation, including Ki67 expression and ex vivo bromodeoxyuridine incorporation in 22 individuals with early untreated HIV disease and in 15 HIV-infected individuals undergoing temporary interruption of therapy. We found an inverse association between increased T cell proliferation with rapid viral recrudescence and a decrease in TREC levels. However, during early HIV infection, we found that CD45RO(-)CD27(high) (naive) CD4(+) T cell proliferation did not increase, despite a loss of TREC within naive CD4(+) T cells. A possible explanation for this is that decreased thymic output occurs in HIV-infected humans. This suggests that the loss of TREC during HIV infection can arise from a combination of increased T cell proliferation and decreased thymic output, and that both mechanisms can contribute to the perturbations in T cell homeostasis that underlie the pathogenesis of AIDS. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, Clin & Mol Retrovirol Sect, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, La Jolla, CA 92093 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Sci Applicat Int Corp, Clin Serv Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NCI, Dept Expt Transplant & Immunol, Med Branch, Bethesda, MD 20892 USA. RP Douek, DC (reprint author), NIAID, Vaccine Res Ctr, NIH, Room 3509,40 Convent Dr, Bethesda, MD 20892 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X FU NCI NIH HHS [N01-CO-56000]; NIAID NIH HHS [AI36214, AI291674, AI35522, AI43638] NR 50 TC 153 Z9 158 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2001 VL 167 IS 11 BP 6663 EP 6668 PG 6 WC Immunology SC Immunology GA 494WU UT WOS:000172309500077 PM 11714838 ER PT J AU Peebles, RS Hashimoto, K Collins, RD Jarzecka, K Furlong, J Mitchell, DB Sheller, JR Graham, BS AF Peebles, RS Hashimoto, K Collins, RD Jarzecka, K Furlong, J Mitchell, DB Sheller, JR Graham, BS TI Immune interaction between respiratory syncytial virus infection and allergen sensitization critically depends on timing of challenges SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INDUCED AIRWAY HYPERRESPONSIVENESS; FORMALIN-INACTIVATED RSV; BALB/C MICE; DAY-CARE; ASTHMA; BRONCHIOLITIS; INFANCY; EXPRESSION; CHILDHOOD; RESPONSES AB Severe respiratory syncytial virus (RSV) infection has been hypothesized to be a risk factor for the development of allergy and asthma, but epidemiologic studies in humans have been inconclusive. By use of a well-characterized murine model of RSV infection and allergic sensitization with ovalbumin, the effect of a preceding severe RSV infection on the development of the pulmonary allergic inflammatory response and airway hyperresponsiveness (AHR) was tested. The impact of prior allergic sensitization on RSV-induced illness, as measured by weight loss, also was evaluated. RSV infection before allergic sensitization decreased allergen-induced AHR, production of interleukin-13 in lung tissue, and lung eosinophilia. In contrast, allergic sensitization before RSV infection increased AHR and decreased RSV-related weight loss and lung levels of interferon-gamma but did not alter viral clearance. These data provide evidence that RSV-associated AHR occurs in hosts with allergic responses and that allergic inflammation is diminished when preceded by RSV infection. C1 NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA. RP Graham, BS (reprint author), NIH, Vaccine Res Ctr, Bldg 40,Rm 2502,40 Covent Dr,MSC 3017, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL-03730]; NIAID NIH HHS [AI-44512]; NIGMS NIH HHS [GM-15431] NR 29 TC 45 Z9 46 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2001 VL 184 IS 11 BP 1374 EP 1379 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 492BG UT WOS:000172145400002 PM 11709778 ER PT J AU Fischer, S Gill, VJ Kovacs, J Miele, P Keary, J Silcott, V Huang, S Borio, L Stock, F Fahle, G Brown, D Hahn, B Townley, E Lucey, D Masur, H AF Fischer, S Gill, VJ Kovacs, J Miele, P Keary, J Silcott, V Huang, S Borio, L Stock, F Fahle, G Brown, D Hahn, B Townley, E Lucey, D Masur, H TI The use of oral washes to diagnose Pneumocystis carinii pneumonia: A blinded prospective study using a polymerase chain reaction-based detection system SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NONINVASIVE DIAGNOSIS; PCR; DNA; AMPLIFICATION; SAMPLES; GENES AB Pneumocystis carinii pneumonia (PCP) can be diagnosed by direct microscopic examination of induced sputum or by bronchoalveolar lavage (BAL). However, many institutions have little diagnostic success with induced sputum, and BAL is invasive and expensive. This prospective, blinded study assessed oral washes as a more convenient specimen than either sputum or BAL fluid and used a dissociation-enhanced lanthanide fluoroimmunoassay time-resolved fluorescent hybridization polymerase chain reaction (PCR) detection system that is feasible for clinical laboratories. The study assessed 175 oral washes, each paired with either an induced sputum that was positive for Pneumocystis or a BAL sample. The PCR test based on the Pneumocystis major surface glycoprotein primers had a sensitivity of 91% and a specificity of 94%, compared with a test based on mitochondrial large subunit rRNA primers, which had a sensitivity of 75% and a specificity of 96%. These results suggest that oral washes can provide a useful sample for diagnosis of PCP when a sensitive PCR detection system is used. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. Div Infect Dis, Washington, DC USA. Washington Hosp Ctr, Washington, DC 20010 USA. RP Masur, H (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Rm 7D43, Bethesda, MD 20892 USA. NR 15 TC 38 Z9 39 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2001 VL 184 IS 11 BP 1485 EP 1488 DI 10.1086/324520 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 492BG UT WOS:000172145400019 PM 11709795 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI Progress in the development of immunotherapy for the treatment of patients with cancer SO JOURNAL OF INTERNAL MEDICINE LA English DT Review DE cancer; immunotherapy; melanoma; antigens; interleukin-2 ID TUMOR-INFILTRATING LYMPHOCYTES; DOSE RECOMBINANT INTERLEUKIN-2; CYTOTOXIC T-LYMPHOCYTES; MELANOMA ANTIGEN GP100; ACTIVATED KILLER CELLS; METASTATIC MELANOMA; AUTOLOGOUS TUMOR; ADOPTIVE IMMUNOTHERAPY; PEPTIDE VACCINE; INVITRO GROWTH AB Several recent developments have hallmarked progress in tumour immunology and immunotherapy. The use of interleukin-2 (IL-2) in cancer patients demonstrated that an immunological manipulation was capable of mediating the regression of established growing cancers in humans. The identification of the genes encoding cancer antigens and the development of means for effectively immunizing patients against these antigens has opened important new avenues of exploration for the development of effective active and cell-transfer immunotherapies for patients with cancer. C1 NCI, Inst Hlth, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Inst Hlth, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC003811-33] NR 68 TC 94 Z9 96 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD DEC PY 2001 VL 250 IS 6 BP 462 EP 475 DI 10.1046/j.1365-2796.2001.00911.x PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 499AY UT WOS:000172549200002 PM 11902815 ER PT J AU Boffetta, P Gridley, G Lindelof, B AF Boffetta, P Gridley, G Lindelof, B TI Cancer risk in a population-based cohort of patients hospitalized for psoriasis in Sweden SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE alcohol drinking; epidemiology; malignant melanoma; psoriasis; skin neoplasms ID SQUAMOUS-CELL CARCINOMA; 8-YEAR FOLLOW-UP; A RADIATION PUVA; MALIGNANT-TUMORS; ULTRAVIOLET-A; SKIN-CANCER; METHOXSALEN PSORALEN; ALCOHOL-CONSUMPTION; FINNISH PATIENTS; MELANOMA AB Studies of clinical series of psoriasis patients have suggested an increased risk of nonmelanoma skin cancer and melanoma; the risk of other neoplasms has rarely been studied. In order to assess the incidence of cancer in a nationwide series of psoriasis patients from Sweden, we followed up, for the years 1965-89, 9773 patients with a hospital discharge diagnosis of psoriasis made during 1965-83, who were alive and free from malignancy 1 y after first discharge. We compared their incidence of neoplasms with that of the national population by computing standardized incidence ratios (SIR). We observed a total of 789 neoplasms [SIR 1.37, 95% confidence interval (CI) 1.28, 1.47]. There was an increase in the risk of cancers of the oral cavity and pharynx (SIR 2.80, 95% CI 1.96, 3.87), liver (SIR 1.91, 95% CI 1.28, 2.74), pancreas (SIR 1.56, 95% CI 1.02, 2.23), lung (SIR 2.13, 95% CI 1.71, 2.61), skin (squamous cell carcinoma, SIR 2.46, 95% CI 1.82, 3.27), female breast (SIR 1.27, 95% CI 1.00, 1.58), vulva (SIR 3.24, 95% CI 1.18, 7.06), penis (SIR 4.66, 95% CI 1.50, 10.9), bladder (SIR 1.43, 95% CI 1.03, 1.92), and kidney (SIR 1.56, 95% CI 1.04, 2.25). The risk of malignant melanoma was decreased (SIR 0.32, 95% CI 0.10, 0.74). Despite some limitations (possible diagnostic misclassification, lack of data on treatment, relatively short follow-up), our study provides evidence against an increased risk of melanoma among patients hospitalized for psoriasis. In addition to nonmelanoma skin and genital cancers, patients hospitalized for psoriasis were at increased risk of several malignancies, in particular those associated with alcohol drinking and tobacco smoking. C1 Int Agcy Res Canc, Unit Environm Canc Epidemiol, F-69008 Lyon, France. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. Karolinska Hosp, Dept Dermatol, S-10401 Stockholm, Sweden. RP Boffetta, P (reprint author), Int Agcy Res Canc, Unit Environm Canc Epidemiol, 150 Cours Albert Thomas, F-69008 Lyon, France. NR 46 TC 92 Z9 94 U1 0 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2001 VL 117 IS 6 BP 1531 EP 1537 DI 10.1046/j.0022-202x.2001.01520.x PG 7 WC Dermatology SC Dermatology GA 505FR UT WOS:000172903200028 PM 11886519 ER PT J AU Blauvelt, A AF Blauvelt, A TI Skin diseases associated with human herpesvirus 6, 7, and 8 infection SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 49th Montagna Annual Symposium on the Biology of Skin CY AUG 12-16, 2000 CL SNOWMASS, COLORADO DE pityriasis rosea; KSHV; Kaposi's sarcoma; pathogenesis ID SARCOMA-ASSOCIATED HERPESVIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; PRIMARY EFFUSION LYMPHOMA; MULTICENTRIC CASTLEMANS-DISEASE; KAPOSIS-SARCOMA; HUMAN-HERPESVIRUS-8 INFECTION; PITYRIASIS-ROSEA; NUCLEAR ANTIGEN; DNA-SEQUENCES; PERIPHERAL-BLOOD AB Relatively recently, the discovery and analysis of three new human herpesviruses, human herpesvirus (HHV)-6, HHV-7, and Kaposi's sarcoma-associated herpesvirus (KSHV), also known as HHV-8, has contributed greatly to our understanding of the pathogenesis of several common dermatoses. HHV-6 and HHV-7 are closely related P-herpesviruses that have been linked with roseola (mostly HHV-6), severe drug eruptions (HHV-6), and pityriasis rosea (mostly HHV-7). KSHV is a gamma-herpesvirus that is now believed to be the long sought after etiologic agent of Kaposi's sarcoma. The evidence for these skin disease associations and key findings from recent basic science investigations on viral pathogenesis are discussed in this review. In addition, possible therapeutic implications of these research studies are explored. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Blauvelt, A (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12 N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. NR 98 TC 16 Z9 16 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD DEC PY 2001 VL 6 IS 3 BP 197 EP 202 DI 10.1046/j.0022-202x.2001.00040.x PG 6 WC Dermatology SC Dermatology GA 533FP UT WOS:000174519000007 PM 11924827 ER PT J AU Marovich, M Grouard-Vogel, G Louder, M Eller, M Sun, W Wu, SJ Putvatana, R Murphy, G Tassaneetrithep, B Burgess, T Birx, D Hayes, C Schlesinger-Frankel, S Mascola, J AF Marovich, M Grouard-Vogel, G Louder, M Eller, M Sun, W Wu, SJ Putvatana, R Murphy, G Tassaneetrithep, B Burgess, T Birx, D Hayes, C Schlesinger-Frankel, S Mascola, J TI Human dendritic cells as targets of dengue virus infection SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 49th Montagna Annual Symposium on the Biology of Skin CY AUG 12-16, 2000 CL SNOWMASS, COLORADO DE hemorrhagic virus infects APC ID HEMORRHAGIC-FEVER; DISEASE SEVERITY; HUMAN-MONOCYTES; PATHOGENESIS; VIREMIA AB Dengue virus infections are an emerging global threat. Severe dengue infection is manifested as dengue hemorrhagic fever and dengue shock syndrome, both of which can be fatal complications. Factors predisposing to complicated disease and pathogenesis of severe infections are discussed. Using immunohistochemistry, immunofluorescence, flow cytometry, and ELISA techniques, we studied the cellular targets of dengue virus infection, at both the clinical (in vivo) and the laboratory (in vitro) level. Resident skin dendritic cells are targets of dengue virus infection as demonstrated in a skin biopsy from a dengue vaccine recipient. We show that factors influencing infection of monocytes/macrophages and dendritic cells are different. Immature dendritic cells were found to be the cells most permissive for dengue infection and maybe early targets for infection. Immature dendritic cells exposed to dengue virus produce TNF-alpha protein. Some of these immature dendritic cells undergo TNF-alpha mediated maturation as a consequence of exposure to the dengue virus. C1 Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD 20850 USA. Henry M Jackson Fdn, Rockville, MD 20850 USA. Walter Reed Army Inst Res, Div Viral Dis, Silver Spring, MD USA. USN, Viral & Rickettsial Dis Dept, Med Res Ctr, Bethesda, MD 20084 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Marovich, M (reprint author), Walter Reed Army Inst Res, Div Retrovirol, 13 Taft Ct,Suite 200, Rockville, MD 20850 USA. NR 26 TC 88 Z9 92 U1 1 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD DEC PY 2001 VL 6 IS 3 BP 219 EP 224 DI 10.1046/j.0022-202x.2001.00037.x PG 6 WC Dermatology SC Dermatology GA 533FP UT WOS:000174519000011 PM 11924831 ER PT J AU Weng, NP AF Weng, NP TI Interplay between telomere length and telomerase in human leukocyte differentiation and aging SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE lymphocyte; monocyte; granulocyte; mast cells ID HEMATOPOIETIC STEM-CELLS; MEMORY T-CELLS; BONE-MARROW; IN-VIVO; REPLICATIVE SENESCENCE; LYMPHOCYTE DEVELOPMENT; ANTIGEN RECEPTOR; B-LYMPHOCYTES; HL-60 CELLS; ACTIVATION AB Blood leukocytes derive from bone marrow hematopoietic stem cells and differentiate into multiple types of mature cells that include granulocytes, monocytes, mast cells of myeloid lineage, and T and B lymphocytes of lymphoid lineage. Their distinctive paths of differentiation and unique roles in immune response provide a model for comparative analysis of biological parameters, such as telomere length and telomerase activity, in different types of leukocytes. Age has also been associated with the decline in immune functions and with the attrition of telomere length in leukocytes. This review will summarize recent progress in the study of telomere length and telomerase expression in leukocytes during differentiation and aging. In addition, I will attempt to shed new light on the roles of telomere and telomerase in leukocyte function and potential clinical interventions. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Weng, NP (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. NR 62 TC 44 Z9 45 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 2001 VL 70 IS 6 BP 861 EP 867 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 499TQ UT WOS:000172586800003 PM 11739547 ER PT J AU Sayers, EW Torchia, DA AF Sayers, EW Torchia, DA TI Use of the carbonyl chemical shift to relieve degeneracies in triple-resonance assignment experiments SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE carbonyl chemical shift; CBCACO(N)H; H(CA)CON; proline; ribosomal protein S4; resonance overlap ID ISOTOPICALLY ENRICHED PROTEINS; SEQUENTIAL ASSIGNMENT; NMR-SPECTROSCOPY; C-13/N-15-LABELED PROTEINS; BACKBONE RESONANCES; S4 DELTA-41; RESOLUTION; COUPLINGS; REVEALS; SURFACE AB We illustrate an approach that uses the backbone carbonyl chemical shift to relieve resonance overlaps in triple-resonance assignment experiments conducted on protein samples. We apply this approach to two cases of simultaneous overlaps: those of (H-1(N), N-15) spin pairs and those of (H-1(alpha), C-13(alpha)) spin pairs in residues preceding prolines. For these cases we employed respectively CBCACO(N)H and H(CA)CON experiments, simple variants of the commonly used CBCA(CO)NH and HCA(CO)N experiments obtained by replacing one of the indirect dimensions with a carbonyl dimension. We present data collected on ribosomal protein S4 using these experiments, along with overlap statistics for four other polypeptides ranging in size from 76 to 263 residues. These data indicate that the CBCACO(N)H, in combination with the CBCA(CO)NH, can relieve >83% of the (H-1(N), N-15) and (H-1(N), C-13') overlaps for these proteins. The data also reveal how the H(CA)CON experiment successfully completed the assignment of triply and quadruply degenerate X-Pro spin systems in a mobile, proline-rich region of S4, even when X was a glycine. Finally, we discuss the relative sensitivities of these experiments compared to those of existing sequences, an analysis that reinforces the usefulness of these experiments in assigning extensively overlapped and/or proline-rich sequences in proteins. C1 Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. RP Sayers, EW (reprint author), Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, 30 Convent Dr,MSC 4307, Bethesda, MD 20892 USA. NR 29 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD DEC PY 2001 VL 153 IS 2 BP 246 EP 253 DI 10.1006/jmre.2001.2440 PG 8 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 511TV UT WOS:000173282400011 PM 11740901 ER PT J AU Weiss, CR Arai, AE Bui, MN Agyeman, KO Waclawiw, MA Balaban, RS Cannon, RO AF Weiss, CR Arai, AE Bui, MN Agyeman, KO Waclawiw, MA Balaban, RS Cannon, RO TI Arterial wall MRI characteristics are associated with elevated serum markers of inflammation in humans SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE inflammation; magnetic resonance imaging; atherosclerosis; cell adhesion molecules; hyperlipidemia ID C-REACTIVE PROTEIN; FUTURE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; APPARENTLY HEALTHY-MEN; AMYLOID-A PROTEIN; HUMAN ATHEROSCLEROSIS; PLASMA-CONCENTRATION; ADHESION MOLECULES; IN-VIVO; PLAQUE AB Inflammation contributes to atherosclerosis, but assessment in humans is largely restricted to measurement of markers in blood. We determined whether MRI properties of large arteries were associated with markers of inflammation in serum. Double inversion recovery, fast spin-echo images of the common carotid arteries and infrarenal aorta were obtained at 1.5 T both before and after gadolinium-DTPA (0.1 mmol/kg) in 52 subjects greater than or equal to40 years of age, 17 of whom had no risk factors for atherosclerosis and thus served as controls. Twenty-two study participants had increases in wall thickness (14), T2-weighted signal intensity (11), and/or contrast enhancement values (7) that were >2 standard deviations (SDs) from control group mean values. Ten subjects in this group had evidence of focal plaques in the carotids (5) and/or aorta (6). Compared with the remaining 30 subjects, these 22 had significantly higher levels of interleukin-6 (3.53 +/- 2.46 vs. 1.97 +/- 1.37 pg/mL, P = 0.004), C-reactive protein (0.56 +/- 0.98 vs. 0.30 +/- 0.52 mg/dL, P = 0.019), vascular cell adhesion molecule-1 (572 +/- 153 vs. 471 +/- 130 ng/mL, P = 0.012), and intercellular adhesion molecule-1 (244 +/- 80 vs. 202 +/- 45 ng/mL, P = 0.015), and nonsignificant differences in levels of E-selectin (46.1 +/- 18.9 vs. 42.3 +/- 11.3 ng/mL, P = 0.369). Thus, MRI characteristics of the aorta and carotid arteries were associated with elevated serum markers of inflammation, frequently in the absence of definite atheroma. MRI of large arteries may provide a new approach to investigate the contribution of inflammation to atherogenesis. (C) 2001 Wiley-Liss, Inc. C1 NIH, NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIH, NHLBI, Cardiac Energet Lab, Bethesda, MD USA. NIH, NHLBI, Off Biostat Res, Bethesda, MD USA. RP Cannon, RO (reprint author), NIH, NHLBI, Cardiol Branch, Bldg 10,Room 7B-15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 25 TC 38 Z9 39 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD DEC PY 2001 VL 14 IS 6 BP 698 EP 704 DI 10.1002/jmri.10023 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 537LE UT WOS:000174759300006 PM 11747026 ER PT J AU Kobayashi, H Kawamoto, S Saga, T Sato, N Hiraga, A Konishi, J Togashi, K Brechbiel, MW AF Kobayashi, H Kawamoto, S Saga, T Sato, N Hiraga, A Konishi, J Togashi, K Brechbiel, MW TI Micro-MR angiography of normal and intratumoral vessels in mice using dedicated intravascular MR contrast agents with high generation of polyamidoamine dendrimer core: Reference to pharmacokinetic properties of dendrimer-based MR contrast agents SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance imaging; MR angiography; pharmacokinetics; contrast media; dendrimers ID DTPA-LABELED DEXTRAN; GD-DTPA; MACROMOLECULAR THERAPEUTICS; VASCULAR-PERMEABILITY; MONOCLONAL-ANTIBODY; FLEXIBILITY; SIZE AB Pharmacokinetic characteristics of intravascular macromolecular magnetic resonance imaging (MRI) contrast agents with polyamidoamine dendrimer cores smaller than generation-7 were previously studied in the literature. To evaluate the effects of greater hepatic uptake on the pharmacokinetics of the larger generation dendrimers, the MRI contrast agents GxD-(1B4M-Gd)(2x+2) were synthesized with generation-7, -8, and -9 polyamidoamine dendrimers and 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M). Their pharmacokinetic characteristics in mice were compared with that of G6D-(1B4M-Gd)(256). In biodistribution and dynamic micro-MRI studies, significantly less renal accumulation of G7D-(1B4M-Gd)(512), G8D-(1B4M-Gd)(1024), and G9D-(1B4M-Gd)(2048) was shown compared to G6D-(1B4M-Gd)(256) (P < 0.01). There was a significantly greater accumulation of G8D-(1B4M-Gd)(1024) and G9D-(1B4M-Gd)(2048) in the liver compared to G6D-(1B4M-Gd)(256) and G7D-(1B4M-Gd)(512) (P < 0.01). The highest blood retention of all dendrimer-based MRI contrast agents was exhibited by G7D-(1B4M-Gd)(512) (P < 0.01). The normal and intratumoral fine vessels of approximately 100 mum diameter were visualized in normal or tumor-bearing mice by high resolution three-dimensional-micro-MR angiographs with G7D-(1B4M-Gd)(512) and GSD-(1B4M-Gd)(1024) with good vessel-to-soft tissue contrast. In summary, increased accumulation in the liver with concomitant decreased uptake in the kidney was caused by increased molecular sizes of the dendrimer-based MRI contrast agents. (C) 2001 Wiley-Liss, Inc. C1 Kyoto Univ, Dept Diagnost & Intervent Radiol, Grad Sch Med, Hitachi Med Co Chaired, Sakyo, Kyoto 6068507, Japan. Kyoto Univ, Dept Nucl Med & Diagnost Imaging, Kyoto, Japan. Kyoto Univ, Dept Radiol, Kyoto, Japan. Otsu Municipal Hosp, Dept Radiol, Otsu, Shiga, Japan. NIH, NCI, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD USA. RP Kobayashi, H (reprint author), Kyoto Univ, Dept Diagnost & Intervent Radiol, Grad Sch Med, Hitachi Med Co Chaired, 54 Kawahara Cho, Sakyo, Kyoto 6068507, Japan. NR 30 TC 70 Z9 74 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD DEC PY 2001 VL 14 IS 6 BP 705 EP 713 DI 10.1002/jmri.10025 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 537LE UT WOS:000174759300007 PM 11747027 ER PT J AU Eng, C Brody, LC Wagner, TMU Devilee, P Vijg, J Szabo, C Tavtigian, SV Nathanson, KL Ostrander, E Frank, TS AF Eng, C Brody, LC Wagner, TMU Devilee, P Vijg, J Szabo, C Tavtigian, SV Nathanson, KL Ostrander, E Frank, TS CA Steering Comm Brest Canc Inform TI Interpreting epidemiological research: blinded comparison of methods used to estimate the prevalence of inherited mutations in BRCA1 SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE BRCA1; mutation detection; cancer genetics ID CONFORMATION POLYMORPHISM ANALYSIS; PERFORMANCE LIQUID-CHROMATOGRAPHY; SENSITIVE GEL-ELECTROPHORESIS; ENDOCRINE NEOPLASIA TYPE-2; PROTEIN TRUNCATION TEST; POPULATION-BASED SAMPLE; BREAST-CANCER FAMILIES; OVARIAN-CANCER; HETERODUPLEX ANALYSIS; RET PROTOONCOGENE AB While sequence analysis is considered by many to be the most sensitive method of detecting unknown mutations in large genes such as BRCA1, most published estimates of the prevalence of mutations in this gene have been derived from studies that have used other methods of gene analysis. In order to determine the relative sensitivity of techniques that are widely used in research on BRCA1, a set of blinded samples containing 58 distinct mutations were analysed by four separate laboratories. Each used one of the following methods: single strand conformational polymorphism analysis (SSCP), conformation sensitive gel electrophoresis (CSGE), two dimensional gene scanning (TDGS), and denaturing high performance liquid chromatography (DHPLC). Only the laboratory using DHPLC correctly identified each of the mutations. The laboratory using TDGS correctly identified 91% of the mutations but produced three apparent false positive results. The laboratories using SSCP and CSGE detected abnormal migration for 72% and 76% of the mutations, respectively, but subsequently confirmed and reported only 65% and 60% of mutations, respectively. False negatives therefore resulted not only from failure of the techniques to distinguish wild type from mutant, but also from failure to confirm the mutation by sequence analysis as well as from human errors leading to misreporting of results. These findings characterise sources of error in commonly used methods of mutation detection that should be addressed by laboratories using these methods. Based upon sources of error identified in this comparison, it is likely that mutations in BRCA1 and BRCA2 are more prevalent than some studies have previously reported. The findings of this comparison provide a basis for interpreting studies of mutations in susceptibility genes across many inherited cancer syndromes. C1 Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Tzagournis MRF, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA. Univ Cambridge, CRC, Human Canc Genet Res Grp, Cambridge, England. NIH, Bethesda, MD 20892 USA. Univ Vienna, Div Senol, Dept Obstet & Gynecol, A-1010 Vienna, Austria. Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands. Canc Therapy & Res Ctr S Texas, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Int Agcy Res Canc, F-69372 Lyon, France. Myriad Genet Labs, Salt Lake City, UT USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Tzagournis MRF, 420 W 12th Ave,Suite 690, Columbus, OH 43210 USA. OI Eng, Charis/0000-0002-3693-5145; Ostrander, Elaine/0000-0001-6075-9738 NR 33 TC 121 Z9 123 U1 0 U2 7 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD DEC PY 2001 VL 38 IS 12 BP 824 EP 833 DI 10.1136/jmg.38.12.824 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 501ZT UT WOS:000172718400004 PM 11748305 ER PT J AU Bukh, J Apgar, CL Govindarajan, S Purcell, RH AF Bukh, J Apgar, CL Govindarajan, S Purcell, RH TI Host range studies of GB virus-B hepatitis agent, the closest relative of hepatitis C virus, in New World monkeys and chimpanzees SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE Flavirividae; GB agent; tamarins; owl monkeys; chimpanzees; acute hepatitis ID FLAVIVIRIDAE; CLONE AB GB virus-B (GBV-B) is a member of the Flavi-viridae family of viruses. This RNA virus causes acute resolving hepatitis in experimentally infected tamarins, but its natural host remains unknown. GBV-B and a related virus, GBV-A, were recovered from serum containing the "GB agent," which was believed to have originated from a surgeon (initials: GB) with acute hepatitis. GBV-B has special interest because it is the virus related most closely to hepatitis C virus, which is an important cause of acute and chronic liver disease in humans. In the present study, we found that the host range of GBV-B includes owl monkeys. Tamarins and owl monkeys belong to two different families of New World monkeys. The natural history of GBV-B in the two owl monkeys studied was similar to that previously found for tamarins and was characterized by early appearance of viremia and viral clearance. However, the peak viral titers of GBV-B observed in owl monkeys (10(5) genome equivalents [GE] /ml) were lower than those observed in experimentally infected tamarins (10(7) - 10(8) GE/ml) and acute hepatitis was observed in only one animal. If GBV-B were indeed a virus of humans, it would be expected to infect chimpanzees, a surrogate of humans, because all recognized human hepatitis viruses are transmissible to chimpanzees and cause hepatitis. However, in the present study, we failed to transmit GBV-B to a naive chimpanzee. In addition, a second naive chimpanzee transfected intra hepatica[ ly with RNA transcripts from an infectious clone of GBV-B did not become infected. Thus, chimpanzees are apparently not susceptible to GBV-B. Finally, we failed to detect GBV-B in acute-phase serum from surgeon GB. Our data suggest that GBV-B is not a human virus and that GBV-B, like GBV-A, is a virus of New World monkeys. (C) 2001 Wiley-Liss,Inc. C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Rancho Los Amigos Med Ctr, Liver Res Lab, Downey, CA USA. RP Bukh, J (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bldg 7,Room 201,7 Ctr Dr MSC 0740, Bethesda, MD 20892 USA. FU PHS HHS [N01-A1-52705] NR 15 TC 56 Z9 57 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD DEC PY 2001 VL 65 IS 4 BP 694 EP 697 DI 10.1002/jmv.2092 PG 4 WC Virology SC Virology GA 489LY UT WOS:000171993900010 PM 11745933 ER PT J AU Veatch, RM Miller, FG AF Veatch, RM Miller, FG TI The internal morality of medicine: An introduction SO JOURNAL OF MEDICINE AND PHILOSOPHY LA English DT Editorial Material C1 Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA. NIH, Bethesda, MD 20892 USA. RP Veatch, RM (reprint author), Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0360-5310 J9 J MED PHILOS JI J. Med. Philos. PD DEC PY 2001 VL 26 IS 6 BP 555 EP 557 DI 10.1076/jmep.26.6.555.2994 PG 3 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 497YW UT WOS:000172483900001 ER PT J AU Miller, FG Brody, H AF Miller, FG Brody, H TI The internal morality of medicine: An evolutionary perspective SO JOURNAL OF MEDICINE AND PHILOSOPHY LA English DT Article DE internal morality; medical ethics; professional integrity ID CARE AB A basic question of medical ethics is whether the norms governing medical practice should be understood as the application of principles and rules of 'the common morality' to medicine or whether some of these norms are 'internal' or 'proper' to medicine. In this article we describe and defend an evolutionary perspective on 'the internal morality of medicine' that is defined in terms of the goals of clinical medicine and a set of duties that constrain medical practice in pursuit of these goals. This perspective is developed by means of a critical examination of the 'essentialist' conception of the internal morality of medicine advocated by Edmund Pellegrino and the critique of internal morality approaches by Robert Veatch and Torn Beauchamp. C1 NIMH, Intramural Res Program, Dept Clin Bioeth, NIH, Bethesda, MD 20892 USA. Michigan State Univ, E Lansing, MI 48824 USA. RP Miller, FG (reprint author), NIMH, Intramural Res Program, Dept Clin Bioeth, NIH, Bethesda, MD 20892 USA. NR 17 TC 33 Z9 33 U1 0 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0360-5310 J9 J MED PHILOS JI J. Med. Philos. PD DEC PY 2001 VL 26 IS 6 BP 581 EP 599 DI 10.1076/jmep.26.6.581.2993 PG 19 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 497YW UT WOS:000172483900003 PM 11735051 ER PT J AU Praetorius, J Backlund, P Yergey, AL Spring, KR AF Praetorius, J Backlund, P Yergey, AL Spring, KR TI Specific lectin binding to betal integrin and fibronectin on the apical membrane of Madin-Darby canine kidney cells SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE fluorescence; mass spectrometry; glycoprotein; lectin ID MITOCHONDRIA-RICH CELLS; FROG-SKIN EPITHELIUM; BRANCHING MORPHOGENESIS; MASS-SPECTROMETRY; MDCK CELLS; DEPOSITION; EXPRESSION; TRANSPORT; SITES; ACID AB Although lectins have previously been used to identify specific cell types in the kidney and various other tissues, the proteins labeled were not identified. We hypothesized that fluorescently labeled lectins could provide a useful tool for direct labeling of membrane-associated glycoproteins. Protein fractions from Madin-Darby canine kidney (MDCK) cells were exposed to a panel of 16 fluorescently labeled lectins to identify suitable lectin-protein pairs. Peanut agglutinin (PNA) selectively bound a 220-240 kDa O-linked glycoprotein with a slightly acidic isoelectric point, while Sambucus nigra agglutinin (SNA) labeled a 130 kDa glycoprotein with a highly acidic isoelectric point. Both proteins were readily labeled by lectins applied to the apical surface of living confluent cells. The proteins were isolated by lectin affinity columns and identified by mass spectrometry. Peptides from the PNA-binding protein shared molecular weight and amino acid composition with fibronectin. Fragments of the SNA-binding protein showed amino-acid identity with peptides from betal integrin. The identities of these proteins were validated by Western blotting. Binding of PNA to a 220 kDa protein was inhibited by an anti-fibronectin antibody, and binding of a 130 kDa protein by SNA was diminished by an anti-betal integrin antibody. We conclude that PNA and SNA can be used as specific markers for fibronectin and betal integrin, respectively, in MDCK cells. C1 NHLBI, Transport Physiol Sect, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Mass Spectrometry & Metab, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Praetorius, J (reprint author), NHLBI, Transport Physiol Sect, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,Bld 10,Room 6N260, Bethesda, MD 20892 USA. NR 34 TC 10 Z9 10 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD DEC 1 PY 2001 VL 184 IS 3 BP 273 EP 281 DI 10.1007/s00232-001-0093-2 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 507YZ UT WOS:000173060400011 PM 11891552 ER PT J AU Lenfant, C Drugan, JK Roth, CA AF Lenfant, C Drugan, JK Roth, CA TI The last frontier in cardiovascular health: A landmark lecture for the XVII World Congress of the International Society for Heart Research SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE consilience; government-supported research; health promotion; research funding; translational research ID RACE; SEX AB Following World War II, Vannevar Bush described science as an "endless frontier" that should be made accessible to all Americans. Since then, cardiovascular health has improved markedly, largely because substantial investments in biomedical research led to numerous therapies and prevention strategies for cardiovascular disease. Despite these advances, however, science remains an endless frontier and we continue to face an infinite array of opportunities for improving cardiovascular health. A standard definition for "frontier" is the "farthermost limit of knowledge or achievement". The limits of our knowledge are expanding at an ever accelerated pace. Unfortunately, we do not always apply what we know, and therefore fail to achieve all we could. For example, we have known for two decades that heart attack patients benefit from beta-blockers, but even today, the drugs are not always prescribed. And, health disparities continue to exist among races and communities, Therefore, the "last frontier of cardiovascular health" is the translation and application of our knowledge to improve the cardiovascular health of all people. We will not reach the farthermost limit of achievement without new knowledge. But, in our zeal to expand our knowledge of cardiovascular diseases, we must remember to ensure that what we learn is rapidly applied to improve cardiovascular health. (C) 2001 Academic Press. C1 NHLBI, Bethesda, MD 20892 USA. RP Lenfant, C (reprint author), NHLBI, 31 Ctr Dr,MSC 2486,Bldg 31,Room 5A52, Bethesda, MD 20892 USA. EM lenfantc@nih.gov NR 37 TC 1 Z9 1 U1 1 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD DEC PY 2001 VL 33 IS 12 BP 2063 EP 2069 DI 10.1006/jmcc.2001.1479 PG 7 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 514TQ UT WOS:000173457500001 PM 11735252 ER PT J AU Jordan, IK Natale, DA Koonin, EV Galperin, MY AF Jordan, IK Natale, DA Koonin, EV Galperin, MY TI Independent evolution of heavy metal-associated domains in copper chaperones and copper-transporting ATPases SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE P-type ATPases; cation transport; metalloenzyme; copper poisoning; Wilson disease; Menkes disease; mercury-binding protein ID DNA-SEQUENCE DATA; P-TYPE ATPASE; SUPEROXIDE-DISMUTASE; ENTEROCOCCUS-HIRAE; PHYLOGENETIC TREES; CRYSTAL-STRUCTURE; COMPLETE GENOMES; GENE-PRODUCTS; COG DATABASE; PROTEIN AB Copper chaperones are small cytoplasmic proteins that bind intracellular copper (Cu) and deliver it to Cu-dependent enzymes such as cytochrome oxidase, superoxide dismutase, and amine oxidase. Copper chaperones are similar in sequence and structure to the Cu-binding heavy metal-associated (HMA) domains of Cu-transporting ATPases (Cu-ATPases), and the genes for copper chaperones and Cu-ATPases are often located in the same operon. Phylogenetic analysis shows that Cu chaperones and I-IMA domains of Cu-ATPases represent ancient and distinct lineages that have evolved largely independently since their initial separation. Copper chaperone-Cu-ATPase operons appear to have evolved independently in different prokaryotic lineages, probably due to a strong selective pressure for coexpression of these genes. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 66 TC 20 Z9 21 U1 0 U2 6 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD DEC PY 2001 VL 53 IS 6 BP 622 EP 633 DI 10.1007/s002390010249 PG 12 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 485XL UT WOS:000171788700004 PM 11677622 ER PT J AU Appel, E Kazimirsky, G Ashkenazi, E Kim, SG Jacobson, KA Brodie, C AF Appel, E Kazimirsky, G Ashkenazi, E Kim, SG Jacobson, KA Brodie, C TI Roles of BCL-2 and caspase 3 in the adenosine A(3) receptor-induced apoptosis SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE astrocytes; agonists; adenosine receptor; apoptosis; Bcl-2 ID GLIAL-CELLS; ACTIVATION; EXPRESSION; ANTAGONISTS; STIMULATION; MEDIATION; INDUCTION; VIRUS; GENE AB Selective A(3) adenosine receptor agonists have been shown to induce apoptosis in a variety of cell types. In this study we examined the effects of adenosine receptor agonists selective for A(1), A(2)A, or A(3) receptors on the induction of apoptosis in primary cultures of rat astrocytes and in C6 glial cells. Treatment of the cells with the A(3) receptor agonist CI-IB-MECA (10 muM) induced apoptosis in both cell types. The effects of CI-IB-MECA were partially antagonized by the A(3) receptor-selective antagonist MRS 1191. In contrast, the A(1) and A(2A) receptor agonists, CPA and CGS 21680, respectively, did not have significant effects on apoptosis in these cells. CI-IB-MECA reduced the expression of endogenous Bcl-2, whereas it did not affect the expression of Bax. Overexpression of Bcl-2 in C6 cells abrogated the induction of apoptosis induced by the A(3) agonist. CI-IB-MECA also induced an increase in caspase 3 activity and caspase inhibitors decreased the apoptosis induced by the A(3) agonist. These findings suggest that intense activation of the A(3) receptor is pro-apoptotic in glial cells via bcl2 and caspase-3 dependent pathways. C1 Bar Ilan Univ, Fac Life Sci, Gonda Goldschmied Med Diag Res Ctr, IL-52900 Ramat Gan, Israel. Hadassa Hosp, Dept Neurosurg, Jerusalem, Israel. NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RP Brodie, C (reprint author), Bar Ilan Univ, Fac Life Sci, Gonda Goldschmied Med Diag Res Ctr, IL-52900 Ramat Gan, Israel. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 23 TC 29 Z9 29 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD DEC PY 2001 VL 17 IS 3 BP 285 EP 292 DI 10.1385/JMN:17:3:285 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 521RR UT WOS:000173855800003 PM 11859924 ER PT J AU Jiang, H Movsesyan, V Liu, XW Katagiri, Y Monshipouri, M Lazarovici, P AF Jiang, H Movsesyan, V Liu, XW Katagiri, Y Monshipouri, M Lazarovici, P TI A double cysteine trkA mutant exhibiting reduced NGF binding and delayed Erk signaling SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE NGF; bFGF; trkA; cysteine; mutation; proliferation ID NERVE GROWTH-FACTOR; HIGH-AFFINITY RECEPTOR; EXTRACELLULAR DOMAIN; CONGENITAL INSENSITIVITY; ACETYLCHOLINE-RECEPTOR; LIGAND-BINDING; BETA-2-ADRENERGIC RECEPTOR; NEUROTROPHIN RECEPTOR; JUXTAMEMBRANE REGION; PALMITOYLATION SITE AB The NGF receptor trkA is a tyrosine kinase receptor comprising an extracellular domain with a ligand-binding site, a transmembrane-spanning domain (TMD), and an intracellular domain composed of a juxtamembrane region (JMR), a tyrosine kinase domain, and a short carboxy-terminal tail. Nerve growth factor (NGF) binds and activates this receptor, leading to phosphorylation of signaling substrates involved in neuronal proliferation, differentiation, and survival. Human trkA contains one cysteine residue in the TMD (C423) and another, separated by 12 residues, in the JMR (C436). We hypothesized that the removal of one or both of the cysteines would affect NGF-induced signaling of the trkA receptor. Here we show that NGF induces rapid receptor autophosphorylation in a wild-type, trkA-expressing clone (WT11), in a single cysteine trkA mutants (C423T or C436A), but lower autophosphorylation activity in a double-cysteine trkA mutant (C423T/C436A). WT11 and SM cells had similar binding affinity, but that of DM cells was lower, according to the NGF radioreceptor assay. NGF-induced Erk phosphorylation was rapid in WT11 and C423T cells, but delaved in C436A and C423T/C436A cells. NGF induced [H-3]thymidine incorporation into WT11 and SM cells, but had no effect on DM cells. However, basic fibroblast growth factor (bFGF) induced rapid phosphorylation of Erk1/2, and [H-3]thymidine incorporation in NIH3T3, WT11, single mutant (SM), and double mutant (DM) cells, suggesting that the impaired NGF-induced Erk phosphorylation and thymidine incorporation observed in DM cells are due to the double-cysteine mutations in the trkA receptor. Cumulatively, our findings support a model in which Cys436 of the trkA is responsible for the rapid transfer of the transmembrane occupancy signal to the SHC adaptor protein for activation of the Ras-Erk pathway and DNA synthesis. C1 Hebrew Univ Jerusalem, Sch Pharm, Fac Med, Dept Pharmacol & Expt Therapeut, IL-91010 Jerusalem, Israel. Henry Ford Hlth Sci Ctr, William T Gossett Neurol Labs, Detroit, MI 48202 USA. John D Dingell VA Med Ctr, Detroit, MI 48201 USA. Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA. NICHHD, Growth Factors Sect, NIH, Bethesda, MD 20892 USA. US Dept Commerce, Tech Ctr 1600, Patent & Trade Mark Off, Washington, DC 20231 USA. RP Lazarovici, P (reprint author), Hebrew Univ Jerusalem, Sch Pharm, Fac Med, Dept Pharmacol & Expt Therapeut, IL-91010 Jerusalem, Israel. NR 46 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD DEC PY 2001 VL 17 IS 3 BP 293 EP 302 DI 10.1385/JMN:17:3:293 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 521RR UT WOS:000173855800004 PM 11859925 ER PT J AU Sharma, A Walters, J Gozes, Y Fridkin, M Brenneman, D Gozes, I Moody, TW AF Sharma, A Walters, J Gozes, Y Fridkin, M Brenneman, D Gozes, I Moody, TW TI A vasoactive intestinal peptide antagonist inhibits the growth of glioblastoma cells SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE PACAP receptors; glioblastoma; VIP antagonist; proliferation ID ACTIVATING POLYPEPTIDE PACAP; LUNG-CANCER CELLS; HIGH-AFFINITY; FUNCTIONAL EXPRESSION; RECEPTOR ANTAGONISTS; ENERGY-METABOLISM; RAT ASTROCYTES; VIP; DISCOVERY; LINES AB The effects of a vasoactive intestinal peptide (VIP) receptor antagonist (VIPhyb) on human glioblastoma cells were characterized. Pituitary adenylate cyclase activating polypeptide (I-125-PACAP-27) bound with high affinity to U87, U118, and U373 cells. Specific I-125-PACAP-27 binding to U87 cells was inhibited, with high affinity, by PACAP but not VIP or VIPhyb (IC50 = 10, 1500, and 500 nM, respectively). By reverse transcriptasepolymerase chain reaction (RT-PCR), a major 305bp band was observed indicative of PAC1 receptors. PACAP-27 caused cAMP elevation and the increase in cAMP caused by PACAP-27, was inhibited by the VIPhyb. Also, PACAP-27 caused cytosolic Ca2+ elevation in Fura-2AM loaded U87 cells and the VIPhyb inhibited this increase. Using the MTT growth assay, the VIPhyb was shown to inhibit glioblastoma growth in a concentration dependent manner. Using a clonogenic assay in vitro, 10 muM VIPhyb significantly inhibited proliferation of U87, U118, and U373 cells. In vivo, 0.4 mug/kg VIPhyb inhibited U87 xenograft proliferation in nude mice. These results suggest that the VIPhyb antagonizes PAC1 receptors on glioblastoma cells and inhibits their proliferation. C1 NCI, Med Branch, Rockville, MD 20850 USA. Israel Inst Biol Res, IL-74100 Ness Ziona, Israel. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. NICHHD, Dev Neurobiol Lab, Sect Dev & Mol Pharmacol, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. RP Moody, TW (reprint author), NCI, Med Branch, Rockville, MD 20850 USA. NR 45 TC 16 Z9 19 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD DEC PY 2001 VL 17 IS 3 BP 331 EP 339 DI 10.1385/JMN:17:3:331 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 521RR UT WOS:000173855800008 PM 11859929 ER PT J AU Luo, YQ Long, JM Spangler, EL Longo, DL Ingram, DK Weng, NP AF Luo, YQ Long, JM Spangler, EL Longo, DL Ingram, DK Weng, NP TI Identification of maze learning-associated genes in rat hippocampus by cDNA microarray SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE memory; RT-PCR; neuronal growth; neuronal remodeling; signal transduction; gene expression ID MESSENGER-RNA EXPRESSION; LONG-TERM POTENTIATION; MOLECULAR-CLONING; NEURONAL PLASTICITY; SIGNALING MOLECULES; MEMORY FORMATION; DEFICIENT MICE; NITRIC-OXIDE; BRAIN; ADHESION AB Long-term memory formation requires de novo RNA and protein synthesis. To assess gene-expression changes associated with learning and memory processes, we used cDNA microarray to analyze hippocampal gene expression in male Fischer-344 rats following training in a multiunit T-maze. Here, we report the identification of 28 clones (18 known genes and 10 ESTs) for which expression increased after the maze learning. Some of the known genes appear to be involved in Ca2+ signaling, Ras activation, kinase cascades, and extracellular matrix (ECM) function, which may regulate neural transmission, synaptic plasticity, and neurogenesis. The geneexpression profile presented here provides the groundwork for future, more focused research to elucidate the contribution of these genes in learning and memory processes. C1 NIA, Gerontol Res Ctr, Immunol Lab, NIH, Baltimore, MD 21224 USA. NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. RP Weng, NP (reprint author), NIA, Gerontol Res Ctr, Immunol Lab, NIH, 4C16,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 35 TC 26 Z9 26 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD DEC PY 2001 VL 17 IS 3 BP 397 EP 404 DI 10.1385/JMN:17:3:397 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 521RR UT WOS:000173855800015 PM 11859936 ER PT J AU Silva, GL Cui, BL Chavez, D You, M Chai, HB Rasoanaivo, P Lynn, SM O'Neill, MJ Lewis, JA Bestermam, JM Monks, A Farnsworth, NR Cordell, GA Pezzuto, JM Kinghorn, AD AF Silva, GL Cui, BL Chavez, D You, M Chai, HB Rasoanaivo, P Lynn, SM O'Neill, MJ Lewis, JA Bestermam, JM Monks, A Farnsworth, NR Cordell, GA Pezzuto, JM Kinghorn, AD TI Modulation of the multidrug-resistance phenotype by new tropane alkaloid aromatic esters from Erythroxylum pervillei SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; GENUS ERYTHROXYLUM; ROOT-BARK; N-OXIDES; CYTOTOXICITY AB Nine tropane alkaloid aromatic esters (1-9) were isolated from the roots of Erythroxylum pervillei by following their potential to reverse multidrug-re si stance with vinblastine-resistant oral epidermoid carcinoma (KB-V1) cells. All isolates, including seven new structures (3-9), were evaluated against a panel of human cancer cell lines, and it was found that alkaloids 3 and 5-9 showed the greatest activity with KB-V1 cells assessed in the presence of vinblastine, suggesting that these new compounds are potent modulators of P-glycoprotein. Confirmatory results were obtained with human ovarian adenocarcinoma (SKVLB) cells evaluated in the presence of adriamycin and synergistic studies performed with several cell lines from the NCI tumor panel. The structures of the new compounds were determined using spectroscopic techniques. Single-crystal X-ray analysis was performed on the monoester, tropane-3alpha,6beta,7beta-triol 3-phenylacetate (1). C1 Univ Illinois, Coll Pharm, Program Collaborat Res Pharmaceut Sci, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. GlaxoSmithKline Med Res Ctr, Stevenage SG1 2NY, Herts, England. Inst Malgashe Resch Appl, Antananarivo 101, Malagasy Republ. GlaxoSmithKline Inc, Dept Cell Biol, Res Triangle Pk, NC 27709 USA. NCI, Frederick Canc Res Facil, Ft Detrick, MD 21702 USA. RP Kinghorn, AD (reprint author), Univ Illinois, Coll Pharm, Program Collaborat Res Pharmaceut Sci, Chicago, IL 60612 USA. RI You, Min/I-4973-2012; OI Silva, Gloria/0000-0002-0763-8096; Kinghorn, A. Douglas/0000-0002-6647-8707 FU NCI NIH HHS [U01/U19 CA52956] NR 25 TC 37 Z9 37 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD DEC PY 2001 VL 64 IS 12 BP 1514 EP 1520 DI 10.1021/np010295+ PG 7 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 508NK UT WOS:000173095200007 PM 11754602 ER PT J AU Campbell, JL Nash, HA AF Campbell, JL Nash, HA TI Volatile general anesthetics reveal a neurobiological role for the white and brown genes of Drosophila melanogaster SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE halothane; enflurane; ABC transporter; sine oculis ID TYROSINE-HYDROXYLASE; HUMAN HOMOLOG; EXPRESSION; MUTANTS; LOCUS; MUTATIONS; TRANSPORT; COURTSHIP; BEHAVIOR; PROTEIN AB Molecular and cellular evidence argues that a heterodimer between two ABC transporters, the White protein and the Brown protein, is responsible for pumping guanine into pigment-synthesizing cells of the fruit fly, Drosophila melanogaster. Previous studies have not detected White or Brown outside pigment-synthesizing cells nor have behavioral effects of null mutants been reported, other than those that are visually dependent. Nevertheless, we show here that exposure to the volatile general anesthetic (VGA) enflurane reveals a difference in neuromuscular performance between wild-type flies and those that carry a null allele in either the white or brown gene. Specifically, in a test of climbing ability, w(1118) or bw(1) flies are much less affected by enflurane than are congenic controls. Altered anesthetic sensitivity is still observed when visual cues are reduced or eliminated, arguing that white and brown contribute to neural function outside the eye. This hypothesis is supported by the detection of white message in heads of flies that are genetically altered so as to lack pigment-producing cells. The w(1118) or bw(1) mutations also alter the response to a second VGA, halothane, albeit somewhat differently. Under some conditions, the combination of w(1118) with another mutation that affects anesthesia leads to a drastically altered phenotype. We consider several ways by which diminished transport of guanine could influence neural function and anesthetic sensitivity. (C) 2001 John Wiley & Sons, Inc. C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Nash, HA (reprint author), NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RI Marion-Poll, Frederic/D-8882-2011 OI Marion-Poll, Frederic/0000-0001-6824-0180 NR 45 TC 52 Z9 54 U1 1 U2 13 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD DEC PY 2001 VL 49 IS 4 BP 339 EP 349 DI 10.1002/neu.10009 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 494WX UT WOS:000172309800007 PM 11745669 ER PT J AU Contreras, MA Chang, MCJ Rosenberger, TA Greiner, RS Myers, CS Salem, N Rapoport, SI AF Contreras, MA Chang, MCJ Rosenberger, TA Greiner, RS Myers, CS Salem, N Rapoport, SI TI Chronic nutritional deprivation of n-3 alpha-linolenic acid does not affect n-6 arachidonic acid recycling within brain phospholipids of awake rats SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE arachidonic acid; alpha-linolenic acid; docosapentaenoic acid; docosahexaenoic acid; phospholipids; polyunsaturated fatty acids (PUFA) ID POLYUNSATURATED FATTY-ACIDS; ACYL-COA SYNTHETASE; DOCOSAHEXAENOIC ACID; SIGNAL-TRANSDUCTION; PEROXISOMAL DISORDERS; MAMMALIAN-CELLS; CHRONIC LITHIUM; LEARNING-TASKS; FETAL-RAT; IN-VIVO AB Using an in vivo fatty acid model and operational equations, we reported that esterified and unesterified concentrations of docosahexaenoic acid (DHA, 22:6 n-3) were markedly reduced in brains of third-generation (F3) rats nutritionally deprived of a-linolenic acid (18:3 n-3), and that DHA turnover within phospholipids was reduced as well. The concentration of docosapentaenoic acid (DPA, 22 : 5 n-6), an arachidonic acid (AA, 20 : 4 n-6) elongation/desaturation product, was barely detectable in control rats but was elevated in the deprived rats. In the present study, we used the same in vivo model, involving the intravenous infusion of radio-labeled AA to demonstrate that concentrations of unesterified and esterified AA, and turnover of AA within phospholipids, were not altered in brains of awake F3-generation n-3-deficient rats, compared with control concentrations. Brain DPA-CoA could be measured in the deprived but not control rats, and AA-CoA was elevated in the deprived animals. These results indicated that AA and DHA are recycled within brain phospholipids independently of each other, suggesting that recycling is regulated independently by AA- and DHA-selective enzymes, respectively. Competition among n-3 and n-6 fatty acids within brain probably does not occur at the level of recycling, but at levels of elongation anti desaturation (hence greater production of DPA during n-3 deprivation), or conversion to bioactive eicosanoids and other metabolites. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. RP NIA, Brain Physiol & Metab Sect, NIH, Bldg 10,6 N-202,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sir@helix.nih.gov NR 74 TC 35 Z9 36 U1 0 U2 2 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2001 VL 79 IS 5 BP 1090 EP 1099 DI 10.1046/j.1471-4159.2001.00658.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 499BX UT WOS:000172552100021 PM 11739623 ER PT J AU Jeitner, TM Bogdanov, MB Matson, WR Daikhin, Y Yudkoff, M Folk, JE Steinman, L Browne, SE Beal, MF Blass, JP Cooper, AJL AF Jeitner, TM Bogdanov, MB Matson, WR Daikhin, Y Yudkoff, M Folk, JE Steinman, L Browne, SE Beal, MF Blass, JP Cooper, AJL TI N-epsilon-(gamma-L-glutamyl)-L-lysine (GGEL) is increased in cerebrospinal fluid of patients with Huntington's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cerebrospinal fluid; N-epsilon-(gamma-L-glutamyl)-L-lysine; Huntington's disease; neurodegenerative diseases; transglutaminases ID TISSUE TRANSGLUTAMINASE; POLYGLUTAMINE DOMAINS; NEURODEGENERATIVE DISEASES; CROSS-LINKING; BRAIN; AMINO; PATHOGENESIS; PEPTIDES; LENGTH AB Pathological-length polyglutamine (Q(n)) expansions, such as those that occur in the huntingtin protein (htt) in Huntington's disease (HD), are excellent substrates for tissue transglutaminase in vitro, and transglutaminase activity is increased in post-mortem HD brain. However, direct evidence for the participation of tissue transglutaminase (or other transglutaminases) in HD patients in vivo is scarce. We now report that levels of N-epsilon-(gamma -L-glutamyl)-L-lysine (GGEL) - a 'marker' isodipeptide produced by the transglutaminase reaction - are elevated in the CSF of HD patients (708 +/- 41 pmol/mL, SEM, n = 36) vs. control CSF (228 +/- 36, n = 27); p < 0.0001. These data support the hypothesis that transglutaminase activity is increased in HD brain in vivo. C1 Cornell Univ, Coll Med, Burke Med Res Inst, White Plains, NY 10605 USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA. ESA Labs Inc, Chelmsford, MA USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Child Dev & Rehabil Med, Philadelphia, PA 19104 USA. NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Stanford Univ, Ctr Med, Stanford, CA 94305 USA. RP Cooper, AJL (reprint author), Cornell Univ, Coll Med, Burke Med Res Inst, 785 Mamaroneck Ave, White Plains, NY 10605 USA. RI Cooper, Arthur/H-5171-2016 FU NIA NIH HHS [P01 AG14930] NR 30 TC 67 Z9 67 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2001 VL 79 IS 5 BP 1109 EP 1112 DI 10.1046/j.1471-4159.2001.00673.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 499BX UT WOS:000172552100023 PM 11739625 ER PT J AU Itoh, Y Esaki, T Cook, M Qasba, P Shimoji, K Alroy, J Brady, RO Sokoloff, L Moore, DF AF Itoh, Y Esaki, T Cook, M Qasba, P Shimoji, K Alroy, J Brady, RO Sokoloff, L Moore, DF TI Local and global cerebral blood flow and glucose utilization in the alpha-galactosidase A knockout mouse model of Fabry disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE brain pathology; cerebral energy metabolism; 2-deoxyglucose; genetic model; lysosomal disorder ID NEURONAL INVOLVEMENT; MANIFESTATIONS; COMPLICATIONS; HYPOGLYCEMIA; MICE AB Fabry disease is an X-linked lysosomal disorder characterized by deficient alpha -galactosidase A activity and intracellular accumulations of glycosphingolipids, mainly globotriaosylceramide (Gb3). Clinically, patients occasionally present CNS dysfunction. To examine the pathophysiology underlying brain dysfunction, we examined glucose utilization (CMRglc) and cerebral blood flow (CBF) globally and locally in 18 brain structures in the a-galactosidase A gene knockout mouse. Global CMRglc was statistically significantly reduced by 22% in Fabry mice (p < 0.01). All 18 structures showed decreases in local CMRglc ranging from 14% to 33%. The decreases in all structures of the diencephalon, caudate-putamen, brain stem, and cerebellar cortex were statistically significant (p < 0.05). Global cerebral blood flow (CBF) and local CBF measured in the same 18 structures were lower in Fabry mice than in control mice, but none statistically significantly. Histological examination of brain revealed no cerebral infarcts but abundant Gb3 deposits in the walls of the cerebral vessels with neuronal deposits localized to the medulla oblongata. These results indicate an impairment in cerebral energy metabolism in the Fabry mice, but one not necessarily due to circulatory insufficiency. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NINCDS, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. NIH, PET Dept, Clin Ctr, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Tufts Univ, Sch Vet Med, Boston, MA 02111 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,1 A-07,36 Convent Dr,MSC 4030, Bethesda, MD 20892 USA. NR 34 TC 22 Z9 24 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2001 VL 79 IS 6 BP 1217 EP 1224 DI 10.1046/j.1471-4159.2001.00669.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 505BE UT WOS:000172890500011 PM 11752062 ER PT J AU Laforet, GA Sapp, E Chase, K McIntyre, C Boyce, FM Campbell, M Cadigan, BA Warzecki, L Tagle, DA Reddy, PH Cepeda, C Calvert, CR Jokel, ES Klapstein, GJ Ariano, MA Levine, MS DiFiglia, M Aronin, N AF Laforet, GA Sapp, E Chase, K McIntyre, C Boyce, FM Campbell, M Cadigan, BA Warzecki, L Tagle, DA Reddy, PH Cepeda, C Calvert, CR Jokel, ES Klapstein, GJ Ariano, MA Levine, MS DiFiglia, M Aronin, N TI Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cortex; Huntington's disease; NMDA; neuronal morphology; striatum; transgenic mice ID LENGTH HD CDNA; INTRANUCLEAR INCLUSIONS; MUTANT HUNTINGTIN; METABOLIC DYSFUNCTION; PYRAMIDAL NEURONS; MICE; EXPRESSION; BRAIN; NEUROPATHOLOGY; LOCALIZATION AB Neurons in Huntington's disease exhibit selective morphological and subcellular alterations in the striatum and cortex. The link between these neuronal changes and behavioral abnormalities is unclear. We investigated relationships between essential neuronal changes that predict motor impairment and possible involvement of the corticostriatal pathway in developing behavioral phenotypes. We therefore generated heterozygote mice expressing the N-terminal one-third of huntingtin with normal (CT18) or expanded (HD46, HD100) glutamine repeats. The HD mice exhibited motor deficits between 3 and 10 months. The age of onset depended on an expanded polyglutamine length; phenotype severity correlated with increasing age. Neuronal changes in the striatum (nuclear inclusions) preceded the onset of phenotype, whereas cortical changes, especially the accumulation of huntingtin in the nucleus and cytoplasm and the appearance of dysmorphic dendrites, predicted the onset and severity of behavioral deficits. Striatal neurons in the HD mice displayed altered responses to cortical stimulation and to activation by the excitotoxic agent NMDA. Application of NMDA increased intracellular Ca2+ levels in HD100 neurons compared with wild-type neurons. Results suggest that motor deficits in Huntington's disease arise from cumulative morphological and physiological changes in neurons that impair corticostriatal circuitry. C1 Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Natl Genome Res Inst, NIH, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Mental Retardat Res Ctr, Los Angeles, CA 90095 USA. Chicago Med Sch, Dept Neurosci, N Chicago, IL 60064 USA. RP Aronin, N (reprint author), Univ Massachusetts, Sch Med, Dept Med, 55 Lake Ave N, Worcester, MA 01655 USA. FU NIDDK NIH HHS [DK32520]; NINDS NIH HHS [NS 16367, NS 35711, NS 38194] NR 52 TC 186 Z9 188 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 2001 VL 21 IS 23 BP 9112 EP 9123 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 494BL UT WOS:000172258400007 PM 11717344 ER PT J AU Zimmer, A Valjent, E Konig, M Zimmer, AM Robledo, P Hahn, H Valverde, O Maldonado, R AF Zimmer, A Valjent, E Konig, M Zimmer, AM Robledo, P Hahn, H Valverde, O Maldonado, R TI Absence of Delta-9-tetrahydrocannabinol dysphoric effects in dynorphin-deficient mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cannabinoid; opioid; mice; mutation; withdrawal; addiction; place aversion ID CONDITIONED PLACE PREFERENCE; RECEPTOR MESSENGER-RNA; CANNABINOID-INDUCED ANTINOCICEPTION; MU-OPIOID RECEPTOR; RAT-BRAIN; KNOCKOUT MICE; ENDOGENOUS CANNABINOIDS; GENE-EXPRESSION; MORPHINE; LOCALIZATION AB The involvement of dynorphin on Delta -9-tetrahydrocannabinol (THC) and morphine responses has been investigated by using mice with a targeted inactivation of the prodynorphin (Pdyn) gene. Dynorphin-deficient mice show specific changes in the behavioral effects of THC, including a reduction of spinal THC analgesia and the absence of THC-induced conditioned place aversion. In contrast, acute and chronic opioid effects were normal. The lack of negative motivational effects of THC in the absence of dynorphin demonstrates that this endogenous opioid peptide mediates the dysphoric effects of marijuana. C1 Univ Bonn, Psychiat Clin, D-53105 Bonn, Germany. NIMH, Genet Lab, Bethesda, MD 20892 USA. Univ Pompeu Fabra, Fac Ciencies Salut & Vida, Lab Neurofarmacol, Barcelona 08003, Spain. RP Zimmer, A (reprint author), Univ Bonn, Psychiat Clin, Mol Neurobiol Lab, Sigmund Freud Str 25, D-53125 Bonn, Germany. RI Valverde, Olga/D-8654-2012; Zimmer, Andreas/B-8357-2009; Maldonado, Rafael/F-5657-2014; Robledo, P/H-8512-2014 OI Maldonado, Rafael/0000-0002-4359-8773; Robledo, P/0000-0002-7941-0939 NR 61 TC 99 Z9 102 U1 2 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 2001 VL 21 IS 23 BP 9499 EP 9505 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 494BL UT WOS:000172258400047 PM 11717384 ER PT J AU Ratliff, JK Oldfield, EH AF Ratliff, JK Oldfield, EH TI Convection-enhanced delivery in intact and lesioned peripheral nerve SO JOURNAL OF NEUROSURGERY LA English DT Article DE peripheral nerve; neurotrophin; spinal cord; nerve regeneration drug delivery; rat; Macaca mulatta ID POOR FUNCTIONAL RECOVERY; WALKING-TRACK ANALYSIS; GROWTH-FACTOR; CONTRIBUTING FACTORS; ISAXONINE HEPATITIS; REGENERATION; REPAIR; RAT; MUSCLE; MACROMOLECULES AB Object. Although the use of multiple agents is efficacious in animal models of peripheral nerve injury, translation to clinical applications remains wanting. Previous agents used in trials in humans either engendered severe side effects or were ineffective. Because the blood-central nervous system barrier exists in nerves as it does in the brain, limited drug delivery poses a problem for translation of basic science advances into clinical applications. Convection-enhanced delivery (CED) is a promising adjunct to current therapies for peripheral nerve injury. In the present study the authors assessed the capacity of convection to ferry macromolecules across sites of nerve injury in rat and primate models, examined the functional effects of convection on the intact nerve, and investigated the possibility of delivering a macromolecule to the spinal cord via retrograde convection from a peripherally introduced catheter. Methods. The authors developed a rodent model of convective delivery to lesioned sciatic nerves (injury due to crush or laceration in 76 nerves) and compared the results to a smaller series of five primates with similar injuries. In the intact nerve, convective delivery of vehicle generated only a transient neurapraxic deficit. Early after injury (postinjury Days 1, 3, 7, and 10), infusion failed to cross the site of injury in crushed or lacerated nerves. Fourteen days after crush injury, CED of radioactively-labeled albumin resulted in perfusion through the site of injury to distal growing neurites. In primates, successful convection through the site of crush injury occurred by postinjury Day 28. In contrast, in laceration models there was complete occlusion of the extracellular space to convective distribution at the site of laceration and repair, and convective distribution in the extracellular space crossed the site of injury only after there was histological evidence of completion of nerve regeneration. Finally, in two primates, retrograde infusion into the spinal cord through a peripheral nerve was achieved. Conclusions. Convection provides a safe and effective means to deliver macromolecules to regenerating neurites in crush-injured peripheral nerves. Convection block in lacerated and suture-repaired nerves indicates a significant intraneural obstruction of the extracellular space, a disruption that suggests an anatomical obstruction to extracellular and, possibly, intraaxonal flow, which may impair nerve regeneration. Through peripheral retrograde infusion, convection can be used for delivery to spinal cord gray matter. Convection-enhanced delivery provides a promising approach to distribute therapeutic agents to targeted sites for treatment of disorders of the nerve and spinal cord. C1 Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Dept Neurosurg, New Orleans, LA USA. RP Oldfield, EH (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. NR 45 TC 16 Z9 16 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 2001 VL 95 IS 6 BP 1001 EP 1011 DI 10.3171/jns.2001.95.6.1001 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 499HA UT WOS:000172564600014 PM 11765815 ER PT J AU Proescholdt, MA Merrill, MJ Ikejiri, B Walbridge, S Akbasak, A Jacobson, S Oldfield, EH AF Proescholdt, MA Merrill, MJ Ikejiri, B Walbridge, S Akbasak, A Jacobson, S Oldfield, EH TI Site-specific immune response to implanted gliomas SO JOURNAL OF NEUROSURGERY LA English DT Article DE inflammation; brain tumor; blood-brain barrier; apoptosis; rat ID BLOOD-BRAIN-BARRIER; MAJOR HISTOCOMPATIBILITY ANTIGENS; TUMOR-INFILTRATING LYMPHOCYTES; EXPERIMENTAL RAT GLIOMA; MALIGNANT GLIOMAS; B7 COSTIMULATION; NERVOUS-SYSTEM; CELL; IMMUNOTHERAPY; EXPRESSION AB Object. Immunotherapy for glioblastoma, has been uniformly ineffective. The immunological environment of the brain, with its low expression of major histocompatibility complex (MHC) molecules and limited access for inflammatory cells and humoral immune effectors due to the blood-brain barrier (BBB), may contribute to the failure of immunotherapy. The authors hypothesize that brain tumors are protected from immune surveillance by an intact BBB at early stages of development. To investigate the immunological characteristics of early tumor growth, the authors compared the host response to a glioma implanted into the brain and into subcutaneous tissue. Methods. Samples of tumors growing in the brain or subcutaneously in rats were obtained for 7 consecutive days and were examined immunohistochemically for MHC Class I & II molecules, and for CD4 and CD8 lymphocyte markers. Additionally, B7-1 costimulatory molecule expression and lymphocyte-specific apoptosis were examined. Conclusions. On Days 3 and 4 after implantation, brain tumors displayed significantly lower MHC Class ll expression and lymphocytic infiltration (p < 0.05). After Day 5, however, no differences were detected. The MHC Class II expressing cells within the brain tumors appeared to be infiltrating microglia. Minimal B7-1 expression combined with lymphocyte-specific apoptosis were detected in both brain and subcutaneous tumors. Low MHC Class ll expression and low lymphocytic infiltration at early time points indicate the importance of the immunologically privileged status of the brain during early tumor growth. These characteristics disappeared at later time points, possibly because the increasing perturbation of the BBB alters the specific immunological environment of the brain. The lack of B7-1 expression combined with lymphocyte apoptosis indicates clonal anergy of glioma-infiltrating lymphocytes regardless of implantation site. C1 Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5D37 MSC 1414, Bethesda, MD 20892 USA. NR 44 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 2001 VL 95 IS 6 BP 1012 EP 1019 DI 10.3171/jns.2001.95.6.1012 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 499HA UT WOS:000172564600015 PM 11765816 ER PT J AU Governale, LS Vortmeyer, AO Zhuang, ZP Oldfield, EH AF Governale, LS Vortmeyer, AO Zhuang, ZP Oldfield, EH TI Fibrous meningioma in a patient with von Hippel-Lindau disease: a genetic analysis - Case report SO JOURNAL OF NEUROSURGERY LA English DT Article DE von Hippel-Lindau disease; meningioma; loss of heterozygosity ID TUMOR-SUPPRESSOR GENE; DELETION; PRODUCT; PROTEIN; CANCER; MICRODISSECTION; IDENTIFICATION; FEATURES; LESIONS AB Meningioma has been included in the constellation of tumors associated with von Hippel-Lindau (VHL) disease in previously published reports. It is unclear whether these tumors are an uncommon component of VHL disease or are more readily detected in these patients because of the frequency with which they undergo central nervous system imaging as part of the routine management of VHL disease. The authors report the case of a patient with VHL disease in whom a progressively enlarging supratentorial mass developed and was diagnosed as a hemangioblastoma because of its appearance on serial magnetic resonance images. At surgery the tumor displayed the typical features of a meningioma and was given the histological diagnosis of fibrous meningioma. Single-stranded conformational polymorphism analysis of the tumor DNA revealed a loss of heterozygosity at the neurofibromatosis Type 2 gene locus, known to be associated with sporadically occurring meningiomas. Despite this finding, the VHL gene locus on the allele from the patient's unaffected parent was normal. Thus it is unlikely that the occurrence of this patient's fibrous meningioma was associated with underlying VHL disease. Given the high frequency of neuroimaging sessions in patients with VHL disease, some supratentorial lesions that have been given radiological diagnoses of hemangioblastomas may be incidental meningiomas. C1 NINCDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINCDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. NR 38 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 2001 VL 95 IS 6 BP 1045 EP 1049 DI 10.3171/jns.2001.95.6.1045 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 499HA UT WOS:000172564600020 PM 11765821 ER PT J AU Guo, TL McCay, JA Zhang, LX Brown, RD You, L Karrow, NA Germolec, DR White, KL AF Guo, TL McCay, JA Zhang, LX Brown, RD You, L Karrow, NA Germolec, DR White, KL TI Genistein modulates immune responses and increases host resistance to B16F10 tumor in adult female B6C3F1 mice SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the Society-of-Toxicology CY MAR 24-29, 2001 CL SAN FRANCISCO, CALIFORNIA SP Soc Toxicol DE genistein; cytotoxic T cell activity; natural killer cell activity; antibody forming cell responses; B16F10 tumor model ID IN-VITRO; COMBINATION THERAPY; SOYBEAN ISOFLAVONES; LUNG METASTASIS; INHIBITS GROWTH; MELANOMA-CELLS; KILLER-CELLS; CANCER; RATS; DIFFERENTIATION AB The isoflavone genistein (4,7,4'-trihydroxyisoflavone) is a phytoestrogen found in high levels in soy products that has been associated with decreased incidences of breast and prostate cancers. The potential effects of genistein on the immune system were evaluated in adult female B6C3F1 mice. Groups of mice were exposed to vehicle or genistein by gavage for 28 d. The doses of genistein used were 2, 6 and 20 mg/kg body. Consistent with the chemopreventive effect of genistein, exposure to this compound significantly increased host resistance to B16F10 tumor as reflected by a decrease in the number of lung tumor nodules after tumor cell injection at the middle and high dose levels. Inhibition of B16F10 tumor formation was not due to a direct effect of serum genistein and/or its metabolites on the proliferation of B16F10 tumor cells. When innate and acquired immune responses were evaluated, a dose-related increase of cytotoxic T-cell activity was observed in genistein-treated mice with significant changes observed at the middle and high dose levels. Furthermore, in vitro interleukin (IL)-2-stimulated natural killer (NK) cell activity was significantly enhanced in the high genistein dose group, although the basal NK cell activity was not affected. Although no affect on the mixed lymphocyte responses and anti-CD3 antibody-mediated splenocyte proliferation was observed, exposure to genistein significantly increased basal splenocyte proliferation. Exposure to genistein did not alter the activity of the mononuclear phagocyte system and the cytotoxic/cytostatic function of thioglycollate-recruited peritoneal cells on B16F10 tumor cells. Finally, exposure to genistein did not produce biologically meaningful changes in spleen immunoglobulin (Ig)M and IgG antibody-forming cell responses. In conclusion, genistein enhanced host resistance as evaluated in the B16F10 tumor model, which may be related to the increases in the activities of cytotoxic T cells and NK cells. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. CIIT Ctr Hlth Res, Endocrine Reprod & Dev Toxicol Program, Res Triangle Pk, NC 27709 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Guo, TL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. FU NIEHS NIH HHS [ES-05454] NR 43 TC 68 Z9 76 U1 0 U2 3 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2001 VL 131 IS 12 BP 3251 EP 3258 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 502LR UT WOS:000172745500017 PM 11739876 ER PT J AU Hahn, CS AF Hahn, CS TI Review: Psychosocial well-being of parents and their children born after assisted reproduction SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Review DE reproductive technology; parenting; family interaction; child development ID IN-VITRO FERTILIZATION; INVITRO FERTILIZATION; FOLLOW-UP; INFERTILITY; ADJUSTMENT; PREGNANCY; INSEMINATION; QUALITY; DONOR; TEMPERAMENT AB Objective: To critically review the empirical literature published from 1980 through June 2000 on the psychosocial well-being of parents and their children born after assisted reproduction. Methods: A computer-based literature search of PsycINFO and Medline was conducted. Empirical studies were reviewed to document the psychosocial impact of infertility and its treatment on the families involved in terms of quality of parenting, family functioning, and child development. Results: Several common findings appeared across the studies reviewed. With regard to quality of parenting and family functioning, mothers of children born using assisted reproduction report less parenting stress and more positive mother- and father-child relationships than mothers of naturally conceived children. In most cases, no statistically significant differences in child functioning in terms of emotions, behavior, self-esteem, or perceptions of family relationship have been reported. Conclusions: The summary findings are positive and reassuring for parents and their children born after assisted reproduction. This critique of the published literature provides interpretative and methodological refinements for future research. C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Hahn, CS (reprint author), NICHHD, Child & Family Res Sect, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. NR 97 TC 25 Z9 25 U1 5 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD DEC PY 2001 VL 26 IS 8 BP 525 EP 538 DI 10.1093/jpepsy/26.8.525 PG 14 WC Psychology, Developmental SC Psychology GA 498YE UT WOS:000172540500008 PM 11700337 ER PT J AU Genuth, S Nathan, D Shamoon, H Duffy, H Engel, S Engel, H Dahms, W Mayer, L Pendegras, S Zegarra, H Miller, D Singerman, L Brillion, D Lackaye, M Heinemann, M Rahhal, F Reppuci, V Lee, T Whitehouse, F Kruger, D Carey, JD Bergenstal, R Johnson, M Kendall, D Spencer, M Noller, D Morgan, K Etzwiler, D Jacobson, A Golden, E Soroko, D Sharuk, G Arrigg, P Doyle, J Nathan, D Fritz, S Crowell, S Godine, J McKitrick, C Lou, P Service, J Ziegler, G Pach, J Colwell, J Wood, D Mayfield, R Hermayer, K Szpiech, M Lyons, T Parker, J Farr, A Elsing, S Thompson, T Molitch, M Schaefer, B Jampol, L Weinberg, D Lyon, A Kolterman, O Lorenzi, G Goldbaum, M Sivitz, W Bayless, M Zeither, R Weingeist, T Stone, E Boidt, HC Gehries, K Russell, S Counts, D Kowarski, A Ostrowski, D Donner, T Steidl, S Jones, B Herman, W Greene, D Martin, C Stevens, MJ Vine, AK Elner, S Bantle, J Rogness, B Olsen, T Steuer, E Kaushel, S Goldstein, D Hitt, S Giangiacomo, J Ormerod, LD Schade, D Canady, J Schluster, M Das, A Hornbeck, D Schwartz, S Maschak-Carey, BJ Baker, L Braunstein, S Brucker, A Orchard, T Silvers, N Songer, T Doft, B Olson, S Bergren, RL Fineman, M Malone, J Vacarro-Kish, J Berger, C Gstalder, R Pavan, PR Bryer-Ash, M Kitabchi, A Lambeth, H Murphy, MB Moser, S Meyer, D Iannacone, A Raskin, P Strowig, S Edwards, A Alappatt, J Wilson, C Park, S Zinman, B Barnie, A MacLean, S Devenyi, R Mandelcorn, M Brent, M Palmer, J Catton, S Kinyoun, J Van Ottingham, L Dupre, J Harth, J Canny, C Nicolle, D May, M Lorenz, R Lipps, J Survant, L Feman, S Tawansy, K Agarwal, A White, N Santiago, J Levandoski, L Boniuk, I Grand, G Thomas, M Burgess, D Joseph, D Blinder, K Tamborlane, W Gatcomb, P Stroessel, K Dahms, B Trail, R Quin, J Lachin, J Cleary, P Kenny, D Backlund, J Diminick, L Henry, A Klump, K Lamas, D Cowie, C Eastman, R Fradkin, J Davis, M Hubbard, L Geithman, P Brickbauer, J Kastorff, L Neider, M Badal, D Esser, B Miner, K Wabers, H Steffes, M Bucksa, J Chavers, B O'Leary, D Funk, I Crow, R O'Donnell, C Gloeb, B Thomas, S Weir, G Clark, C D'Agostino, R Espeland, M Klein, B Jacobson, H Manolio, T Rand, L Singer, D Stern, M Garvey, WT Lyons, TJ Jenkins, A Klein, R Lopes-Virella, M Virella, G Jaffa, AA Zheng, D Lackland, D McGee, D Mayfield, RK Boright, A Paterson, A Scherer, S Zinman, B Brunzell, J Hokanson, J Marcovina, S Purnell, J Sibley, S AF Genuth, S Nathan, D Shamoon, H Duffy, H Engel, S Engel, H Dahms, W Mayer, L Pendegras, S Zegarra, H Miller, D Singerman, L Brillion, D Lackaye, M Heinemann, M Rahhal, F Reppuci, V Lee, T Whitehouse, F Kruger, D Carey, JD Bergenstal, R Johnson, M Kendall, D Spencer, M Noller, D Morgan, K Etzwiler, D Jacobson, A Golden, E Soroko, D Sharuk, G Arrigg, P Doyle, J Nathan, D Fritz, S Crowell, S Godine, J McKitrick, C Lou, P Service, J Ziegler, G Pach, J Colwell, J Wood, D Mayfield, R Hermayer, K Szpiech, M Lyons, T Parker, J Farr, A Elsing, S Thompson, T Molitch, M Schaefer, B Jampol, L Weinberg, D Lyon, A Kolterman, O Lorenzi, G Goldbaum, M Sivitz, W Bayless, M Zeither, R Weingeist, T Stone, E Boidt, HC Gehries, K Russell, S Counts, D Kowarski, A Ostrowski, D Donner, T Steidl, S Jones, B Herman, W Greene, D Martin, C Stevens, MJ Vine, AK Elner, S Bantle, J Rogness, B Olsen, T Steuer, E Kaushel, S Goldstein, D Hitt, S Giangiacomo, J Ormerod, LD Schade, D Canady, J Schluster, M Das, A Hornbeck, D Schwartz, S Maschak-Carey, BJ Baker, L Braunstein, S Brucker, A Orchard, T Silvers, N Songer, T Doft, B Olson, S Bergren, RL Fineman, M Malone, J Vacarro-Kish, J Berger, C Gstalder, R Pavan, PR Bryer-Ash, M Kitabchi, A Lambeth, H Murphy, MB Moser, S Meyer, D Iannacone, A Raskin, P Strowig, S Edwards, A Alappatt, J Wilson, C Park, S Zinman, B Barnie, A MacLean, S Devenyi, R Mandelcorn, M Brent, M Palmer, J Catton, S Kinyoun, J Van Ottingham, L Dupre, J Harth, J Canny, C Nicolle, D May, M Lorenz, R Lipps, J Survant, L Feman, S Tawansy, K Agarwal, A White, N Santiago, J Levandoski, L Boniuk, I Grand, G Thomas, M Burgess, D Joseph, D Blinder, K Tamborlane, W Gatcomb, P Stroessel, K Dahms, B Trail, R Quin, J Lachin, J Cleary, P Kenny, D Backlund, J Diminick, L Henry, A Klump, K Lamas, D Cowie, C Eastman, R Fradkin, J Davis, M Hubbard, L Geithman, P Brickbauer, J Kastorff, L Neider, M Badal, D Esser, B Miner, K Wabers, H Steffes, M Bucksa, J Chavers, B O'Leary, D Funk, I Crow, R O'Donnell, C Gloeb, B Thomas, S Weir, G Clark, C D'Agostino, R Espeland, M Klein, B Jacobson, H Manolio, T Rand, L Singer, D Stern, M Garvey, WT Lyons, TJ Jenkins, A Klein, R Lopes-Virella, M Virella, G Jaffa, AA Zheng, D Lackland, D McGee, D Mayfield, RK Boright, A Paterson, A Scherer, S Zinman, B Brunzell, J Hokanson, J Marcovina, S Purnell, J Sibley, S CA Diabet Control Complications Trial Epidemiology Diabet Interventions TI Beneficial effects of intensive therapy of diabetes during adolescence: Outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT) SO JOURNAL OF PEDIATRICS LA English DT Article AB Objective: The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy of type I diabetes mellitus reduces the risk of development and progression of microvascular complications. The Epidemiology, of Diabetes Interventions and Complications (EDIC) study assessed whether these benefits persisted after the end of DCCT. Results for the adolescent DCCT cohort are reported here. Study design: Of the DCCT adolescent cohort (n = 195), 175 participated in EDIC, 151 had fundus photography, and 156 had albumin excretion rate measured at year 3 or 4. The odds of progression of retinopathy and albuminuria from closeout of the DCCT until ED IC year 4 were assessed. Results: In contrast to the 7.4 years of the DCCT during which mean hemoglobin A,, levels were significantly lower with intensive therapy than conventional therapy (8.06% vs 9.76%; P < .0001), the subsequent first 4 years of EDIC had mean hemoglobin Alc levels that were similar between the former intensive and the former conventional groups (8.38% vs 8.45%). However, the prevalence of worsening of 3 steps or more in retinopathy and of progression to proliferative or severe nonproliferative retinopathy were reduced by 74% (P < .001) and 78% (P < .007), respectively, in the former intensive therapy group compared with the Former conventional group. Conclusions: These findings provide further support for the DCCT recommendation that most adolescents with type I diabetes receive intensive therapy aimed at achieving glycemic control as close to normal as possible to reduce the risk of microvascular complications. C1 Albert Einstein Coll Med, Bronx, NY USA. Case Western Reserve Univ, Clin Coordinating Ctr, Cleveland, OH 44106 USA. Cornell Univ, Med Ctr, Ithaca, NY 14853 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Northwestern Univ, Evanston, IL 60208 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Iowa, Iowa City, IA 52242 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Missouri, Columbia, MO 65211 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ S Florida, Tampa, FL 33620 USA. Univ Tennessee, Knoxville, TN 37996 USA. Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. Univ Toronto, Toronto, ON, Canada. Univ Washington, Lipoprot Distribut Grp, Seattle, WA 98195 USA. Univ Western Ontario, London, ON N6A 3K7, Canada. Vanderbilt Univ, Nashville, TN 37240 USA. Washington Univ, St Louis, MO 63130 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. George Washington Univ, Data Coordinating Ctr, Ctr Biostat, Washington, DC 20052 USA. NIDDKD, Program Off, Bethesda, MD USA. Univ Wisconsin, Cent Fundus Photograph Reading Ctr, Madison, WI 53706 USA. Univ Minnesota, Cent Biochem Lab, Minneapolis, MN 55455 USA. Univ Minnesota, Cent ECG Reading Unit, Minneapolis, MN 55455 USA. Med Univ S Carolina, Mol Risk Factors Program Project, Charleston, SC USA. Hosp Sick Children, Genet Studies Grp, Toronto, ON, Canada. RP Genuth, S (reprint author), Albert Einstein Coll Med, Bronx, NY USA. RI Paterson, Andrew/A-4088-2011; OI Paterson, Andrew/0000-0002-9169-118X; Shamoon, Harry/0000-0002-5014-5211 NR 20 TC 64 Z9 69 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2001 VL 139 IS 6 BP 804 EP 812 DI 10.1067/mpd.2001.118887 PG 9 WC Pediatrics SC Pediatrics GA 505JA UT WOS:000172908600012 ER PT J AU Russell, DL Keil, MF Bonat, SH Uwaifo, GI Nicholson, JC McDuffie, JR Hill, SC Yanovski, JA AF Russell, DL Keil, MF Bonat, SH Uwaifo, GI Nicholson, JC McDuffie, JR Hill, SC Yanovski, JA TI The relation between skeletal maturation and adiposity in African American and Caucasian children SO JOURNAL OF PEDIATRICS LA English DT Article ID WHITE GIRLS; PREPUBERTAL GIRLS; BONE-AGE; OBESITY; GROWTH; ANDROSTENEDIONE; ADOLESCENCE; METABOLISM; ESTRADIOL; ADULTHOOD AB Objective: African Amer can children have earlier pubertal and skeletal maturation and a higher body mass index (BMI) than Caucasian children. We tested the hypothesis that advanced bone age in African American children is accounted for, by their greater adiposity. Study design: We studied 252 African American (n = 97) and Caucasian (n = 155) children aged 5 to 12 years. Skeletal age was determined by a radiologist blinded to clinical details. The difference between bone age (BA) and chronological age (CA) (noted as BA - CA) and the ratio of bone age to chronological age (BA/CA) were determined. Analysis of covariance was used to adjust skeletal maturation for the effects of adiposity, as measured by BMI, BMI standard deviation score (Bmi SDS), and Cat mass by dual energy x-ray absorptiometry (DXA). Results: African American children were significantly heavier than Caucasians (BMI SDS 2.7 +/- 3.4 vs 1.7 +/- 2.4, P < .05). Both BA-CA (0.75 +/- 1.46 vs 0.28 +/- 1.38, P < .05) and BA/CA (1.09 +/- 0.17 vs 1.03 +/- 0.16, P < .05) were significantly greater in African Americans than Caucasians. BA - CA and BA/CA were significantly correlated with lean body mass, BMI, BMI SIDS, and DXA fat mass (all r > 0.46, P < .001). Neither BA - CA nor BA/CA of African Americans and Caucasians were significantly different after correction for lean body mass and measures of adiposity, including BMI, BMI SIDS, or DXA fat mass. Conclusion: Skeletal age is more advanced in African American than Caucasian children and is significantly related to body mass. In large measure, the advancement in skeletal maturation of prepubertal and early pubertal African American children can be accounted for by their greater adiposity. C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), Bldg 10,Room 10N262,MSC 1862,10 Ctr Dr, Bethesda, MD 20892 USA. RI Uwaifo, Gabriel/M-2361-2016; OI Uwaifo, Gabriel/0000-0002-6962-9304; Yanovski, Jack/0000-0001-8542-1637 NR 31 TC 37 Z9 41 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2001 VL 139 IS 6 BP 844 EP 848 DI 10.1067/mpd.2001.119446 PG 5 WC Pediatrics SC Pediatrics GA 505JA UT WOS:000172908600018 PM 11743511 ER PT J AU McCrae, RR AF McCrae, RR TI Trait psychology and culture: Exploring intercultural comparisons SO JOURNAL OF PERSONALITY LA English DT Article; Proceedings Paper CT 27th International Congress of Psychology CY JUL, 2000 CL STOCKHOLM, SWEDEN AB Personality traits, studied for decades by Western personality psychologists, have recently been reconceptualized as endogenous basic tendencies that, within a cultural context, give rise to habits, attitudes, skills, beliefs, and other characteristic adaptations. This conceptualization provides a new framework for studying personality and culture at three levels. Transcultural research focuses on identifying human universals, such as trait structure and development; intracultural studies examine the unique expression of traits in specific cultures; and intercultural research characterizes cultures and their subgroups in terms of mean levels of personality traits and seeks associations between cultural variables and aggregate personality traits. As an example of the problems and possibilities of intercultural analyses, data on mean levels of Revised NEO Personality Inventory scales from college age and adult samples (N = 23,031) of men and women from 26 cultures are examined. Results showed that age and gender differences resembled those found in American samples; different subsamples from each culture showed similar levels of personality traits; intercultural factor analysis yielded a close approximation to the Five-Factor Model; and factor scores were meaningfully related to other culture-level variables. However, mean trait levels were not apparent to expert raters, casting doubt on the accuracy of national stereotypes. Trait psychology can serve as a useful complement to cultural perspectives on human nature and personality. C1 NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 0 TC 118 Z9 124 U1 1 U2 21 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0022-3506 J9 J PERS JI J. Pers. PD DEC PY 2001 VL 69 IS 6 BP 819 EP 846 DI 10.1111/1467-6494.696166 PG 28 WC Psychology, Social SC Psychology GA 496YU UT WOS:000172426600003 PM 11767820 ER PT J AU Dai, D Tang, J Rose, R Hodgson, E Bienstock, RJ Mohrenweiser, HW Goldstein, JA AF Dai, D Tang, J Rose, R Hodgson, E Bienstock, RJ Mohrenweiser, HW Goldstein, JA TI Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ADULT HUMAN-LIVER; AMINO-ACID; GENETIC VARIANT; CLINICAL PRESENTATION; CYTOCHROME-P450 3A4; PROSTATE TUMORS; SMALL-BOWEL; BIOTRANSFORMATION; SUBSTITUTIONS; POLYMORPHISM AB CYP3A4 is the most abundant isoform of cytochrome P450 (CYP) in adult human liver. It metabolizes numerous clinically, physiologically, and toxicologically important compounds. The expression of CYP3A4 varies 40-fold in individual human livers, and metabolism of CYP3A4 substrates varies at least 10-fold in vivo. Single nucleotide polymorphisms (SNPs) in CYP3A4 were identified by direct sequencing of genomic DNA in 72 individuals from three different ethnic groups, including Caucasians, Blacks (African-Americans and African pygmies), and Asians. A total of 28 SNPs were identified, including five which produced coding changes M445T (CYP3A4*3), R162Q (CYP3A4*15), F189S (CYP3A4*17), L293P (CYP3A4*18), and P467S (CYP3A4*19). The latter four represent new alleic variants. Racial variability was observed for the frequency of individual SNPs. CYP3A R162Q was identified only in Black populations with an allelic frequency of 4%. CYP3A4 F189S and CYP3A4 M445T were identified in Caucasians with allelic frequencies 2% and 4%, respectively. L293P and P467S were only observed in Asians at allelic frequencies of 2%. The cDNAs for the F189S, L293P, M445T, and P467S mutant alleles were constructed by site-directed mutagenesis and expressed in an Escherichia coli expression system. Testosterone and the insecticide chlorpyrifos were used to assess the catalytic activities of the most common CYP3A4 allele (CYP3A4*1) and its allelic variants. CYP3A4 F189S exhibited lower turnover numbers for testosterone and chlorpyrifos, while CYP3A4 L293P had higher turnover numbers for both substrates. The turnover numbers of the CYP3A4 M445T and P467S alleles to metabolize these compounds were not significantly different from those of wild-type CYP3A4. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. Lawrence Livermore Natl Lab, Livermore, CA USA. RP Goldstein, JA (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Goldstein, Joyce/A-6681-2012 FU NIEHS NIH HHS [Y1-ES-8054-05] NR 41 TC 224 Z9 252 U1 2 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2001 VL 299 IS 3 BP 825 EP 831 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 497YY UT WOS:000172484100003 PM 11714865 ER PT J AU Moody, TW Jensen, RT AF Moody, TW Jensen, RT TI CI-988 inhibits growth of small cell lung cancer cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PANCREATIC ACINAR-CELLS; CCK-B; PHARMACOLOGICAL CHARACTERIZATION; B/GASTRIN RECEPTOR; CHOLECYSTOKININ; GASTRIN; ANTAGONIST; POTENT; ADENOCARCINOMA; CARCINOMA AB The effects of cholecystokinin (CCK) antagonists on small cell lung cancer (SCLC) cells were investigated. CI-988, L-365,260, and L-364,718 inhibited specific I-125-CCK-8 binding to NCI-H209 cells with IC50 values of 5, 2, and 200 nM. ([R-(R*,R*)]-4[[2-[[3-(1H-Indole-3-yl)-2-methyl-1-oxo-2-[[tricyclo[3.3.1.1(3,7)]-dec-2-yloxy)carbonyl[amino]propyl]amino]-1-phenylethyl-]amino]-4-oxobutanoic acid) (CI-988; 100 nM) inhibited the ability of 10 nM CCK-8 to elevate cytosolic Ca2+ in 1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2'-amino-5'-methylphenoxy)-ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester-loaded NCI-H209 cells. By Western blot, CI-988 inhibited tyrosine phosphorylation of focal adhesion kinase and paxillin stimulated by CCK-8. Also, CI-988 inhibited tyrosine phosphorylation of mitogen-activated protein kinase stimulated by CCK-8. By Northern blot, CI-988 antagonized the ability of 10 nM CCK-8 to increase c-fos mRNA in NCI-H209 cells. Also, CI-988 inhibited the ability of CCK-8 to increase vascular endothelial cell growth factor mRNA. Using a [3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] and clonogenic assay, CI-988 inhibited the proliferation of NCI-H209 cells in vitro. Using nude mice, CI-988 inhibited the proliferation of NCI-H209 xenografts. These results suggest that CI-988 is a CCK2 receptor antagonist that inhibits the proliferation of SCLC cells. C1 NCI, Dept Cell & Canc Biol, Med Branch, Rockville, MD 20850 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Moody, TW (reprint author), NCI, Dept Cell & Canc Biol, Med Branch, Bldg KWC,Rm 300,9610 Med Ctr Dr, Rockville, MD 20850 USA. NR 40 TC 14 Z9 15 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2001 VL 299 IS 3 BP 1154 EP 1160 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 497YY UT WOS:000172484100045 PM 11714907 ER PT J AU Watson, MR Horowitz, AM Garcia, I Canto, MT AF Watson, MR Horowitz, AM Garcia, I Canto, MT TI A community participatory oral health promotion program in an inner-city Latino community SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE public health dentistry; community dentistry; community intervention research; community-based research; behavioral risk factors interventions; participatory health promotion; public health partnerships; immigrants; Latinos; Hispanics; Central Americans; child; preschool; mothers; families ID CARIES; EDUCATION; CHILDREN; CARE AB Objectives: This paper reports the planning, implementation, process evaluation, and refinement of an oral health community participatory project in Mount Pleasant, an inner-city Latino neighborhood of Washington, DC. The main goal was to explore the feasibility of implementing such a project. Methods: The PRECEDE-PROCEED model was used to guide the planning and process evaluation of this project, in conjunction with community organizational methods. A steering committee, which met periodically, was formed to assist in program planning, implementation, and evaluation. The needs assessment of the community identified extensive dental health problems among children and deficiencies in their parents' oral health knowledge, opinions, and practices. in response, culturally appropriate health education and promotion activities were planned and implemented in collaboration with local community organizations volunteers, and local practitioners. Process evaluation was used to provide feedback into the refinement of the community approach, which included record keeping and an inventory approach to activities completed and resources used. The overall impact and usefulness of this program were assessed informally using an anonymous open-ended questionnaire directed to members of the steering committee, and an outreach survey using a convenience sample at a local Latino health fair. Results: The implementation of such a community participatory approach was feasible and useful for building upon existing local resources and addressing oral health concerns in a community not reached by traditional dental care and health promotion initiatives, individuals in this community showed a substantial interest in oral health matters and participated in a variety of oral health prevention activities. The community approach adhered to community-based research principles. C1 Univ Maryland, Baltimore Coll Dent Surg, Sch Dent, Dept Pediat Dent, Baltimore, MD 21201 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Watson, MR (reprint author), Univ Maryland, Baltimore Coll Dent Surg, Sch Dent, Dept Pediat Dent, 666 W Baltimore St, Baltimore, MD 21201 USA. NR 31 TC 21 Z9 21 U1 2 U2 10 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 2001 VL 61 IS 1 BP 34 EP 41 DI 10.1111/j.1752-7325.2001.tb03353.x PG 8 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 422JE UT WOS:000168114100006 PM 11317603 ER PT J AU Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS AF Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS TI Smoking and use of hair treatments in relation to risk of developing systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; autoimmune disease; tobacco; aromatic amines ID REVISED CRITERIA; DISEASE; CLASSIFICATION AB Objective. To examine the association between smoking and hair treatments (dyes, permanents) and risk of developing systemic lupus erythematosus (SLE). Methods. Patients (n = 265) diagnosed between January 1, 1995, and July 31, 1999, were recruited through 4 university based and 30 community based rheumatology practices in eastern North Carolina and South Carolina. Controls (n = 355) were identified through driver's license records and were frequency matched to patients by age, sex, and state. Data collection included a 60 min in-person interview. Analyses were limited to experiences that occurred before age at diagnosis (patients) or reference age (controls). Because the prevalence of use of hair treatments among men was very low, the analyses of those exposures were limited to women. Results. There was no association with smoking history and risk of developing SLE when analyzed as status (current, former, or never-smoker) or measures of dose (duration or pack-years). Use of permanent hair dyes in women was associated with a small increased risk of developing SLE (OR 1.5, 95% CI 1.0, 2.2). This association increased with longer duration of use (compared with nonusers, OR 1.7, 95% CI 1.0, 2.7 for 6 or more years). There was little evidence of an association between SLE and use of temporary dyes or of permanents and straighteners. Conclusion. These results suggest at most a weak association between SLE risk and permanent hair dyes or smoking. Genetic variability in the metabolism of these products may be important to assess in future studies. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Div Rheumatol, Chapel Hill, NC USA. E Carolina Univ, Sch Med, Div Rheumatol, Greenville, NC USA. Duke Univ, Med Ctr, Div Rheumatol Allergy & Clin Immunol, Durham, NC USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. NR 15 TC 25 Z9 27 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 2001 VL 28 IS 12 BP 2653 EP 2656 PG 4 WC Rheumatology SC Rheumatology GA 498NP UT WOS:000172517800016 PM 11764212 ER PT J AU Pendarvis, WT Pillemer, SR AF Pendarvis, WT Pillemer, SR TI Widespread pain and Sjogren's syndrome SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE widespread pain; Sjogren's syndrome; fibromyalgia ID FIBROMYALGIA; PREVALENCE; CLASSIFICATION; MULTICENTER; POPULATION; CRITERIA; SICCA AB Objective. Reports exist of an association between fibromyalgia (FM) and Sjogren's syndrome (SS). Widespread pain is a necessary component of FM. We explored the association of widespread pain and SS. Methods. Data were abstracted from the records of the most recent 100 patients evaluated in the SS clinic. The subjects included individuals with or without SS who had screened for features of the disorder. Patients with confounding disorders or missing data were excluded. The presence of widespread pain was established by questionnaire in 92 subjects. Widespread pain followed the definition in the 1990 American College of Rheumatology classification criteria for FM. By objective criteria used in the clinic, patients were initially classified into SS (requiring keratoconjunctivitis sicca, positive labial salivary gland biopsy, and serological evidence of autoimmunity), incomplete SS (at least one of the latter objective findings), or non-SS (if all 3 objective findings were negative). For subsequent analyses, the study population was also classified into cases by applying the European criteria for SS, and the subjective or objective components of European criteria. Descriptive statistics and Cochran-Mantel chi-square tests were performed. Results. Only 2/27 (7%) of those diagnosed with SS reported symptoms of widespread pain. The incomplete SS group consisted of 8/56 (14%), while the non-SS were 1/9 (11%). There was a trend toward greater widespread pain in those 9 of 52 (17%) subjects meeting the European criteria for SS who had widespread pain compared with 2 of 50 (5%) who did not. However, this was not significant (p = 0.0728). The greater the subjectivity of the criteria applied to classify cases of SS, the higher was the prevalence of widespread pain. No significant association was found between widespread pain and SS for any of the criteria applied. Conclusion. No significant association between widespread pain and SS was found in our study population. Further study is indicated to explore a possible lack of association between SS and FM. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Pillemer, SR (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. NR 18 TC 3 Z9 3 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 2001 VL 28 IS 12 BP 2657 EP 2659 PG 3 WC Rheumatology SC Rheumatology GA 498NP UT WOS:000172517800017 PM 11764213 ER PT J AU Gallena, S Smith, PJ Zeffiro, T Ludlow, CL AF Gallena, S Smith, PJ Zeffiro, T Ludlow, CL TI Effects of levodopa on laryngeal muscle activity for voice onset and offset in Parkinson disease SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE thyroarytenoid muscle; dysphonia; pathophysiology; idiopathic Parkinson disease; vocal fold movement ID THYROARYTENOID MUSCLE; MOTOR UNITS; SPEECH; MOVEMENTS; ADDUCTION; PHONATION AB The laryngeal pathophysiology underlying the speech disorder in idiopathic Parkinson disease (IPD) was addressed in this electromyographic study of laryngeal muscle activity. This muscle activity was examined during voice onset and offset gestures in 6 persons in the early stages of IPD who were not receiving medication. The purpose was to determine (a) if impaired voice onset and offset control for speech and vocal fold bowing were related to abnormalities in laryngeal muscle activity in the nonmedicated state and (b) if these attributes change with levodopa. Blinded listeners rated the IPD participants' voice onset and offset control before and after levodopa was administered. In the nonmedicated state, the IPD participants vocal fold bowing was examined on nasoendoscopy, and laryngeal muscle activity levels were compared with normal research volunteers. The IPD participants were then administered a therapeutic dose of levodopa, and changes in laryngeal muscle activity for voice onset and offset gestures were measured during the same session. Significant differences were found between IPD participants in the nonmedicated state: those with higher levels of muscle activation had vocal fold bowing and greater impairment in voice onset and offset control for speech. Similarly, following levodopa administration, those with thyroarytenoid muscle activity reductions had greater improvements in voice onset and offset control for speech. In this study, voice onset and offset control difficulties and vocal fold bowing were associated with increased levels of laryngeal muscle activity in the absence of medication. C1 NINCDS, Laryngeal & Speech Sect, Med Neurol Branch, Bethesda, MD 20892 USA. Univ Maryland, Dept Math, Math Stat Program, College Pk, MD 20742 USA. NINCDS, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), Bldg 10,Room 5D38,MSC 1416,10 Ctr Dr, Bethesda, MD 20892 USA. OI Ludlow, Christy/0000-0002-2015-6171 NR 35 TC 53 Z9 56 U1 0 U2 0 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD DEC PY 2001 VL 44 IS 6 BP 1284 EP 1299 DI 10.1044/1092-4388(2001/100) PG 16 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 506JC UT WOS:000172965600009 PM 11776365 ER PT J AU Swedo, SE AF Swedo, SE TI Genetics of childhood disorders: XXXIII. Autoimmunity, Part 6: Poststreptococcal autoimmunity SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; NEUROPSYCHIATRIC DISORDERS; STREPTOCOCCAL INFECTIONS; RHEUMATIC-FEVER; CHILDREN; PANDAS C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. RP Swedo, SE (reprint author), Yale Univ, Sch Med, Ctr Child Study, 230 S Frontage Rd, New Haven, CT 06520 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2001 VL 40 IS 12 BP 1479 EP 1482 DI 10.1097/00004583-200112000-00021 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 496HE UT WOS:000172389500021 PM 11765296 ER PT J AU Bailey, JJ Berson, AS Handelsman, H Hodges, M AF Bailey, JJ Berson, AS Handelsman, H Hodges, M TI Utility of current risk stratification tests for predicting major arrhythmic events after myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HEART-RATE-VARIABILITY; SIGNAL-AVERAGED ELECTROCARDIOGRAM; SUDDEN CARDIAC DEATH; PROGRAMMED VENTRICULAR STIMULATION; TERM FOLLOW-UP; SPECTRAL TURBULENCE ANALYSIS; FIRST-CHOICE THERAPY; PROGNOSTIC-SIGNIFICANCE; LATE POTENTIALS; IMPLANTABLE DEFIBRILLATOR AB Objectives We surveyed the literature to estimate prediction values for five common tests for risk of major arrhythmic events (MAEs) after myocardial infarction. We then determined feasibility of a staged risk stratification using combinations of noninvasive tests, reserving an electrophysiologic study (EPS) as the final test. Background Improved approaches are needed for identifying those patients at highest risk for subsequent MAE and candidates for implantable cardioverter-defibrillators. Methods We located 44 reports for which values of MAE incidence and predictive accuracy could be inferred: signal-averaged electrocardiography; heart rate variability severe ventricular arrhythmia on ambulatory electrocardiography; left ventricular ejection fraction; and EPS. A meta-analysis of reports used receiver-operating characteristic curves to estimate mean values for sensitivity and specificity for each test and 95% confidence limits. We then simulated a clinical situation in which risk was estimated by combining tests in three stages. Results Test sensitivities ranged from 42.8% to 62.4%; specificities from 77.4% to 85.8%. A three-stage stratification yielded a low-risk group (80.0% with a two-year MAE risk of 2.9%), a high-risk group (11.8% with a 41.4% risk) and an unstratified group (8.2% with an 8.9% risk equivalent to a two-year incidence of 7.9%). Conclusions Sensitivities and specificities for the five tests were relatively similar. No one test was satisfactory alone for predicting risk. Combinations of tests in stages allowed us to stratify 91.8% of patients as either high-risk or low-risk. These data suggest that a large prospective study to develop a robust prediction model is feasible and desirable. (J Am Coll Cardiol 2001; 38:1902-11) (C) 2001 by the American College of Cardiology. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. NHLBI, Bioengn Sci Res Grp, Bethesda, MD 20892 USA. Agcy Hlth Care Res & Qual, Ctr Practice & Technol Assessment, Bethesda, MD USA. Minneapolis Heart Inst Fdn, Minneapolis, MN USA. RP Bailey, JJ (reprint author), NIH, Ctr Informat Technol, Bldg 12A,Room 2007,MSC 5620,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 70 TC 94 Z9 96 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 2001 VL 38 IS 7 BP 1902 EP 1911 DI 10.1016/S0735-1097(01)01667-9 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 497LX UT WOS:000172458000020 PM 11738292 ER PT J AU Wagner, JA Hu, K Bauersachs, J Karcher, J Wiesler, M Goparaju, SK Kunos, G Ertl, G AF Wagner, JA Hu, K Bauersachs, J Karcher, J Wiesler, M Goparaju, SK Kunos, G Ertl, G TI Endogenous cannabinoids mediate hypotension after experimental myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; CARDIOGENIC-SHOCK; MESENTERIC VASODILATION; PLASMA-LEVELS; RECEPTOR; CB1; ENDOTOXEMIA; EXPRESSION; ACTIVATION; ANTAGONIST AB OBJECTIVES We sought to determine whether endocannabinoids influence hemodynamic variables in an experimental models of acute myocardial infarction (MI). BACKGROUND Hypotension and cardiogenic shock are common complications in acute MI. Cannabinoids are strong vasodilators, and endocannabinoids are involved in hypotension in hemorrhagic and septic shock. METHODS The early effect of left coronary artery ligation on hemodynamic variables was measured in rats pretreated with the selective cannabinoid, receptor (CB1) antagonist SR141716A (herein referred to as SR, 6.45 mu mol/kg body weight intravenously) or vehicle. Endocannabinoids produced in monocytes and platelets were quantified by liquid chromatography/mass spectrometry (LC/MS), and their effects on blood pressure and vascular reactivity were determined. RESULTS After MI, mean arterial pressure (MAP) dropped from 126 +/- 2 min Hg to 76 +/- 3 mm Hg in control rats, whereas the decline in blood pressure was smaller (from 121 3 mm Hg to 108 +/- 7 min Hg, p < 0.01) in rats pretreated with SR. SR increased the tachycardia that follows MI (change [] in heart rate [HR] = +107 +/- 21 beate/min vs. + 49 +/- 9 beats/min in control rats, p < 0.05). The MI sizes were the same in control rats and SR-treated rats. Circulating monocytes and platelets isolated 30 min after MI only, decreased MAP when injected into untreated rats (MAP = -20 +/- 5 min Hg), but not in SR-pretreated rats. The endocannabinoids anandamide and 2-arachidonyl glycerol were detected in monocytes and platelets isolated after MI, but not in cells from sham rats. Survival rates at 2 h after MI were 70% for control rats and 36% for SR-treated rats (p < 0.05). Endothelium-dependent arterial relaxation was attenuated after MI (maximal relaxation: 44 +/- 3% [p < 0.01] vs. 70 3% in control rats) and further depressed by, SR treatment (24 +/- 5%, p < 0.01 vs. MI placebo). CONCLUSIONS Cannabinoids generated in monocytes and platelets contribute to hypotension in acute MI. Cannabinoid, receptor blockade restores MAP but increases 2-h mortality, possibly by impairing endothelial function. (J Am Coll Cardiol 2001;38:2048-54) (C) 2001 by the American College of Cardiology. C1 Univ Wurzburg, Dept Med, D-97080 Wurzburg, Germany. NIAAA, NIH, Bethesda, MD USA. RP Wagner, JA (reprint author), Univ Wurzburg, Dept Med, Josef Schneider Str 2, D-97080 Wurzburg, Germany. RI Goparaju, Sravan/H-3422-2011 NR 33 TC 99 Z9 105 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 2001 VL 38 IS 7 BP 2048 EP 2054 DI 10.1016/S0735-1097(01)01671-0 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 497LX UT WOS:000172458000042 PM 11738314 ER PT J AU Janket, SJK Baird, A Chuang, SK Jones, JA AF Janket, SJK Baird, A Chuang, SK Jones, JA TI Heart of the matter SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter ID CHLAMYDIA-PNEUMONIAE; DISEASE C1 VA Med Ctr, Dent Serv, Bedford, MA USA. NINCDS, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Boston Univ, Goldman Sch Dent Med, Boston, MA 02215 USA. Boston Univ, Goldman Sch Publ Hlth, Boston, MA 02215 USA. RP Janket, SJK (reprint author), VA Med Ctr, Dent Serv, Bedford, MA USA. NR 8 TC 8 Z9 8 U1 0 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD DEC PY 2001 VL 132 IS 12 BP 1648 EP + PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 507CU UT WOS:000173010000010 PM 11780981 ER PT J AU Fontaine, KR Cheskin, LJ Carriero, NJ Jefferson, L Finley, CJ Gorelick, DA AF Fontaine, KR Cheskin, LJ Carriero, NJ Jefferson, L Finley, CJ Gorelick, DA TI Body mass index and effects of refeeding on liver tests in drug-dependent adults in a residential research unit SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID NUTRITIONAL-STATUS; ADDICTS; TRANSAMINASE; PREVALENCE; MARIJUANA; HEROIN; USERS C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Rheumatol,Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Div Gastroenterol,Dept Med, Baltimore, MD USA. RP Gorelick, DA (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 21 TC 2 Z9 2 U1 0 U2 1 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD DEC PY 2001 VL 101 IS 12 BP 1467 EP 1469 DI 10.1016/S0002-8223(01)00354-6 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 499AL UT WOS:000172547300024 PM 11762745 ER PT J AU Foley, D Monjan, A Masaki, K Ross, W Havlik, R White, L Launer, L AF Foley, D Monjan, A Masaki, K Ross, W Havlik, R White, L Launer, L TI Daytime sleepiness is associated with 3-year incident dementia and cognitive decline in older Japanese-American men SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Alzheimer's disease; dementia; sleep apnea; daytime sleepiness; snoring; epidemiology ID ALZHEIMERS-DISEASE; IMPAIRMENT; HAWAII; HEALTH; APNEA; DESIGN; IMPACT; STATE; RISK AB OBJECTIVES: To assess the longitudinal association between sleep disturbances (insomnia and daytime sleepiness) and incidence of dementia and cognitive decline in older men. DESIGN: Community-based longitudinal cohort study. SETTING: The Honolulu-Asia Aging Study of dementia that is linked to the Honolulu Heart Program's fourth examination, conducted 1991-1993, and the 3-year followup fifth examination, conducted 1994-1996. PARTICIPANTS: Two thousand three hundred forty-six Japanese-American men age 71 to 93 years who screened negative for prevalent dementia at baseline and were screened again for dementia incidence in a 3-year follow-up examination. MEASUREMENTS: Baseline self-reports of trouble falling asleep or early morning awakening (insomnia) and being sleepy during the day (daytime sleepiness); Cognitive Abilities Screening Instrument (CASI) scores from baseline and followup; clinical diagnosis of incident dementia; and other baseline measures including age, years of education, body mass index, depressive symptoms, and history of hypertension, heart disease, diabetes mellitus, asthma, and use of benzodiazepines. RESULTS: After adjusting for age and other factors, persons reporting excessive daytime sleepiness at baseline (8%) were twice as likely to be diagnosed with incident dementia than were those not reporting daytime sleepiness (odds ratio (OR) = 2.19, 95% confidence interval (CI) = 1.37-3.50) and about 40% more likely to have greater than or equal to9 point drop in their CASI score between examinations (OR 1.44, 95% CI = 1.01-2.08). In contrast, insomnia was not associated with cognitive decline or incidence of dementia. CONCLUSIONS: Daytime sleepiness in older adults may be an early indicator of decline in cognitive functioning and onset of dementia. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. NIA, Neurosci & Neuropsychol Program, Bethesda, MD 20892 USA. Univ Hawaii, Sch Med, Honolulu Heart Program, Kuakini Med Ctr, Honolulu, HI USA. Univ Hawaii, Sch Med, Geriatr Med Program, Honolulu, HI USA. Dept Vet Affairs, Honolulu, HI USA. RP Foley, D (reprint author), NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149] NR 35 TC 99 Z9 99 U1 3 U2 8 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2001 VL 49 IS 12 BP 1628 EP 1632 DI 10.1046/j.1532-5415.2001.t01-1-49271.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 505JH UT WOS:000172909300006 PM 11843995 ER PT J AU Katzel, LI Sorkin, JD Fleg, JL AF Katzel, LI Sorkin, JD Fleg, JL TI A comparison of longitudinal changes in aerobic fitness in older endurance athletes and sedentary men SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE fitness; aging; exercise; longitudinal studies; athlete ID 20-YEAR FOLLOW-UP; BODY-COMPOSITION; RISK-FACTORS; AGE; CAPACITY; HEALTHY; DECLINE; REDUCTION; EXERCISE; VO2MAX AB OBJECTIVES: To compare the longitudinal changes in maximal aerobic capacity (VO(2)max) in healthy middle aged and older athletes and sedentary men. DESIGN: A cohort study with mean follow-up of 8.7 years (range 4.0-12.8). SETTING: Outpatient research at a tertiary hospital. PARTICIPANTS: Forty-two healthy, middle aged, and older athletes (initial age 64 +/- 1 year) and 47 healthy sedentary men of comparable age recruited for research studies. MEASUREMENTS: VO(2)max during a maximal treadmill test. RESULTS: At baseline, the cross-sectional rates of decline in VO(2)max with age (slope) were virtually identical in the athletes and sedentary men (-0.42 versus -0.43 mL(.)kg(-1.)min(-1.)year(-1)). At follow-up, the VO(2)max had declined by 11.9 +/- 1.1 mL(.)kg(-1.)min(-1) (22%) in the athletes, a crude average rate of -1.4 +/- 0.14 mL(.)kg(-1.)min(-1.)year(-1). By comparison, the VO(2)max declined by 4.4 +/- 0.6 mL(.)kg(-1.)min(-1) (14%) in the sedentary men, a crude average rate of change of -0.48 +/- 0.07 mL(.)kg(-1.)min(-1.)year(-1). Therefore, the observed absolute rate of longitudinal decline in VO(2)max in the athletes was triple that of the sedentary men (P = .001) and significantly greater than the decline predicted by their baseline cross-sectional data (P = .001). Post hoc analyses of the longitudinal data in the athletes based on the training regimens over the follow-up period demonstrated that the seven individuals who continued to train vigorously ("high training") had no significant decline in VO(2)max (0.28% change in VO(2)max per year). By contrast, the VO(2)max declined by 2.6% per year in the 'moderate training" group (N = 21), 4.6% per year in the "low training" group (N = 13), and 4.7% per year in the two individuals who developed cardiovascular disease. CONCLUSION: The longitudinal decline in VO(2)max in older male endurance athletes is highly dependent upon the continued magnitude of the training stimulus. The majority of the athletes reduced their training levels over time, resulting in longitudinal reductions in VO(2)max two to three times as large as those predicted by cross-sectional analyses or those observed longitudinally in their sedentary peers. C1 Baltimore Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Div Gerontol, Baltimore, MD 21201 USA. NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD USA. RP Katzel, LI (reprint author), Baltimore Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, BT-18-GR, Baltimore, MD 21201 USA. FU NCRR NIH HHS [M01 RR02719-06]; NIA NIH HHS [K24 AG00930, P01 AG04402] NR 30 TC 41 Z9 41 U1 0 U2 6 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2001 VL 49 IS 12 BP 1657 EP 1664 DI 10.1046/j.1532-5415.2001.t01-1-49276.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 505JH UT WOS:000172909300011 PM 11844000 ER PT J AU Hu, PF Seeman, TE Harris, TB Reuben, DB AF Hu, PF Seeman, TE Harris, TB Reuben, DB TI Is serum uric acid level associated with all-cause mortality in high-functioning older persons: MacArthur studies of successful aging? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE serum uric acid; mortality; inflammation; aged ID C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; RISK; INFLAMMATION; MARKERS; WOMEN; MEN AB OBJECTIVES: To explore the effect of serum uric acid level on subsequent all-cause mortality in high-functioning community-dwelling older persons. It is controversial whether high serum uric acid level is a true independent risk factor for cardiovascular and total mortality or the association is due to other confounding variables. Furthermore, it remains unclear whether the predictive value of uric acid level on mortality observed in younger cohorts can be extended to older people. DESIGN: Prospective cohort study. SETTING: A sample of community-dwelling older people. PARTICIPANTS: A cohort of 870 participants from the MacArthur Studies of Successful Aging. MEASUREMENTS: Baseline information was obtained for serum uric acid level, C-reactive protein (CRP), interleukin-6 (IL-6), prevalent medical conditions, and health behaviors. Crude and multivariate logistic regression analyses were used to examine the association between serum uric acid levels and 7-year all-cause mortality, while adjusting for potential confounders. RESULTS: In men, the multiply adjusted risk ratios for 7-year total mortality were 1.07 (95 % CI = 0.61-1.88) for the mid tertile of uric acid level and 1.24 (95% CI = 0.70-2.20) for the top tertile. In women, the multiply adjusted risk ratios were 0.58 (95% CI = 0.29-1.18) and 0.47 (95% CI = 0.22-0.99), for the mid and top tertiles respectively. CRP and IL-6 were important confounders in the relationship between serum uric acid and overall mortality. CONCLUSIONS: High serum uric acid level is not independently associated with increased total mortality in high-functioning older men and women. When evaluating the association between serum uric acid and mortality, the potential confounding effect of underlying inflammation and other risk factors must be considered. C1 Univ Calif Los Angeles, Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD USA. RP Hu, PF (reprint author), Univ Calif Los Angeles, Sch Med, Multicampus Program Geriatr Med & Gerontol, 10945 Le Conet Ave,Suite 2339, Los Angeles, CA 90095 USA. NR 18 TC 19 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2001 VL 49 IS 12 BP 1679 EP 1684 DI 10.1046/j.1532-5415.2001.t01-1-49279.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 505JH UT WOS:000172909300014 PM 11844003 ER PT J AU Fraser, L Locatis, C AF Fraser, L Locatis, C TI Effects of link annotations on search performance in layered and unlayered hierarchically organized information spaces SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE AND TECHNOLOGY LA English DT Article ID WORLD-WIDE-WEB; HYPERMEDIA; CYBERSPACE; RETRIEVAL; HYPERTEXT AB The effects of link annotations on user search performance in hypertext environments having deep (layered) and shallow link structures were investigated in this study. Four environments were tested-layered-annotated, layered-unannotated, shallow-annotated, and shallow-unannotated. A single document was divided into 48 sections, and layered and unlayered versions were created. Additional versions were created by adding annotations to the links in the layered and unlayered versions. Subjects were given three queries of varying difficulty and then asked to find the answers to the queries that were contained within the hypertext environment to which they were randomly assigned. Correspondence between the wording links and queries was used to define difficulty level. The results of the study confirmed previous research that shallow link structures are better than deep (layered) link structures. Annotations had virtually no effect on the search performance of the subjects. The subjects performed similarly in the annotated and unannotated environments, regardless of whether the link structures were shallow or deep. An analysis of question difficulty suggests that the wording in links has primacy over the wording in annotations in influencing user search behavior. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Fraser, L (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 21 TC 7 Z9 7 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1532-2882 J9 J AM SOC INF SCI TEC JI J. Am. Soc. Inf. Sci. Technol. PD DEC PY 2001 VL 52 IS 14 BP 1255 EP 1261 DI 10.1002/asi.1194 PG 7 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA 497HU UT WOS:000172450000008 ER PT J AU Yin, M Wheeler, MD Connor, HD Zhong, Z Bunzendahl, H Dikalova, A Samulski, RJ Schoonhoven, R Mason, RP Swenberg, JA Thurman, RG AF Yin, M Wheeler, MD Connor, HD Zhong, Z Bunzendahl, H Dikalova, A Samulski, RJ Schoonhoven, R Mason, RP Swenberg, JA Thurman, RG TI Cu/Zn-Superoxide dismutase gene attenuates ischemia-reperfusion injury in the rat kidney SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; FREE-RADICALS; ANTIOXIDANT ENZYMES; TISSUE-INJURY; IN-VIVO; ADHESION; TRANSPLANTATION; NEUTROPHILS; EXPRESSION; INVIVO AB Evidence has accumulated for a role of toxic oxygen radicals in the pathogenesis of ischemia-reperfusion injury in the kidney. The aim of this study was to evaluate the hypothesis that reducing postischemic renal injury is possible by delivery of the gene for the antioxidant enzyme superoxide dismutase (SOD). Female Sprague-Dawley rats received intravenous injections of recombinant adenovirus (1 x 10(9) pfu) containing the transgenes for Escherichia coli beta -galactosidase (Ad-LacZ as control) or human Cu/Zn-SOD (Ad-SOD). Three days later, renal ischemia was produced by cross-clamping the left renal vessels for 60 min. The right kidney was removed before reperfusion and processed for the transgene. Renal SOD protein and activity in rats given Ad-SOD was 2.5-fold hi her than from the animals receiving Ad-LacZ Urinary lactate dehydrogenase concentrations were elevated by ischemia-reperfusion in the Ad-LacZ group (1403 +/- 112 U/L), yet values were 50% lower in Ad-SOD-treated rats. Free radical production was elevated by ischemia-reperfusion but was significantly lower in SOD-treated animals. Importantly, on postischemic day 1, glomerular filtration rates were reduced to 0.21 ml/min per 100 in the Ad-LacZ group, whereas values remained significantly higher (0.39) in the Ad-SOD group. Two weeks after ischemia-reperfusion, inflammation, interstitial fibrosis, tubular atrophy and tissue levels of tumor necrosis factor alpha and interleukin-1 were significantly higher in the Ad-LacZ-treated than in Ad-SOD-treated rats. In conclusion, these results indicate that SOD expression can be increased by delivery of the sod gene to the kidney by intravenous injection and that sod gene transduction minimized ischemia-reperfusion-induced acute renal failure. C1 Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Surg, Chapel Hill, NC 27599 USA. Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Thurman, RG (reprint author), Univ N Carolina, Dept Pharmacol, CB 7365,Mary Ellen Jones Bldg, Chapel Hill, NC 27599 USA. NR 41 TC 54 Z9 55 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2001 VL 12 IS 12 BP 2691 EP 2700 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 496TM UT WOS:000172412900017 PM 11729238 ER PT J AU Lee, W Deter, RL Ebersole, JD Huang, R Blanckaert, K Romero, R AF Lee, W Deter, RL Ebersole, JD Huang, R Blanckaert, K Romero, R TI Birth weight prediction by three-dimensional ultrasonography - Fractional limb volume SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE birth weight prediction; three-dimensional ultrasonography; fetus; prenatal diagnosis ID INTRAUTERINE GROWTH-RETARDATION; FETAL WEIGHT; 3-DIMENSIONAL ULTRASONOGRAPHY; DIABETIC MOTHERS; BODY-COMPOSITION; GESTATIONAL-AGE; THIGH; ULTRASOUND; FORMULAS; INFANTS AB Objective. To introduce fractional limb volume as a new ultrasonographic parameter, validate reliability of fractional limb volume measurements, develop new birth weight prediction models, and examine their practical utility for estimating fetal weight during late pregnancy. Methods. Healthy late-third-trimester fetuses were prospectively scanned by two- and three-dimensional ultrasonography within 4 days-of delivery. Volume data sets were subsequently used to extract several standard ultrasonographic measurements. Fractional limb volumes of the upper arm and-thigh were based on 50% of diaphyseal bone length. Intraclass correlation was used to analyze interobserver and intraobserver reliability of fractional limb volume measurements. Several weight prediction models were developed by linear regression analysis. New prediction models were prospectively compared with the Hadlock formula in 30 healthy late-third-trimester fetuses. Results. One hundred fetuses were scanned at a mean SD menstrual age of 39.2 +/- 1.2 weeks, Intraclass correlation indicated a significant degree of interobserver and intraobserver reliability for fractional thigh volume. Fractional thigh volume (r = 0.86), fractional upper arm volume (r = 0.83), abdominal circumference (r = 0.83), and midthigh circumference (r = 0.82) were most highly correlated with birth weight. The best prediction model (abdominal circumference and fractional thigh volume) gave weight estimates that deviated from actual birth weight by -0.025% +/- 7.8%. For late-third-trimester fetuses, the Hadlock model yielded errors of 9.0% +/- 9.0%. Prospective testing confirmed superior performance of the new prediction model, which gave accuracy of 2.3% +/- 6.6% (Hadlock method, 8.4% +/- 8.7%). It correctly predicted 20 of 30 birth weights to within 5% of actual weight. By comparison, the Hadlock model predicted only 6 of 30 birth weights to within 5% of actual weight. Conclusions. A new birth weight prediction model, based on fractional thigh volume and abdominal circumference, is reliable during the late third trimester. It provides a means for including soft tissue evaluation for birth weight prediction. This rapid technique avoids technical limitations that currently hinder the practical implementation of three-dimensional ultrasonography for estimating birth weight. C1 William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48073 USA. William Beaumont Hosp, Div Biostat, Royal Oak, MI 48073 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Wayne State Univ, Perinatol Res Branch, NICHHD, Detroit, MI USA. RP Lee, W (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. NR 26 TC 64 Z9 68 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 2001 VL 20 IS 12 BP 1283 EP 1292 PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 498DL UT WOS:000172494500005 PM 11762540 ER PT J AU Brooks, JD Metter, EJ Chan, DW Sokoll, LJ Landis, P Nelson, WG Muller, D Andres, R Carter, HB AF Brooks, JD Metter, EJ Chan, DW Sokoll, LJ Landis, P Nelson, WG Muller, D Andres, R Carter, HB TI Plasma selenium level before diagnosis and the risk of prostate cancer development SO JOURNAL OF UROLOGY LA English DT Article DE prostate; neoplasm; selenium ID SUBSEQUENT RISK; SERUM SELENIUM; PREVENTION; SUPPLEMENTATION; METHYLATION; TRANSFERASE; TRIAL; GENE; MEN AB Purpose: Epidemiological studies and a randomized intervention trial suggest that the risk of prostate cancer may be reduced by selenium intake. We investigated whether plasma selenium level before diagnosis correlated with the risk of later developing prostate cancer. Materials and Methods: A case control study was performed on men from the Baltimore Longitudinal Study of Aging registry, including 52 with known prostate cancer and 96 age matched controls with no detectable prostatic disease. Plasma selenium was measured at an average time plus or minus standard deviation of 3.83 +/- 1.85 years before the diagnosis of prostate cancer by graphite furnace atomic absorption spectrophotometry. Adjusted odds ratio and 95% confidence interval were computed with logistic regression. Results: After correcting for years before diagnosis, body mass index, and smoking and alcohol use history, higher selenium was associated with a lower risk of prostate cancer. Compared with the lowest quartile of selenium (range 8.2 to 10.7 mug./dl.), the odds ratios of the second (10.8 to 11.8), third (11.9 to 13.2) and fourth (13.3 to 18.2) quartiles were 0.15 (95% confidence interval 0.05 to 0.50), 0.21 (0.07 to 0.68) and 0.24 (0.08 to 0.77, respectively, p =0.01). Furthermore, plasma selenium decreased significantly with patient age (p <0.001). Conclusions: Low plasma selenium is associated with a 4 to 5-fold increased risk of prostate cancer. These results support the hypothesis that supplemental selenium may reduce the risk of prostate cancer. Because plasma selenium decreases with patient age, supplementation may be particularly beneficial to older men. C1 Stanford Univ, Med Ctr, Dept Urol, Stanford, CA 94305 USA. NIA, Clin Invest Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Brooks, JD (reprint author), Stanford Univ, Med Ctr, Dept Urol, Stanford, CA 94305 USA. FU NCI NIH HHS [CA58236] NR 22 TC 159 Z9 167 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2001 VL 166 IS 6 BP 2034 EP 2038 DI 10.1016/S0022-5347(05)65500-0 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 491WW UT WOS:000172133900004 PM 11696701 ER PT J AU Wood, BJ Grippo, J Pavlovich, CP AF Wood, BJ Grippo, J Pavlovich, CP TI Percutaneous radio frequency ablation for hematuria SO JOURNAL OF UROLOGY LA English DT Article DE ablation; radiofrequency ablation; renal cell carcinoma; therapeutic embolization; hematuria ID RENAL-CELL CARCINOMA; RADIOFREQUENCY ABLATION; EMBOLIZATION C1 NCI, Special Procedure Diagnost Radiol Dept, Ctr Clin, Urol Oncol Branch,NIH, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), NCI, Special Procedure Diagnost Radiol Dept, Ctr Clin, Urol Oncol Branch,NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 3 TC 15 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2001 VL 166 IS 6 BP 2303 EP 2304 DI 10.1016/S0022-5347(05)65560-7 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 491WW UT WOS:000172133900080 PM 11696761 ER PT J AU Pautler, S Walther, MM AF Pautler, S Walther, MM TI Re: Management of diaphragmatic injury during laparoscopic nephrectomy SO JOURNAL OF UROLOGY LA English DT Letter C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Pautler, S (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2001 VL 166 IS 6 BP 2321 EP 2321 DI 10.1016/S0022-5347(05)65570-X PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 491WW UT WOS:000172133900090 PM 11696771 ER PT J AU Miller, DL AF Miller, DL TI Re: Renal artery embolization with diluted hot contrast medium: An experimental study SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter C1 Natl Naval Med Res Inst, Dept Radiol, Bethesda, MD 20889 USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Radiol & Nucl Med, Bethesda, MD 20814 USA. NCI, Med Oncol Clin Res Unit, Ctr Canc Res, Bethesda, MD 20892 USA. RP Miller, DL (reprint author), Natl Naval Med Res Inst, Dept Radiol, Bethesda, MD 20889 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2001 VL 12 IS 12 BP 1459 EP 1459 DI 10.1016/S1051-0443(07)61712-6 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 502BN UT WOS:000172724000018 PM 11742028 ER PT J AU Wedemeyer, H Mizukoshi, E Davis, AR Bennink, JR Rehermann, B AF Wedemeyer, H Mizukoshi, E Davis, AR Bennink, JR Rehermann, B TI Cross-reactivity between hepatitis C virus and influenza A virus determinant-specific cytotoxic T cells SO JOURNAL OF VIROLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; NUCLEOTIDE-SEQUENCES; HETEROLOGOUS VIRUSES; LYMPHOCYTE RESPONSE; PERIPHERAL-BLOOD; IMMUNE-RESPONSES; CTL RESPONSE; IN-VITRO; MEMORY; INFECTION AB The cellular immune response contributes to viral clearance as well as to liver injury in acute and chronic hepatitis C virus (HCV) infection. An immunodominant determinant frequently recognized by liver-infiltrating and circulating CD8(+) T cells of HCV-infected patients is the HCVNS3-1073 peptide CVNGVCWTV. Using a sensitive in vitro technique with HCV peptides and multiple cytokines, we were able to expand cytotoxic T cells specific for this determinant not only from the blood of 11 of 20 HCV-infected patients (55%) but also from the blood of 9 of 15 HCV-negative blood donors (60%), while a second HCV NS3 determinant was recognized only by HCV-infected patients and not by seronegative controls. The T-cell response of these healthy blood donors was mediated by memory T cells, which cross-reacted with a novel T-cell determinant of the A/PR/8/34 influenza A virus (IV) that is endogenously processed from the neuraminidase (NA) protein. Both the HCV NS3 and the IV NA peptide displayed a high degree of sequence homology, bound to the HLA-A2 molecule with high affinity, and were recognized by cytotoxic T lymphocytes with similar affinity (10(-8) M). Using the HLA-A2-transgenic mouse model, we then demonstrated directly that HCV-specific T cells could be induced in vivo by IV infection. Splenocytes harvested from IV-infected mice at the peak of the primary response (day 7 effector cells) or following complete recovery (day 21 memory cells) recognized the HCV NS3 peptide, lysed peptide-pulsed target cells, and produced gamma interferon. These results exemplify that host responses to an infectious agent are influenced by cross-reactive memory cells induced by past exposure to heterologous viruses, which could have important consequences for vaccine development. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. NIAID, Viral Immunol Sect, Viral Dis Lab, NIH, Bethesda, MD 20982 USA. RP Rehermann, B (reprint author), NIDDK, Liver Dis Sect, NIH, Bldg 10,Room 9B16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. NR 50 TC 163 Z9 165 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2001 VL 75 IS 23 BP 11392 EP 11400 DI 10.1128/JVI.75.23.11392-11400.2001 PG 9 WC Virology SC Virology GA 490CP UT WOS:000172033100015 PM 11689620 ER PT J AU Hel, Z Nacsa, J Kelsall, B Tsai, WP Letvin, N Parks, RW Tryniszewska, E Picker, L Lewis, MG Edghill-Smith, Y Moniuszko, M Pal, R Stevceva, L Altman, JD Allen, TM Watkins, D Torres, JV Berzofsky, JA Belyakov, IM Strober, W Franchini, G AF Hel, Z Nacsa, J Kelsall, B Tsai, WP Letvin, N Parks, RW Tryniszewska, E Picker, L Lewis, MG Edghill-Smith, Y Moniuszko, M Pal, R Stevceva, L Altman, JD Allen, TM Watkins, D Torres, JV Berzofsky, JA Belyakov, IM Strober, W Franchini, G TI Impairment of Gag-specific CD8(+) T-cell function in mucosal and systemic compartments of simian immunodeficiency virus mac251-and simian-human immunodeficiency virus KU2-infected macaques SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTED RHESUS-MONKEYS; PRIMARY IMMUNE-RESPONSE; MHC CLASS-I; LYMPHOCYTE RESPONSE; DISEASE PROGRESSION; GAMMA-INTERFERON; HIV-1 INFECTION; LAMINA PROPRIA; VACCINIA VIRUS; PLASMA VIREMIA AB The identification of several simian immunodeficiency virus mac251 (SIVmac251) cytotoxic T-lymphocyte epitopes recognized by CD8(+) T cells of infected rhesus macaques carrying the Mamu-A*01 molecule and the use of peptide-major histocompatibility complex tetrameric complexes enable the study of the frequency, breadth, functionality, and distribution of virus-specific CD8(+) T cells in the body. To begin to address these issues, we have performed a pilot study to measure the virus-specific CD8(+) and CD4(+) T-cell response in the blood, lymph nodes, spleen, and gastrointestinal lymphoid tissues of eight Mamu-A*01-positive macaques, six of those infected with SIVmac251 and two infected with the pathogenic simian-human immunodeficiency virus KU2. We focused on the analysis of the response to peptide p11C, C-M (Gag 181), since it was predominant in most tissues of all macaques. Five macaques restricted viral replication effectively, whereas the remaining three failed to control viremia and experienced a progressive loss of CD4(+) T cells. The frequency of the Gag 181 (p11C, C-->M) immunodominant response varied among different tissues of the same animal and in the same tissues from different animals. We found that the functionality of this virus-specific CD8(+) T-cell population could not be assumed based on the ability to specifically bind to the Gag 181 tetramer, particularly in the mucosal tissues of some of the macaques infected by SIVmac251 that were progressing to disease. Overall, the functionality of CD8(+) tetramer-binding T cells in tissues assessed by either measurement of cytolytic activity or the ability of these cells to produce gamma interferon or tumor necrosis factor alpha was low and was even lower in the mucosal tissue than in blood or spleen of some SIVmac251-infected animals that failed to control viremia. The data obtained in this pilot study lead to the hypothesis that disease progression may be associated with loss of virus-specific CD8(+) T-cell function. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. NIAID, Lab Clin Invest, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. So Res Inst, Frederick, MD 21701 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Adv Biosci Labs Inc, Kensington, MD 20895 USA. Emory Univ, Vaccine Ctr Yerkes, Atlanta, GA 30329 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. Univ Calif Davis, Sch Med, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. RI Allen, Todd/F-5473-2011; OI Hel, Zdenek/0000-0002-4923-4794 FU NIAID NIH HHS [AI-65312, R21 AI065312] NR 47 TC 60 Z9 62 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2001 VL 75 IS 23 BP 11483 EP 11495 DI 10.1128/JVI.75.23.11483-11495.2001 PG 13 WC Virology SC Virology GA 490CP UT WOS:000172033100025 PM 11689630 ER PT J AU Mayne, M Cheadle, C Soldan, SS Cermelli, C Yamano, Y Akhyani, N Nagel, JE Taub, DD Becker, KG Jacobson, S AF Mayne, M Cheadle, C Soldan, SS Cermelli, C Yamano, Y Akhyani, N Nagel, JE Taub, DD Becker, KG Jacobson, S TI Gene expression profile of herpesvirus-infected T cells obtained using immunomicroarrays: Induction of proinflammatory mechanisms SO JOURNAL OF VIROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; MULTIPLE-SCLEROSIS; CELLULAR RECEPTOR; HHV-6 VARIANTS; LYMPHOCYTES-T; BRAIN-TISSUE; HUMAN-HERPESVIRUS-6; VIRUS; INTERLEUKIN-18; IDENTIFICATION AB Herpesvirus infections can frequently lead to acute inflammation, yet the mechanisms regulating this event remain poorly understood. In order to determine some of the immunological mechanisms regulated by human herpesvirus infections, we studied the gene expression profile of lymphocytes infected with human herpesvirus 6 (HHV-6) by using a novel immunomicroarray. Our nylon-based immunomicroarray contained more than 1,150 immune response-related genes and was highly consistent between experiments. Experimentally, we found that independently of the HHV-6 strain used to infect T cells, multiple proinflammatory genes were increased and anti-inflammatory genes were decreased at the mRNA and protein levels. HHV-6 strains A and B increased expression of the genes for interleukin-18 (IL-18), the IL-2 receptor, members of the tumor necrosis factor alpha superfamily receptors, mitogen-activated protein kinase, and Janus kinase signaling proteins. As reported previously, CD4 protein levels were also increased significantly. Specific type 2 cytokines, including IL-10, its receptor, and IL-14, were downregulated by HHV-6 infection and, interestingly, amyloid precursor proteins and type 1 and 2 presenilins. Thus, T cells respond to HHV-6 infection by inducing a type I immune response that may play a significant role in the development and progression of diseases associated with HHV-6, including pediatric, hematologic, transplant, and neurologic disorders. C1 Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB R2H 2A6, Canada. NIA, Microarray Unit, NIH, Baltimore, MD 21224 USA. NINCDS, Viral Immunol Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Genet, Inst Biomed Sci, Washington, DC USA. Univ Modena & Reggio Emilia, Dept Hyg Microbiol & Biostat, Modena, Italy. RP Mayne, M (reprint author), Univ Manitoba, St Boniface Hosp Res Ctr R4050, Dept Pharmacol & Therapeut, Winnipeg, MB R2H 2A6, Canada. RI Cermelli, Claudio/L-1501-2016; OI Cermelli, Claudio/0000-0003-3396-0000; Becker, Kevin/0000-0002-6794-6656 NR 49 TC 51 Z9 53 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2001 VL 75 IS 23 BP 11641 EP 11650 DI 10.1128/JVI.75.23.11641-11650.2001 PG 10 WC Virology SC Virology GA 490CP UT WOS:000172033100041 PM 11689646 ER PT J AU Ward, BM Moss, B AF Ward, BM Moss, B TI Vaccinia virus intracellular movement is associated with microtubules and independent of actin tails SO JOURNAL OF VIROLOGY LA English DT Article ID EXTRACELLULAR ENVELOPED VIRUS; CONTAINING MICROVILLI; GOLGI NETWORK; CELL-FUSION; PROTEIN; MEMBRANE; GENE; TRANSPORT; PARTICLES; MOTILITY AB Two mechanisms have been proposed for the intracellular movement of enveloped vaccinia virus virions: rapid actin polymerization and microtubule association. The first mechanism is used by the intracellular pathogens Listeria and Shigella, and the second is used by cellular vesicles transiting from the Golgi network to the plasma membrane. To distinguish between these models, two recombinant vaccinia viruses that express the B5R membrane protein fused to enhanced green fluorescent protein (GFP) were constructed. One had Tyr(112) and Tyr(132) of the A36R membrane protein, which are required for phosphorylation and the nucleation of actin tails, conservatively changed to Phe residues; the other had the A36R open reading frame deleted. Although the Tyr mutant was impaired in Tyr phosphorylation and actin tail formation, digital video and time-lapse confocal microscopy demonstrated that virion movement from the juxtanuclear region to the periphery was saltatory with maximal speeds of >2 mum/s and was inhibited by the microtubule-depolymerizing drug nocodazole. Moreover, this actin tail-independent movement was indistinguishable from that of a control virus with an unmutated A36R gene and closely resembled the movement of vesicles on microtubules. However, in the absence of actin tails, the Tyr mutant did not induce the formation of motile, virus-tipped microvilli and had a reduced ability to spread from cell to cell. The deletion mutant was more severely impaired, suggesting that the A36R protein has additional roles. Optical sections of unpermeabilized, B5R antibody-stained cells that expressed GFP-actin and were infected with wild-type vaccinia virus revealed that all actin tails were associated with virions on the cell surface. We concluded that the intracellular movement of intracellular enveloped virions occurs on microtubules and that the motile actin tails enhance extracellular virus spread to neighboring cells. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 39 TC 111 Z9 116 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2001 VL 75 IS 23 BP 11651 EP 11663 DI 10.1128/JVI.75.23.11651-11663.2001 PG 13 WC Virology SC Virology GA 490CP UT WOS:000172033100042 PM 11689647 ER PT J AU Iyer, LM Aravind, L Koonin, EV AF Iyer, LM Aravind, L Koonin, EV TI Common origin of four diverse families of large eukaryotic DNA viruses SO JOURNAL OF VIROLOGY LA English DT Article ID SWINE FEVER VIRUS; HOLLIDAY JUNCTION RESOLVASES; MULTIPLE SEQUENCE ALIGNMENT; VACCINIA VIRUS; GENOME SEQUENCE; REVERSE-TRANSCRIPTASE; CELLULAR GENES; FIBROMA VIRUS; PBCV-1 GENOME; PSI-BLAST AB Comparative analysis of the protein sequences encoded in the genomes of three families of large DNA viruses that replicate, completely or partly, in the cytoplasm of eukaryotic cells (poxviruses, asfarviruses, and iridoviruses) and phycodnaviruses that replicate in the nucleus reveals 9 genes that are shared by all of these viruses and 22 more genes that are present in at least three of the four compared viral families. Although orthologous proteins from different viral families typically show weak sequence similarity, because of which some of them have not been identified previously, at least five of the conserved genes appear to be synapomorphies (shared derived characters) that unite these four viral families, to the exclusion of all other known viruses and cellular life forms. Cladistic analysis with the genes shared by at least two viral families as evolutionary characters supports the monophyly of poxviruses, asfarviruses, iridoviruses, and phycodnaviruses. The results of genome comparison allow a tentative reconstruction of the ancestral viral genome and suggest that the common ancestor of all of these viral families was a nucleocytoplasmic virus with an icosahedral capsid, which encoded complex systems for DNA replication and transcription, a redox protein involved in disulfide bond formation in virion membrane proteins, and probably inhibitors of apoptosis. The conservation of the disulfide-oxidoreductase, a major capsid protein, and two virion membrane proteins indicates that the odd-shaped virions of poxviruses have evolved from the more common icosahedral virion seen in asfarviruses, iridoviruses, and phycodnaviruses. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 76 TC 309 Z9 316 U1 2 U2 26 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2001 VL 75 IS 23 BP 11720 EP 11734 DI 10.1128/JVI.75.23.11720-11734.2001 PG 15 WC Virology SC Virology GA 490CP UT WOS:000172033100048 PM 11689653 ER PT J AU Gao, HQ Sarafianos, SG Arnold, E Hughes, SH AF Gao, HQ Sarafianos, SG Arnold, E Hughes, SH TI RNase H cleavage of the 5 ' end of the human immunodeficiency virus type 1 genome SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; DOUBLE-STRANDED DNA; ANGSTROM RESOLUTION; POLYMERASE; MUTAGENESIS; MUTATIONS; DOMAIN AB The synthesis of retroviral DNA is initiated near the 5' end of the RNA. DNA synthesis is transferred from the 5' end to the 3' end of viral RNA in an RNase H-dependent step. In the case of human immunodeficiency virus type 1 (HIV-1) (and certain other retroviruses that have complex secondary structures at the ends of the viral RNA), there is the possibility that DNA synthesis can lead to a self-priming event that would block viral replication. The extent of RNase H cleavage must be sufficient to allow the strand transfer reaction to occur, but not so extensive that self-priming occurs. We have used a series of model RNA substrates, with and without a 5' cap, to investigate the rules governing RNase H cleavage at the 5' end of the HIV-1 genome. These in vitro RNase H cleavage reactions produce an RNA fragment of the size needed to block self-priming but still allow strand transfer. The cleavages seen in vitro can be understood in light of the structure of HIV-1 reverse transcriptase in a complex with an RNA/DNA substrate. C1 NCI, HIV Drug Resistance Program, FCRDC, Frederick, MD 21702 USA. NCI, ABL Basic Res Program, Frederick, MD 21702 USA. Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, FCRDC, POB B,Bldg 539,Room 130A, Frederick, MD 21702 USA. OI Sarafianos, Stefan G/0000-0002-5840-154X FU PHS HHS [A1 09578, A1 27690] NR 20 TC 5 Z9 6 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2001 VL 75 IS 23 BP 11874 EP 11880 DI 10.1128/JVI.75.23.11874-11880.2001 PG 7 WC Virology SC Virology GA 490CP UT WOS:000172033100064 PM 11689669 ER PT J AU Betts, MR Ambrozak, DR Douek, DC Bonhoeffer, S Brenchley, JM Casazza, JP Koup, RA Picker, LJ AF Betts, MR Ambrozak, DR Douek, DC Bonhoeffer, S Brenchley, JM Casazza, JP Koup, RA Picker, LJ TI Analysis of total human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T-cell responses: Relationship to viral load in untreated HIV infection SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM NONPROGRESSORS; COMBINATION ANTIRETROVIRAL THERAPY; LYMPHOCYTE RESPONSE; DISEASE PROGRESSION; TYPE-1 INFECTION; ESCAPE VARIANTS; CLASS-I; VIREMIA; ASSOCIATION; AIDS AB Human immunodeficiency virus (HIV)-specific T-cell responses are thought to play a key role in viral load decline during primary infection and in determining the subsequent viral load set point. The requirements for this effect are unknown, partly because comprehensive analysis of total HIV-specific CD4(+) and CD8(+) T-cell responses to all HIV-encoded epitopes has not been accomplished. To assess these responses, we used cytokine How cytometry and overlapping peptide pools encompassing all products of the HIV-1 genome to study total HIV-specific T-cell responses in 23 highly active antiretroviral therapy naive HIV-infected patients. HIV-specific CD8(+) T-cell responses were detectable in all patients, ranging between 1.6 and 18.4% of total CD8(+) T cells. HIV-specific CD4(+) T-cell responses were present in 21 of 23 patients, although the responses were lower (0.2 to 2.94%). Contrary to previous reports, a positive correlation was identified between the plasma viral load and the total HIV-, Env-, and Nef-specific CD8(+) T-cell frequency. No correlation was found either between viral load and total or Gag-specific CD4(+) T-cell response or between the frequency of HIV-specific CD4(+) and CD8(+) T cells. These results suggest that overall frequencies of HIV-specific T cells are not the sole determinant of immune-mediated protection in HIV-infection. C1 Oregon Hlth Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97201 USA. ETH Zurich, CH-8092 Zurich, Switzerland. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. RP Betts, MR (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 3614B,40 Convent Dr,MSC 3022, Bethesda, MD 20892 USA. RI Bonhoeffer, Sebastian/A-2735-2008 OI Bonhoeffer, Sebastian/0000-0001-8052-3925 FU NIAID NIH HHS [AI 47606, AI 35522, AI 43638, AI 47603, R01 AI035522, R01 AI047603, R01 AI047606, R37 AI035522, U01 AI043638] NR 46 TC 545 Z9 560 U1 2 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2001 VL 75 IS 24 BP 11983 EP 11991 DI 10.1128/JVI.75.24.11983-11991.2001 PG 9 WC Virology SC Virology GA 495RZ UT WOS:000172355300005 PM 11711588 ER PT J AU Beer, BE Foley, BT Kuiken, CL Tooze, Z Goeken, RM Brown, CR Hu, JJ St Claire, M Korber, BT Hirsch, VM AF Beer, BE Foley, BT Kuiken, CL Tooze, Z Goeken, RM Brown, CR Hu, JJ St Claire, M Korber, BT Hirsch, VM TI Characterization of novel simian immunodeficiency viruses from red-capped mangabeys from Nigeria (SIVrcmNG409 and-NG411) SO JOURNAL OF VIROLOGY LA English DT Article ID AFRICAN-GREEN MONKEYS; WILD-CAPTURED CHIMPANZEE; NATURAL INFECTION; HIGHLY DIVERGENT; MOLECULAR CHARACTERIZATION; SEROEPIDEMIOLOGIC SURVEY; CERCOPITHECUS-AETHIOPS; PRIMATE LENTIVIRUS; TANTALUS MONKEYS; GRIVET MONKEYS AB Two novel simian immunodeficiency virus (SIV) strains from wild-caught red-capped mangabeys (Cercocebus torquatus torquatus) from Nigeria were characterized. Sequence analysis of the fully sequenced SIV strain rcmNG411 (SIVrcmNG411) and gag and pol sequence of SIVrcmNG409 revealed that they were genetically most closely related to the recently characterized SIVrcm from Gabon (SIVrcmGB1). Thus, red-capped mangabeys from distant geographic locations harbor a common lineage of SIV. SIVrcmNG411 carried a vpx gene in addition to vpr, suggesting a common evolutionary ancestor with SIVsm (from sooty mangabeys). However, SIVrcm was only marginally closer to SIVsm in that region than to any of the other lentiviruses. SIVrcm showed the highest similarity in pol with SIVdrl, isolated from a drill, a primate that is phylogenetically distinct from mangabey monkeys, and clustered with other primate lentiviruses (primarily SIVcpz [from chimpanzees] and SIVagmSab [from African green monkeys]) discordantly in different regions of the genome, suggesting a history of recombination. Despite the genetic relationship to SIVcpz in the pol gene, SIVrcmNG411 did not replicate in chimpanzee peripheral blood mononuclear cells (PBMC), although two other viruses unrelated to SIVcpz, SIVmndGB1 (from mandrills) and SIVlhoest (from L'Hoest monkeys), were able to grow in chimpanzee PBMC. The CCR5 24-bp deletion previously described in red-capped mangabeys from Gabon was also observed in Nigerian red-capped mangabeys, and SIVrcmNG411, like SIVrcmGB1, used CCR2B and STRL33 as coreceptors for virus entry. SIVrcm, SIVsm, SIVmndGB1, and all four SIvlhoest isolates but not SfVsun (from sun-tailed monkeys) replicated efficiently in human PBMC, suggesting that the ability to infect the human host can vary within one lineage. C1 NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. Los Alamos Natl Lab, Grp T10, Los Alamos, NM 87545 USA. Bioqual Inc, Rockville, MD 20850 USA. Cercopan, Calabar, CRS, Nigeria. RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. OI Foley, Brian/0000-0002-1086-0296; Korber, Bette/0000-0002-2026-5757 NR 47 TC 80 Z9 80 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2001 VL 75 IS 24 BP 12014 EP 12027 DI 10.1128/JVI.75.24.12014-12027.2001 PG 14 WC Virology SC Virology GA 495RZ UT WOS:000172355300009 PM 11711592 ER PT J AU Satoi, J Murata, K Lechmann, M Manickan, E Zhang, ZS Wedemeyer, H Rehermann, B Liang, TJ AF Satoi, J Murata, K Lechmann, M Manickan, E Zhang, ZS Wedemeyer, H Rehermann, B Liang, TJ TI Genetic immunization of wild-type and hepatitis C virus transgenic mice reveals a hierarchy of cellular immune response and tolerance induction against hepatitis C virus structural proteins SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; DNA-BASED IMMUNIZATION; CELLS; EXPRESSION; ANTIGEN; INFECTION; LIVER; HLA-A2.1; EPITOPES; BREAKING AB To study the effect of genetic immunization on transgenic expression of hepatitis C virus (HCV) proteins, we evaluated the immunological response of HCV transgenic mice to HCV expression plasmids. FVB/n transgenic mice expressing HCV structural proteins (core, E1, and E2) and wild-type (WT) FVB/n mice were immunized intramuscularly with plasmids expressing core (pHCVcore) or core/E1/E2 (pHCVSt). After immunization, HCV-specific Immoral and cellular immune response was studied. Both WT and transgenic mice immunized with either HCV construct produced antibodies and exhibited T-cell proliferative responses against core or envelope. In WT mice immunized with pHCVSt, cytotoxic T-lymphocyte (CTL) activities were detected against E2 but not against core or E1, whereas strong CTL activities against core could be detected in WT mice immunized with pHCVcore. In pHCVSt-immunized, transgenic mice, CTL activities against the core or envelope were completely absent, but core-specific CTL activities could be detected in pHCVcore-immunized transgenic mice. A similar pattern of immune responses was also observed in other mouse strains, including a transgenic line expressing human HLA-A2.1 molecules (AAD mice). Despite the presence of a peripheral cellular immunity against HCV, no liver pathology or lymphocytic infiltrate was observed in these transgenic mice. Our study suggests a hierarchy of CTL response against the HCV structural proteins (E2 > core > E1) in vivo when the proteins are expressed as a polyprotein. The HCV transgenic mice can be induced by DNA immunization to generate anti-HCV antibodies and anticore CTLs. However, they are tolerant at the CTL level against the E2 protein despite DNA immunization. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr,Rm 9B16, Bethesda, MD 20892 USA. NR 39 TC 27 Z9 30 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2001 VL 75 IS 24 BP 12121 EP 12127 DI 10.1128/JVI.75.24.12121-12127.2001 PG 7 WC Virology SC Virology GA 495RZ UT WOS:000172355300020 PM 11711603 ER PT J AU Bukreyev, A Belyakov, IM Berzofsky, JA Murphy, BR Collins, PL AF Bukreyev, A Belyakov, IM Berzofsky, JA Murphy, BR Collins, PL TI Granulocyte-macrophage colony-stimulating factor expressed by recombinant respiratory syncytial virus attenuates viral replication and increases the level of pulmonary antigen-presenting cells SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSCRIPTION ELONGATION-FACTOR; FORMALIN-INACTIVATED RSV; CYTOTOXIC T-LYMPHOCYTES; BALB/C MICE; IMMUNE-RESPONSES; IMMUNIZATION; CHALLENGE; VACCINE; INFECTION; CYTOKINES AB An obstacle to developing a vaccine against human respiratory syncytial virus (RSV) is that natural infection typically does not confer solid immunity to reinfection. To investigate methods to augment the immune response, recombinant RSV (rRSV) was constructed that expresses murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) from a transcription cassette inserted into the G-F intergenic region. Replication of rRSV/mGM-CSF in the upper and lower respiratory tracts of BALB/c mice was reduced 23- to 74- and 5- to 588-fold, respectively, compared to that of the parental rRSV. Despite this strong attenuation of replication, the level of RSV-specific serum antibodies induced by rRSV/mGM-CSF was comparable to, or marginally higher than, that of the parental rRSV. The induction of RSV-specific CD8(+) cytotoxic T cells was moderately reduced during the initial infection, which might be a consequence of reduced antigen expression. Mice infected with rRSV/mGM-CSF had elevated levels of pulmonary mRNA for gamma interferon (IFN-gamma) and interleukin 12 (IL-12) p40 compared to animals infected by wild-type rRSV. Elevated synthesis of IFN-gamma could account for the restriction of RSV replication, as was observed previously with an IFN-gamma -expressing rRSV. The accumulation of total pulmonary mononuclear cells and total CD4(+) T lymphocytes was accelerated in animals infected with rRSV/mGM-CSF compared to that in animals infected with the control virus, and the level of IFN-gamma -positive or IL-4-positive pulmonary CD4(+) cells was elevated approximately twofold. The number of pulmonary lymphoid and myeloid dendritic cells and macrophages was increased up to fourfold in mice infected with rRSV/mGM-CSF compared to those infected with the parental rRSV, and the mean expression of major histocompatibility complex class II molecules, a marker of activation, was significantly increased in the two subsets of dendritic cells. Enhanced antigen presentation likely accounts for the maintenance of a strong antibody response despite reduced viral replication and would be a desirable property for a live attenuated rRSV vaccine. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD USA. RP Bukreyev, A (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 7,Room 100,7 Ctr MSC 0720, Bethesda, MD 20892 USA. FU NIAID NIH HHS [Z01 AI000099] NR 37 TC 51 Z9 51 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2001 VL 75 IS 24 BP 12128 EP 12140 DI 10.1128/JVI.75.24.12128-12140.2001 PG 13 WC Virology SC Virology GA 495RZ UT WOS:000172355300021 PM 11711604 ER PT J AU Jinno-Oue, A Oue, M Ruscetti, SK AF Jinno-Oue, A Oue, M Ruscetti, SK TI A unique heparin-binding domain in the envelope protein of the neuropathogenic PVC-211 murine leukemia virus may contribute to its brain capillary endothelial cell tropism SO JOURNAL OF VIROLOGY LA English DT Article ID SULFATE PROTEOGLYCANS; ANTITHROMBIN-III; SITES; POLYSACCHARIDES; LOCALIZATION; TRANSDUCTION; SURFACE; VARIANT AB Previous studies from our laboratory demonstrated that PVC-211 murine leukemia virus (MuLV), a neuropathogenic variant of Friend MuLV (F-MuLV), had undergone genetic changes which allowed it to efficiently infect rat brain capillary endothelial cells (BCEC) in vivo and in vitro. Two amino acid changes from F-MuLV in the putative receptor binding domain (RBD) of the envelope surface protein of PVC-211 MuLV (Glu-116 to Gly and Glu-129 to Lys) were shown to be sufficient for conferring BCEC tropism on PVC-211 MuLV. Recent examination of the unique RBD of PVC-211 MuLV revealed that the substitution of Lys for Gin at position 129 created a new heparin-binding domain that overlapped a heparin-binding domain common to ecotropic MuLVs. In this study we used heparin-Sepharose columns to demonstrate that PVC-211 MuLV, but not F-MuLV, can bind efficiently to heparin and that one or both of the amino acids in the RBD of PVC-211 MuLV that are associated with BCEC tropism are responsible. We further showed that heparin can enhance or inhibit MuLV infection and that the mode of action is dependent on heparin concentration, sulfation of heparin, and the affinity of the virus for heparin. Our results suggest that the amino acid changes that occurred in the envelope surface protein of PVC-211 MuLV may allow the virus to bind strongly to the surface of BCEC via heparin-like molecules, increasing the probability that the virus will bind to its cell surface receptor and efficiently infect these cells. C1 NCI, Basic Res Lab, Frederick, MD 21702 USA. RP Ruscetti, SK (reprint author), NCI, Basic Res Lab, Bldg 469,Room 205, Frederick, MD 21702 USA. NR 30 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2001 VL 75 IS 24 BP 12439 EP 12445 DI 10.1128/JVI.75.24.12439-12445.2001 PG 7 WC Virology SC Virology GA 495RZ UT WOS:000172355300051 PM 11711634 ER PT J AU Ainsworth, BE Anderson, LA Becker, DM Blalock, SJ Brown, DR Brownson, RC Brownstein, N Cornell, CE Devellis, BM Finnegan, LP Folger, S Fulton, JE Groff, JY Herman, C Jones, D Keyserling, TC Koffman, DM Lewis, C Masse, LC McKeown, RE Orenstein, D Spadaro, AJ AF Ainsworth, BE Anderson, LA Becker, DM Blalock, SJ Brown, DR Brownson, RC Brownstein, N Cornell, CE Devellis, BM Finnegan, LP Folger, S Fulton, JE Groff, JY Herman, C Jones, D Keyserling, TC Koffman, DM Lewis, C Masse, LC McKeown, RE Orenstein, D Spadaro, AJ CA Womens Hlth Initiative Comm Preven TI Community Prevention Study: Contributions to women's health and prevention research SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID AFRICAN-AMERICAN WOMEN; CULTURAL ACTIVITY PARTICIPATION; PHYSICAL-ACTIVITY PATTERNS; MINORITY WOMEN; UNITED-STATES; OLDER; WALKING; INTERVENTIONS; MANAGEMENT; PROGRAM C1 Natl Ctr Chron Dis Prevent & Hlth Promot, Prevent Res Ctr Off, Div Adult & Community Hlth, Atlanta, GA 30341 USA. Univ S Carolina, Columbia, SC 29208 USA. Univ Pacific, Stockton, CA 95211 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21224 USA. Univ Alabama, Birmingham, AL 35294 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. Univ New Mexico, Albuquerque, NM 87131 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Texas, Houston, TX 77030 USA. RP Anderson, LA (reprint author), Natl Ctr Chron Dis Prevent & Hlth Promot, Prevent Res Ctr Off, Div Adult & Community Hlth, MS-45,4770 Buford Highway NE, Atlanta, GA 30341 USA. NR 58 TC 3 Z9 3 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD DEC PY 2001 VL 10 IS 10 BP 913 EP 920 DI 10.1089/152460901317193495 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 509FZ UT WOS:000173136800001 PM 11788102 ER PT J AU Deng, JP Kohda, Y Chiao, H Wang, YQ Hu, XH Hewitt, SM Miyaji, T McLeroy, P Nibhanupudy, B Li, SJ Star, RA AF Deng, JP Kohda, Y Chiao, H Wang, YQ Hu, XH Hewitt, SM Miyaji, T McLeroy, P Nibhanupudy, B Li, SJ Star, RA TI Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury SO KIDNEY INTERNATIONAL LA English DT Article DE ischemia-reperfusion injury; inflammation; leukocytes; renal transplantation; nitric oxide synthase; alpha-melanocyte stimulating hormone ID MELANOCYTE-STIMULATING HORMONE; NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; REPERFUSION INJURY; ISCHEMIA/REPERFUSION INJURY; RAT-KIDNEY; NEUTROPHIL INFILTRATION; INDUCED NEPHROTOXICITY; ACCELERATES RECOVERY; GRAFT FUNCTION AB Background. Acute renal failure (ARF) is caused by ischemic and nephrotoxic insults acting alone or in combination. Anti-inflammatory agents have been shown to decrease renal ischemia-reperfusion and cisplatin-induced injury and leukocyte infiltration. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that inhibits inflammatory and cytotoxic pathways implicated in acute renal injury. Therefore, we sought to determine if IL-10 inhibits acute renal injury. Methods. The effects of IL-10 were studied in mice following cisplatin administration and bilateral renal ischemia-reperfusion, in a rat model of renal transplantation, and in cultured mouse cortical tubule cells. Results. IL-10 significantly decreased renal injury following cisplatin administration and following renal ischemia/reperfusion. Delay of IL-10 treatment for one hour after cisplatin also significantly inhibited renal damage. IL-10 and alpha -melanocyte stimulating hormone (alpha -MSH) increased recovery following transplantation of a kidney subjected to warm ischemia. To explore the mechanism of action of IL-10, its effects were measured on mediators of leukocyte trafficking and inducible nitric oxide synthase (NOS-II). IL-10 inhibited cisplatin and ischemia-induced increases in mRNA for tumor necrosis factor-a (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), and NOS-II. IL-10 also inhibited staining for markers of apoptosis and cell cycle activity following cisplatin administration, and nitric oxide production in cultured mouse cortical tubules. Conclusions. IL-10 protects against renal ischemic and cisplatin-induced injury. IL-10 may act, in part, by inhibiting the maladaptive activation of genes that cause leukocyte activation and adhesion, and induction of iNOS. C1 NIH, NIDDK, Renal Diagnost & Therapeut Unit, Bethesda, MD 20892 USA. NIDDK, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Surg, Dallas, TX 75235 USA. RP Star, RA (reprint author), NIH, NIDDK, Renal Diagnost & Therapeut Unit, 10 Ctr Dr,Room 3N108, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788 FU NIDDK NIH HHS [DK-45923, DK-54396] NR 69 TC 220 Z9 234 U1 1 U2 8 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2001 VL 60 IS 6 BP 2118 EP 2128 DI 10.1046/j.1523-1755.2001.00043.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 493RN UT WOS:000172237400006 PM 11737586 ER PT J AU Kaysen, GA Dubin, JA Muller, HG Mitch, WE Levin, NW AF Kaysen, GA Dubin, JA Muller, HG Mitch, WE Levin, NW CA HEMO Grp TI Levels of alpha 1 acid glycoprotein and ceruloplasmin predict future albumin levels in hemodialysis patients SO KIDNEY INTERNATIONAL LA English DT Article DE inflammation; hypoalbuminemia; hemodialysis; C reactive protein; acute phase proteins ID C-REACTIVE PROTEIN; MESSENGER RIBONUCLEIC-ACID; ACUTE-PHASE RESPONSE; RAT-LIVER; CARDIOVASCULAR-DISEASE; PERITONEAL-DIALYSIS; NEPHROTIC PATIENTS; SERUM-ALBUMIN; RISK; INFLAMMATION AB Background. Serum albumin concentration predicts mortality in hemodialysis (HD) patients. While serum albumin concentration correlates with serum concentration of C-reactive protein (CRP) and is dependent upon CRP in multiple regression models in cross sectional studies, CRP does not predict future albumin levels, possibly because CRP changes rapidly, yielding large month-to-month variability in CRP. If inflammation causes rather than is simply associated with hypoalbuminemia, then changes in the levels of acute phase proteins should precede changes in serum albumin concentration. Methods. The levels of long-lived positive and negative acute-phase proteins (APPs) (C-reactive protein, ceruloplasmin, alpha1 acid glycoprotein, transferrin and albumin) were measured longitudinally in 64 HD patients and a regression model was constructed to predict future albumin levels. Normalized protein catabolic rate (nPCR) was measured monthly. The number of repeated measurements ranged from 9 to 39 in each patient (median 22 and a mean of 23 measurements). To construct a model that would predict serum albumin concentration at any time j, values of all longitudinally measured APPs, positive and negative at any time j - 1, approximately 30 days prior to time j,: were used. Other demographic factors (such as, race, access type, and cause of renal failure) also were incorporated into the model. Results. The model with the best fit for predicting serum albumin at time j included albumin, ceruloplasmin, and al acid glycoprotein measured at time j - 1. The only demographic variable with subsequent predictive value was diabetes. Conclusions. The finding that changes in the concentration of the long lived APPs measured one month earlier are associated with predictable changes in the future concentration of serum albumin suggest that changes in inflammation are likely to be causal in determining serum albumin concentration in hemodialysis patients. C1 Univ Calif Davis, Dept Internal Med, Div Nephrol, Davis, CA 95616 USA. Univ Calif Davis, Res Serv, VANCHCS, Davis, CA USA. Univ Calif Davis, Dept Stat, Davis, CA USA. Emory Univ, Dept Med, Div Nephrol, Atlanta, GA USA. Renal Res Inst, New York, NY USA. HEMO Study Grp, NIDDK, Bethesda, MD USA. Yale Univ, Div Biostat, New Haven, CT USA. RP Kaysen, GA (reprint author), Univ Calif Davis, Dept Internal Med, Div Nephrol, TB 136, Davis, CA 95616 USA. FU NCRR NIH HHS [M01-RR00039]; NIDDK NIH HHS [R01 DK 50777] NR 36 TC 25 Z9 27 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2001 VL 60 IS 6 BP 2360 EP 2366 DI 10.1046/j.1523-1755.2001.00052.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 493RN UT WOS:000172237400031 PM 11737611 ER PT J AU Periyasamy, SM Chen, J Cooney, D Carter, P Omran, E Tian, J Priyadarshi, S Bagrov, A Fedorova, O Malhotra, D Xie, ZJ Shapiro, JI AF Periyasamy, SM Chen, J Cooney, D Carter, P Omran, E Tian, J Priyadarshi, S Bagrov, A Fedorova, O Malhotra, D Xie, ZJ Shapiro, JI TI Effects of uremic serum on isolated cardiac myocyte calcium cycling and contractile function SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the American-Society-of-Nephrology CY OCT 11-16, 2000 CL TORONTO, CANADA SP Amer Soc Nephrol DE sodium pump; potassium; ATPase; ventricular dysfunction; myocardial calcium; diastolic dysfunction; Na,K-ATPase; uremic cardiomyopathy ID ERYTHROCYTE SODIUM-TRANSPORT; K-ATPASE INHIBITOR; VENTRICULAR MYOCYTES; ENDOGENOUS OUABAIN; DIASTOLIC FUNCTION; NA+/K+-ATPASE; RELAXATION; HYPERTENSION; DIALYSIS; DISEASE AB Background. Diastolic dysfunction occurs in patients with chronic renal failure. Moreover, serum from uremic patients contains one or more inhibitors of the plasmalemmal Na,K-ATPase (sodium pump). We hypothesized that a circulating substance present in uremic sera contributes to both sodium pump inhibition and diastolic dysfunction. Methods. Serum samples were obtained from six patients with chronic renal failure and diastolic dysfunction. Results. Their serum samples caused marked inhibition of Na,K-ATPase purified from dog kidney at all concentrations studied (all P < 0.01) and also impaired ouabain-sensitive rubidium uptake by myocytes isolated from Sprague-Dawley rats (P < 0.01). These cardiac myocytes were studied for their contractile function with video-edge detection and calcium metabolism with indo-1 fluorescence spectroscopy after exposure to these uremic sera. These uremic sera caused increases in myocyte fractional shortening (P < 0.01) as well as an increase in the time constant of relengthening (P < 0.01). Examining the calcium transient, the time constant for calcium recovery was also increased (P < 0.01). Exposure of these cells to sera from age- and sex-matched healthy subjects did not result in significant changes in contraction or calcium cycling. Extracts of uremic serum samples inhibited isolated Na,K-ATPase whereas extracts of normal serum samples did not. The effect of uremic serum extracts on contractile function and calcium cycling were quite similar to that of intact serum or the addition of ouabain. Co-incubation of uremic serum extract with an antibody fragment directed against digoxin markedly attenuated the inhibition of Na,K-ATPase activity and completely prevented any effects on calcium cycling or contractile function. Conclusion. These data show that one or more substances are present in uremic sera that acutely cause increased force of contraction and impaired recovery of cardiac myocyte calcium concentration as well as impaired relaxation. As these effects are similar to that seen with ouabain and can be prevented by co-incubation with an antibody fragment to digitalis, which also attenuates the sodium pump inhibitory effect, we suggest that this (these) substance(s) circulating in uremic sera and inhibiting the sodium pump also causes the acute diastolic dysfunction seen in our system. C1 Med Coll Ohio, Dept Med, Toledo, OH 43614 USA. Med Coll Ohio, Dept Pharmacol, Toledo, OH 43614 USA. NIA, Natl Inst Hlth, Bethesda, MD USA. RP Shapiro, JI (reprint author), Med Coll Ohio, Dept Med, 3120 Glendale Ave, Toledo, OH 43614 USA. FU NHLBI NIH HHS [HL57144] NR 39 TC 24 Z9 25 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2001 VL 60 IS 6 BP 2367 EP 2376 DI 10.1046/j.1523-1755.2001.00053.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 493RN UT WOS:000172237400032 PM 11737612 ER PT J AU Elizegi, E Pino, I Vicent, S Blanco, D Saffiotti, U Montuenga, LM AF Elizegi, E Pino, I Vicent, S Blanco, D Saffiotti, U Montuenga, LM TI Hyperplasia of alveolar neuroendocrine cells in rat lung carcinogenesis by silica with selective expression of proadrenomedullin-derived peptides and amidating enzymes SO LABORATORY INVESTIGATION LA English DT Article ID GENE-RELATED PEPTIDE; BOMBESIN-LIKE PEPTIDES; NEUROEPITHELIAL BODIES; MURINE MACROPHAGES; EPITHELIAL-CELLS; ENDOCRINE-CELLS; CHROMOGRANIN-A; PULMONARY; ADRENOMEDULLIN; CALCITONIN AB Pulmonary neuroendocrine (NE) cells are found as clusters called neuroepithelial bodies (NEBs) or as single cells scattered in the respiratory epithelium. They express a variety of bioactive peptides, and they are thought to be the origin of NE lung tumors. Proadrenomedullin N-terminal 20 peptide (PAMP) is a peptide derived from the same precursor as adrenomedullin (AM). AM and PAMP are C-terminally amidated during their processing by a well-characterized amidating enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). We explored AM, PAMP, and PAM expression as markers for NE hyperplasia in three rodent species (Fischer 344 rats, Syrian golden hamsters, and A/J mice) after a single intratracheal instillation of crystalline silica (quartz), which was previously found to induce different reactions in the three species. Rats developed a marked silicosis, with alveolar and bronchiolar hyperplasia and formation of peripheral lung epithelial tumors. Mice developed a moderate degree of silicosis, but not epithelial hyperplasia or tumors. Hamsters showed dust-storage lesions, but not silicosis or tumors. NE cells were immunolabeled for calcitonin gene-related peptide (CGRP), AM, PAMP, and PAM in serial sections of each lung. The numbers of positive NEBs per lung area and positive cells per NEB were quantified. A marked hyperplastic reaction in the NEBs of silica treated rats occurred only in alveolar NEBs, but not in bronchiolar NEBs. From Month 11 onwards, there were marked differences in the number of alveolar NEBs per section and in the number of cells per alveolar NEB immunoreactive for CGRP. No hyperplastic NE cell reaction was observed in silica-treated mice and hamsters. Significant PAMP and PAM expression was seen only in rat hyperplastic alveolar and in bronchiolar NEBs from Month 11 onwards. In E18, rat fetal lung NEBs were found to be strongly positive for PAMP and PAM. C1 Univ Navarra, Dept Histol & Pathol, Navarra 31008, Spain. NCI, Bethesda, MD 20892 USA. RP Montuenga, LM (reprint author), Univ Navarra, Dept Histol & Pathol, Edif Invest,C Irunlarrea 1, Navarra 31008, Spain. NR 55 TC 13 Z9 13 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 2001 VL 81 IS 12 BP 1627 EP 1638 PG 12 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 505JP UT WOS:000172909900004 PM 11742033 ER PT J AU Curtis, DJ Dougherty, L Bodine, DM AF Curtis, DJ Dougherty, L Bodine, DM TI NF-Y regulates LIF-induced transcription of the signaling adaptor SKAP55R in myeloid cells SO LEUKEMIA LA English DT Article DE SKAP55R; NF-Y; IL-6; LIF; promoter; myeloid ID PHASE RESPONSE FACTOR; DNA-BINDING PROTEINS; MOLECULAR-CLONING; NUCLEAR FACTOR; GROWTH ARREST; GENE PROMOTER; MYD GENES; KAPPA-B; INTERLEUKIN-6; GP130 AB Previously, we have shown that interleukin-6 (IL-6) or leukemia inhibitory factor (LIF)-induced differentiation of the myeloid cell line M1 was associated with a rapid increase in the level of mRNA encoding the signaling adaptor protein, SKAP55R. Furthermore, enforced over-expression of SKAP55R in primary bone marrow cells inhibited colony growth. In this study, we have identified the cis-acting elements that control SKAP55R transcription in myeloid cells. The 980 bp genomic sequence upstream of the transcriptional start site was cloned into a GFP reporter vector for transient (293 cells) or stable (Ml cells) transfection assays. This region contained cis-acting elements necessary for transcriptional activity in unstimulated 293 cells (10-fold higher levels than the control vector) or unstimulated M1 cells (two-fold higher levels). Significant LIF-induced transcription was observed in M1 (3.4-fold induction, P < 0.001), but not 293 cells. Deletion reporter constructs defined a promoter region (-317/-137) essential for the transcriptional activity in M1 cells. This region contained a CCAAT element recently implicated in IL-6/LIF-induced transcriptional regulation of junB in M1 cells. Mutation of the CCAAT element (-250/-246) significantly reduced both basal and LIF-induced transcription (P < 0.01). Electrophoretic mobility shift assays demonstrated that NF-Y bound to the CCAAT element of both SKAP55R and junB. These results suggest NF-Y binding may be a common mechanism of IL-6/LIF-regulated transcription in myeloid cells. C1 NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. Walter & Eliza Hall Inst Med Res, Canc & Haematol Div, Melbourne, Vic 3050, Australia. RP Curtis, DJ (reprint author), Royal Melbourne Hosp, Res Labs, Parkville, Vic 3050, Australia. NR 42 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 2001 VL 15 IS 12 BP 1932 EP 1940 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 499VV UT WOS:000172591900017 PM 11753615 ER PT J AU Epperson, DE Nakamura, R Saunthararajah, Y Melenhorst, J Barrett, AJ AF Epperson, DE Nakamura, R Saunthararajah, Y Melenhorst, J Barrett, AJ TI Oligoclonal T cell expansion in myelodysplastic syndrome: evidence for an autoimmune process SO LEUKEMIA RESEARCH LA English DT Article DE Myelodysplastic syndrome; T cell repertoire; T cell receptor; spectratyping; immunosuppressive treatment ID POLYMERASE CHAIN-REACTION; APLASTIC-ANEMIA; BONE-MARROW; ANTITHYMOCYTE GLOBULIN; MEDIATED INHIBITION; PATHOPHYSIOLOGY; REPERTOIRE; APOPTOSIS; SUBSETS; CD4(+) AB There is accumulating evidence that the marrow-failure of myelodysplastic syndrome (MDS) is immune-mediated. We studied patients with MDS to look for oligoclonal or clonal. expansion in T cells indicative of an autoimmune process. We used a PCR-based technique (spectratyping) to characterize the T cell repertoire in MDS (n = 15; 9 RA, 4 RARS, 2 RAEB) and compared results with age-matched healthy donors (n = 20) and transfusion-dependent (TD) patients with hemoglobinopathy (n = 5). We found a significantly higher number of skewed V beta profiles in the MDS patients compared with controls. In peripheral blood T cells, 60/345 V beta profiles examined were skewed in MDS patients compared with 3/115 V beta profiles in TD controls (P < 0.0001), and 58/460 V beta profiles in age-matched controls (P = 0.05). A study of J beta region within the skewed V beta profiles revealed preferential usage of J beta 2.1 in MDS in contrast with a wide distribution over the entire J beta spectrum in controls, consistent with non-random T cell clonal. expansion in MDS. These findings provide further evidence that T cell mediated immune processes are a feature of MDS. Published by Elsevier Science Ltd. C1 NHLBI, Hematol Branch, Bone Marrow Transplant Unit, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, Bone Marrow Transplant Unit, NIH, Bldg 10,2000 Rochville Pike,Rm 7C 103, Bethesda, MD 20892 USA. NR 23 TC 80 Z9 85 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD DEC PY 2001 VL 25 IS 12 BP 1075 EP 1083 DI 10.1016/S0145-2126(01)00083-2 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 492QU UT WOS:000172179700006 PM 11684279 ER PT J AU Mark, SD Katki, H AF Mark, SD Katki, H TI Influence function based variance estimation and missing data issues in case-cohort studies SO LIFETIME DATA ANALYSIS LA English DT Article DE case-cohort; confounding; Cox proportional hazards model; influence function; missing covariates; nested case-control; stratified sample; robust variance; weighted estimating equations ID PROPORTIONAL HAZARDS MODEL; REGRESSION; DESIGNS AB Recognizing that the efficiency in relative risk estimation for the Cox proportional hazards model is largely constrained by the total number of cases, Prentice (1986) proposed the case-cohort design in which covariates are treasured on all cases and on a random sample of the cohort. Subsequent to Prentice, other methods of estimation and sampling have been proposed for these designs. We formalize an approach to variance estimation suggested by Barlow (1994), and derive a robust variance estimator based on the influence function. We consider the applicability of the variance estimator to all the proposed case-cohort estimators, and derive the influence function when known sampling probabilities in the estimators are replaced by observed sampling fractions. We discuss the modifications required when cases are missing covariate information. The missingness may occur by chance, and be completely at random; or may occur as part of the sampling design, and depend upon other observed covariates. We provide an adaptation of S-plus code that allows estimating influence function variances in the presence of such missing covariates. Using examples from our current case-cohort studies on esophageal and gastric cancer, we illustrate how our results our useful in solving design and analytic issues that arise in practice. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Mark, SD (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Katki, Hormuzd/B-4003-2015 NR 21 TC 13 Z9 13 U1 0 U2 7 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD DEC PY 2001 VL 7 IS 4 BP 331 EP 344 DI 10.1023/A:1012533130596 PG 14 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 498XZ UT WOS:000172540000001 PM 11763542 ER PT J AU David-Beabes, GL London, SJ AF David-Beabes, GL London, SJ TI Genetic polymorphism of XRCC1 and lung cancer risk among African-Americans and Caucasians SO LUNG CANCER LA English DT Article DE XRCC1; polymorphism; susceptibility; lung cancer ID LOS-ANGELES-COUNTY; DNA-REPAIR GENES; FREQUENCY AB Reduced DNA repair capacity may influence susceptibility to lung cancer. XRCC1 plays an important role in base excision repair and in rejoining DNA strand breaks. In the XRCC1 gene. two common polymorphisms induce amino acid changes in codon 194 and codon 399 and correlate with levels of genotoxic damage. We examined the relation between these two polymorphisms and susceptibility to lung cancer among 334 incident cases and 704 population controls of African-American and Caucasian ethnicity in Los Angeles County, California. African-American and Caucasian subjects smoking 20+ cigarettes/day and carrying at least one copy of the codon 194 variant allele were at somewhat decreased risk of lung cancer (African-Americans OR = 0.2, 95%, CI 0.1-0.9; Caucasians OR = 0.5, 95% CI 0.2-1.1). Similarly, for the codon 399 polymorphism, there was some evidence of a decreased risk for the homozygous variant genotype among heavier smokers (African-Americans OR = 0.3, 95% CI 0.0-2.9; Caucasians OR= 0.4, 95% CI 0.2-1.0). These results suggest that genetic variation in XRCC1 might contribute to lung cancer and may interact with the amount smoked. C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP London, SJ (reprint author), NIEHS, Pulm Pathobiol Lab, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. OI London, Stephanie/0000-0003-4911-5290 FU NIEHS NIH HHS [Z01-ES-49017] NR 19 TC 109 Z9 113 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD DEC PY 2001 VL 34 IS 3 BP 333 EP 339 DI 10.1016/S0169-5002(01)00256-2 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 512EB UT WOS:000173307200003 PM 11714530 ER PT J AU Zhou, J Nong, L Wloch, M Cantor, A Mulshine, JL Tockman, MS AF Zhou, J Nong, L Wloch, M Cantor, A Mulshine, JL Tockman, MS TI Expression of early lung cancer detection marker: hnRNP-A2/B1 and its relation to microsatellite alteration in non-small cell lung cancer SO LUNG CANCER LA English DT Article DE early detection marker; microsatellite instability; loss of heterozygosity; hnRNP-A2/B1 ID NUCLEAR RIBONUCLEOPROTEIN A2/B1; GENETIC ALTERATIONS; INSTABILITY; CARCINOMA; HETEROZYGOSITY; MUTATIONS; TUMOR; IDENTIFICATION; OVEREXPRESSION; ABNORMALITIES AB We have reported that a mouse monoclonal antibody, 703134, which recognizes heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) can frequently detect lung cancer in exfoliated sputum epithelial cells 1-2 years earlier than routine chest X-ray or sputum cytomorphology. We along with. others have shown that microsatellite alteration (MA) at selected loci can be recognized in sputum cells prior to clinical lung cancer. The present study was undertaken to determine how frequently the expression of hnRNP-A2/B1 message is associated with neoplastic clonal expansion as shown by MA in 41 cases of non-small cell lung cancer (NSCLC). We used Northern blotting to evaluate hnRNP-A2/B1 mRNA expression in lung tumor and remote noninvolved lung. We evaluated microsatellite instability (i.e. shifts; MI) or loss of heterozygosity (LOH) with a panel of 13 microsatellite markers at loci identified previously as susceptible in NSCLC. Of the 41 tumors, 25 (61%) over-expressed hnRNP-A2/B1 and 33 (80%) demonstrated MA in at least one of 13 loci (58% in at least two loci). The association between MA (one locus) and the overexpression of hnRNP-A2/B1 is statistically significant (P=0.0082), and those lung tumors with MA at two or more loci were significantly more likely to over-express hnRNP-A2/B1 mRNA (P=0.004). MA of loci on 3p were the only MA statistically associated with hnRNP-A2/B1 message overexpression (P=0.001). We conclude that lung tumor cells undergoing clonal expansion frequently upregulate hnRNP-A2/B1. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ S Florida, Mol Screening Lab, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33613 USA. Univ S Florida, Tissue Procurement Sect, H Lee Moffitt Canc Ctr & Res Inst, Pathol Core Facil, Tampa, FL 33613 USA. NCI, Dept Cell & Canc Biol, Intervent Sect, Med Branch,Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Tockman, MS (reprint author), Univ S Florida, Mol Screening Lab, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33613 USA. FU NCI NIH HHS [U01 CA84973, P50 CA58184] NR 41 TC 35 Z9 50 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD DEC PY 2001 VL 34 IS 3 BP 341 EP 350 DI 10.1016/S0169-5002(01)00254-9 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 512EB UT WOS:000173307200004 PM 11714531 ER PT J AU Hussain, SP Hofseth, LJ Harris, CC AF Hussain, SP Hofseth, LJ Harris, CC TI Tumor suppressor genes: at the crossroads of molecular carcinogenesis, molecular epidemiology and human risk assessment SO LUNG CANCER LA English DT Article; Proceedings Paper CT International Conference on Non-Small Cell Lung Cancer: Standards and New Trends in Diagnosis and Therapy CY OCT 05-07, 2001 CL MED ACAD BIALYSTOK, BIALYSTOK, POLAND HO MED ACAD BIALYSTOK DE p53 mutations; AFB(1); nitric oxide; cigarette smoking; HBV ID NITRIC-OXIDE SYNTHASE; HEPATITIS-B-VIRUS; ENDOTHELIAL GROWTH-FACTOR; HUMAN HEPATOCELLULAR-CARCINOMA; NUCLEOTIDE EXCISION-REPAIR; HUMAN COLORECTAL-CANCER; HUMAN BREAST-CANCER; P53 MUTATION LOAD; LUNG-CANCER; X-PROTEIN AB The p53 tumor suppressor gene is mutated in about half of all human cancer cases. The p53 protein modulates multiple cellular functions, such as gene transcription, DNA synthesis and repair, cell cycle arrest, senescence, and apoptosis. Mutations in the p53 gene can abrogate these functions and may lead to genetic instability and progress to cancer. The molecular archeology of the p53 mutation spectrum generates hypotheses concerning the etiology and molecular pathogenesis of cancer. The spectrum of somatic mutations in the p53 gene implicates environmental carcinogens and endogenous processes in the etiology of human cancer. The presence of a characteristic p53 mutation also can manifest a molecular link between exposure to a particular carcinogen and a specific type of human cancer, e.g. aflatoxin B(1) (AFB(1)) exposure and codon 249(scr) mutations in hepatocellular carcinoma, ultraviolet (UV) exposure and CC to TT tandem mutations in skin cancer; and cigarette smoke and the prevalence of G to T transversions in lung cancer. Although several different exogenous carcinogens have been shown to selectively target p53, evidence supporting the endogenous insult of p53 from oxyradical and nitrogen-oxyradicals is accumulating. p53 mutations can be a biomarker of carcinogen effect. Determining the characteristic p53 mutation load in nontumorous tissue, with a highly sensitive mutation assay, can indicate a specific carcinogen exposure and also may help in identifying individuals at an increased risk of cancer. Published by Elsevier Science Ireland Ltd. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 2CO5,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov NR 119 TC 43 Z9 44 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD DEC PY 2001 VL 34 SU 2 BP S7 EP S15 DI 10.1016/S0169-5002(01)00339-7 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 506KP UT WOS:000172970000002 PM 11720736 ER PT J AU Kaye, FJ AF Kaye, FJ TI Molecular biology of lung cancer SO LUNG CANCER LA English DT Article; Proceedings Paper CT International Conference on Non-Small Cell Lung Cancer: Standards and New Trends in Diagnosis and Therapy CY OCT 05-07, 2001 CL MED ACAD BIALYSTOK, BIALYSTOK, POLAND HO MED ACAD BIALYSTOK DE small cell lung cancer; non-small cell lung cancer; tumor suppressor gene; genetics ID TUMOR-SUPPRESSOR LOCUS; CARCINOMA CELL-LINES; P53 GENE-MUTATIONS; LARGE-T-ANTIGEN; L-MYC GENE; C-MYC; N-MYC; MALIGNANT MESOTHELIOMA; PHOSPHATASE-ACTIVITY; TELOMERASE ACTIVITY AB Lung cancer develops slowly over many years from the sequential accumulation of gene alterations in susceptible pulmonary cells. The global epidemic of tobacco addiction has accelerated the incidence of lung cancer and has now focused increased attention on this disease worldwide. This review will briefly outline some of the tumor suppressor gene pathways that are known or suspected to play an important role in the development of this deadly malignancy. Published by Elsevier Science Ireland Ltd. C1 NCI, Genet Branch, Ctr Canc Res, Navy Oncol, Bethesda, MD 20889 USA. Naval Hosp, Natl Naval Med Ctr, Bethesda, MD 20889 USA. RP Kaye, FJ (reprint author), NCI, Genet Branch, Ctr Canc Res, Navy Oncol, Bldg 8,Room 5105, Bethesda, MD 20889 USA. RI kaye, frederic/E-2437-2011 NR 87 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD DEC PY 2001 VL 34 SU 2 BP S35 EP S41 DI 10.1016/S0169-5002(01)00342-7 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 506KP UT WOS:000172970000005 PM 11720739 ER PT J AU Mulshine, JL Hong, S Martinez, A Tauler, J Avis, I Tockman, MS De Luca, LM Placke, ME Cuttitta, F AF Mulshine, JL Hong, S Martinez, A Tauler, J Avis, I Tockman, MS De Luca, LM Placke, ME Cuttitta, F TI Moving to the routine management of pre symptomatic lung cancer SO LUNG CANCER LA English DT Article; Proceedings Paper CT International Conference on Non-Small Cell Lung Cancer: Standards and New Trends in Diagnosis and Therapy CY OCT 05-07, 2001 CL MED ACAD BIALYSTOK, BIALYSTOK, POLAND HO MED ACAD BIALYSTOK DE lung cancer; prevention screening; chemoprevention; aerosols ID ACTION PROJECT; PREVENTION; CHEMOPREVENTION; ISOTRETINOIN; CARCINOMA; RETINOIDS; DESIGN; ACID; TIME AB Lung cancer is the world's leading cause of cancer death. Since progress in the treatment of this cancer has been exceedingly slow, the upswing in tobacco consumption in many sectors becomes even more tragic. One area for cautious optimism is the recent pilot reports of improved early lung cancer detection using new spiral CT techniques from institutions in Japan and New York. The prospect of improved early detection in a major cancer raises a number of public health concerns and highlights the importance of critical validation of this proposed new tool. From experience with early detection-based management of other cancers, it is evident that the entire process of detection. case validation, intervention, monitoring and public education needs to be carefully developed. The International Association for the Study of Lung Cancer has worked with the National Cancer Institute over the last decade to nurture interest and expertise in conducting; population-based management of early lung cancer. A distillation of this process up to the current time is reviewed in this manuscript. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Intervent Sect, Ctr Canc Res, NIH, Rockville, MD 20850 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33612 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Differentiat & Cell Regulat Sect, NIH, Bethesda, MD 20892 USA. Battelle Pulm Therapeut, Columbus, OH USA. RP Mulshine, JL (reprint author), NCI, Intervent Sect, Ctr Canc Res, NIH, Rockville, MD 20850 USA. EM mulshinej@bprb.nci.nih.gov NR 32 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD DEC PY 2001 VL 34 SU 2 BP S1 EP S5 DI 10.1016/S0169-5002(01)00401-9 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 506KP UT WOS:000172970000001 PM 11720735 ER PT J AU Zajac-Kaye, M AF Zajac-Kaye, M TI Myc oncogene: a key component in cell cycle regulation and its implication for lung cancer SO LUNG CANCER LA English DT Article; Proceedings Paper CT International Conference on Non-Small Cell Lung Cancer: Standards and New Trends in Diagnosis and Therapy CY OCT 05-07, 2001 CL MED ACAD BIALYSTOK, BIALYSTOK, POLAND HO MED ACAD BIALYSTOK DE Myc; lung cancer; cell cycle; pRB pathway; cyclins; cdk; cdk1 ID C-MYC; EXPRESSION; GENE; KINASE; GROWTH; INDUCTION; P27; IDENTIFICATION; TRANSCRIPTION; AMPLIFICATION AB The Myc gene family which includes c-Myc, N-Myc and L-Myc, are transcription factors that play a role in cell proliferation, apoptosis and in the development of human tumors. Myc amplification and overexpression has been detected in lung cancer of different histologic subtypes. Although the mechanism of Myc action is not yet fully understood, Myc has been proposed to play a role in growth control and cell cycle progression by stimulating and repressing the expression of key cell cycle regulators. This review will focus on the role of Myc in stimulating the G1/S transition of the cell cycle by regulating the levels and activity of cyclins, cyclin dependent kinases (cdk), cdk inhibitors and the pRb-binding transcription factor E2F. It is proposed that both the overexpression of Myc and the deregulation of the pRB/E2F pathway promotes the G1 to S transition in parallel by activating cyclinE/cdk2 complexes in lung cancer cells. Published by Elsevier Science Ireland Ltd. C1 Naval Hosp, Ctr Canc Res, NCI, NIH,Navy Oncol Branch, Bethesda, MD 20889 USA. RP Zajac-Kaye, M (reprint author), Naval Hosp, Ctr Canc Res, NCI, NIH,Navy Oncol Branch, Bldg 8,R 5101, Bethesda, MD 20889 USA. NR 33 TC 60 Z9 62 U1 0 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD DEC PY 2001 VL 34 SU 2 BP S43 EP S46 DI 10.1016/S0169-5002(01)00343-9 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 506KP UT WOS:000172970000006 PM 11720740 ER PT J AU Gedat, E Schreiber, A Findenegg, GH Shenderovich, I Limbach, HH Buntkowsky, G AF Gedat, E Schreiber, A Findenegg, GH Shenderovich, I Limbach, HH Buntkowsky, G TI Stray field gradient NMR reveals effects of hydrogen bonding on diffusion coefficients of pyridine in mesoporous silica SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE NMR; stray field gradient NMR; hydrogen bonding; diffusion; pyridine; mesoporous silica; MCM-41 ID ANOMALOUS SEGMENT DIFFUSION; ANISOTROPIC SELF-DIFFUSION; MOLECULAR-SIEVES; WATER-MOLECULES; PORE STRUCTURE; POLYMER MELTS; FRINGE-FIELD; RABBIT LENS; H-1-NMR; MCM-41 AB The diffusion of pyridine confined in mesoporous silica MCM-41 (d(pore) = 3.3 nm) was studied with stray field gradient (SFG) NMR diffusometry as a function of the filling factor of the mesopores at room temperature, employing a laboratory-built SFG setup. The translational diffusion of pyridine in MCM-41 is found to be anisotropic and the diffusion parallel to the pores' cylinder axes is much faster than that perpendicular to them. The parallel diffusion coefficient depends strongly on the filling level of the guest liquid inside the pores. For a filling level of 25%, which corresponds approximately to a monomolecular layer of pyridine molecules hydrogen bonded to surface-SiOH groups, a parallel diffusion coefficient of D-parallel to = 1.0 X 10(-9) m(2) s(-1) is found, which is slower than the diffusion coefficient of the bulk liquid (D = 1.6 X 10(-9) m(2) s(-1)). For higher filling factors the parallel diffusion coefficient increases and at a filling factor of 85% a diffusion coefficient of D-parallel to = 6.8 X 10(-9) m(2) s(-1) is reached. The perpendicular diffusion coefficient of D-perpendicular to = 3.7 +/- 2.0 X 10(-11) m(2) s(-1) is independent of the filling factor. Employing additional N-15 MAS data for the pyridine inside the mesopores, a microscopic model of the diffusion is proposed, which depends on the exchange of the slowly diffusing hydrogen-bonded surface pyridine molecules with fast-diffusing free pyridine molecules inside the pores. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 Tech Univ Berlin, Iwan N Stranski Inst Phys & Theoret Chem, D-10623 Berlin, Germany. Free Univ Berlin, Inst Chem, D-14195 Berlin, Germany. RP Buntkowsky, G (reprint author), NIDDK, Phys Chem Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Shenderovich, Ilya/C-4301-2011; Buntkowsky, Gerd/B-3206-2010; Limbach, Hans-Heinrich/G-8858-2011 OI Shenderovich, Ilya/0000-0001-6713-9080; Buntkowsky, Gerd/0000-0003-1304-9762; Limbach, Hans-Heinrich/0000-0002-2084-6359 NR 40 TC 8 Z9 8 U1 1 U2 9 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD DEC PY 2001 VL 39 SI SI BP S149 EP S157 DI 10.1002/mrc.932 PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 495NK UT WOS:000172347100019 ER PT J AU Constantinides, CD Rogers, J Herzka, DA Boada, FE Bolar, D Kraitchman, D Gillen, J Bottomley, PA AF Constantinides, CD Rogers, J Herzka, DA Boada, FE Bolar, D Kraitchman, D Gillen, J Bottomley, PA TI Superparamagnetic iron oxide MION as a contrast agent for sodium MRI in myocardial infarction SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE contrast agent; paramagnetism; sodium; myocardial infarction ID MAGNETITE AB An intravascular iron-based contrast agent was used as a sodium (Na-23) MRI T-2 relaxant in an effort to suppress the blood signal from the ventricular cavities in normal and infarcted canine myocardium in Vivo. Na-23 MRI signal decreases in blood were attributed to decreases in the fast (T-2f) and slow (T-2s) transverse relaxation components, which were quantified as a function of dose and MRI echo time (TE). In VIVO Na-23 MRI signal decreases up to 65% were noted in ventricular blood when imaging under dose and TE conditions of 10 mg/kg body weight and 5 ms, respectively. Contrast injection followed by subsequent Na-23 MRI in canine myocardial infarction led to a clear delineation of the location of the injured tissue, as identified by postmortem triphenyltetrazolium chloride staining, and to an improvement in the contrast-to-noise ratio between the blood in the ventricular chamber and the infarcted tissue that was as high as 3.3-fold in the postcontrast images in comparison to the precontrast images. (C) 2001 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. Adv Magnet Inc, Cambridge, MA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15261 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. RP Constantinides, CD (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,Bldg 10B1D,Room 416, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [R01 HL61695] NR 16 TC 9 Z9 9 U1 0 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2001 VL 46 IS 6 BP 1164 EP 1168 DI 10.1002/mrm.1313 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 497BM UT WOS:000172432900017 PM 11746583 ER PT J AU Sato, N Kobayashi, H Hiraga, A Saga, T Togashi, K Konishi, J Brechbiel, MW AF Sato, N Kobayashi, H Hiraga, A Saga, T Togashi, K Konishi, J Brechbiel, MW TI Pharmacokinetics and enhancement patterns of macromolecular MR contrast agents with various sizes of polyamidoamine dendrimer cores SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance imaging; pharmacokinetics; macromolecule; MR contrast agent; dendrimer ID DISULFIDE-STABILIZED FV; BLOCKS RENAL UPTAKE; GD-DTPA; ANGIOGRAPHY; MEDIA AB Four macromolecular contrast agents are synthesized to visualize small vessels by MRI using generation-3 (G3D), -4 (G4D), -5 (G5D), and -6 (G6D) polyamidoamine dendrimers conjugated to chelated gadolinium (Gd). The pharmacokinetics, enhancement patterns, and the ability of these constructs to visualize fine vessels is evaluated by dynamic MRI in relationship to their size. Gd-G6D and -G5D exhibit a prolonged high vascular (ventricular) signal intensity (SI) with high ventricle-to-organ SI ratios. The initial high vascular SI with Gd-G4D decreases to a value as low as that obtained with Gid-G3D and Gd-dimeglumine-diethylenetriaminepentaacetic acid (Gd-DTPA). Gd-G5D, -G4D, and -G3D show high renal Isis, and Gd-DTPA prominently enhances the skin. Gd-G6D and -G5D present fine vasculature significantly more clearly than Gd-G3D and -DTPA (P < 0.005). As the molecular size increases, the excretion of the Gd-153-conjugates is retarded. In conclusion, Gd-G6D and -G5D are retained in the blood and present fine vessels with high quality and detail, and should be adequate for visualizing small tumor vasculature. (C) 2001 Wiley-Liss, Inc. C1 Kyoto Univ, Grad Sch Med, Chaired Dept Diagnost & Intervent Radiol, Hitachi Med Co,Sakyo Ku, Kyoto 6068507, Japan. Kyoto Univ, Dept Nucl Med & Diagnost Imaging, Kyoto 6110011, Japan. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), Kyoto Univ, Grad Sch Med, Chaired Dept Diagnost & Intervent Radiol, Hitachi Med Co,Sakyo Ku, 54 Kawaharacho,Shogoin, Kyoto 6068507, Japan. NR 16 TC 89 Z9 95 U1 2 U2 6 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2001 VL 46 IS 6 BP 1169 EP 1173 DI 10.1002/mrm.1314 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 497BM UT WOS:000172432900018 PM 11746584 ER PT J AU Brannan, CI Disteche, CM Park, LS Copeland, NG Jenkins, NA AF Brannan, CI Disteche, CM Park, LS Copeland, NG Jenkins, NA TI Autosomal telomere exchange results in the rapid amplification and dispersion of Csf2ra genes in wild-derived mice SO MAMMALIAN GENOME LA English DT Article ID PSEUDOAUTOSOMAL REGION; CHROMOSOMAL LOCALIZATION; MOUSE CHROMOSOME-10; SEX-CHROMOSOMES; LINKAGE MAP; RECEPTOR; GENOME AB Common laboratory strains such as C57BL/6J carry a single Csf2ra gene that maps to the distal end of Chromosome (Chr) 19. Here we report that several species of wild mice contain multiple Csf2ra genes. Using interspecific backcross mapping and in situ hybridization, we demonstrate that one of these species, Mus spretus, carries four Csf2ra genes dispersed among the distal tips of Chrs 4, 10, 13, and 19. Our data further suggest that these additional Csf2ra genes are not generated by retrotransposition, but rather by nonhomologous subtelomeric exchanges that could be mediated in part by ribosomal genes located at the subtelomeric regions of Chrs 4, 13, and 19. Although we do not know whether these additional Csf2ra genes are functionally active, our studies suggest that subtelomeric exchange provides a potent means for rapid gene amplification in the mouse. C1 Natl Canc Inst, Mouse Canc Genet Program, Frederick, MD 21702 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Dept Genet, Seattle, WA 98195 USA. RP Brannan, CI (reprint author), Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Box 100266 JHMHC, Gainesville, FL 32610 USA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD DEC PY 2001 VL 12 IS 12 BP 882 EP 886 DI 10.1007/s00335-001-2084-0 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 495UN UT WOS:000172358900002 PM 11707773 ER PT J AU Lepperdinger, G Mullegger, J Kreil, G AF Lepperdinger, G Mullegger, J Kreil, G TI Hyal2 - less active, but more versatile? SO MATRIX BIOLOGY LA English DT Review DE hyaluronidase; Hyal2; hyaluronan; Xenopus development ID LYSOSOMAL HYALURONIDASE; XENOPUS EMBRYOGENESIS; GENE; PH-20; SPERM; EXPRESSION; PROTEIN; LOCUS; VENOM; CELLS AB Hyal2 is one of several hyaluronidases present in vertebrates. The human gene encoding this enzyme is present on chromosome 3p.21.3, close to two additional hyaluronidase genes. cDNAs encoding Hyal2 homologues have been characterized from mouse and Xenopus laevis. These enzymes hydrolyze high molecular mass hyaluronan to intermediates of approximately 20 kDa, a finding which implies that structural domains of this size exist in this polysaccharide which was mostly thought to be a random coil. Hyal2 enzymes have an acidic pH-optimum with an activity that is considerably lower than observed for other types of hyaluronidases. Originally considered to be a typical lysosomal enzyme, more recent evidence has shown that Hya12 proteins can also be exposed on the cell surface bound to the plasma membrane via a GPI anchor. Hyal2 is present in many tissues, one exception being the adult brain. In this tissue, the gene is silenced after birth by methylation. Current evidence about the role of Hya12 in tumor growth, inflammation and frog embryogenesis is discussed. (C) 2001 Elsevier Science B.V./International Society of Matrix Biology. All rights reserved. C1 Austrian Acad Sci, Inst Mol Biol, A-5020 Salzburg, Austria. RP Lepperdinger, G (reprint author), NICHHD, Genet Mol Lab, NIH, Bldg 6B,Room 412, Bethesda, MD 20892 USA. NR 37 TC 111 Z9 115 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD DEC PY 2001 VL 20 IS 8 BP 509 EP 514 DI 10.1016/S0945-053X(01)00170-6 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 504UV UT WOS:000172875000003 PM 11731268 ER PT J AU Koban, MU Brugh, SA Riordon, DR Dellow, KA Yang, HT Tweedie, D Boheler, KR AF Koban, MU Brugh, SA Riordon, DR Dellow, KA Yang, HT Tweedie, D Boheler, KR TI A distant upstream region of the rat multipartite Na+-Ca2+ exchanger NCX1 gene promoter is sufficient to confer cardiac-specific expression SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Na+-Ca2+ exchanger; promoter; transgenic mice; embryology; development; aging; gene expression regulation; LacZ; beta-galactosidase; heart; heart conduction system; gall bladder; brain; electrophoretic mobility shift assay; GATA transcription factors; transfection assays; PC12 cells; primary neonatal rat cardiac myocytes; COS cells; NRK52 cells ID SODIUM-CALCIUM EXCHANGER; SARCOPLASMIC-RETICULUM CA2+-ATPASE; HEART TUBE FORMATION; NA+/CA2+ EXCHANGER; ADRENERGIC-STIMULATION; TRANSCRIPTION FACTOR; VENTRAL MORPHOGENESIS; CLONING; CELLS; GATA-4 AB The Na+-Ca2+ exchanger (NCX) regulates intracellular calcium homeostasis. We report on an upstream region of the rat NCX1 multipartite promoter that is active in cardiac myocytes. Although inactive in most non-cardiac cell Lines, its activity can be rescued by cotransfection with GATA-4 and -6, but not GATA-5 transcription factors. In transgenic mice and similar to endogenous NCX1 mRNA expression. the upstream promoter region directs uniform beta -galactosidase expression in cardiac myocytes from similar to7.75 dpc. In adult mouse hearts, promoter activity is, however, significantly reduced and heterogeneous, except in the conduction system (sinoatrial and atrioventricular node, atrioventricular bundles). The upstream NCX1 promoter region thus directs appropriate spatial and temporal control of cardiac expression throughout development. Published by Elsevier Science Ireland Ltd. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Dept Cardiothorac Surg, London, England. RP Boheler, KR (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 40 TC 18 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD DEC PY 2001 VL 109 IS 2 BP 267 EP 279 DI 10.1016/S0925-4773(01)00548-2 PG 13 WC Developmental Biology SC Developmental Biology GA 502HF UT WOS:000172737400013 PM 11731239 ER PT J AU Walton, KD Wagner, KU Rucker, EB Shillingford, JM Miyoshi, K Hennighausen, L AF Walton, KD Wagner, KU Rucker, EB Shillingford, JM Miyoshi, K Hennighausen, L TI Conditional deletion of the bcl-x gene from mouse mammary epithelium results in accelerated apoptosis during involution but does not compromise cell function during lactation SO MECHANISMS OF DEVELOPMENT LA English DT Article DE conditional gene deletion; mammary gland; epithelium; bcl-x; bax; apoptosis; involution; Cre-recombinase ID GLAND INVOLUTION; SIGNAL TRANSDUCER; DEFICIENT MICE; IN-VIVO; DEATH; BAX; EXPRESSION; TRANSCRIPTION; DIFFERENTIATION; INDUCTION AB In the mammary gland Bcl-x is the most abundant cell survival factor from the Bcl-2 family. Since Bcl-x null mice die a-round day 12 of embryogenesis, the relevance of this protein in organ development and function is poorly understood. In erythroid. cells bcl-x gene expression is controlled by cytokines and the transcription factor Stat5 (signal transducer and activator of transcription). However. we identified that bcl-x RNA levels in mammary tissue from prolactin receptor- and Stat5-null mice were indistinguishable from wild type mice. We have proposed that Bcl-x might control the survival of mammary epithelial cells throughout pregnancy. lactation, and the early stages of involution, and we have now tested this hypothesis through the conditional deletion of the bcl-x gene from mouse mammary epithelium. Conditional (floxed) bcl-x alleles were excised from alveolar cells during pregnancy using a Cre transgene under the control of the whey acidic protein gene promoter. Deletion of the bcl-x gene from the entire epithelial compartment (ducts and alveoli) was achieved by expressing Cre-recombinase under control of the mouse mammary tumor virus long terminal repeat. The absence of Bcl-x did not compromise proliferation and differentiation of mammary ductal and alveolar epithelial cells in virgin mice and during pregnancy and lactation. However, epithelial cell death and tissue remodeling were accelerated in the bcl-x conditional knockout mice during the first stage of involution. Concomitant deletion of the bax gene did not significantly modify the Bcl-x phenotype. Our results suggest that Bcl-x is not essential during mammopoiesis, but is critical for controlled apoptosis during the first phase of involution. Published by Elsevier Science Ireland Ltd. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. EM hennighausen@nih.gov RI Wagner, Kay-Uwe/B-6044-2009; OI Walton, Katherine/0000-0001-9108-5617 NR 44 TC 50 Z9 51 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD DEC PY 2001 VL 109 IS 2 BP 281 EP 293 DI 10.1016/S0925-4773(01)00549-4 PG 13 WC Developmental Biology SC Developmental Biology GA 502HF UT WOS:000172737400014 PM 11731240 ER PT J AU Favara, BE AF Favara, BE TI Langerhans cell histiocytosis: An identity crisis SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Editorial Material ID CYTOKINES; DISORDERS C1 Univ Utah, Special Volunteer Fac, Rocky Mt Labs, Persistent Viral Dis Lab,NIH,Dept Pathol, Salt Lake City, UT USA. RP Favara, BE (reprint author), 1114 W Main St, Hamilton, MT 59840 USA. NR 12 TC 5 Z9 5 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD DEC PY 2001 VL 37 IS 6 BP 545 EP 545 DI 10.1002/mpo.1250 PG 1 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 503JH UT WOS:000172795000010 PM 11745895 ER PT J AU Bloom, JR Stewart, SL Koo, J Hiatt, RA AF Bloom, JR Stewart, SL Koo, J Hiatt, RA TI Cancer screening in public health clinics - The importance of clinic utilization SO MEDICAL CARE LA English DT Article DE cancer; health behaviors; health-services utilization; prevention, secondary ID BREAST-CANCER; PRIMARY-CARE; PREVENTION SERVICES; MAMMOGRAPHY; IMPROVE; WOMEN; INTERVENTIONS; PHYSICIANS; MORTALITY; PATTERNS AB OBJECTIVES. To determine how screening for breast and cervical cancer in public health clinics was associated with overall clinic utilization. METHODS. Evidence of screening and clinic visits between June 1989 and May 1992 was obtained by medical record audit for a random sample of 1825 women aged 40 to 75 attending eight public health clinics in the San Francisco Bay Area. RESULTS. With an average number of visits (4 per year), women who did not receive a physical examination were much less likely than those who did to obtain a clinical breast examination (OR = 0.03), mammography referral (OR = 0.1), or a mammogram (OR = 0.4) within 2 years, or a Papanicolaou smear (OR = 0.1) within 3 years. Without a physical examination, the odds of screening or referral increased with the first visit (OR = 1.2 for referral, breast examination, and Pap; 1.3 for mammography), but with a decreasing marginal effect of each additional visit (ratio of successive one-visit OR values = 0.992 for referral and breast examination; 0.995 for Pap; 0.98 for mammography). With a physical exam, visits were associated with mammography only (first visit OR = 1.2; OR ratio = 0.992). CONCLUSIONS. In public health clinics, screening is associated either with receipt of routine care or repeated visits for treatment. Women who fall through the cracks are those who come to the clinic with a medical problem but otherwise receive few services. Interventions in public health clinics need to facilitate the provider's ability to use medically related visits as opportunities to increase adherence to screening recommendations. C1 Univ Calif Berkeley, Berkeley, CA 94720 USA. No Calif Canc Ctr, Union City, CA USA. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Bloom, JR (reprint author), Univ Calif Berkeley, 409 Warren Hall, Berkeley, CA 94720 USA. FU NCI NIH HHS [CA54605-05] NR 19 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD DEC PY 2001 VL 39 IS 12 BP 1345 EP 1351 DI 10.1097/00005650-200112000-00010 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 499PF UT WOS:000172579000009 PM 11717576 ER PT J AU Schmitz, KH Arnett, DK Bank, A Liao, DP Evans, GW Evenson, KR Stevens, J Sorlie, P Folsom, AR AF Schmitz, KH Arnett, DK Bank, A Liao, DP Evans, GW Evenson, KR Stevens, J Sorlie, P Folsom, AR TI Arterial distensibility and physical activity in the ARIC study SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE arterial distensibility; exercise; cardiovascular disease ID STIFFNESS; ATHEROSCLEROSIS; EXERCISE; RISK; QUESTIONNAIRE; ELASTICITY; PRESSURE; ADULTS; WOMEN; AGE AB Purpose: Arterial distensibility decreases with age. This decrease may be associated with the initiation and/or progression of hypertension and atherosclerosis and may be attenuated by positive lifestyle habits, including habitual physical activity. We tested the hypothesis that self-reported sport, leisure, and work, physical activity is associated with greater arterial distensibility (i.e., carotid artery pulsatile diameter changes). Methods: The Atherosclerosis Risk in Communities (ARIC) study assessed left common carotid arterial diameters and intimal-medial wall thickness (IMT) using B-mode ultrasound techniques, in 10,644 African-American and white men and women abed 45-64 yr and free of cardiovascular disease. Results: Work activity, but not sports or leisure activity, was weakly associated with greater arterial distensibility in an ANCOVA model adjusted for blood pressure and other covariates (diastolic arterial diameter, pulse pressure, pulse pressure squared, age, race, sex, smoking, dietary fat intake, height, education, and clinical center) (P for linear trend = 0.03). Vigorous sports activity was weakly positively associated with arterial distensibility (arterial diameter change (mean +/- SE in mm) 0.42 +/- 0.004 vs 0.41 +/- 0.002 for the 12.7% of participants reporting any vs no vigorous activity, P = 0.02), and this association was not attenuated by adjustment for IMT, body mass index, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or diabetes. Repeated analyses with traditional arterial stiffness indices showed similar findings for vigorous but not work activity. Conclusion: In contrast to several smaller studies, these findings do not support the hypothesis that habitual physical activity has a strong, consistent positive effect on arterial distensibility. C1 Univ Minnesota, Div Epidemiol, Minneapolis, MN 55454 USA. St Paul Heart Clin, St Paul, MN USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Hlth Evaluat Serv, Hershey, PA 17033 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Schmitz, KH (reprint author), Univ Minnesota, Div Epidemiol, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. RI Schmitz, Kathryn/B-7154-2011 FU NHLBI NIH HHS [N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, T32-HL07036] NR 35 TC 26 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD DEC PY 2001 VL 33 IS 12 BP 2065 EP 2071 DI 10.1097/00005768-200112000-00014 PG 7 WC Sport Sciences SC Sport Sciences GA 500CA UT WOS:000172607300014 PM 11740300 ER PT J AU Roy, MJ Perkins, JG Roy, MJ Bolan, CD Phillips, YY AF Roy, MJ Perkins, JG Roy, MJ Bolan, CD Phillips, YY TI Operational experiences during medical residency: Perspectives from the Walter Reed Army Medical Center Department of Medicine SO MILITARY MEDICINE LA English DT Article ID CURRICULUM AB The preparation of military primary care physicians for practice in operational environments has taken on greater importance during the past decade. The Department of Defense military-unique curriculum identifies the elements that should be incorporated into residency training programs to accomplish comprehensive training in operational matters. We describe efforts to integrate the military-unique curriculum into internal medicine residency, including obstacles encountered, so that other programs may learn from our experience. C1 Walter Reed Army Med Ctr, Dept Med, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. SE Permanente Med Grp, Atlanta, GA USA. RP Roy, MJ (reprint author), Walter Reed Army Med Ctr, Dept Med, Washington, DC 20307 USA. NR 4 TC 2 Z9 3 U1 0 U2 0 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD DEC PY 2001 VL 166 IS 12 BP 1038 EP 1045 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 653DJ UT WOS:000181419700005 ER PT J AU Hedvat, CV Jaffe, ES Qin, J Filippa, DA Cordon-Cardo, C Tosato, G Nimer, SD Teruya-Feldstein, J AF Hedvat, CV Jaffe, ES Qin, J Filippa, DA Cordon-Cardo, C Tosato, G Nimer, SD Teruya-Feldstein, J TI Macrophage-derived chemokine expression in classical Hodgkin's lymphoma: Application of tissue microarrays SO MODERN PATHOLOGY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 03-09, 2001 CL ATLANTA, GEORGIA SP US & Canadian Acad Pathol DE chemokine; Hodgkin's lymphoma; lymphoma; MDC; tissue microarray ID GENE AMPLIFICATION; DISEASE; CELLS; TUMOR; MDC; CHEMOATTRACTANT; ASSOCIATION AB Hodgkin's disease (HD) is a lymphoid malignancy characterized by the presence of Reed-Sternberg (RS) and Hodgkin's cells in a background of mixed inflammatory cells and stromal reaction. Studies have documented that HD is a neoplasm associated with abnormal cytokine, and chemokine production. To define the expression of macrophage-derived chemokine (MDC) in HD, 57 cases (18 lymphocyte predominant, 11 mixed cellularity, 28 nodular sclerosis) were stained for MDC by immunohistochemistry and compared with reactive lymph nodes as controls. MDC was expressed by RS cells in classical HD (CHD) and showed a distinct cytoplasmic and Golgi localization. Accumulating evidence suggests that lymphocyte-predominant HD (LPHD) represents an entity distinct from CHD, with different biological properties and clinical course. On the basis of the high level of MDC staining alone, CHD could be distinguished from LPHD (P <.001), which showed only faint staining of scattered histiocytes similar to control tissues. CHD cases with high MDC mRNA levels showed high levels of MDC protein expression by immunohistochemistry (P <.001) and significant eosinophil infiltration, suggesting that MDC may represent another molecule that plays a critical role In eosinophil recruitment. We also analyzed 102 cases of non-Hodgkin's lymphoma and normal spleen, lymph node, and thymic tissue. High levels of MDC expression were specific to CHD cases because only low levels of MDC were observed in a minor subset of LPHD, NHL or normal lymphoid tissues. C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. NCI, NIH, Bethesda, MD 20892 USA. Sloan Kettering Inst, Dept Med, Mol Pharmacol & Therapeut Program, New York, NY USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. RP Teruya-Feldstein, J (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. OI HEDVAT, CYRUS/0000-0003-0045-3491 NR 25 TC 37 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 2001 VL 14 IS 12 BP 1270 EP 1276 DI 10.1038/modpathol.3880473 PG 7 WC Pathology SC Pathology GA 504UN UT WOS:000172874400011 PM 11743050 ER PT J AU Carlton, JMR Muller, R Yowell, CA Fluegge, MR Sturrock, KA Pritt, JR Vargas-Serrato, E Galinski, MR Barnwell, JW Mulder, N Kanapin, A Cawley, SE Hide, WA Dame, JB AF Carlton, JMR Muller, R Yowell, CA Fluegge, MR Sturrock, KA Pritt, JR Vargas-Serrato, E Galinski, MR Barnwell, JW Mulder, N Kanapin, A Cawley, SE Hide, WA Dame, JB TI Profiling the malaria genome: a gene survey of three species of malaria parasite with comparison to other apicomplexan species SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE malaria; apicomplexa; comparative genomics; proteome ID MUNG BEAN NUCLEASE; EXPRESSED SEQUENCE TAGS; PLASMODIUM-FALCIPARUM; FINDING GENES; PROTEIN; DNA; MEROZOITES; BIOINFORMATICS; GENERATION; DATABASE AB We have undertaken the first comparative pilot gene discovery analysis of approximately 25 000 random genomic and expressed sequence tags (ESTs) from three species of Plasmodium, the infectious agent that causes malaria. A total of 5482 genome survey sequences (GSSs) and 5582 ESTs were generated from mung bean nuclease (MBN) and cDNA libraries, respectively, of the ANKA line of the rodent malaria parasite Plasmodium? berghei, and 10 874 GSSs generated from MBN libraries of the Salvador I and Belem lines of Plasmodium vivax, the most geographically wide-spread human malaria pathogen. These tags. together with 2438 Plasmodium falciparum sequences present in GenBank, were used to perform first-pass assembly and transcript reconstruction, and non-redundant consensus sequence datasets created. The datasets were compared against public protein databases and more than 1000 putative new Plasmodium proteins identified based on sequence similarity. Homologs of previously characterized Plasmodium genes were also identified, increasing the number of P. vivax and P. berghei sequences in public databases at least 10-fold. Comparative studies with other species of Apicomplexa identified interesting homologs of possible therapeutic or diagnostic value. A gene prediction program, Phat, was used to predict probable open reading frames for proteins in all three datasets. Predicted and non-redundant BLAST-matched proteins were submitted to InterPro, an integrated database of protein domains, signatures and families, for functional classification. Thus a partial predicted proteome was created for each species. This first comparative analysis of Plasmodium protein coding sequences represents a valuable resource for further studies on the biology of this important pathogen. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. Univ Florida, Coll Vet Med, Dept Pathobiol, Gainesville, FL 32608 USA. Univ Western Cape, S African Natl Bioinformat Inst, ZA-7535 Bellville, South Africa. Emory Univ, Sch Med, Yerkes Reg Primate Res Ctr, Emory Vaccine Res Ctr, Atlanta, GA 30329 USA. Ctr Dis Control & Prevent, Div Parasit Dis, Atlanta, GA 30341 USA. European Bioinformat Inst, EMBL Outstn, Hinxton CB10 1SD, Cambs, England. Affymetrix, Emeryville, CA 94608 USA. RP Carlton, JMR (reprint author), Inst Genom Res, 9712 Med Ctr Dr, Rockville, MD 20850 USA. RI Hide, Winston Hide/C-7217-2009; Kanapin, Alexander/E-7632-2013; Kanapin, Alexander/Q-7590-2016 OI Hide, Winston Hide/0000-0002-8621-3271; Kanapin, Alexander/0000-0001-9802-5297 FU PHS HHS [N01-A1-65315] NR 50 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD DEC PY 2001 VL 118 IS 2 BP 201 EP 210 DI 10.1016/S0166-6851(01)00371-1 PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 511EL UT WOS:000173251600009 PM 11738710 ER PT J AU Mullins, C Bonifacino, JS AF Mullins, C Bonifacino, JS TI Structural requirements for function of yeast GGAs in vacuolar protein sorting, alpha-factor maturation, and interactions with clathrin SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GOLGI MEMBRANE-PROTEIN; AP-3 ADAPTER COMPLEX; SACCHAROMYCES-CEREVISIAE; GAMMA-ADAPTIN; TRANS-GOLGI; SELECTIVE TRANSPORT; GENE-PRODUCTS; DOMAIN; RECEPTOR; FAMILY AB The GGAs (Golgi-localized, gamma-ear-containing, ARF-binding proteins) are a family of multidomain adaptor proteins involved in protein sorting at the trans-Golgi network of eukaryotic cells. Here we present results from a functional characterization of the two Saccharomyces cerevisiae GGAs, Gga1p and Gga2p. We show that deletion of both GGA genes causes defects in sorting of carboxypeptidase Y (CPY) and proteinase A to the vacuole, vacuolar morphology, and maturation of alpha -factor. A structure-function analysis reveals a requirement of the VHS, GAT, and hinge for function, while the GAE domain is less important. We identify putative clathrin-binding motifs in the hinge domain of both yeast GGAs. These motifs are shown to mediate clathrin binding in vitro. While mutation of these motifs alone does not block function of the GGAs in vivo, combining these mutations with truncations of the hinge and GAE domains diminishes function, suggesting functional cooperation between different clathrin-binding elements. Thus, these observations demonstrate that the yeast GGAs play important roles in the CPY pathway, vacuole biogenesis, and alpha -factor maturation and identify structural determinants that are critical for these functions. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101,18 Lib Dr,MSC 5430, Bethesda, MD 20892 USA. EM juan@helix.nih.gov NR 56 TC 46 Z9 46 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2001 VL 21 IS 23 BP 7981 EP 7994 DI 10.1128/MCB.21.23.7981-7994.2001 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 490NZ UT WOS:000172059100010 PM 11689690 ER PT J AU Kong, DC DePamphilis, ML AF Kong, DC DePamphilis, ML TI Site-specific DNA binding of the Schizosaccharomyces pombe origin recognition complex is determined by the Orc4 subunit SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MOBILITY-GROUP PROTEIN; FISSION YEAST; REPLICATION ORIGINS; CELL-CYCLE; ARS ELEMENTS; DROSOPHILA-MELANOGASTER; CHROMATIN; INITIATION; HOMOLOG; CDC6 AB The mechanism by which origin recognition complexes (ORCs) identify replication origins was investigated using purified Orc proteins from Schizosaccharomyces pombe. Orc4p alone bound tightly and specifically to several sites within S. pombe replication origins that are genetically required for origin activity. These sites consisted of clusters of A or T residues on one strand but were devoid of either alternating A and T residues or GC-rich sequences. Addition of a complex consisting of Orc1, -2, -3, -5, and -6 proteins (ORC-5) altered neither Orc4p binding to origin DNA nor Orc4p protection of specific sequences. ORC-5 alone bound weakly and nonspecifically to DNA; strong binding required the presence of Orc4p. Under these conditions, all six subunits remained bound to chromatin isolated from each phase of the cell division cycle. These results reveal that the S. pombe ORC binds to multiple, specific sites within replication origins and that site selection, at least in vitro, is determined solely by the Orc4p subunit. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP DePamphilis, ML (reprint author), NICHHD, NIH, Bldg 6,Room 416,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 50 TC 74 Z9 77 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2001 VL 21 IS 23 BP 8095 EP 8103 DI 10.1128/MCB.21.23.8095-8103.2001 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 490NZ UT WOS:000172059100019 PM 11689699 ER PT J AU Kaffer, CR Grinberg, A Pfeifer, K AF Kaffer, CR Grinberg, A Pfeifer, K TI Regulatory mechanisms at the mouse Igf2/H19 locus SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID IMPRINTED H19 GENE; BIALLELIC EXPRESSION; CHROMATIN CONFORMATION; METHYLATION IMPRINT; CHROMOSOME 11P15.5; SILENCER ELEMENT; PRIMER EXTENSION; H19/IGF2 LOCUS; 130 KB; REGION AB The closely linked H19 and Igf2 genes show highly similar patterns of gene expression but are reciprocally imprinted. H19 is expressed almost exclusively from the maternally inherited chromosome, while Igf2 expression is mostly from the paternal chromosome. In humans, loss of imprinting at this locus is associated with tumors and with developmental disorders. Monoallelic expression at the imprinted Igf2/H19 locus occurs by at least two distinct mechanisms: a developmentally regulated silencing of the paternal H19 promoter, and transcriptional insulation of the maternal Igf2 promoters. Both mechanisms of allele-specific silencing are ultimately dependent on a common cis-acting element located just upstream of the H19 promoter. The coordinated expression patterns and some experimental data support the idea that positive regulatory elements are also shared by the two genes. To clarify the organization and function of positive and negative regulatory elements at the H19/Igf2 locus, we analyzed two mouse mutations. First, we generated a deletion allele to localize enhancers used in vivo for expression of both H19 and Igf2 in mesodermal tissues to sequences downstream of the H19 gene. Coincidentally, we demonstrated that some expression of Igf2 is independent of the shared enhancer element. Second, we used this new information to further characterize an ectopic H19 differentially regulated region and the associated insulator. We demonstrated that its activity is parent-of-origin dependent. In contrast to recent results from Drosophila model systems; we showed that this duplication of a mammalian insulator does not interfere with its normal function. Implications of these findings for current models for monoallelic gene expression at this locus are discussed. C1 NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. RP Pfeifer, K (reprint author), NICHHD, 9000 Rockville Pike,Bldg 6B,Room 2B206, Bethesda, MD 20892 USA. OI Pfeifer, Karl/0000-0002-0254-682X NR 49 TC 61 Z9 62 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2001 VL 21 IS 23 BP 8189 EP 8196 DI 10.1128/MCB.21.23.8189-8196.2001 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 490NZ UT WOS:000172059100027 PM 11689707 ER PT J AU Takasaki, N Rankin, T Dean, J AF Takasaki, N Rankin, T Dean, J TI Normal gonadal development in mice lacking GPBOX, a homeobox protein expressed in germ cells at the onset of sexual dimorphism SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; TRANSCRIPTION FACTOR; GENE; PEM; DIFFERENTIATION; PLACENTA; PSX; MUTATION AB Gpbox is a paired-like homeobox gene that colocalizes with two other members of the family, PsxI and Pern, on the proximal portion of the mouse X chromosome. Gpbox is expressed in the extraembryonic placenta and within the germ cells of the embryonic gonad. Beginning with the onset of sexual dimorphism (embryonic day [E] 11.5 to 12.5), GPBOX transcripts accumulate faster in female than in male germ cells but disappear later in embryogenesis (E16) and have not been reported in adult tissues. To investigate the function of Gpbox, mouse cell lines lacking GPBOX were established using targeted mutagenesis in embryonic stem cells. Both homozygous Gpbox null female and hemizygous Gpbox null male mice were fertile and reproduced normally. Additionally, the development of male and female gonads in the null background was indistinguishable from that observed in normal littermates. The lack of an obvious phenotype raises the possibility that another member of this homeobox gene family provides the absent Gpbox function. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dean, J (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 50,Room 3134, Bethesda, MD 20892 USA. NR 23 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2001 VL 21 IS 23 BP 8197 EP 8202 DI 10.1128/MCB.21.23.8197-8202.2001 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 490NZ UT WOS:000172059100028 PM 11689708 ER PT J AU Li, J Gorospe, M Hutter, D Barnes, J Keyse, SM Liu, YS AF Li, J Gorospe, M Hutter, D Barnes, J Keyse, SM Liu, YS TI Transcriptional induction of MKP-1 in response to stress is associated with histone H3 phosphorylation-acetylation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; IMMEDIATE-EARLY GENE; MAP KINASE; TYROSINE-PHOSPHATASE; INFLAMMATORY CYTOKINES; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS; TERMINAL DOMAIN; CL100 GENE; HEAT-SHOCK AB Mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) has been shown to play a critical role in mediating the feedback control of MAP kinase cascades in a variety of cellular processes, including proliferation and stress responsiveness. Although MKP-1 expression is induced by a broad array of extracellular stimuli, the mechanisms mediating its induction remain poorly understood. Here we show that MKP-1 mRNA was potently induced by arsenite and ultraviolet light and modestly increased by heat shock and hydrogen peroxide. Interestingly, arsenite also dramatically induces phosphorylation-acetylation of histone H3 at a global level which precedes the induction of MKP-1 mRNA. The transcriptional induction of MKP-1, histone H3 modification, and elevation in MKP-1 mRNA in response to arsenite are all partially prevented by the p38 MAP kinase inhibitor SB203580, suggesting that the p38 pathway is involved in these processes. Finally, analysis of the DNA brought down by chromatin immunoprecipitation (ChIP) reveals that arsenite induces phosphorylation-acetylation of histone H3 associated with the MKP-1 gene and enhances binding of RNA polymerase II to MKP-1 chromatin. ChIP assays following exposure to other stress agents reveal various degrees of histone H3 modification at the MKP-1 chromatin. The differential contribution of p38 and ERK MAP kinases in mediating MKP-1 induction by different stress agents further illustrates the complexity and versatility of stress-induced MKP-1 expression. Our results strongly suggest that chromatin remodeling after stress contributes to the transcriptional induction of MKP-1. C1 NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Ninewells Hosp, Biomed Res Ctr, Imperial Canc Res Fund, Mol Pharmacol Unit, Dundee DD1 9SY, Scotland. RP Liu, YS (reprint author), NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Keyse, Stephen/B-9575-2009; Liu, Yusen/E-3527-2011 OI Keyse, Stephen/0000-0002-5150-8221; NR 64 TC 148 Z9 150 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2001 VL 21 IS 23 BP 8213 EP 8224 DI 10.1128/MCB.21.23.8213-8224.2001 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 490NZ UT WOS:000172059100030 PM 11689710 ER PT J AU Kovarova, M Tolar, P Arudchandran, R Draberova, L Rivera, J Draber, P AF Kovarova, M Tolar, P Arudchandran, R Draberova, L Rivera, J Draber, P TI Structure-function analysis of Lyn kinase association with lipid rafts and initiation of early signaling events after Fc epsilon receptor I aggregation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; PROTEIN-TYROSINE KINASE; HIGH-AFFINITY RECEPTOR; DETERGENT-RESISTANT MEMBRANES; IMMUNOGLOBULIN-E; IGE RECEPTOR; BETA-SUBUNIT; MAST-CELLS; THY-1-MEDIATED ACTIVATION; ANTIGEN RECEPTOR AB The first step in immunoreceptor signaling is represented by ligand-dependent receptor aggregation, followed by receptor phosphorylation mediated by tyrosine kinases of the Src family. Recently, sphingolipid- and cholesterol-rich plasma membrane microdomains, called lipid rafts, have been identified and proposed to function as platforms where signal transduction molecules may interact with the aggregated immunoreceptors. Here we show that aggregation of the receptors with high affinity for immunoglobulin E (Fee RI) in mast cells is accompanied by a co-redistribution of the Src family kinase Lyn. The co-redistribution requires Lyn dual fatty acylation, Src homology 2 (SH2) and/or SH3 domains, and Lyn kinase activity, in cis or in trans. Palmitoylation site-mutated Lyn, which is anchored to the plasma membrane but exhibits reduced sublocalization into lipid rafts, initiates the tyrosine phosphorylation of Fc epsilon RI subunits, Syk protein tyrosine kinase, and the linker for activation of T cells, along with an increase in the concentration of intracellular Ca2+. However, Lyn mutated in both the palmitoylation and myristoylation sites does not anchor to the plasma membrane and is incapable of initiating Fc epsilon RI phosphorylation and early signaling events. These data, together with our finding that a constitutively tyrosine-phosphorylated Fc epsilon RI does not exhibit an increased association with lipid rafts, suggest that Fc epsilon RI phosphorylation and early activation events can be initiated outside of lipid rafts. C1 NIAMSD, NIH, Mol Inflammat Sect, Bethesda, MD 20892 USA. Acad Sci Czech Republ, Inst Genet Mol, Prague 14220, Czech Republic. RP Rivera, J (reprint author), NIAMS, NIH, Bldg 10,Rm 9N228, Bethesda, MD 20892 USA. RI Draberova, Lubica/G-3505-2014; Draber, Petr/G-3412-2014 OI Draberova, Lubica/0000-0002-2459-4435; Draber, Petr/0000-0002-3986-2025 NR 53 TC 119 Z9 119 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2001 VL 21 IS 24 BP 8318 EP 8328 DI 10.1128/MCB.21.24.8318-8328.2001 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 494ZM UT WOS:000172315800007 PM 11713268 ER PT J AU Collins, I Weber, A Levens, D AF Collins, I Weber, A Levens, D TI Transcriptional consequences of topoisomerase inhibition SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID C-MYC GENE; RNA-POLYMERASE-II; BURKITTS-LYMPHOMA CELLS; LARGE T-ANTIGEN; CHROMATIN STRUCTURE; MESSENGER-RNA; HEAT-SHOCK; IN-VIVO; POSTTRANSCRIPTIONAL REGULATION; DOWN-REGULATION AB In principle, the generation, transmission, and dissipation of supercoiling forces are determined by the arrangement of the physical barriers defining topological boundaries and the disposition of enzymes creating (polymerases and helicases, etc.) or releasing (topoisomerases) torsional strain in DNA. These features are likely to be characteristic for individual genes. By using topoisomerase: inhibitors to alter the balance between supercoiling forces in vivo, we monitored changes in the basal transcriptional activity and DNA conformation for several genes. Every gene examined displayed an individualized profile in response to inhibition of topoisomerase I or II. The expression changes elicited by camptothecin (topoisomerase I inhibitor) or adriamycin (topoisomerase II inhibitor) were not equivalent. Camptothecin generally caused transcription complexes to stall in the midst of transcription units, while provoking little response at promoters. Adriamycin, in contrast, caused dramatic changes at or near promoters and prevented transcription. The response to topoisomerase inhibition was also context dependent, differing between chromosomal or episomal c-myc promoters. In addition to being well-characterized DNA-damaging agents, topoisomerase inhibitors may evoke a biological response determined in part from transcriptional effects. The results have ramifications for the use of these drugs as antineoplastic agents. C1 NCI, Ctr Canc Res, Lab Pathol, Bethesda, MD 20892 USA. RP Levens, D (reprint author), NCI, Ctr Canc Res, Lab Pathol, Bldg 10,Rm 2N106, Bethesda, MD 20892 USA. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 75 TC 90 Z9 90 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2001 VL 21 IS 24 BP 8437 EP 8451 DI 10.1128/MCB.21.24.8437-8451.2001 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 494ZM UT WOS:000172315800018 PM 11713279 ER PT J AU Calvo, S Vullhorst, D Venepally, P Cheng, J Karavanova, I Buonanno, A AF Calvo, S Vullhorst, D Venepally, P Cheng, J Karavanova, I Buonanno, A TI Molecular dissection of DNA sequences and factors involved in slow muscle-specific transcription SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID WILLIAMS-BEUREN-SYNDROME; HELIX-LOOP-HELIX; SKELETAL-MUSCLE; FIBER-TYPE; TFII-I; TRANSGENIC MICE; GENE-EXPRESSION; REGULATORY ELEMENTS; BINDING PROTEIN; MESSENGER-RNA AB Transcription is a major regulatory mechanism for the generation of slow- and fast-twitch myofibers. We previously identified an upstream region of the slow TnI gene (slow upstream regulatory element [SURE]) and an intronic region of the fast TnI gene (fast intronic regulatory element [FIRE]) that are sufficient to direct fiber type-specific transcription in transgenic mice. Here we demonstrate that the downstream half of TnI SURE, containing E box, NFAT, MEF-2, and CACC motifs, is sufficient to confer pan-skeletal muscle-specific expression in transgenic mice. However, upstream regions of SURE and FIRE are required for slow and fast fiber type specificity, respectively. By adding back upstream SURE sequences to the pan-muscle-specific enhancer, we delineated a 15-bp region necessary for slow muscle specificity. Using this sequence in a yeast one-hybrid screen, we isolated cDNAs for general transcription factor 3 (GTF3)/muscle TFII-I repeat domain-containing protein 1 (MusTRD1). GTF3 is a multidomain nuclear protein related to initiator element-binding transcription factor TF II-I; the genes for both proteins are deleted in persons with Williams-Beuren syndrome, who often manifest muscle weakness. Gel retardation assays revealed that full-length GTF3, as well as its carboxy-terminal half, specifically bind the bicoid-like motif of SURE (GTTAATCCG). GTF3 expression is neither muscle nor fiber type specific. Its levels are highest during a period of fetal development that coincides with the emergence of specific fiber types and transiently increases in regenerating muscles damaged by bupivacaine. We further show that transcription from TnI SURE is repressed by GTF3 when overexpressed in electroporated adult soleus muscles. These results suggest a role for GTF3 as a regulator of slow TnI expression during early stages of muscle development and suggest how it could contribute to Williams-Beuren syndrome. C1 NICHHD, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Buonanno, A (reprint author), NICHHD, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NR 73 TC 49 Z9 50 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2001 VL 21 IS 24 BP 8490 EP 8503 DI 10.1128/MCB.21.24.8490-8503.2001 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 494ZM UT WOS:000172315800023 PM 11713284 ER PT J AU Lohrum, MAE Woods, DB Ludwig, RL Balint, E Vousden, KH AF Lohrum, MAE Woods, DB Ludwig, RL Balint, E Vousden, KH TI C-terminal ubiquitination of p53 contributes to nuclear export SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN-PAPILLOMAVIRUS E6; TUMOR-SUPPRESSOR P53; RING-FINGER DOMAIN; ONCOPROTEIN MDM2; DEGRADATION; PROTEIN; LOCALIZATION; ACTIVATION; STABILITY; LIGASE AB The growth inhibitory functions of p53 are controlled in unstressed cells by rapid degradation of the p53 protein. One of the principal regulators of p53 stability is MDM2, a RING finger protein that functions as an E3 ligase to ubiquitinate p53. MDM2 promotes p53 nuclear export, and in this study, we show that ubiquitination of the C terminus of p53 by MDM2, contributes to the efficient export of p53 from the nucleus to the cytoplasm. In contrast, MDM2 did not promote nuclear export of the p53-related protein, p73. p53 nuclear export was enhanced by overexpression of the export receptor CRM1, although no significant relocalization of MDM2 was seen in response to CRM1. However, nuclear export driven by CRM1 overexpression did not result in the degradation of p53, and nuclear export was not essential for p53 degradation. These results indicate that MDM2 mediated ubiquitination of p53 contributes to both nuclear export and degradation of p53 but that these activities are not absolutely dependent on each other. C1 NCI, Regulat Cell Growth Lab, Frederick, MD 21702 USA. RP Vousden, KH (reprint author), NCI, Regulat Cell Growth Lab, Bldg 560,Room 22-96,1050 Boyles St, Frederick, MD 21702 USA. RI Balint, Eva/B-8695-2008 NR 51 TC 156 Z9 159 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2001 VL 21 IS 24 BP 8521 EP 8532 DI 10.1128/MCB.21.24.8521-8532.2001 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 494ZM UT WOS:000172315800026 PM 11713287 ER PT J AU Angeloni, D Lee, JD Johnson, BE Teh, BT Dean, M Lerman, MI Sterneck, E AF Angeloni, D Lee, JD Johnson, BE Teh, BT Dean, M Lerman, MI Sterneck, E TI C306A single nucleotide polymorphism in the human CEBPD gene that maps at 8p11.1-p11.2 SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE CEBPD; single nucleotide polymorphism (SNP) ID C/EBP-DELTA; LUNG; EXPRESSION; PROTEIN; FAMILY C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Van Andel Res Inst, Gran Rapids, MI 48503 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Regulat Cell Growth Lab, Frederick, MD 21702 USA. RP Angeloni, D (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CO-56000] NR 11 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD DEC PY 2001 VL 15 IS 6 BP 395 EP 397 DI 10.1006/mcpr.2001.0377 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 524RN UT WOS:000174026800010 PM 11851384 ER PT J AU Boissinot, SP Furano, AV AF Boissinot, SP Furano, AV TI Adaptive evolution in LINE-1 retrotransposons SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE L1/LINE-1; human; retrotransposon; positive selection ID INTERSPERSED REPEATED DNA; POSITIVE SELECTION; ORF1 PROTEIN; MOUSE LINE-1; L1 RETROTRANSPOSONS; REPEAT FAMILY; COILED COILS; MAMMALIAN L1; SEQUENCES; ELEMENTS AB We traced the sequence evolution of the active lineage of LINE-1 (L1) retrotransposons over the last similar to 25 Myr of human evolution. Five major families (L1PA5, L1PA4, L1PA3B, L1PA2, and L1PA1) of elements have succeeded each other as a single lineage. We found that part of the first open-reading frame (ORFI) had a higher rate of nonsynonymous (amino acid replacement) substitution than synonymous substitution during the evolution of the ancestral L1PA5 through the L1PA3B families. This segment encodes the coiled coil region of the protein-protein interaction domain of the ORFI protein (ORFIp). Statistical analysis of these changes indicates that positive selection had been acting on this region. In contrast, the coiled coil segment hardly changed during the evolution of the L1PA3B to the present L1PA1 family. Therefore, selective pressure on the coiled coil segment has changed over time. We suggest that the fast rate of amino acid replacement in the coiled coil segment reflects the adaptation of L1 either to a changing genomic environment or to host repression factors. In contrast, the second open-reading frame and the nucleic acid-binding domain of the first open-reading frame are extremely well conserved, attesting to the strong purifying selection acting on these regions. C1 NIDDKD, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Furano, AV (reprint author), NIDDKD, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bldg 8,Room 203,8 Ctr DR MSC 0830, Bethesda, MD 20892 USA. EM avf@helix.nih.gov 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 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD DEC PY 2001 VL 18 IS 12 BP 2186 EP 2194 PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 500ZE UT WOS:000172657900007 PM 11719568 ER PT J AU Kaldis, P Ojala, PM Tong, L Makela, TP Solomon, MJ AF Kaldis, P Ojala, PM Tong, L Makela, TP Solomon, MJ TI CAK-independent activation of CDK6 by a viral cyclin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; DEPENDENT KINASE INHIBITOR; TRANSCRIPTION FACTOR TFIIH; RING FINGER PROTEIN; B-TYPE CYCLINS; CELL-CYCLE; KAPOSIS-SARCOMA; RETINOBLASTOMA PROTEIN; POTENTIAL MEDIATOR; CATALYTIC SUBUNIT AB In normal cells, activation of cyclin-dependent kinases (cdks) requires binding to a cyclin and phosphorylation by the cdk-activating kinase (CAK). The Kaposi's sarcoma-associated herpesvirus encodes a protein with similarity to D-type cyclins. This KSHV-cyclin activates CDK6, alters its substrate specificity, and renders CDK6 insensitive to inhibition by the cdk inhibitor P16(INK4a). Here we investigate the regulation of the CDK6/KSHV-cyclin kinase with the use of purified proteins and a cell-based assay. We find that KSHV-cyclin can activate CDK6 independent of phosphorylation by CAK in vitro. In addition, CAK phosphorylation decreased the p16(INK4a) sensitivity of CDK6/KSHV-cyclin complexes. In cells, expression of CDK6 or to a lesser degree of a nonphosphorylatable CDK6(T177A) together with KSHV-cyclin induced apoptosis, indicating that CDK6 activation by KSHV-cyclin can proceed in the absence of phosphorylation by CAK in vivo. Coexpression of p16 partially protected cells from cell death. p16 and KSHV-cyclin can form a ternary complex with CDK6 that can be detected by binding assays as well as by conformational changes in CDK6. The Kaposi's sarcoma-associated herpesvirus has adopted a clever strategy to render cell cycle progression independent of mitogenic signals, cdk inhibition, or phosphorylation by CAK. C1 Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. Haartman Inst, SF-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, SF-00014 Helsinki, Finland. Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA. RP Kaldis, P (reprint author), NCI, Frederick Canc Res & Dev Ctr, Regulat Cell Growth Lab, Bldg 560-12-91A,W 7th St, Frederick, MD 21702 USA. RI Kaldis, Philipp/G-2714-2010; makela, tomi/B-3734-2009 OI Kaldis, Philipp/0000-0002-7247-7591; makela, tomi/0000-0002-4869-8044 FU NIGMS NIH HHS [GM-47830, R01 GM047830] NR 79 TC 32 Z9 34 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2001 VL 12 IS 12 BP 3987 EP 3999 PG 13 WC Cell Biology SC Cell Biology GA 501TA UT WOS:000172701100021 PM 11739795 ER PT J AU Bera, TK Williams-Gould, J Beers, R Chowdhury, P Pastan, I AF Bera, TK Williams-Gould, J Beers, R Chowdhury, P Pastan, I TI Bivalent disulfide-stabilized fragment variable immunotoxin directed against mesotheliomas and ovarian cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID SINGLE-CHAIN FV; IMPROVED ANTIGEN-BINDING; RECOMBINANT IMMUNOTOXIN; ANTITUMOR-ACTIVITY; IMMUNOGLOBULIN FORMS; ANTIBODY FRAGMENTS; TUMOR PENETRATION; ESCHERICHIA-COLI; MICE; CELL AB We have used protein engineering to generate a stable bivalent fragment variable (Fv) molecule from the antimesothelin antibody SS, in which the V-H and V-L domains of the Fv are linked to each other by a disulfide bond, and the two Fvs are connected by a flexible 15-amino acid (Gly(4)-Ser)(3) linker. The SS (dsFV)(2) molecule is fused to a M-r 38,000 truncated form of Pseudomonas exotoxin to generate a bivalent, disulfide stabilized, (dsFV)(2) immunotoxin. The immunotoxin was expressed in Escherichia coli, refolded in vitro, and purified to similar to95% purity with a high yield of >10%. Binding studies demonstrated that the (dsFV)(2) molecule has 40 times higher apparent affinity for recombinant mesothelin than a monovalent dsFv molecule. The (dsFV)(2) immunotoxin was 4-10-fold more cytotoxic to three mesothelin antigen-positive cell lines than the monovalent dsFv immunotoxin. However, when tested in mice bearing tumor cells expressing mesothelin, the antitumor activity of the bivalent immunotoxin is very similar to the activity of the lower affinity monovalent immunotoxin. Our data indicate that increasing affinity of an antibody fragment does not necessarily lead to higher antitumor activity of an immunotoxin in vivo. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 5106,37 Convent Dr,MSC 4264, Bethesda, MD 20892 USA. NR 25 TC 15 Z9 17 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2001 VL 1 IS 2 BP 79 EP 84 PG 6 WC Oncology SC Oncology GA 606LZ UT WOS:000178736600001 PM 12467225 ER PT J AU Thompson, KL Rosenzweig, BA Honchel, R Cannon, RE Blanchard, KT Stoll, RE Sistare, FD AF Thompson, KL Rosenzweig, BA Honchel, R Cannon, RE Blanchard, KT Stoll, RE Sistare, FD TI Loss of critical palindromic transgene promoter sequence in chemically induced Tg.AC mouse skin papillomas expressing transgene-derived mRNA SO MOLECULAR CARCINOGENESIS LA English DT Article DE Ha-ras genes; hypomethylation; DNA instability; zeta-globin ID V-HA-RAS; DNA METHYLATION; MICE; CARCINOGENESIS; RECOMBINATION AB The Tg.AC transgenic mouse carries a v-Ha-ras transgene. Skin papillomas develop in Tg.AC mice upon repeated dermal application of tumor promoters and carcinogens. The transgene is inserted at a single site on chromosome 11 in a multiple-copy array. Although most of the greater than or equal to 40 copies are arranged in a direct-repeat orientation, two copies of the transgene are inserted in a palindromic, inverted-repeat orientation. Deletion of the palindromic transgene promoter sequence is associated strongly with and diagnostic of loss of phenotypic responsiveness to Tg.AC papillomagens, such as 12-O-tetradecanoylphorbol-13-acetate (TPA). Unexpectedly, a loss of palindromic transgene sequence, in the absence of an observable reduction in copy number of the direct-repeat-oriented transgene sequence, is seen in DNA from papillomas when compared to genomic DNA from tail clips or skin samples away from the application site. Transgene-derived transcripts were detectable in all Tg.AC papillomas sampled. The transgene locus was hypomethylated in papillomas but not in samples from tail clips from the same animal or from skin samples away from the application site in responder Tg.AC mice, as shown by loss of resistance to digestion by Hpall. A cell line derived from a Tg,AC squamous cell carcinoma showed complete loss of the palindromic transgene sequence, hypomethylation of the transgene locus, and strong expression of v-Ha-ras mRNA. These data indicate that the palindromic transgene sequence, which appears to be necessary for initial responsiveness to tumorigens, may be susceptible to deletion during rapid cellular proliferation and is not required for transgene expression in later phases of papilloma growth. Published 2001 Wiley-Liss, Inc. C1 Boehringer Ingelheim Pharmaceut Inc, Dept Toxicol & Safety Assessment, Ridgefield, CT 06877 USA. NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Sistare, FD (reprint author), US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 23 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD DEC PY 2001 VL 32 IS 4 BP 176 EP 186 DI 10.1002/mc.10009 PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 498QP UT WOS:000172522200002 PM 11746829 ER PT J AU Li, SF Ma, L Chiang, TC Burow, M Newbold, RR Negishi, M Barrett, JC Mclachlan, JA AF Li, SF Ma, L Chiang, TC Burow, M Newbold, RR Negishi, M Barrett, JC Mclachlan, JA TI Promoter CpG methylation of Hox-a10 and Hox-a11 in mouse uterus not altered upon neonatal diethylstilbestrol exposure SO MOLECULAR CARCINOGENESIS LA English DT Article DE diethylstilbestrol (DES); methylation; Hoxa-11; Hoxa-10; uterus ID DNA METHYLATION; GENE-EXPRESSION; IN-UTERO; ESTROGEN; VAGINA; ADENOCARCINOMA; DEMETHYLATION; LACTOFERRIN; MECHANISMS; FERTILITY AB Mouse abdominal B-like Hoxa genes are expressed and functionally required in the developing reproductive tracts. Mice lacking either Hoxa-10 or Hoxa-11, two of the AbdB Hoxa genes, exhibit abnormal uterine development similar to that induced by in utero diethylstilbestrol (DES) exposure. Indeed, uterine Hoxa-10 and Hoxa-11 expression is potently repressed by perinatal DES exposure, providing a potential molecular mechanism for DES-induced reproductive tract malformations. We have shown previously that DES can permanently alter uterine lactoferrin gene expression through modulation of the lactoferrin promoter methylation pattern. Here we ask whether a similar mechanism also functions to deregulate uterine Hoxa-10 or Hoxa-11 expression during neonatal DES exposure. We mapped the Hoxa-10 promoter by cloning a 1.485 kb DNA fragment 5' of the Hoxa-10 exon1a. A 5' rapid amplification of cDNA ends (RACE) experiment revealed a transcription start site for the a 10-1 transcript. Functional analysis of the proximal 200-bp sequences demonstrated significant promoter activity, confirming the location of the Hoxa-10 promoter. Moreover, methylation assays performed on eight CpGs in Hoxa-10 and 19 CpGs in Hoxa-11 proximal promoters demonstrated that all these CpGs were highly unmethylated in both control and DES-dosed mice from postnatal day 5 to day 30. Significant methylation around Hoxa-10 and Hoxa-11 promoters was only observed in DES-induced uterine carcinomas in 18-mo-old mice. Our results suggest that DES-induced downregulations of Hoxa10 or Hoxa-11 gene expression are not associated with methylation changes in their proximal promoters and that gene imprinting by developmental DES exposure may be a gene-specific phenomenon. Published 2001 Wiley-Liss, Inc. C1 Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA. Tulane Univ, Med Ctr, Dept Pharmacol, New Orleans, LA 70118 USA. Tulane Univ, Med Ctr, Tulane Xavier Ctr Bioenvironm Res, New Orleans, LA 70118 USA. NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. NIEHS, Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Li, SF (reprint author), NIEHS, LBC, NIH, POB 12233,C2-10, Res Triangle Pk, NC 27709 USA. RI Burow, Matthew/D-6351-2013 OI Burow, Matthew/0000-0002-0642-6630 NR 22 TC 35 Z9 38 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD DEC PY 2001 VL 32 IS 4 BP 213 EP 219 DI 10.1002/mc.10015 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 498QP UT WOS:000172522200006 PM 11746833 ER PT J AU Denger, S Reid, G Kos, M Flouriot, G Parsch, D Brand, H Korach, KS Sonntag-Buck, V Gannon, F AF Denger, S Reid, G Kos, M Flouriot, G Parsch, D Brand, H Korach, KS Sonntag-Buck, V Gannon, F TI ER alpha gene expression in human primary osteoblasts: Evidence for the expression of two receptor proteins SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HUMAN ESTROGEN-RECEPTOR; PROMOTER-CONTEXT; RESPONSE ELEMENT; IN-VIVO; BETA; ACTIVATION; MOUSE; IDENTIFICATION; ISOFORMS; MICE AB The beneficial influence of E2 in the maintenance of healthy bone is well recognized. However, the way in which the actions of this hormone are mediated is less clearly understood. Western blot analysis of ER alpha in osteoblasts clearly demonstrated that the well characterized 66-kDa ER alpha was only one of the ER alpha isoforms present. Here we describe a 46-kDa isoform of ER alpha, expressed at a level similar to the 66-kDa isoform, that is also present in human primary osteoblasts. This shorter isoform is generated by alternative splicing of an ER alpha gene product, which results in exon 1 being skipped with a start codon in exon 2 used to initiate translation of the protein. Consequently, the transactivation domain AF-1 of this ER alpha isoform is absent. Functional analysis revealed that human (h)ER alpha 46 is able to heterodimerize with the full-length ER alpha and also with ERP. Further, a DNA-binding complex that corresponds to hER alpha 46 is detectable in human osteoblasts. We have shown that hER alpha 46 is a strong inhibitor of hER alpha 66 when they are coexpressed in the human osteosarcoma cell line SaOs. As a functional consequence, proliferation of the transfected cells is inhibited when increasing amounts of hER alpha 46 are cotransfected with hER alpha 66. In addition to human bone, the expression of the alternatively spliced ER alpha mRNA variant is also detectable in bone of ER alpha knockout mice. These data suggest that, in osteoblasts, E2 can act in part through an ER alpha isoform that is markedly different from the 66-kDa receptor. The expression of two ER alpha protein isoforms may account, in part, for the differential action that estrogens and estrogen analogs have in different tissues. In particular, the current models of the action of estrogens should be reevaluated to take account of the presence of at least two ER alpha protein isoforms in bone and perhaps in other tissues. C1 European Mol Biol Lab, D-69117 Heidelberg, Germany. CNRS, UPRES A 6026, F-35042 Rennes, France. Univ Heidelberg, Dept Orthoped, D-69118 Heidelberg, Germany. NIEHS, Res Triangle Pk, NC 27709 USA. RP Denger, S (reprint author), European Mol Biol Lab, Meyerhofstr 1, D-69012 Heidelberg, Germany. RI Kos, Martin/E-2534-2011; Gannon, Frank/G-1194-2015; Flouriot, Gilles/K-1833-2015; OI Kos, Martin/0000-0002-3337-9681; Korach, Kenneth/0000-0002-7765-418X NR 38 TC 108 Z9 111 U1 1 U2 5 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2001 VL 15 IS 12 BP 2064 EP 2077 DI 10.1210/me.15.12.2064 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 497PN UT WOS:000172464800002 PM 11731609 ER PT J AU Edgar, R Chattoraj, DK Yarmolinsky, M AF Edgar, R Chattoraj, DK Yarmolinsky, M TI Pairing of P1 plasmid partition sites by ParB SO MOLECULAR MICROBIOLOGY LA English DT Article ID INTEGRATION HOST FACTOR; ESCHERICHIA-COLI; F-PLASMID; MINI-F; CHROMOSOME SEGREGATION; SOPB PROTEIN; DNA; REPLICATION; COMPLEX; LOCALIZATION AB The mechanisms by which bacterial plasmids and chromosomes are partitioned are largely obscure, but it has long been assumed that the molecules to be separated are initially paired, as are sister chromatids in mitosis. We offer in vivo evidence that the partition protein ParB encoded by the bacterial plasmid P1 can pair cis-acting partition sites of P1 inserted in a small, multicopy plasmid. ParB was shown previously to be capable of extensive spreading along DNA flanking the partition sites. Experiments in which ParB spreading was constrained by physical roadblocks suggest that extensive spreading is not required for the pairing process. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Yarmolinsky, M (reprint author), NCI, Biochem Lab, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. NR 40 TC 58 Z9 58 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 2001 VL 42 IS 5 BP 1363 EP 1370 DI 10.1046/j.1365-2958.2001.02717.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 503QX UT WOS:000172812700018 PM 11886565 ER PT J AU Corchero, J Granvil, CP Akiyama, TE Hayhurst, GP Pimprale, S Feigenbaum, L Idle, JR Gonzalez, FJ AF Corchero, J Granvil, CP Akiyama, TE Hayhurst, GP Pimprale, S Feigenbaum, L Idle, JR Gonzalez, FJ TI The CYP2D6 humanized mouse: Effect of the human CYP2D6 transgene and HNF4 alpha on the disposition of debrisoquine in the mouse SO MOLECULAR PHARMACOLOGY LA English DT Article ID DRUG OXIDATION; LIQUID-CHROMATOGRAPHY; RENAL-FUNCTION; GENE; METABOLISM; FAMILY; 4-HYDROXYLATION; SUPERFAMILY; POPULATION; LIVER AB CYP2D6 is a highly polymorphic human gene responsible for a large variability in the disposition of more than 100 drugs to which humans may be exposed. Animal models are inadequate for preclinical pharmacological evaluation of CYP2D6 substrates because of marked species differences in CYP2D isoforms. To overcome this issue, a transgenic mouse line expressing the human CYP2D6 gene was generated. The complete wild-type CYP2D6 gene, including its regulatory sequence, was microinjected into a fertilized FVB/N mouse egg, and the resultant offspring were genotyped by both polymerase chain reaction and Southern blotting. CYP2D6-specific protein expression was detected in the liver, intestine, and kidney from only the CYP2D6 humanized mice. Pharmacokinetic analysis revealed that debrisoquine (DEB) clearance was markedly higher (94.1 +/- 22.3 l/h/kg), and its half-life significantly reduced (6.9 +/-1.6 h), in CYP2D6 humanized mice compared with wild-type animals (15.2 +/-0.9 l/h/kg and 16.5 +/-4.5 h, respectively). Mutations in hepatic nuclear factor 4 alpha (HNF4 alpha), a hepatic transcription factor known to regulate in vitro expression of the CYP2D6 gene, could affect the disposition of CYP2D6 drug substrates. To determine whether the HNF4 alpha gene modulates in vivo pharmacokinetics of CYP2D6 substrates, a mouse line carrying both the CYP2D6 gene and the HNF4 alpha conditional mutation was generated and phenotyped using DEB. After deletion of HNF4 alpha, DEB 4-hydroxylase activity in CYP2D6 humanized mice decreased more than 50%. The data presented in this study show that only CYP2D6 humanized mice but not wild-type mice display significant DEB 4-hydroxylase activity and that HNF4 alpha regulates CYP2D6 activity In vivo. The CYP2D6 humanized mice represent an attractive model for future preclinical studies on the pharmacology, toxicology, and physiology of CYP2D6-mediated metabolism. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NCI, Lab Anim Resources, NIH, Bethesda, MD 20892 USA. Norwegian Univ Sci & Technol, Inst Canc Res & Mol Biol, N-7034 Trondheim, Norway. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3E24, Bethesda, MD 20892 USA. NR 36 TC 98 Z9 102 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2001 VL 60 IS 6 BP 1260 EP 1267 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 500LQ UT WOS:000172629400015 PM 11723233 ER PT J AU Jhaveri, MS Wagner, C Trepel, JB AF Jhaveri, MS Wagner, C Trepel, JB TI Impact of extracellular folate levels on global gene expression SO MOLECULAR PHARMACOLOGY LA English DT Article ID H-CADHERIN CDH13; BINDING-PROTEINS; KB-CELLS; S-ADENOSYLMETHIONINE; DNA METHYLATION; BREAST-CANCER; DEFICIENCY; ADHESION; METABOLISM; RECEPTORS AB Methylation of DNA is associated with gene silencing. DNA methylation uses S-adenosylmethionine (SAM) as the methyl donor and the formation of SAM requires a continuous supply of folate from the extracellular milieu. Low extracellular folate levels are known to result in induction of expression of the human a folate receptor in nasopharyngeal epidermoid carcinoma cells. Low folate levels have been implicated in global activation of gene expression. We have investigated the impact of lowering the level of extracellular folate by performing cDNA microarray analysis of global gene expression in human nasopharyngeal carcinoma KB cells grown in folate-deplete and folate-replete medium. We found that expression of only eight genes reproducibly responded to variation of folate levels. Among those, three were up-regulated and five were downregulated. Examination of one gene, H-cadherin, demonstrated down-regulation in response to folate depletion. Despite the low level of extracellular folate, there was hypermethylation of H-cadherin 5' sequences. These data indicate that low extracellular folate positively and negatively influences the expression levels of a small cohort of genes. The data suggest that folate deficiency is associated with gene-specific methylation/demethylation, rather than global DNA demethylation and transcriptional activation. C1 NCI, Dept Cell & Canc Biol, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37212 USA. RP Jhaveri, MS (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Dept Oncol, Washington, DC 20007 USA. NR 34 TC 120 Z9 124 U1 0 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2001 VL 60 IS 6 BP 1288 EP 1295 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 500LQ UT WOS:000172629400018 PM 11723236 ER PT J AU Nabel, EG AF Nabel, EG TI Dr. Jeffrey M. Isner 1947-2001 - In memoriam SO MOLECULAR THERAPY LA English DT Biographical-Item C1 NHLBI, Clin Res Program, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, Clin Res Program, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD DEC PY 2001 VL 4 IS 6 BP 510 EP 510 DI 10.1006/mthe.2001.0505 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 500MX UT WOS:000172632300002 ER PT J AU Bulte, JWM Douglas, T Witwer, B Zhang, SC Strable, E Lewis, BK Zywicke, H Miller, B van Gelderen, P Moskowitz, BM Duncan, ID Frank, JA AF Bulte, JWM Douglas, T Witwer, B Zhang, SC Strable, E Lewis, BK Zywicke, H Miller, B van Gelderen, P Moskowitz, BM Duncan, ID Frank, JA TI Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells SO NATURE BIOTECHNOLOGY LA English DT Article ID MR CONTRAST AGENT; POLYAMIDOAMINE DENDRIMERS; MAMMALIAN-CELLS; GENE DELIVERY; IN-VIVO; RAT; RELAXOMETRY; GENERATION; PEPTIDE; BRAIN AB Magnetic resonance (MR) tracking of magnetically labeled stem and progenitor cells is an emerging technology, leading to an urgent need for magnetic probes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnetic tags that can efficiently label mammalian cells, including human neural stem cells (NSCs) and mesenchymal stem cells (MSCs), through a nonspecific membrane adsorption process with subsequent intracellular (non-nuclear) localization in endosomes. The superparamagnetic iron oxide nanocomposites have been optimized to exhibit superior magnetic properties and to induce sufficient MR cell contrast at incubated doses as low as 1 mug iron/ml culture medium. When containing between 9 and 14 pg iron/cell, labeled cells exhibit an ex vivo nuclear magnetic resonance (NMR) relaxation rate (1/T2) as high as 24-39 s(-1)/mM iron. Labeled cells are unaffected in their viability and proliferating capacity, and labeled human NSCs differentiate normally into neurons. Furthermore, we show here that NSC-derived (and LacZ-transfected), magnetically labeled oligodendroglial progenitors can be readily detected in vivo at least as long as six weeks after transplantation, with an excellent correlation between the obtained MR contrast and staining for beta -galactosidase expression. The availability of magnetodendrimers opens up the possibility of MR tracking of a wide variety of (stem) cell transplants. C1 NIH, Lab Diagnost Radiol Res CC, Bethesda, MD 20892 USA. Temple Univ, Dept Chem, Philadelphia, PA 19122 USA. Univ Wisconsin, Sch Vet Med, Dept Med Sci, Madison, WI 53705 USA. NINCDS, Adv Magnet Resonance Imaging, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Geol & Geophys, Inst Rock Magnetism, Minneapolis, MN 55455 USA. RP Bulte, JWM (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. RI Bulte, Jeff/A-3240-2008; Douglas, Trevor/F-2748-2011; Miller, Bradley/G-7426-2014 OI Bulte, Jeff/0000-0003-1202-1610; NR 38 TC 761 Z9 811 U1 12 U2 79 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2001 VL 19 IS 12 BP 1141 EP 1147 DI 10.1038/nbt1201-1141 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 498RN UT WOS:000172524400027 PM 11731783 ER PT J AU Churchill, GA Oliver, B AF Churchill, GA Oliver, B TI Sex, flies and microarrays SO NATURE GENETICS LA English DT Editorial Material ID GENE-EXPRESSION; DNA MICROARRAY AB In a typical microarray study, experimental RNA samples are compared to a reference sample and expression ratios are clustered. A new study of the effects of sex, aging and genotype on gene expression in Drosophila melanogaster departs from this paradigm. Highly replicated comparisons generate measures of expression that are analyzed using classical analysis of variance (ANOVA) techniques, revealing substantial differences in gene expression between the two sexes as well as smaller effects of age and strain. Moreover, this study demonstrates that replication and experimental design are essential to detecting small but biologically important differences in expression patterns. C1 Jackson Lab, Bar Harbor, ME 04609 USA. NIDDK, NIH, Cellular & Dev Biol Lab, Bethesda, MD USA. RP Churchill, GA (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. NR 12 TC 28 Z9 29 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2001 VL 29 IS 4 BP 355 EP 356 DI 10.1038/ng1201-355 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 498JZ UT WOS:000172507500002 PM 11726914 ER PT J AU Bennett, CB Lewis, LK Karthikeyan, G Lobachev, KS Jin, YH Sterling, JF Snipe, JR Resnick, MA AF Bennett, CB Lewis, LK Karthikeyan, G Lobachev, KS Jin, YH Sterling, JF Snipe, JR Resnick, MA TI Genes required for ionizing radiation resistance in yeast SO NATURE GENETICS LA English DT Article ID PUTATIVE RNA HELICASE; SACCHAROMYCES-CEREVISIAE; DNA-DAMAGE; CELL-CYCLE; REPAIR; EXPRESSION; PROTEIN; CHECKPOINT; END; RECOMBINATION AB The ability of Saccharomyces cerevisiae to tolerate ionizing radiation damage requires many DNA-repair and checkpoint genes, most having human orthologs. A genome-wide screen of diploid mutants homozygous with respect to deletions of 3,670 nonessential genes revealed 107 new loci that influence gamma -ray sensitivity. Many affect replication, recombination and checkpoint functions. Nearly 90% were sensitive to other agents, and most new genes could be assigned to the following functional groups: chromatin remodeling, chromosome segregation, nuclear pore formation, transcription, Golgi/vacuolar activities, ubiquitin-mediated protein degradation, cytokinesis, mitochondrial activity and cell wall maintenance. Over 50% share homology with human genes, including 17 implicated in cancer, indicating that a large set of newly identified human genes may have related roles in the toleration of radiation damage. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Resnick, MA (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 50 TC 229 Z9 236 U1 2 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2001 VL 29 IS 4 BP 426 EP 434 DI 10.1038/ng778 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 498JZ UT WOS:000172507500018 PM 11726929 ER PT J AU Mears, AJ Kondo, M Swain, PK Takada, Y Bush, RA Saunders, TL Sieving, PA Swaroop, A AF Mears, AJ Kondo, M Swain, PK Takada, Y Bush, RA Saunders, TL Sieving, PA Swaroop, A TI Nrl is required for rod photoreceptor development SO NATURE GENETICS LA English DT Article ID NUCLEAR RECEPTOR; LEUCINE-ZIPPER; CELL FATE; RETINA; PROTEIN; MICE; MOUSE; GENE; CRX; DEGENERATION AB The protein neural retina leucine zipper (Nrl) is a basic motif-leucine zipper transcription factor that is preferentially expressed in rod photoreceptors(1,2). it acts synergistically with Crx to regulate rhodopsin transcription(3-5). Missense mutations in human NRL have been associated with autosomal dominant retinitis pigmentosa(6,7). Here we report that deletion of Nrl in mice results in the complete loss of rod function and super-normal cone function, mediated by S cones. The photoreceptors in the Nrl(-/-) retina have cone-like nuclear morphology(8) and short, sparse outer segments with abnormal disks. Analysis of retinal gene expression confirms the apparent functional transformation of rods into S cones in the Nrl(-/-) retina. On the basis of these findings, we postulate that Nrl acts as a 'molecular switch' during rod-cell development by directly modulating rod-specific genes while simultaneously inhibiting the S-cone pathway through the activation of Nr2e3. C1 Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. Nagoya Univ, Sch Med, Dept Ophthalmol, Nagoya, Aichi 4668550, Japan. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Swaroop, A (reprint author), Univ Michigan, Dept Ophthalmol & Visual Sci, 1500 E Med Ctr Dr, Ann Arbor, MI 48105 USA. OI Swaroop, Anand/0000-0002-1975-1141 FU NEI NIH HHS [EY07003, EY11115] NR 31 TC 520 Z9 526 U1 3 U2 17 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2001 VL 29 IS 4 BP 447 EP 452 DI 10.1038/ng774 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 498JZ UT WOS:000172507500021 PM 11694879 ER PT J AU McIntire, JJ Umetsu, SE Akbari, O Potter, M Kuchroo, VK Barsh, GS Freeman, GJ Umetsu, DT DeKruyff, RH AF McIntire, JJ Umetsu, SE Akbari, O Potter, M Kuchroo, VK Barsh, GS Freeman, GJ Umetsu, DT DeKruyff, RH TI Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family SO NATURE IMMUNOLOGY LA English DT Article ID HEPATITIS-A VIRUS; ETHNICALLY DIVERSE POPULATIONS; HEAT-KILLED LISTERIA; GENOME-WIDE SEARCH; CD4(+) T-CELLS; CELLULAR RECEPTOR; CHROMOSOME 5Q31-Q33; ATOPIC DISORDER; ASTHMA; MICE AB To simplify the analysis of asthma susceptibility genes located at human chromosome 5q23-35, we examined congenic mice that differed at the homologous chromosomal segment. We identified a Mendelian trait encoded by T cell and Airway Phenotype Regulator (Tapr). Tapr is genetically distinct from known cytokine genes and controls the development of airway hyperreactivity and T cell production of interleukin 4 (IL-4) and IL-13. Positional cloning identified a gene family that encodes T cell membrane proteins (TIMs); major sequence variants of this gene family (Tim) completely cosegregated with Tapr. The human homolog of TIM-I is the hepatitis A virus (HAV) receptor, which may explain the inverse relationship between HAV infection and the development of atopy. C1 Stanford Univ, Dept Pediat, Div Immunol & Allergy, Stanford, CA 94305 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA. NCI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP DeKruyff, RH (reprint author), Stanford Univ, Dept Pediat, Div Immunol & Allergy, Stanford, CA 94305 USA. EM rdk@stanford.edu RI Jones, Jennifer/C-8691-2015 OI Jones, Jennifer/0000-0002-9488-7719 FU NCI NIH HHS [CA84500, CA09302]; NIAID NIH HHS [AI-24571] NR 63 TC 321 Z9 372 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2001 VL 2 IS 12 BP 1109 EP 1116 DI 10.1038/ni739 PG 8 WC Immunology SC Immunology GA 497UE UT WOS:000172473200012 PM 11725301 ER PT J AU Schaeffer, EM Yap, GS Lewis, CM Czar, MJ McVicar, DW Cheever, AW Sher, A Schwartzberg, PL AF Schaeffer, EM Yap, GS Lewis, CM Czar, MJ McVicar, DW Cheever, AW Sher, A Schwartzberg, PL TI Mutation of Tec family kinase alters T helper cell differentiation SO NATURE IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-3; IN-VIVO; PEPTIDE LIGANDS; TYROSINE KINASE; TH2 DEVELOPMENT; MICE LACKING; NFAT FAMILY; EXPRESSION; CD4; ANTIGEN AB The Tec kinases RIk and Itk are critical for full T cell receptor (TCR)-induced activation of phospholipase C-gamma and mitogen-activated protein kinase. We show here that the mutation of RIk and Itk impaired activation of the transcription factors NFAT and AP-1 and production of both T helper type I (T(H)1) and T(H)2 cytokines. Consistent with these biochemical defects, Itk(-/-) mice did not generate effective T(H)2 responses when challenged with Schistosoma mansoni eggs. Paradoxically, the more severely impaired RIk(-/-)Itk(-/-) mice were able to mount a T(H)2 response and produced T(H)2 cytokines in response to this challenge. In addition, RIk(-/-)Itk(-/-) cells showed impaired TCR-induced repression of the T(H)2-inducing transcription factor GATA-3, suggesting a potential mechanism for T(H)2 development in these hyporesponsive cells. Thus, mutations that affect Tec kinases lead to complex alterations in CD4(+)T(H) cell differentiation. C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Biomed Res Inst, Rockville, MD 20852 USA. Brown Univ, Dept Med Microbiol & Immunol, Providence, RI 02912 USA. RP Schwartzberg, PL (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. RI McVicar, Daniel/G-1970-2015 NR 45 TC 130 Z9 133 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2001 VL 2 IS 12 BP 1183 EP 1188 DI 10.1038/ni734 PG 6 WC Immunology SC Immunology GA 497UE UT WOS:000172473200022 PM 11702066 ER PT J AU Lane, HC La Montagne, J Fauci, AS AF Lane, HC La Montagne, J Fauci, AS TI Bioterrorism: A clear and present danger SO NATURE MEDICINE LA English DT Editorial Material ID ANTHRAX; VACCINE AB The anthrax attacks in the United States, juxtaposed against the September 11 terrorist attacks on New York and Washington, DC, have transformed a theoretical threat to stark reality. The biomedical research community will be an Integral part of the preparation for, defense against and response to bioterrorism. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Lane, HC (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 123 Z9 131 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2001 VL 7 IS 12 BP 1271 EP 1273 DI 10.1038/nm1201-1271 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 500DH UT WOS:000172610300019 PM 11726956 ER PT J AU Lei, BF DeLeo, FR Hoe, NP Graham, MR Mackie, SM Cole, RL Liu, MY Hill, HR Low, DE Federle, MJ Scott, JR Musser, JM AF Lei, BF DeLeo, FR Hoe, NP Graham, MR Mackie, SM Cole, RL Liu, MY Hill, HR Low, DE Federle, MJ Scott, JR Musser, JM TI Evasion of human innate and acquired immunity by a bacterial homolog of CD11b that inhibits opsonophagocytosis SO NATURE MEDICINE LA English DT Article ID GROUP-A STREPTOCOCCUS; COMPLEMENT RECEPTOR TYPE-3; HYALURONIC-ACID CAPSULE; FC-GAMMA-RIII; M-PROTEIN; BINDING-SITE; INTEGRIN; MAC-1; PHAGOCYTOSIS; ACTIVATION AB Microbial pathogens must evade the human immune system to survive, disseminate and cause disease. By proteome analysis of the bacterium Group A Streptococcus (GAS), we identified a secreted protein with homology to the alpha -subunit of Mac-1, a leukocyte beta (2) integrin required for innate immunity to invading microbes. The GAS Mac-1-like protein (Mac) was secreted by most pathogenic strains, produced in log-phase and controlled by the covR-covS two-component gene regulatory system, which also regulates transcription of other GAS virulence factors. Patients with GAS infection had titers of antibody specific to Mac that correlated with the course of disease, demonstrating that Mac was produced in vivo. Mac bound to CD16 (Fc gamma RIIIB) on the surface of human polymorphonuclear leukocytes and inhibited opsonophagocytosis and production of reactive oxygen species, which resulted in significantly decreased pathogen killing. Thus, by mimicking a host-cell receptor required for an innate immune response, the GAS Mac protein inhibits professional phagocyte function by a novel strategy that enhances pathogen survival, establishment of infection and dissemination. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Med, Salt Lake City, UT USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Mt Sinai Hosp, Dept Microbiol, Toronto, ON M5G 1X5, Canada. Univ Toronto, Toronto, ON, Canada. RP Lei, BF (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. RI Low, Donald/B-1726-2012; Federle, Michael/E-5522-2017; OI DeLeo, Frank/0000-0003-3150-2516 FU NIAID NIH HHS [AI20823, T32AI07470] NR 38 TC 120 Z9 122 U1 0 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2001 VL 7 IS 12 BP 1298 EP 1305 DI 10.1038/nm1201-1298 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 500DH UT WOS:000172610300034 PM 11726969 ER PT J AU Chen, WS Calvo, PA Malide, D Gibbs, J Schubert, U Bacik, I Basta, S O'Neill, R Schickli, J Palese, P Henklein, P Bennink, JR Yewdell, JW AF Chen, WS Calvo, PA Malide, D Gibbs, J Schubert, U Bacik, I Basta, S O'Neill, R Schickli, J Palese, P Henklein, P Bennink, JR Yewdell, JW TI A novel influenza A virus mitochondrial protein that induces cell death SO NATURE MEDICINE LA English DT Article ID A VIRUS; MESSENGER-RNA; EPITOPES; GENE AB While searching for alternative reading-frame peptides encoded by influenza A virus that are recognized by CD8(+)T cells, we found an abundant immunogenic peptide encoded by the +1 reading frame of PB1. This peptide derives from a novel conserved 87-residue protein, PB1-F2, which has several unusual features compared with other influenza gene products in addition to its mode of translation. These include its absence from some animal (particularly swine) influenza virus Isolates, variable expression in individual infected cells, rapid proteasome-dependent degradation and mitochondrial localization. Exposure of cells to a synthetic version of PB1-F2 induces apoptosis, and influenza viruses with targeted mutations that interfere with PB1-F2 expression Induce less extensive apoptosis in human monocytic cells than those with intact PB1-F2. We propose that PB1-F2 functions to kill host immune cells responding to influenza virus infection. C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-2000 Hamburg, Germany. Humboldt Univ, Inst Biochem, Berlin, Germany. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012; Chen, Weisan/E-7828-2012; OI Palese, Peter/0000-0002-0337-5823 NR 25 TC 571 Z9 624 U1 2 U2 86 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2001 VL 7 IS 12 BP 1306 EP 1312 DI 10.1038/nm1201-1306 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 500DH UT WOS:000172610300035 PM 11726970 ER PT J AU Belyakov, IM Hel, Z Kelsall, B Kuznetsov, VA Ahlers, JD Nacsa, J Watkins, DI Allen, TM Sette, A Altman, J Woodward, R Markham, PD Clements, JD Franchini, G Strober, W Berzofsky, JA AF Belyakov, IM Hel, Z Kelsall, B Kuznetsov, VA Ahlers, JD Nacsa, J Watkins, DI Allen, TM Sette, A Altman, J Woodward, R Markham, PD Clements, JD Franchini, G Strober, W Berzofsky, JA TI Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; HIV-1 PEPTIDE VACCINE; RHESUS-MONKEYS; NEUTRALIZING ANTIBODY; ENVELOPE GLYCOPROTEIN; CELL RESPONSES; SIV INFECTION; CTL; IMMUNIZATION AB Given the mucosal transmission of HIV-1, we compared whether a mucosal vaccine could Induce mucosal cytotoxic T lymphocytes (CTLs) and protect rhesus macaques against mucosal infection with simian/human immunodeficiency virus (SHIV) more effectively than the same vaccine given subcutaneously. Here we show that mucosal CTLs specific for simian immunodeficiency virus can be induced by intrarectal immunization of macaques with a synthetic-peptide vaccine incorporating the LT(R192G) adjuvant. This response correlated with the level of T-helper response. After intrarectal challenge with pathogenic SHIV-Ku2, viral titers were eliminated more completely (to undetectable levels) both in blood and intestine, a major reservoir for virus replication, in intrarectally immunized animals than in subcutaneously immunized or control macaques. Moreover, CD4(+) T cells were better preserved. Thus, induction of CTLs in the intestinal mucosa, a key site of virus replication, with a mucosal AIDS vaccine ameliorates infection by SHIV in non-human primates. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, Bethesda, MD 20892 USA. NCI, Anim Model & Retroviral Vaccines Sect, Basic Res Lab, Bethesda, MD 20892 USA. NIAID, Mucosal Immun Sect, Clin Invest Lab, Bethesda, MD 20892 USA. NICHHD, Sect Med Biophys, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI USA. Epimmune, San Diego, CA USA. Emory Univ, Vaccine Ctr Yerkes, Atlanta, GA 30322 USA. Adv Biosci Labs, Kensington, MD USA. Tulane Univ, Sch Med, Dept Microbiol & Immunol, Program Mol Pathogenesis & Immun, New Orleans, LA 70112 USA. RP Belyakov, IM (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, Bethesda, MD 20892 USA. RI Allen, Todd/F-5473-2011; OI Hel, Zdenek/0000-0002-4923-4794 FU NCRR NIH HHS [R24 RR 15731]; NIAID NIH HHS [N01-AI-95362] NR 44 TC 201 Z9 203 U1 2 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2001 VL 7 IS 12 BP 1320 EP 1326 DI 10.1038/nm1201-1320 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 500DH UT WOS:000172610300037 PM 11726972 ER PT J AU Atzori, M Lei, S Evans, DIP Kanold, PO Phillips-Tansey, E McIntyre, O McBain, CJ AF Atzori, M Lei, S Evans, DIP Kanold, PO Phillips-Tansey, E McIntyre, O McBain, CJ TI Differential synaptic processing separates stationary from transient inputs to the auditory cortex SO NATURE NEUROSCIENCE LA English DT Article ID RECEPTOR CHANNELS; PYRAMIDAL NEURONS; PLASTICITY; CAT; AI; ORGANIZATION; CONNECTIONS; DEPRESSION; KAINATE; TOXINS AB Sound features are blended together en route to the central nervous system before being discriminated for further processing by the cortical synaptic network. The mechanisms underlying this synaptic processing, however, are largely unexplored. Intracortical processing of the auditory signal was investigated by simultaneously recording from pairs of connected principal neurons in layer II/III in slices from A1 auditory cortex. Physiological patterns of stimulation in the presynaptic cell. revealed two populations of postsynaptic events that differed in mean amplitude, failure rate, kinetics and short-term plasticity. In contrast, transmission between layer II/III pyramidal neurons in barrel cortex were uniformly of large amplitude and high success (release) probability (P-r). These unique features of auditory cortical transmission may provide two distinct mechanisms for discerning and separating transient from stationary features of the auditory signal at an early stage of cortical processing. C1 NICHHD, LCMN, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21205 USA. RP McBain, CJ (reprint author), NICHHD, LCMN, NIH, Rm 5A72,Bldg 49,Convent Dr, Bethesda, MD 20892 USA. OI Kanold, Patrick/0000-0002-7529-5435 NR 27 TC 87 Z9 87 U1 1 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2001 VL 4 IS 12 BP 1230 EP 1237 DI 10.1038/nn760 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 498RV UT WOS:000172525000020 PM 11694887 ER PT J AU Gearhart, PJ Wood, RD AF Gearhart, PJ Wood, RD TI Emerging links between hypermutation of antibody genes and DNA polymerases SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID IMMUNOGLOBULIN VARIABLE GENES; DOUBLE-STRAND BREAKS; SOMATIC HYPERMUTATION; IMMUNE-RESPONSE; ERROR-PRONE; B-CELLS; SACCHAROMYCES-CEREVISIAE; EMBRYONIC LETHALITY; CATALYTIC SUBUNIT; GERMINAL-CENTERS AB Substantial antibody variability is created when nucleotide substitutions are introduced into immunoglobulin variable genes by a controlled process of hypermutation. Evidence points to a mechanism involving DNA repair events at sites of targeted breaks. In vertebrate cells, there are many recently identified DNA polymerases that inaccurately copy templates. Some of these are candidates for enzymes that introduce base changes during hypermutation. Recent research has focused on possible roles for DNA polymerases zeta (POLZ), eta (POLH), iota (POLI), and tau (POLM) in the process. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15261 USA. RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Wood, Richard/E-7855-2011 OI Wood, Richard/0000-0002-9495-6892 NR 80 TC 40 Z9 41 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD DEC PY 2001 VL 1 IS 3 BP 187 EP 192 DI 10.1038/35105009 PG 6 WC Immunology SC Immunology GA 635KN UT WOS:000180398200020 PM 11905827 ER PT J AU Leonard, WJ AF Leonard, WJ TI Cytokines and immunodeficiency diseases SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID RECEPTOR-GAMMA-CHAIN; DEFECTIVE LYMPHOID DEVELOPMENT; RESCUES T-LYMPHOPOIESIS; BACILLE CALMETTE-GUERIN; HUMAN IL-2 RECEPTOR; JAK-3 JANUS KINASE; NF-KAPPA-B; INTERLEUKIN-2 RECEPTOR; DEFICIENT MICE; ALPHA-CHAIN AB Severe combined immunodeficiency disease (SCID) refers to a spectrum of inherited immunodeficiencies that together represent the most severe forms of primary immunodeficiency in humans. Recent work has shown that many of these diseases, as well as other forms of immunodeficiency, result from defects in cytokine signalling pathways. Such defects can prevent normal development of lymphoid lineages and/or compromise cytokine signalling by these cells. These natural 'experiments' in human genetics have shown the non-redundant role for several cytokines or cytokine signalling molecules. Moreover, a comparison of the phenotypes of humans with SCID to analogous mouse-knockout models has shown not only expected similarities, but also unexpected differences in cytokine signalling between humans and mice. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 115 TC 211 Z9 216 U1 2 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD DEC PY 2001 VL 1 IS 3 BP 200 EP 208 DI 10.1038/35105066 PG 9 WC Immunology SC Immunology GA 635KN UT WOS:000180398200022 PM 11905829 ER PT J AU Berzofsky, JA Ahlers, JD Belyakov, IM AF Berzofsky, JA Ahlers, JD Belyakov, IM TI Strategies for designing and optimizing new generation vaccines SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID CYTOTOXIC T-LYMPHOCYTE; HUMAN-IMMUNODEFICIENCY-VIRUS; COLONY-STIMULATING FACTOR; PULSED DENDRITIC CELLS; TUMOR-NECROSIS-FACTOR; ANTIGEN-PRESENTING CELLS; ATTENUATED SALMONELLA-TYPHIMURIUM; MELANOMA-REACTIVE CTL; GENE-BASED VACCINES; HIV-1 DNA VACCINE AB Although the field of immunology developed in part from the early vaccine studies of Edward Jenner, Louis Pasteur and others, vaccine development had largely become the province of virologists and other microbiologists, because the model for classic vaccines was to isolate the pathogen and prepare a killed or attenuated pathogen vaccine. Only recently has vaccinology returned to the realm of immunology, because a new understanding of immune mechanisms has allowed translation of basic discoveries into vaccine strategies. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 178 TC 244 Z9 264 U1 3 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD DEC PY 2001 VL 1 IS 3 BP 209 EP 219 DI 10.1038/35105075 PG 11 WC Immunology SC Immunology GA 635KN UT WOS:000180398200023 PM 11905830 ER PT J AU Phair, RD Misteli, T AF Phair, RD Misteli, T TI Kinetic modelling approaches to in vivo imaging SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID FLUORESCENCE CORRELATION SPECTROSCOPY; LIVING CELLS; CHEMICAL-REACTIONS; MEMBRANE PROTEIN; IN-VIVO; DYNAMICS; VISUALIZATION; MICROSCOPY; DIFFUSION; MOBILITY AB The ability to visualize protein dynamics and biological processes by in vivo microscopy is revolutionizing many areas of biology. These methods generate large, kinetically complex data sets, which often cannot be intuitively interpreted. The combination of dynamic imaging and computational modelling is emerging as a powerful tool for the quantitation of biophysical properties of molecules and processes. The new discipline of computational cell biology will be essential in uncovering the pathways, mechanisms and controls of biological processes and systems as they occur in vivo. C1 BioInformat Serv, Rockville, MD 20854 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Phair, RD (reprint author), BioInformat Serv, Rockville, MD 20854 USA. NR 66 TC 183 Z9 188 U1 0 U2 17 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD DEC PY 2001 VL 2 IS 12 BP 898 EP 907 DI 10.1038/35103000 PG 10 WC Cell Biology SC Cell Biology GA 501AQ UT WOS:000172661200017 PM 11733769 ER PT J AU Abbott, KC Hypolite, I Tveit, DP Hshieh, P Cruess, D Agodoa, LY AF Abbott, KC Hypolite, I Tveit, DP Hshieh, P Cruess, D Agodoa, LY TI Hospitalizations for fungal infections after initiation of chronic dialysis in the United States SO NEPHRON LA English DT Article DE fungal infection; diabetes mellitus; meningitis; dialysis; USRDS; Zygomyces; Aspergillus; Candida; cryptococcosis; coccidioidomycosis; mycoses ID AMBULATORY PERITONEAL-DIALYSIS; STAGE RENAL-DISEASE; CRYPTOCOCCAL PERITONITIS; RISK-FACTORS; IMMUNOCOMPROMISED HOST; CHILDREN AB Aims: Hospitalized fungal infections are reported frequently in renal transplant recipients and peritoneal dialysis patients, but the frequency of hospitalized fungal infections in dialysis patients has not been studied in a national population. Methods: 327,993 dialysis patients in the United States Renal Data System initiated from January 1, 1992 to June 30, 1997 were analyzed in a retrospective registry study of fungal infections (based on ICD9 Coding). Results: Dialysis patients had an age-adjusted incidence ratio for fungal infections of 9.80 (95% confidence interval (CI) 6.34-15.25)) compared to the general population in 1996 (the National Hospital Discharge Survey). Candidiasis accounted for 79% of all fungal infections, followed by cryptococcosis (6.0%) and coccidioidomycosis (4.1%). In multivariate analysis, fungal infections were associated with earlier year of dialysis, diabetes, female gender, decreased weight and serum creatinine at initiation of dialysis, chronic obstructive lung disease and AIDS. In Cox regression analysis the hazard ratio for mortality of fungal infections was 1.35 (95% CI 1.28-1.42). Conclusions: Dialysis patients were at increased risk for fungal infections compared to the general population, which substantially decreased patient survival. Female and diabetic patients were at increased risk for fungal infections. Although candidiasis was the dominant etiology of fungal infections, the frequency of cryptococcosis and coccidioidomycosis were higher than previously reported. Copyright (C) 2001 S. Karger AG, Basel. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDDK, Off Minor Hlth Res Coordinat, NIH, Bethesda, MD USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 30 TC 26 Z9 28 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-2766 J9 NEPHRON JI Nephron PD DEC PY 2001 VL 89 IS 4 BP 426 EP 432 DI 10.1159/000046115 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 498MN UT WOS:000172515200012 PM 11721161 ER PT J AU Basile, AS Koustova, E Ioan, P Rizzoli, S Rogawski, MA Usherwood, PNR AF Basile, AS Koustova, E Ioan, P Rizzoli, S Rogawski, MA Usherwood, PNR TI IgG isolated from LP-BM5 infected mouse brain activates ionotropic glutamate receptors SO NEUROBIOLOGY OF DISEASE LA English DT Article ID HIPPOCAMPAL-NEURONS; NERVOUS-SYSTEM; NMDA-RECEPTORS; AMPA RECEPTOR; AMINO-ACIDS; AUTOANTIBODIES; MICE; RESPONSES; 2,3-BENZODIAZEPINE; DESENSITIZATION AB Biochemical and immunological studies have shown that mice infected with LP-BM5 virus develop antibodies to ionotropic glutamate receptors. Here, IgG isolated from brain of infected mice has been tested electrophysiologically on cultured rat cortical and hippocampal neurons. The IgG elicited glycine-independent currents that reversed at similar to0 mV. Equivalent concentrations of IgG from uninfected mice were inactive. The glycine-independent currents were less influenced by DNQX and GYKI-52466 than currents elicited by AMPA and KA. The IgG also elicited glycine-dependent currents that reversed at -10 mV and were blocked by dl-AP5, 5,7-DCKA, and polyamine amides. Glycine-dependent and -independent currents were unaffected by tetrodotoxin, strychnine, the transmembrane Cl- gradient or d-tubocurare. Although part of the glycine-independent current remains uncharacterized, these results confirm that a virus-induced immunopathology produces IgG clones that activate ionotropic glutamate receptors and that could, thereby, contribute to the excitotoxic neurological syndrome observed in LP-BM5-infected mice. (C) 2001 Elsevier Science. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NINCDS, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. Univ Nottingham, Sch Life & Environm Sci, Div Mol Toxicol, Nottingham NG7 2RD, England. RP Basile, AS (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 41 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD DEC PY 2001 VL 8 IS 6 BP 1069 EP 1081 DI 10.1006/nbdi.2001.0442 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 505BV UT WOS:000172892100015 PM 11741402 ER PT J AU Davatzikos, C Genc, A Xu, DR Resnick, SM AF Davatzikos, C Genc, A Xu, DR Resnick, SM TI Voxel-based morphometry using the RAVENS maps: Methods and validation using simulated longitudinal atrophy SO NEUROIMAGE LA English DT Article ID BRAIN IMAGES; DEFORMABLE MODELS; REGISTRATION; DEFORMATIONS; TRANSFORMATION; INFORMATION; ATLAS; MRI AB Statistical analysis of anatomical maps in a stereotaxic space has been shown to be a useful tool in population-based studies for quantifying local anatomical differences or changes, without a priori assumptions about the location and extent of the regions of interest. This paper presents an extension and validation of a previously published methodology, referred to as RAVENS, for characterizing regional atrophy in the brain. A new method for elastic, volume-preserving spatial normalization, which allows for accurate quantification of very localized atrophy, is used. The RAVENS methodology was tested on images with simulated atrophy within two gyri: precentral and superior temporal. It was found to accurately determine the regions of atrophy, despite their localized nature and the interindividual variability of cortical structures. Moreover, it was found to perform substantially better than the voxel-based morphology method of SPM'99. Improved sensitivity was achieved at the expense of human effort involved in defining a number of sulcal curves that serve as constraints on the 3D elastic warping. (C) 2001 Academic Press. C1 Johns Hopkins Univ, Sch Med, Dept Radiol, Ctr Biomed Image Comp, Baltimore, MD 21287 USA. NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. RP Johns Hopkins Univ, Sch Med, Dept Radiol, Ctr Biomed Image Comp, 600 N Wolfe St, Baltimore, MD 21287 USA. FU NIA NIH HHS [AG-93-07, R01-AG14971] NR 40 TC 247 Z9 250 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2001 VL 14 IS 6 BP 1361 EP 1369 DI 10.1006/nimg.2001.0937 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 498RP UT WOS:000172524500013 PM 11707092 ER PT J AU Matsumoto, RR Hewett, KL Pouw, B Bowen, WD Husbands, SM Cao, JJ Newman, AH AF Matsumoto, RR Hewett, KL Pouw, B Bowen, WD Husbands, SM Cao, JJ Newman, AH TI Rimcazole analogs attenuate the convulsive effects of cocaine: correlation with binding to sigma receptors rather than dopamine transporters SO NEUROPHARMACOLOGY LA English DT Article DE cocaine; dopamine transporter; LR176; rimcazole; sigma receptor ID CONDITIONED PLACE PREFERENCE; ISOTHIOCYANATE DERIVATIVES; LOCOMOTOR-ACTIVITY; UPTAKE INHIBITORS; INDUCED TOXICITY; KNOCKOUT MICE; LIGANDS; SITES; DRUGS; BRAIN AB Cocaine interacts with dopamine transporters and sigma receptors at concentrations that are achievable in vivo, suggesting that they may both be viable targets for the development of anti-cocaine agents. Rimeazole binds to both of these targets and also attenuates cocaine-induced locomotor activity and sensitization. To further characterize the mechanisms(s) underlying the attenuation of cocaine-induced convulsions and lethality, rimeazole and three analogs (SH3/24, SH2/21, SH1/57), with a range of affinities for dopamine transporters and sigma receptors, were evaluated. The highly selective and potent sigma receptor ligand LR176 was used as a reference. Competition binding studies confirmed that the rank order of the compounds at dopamine transporters vs. sigma receptors differed, thus enabling a correlation between the relative anti-cocaine activities of the compounds in behavioral Studies and their affinities for dopamine transporters vs. sigma receptors. In behavioral studies, male Swiss Webster mice were pre-treated with one of the compounds (0-60 mg/kg, i.p.), then challenged 15 min later with either a convulsive (60 mg/kg, i.p.) or lethal ( 125 mg/kg, i.p.) dose of cocaine. When the compounds were ranked according to their protective effect, there was a significant correlation between their anticonvulsant actions and their affinities for sigma receptors, but not dopamine transporters. Although the rimeazole analogs were ineffective against the lethal effects of cocaine, the selective sigma receptor ligand LR176 provided significant protection. These data thus suggest that sigma receptors may mediate some of the toxic effects associated with cocaine and that sigma receptor antagonists may be developed as pharmacotherapeutic agents for this application. Published by Elsevier Science Ltd. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Pharmaceut Sci, Oklahoma City, OK 73190 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NIDA, Med Chem Sect, Intramural Res Program, Baltimore, MD 21224 USA. RP Matsumoto, RR (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Pharmaceut Sci, POB 26901, Oklahoma City, OK 73190 USA. RI Husbands, Stephen/D-5926-2011; OI Husbands, Stephen/0000-0002-9928-6322 FU NIDA NIH HHS [DA11979] NR 45 TC 37 Z9 38 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD DEC PY 2001 VL 41 IS 7 BP 878 EP 886 DI 10.1016/S0028-3908(01)00116-2 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 493HE UT WOS:000172215900009 PM 11684152 ER PT J AU Di Monte, D Lawler, CP AF Di Monte, D Lawler, CP TI Mechanisms of Parkinsonism: Session X summary and research needs SO NEUROTOXICOLOGY LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. Parkinsons Inst, Sunnyvale, CA USA. RP Lawler, CP (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 3 Z9 3 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 2001 VL 22 IS 6 BP 853 EP 854 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 516LG UT WOS:000173554300015 PM 11829421 ER PT J AU Shokolenko, I Oberyszyn, TM D'Ambrosio, SM Saavedra, JE Keefer, LK LeDoux, SP Wilson, GL Robertson, FM AF Shokolenko, I Oberyszyn, TM D'Ambrosio, SM Saavedra, JE Keefer, LK LeDoux, SP Wilson, GL Robertson, FM TI Protection of human keratinocyte mtDNA by low-level nitric oxide SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE nitric oxide; DNA damage; mtDNA; keratinocytes ID ALPHA-INDUCED APOPTOSIS; MITOCHONDRIAL-DNA; RAT HEPATOCYTES; HUMAN-CELLS; DAMAGE; REPAIR; GENOTOXICITY; METABOLITES; NITROGEN; OXYGEN AB This study was designed to evaluate the DNA damaging effects of nitric oxide and to determine whether the endogenous generation of nitric oxide at low levels in the cell exerts a protective effect against this damage. Damage to mitochondrial and nuclear DNA in normal human epidermal keratinocytes (NHEK) was assessed after treatment of these cells with varying concentrations of S-nitroso-N-acetylpenicillamine, which decomposes to release nitric oxide. The results showed that mitochondrial DNA was more vulnerable to nitric oxide-induced damage than was a similarly sized fragment of the beta -globin gene. To evaluate the effects on DNA damage by pretreatment of cells with low-levels of nitric oxide, NHEK cells were treated with the prodrug V-PYRRO/NO. This agent is metabolized inside these cells and releases small quantities of nitric oxide. The cells then were exposed to damaging amounts of nitric oxide produced by S-nitroso-N-acetylpenicillamine. The results of these studies showed that pretreatment of NHEK cells with V-PYRRO/NO attenuated the mtDNA damage and loss of cell viability produced by exposure to S-nitroso-N-acetylpenicillamine. (C) 2001 Elsevier Science. C1 Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. Univ S Alabama, Coll Med, Dept Cell Biol & Neurosci, Mobile, AL 36688 USA. Ohio State Univ, Coll Med, Dept Radiol, Div Radiobiol, Columbus, OH 43210 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. RP Robertson, FM (reprint author), Ohio State Univ, Dept Mol Virol Immunol & Med Genet, 2184 Graves Hall,333 W 10th Ave, Columbus, OH 43210 USA. EM Robertson.48@osu.edu RI Oberyszyn, Tatiana/E-3774-2011; Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [CA-69872]; NIEHS NIH HHS [ES-03456] NR 25 TC 6 Z9 6 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 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD DEC PY 2001 VL 5 IS 6 BP 555 EP 560 DI 10.1006/niox.2001.0381 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 503AX UT WOS:000172775900005 PM 11730362 ER PT J AU Schneider, TD AF Schneider, TD TI Strong minor groove base conservation in sequence logos implies DNA distortion or base flipping during replication and transcription initiation SO NUCLEIC ACIDS RESEARCH LA English DT Review ID EPSTEIN-BARR-VIRUS; COLI RNA-POLYMERASE; P1 PLASMID REPLICATION; OPEN-COMPLEX-FORMATION; LAC UV5 PROMOTER; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; BINDING-SITES; INFORMATION ANALYSIS; ORIGIN RECOGNITION AB The sequence logo for DNA binding sites of the bacteriophage P1 replication protein RepA shows unusually high sequence conservation (similar to2 bits) at a minor groove that faces RepA. However, B-form DNA can support only 1 bit of sequence conservation via contacts into the minor groove. The high conservation in RepA sites therefore implies a distorted DNA helix with direct or indirect contacts to the protein. Here I show that a high minor groove conservation signature also appears in sequence logos of sites for other replication origin binding proteins (Rts1, DnaA, P4 alpha, EBNA1, ORC) and promoter binding proteins (sigma (70), sigma (D) factors). This finding implies that DNA binding proteins generally use non-B-form DNA distortion such as base flipping to initiate replication and transcription. C1 NCI, Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Schneider, TD (reprint author), NCI, Lab Expt & Computat Biol, Bldg 469,POB B, Frederick, MD 21702 USA. OI Schneider, Thomas/0000-0002-9841-1531 NR 117 TC 37 Z9 37 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 1 PY 2001 VL 29 IS 23 BP 4881 EP 4891 DI 10.1093/nar/29.23.4881 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497GJ UT WOS:000172446800016 PM 11726698 ER PT J AU Lyakhov, IG Hengen, PN Rubens, D Schneider, TD AF Lyakhov, IG Hengen, PN Rubens, D Schneider, TD TI The P1 phage replication protein RepA contacts an otherwise inaccessible thymine N3 proton by DNA distortion or base flipping SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PLASMID REPLICATION; BINDING-SITES; INFORMATION ANALYSIS; INITIATOR REPA; NUCLEIC-ACIDS; ORIGIN; RECOGNITION; COMPLEX; HEAT; SEQUENCES AB The RepA protein from bacteriophage P1 binds DNA to initiate replication. RepA covers one face of the DNA and the binding site has a completely conserved T that directly faces RepA from the minor groove at position +7. Although all four bases can be distinguished through contacts in the major groove of B-form DNA, contacts in the minor groove cannot easily distinguish between A and T bases. Therefore the 100% conservation at this position cannot be accounted for by direct contacts approaching into the minor groove of B-form DNA. RepA binding sites with modified base pairs at position +7 were used to investigate contacts with RepA. The data show that RepA contacts the N3 proton of T at position +7 and that the T=A hydrogen bonds are already broken in the DNA before RepA binds. To accommodate the N3 proton contact the T+7 /A(+7') base pair must be distorted. One possibility is that T+7 is flipped out of the helix. The energetics of the contact allows RepA to distinguish between all four bases, accounting for the observed high sequence conservation. After protein binding, base pair distortion or base flipping could initiate DNA melting as the second step in DNA replication. C1 NCI, Lab Expt & Computat Biol, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC, Frederick, MD 21702 USA. RP Schneider, TD (reprint author), NCI, Lab Expt & Computat Biol, Bldg 469,POB B, Frederick, MD 21702 USA. OI Schneider, Thomas/0000-0002-9841-1531 FU PHS HHS [N01-C0-56000] NR 33 TC 15 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 1 PY 2001 VL 29 IS 23 BP 4892 EP 4900 DI 10.1093/nar/29.23.4892 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497GJ UT WOS:000172446800017 PM 11726699 ER PT J AU Swerdlow, RD Zwiebel, JA Gravell, AE Cheson, BD AF Swerdlow, RD Zwiebel, JA Gravell, AE Cheson, BD TI Clinical Trials Referral Resource - Current clinical trials of fenretinide SO ONCOLOGY-NEW YORK LA English DT Article ID CANCER CELL-LINES; RETINOID N-(4-HYDROXYPHENYL) RETINAMIDE; CERVICAL-CARCINOMA CELLS; GROWTH-INHIBITION; LEUKEMIA-CELLS; APOPTOSIS; INDUCTION; PROSTATE; 4-HPR; ACID C1 NCI, Bethesda, MD 20892 USA. RP Swerdlow, RD (reprint author), NCI, Bethesda, MD 20892 USA. NR 33 TC 3 Z9 3 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2001 VL 15 IS 12 BP 1595 EP + PG 4 WC Oncology SC Oncology GA 525LK UT WOS:000174071400013 PM 11780702 ER PT J AU Wellmann, A Rohde, V Rosenwald, A Augustin, AJ AF Wellmann, A Rohde, V Rosenwald, A Augustin, AJ TI Lasers and chips: molecular medicine in the age of high-technology SO OPHTHALMOLOGE LA German DT Editorial Material ID GENE-EXPRESSION; CAPTURE MICRODISSECTION; OLIGONUCLEOTIDE ARRAYS; HUMAN CYTOMEGALOVIRUS; TISSUE MICROARRAYS; CDNA ARRAYS; CELL; ELECTROPHORESIS; AMPLIFICATION; SPECIMENS C1 Univ Bonn, Inst Pathol, D-53127 Bonn, Germany. Univ Giessen, Klin & Poliklin Urol, D-35390 Giessen, Germany. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Stadt Klinikum, Augenklin, Karlsruhe, Germany. RP Wellmann, A (reprint author), Univ Bonn, Inst Pathol, Siegmund Freud Str 25, D-53127 Bonn, Germany. NR 20 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0941-293X J9 OPHTHALMOLOGE JI Ophthalmologe PD DEC PY 2001 VL 98 IS 12 BP 1138 EP 1144 PG 7 WC Ophthalmology SC Ophthalmology GA 510HZ UT WOS:000173203800003 PM 11799895 ER PT J AU Hertle, RW FitzGibbon, EJ Avallone, JM Cheeseman, E Tsilou, EK AF Hertle, RW FitzGibbon, EJ Avallone, JM Cheeseman, E Tsilou, EK TI Onset of oscillopsia after visual maturation in patients with congenital nystagmus SO OPHTHALMOLOGY LA English DT Article ID FOVEATION DYNAMICS; IDIOPATHIC NYSTAGMUS; HEAD POSTURES; ACUITY; MOTION; EYE; MOVEMENTS; SURGERY AB Purpose: To describe the clinical and oculographic characteristics of a cohort of five patients with congenital nystagmus (CN) and late-onset oscillopsia caused by a coincidental decline in other visual and/or ocular motor functions. Design: Retrospective, observational, case series. Participants: Five visually mature patients with CN and recent-onset oscillopsia were evaluated clinically and with motility recordings. Intervention: Eye movement analysis was performed off-line by computer analysis of digitized data. Nystagmus was analyzed for null-zone characteristics, waveforms, frequency, amplitudes, and slow-phase drift velocity during foveation. Surgical and medical treatment of associated ocular conditions in four of five patients. Main Outcome Measures: Presence of symptomatic oscillopsia and average time during foveation periods of slow-phase drift velocity less than 10 degrees /second. Results: One of the five patients had associated rod-cone dystrophy, and another had recurrence of childhood head posturing with return of an eccentric null zone. The remaining three patients had decompensated strabismus associated with their oscillopsia. All five patients complained of oscillopsia in primary position that was relieved in the four who received treatment. Treatment included prismatic correction in one patient and surgery in three. Recordings in primary position after treatment showed increased duration during foveation periods of slow-phase drift velocity less than 10 degrees /second and an overall decreased intensity (amplitude/frequency) of the nystagmus. Conclusions: Symptomatic oscillopsia in patients with CN is unusual. This visually disturbing symptom can be precipitated by new or changing associated visual sensory conditions (e.g., decompensating strabismus, retinal degeneration). If the associated conditions can be treated, then accompanying oscillopsia may be relieved. (C) 2001 by the American Academy of Ophthalmology. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. NEI, Ophthalm Genet & Clin Serv Branch, NIH, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Dept Ophthalmol, Bethesda, MD USA. RP Hertle, RW (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49 Room 2A50, Bethesda, MD 20892 USA. NR 35 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2001 VL 108 IS 12 BP 2301 EP 2307 DI 10.1016/S0161-6420(01)00815-6 PG 7 WC Ophthalmology SC Ophthalmology GA 496VM UT WOS:000172417800046 PM 11733274 ER PT J AU Gatton, ML Hogarth, W Saul, A AF Gatton, ML Hogarth, W Saul, A TI Time of treatment influences the appearance of drug-resistant parasites in Plasmodium falciparum infections SO PARASITOLOGY LA English DT Article DE malaria; Plasmodium falciparum; drug resistance; antibodies; PfEMP1; mathematical modelling ID DIHYDROFOLATE-REDUCTASE; POPULATION-DYNAMICS; ANTIMALARIAL-DRUGS; MALARIA PARASITES; CHEMOTHERAPY; COMBINATION; ATOVAQUONE; EMERGENCE; SELECTION; MUTATIONS AB A deterministic mathematical model which predicts the probability of developing a new drug-resistant parasite population within the human host is reported, The model incorporates the host's specific antibody response to PfEMP1, and also investigates the influence of chemotherapy on the probability of developing a viable drug-resistant parasite population within the host. Results indicate that early, treatment, and a high antibody threshold coupled with a long lag time between antibody stimulation and activity, are risk factors which increase the likelihood of developing a viable drug-resistant parasite population. High parasite mutation rates and fast PfEMP1 var gene switching are also identified as risk factors. The model output allows the relative importance of the various risk factors as well as the relationships between them to be established, thereby increasing the understanding of the conditions which favour the development of a new drug-resistant parasite population. C1 Royal Brisbane Hosp, Malaria Biol Lab, Queensland Inst Med Res, Brisbane, Qld 4029, Australia. Griffith Univ, Fac Environm Sci, Brisbane, Qld 4111, Australia. NIAID, Malaria Vaccine Dev Unit, NIH, Bethesda, MD 20852 USA. RP Gatton, ML (reprint author), Royal Brisbane Hosp, Malaria Biol Lab, Queensland Inst Med Res, Brisbane, Qld 4029, Australia. RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 FU NIAID NIH HHS [AI47500-02] NR 27 TC 12 Z9 12 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0031-1820 J9 PARASITOLOGY JI Parasitology PD DEC PY 2001 VL 123 BP 537 EP 546 PN 6 PG 10 WC Parasitology SC Parasitology GA 518NP UT WOS:000173675000001 PM 11814040 ER PT J AU Taranger, J Trollfors, B Bergfors, E Knutsson, N Lagergard, T Schneerson, R Robbins, JB AF Taranger, J Trollfors, B Bergfors, E Knutsson, N Lagergard, T Schneerson, R Robbins, JB TI Immunologic and epidemiologic experience of vaccination with a monocomponent pertussis toxoid vaccine SO PEDIATRICS LA English DT Article DE pertussis; pertussis toxoid; vaccine ID COMPONENT DTP VACCINE; SERUM IGG ANTIBODIES; BORDETELLA-PERTUSSIS; WHOOPING-COUGH; HOUSEHOLD EXPOSURE; FILAMENTOUS HEMAGGLUTININ; HYDROGEN-PEROXIDE; CONTROLLED TRIAL; PARAPERTUSSIS INFECTION; COMPARATIVE EFFICACY AB Pertussis re-emerged in Sweden with a cumulative incidence of about 60% during the first 10 years of life, when the locally produced cellular vaccine lost its efficacy around 1970 and general vaccination was discontinued in 1979. The epidemiology, clinical features, and immunology of pertussis and a monocomponent pertussis toxoid vaccine were studied in Goteborg, Sweden. After phase 1 and 2 studies, a randomized, double-blind, placebo-controlled trial of pertussis toxoid (PTox), compounded with diphtheria and tetanus toxoids, was administered to 3450 children according to the Swedish schedule at 3, 5, and 12 months of age. After a mean follow-up of 18 months, the efficacy was 71% overall and 75% in household contacts, respectively. A statistically significant correlation was found between the level of PTox-induced antibodies and protection against pertussis. As observed with cellular and with multicomponent acellular vaccines, PTox reduced the severity of disease and the percent of children with positive cultures. Furthermore, vaccination reduced the transmission of Bordetella pertussis to household contacts in the vaccinees compared with the controls who received only diphtheria and tetanus toxoids. Patients with culture-verified Bordetella parapertussis infection reacted with antibodies to pertactin and to filamentous hemagglutinin but not to pertussis toxin, and some subsequently developed pertussis. The antibody responses of patients with pertussis to the surface polysaccharides of B pertussis and to B parapertussis were cross-reactive serologically. Serosurveys showed that only antibodies to pertussis toxin were related to the occurrence of pertussis in the general population: antibodies to filamentous hemagglutinin and pertactin were probably stimulated by antigens of other bacteria as well as Bordetellae. Mass vaccination of Goteborg children born in the 1990s was started in 1995. In February 1999, about 55% had been vaccinated and both B pertussis and pertussis decreased significantly in individuals of all ages (herd immunity). Similar to diphtheria, PTox-induced immunity to pertussis occurs both on an individual and community basis. The apparent greater efficacy of multicomponent acellular pertussis vaccines compared with monocomponent PTox was proposed to be an artifact created when the diagnosis of pertussis was made by the serologic criteria of the World Health Organization only. Our conclusion is that PTox is both an essential and alone sufficient antigen in acellular pertussis vaccines. C1 Goteborg Primary Hlth Care, Goteborg Pertussis Vaccine Study, Gothenburg, Sweden. NICHHD, NIH, Bethesda, MD 20892 USA. RP Taranger, J (reprint author), Pediat Outpatient Clin, Topasgatan 59, S-42148 Vastra Frolunda, Sweden. NR 71 TC 14 Z9 14 U1 0 U2 1 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 2001 VL 108 IS 6 AR e115 DI 10.1542/peds.108.6.e115 PG 6 WC Pediatrics SC Pediatrics GA 498EZ UT WOS:000172498000019 PM 11731642 ER PT J AU Kidd, RS Curry, TB Gallagher, S Edeki, T Blaisdell, J Goldstein, JA AF Kidd, RS Curry, TB Gallagher, S Edeki, T Blaisdell, J Goldstein, JA TI Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin SO PHARMACOGENETICS LA English DT Article DE cytochrome P450; polymorphism; pharmacokinetics; phenytoin ID HUMAN LIVER-MICROSOMES; GENETIC-DEFECT; S-MEPHENYTOIN; BLEEDING COMPLICATIONS; CYTOCHROME P4502C9; POOR METABOLIZER; DRUG-METABOLISM; POLYMORPHISM; SUBFAMILY; CYP2C9-ASTERISK-3 AB Cytochrome P450 (CYP) 2C9 is the principal enzyme responsible for the metabolism of numerous clinically important drugs. Two polymorphic alleles CYP2C9*2 and CYP2C9*3 have been documented which affect the metabolism and clinical toxicity of drugs such as phenytoin, warfarin, glipizide, and tolbutamide. The present study reports the first example of a null polymorphism in CYP2C9. This mutation dramatically affects the half-life and clinical toxicity of phenytoin. The study subject was a female African-American presented to the emergency department with phenytoin toxicity evidenced by mental confusion, slurred speech, memory loss and the inability to stand. She exhibited extremely poor clearance of phenytoin with an elimination half-life of approximately 13 days. Genotyping studies demonstrated that the patient did not possess any known variant CYP2C9 alleles. Phenytoin is metabolized to a minor extent by the polymorphic CYP2C19, but this individual did not possess any variant CYP2C19 alleles. Sequencing studies revealed that the individual was homozygous for a new CYP2C9 allele (CYP2C9*6) with the deletion of an adenine at base pair 818 of the cDNA. The clearance of phenytoin in this individual is estimated to be approximately 17% of that observed in normal patients. The frequency of this allele was 0.6% (95% confidence limits of 0.1 to 3.5%) in 79 African-Americans and 0% (95% confidence limits of 0 to 1.1%) in 172 Caucasians. The study also demonstrates the severe clinical consequences to patients with a null mutation in CYP2C9 after treatment with normal doses of phenytoin. Pharmacogenetics 11:803-808 (C) 2001 Lippincott Williams & Wilkins. C1 Shenandoah Univ, Bernard J Dunn Sch Pharm, Dept Biopharmaceut Sci, Winchester, VA 22601 USA. SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Morehouse Sch Med, Atlanta, GA 30310 USA. RP Kidd, RS (reprint author), Shenandoah Univ, Bernard J Dunn Sch Pharm, Dept Biopharmaceut Sci, 1775 N Sector Court, Winchester, VA 22601 USA. RI Goldstein, Joyce/A-6681-2012 FU NCRR NIH HHS [2P20RR11104-06] NR 41 TC 171 Z9 186 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 2001 VL 11 IS 9 BP 803 EP 808 DI 10.1097/00008571-200112000-00008 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 502KH UT WOS:000172742400008 PM 11740344 ER PT J AU Fredholm, BB Ijzerman, AP Jacobson, KA Klotz, KN Linden, J AF Fredholm, BB Ijzerman, AP Jacobson, KA Klotz, KN Linden, J TI International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors SO PHARMACOLOGICAL REVIEWS LA English DT Review ID PROTEIN-COUPLED RECEPTORS; RAT HIPPOCAMPAL SLICES; SMOOTH-MUSCLE CELLS; CYCLIC-AMP ACCUMULATION; SITE-DIRECTED MUTAGENESIS; DOPAMINE D-1 RECEPTORS; CENTRAL-NERVOUS-SYSTEM; AGONIST H-3 CGS-21680; HAMSTER OVARY CELLS; HORMONE SECRETAGOGUE RECEPTOR AB Four adenosine receptors have been cloned and characterized from several mammalian species. The receptors are named adenosine Al, AIA, A(2B), and A(3). The A(2A) and A(2B) receptors preferably interact with members of the G(s) family of G proteins and the A(1) and A(3) receptors with G(i/o) proteins. However, other G protein interactions have also been described. Adenosine is the preferred endogenous agonist at all these receptors, but inosine can also activate the A(3) receptor. The levels of adenosine seen under basal conditions are sufficient to cause some activation of all the receptors, at least where they are abundantly expressed. Adenosine levels during, e.g., ischemia can activate all receptors even when expressed in low abundance. Accordingly, experiments with receptor antagonists and mice with targeted disruption of adenosine A(1), A(2A), and A(3) expression reveal roles for these receptors under physiological and particularly pathophysiological conditions. There are pharmacological tools that can be used to classify A(1), A(1A), and A(3) receptors but few drugs that interact selectively with A(2B) receptors. Testable models of the interaction of these drugs with their receptors have been generated by site-directed mutagenesis and homology-based modelling. Both agonists and antagonists are being developed as potential drugs. C1 Karolinska Inst, Dept Physiol & Pharmacol, Sect Mol Neuropharmacol, S-17177 Stockholm, Sweden. Gorlaeus Labs, Leiden Amsterdam Ctr Drug Res, NL-2300 RA Leiden, Netherlands. NIH, Mol Recognit Sect, Bethesda, MD 20892 USA. Univ Wurzburg, Inst Pharmakol & Toxikol, Wurzburg, Germany. Univ Virginia, Hlth Sci Ctr, Dept Physiol, Charlottesville, VA 22908 USA. RP Fredholm, BB (reprint author), Karolinska Inst, Dept Physiol & Pharmacol, Sect Mol Neuropharmacol, S-17177 Stockholm, Sweden. RI Jacobson, Kenneth/A-1530-2009; OI Jacobson, Kenneth/0000-0001-8104-1493; Klotz, Karl-Norbert/0000-0003-3553-3205 NR 359 TC 1754 Z9 1795 U1 12 U2 53 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 2001 VL 53 IS 4 BP 527 EP 552 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 505GH UT WOS:000172904700003 PM 11734617 ER PT J AU Li, MY Cline, CS Koker, EB Carmichael, HH Chignell, CF Bilski, P AF Li, MY Cline, CS Koker, EB Carmichael, HH Chignell, CF Bilski, P TI Quenching of singlet molecular oxygen (O-1(2)) by azide anion in solvent mixtures SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID AQUEOUS-SOLUTION; ROSE-BENGAL; INFRARED LUMINESCENCE; VARIABLE-TEMPERATURE; CATIONIC SURFACTANT; RATE-CONSTANT; PHOTOPROCESSES; OXIDATION; 1-DELTA-G; EOSIN AB The azide ion is a strong physical quencher of singlet molecular oxygen (O-1(2)) and is frequently employed to show involvement of O-1(2) in oxidation processes. Rate constants (k(q)) for the quenching of O-1(2) by azide are routinely used as standards to calculate k(q) values for quenching by other substrates. We have measured k(q) for azide in solvent mixtures containing deuterium oxide (D2O), acetonitrile (MeCN), 1,4-dioxane, ethanol (EtOH), propylene carbonate (PC), or ethylene carbonate (EC), mixtures commonly used for many experimental studies. The rate constants were calculated directly from O-1(2) phosphorescence lifetimes observed after laser pulse excitation of rose bengal (RB), used to generate O-1(2). In aqueous mixtures with MeCN and carbonates, the rate constant increased nonlinearly with increasing volume of organic solvent in the mixtures. k(q) was 4.78 x 10(8) M-1 s(-1) in D2O and increased to 26.7 x 10(8) and 27.7 x 10(8) M-1 s(-1) in 96% MeCN and 97.7% EC/PC, respectively. However, in EtOH/D2O mixtures, kq decreased with increasing alcohol concentration. This shows that a higher solvent polarity increases the quenching efficiency, which is unexpectedly decreased by the proticity of aqueous and alcohol solvent mixtures. The rate constant values increased with increasing temperature, yielding a quenching activation energy of 11.3 kJ mol(-1) in D2O. Our results show that rate constants in most solvent mixtures cannot be derived reliably from kq values measured in pure solvents by using a simple additivity rule. We have measured the rate constants with high accuracy, and they may serve as a reliable reference to calculate unknown kq values. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NCSU, Dept Chem, Raleigh, NC USA. ECSU, Dept Chem, Elizabeth City, NC USA. RP Bilski, P (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. NR 29 TC 65 Z9 65 U1 1 U2 12 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD DEC PY 2001 VL 74 IS 6 BP 760 EP 764 DI 10.1562/0031-8655(2001)074<0760:QOSMOO>2.0.CO;2 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 504NY UT WOS:000172863800003 PM 11783930 ER PT J AU Berezhkovskii, AM Larralde, H Weiss, GH AF Berezhkovskii, AM Larralde, H Weiss, GH TI Region visited by a spherical Brownian particle in the presence of an absorbing boundary SO PHYSICAL REVIEW E LA English DT Article ID WIENER SAUSAGE AB We calculate the time dependence of the average volume of a Wiener sausage in the presence of an absorbing boundary in one and three dimensions. In one dimension it is shown that the presence of an absorbing point reduces the time dependence of the average span from being proportional to roott in an unbounded space, to being proportional to ln(t) at long times. In three dimensions the average volume increases as roott at long times rather than being proportional to t as in free space. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Nacl Autonoma Mexico, Ctr Ciencias, Cuernavaca 62191, Morelos, Mexico. LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. RP Berezhkovskii, AM (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD DEC PY 2001 VL 64 IS 6 AR 062104 DI 10.1103/PhysRevE.64.062104 PN 1 PG 3 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 502CN UT WOS:000172726300061 PM 11736219 ER PT J AU Drinkard, B McDuffie, J McCann, S Uwaifo, GI Nicholson, J Yanovski, JA AF Drinkard, B McDuffie, J McCann, S Uwaifo, GI Nicholson, J Yanovski, JA TI Relationships between walk/run performance and cardiorespiratory fitness in adolescents who are overweight SO PHYSICAL THERAPY LA English DT Article; Proceedings Paper CT Annual Meeting of the North-American-Association-for-the-Study-of-Obesity CY OCT, 2000 CL LONG BEACH, CALIFORNIA SP N Amer Assoc Study Obes DE adolescence; body adiposity; exercise testing; obesity; physical fitness; walking ID OBESE CHILDREN; UNITED-STATES; BODY SIZE; EXERCISE; PARAMETERS; DISEASE; GROWTH; WEIGHT; POWER; TESTS AB Background and Purpose. Little is known about the methods used to assess the physical fitness of adolescents who are overweight. We investigated the relationship between walk/run performance and cardiorespiratory fitness in adolescents who are overweight. Subjects. Eight African-American adolescents (5 female, 3 male) and 10 Caucasian adolescents (5 female, 5 male) who were overweight (mean age=14.5 years, SD=2.0, range=12-17; mean body mass index [BMI] = 42.9 kg/m(2), SD=11.5) participated in this study. Methods. Subjects performed a 12-minute walk/run test. The distances traveled at both 9 minutes (D-9) and 12 minutes (D-12) were recorded, and the distance traveled between 9 and 12 minutes (D9-12) was calculated. Subjects also completed a maximal cycle ergometry test, during which peak oxygen uptake (Vo(2)peak), anaerobic threshold (AT), peak power (Wpeak), and power at the anaerobic threshold (WAT) were determined. Body composition was determined by air displacement plethysmography. Results. The mean percentage of body fat was 48.6% (SD=5.3%, range =40.3%-60.4%). Percentage of body fat and BMI were each inversely related to D-9, D-12, and Vo(2)peak (all P < .005). Peak oxygen uptake (r=.72, P=,0001),Vo(2)peak/kg lean body mass (r=.60, P < .005), Wpeak (r=.88, P < .0001), and WAT (r=.72, P=.0007) were all related to D-12 with greater r values than for D-9. If D9-12 was included in regression analyses, D-9 did not account for additional variance in any of the cycle ergometry variables. Discussion and Conclusion. These results suggest that an easily obtained measurement of physical performance (distance traveled during a 12-minute walk/run test) is related to cardiorespiratory fitness and to body composition in adolescents who are overweight. The 12-minute walk/run distance is more predictive of cycle ergometry test results than the 9-minute distance. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Rehabil Med, Bethesda, MD 20892 USA. NIDDK, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Drinkard, B (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Rehabil Med, Bethesda, MD 20892 USA. RI Uwaifo, Gabriel/M-2361-2016 OI Uwaifo, Gabriel/0000-0002-6962-9304 FU NICHD NIH HHS [Z01-HD-04-00641] NR 40 TC 40 Z9 45 U1 1 U2 2 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD DEC PY 2001 VL 81 IS 12 BP 1889 EP 1896 PG 8 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 499KC UT WOS:000172569500004 PM 11736623 ER PT J AU Le Poole, IC Sarangarajan, R Zhao, Y Stennett, LS Brown, TL Sheth, P Miki, T Boissy, RE AF Le Poole, IC Sarangarajan, R Zhao, Y Stennett, LS Brown, TL Sheth, P Miki, T Boissy, RE TI 'VIT1', a novel gene associated with, vitiligo SO PIGMENT CELL RESEARCH LA English DT Article DE depigmentation; gene expression; differential display; calmodulin; hMSH6 ID POLYMERASE CHAIN-REACTION; ENDOPLASMIC-RETICULUM; CARNEY COMPLEX; MELANOCYTES; MOUSE; ADENOSINE; APOPTOSIS; CULTURES; CALCIUM; CELL AB To define genes associated with the pigmentary disorder vitiligo, gene expression was compared in non-lesional melanocytes cultured from three vitiligo patients and from three control melanocyte cultures by differential display. A basic local alignment search tool search did not reveal homology of six differentially expressed cDNA fragments to previously identified expressed sequence tags; thus, one was used to screen a melanocyte cDNA library. The underlying VIT1 gene maps to chromosome 2p16. The 3' portion of the VIT1 message is complementary to the 3' end of hMSH6 mRNA, enabling the formation of RNA-RNA hybrids, which may interfere with G/T mismatch repair function. Moreover, the aligned cDNA sequence revealed an open reading frame identical to a hypothetical protein expressed in brain, with a similarity to Drosophila calmodulin, and containing a zinc-finger motif partially identical to N-recognin. Expression of ORF mRNA was confirmed for multiple skin cell types, suggesting its importance for skin physiology. C1 Loyola Univ, Med Ctr, Dept Pathol, Cardinal Bernardin Canc Ctr, Maywood, IL 60513 USA. Univ Cincinnati, Dept Dermatol, Cincinnati, OH 45221 USA. Wright State Univ, Dept Microbiol & Immunol, Dayton, OH USA. NIH, Mol Tumor Biol Sect, NCI, Bethesda, MD USA. RP Le Poole, IC (reprint author), Loyola Univ, Med Ctr, Dept Pathol, Cardinal Bernardin Canc Ctr, Rm 303,2160 S 1st Ave, Maywood, IL 60513 USA. FU NIAMS NIH HHS [R01 AR046115, R01 AR046115-02, AR46115] NR 39 TC 47 Z9 51 U1 1 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD DEC PY 2001 VL 14 IS 6 BP 475 EP 484 DI 10.1034/j.1600-0749.2001.140608.x PG 10 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 502GF UT WOS:000172734800007 PM 11775060 ER PT J AU Park, G Dadachova, E Przyborowska, A Lai, SJ Ma, DS Broker, G Rogers, RD Planalp, RP Brechbiel, MW AF Park, G Dadachova, E Przyborowska, A Lai, SJ Ma, DS Broker, G Rogers, RD Planalp, RP Brechbiel, MW TI Synthesis of novel 1,3,5-cis,cis-triaminocyclohexane ligand based Cu(II) complexes as potential radiopharmaceuticals and correlation of structure and serum stability SO POLYHEDRON LA English DT Article DE Cu(II) complexes; crystal structures; structure-activity relationship; serum stability; radiopharmaceuticals ID METAL-COMPLEXES; CIS,CIS-1,3,5-TRIAMINOCYCLOHEXANE; CU-67-2IT-BAT-LYM-1; DERIVATIVES; CHELATORS; LYMPHOMA; AGENTS AB The present study describes the synthesis of Cu(II) and radioactive Cu-67.64(II) complexes with N,N',N"-tris(2-pyridylmethyl)-1,3,5-cis,cis-triaminocyclohexane (tachpyr) and a new pyridyl ring alkylated derivative, N,N',N"-tris(6-methyl-2-pyridylmethyl)1,3,5-cis,cis-triaminocyclohexane (tach-6-Me-pyr) and the investigation of their structural and solution properties as well as stability in human serum. Facile formation of both the `cold' and Cu-67.64-radiolabeled complexes, [Cu(tachpyr)](2+) and [Cu(tach-6-Me-pyr)](2+), occurs in aqueous (0.15 M NH4OAc buffer, pH 6.5) or methanolic solvent. X-ray crystallography reveals that Cu(II) is hexacoordinate in [Cu(tachpyr)](2+) while methylation at the 6-position of the pyridyl donors in tachpyr produces considerable steric hindrance. Thus one pyridyl arm of tach-6-Mepyr is rotated entirely away from copper in [Cu(tach-6-Mepyr)](2+), resulting in a highly distorted trigonal-bipyramidal coordination geometry. The solid-state structures of the complexes correlate well with their stabilities in human serum at 37 degreesC. Thus, [Cu-67(tachpyr)](2+) possesses excellent stability, being unchanged after a period of 7 days, while [Cu-67(tach-6-Mepyr)](2+) decomposes within 1 h. Tachpyr may be an excellent candidate for developing new Cu(II) radiopharmaceuticals for diagnosis and therapy. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 NIH, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 USA. RP Brechbiel, MW (reprint author), NIH, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bldg 10,Room 3B69, Bethesda, MD 20892 USA. RI Rogers, Robin/C-8265-2013; Dadachova, Ekaterina/I-7838-2013 OI Rogers, Robin/0000-0001-9843-7494; NR 25 TC 24 Z9 24 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-5387 J9 POLYHEDRON JI Polyhedron PD DEC 1 PY 2001 VL 20 IS 26-27 BP 3155 EP 3163 DI 10.1016/S0277-5387(01)00927-5 PG 9 WC Chemistry, Inorganic & Nuclear; Crystallography SC Chemistry; Crystallography GA 502MC UT WOS:000172746500016 ER PT J AU Bass, LE Casper, LM AF Bass, LE Casper, LM TI Differences in registering and voting between native-born and naturalized Americans SO POPULATION RESEARCH AND POLICY REVIEW LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Sociological-Association CY AUG 20-27, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Sociol Assoc DE citizens; electoral; immigrant; naturalized; voting ID IMMIGRANT; EARNINGS; TURNOUT AB Relatively little is known about the differences in voting behavior between immigrants and native-born Americans, primarily due to a lack of good quality data on the national level. Using data from the Voting and Registration Supplement to the November 1996 Current Population Survey (CPS), we examine whether variables known to affect electoral participation among the citizen population are also important among naturalized citizens. We find that naturalized citizens are less likely to register and to vote than native-born citizens, net of other factors. Citizens born abroad in Europe, Latin America, and Asia are less likely to register and those born abroad in Europe and Asia are less likely to vote than those born in the U.S. Among naturalized citizens, region of origin does not remain a major explanatory variable once time in the U.S. is considered. C1 Univ Oklahoma, Norman, OK 73019 USA. NICHHD, Demog & Behav Sci Branch, Bethesda, MD 20892 USA. RP Bass, LE (reprint author), Univ Oklahoma, Haufman Hall,Room 331,780 Van Vleet Oval, Norman, OK 73019 USA. NR 44 TC 15 Z9 15 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-5923 J9 POPUL RES POLICY REV JI Popul. Res. Policy Rev. PD DEC PY 2001 VL 20 IS 6 BP 483 EP 511 DI 10.1023/A:1015635717294 PG 29 WC Demography SC Demography GA 555LX UT WOS:000175796500003 ER PT J AU Kinney, AY Croyle, RT Dudley, WN Bailey, CA Pelias, MK Neuhausen, SL AF Kinney, AY Croyle, RT Dudley, WN Bailey, CA Pelias, MK Neuhausen, SL TI Knowledge, attitudes, and interest in breast-ovarian cancer gene testing: A survey of a large African-American kindred with a BRCA1 mutation SO PREVENTIVE MEDICINE LA English DT Article DE genetic testing; African American; breast cancer; screening ID HEREDITARY BREAST; DECISION-MAKING; RISK PERCEPTIONS; SUSCEPTIBILITY; WOMEN; FAMILIES; POPULATION; CARRIERS; IMPACT; SCALE AB Background. This study assessed counseling and testing needs from the perspective of adult members of a large African-American kindred with a BRCA1 mutation. Methods. Interviews were conducted with 95 male and female kindred members to elicit information on sociodemographics, attitudes toward health care providers, breast cancer screening behaviors, and religious/spiritual beliefs, as well as to evaluate psychological distress, beliefs, knowledge, and attitudes related to genetic testing. Results. Knowledge about breast and ovarian cancer genetics was limited. Adherence to screening recommendations was low among females with no persona breast or ovarian cancer history. The majority (67%) wished to discuss risk factors with a health care provider. Most participants (82%) indicated that they would have a genetic test if it were available. Significant predictors of intent to undergo testing were having at least one first-degree relative with breast and/or ovarian cancer (OR=5.1; 95% CI=1.2-20.9) and perceived risk of being a gene carrier greater than or equal to50% (OR = 64.3; 95% CI=5.1-803.9) or reporting that they did not know their risk of being a gene carrier (OR = 10.9; 95% CI=2.1-57.7). Cited barriers to testing included cost and availability. Conclusion. There is a high interest level in genetic testing despite limited knowledge about cancer genetics among these high-risk African Americans. Our study provides information for designing a genetic education and counseling intervention for this and similar families. (C) 2001 American Health Foundation and Elsevier Science. C1 Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. Univ Utah, Dept Med Informat, Salt Lake City, UT 84112 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA 70122 USA. RP Kinney, AY (reprint author), Univ Utah, Coll Nursing, 10 S 2000 E Front St, Salt Lake City, UT 84112 USA. NR 40 TC 53 Z9 53 U1 3 U2 5 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 2001 VL 33 IS 6 BP 543 EP 551 DI 10.1006/pmed.2001.0920 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 508RH UT WOS:000173102800005 PM 11716649 ER PT J AU Kapust, RB Tozser, J Fox, JD Anderson, DE Cherry, S Copeland, TD Waugh, DS AF Kapust, RB Tozser, J Fox, JD Anderson, DE Cherry, S Copeland, TD Waugh, DS TI Tobacco etch virus protease: mechanism of autolysis and rational design of stable mutants with wild-type catalytic proficiency SO PROTEIN ENGINEERING LA English DT Article DE autoproteolysis; fusion proteins; TEV protease; tobacco etch virus ID POLYPROTEIN CLEAVAGE SITE; ESCHERICHIA-COLI; FUSION PROTEINS; NUCLEAR INCLUSION; PURIFICATION; EXPRESSION; AUTOPROTEOLYSIS; ENZYME; SPECIFICITY; EXTENSION AB Because of its stringent sequence specificity, the catalytic domain of the nuclear inclusion protease from tobacco etch virus (TEV) is a useful reagent for cleaving genetically engineered fusion proteins. However, a serious drawback of TEV protease is that it readily cleaves itself at a specific site to generate a truncated enzyme with greatly diminished activity. The rate of autoinactivation is proportional to the concentration of TEV protease, implying a bimolecular reaction mechanism. Yet, a catalytically active protease was unable to convert a catalytically inactive protease into the truncated form. Adding increasing concentrations of the catalytically inactive protease to a fixed amount of the wild-type enzyme accelerated its rate of autoinactivation. Taken together, these results suggest that autoinactivation of TEV protease may be an intramolecular reaction that is facilitated by an allosteric interaction between protease molecules. In an effort to create a more stable protease, we made amino acid substitutions in the P2 and P1' positions of the internal cleavage site and assessed their impact on the enzyme's stability and catalytic activity. One of the P1' mutants, S219V, was not only far more stable than the wild-type protease (similar to100-fold), but also a more efficient catalyst. C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, Debrecen, Hungary. RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, POB B, Frederick, MD 21702 USA. EM waughd@ncifcrf.gov RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 NR 40 TC 401 Z9 414 U1 8 U2 52 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD DEC PY 2001 VL 14 IS 12 BP 993 EP 1000 DI 10.1093/protein/14.12.993 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 521CU UT WOS:000173821900007 PM 11809930 ER PT J AU Thompson, J Stavrou, S Weetall, M Hexham, JM Digan, ME Wang, ZR Woo, JH Yu, YJ Mathias, A Liu, YY Mas, SL Gordienko, I Lake, P Neville, DM AF Thompson, J Stavrou, S Weetall, M Hexham, JM Digan, ME Wang, ZR Woo, JH Yu, YJ Mathias, A Liu, YY Mas, SL Gordienko, I Lake, P Neville, DM TI Improved binding of a bivalent single-chain immunotoxin results in increased efficacy for in vivo T-cell depletion SO PROTEIN ENGINEERING LA English DT Article DE CD3; depletion; divalent; immunotoxin; T cell; transplantation ID TRUNCATED DIPHTHERIA-TOXIN; GENETIC CONSTRUCTION; MYELOMA CELLS; HUMAN CD3; ANTIBODY; FV; EXPRESSION; PROTEIN; FRAGMENT; RECEPTOR AB Anti-CD3 immunotoxins exhibit considerable promise for the induction of transplantation tolerance in pre-clinical large animal models. Recently an anti-human anti-CD3epsilon single-chain immunotoxin based on truncated diphtheria toxin has been described that can be expressed in CHO cells that have been mutated to diphtheria toxin resistance. After the two toxin glycosylation sites were removed, the bioactivity of the expressed immunotoxin was nearly equal to that of the chemically conjugated immunotoxin: This immunotoxin, A-dmDT390-sFv, contains diphtheria toxin to residue 390 at the N-terminus followed by VL and VH domains of antibody UCHT1 linked by a (G(4)S)(3) spacer (sFv). Surprisingly, we now report that this immunotoxin is severely compromised in its binding affinity toward CD3+ cells as compared with the intact parental UCHT1 antibody, the UCHT1 Fab fragment or the engineered UCHT1 sFv domain alone. Binding was increased 7-fold by adding an additional identical sFv domain to the immunotoxin generating a divalent construct, A-dmDT390-bisFv (G(4)S). In vitro potency increased 10-fold over the chemically conjugated immunotoxin, UCHT1-CRM9 and the monovalent A-dmDT390-sFv. The in vivo potency of the genetically engineered immunotoxins was assayed in the transgenic heterozygote mouse, tgepsilon 600, in which the T-cells express human CD3epsilon as well as murine CD3epsilon. T-cell depletion in the spleen and lymph node observed with the divalent construct was increased 9- and 34-fold, respectively, compared with the monovalent construct. The additional sFv domain appears partially to compensate for steric hindrance of immunotoxin binding due to the large N-terminal toxin domain. C1 NIMH, Sect Biophys Chem, Mol Biol Lab, Bethesda, MD 20892 USA. Fenske Lab, University Pk, PA 16802 USA. Novartis Pharmaceut, Summit, NJ 07901 USA. Univ Alabama, Div Transplantat Immunol, Birmingham, AL 35294 USA. RP Neville, DM (reprint author), NIMH, Sect Biophys Chem, Mol Biol Lab, Bethesda, MD 20892 USA. NR 36 TC 44 Z9 47 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD DEC PY 2001 VL 14 IS 12 BP 1035 EP 1041 DI 10.1093/protein/14.12.1035 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 521CU UT WOS:000173821900011 PM 11809934 ER PT J AU Brady, CP Shimp, RL Miles, AR Whitmore, M Stowers, AW AF Brady, CP Shimp, RL Miles, AR Whitmore, M Stowers, AW TI High-level production and purification of P30P2MSP1(19), an important vaccine antigen for malaria, expressed in the methylotropic yeast Pichia pastoris SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; CARBOXYL-TERMINAL FRAGMENT; B-CELL EPITOPES; AOTUS MONKEYS; PROTECTIVE IMMUNITY; RECOMBINANT PROTEIN; C-TERMINUS; T-CELL; ANTIBODIES; EFFICACY AB P30P2MSP1(19) is a recombinant subunit vaccine derived from merozoite surface protein 1 (MSP1) of Plasmodium falciparum, the causative agent of malaria. P301P2MSP1(19) consists of two universal T-cell epitopes fused to the most C-terminal 19-kDa portion of MSP1, and this protein has previously shown promising potential as a vaccine for malaria. However, previous attempts at producing this molecule in Saccharomyces cerevisiae resulted in the production of a truncated form of the molecule missing most of the universal T-cell epitopes. Here, we report the production of full-length P30P2MSP1(19) in Pichia pastoris. As salt precipitation is a common problem during P. pastoris high-density fermentation, we utilized an alternative low-salt, fully defined medium that did not reduce growth rates or biomass yields to avoid precipitation. A total of 500 mg/L of secreted purified protein was produced in high cell density fermentation and the protein was purified in one step utilizing nickel-chelate chromatography. P30P2MSP119 produced in Pichia was reactive with monoclonal antibodies that recognize only conformational epitopes on correctly folded MSPI. Rabbits immunized with this molecule generated higher and more uniform antibody titers than rabbits immunized with the protein produced in Saccharomyces. P30P2MSP1(19) produced in Pichia may prove to be a more efficacious vaccine than that produced in Saccharomyces and Pichia would provide a system for the cost-effective production of such a vaccine. C1 NIAID, Malaria Vaccine Dev Unit, Parasit Dis Lab, NIH, Rockville, MD 20852 USA. RP Brady, CP (reprint author), NIAID, Malaria Vaccine Dev Unit, Parasit Dis Lab, NIH, Rockville, MD 20852 USA. NR 22 TC 42 Z9 50 U1 0 U2 9 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 2001 VL 23 IS 3 BP 468 EP 475 DI 10.1006/prep.2001.1526 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 512CT UT WOS:000173304100014 PM 11722185 ER PT J AU Galperin, MY Jedrzejas, MJ AF Galperin, MY Jedrzejas, MJ TI Conserved core structure and active site residues in alkaline phosphatase superfamily enzymes SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE alkaline phosphodiesterase; nucleotide pyrophosphatase PC-1; autotaxin; glycosylphosphatidylinositol; phosphoethanolaminetransferase; MCD4; Pig-O; phosphonoacetate hydrolase; phosphonate monoesterase ID INDEPENDENT PHOSPHOGLYCERATE MUTASE; PHOSPHONOPYRUVATE DECARBOXYLASE; BACILLUS-STEAROTHERMOPHILUS; FLAVOBACTERIUM-ODORATUM; CRYSTAL-STRUCTURE; MECHANISM; GENE; GLYCOSYLPHOSPHATIDYLINOSITOL; CLONING; YEAST AB Cofactor-independent phosphoglycerate mutase (iPGM) has been previously identified as a member of the alkaline phosphatase (AlkP) superfamily of enzymes, based on the conservation of the predicted metal-binding residues. Structural alignment of iPGM with AlkP and cerebroside sulfatase confirmed that all these enzymes have a common core structure and revealed similarly located conserved Ser (in iPGM and AlkP) or Cys (in sulfatases) residues in their active sites. In AlkP, this Ser residue is phosphorylated during catalysis, whereas in sulfatases the active site Cys residues are modified to formylglycine and sulfatated. Similarly located Thr residue forms a phosphoenzyme intermediate in one more enzyme of the AlkP superfamily, alkaline phosphodiesterase/nucleotide pyrophosphatase PC-1 (autotaxin). Using structure-based sequence alignment, we identified homologous Ser, Thr, or Cys residues in other enzymes of the AlkP superfamily, such as phosphopentomutase, phosphoglycerol transferase, phosphonoacetate hydrolase, and GPI-anchoring enzymes (glycosylphosphatidyllnositol phosphoethanolamine transferases) MCD4, GPI7, and GPI13. We predict that catalytical cycles of all the enzymes of AlkP superfamily include phosphoenzyme (or sulfoenzyme) intermediates. (C) 2001 Wiley-Liss, Inc.* C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 50 TC 80 Z9 82 U1 0 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD DEC 1 PY 2001 VL 45 IS 4 BP 318 EP 324 DI 10.1002/prot.1152 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 499KD UT WOS:000172569600004 PM 11746679 ER PT J AU Pine, DS AF Pine, DS TI Affective neuroscience and the development of social anxiety disorder SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID EMOTIONAL FACIAL EXPRESSIONS; HUMAN AMYGDALA; NEGATIVE INFORMATION; SELECTIVE ATTENTION; CHILDHOOD ANXIETY; MAJOR DEPRESSION; CLINICAL ANXIETY; EXPLICIT MEMORY; COUNTING STROOP; AGE 15 AB This article reviews recent data on social anxiety disorder from the dual perspectives of affective neuroscience and developmental psychopathology. The perspective of affective neuroscience attempts to understand emotional phenomena by delineating neural systems that mediate such phenomena. Advances in basic neuroscience techniques for research with animals and neuroimaging methods for research with humans have generated considerable enthusiasm for this perspective. The perspective of developmental psychopathology attempts to delineate changes in behaviors and mental phenomena that occur as children mature, with the ultimate goal of enhancing understandings of both normal and abnormal phenomena. C1 NIMH, Intramural Res Program, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. NIMH, Program Mood & Anxiety Disorders, Bethesda, MD 20892 USA. RP Pine, DS (reprint author), NIMH, Intramural Res Program, Sect Dev & Affect Neurosci, Bldg 1,Room B10-0135, Bethesda, MD 20892 USA. NR 95 TC 5 Z9 6 U1 10 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2001 VL 24 IS 4 BP 689 EP + DI 10.1016/S0193-953X(05)70258-6 PG 19 WC Psychiatry SC Psychiatry GA 490ZU UT WOS:000172084200006 PM 11723628 ER PT J AU Chowdari, KV Brandstaetter, B Semwal, P Bhatia, T Deshpande, S Reddy, R Wood, J Weinberg, CR Thelma, BK Nimgaonkar, VL AF Chowdari, KV Brandstaetter, B Semwal, P Bhatia, T Deshpande, S Reddy, R Wood, J Weinberg, CR Thelma, BK Nimgaonkar, VL TI Association studies of cytosolic phospholipase A2 polymorphisms and schizophrenia among two independent family-based samples SO PSYCHIATRIC GENETICS LA English DT Article DE schizophrenia; genetic; association; phospholipase A2 ID EXTENDED TRANSMISSION/DISEQUILIBRIUM TEST; MAGNETIC-RESONANCE SPECTROSCOPY; I DIMORPHIC SITE; DIAGNOSTIC INTERVIEW; ARACHIDONIC-ACID; A(2) GENE; BRAIN; METABOLISM; DISORDERS; LINKAGE AB An association between the cytosolic phospholipase A2 locus (cPLA2) and schizophrenia has been reported using two polymorphic DNA markers. In an attempt to replicate these results, two independent family-based samples were ascertained from the United States and India (86 and 159 families, respectively). No significant associations were detected in either sample. Psychiatr Genet 11:207-212 (C) 2001 Lippincott Williams Wilkins. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Human Genet, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Delhi, Dept Genet, New Delhi, India. Indo US Project Schizophrenia Genet, New Delhi, India. DR RML Hosp, Dept Psychiat, New Delhi, India. NIEHS, Res Triangle Pk, NC 27709 USA. FU FIC NIH HHS [R03 TW00730]; NIMH NIH HHS [MH01489, MH53459, MH56242, R01 MH056242] NR 33 TC 28 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIATR GENET JI Psychiatr. Genet. PD DEC PY 2001 VL 11 IS 4 BP 207 EP 212 DI 10.1097/00041444-200112000-00005 PG 6 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 516GK UT WOS:000173545400005 PM 11807411 ER PT J AU Sailstad, DM Hattan, D Hill, RN Stokes, WS AF Sailstad, DM Hattan, D Hill, RN Stokes, WS TI ICCVAM evaluation of the murine local lymph node assay - I. The ICCVAM review process SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE ICCVAM; local lymph node assay; validation; alternative toxicological method ID CONTACT ALLERGENS; MAXIMIZATION TEST; SENSITIZATION; IDENTIFICATION; VALIDATION; TRIAL AB New test methods are being developed to improve the prediction of human and environmental risks and to benefit animal welfare by reducing, refining, and replacing animal use. Regulatory adoption of new test methods is often a complex and protracted process, requiring test method validation, regulatory acceptance, and implementation. Assessments of new test methods have not always been uniform within or among regulatory agencies. Thus, there have been increased pressures for a harmonized approach to test method evaluation and acceptance. In 1997, in response to these pressures and to U.S. Public Law 103-43, the National Institute of Environmental Health Sciences (NIEHS) established the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) to coordinate interagency consideration of new and revised test methods. This article describes the validation and acceptance criteria and process used for the first test method evaluated by ICCVAM, the murine local lymph node assay (LLNA). Based on ICCVAM's conclusions and recommendations, the LLNA has been accepted by U.S. regulatory agencies as a stand-alone assay for allergic contact dermatitis. Two related articles in this series of three present the results of the independent peer review evaluation of the LLNA and summarize the performance characteristics of the database substantiating the validity of the LLNA. C1 US EPA, Expt Toxicol Div, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Hlth Effects Evaluat, Bethesda, MD 20205 USA. US EPA, Off Pollut Prevent & Tox Subst, Washington, DC 20460 USA. NIEHS, NTP Interagcy Ctr Evaluat Alternat Toxicol Method, Res Triangle Pk, NC 27709 USA. RP Sailstad, DM (reprint author), US EPA, Expt Toxicol Div, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, MD 92, Res Triangle Pk, NC 27711 USA. NR 23 TC 33 Z9 35 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 2001 VL 34 IS 3 BP 249 EP 257 DI 10.1006/rtph.2001.1496 PG 9 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 511HY UT WOS:000173259600005 PM 11754529 ER PT J AU Dean, JH Twerdok, LE Tice, RR Sailstad, DM Hattan, DG Stokes, WS AF Dean, JH Twerdok, LE Tice, RR Sailstad, DM Hattan, DG Stokes, WS TI ICCVAM evaluation of the murine local lymph node assay - II. Conclusions and recommendations of an independent scientific peer review panel SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE allergic contact dermatitis; local lymph node assay; guinea pig; mice ID SKIN SENSITIZATION TESTS; PIG MAXIMIZATION TEST; EAR SWELLING TEST; CONTACT ALLERGENS; GUINEA-PIG; METAL-SALTS; INTERLABORATORY EVALUATION; CELL-PROLIFERATION; DERMAL APPLICATION; SENSITIVITY AB The validation status of the murine local lymph node assay (LLNA), a method for assessing the allergic contact dermatitis potential of chemicals, was evaluated by an independent peer review panel (Panel) convened by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). The LLNA measures lymphocyte proliferation using incorporation of radioactive thymidine or iododeoxyuridine into cells of the draining lymph nodes of mice topically exposed to a test article. The Panel concluded that the assay performed as well as currently accepted guinea pig methods [guinea pig maximization test (GPMT)/Buehler assay (BA)] for the hazard identification of strong to moderate chemical sensitizing agents, but that it might not correctly identify all weak sensitizers or metals (potential false negative response) or all strong irritants (potential false positive response). The Panel concluded also that the LLNA involves less pain and distress than conventional guinea pig methods. The Panel unanimously recommended the LLNA as a stand-alone alternative for contact sensitization hazard assessment, provided that certain protocol modifications were made. These included collection of individual, rather than pooled, animal response data; the inclusion of a concurrent positive control; and consideration of dose-response information and statistical analyses. A standardized LLNA protocol is provided. (C) 2001 Elsevier Science. C1 Sanofi Synthelabo Inc, Sanofi Synthelabo Res, Malvern, PA 19355 USA. Amer Petr Inst, Washington, DC 20005 USA. NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Res Triangle Pk, NC 27709 USA. ILS Inc, Res Triangle Pk, NC 27709 USA. US EPA, Expt Toxicol Div, Res Triangle Pk, NC 27711 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20205 USA. RP Sanofi Synthelabo Inc, Sanofi Synthelabo Res, POB 3026, Malvern, PA 19355 USA. FU NIEHS NIH HHS [N01-ES-85424] NR 62 TC 92 Z9 95 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 0273-2300 EI 1096-0295 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 2001 VL 34 IS 3 BP 258 EP 273 DI 10.1006/rtph.2001.1497 PG 16 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 511HY UT WOS:000173259600006 PM 11754530 ER PT J AU Haneke, KE Tice, RR Carson, BL Margolin, BH Stokes, WS AF Haneke, KE Tice, RR Carson, BL Margolin, BH Stokes, WS TI ICCVAM evaluation of the murine local lymph node assay - III. Data analyses completed by the national toxicology program interagency center for the evaluation of alternative toxicological methods SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE allergic contact dermatitis; local lymph node assay; guinea pig; mice AB To evaluate the reliability of the murine local lymph node assay (LLNA), a test for allergic contact dermatitis activity, the inter- and intralaboratory consistency statistics (h and k, respectively) were calculated for validation studies testing multiple chemicals. The analysis indicated the absence of excessive variability in the dose calculated to induce a threefold or greater increase in the stimulation index (SI). To assess the appropriateness of using an SI of 3 as the decision criteria for identifying a sensitizing compound, LLNA results based on SI values of 2.0,2.5,3.0,3.5, and 4.0 were compared with guinea pig or human results. The results supported the use of an SI of 3 as the decision criteria. Assay performance was determined by comparing LLNA results to results obtained for guinea pigs or humans. The accuracy of the LLNA was 89% when compared with results from the guinea pig maximization test (GPMT)/Buehler assay (BA). The performance of the LLNA and the GPMT/BA was similar when each was compared to human maximization test results plus substances included as human patch test allergens. The LLNA offered advantages over the GPMT in respect to both the time required to conduct the test and the assay cost. (C) 2001 Elsevier Science. C1 NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Res Triangle Pk, NC 27709 USA. ILS Inc, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. RP Haneke, KE (reprint author), NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, MD EC-17,POB 12233, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [N01-ES-85424] NR 6 TC 64 Z9 66 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 2001 VL 34 IS 3 BP 274 EP 286 DI 10.1006/rtph.2001.1498 PG 13 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 511HY UT WOS:000173259600007 PM 11754531 ER PT J AU Chalela, JA AF Chalela, JA TI Pearls and pitfalls in the intensive care management of Guillain-Barre syndrome SO SEMINARS IN NEUROLOGY LA English DT Article DE Guillain-Barre syndrome; intensive care; management; complications; neuromuscular respiratory failure ID INTRAVENOUS IMMUNOGLOBULIN; PLASMA-EXCHANGE; PAIN AB Approximately one third of patients with Guillain-Barre syndrome (GBS) need to be admitted to the intensive care unit (ICU) because of respiratory failure. A significant proportion of patients require ICU admission because of dysautonomia or because of medical or iatrogenic complications. Recognition of the clinical manifestations and the paraclinical findings in patients with neuromuscular respiratory failure is essential to ensure mechanical ventilation promptly. In the ICU, attention to positioning, nutrition, analgesia, and psychological support are crucial. Recognition of autonomic dysfunction and of the rare need for intervention is important to avoid iatrogenic complications. Prognosis determination in GBS is based on the clinical history, epidemiological factors, and neurologic examination. C1 NINCDS, NIH, Bethesda, MD 20892 USA. RP Chalela, JA (reprint author), NINCDS, NIH, 36 Convent Dr,Room 4A03,MSC 4129, Bethesda, MD 20892 USA. NR 19 TC 10 Z9 10 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 2001 VL 21 IS 4 BP 399 EP 405 DI 10.1055/s-2001-19411 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 509FM UT WOS:000173135700007 PM 11774055 ER PT J AU Kruger, EA Duray, PH Price, DK Pluda, JM Figg, WD AF Kruger, EA Duray, PH Price, DK Pluda, JM Figg, WD TI Approaches to preclinical screening of antiangiogenic agents SO SEMINARS IN ONCOLOGY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; EMBRYO CHORIOALLANTOIC MEMBRANE; RAT AORTA MODEL; TUMOR ANGIOGENESIS; CHICK-EMBRYO; IN-VIVO; BLOOD-VESSELS; INVITRO; ASSAY; NEOVASCULARIZATION C1 NCI, Med Branch, Lab Pathol, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Invest Drug Branch, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Branch, Lab Pathol, 10 Ctr Dr,Bldg 10,Rm 5A-01, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 52 TC 28 Z9 30 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 2001 VL 28 IS 6 BP 570 EP 576 DI 10.1053/sonc.2001.28600 PG 7 WC Oncology SC Oncology GA 499JC UT WOS:000172567200007 PM 11740811 ER PT J AU Longo, NS Lipsky, PE AF Longo, NS Lipsky, PE TI Somatic hypermutation in human B cell subsets SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Review ID MISMATCH REPAIR PROTEIN; HYPER-IGM SYNDROME; IMMUNOGLOBULIN GENE HYPERMUTATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CYTIDINE DEAMINASE AID; DOUBLE-STRAND BREAKS; HEAVY-CHAIN GENES; V-H GENES; GERMINAL-CENTERS; DNA-POLYMERASE C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMSD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 116 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD DEC PY 2001 VL 23 IS 4 BP 367 EP 385 DI 10.1007/s281-001-8165-0 PG 19 WC Immunology; Pathology SC Immunology; Pathology GA 516LH UT WOS:000173554400004 PM 11826615 ER PT J AU Warach, S AF Warach, S TI Studying stroke syndromes with diffusion and perfusion MRI - Editorial comment SO STROKE LA English DT Editorial Material C1 NINCDS, NIH, Bethesda, MD 20892 USA. RP Warach, S (reprint author), NINCDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2001 VL 32 IS 12 BP 2781 EP 2781 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 499YX UT WOS:000172599500012 ER PT J AU Peila, R White, LR Petrovich, H Masaki, K Ross, GW Havlik, RJ Launer, LJ AF Peila, R White, LR Petrovich, H Masaki, K Ross, GW Havlik, RJ Launer, LJ TI Joint effect of the APOE gene and midlife systolic blood pressure on late-life cognitive impairment - The Honolulu-Asia aging study SO STROKE LA English DT Article DE blood pressure; cognition; genetics ID APOLIPOPROTEIN-E POLYMORPHISM; ISOFORM-SPECIFIC DIFFERENCES; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; RISK-FACTORS; IN-VITRO; DEMENTIA; HYPERTENSION; DECLINE; ALLELE AB Background and Purpose-The aim of this study, was to explore the joint effect of the APOE epsilon4 allele and midlife systolic blood pressure (SBP) on the risk for poor cognitive function in late life. Methods-The study includes 3605 surviving members of the cohort of the Japanese-American men followed prospectively over 26 years (1965-1991) as a part of the Honolulu Heart Program, In 1965 men were aged 45 to 68 years and were living in the island of Oahu, Hawaii. For this study the sample was divided into 4 categories: normal SBP (< 160 mm Hg)/No epsilon4, as the reference category; normal SBP/epsilon4; high S betaP/no epsilon4 high SBP/epsilon4. The relative risk (RR) of late-life intermediate and poor cognitive function relative to good function was measured by the Cognitive Abilities Screening Instrument (CASI) test. Results-After adjusting for age, education, smoking, alcohol use, and body mass index, the RR for poor cognitive function (CASI < 74) compared with good cognitive function (CASI > 82) in never-treated subjects, was 1.3 (95% CI 0.9 to 1.9) for the normal SBP/epsilon4 category, 2.6 (0.7 to 10.0) for the high SBP/no epsilon4, and 13.0 (1.9 to 83.8) for the high SBP/epsilon4. Adjustment for diabetes, prevalent stroke. coronary disease, and ankle-brachial index reduced the RR of poor cognition by 25.5% (RR 13.0 to 10.8) in those with both risk factors. In the treated group, the RR was 1.9 (0.7 to 4.5) for those with both risk factors. Conclusions-The results suggest that midlife high SBP has a stronger adverse effect oil cognitive function in persons with higher genetic susceptibility, but this effect may be modified by antihypertensive treatment. C1 NIA, EDBP, NIH, Bethesda, MD 20892 USA. Dept Vet Affairs, Pacific Hlth Res Inst, Honolulu, HI USA. RP Peila, R (reprint author), NIA, EDBP, NIH, Gateway Bldg 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. NR 48 TC 73 Z9 77 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 2001 VL 32 IS 12 BP 2882 EP 2887 DI 10.1161/hs1201.100392 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 499YX UT WOS:000172599500033 PM 11739991 ER PT J AU Sinha, N Kumar, S Nussinov, R AF Sinha, N Kumar, S Nussinov, R TI Interdomain interactions in hinge-bending transitions SO STRUCTURE LA English DT Article DE domain movements; interdomain interactions; hinge-bending; population shifts; electrostatic interactions ID PROTEIN-PROTEIN INTERFACES; SALT BRIDGES; DOMAIN MOTIONS; MOLECULAR-DYNAMICS; STATISTICAL-ANALYSIS; GLOBULAR-PROTEINS; BINDING CASCADES; FOLDING FUNNELS; STABILITY; LYSOZYME AB Background: The mechanisms that allow or constrain protein movement have not been understood. Here we study interdomain interactions in proteins to investigate hinge-bending motions. Results: We find a limited number of salt bridges and hydrogen bonds at the interdomain interface, in both the "closed" and the "open" conformations. Consistently, analysis of 222 salt bridges in an independently selected database indicates that most salt bridges form within rather than between independently folding hydrophobic units. Calculations show that these interdomain salt bridges either destabilize or only marginally stabilize the closed conformation in most proteins. In contrast, the nonpolar buried surface area between the moving parts can be extensive in the closed conformations. However when the nonpolar buried surface area is large, we find that at the interdomain interface in the open conformation it may be as large or larger than in the closed conformation. Hence, the energetic penalty of opening the closed conformation is overcome. Consistently, a large nonpolar surface area buried in the closed interdomain interface accompanies limited opening of the domains, yielding a larger interface. Conclusions: Short-range electrostatic interactions are largely absent between moving domains. Interdomain nonpolar buried surface area may be large in the closed conformation, but it is largely offset by the area buried in the open conformation. In such cases the opening of the domains appears to be relatively small. This may allow prediction of the extent of domain opening. Such predictions may have implications for the shape and size of the binding pockets in drug/protein design. C1 NCI, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Sci Applicat Int Corp, Intramural Res Support Program, Mclean, VA 22102 USA. Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Lab Expt & Computat Biol, Bldg 469,Rm 151, Frederick, MD 21702 USA. OI Kumar, Sandeep/0000-0003-2840-6398 FU NCI NIH HHS [N01-CO-56000] NR 60 TC 22 Z9 22 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD DEC PY 2001 VL 9 IS 12 BP 1165 EP 1181 DI 10.1016/S0969-2126(01)00687-6 PG 17 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 500ZN UT WOS:000172658700005 PM 11738043 ER PT J AU Tomschik, M Karymov, MA Zlatanova, J Leuba, SH AF Tomschik, M Karymov, MA Zlatanova, J Leuba, SH TI The archaeal histone-fold protein HMf organizes DNA into bona fide chromatin fibers SO STRUCTURE LA English DT Article DE atomic force microscope; Archaea; chromatin fibers; HMf; in vitro reconstitution; tetrasomes ID SCANNING FORCE MICROSCOPY; NUCLEOSOME CORE PARTICLE; METHANOTHERMUS-FERVIDUS; LINKER HISTONES; RNA-POLYMERASE; BINDING; RESOLUTION; SEQUENCES; TETRAMER; H3 AB Background: The discovery of histone-like proteins in Archaea urged studies into the possible organization of archaeal genomes in chromatin. Despite recent advances, a variety of structural questions remain unanswered. Results: We have used the atomic force microscope (AFM) with traditional nuclease digestion assays to compare the structure of nucleoprotein complexes reconstituted from tandemly repeated eukaryal nucleosome-positioning sequences and histone octamers, H3/H4 tetramers, and the histone-fold archaeal protein HMf. The data unequivocally show that HMf reconstitutes are indeed organized as chromatin fibers, morphologically indistinguishable from their eukaryal counterparts. The nuclease digestion patterns revealed a clear pattern of protection at regular intervals, again similar to the patterns observed with eukaryal chromatin fibers. In addition, we studied HMf reconstitutes on mononucleosome-sized DNA fragments and observed a great degree of similarity in the internal organization of these particles and those organized by H3/H4 tetramers. A difference in stability was observed at the level of mono-, di-, and triparticles between the HMf particles and canonical octamer-containing nucleosomes. Conclusions: The in vitro reconstituted HMf-nucleo-protein complexes can be considered as bona fide chromatin structures. The differences in stability at the monoparticle level should be due to structural differences between HMf and core histone H3/H4 tetramers, i.e., to the complete absence in HMf of histone tails beyond the histone fold. We speculate that the existence of core histone tails in eukaryotes may provide a greater stability to nucleosomal particles and also provide the additional ability of chromatin structure to regulate DNA function in eukaryotic cells by posttranslational histone tail modifications. C1 Polytech Univ, Dept Chem & Chem Engn, Brooklyn, NY 11201 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Leuba, SH (reprint author), Polytech Univ, Dept Chem & Chem Engn, 6 Metrotech Ctr, Brooklyn, NY 11201 USA. RI Zlatanova, Jordanka/B-3273-2009 NR 54 TC 40 Z9 40 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD DEC PY 2001 VL 9 IS 12 BP 1201 EP 1211 DI 10.1016/S0969-2126(01)00682-7 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 500ZN UT WOS:000172658700008 PM 11738046 ER PT J AU Blaszczyk, J Tropea, JE Bubunenko, M Routzahn, KM Waugh, DS Court, DL Ji, XH AF Blaszczyk, J Tropea, JE Bubunenko, M Routzahn, KM Waugh, DS Court, DL Ji, XH TI Crystallographic and modeling studies of RNase III suggest a mechanism for double-stranded RNA cleavage SO STRUCTURE LA English DT Article DE RNase III; endonuclease domain; compound active center; dsRNA; RNA processing; RNA interference ID COLI RIBONUCLEASE-III; DSRNA-BINDING DOMAIN; GLUTATHIONE-S-TRANSFERASE; ESCHERICHIA-COLI; CAENORHABDITIS-ELEGANS; GENETIC INTERFERENCE; PROCESSING ACTIVITY; MOLECULAR-BASIS; PROTEIN; REFINEMENT AB Background: Aquifex aeolicus Ribonuclease III (Aa-RNase III) belongs to the family of Mg2(+)-dependent endonucleases that show specificity for double-stranded RNA (dsRNA). RNase III is conserved in all known bacteria and eukaryotes and has 1-2 copies of a 9-residue consensus sequence, known as the RNase III signature motif. The bacterial RNase III proteins are the simplest, consisting of two domains: an N-terminal endonuclease domain, followed by a double-stranded RNA binding domain (dsRBD). The three-dimensional structure of the dsRBD in Escherichia coli RNase III has been elucidated; no structural information is available for the endonuclease domain of any RNase III. Results: We present the crystal structures of the Aa-RNase III endonuclease domain in its ligand-free form and in complex with Mn2+. The structures reveal a novel protein fold and suggest a mechanism for dsRNA cleavage. On the basis of structural, genetic, and biological data, we have constructed a hypothetical model of Aa-RNase III in complex with dsRNA and Mg2+ ion, which provides the first glimpse of RNase III in action. Conclusions: The functional Aa-RNase III dimer is formed via mainly hydrophobic interactions, including a "ball-and-socket" junction that ensures accurate alignment of the two monomers. The fold of the polypeptide chain and its dimerization create a valley with two compound active centers at each end of the valley. The valley can accommodate a dsRNA substrate. Mn2+ binding has significant impact on crystal packing, intermolecular interactions, thermal stability, and the formation of two RNA-cuffing sites within each compound active center. C1 NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. NCI, Macromol Crystallog Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Court, DL (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 NR 63 TC 164 Z9 181 U1 2 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD DEC PY 2001 VL 9 IS 12 BP 1225 EP 1236 DI 10.1016/S0969-2126(01)00685-2 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 500ZN UT WOS:000172658700010 PM 11738048 ER PT J AU Kivlen, MH Bartlett, DL Libutti, SF Skarulis, MC Marx, SJ Simonds, WF Weinstein, LS Jensen, RT McCart, JA Naik, AM Kranda, KC Brennan, MF Norton, JA Fraker, DL Alexander, HR AF Kivlen, MH Bartlett, DL Libutti, SF Skarulis, MC Marx, SJ Simonds, WF Weinstein, LS Jensen, RT McCart, JA Naik, AM Kranda, KC Brennan, MF Norton, JA Fraker, DL Alexander, HR TI Reoperation for hyperparathyroidism in multiple endocrine neoplasia type 1 SO SURGERY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 28-MAY 01, 2001 CL ATLANTA, GEORGIA SP Amer Assoc Endocrine Surg ID ZOLLINGER-ELLISON SYNDROME; SURGICAL-MANAGEMENT; PARATHYROID-GLANDS AB Background. Patients with multiple endocrine neoplasia type 1 and hyperparathyroidism often undergo multiple operations because of inadequate initial surgery, presence of supernumerary and ectopic glands, regrowth of remnant glands, or autograft hyperfunction. Management of this patient population is complex. Methods. From Januray 1975 to December 2000 we performed 94 reoperative parathyroidectomies consisting of 79 neck reexplorations, 12 autograft removals, and 3 median sternotomies in 75 patients. Data were gathered by retrospective chart review and follow-up telephone interviews. Results. Excluding autograft excision, reoperative surgery was successful (normocalcemia longer than 6 months) in 91 %; autograft removal was successful in only 58 %. With a median follow-up of 59 months, 64 % of patients are currently free from hypercalcemia, and this outcome was not influenced by the total number of glands resected. The median time to recurrent hypercalcemia was 125 months. Thirty patients received an autograft after reoperation. The complication rate for all reoperations was 12 %, including permanent recurrent laryngeal nerve injury in 2 patients (2.1 %). Conclusions. Reoperative parathyroidectomy in patients with multiple endocrine neoplasia type 1 was safe and successful in the majority of patients; however; recurrent hyperparathyroidism is likely to develop in most individuals beyond 10 years of follow-up. The total number of glands accounted for after reoperation is not associated with successful outcome. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. RP Alexander, HR (reprint author), NCI, Surg Branch, NIH, Bldg 10,Rm 2B07,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Brennan, Murray/0000-0003-2358-4371; Weinstein, Lee/0000-0002-1899-5152 NR 24 TC 42 Z9 42 U1 1 U2 1 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 2001 VL 130 IS 6 BP 991 EP 998 DI 10.1067/msy.2001.118379 PG 8 WC Surgery SC Surgery GA 507FA UT WOS:000173015300026 PM 11742328 ER PT J AU McCrae, RR AF McCrae, RR TI Facts and interpretations of personality trait stability - A reply to Quackenbush SO THEORY & PSYCHOLOGY LA English DT Editorial Material DE personality; personality traits; stability; tautology ID LIFE-SPAN; PSYCHOLOGY; SELF; OPENNESS; AGE AB The strong claim that the stability of personality is not falsifiable is wrong because it has been falsified under some conditions. The weaker claim that it is trivial because traits are defined as transcontextual consistencies does not hold because the transcontextual nature of traits has no implications for long-term stability. Traits are important both because of their pervasive influence on thoughts, feelings and actions, and because of their centrality in many people's identity. Nevertheless, there is more to personality than traits, and many other psychological phenomena also merit study by personality psychologists. C1 NIA, Lab Personal & Cognit, NIH, Bethesda, MD 20892 USA. RP McCrae, RR (reprint author), Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 35 TC 3 Z9 3 U1 1 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 0959-3543 J9 THEOR PSYCHOL JI Theory Psychol. PD DEC PY 2001 VL 11 IS 6 BP 837 EP 844 DI 10.1177/0959354301116009 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 520DK UT WOS:000173765100009 ER PT J AU Shimoda, R Nagamine, T Takagi, H Mori, M Waalkes, MP AF Shimoda, R Nagamine, T Takagi, H Mori, M Waalkes, MP TI Induction of apoptosis in cells by cadmium: Quantitative negative correlation between basal or induced metallothionein concentration and apoptotic rate SO TOXICOLOGICAL SCIENCES LA English DT Article DE cadmium; human; hepatoma; apoptosis; metallothionein; zinc; in vitro ID B6C3F1 MOUSE-LIVER; EPITHELIAL-CELLS; GENE-EXPRESSION; CYTO-TOXICITY; NULL MICE; GROWTH; CARCINOMA; LUNG; INHIBITION; KIDNEY AB Metallothionein (MT) often reduces the adverse effects of cadmium (Cd), but how it may alter Cd-induced apoptosis is unclear. The goal of this study was to define the role of MT in Cd-induced apoptosis using cell lines with widely varying sensitivity to Cd. Effects of Cd on growth of human hepatocellular carcinoma cell lines (HepG2 and PLC/PRF/5) were investigated and compared with Chang cells. These cells were cultured with 0, 5, 10, 20, 40, 80, and 120 muM of Cd for 3, 6, 12, and 24 h. Significant cytolethality was observed in HepG2 and PLC/PRF/5 cells in a time- and concentration-dependent manner, with LC50 values of 24 muM and 13 muM, respectively. However, Chang cells were much less sensitive to Cd-induced cytotoxicity (LC50, 64 muM). Apoptotic cell death occurring at cytolethal concentrations was demonstrated in all cell lines by DNA fragmentation on agarose gel electrophoresis or by ELISA. When MT was measured, there was a highly significant negative linear correlation between the basal cellular MT concentration or Cd-induced MT and the rate of apoptosis induced by Cd in these cell lines. Treating HepG2 cells with zinc (Zn) made the relatively sensitive HepG2 cell line resistant to Cd-induced apoptosis, likely due to Zn-induced MT. In fact, there was also a significant negative linear correlation between the amount of Zn-induced MT in HepG2 cells and the rate of Cd-induced apoptosis. These findings revealed that basal or induced MT perturbs Cd-induced apoptotic cell death in various cell lines, and a strong negative correlation exists between cellular MT content and the rate of apoptosis induced by Cd. C1 NIEHS, Inorgan Carcinogenesis Sect, NCI, Res Triangle Pk, NC 27709 USA. Gunma Univ, Sch Med, Dept Internal Med 1, Maebashi, Gumma 3718511, Japan. Gunma Univ, Sch Med, Dept Hlth Sci, Maebashi, Gumma 3718511, Japan. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, NCI, POB 12233,Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 44 TC 51 Z9 56 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2001 VL 64 IS 2 BP 208 EP 215 DI 10.1093/toxsci/64.2.208 PG 8 WC Toxicology SC Toxicology GA 497ZQ UT WOS:000172485700009 PM 11719703 ER PT J AU Torti, VR Cobb, AJ Everitt, JI Marshall, MW Boorman, GA Butterworth, BE AF Torti, VR Cobb, AJ Everitt, JI Marshall, MW Boorman, GA Butterworth, BE TI Nephrotoxicity and hepatotoxicity induced by inhaled bromodichloromethane in wild-type and p53-heterozygous mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE bromodichloromethane; BDCM; P53(+/-); transgenic mice; C57BL/6; FVB/N; inhalation; nephrotoxicity; hepatotoxicity ID 90-DAY CHLOROFORM INHALATION; CHLORINATION BY-PRODUCTS; FEMALE B6C3F(1) MICE; DRINKING-WATER SOURCE; IN-VIVO; CELL-PROLIFERATION; CANCER INCIDENCE; BLADDER-CANCER; ACUTE TOXICITY; TAP WATER AB Bromodichloromethane (BDCM) is a common municipal drinking water disinfection by-product, resulting in widespread trace human exposure via ingestion and inhalation. The present studies were designed to define organ-specific, BDCM-induced toxicity in wild type (p53(+/+)) and heterozygous (p53(+/-)) mice on both the FVB/N and C57BL/6 genetic backgrounds. Mice were exposed to BDCM vapor daily for 6 h/day and 7 days/week at concentrations of 0, 1, 10, 30, 100, or 150 ppm for 1 week and at 0, 0.3, 1, 3, 10, or 30 ppm for 3 weeks. In the 1-week exposure study, dose-dependent mortality and morbidity were observed at concentrations of 30 ppm and above and were as high as 100% at 150 ppm. In the 3-week exposure study, mortality and morbidity were found only in the 30-ppm exposure groups and were 0, 17, 67, and 33% for the wild-type C57BL/6, p53(+/-) C57BL/6, wild-type FVB/N, and p53(+/-) FVB/N mice, respectively. BDCM was a particularly potent kidney cytotoxicant. Dose-dependent tubular degeneration, necrosis, and associated regenerative cell proliferation greater than 10-fold over controls were seen at concentrations as low as 10 ppm in the kidneys of all strains at 1 week. Similar dose-dependent increases in hepatic necrosis, degeneration, and regenerative cell proliferation were observed but were induced only at concentrations of 30 ppm and higher. Pathological changes were more severe in the FVB/N compared to the C57BL/6 mice and were more severe in the heterozygotes compared to the wild-type mice. However, recovery and return of the percentage of kidney cells in S-phase to control levels was seen at 3 weeks. The estimated maximum tolerated dose for longer-term exposures was 15 ppm, based on mortality, induced kidney pathology, and regenerative cell proliferation. A one-year cancer bioassay was initiated with doses of 0, 0.5, 3, 10, and 15 ppm, based on this information. No pathological changes in the livers were found at the 13-week time point of that study. At 13 weeks, the kidney lesions and regenerative cell proliferation seen at the 1-week time point at doses of 10 ppm and above had resolved, and the cell proliferation rates had returned to baseline. Differences in toxicity indicate that caution be used in substituting wild-type mice for transgenic mice for range-finding studies to select doses for p53(+/-) cancer studies. Resolution of the kidney lesions indicates that periods of very high regenerative cell proliferation, potentially important in the carcinogenic process, may not be observed if measurements are taken only at 3 weeks of exposure or later. C1 Chem Ind Inst Toxicol, Ctr Hlth Res, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Butterworth, BE (reprint author), Butterworth Consulting, 4820 Regalwood Dr, Raleigh, NC 27613 USA. EM bebutterworth@earthlink.net NR 39 TC 13 Z9 13 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2001 VL 64 IS 2 BP 269 EP 280 DI 10.1093/toxsci/64.2.269 PG 12 WC Toxicology SC Toxicology GA 497ZQ UT WOS:000172485700016 PM 11719710 ER PT J AU Hulla, JE AF Hulla, JE TI Untitled SO TOXICOLOGICAL SCIENCES LA English DT Letter C1 NIEHS, Lab Environm Carcinogenesis & Mutagenesis, NIH, Res Triangle Pk, NC 27709 USA. RP Hulla, JE (reprint author), NIEHS, Lab Environm Carcinogenesis & Mutagenesis, NIH, F1-05,POB 12233, Res Triangle Pk, NC 27709 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2001 VL 64 IS 2 BP 281 EP 281 DI 10.1093/toxsci/64.2.281 PG 1 WC Toxicology SC Toxicology GA 497ZQ UT WOS:000172485700017 PM 11719711 ER PT J AU Huff, J AF Huff, J TI Untitled SO TOXICOLOGICAL SCIENCES LA English DT Letter ID B6C3F1 MICE; CARCINOGENICITY; TOXICITY; EXPOSURE C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 19 TC 16 Z9 16 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2001 VL 64 IS 2 BP 282 EP 283 DI 10.1093/toxsci/64.2.282 PG 2 WC Toxicology SC Toxicology GA 497ZQ UT WOS:000172485700018 PM 11719712 ER PT J AU Peters, PJ Gao, MG Gaschet, J Ambach, A van Donselaar, E Traverse, JF Bos, E Wolffe, EJ Hsu, VW AF Peters, PJ Gao, MG Gaschet, J Ambach, A van Donselaar, E Traverse, JF Bos, E Wolffe, EJ Hsu, VW TI Characterization of coated vesicles that participate in endocytic recycling SO TRAFFIC LA English DT Article DE ARF6 coat protein; endocytosis; recycling; vesicles ID ADP-RIBOSYLATION FACTOR; GTP-BINDING PROTEIN; GOLGI MEMBRANES; PLASMA-MEMBRANE; SIGNAL-TRANSDUCTION; NUCLEOTIDE-EXCHANGE; EPITHELIAL-CELLS; PHOSPHOLIPASE-D; ARF FAMILY; RECRUITMENT AB While the recycling pathway of endocytosis has been shown to participate in many cellular functions, little is known regarding the transport carriers that mediate this pathway. In this study, we overexpressed a point mutant of ADP-ribosylation factor 6 (ARF6), that perturbs its GTPase cycle, to accumulate endosome-derived coated vesicles. Characterization by their purification revealed that, upon cell homogenization, these vesicles were mostly aggregated with larger noncoated membranes, and could be released with high-salt treatment. Equilibrium centrifugation revealed that these vesicles had buoyant density similar to the COP-coated vesicles. To purify the ARF6-regulated vesicles to homogeneity, enriched fractions from equilibrium centrifugation were subjected to immunoisolation through the hemagglutinin (HA) epitope of the mutant ARF6, by using a newly developed, high-affinity, anti-HA monoclonal antibody. Surface iodination of the purified vesicles revealed multiple prominent proteins. Immunoblotting with antibodies against subunits of the currently known coat proteins suggested that these vesicles have a novel coat complex. These vesicles are carriers for endocytic recycling, because they are enriched for transferrin receptor and also the v-SNARE cellubrevin that functions in transport from the recycling endosome to the plasma membrane. Thus, we have characterized transport vesicles that participate in endocytic recycling. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Netherlands Canc Inst, Sect Tumor Biol, NL-1066 CX Amsterdam, Netherlands. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Peters, PJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. RI Gaschet, Joelle/F-6761-2013 OI Gaschet, Joelle/0000-0003-2154-1255 NR 48 TC 21 Z9 21 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-9219 J9 TRAFFIC JI Traffic PD DEC PY 2001 VL 2 IS 12 BP 885 EP 895 DI 10.1034/j.1600-0854.2001.21204.x PG 11 WC Cell Biology SC Cell Biology GA 496NE UT WOS:000172401000004 PM 11737826 ER PT J AU Wagner, KU McAllister, K Ward, T Davis, B Wiseman, R Hennighausen, L AF Wagner, KU McAllister, K Ward, T Davis, B Wiseman, R Hennighausen, L TI Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice SO TRANSGENIC RESEARCH LA English DT Article DE Cre; mammary; MMTV-LTR; ROSA26; transgenic mice ID BCL-X; CELLS; DISRUPTION; DELETION; STRAIN AB Cre-loxP based gene deletion approaches hold great promise to enhance our understanding of molecular pathways controlling mammary development and breast cancer. We reported earlier the generation of transgenic mice that express the Cre recombinase under the control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR). These mice have become a valuable research tool to delete genes specifically in the mammary gland, other secretory organs, and the female germline. We have now characterized in depth the expression of the MMTV-Cre transgene using the ROSA26-lox-Stop-lox-LacZ reporter strain to determine the temporal and spatial activation of Cre on the level of single cells. Our results show that MMTV-mediated Cre-activation is restricted to specific cell types of various secretory tissues and the hematopoietic system. Secondly, the timing of Cre expression varies between tissues and cell types. Some tissues express Cre during embryonic development, while other selected cell types highly activate Cre around puberty, suggesting a strong influence of steroid hormones on the transcriptional activation of the MMTV-LTR. Thirdly, Cre expression in the female germline is restricted to individual mouse lines and is therefore dependent on the site of integration of the transgene. Information provided by this study will guide the researcher to those cell types and developmental stages at which a phenotype can be expected upon deletion of relevant genes. C1 Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. NIEHS, Lab Womens Hlth, NIH, Res Triangle Pk, NC 27709 USA. RP Wagner, KU (reprint author), Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, 986805 Nebraska Med Ctr,Room 8009, Omaha, NE 68198 USA. RI Wagner, Kay-Uwe/B-6044-2009 NR 11 TC 190 Z9 191 U1 0 U2 7 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD DEC PY 2001 VL 10 IS 6 BP 545 EP 553 DI 10.1023/A:1013063514007 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 497KV UT WOS:000172455300007 PM 11817542 ER PT J AU Wickner, RB Edskes, HK Roberts, BT Pierce, MM Baxa, U Ross, E AF Wickner, RB Edskes, HK Roberts, BT Pierce, MM Baxa, U Ross, E TI Prions beget prions: the [PIN+] mystery! SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; DE-NOVO APPEARANCE; IN-VITRO; PROTEIN; SUP35; PSI+; DETERMINANT; PSI(+); DOMAIN; URE2P AB Prions are infectious proteins. [PIN+] is a non-chromosomal genetic element of Saccharomyces cerevisiae that is necessary for the de novo induction of the [PSI+] prion. Recently, [PIN+] has been found to be itself a prion of the Rnq1 protein. [URE3], another yeast prion, can also promote [PSI+] generation. Thus, one prion can promote the generation of another. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. OI Ross, Eric/0000-0002-6473-9977 NR 23 TC 7 Z9 7 U1 1 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD DEC PY 2001 VL 26 IS 12 BP 697 EP 699 DI 10.1016/S0968-0004(01)02020-5 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502HK UT WOS:000172737800002 PM 11738587 ER PT J AU Roll-Mecak, A Shin, BS Dever, TE Burley, SK AF Roll-Mecak, A Shin, BS Dever, TE Burley, SK TI Engaging the ribosome: universal IFs of translation SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID INITIATION-FACTOR IF1; ELONGATION-FACTOR TU; ESCHERICHIA-COLI; ANGSTROM RESOLUTION; EF-TU; CONFORMATIONAL-CHANGES; THERMUS-THERMOPHILUS; CRYSTAL-STRUCTURE; TERNARY COMPLEX; GTP HYDROLYSIS AB Eukaryotic initiation factor 1A (eIF1A) and the GTPase IF2/eIF5B are the only universally conserved translation initiation factors. Recent structural, biochemical and genetic data indicate that these two factors form an evolutionarily conserved structural and functional unit in translation initiation. Based on insights gathered from studies of the translation elongation factor GTPases, we propose that these factors occupy the aminoacyl-tRNA site (A site) on the ribosome, and promote initiator tRNA binding and ribosomal subunit joining. These processes yield a translationally competent ribosome with Met-tRNA in the ribosomal peptidyl-tRNA site (P site), base-paired to the AUG start codon of a mRNA. C1 Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Biophys, New York, NY 10021 USA. NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Roll-Mecak, A (reprint author), Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Biophys, 1230 York Ave, New York, NY 10021 USA. FU NIGMS NIH HHS [GM61262] NR 32 TC 52 Z9 53 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD DEC PY 2001 VL 26 IS 12 BP 705 EP 709 DI 10.1016/S0968-0004(01)02024-2 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502HK UT WOS:000172737800007 PM 11738593 ER PT J AU Ko, MSH AF Ko, MSH TI Embryogenomics: developmental biology meets genomics SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID EXPRESSED SEQUENCE TAGS; EQUALIZED CDNA LIBRARY; PRIMORDIAL GERM-CELLS; EMBRYONIC STEM-CELLS; GENE-EXPRESSION; MOUSE EMBRYOS; COMPUTATIONAL ANALYSIS; FUNCTIONAL ANNOTATION; HUMAN BLASTOCYSTS; MESSENGER-RNA AB Fundamental questions in developmental biology are: what genes are expressed, where and when they are expressed, what is the level of expression and how are these programs changed by the functional and structural alteration of genes? These questions have been addressed by studying one gene at a time, but a new research field that handles many genes in parallel is emerging. The methodology is at the interface of large-scale genomics approaches and developmental biology. Genomics needs developmental biology because one of the goals of genomics-collection and analysis of all genes in an organism - cannot be completed without working on embryonic tissues in which many genes are uniquely expressed. However, developmental biology needs genomics-the high-throughput approaches of genomics generate information about genes and pathways that can give an integrated view of complex processes. This article discusses these new approaches and their applications to mammalian developmental biology. C1 NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. EM KoM@grc.nia.nih.gov RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 69 TC 45 Z9 45 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD DEC PY 2001 VL 19 IS 12 BP 511 EP 518 DI 10.1016/S0167-7799(01)01806-6 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 498KN UT WOS:000172508900009 PM 11711195 ER PT J AU Futaki, M Liu, JM AF Futaki, M Liu, JM TI Chromosomal breakage syndromes and the BRCA1 genome surveillance complex SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID DNA-DAMAGE RESPONSE; SYNDROME GENE-PRODUCT; INTERACT IN-VIVO; TUMOR-SUPPRESSOR; BREAST-CANCER; FANCONIS ANEMIA; MEIOTIC CELLS; PROTEIN; REPAIR; PHOSPHORYLATION AB Chromosomal instability can occur when the DNA damage response and repair process fails, resulting in syndromes characterized by growth abnormalities, hematopoietic defects, mutagen sensitivity, and cancer predisposition. Mutations in ATM, NBS1, MRE11, BLM, WRN, and FANCD2 are responsible for ataxia telangiectasia (AT), Nijmegen breakage syndrome, AT-like disorder, Bloom and Werner syndrome, and Fanconi anemia group D2, respectively. This diverse group of disorders is thought to be linked through protein interactions with the breast cancer tumor susceptibility gene product, BRCA1. BRCA1 forms a multi-subunit protein complex referred to as the BRCA1-associated genome surveillance complex (BASC), which includes DNA damage repair proteins such as MSH2-MSH6 and MLH1, as well as ATM, NBS1, MRE11, and BLM. Although still controversial, this finding suggests similarities in the pathogenesis of the human chromosome breakage syndromes and a complementary role for each protein in DNA structure surveillance or damage repair. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Futaki, M (reprint author), NHLBI, Hematol Branch, Bldg 10,Room 7C103, Bethesda, MD 20892 USA. NR 60 TC 50 Z9 53 U1 0 U2 2 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 2001 VL 7 IS 12 BP 560 EP 565 DI 10.1016/S1471-4914(01)02178-5 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 500FP UT WOS:000172615700011 PM 11733219 ER PT J AU Cook, JA Steel, C Ottesen, EA AF Cook, JA Steel, C Ottesen, EA TI Towards a vaccine for onchocerciasis SO TRENDS IN PARASITOLOGY LA English DT Editorial Material ID ANTIBODY-RESPONSES; VOLVULUS LARVAL; ANTIGENS; IMMUNITY; CELLS C1 Int Trachoma Initiat, New York, NY 10017 USA. NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Int Hlth, Lymphat Filariasis Support Ctr, Atlanta, GA 30322 USA. RP Steel, C (reprint author), Int Trachoma Initiat, 441 Lexington Ave,Suite 1600, New York, NY 10017 USA. NR 12 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4922 J9 TRENDS PARASITOL JI Trends Parasitol. PD DEC PY 2001 VL 17 IS 12 BP 555 EP 558 DI 10.1016/S1471-4922(01)02115-8 PG 4 WC Parasitology SC Parasitology GA 498ZR UT WOS:000172544500001 PM 11756017 ER PT J AU Kruger, A Rech, A Su, XZ Tannich, E AF Kruger, A Rech, A Su, XZ Tannich, E TI Short communication: Two cases of autochthonous Plasmodium falciparum malaria in Germany with evidence for local transmission by indigenous Anopheles plumbeus SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Article DE autochthonous malaria; Plasmodium falciparum; Anopheles plumbeus ID AIRPORT MALARIA; MOSQUITOS AB Autochthonous Plasmodium falciparum malaria (PFM) in Central Europe has been reported repeatedly, transmission of the parasite being attributed to blood transfusion or imported P. falciparum-infected vectors. We report two cases of PFM in German children without travel history to malaria-endemic areas. Both infections occurred during a stay in a hospital where a child from Angola with chronic P. falciparum infection was hospitalized at the time. Known routes of transmission, such as imported mosquitoes or blood transfusion, were very unlikely or could be excluded, whereas evidence was obtained for transmission by the indigenous mosquito species Anopheles plumbeus. C1 Bernhard Nocht Inst Trop Med, Dept Mol Parasitol, D-20359 Hamburg, Germany. Klinikum Duisburg, Duisburg, Germany. NIAID, NIH, Bethesda, MD 20892 USA. RP Tannich, E (reprint author), Bernhard Nocht Inst Trop Med, Dept Mol Parasitol, Bernhard Nocht Str 74, D-20359 Hamburg, Germany. NR 15 TC 61 Z9 66 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD DEC PY 2001 VL 6 IS 12 BP 983 EP 985 DI 10.1046/j.1365-3156.2001.00816.x PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 503MP UT WOS:000172802500004 PM 11737834 ER PT J AU Lieberman, R Bermejo, C Akaza, H Greenwald, P Fair, W Thompson, I AF Lieberman, R Bermejo, C Akaza, H Greenwald, P Fair, W Thompson, I TI Progress in prostate cancer chemoprevention: Modulators of promotion and progression SO UROLOGY LA English DT Review ID INTRAEPITHELIAL NEOPLASIA; CONTROLLED TRIAL; CLINICAL-TRIALS; CARCINOMA; INHIBITOR; RISK; SUPPLEMENTATION; PREVENTION; MORTALITY; KINASE C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Div Urol, San Antonio, TX USA. Inst Clin Med Urol, Tsukuba, Ibaraki, Japan. Mem Sloan Kettering Canc Ctr, Dept Urol, New York, NY 10021 USA. RP Lieberman, R (reprint author), NCI, Div Canc Prevent, EPN 2102, 6130 Execut Blvd, Rockville, MD 20852 USA. NR 29 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD DEC PY 2001 VL 58 IS 6 BP 835 EP 842 DI 10.1016/S0090-4295(01)01416-9 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 502PP UT WOS:000172752200001 PM 11744441 ER PT J AU Khan, NW Jamison, JA Kemp, JA Sieving, PA AF Khan, NW Jamison, JA Kemp, JA Sieving, PA TI Analysis of photoreceptor function and inner retinal activity in juvenile X-linked retinoschisis SO VISION RESEARCH LA English DT Article DE electroretinogram (ERG); flicker; photoreceptor; a-wave; retinoschisis ID STATIONARY NIGHT BLINDNESS; ERG A-WAVE; RETINITIS-PIGMENTOSA; B-WAVE; FLICKER ELECTRORETINOGRAM; PHOTOPIC ELECTRORETINOGRAM; ACTIVATION STEPS; PHOTOTRANSDUCTION; COMPONENT; ABNORMALITIES AB Thirteen retinoschisis males with genotyped XLRS1 gene mutations were examined by electroretinogram (ERG) techniques to determine photoreceptor involvement and ON-pathway and OFF-pathway sites of dysfunction. Parameters R-max and log S determined by fitting the mathematical model of the activation phase of phototransduction to the scotopic and photopic a-wave responses, were not significantly different from normal. However, the XLRS photopic a-wave amplitudes were significantly lower than normal across all intensities. consistent with defective signaling in the OFF pathway. Long flash (150 ms) ON-OFF photopic responses showed reduced b-wave amplitude but normal d-wave amplitude, giving a reduced b/d ratio of < 1.32 Hz photopic flicker ERG fundamental frequency responses showed reduced amplitude and delayed phase. consistent with abnormal signaling by both the ON- and OFF-pathway components. These results indicate that the XLRS1 protein appears not to affect photoreceptor function directly for most XLRS males. and that ERG signaling abnormalities occur in both the ON- and OFF-pathway components that originate in the proximal retina. (C) 2001 Published by Elsevier Science Ltd. C1 Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. RP Sieving, PA (reprint author), NEI, Bldg 31,Room 6A03,31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY07003, R01-EY06094] NR 46 TC 39 Z9 39 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD DEC PY 2001 VL 41 IS 28 BP 3931 EP 3942 DI 10.1016/S0042-6989(01)00188-2 PG 12 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 518QV UT WOS:000173680100013 PM 11738458 ER PT J AU Warner, HR AF Warner, HR TI The case for supporting basic research in gerontology SO ZEITSCHRIFT FUR GERONTOLOGIE UND GERIATRIE LA English DT Article DE gerintological research; caloric restriction; longevity; genetic interventions ID GENE-EXPRESSION PROFILE; LIFE-SPAN; CAENORHABDITIS-ELEGANS; LONGEVITY; MICE; RESTRICTION; METHUSELAH; DIAPAUSE; EXTEND AB Basic research on aging has moved well beyond describing the aging of physiological systems and developing theories of aging, to the pursuit of mechanistic answers to questions such as: Why do we age? Why do individuals within a population age differently? Why do different species have such different life spans? How do aging changes increase the risk of developing age-related disease? and Can we develop safe and effective interventions to reduce age-related disability? Two general areas of research promise to provide answers to these questions. One is the attempt to understand the mechanisms by which caloric restriction extends longevity and delays the onset of age-related disease. The other is the identification of genes which strongly influence the rate of aging in various animal model systems. Recent results in the latter area of research are providing new in-sights into the answers to these central aging questions and may help us understand how caloric restriction retards aging. C1 NIA, NIH, Biol Aging Program, Bethesda, MD 20892 USA. RP Warner, HR (reprint author), NIA, NIH, Biol Aging Program, Bethesda, MD 20892 USA. NR 25 TC 0 Z9 1 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0948-6704 J9 Z GERONTOL GERIATR JI Z. Gerontol. Geriatr. PD DEC PY 2001 VL 34 IS 6 BP 486 EP 490 DI 10.1007/s003910170024 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 511BC UT WOS:000173242300013 PM 11828890 ER PT J AU Agbaria, R Candotti, F Kelley, JA Hao, Z Johns, DG Cooney, DA Blaese, RM Ford, H AF Agbaria, R Candotti, F Kelley, JA Hao, Z Johns, DG Cooney, DA Blaese, RM Ford, H TI Biosynthetic ganciclovir triphosphate: Its isolation and characterization from ganciclovir-treated herpes simplex thymidine kinase-transduced murine cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE ganciclovir triphosphate; herpes simplex thymidine kinase; adenocarcinoma cells; DNA polymerase; biosynthesis ID DNA-POLYMERASE; VIRUS TYPE-1; 9-(1,3-DIHYDROXY-2-PROPOXYMETHYL)GUANINE; 9-(2-HYDROXYETHOXYMETHYL)GUANINE; REPLICATION; INHIBITION; GENE AB A method is described for the preparation of ganciclovir triphosphate (GCV-TP) using murine colon cancer cells (MC38) transduced with the herpes simplex virus-thymidine kinase (MC38/HSV-tk). Murine cells transduced with viral-tk contain required viral and host enzymes needed for complete cellular synthesis of this potent antiviral metabolite. Dose response studies showed optimal intracellular levels of GCV-TP occurred after exposure of MC38/HSV-tk cells to 300 muM ganciclovir for 24 h producing 7.5 nmol GCV-TP/10(6) cells. This reflects cellular accumulation of GCV-TP to levels 25-fold greater than the medium concentration of parent drug. A simple isolation scheme included methanolic extraction and anion-exchange chromatography to recover the target triphosphate. Mass spectral analysis and selective enzyme degradation provided structural confirmation of the purified product. Biological activity of the purified GCV-TP was demonstrated by competitive inhibition experiments using human DNA polymerase a and HSV DNA polymerase that showed substantially greater sensitivity for the viral polymerase in agreement with previous reports. The GCV-TP obtained was further used to enzymatically prepare GCV mono- and diphosphate in high yield. This method provides an easily scalable means of preparing milligram amounts of the triphosphates of pharmacologically active acyclic nucleosides like ganciclovir. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, Beer Sheva, Israel. NCI, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. RP Ford, H (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 21 TC 10 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 30 PY 2001 VL 289 IS 2 BP 525 EP 530 DI 10.1006/bbrc.2001.6011 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 500CG UT WOS:000172607900033 PM 11716505 ER PT J AU Maric, D Millward, JM Ballok, DA Szechtman, H Denburg, JA Barker, JL Sakic, B AF Maric, D Millward, JM Ballok, DA Szechtman, H Denburg, JA Barker, JL Sakic, B TI Neurotoxic properties of cerebrospinal fluid from behaviorally impaired autoimmune mice SO BRAIN RESEARCH LA English DT Article DE autoimmunity; cerebrospinal fluid; neurotoxicity; pyramidal neuron; astrocyte; neuropsychiatric lupus; cell culture; fluorescence; MRL mouse ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MRL-LPR MICE; NITRIC-OXIDE PRODUCTION; PITUITARY-ADRENAL AXIS; ANTICARDIOLIPIN ANTIBODIES; LPR/LPR MICE; ANIMAL-MODEL; COGNITIVE IMPAIRMENT; PSYCHIATRIC-SYMPTOMS; GENE-EXPRESSION AB The chronic, lupus-like autoimmune disease in MRL-lpr mice is associated with leucocyte infiltration into the choroid plexus, brain cell death, and deficits in motivated behavior. The presence of lymphoid cells in the ventricular lumen and the increased number of TUNEL-positive cells in periventricular areas led to the hypothesis that immune cells enter into the cerebrospinal fluid (CSF) and induce primary neuronal damage in regions bordering the cerebral ventricles. Using an in vitro approach, we presently examine the possibility that CSF from autoimmune nice is neurotoxic and/or gliotoxic. The CSF and serum from diseased MRL-lpr mice, less symptomatic MRL +/+ controls, and healthy Swiss/Webster mice (non-autoimmune controls) were frozen until their effects on the viability of pyramidal neurons and astrocytes were assessed in a two-color fluorescence assay. Significant reduction in neuronal viability (in some cases as low as 67%) was observed in the co-cultures of hippocampal neurons and astrocytes incubated for 24 h with CSF from autoimmune MRL-1pr mice. The viability of astrocytes did not differ among the groups, and the CSF from autoimmune trice appeared more toxic than the serum. The behavior of MRL-lpr mice differed significantly from the control groups, as indicated by impaired exploration, reduced intake of palatable food, and excessive immobility in the forced swim test. The present results suggest that CSF from the behaviorally impaired lupus-prone mice is neurotoxic and are consistent with the hypothesis that neuroactive metabolites are produced intrathecally in neuropsychiatric lupus erythematosus. (C) 2001 Elsevier Science BY. All rights reserved. C1 McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON L8N 3Z5, Canada. McMaster Univ, Dept Med, Hamilton, ON L8N 3Z5, Canada. NINCDS, Lab Neurophysiol, NIH, Bethesda, MD USA. RP Sakic, B (reprint author), McMaster Univ, Dept Psychiat & Behav Neurosci, 1200 Main St West,HSC Rm 4N77A, Hamilton, ON L8N 3Z5, Canada. RI Szechtman, Henry/A-4706-2009 OI Szechtman, Henry/0000-0003-3986-4482 NR 75 TC 31 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 30 PY 2001 VL 920 IS 1-2 BP 183 EP 193 DI 10.1016/S0006-8993(01)03060-8 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 503GT UT WOS:000172791300020 PM 11716824 ER PT J AU Misra, S Miller, GJ Hurley, JH AF Misra, S Miller, GJ Hurley, JH TI Recognizing phosphatidylinositol 3-phosphate SO CELL LA English DT Review ID BINDING DOMAINS AB Phosphatidylinositol 3-phosphate directs the endosomal localization of regulatory proteins by binding to FYVE and PX domains. New structures of these domains complexed with the phosphoinositide headgroup show how interactions with phosphate and hydroxyl groups differentiate this lipid from all others. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. OI Misra, Saurav/0000-0002-1385-8554 NR 20 TC 66 Z9 66 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 30 PY 2001 VL 107 IS 5 BP 559 EP 562 DI 10.1016/S0092-8674(01)00594-3 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 499MQ UT WOS:000172575300003 PM 11733055 ER PT J AU Davis, JS Hassanzadeh, S Winitsky, S Lin, H Satorius, C Vemuri, R Aletras, AH Wen, H Epstein, ND AF Davis, JS Hassanzadeh, S Winitsky, S Lin, H Satorius, C Vemuri, R Aletras, AH Wen, H Epstein, ND TI The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation SO CELL LA English DT Article ID HYPERTROPHIC CARDIOMYOPATHY; SKELETAL-MUSCLE; STRETCH-ACTIVATION; LEFT-VENTRICLE; BETA-MYOSIN; MUTATIONS; DEFORMATION; EXPRESSION; FILAMENTS; KINASE AB Evolution of the human heart has incorporated a variety of successful strategies for motion used throughout the animal kingdom. One such strategy is to add the efficiency of torsion to compression so that blood is wrung, as well as pumped, out of the heart. Models of cardiac torsion have assumed uniform contractile properties of muscle fibers throughout the heart. Here, we show how a spatial gradient of myosin light chain phosphorylation across the heart facilitates torsion by inversely altering tension production and the stretch activation response. To demonstrate the importance of cardiac light chain phosphorylation, we, cloned a myosin light chain kinase from a human heart and have identified a gain-in-function mutation in two individuals with cardiac hypertrophy. C1 NHLBI, Mol Physiol Sect, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Epstein, ND (reprint author), NHLBI, Mol Physiol Sect, Cardiol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Wen, Han/G-3081-2010; OI Wen, Han/0000-0001-6844-2997; Aletras, Anthony/0000-0002-3786-3817 NR 30 TC 171 Z9 182 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 30 PY 2001 VL 107 IS 5 BP 631 EP 641 DI 10.1016/S0092-8674(01)00586-4 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 499MQ UT WOS:000172575300010 PM 11733062 ER PT J AU Shchelkunov, SN Totmenin, AV Babkin, IV Safronov, PF Ryazankina, OI Petrov, NA Gutorova, VV Uvarova, EA Mikheev, MV Sisler, JR Esposito, JJ Jahrling, PB Moss, B Sandakhchiev, LS AF Shchelkunov, SN Totmenin, AV Babkin, IV Safronov, PF Ryazankina, OI Petrov, NA Gutorova, VV Uvarova, EA Mikheev, MV Sisler, JR Esposito, JJ Jahrling, PB Moss, B Sandakhchiev, LS TI Human monkeypox and smallpox viruses: genomic comparison SO FEBS LETTERS LA English DT Article DE monkeypox virus; smallpox virus; genome; virulence factor; ankyrin-like protein ID DOUBLE-STRANDED-RNA; COMPLEMENT CONTROL PROTEINS; VACCINIA VIRUS; VARIOLA VIRUSES; NUCLEOTIDE-SEQUENCE; ORTHOPOXVIRUS DNA; BINDING; INHIBITION; INTERFERON; MECHANISM AB Monkeypox virus (MPV) causes a human disease which resembles smallpox but with a lower person-to-person transmission rate. To determine the genetic relationship between the orthopoxviruses causing these two diseases, we sequenced the 197-kb genome of MPV isolated from a patient during a large human monkeypox outbreak in Zaire in 1996. The nucleotide sequence within the central region of the MPV genome, which encodes essential enzymes and structural proteins, was 96.3% identical with that of variola (smallpox) virus (VAR). In contrast, there were considerable differences between MPV and VAR in the regions encoding virulence and host-range factors near the ends of the genome. Our data indicate that MPV is not the direct ancestor of VAR and is unlikely to naturally acquire all properties of VAR. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 State Res Ctr Virol & Biotechnol Vector, Koltsov 630559, Novosibirsk Reg, Russia. NIAID, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. RP Shchelkunov, SN (reprint author), State Res Ctr Virol & Biotechnol Vector, Koltsov 630559, Novosibirsk Reg, Russia. RI Sandakhchiev, Lev/B-7035-2012; Babkin, Igor/R-1598-2016 NR 41 TC 78 Z9 92 U1 0 U2 5 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 30 PY 2001 VL 509 IS 1 BP 66 EP 70 DI 10.1016/S0014-5793(01)03144-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 499XN UT WOS:000172596100013 PM 11734207 ER PT J AU Botos, I Wu, ZB Lu, WY Wlodawer, A AF Botos, I Wu, ZB Lu, WY Wlodawer, A TI Crystal structure of a cyclic form of bovine pancreatic trypsin inhibitor SO FEBS LETTERS LA English DT Article DE bovine pancreatic trypsin inhibitor; cyclic protein; atomic resolution ID CHEMICAL LIGATION; ALPHA-DEFENSINS; PEPTIDE; REFINEMENT; MOLSCRIPT; PROTEINS AB The crystal structure of a cyclic form of a mutant of bovine pancreatic trypsin inhibitor has been solved at 1.0 Angstrom resolution. The protein was synthesized by native chemical ligation and its structure is almost indistinguishable from the previously described recombinant form of the same mutant; however, the new loop containing the former termini became much better ordered. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. RP Wlodawer, A (reprint author), NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. RI Lu, Wuyuan/B-2268-2010 NR 27 TC 16 Z9 16 U1 0 U2 4 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 30 PY 2001 VL 509 IS 1 BP 90 EP 94 DI 10.1016/S0014-5793(01)03113-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 499XN UT WOS:000172596100018 PM 11734212 ER PT J AU Toyoda, M Takayama, H Horiguchi, N Otsuka, T Fukusato, T Merlino, G Takagi, H Mori, M AF Toyoda, M Takayama, H Horiguchi, N Otsuka, T Fukusato, T Merlino, G Takagi, H Mori, M TI Overexpression of hepatocyte growth factor/scatter factor promotes vascularization and granulation tissue formation in vivo SO FEBS LETTERS LA English DT Article DE hepatocyte growth factor/scatter factors; vascular endothelial growth factor; wound healing; angiogenesis; transgenic mouse ID FACTOR SCATTER FACTOR; MICROVASCULAR ENDOTHELIAL-CELLS; HUMAN WOUND FLUID; C-MET RECEPTOR; PERMEABILITY FACTOR; PLASMINOGEN-ACTIVATOR; FACTOR STIMULATION; ANGIOGENESIS; EXPRESSION; MODEL AB The effect of hepatocyte growth factor/scatter factor (HGF/SF) during wound healing in the skin was investigated, using HGF/SF-overexpressing transgenic mouse model. Histological analysis of HGF/SF transgenic mouse excisional wound sites revealed increased granulation tissue with marked vascularization. Northern blot analysis demonstrated that, relative to control, vascular endothelial growth factor (VEGF) expression in transgenic skin was significantly higher at baseline and was robustly up-regulated during wound healing. Elevated levels of VEGF protein were detected immunohistochemically, predominantly in endothelial cells and fibroblasts within the granulation tissue of HGF/SF transgenic skin. Serum levels of VEGF were also elevated in HGF/SF transgenic mice. Thus, results from our study suggest that HGF/SF has a significant effect on vascularization and granulation tissue formation during wound healing in vivo, involving with induction of VEGF. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Gunma Univ, Sch Med, Dept Internal Med 1, Maebashi, Gumma 3718511, Japan. Gunma Univ, Sch Med, Div Diagnost Pathol, Maebashi, Gumma 3718511, Japan. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Takagi, H (reprint author), Gunma Univ, Sch Med, Dept Internal Med 1, Showa Machi 3-39-15, Maebashi, Gumma 3718511, Japan. NR 46 TC 49 Z9 53 U1 0 U2 0 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 30 PY 2001 VL 509 IS 1 BP 95 EP 100 DI 10.1016/S0014-5793(01)03126-X PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 499XN UT WOS:000172596100019 PM 11734213 ER PT J AU Park, SW Ye, ZP Schubert, M Paik, SY AF Park, SW Ye, ZP Schubert, M Paik, SY TI Defective interfering HIV-1 pseudotypes carrying chimeric CD4 protein SO JOURNAL OF BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE HIV-1 pseudotype; CD4; CXCR4 ID VESICULAR STOMATITIS-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 INFECTION; ENVELOPE PROTEIN; CELLS; PARTICLES; RECEPTORS; VIRIONS; PR55GAG; SIGNAL AB Chimeric CD4 proteins were assembled. They contained the entire CD4 ectodomain that is linked to different membrane anchors. Membrane anchors consisted of either glucosyl phosphatidyl inositol (gpi), the transmembrane and cytoplasmic regions of HIV-1 Env protein, or the vesicular stomatitis virus G glycoprotein, respectively. The HIV-1 co-receptor CXCR4 and CD4 were independently inserted into viral envelopes. We compared the insertion of six different CD4/CXCR4 constructs into HIV-1 envelopes, as well as their functionality in targeting and specific infection of cells that constitutively express the HIV-1 Env protein. All of the six different HIV-1 (CD4/CXCR4) pseudotypes were able to transduce Env (+) cells at similar efficiency: In addition, stable transduction of the Env (+) recipient cells demonstrated that all chimeric proteins were functional as receptors for Env when inserted into HIV-1 envelopes. In fact, these results demonstrate for the first time a stable transduction by a targeted HIV-1 pseudotype virus. C1 Catholic Univ Korea, Coll Med, Dept Microbiol, Seoul 137701, South Korea. NINCDS, NIH, Bethesda, MD 20892 USA. RP Paik, SY (reprint author), Catholic Univ Korea, Coll Med, Dept Microbiol, Seoul 137701, South Korea. NR 31 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG SINGAPORE PTE LTD PI SINGAPORE PA #04-01 CENCON I, 1 TANNERY RD, SINGAPORE 347719, SINGAPORE SN 1225-8687 J9 J BIOCHEM MOL BIOL JI J. Biochem. Mol. Biol. PD NOV 30 PY 2001 VL 34 IS 6 BP 566 EP 572 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 496TN UT WOS:000172413000012 ER PT J AU Stadtman, ER AF Stadtman, ER TI The story of glutamine synthetase regulation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Editorial Material ID INTERCONVERTIBLE ENZYME CASCADES; ESCHERICHIA-COLI; METABOLIC-REGULATION; PROTEIN OXIDATION; ADENYLYLATION; SYSTEMS; URIDYLYLTRANSFERASE; DEADENYLYLATION; PURIFICATION; SUPERIORITY C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA. NR 54 TC 75 Z9 77 U1 3 U2 15 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 30 PY 2001 VL 276 IS 48 BP 44357 EP 44364 DI 10.1074/jbc.R100055200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 496QD UT WOS:000172406700001 PM 11585846 ER PT J AU Cho, EG Kim, MG Kim, C Kim, SR Seong, IS Chung, CH Schwartz, RH Park, D AF Cho, EG Kim, MG Kim, C Kim, SR Seong, IS Chung, CH Schwartz, RH Park, D TI N-terminal processing is essential for release of epithin, a mouse type II membrane serine protease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX-DEGRADING PROTEASE; BREAST-CANCER CELLS; HAGEMAN-FACTOR; DEPENDENT AUTOACTIVATION; PLASMINOGEN-ACTIVATOR; BLOOD-COAGULATION; 1ST COMPONENT; FACTOR-VII; IDENTIFICATION; MATRIPTASE AB Epithin was originally identified as a mouse type II membrane serine protease. Its human orthologue membrane type-serine protease 1 (MT-SP1)/matriptase has been reported to be localized on the plasma membrane. In addition, soluble forms of matriptase were isolated from human breast milk and breast cancer cell-conditioned medium. In this paper, we report a processing mechanism that appears to be required for the release of epithin. CHO-K1 or COS7 cells transfected with single full-length epithin cDNA generated two different-sized proteins in cell lysates, 110 and 92 kDa. The 92-kDa epithin was found to be an N-terminally truncated form of the 110-kDa epithin, and it was the only form detected in the culture medium. The 92-kDa epithin was also found on the cell surface, where it was anchored by the N-terminal fragment. The results of in vivo cell labeling experiments indicate that the 110-kDa epithin is rapidly processed to the 92-kDa epithin. Using site-directed mutagenesis experiments, we identified Gly(149) of the GSVIA sequence in epithin as required for the processing and release of the protein. These results suggest that N-terminal processing of epithin at Gly149 is a necessary prerequisite step for release of the protein. C1 Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea. NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. Chungbuk Natl Univ, Coll Med, Cheongju 361763, South Korea. RP Park, D (reprint author), Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea. NR 22 TC 57 Z9 57 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 30 PY 2001 VL 276 IS 48 BP 44581 EP 44589 DI 10.1074/jbc.M107059200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 496QD UT WOS:000172406700034 PM 11567025 ER PT J AU Pawliczak, R Cowan, MJ Huang, XL Nanavaty, UB Alsaaty, S Logun, C Shelhamer, JH AF Pawliczak, R Cowan, MJ Huang, XL Nanavaty, UB Alsaaty, S Logun, C Shelhamer, JH TI p11 expression in human bronchial epithelial cells is increased by nitric oxide in a cGMP-dependent pathway involving protein kinase G activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANNEXIN-II TETRAMER; BIOCHEMICAL-CHARACTERIZATION; PHOSPHOLIPASE A(2); C-JUN; TRANSCRIPTION; BINDING; PHOSPHORYLATION; STIMULATION; SUBSTRATE; RELEASE AB The effect of nitric oxide on p11 expression was studied in an immortalized human bronchial epithelial cell line (BEAS-2B cells). Three nitric oxide donors were used: spermine NONOate (SP), (+/-)-S-nitroso-N-acetylpenicillamine (SNAP), and S-nitrosoglutathione (SNOG). All three nitric oxide donors had similar effects resulting in dose-dependent and time-dependent accumulation of pll protein and an increase of steady-state p11 mRNA. Studies using a reporter gene containing the region from -1499 to +89 of the pll promoter demonstrated an increase in transcriptional activity after stimulation with NO donors for 4 h. These effects were abolished at the promoter and protein level using protein kinase G inhibitors (KT5823 and R-p-8-pCPT-cGMPS). Incubation of transfected cells with a cell permeable cGMP analogue (8-Br-cGMP) resulted in a dose-related increase of promoter activity. An electrophoretic mobility shift assay of nuclear proteins extracted from BEAS-2B cells identified an AP-1 site located at -82 to -77 of the p11 promoter region as an NO- and cGMP- dependent response element. These data were confirmed using a c-jun dominant negative mutant vector and a e-jun expression plasmid. Therefore, we conclude that nitric oxide-induced p11 expression in human bronchial epithelial cells is mediated at least in part through increased binding of activator protein one to the p11 promoter. C1 NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Med Univ Lodz, Dept Allergy & Clin Immunol, PL-92211 Lodz, Poland. RP Shelhamer, JH (reprint author), NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Rm 7D43,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Pawliczak, Rafal/S-9649-2016 NR 30 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 30 PY 2001 VL 276 IS 48 BP 44613 EP 44621 DI 10.1074/jbc.M104993200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 496QD UT WOS:000172406700038 PM 11571284 ER PT J AU Zhou, MS Nekhai, S Bharucha, DC Kumar, A Ge, H Price, DH Egly, JM Brady, JN AF Zhou, MS Nekhai, S Bharucha, DC Kumar, A Ge, H Price, DH Egly, JM Brady, JN TI TFIIH inhibits CDK9 phosphorylation during human immunodeficiency virus type 1 transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID RNA-POLYMERASE-II; CARBOXYL-TERMINAL DOMAIN; TAT-ASSOCIATED KINASE; HUMAN CYCLIN T1; PROTEINS SPECIFICALLY ASSOCIATE; ELONGATION-FACTOR-B; FACTOR P-TEFB; HIV-1 TAT; ACTIVATING KINASE; SACCHAROMYCES-CEREVISIAE AB Tat stimulates human immunodeficiency virus, type 1 (HIV-1), transcription elongation by recruitment of the human transcription elongation factor P-TEFb, consisting of CDK9 and cyclin T1, to the TAR RNA structure. It has been demonstrated further that CDK9 phosphorylation is required for high affinity binding of Tat/P-TEFb to the TAR RNA structure and that the state of P-TEFb phosphorylation may regulate Tat transactivation. We now demonstrate that CDK9 phosphorylation is uniquely regulated in the HIV-1 preinitiation and elongation complexes. The presence of TFIIH in the HIV-1 preinitiation complex inhibits CDK9 phosphorylation. As TFIIH is released from the elongation complex between +14 and +36, CDK9 phosphorylation is observed. In contrast to the activity in the "soluble" complex, phosphorylation of CDK9 is increased by the presence of Tat in the transcription complexes. Consistent with these observations, we have demonstrated that purified TFIIH directly inhibits CDK9 autophosphorylation. By using recombinant TFIIH subcomplexes, our results suggest that the XPB subunit of TFIIH is responsible for this inhibition of CDK9 phosphorylation. Interestingly, our results further suggest that the phosphorylated form of CDK9 is the active kinase for RNA polymerase II carboxyl-terminal domain phosphorylation. C1 NCI, Virus Tumor Biol Sect, Basic Res Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. NICHHD, Mol Embryol Lab, Bethesda, MD 20892 USA. Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA. ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, CU De Strasbour, France. RP Brady, JN (reprint author), NCI, Virus Tumor Biol Sect, Basic Res Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA. RI Price, David/F-6173-2010 NR 105 TC 40 Z9 41 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 30 PY 2001 VL 276 IS 48 BP 44633 EP 44640 DI 10.1074/jbc.M107466200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 496QD UT WOS:000172406700041 PM 11572868 ER PT J AU Opresko, PL Laine, JP Brosh, RM Seidman, MM Bohr, VA AF Opresko, PL Laine, JP Brosh, RM Seidman, MM Bohr, VA TI Coordinate action of the helicase and 3 ' to 5 ' exonuclease of Werner syndrome protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SINGLE-STRANDED-DNA; SYNDROME FIBROBLASTS; SYNDROME CELLS; WRN PROTEIN; REPLICATION; REPAIR; KU; BINDING; DAMAGE; 3'->5'-EXONUCLEASE AB Werner syndrome is a human disorder characterized by premature aging, genomic instability, and abnormal telomere metabolism. The Werner syndrome protein (WRN) is the only known member of the RecQ DNA helicase family that contains a 3' --> 5'-exonuclease. However, it is not known whether both activities coordinate in a biological pathway. Here, we describe DNA structures, forked duplexes containing telomeric repeats, that are substrates for the simultaneous action of both WRN activities. We used these substrates to study the interactions between the WRN helicase and exonuclease on a single DNA molecule. WRN helicase unwinds at the forked end of the substrate, whereas the WRN exonuclease acts at the blunt end. Progression of the WRN exonuclease is inhibited by the action of WRN helicase converting duplex DNA to single strand DNA on forks of various duplex lengths. The WRN helicase and exonuclease act in concert to remove a DNA strand from a long forked duplex that is not completely unwound by the helicase. We analyzed the simultaneous action of WRN activities on the long forked duplex in the presence of the WRN protein partners, replication protein A (RPA), and the Ku70/80 heterodimer. RPA stimulated the WRN helicase, whereas Ku stimulated the WRN exonuclease. In the presence of both RPA and Ku, the WRN helicase activity dominated the exonuclease activity. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Univ Strasbourg 1, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Opresko, Patricia/0000-0002-6470-2189 NR 45 TC 78 Z9 78 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 30 PY 2001 VL 276 IS 48 BP 44677 EP 44687 DI 10.1074/jbc.M107548200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 496QD UT WOS:000172406700047 PM 11572872 ER PT J AU Gomez-Angelats, M Cidlowski, JA AF Gomez-Angelats, M Cidlowski, JA TI Protein kinase C regulates FADD recruitment and death-inducing signaling complex formation in Fas/CD95-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FAS-MEDIATED APOPTOSIS; RECEPTOR-INDUCED APOPTOSIS; T-CELL ACTIVATION; CYTOCHROME-C; CD95-MEDIATED APOPTOSIS; CD95 FAS/APO-1; LEUKEMIA-CELLS; LYMPHOMA-CELLS; PHORBOL ESTER; EXPRESSION AB Activation of protein kinase C (PKC) triggers cellular signals that inhibit Fas/CD95-induced cell death in Jurkat T-cells by poorly defined mechanisms. Previously, we have shown that one effect of PKC on Fas/CD95-dependent cell death occurs through inhibition of cell shrinkage and K+ efflux (Gomez-Angelats, M., Bortner, C. D., and Cidlowski, J. A. (2000) J. Biol. Chem. 275, 19609-19619). Here we report that PKC alters Fas/CD95 signaling from the plasma membrane to the activation of caspases by exerting a profound action on survival/cell death decisions. Specific activation of PKC with 12-O-tetradecanoylphorbol-13-acetate or bryostatin-1 induced translocation of PKC from the cytosol to the membrane and effectively inhibited cell shrinkage and cell death triggered by anti-Fas antibody in Jurkat cells. In contrast, inhibition of classical PKC isotypes with Go6976 exacerbated the effect of Fas activation on both apoptotic volume decrease and cell death. PKC activation/inhibition did not affect anti-Fas antibody binding to the cell surface, intracellular levels of FADD ((F) under bar as-(a) under bar ssociated protein with (d) under bar eath (d) under bar omain), or c-FLIP (cellular (FL) under bar ICE-like (i) under bar nhibitory (p) under bar rotein) expression. However, processing/activation of both caspase-8 and caspase-3 and BID cleavage were markedly blocked upon PKC activation and, conversely, were augmented during PKC inhibition, suggesting a role for PKC upstream of caspase-8 processing and activation. Analysis of death-inducing signaling complex (DISC) formation was carried out to examine the influence of PKC on recruitment of both FADD and procaspase-8 to the Fas receptor. PKC activation blocked FADD recruitment and caspase-8 activation and thus DISC formation in both type I and II cells. In contrast, inhibition of classical PKCs promoted the opposite effect on the Fas pathway by rapidly increasing FADD recruitment, caspase-8 activation, and DISC formation. Together, these data show that PKC finely modulates Fas/CD95 signaling by altering the efficiency of DISC formation. C1 NIEHS, Lab Signal Transduct, Mol Endocrinol Grp, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, Mol Endocrinol Grp, NIH, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 58 TC 80 Z9 82 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 30 PY 2001 VL 276 IS 48 BP 44944 EP 44952 DI 10.1074/jbc.M104919200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 496QD UT WOS:000172406700082 PM 11581255 ER PT J AU Liu, A Prenger, MS Norton, DD Mei, L Kusiak, JW Bai, G AF Liu, A Prenger, MS Norton, DD Mei, L Kusiak, JW Bai, G TI Nerve growth factor uses Ras/ERK and phosphatidylinositol 3-kinase cascades to up-regulate the N-methyl-D-aspartate receptor 1 promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; FACTOR INDUCES TRANSCRIPTION; PC12 CELLS; DNA-BINDING; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; SP1 PHOSPHORYLATION; SUBUNIT-1 PROMOTER; NMDA RECEPTOR; RAT-BRAIN AB We reported previously that nerve growth factor (NGF) up-regulates activity of the N-methyl-D-aspartate receptor 1 (NR1) promoter. We have explored the pathways and nuclear targets of NGF signaling in regulating the NR1 promoter. PD98059 and wortmannin, but not rapamycin, significantly attenuated NGF-induced transcriptional activity from an NR1 promoter-luciferase construct. Coexpressing constitutively active forms of Ras, Raf, or MAPK/ERK kinase 1 (MEK1) increased promoter activity dramatically. The MEK1-induced increase was largely prevented by mutations of the tandem GC boxes in the promoter. Promoter activity was also increased significantly by coexpressed GC box-binding proteins (Sp1, 3, or 4) in nonstimulated PC12 cells. Either an extracellular signal-regulated kinase-1 (ERK1)- or Sp1-specific antibody coprecipitated Spl with ERKs, and the coprecipitation was enhanced significantly by NGF treatment of PC12 cells. ERK2 also incorporated radioactivity of [gamma P-32]ATP into recombinant Sp1. However, ERK2-treated Sp1 and PC12 nuclear extracts or nuclear extracts from NGF-treated cells exhibited reduced binding to the promoter or a consensus GC box. Our results suggest that NGF utilizes both the Ras/ERK and phosphatidylinositol 3-kinase pathways to up-regulate NR1 promoter activity and that Sp1 is a novel substrate of NGF-activated ERKs. NGF-increased NR1 promoter activity may involve a complicated mechanism of Sp1 phosphorylation and possible transcription factor exchange. C1 Univ Maryland, Sch Dent, Dept Oral & Craniofacial Biol Sci, Baltimore, MD 21201 USA. Univ Maryland, Program Neurosci, Baltimore, MD 21201 USA. NIA, Mol Neurobiol Unit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Alabama, Dept Neurobiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Dept Phys Med & Rehabil, Birmingham, AL 35294 USA. RP Bai, G (reprint author), Univ Maryland, Sch Dent, Dept Oral & Craniofacial Biol Sci, 666 W Baltimore St, Baltimore, MD 21201 USA. RI Mei, Lin/G-8755-2012 FU NINDS NIH HHS [NS34062, NS38077] NR 67 TC 42 Z9 42 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 30 PY 2001 VL 276 IS 48 BP 45372 EP 45379 DI 10.1074/jbc.M105399200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 496QD UT WOS:000172406700133 PM 11571288 ER PT J AU Ghribi, O Herman, MM DeWitt, DA Forbes, MS Savory, J AF Ghribi, O Herman, MM DeWitt, DA Forbes, MS Savory, J TI A beta(1-42) and aluminum induce stress in the endoplasmic reticulum in rabbit hippocampus, involving nuclear translocation of gadd 153 and NF-kappa B SO MOLECULAR BRAIN RESEARCH LA English DT Article DE endoplasmic reticulum; A beta(1-42); aluminum; gadd 153; caspase-12; NF-kappa B ID AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID-BETA-PEPTIDE; DISTINCT PATHWAYS; CEREBRAL-ISCHEMIA; CYTOCHROME-C; BCL-2; APOPTOSIS; NEURONS; ACTIVATION; DISEASE AB Apoptosis may represent a prominent form of neuronal death in chronic neurodegenerative disorders. such as Alzheimer's disease. Although apoptosis under mitochondrial control has received considerable attention, mechanisms used within the endoplasmic reticulum (ER) and nucleus in mediating apoptotic signals are not well understood. A growing body of evidence is emerging from different studies which suggests an active role for the ER in regulating apoptosis. Disturbances of ER function have been shown to trigger two different apoptotic pathways; one involves cross-talk with mitochondria and is regulated by the antiapoptotic Bcl-2, and the second is characterized by the activation of caspase-12. Also, stress in the ER has been suggested to result in the activation of a number of proteins, such as gadd 153 and NF-kappa. and in the downregulation of the antiapoptotic protein, Bcl-2. In the present study, the intracisternal injection in aged rabbits of either the neurotoxin aluminum maltolate or of A beta (1-42), has been found to induce nuclear translocation of gadd 15.3 and the inducible transcription factor, NF-kappaB. Translocation of these two proteins is accompanied by decreased levels of Bcl-2 in both the ER and the nucleus. Aluminum maltolate. but not A beta, induces caspase-12 activation which is a mediator of ER-specific apoptosis; this is the first report of the in vivo activation of caspase-12. These findings indicate that the ER may play a role in regulating apoptosis in vivo, and could be of significance in the pathology of neurodegeneration and related disorders. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22908 USA. Univ Virginia, Dept Biochem & Mol Genet & Chem, Charlottesville, VA 22908 USA. NIMH, IRP, NIH, Bethesda, MD 20892 USA. Univ Lib, Dept Biol, Lynchburg, VA USA. Univ Lib, Dept Chem, Lynchburg, VA USA. RP Savory, J (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Pathol, Box 168, Charlottesville, VA 22908 USA. NR 39 TC 30 Z9 30 U1 1 U2 2 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 30 PY 2001 VL 96 IS 1-2 BP 30 EP 38 DI 10.1016/S0169-328X(01)00256-X PG 9 WC Neurosciences SC Neurosciences & Neurology GA 505HW UT WOS:000172908200004 ER PT J AU Eisen, JL Leonard, HL Swedo, SE Price, LH Zabriskie, JB Chiang, SY Karitani, M Rasmussen, SA AF Eisen, JL Leonard, HL Swedo, SE Price, LH Zabriskie, JB Chiang, SY Karitani, M Rasmussen, SA TI The use of antibody D8/17 to identify B cells in adults with obsessive-compulsive disorder SO PSYCHIATRY RESEARCH LA English DT Article DE PANDAS, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus; Sydenham's chorea; rheumatic fever ID AUTOIMMUNE NEUROPSYCHIATRIC DISORDERS; LYMPHOCYTE ANTIGEN D8/17; RHEUMATIC-FEVER PATIENTS; REPETITIVE BEHAVIORS; MARKER AB Compared with healthy control subjects, individuals with childhood-onset obsessive-compulsive disorder (OCD) have been reported to have a higher percentage of B cells that react with the monoclonal antibody D8/17, a marker for rheumatic fever. This study sought to replicate these findings in adults with OCD. Double-blind analyses of blood samples from 29 consecutive adults with primary OCD and 26 healthy control subjects were conducted to determine the percentage of B cells identified by D8/17. Using a standard criterion of greater than or equal to 12% labeled B cells to denote positivity, rates of D8/17 positive individuals did not significantly differ between the OCD (58.6%) and control (42.3%) groups. Early age of onset was not a predictor of D8/17 positivity in the OCD group. The percentage of B cells identified by the monoclonal antibody marker D8/17 did not distinguish adults with OCD from control subjects, nor did it distinguish a sub-group of adults with OCD who described pre-pubertal onset of their OCD symptoms. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Brown Univ, Sch Med, Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02906 USA. Brown Univ, Sch Med, Rhode Isl Hosp, Dept Psychiat & Human Behav, Providence, RI 02906 USA. NIMH, Bethesda, MD 20892 USA. Rockefeller Univ, Lab Clin Microbiol & Immunol, New York, NY 10021 USA. RP Eisen, JL (reprint author), Brown Univ, Sch Med, Butler Hosp, Dept Psychiat & Human Behav, 345 Blackstone Blvd, Providence, RI 02906 USA. NR 11 TC 19 Z9 20 U1 2 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV 30 PY 2001 VL 104 IS 3 BP 221 EP 225 DI 10.1016/S0165-1781(01)00323-7 PG 5 WC Psychiatry SC Psychiatry GA 508AU UT WOS:000173065500004 PM 11728611 ER PT J AU Shalev, U Weiner, I AF Shalev, U Weiner, I TI Gender-dependent differences in latent inhibition following prenatal stress and corticosterone administration SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE corticosterone; environmental manipulations; footshock; latent inhibition; prenatal stress; restraint; schizophrenia ID PITUITARY-ADRENAL RESPONSES; ADULT-RATS; NUCLEUS-ACCUMBENS; SWITCHING MODEL; SEX-DIFFERENCES; NORWAY RATS; SCHIZOPHRENIA; ALTERS; RECEPTORS; EXPOSURE AB Latent inhibition (LI) indexes an organisms' ability to ignore irrelevant stimuli. Its disruption in the rat is considered to provide an animal model of the impaired ability to ignore irrelevant stimuli in schizophrenia. Given the importance of neurodevelopmental factors in the pathophysiology of schizophrenia, the present experiments investigated the effects of restraint, exposure to inescapable footshock and corticosterone administration during the last trimester of pregnancy, on the development of LI in the adult male and Female offspring. Prenatal restraint had no effect on LI in the adult offspring of both sexes. Inescapable footshock exposure and corticosterone administration led to LI disruption in the male, but not the female offspring. These gender-dependent effects of prenatal treatments on LI suggest that it may provide a neurodevelopmental model of at least a sub-group of schizophrenia, in which environmental factors and gender are considered to play a significant role. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Tel Aviv Univ, IL-69978 Tel Aviv, Israel. RP Shalev, U (reprint author), NIDA, Behav Neurosci Sect, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 55 TC 36 Z9 38 U1 1 U2 2 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 29 PY 2001 VL 126 IS 1-2 BP 57 EP 63 DI 10.1016/S0166-4328(01)00250-9 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 496YD UT WOS:000172425200007 PM 11704252 ER PT J AU Cornish, JL Kalivas, PW AF Cornish, JL Kalivas, PW TI Repeated cocaine administration into the rat ventral tegmental area produces behavioral sensitization to a systemic cocaine challenge SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE cocaine; GBR 12909; behavioral sensitization; psychostimulant; ventral tegmental area; locomotor activity; rat ID NUCLEUS-ACCUMBENS; INVIVO MICRODIALYSIS; DOPAMINE D-1; AMPHETAMINE; INJECTION; ANTAGONISTS; EXPRESSION; ADDICTION; INDUCTION; CORTEX AB The aim of the present study was to investigate the capacity of repeated administration of cocaine (5 nmol/side) or the selective dopamine re-uptake inhibitor GBR 12909 (15 nmol/side) into the ventral tegmental area (VTA) to initiate behavioral sensitization to systemically administered cocaine (15 mg/kg, intraperitoneally). Following 1 week of withdrawal from intra-VTA treatment, cocaine or GBR 12909 pretreated animals displayed sensitized locomotor and rearing behavior to acute systemic cocaine administration. These data support the possibility that increased dopamine transmission in the VTA is involved in the cellular events that determine the initiation of behavioral sensitization to cocaine. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. RP Cornish, JL (reprint author), NIDA, Dept Psychobiol, Medicat Discovery Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 29 TC 32 Z9 32 U1 0 U2 1 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 29 PY 2001 VL 126 IS 1-2 BP 205 EP 209 DI 10.1016/S0166-4328(01)00239-X PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 496YD UT WOS:000172425200020 PM 11704265 ER PT J AU Neary, CL Cho-Chung, YS AF Neary, CL Cho-Chung, YS TI Nuclear translocation of the catalytic subunit of protein kinase A induced by an antisense oligonucleotide directed against the RI alpha regulatory subunit SO ONCOGENE LA English DT Article DE cAMP; protein kinase A; antisense; immunocytochemistry; nuclear localization ID CYCLIC-AMP; SOMATOSTATIN GENE; RESPONSE ELEMENT; OVARIAN-CANCER; FACTOR CREB; CAMP; GROWTH; DIFFERENTIATION; BINDING; CELLS AB The regulatory (R) subunits of cAMP-dependent protein kinase (PKA) are implicated in the regulation of cell proliferation and differentiation. There are two isoforms of PKA that are distinguished by two types of R subunit, RI and RII Evidence suggests that RI is associated with proliferation and RII is associated with cell differentiation. Previous work in this laboratory has demonstrated that depletion of the RI alpha subunit by treatment with an antisense oligonucleotide (ODN) induces differentiation in leukemia cells and growth arrest and apoptosis in epithelial cancer cells. Using the prostate cancer cell line PC3M as a model system, we have developed a cell line that overexpresses a retroviral vector construct containing the RI alpha antisense gene. This cell tine has been characterized and the effectiveness of the construct determined. In the work presented here, we demonstrate by immunocytochemistry that treatment with RI alpha antisense ODN induces translocation of the C alpha subunit of PKA to the nucleus of PC3M prostate cancer cells. The translocation of Ca triggered by exogenous antisense ODN treatment mirrors that observed in cells endogenously overexpressing the antisense gene. Triggering the nuclear translocation of the C alpha subunit of PKA in the cell may be an important mechanism of action of RIa antisense that regulates cell growth independent of adenylate cyclase and cellular cAMP levels. The nuclear localization of the Ca subunit of PKA may be an essential step in revealing the mechanism whereby this critical kinase regulates cell growth. C1 NCI, Cellular Biochem Sect, Basic Res Labs, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), Bldg 10,Room 5B05, Bethesda, MD 20892 USA. FU NCI NIH HHS [N02-BC-76212] NR 33 TC 14 Z9 15 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 29 PY 2001 VL 20 IS 55 BP 8019 EP 8024 DI 10.1038/sj.onc.1204992 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 494NL UT WOS:000172288700011 PM 11753685 ER PT J AU Stuart, D Khan, QA Brown, R Dipple, A AF Stuart, D Khan, QA Brown, R Dipple, A TI Hydrocarbon carcinogens induce p53 activity in normal mouse tissue SO CANCER LETTERS LA English DT Article DE hydrocarbon carcinogen; p53; transgenic mouse ID MCF-7 CELLS; RADIATION; P21 AB Previous studies led to the suggestion that a sub class of hydrocarbon carcinogens have the capacity of damage DNA and evade normal cellular defence mechanisms. To examine the ability of hydrocarbon carcinogens to induce p53 transcriptional activity in normal tissues, we have used transgenic mice in which LacZ transgene is driven by a p53 response element. We demonstrate that transcriptionally active p53 is induced in normal tissue after exposure to putative stealth carcinogens in an identical manner to non-stealth agents. (C) 2001 Published by Elsevier Science Ireland Ltd. C1 CRC, Dept Med Oncol, Glasgow G61 1BD, Lanark, Scotland. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Chem Carcinogenesis Lab, Ft Detrick, MD 21702 USA. RP Stuart, D (reprint author), CRC, Dept Med Oncol, Alexander Stone Bldg,Garscube Estate,Switchback R, Glasgow G61 1BD, Lanark, Scotland. NR 11 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 28 PY 2001 VL 173 IS 2 BP 111 EP 114 DI 10.1016/S0304-3835(01)00629-2 PG 4 WC Oncology SC Oncology GA 487WG UT WOS:000171901600002 PM 11597784 ER PT J AU Mao, ZK Shay, B Hekmati, M Fermon, E Taylor, A Dafni, L Heikinheimo, K Lustmann, J Fisher, LW Young, MF Deutsch, D AF Mao, ZK Shay, B Hekmati, M Fermon, E Taylor, A Dafni, L Heikinheimo, K Lustmann, J Fisher, LW Young, MF Deutsch, D TI The human tuftelin gene: cloning and characterization SO GENE LA English DT Article DE odontogenesis; enamel biomineralization; alternative mRNA splicing; promoter; non-mineralizing tissues ID ENAMELIN TUFTELIN; TOOTH DEVELOPMENT; PROTEIN; EXPRESSION; AMELOGENIN; INITIATION; SEQUENCE; PRODUCTS; MATRIX; TEETH AB Tuftelin has been suggested to play an important role during the development and mineralization of enamel. We isolated the full-length human tuftelin cDNA using reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (5' RACE and 3' RACE) methods. Sequence analysis of the tuftelin cDNA revealed an open reading frame of 1170 bp encoding a 390 amino acid protein with a molecular mass of 44.3 kDa and an isoelectric point of 5.7. The human tuftelin protein shares 89 and 88% amino acid sequence identity with the bovine and mouse tuftelin, respectively. It contains a coiled-coil region, recently reported to be involved with tuftelin self-assembly and with the interaction of tuftelin with TIP39 (a novel tuftelin interacting protein). Detailed DNA analysis of the cloned genomic DNA revealed that the human tuftelin gone contains 13 exons and is larger than 26 kb. Two alternatively spliced tuftelin mRNA transcripts have now been identified in the human tooth bud, one lacking exon 2, and the other lacking exon 2 and exon 3. Primer extension analysis, corroborated by RT-PCR and DNA sequencing, revealed multiple transcription initiation sites. The cloned 1.6 kb promoter region contained several GC boxes and several transcription factor binding sites such as those for activator protein 1 and stimulatory protein 1. Our blast search of the human and mouse expressed sequence tag data bases, as well as our RT-PCR and DNA sequencing results, and a previous study using Northern blot analysis revealed that tuftelin cDNA sequences are also expressed in normal and cancerous non-mineralizing soft tissues, suggesting that tuftelin has a universal function. We have now identified and characterized different alternatively spliced mouse tuftelin mRNAs in several non-mineralizing tissues. These results provide an important baseline for future understanding of the biological role of tuftelin. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Hebrew Univ Jerusalem, Hadassah Fac Dent Med, Inst Dent Sci, Dept Oral Biol,Dent Res Unit, IL-91120 Jerusalem, Israel. Univ Turku, Inst Dent, Dept Oral Maxillofacial Surg, SF-20500 Turku, Finland. Hebrew Univ Jerusalem, Hadassah Fac Dent Med, Dept Oral Maxillofacial Surg, IL-91120 Jerusalem, Israel. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Deutsch, D (reprint author), Hebrew Univ Jerusalem, Hadassah Fac Dent Med, Inst Dent Sci, Dept Oral Biol,Dent Res Unit, POB 12272, IL-91120 Jerusalem, Israel. NR 27 TC 19 Z9 22 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 28 PY 2001 VL 279 IS 2 BP 181 EP 196 DI 10.1016/S0378-1119(01)00749-1 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 504ZG UT WOS:000172885800009 PM 11733143 ER PT J AU Borio, L Frank, D Mani, V Chiriboga, C Pollanen, M Ripple, M Ali, S DiAngelo, C Lee, J Arden, J Titus, J Fowler, D O'Toole, T Masur, H Bartlett, J Inglesby, T AF Borio, L Frank, D Mani, V Chiriboga, C Pollanen, M Ripple, M Ali, S DiAngelo, C Lee, J Arden, J Titus, J Fowler, D O'Toole, T Masur, H Bartlett, J Inglesby, T TI Death due to bioterrorism-related inhalational anthrax - Report of 2 patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB On October 9, 2001, a letter containing anthrax spores was mailed from New Jersey to Washington, DC. The letter was processed at a major postal facility in Washington, DC, and opened in the Senate's Hart Office Building on October 15. Between October 19 and October 26, there were 5 cases of inhalational anthrax among postal workers who were employed at that major facility or who handled bulk mail originating from that facility. The cases of 2 postal workers who died of inhalational anthrax are reported here. Both patients had nonspecific prodromal illnesses. One patient developed predominantly gastrointestinal symptoms, including nausea, vomiting, and abdominal pain. The other patient had a "flulike" illness associated with myalgias and malaise. Both patients ultimately developed dyspnea, retrosternal chest pressure, and respiratory failure requiring mechanical ventilation. Leukocytosis and hemoconcentration were noted in both cases prior to death. Both patients had evidence of mediastinitis and extensive pulmonary infiltrates late in their course of illness. The durations of illness were 7 days and 5 days from onset of symptoms to death; both patients died within 24 hours of hospitalization. Without a clinician's high index of suspicion, the diagnosis of inhalational anthrax is difficult during nonspecific prodromal illness. Clinicians have an urgent need for prompt communication of vital epidemiologic information that could focus their diagnostic evaluation. Rapid diagnostic assays to distinguish more common infectious processes from agents of bioterrorism also could improve management strategies. C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Ctr Civilian Biodef Studies, Baltimore, MD 21202 USA. Johns Hopkins Univ, Sch Publ Hlth, Johns Hopkins Ctr Civilian Biodef Studies, Baltimore, MD 21202 USA. Off Chief Med Examiner State Maryland, Baltimore, MD USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. Greater SE Community Hosp, Washington, DC USA. Off Chief Med Examiner Dist Columbia, Washington, DC USA. So Maryland Hosp Ctr, Clinton, MD USA. RP Borio, L (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Ctr Civilian Biodef Studies, Chandler Bldg,Suite 850,111 Market Pl, Baltimore, MD 21202 USA. NR 5 TC 119 Z9 124 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 28 PY 2001 VL 286 IS 20 BP 2554 EP 2559 DI 10.1001/jama.286.20.2554 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 496FH UT WOS:000172385200029 PM 11722269 ER PT J AU Reynolds, EE Hyman, SE AF Reynolds, EE Hyman, SE TI A 28-year-old man addicted to cocaine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID DRUG-ABUSE; FAMILIAL TRANSMISSION; SUBSTANCE USE; DEPENDENCE; DISORDERS; ALCOHOL; PREVALENCE; DOPAMINE; OUTCOMES; NEURONS C1 NIMH, Bethesda, MD 20892 USA. RP Hyman, SE (reprint author), NIMH, 6001 Execut Blvd,Room 8235,MSC 9669, Bethesda, MD 20892 USA. NR 50 TC 9 Z9 9 U1 2 U2 4 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 28 PY 2001 VL 286 IS 20 BP 2586 EP 2594 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 496FH UT WOS:000172385200033 ER PT J AU Lane, HC Fauci, AS AF Lane, HC Fauci, AS TI Bioterrorism on the home front - A new challenge for American medicine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID ANTHRAX C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Lane, HC (reprint author), NIAID, NIH, Bldg 10,Room 11S231, Bethesda, MD 20892 USA. NR 15 TC 33 Z9 33 U1 0 U2 1 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 28 PY 2001 VL 286 IS 20 BP 2595 EP 2597 DI 10.1001/jama.286.20.2595 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 496FH UT WOS:000172385200035 PM 11722275 ER PT J AU Kumar, S Tsai, CJ Nussinov, R AF Kumar, S Tsai, CJ Nussinov, R TI Thermodynamic differences among homologous thermophilic and mesophilic proteins SO BIOCHEMISTRY LA English DT Article ID COLD-SHOCK PROTEIN; SMALL GLOBULAR-PROTEINS; AMINO-ACID-RESIDUES; HEAT-CAPACITY; CONFORMATIONAL STABILITY; SALT BRIDGES; HYPERTHERMOPHILIC PROTEINS; STAPHYLOCOCCAL NUCLEASE; HYDROPHOBIC INTERACTION; ALPHA-LACTALBUMIN AB Here, we analyze the thermodynamic parameters and their correlations in families containing homologous thermophilic and mesophilic proteins which show reversible two-state folding reversible arrow unfolding transitions between the native and the denatured states. For the proteins in these families, the melting temperatures correlate with the maximal protein stability change (between the native and the denatured states) as well as with the enthalpic and entropic changes at the melting temperature. In contrast, the heat capacity change is uncorrelated with the melting temperature. These and additional results illustrate that higher melting temperatures are largely obtained via an upshift and broadening of the protein stability curves. Both thermophilic and mesophilic proteins are maximally stable around room temperature. However, the maximal stabilities of thermophilic proteins are considerably greater than those of their mesophilic homologues. At the living temperatures of their respective source organisms, homologous thermophilic and mesophilic proteins have similar stabilities. The protein stability at the living temperature of the source organism does not correlate with the living temperature of the protein. We tie thermodynamic observations to microscopics via the hydrophobic effect and a two-state model of the water structure. We conclude that, to achieve higher stability and greater resistance to high and low temperatures, specific interactions, particularly electrostatic, should be engineered into the protein. The effect of these specific interactions is largely reflected in an increased enthalpy change at the melting temperature. C1 NCI, FCRF, Intramural Res Support Program, SAIC,Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, FCRF, Intramural Res Support Program, SAIC,Lab Expt & Computat Biol, Bldg 469,Rm 151, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 62 TC 93 Z9 94 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 27 PY 2001 VL 40 IS 47 BP 14152 EP 14165 DI 10.1021/bi0106383 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497PP UT WOS:000172464900005 PM 11714268 ER PT J AU Vitiello, B AF Vitiello, B TI Methylphenidate in the treatment of children with attention-deficit hyperactivity disorder SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material C1 NIMH, Child & Adolescent Treatment & Prevent Intervent, NIH, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Child & Adolescent Treatment & Prevent Intervent, NIH, Rm 7147,MSC 9633,6001 Execut Blvd, Bethesda, MD 20892 USA. NR 17 TC 12 Z9 12 U1 1 U2 2 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD NOV 27 PY 2001 VL 165 IS 11 BP 1505 EP 1506 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 496YN UT WOS:000172426100016 PM 11762576 ER PT J AU Topol, EJ McCarthy, J Gabriel, S Moliterno, DJ Rogers, WJ Newby, LK Freedman, M Metivier, J Cannata, R O'Donnell, CJ Kottke-Marchant, K Murugesan, G Plow, EF Stenina, O Daley, GQ AF Topol, EJ McCarthy, J Gabriel, S Moliterno, DJ Rogers, WJ Newby, LK Freedman, M Metivier, J Cannata, R O'Donnell, CJ Kottke-Marchant, K Murugesan, G Plow, EF Stenina, O Daley, GQ CA GeneQuest Investigators Collaborat TI Single nucleotide polymorphisms in multiple novel thrombospondin genes may be associated with familial premature myocardial infarction SO CIRCULATION LA English DT Article; Proceedings Paper CT 73rd Annual Scientific Sessions of the American-Heart-Association CY NOV 12-15, 2000 CL NEW ORLEANS, LA SP Amer Heart Assoc DE genetics; coronary disease; myocardial infarction; atherosclerosis; genes ID CORONARY-ARTERY DISEASE; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; MATRICELLULAR PROTEINS; VENOUS THROMBOSIS; INCREASED RISK; FACTOR-V; MUTATION; MEN; EXPRESSION; CARRIERS AB Background-Recent advances in high-throughput genomics technology have expanded our ability to catalogue allelic variants in large sets of candidate genes related to premature coronary artery disease. Methods and Results-A total of 398 families were identified in 15 participating medical centers; they fulfilled the criteria of myocardial infarction, revascularization, or a significant coronary artery lesion diagnosed before 45 years in men or 50 years in women. A total of 62 vascular biology genes and 72 single-nucleotide polymorphisms were assessed. Previously undescribed variants in 3 related members of the thrombospondin protein family were prominent among a small set of single-nucleotide polymorphisms that showed a statistical association with premature coronary artery disease. A missense variant of thrombospondin 4 (A387P) showed the strongest association, with an adjusted odds ratio for myocardial infarction of 1.89 (P=0.002 adjusted for covariates) for individuals carrying the P allele. A variant in the 3' untranslated region of thrombospondin-2 (change of thymidine to guanine) seemed to have a protective effect against myocardial in individuals homozygous for the variant (adjusted odds ratio of 0.31; P=0.0018). A missense variant in thrombospondin-1 (N700S) was associated with an adjusted odds ratio for coronary artery disease of 11.90 (P=0.041) in homozygous individuals, who also had the lowest level of thrombospondin-1 by plasma assay (P=0.0019). Conclusions-This large-scale genetic study has identified the potential of multiple novel variants in the thrombospondin gene family to be associated with familial premature myocardial infarction. Notwithstanding multiple caveats, thrombospondins specifically and high-throughput genomic technology in general deserve further study in familial ischemic heart disease. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. MIT, Ctr Genome Res, Whitehead Inst, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA USA. Natl Heart Lung & Blood Inst Framingham Heart Stu, Boston, MA USA. Univ Alabama Birmingham, Ctr Med, Birmingham, AL USA. Duke Univ, Ctr Med, Durham, NC USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RP Topol, EJ (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, 9500 Euclid Ave,Desk F25, Cleveland, OH 44195 USA. EM topole@ccf.org OI Topol, Eric/0000-0002-1478-4729 NR 24 TC 193 Z9 209 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 27 PY 2001 VL 104 IS 22 BP 2641 EP 2644 DI 10.1161/hc4701.100910 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 497BH UT WOS:000172432500023 PM 11723011 ER PT J AU White, CW Gobel, FL Campeau, L Knatterud, GL Forman, SA Forrester, JS Geller, NL Herd, JA Hickey, A Hoogwerf, BJ Hunninghake, DB Rosenberg, Y Terrin, ML AF White, CW Gobel, FL Campeau, L Knatterud, GL Forman, SA Forrester, JS Geller, NL Herd, JA Hickey, A Hoogwerf, BJ Hunninghake, DB Rosenberg, Y Terrin, ML CA Post Coronary Artery Bypass Graft TI Effect of an aggressive lipid-lowering strategy on progression of atherosclerosis in the left main coronary artery from patients in the Post Coronary Artery Bypass Graft Trial SO CIRCULATION LA English DT Article DE coronary disease; lipids; cholesterol; angiography ID LOW-DOSE ANTICOAGULATION; AVERAGE CHOLESTEROL LEVELS; MYOCARDIAL-INFARCTION; HEART-DISEASE; EVENTS; WOMEN; ARTERIOGRAPHY; PRAVASTATIN; PREVENTION; OUTCOMES AB Background-The Post Coronary Artery Bypass Graft Trial, designed to compare the effects of two lipid-lowering re-imens and low-dose anticoaculation versus lacebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol levels to a mean yearly cholesterol level from 93 to 97 mg/dL compared with a moderate reduction to a level of 132 to 136 mg/dL decreased the progression of atherosclerosis in saphenous vein grafts. Low-dose anticoagulation did not affect progression. This secondary analysis tested the hypothesis that a similar decrease in progression of atherosclerosis would also be present in native coronary arteries as measured in the left main coronary artery (LMCA). Methods and Results-A sample of 402 patients was randomly selected from 1102 patients who had baseline and follow-up views of the LMCA suitable for analysis. Patients treated with the aggressive lipid-lowering strategy had less progression of atherosclerosis in the LMCA as measured by changes in minimum (P=0.0003) lumen diameter or the maximum percent stenosis (P=0.001), or the presence of substantial progression (P=0.008), or vascular occlusion (P=0.005) when compared with the moderate strategy. Conclusions-A strategy of aggressive lipid lowering results in significantly less atherosclerosis progression than a moderate approach in LMCAs. C1 Maryland Med Res Inst, Post CABG Coordinating Ctr, Baltimore, MD 21210 USA. Univ Minnesota, Minneapolis, MN USA. Minneapolis Heart Inst Fdn, Minneapolis, MN USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Baylor Coll Med, Houston, TX 77030 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NHLBI, Clin Trials Grp, Bethesda, MD 20892 USA. RP Knatterud, GL (reprint author), Maryland Med Res Inst, Post CABG Coordinating Ctr, 600 Wyndhurst Ave, Baltimore, MD 21210 USA. NR 27 TC 32 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 27 PY 2001 VL 104 IS 22 BP 2660 EP 2665 DI 10.1161/hc4701.099730 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 497BH UT WOS:000172432500027 PM 11723015 ER PT J AU Galperin, MY Gaidenko, TA Mulkidjanian, AY Nakano, M Price, CW AF Galperin, MY Gaidenko, TA Mulkidjanian, AY Nakano, M Price, CW TI MHYT, a new integral membrane sensor domain SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE genome analysis; protein domain; sequence conservation; anaerobic growth; signal transduction; metal binding ID BACILLUS-SUBTILIS; ESCHERICHIA-COLI; RESPONSE REGULATOR; CYTOCHROME BO(3); CU-B; PROTEIN; IDENTIFICATION; DATABASE; TRANSCRIPTION; POLYMERASE AB MHYT. a new conserved protein domain with a likely signaling function. is described. This domain consists of six transmembrane segments, three of which contain conserved methionine, histidine, and tyrosine residues that are projected to lie near the outer face of the cytoplasmic membrane. In Synechocystis sp. PCC6803, this domain forms the N-terminus of the sensor histidine kinase Slr2098. In Pseudomonas aeruginosa and several other organisms, the MHYT domain forms the N-terminal part of a three-domain protein together with previously described GGDEF and EAL domains. both of which have been associated with signal transduction due to their presence in likely signaling proteins. In Bacillus subtilis YkoW protein. an additional PAS domain is found between the MHYT and GGDEF domains. A ykoW null mutant of B. subtilis did not exhibit any growth alterations, consistent with a non-essential, signaling role of this protein. A model of the membrane topology of the MHYT domain indicates that its conserved residues could coordinate one or two copper ions. suggesting a role in sensing oxygen, CO, or NO. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA. Univ Osnabruck, Div Biophys, D-49069 Osnabruck, Germany. Oregon Grad Inst Sci & Technol, Dept Biochem & Mol Biol, Beaverton, OR 97006 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RI Mulkidjanian, Armen/J-8086-2013; OI Mulkidjanian, Armen/0000-0001-5844-3064; Galperin, Michael/0000-0002-2265-5572 FU NIGMS NIH HHS [GM 42077] NR 33 TC 38 Z9 39 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD NOV 27 PY 2001 VL 205 IS 1 BP 17 EP 23 DI 10.1111/j.1574-6968.2001.tb10919.x PG 7 WC Microbiology SC Microbiology GA 497TQ UT WOS:000172471900003 PM 11728710 ER PT J AU Bibbiani, F Oh, JD Chase, TN AF Bibbiani, F Oh, JD Chase, TN TI Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models SO NEUROLOGY LA English DT Article ID LEVODOPA-INDUCED DYSKINESIAS; L-DOPA; RECEPTOR ANTAGONIST; INDUCED CATALEPSY; NEURONS; MONKEYS; RAT; STRIATUM; DISEASE; DRUGS AB Background: Serotoninergic transmission in the basal ganglia is known to influence dopaminergic mechanisms and motor function. Objective: To evaluate the possibility that serotoninergic 5-HT1A autoreceptors (by regulating the release of serotonin as well as dopamine formed from exogenous levodopa) affect the response alterations complicating levodopa treatment of PD. Methods: The 5-HT1A receptor agonist sarizotan (EMD128130) was systemically administered alone and together with levodopa to parkinsonian rats and nonhuman primates. Results: In 6-hydroxydopamine-lesioned rats, sarizotan (2.5 mg/kg PO) had no effect on the acute rotational response to levodopa but did attenuate the shortening in motor response duration induced by chronic levodopa treatment. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys, sarizotan (2 mg/kg PO) alone had no effect on parkinsonian severity or on the antiparkinsonian response to levodopa. In contrast, the same dose of sarizotan reduced levodopa-induced choreiform dyskinesias by 91 +/- 5.9%. In both species, the motoric effects of sarizotan were blocked by the selective 5-HT1A antagonist WAY100635 (0.1 mg/kg SC), indicating that the observed sarizotan responses were probably mediated at the 5-HT1A autoreceptor. Conclusion: Pharmaceuticals acting to stimulate 5-HT1A receptors could prove useful in the treatment of the motor response complications in parkinsonian patients. C1 NINCDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINCDS, Expt Therapeut Branch, NIH, Bldg 10,Rm 5C103, Bethesda, MD 20892 USA. NR 40 TC 164 Z9 168 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 27 PY 2001 VL 57 IS 10 BP 1829 EP 1834 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 495HP UT WOS:000172334700017 PM 11723272 ER PT J AU Bazzano, LA He, J Ogden, LG Loria, C Vupputuri, S Myers, L Whelton, PK AF Bazzano, LA He, J Ogden, LG Loria, C Vupputuri, S Myers, L Whelton, PK TI Legume consumption and risk of coronary heart disease in US men and women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HYPERCHOLESTEROLEMIC MEN; CARDIOVASCULAR-DISEASE; DIETARY-SODIUM; SERUM-LIPIDS; FOOD; FIBER; MORTALITY; ADULTS; REPRODUCIBILITY; INFORMATION AB Background: Soybean protein and dietary fiber supplementation reduce serum cholesterol in randomized controlled trials. Consumption of legumes, which are high in bean protein and water-soluble fiber, may be associated with a reduced risk of coronary heart disease (CHD). Methods: A total of 9632 men and women who participated in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (NHEFS) and were free of cardiovascular disease (CVD) at their baseline examination were included in this prospective cohort study. Frequency of legume intake was estimated using a 3-month food frequency questionnaire, and incidence of CHD and CVD was obtained from medical records and death certificates. Results: Over an average of 19 years of follow-up, 1802 incident cases of CHD and 3680 incident cases of CVD were documented. Legume consumption was significantly and inversely associated with risk of CHD (P=.002 for trend) and CVD (P=.02 for trend) after adjustment for established CVD risk factors. Legume consumption 4 times or more per week compared with less than once a week was associated with a 22% lower risk of CHD (relative risk, 0.78; 95% confidence interval, 0.68-0.90) and an 11% lower risk of CVD (relative risk, 0.89; 95% confidence interval, 0.80-0.98). Conclusions: Our study indicates a significant inverse relationship between legume intake and risk of CHD and suggests that increasing legume intake may be an important part of a dietary approach to the primary prevention of CHD in the general population. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. NIHNH, NIH, Bethesda, MD USA. RP He, J (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1430 Tulane Ave,SL18, New Orleans, LA 70112 USA. FU NHLBI NIH HHS [R03 HL61954, R01HL60300] NR 41 TC 181 Z9 183 U1 1 U2 11 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 26 PY 2001 VL 161 IS 21 BP 2573 EP 2578 DI 10.1001/archinte.161.21.2573 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 493UQ UT WOS:000172242200006 PM 11718588 ER PT J AU Lu, CB Fu, WM Mattson, MP AF Lu, CB Fu, WM Mattson, MP TI Telomerase protects developing neurons against DNA damage-induced cell death SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE apoptosis; camptothecin; cancer; etoposide; hippocampus; p53; TERT; topoisomerase ID ALZHEIMERS-DISEASE; CATALYTIC SUBUNIT; INDUCED APOPTOSIS; BRAIN; REPAIR; DIFFERENTIATION; PROLIFERATION; CAMPTOTHECIN; POLYMERASE; STABILITY AB In mitotic cells, telomerase adds repeats of a DNA sequence (TTAGGG) to the ends of chromosomes (telomeres) thereby maintaining their length and preventing cellular senescence. We recently reported that the catalytic subunit of telomerase (TERT) is expressed in neuronal progenitor cells and in early postmitotic neurons in the developing rodent brain. We now report that TERT can protect cultured PC12 cells and embryonic hippocampal neurons against death induced by DNA damage. Overexpression of TERT in PC12 cells increases their resistance to the topoisomerase inhibitors camptothecin and etoposide. Hippocampal neurons in which TERT levels are decreased using antisense technology exhibit increased vulnerability to the DNA-damaging agents. Emerging findings suggest that DNA damage may trigger the death of neurons during brain development and in neurodegenerative disorders. Our data therefore suggest roles for TERT in modulating such cell deaths. Published by Elsevier Science B.V. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 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 34 TC 29 Z9 29 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD NOV 26 PY 2001 VL 131 IS 1-2 BP 167 EP 171 DI 10.1016/S0165-3806(01)00237-1 PG 5 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 498QK UT WOS:000172517100019 ER PT J AU Gillespie, PG Albanesi, JP Bahler, M Bement, WM Berg, JS Burgess, DR Burnside, B Cheney, RE Corey, DP Coudrier, E de Lanerolle, P Hammer, JA Hasson, T Holt, JR Hudspeth, AJ Ikebe, M Kendrick-Jones, J Korn, E Li, R Mercer, JA Milligan, RA Mooseker, M Ostap, EM Petit, C Pollard, TD Sellers, JR Soldati, T Titus, MA AF Gillespie, PG Albanesi, JP Bahler, M Bement, WM Berg, JS Burgess, DR Burnside, B Cheney, RE Corey, DP Coudrier, E de Lanerolle, P Hammer, JA Hasson, T Holt, JR Hudspeth, AJ Ikebe, M Kendrick-Jones, J Korn, E Li, R Mercer, JA Milligan, RA Mooseker, M Ostap, EM Petit, C Pollard, TD Sellers, JR Soldati, T Titus, MA TI Myosin-I nomenclature SO JOURNAL OF CELL BIOLOGY LA English DT Editorial Material AB We suggest that the vertebrate myosin-I field adopt a common nomenclature system based on the names adopted by the Human Genome Organization (HUGO). At present, the myosin-I nomenclature is very confusing; not only are several systems in use, but several different genes have been given the same name. Despite their faults, we believe that the names adopted by the HUGO nomenclature group for genome annotation are the best compromise, and we recommend universal adoption. C1 Oregon Hlth Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Vollum Inst, Portland, OR 97201 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. Univ Munster, Inst Allgemeine Zool & Genet, Munster, Germany. Univ Wisconsin, Dept Zool, Madison, WI 53706 USA. Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. Inst Curie, Unite Mixte Rech 144, Ctr Natl Rech Sci, F-75248 Paris 05, France. Univ Illinois, Dept Physiol, Chicago, IL 60612 USA. Natl Inst Hlth, Lab Cell Biol, Bethesda, MD 20892 USA. Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA. Univ Virginia, Sch Med, Dept Neurosci & Otolaryngol, Charlottesville, VA 22908 USA. Rockefeller Univ, Lab Sensory Neurosci, New York, NY 10021 USA. Rockefeller Univ, Howard Huges Med Inst, New York, NY 10021 USA. Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA 01655 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. Natl Heart & Lung Inst, Lab Cell Biol, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. McLaughlin Res Inst, Great Falls, MT 59405 USA. Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Penn Muscle Inst, Philadelphia, PA 19104 USA. Inst Pasteur, CNRS, URA 1968, Unite Genet Deficits Sensoriels, F-75724 Paris 15, France. Natl Heart Lung & Blood Inst, Lab Mol Cardiol, NIH, Bethesda, MD 20892 USA. Imperial Coll Sci Technol & Med, Dept Sci Biol, London SW7 2AZ, England. Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. RP Gillespie, PG (reprint author), Oregon Hlth Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97201 USA. RI SOLDATI, Thierry/A-2902-2009; OI SOLDATI, Thierry/0000-0002-2056-7931; Corey, David/0000-0003-4497-6016; Barr-Gillespie, Peter/0000-0002-9787-5860 FU NIDCD NIH HHS [R29 DC003299]; NIGMS NIH HHS [R01 GM057247] NR 1 TC 50 Z9 50 U1 0 U2 4 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 26 PY 2001 VL 155 IS 5 BP 703 EP 704 DI 10.1083/jcb.200110032 PG 2 WC Cell Biology SC Cell Biology GA 497MQ UT WOS:000172459900003 PM 11724811 ER PT J AU Okamoto, I Kawano, Y Murakami, D Sasayama, T Araki, N Miki, T Wong, AJ Saya, H AF Okamoto, I Kawano, Y Murakami, D Sasayama, T Araki, N Miki, T Wong, AJ Saya, H TI Proteolytic release of CD44 intracellular domain and its role in the CD44 signaling pathway SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SMALL G-PROTEINS; CALCIUM INFLUX; CELL-MIGRATION; RHO-FAMILY; GROWTH; CLEAVAGE; ONCOPROTEIN; HYALURONATE; ADHESION; RECEPTOR AB CD44 is a widely distributed cell surface adhesion molecule and is implicated in diverse biological processes. However, the nature of intracellular signaling triggered by CD44 remains to be elucidated. Here, we show that CD44 undergoes sequential proteolytic cleavage in the ectodomain and intracellular domain, resulting in the release of a CD44 intracellular domain (ICD) fragment. Consequently, CD44ICD acts as a signal transduction molecule, where it translocates to the nucleus and activates transcription mediated through the 12-O-tetradecanoylphorbol 13-acetate-responsive element, which is found in numerous genes involved in diverse cellular processes. Expression of an uncleavable CD44 mutant as well as metalloprotease inhibitor treatment blocks CD44-mediated transcriptional activation. In search of the underlying mechanism, we have found that CD44ICD potentiates transactivation mediated by the transcriptional coactivator CBP/p300. Furthermore, we show that cells expressing CD44ICD produce high levels of CD44 messenger RNA, suggesting that the CD44 gene is one of the potential targets for transcriptional activation by CD44ICD. These observations establish a novel CD44 signaling pathway and shed new light on the functional link between proteolytic processing of an adhesion molecule at the cell surface and transcriptional activation in the nucleus. C1 Kumamoto Univ, Sch Med, Dept Tumor Genet & Biol, Kumamoto 8600811, Japan. Thomas Jefferson Univ, Kimmel Canc Inst, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. NCI, Basic Res Lab, Mol Tumor Biol Sect, Bethesda, MD 20892 USA. RP Saya, H (reprint author), Kumamoto Univ, Sch Med, Dept Tumor Genet & Biol, 2-2-1 Honjo, Kumamoto 8600811, Japan. RI Saya, Hideyuki/J-4325-2013 FU NCI NIH HHS [CA51093, CA69495, R01 CA069495] NR 28 TC 216 Z9 223 U1 0 U2 4 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 26 PY 2001 VL 155 IS 5 BP 755 EP 762 DI 10.1083/jcb.200108159 PG 8 WC Cell Biology SC Cell Biology GA 497MQ UT WOS:000172459900011 PM 11714729 ER PT J AU Markovic, I Leikina, E Zhukovsky, M Zimmerberg, J Chernomordik, LV AF Markovic, I Leikina, E Zhukovsky, M Zimmerberg, J Chernomordik, LV TI Synchronized activation and refolding of influenza hemagglutinin in multimeric fusion machines SO JOURNAL OF CELL BIOLOGY LA English DT Article DE viral fusion; influenza hemagglutinin; cooperativity; hemagglutinin interaction; inactivation ID INDUCED MEMBRANE-FUSION; VIRUS HEMAGGLUTININ; LOW-PH; CONFORMATIONAL CHANGE; RECEPTOR-BINDING; SURFACE-DENSITY; TRANSMEMBRANE DOMAIN; BACULOVIRUS GP64; MEDIATED FUSION; CELL-SURFACE AB At the time of fusion, membranes are packed with fusogenic proteins. Do adjacent individual proteins interact with each other in the plane of the membrane? Or does each of these proteins serve as an independent fusion machine? Here we report that the low pH-triggered transition between the initial and final conformations of a prototype fusogenic protein, influenza hemagglutinin (HA), involves a preserved interaction between individual HAs. Although the HAs of subtypes H3 and H2 show notably different degrees of activation, for both, the percentage of low pH-activated HA increased with higher surface density of HA, indicating positive cooperativity. We propose that a concerted activation of HAs, together with the resultant synchronized release of their conformational energy, is an example of a general strategy of coordination in biological design, crucial for the functioning of multiprotein fusion machines. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Chernomordik, LV (reprint author), Bldg 10,Rm 10D04,10 Ctr Dr,MSC 1855, Bethesda, MD 20892 USA. NR 46 TC 71 Z9 72 U1 0 U2 4 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 26 PY 2001 VL 155 IS 5 BP 833 EP 843 DI 10.1083/jcb.200103005 PG 11 WC Cell Biology SC Cell Biology GA 497MQ UT WOS:000172459900018 PM 11724823 ER PT J AU Kim, IH Kirk, KL AF Kim, IH Kirk, KL TI A convenient synthesis of 2-fluoro- and 6-fluoro-(2S,3R)-threo-(3,4-dihydroxyphenyl)serine using Sharpless asymmetric aminohydroxylation SO TETRAHEDRON LETTERS LA English DT Article DE 2-fluoro- and 6-fluoro-(2S,3R)-threo-(3,4-dihydroxyphenyl)serine; Sharpless asymmetric aminohydroxylation; regioselectivity; enantioselectivity ID NOREPINEPHRINE; FACILITATE; REVERSAL AB Ring-fluorinated beta -hydroxy alpha -amino methyl esters 3b,c were synthesized enantio selectively using Sharpless asymmetric amino hydroxylation. These were converted to 2-fluoro- and 6-fluoro-(2S,3R)-threo-(3,4-dihydroxyphenyl)serine 1b,c using our previously published procedure. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 10 TC 15 Z9 15 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD NOV 26 PY 2001 VL 42 IS 48 BP 8401 EP 8403 DI 10.1016/S0040-4039(01)01816-0 PG 3 WC Chemistry, Organic SC Chemistry GA 492QF UT WOS:000172178500001 ER PT J AU Da Silva, DM Pastrana, DV Schiller, JT Kast, WM AF Da Silva, DM Pastrana, DV Schiller, JT Kast, WM TI Effect of preexisting neutralizing antibodies on the anti-tumor immune response induced by chimeric human papillomavirus virus-like particle vaccines SO VIROLOGY LA English DT Article DE virus-like particle; vaccine; neutralization; papillomavirus; HPV16; pseudovirion ID COTTONTAIL RABBIT PAPILLOMAVIRUS; LONG-TERM PROTECTION; MONOCLONAL-ANTIBODIES; NASAL IMMUNIZATION; CERVICAL-CANCER; GENE-THERAPY; TYPE-16 L1; CELLS; VACCINATION; MICE AB Chimeric human papillomavirus virus-like particles (HPV cVLPs) carrying HPV16 E7 protein are potent vaccines for inducing cell-mediated immunity (CMI) against HPV-induced tumors in animal models. We tested the hypothesis that virion-neutralizing antibodies generated during an initial vaccination might prevent effective boosting of CMI to the cVLPs. Mice with circulating HPV16-neutralizing antibodies, generated by direct immunization with wild-type VLPs or by passive transfer of hyperimmune anti-HPV16 VLP mouse sera, were subsequently vaccinated with HPV16 E7-containing cVLPs. Mice with preexisting neutralizing antibodies were not protected from HPV16 E7-positive TC-1 tumor challenge, compared to the protection seen in mice lacking these antibodies. Antibody-coated VLPs bound very inefficiently to receptor-positive cell lines, suggesting that one of the mechanisms of antibody interference is blocking of VLP binding to its receptor and thereby uptake of VLPs by antigen-presenting cells. Our results suggest that repetitive vaccination with a cVLP for induction of cellular immune responses to an incorporated antigen may be of limited effectiveness due to the presence of neutralizing antibodies against the capsid proteins induced after the first application. This limitation could potentially be overcome by boosting with cVLPs containing the same target antigen incorporated into other papillomavirus-type VLPs. (C) 2001 Academic Press. C1 Loyola Univ, Cardinal Bernardin Canc Ctr, Canc Immunol Program, Maywood, IL 60153 USA. Loyola Univ, Dept Microbiol & Immunol, Maywood, IL 60153 USA. NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Kast, WM (reprint author), Loyola Univ, Cardinal Bernardin Canc Ctr, Canc Immunol Program, 2160 S 1st Ave, Maywood, IL 60153 USA. FU NCI NIH HHS [P01 CA74182, R01 CA74397] NR 54 TC 44 Z9 48 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 0042-6822 J9 VIROLOGY JI Virology PD NOV 25 PY 2001 VL 290 IS 2 BP 350 EP 360 DI 10.1006/viro.2001.1179 PG 11 WC Virology SC Virology GA 502QD UT WOS:000172753500018 PM 11883199 ER PT J AU Polis, MA Sidorov, IA Yoder, C Jankelevich, S Metcalf, J Mueller, BU Dimitrov, MA Pizzo, P Yarchoan, R Dimitrov, DS AF Polis, MA Sidorov, IA Yoder, C Jankelevich, S Metcalf, J Mueller, BU Dimitrov, MA Pizzo, P Yarchoan, R Dimitrov, DS TI Correlation between reduction in plasma HIV-1 RNA concentration 1 week after start of antiretroviral treatment and longer-term efficacy SO LANCET LA English DT Article ID LYMPHOCYTE COUNTS; PHASE I/II; THERAPY; INFECTION; SUPPRESSION; DURATION; CHILDREN; VIRUS AB Background Early assessment of antiretroviral drug efficacy is important for prevention of the emergence of drug-resistant virus and unnecessary exposure to ineffective drug regimens. Current US guidelines for changing therapy are based on measurements of plasma HIV-1 RNA concentrations 4 or 8 weeks after the start of treatment with cut-off points of 0.75 or 1.00 log, respectively. We investigated the possibility of assessing drug efficacy from measurements of plasma HIV-1 concentrations made during the first week on therapy. Methods The kinetics of virus decay in plasma during the first 12 weeks of treatment was analysed for 124 HIV-1-infected patients being treated for the first time with a protease inhibitor. Patients with a continuous decline of HIV-1 concentrations and in whom HIV-1 was either undetectable or declined by more than 1.5 log at 12 weeks were defined as good responders; the rest were poor responders. Findings The individual virus decay rate constants (k) at day 6 correlated significantly (r>0.66, p<0.0001) with changes in HIV-1 concentrations at 4, 8, and 12 weeks, and correctly predicted 84% of the responses with a cut-off value of k=0.21 per day (in log scale). Reduction in plasma HIV-1 of less than 0.72 log by day 6 after initiation of therapy predicted poor long-term responses in more than 99% of patients. Interpretation These results suggest that changes in HIV-1 concentration at day 6 after treatment initiation are major correlates of longer-term virological responses. They offer a very early measure of individual long-term responses, suggesting that treatment could be optimised after only a few days of therapy. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Expt & Computat Biol, NIH, Frederick, MD 21701 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. Baylor Coll Med, Hematol Serv, Houston, TX 77030 USA. NIH, Ctr Sci Review, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD USA. RP Polis, MA (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11C103, Bethesda, MD 20892 USA. OI Polis, Michael/0000-0002-9151-2268 NR 25 TC 76 Z9 77 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 24 PY 2001 VL 358 IS 9295 BP 1760 EP 1765 DI 10.1016/S0140-6736(01)06802-7 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 496FG UT WOS:000172385100010 PM 11734232 ER PT J AU Goedert, JJ O'Brien, TR Hatzakis, A Kostrikis, LG AF Goedert, JJ O'Brien, TR Hatzakis, A Kostrikis, LG CA Multictr Hemophilia Cohort Study TI T cell receptor excision circles and HIV-1 2-LTR episomal DNA to predict AIDS in patients not receiving effective therapy SO AIDS LA English DT Article DE AIDS incidence; prospective cohort study; hemophilia; T-cell production; HIV-1 replication ID ACTIVE ANTIRETROVIRAL THERAPY; RECENT THYMIC EMIGRANTS; VIRUS TYPE-1 INFECTION; PROGRESSION; DISEASE; HEMOPHILIA; RNA AB Objective: To determine whether improved prediction of AIDS-free survival following HIV-1 seroconversion is achieved by measuring HIV-1 2-LTR episomal DNA (2-LTR) circles and T cell receptor rearrangement excision circles (TREC), reflecting HIV replication and lymphocyte emigration from the thymus, respectively. Design: Subanalysis of a cohort of 154 patients with hemophilia who became HIV positive between 1978 and 1985 and were followed prospectively. Methods: Relative hazards (RH) of AIDS, in the absence of highly effective anti-HIV therapy, were estimated for age, HIV-1 viral load, CD4 lymphocyte count and levels of HIV-1 2-LTR circles and TREC [per 10(6) peripheral blood mononuclear cells (PBMC)] Results: TREC correlated significantly with CD4 cell counts (r = 0.30) and age (r = -0.60). 2-LTR circles correlated significantly with HIV-1 viral load (r = 0.35). If viral load, CD4 lymphocytes and age were included in a proportional hazards model, the risk of AIDS during a median of 11.6 years of follow-up was increased significantly with fewer TREC (adjusted RH, 2.0 per log(10) copies/10(6) PBMC) and more 2-LTR circles (RH, 1.7 per log(10) copies/10(6) PBMC). AIDS prediction with TREC and 2-LTR circles held for most subgroups defined by median viral load, CD4 lymphocytes and age. Conclusions: PBMC that have high levels of HIV-1 replication and low levels of recent thymic emigrants are associated with a substantially increased risk of AIDS. It is not known if measurement of either TREC or 2-LTR circles will complement HIV-11 viral load as an estimation of the risk of AIDS for patients who are receiving highly effective anti-HIV therapy. (C) 2001 Lippincott Williams Wilkins. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA. Univ Athens, Sch Med, Dept Hyg & Epidemiol, Natl Retrovirus Reference Ctr, GR-11527 Athens, Greece. RP Goedert, JJ (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RI Kostrikis, Leondios/A-5330-2016 OI Kostrikis, Leondios/0000-0002-5340-7109 FU NCI NIH HHS [N01-CP-33002]; NIAID NIH HHS [R01-AI-43868] NR 16 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 23 PY 2001 VL 15 IS 17 BP 2245 EP 2250 DI 10.1097/00002030-200111230-00005 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 555GW UT WOS:000175787200005 PM 11698697 ER PT J AU Xu, KY Wang, SQ Cheng, HP AF Xu, KY Wang, SQ Cheng, HP TI Site-specific antibody of (Na++K+)-ATPase augments cardiac myocyte contraction without inactivating enzyme activity SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE (Na+ + K+)-ATPase; site-specific antibody; Ca2+ transients; positive inotropic effect; digitalis glycosides ID SODIUM-PUMP; ADENOSINE-TRIPHOSPHATASE; MOLECULAR-CLONING; CATALYTIC SUBUNIT; ALPHA-SUBUNIT; RAT-BRAIN; NA+,K+-ATPASE; NA,K-ATPASE; BINDING; POLYPEPTIDE AB (Na+ + K+)-ATPase regulates both excitability and contractility of the heart. Little is known about the molecular basis of the enzyme that underlies its cardiac regulatory functions. Here we demonstrate that the (833)KRQPRNPKTDKLVNE(847), region, which resides in the a-subunit of rat (Na+ + K+)-ATPase, directly participates in the regulation of cardiac contraction. A site-specific antibody (SSA95) against this peptide sequence markedly increased intracellular Ca2+ transients and contraction (EC50 = 11.4 nM) in intact rat heart cells without inactivating the (Na+ + K+)-ATPase. These novel findings establish the first link between a precise structural region of the (Na+ + K+)-ATPase and cardiac positive inotropy. (C) 2001 Academic Press. C1 Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. Peking Univ, Coll Life Sci, Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. RP Johns Hopkins Med Inst, Dept Med, Div Cardiol, 5501 Hopkins Bayview Circle,1A-2, Baltimore, MD 21224 USA. EM kxu@jhmi.edu FU NHLBI NIH HHS [HL52175] NR 31 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 23 PY 2001 VL 289 IS 1 BP 167 EP 172 DI 10.1006/bbrc.2001.5974 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 497JF UT WOS:000172451100029 PM 11708795 ER PT J AU Chan, JCC Brunklaus, G AF Chan, JCC Brunklaus, G TI R sequences for the scalar-coupling mediated homonuclear correlation spectroscopy under fast magic-angle spinning SO CHEMICAL PHYSICS LETTERS LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; CARBON-CARBON CONNECTIVITIES; SOLID-STATE NMR; P-31 MAS-NMR; PULSE SEQUENCES; ROTATING SOLIDS; SYSTEMS AB High efficiency of homonuclear polarization transfer via scalar spin-spin coupling is achieved using a pulse sequence designed based on R pulse symmetry. Numerical simulations show that this new pulse sequence is robust with respect to rf inhomogeneity and resonance offsets. The required rf nutation frequency is five times the spinning frequency. Experimental data obtained for Ag4P2S6-II indicate that the new pulse sequence has a maximum efficiency about 75% and therefore is very promising for the measurement of homonuclear correlation spectra. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Munster, Inst Chem Phys, D-48149 Munster, Germany. RP Chan, JCC (reprint author), NIH, Phys Chem Lab, Room 406,Bldg 5, Bethesda, MD 20892 USA. RI Chan, Jerry/F-8075-2010 OI Chan, Jerry/0000-0002-5108-4166 NR 21 TC 35 Z9 35 U1 0 U2 12 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 23 PY 2001 VL 349 IS 1-2 BP 104 EP 112 DI 10.1016/S0009-2614(01)01132-0 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 500AL UT WOS:000172603600018 ER PT J AU Halcox, JPJ Nour, KRA Zalos, G Quyyumi, AA AF Halcox, JPJ Nour, KRA Zalos, G Quyyumi, AA TI Coronary vasodilation and improvement in endothelial dysfunction with endothelin ETA receptor blockade SO CIRCULATION RESEARCH LA English DT Article DE endothelin; coronary circulation; endothelial function; atherosclerosis ID CHRONIC HEART-FAILURE; CONVERTING ENZYME-INHIBITION; ESSENTIAL-HYPERTENSION; ENDOGENOUS ENDOTHELIN; ARTERY DISEASE; NITRIC-OXIDE; EXPERIMENTAL HYPERCHOLESTEROLEMIA; VASCULAR TONE; VASOCONSTRICTION; PLASMA AB The endothelium-derived peptide endothelin-1 (ET-1) causes vasoconstriction predominantly via smooth muscle ETA receptor activation. We hypothesized that ETA receptor inhibition would improve human coronary vascular function. We studied unobstructed coronary arteries of 44 patients with atherosclerosis or its risk factors. Epicardial diameter (D) and Doppler flow velocity were measured, and coronary vascular resistance (CVR) was calculated during intracoronary infusions of acetylcholine (ACH) and sodium nitroprusside (SNP), and during cold pressor testing, before and after a 60-minute intracoronary infusion of the ETA receptor antagonist BQ-123. BQ-123 dilated the coronary circulation; D increased by 5.6+/-1.0% (P<0.0001), and CVR fell by 12+/-3% (P<0.01). The D response to ACH, corrected for the SNP response, improved in segments that constricted with ACH at baseline (P=0.03), whereas segments that initially dilated with ACH did not change with BQ-123 (P=NS). Improvement in D and CVR responses to ACH with BQ-123 inversely correlated with baseline ACH responses (r=-0.44 [P=0.006] and r=-0.78 [P=0.001], respectively), indicating greater improvement in those with endothelial dysfunction. Similarly, cold pressor testing-mediated epicardial vasoconstriction (-2.0+/-1.1%) was reversed after BQ-123 (+1.0+/-0.7%), especially in dysfunctional segments (from -5.6+/-0.9% to +2.2+/-0.9%, P<0.001). There was no correlation between any risk factor and the response to BQ-123. An arteriovenous difference in ET-1 levels developed after BQ-123, which was consistent with enhanced cardiac clearance of ET-1, probably via ETB receptors. Thus, ET-1 acting via the ETA receptor contributes to basal human coronary vasoconstrictor tone and endothelial dysfunction. This suggests that ETA receptor antagonism may have therapeutic potential in the treatment of endothelial dysfunction and atherosclerosis. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Quyyumi, AA (reprint author), Emory Univ Hosp, Suite F606,1364 Clifton Rd NE, Atlanta, GA 30322 USA. OI Halcox, Julian/0000-0001-6926-2947 NR 45 TC 46 Z9 50 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV 23 PY 2001 VL 89 IS 11 BP 969 EP 976 DI 10.1161/hh2301.100980 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 498CJ UT WOS:000172492000006 PM 11717152 ER PT J AU Takahashi, A Wada, A Ogushi, K Maeda, K Kawahara, T Mawatari, K Kurazono, H Moss, J Hirayama, T Nakaya, Y AF Takahashi, A Wada, A Ogushi, K Maeda, K Kawahara, T Mawatari, K Kurazono, H Moss, J Hirayama, T Nakaya, Y TI Production of beta-defensin-2 by human colonic epithelial cells induced by Salmonella enteritidis flagella filament structural protein SO FEBS LETTERS LA English DT Article DE phospholipase C; inositol 1,4,5-trisphosphate; intracellular Ca2+ concentration; nuclear factor kappa B; human beta-defensin-2 ID NF-KAPPA-B; HUMAN MONOCYTES; CALCIUM STORES; TYPHI FLAGELLA; ACTIVATION; RECEPTOR; TYPHIMURIUM; PATHWAY; MICE AB We recently showed that FliC of Salmonella enteritidis increased human beta -defensin-2 (hBD-2) expression, and now describe the signaling responsible pathway. FliC increased the intracellular Ca2+ concentration ([Ca2+](in)) in Caco-2 cells. The [Ca2+](in) increase induced by FliC was prevented by U73122 and heparin, but not by chelating extracellular Ca2+ or pertussis toxin. The FliC-induced increase in hBD-2 promoter activity via nuclear factor kappaB (NF-kappaB) was also inhibited by chelation of intracellular Ca2+ or by U73122. We conclude that FliC increased [Ca2+](in). via inositol 1,4,5-trisphosphate, which was followed by up-regulating hBD-2 mRNA expression via an NF-kappaB-dependent pathway. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Univ Tokushima, Sch Med, Dept Nutr, Tokushima 7708503, Japan. Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. Fac Hlth Sci, Okayama 7008558, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Takahashi, A (reprint author), Univ Tokushima, Sch Med, Dept Nutr, 3-18-15 Kuramoto Cho, Tokushima 7708503, Japan. NR 29 TC 52 Z9 55 U1 0 U2 4 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 23 PY 2001 VL 508 IS 3 BP 484 EP 488 DI 10.1016/S0014-5793(01)03088-5 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 496UW UT WOS:000172416300042 PM 11728477 ER PT J AU Burgers, PMJ Koonin, EV Bruford, E Blanco, L Burtis, KC Christman, MF Copeland, WC Friedberg, EC Hanaoka, F Hinkle, DC Lawrence, CW Nakanishi, M Ohmori, H Prakash, L Prakash, S Reynaud, CA Sugino, A Todo, T Wang, ZG Weill, JC Woodgate, R AF Burgers, PMJ Koonin, EV Bruford, E Blanco, L Burtis, KC Christman, MF Copeland, WC Friedberg, EC Hanaoka, F Hinkle, DC Lawrence, CW Nakanishi, M Ohmori, H Prakash, L Prakash, S Reynaud, CA Sugino, A Todo, T Wang, ZG Weill, JC Woodgate, R TI Eukaryotic DNA polymerases: Proposal for a revised nomenclature SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID BASE EXCISION-REPAIR; HUMAN DINB1 GENE; TRANSLESION REPLICATION; DROSOPHILA-MELANOGASTER; LYASE ACTIVITY; DAMAGE CONTROL; LESION BYPASS; IN-VITRO; MUTAGENESIS; IOTA C1 Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. UCL, Galton Lab, HUGO Nomenclature Comm, London NW1 2HE, England. Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. Univ Calif Davis, Sect Mol & Cellular Biol, Davis, CA 95616 USA. Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75235 USA. Osaka Univ, Inst Mol & Cellular Biol, Osaka 5650871, Japan. Univ Rochester, Dept Biol, Rochester, NY 14627 USA. Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA. Nagoya City Univ, Dept Biochem, Sch Med, Nagoya, Aichi 4678601, Japan. Kyoto Univ, Inst Virus Res, Kyoto 6068507, Japan. Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA. Fac Med Necker Enfants Malad, F-75730 Paris 15, France. Osaka Univ, Microbial Dis Res Inst, Osaka 5650871, Japan. Kyoto Univ, Ctr Radiat Biol, Kyoto 6068501, Japan. Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, Bethesda, MD 20892 USA. RP Burgers, PMJ (reprint author), Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. EM burgers@biochem.wustl.edu RI Prakash, Satya/C-6420-2013; Blanco, Luis/I-1848-2015; OI Burtis, Kenneth/0000-0002-9644-3265 FU NIGMS NIH HHS [GM58534, R01 GM032431] NR 63 TC 236 Z9 245 U1 4 U2 10 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 23 PY 2001 VL 276 IS 47 BP 43487 EP 43490 DI 10.1074/jbc.R100056200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 494QQ UT WOS:000172297700001 PM 11579108 ER PT J AU Ito, Y Zhao, J Mogharei, A Shuler, CF Weinstein, M Deng, CX Chai, Y AF Ito, Y Zhao, J Mogharei, A Shuler, CF Weinstein, M Deng, CX Chai, Y TI Antagonistic effects of Smad2 versus Smad7 are sensitive to their expression level during tooth development SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-BETA; LUNG BRANCHING MORPHOGENESIS; MAD-RELATED PROTEIN; TGF-BETA; ANTISENSE OLIGODEOXYNUCLEOTIDES; MANDIBULAR MORPHOGENESIS; TARGETED DISRUPTION; RECEPTOR; MICE; LACKING AB Members of the transforming growth factor-beta (TGF-beta) superfamily regulate cell proliferation, differentiation, and apoptosis, controlling the development and maintenance of most tissues. TGF-beta signal is transmitted through the phosphorylation of Smad proteins by TGF-beta receptor serine/threonine kinase. During early tooth development, TGF-beta inhibits proliferation of enamel organ epithelial cells but the underlying molecular mechanisms are largely unknown. Here we tested the hypothesis that antagonistic effects between Smad2 and Smad7 regulate TGF-beta signaling during tooth development. Attenuation of Smad2 gene expression resulted in significant advancement of embryonic tooth development with increased proliferation of enamel organ epithelial cells, while attenuation of Smad7 resulted in significant inhibition of embryonic tooth development with increased apoptotic activity within enamel organ epithelium. These findings suggest that different Smads may have differential activities in regulating TGF-beta -mediated cell proliferation and death. Furthermore, functional haplo-insufficiency of Smad2, but not Smad3, altered TGF-beta -mediated tooth development. The results indicate that Smads are critical factors in orchestrating TGF-beta -mediated gene regulation during embryonic tooth development. The effectiveness of TGF-beta signaling is highly sensitive to the level of Smad gene expression. C1 Univ So Calif, Ctr Craniofacial Mol Biol, Sch Dent, Los Angeles, CA 90033 USA. Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Chai, Y (reprint author), Univ So Calif, Ctr Craniofacial Mol Biol, Sch Dent, 2250 Alcazar St,CSA 103, Los Angeles, CA 90033 USA. RI deng, chuxia/N-6713-2016 FU NIDCR NIH HHS [DE12711, DE12941] NR 57 TC 20 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 23 PY 2001 VL 276 IS 47 BP 44163 EP 44172 DI 10.1074/jbc.M011424200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 494QQ UT WOS:000172297700087 PM 11557747 ER PT J AU Cukierman, E Pankov, R Stevens, DR Yamada, KM AF Cukierman, E Pankov, R Stevens, DR Yamada, KM TI Taking cell-matrix adhesions to the third dimension SO SCIENCE LA English DT Article ID EXTRACELLULAR-MATRIX; FOCAL ADHESIONS; INTEGRINS; DYNAMICS; FIBRONECTIN; MIGRATION AB Adhesions between fibroblastic cells and extracellular matrix have been studied extensively in vitro, but tittle is known about their in vivo counterparts. Here, we characterized the composition and function of adhesions in three-dimensional (3D) matrices derived from tissues or cell culture. "3D-matrix adhesions" differ from focal and fibrillar adhesions characterized on 2D substrates in their content of alpha (5)beta (1) and alpha (v)beta (3) integrins, paxillin, other cytoskeletal components, and tyrosine phosphorylation of focal adhesion kinase (FAK). Relative to 2D substrates, 3D-matrix interactions also display enhanced cell biological activities and narrowed integrin usage. These distinctive in vivo 3D-matrix adhesions differ in structure, localization, and function from classically described in vitro adhesions, and as such they may be more biologically relevant to living organisms. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RI Ladoux, Benoit/A-9879-2013; Pankov, Roumen/B-3284-2014; OI Pankov, Roumen/0000-0002-3157-3659; Yamada, Kenneth/0000-0003-1512-6805 NR 23 TC 1681 Z9 1717 U1 33 U2 338 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 23 PY 2001 VL 294 IS 5547 BP 1708 EP 1712 DI 10.1126/science.1064829 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 494VW UT WOS:000172307400042 PM 11721053 ER PT J AU Yu, QS Holloway, HW Flippen-Anderson, JL Hoffman, B Brossi, A Greig, NH AF Yu, QS Holloway, HW Flippen-Anderson, JL Hoffman, B Brossi, A Greig, NH TI Methyl analogues of the experimental Alzheimer drug phenserine: Synthesis and structure/activity relationships for acetyl- and butyrylcholinesterase inhibitory action SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ACETYLCHOLINESTERASE INHIBITION; ANTICHOLINESTERASE ACTIVITIES; CHOLINESTERASE-INHIBITORS; SELECTIVE INHIBITORS; ANTIPODAL ISOMERS; SENILE DEMENTIA; PHYSOSTIGMINE; DISEASE; SPECIFICITY; KINETICS AB With the goal of developing potential Alzheimer's pharmacotherapeutics, we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1). These derivatives contain methyl (3, 4, 6), dimethyl (5, 7, 8, 10, 11) and trimethyl (14) substituents in each position of the phenyl group of the phenylcarbamoyl moieties, and with N-methyl and 6-methyl substituents (12, 13, 31, 33). We also quantified the inhibitory action of these compounds against human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). An analysis of the structure/anticholinesterase activity relationship of the described compounds, together with molecular modeling, confirmed the catalytic triad mechanism of the binding of this class of carabamate analogues within AChE and BChE and defined structural requirements for their differential inhibition. C1 NIA, Drug Design & Dev Sect, Neurosci Lab, Gerontol Res Ctr 4E02,NIH, Baltimore, MD 21224 USA. USN, Res Lab, Dept Navy, Struct Matter Lab, Washington, DC 20375 USA. NIDA, Med Chem Sect, Baltimore, MD 21224 USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Gerontol Res Ctr 4E02,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM GreigN@vax.grc.nia.nih.gov NR 43 TC 65 Z9 68 U1 1 U2 12 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 22 PY 2001 VL 44 IS 24 BP 4062 EP 4071 DI 10.1021/jm010080x PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 493WV UT WOS:000172247200007 PM 11708910 ER PT J AU Jacobson, KA Gao, ZG Chen, AS Barak, D Kim, SA Lee, K Link, A Van Rompaey, P van Calenbergh, S Liang, BT AF Jacobson, KA Gao, ZG Chen, AS Barak, D Kim, SA Lee, K Link, A Van Rompaey, P van Calenbergh, S Liang, BT TI Neoceptor concept based on molecular complementarity in GPCRs: A mutant adenosine A(3) receptor with selectively enhanced affinity for amine-modified nucleosides SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; LIGAND RECOGNITION; BINDING-SITE; TRANSMEMBRANE DOMAIN; KINASE INHIBITORS; GENE-TRANSFER; RAT-BRAIN; DERIVATIVES; ANTAGONISTS; A(2A) AB Adenosine A(3) receptors are of interest in the treatment of cardiac ischemia, inflammation, and neurodegenerative diseases. In an effort to create a unique receptor mutant that would be activated by tailor-made synthetic ligands, we mutated the human As receptor at the site of a critical His residue in TM7, previously proposed to be involved in ligand recognition through interaction with the ribose moiety. The H272E mutant receptor displayed reduced affinity for most of the uncharged A(3) receptor agonists and antagonists examined. For example, the nonselective agonist 1a was 19-fold less potent at the mutant receptor than at the wild-type receptor. The introduction of an amino group on the ribose moiety of adenosine resulted in either equipotency or enhanced binding affinity at the H272E mutant relative to wild-type (A)3 receptors, depending on the position of the amino group. 3'-Amino-3'-deoxyadenosine proved to be 7-fold more potent at the H272E mutant receptor than at the wild-type receptor, while the corresponding 2'- and 5'-amino analogues did not display significantly enhanced affinities. An 3'-amino-N-6-iodobenzyl analogue showed only a small enhancement at the mutant (K-i = 320 nM) vs wild-type receptors. The 3'-amino group was intended for a direct electrostatic interaction with the negatively charged ribose-binding region of the mutant receptor, yet molecular modeling did not support this notion. This design approach is an example of engineering the structure of mutant receptors to recognize synthetic ligands for which they are selectively matched on the basis of molecular complementarity between the mutant receptor and the ligand. We have termed such engineered receptors "neoceptors", since the ligand recognition profile of such mutant receptors need not correspond to the profile of the parent, native receptor. C1 NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Med Ctr, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Pharmacol, Philadelphia, PA 19104 USA. Med Chem Lab, FFW, B-9000 Ghent, Belgium. Univ Hamburg, Fachbereich Chem, Inst Pharm, D-20146 Hamburg, Germany. RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Van Calenbergh, Serge/A-3167-2008; Jacobson, Kenneth/A-1530-2009; Link, Andreas/H-5067-2013 OI Van Calenbergh, Serge/0000-0002-4201-1264; Jacobson, Kenneth/0000-0001-8104-1493; Link, Andreas/0000-0003-1262-6636 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999, ZIA DK031126-03]; NHLBI NIH HHS [R01 HL048225, R01-HL48225] NR 57 TC 71 Z9 71 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 22 PY 2001 VL 44 IS 24 BP 4125 EP 4136 DI 10.1021/jm010232o PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 493WV UT WOS:000172247200012 PM 11708915 ER PT J AU Bartke, A Wright, JC Mattison, JA Ingram, DK Miller, RA Roth, GS AF Bartke, A Wright, JC Mattison, JA Ingram, DK Miller, RA Roth, GS TI Longevity - Extending the lifespan of long-lived mice SO NATURE LA English DT Article ID AMES DWARF MICE; CALORIC RESTRICTION; GENE C1 So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. NIA, NIH, Anim Ctr, Poolesville, MD 20837 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Bartke, A (reprint author), So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. RI Bartke, Andzej/D-6640-2017 OI Bartke, Andzej/0000-0002-2569-557X NR 11 TC 244 Z9 253 U1 1 U2 20 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 22 PY 2001 VL 414 IS 6862 BP 412 EP 412 DI 10.1038/35106646 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 494UP UT WOS:000172304500033 PM 11719795 ER PT J AU in 't Veld, BA Ruitenberg, A Hofman, A Launer, LJ van Duijn, CM Stijnen, T Breteler, MMB Stricker, BHC AF in 't Veld, BA Ruitenberg, A Hofman, A Launer, LJ van Duijn, CM Stijnen, T Breteler, MMB Stricker, BHC TI Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OCCUPATIONAL EPIDEMIOLOGY; RHEUMATOID-ARTHRITIS; VASCULAR DEMENTIA; RECEPTOR-GAMMA; MENTAL STATE; ROTTERDAM; POPULATION; DIAGNOSIS; INFLAMMATION; ASSOCIATION AB Background: Previous studies have suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDs) may help to prevent Alzheimer's disease. The results, however, have been inconsistent. Methods: We studied the association between the use of NSAIDs and Alzheimer's disease and vascular dementia in a prospective, population-based cohort study of 6989 subjects 55 years of age or older who were free of dementia at base line. The risk of Alzheimer's disease was estimated in relation to the use of NSAIDs as documented in pharmacy records. We defined four mutually exclusive categories of use: nonuse, short-term use (1 month or less of cumulative use), intermediate-term use (more than 1 but less than 24 months of cumulative use), and long-term use (24 months or more of cumulative use). Adjustments were made by Cox regression analysis for age, sex, education, smoking status, and the use or nonuse of salicylates, histamine H(sub 2)-receptor antagonists, antihypertensive agents, and hypoglycemic agents. Results: During an average follow-up period of 6.8 years, dementia developed in 394 subjects, of whom 293 had Alzheimer's disease, 56 vascular dementia, and 45 other types of dementia. The relative risk of Alzheimer's disease was 0.95 (95 percent confidence interval, 0.70 to 1.29) in subjects with short-term use of NSAIDs, 0.83 (95 percent confidence interval, 0.62 to 1.11) in those with intermediate-term use, and 0.20 (95 percent confidence interval, 0.05 to 0.83) in those with long-term use. The risk did not vary according to age. The use of NSAIDs was not associated with a reduction in the risk of vascular dementia. Conclusions: The long-term use of NSAIDs may protect against Alzheimer's disease but not against vascular dementia. (N Engl J Med 2001;345:1515-21.) Copyright (C) 2001 Massachusetts Medical Society. C1 Erasmus Med Ctr, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Inspectorate Hlth Care, The Hague, Netherlands. RP Stricker, BHC (reprint author), Erasmus Med Ctr, Dept Epidemiol & Biostat, POB 1738, NL-3000 DR Rotterdam, Netherlands. RI Breteler, Monique /J-5058-2014 NR 46 TC 649 Z9 677 U1 7 U2 45 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 22 PY 2001 VL 345 IS 21 BP 1515 EP 1521 DI 10.1056/NEJMoa010178 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 494DC UT WOS:000172265200001 PM 11794217 ER PT J AU Wang, Y Hu, L Yao, RS Wang, M Crist, KA Grubbs, CJ Johanning, GL Lubet, RA You, M AF Wang, Y Hu, L Yao, RS Wang, M Crist, KA Grubbs, CJ Johanning, GL Lubet, RA You, M TI Altered gene expression profile in chemically induced rat mammary adenocarcinomas and its modulation by an aromatase inhibitor SO ONCOGENE LA English DT Article DE rat; mammary; adenocarcinoma; gene expression; competitive cDNA library screening; vorozole; chemoprevention ID BINDING PROTEIN-1 CONCENTRATION; BREAST-CANCER; CELL-CYCLE; VOROZOLE R-83842; OVARIAN-CANCER; DNA MICROARRAY; CARCINOMA; RNA; D1; TUMORS AB In the present study, competitive cDNA library screening (CCLS) and cDNA microarray analyses were employed to identify differentially expressed genes in methylnitrosourea-induced rat mammary adenocarcinomas. The preliminary screening of 100 000 plaques by CCLS identified 1217 clones with differential expression. Dot-blot analysis of the isolated clones verified differential expression in 471 distinct genes. Confirmation of these 471 genes was conducted by performing reverse transcription-polymerase chain reactions, and a total of 160 genes were confirmed after comparing six rat mammary adenocarcinomas and three normal rat mammary glands. Fifty-nine of these showed lower expression in the adenocarcinomas while the remaining 101 were overexpressed in the tumors. Employing a cDNA microarray containing 588 known genes revealed an additional 33 differentially expressed genes in these tumors. Importantly, most of the identified genes demonstrated relatively reproducible overexpression or underexpression in individual tumors. Many of the altered genes determined by cDNA microarray analysis were oncogenes, tumor suppressor genes, or genes involved in cell cycle control and apoptosis. CCLS identified many others not previously associated with mammary carcinogenesis, including a novel gene named RMT-7. Preliminary studies to determine the applicability of this gene expression approach for detecting potential biomarkers for cancer chemoprevention was evaluated in rat mammary tumors obtained from animals treated with vorozole, a potent aromatase inhibitor. When genes exhibiting differential expression as determined by CCLS or cDNA microarray analysis were examined in control and vorozole-treated tumors, expression of 19 genes was found to be modulated significantly in tumors treated with vorozole. Further investigations into these identified genes should contribute significantly to our understanding of the molecular mechanisms of rat mammary tumorigenesis. In addition, the identified genes may become useful targets for drug development and potential biomarkers for monitoring treatment and prevention of breast cancer in humans. C1 Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Sch Publ Hlth, Columbus, OH 43210 USA. Med Coll Ohio, Toledo, OH 43614 USA. Ohio State Univ, Div Human Canc Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA. Univ Alabama, Chemoprevent Ctr, Birmingham, AL 35294 USA. Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. RP You, M (reprint author), Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Sch Publ Hlth, Columbus, OH 43210 USA. RI Johanning, Gary/A-9671-2008 FU NCI NIH HHS [CA78797, CA16058, CN05113, CA58554] NR 46 TC 19 Z9 22 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 22 PY 2001 VL 20 IS 53 BP 7710 EP 7721 DI 10.1038/sj.onc.1204941 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 492HE UT WOS:000172161700002 PM 11753649 ER PT J AU Koch, CA Huang, SC Moley, JF Azumi, N Chrousos, GP Gagel, RF Zhuang, ZP Pacak, K Vortmeyer, AO AF Koch, CA Huang, SC Moley, JF Azumi, N Chrousos, GP Gagel, RF Zhuang, ZP Pacak, K Vortmeyer, AO TI Allelic imbalance of the mutant and wild-type RET allele in MEN 2A-associated medullary thyroid carcinoma SO ONCOGENE LA English DT Article DE RET; MEN 2; medullary thyroid carcinoma; allelic imbalance ID NONRANDOM DUPLICATION; PROTOONCOGENE; DISEASE AB Germline mutations of the RET proto-oncogene are responsible for the familial tumor syndrome called multiple endocrine neoplasia type 2 (MEN 2) that includes medullary thyroid carcinoma (MTC). Although inherited mutations of RET lead to tumor formation in patients with MEN 2, it is not understood why only selected cells develop into tumors. We have recently shown that duplication of the mutated RET allele or loss of the wild-type allele might represent mechanisms of tumorigenesis in patients with MEN 2A-related pheochromocytoma. We now analysed 19 DNA samples of MTC (15 of which were non-microdissected, four of which were microdissected) from patients with MEN 2A. Using polymorphic marker and phosphorimage densitometry analyses, we found allelic imbalance of the mutated and wild-type RET allele in six of 19 DNA MTC samples. Of note, two of the four microdissected tumor DNA samples showed allelic imbalance of RET, whereas only four of the 15 non-microdissected MTC samples did. These results underscore the significance of microdissection in the analysis of tumor DNA. In our study, some of the non-microdissected tumor DNA samples may have failed to display allelic imbalance of RET, because of contamination of tumor DNA with nonneoplastic. DNA or noninformative microsatellite marker analysis. Taken together, our results suggest allelic imbalance between mutated and wild-type RET as a possible mechanism for tumor formation in some patients with MEN 2A-related MTC. C1 NINDS, Mol Pathogenesis Unit, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. Washington Univ, Sch Med, Dept Surg, St Louis, MO USA. Georgetown Univ, Washington, DC USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Koch, CA (reprint author), NINDS, Mol Pathogenesis Unit, Surg Neurol Branch, NIH, Bldg 10,Rm 9D42, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 11 TC 30 Z9 30 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 22 PY 2001 VL 20 IS 53 BP 7809 EP 7811 DI 10.1038/sj.onc.1204991 PG 3 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 492HE UT WOS:000172161700013 PM 11753660 ER PT J AU Grundy, SM Cleeman, JL AF Grundy, SM Cleeman, JL TI Guidelines for diagnosis and treatment of high cholesterol - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. NHLBI, Natl Cholesterol Educ Program, Bethesda, MD 20892 USA. RP Grundy, SM (reprint author), Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 21 PY 2001 VL 286 IS 19 BP 2401 EP 2402 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 494DH UT WOS:000172266100016 ER PT J AU Goldman, LR Newbold, R Swan, SH AF Goldman, LR Newbold, R Swan, SH TI Exposure to soy-based formula in infancy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Missouri, Dept Family & Community Med, Columbia, MO USA. RP Goldman, LR (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. RI Goldman, Lynn/D-5372-2012 NR 5 TC 21 Z9 21 U1 0 U2 2 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 21 PY 2001 VL 286 IS 19 BP 2402 EP 2403 DI 10.1001/jama.286.19.2402 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 494DH UT WOS:000172266100017 PM 11712933 ER PT J AU Kovacs, JA Gill, VJ Meshnick, S Masur, H AF Kovacs, JA Gill, VJ Meshnick, S Masur, H TI New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DIHYDROPTEROATE SYNTHASE GENE; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; POLYMERASE CHAIN-REACTION; DIHYDROFOLATE-REDUCTASE GENE; MAJOR SURFACE GLYCOPROTEIN; TRIMETHOPRIM-SULFAMETHOXAZOLE; RIBOSOMAL-RNA; AIDS PATIENTS; PLASMODIUM-FALCIPARUM; MONOCLONAL-ANTIBODIES AB Pneumocystis carinii has been recognized as a human pathogen for nearly 50 years. We present a case of P carinii infection that typifies clinical presentation in the era of the acquired immunodeficiency syndrome epidemic. The high incidence of P carinii pneumonia in persons infected with human immunodeficiency virus (HIV) has served to focus laboratory and clinical research efforts on better understanding the biology of the organism and on improving diagnosis, treatment, and prevention of this disease. Although inability to culture P carinii has hampered research efforts, molecular and immunologic approaches have led to the recognition that the organism represents a family of fungi with a very restricted host range and have allowed characterization of clinically relevant antigens and enzymes. Molecular epidemiologic studies have identified more than 50 strains of human-derived P carinii and have suggested that recently acquired infection, as opposed to reactivation of latent infection, may account for many cases of clinical disease. Diagnosis has been improved by the development of organism-specific monoclonal antibodies and, more recently, by polymerase chain reaction using multicopy gene targets, together with induced sputum or oral wash samples. Chemotherapeutic prophylaxis is very effective in preventing P carinii pneumonia; the combination of trimethoprimsulfamethoxazole remains the first-line agent for both therapy and prophylaxis. Prophylaxis needs to be administered only during periods of high risk; in HIV-infected patients responding to effective antiretroviral therapies, prophylaxis no longer needs to be lifelong. Molecular studies have identified mutations in the target of sulfa drugs that appear to represent emerging resistance in P carinii. Resistance to atovaquone, a second-line agent, may also be developing. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NIH, Ctr Clin, Microbiol Serv, Dept Lab Med, Bethesda, MD 20892 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. RP Kovacs, JA (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 7D43,MSC1662, Bethesda, MD 20892 USA. NR 96 TC 120 Z9 126 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 21 PY 2001 VL 286 IS 19 BP 2450 EP 2460 DI 10.1001/jama.286.19.2450 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 494DH UT WOS:000172266100025 PM 11712941 ER PT J AU Jampol, LM Ferris, FL AF Jampol, LM Ferris, FL TI Antioxidants and zinc to prevent progression of age-related macular degeneration SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CATARACT; EYE AB Background: Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss. Objective: To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity. Design: The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg); (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo. Main Outcome Measures: (1) Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline ( :15 letters). Primary analyses used repeated-measures logistic regression with a significance level of .01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring. Results: Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 13% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations. Conclusions: Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study. C1 Northwestern Univ, Sch Med, Dept Ophthalmol, Chicago, IL 60611 USA. NEI, Bethesda, MD 20892 USA. RP Jampol, LM (reprint author), Northwestern Univ, Sch Med, Dept Ophthalmol, 645 N Michigan Ave,Suite 440, Chicago, IL 60611 USA. NR 10 TC 18 Z9 20 U1 0 U2 1 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 21 PY 2001 VL 286 IS 19 BP 2466 EP 2468 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 494DH UT WOS:000172266100028 PM 14619914 ER PT J AU Chang, SL Tjandra, N AF Chang, SL Tjandra, N TI Analysis of NMR relaxation data of biomolecules with slow domain motions using wobble-in-a-cone approximation SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MODEL-FREE APPROACH; MAGNETIC-RESONANCE RELAXATION; MACROMOLECULES; CALMODULIN C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50, Bethesda, MD 20892 USA. NR 12 TC 20 Z9 20 U1 0 U2 4 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 21 PY 2001 VL 123 IS 46 BP 11484 EP 11485 DI 10.1021/ja016862x PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 493TT UT WOS:000172240100023 PM 11707129 ER PT J AU Breen, N Wagener, DK Brown, ML Davis, WW Ballard-Barbash, R AF Breen, N Wagener, DK Brown, ML Davis, WW Ballard-Barbash, R TI Progress in cancer screening over a decade: Results of cancer screening from the 1987, 1992, and 1998 National Health Interview Surveys SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID UNITED-STATES; OLDER WOMEN; MAMMOGRAPHY; BREAST; CARE; PREDICTORS; GUIDELINES; AUDIT AB Background: Screening to detect cancer early, an increasingly important cancer control activity, cannot be effective unless it is widely used. Methods: Use of Pap smears, mammography, fecal occult blood tests (FOBTs), sigmoidoscopy, and digital rectal examination (DRE) was evaluated in the 1987, 1992, and 1998 National Health Interview Surveys. Levels and trends in screening use were examined by sex, age; and racial/ethnic group. The effects of income, educational level, and health care coverage were examined within age groups. Logistic regression analyses of 1998 data were used to develop a parsimonious, policy-relevant model. Results: Use of all screening modalities increased over the period examined; for mammography and DRE, the increase was more rapid in the first half of the decade; for the Pap test and sigmoidoscopy, the increase was more rapid in the second half of the decade. Levels of colorectal cancer screening (both sigmoidoscopy and FOBTs) in 1998 were less than the level that prevailed a decade earlier for mammography. Patterns of change for all screening modalities differed between age, sex, and racial/ethnic groups, but prevalence of use during the study, within recommended time intervals, was consistently lower among groups with lower income and less education. Logistic regression analyses indicated that insurance coverage and, to a greater extent, usual source of care had strong independent associations with screening usage when age, sex, racial/ethnic group, and educational level were taken into account. Conclusions: While cancer screening is generally increasing in the United States, usage is relatively low for colorectal cancer screening and among groups that lack health insurance or a usual source of care. C1 NCI, Div Canc Control & Populat Sci, Appl Res Program, NIH, Bethesda, MD 20892 USA. NCI, Surveillance Res Program, Stat Res Applicat Branch, Div Canc Control & Populat Sci,NIH, Hyattsville, MD USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Promot Stat, Hyattsville, MD USA. RP Breen, N (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, NIH, EPN-4005,6130 Execut Plaza, Bethesda, MD 20892 USA. NR 32 TC 389 Z9 393 U1 0 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 21 PY 2001 VL 93 IS 22 BP 1704 EP 1713 DI 10.1093/jnci/93.22.1704 PG 10 WC Oncology SC Oncology GA 494MX UT WOS:000172287400010 PM 11717331 ER PT J AU Lee, SP Fuior, E Lewis, MS Han, MK AF Lee, SP Fuior, E Lewis, MS Han, MK TI Analytical ultracentrifugation studies of translin: Analysis of protein-DNA interactions using a single-stranded fluorogenic oligonucleotide SO BIOCHEMISTRY LA English DT Article ID RNA-BINDING PROTEIN; CHROMOSOMAL TRANSLOCATIONS; MESSENGER-RNAS; BRAIN; SEQUENCES; GENE; SITE; TRAX AB Translin is a recently identified nucleic acid binding protein that appears to be involved in the recognition of conserved sequences found at many chromosomal breakpoints. Previous reports indicate that, based on gel filtration analysis and electron microscopy of protein-DNA complexes, translin forms an octameric structure that binds the DNA. In this study, we further examine the possibility of self-association of translin and its interactions with DNA by analytical ultracentrifugation. Sedimentation velocity analysis of translin indicates that the predominant species sediments with a sedimentation coefficient of 8.5 S and has a frictional ratio, f/f(o), of 1.35; these data are consistent with the presence of an octamer with an ellipsoidal configuration; a small amount of a component with significantly higher mass is also present. Equilibrium sedimentation studies of translin at three different protein concentrations also indicate that the predominant species present is an octamer with a minor fraction of aggregated species. Neither monomer nor dimer was detected. Sedimentation equilibrium studies of translin with an FITC-labeled single-stranded oligonucleotide were performed to examine the interaction. A novel analysis method has been developed to analyze protein-nucleic acid interactions based on global fitting of scans of 280 and 490 nm to appropriate mathematical models. Utilizing this method, it was determined that the DNA binding species of translin is an octamer binding a single-stranded oligonucleotide with a DeltaG degrees value of -9.49 +/- 0.12 kcal/mol, corresponding to a dissociation constant, K-d, of 84 +/- 17 nM. On the basis of this evidence and electron microscopy, it is envisioned that translin forms an annular structure of eight subunits, hydrodynamically an oblate ellipsoid, which binds DNA at chromosomal breakpoints. C1 Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Han, MK (reprint author), Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA. NR 20 TC 17 Z9 17 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 20 PY 2001 VL 40 IS 46 BP 14081 EP 14088 DI 10.1021/bi010302t PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 493VQ UT WOS:000172244500039 PM 11705401 ER PT J AU Chang, BL Zheng, SQL Isaacs, SD Wiley, KE Carpten, JD Hawkins, GA Bleecker, ER Walsh, PC Trent, JM Meyers, DA Isaacs, WB Xu, JF AF Chang, BL Zheng, SQL Isaacs, SD Wiley, KE Carpten, JD Hawkins, GA Bleecker, ER Walsh, PC Trent, JM Meyers, DA Isaacs, WB Xu, JF TI Linkage and association of CYP17 gene in hereditary and sporadic prostate cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE prostate cancer; linkage; association; genetic; hereditary; CYP17 ID BREAST-CANCER; ALLELIC LOSS; DOMINANT INHERITANCE; SUSCEPTIBILITY LOCUS; HORMONE LEVELS; LOD SCORES; POLYMORPHISM; RISK; CHROMOSOME; METABOLISM AB Androgens are essential for prostate development, growth and maintenance and the association between androgen levels and prostate cancer is well established. Since the CYP17 gene encodes the enzyme cytochrome P450c 17 alpha, which mediates 17 alpha -hydroxylase and 17,20-lyase activities in the androgen biosynthesis pathway, sequence variations in the gene and association with increased risk to prostate cancer has been studied. In particular, several groups have studied the association between a polymorphism in the 5 ' promoter region and prostate cancer using a population-based association approach. However, the results from these studies were inconclusive. To further study this polymorphism and its possible role in hereditary prostate cancer (HPC), we performed a genetic linkage analysis and family-based association analysis in 159 families, each of which contains at least 3 first-degree relatives with prostate cancer. In addition, we performed a population-based association analysis to compare the risk of this polymorphism to hereditary and sporadic prostate cancer in 159 HPC probands, 249 sporadic prostate cancer patients and 211 unaffected control subjects. Evidence for linkage at the CYP17 gene region was found in the total 159 HPC families (LOD = 1.3, p = 0.01, at marker D10S222). However, family-based association tests did not provide evidence for overtransmission of either allele of the CYP17 polymorphism to affected individuals in the HPC families. The allele and genotype frequencies of the polymorphism were not statistically different among the HPC probands, sporadic cases and unaffected control subjects. In conclusion, our results suggest that the CYP17 gene or other genes in the region may increase the susceptibility to prostate cancer in men; however, the polymorphism in the 5 ' promoter region has a minor role If any in increasing prostate cancer susceptibility in our study sample.(C) 2001 Wiley-Liss, Inc. C1 Wake Forest Univ, Sch Med, Ctr Human Genom, Winston Salem, NC 27157 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Xu, JF (reprint author), Wake Forest Univ, Sch Med, Ctr Human Genom, Med Ctr Blvd, Winston Salem, NC 27157 USA. FU NCI NIH HHS [CA58236] NR 64 TC 36 Z9 38 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 2001 VL 95 IS 6 BP 354 EP 359 DI 10.1002/1097-0215(20011120)95:6<354::AID-IJC1062>3.0.CO;2-3 PG 6 WC Oncology SC Oncology GA 487HZ UT WOS:000171870200003 PM 11668516 ER PT J AU Monuki, ES Porter, FD Walsh, CA AF Monuki, ES Porter, FD Walsh, CA TI Patterning of the dorsal telencephalon and cerebral cortex by a roof plate-Lhx2 pathway SO NEURON LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; IN-SITU HYBRIDIZATION; PROMOTER DIRECTS EXPRESSION; REGULATORY GENES; TRANSGENIC MICE; NEURAL CREST; FOREBRAIN DEVELOPMENT; CORTICAL-NEURONS; SPINAL-CORD; DLX GENES AB The organizing centers and molecules that pattern the cerebral cortex have been elusive. Here we show that cortical patterning involves regulation of the Lhx2 homeobox gene by the roof plate. Roof plate ablation results in reduced cortical size and Lhx2 expression defects that implicate roof plate signals in the bimodal regulation of Lhx2 in vivo. Bimodal Lhx2 regulation can be recapitulated in explants using two roof plate-derived signaling molecules, Bmp4 and Bmp2. Loss of Lhx2 function results in profound losses of cortical progenitors and neurons, but Lhx2 mutants continue to generate cortical neurons from dorsal sources that may include the roof plate region itself. These findings provide evidence for the roof plate as an organizing center of the developing cortex and for a roof plate-Lhx2 pathway in cortical patterning. C1 Beth Israel Deaconess Med Ctr, Div Neurogenet, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Walsh, CA (reprint author), Univ Calif Irvine, Coll Med, Dept Pathol, Irvine, CA 92697 USA. OI Monuki, Edwin/0000-0001-5130-781X FU NIMH NIH HHS [MH K08]; NINDS NIH HHS [R01 NS32457] NR 63 TC 193 Z9 198 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 20 PY 2001 VL 32 IS 4 BP 591 EP 604 DI 10.1016/S0896-6273(01)00504-9 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 495WT UT WOS:000172363900007 PM 11719201 ER PT J AU Dikalova, AE Kadiiska, MB Mason, RP AF Dikalova, AE Kadiiska, MB Mason, RP TI An in vivo ESR spin-trapping study: Free radical generation in rats from formate intoxication - role of the Fenton reaction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SPRAGUE-DAWLEY RATS; LIPID-PEROXIDATION; FORMIC-ACID; METABOLIC-ACIDOSIS; XANTHINE-OXIDASE; METHANOL; MECHANISM; TOXICITY; ELECTRON; ALLOPURINOL AB Electron spin resonance spectroscopy has been used to study free radical generation in rats with acute sodium formate poisoning. The in vivo spin-trapping technique was used with alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN), which reacts with free radical metabolites to form radical adducts, which were detected in the bile and urine samples from Fischer rats. The use of [C-13]-sodium formate and computer simulations of the spectra identified the 12-line spectrum as arising from the POBN/carbon dioxide anion radical adduct. The identification of POBN/(CO2-)-C-. radical adduct provides direct electron spin resonance spectroscopy evidence for the formation of (CO2-)-C-. radicals during acute intoxication by sodium formate, suggesting a free radical metabolic pathway. To study the mechanism of free radical generation by formate, we tested several known inhibitors. Both allopurinol, an inhibitor of xanthine oxidase, and aminobenzotriazole, a cytochrome P450 inhibitor, decreased free radical formation from formate, which may imply a dependence on hydrogen peroxide. In accord with this hypothesis, the catalase inhibitor 3-aminotriazole caused a significant increase in free radical formation. The iron chelator Desferal decreased the formation of free radicals up to 2-fold. Presumably, iron plays a role in the mechanism of free radical generation by formate via the Fenton reaction. The detection of formate free radical metabolites generated in vivo and the key role of the Fenton reaction in this process may be important for understanding the pathogenesis of both formate and methanol intoxication. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Mason, RP (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233,111 Alexander Dr,Mail Drop F-01, Res Triangle Pk, NC 27709 USA. NR 40 TC 49 Z9 50 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 20 PY 2001 VL 98 IS 24 BP 13549 EP 13553 DI 10.1073/pnas.251091098 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 495EW UT WOS:000172328100017 PM 11717423 ER PT J AU McNeil, AC Shupert, WL Iyasere, CA Hallahan, CW Mican, J Davey, RT Connors, M AF McNeil, AC Shupert, WL Iyasere, CA Hallahan, CW Mican, J Davey, RT Connors, M TI High-level HIV-1 viremia suppresses viral antigen-specific CD4(+) T cell proliferation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COMBINATION ANTIRETROVIRAL THERAPY; LONG-TERM NONPROGRESSORS; VIRUS TYPE-1 INFECTION; IMMUNE FUNCTION; IMMUNODEFICIENCY; RESPONSES; CD8(+); DISEASE; REPLICATION; LYMPHOCYTE AB in chronic viral infections of humans and experimental animals, virus-specific CD4(+) T cell function is believed to be critical for induction and maintenance of host immunity that mediates effective restriction of viral replication. Because in vitro proliferation of HIV-specific memory CD4(+) T cells is only rarely demonstrable in HIV-infected individuals, it is presumed that HIV-specific CD4(+) T cells are killed upon encountering the virus, and maintenance of CD4(+) T cell responses in some patients causes the restriction of virus replication. In this study, proliferative responses were absent in patients with poorly restricted virus replication although HIV-specific CD4(+) T cells capable of producing IFN-gamma were detected. In a separate cohort, interruption of antiretroviral therapy resulted in the rapid and complete abrogation of virus-specific proliferation although HIV-1-specific CD4(+) T cells were present. HIV-specific proliferation returned when therapy was resumed and virus replication was controlled. Further, HIV-specific CD4(+) T cells of viremic patients could be induced to proliferate in response to HIV antigens when costimulation was provided by anti-CD28 antibody in vitro. Thus, HIV-1-specific CD4(+) T cells persist but remain poorly responsive (produce IFN-gamma but do not proliferate) in viremic patients. Unrestricted virus replication causes diminished proliferation of virus-specific CD4(+) T cells. Suppression of proliferation of HIV-specific CD4(+) T cells in the context of high levels of antigen may be a mechanism by which HIV or other persistently replicating viruses limit the precursor frequency of virus-specific CD4(+) T cells and disrupt the development of effective virus-specific immune responses. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Connors, M (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11B-09,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. NR 35 TC 167 Z9 168 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 20 PY 2001 VL 98 IS 24 BP 13878 EP 13883 DI 10.1073/pnas.251539598 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 495EW UT WOS:000172328100074 PM 11717444 ER PT J AU Wang, L Chun, HJ Wong, W Spencer, DM Lenardo, MJ AF Wang, L Chun, HJ Wong, W Spencer, DM Lenardo, MJ TI Caspase-10 is an initiator caspase in death receptor signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INDUCED-PROXIMITY MODEL; APOPTOSIS; FAS; DOMAIN; ACTIVATION; PROTEIN; FADD; TNF; INHIBITION; MUTATIONS AB A role for caspase-10, previously implicated in the autoimmune lymphoproliferative syndrome, in death receptor signaling has not been directly shown. Here we show that caspase-10 can function independently of caspase-8 in initiating Fas- and tumor necrosis factor-related apoptosis-inducing ligand-receptor-mediated apoptosis. Moreover, Fas crosslinking in primary human T cells leads to the recruitment and activation of caspase-10. Fluorescent resonance energy transfer analysis indicates that the death-effector domains of caspase-8 and -10 both interact with the death-effector domain of FADD. Nonetheless, we find that caspase-8 and -10 may have different apoptosis substrates and therefore potentially distinct roles in death receptor signaling or other cellular processes. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM lenardo@nih.gov RI Chun, Hyung/K-1859-2013 NR 19 TC 82 Z9 83 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 20 PY 2001 VL 98 IS 24 BP 13884 EP 13888 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 495EW UT WOS:000172328100075 ER PT J AU Ono, A Freed, EO AF Ono, A Freed, EO TI Plasma membrane rafts play a critical role in HIV-1 assembly and release SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VESICULAR STOMATITIS-VIRUS; SEMLIKI-FOREST-VIRUS; TYPE-1 MATRIX PROTEIN; LIPID RAFTS; PARTICLE-PRODUCTION; CELLULAR PROTEINS; GENE DELIVERY; LIFE-CYCLE; CELLS AB HIV-1 particle production occurs in a series of steps promoted by the viral Gag protein. Although it is well established that assembly and release take place at the plasma membrane, the nature of membrane assembly sites remains poorly understood. We show here that Gag specifically associates with cholesterol-enriched microdomains ("rafts") at the plasma membrane. Kinetic studies demonstrate that raft association follows membrane binding, and the analysis of Gag mutants reveals that, whereas the N terminus of Gag mediates raft binding, this association is greatly enhanced by Gag-Gag interaction domains. We observe that depletion of cellular cholesterol markedly and specifically reduces HIV-1 particle production. Furthermore, treatment of virus-producing cells or virus particles with raft-disrupting agents significantly impairs virus infectivity. These results identify the association of Gag with plasma membrane rafts as an important step in HIV-1 replication. These findings may lead to novel strategies for suppressing HIV-1 replication in vivo. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Freed, EO (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 307,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 57 TC 458 Z9 468 U1 2 U2 22 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 20 PY 2001 VL 98 IS 24 BP 13925 EP 13930 DI 10.1073/pnas.241320298 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 495EW UT WOS:000172328100082 PM 11717449 ER PT J AU Tomizawa, Y Sekido, Y Kondo, M Gao, BN Yokota, J Roche, J Drabkin, H Lerman, MI Gazdar, AF Minna, JD AF Tomizawa, Y Sekido, Y Kondo, M Gao, BN Yokota, J Roche, J Drabkin, H Lerman, MI Gazdar, AF Minna, JD TI Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE semaphorin; neuropilin; methylation ID SEMAPHORIN RECEPTORS; CHROMOSOME 3P21.3; DELETION REGION; AXON GUIDANCE; IN-VIVO; IDENTIFICATION; EXPRESSION; NEUROPILIN-1; MORPHOGENESIS; VERTEBRATES AB Semaphorins SEMA3B and its homologue SEMA3F are 3p21.3 candidate tumor suppressor genes (TSGs), the expression of which is frequently lost in lung cancers. To test the TSG candidacy of SEMA3B and SEMA3F, we transfected them into lung cancer NCl-H1299 cells, which do not express either gene. Colony formation of H1299 cells was reduced 90% after transfection with wild-type SEMA3B compared with the control vector. By contrast, only 30-40% reduction in colony formation was seen after the transfection of SEMA3F or SEMA3B variants carrying lung cancer-associated single amino acid missense mutations. H1299 cells transfected with wild-type but not mutant SEMA3B underwent apoptosis. We found that lung cancers (n = 34) always express the neuropilin-1 receptor for secreted semaphorins, whereas 82% expressed the neuropilin-2 receptor. Because SEMA3B and SEMA3F are secreted proteins, we tested conditioned medium from COS-7 cells transfected with SEMA3B and SEMA3F and found that medium from wild-type SEMA3B transfectants reduced the growth of several lung cancer lines 30-90%, whereas SEMA3B mutants or SEMA3F had little effect in the same assay. Sequencing of sodium bisulfite-treated DNA showed dense methylation of CpG sites in the SEMA3B 5' region of lung cancers not expressing SEMA3B but no methylation in SEMA3B-expressing tumors. These results are consistent with SEMA3B functioning as a TSG, the expression of which is inactivated frequently in lung cancers by allele loss and promoter region methylation. C1 Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dept Internal Med, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dept Pharmacol & Pathol, Dallas, TX 75390 USA. Natl Canc Ctr, Res Inst, Div Biol, Tokyo 1040045, Japan. Nagoya Univ, Sch Med, Dept Clin Prevent Med, Nagoya, Aichi 4668550, Japan. NCI, Immunobiol Lab, Canc Res Ctr, Frederick, MD 21702 USA. Univ Poitiers, Inst Biol Mol & Ingn, CNRS, FRE 2224, F-86022 Poitiers, France. Univ Colorado, Hlth Sci Ctr, Div Med Oncol, Denver, CO 80262 USA. RP Minna, JD (reprint author), Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dept Internal Med, 6000 Harry Hines Blvd,NB8-206, Dallas, TX 75390 USA. RI KONDO, Masashi/I-7378-2014; Sekido, Yoshitaka/P-9756-2015 FU NCI NIH HHS [CA71618, N01-CO-56000, P50 CA070907, P50 CA70907, R01 CA071618] NR 33 TC 164 Z9 178 U1 0 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 20 PY 2001 VL 98 IS 24 BP 13954 EP 13959 DI 10.1073/pnas.231490898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 495EW UT WOS:000172328100087 PM 11717452 ER PT J AU Belland, RJ Scidmore, MA Crane, DD Hogan, DM Whitmire, W McClarty, G Caldwell, HD AF Belland, RJ Scidmore, MA Crane, DD Hogan, DM Whitmire, W McClarty, G Caldwell, HD TI Chlamydia trachomatis cytotoxicity associated with complete and partial cytotoxin genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LARGE CLOSTRIDIAL CYTOTOXINS; ESCHERICHIA-COLI; LYMPHOCYTE-ACTIVATION; EPITHELIAL-CELLS; GENOME SEQUENCES; IN-VITRO; GLYCOSYLTRANSFERASES; PNEUMONIAE; INFECTIONS; BINDING AB Chlamydia trachomatis is an obligate intracellular human bacterial pathogen that infects epithelial cells of the eye and genital tract. Infection can result in trachoma, the leading cause of preventable blindness worldwide, and sexually transmitted diseases. A common feature of infection is a chronic damaging inflammatory response for which the molecular pathogenesis is not understood. It has been proposed that chlamydiae have a cytotoxic activity that contributes to this pathology, but a toxin has not been identified. The C trachomatis genome contains genes that encode proteins with significant homology to large clostridial cytotoxins. Here we show that C trachomatis makes a replication-independent cytotoxic activity that produces morphological and cytoskeletal changes in epithelial cells that are indistinguishable from those mediated by clostridial toxin B. A mouse chlamydial strain that encodes a full-length cytotoxin caused pronounced cytotoxicity, as did a human strain that has a shorter ORF with homology to only the enzymatically active site of clostridial toxin B. Cytotoxin gene transcripts were detected in chlamydiae-infected cells, and a protein with the expected molecular mass was present in lysates of infected epithelial cells. The protein was present transiently in infected cells during the period of cytotoxicity. Together, these data provide compelling evidence for a chlamydial cytotoxin for epithelial cells and imply that the cytotoxin is present in the elementary body and delivered to host cells very early during infection. We hypothesize that the cytotoxin is a virulence factor that contributes to the pathogenesis of C. trachomatis diseases. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Lab Intracellular Parasites, NIH, Hamilton, MT 59840 USA. Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Ithaca, NY 14853 USA. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0W3, Canada. RP Belland, RJ (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. NR 25 TC 114 Z9 124 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 20 PY 2001 VL 98 IS 24 BP 13984 EP 13989 DI 10.1073/pnas.241377698 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 495EW UT WOS:000172328100092 PM 11707582 ER PT J AU Su, QN Mochida, S Tian, JH Mehta, R Sheng, ZH AF Su, QN Mochida, S Tian, JH Mehta, R Sheng, ZH TI SNAP-29: A general SNARE protein that inhibits SNARE disassembly and is implicated in synaptic transmission SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MEMBRANE-FUSION; CORE COMPLEX; ALPHA-SNAP; SYNTAXIN; SPECIFICITY; RELEASE; VESICLES; RECEPTOR; DOCKING; FAMILY AB Using the yeast two-hybrid system with syntaxin-1A as bait, we isolated soluble NSF attachment protein (SNAP)-29 from a human brain cDNA library. Synaptosomal fractionation and immunocytochemical staining of hippocampal neurons in culture showed that SNAP-29 is present at synapses and is predominantly associated with synaptic vesicles. The interaction of SNAP-29 with syntaxin-1 was further confirmed with immunoprecipitation analysis. Binding competition studies with SNAP-29 demonstrated that it could compete with a-SNAP for binding to synaptic SNAP receptors (SNARES) and consequently inhibit disassembly of the SNARE complex. Introduction of SNAP-29 into presynaptic superior cervical ganglion neurons in culture significantly inhibited synaptic transmission in an activity-dependent manner. Although SNAP-29 has been suggested to be a general SNARE component in membrane trafficking, our findings suggest that it may function as a regulator of SNARE complex disassembly and modulate the process of postfusion recycling of the SNARE components. C1 NINCDS, Synapt Funct Unit, NIH, Bethesda, MD 20892 USA. Tokyo Med Univ, Dept Physiol, Tokyo 1608402, Japan. RP Sheng, ZH (reprint author), NINCDS, Synapt Funct Unit, NIH, Bethesda, MD 20892 USA. NR 41 TC 49 Z9 52 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 20 PY 2001 VL 98 IS 24 BP 14038 EP 14043 DI 10.1073/pnas.251532398 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 495EW UT WOS:000172328100102 PM 11707603 ER PT J AU Yamada, M Lamping, KG Duttaroy, A Zhang, WL Cui, YH Bymaster, FP McKinzie, DL Felder, CC Deng, CX Faraci, FM Wess, J AF Yamada, M Lamping, KG Duttaroy, A Zhang, WL Cui, YH Bymaster, FP McKinzie, DL Felder, CC Deng, CX Faraci, FM Wess, J TI Cholinergic dilation of cerebral blood vessels is abolished in M-5 muscarinic acetylcholine receptor knockout mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NITRIC-OXIDE SYNTHASE; VENTRAL TEGMENTAL AREA; MESSENGER-RNA; RAT-BRAIN; CORTICAL MICROVESSELS; SMOOTH-MUSCLE; BASAL GANGLIA; M5 SUBTYPES; STIMULATION; EXPRESSION AB The M-5 muscarinic receptor is the most recent member of the muscarinic acetylcholine receptor family (M-1-M-5) to be cloned. At present, the physiological relevance of this receptor subtype remains unknown, primarily because of its low expression levels and the lack of M-5 receptor-selective ligands. To circumvent these difficulties, we used gene targeting technology to generate M-5 receptor-deficient mice (M5R(-/-) mice). M5R(-/-) mice did not differ from their wild-type littermates in various behavioral and pharmacologic tests. However, in vitro neurotransmitter release experiments showed that M-5 receptors play a role in facilitating muscarinic agonist-induced dopamine release in the striatum. Because M-5 receptor mRNA has been detected in several blood vessels, we also investigated whether the lack of M-5 receptors led to changes in vascular tone by using several in vivo and in vitro vascular preparations. Strikingly, acetylcholine, a powerful dilator of most vascular beds, virtually lost the ability to dilate cerebral arteries and arterioles in M5R(-/-) mice. This effect was specific for cerebral blood vessels, because acetylcholine-mediated dilation of extracerebral arteries remained fully intact in M5R(-/-) mice. Our findings provide direct evidence that M-5 muscarinic receptors are physiologically relevant. Because it has been suggested that impaired cholinergic dilation of cerebral blood vessels may play a role in the pathophysiology of Alzheimer's disease and focal cerebral ischemia, cerebrovascular M-5 receptors may represent an attractive therapeutic target. C1 NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NIDDK, Biochem & Metab Lab, Bethesda, MD 20892 USA. Univ Iowa, Dept Internal Med, Ctr Cardiovasc, Iowa City, IA 52242 USA. Univ Iowa, Dept Pharmacol, Ctr Cardiovasc, Iowa City, IA 52242 USA. Vet Adm Med Ctr, Iowa City, IA 52242 USA. Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Wess, J (reprint author), NIDDK, Bioorgan Chem Lab, Bldg 8A,Room B1A-05, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 FU NHLBI NIH HHS [HL-38901, HL-39050, HL-62984, P01 HL062984, R01 HL038901]; NINDS NIH HHS [NS-26421, P01 NS024621] NR 57 TC 132 Z9 140 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 20 PY 2001 VL 98 IS 24 BP 14096 EP 14101 DI 10.1073/pnas.251542998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 495EW UT WOS:000172328100112 PM 11707605 ER PT J AU Belkaid, Y Hoffmann, KF Mendez, S Kamhawi, S Udey, MC Wynn, TA Sacks, DL AF Belkaid, Y Hoffmann, KF Mendez, S Kamhawi, S Udey, MC Wynn, TA Sacks, DL TI The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE Leishmania major; IL-10; skin; chronic infection; CD8(+) T cells ID T-CELL CLONES; AZAR DERMAL LEISHMANIASIS; NITRIC-OXIDE SYNTHASE; HUMAN DENDRITIC CELLS; CUTANEOUS LEISHMANIASIS; INTERFERON-GAMMA; IMMUNE-RESPONSES; ACTIVATED MACROPHAGES; LATENT LEISHMANIASIS; MONOCLONAL-ANTIBODY AB Some pathogens (e.g., Mycobacterium tuberculosis, Toxoplasma gondii, Leishmania spp) have been shown to persist in their host after clinical cure, establishing the risk of disease reactivation. We analyzed the conditions necessary for the long term maintenance of Leishmania major in genetically resistant C57BL/6 mice after spontaneous healing of their dermal lesions. Interleukin (IL)-10 was found to play an essential role in parasite persistence as sterile cure was achieved in IL-10-deficient and IL-4/IL-10 double-deficient mice. The requirement for IL-10 in establishing latency associated with natural infection was confirmed in IL-10-deficient mice challenged by bite of infected sand flies. The host-parasite equilibrium was maintained by CD4(+) and CD8(+) T cells which were each able to release IL-10 or interferon (IFN)-gamma, and were found to accumulate in chronic sites of infection, including the skin and draining lymph node. A high frequency of the dermal CD4(+) T cells released both IL-10 and IFN-gamma. Wild-type mice treated transiently during the chronic phase with anti-IL-10 receptor antibodies achieved sterile cure, suggesting a novel therapeutic approach to eliminate latency, infection reservoirs, and the risk of reactivation disease. C1 NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Sacks, DL (reprint author), NIAID, Parasit Dis Lab, Bldg 4,Rm 126,Ctr Dr MSC 0425, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 53 TC 363 Z9 370 U1 1 U2 7 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 19 PY 2001 VL 194 IS 10 BP 1497 EP 1506 DI 10.1084/jem.194.10.1497 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 495QK UT WOS:000172351700011 PM 11714756 ER PT J AU Lorman, V Podgornik, R Zeks, B AF Lorman, V Podgornik, R Zeks, B TI Positional, reorientational, and bond orientational order in DNA mesophases SO PHYSICAL REVIEW LETTERS LA English DT Article ID LIQUID-CRYSTALS; PHASES AB We investigate the orientational order of transverse polarization vectors of long,, stiff polymer molecules and their coupling to bond orientational. and positional order in high density mesophases. Homogeneous ordering of transverse polarization vector promotes distortions in the hexatic phase, whereas inhomogeneous ordering precipitates crystallization of the 2D sections with different orientations of the transverse polarization vector on each molecule in the unit cell. We propose possible scenarios for going from the hexatic phase, through the distorted hexatic phase, to the crystalline phase with an orthorhombic unit cell observed experimentally for the case of DNA. C1 Univ Montpellier 2, Lab Phys Math & Theor, F-34095 Montpellier, France. Univ Ljubljana, Fac Math & Phys, Dept Phys, SI-1000 Ljubljana, Slovenia. Jozef Stefan Inst, Dept Theoret Phys, SI-1000 Ljubljana, Slovenia. NICHHD, LPSB, NIH, Bethesda, MD 20892 USA. Univ Ljubljana, Fac Med, Inst Biophys, SI-1000 Ljubljana, Slovenia. RP Lorman, V (reprint author), Univ Montpellier 2, Lab Phys Math & Theor, F-34095 Montpellier, France. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 11 TC 30 Z9 30 U1 1 U2 5 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 19 PY 2001 VL 87 IS 21 AR 218101 DI 10.1103/PhysRevLett.87.218101 PG 4 WC Physics, Multidisciplinary SC Physics GA 496NA UT WOS:000172400600059 PM 11736381 ER PT J AU Vasan, RS Larson, MG Leip, EP Kannel, WB Levy, D AF Vasan, RS Larson, MG Leip, EP Kannel, WB Levy, D TI Assessment of frequency of progression to hypertension in nonhypertensive participants in the Framingham Heart Study: a cohort study SO LANCET LA English DT Article ID NUTRITION EXAMINATION SURVEY; NORMAL BLOOD-PRESSURE; NATIONAL-HEALTH; UNITED-STATES; POPULATION; PREVALENCE; DISEASE; MEN AB Background Patients with optimum (<120/80 mm Hg), normal (120-129/80-84 mm Hg), and high normal (130-139/85-89 mm Hg) blood pressure (BP) may progress to hypertension (140/90 mm Hg) over time. We aimed to establish the best frequency of BP screening by assessing the rates and determinants of progression to hypertension. Methods We assessed repeated BP measurements in individuals without hypertension (BP<140/90 mm Hg) from the Framingham Study (4200 men, 5645 women; mean age 52 years) who attended clinic examinations during 1978-94. The incidence of hypertension (or use of anti hypertensive treatment) and its determinants were studied. Findings A stepwise, increase in hypertension incidence occurred across the three non-hypertensive BP categories; 5.3% (95% CI 4.4-6.3%) of participants with optimum BP, 17.6% (15.2-20.3%) with normal, and 37.3% (33.3-41.5%) with high normal BP aged below age 65 years progressed to hypertension over 4 years. Corresponding 4-year rates of progression for patients 65 years and older were 16.0% (12.0-20.9), 25.5% (20.4-31.4), and 49.5% (42.6-56.4), respectively. Obesity and weight gain also contributed to progression; a 5% weight gain on follow-up was associated with 20-30% increased odds of hypertension. Interpretation High normal BP and normal BP frequently progress to hypertension over a period of 4 years, especially in older adults. These findings support recommendations for monitoring individuals with high normal BP once a year, and monitoring those with normal BP every 2 years, and they emphasise the importance of weight control as a measure for primary prevention of hypertension. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Beth Israel Hosp, Div Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Hosp, Div Clin Epidemiol, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [K24 HL04334, N01-HC-38038] NR 25 TC 518 Z9 555 U1 2 U2 12 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 17 PY 2001 VL 358 IS 9294 BP 1682 EP 1686 DI 10.1016/S0140-6736(01)06710-1 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 495MC UT WOS:000172344100012 PM 11728544 ER PT J AU La Montagne, JR AF La Montagne, JR TI Biotechnology and research: promise and problems SO LANCET LA English DT Article AB Biotechnology has expanded greatly during the last two decades. This expansion is due to worldwide investment in basic biomedical research. The new knowledge generated by this investment has led to a bounty of potential applications for improvement of health, which are being explored for commercial purposes by the biotechnology industry. Private investment is thus ever present In development of these biotechnological products. All these factors raise important questions, including increasing concerns about intellectual property and conflict of interest. As this expansion continues, the established processes of peer review should be strengthened. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP La Montagne, JR (reprint author), NIAID, NIH, Bldg 31,Room 7A03, Bethesda, MD 20892 USA. NR 3 TC 3 Z9 3 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 17 PY 2001 VL 358 IS 9294 BP 1723 EP 1724 DI 10.1016/S0140-6736(01)06717-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 495MC UT WOS:000172344100036 PM 11728568 ER PT J AU Ramirez, CM Yau, YY Mason, G Browning, J Conry-Cantilena, C Leitman, SF Bolan, CD AF Ramirez, CM Yau, YY Mason, G Browning, J Conry-Cantilena, C Leitman, SF Bolan, CD TI Effect of iron burden and carefully controlled phlebotomy therapy on arthritic symptoms in hereditary hemochromatosis (HH). SO BLOOD LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Sch Med, Washington, DC 20007 USA. NIH, Dept Transfus 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 2001 VL 98 IS 11 MA 18 BP 7A EP 8A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134100019 ER PT J AU Nilson, DG Wong, C Cline, AP Sabatino, DE Garrett, LJ Basseres, DS Bodine, DM Gallagher, PG AF Nilson, DG Wong, C Cline, AP Sabatino, DE Garrett, LJ Basseres, DS Bodine, DM Gallagher, PG TI A dinucleotide deletion in the downstream promoter element of the ankyrin gene associated with hereditary spherocytosis disrupts promoter function in transgenic mice. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, GMBB, Bethesda, MD 20892 USA. UNICAMP, Hemoctr, Campinas, Brazil. Yale Univ, New Haven, CT 06520 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 2001 VL 98 IS 11 MA 21 BP 8A EP 8A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100022 ER PT J AU Igarashi, T Miyazato, A Kajigaya, S Young, NS Childs, R AF Igarashi, T Miyazato, A Kajigaya, S Young, NS Childs, R TI CD-40 ligand (CD40-L) and lipopolysaccrides (LPS) induce dendritic cell (DC) maturation through distinct molecular pathways as determined by high-density nucleotide arrays. SO BLOOD LA English DT Meeting Abstract C1 NIH, NHLBI, Hematol 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 2001 VL 98 IS 11 MA 49 BP 15A EP 15A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100050 ER PT J AU Donahue, RE Wersto, R Metzger, ME Haley, J Smith, D Schechter, AN AF Donahue, RE Wersto, R Metzger, ME Haley, J Smith, D Schechter, AN TI Rhesus macaques as a model for the study of human hemoglobin switching: Enhancement of Hb F expression in non-anemic animals. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Rockville, MD USA. OSI Pharmaceut Inc, Uniondale, NY USA. 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 2001 VL 98 IS 11 MA 3672 BP 21B EP 21B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200085 ER PT J AU Wang, M Tang, DC Liu, WL Chin, K Zhu, JQ Fibach, E Rodgers, GP AF Wang, M Tang, DC Liu, WL Chin, K Zhu, JQ Fibach, E Rodgers, GP TI Hydroxyurea exerts bi-modal dose-dependent effects on erythropoiesis in human cultured erythroid cells. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, NIH, Mol & Clin Hematol Branch, Bethesda, MD USA. Chinese Acad Med Sci, Inst Hematol, Tianjin, Peoples R China. Beijing Union Med Coll, Tianjin, Peoples R China. Hadassah Univ Hosp, Dept Hematol, IL-91120 Jerusalem, Israel. 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 2001 VL 98 IS 11 MA 3684 BP 23B EP 23B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200097 ER PT J AU Provenzano, M Lim, JB Bettinotti, M Mocellin, S Marincola, FM Stroncek, DF AF Provenzano, M Lim, JB Bettinotti, M Mocellin, S Marincola, FM Stroncek, DF TI Matrix protein pp65(341-350), a peptide that induces HLA-restricted CMV-specific CTL in both HLA-A*2402 and A*0101 subjects. SO BLOOD LA English DT Meeting Abstract C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NCI, 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 2001 VL 98 IS 11 MA 90 BP 24A EP 24A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100091 ER PT J AU Salvucci, O Yao, L Villalba, S Sajewicz, A Pittaluga, S Tosato, G AF Salvucci, O Yao, L Villalba, S Sajewicz, A Pittaluga, S Tosato, G TI Involvement of the chemokine stromal-derived factor-1 in regulation of endothelial cell branching morphogenesis. SO BLOOD LA English DT Meeting Abstract C1 NCI, Expt Trasplantat & Immunol Dept, NIH, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, 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 2001 VL 98 IS 11 MA 116 BP 30A EP 30A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100117 ER PT J AU Hill, JM Backer, MV Backer, JM Finkel, T AF Hill, JM Backer, MV Backer, JM Finkel, T TI Selective targeting of human endothelial progenitor cells with chimeric VEGF fusion toxin. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 126 BP 32A EP 32A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100127 ER PT J AU Grimes, HL Doan, LL Yu, Q Singer, A Visser, JW Bear, SE Alexander, MA Morse, HC Tsichlis, PN Kitay, MK AF Grimes, HL Doan, LL Yu, Q Singer, A Visser, JW Bear, SE Alexander, MA Morse, HC Tsichlis, PN Kitay, MK TI GFI1B repression of GFI1 leads to defects in T-cell activation, IL-7R alpha expression and T-cell lineage commitment. SO BLOOD LA English DT Meeting Abstract C1 Univ Louisville, Inst Cellular Therapeut, Louisville, KY USA. NIH, NCI, Expt Immunol Branch, Bethesda, MD USA. New York Blood Ctr, Lab Stem Cell Biol, New York, NY USA. NIH, NIAID, Immunopathol Lab, Bethesda, MD USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 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 2001 VL 98 IS 11 MA 3740 BP 35B EP 35B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200153 ER PT J AU Lozier, JN Dutra, A Pak, E Zhou, N Zheng, ZL Nichols, TC Bellinger, DA Read, MS Morgan, RA AF Lozier, JN Dutra, A Pak, E Zhou, N Zheng, ZL Nichols, TC Bellinger, DA Read, MS Morgan, RA TI Evidence for a canine homologue to human F8A in and near the canine factor VIII gene: A possible mediator of an inversion in the Chapel Hill hemophilia A dog colony? SO BLOOD LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Pathol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 1 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 2001 VL 98 IS 11 MA 154 BP 39A EP 39A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100155 ER PT J AU Zhang, H Chua, KS Telford, W Khanna, C Helman, LJ Thomas, EK Mackall, CL AF Zhang, H Chua, KS Telford, W Khanna, C Helman, LJ Thomas, EK Mackall, CL TI Tumor-lytic CD28-CD8+T cells circulate in patients with Ewing's sarcoma and require alternative costimulation via tumor expression of 4-1BBL. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, Bethesda, MD USA. NCI, Transplantat & Exptl Therapeut Branch, Bethesda, MD USA. Immunex Inc, Div Extramural Res, Seattle, WA 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 2001 VL 98 IS 11 MA 3771 BP 41B EP 41B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200184 ER PT J AU Stroncek, DF Njoroge, JM Procter, JL Griffith, LM Childs, RW Miller, J AF Stroncek, DF Njoroge, JM Procter, JL Griffith, LM Childs, RW Miller, J TI Flow cytometry is more sensitive at detecting RBC-associated C3d than the tube agglutination assay. SO BLOOD LA English DT Meeting Abstract C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NIDDK, Lab Chem Biol, NIH, Bethesda, MD 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 2001 VL 98 IS 11 MA 249 BP 61A EP 62A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134100250 ER PT J AU Bolan, CD Yau, YY Mason, G Browning, J Cathy, CC Leitman, SF AF Bolan, CD Yau, YY Mason, G Browning, J Cathy, CC Leitman, SF TI Controlled study of changes in iron parameters during MCV-guided phlebotomy therapy for hereditary hemochromatosis (HH). SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, 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 2001 VL 98 IS 11 MA 250 BP 62A EP 62A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100251 ER PT J AU Bolan, CD Cecco, SA Wesley, RA Yau, YY Horne, M Remaley, AT Childs, RW Barrett, AJ Rehak, NN Leitman, SF AF Bolan, CD Cecco, SA Wesley, RA Yau, YY Horne, M Remaley, AT Childs, RW Barrett, AJ Rehak, NN Leitman, SF TI Controlled study of donor symptoms, citrate effects and responses to intravenous calcium in large volume leukapheresis (LVL). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Dept Transfus Med, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NHLBI, Off Director, 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 2001 VL 98 IS 11 MA 255 BP 63A EP 63A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100256 ER PT J AU Aronson, DL Krizek, DM Hortin, GL Kempner, ES Rick, ME AF Aronson, DL Krizek, DM Hortin, GL Kempner, ES Rick, ME TI Characteristics of the von Willebrand factor protease: Size heterogeneity evaluated by target mass, gel filtration, and HPLC. SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NIAMS, 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 2001 VL 98 IS 11 MA 3888 BP 67B EP 67B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200301 ER PT J AU Francischetti, IM Valenzuela, JG Mather, TN Ribeiro, JM AF Francischetti, IM Valenzuela, JG Mather, TN Ribeiro, JM TI Protease inhibitors in the salivary gland of the Lyme disease vector, Ixodes scapularis. SO BLOOD LA English DT Meeting Abstract C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Rhode Isl, Ctr Vector Borne Dis, Kingston, RI 02881 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 2001 VL 98 IS 11 MA 3907 BP 71B EP 71B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200320 ER PT J AU Akel, S Sadowski, C Ruscetti, F AF Akel, S Sadowski, C Ruscetti, F TI Neutralization of TGF-beta 1 in human CD34+Lin- cord blood cells reveals erythropoietin independent early erythroid differentiation in serum-free conditions and reduces terminal differentiation. SO BLOOD LA English DT Meeting Abstract C1 NCI, Basic Res Lab, CCR, Frederick, MD 21701 USA. NCI, SAIC Frederick, 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 2001 VL 98 IS 11 MA 304 BP 74A EP 74A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100305 ER PT J AU Krupa, S Watering, N Linnekin, D AF Krupa, S Watering, N Linnekin, D TI An oncogenic c-Kit mutant induces factor-independent growth via PI3 kinase and Jnk-dependent pathways. SO BLOOD LA English DT Meeting Abstract C1 NCI, BRL, CCR, NIH, 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 2001 VL 98 IS 11 MA 314 BP 76A EP 76A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100315 ER PT J AU Krupa, S Linnekin, D AF Krupa, S Linnekin, D TI Lyn contributes to c-Kit mediated activation of multiple signaling pathways in murine bone marrow mast cells. SO BLOOD LA English DT Meeting Abstract C1 NCI, BRL, CCR, NIH, 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 2001 VL 98 IS 11 MA 312 BP 76A EP 76A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100313 ER PT J AU Radosevic, N Winterstein, D Pfeffer, K Neubauer, H Linnekin, D AF Radosevic, N Winterstein, D Pfeffer, K Neubauer, H Linnekin, D TI JAK2 plays a lineage-specific role in SCF-mediated responses of primary hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 NCI, BRL, CCR, Frederick, MD 21701 USA. IRSP, Frederick, MD USA. SAIC Frederick, Frederick, MD USA. Tech Univ Munich, D-8000 Munich, Germany. RI Neubauer, Hans/C-4467-2016 OI Neubauer, Hans/0000-0002-3467-4105 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 2001 VL 98 IS 11 MA 313 BP 76A EP 76A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100314 ER PT J AU Qi, CF Li, D McCarty, T Lobanenkov, VV Morse, HC AF Qi, CF Li, D McCarty, T Lobanenkov, VV Morse, HC TI CTCF functions as a central control element for induction of cell cycle arrest and apoptosis following BCR ligation of immature B cells. SO BLOOD LA English DT Meeting Abstract C1 NIAID, Immunopathol 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 2001 VL 98 IS 11 MA 328 BP 79A EP 79A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100329 ER PT J AU Boyd, KE Jenkins, NA Copeland, NG Perkins, AS AF Boyd, KE Jenkins, NA Copeland, NG Perkins, AS TI Identification of Sox4 as a potential oncogene cooperating with Evil in retrovirally-induced murine myeloid leukemias. SO BLOOD LA English DT Meeting Abstract C1 Yale Univ, Sch Med, New Haven, CT USA. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, 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 2001 VL 98 IS 11 MA 392 BP 94A EP 94A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100393 ER PT J AU Emerling, BM Bonifas, JM Kratz, CP Donovan, S Taylor, BR Green, ED Le Beau, MM Shannon, KM AF Emerling, BM Bonifas, JM Kratz, CP Donovan, S Taylor, BR Green, ED Le Beau, MM Shannon, KM TI Cloning and characterization of M7LDS1, a novel Drosophila trithorax homolog from a segment of chromosome band 7q22 implicated in myeloid leukemia. SO BLOOD LA English DT Meeting Abstract C1 Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. NHGRI, Genome Technol Branch, Bethesda, MD USA. Univ Chicago, Sect Hematol & Oncol, Dept Med, Chicago, IL USA. Univ Chicago, Canc Res Inst, Chicago, IL 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 2001 VL 98 IS 11 MA 409 BP 98A EP 98A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100410 ER PT J AU Changou, AC Hilgenfeld, E McNell, N He, LZ Montagna, C Ried, T Pandolfi, PP AF Changou, AC Hilgenfeld, E McNell, N He, LZ Montagna, C Ried, T Pandolfi, PP TI A recurring nonrandom pattern of chromosomal aberrations associate with the development of acute promelocytic leukemia in PLZF-RAR alpha and PLZF-RAR alpha/RAR alpha-PLZF transgenic mice. SO BLOOD LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst Canc Res, Dept Pathol, Program Mol Biol, New York, NY 10021 USA. NCI, Genet Branch, Ctr Canc Res, 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 2001 VL 98 IS 11 MA 414 BP 99A EP 99A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100415 ER PT J AU Fraser, JK Wagner, EL Carter, SL Kernan, NA Jensen, L Rowan, E Kurtzberg, J AF Fraser, JK Wagner, EL Carter, SL Kernan, NA Jensen, L Rowan, E Kurtzberg, J TI Cord blood donor pre-screening: Impact of exclusion criteria on minority recruitment. SO BLOOD LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Los Angeles, CA 90024 USA. EMMES Corp, Potomac, MD USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. NIH, NHLBI, Bethesda, MD USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 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 2001 VL 98 IS 11 MA 4058 BP 104B EP 104B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200471 ER PT J AU Risitano, AM Holada, K Chen, GB Simak, J Vostal, JG Young, NS Maciejewski, JP AF Risitano, AM Holada, K Chen, GB Simak, J Vostal, JG Young, NS Maciejewski, JP TI CD34+cells from paroxysmal nocturnal hemoglobinuria patients are deficient in surface expression of cellular prion protein (PrPc). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD USA. RI Simak, Jan/C-1153-2011 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 2001 VL 98 IS 11 MA 4131 BP 119B EP 120B PN 2 PG 2 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200544 ER PT J AU Zeng, WH Miyazato, A Chen, GB Kajigaya, S Dunbar, CE Young, NS Maciejewski, JP AF Zeng, WH Miyazato, A Chen, GB Kajigaya, S Dunbar, CE Young, NS Maciejewski, JP TI Changes in the gene expression profile in bone marrow CD34 cells after exposure to interferon-gamma in culture. SO BLOOD LA English DT Meeting Abstract 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 2001 VL 98 IS 11 MA 4141 BP 122B EP 122B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200554 ER PT J AU Schurman, SH Hawley, TS Candotti, F AF Schurman, SH Hawley, TS Candotti, F TI Hoechst staining of murine embryonic stem cells. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Holland Lab, Hematopoiesis Dept, Rockville, 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 2001 VL 98 IS 11 MA 4156 BP 124B EP 125B PN 2 PG 2 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200567 ER PT J AU Hegde, U Kingma, D Stetler-Stevenson, M Drbohlav, N Little, RF Steinberg, S Filie, A Abati, A Wilson, WH AF Hegde, U Kingma, D Stetler-Stevenson, M Drbohlav, N Little, RF Steinberg, S Filie, A Abati, A Wilson, WH TI High incidence of occult leptomeningeal disease detected by flow cytometry in at risk newly diagnosed B-cell lymphomas. SO BLOOD LA English DT Meeting Abstract C1 NCI, Canc Res Ctr, 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 2001 VL 98 IS 11 MA 535 BP 127A EP 127A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100536 ER PT J AU Miyazato, A Khaiboullina, S Kajigaya, S StJeor, S Young, NS Jaroslaw, MP AF Miyazato, A Khaiboullina, S Kajigaya, S StJeor, S Young, NS Jaroslaw, MP TI Gene expression profile of the cellular response to human cytomegalovirus (HCMV) infection in hematopoietic tissues. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Nevada, Sch Med, Dept Microbiol, Reno, NV 89557 USA. RI Khaiboullina, Svetlana/M-4793-2016 OI Khaiboullina, Svetlana/0000-0002-5064-570X 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 2001 VL 98 IS 11 MA 4176 BP 129B EP 129B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200587 ER PT J AU Linnekin, D Krupa, S Winterstein, D Jelacic, T Pfeffer, K Neubauer, H Ronnstrand, L Radosevic, N AF Linnekin, D Krupa, S Winterstein, D Jelacic, T Pfeffer, K Neubauer, H Ronnstrand, L Radosevic, N TI Signal transduction mechanisms of c-Kit that mediate the growth and transformation of hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 NCI, Basic Res Lab, Frederick, MD 21701 USA. SAIC Frederick, Intramural Res & Support Program, Frederick, MD USA. Tech Univ Munich, D-8000 Munich, Germany. Ludwig Inst Canc Res, S-75124 Uppsala, Sweden. RI Ronnstrand, Lars/A-2429-2011; Neubauer, Hans/C-4467-2016 OI Neubauer, Hans/0000-0002-3467-4105 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 2001 VL 98 IS 11 MA 4201 BP 134B EP 134B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200612 ER PT J AU Zhu, JQ Tang, DC Chin, K Rodgers, GP AF Zhu, JQ Tang, DC Chin, K Rodgers, GP TI MAPK pathway response to hydroxyurea mediated K562 cell differentiation. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, MCHB, 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 2001 VL 98 IS 11 MA 4233 BP 141B EP 141B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200644 ER PT J AU Schop, RFJ Kuehl, WM Van Wier, SA Price-Troska, T Bailey, RJ Ahmann, GJ Greipp, PR Jalal, SM Fonseca, R AF Schop, RFJ Kuehl, WM Van Wier, SA Price-Troska, T Bailey, RJ Ahmann, GJ Greipp, PR Jalal, SM Fonseca, R TI Genomic aberrations in Waldenstrom's macroglobulinemia clonal cells detected by FISH. SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. NCI, Dept Genet, 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 2001 VL 98 IS 11 MA 650 BP 154A EP 154A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100651 ER PT J AU Schop, RFJ Price-Troska, T Kuehl, WM Kyle, RA Fonseca, R AF Schop, RFJ Price-Troska, T Kuehl, WM Kyle, RA Fonseca, R TI Mutation analysis of the CD40 gene in Waldenstrom's macroglobulinemia. SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. NCI, Dept Genet, 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 2001 VL 98 IS 11 MA 4292 BP 155B EP 155B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200703 ER PT J AU Murphy, WJ Raziuddin, A Bennett, M Winkler-Pickett, RT Ortaldo, JR Longo, DL AF Murphy, WJ Raziuddin, A Bennett, M Winkler-Pickett, RT Ortaldo, JR Longo, DL TI Augmentation of bone marrow allograft rejection by removal of opposing inhibitory Ly49 NK subsets. SO BLOOD LA English DT Meeting Abstract C1 SAIC Frederick, IRSP, Frederick, MD USA. Univ Texas, SW Med Ctr, Dallas, TX USA. NCI, LEI, Frederick, MD 21701 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 2001 VL 98 IS 11 MA 708 BP 168A EP 168A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100709 ER PT J AU Sun, K Raziuddin, A Koh, CY Murphy, WJ AF Sun, K Raziuddin, A Koh, CY Murphy, WJ TI Role of NK cell subsets in the rejection of allogeneic BMC under nonmyeloablative conditions. SO BLOOD LA English DT Meeting Abstract C1 SAIC Frederick, IRSP, Frederick, MD USA. NCI, LMI, Frederick, MD 21701 USA. RI Koh, Crystal/D-9986-2013 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 2001 VL 98 IS 11 MA 709 BP 168A EP 168A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100710 ER PT J AU Yavuz, AS Yavuz, S Longo, N Kraemer, KH Lipsky, PE AF Yavuz, AS Yavuz, S Longo, N Kraemer, KH Lipsky, PE TI Different mutational patterns of immunoglobulin and bcl-6 genes in Xeroderma pigmentosum patients imply different mutational mechanisms of mutation. SO BLOOD LA English DT Meeting Abstract C1 NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NCI, Mol Carcinogenesis 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 2001 VL 98 IS 11 MA 4382 BP 174B EP 174B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200793 ER PT J AU Broxmeyer, HE Srour, EF Hangoc, G Cooper, S Anderson, SA Bodine, D AF Broxmeyer, HE Srour, EF Hangoc, G Cooper, S Anderson, SA Bodine, D TI High efficiency recovery of hematopoietic progenitor cells with extensive proliferative and ex vivo expansion activity and of hematopoietic stem cells with NOD/SCID mouse repopulating ability from human cord blood stored frozen for 15 years. SO BLOOD LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Wells Ctr Ped Res, Indianapolis, IN 46202 USA. Walther Canc Inst, Indianapolis, IN USA. NIH, NHGRI, GMBB, 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 2001 VL 98 IS 11 MA 768 BP 183A EP 183A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100769 ER PT J AU Joshi, SS Bishop, MR Lynch, JC Pusic, I Sharp, JG Tarantolo, SR Whalen, V Kessinger, A Pavletic, SZ AF Joshi, SS Bishop, MR Lynch, JC Pusic, I Sharp, JG Tarantolo, SR Whalen, V Kessinger, A Pavletic, SZ TI Immunological properties of allogeneic blood stem cell collections as predictor of outcomes after transplantation. SO BLOOD LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE 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 2001 VL 98 IS 11 MA 770 BP 183A EP 183A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100771 ER PT J AU Battiwalla, M Middleton, PG Childs, RW Neylon, AJ Barrett, J AF Battiwalla, M Middleton, PG Childs, RW Neylon, AJ Barrett, J TI Do adverse cytokine expression profiles in nonmyeloablative stem cell transplant (NST) recipients play a lesser role than in standard transplantation? SO BLOOD LA English DT Meeting Abstract C1 NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Med Sch Newcastle Upon Tyne, LRF Lab, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 791 BP 189A EP 189A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100792 ER PT J AU Bishop, MR Marchigiani, D Kasten-Sportes, C Castro, K Carter, C Read, E Leitman, S Hou, J Gress, R Fowler, D AF Bishop, MR Marchigiani, D Kasten-Sportes, C Castro, K Carter, C Read, E Leitman, S Hou, J Gress, R Fowler, D TI Pre-transplant quantitation of host T-cells as a method to determine adequate host immune depletion for successful engraftment of T-cell depleted allografts after reduced-intensity conditioning. SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 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 2001 VL 98 IS 11 MA 792 BP 189A EP 189A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100793 ER PT J AU Anaissie, EJ Owens, S Dignani, MC Lee, CK Rex, J Walsh, T AF Anaissie, EJ Owens, S Dignani, MC Lee, CK Rex, J Walsh, T TI Cleaning bathrooms: A novel approach to reducing patient exposure to aerosolized Aspergillus spp. SO BLOOD LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. Univ Texas, Sch Med, Houston, TX USA. 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 2001 VL 98 IS 11 MA 863 BP 207A EP 207A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100864 ER PT J AU Hu, J Kelly, P Bonifacino, A Agricola, B Donahue, R Dunbar, C Vanin, E AF Hu, J Kelly, P Bonifacino, A Agricola, B Donahue, R Dunbar, C Vanin, E TI Evaluation of RD114-pseudotyped retroviral vector and amphotropic pseudotyped vector transduction in CD34+cells in rhesus monkey autologous transplantation model. SO BLOOD LA English DT Meeting Abstract C1 NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Dept Hematol Oncol, 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 2001 VL 98 IS 11 MA 868 BP 208A EP 208A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100869 ER PT J AU Mordini, N Mattei, D Lo Nigro, C Gallamini, A Ghirardo, D Priotto, R Ferrua, MT Viscoli, C AF Mordini, N Mattei, D Lo Nigro, C Gallamini, A Ghirardo, D Priotto, R Ferrua, MT Viscoli, C TI Detection of early stage pulmonary aspergillosis by combined ELISA assay and chest CT scan. SO BLOOD LA English DT Meeting Abstract C1 S Croce Hosp, Dept Hematol, Cuneo, Italy. S Croce Hosp, Dept Radiol, Cuneo, Italy. S Croce Hosp, Dept Lab, Cuneo, Italy. Natl Canc Inst, Compromised Host Unit, Genoa, 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 2001 VL 98 IS 11 MA 866 BP 208A EP 208A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100867 ER PT J AU Brenner, S Whiting-Theobald, NL Linton, GF Holmes, KL Kelly, PF Vanin, EF Horwitz, ME Malech, HL AF Brenner, S Whiting-Theobald, NL Linton, GF Holmes, KL Kelly, PF Vanin, EF Horwitz, ME Malech, HL TI Concentrated RD114 pseudotyped MFGS-gp91phox vector achieves functional correction of 17-20% of NOD/SCID/beta2m-repopulating peripheral blood CD34+cells from patients with human X-linked chronic granulomatous disease. SO BLOOD LA English DT Meeting Abstract C1 NIH, NIAID, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Dept Hematol Oncol, Div Expt Hematol, Memphis, TN 38105 USA. RI Brenner, Sebastian/D-7456-2013 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 869 BP 209A EP 209A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100873 ER PT J AU Shi, PA De Angioletti, M Donahue, RE Notaro, R Luzzatto, L Dunbar, CE AF Shi, PA De Angioletti, M Donahue, RE Notaro, R Luzzatto, L Dunbar, CE TI Comparison in the rhesus monkey model of in vivo gene marking with amphotrophic and VSV-G pseudotyped retroviral vectors. SO BLOOD LA English DT Meeting Abstract C1 NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Natl Inst Canc Res, IST, Genoa, Italy. 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 2001 VL 98 IS 11 MA 871 BP 209A EP 209A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100875 ER PT J AU Ting, SS Brenner, S Hartnett, B Haskins, M Felsburg, P Malech, H AF Ting, SS Brenner, S Hartnett, B Haskins, M Felsburg, P Malech, H TI High transduction efficiencies (> 80%) of canine bone marrow CD34 enriched cells can be achieved by RD114 pseudotyped oncoretroviral vectors. SO BLOOD LA English DT Meeting Abstract C1 NIH, NIAID, Bethesda, MD 20892 USA. Univ Penn, Sch Vet Med, Dept Clin Studies, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. RI Brenner, Sebastian/D-7456-2013 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 2001 VL 98 IS 11 MA 874 BP 210A EP 210A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100878 ER PT J AU Cortes, J Plunkett, WK Estey, EH Keating, MJ Madden, T Sampath, D Faderl, S Beran, M Dancey, J Kantarjian, HM AF Cortes, J Plunkett, WK Estey, EH Keating, MJ Madden, T Sampath, D Faderl, S Beran, M Dancey, J Kantarjian, HM TI Phase I study of UCN-01 and ara-C for patients with refractory or relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, CTEP, Bethesda, MD 20892 USA. RI Sampath, Deepa/J-3298-2016 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 2001 VL 98 IS 11 MA 4555 BP 211B EP 211B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200966 ER PT J AU Waisfisz, Q Miyazato, A de Winter, JP Joenje, H Liu, JM AF Waisfisz, Q Miyazato, A de Winter, JP Joenje, H Liu, JM TI Oligonucleotide microarray-based expression analysis of mutant Fanconi anemia cells. SO BLOOD LA English DT Meeting Abstract C1 Free Univ Amsterdam, Med Ctr, Dept Clin Genet & Human Genet, Amsterdam, Netherlands. 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 2001 VL 98 IS 11 MA 904 BP 217A EP 217A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100908 ER PT J AU Kang, EM Giri, N Wisch, L Meade, K Tisdale, JR Young, NS Dunbar, CE AF Kang, EM Giri, N Wisch, L Meade, K Tisdale, JR Young, NS Dunbar, CE TI Treatment of refractory Diamond-Blackfan Anemia with anti-thymocyte globulin (ATG) and cyclosporine (CYSA). SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 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 2001 VL 98 IS 11 MA 909 BP 218A EP 218A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100913 ER PT J AU Kearns, WG Sutton, JF Young, NS Liu, JM AF Kearns, WG Sutton, JF Young, NS Liu, JM TI Centrosome amplification and chromosomal instability in patients with bone marrow failure syndromes. SO BLOOD LA English DT Meeting Abstract 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 2001 VL 98 IS 11 MA 913 BP 219A EP 219A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100917 ER PT J AU Holada, K Simak, J Risitano, AM Maciejewski, J Young, NS Vostal, JG AF Holada, K Simak, J Risitano, AM Maciejewski, J Young, NS Vostal, JG TI Activated platelets of patients with paroxysmal noctural hemoglobinuria express cellular prion protein (PrPc). SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD USA. NIH, NHLBI, Hematol Branch, Bethesda, MD USA. RI Simak, Jan/C-1153-2011 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 2001 VL 98 IS 11 MA 923 BP 221A EP 221A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100927 ER PT J AU Ishihara, S Nagakura, S Dunn, DE Nishimura, J Kawaguchi, T Horikawa, K Hidaka, M Kagimoto, T Eto, N Mitsuya, H Kinoshita, T Young, NS Nakakuma, H AF Ishihara, S Nagakura, S Dunn, DE Nishimura, J Kawaguchi, T Horikawa, K Hidaka, M Kagimoto, T Eto, N Mitsuya, H Kinoshita, T Young, NS Nakakuma, H TI PIG-A mutations decrease the susceptibility of blood cells to natural killer cells in vitro. SO BLOOD LA English DT Meeting Abstract C1 Kumamoto Univ, Kumamoto, Japan. NIH, NHLBI, Bethesda, MD USA. Osaka Univ, Osaka, Japan. Miyazaki Univ, Miyazaki, 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 2001 VL 98 IS 11 MA 922 BP 221A EP 221A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100926 ER PT J AU Miyazato, A Maciejewski, JP Kajigaya, S Young, NS AF Miyazato, A Maciejewski, JP Kajigaya, S Young, NS TI Comparative analysis of gene expression in paroxysmal nocturnal hemoglobinuria (PNH) cells by high density oligonucleotide arrays. SO BLOOD LA English DT Meeting Abstract C1 NIH, 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 2001 VL 98 IS 11 MA 926 BP 222A EP 222A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100930 ER PT J AU Kook, H Risitano, AM Zeng, WH Wlodarski, M Lottermann, C Nakamura, R Barrett, J Young, NS Maciejewski, JP AF Kook, H Risitano, AM Zeng, WH Wlodarski, M Lottermann, C Nakamura, R Barrett, J Young, NS Maciejewski, JP TI Changes in T-cell receptor VB repertoire in aplastic anemia. Effects of different immunosuppressive regimens. SO BLOOD LA English DT Meeting Abstract C1 NIH, 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 2001 VL 98 IS 11 MA 931 BP 223A EP 223A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100935 ER PT J AU Tisdale, JF Maciejewski, JP Nunez, O Rosenfeld, SJ Young, NS AF Tisdale, JF Maciejewski, JP Nunez, O Rosenfeld, SJ Young, NS TI A randomized trial comparing antithymocyte globulin and cyclosporin to cyclophosphamide and cyclosporin for initial treatment in severe aplastic anemia: Results of long-term follow-up. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD USA. NIH, Ctr Clin, 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 2001 VL 98 IS 11 MA 932 BP 223A EP 223A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100936 ER PT J AU Basu, A Wong, S Young, NS Brown, KE AF Basu, A Wong, S Young, NS Brown, KE TI No association of specific genotypes of CMV and HHV6 in hepatic tissues of patients with hepatitis-associated aplastic anemia (HAA). SO BLOOD LA English DT Meeting Abstract 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 2001 VL 98 IS 11 MA 934 BP 224A EP 224A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100938 ER PT J AU Erichsen, HC Bell, EM Tollerud, DJ Choi, E Jayaprakash, A Rothman, N Chanock, SJ AF Erichsen, HC Bell, EM Tollerud, DJ Choi, E Jayaprakash, A Rothman, N Chanock, SJ TI Single nucleotide polymorphism in the IL12A gene, encoding for IL12-p35 is associated with plasma levels of IL12 and GM-CSF. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, Gaithersburg, MD USA. NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. Med Coll Penn & Hahnemann Univ, Sch Publ Hlth, Philadelphia, PA 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 2001 VL 98 IS 11 MA 945 BP 227A EP 227A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100949 ER PT J AU Risitano, AM Kook, H Zeng, WH Chen, GB Young, NS Maciejewski, JP AF Risitano, AM Kook, H Zeng, WH Chen, GB Young, NS Maciejewski, JP TI Significance of oligoclonal and polyclonal expansion within CD8 and CD4 lymphocytes in aplastic anemia and paroxysmal nocturnal hemoglobinuria measured by VBCDR3 spectratyping and flow cytometry. SO BLOOD LA English DT Meeting Abstract 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 2001 VL 98 IS 11 MA 970 BP 232A EP 232A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100974 ER PT J AU Tsujimura, H Tamura, T Gongora, C Ozato, K AF Tsujimura, H Tamura, T Gongora, C Ozato, K TI Interferon consensus sequence binding protein (ICSBP) is a key regulator of dendritic cell development. SO BLOOD LA English DT Meeting Abstract C1 NICHHD, Lab Mol Growth Regulat, 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 2001 VL 98 IS 11 MA 971 BP 232A EP 232A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100975 ER PT J AU Bleesing, JJH Janik, J Fleisher, TA AF Bleesing, JJH Janik, J Fleisher, TA TI The abnormal T cells in large ganular lymphocyte leukemia express a novel CD45R isoform, similar to patients with the autoimmune lymphoproliferative syndrome SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Lab Med, Bethesda, MD 20892 USA. NCI, Metab 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 2001 VL 98 IS 11 MA 974 BP 233A EP 233A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100978 ER PT J AU ElKassar, N Lucas, P Byrne, K Guinter, T Singer, A Gress, RE AF ElKassar, N Lucas, P Byrne, K Guinter, T Singer, A Gress, RE TI A new model of IL-7 transgenic mice under the lck proximal promoter underlines the role of IL-7 as a modulator of thymic function. SO BLOOD LA English DT Meeting Abstract C1 NCI, Expt 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 2001 VL 98 IS 11 MA 996 BP 238A EP 238A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101000 ER PT J AU Link, BK Wang, H Byrd, JC Leonard, JP Davis, TA Flinn, I Hall, WC Turner, JF Bowles, J Shannon, M Levitt, D Weiner, GJ AF Link, BK Wang, H Byrd, JC Leonard, JP Davis, TA Flinn, I Hall, WC Turner, JF Bowles, J Shannon, M Levitt, D Weiner, GJ TI Prolonged clinical responses in patients with follicular lymphoma treated on a phase I trial of the anti-HLA-DR monoclonal antibody Remitogen (TM) (Hu1D10). SO BLOOD LA English DT Meeting Abstract C1 Univ Iowa, Iowa City, IA USA. Prot Design Labs, Fremont, CA USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Cornell Univ, Weil Med Coll, New York, NY USA. NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Pathol Associates Inc, Rockville, MD 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 2001 VL 98 IS 11 MA 4703 BP 244B EP 244B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201114 ER PT J AU Taylor, JG Choi, EH Savage, S Rodgers, GP Chanock, SJ AF Taylor, JG Choi, EH Savage, S Rodgers, GP Chanock, SJ TI Genomic diversity of the VCAM1 locus in human populations. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, Ctr Adv Technol, NIH, Gaithersburg, MD USA. NIDDK, Mol & Clin Hematol Branch, 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 2001 VL 98 IS 11 MA 1026 BP 244A EP 245A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134101030 ER PT J AU Beleslin-Cokic, BB Cokic, VP Yu, XB Weksler, BB Schechter, AN Noguchi, CT AF Beleslin-Cokic, BB Cokic, VP Yu, XB Weksler, BB Schechter, AN Noguchi, CT TI Erythropoietin induction of NO synthase and NO levels in human bone marrow endothelial cells. SO BLOOD LA English DT Meeting Abstract C1 NIH, NIDDK, Biol Chem Lab, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY 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 2001 VL 98 IS 11 MA 1040 BP 248A EP 248A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101044 ER PT J AU Chen, L Zhang, JC Tang, DC Rodgers, GP AF Chen, L Zhang, JC Tang, DC Rodgers, GP TI Commitment of hematopoietic stem cells relies on both autonomous and instructive mechanisms. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Mol & Clin Hematol 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 2001 VL 98 IS 11 MA 1155 BP 275A EP 275A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101159 ER PT J AU Hinds, KA Balaban, R Koretsky, A Silva, A Johnson, J Dunbar, CE AF Hinds, KA Balaban, R Koretsky, A Silva, A Johnson, J Dunbar, CE TI A new method for labeling and imaging viable primitive hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NINCDS, 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 2001 VL 98 IS 11 MA 1175 BP 279A EP 279A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101179 ER PT J AU Lekstrom-Himes, JA Khanna-Gupta, A Clarke, M Boxer, LA Berliner, N AF Lekstrom-Himes, JA Khanna-Gupta, A Clarke, M Boxer, LA Berliner, N TI Abnormalities in C/EBP epsilon expression in a patient with neutrophil specific granule deficiency. SO BLOOD LA English DT Meeting Abstract C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Sect Hematol, New Haven, CT 06520 USA. Univ Michigan, Med Ctr, Dept Pediat, Ann Arbor, MI 48109 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 2001 VL 98 IS 11 MA 1178 BP 280A EP 280A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101182 ER PT J AU Nagamura-Inoue, T Tsujimura, H Tamura, T Takahashi, TA Ozato, K AF Nagamura-Inoue, T Tsujimura, H Tamura, T Takahashi, TA Ozato, K TI ICSBP-dependent induction of macrophage differentiation and inhibition of granulocytes differentiation augmented by interferon-gamma. SO BLOOD LA English DT Meeting Abstract C1 NIH, NICHHD, Lab Mol Growth Regulat, Bethesda, MD USA. Univ Tokyo, Inst Med Sci, Div Cell Proc, Tokyo, 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 2001 VL 98 IS 11 MA 1208 BP 287A EP 287A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101212 ER PT J AU Ladd, A Farese, AM Reidinger, CJ Douek, D Woulfe, SL MacVittie, TJ AF Ladd, A Farese, AM Reidinger, CJ Douek, D Woulfe, SL MacVittie, TJ TI Radiation-induced T cell deficiencies can be abbreviated with administration of the chimeric growth factor receptor agonist Progenipoietin. SO BLOOD LA English DT Meeting Abstract C1 Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD USA. NIH, Vaccine Res Ctr, Bethesda, MD USA. Pharmacia Corp, Discovery Res, St Louis, MO 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 2001 VL 98 IS 11 MA 1247 BP 296A EP 296A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101251 ER PT J AU Griffith, LM Horwitz, M Eniafe, R Linton, GF Childs, RW AF Griffith, LM Horwitz, M Eniafe, R Linton, GF Childs, RW TI Quantitation of engraftment following nonmyeloablative allogeneic stem cell transplantation (NST) using fluorescent polymerase chain reaction primers for short tandem repeat (STR) polymorphisms. SO BLOOD LA English DT Meeting Abstract C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NIAID, Host Def Lab, 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 2001 VL 98 IS 11 MA 5021 BP 316B EP 316B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201432 ER PT J AU Melenhorst, JJ Eniafe, R Kirby, M Nakamura, R El Ouriaghli, F Barrett, AJ AF Melenhorst, JJ Eniafe, R Kirby, M Nakamura, R El Ouriaghli, F Barrett, AJ TI Flow cytometric analysis reveals massive expansions of effector CD8 clones in large granular lymphocyte leukemia (LGL). SO BLOOD LA English DT Meeting Abstract 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 2001 VL 98 IS 11 MA 1358 BP 322A EP 322A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101362 ER PT J AU Paul, JT Johnston, JB Mushinski, JF Mai, S AF Paul, JT Johnston, JB Mushinski, JF Mai, S TI Correlation of the D-type cyclins with clinical features and survival in CLL. SO BLOOD LA English DT Meeting Abstract C1 Manitoba Inst Cell Biol, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada. Univ Manitoba, Dept Internal Med, Winnipeg, MB, Canada. NCI, Mol Genet Sect, 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 2001 VL 98 IS 11 MA 1361 BP 322A EP 322A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101365 ER PT J AU Srinivasan, R Igarashi, T Mena, O Re, F Fischette, M Takahashi, Y Carvallo, C Young, NS Linehan, WM Childs, RW AF Srinivasan, R Igarashi, T Mena, O Re, F Fischette, M Takahashi, Y Carvallo, C Young, NS Linehan, WM Childs, RW TI Characterization of tumor-dendritic cell hybrids generated by electrofusion (EF) and polyethylene glycol (PEG) treatment. SO BLOOD LA English DT Meeting Abstract C1 NCI, Med & 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 2001 VL 98 IS 11 MA 5071 BP 327B EP 328B PN 2 PG 2 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201482 ER PT J AU Raphael, M Poirel, H Bosq, J Felman, P Berger, F Avet-Loiseau, H Launay, E Martin, A Bryon, PA Ott, G Muller-Hermelink, K Diebold, J Jaffe, ES Nathwani, B AF Raphael, M Poirel, H Bosq, J Felman, P Berger, F Avet-Loiseau, H Launay, E Martin, A Bryon, PA Ott, G Muller-Hermelink, K Diebold, J Jaffe, ES Nathwani, B TI Identification of the morphological, immunophenotypic and genomic profile of Burkitt lymphoma (BL) and its variants. SO BLOOD LA English DT Meeting Abstract C1 Inst Gustave Roussy, Villejuif, France. Hop Avicenne, F-93009 Bobigny, France. Hop Lyon Sud, Lyon, France. Hop Edouard Herriot, Lyon, France. Inst Biol, Nantes, France. Hop Hotel Dieu, F-75181 Paris, France. Univ Wurzburg, Wurzburg, Germany. NIH, Bethesda, MD 20892 USA. Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA. RI AMSELLEM, Sophie/B-3645-2012 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 2001 VL 98 IS 11 MA 1408 BP 333A EP 334A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134101412 ER PT J AU Wilson, WH Pittaluga, S O'Connor, P Hegde, U Drbohlav, N Janik, J Little, R Steinberg, S Cheson, B Staudt, L Raffeld, M Chabner, B Jaffe, ES AF Wilson, WH Pittaluga, S O'Connor, P Hegde, U Drbohlav, N Janik, J Little, R Steinberg, S Cheson, B Staudt, L Raffeld, M Chabner, B Jaffe, ES TI Rituximab may overcome bcl-2-associated chemotherapy resistance in untreated diffuse large B-cell lymphomas. SO BLOOD LA English DT Meeting Abstract C1 Natl Canc Inst, Ctr Canc Res, Bethesda, MD USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1447 BP 343A EP 343A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101451 ER PT J AU Melenhorst, JJ Eniafe, R Kirby, M Nakamura, R El Ouriaghli, F Barrett, AJ AF Melenhorst, JJ Eniafe, R Kirby, M Nakamura, R El Ouriaghli, F Barrett, AJ TI Identification of a highly skewed T cell receptor (TCR) V beta repertoire in CD4 cells and CD8 cells of patients with myelodysplastic syndrome (MDS) SO BLOOD LA English DT Meeting Abstract 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 2001 VL 98 IS 11 MA 1479 BP 351A EP 351A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101483 ER PT J AU Rezvani, K Mocellin, S Provenzano, M Melenhorst, J Hensel, N Fujiwara, H Sconocchia, G Stroncek, D Barrett, J AF Rezvani, K Mocellin, S Provenzano, M Melenhorst, J Hensel, N Fujiwara, H Sconocchia, G Stroncek, D Barrett, J TI Real time reverse transcriptase PCR can be used to demonstrate the presence of cytotoxic T lymphocytes against PR1 in healthy donors. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus 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 2001 VL 98 IS 11 MA 5258 BP 370B EP 371B PN 2 PG 2 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201669 ER PT J AU Welniak, A Sun, R Tian, ZG Richards, S Murphy, WJ AF Welniak, A Sun, R Tian, ZG Richards, S Murphy, WJ TI Recombinant human prolactin promotes hematopoietic reconstitution after syngeneic bone marrow transplantation in mice. SO BLOOD LA English DT Meeting Abstract C1 NCI, LMI, Frederick, MD 21701 USA. SAIC Frederick, IRSP, Frederick, MD 21701 USA. Genzyme Corp, Framingham, MA 01701 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 2001 VL 98 IS 11 MA 1599 BP 380A EP 380A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101603 ER PT J AU Igarashi, T Srinivasan, R Parkhurst, M Takahashi, Y Re, F Mena, O Barrett, AJ Liu, JM Young, NS Childs, RW AF Igarashi, T Srinivasan, R Parkhurst, M Takahashi, Y Re, F Mena, O Barrett, AJ Liu, JM Young, NS Childs, RW TI In vitro generation of human telomerase enzyme (HTERT) specific CD4 and CD8 T-cell clones from healthy donors using dendritic cells (DCs) transduced with an adenovirus encoding the HTERT transgene. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Urolog Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Surg Branch, 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 2001 VL 98 IS 11 MA 1619 BP 385A EP 385A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101623 ER PT J AU Jung, US Foley, JE Coppins, JL Eckhaus, MA Bishop, MR Fowler, DH AF Jung, US Foley, JE Coppins, JL Eckhaus, MA Bishop, MR Fowler, DH TI Co-stimulated allogeneic Tc1 cells mediate a curative GVT effect against murine breast cancer in a FasL-independent manner. SO BLOOD LA English DT Meeting Abstract C1 NIH, NCI, Bethesda, MD 20892 USA. NIH, Vet Res Program, Natl Ctr Res Resources, 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 2001 VL 98 IS 11 MA 1621 BP 385A EP 385A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101625 ER PT J AU Fry, TJ McKirdy, MA Medeiros, F Mackall, CL AF Fry, TJ McKirdy, MA Medeiros, F Mackall, CL TI Progressive tumor growth in a model tumor antigen system does not induce immunologic tolerance but appears to induce weak immunity toward tumor antigens. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat 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 2001 VL 98 IS 11 MA 1623 BP 386A EP 386A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101627 ER PT J AU Melchionda, F Sinha, M Khanna, C Merchant, MS Fry, TJ Helman, LJ Mackall, CL AF Melchionda, F Sinha, M Khanna, C Merchant, MS Fry, TJ Helman, LJ Mackall, CL TI T cell mediated endogenous immune responses are unable to protect against primary tumor growth, but modulate the development of recurrent disease in murine osterosarcoma. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat 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 2001 VL 98 IS 11 MA 1631 BP 387A EP 388A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134101635 ER PT J AU Nakamura, R Cortez, K Childs, R Solomon, S Battiwalla, M Gill, VJ Read, EJ Leitman, S Bennett, JE Hensel, N Barrett, J AF Nakamura, R Cortez, K Childs, R Solomon, S Battiwalla, M Gill, VJ Read, EJ Leitman, S Bennett, JE Hensel, N Barrett, J TI Prevention of CMV disease by a prophylaxis-monitoring-early treatment (PME) using high-dose acyclovir, pp65 antigenemia, and ganciclovir: Elimination of CMV mortality and low risk in non-myeloablative transplant (NMT). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Natl Inst Allergy, Bethesda, MD USA. Infect Dis Inst, Bethesda, MD USA. NIH, Dept Lab Med, 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 2001 VL 98 IS 11 MA 1656 BP 394A EP 394A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101660 ER PT J AU Choi, U Malech, HL AF Choi, U Malech, HL TI Green fluorescent protein-methylguanine methyltransferase fusion protein demonstrates nuclear localization and confers drug resistance: An informative model for the development of drug selectable gene therapy. SO BLOOD LA English DT Meeting Abstract C1 NIAID, 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 2001 VL 98 IS 11 MA 5397 BP 403B EP 403B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201808 ER PT J AU Hou, JW Fowler, DH Wilson, W Gress, R Kasten-Sportes, C Castro, K Lietzau, J Marchigiani, D Bishop, MR AF Hou, JW Fowler, DH Wilson, W Gress, R Kasten-Sportes, C Castro, K Lietzau, J Marchigiani, D Bishop, MR TI Potent graft-versus-lymphoma effect after non-myeloablative stem cell transplant in refractory non-Hodgkin's lymphoma: Role of rapid complete donor chimerism. SO BLOOD LA English DT Meeting Abstract C1 NCI, 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 2001 VL 98 IS 11 MA 1696 BP 404A EP 404A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101700 ER PT J AU Fujiwara, H Sconocchia, G Melenhorst, J Hensel, N Barrett, AJ AF Fujiwara, H Sconocchia, G Melenhorst, J Hensel, N Barrett, AJ TI Tissue-restricted responses across HLA barriers: Selection and identification of leukemia-restricted CTL in HLA mismatched stimulator-responder pairs. SO BLOOD LA English DT Meeting Abstract 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 2001 VL 98 IS 11 MA 1699 BP 405A EP 405A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101703 ER PT J AU Storek, J Joseph, A Dawson, MA Douek, DC Storer, B Maloney, DG AF Storek, J Joseph, A Dawson, MA Douek, DC Storer, B Maloney, DG TI Factors influencing T-lymphopoiesis after allogeneic hematopoietic cell transplantation. SO BLOOD LA English DT Meeting Abstract C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NIH, Vaccine Res Ctr, 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 2001 VL 98 IS 11 MA 1701 BP 405A EP 405A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101705 ER PT J AU Pavletic, S Tarantolo, S Lynch, JC Abhyankar, S Bierman, PJ Vose, JM Geller, RB McGuirk, J Foran, J Bociek, RG Hadi, A Day, SD Armitage, JO Kessinger, A Bishop, MR AF Pavletic, S Tarantolo, S Lynch, JC Abhyankar, S Bierman, PJ Vose, JM Geller, RB McGuirk, J Foran, J Bociek, RG Hadi, A Day, SD Armitage, JO Kessinger, A Bishop, MR TI Long term immunological and clinical effects after a randomized, double-blind trial of filgrastim versus placebo in allogeneic blood transplantation. SO BLOOD LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE USA. St Lukes Hosp, Kansas City, MO USA. Arizona Canc Ctr, Scottsdale, AZ 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 2001 VL 98 IS 11 MA 1711 BP 408A EP 408A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101715 ER PT J AU Re, F Srinivasan, R Igarashi, T Tisdale, JF Dunbar, CE Childs, RV AF Re, F Srinivasan, R Igarashi, T Tisdale, JF Dunbar, CE Childs, RV TI Generation of green fluorescent protein (GFP) specific T-lymphocyte clones from humans following transduction of dendritic cells with an adenovirus encoding GFP. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Med & Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Mol & Clin Hematol Branch, 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 2001 VL 98 IS 11 MA 5432 BP 411B EP 411B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201843 ER PT J AU Ringden, O Barrett, AJ Zhang, MJ Loberiza, FR Horowitz, MM AF Ringden, O Barrett, AJ Zhang, MJ Loberiza, FR Horowitz, MM CA GVHD GVL Writing Comm IBMTR TI A high CD34 cell dose is associated with improved leukemia-free survival in recipients of HLA-identical bone marrow or peripheral blood stem cells. SO BLOOD LA English DT Meeting Abstract C1 Med Coll Wisconsin, Int Bone Marrow Transplant Registry Autologous Bl, IBMTR ABMTR, Milwaukee, WI 53226 USA. Huddinge Univ Hosp, Karolinska Inst, S-14186 Huddinge, Sweden. NHLBI, 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 2001 VL 98 IS 11 MA 1735 BP 413A EP 413A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101739 ER PT J AU Solomon, SR Nakamura, R Read, EJ Leitman, SF Childs, RW Dunbar, CE Young, NS Barrett, AJ AF Solomon, SR Nakamura, R Read, EJ Leitman, SF Childs, RW Dunbar, CE Young, NS Barrett, AJ TI Is cyclosporine (CSA) necessary to prevent graft-versus-host-disease (GVHD) after T cell depleted peripheral blood stem cell transplantation (PBSCT)? SO BLOOD LA English DT Meeting Abstract C1 NIH, NHLBI, Hematol Branch, Stem Cell Allotransplantat Sect, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, 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 2001 VL 98 IS 11 MA 1744 BP 416A EP 416A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101748 ER PT J AU Rao, VK Kitazono, M Robey, R Aikou, T Bates, SE Fojo, T Goldsmith, ME AF Rao, VK Kitazono, M Robey, R Aikou, T Bates, SE Fojo, T Goldsmith, ME TI Adenovirus transgene expression is enhanced in normal and malignant hematopoietic cells by pretreatment with the histone deacetylase inhibitor FR901228 (depsipeptide). SO BLOOD LA English DT Meeting Abstract C1 NCI, Canc Res Ctr, 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 2001 VL 98 IS 11 MA 1778 BP 424A EP 424A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101782 ER PT J AU Bevans, MF Nunez, O Wisch, L Chamberlain, C AF Bevans, MF Nunez, O Wisch, L Chamberlain, C TI Management of infusion related toxicities associated with high-dose antithymocyte globulin (ATG). SO BLOOD LA English DT Meeting Abstract C1 NIH, Ctr Clin, 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 2001 VL 98 IS 11 MA 1789 BP 426A EP 427A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134101793 ER PT J AU Frazar, TF Seidel, NE Cline, AP Garrett, LJ Felsenfeld, G Gallagher, PG Bodine, DM AF Frazar, TF Seidel, NE Cline, AP Garrett, LJ Felsenfeld, G Gallagher, PG Bodine, DM TI Insulator elements from the chicken beta-globin locus allow high level, position independent, copy number dependent expression from the erythroid band 3 promoter in transgenic mice. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, GMBB, Bethesda, MD 20892 USA. NHGRI, GDRB, Bethesda, MD 20892 USA. NIDDK, LMB, Bethesda, MD USA. Yale Univ, New Haven, CT 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 2001 VL 98 IS 11 MA 1826 BP 435A EP 436A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134101830 ER PT J AU Wong, EY Nilson, DG Wong, C Garrett, LJ Bodine, DM Gallagher, PG AF Wong, EY Nilson, DG Wong, C Garrett, LJ Bodine, DM Gallagher, PG TI An alternatively spliced intron is required for high level, erythroid-specific expression of the human alpha-spectrin gene in vivo. SO BLOOD LA English DT Meeting Abstract C1 Yale Univ, New Haven, CT USA. NHGRI, GMMB, 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 2001 VL 98 IS 11 MA 1830 BP 436A EP 437A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134101834 ER PT J AU Fogarty, PF Huhn, RD Nakamura, R Read, EJ Rick, ME Leitman, SF Greene, A Gratwohl, A Young, NS Barrett, AJ Dunbar, CE AF Fogarty, PF Huhn, RD Nakamura, R Read, EJ Rick, ME Leitman, SF Greene, A Gratwohl, A Young, NS Barrett, AJ Dunbar, CE TI Intensive immunosuppression with high-dose cyclophosphamide and autologous CD34+selected hematopoietic cell support for chronic refractory autoimmune thrombocytopenia (AITP): A follow-up report. SO BLOOD LA English DT Meeting Abstract C1 NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Corriel inst Med Res, Camden, NJ USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. Univ Basel, Basel, Switzerland. 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 2001 VL 98 IS 11 MA 1855 BP 442A EP 442A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101859 ER PT J AU Curtis, DJ Cline, AP Seidel, NE Garrett, LJ Bodine, DM AF Curtis, DJ Cline, AP Seidel, NE Garrett, LJ Bodine, DM TI Enforced expression of the chromatin binding protein HMG4 inhibits differentiation of hematopoietic stem cells. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Genet & Mol Biol Branch, Bethesda, MD USA. Royal Melbourne Hosp, Rotary Bone Marrow Res Lab, Melbourne, Vic, Australia. 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 2001 VL 98 IS 11 MA 1893 BP 452A EP 452A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101897 ER PT J AU Caruccio, L Bettinotti, MP Olsen, A Stroncek, DF AF Caruccio, L Bettinotti, MP Olsen, A Stroncek, DF TI Use of bioinformatics to identify the genomic structure of the gene encoding Polycythemia Rubra Vera-1 (PRV-1). SO BLOOD LA English DT Meeting Abstract C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. Lawrence Livermore Natl Lab, Joint Genome Inst, Dept Energy, Walnut Creek, 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 2001 VL 98 IS 11 MA 1964 BP 470A EP 470A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101968 ER PT J AU Asakura, T Lian, L Ollinger, F Chen, QK Iyamu, EW Abdulmalik, O Zhang, CJ Brugnara, C Evans, G AF Asakura, T Lian, L Ollinger, F Chen, QK Iyamu, EW Abdulmalik, O Zhang, CJ Brugnara, C Evans, G TI Current status of the NIH Sickle Cell Disease Reference Laboratory: Validation of 7 new therapeutic agents. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Hosp, Boston, MA 02115 USA. NHLBI, Blood Div, NIH, Bethesda, MD 20892 USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 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 2001 VL 98 IS 11 MA 2031 BP 487A EP 487A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102035 ER PT J AU Zhang, CJ Chen, QK Lian, LR Li, X Vassilev, V Lai, M Evans, G Asakura, T AF Zhang, CJ Chen, QK Lian, LR Li, X Vassilev, V Lai, M Evans, G Asakura, T TI Antisickling effect of MX-1520, a prodrug of vanillin. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Medinox Inc, Pharmacol, San Diego, CA USA. NIH, Sickle Cell Sci Res Grp, 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 2001 VL 98 IS 11 MA 2032 BP 487A EP 487A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102036 ER PT J AU Wojda, U Leigh, KR Njoroge, JM Noel, P Miller, JL AF Wojda, U Leigh, KR Njoroge, JM Noel, P Miller, JL TI Hemoblobin production and modulation with cytokines in primary human erythroid cells. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NIH, Ctr Clin, Dept 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 2001 VL 98 IS 11 MA 2038 BP 488A EP 488A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102042 ER PT J AU Cokic, VP Smith, RD Beleslin-Cokic, BB Gladwin, MT Schechter, AN AF Cokic, VP Smith, RD Beleslin-Cokic, BB Gladwin, MT Schechter, AN TI Nitric oxide donors increase gamma-globin mRNA and HbF levels in cultured human erythroid cells. SO BLOOD LA English DT Meeting Abstract 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 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 2001 VL 98 IS 11 MA 2065 BP 495A EP 495A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102069 ER PT J AU Rogers, HM Yu, XB Smith, R Noguchi, CT AF Rogers, HM Yu, XB Smith, R Noguchi, CT TI Modeling bone marrow erythropoiesis: Oxygen dependent proliferation and globin gene expression. SO BLOOD LA English DT Meeting Abstract 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 2001 VL 98 IS 11 MA 2063 BP 495A EP 495A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102067 ER PT J AU Little, JA Dempsey, NJ Ojalvo, LS AF Little, JA Dempsey, NJ Ojalvo, LS TI Short-chain fatty acids can up-regulate an embryonic globin gene promoter through specific transcription factors and factor/historic acetyl transferases acting at specific sequences. SO BLOOD LA English DT Meeting Abstract C1 Univ Minnesota, Minneapolis, MN USA. NIH, NIDDK, LCDB, 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 2001 VL 98 IS 11 MA 2076 BP 498A EP 498A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102080 ER PT J AU Zhu, JQ Tang, DC Chin, K Rodgers, GP AF Zhu, JQ Tang, DC Chin, K Rodgers, GP TI Molecular and cellular effects of a hydroxyurea induced small GTP-binding protein in K562 cells. SO BLOOD LA English DT Meeting Abstract C1 NIH, NIDDK, MCHB, 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 2001 VL 98 IS 11 MA 2075 BP 498A EP 498A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102079 ER PT J AU Wen, J Yu, XB Rogers, HM Noguchi, CT AF Wen, J Yu, XB Rogers, HM Noguchi, CT TI SATB1 activated early globin gene expression by binding to MARs in the beta-globin gene locus. SO BLOOD LA English DT Meeting Abstract C1 NIH, NIDDK, Biol Chem 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 2001 VL 98 IS 11 MA 2081 BP 499A EP 499A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102086 ER PT J AU Fry, TJ Donohue, SJ Hecht, TT Tomaszewski, J Giardina, S Mackall, CL AF Fry, TJ Donohue, SJ Hecht, TT Tomaszewski, J Giardina, S Mackall, CL TI IL-7 expands T cells in non-human primates. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Toxicol & Pharmacol Branch, Bethesda, MD 20892 USA. NCI, Biol Resources Branch, Frederick, MD 21701 USA. SAIC, 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 2001 VL 98 IS 11 MA 2087 BP 500A EP 501A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102092 ER PT J AU Smith, RD Ikonomi, P Cheadle, C Becker, KG Schechter, AN AF Smith, RD Ikonomi, P Cheadle, C Becker, KG Schechter, AN TI Microarray analysis of gene expression in primary CD34+erythroid cells after butyrate induction. SO BLOOD LA English DT Meeting Abstract C1 NIH, Lab Chem Biol, Bethesda, MD 20892 USA. NIA, DNA Array Unit, NIH, 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 2001 VL 98 IS 11 MA 2085 BP 500A EP 500A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102090 ER PT J AU Levine, AM Berhane, K Masri-Lavine, L Young, M Cohen, M Anastos, K Newman, M Augenbraun, M Gange, S Watts, H AF Levine, AM Berhane, K Masri-Lavine, L Young, M Cohen, M Anastos, K Newman, M Augenbraun, M Gange, S Watts, H TI Impact of anemia on the survival of HIV infected women. SO BLOOD LA English DT Meeting Abstract C1 Keck Sch Med, Los Angeles, CA USA. Georgetown Univ, Washington, DC USA. Cook Cty Hosp, Chicago, IL 60612 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Maimonides Hosp, Brooklyn, NY 11219 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NIH, Rockville, MD 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 2001 VL 98 IS 11 MA 2091 BP 501A EP 502A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102096 ER PT J AU Foster, CB Kaslow, R Stein, S Chen, R Springer, G Jacobson, LP Chanock, SJ AF Foster, CB Kaslow, R Stein, S Chen, R Springer, G Jacobson, LP Chanock, SJ TI A genetic variant of FCGR3A could modify the risk of Kaposi's sarcoma in HIV-infected men. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD USA. Univ Alabama, Birmingham, AL USA. Johns Hopkins Sch Publ Hlth, 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 2001 VL 98 IS 11 MA 2110 BP 506A EP 506A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102115 ER PT J AU Sconocchia, G Fujiwara, H Hensel, N Rezvani, K Tisdale, J Barrett, AJ AF Sconocchia, G Fujiwara, H Hensel, N Rezvani, K Tisdale, J Barrett, AJ TI Integrin expression on CD34-derived natural killer cells defines at least two distinct phenotypes: Discrete NK cell subsets or different stages of NK differentiation? SO BLOOD LA English DT Meeting Abstract C1 NIH, Hematol Branch, 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 2001 VL 98 IS 11 MA 2139 BP 512A EP 512A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102144 ER PT J AU Wiestner, A Cho, HJ Asch, AS Michelis, MA Zeller, JA Peerschke, EIB Weksler, BB Schechter, GP AF Wiestner, A Cho, HJ Asch, AS Michelis, MA Zeller, JA Peerschke, EIB Weksler, BB Schechter, GP TI Rituximab in the treatment of acquired factor VIII (FVIII) inhibitors. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Hackensack Univ Med Ctr, Hackensack, NJ USA. George Washington Univ, 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 2001 VL 98 IS 11 MA 2233 BP 534A EP 534A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102238 ER PT J AU Gao, CJ Kang, EM Metzger, M Agricola, B Donahue, RE Tisdale, JF AF Gao, CJ Kang, EM Metzger, M Agricola, B Donahue, RE Tisdale, JF TI Retrovirally transduced muscle derived cells contribute poorly toward hematopoietic reconstitution in nonhuman primates. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Mol & Clin Hematol Branch, Bethesda, MD USA. NIH, NHLBI, Hematol Branch, Bethesda, MD 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 2001 VL 98 IS 11 MA 2282.5 BP 545A EP 546A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102288 ER PT J AU Nilson, DG Orkin, SH Gallagher, PG Bodine, DM AF Nilson, DG Orkin, SH Gallagher, PG Bodine, DM TI The erythrocyte membrane protein genes ankyrin and band 3 (AE1) are non-globin erythroid Krupple-like factor (EKLF) target genes. SO BLOOD LA English DT Meeting Abstract C1 NIH, NHGRI, GMBB, Bethesda, MD USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Yale Univ, New Haven, CT 06520 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 2001 VL 98 IS 11 MA 2309 BP 552A EP 552A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102316 ER PT J AU Hou, JZ Zacharchuk, CM Crock, R AF Hou, JZ Zacharchuk, CM Crock, R TI Molecular cloning and characterization of caspase interacting protein from human leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 Ohio Univ, Coll Med, Affiliated Hosp, Internal Med Residency Program, Canton, OH USA. NIH, NCI, Lab Immune Cell Biol, Bethesda, MD USA. Genet Inst Inc, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2321 BP 555A EP 555A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102328 ER PT J AU Zhang, ML Zhang, Z Garmestani, K Schultz, J Axworthy, DB Zuo, YT Lin, YK Sanderson, J Theodore, L Yau, E Carrasquillo, JA Brechbiel, MW Waldmann, TA AF Zhang, ML Zhang, Z Garmestani, K Schultz, J Axworthy, DB Zuo, YT Lin, YK Sanderson, J Theodore, L Yau, E Carrasquillo, JA Brechbiel, MW Waldmann, TA TI Multistep targeting of ALCL tumor bearing mice with a tetra-valent single-chain antibody-streptavidin fusion protein. SO BLOOD LA English DT Meeting Abstract C1 NIH, NCI, Metab Branch, Bethesda, MD USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NIH, NCI, Radiat Oncol Branch, Bethesda, MD USA. NeoRx Corp, Seattle, WA USA. RI Carrasquillo, Jorge/E-7120-2010 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 2001 VL 98 IS 11 MA 2479 BP 592A EP 592A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102486 ER PT J AU Cortes, J Kurzrock, R O'Brien, SM Thomas, D Faderl, S Manero, GG Wright, J Sonnichsen, D Cooper, M Estey, E Kantarjian, HM AF Cortes, J Kurzrock, R O'Brien, SM Thomas, D Faderl, S Manero, GG Wright, J Sonnichsen, D Cooper, M Estey, E Kantarjian, HM TI Phase I study of a farnesyl transferase inhibitor (FTI), BMS-214662, in patients with refractory or relapsed acute leukemias. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. Bristol Myers Squibb Co, New York, NY 10154 USA. NR 0 TC 9 Z9 9 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 2001 VL 98 IS 11 MA 2489 BP 594A EP 594A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102496 ER PT J AU Shalabi, AM Fallavollita, A Cheson, BD Edwards, M Plante, M Huntley, C Phalen, K Mungo, AJ AF Shalabi, AM Fallavollita, A Cheson, BD Edwards, M Plante, M Huntley, C Phalen, K Mungo, AJ TI Arsenic trioxide in relapsed or refractory Acute Promyelocytic Leukemia - An NCI special exception (compassionate use) program. SO BLOOD LA English DT Meeting Abstract C1 NCI, Div Canc Treatment, Canc Therapy Evaluat Program, 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 2001 VL 98 IS 11 MA 2497 BP 596A EP 596A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102504 ER PT J AU Janik, JE Morris, JC Pittaluga, S Drbohlav, N McDonald, K Gutierrez, M Raffeld, M Waldmann, TA Jaffe, ES Wilson, WH AF Janik, JE Morris, JC Pittaluga, S Drbohlav, N McDonald, K Gutierrez, M Raffeld, M Waldmann, TA Jaffe, ES Wilson, WH TI Serum soluble IL-2 receptor levels are elevated in patients with anaplastic large cell lymphoma (ALCL). SO BLOOD LA English DT Meeting Abstract C1 NCI, Ctr Canc Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2505 BP 598A EP 598A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102512 ER PT J AU Decker, T Hipp, S Kreitman, RJ Pastan, I Peschel, C Licht, T AF Decker, T Hipp, S Kreitman, RJ Pastan, I Peschel, C Licht, T TI Immunostimulatory phosphorothioate oligodeoxynucleotides sensitize B-CLL cells to recombinant immunotoxin. SO BLOOD LA English DT Meeting Abstract C1 Tech Univ Munich, Dept Med 3, D-8000 Munich, Germany. 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 2001 VL 98 IS 11 MA 2548 BP 608A EP 608A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102555 ER PT J AU Kurzrock, R Sebti, SM Kantarjian, HM Wright, J Cortes, JE Thomas, DA Wilson, E Beran, M Koller, CA O'Brien, S Freireich, EJ Talpaz, M AF Kurzrock, R Sebti, SM Kantarjian, HM Wright, J Cortes, JE Thomas, DA Wilson, E Beran, M Koller, CA O'Brien, S Freireich, EJ Talpaz, M TI Phase I study of a farnesyl transferase inhibitor, R115777, in patients with myelodysplastic syndrome. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, CTEP, Bethesda, MD 20892 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. NR 0 TC 21 Z9 21 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 2001 VL 98 IS 11 MA 2609 BP 623A EP 623A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102616 ER PT J AU Nakamura, R Saunthararajah, Y Wisch, L Sloand, E Kim, S Prchal, J Melenhorst, JJ Liu, J Dunbar, CE Young, NS Barrett, J AF Nakamura, R Saunthararajah, Y Wisch, L Sloand, E Kim, S Prchal, J Melenhorst, JJ Liu, J Dunbar, CE Young, NS Barrett, J TI A phase II study of antithymocyte globulin and cyclosporine to treat cytopenia of myelodysplastic syndrome: Interim report SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Univ Illinois, Hematol Oncol Sect, Chicago, IL USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2612 BP 624A EP 624A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102619 ER PT J AU Akin, C Kirshenbaum, AS Metcalfe, DD AF Akin, C Kirshenbaum, AS Metcalfe, DD TI Evaluation of the diagnostic value of flow cytometric analysis of the bone marrow aspirate in systemic mastocytosis. SO BLOOD LA English DT Meeting Abstract C1 NIAID, Lab Allerg Dis, 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 2001 VL 98 IS 11 MA 2640 BP 630A EP 630A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102647 ER PT J AU Magnusson, MK Meade, KE Nakamura, R Barrett, J Dunbar, CE AF Magnusson, MK Meade, KE Nakamura, R Barrett, J Dunbar, CE TI Molecular evidence for efficacy of STI-571 in chronic myelomonocytic leukemia (CMML)with a platelet-derived growth factor beta-receptor (PDGF beta R) fusion oncogene. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2644 BP 631A EP 631A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102651 ER PT J AU Kreitman, RJ Wilson, WH Noel, P Stetler-Stevenson, M Raffeld, M Sorbara, L Squires, D O'Hagan, D Zancan, M Bergeron, K FitzGerald, DJ Pastan, I AF Kreitman, RJ Wilson, WH Noel, P Stetler-Stevenson, M Raffeld, M Sorbara, L Squires, D O'Hagan, D Zancan, M Bergeron, K FitzGerald, DJ Pastan, I TI Complete remission of chemoresistant hairy cell leukemia with recombinant anti-CD22 immunotoxin BL22, relapse, and status of minimal residual disease in the blood and bone marrow. SO BLOOD LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, 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 2001 VL 98 IS 11 MA 2662 BP 635A EP 636A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102669 ER PT J AU Chute, JP Wells, M Clark, W Harlan, D Park, J Stull, M Civin, C AF Chute, JP Wells, M Clark, W Harlan, D Park, J Stull, M Civin, C TI Quantitative ex-vivo expansion of human bone marrow repopulating cells occurs via activation of the primitive bone marrow CD34(+)CD38(-) subset. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Navy TAB, Stem Cell Biol Sect, NIH, Bethesda, MD USA. Johns Hopkins Univ, Med Ctr, Hematopoiesis Sect, 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 2001 VL 98 IS 11 MA 2744 BP 654A EP 654A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102757 ER EF